2024-03-28T12:22:07Zhttps://escholarship.org/oaioai:escholarship.org:ark:/13030/qt6pn2k6dm2024-03-26T21:00:18Zqt6pn2k6dmMolecular mechanism of off-target effects in CRISPR-Cas9Ricci, Clarisse GChen, Janice SMiao, YinglongJinek, MartinDoudna, Jennifer AMcCammon, J AndrewPalermo, Giulia2019-01-01CRISPR-Cas9 is the state-of-the-art technology for editing and manipulating nucleic acids. However, the occurrence of off-target mutations can limit its applicability. Here, all-atom enhanced molecular dynamics (MD) simulations – using Gaussian accelerated MD (GaMD) – are used to decipher the mechanism of off-target binding at the molecular level. GaMD reveals that base pair mismatches in the target DNA at specific distal sites with respect to the Protospacer Adjacent Motif (PAM) induce an extended opening of the RNA:DNA heteroduplex, which leads to newly discovered interactions between the unwound nucleic acids and the protein counterpart. The conserved interactions between the target DNA strand and the L2 loop of the catalytic HNH domain constitute a “lock” effectively decreasing the conformational freedom of the HNH domain and its activation for cleavage. Remarkably, depending on their position at PAM distal sites, DNA mismatches leading to off-target cleavages are unable to “lock” the HNH domain, thereby identifying the ability to “lock” HNH as a key determinant. Consistently, off-target sequences hampering the catalysis have been shown to “trap” somehow the HNH domain in an inactive “conformational checkpoint” state (Dagdas et al. Sci Adv, 2017). As such, this mechanism identifies the molecular basis underlying off-target cleavages and contributes in clarifying a long-lasting open issue of the CRISPR-Cas9 function. It also poses the foundation for designing novel and more specific Cas9 variants, which could be obtained by magnifying the “locking” interactions between HNH and the target DNA in the presence of any incorrect off-target sequence, thus preventing undesired cleavages.Biochemistry and Cell BiologyBioinformatics and Computational BiologyBiological SciencesBiotechnologyGeneticsUnderpinning research1.1 Normal biological development and functioningGeneric health relevancepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6pn2k6dmarticleoai:escholarship.org:ark:/13030/qt0pz439f02024-03-25T21:18:09Zqt0pz439f0Comparative genomics analysis of drought response between obligate CAM and C3 photosynthesis plantsHu, RongbinZhang, JinJawdy, SaraSreedasyam, AvinashLipzen, AnnaWang, MeiNg, VivianDaum, ChristopherKeymanesh, KeykhosrowLiu, DegaoLu, HaiweiRanjan, PriyaChen, Jin-GuiMuchero, WellingtonTschaplinski, Timothy JTuskan, Gerald ASchmutz, JeremyYang, Xiaohan2022-10-01Crassulacean acid metabolism (CAM) plants exhibit elevated drought and heat tolerance compared to C3 and C4 plants through an inverted pattern of day/night stomatal closure and opening for CO2 assimilation. However, the molecular responses to water-deficit conditions remain unclear in obligate CAM species. In this study, we presented genome-wide transcription sequencing analysis using leaf samples of an obligate CAM species Kalanchoë fedtschenkoi under moderate and severe drought treatments at two-time points of dawn (2-h before the start of light period) and dusk (2-h before the dark period). Differentially expressed genes were identified in response to environmental drought stress and a whole genome wide co-expression network was created as well. We found that the expression of CAM-related genes was not regulated by drought stimuli in K. fedtschenkoi. Our comparative analysis revealed that CAM species (K. fedtschenkoi) and C3 species (Arabidopsis thaliana, Populus deltoides 'WV94') share some common transcriptional changes in genes involved in multiple biological processes in response to drought stress, including ABA signaling and biosynthesis of secondary metabolites.Plant BiologyBiological SciencesGeneticsBiotechnologyHuman GenomeClean Water and SanitationCarbon DioxideCrassulacean Acid MetabolismDroughtsGenomicsPhotosynthesisPlantsWaterCrassulacean acid metabolismKalanchoe  fedtschenkoiDrought stressRNA-SeqAbscisic acidSecondary metabolismKalanchoë fedtschenkoiPlant Biology & BotanyPlant biologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0pz439f0articleoai:escholarship.org:ark:/13030/qt79t6410z2024-03-25T20:45:11Zqt79t6410zEnhancing untargeted metabolomics using metadata-based source annotationGauglitz, Julia MWest, Kiana ABittremieux, WoutWilliams, Candace LWeldon, Kelly CPanitchpakdi, MorganDi Ottavio, FrancescaAceves, Christine MBrown, ElizabethSikora, Nicole CJarmusch, Alan KMartino, CameronTripathi, AnupriyaMeehan, Michael JDorrestein, KathleenShaffer, Justin PCoras, RoxanaVargas, FernandoGoldasich, Lindsay DeRightSchwartz, TaraBryant, MacKenzieHumphrey, GregoryJohnson, Abigail JSpengler, KatharinaBelda-Ferre, PedroDiaz, EdgarMcDonald, DanielZhu, QiyunElijah, Emmanuel OWang, MingxunMarotz, ClarisseSprecher, Kate EVargas-Robles, DanielaWithrow, DanaAckermann, GailHerrera, LourdesBradford, Barry JMarques, Lucas Maciel MaurizAmaral, Juliano GeraldoSilva, Rodrigo MoreiraVeras, Flavio ProtasioCunha, Thiago MattarOliveira, Rene Donizeti RibeiroLouzada-Junior, PauloMills, Robert HPiotrowski, Paulina KServetas, Stephanie LDa Silva, Sandra MJones, Christina MLin, Nancy JLippa, Katrice AJackson, Scott ADaouk, Rima KaddurahGalasko, DouglasDulai, Parambir SKalashnikova, Tatyana IWittenberg, CurtTerkeltaub, RobertDoty, Megan MKim, Jae HRhee, Kyung EBeauchamp-Walters, JuliaWright, Kenneth PDominguez-Bello, Maria GloriaManary, MarkOliveira, Michelli FBoland, Brigid SLopes, Norberto PeporineGuma, MonicaSwafford, Austin DDutton, Rachel JKnight, RobDorrestein, Pieter C2022-12-01Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library. Applying this approach to food source data, we show that it increases MS/MS spectral usage 5.1-fold over conventional structural MS/MS library matches and allows empirical assessment of dietary patterns from untargeted data.Medical Biochemistry and MetabolomicsAnalytical ChemistryBiomedical and Clinical SciencesChemical SciencesNeurodegenerativeNeurosciencesNutritionMultiple SclerosisBrain DisordersHumansTandem Mass SpectrometryMetadataMetabolomicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/79t6410zarticleNature Biotechnology, vol 40, iss 121774 - 1779oai:escholarship.org:ark:/13030/qt0tt974fv2024-03-25T14:59:18Zqt0tt974fvGNPS Dashboard: Collaborative Analysis of Mass Spectrometry Data in the Web BrowserPetras, DanielPhelan, Vanessa VAcharya, DeepaAllen, Andrew EAron, Allegra TBandeira, NunoBowen, Benjamin PBelle-Oudry, DeirdreBoecker, SimonCummings, Dale ADeutsch, Jessica MFahy, EoinGarg, NehaGregor, RachelHandelsman, JoNavarro-Hoyos, MirthaJarmusch, Alan KJarmusch, Scott ALouie, KatherineMaloney, Katherine NMarty, Michael TMeijler, Michael MMizrahi, ItzhakNeve, Rachel LNorthen, Trent RMolina-Santiago, CarlosPanitchpakdi, MorganPullman, BenjaminPuri, Aaron WSchmid, RobinSubramaniam, ShankarThukral, MonicaVasquez-Castro, FelipeDorrestein, Pieter CWang, Mingxun2021-01-01Access to web-based platforms has enabled scientists to perform research remotely. A critical aspect of mass spectrometry data analysis is the inspection, analysis, and visualization of the raw data to validate data quality and confirm statistical observations. We developed the GNPS Dashboard, a web-based data visualization tool, to facilitate synchronous collaborative inspection, visualization, and analysis of private and public mass spectrometry data remotely.Analytical ChemistryChemical Sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0tt974fvarticleoai:escholarship.org:ark:/13030/qt42s679jx2024-03-25T00:12:22Zqt42s679jxKey role of the REC lobe during CRISPR–Cas9 activation by ‘sensing’, ‘regulating’, and ‘locking’ the catalytic HNH domainPalermo, GiuliaChen, Janice SRicci, Clarisse GRivalta, IvanJinek, MartinBatista, Victor SDoudna, Jennifer AMcCammon, J Andrew2018-01-01Understanding the conformational dynamics of CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 is of the utmost importance for improving its genome editing capability. Here, molecular dynamics simulations performed using Anton-2 - a specialized supercomputer capturing micro-to-millisecond biophysical events in real time and at atomic-level resolution - reveal the activation process of the endonuclease Cas9 toward DNA cleavage. Over the unbiased simulation, we observe that the spontaneous approach of the catalytic domain HNH to the DNA cleavage site is accompanied by a remarkable structural remodeling of the recognition (REC) lobe, which exerts a key role for DNA cleavage. Specifically, the significant conformational changes and the collective conformational dynamics of the REC lobe indicate a mechanism by which the REC1-3 regions 'sense' nucleic acids, 'regulate' the HNH conformational transition, and ultimately 'lock' the HNH domain at the cleavage site, contributing to its catalytic competence. By integrating additional independent simulations and existing experimental data, we provide a solid validation of the activated HNH conformation, which had been so far poorly characterized, and we deliver a comprehensive understanding of the role of REC1-3 in the activation process. Considering the importance of the REC lobe in the specificity of Cas9, this study poses the basis for fully understanding how the REC components control the cleavage of off-target sequences, laying the foundation for future engineering efforts toward improved genome editing.Biochemistry and Cell BiologyBiological SciencesGenetics1.1 Normal biological development and functioningUnderpinning researchGeneric health relevanceCRISPR-Associated Protein 9CRISPR-Cas SystemsCatalytic DomainClustered Regularly Interspaced Short Palindromic RepeatsDNA CleavageGene EditingHumansMolecular Dynamics SimulationPrincipal Component AnalysisCRISPR-Cas9genome editingmolecular dynamicsprotein/nucleic acid interactionsCRISPR–Cas9Other Physical SciencesBiophysicsBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/42s679jxarticleoai:escholarship.org:ark:/13030/qt58z932ns2024-03-24T18:58:19Zqt58z932nsLatrunculin B and substratum stiffness regulate corneal fibroblast to myofibroblast transformationThomasy, Sara MRaghunathan, Vijay KrishnaMiyagi, HidetakaEvashenk, Alexander TSermeno, Jasmyne CTripp, Geneva KMorgan, Joshua TMurphy, Christopher J2018-05-01The transformation of keratocytes and fibroblasts to myofibroblasts is important to corneal wound healing as well as formation of stromal haze. The purpose of this study was to determine the effect of latrunculin B, an actin cytoskeleton disruptor in conjunction with a fundamental biophysical cue, substrate stiffness, on myofibroblast transformation in vitro and in vivo. Rabbit corneal fibroblasts were cultured on substrates of differing compliance (1.5, 22, and 71 kPa) and tissue culture plastic (TCP; > 1 GPa) in media containing 0 or 10 ng/ml TGFβ1 for 72 h. Cells were treated with 0.4 μM Lat-B or DMSO for 30 min every 24 h for 72 h. RNA was collected from cells and expression of alpha-smooth muscle actin (α-SMA), keratocan, and ALDH1A1 determined using qPCR; immunocytochemistry was used to assess α-SMA protein expression. A rabbit phototherapeutic keratectomy (PTK) model was used to assess the impact of 0.1% Lat-B (n = 3) or 25% DMSO (vehicle control, n = 3) on corneal wound healing by assessment of epithelial wound size with fluorescein stain and semi-quantitative stromal haze scoring by an observer masked to treatment group as well as Fourier-domain optical coherence tomography (FD-OCT) at set time points. Statistical analysis was completed using one-way or two-way analysis of variance. Treatment with Lat-B versus DMSO resulted in significantly less αSMA mRNA (P ≤ 0.007) for RCF cells grown on 22 and 71 kPa substrates as well as TCP without or with TGFβ1, and significantly decreased α-SMA protein expression in RCFs cultured on the intermediate (22 kPa) stiffness in the absence (P = 0.028) or presence (P = 0.018) of TGFβ1. Treatment with Lat-B versus DMSO but did not significantly alter expression of keratocan or ALDH1A1 mRNA in RCFs (P > 0.05) in the absence or presence of TGFβ1, but RCFs grown on stiff hydrogels (71 kPa) had significantly more keratocan mRNA expression versus the 22 kPa hydrogel or TCP (P < 0.001) without TGFβ1. Administration of topical Lat-B BID was well tolerated by rabbits post-PTK but did not significantly alter epithelial wound closure, stromal haze score, stromal haze thickness as measured by FD-OCT in comparison to DMSO-treated rabbits. When corneal stromal cells are cultured on substrates possessing biologically relevant substratum stiffnesses, Lat-B modulates mRNA and protein expression of α-SMA and thus modulates myofibroblast transformation. At a dose and dose-frequency that reduced IOP in human glaucoma patients, Lat-B treatment did not substantially impact corneal epithelial or stromal wound healing in a rabbit PTK model. While a significant impact on wound healing was observed at the concentration and dose frequency reported here was not found, encouraging in vitro data support further investigations of topically applied Lat-B to determine if this compound can reduce stromal fibrosis.Biomedical and Clinical SciencesOphthalmology and OptometryBioengineeringAgingEye Disease and Disorders of VisionEyeActinsAldehyde DehydrogenaseAnimalsBlottingWesternBridged Bicyclo CompoundsHeterocyclicCell TransdifferentiationCellsCulturedCorneaCorneal KeratocytesElasticityFemaleImmunohistochemistryMicroscopyFluorescenceMyofibroblastsPhotorefractive KeratectomyProteoglycansRNAMessengerRabbitsReal-Time Polymerase Chain ReactionThiazolidinesTomographyOptical CoherenceTransforming Growth Factor beta1Latrunculin BMyofibroblast transformationSubstratum stiffnessAlpha smooth muscle actinStromal hazeMedical Biochemistry and MetabolomicsNeurosciencesOpthalmology and OptometryOphthalmology & OptometryOphthalmology and optometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/58z932nsarticleoai:escholarship.org:ark:/13030/qt8br8j1zb2024-03-24T17:12:41Zqt8br8j1zbBiomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma modelRaghunathan, VijayKrishnaEaton, J SethChristian, Brian JMorgan, Joshua TVer Hoeve, James NYang, Chen-Yuan CharlieGong, HaiyanRasmussen, Carol AMiller, Paul ERussell, PaulNork, T MichaelMurphy, Christopher J2017-01-01Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow.Biomedical and Clinical SciencesOphthalmology and OptometryNeurosciencesEye Disease and Disorders of VisionAgingNeurodegenerativeEyeAnimalsElectrophysiological PhenomenaGlaucomaHumansHypertensionIntraocular PressureLasersModelsAnimalPrimatesProteomeTrabecular Meshworkapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8br8j1zbarticleScientific Reports, vol 7, iss 114329oai:escholarship.org:ark:/13030/qt8w50x3cd2024-03-24T16:02:42Zqt8w50x3cdModeling emission rates and exposures from outdoor cookingEdwards, RufusPrincevac, MarkoWeltman, RobertGhasemian, MasoudArora, Narendra KBond, Tami2017-09-01Approximately 3 billion individuals rely on solid fuels for cooking globally. For a large portion of these – an estimated 533 million – cooking is outdoors, where emissions from cookstoves pose a health risk to both cooks and other household and village members. Models that estimate emissions rates from stoves in indoor environments that would meet WHO air quality guidelines (AQG), explicitly don't account for outdoor cooking. The objectives of this paper are to link health based exposure guidelines with emissions from outdoor cookstoves, using a Monte Carlo simulation of cooking times from Haryana India coupled with inverse Gaussian dispersion models. Mean emission rates for outdoor cooking that would result in incremental increases in personal exposure equivalent to the WHO AQG during a 24-h period were 126 ± 13 mg/min for cooking while squatting and 99 ± 10 mg/min while standing. Emission rates modeled for outdoor cooking are substantially higher than emission rates for indoor cooking to meet AQG, because the models estimate impact of emissions on personal exposure concentrations rather than microenvironment concentrations, and because the smoke disperses more readily outdoors compared to indoor environments. As a result, many more stoves including the best performing solid-fuel biomass stoves would meet AQG when cooking outdoors, but may also result in substantial localized neighborhood pollution depending on housing density. Inclusion of the neighborhood impact of pollution should be addressed more formally both in guidelines on emissions rates from stoves that would be protective of health, and also in wider health impact evaluation efforts and burden of disease estimates. Emissions guidelines should better represent the different contexts in which stoves are being used, especially because in these contexts the best performing solid fuel stoves have the potential to provide significant benefits.Earth SciencesEngineeringEnvironmental EngineeringAtmospheric SciencesClimate Change ScienceHealth Effects of Indoor Air PollutionHealth Effects of Household Energy CombustionPreventionClimate-Related Exposures and ConditionsCookstovesExposuresAir quality guidelinesEmissions ratesISO standardsStatisticsMeteorology & Atmospheric SciencesAtmospheric sciencesClimate change scienceEnvironmental engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8w50x3cdarticleoai:escholarship.org:ark:/13030/qt8nk9629z2024-03-24T15:18:44Zqt8nk9629zDetection and Localization of Image Forgeries Using Resampling Features and Deep LearningBunk, JasonBappy, Jawadul HMohammed, Tajuddin ManharNataraj, LakshmananFlenner, ArjunaManjunath, BSChandrasekaran, ShivkumarRoy-Chowdhury, Amit KPeterson, Lawrence2017-07-01Resampling is an important signature of manipulated images. In this paper, we
propose two methods to detect and localize image manipulations based on a
combination of resampling features and deep learning. In the first method, the
Radon transform of resampling features are computed on overlapping image
patches. Deep learning classifiers and a Gaussian conditional random field
model are then used to create a heatmap. Tampered regions are located using a
Random Walker segmentation method. In the second method, resampling features
computed on overlapping image patches are passed through a Long short-term
memory (LSTM) based network for classification and localization. We compare the
performance of detection/localization of both these methods. Our experimental
results show that both techniques are effective in detecting and localizing
digital image forgeries.Information and Computing SciencesComputer Vision and Multimedia Computationcs.CVapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8nk9629zarticleoai:escholarship.org:ark:/13030/qt7gs1w3pb2024-03-24T14:08:47Zqt7gs1w3pbA chromosome conformation capture ordered sequence of the barley genomeMascher, MartinGundlach, HeidrunHimmelbach, AxelBeier, SebastianTwardziok, Sven OWicker, ThomasRadchuk, VolodymyrDockter, ChristophHedley, Pete ERussell, JoanneBayer, MichaRamsay, LukeLiu, HuiHaberer, GeorgZhang, Xiao-QiZhang, QisenBarrero, Roberto ALi, LinTaudien, StefanGroth, MarcoFelder, MariusHastie, AlexŠimková, HanaStaňková, HelenaVrána, JanChan, SakiMuñoz-Amatriaín, MaríaOunit, RachidWanamaker, SteveBolser, DanielColmsee, ChristianSchmutzer, ThomasAliyeva-Schnorr, LalaGrasso, StefanoTanskanen, JaakkoChailyan, AnnaSampath, DharanyaHeavens, DarrenClissold, LeahCao, SujieChapman, BrettDai, FeiHan, YongLi, HuaLi, XuanLin, ChongyunMcCooke, John KTan, CongWang, PenghaoWang, SongboYin, ShuyaZhou, GaofengPoland, Jesse ABellgard, Matthew IBorisjuk, LjudmillaHouben, AndreasDoležel, JaroslavAyling, SarahLonardi, StefanoKersey, PaulLangridge, PeterMuehlbauer, Gary JClark, Matthew DCaccamo, MarioSchulman, Alan HMayer, Klaus FXPlatzer, MatthiasClose, Timothy JScholz, UweHansson, MatsZhang, GuopingBraumann, IlkaSpannagl, ManuelLi, ChengdaoWaugh, RobbieStein, Nils2017-04-01Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution. The composition of genes and repetitive elements differs between distal and proximal regions. Gene family analyses reveal lineage-specific duplications of genes involved in the transport of nutrients to developing seeds and the mobilization of carbohydrates in grains. We demonstrate the importance of the barley reference sequence for breeding by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.AgriculturalVeterinary and Food SciencesBiological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeCell NucleusCentromereChromatinChromosome MappingChromosomesArtificialBacterialChromosomesPlantGenetic VariationGenomePlantGenomicsHaplotypesHordeumMeiosisRepetitive SequencesNucleic AcidSeedsGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7gs1w3pbarticleNature, vol 544, iss 7651427 - 433oai:escholarship.org:ark:/13030/qt7t3309q22024-03-24T14:08:40Zqt7t3309q2Construction of a map-based reference genome sequence for barley, Hordeum vulgare L.Beier, SebastianHimmelbach, AxelColmsee, ChristianZhang, Xiao-QiBarrero, Roberto AZhang, QisenLi, LinBayer, MichaBolser, DanielTaudien, StefanGroth, MarcoFelder, MariusHastie, AlexŠimková, HanaStaňková, HelenaVrána, JanChan, SakiMuñoz-Amatriaín, MaríaOunit, RachidWanamaker, SteveSchmutzer, ThomasAliyeva-Schnorr, LalaGrasso, StefanoTanskanen, JaakkoSampath, DharanyaHeavens, DarrenCao, SujieChapman, BrettDai, FeiHan, YongLi, HuaLi, XuanLin, ChongyunMcCooke, John KTan, CongWang, SongboYin, ShuyaZhou, GaofengPoland, Jesse ABellgard, Matthew IHouben, AndreasDoležel, JaroslavAyling, SarahLonardi, StefanoLangridge, PeterMuehlbauer, Gary JKersey, PaulClark, Matthew DCaccamo, MarioSchulman, Alan HPlatzer, MatthiasClose, Timothy JHansson, MatsZhang, GuopingBraumann, IlkaLi, ChengdaoWaugh, RobbieScholz, UweStein, NilsMascher, Martin2017-01-01Barley (Hordeum vulgare L.) is a cereal grass mainly used as animal fodder and raw material for the malting industry. The map-based reference genome sequence of barley cv. 'Morex' was constructed by the International Barley Genome Sequencing Consortium (IBSC) using hierarchical shotgun sequencing. Here, we report the experimental and computational procedures to (i) sequence and assemble more than 80,000 bacterial artificial chromosome (BAC) clones along the minimum tiling path of a genome-wide physical map, (ii) find and validate overlaps between adjacent BACs, (iii) construct 4,265 non-redundant sequence scaffolds representing clusters of overlapping BACs, and (iv) order and orient these BAC clusters along the seven barley chromosomes using positional information provided by dense genetic maps, an optical map and chromosome conformation capture sequencing (Hi-C). Integrative access to these sequence and mapping resources is provided by the barley genome explorer (BARLEX).Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeChromosome MappingGenomePlantHordeumSequence Analysisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7t3309q2articleScientific Data, vol 4, iss 1170044oai:escholarship.org:ark:/13030/qt3530c67v2024-03-24T05:10:28Zqt3530c67vTransforming Growth Factor Beta 3 Modifies Mechanics and Composition of Extracellular Matrix Deposited by Human Trabecular Meshwork CellsRaghunathan, Vijay KrishnaMorgan, Joshua TChang, Yow-RenWeber, DarrenPhinney, BrettMurphy, Christopher JRussell, Paul2015-02-09Pseudoexfoliation syndrome is a systemic disorder of the extracellular matrix (ECM) with ocular manifestations in the form of chronic open angle glaucoma. Elevated levels of TGFβ3 in the aqueous humor of individuals with pseudoexfoliation glaucoma (PEX) have been reported. The influence of TGFβ3 on the biochemical composition and biomechanics of ECM of human trabecular meshwork (HTM) cells was investigated. HTM cells from eye bank donor eyes were isolated, plated on aminosilane functionalized glass substrates and cultured in the presence or absence of 1 ng/mL TGFβ3 for 4 weeks. After incubation, samples were decellularized and decellularization was verified by immunostaining. The mechanics of the remaining ECM that was deposited by the treated or the control cells were measured by atomic force microscopy (AFM). Imaged by AFM, the surface features of the ECM from both sets of samples had a similar roughness/topography (as determined by RMS values) suggesting surface features of the ECM were similar in both cases; however, the ECM from the HTM cells treated with TGFβ3 was between 3- and 5-fold stiffer than that produced by the control HTM cells. Proteins present in the ECM were solubilized and analyzed using liquid chromatography tandem mass spectroscopy (LC-MS/MS). Data indicate that multiple proteins previously reported to be altered in glaucoma were changed in the ECM as a result of the presence of TGFβ3, including inhibitors of the BMP and Wnt signaling pathways. Gremlin1and 4, SERPINE1 and 2, periostin, secreted frizzled related protein (SFRP) 1 and 4, and ANGPTL4 were among those proteins that were overexpressed in the ECM after TGFβ3 treatment.EngineeringBiomedical EngineeringClinical ResearchNeurodegenerativeAgingEye Disease and Disorders of Visionextracellular matrixbiomechanicsglaucomapseudoexfoliation syndrometrabecular meshworkatomic force microscopyBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3530c67varticleACS Biomaterials Science & Engineering, vol 1, iss 2110 - 118oai:escholarship.org:ark:/13030/qt72v2z79k2024-03-24T03:33:20Zqt72v2z79kWnt inhibition induces persistent increases in intrinsic stiffness of human trabecular meshwork cellsMorgan, Joshua TRaghunathan, Vijay KrishnaChang, Yow-RenMurphy, Christopher JRussell, Paul2015-03-01Wnt antagonism has been linked to glaucoma and intraocular pressure regulation, as has increased stiffness of human trabecular meshwork (HTM) tissue. We have shown culturing HTM cells on substrates that mimic the elevated stiffness of glaucomatous tissue leads to elevated expression of the Wnt antagonist secreted frizzled related protein 1 (SFRP1), suggesting a linkage between SFRP1 and HTM mechanobiology. In this study, we document biomechanical consequences of Wnt antagonism on HTM cells. Cells were treated with the Wnt antagonists (SFRP1, KY02111, and LGK-974) for 8 days and allowed to recover for 4 days. After recovery, intrinsic cell stiffness and activation of the Wnt pathway via β-catenin staining and blotting were assayed. Basal cell stiffness values were 3.71 ± 0.37, 4.33 ± 3.07, and 3.07 ± kPa (median ± S.D.) for cells derived from 3 donors. Cell stiffness increased after 0.25 μg/mL (4.32 ± 5.12, 8.86 ± 8.51, 4.84 ± 3.15 kPa) and 0.5 μg/mL (16.75 ± 5.59, 13.18 ± 7.99, and 8.54 ± 5.77 kPa) SFRP1 treatment. Stiffening was observed after 10 μM KY02111 (10.72 ± 5.63 and 6.57 ± 5.53 kPa) as well as LGK-974 (9.60 ± 7.41 and 11.40 ± 9.24 kPa) treatment compared with controls (3.79 ± 1.01 and 5.16 ± 2.14 kPa). Additionally, Wnt inhibition resulted in decreased β-catenin staining and increased phosphorylation at threonine 41 after recovery. In conclusion, this work demonstrates a causal relationship between Wnt inhibition and cell stiffening. Additionally, these findings suggest transient Wnt inhibition resulted in durable modulation of the mechanical phenotype of HTM cells. When placed in context with previous results, these findings provide a causal link between Wnt antagonism and cell stiffness and suggest a feedback loop contributing to glaucoma progression.Biomedical and Clinical SciencesOphthalmology and OptometryNeurosciencesAging2.1 Biological and endogenous factorsAetiologyCellsCulturedElastic ModulusElasticityHumansIntercellular Signaling Peptides and ProteinsMembrane ProteinsMicroscopyAtomic ForceSignal TransductionTrabecular MeshworkWnt ProteinsWnt Signaling Pathwaybeta CateninHuman trabecular meshworkWntSecreted frizzled related proteinCell stiffnessAtomic force microscopyMedical Biochemistry and MetabolomicsOpthalmology and OptometryOphthalmology & OptometryOphthalmology and optometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/72v2z79karticleoai:escholarship.org:ark:/13030/qt0xw2078z2024-03-24T03:33:15Zqt0xw2078zDexamethasone Stiffens Trabecular Meshwork, Trabecular Meshwork Cells, and MatrixDexamethasone Stiffens TM Cells and MatrixRaghunathan, Vijay KrishnaMorgan, Joshua TPark, Shin AeWeber, DarrenPhinney, Brett SMurphy, Christopher JRussell, Paul2015-07-15PurposeTreatment with corticosteroids can result in ocular hypertension and may lead to the development of steroid-induced glaucoma. The extent to which biomechanical changes in trabecular meshwork (TM) cells and extracellular matrix (ECM) contribute toward this dysfunction is poorly understood.MethodsPrimary human TM (HTM) cells were cultured for either 3 days or 4 weeks in the presence or absence of dexamethasone (DEX), and cell mechanics, matrix mechanics and proteomics were determined, respectively. Adult rabbits were treated topically with either 0.1% DEX or vehicle over 3 weeks, and mechanics of the TM were determined.ResultsTreatment with DEX for 3 days resulted in a 2-fold increase in HTM cell stiffness, and this correlated with activation of extracellular signal-related kinase 1/2 (ERK1/2) and overexpression of α-smooth muscle actin (αSMA). Further, the matrix deposited by HTM cells chronically treated with DEX is approximately 4-fold stiffer, more organized, and has elevated expression of matrix proteins commonly implicated in glaucoma (decorin, myocilin, fibrillin, secreted frizzle-related protein [SFRP1], matrix-gla). Also, DEX treatment resulted in a 3.5-fold increase in stiffness of the rabbit TM.DiscussionThis integrated approach clearly demonstrates that DEX treatment increases TM cell stiffness concurrent with elevated αSMA expression and activation of the mitogen-activated protein kinase (MAPK) pathway, stiffens the ECM in vitro along with upregulation of Wnt antagonists and fibrotic markers embedded in a more organized matrix, and increases the stiffness of TM tissues in vivo. These results demonstrate glucocorticoid treatment can initiate the biophysical alteration associated with increased resistance to aqueous humor outflow and the resultant increase in IOP.Biomedical and Clinical SciencesOphthalmology and OptometryEye Disease and Disorders of VisionAgingActinsAnimalsBiomechanical PhenomenaBlottingWesternCellsCulturedDexamethasoneElasticityExtracellular MatrixExtracellular Matrix ProteinsGene Expression ProfilingGlucocorticoidsHumansMAP Kinase Signaling SystemProteomicsRabbitsTrabecular Meshworkcell and matrix mechanicssteroid-induced glaucomaextracellular matrixelastic modulusproteomicsBiological SciencesMedical and Health SciencesOphthalmology & OptometryOphthalmology and optometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0xw2078zarticleInvestigative Ophthalmology & Visual Science, vol 56, iss 84447 - 4459oai:escholarship.org:ark:/13030/qt9s78g8mx2024-03-24T03:33:11Zqt9s78g8mxThe formation of cortical actin arrays in human trabecular meshwork cells in response to cytoskeletal disruptionMurphy, Kaitlin CMorgan, Joshua TWood, Joshua ASadeli, AdelineMurphy, Christopher JRussell, Paul2014-10-01The cytoskeleton of human trabecular meshwork (HTM) cells is known to be altered in glaucoma and has been hypothesized to reduce outflow facility through contracting the HTM tissue. Latrunculin B (Lat-B) and Rho-associated protein kinase (ROCK) inhibitors disrupt the actin cytoskeleton and are in clinical trials as glaucoma therapeutics. We have previously reported a transient increase in HTM cell stiffness peaking at 90 min after Lat-B treatment with a return to pretreatment values after 270 min. We hypothesize that changes in actin morphology correlate with alterations in cell stiffness induced by Lat-B but this is not a general consequence of other cytoskeletal disrupting agents such as Rho kinase inhibitors. We treated HTM cells with 2 µM Lat-B or 100 µM Y-27632 and allowed the cells to recover for 30-270 min. While examining actin morphology in Lat-B treated cells, we observed striking cortical actin arrays (CAAs). The percentage of CAA positive cells (CPCs) was time dependent and exceeded 30% at 90 min and decreased after 270 min. Y-27632 treated cells exhibited few CAAs and no changes in cell stiffness. Together, these data suggest that the increase in cell stiffness after Lat-B treatment is correlated with CAAs.Biochemistry and Cell BiologyBiological SciencesAgingNeurosciencesActinsAmidesAntihypertensive AgentsBridged Bicyclo CompoundsHeterocyclicCell Physiological PhenomenaCellsCulturedCytoskeletonHumansImage ProcessingComputer-AssistedPyridinesThiazolidinesTrabecular Meshworkrho-Associated KinasesActinRho-associated protein kinaseLatrunculin BClinical SciencesBiochemistry & Molecular BiologyBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9s78g8mxarticleExperimental Cell Research, vol 328, iss 1164 - 171oai:escholarship.org:ark:/13030/qt9zh0x3gz2024-03-24T03:33:07Zqt9zh0x3gzAutomated AFM force curve analysis for determining elastic modulus of biomaterials and biological samplesChang, Yow-RenRaghunathan, Vijay KrishnaGarland, Shaun PMorgan, Joshua TRussell, PaulMurphy, Christopher J2014-09-01The analysis of atomic force microscopy (AFM) force data requires the selection of a contact point (CP) and is often time consuming and subjective due to influence from intermolecular forces and low signal-to-noise ratios (SNR). In this report, we present an automated algorithm for the selection of CPs in AFM force data and the evaluation of elastic moduli. We propose that CP may be algorithmically easier to detect by identifying a linear elastic indentation region of data (high SNR) rather than the contact point itself (low SNR). Utilizing Hertzian mechanics, the data are fitted for the CP. We first detail the algorithm and then evaluate it on sample polymeric and biological materials. As a demonstration of automation, 64 × 64 force maps were analyzed to yield spatially varying topographical and mechanical information of cells. Finally, we compared manually selected CPs to automatically identified CPs and demonstrated that our automated approach is both accurate (< 10nm difference between manual and automatic) and precise for non-interacting polymeric materials. Our data show that the algorithm is useful for analysis of both biomaterials and biological samples.EngineeringMaterials EngineeringMechanical EngineeringBiomedical EngineeringBiotechnologyBioengineeringAcrylic ResinsAlgorithmsAnimalsAutomationBiocompatible MaterialsBiomechanical PhenomenaCorneaDogsElastic ModulusIrisMicroscopyAtomic ForcePolyethylene GlycolsAtomic force microscopyContact pointElastic modulusNano-indentationBiomechanicsBiomedical engineeringMaterials engineeringMechanical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9zh0x3gzarticleoai:escholarship.org:ark:/13030/qt4m9912tf2024-03-24T03:21:52Zqt4m9912tfNesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarizationMorgan, Joshua TPfeiffer, Emily RThirkill, Twanda LKumar, PriyadarsiniPeng, GordonFridolfsson, Heidi NDouglas, Gordon CStarr, Daniel ABarakat, Abdul IGoldman, Robert David2011-11-15Changes in blood flow regulate gene expression and protein synthesis in vascular endothelial cells, and this regulation is involved in the development of atherosclerosis. How mechanical stimuli are transmitted from the endothelial luminal surface to the nucleus is incompletely understood. The linker of nucleus and cytoskeleton (LINC) complexes have been proposed as part of a continuous physical link between the plasma membrane and subnuclear structures. LINC proteins nesprin-1, -2, and -4 have been shown to mediate nuclear positioning via microtubule motors and actin. Although nesprin-3 connects intermediate filaments to the nucleus, no functional consequences of nesprin-3 mutations on cellular processes have been described. Here we show that nesprin-3 is robustly expressed in human aortic endothelial cells (HAECs) and localizes to the nuclear envelope. Nesprin-3 regulates HAEC morpho-logy, with nesprin-3 knockdown inducing prominent cellular elongation. Nesprin-3 also organizes perinuclear cytoskeletal organization and is required to attach the centrosome to the nuclear envelope. Finally, nesprin-3 is required for flow-induced polarization of the centrosome and flow-induced migration in HAECs. These results represent the most complete description to date of nesprin-3 function and suggest that nesprin-3 regulates vascular endothelial cell shape, perinuclear cytoskeletal architecture, and important aspects of flow-mediated mechanotransduction.Biochemistry and Cell BiologyBiological SciencesUnderpinning research1.1 Normal biological development and functioningAortaCell MovementCell NucleusCell PolarityCell ShapeCellsCulturedCentrosomeCytoskeletonEndothelial CellsHumansIntermediate FilamentsMechanotransductionCellularMembrane ProteinsMicrofilament ProteinsNerve Tissue ProteinsNuclear EnvelopeNuclear ProteinsRNA InterferenceRNASmall InterferingMedical and Health SciencesDevelopmental BiologyBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4m9912tfarticleMolecular Biology of the Cell, vol 22, iss 224324 - 4334oai:escholarship.org:ark:/13030/qt17b2n6kw2024-03-24T02:37:30Zqt17b2n6kwRobust and artifact-free mounting of tissue samples for atomic force microscopyMorgan, Joshua TRaghunathan, Vijay KrishnaThomasy, Sara MMurphy, Christopher JRussell, Paul2014-01-01Immobilization of tissue-samples for atomic for microscopy (AFM) is typically done using either semi-dry tissue or by gluing the tissue sample down, both of which can introduce artifacts. Here, we describe the design of a Soft- Clamping Immobilizing Retainer of Tissue (SCIRT) for consistent and nondestructive immobilization of tissues for AFM analysis. We compare the performance of our SCIRT method with glue-immobilization for two difficult to handle tissue types: human trabecular meshwork (HTM) and rabbit cornea (RC). Our results demonstrate that the SCIRT method has several advantages, including: (i) allowing for small sample sizes, (ii) enabling continuous hydration, (iii) eliminating contact with glue or associated solvents, (iv) permitting sample recovery following measurement, and (v) ease of use. In conclusion, the SCIRT method is a simple and effective means of immobilizing soft, hydrated tissue samples consistently and without artifacts.Biological SciencesAnimalsArtifactsHumansMicroscopyAtomic ForceRabbitsSpecimen Handlingatomic force microscopycorneasample preparationtissue mechanicstrabecular meshworkTechnologyBioinformaticsBiological sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/17b2n6kwarticleBioTechniques, vol 56, iss 140 - 42oai:escholarship.org:ark:/13030/qt5vf5t3q82024-03-24T02:36:02Zqt5vf5t3q8Involvement of YAP, TAZ and HSP90 in Contact Guidance and Intercellular Junction Formation in Corneal Epithelial CellsRaghunathan, Vijay KrishnaDreier, BrittaMorgan, Joshua TTuyen, Binh CRose, Brad WReilly, Christopher MRussell, PaulMurphy, Christopher JLjubimov, Alexander V2014-01-01The extracellular environment possesses a rich milieu of biophysical and biochemical signaling cues that are simultaneously integrated by cells and influence cellular phenotype. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (WWTR1; TAZ), two important signaling molecules of the Hippo pathway, have been recently implicated as nuclear relays of cytoskeletal changes mediated by substratum rigidity and topography. These proteins intersect with other important intracellular signaling pathways (e.g. Wnt and TGFβ). In the cornea, epithelial cells adhere to the stroma through a 3-dimensional topography-rich basement membrane, with features in the nano-submicron size-scale that are capable of profoundly modulating a wide range of fundamental cell behaviors. The influences of substratum-topography, YAP/TAZ knockdown, and HSP90 inhibition on cell morphology, YAP/TAZ localization, and the expression of TGFβ2 and CTGF, were investigated. The results demonstrate (a) that knockdown of TAZ enhances contact guidance in a YAP dependent manner, (b) that CTGF is predominantly regulated by YAP and not TAZ, and (c) that TGFβ2 is regulated by both YAP and TAZ in these cells. Additionally, inhibition of HSP90 resulted in nuclear localization and subsequent transcriptional-activation of YAP, formation of cell-cell junctions and co-localization of E-cadherin and β-catenin at adherens junctions. Results presented in this study reflect the complexities underlying the molecular relationships between the cytoskeleton, growth factors, heat shock proteins, and co-activators of transcription that impact mechanotransduction. The data reveal the importance of YAP/TAZ on the cell behaviors, and gene and protein expression.Biochemistry and Cell BiologyBiomedical and Clinical SciencesBiological SciencesNanotechnologyGeneticsBioengineeringAetiology2.1 Biological and endogenous factorsAdaptor ProteinsSignal TransducingBenzoquinonesCadherinsCorneaEpithelial CellsGene Expression RegulationHSP90 Heat-Shock ProteinsHumansIntercellular JunctionsIntracellular Signaling Peptides and ProteinsLactamsMacrocyclicMechanotransductionCellularPhosphoproteinsPrimary Cell CultureRNASmall InterferingTrans-ActivatorsTranscription FactorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTransforming Growth Factor beta2Wnt ProteinsYAP-Signaling Proteinsbeta CateninGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5vf5t3q8articlePLOS ONE, vol 9, iss 10e109811oai:escholarship.org:ark:/13030/qt07j4r1gb2024-03-24T02:19:40Zqt07j4r1gbStereological Study of Amygdala Glial Populations in Adolescents and Adults with Autism Spectrum DisorderMorgan, John TBarger, NicoleAmaral, David GSchumann, Cynthia MHadjikhani, Nouchine2014-01-01The amygdala undergoes aberrant development in autism spectrum disorder (ASD). We previously found that there are reduced neuron numbers in the adult postmortem amygdala from individuals with ASD compared to typically developing controls. The current study is a comprehensive stereological examination of four non-neuronal cell populations: microglia, oligodendrocytes, astrocytes, and endothelial cells, in the same brains studied previously. We provide a detailed neuroanatomical protocol for defining each cell type that may be applied to other studies of the amygdala in neurodevelopmental and psychiatric disorders. We then assess whether cell numbers and average volumes differ between ASD and typically developing brains. We hypothesized that a reduction in neuron numbers in ASD might relate to altered immune function and/or aberrant microglial activation, as indicated by increased microglial number and cell body volume. Overall, average non-neuronal cell numbers and volumes did not differ between ASD and typically developing brains. However, there was evident heterogeneity within the ASD cohort. Two of the eight ASD brains displayed strong microglial activation. Contrary to our original hypothesis, there was a trend toward a positive correlation between neuronal and microglial numbers in both ASD and control cases. There were fewer oligodendrocytes in the amygdala of adult individuals with ASD ages 20 and older compared to typically developing controls. This finding may provide a possible sign of altered connectivity or impaired neuronal communication that may change across the lifespan in ASD.Cognitive and Computational PsychologyPsychologyBrain DisordersNeurosciencesPediatricIntellectual and Developmental Disabilities (IDD)Mental HealthAutismAetiologyUnderpinning research2.1 Biological and endogenous factors1.1 Normal biological development and functioningMental healthNeurologicalAdolescentAdultAge FactorsAmygdalaChild Development DisordersPervasiveHumansImage ProcessingComputer-AssistedImmunohistochemistryMicroscopyNeurogliaStatisticsNonparametricGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/07j4r1gbarticlePLOS ONE, vol 9, iss 10e110356oai:escholarship.org:ark:/13030/qt2hw3x3kv2024-03-24T02:19:23Zqt2hw3x3kvComparative analysis of the dendritic organization of principal neurons in the lateral and central nuclei of the rhesus macaque and rat amygdalaMorgan, John TAmaral, David G2014-02-15The amygdala plays a critical role in emotional processing and has been implicated in the etiology of numerous psychiatric disorders. It is an evolutionarily ancient structure that is enlarged in primates relative to rodents. Certain amygdala nuclei, such as the lateral nucleus, show relatively greater phylogenetic expansion than other nuclei. However, it is unknown whether there is also differential alteration in neuronal features. To address this question, we examined the dendritic arbors of principal neurons, visualized by using the Golgi method, in the lateral and central nuclei of young adult rhesus macaques and rats. Total dendritic length is greater in the macaque than in the rat. Dendritic trees are increased by 250% in length in the lateral nucleus of the monkey compared with the rat (6,009 μm vs. 2,473 μm); dendritic tree length in the central nucleus is increased by 50% (1,786 μm vs. 1,232 μm). Somal volume is increased 62% between species in the lateral nucleus and 48% in the central nucleus. Spine density is lower on macaque lateral nucleus dendrites compared with rat (-22%) but equivalent in the central nucleus. Spines are equally long in the lateral nucleus of rat and macaque, but spines are longer by about 20% in the central nucleus of the macaque. The alterations in dendritic structure that we observed between the two species suggest differences in the number and spacing of inputs into these nuclei that undoubtedly influence amygdala function.Biomedical and Clinical SciencesNeurosciences1.1 Normal biological development and functioningUnderpinning researchAmygdalaAnimalsDendritesElectronic Data ProcessingLinear ModelsMacaca mulattaMaleNeuronsRatsRatsSprague-DawleySilver StainingamygdalaneurondendriteGolgilateral nucleuscentral nucleusZoologyMedical PhysiologyNeurology & Neurosurgeryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2hw3x3kvarticleThe Journal of Comparative Neurology, vol 522, iss 3689 - 716oai:escholarship.org:ark:/13030/qt6184994s2024-03-24T01:57:15Zqt6184994sSubstrate topography guides pore morphology evolution in nanoporous gold thin filmsChapman, Christopher ARDaggumati, PallaviGott, Shannon CRao, Masaru PSeker, Erkin2016-01-01This paper illustrates the effect of substrate topography on morphology evolution in nanoporous gold (np-Au) thin films. One micron-high silicon ridges with widths varying between 150 nm to 50 µm were fabricated and coated with 500 nm-thick np-Au films obtained by dealloying sputtered gold-silver alloy films. Analysis of scanning electron micrographs of the np-Au films following dealloying and thermal annealing revealed two distinct regimes where the ratio of film thickness to ridge width determines the morphological evolution of np-Au films.EngineeringMaterials EngineeringNanotechnologyBioengineeringNanoporous materialAnnealingDealloyingFractureMicrofabricationannealingdealloyingfracturemicrofabricationnanoporous materialCondensed Matter PhysicsMechanical EngineeringMaterialsMaterials engineeringMechanical engineeringCondensed matter physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6184994sarticleoai:escholarship.org:ark:/13030/qt8485v86r2024-03-24T01:56:44Zqt8485v86rThe intrinsic stiffness of human trabecular meshwork cells increases with senescenceMorgan, Joshua TRaghunathan, Vijay KrishnaChang, Yow-RenMurphy, Christopher JRussell, Paul2015-06-20Dysfunction of the human trabecular meshwork (HTM) plays a central role in the age-associated disease glaucoma, a leading cause of irreversible blindness. The etiology remains poorly understood but cellular senescence, increased stiffness of the tissue, and the expression of Wnt antagonists such as secreted frizzled related protein-1 (SFRP1) have been implicated. However, it is not known if senescence is causally linked to either stiffness or SFRP1 expression. In this study, we utilized in vitro HTM senescence to determine the effect on cellular stiffening and SFRP1 expression. Stiffness of cultured cells was measured using atomic force microscopy and the morphology of the cytoskeleton was determined using immunofluorescent analysis. SFRP1 expression was measured using qPCR and immunofluorescent analysis. Senescent cell stiffness increased 1.88±0.14 or 2.57±0.14 fold in the presence or absence of serum, respectively. This was accompanied by increased vimentin expression, stress fiber formation, and SFRP1 expression. In aggregate, these data demonstrate that senescence may be a causal factor in HTM stiffening and elevated SFRP1 expression, and contribute towards disease progression. These findings provide insight into the etiology of glaucoma and, more broadly, suggest a causal link between senescence and altered tissue biomechanics in aging-associated diseases.Biomedical and Clinical SciencesOncology and CarcinogenesisAgingAetiology2.1 Biological and endogenous factorsCellsCulturedCellular SenescenceDisease ProgressionGlaucomaHumansIntercellular Signaling Peptides and ProteinsMembrane ProteinsMicroscopyAtomic ForceReal-Time Polymerase Chain ReactionStress FibersStressMechanicalTrabecular MeshworkVimentintrabecular meshworksenescencemechanobiologycytoskeletonOncology and carcinogenesisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8485v86rarticleOncotarget, vol 6, iss 1715362 - 15374oai:escholarship.org:ark:/13030/qt9m3339bm2024-03-24T01:33:36Zqt9m3339bmIdentifying potential cancer driver genes by genomic data integrationChen, YongHao, JingjingJiang, WeiHe, TongZhang, XuegongJiang, TaoJiang, Rui2013-01-01Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis of copy number aberration (CNA) regions of cancer genomes, by integrating publicly available human genomic data. MAXDRIVER employs several optimization strategies to construct a heterogeneous network, by means of combining a fused gene functional similarity network, gene-disease associations and a disease phenotypic similarity network. MAXDRIVER was validated to effectively recall known associations among genes and cancers. Previously identified as well as novel driver genes were detected by scanning CNAs of breast cancer, melanoma and liver carcinoma. Three predicted driver genes (CDKN2A, AKT1, RNF139) were found common in these three cancers by comparative analysis.Biological SciencesBiomedical and Clinical SciencesBioinformatics and Computational BiologyGeneticsOncology and CarcinogenesisDigestive DiseasesRare DiseasesNetworking and Information Technology R&D (NITRD)CancerBiotechnologyHuman GenomeAetiology2.1 Biological and endogenous factorsBreast NeoplasmsCarcinogenesisComputational BiologyCyclin-Dependent Kinase Inhibitor p16DNA Copy Number VariationsDecision MakingComputer-AssistedFemaleGenomic LibraryHumansLiver NeoplasmsMelanomaMutationOligonucleotide Array Sequence AnalysisProto-Oncogene Proteins c-aktReceptorsCell Surfaceapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9m3339bmarticleScientific Reports, vol 3, iss 13538oai:escholarship.org:ark:/13030/qt8rk2x6pj2024-03-23T23:14:04Zqt8rk2x6pjA chromosome-based draft sequence of the hexaploid bread wheat (Triticum aestivum) genomeConsortium, The International Wheat Genome SequencingMayer, Klaus FXRogers, JaneDoležel, JaroslavPozniak, CurtisEversole, KellyeFeuillet, CatherineGill, BikramFriebe, BerndLukaszewski, Adam JSourdille, PierreEndo, Takashi RKubaláková, MarieČíhalíková, JarmilaDubská, ZdeňkaVrána, JanŠperková, RomanaŠimková, HanaFebrer, MelanieClissold, LeahMcLay, KirstenSingh, KuldeepChhuneja, ParveenSingh, Nagendra KKhurana, JitendraAkhunov, EduardChoulet, FrédéricAlberti, AdrianaBarbe, ValérieWincker, PatrickKanamori, HiroyukiKobayashi, FuminoriItoh, TakeshiMatsumoto, TakashiSakai, HiroakiTanaka, TsuyoshiWu, JianzhongOgihara, YasunariHanda, HirokazuMaclachlan, P RonSharpe, AndrewKlassen, DarrinEdwards, DavidBatley, JacquelineOlsen, Odd-ArneSandve, Simen RødLien, SigbjørnSteuernagel, BurkhardWulff, BrandeCaccamo, MarioAyling, SarahRamirez-Gonzalez, Ricardo HClavijo, Bernardo JWright, JonathanPfeifer, MatthiasSpannagl, ManuelMartis, Mihaela MMascher, MartinChapman, JarrodPoland, Jesse AScholz, UweBarry, KerrieWaugh, RobbieRokhsar, Daniel SMuehlbauer, Gary JStein, NilsGundlach, HeidrunZytnicki, MatthiasJamilloux, VéroniqueQuesneville, HadiWicker, ThomasFaccioli, PrimettaColaiacovo, MorenoStanca, Antonio MicheleBudak, HikmetCattivelli, LuigiGlover, NatashaPingault, LisePaux, EtienneSharma, SapnaAppels, RudiBellgard, MatthewChapman, BrettNussbaumer, ThomasBader, Kai ChristianRimbert, HélèneWang, ShichenKnox, RonKilian, AndrzejAlaux, MichaelAlfama, FrançoiseCouderc, LoïcGuilhot, NicolasViseux, ClaireLoaec, MikaëlKeller, BeatPraud, Sebastien2014-07-18An ordered draft sequence of the 17-gigabase hexaploid bread wheat (Triticum aestivum) genome has been produced by sequencing isolated chromosome arms. We have annotated 124,201 gene loci distributed nearly evenly across the homeologous chromosomes and subgenomes. Comparative gene analysis of wheat subgenomes and extant diploid and tetraploid wheat relatives showed that high sequence similarity and structural conservation are retained, with limited gene loss, after polyploidization. However, across the genomes there was evidence of dynamic gene gain, loss, and duplication since the divergence of the wheat lineages. A high degree of transcriptional autonomy and no global dominance was found for the subgenomes. These insights into the genome biology of a polyploid crop provide a springboard for faster gene isolation, rapid genetic marker development, and precise breeding to meet the needs of increasing food demand worldwide.AgriculturalVeterinary and Food SciencesBiological SciencesGeneticsHuman GenomeBiotechnologyBreadChromosomesPlantEvolutionMolecularGene OrderGenetic VariationGenomePlantMolecular Sequence AnnotationPhylogenyPlant ProteinsPolyploidySequence AnalysisDNATranscriptomeTriticumInternational Wheat Genome Sequencing ConsortiumGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8rk2x6pjarticleScience, vol 345, iss 61941251788oai:escholarship.org:ark:/13030/qt9bm635k82024-03-22T20:02:05Zqt9bm635k8New Approach to Investigate the Cytotoxicity of Nanomaterials Using Single Cell MechanicsZimmer, Christopher CLiu, Ying XMorgan, Joshua TYang, GuohuaWang, Kang-HsinKennedy, Ian MBarakat, Abdul ILiu, Gang-yu2014-02-06Current in vitro methods to assess nanomaterial cytotoxicity involve various assays to monitor specific cellular dysfunction, such as metabolic imbalance or inflammation. Although high throughput, fast, and animal-free, these in vitro methods suffer from unreliability and lack of relevance to in vivo situations. New approaches, especially with the potential to reliably relate to in vivo studies directly, are in critical need. This work introduces a new approach, single cell mechanics, derived from atomic force microscopy-based single cell compression. The single cell based approach is intrinsically advantageous in terms of being able to directly correlate to in vivo investigations. Its reliability and potential to measure cytotoxicity is evaluated using known systems: zinc oxide (ZnO) and silicon dioxide (SiO2) nanoparticles (NP) on human aortic endothelial cells (HAECs). This investigation clearly indicates the reliability of single cell compression. For example, ZnO NPs cause significant changes in force vs relative deformation profiles, whereas SiO2 NPs do not. New insights into NPs-cell interactions pertaining to cytotoxicity are also revealed from this single cell mechanics approach, in addition to a qualitative cytotoxicity conclusion. The advantages and disadvantages of this approach are also compared with conventional cytotoxicity assays.EngineeringNanotechnologyBioengineering2.1 Biological and endogenous factorsAetiologyCell ShapeCell SurvivalElastic ModulusHuman Umbilical Vein Endothelial CellsHumansMetal NanoparticlesMicroscopyAtomic ForceSilicon DioxideSingle-Cell AnalysisZinc OxidePhysical SciencesChemical SciencesChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9bm635k8articleThe Journal of Physical Chemistry B, vol 118, iss 51246 - 1255oai:escholarship.org:ark:/13030/qt1jn5p5sf2024-03-21T21:54:11Zqt1jn5p5sfComprehensive assessment of 11 de novo HiFi assemblers on complex eukaryotic genomes and metagenomes.Yu, WenjuanLuo, HaohuiYang, JinbaoZhang, ShengchenJiang, HelingZhao, XianjiaHui, XingqiSun, DaLi, LiangWei, Xiu-QingLonardi, StefanoPan, Weihua2024-03-01Pacific Biosciences (PacBio) HiFi sequencing technology generates long reads (>10 kbp) with very high accuracy (<0.01% sequencing error). Although several de novo assembly tools are available for HiFi reads, there are no comprehensive studies on the evaluation of these assemblers. We evaluated the performance of 11 de novo HiFi assemblers on (1) real data for three eukaryotic genomes; (2) 34 synthetic data sets with different ploidy, sequencing coverage levels, heterozygosity rates, and sequencing error rates; (3) one real metagenomic data set; and (4) five synthetic metagenomic data sets with different composition abundance and heterozygosity rates. The 11 assemblers were evaluated using quality assessment tool (QUAST) and benchmarking universal single-copy ortholog (BUSCO). We also used several additional criteria, namely, completion rate, single-copy completion rate, duplicated completion rate, average proportion of largest category, average distance difference, quality value, run-time, and memory utilization. Results show that hifiasm and hifiasm-meta should be the first choice for assembling eukaryotic genomes and metagenomes with HiFi data. We performed a comprehensive benchmarking study of commonly used assemblers on complex eukaryotic genomes and metagenomes. Our study will help the research community to choose the most appropriate assembler for their data and identify possible improvements in assembly algorithms.Biological SciencesBioinformatics and Computational BiologyMedical and Health SciencesBioinformaticsGeneticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1jn5p5sfarticleoai:escholarship.org:ark:/13030/qt7wn084zt2024-03-21T21:34:57Zqt7wn084ztA view of the pan‐genome of domesticated Cowpea (Vigna unguiculata [L.] Walp.)Liang, QihuaMuñoz‐Amatriaín, MaríaShu, ShengqiangLo, SassoumWu, XinyiCarlson, Joseph WDavidson, PatrickGoodstein, David MPhillips, JeremyJanis, Nadia MLee, Elaine JLiang, ChenxiMorrell, Peter LFarmer, Andrew DXu, PeiClose, Timothy JLonardi, Stefano2023-03-22Cowpea, Vigna unguiculata L. Walp., is a diploid warm-season legume of critical importance as both food and fodder in sub-Saharan Africa. This species is also grown in Northern Africa, Europe, Latin America, North America, and East to Southeast Asia. To capture the genomic diversity of domesticates of this important legume, de novo genome assemblies were produced for representatives of six subpopulations of cultivated cowpea identified previously from genotyping of several hundred diverse accessions. In the most complete assembly (IT97K-499-35), 26,026 core and 4963 noncore genes were identified, with 35,436 pan genes when considering all seven accessions. GO terms associated with response to stress and defense response were highly enriched among the noncore genes, while core genes were enriched in terms related to transcription factor activity, and transport and metabolic processes. Over 5 million single nucleotide polymorphisms (SNPs) relative to each assembly and over 40 structural variants >1 Mb in size were identified by comparing genomes. Vu10 was the chromosome with the highest frequency of SNPs, and Vu04 had the most structural variants. Noncore genes harbor a larger proportion of potentially disruptive variants than core genes, including missense, stop gain, and frameshift mutations; this suggests that noncore genes substantially contribute to diversity within domesticated cowpea.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeAetiology2.1 Biological and endogenous factorsZero HungerPlant BiologyCrop and Pasture ProductionCrop and pasture productionPlant biologyapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/7wn084ztarticleThe Plant Genome, vol 17, iss 1e20319oai:escholarship.org:ark:/13030/qt0532g36v2024-03-21T20:05:54Zqt0532g36vMultiscale homogenization of aluminum honeycomb structures: Thermal analysis with orthotropic representative volume element and finite element methodAl-Masri, AliKhanafer, KhalilVafai, Kambiz2024-01-01This study develops a thermal homogenization model for an aluminum honeycomb panel using the representative volume element (RVE) concept, considering the orthotropic nature of the structure. The RVE thermal homogenization method is a numerical approach for analyzing heterogeneous materials. It employs a constitutive model based on RVE performance to represent thermal behavior. Effective parameters are determined through averaging techniques, and the finite element method solves the thermal problem, accounting for structure topology and material behavior. The resulting heat conduction problem is solved using the finite element method (FEM) to evaluate the effective thermal characteristics. A 3D RVE is generated based on the honeycomb panel's geometry, evaluating thermal conductivity tensor and describing the medium's thermal performance. Numerical tests validate the model by comparing it with the real honeycomb structure under sinusoidal heat flux. Results show good correlation, with maximum temperatures of 1101.9 °C in the real structure and 1096.4 °C in the medium. The homogeneous medium is further used to investigate thermal performance under convective conditions with varying panel thicknesses, achieving over 77 °C temperature reduction with the thickest panel. Natural vibration behavior is considered, demonstrating strong correlation between modal responses and natural frequencies. This modeling approach efficiently analyzes thermal behavior in large honeycomb structures, reducing computational time significantly.Macromolecular and Materials ChemistryEngineeringChemical SciencesHomogenizationHoneycombThermalFinite elementAnd RVEapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0532g36varticleHeliyon, vol 10, iss 2e24166oai:escholarship.org:ark:/13030/qt9d4967pm2024-03-18T15:13:53Zqt9d4967pmDrug target prediction through deep learning functional representation of gene signatures.Chen, HaoKing, FrederickZhou, BinWang, YuCanedy, CarterHayashi, JoelZhong, YangChang, MaxPache, LarsWong, JulianJia, YongJoslin, JohnChanda, SumitZhou, YingyaoJiang, TaoBenner, Christopher2024-02-29Many machine learning applications in bioinformatics currently rely on matching gene identities when analyzing input gene signatures and fail to take advantage of preexisting knowledge about gene functions. To further enable comparative analysis of OMICS datasets, including target deconvolution and mechanism of action studies, we develop an approach that represents gene signatures projected onto their biological functions, instead of their identities, similar to how the word2vec technique works in natural language processing. We develop the Functional Representation of Gene Signatures (FRoGS) approach by training a deep learning model and demonstrate that its application to the Broad Institutes L1000 datasets results in more effective compound-target predictions than models based on gene identities alone. By integrating additional pharmacological activity data sources, FRoGS significantly increases the number of high-quality compound-target predictions relative to existing approaches, many of which are supported by in silico and/or experimental evidence. These results underscore the general utility of FRoGS in machine learning-based bioinformatics applications. Prediction networks pre-equipped with the knowledge of gene functions may help uncover new relationships among gene signatures acquired by large-scale OMICs studies on compounds, cell types, disease models, and patient cohorts.HumansDeep LearningMachine LearningComputational BiologyDrug Developmentapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9d4967pmarticleNature Communications, vol 15, iss 1oai:escholarship.org:ark:/13030/qt2x3846b92024-03-16T18:32:05Zqt2x3846b9Design Automation for Paper Microfluidics with Passive Flow SubstratesPotter, JoshuaGrover, WilliamBrisk, PhilipBehjat, LalehHan, JieVelev, Miroslav NChen, Deming2017-05-10This paper introduces a novel software framework to support automated development of paper-based microuidic devices. Compared to existing lab-on-a-chip technologies, paper-based microuidics difiers in terms of substrate technologies and point-of-care usage across a wide variety environmental conditions. This paper addresses the contexts in which the software can address these challenges and presents several initial case studies that demonstrate the capabilities of the framework to produce workable and usable paper microuidic devices.EngineeringInformation and Computing SciencesFluid Mechanics and Thermal EngineeringMaterials EngineeringSoftware EngineeringBiotechnologyBioengineeringPaper MicrofluidicsDesign AutomationCapillaryPassive FlowAssayapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2x3846b9articleoai:escholarship.org:ark:/13030/qt6k3914662024-03-16T15:39:01Zqt6k391466High-fidelity, hyper-accurate, and evolved mutants rewire atomic-level communication in CRISPR-Cas9.Skeens, ErinSinha, SouvikAhsan, MohdDOrdine, AlexandraJogl, GerwaldPalermo, GiuliaLisi, George2024-03-08The high-fidelity (HF1), hyper-accurate (Hypa), and evolved (Evo) variants of the CRISPR-associated protein 9 (Cas9) endonuclease are critical tools to mitigate off-target effects in the application of CRISPR-Cas9 technology. The mechanisms by which mutations in recognition subdomain 3 (Rec3) mediate specificity in these variants are poorly understood. Here, solution nuclear magnetic resonance and molecular dynamics simulations establish the structural and dynamic effects of high-specificity mutations in Rec3, and how they propagate the allosteric signal of Cas9. We reveal conserved structural changes and dynamic differences at regions of Rec3 that interface with the RNA:DNA hybrid, transducing chemical signals from Rec3 to the catalytic His-Asn-His (HNH) domain. The variants remodel the communication sourcing from the Rec3 α helix 37, previously shown to sense target DNA complementarity, either directly or allosterically. This mechanism increases communication between the DNA mismatch recognition helix and the HNH active site, shedding light on the structure and dynamics underlying Cas9 specificity and providing insight for future engineering principles.CRISPR-Cas SystemsCommunicationCRISPR-Associated Protein 9CatalysisDNAapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6k391466articleScience Advances, vol 10, iss 10oai:escholarship.org:ark:/13030/qt7hb7z44q2024-03-15T07:02:21Zqt7hb7z44qAn End-to-End System for Content-Based Video Retrieval Using Behavior, Actions, and Appearance with Interactive Query RefinementHoogs, APerera, AGACollins, RBasharat, AFieldhouse, KAtkins, CSherrill, LBoeckel, BBlue, RWoehlke, MGreco, CSun, ZSwears, ECuntoor, NLuck, JDrew, BHanson, DRowley, DKopaz, JRude, TKeefe, DSrivastava, AKhanwalkar, SKumar, AChen, CCAggarwal, JKDavis, LYacoob, YJain, ALiu, DChang, S-FSong, BRov-Chowdhurv, ASullivan, KTesi, JChandrasekaran, SManiunath, BSWang, XJi, QReddy, KLiu, JShah, MChang, KChen, TDesai, M2015-08-01Information and Computing SciencesComputer Vision and Multimedia ComputationBasic Behavioral and Social ScienceBehavioral and Social Scienceapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7hb7z44qarticleoai:escholarship.org:ark:/13030/qt348352w22024-03-14T19:11:09Zqt348352w2Incomplete Wood–Ljungdahl pathway facilitates one-carbon metabolism in organohalide-respiring Dehalococcoides mccartyiZhuang, Wei-QinYi, ShanBill, MarkusBrisson, Vanessa LFeng, XueyangMen, YujieConrad, Mark ETang, Yinjie JAlvarez-Cohen, Lisa2014-04-29The acetyl-CoA "Wood-Ljungdahl" pathway couples the folate-mediated one-carbon (C1) metabolism to either CO2 reduction or acetate oxidation via acetyl-CoA. This pathway is distributed in diverse anaerobes and is used for both energy conservation and assimilation of C1 compounds. Genome annotations for all sequenced strains of Dehalococcoides mccartyi, an important bacterium involved in the bioremediation of chlorinated solvents, reveal homologous genes encoding an incomplete Wood-Ljungdahl pathway. Because this pathway lacks key enzymes for both C1 metabolism and CO2 reduction, its cellular functions remain elusive. Here we used D. mccartyi strain 195 as a model organism to investigate the metabolic function of this pathway and its impacts on the growth of strain 195. Surprisingly, this pathway cleaves acetyl-CoA to donate a methyl group for production of methyl-tetrahydrofolate (CH3-THF) for methionine biosynthesis, representing an unconventional strategy for generating CH3-THF in organisms without methylene-tetrahydrofolate reductase. Carbon monoxide (CO) was found to accumulate as an obligate by-product from the acetyl-CoA cleavage because of the lack of a CO dehydrogenase in strain 195. CO accumulation inhibits the sustainable growth and dechlorination of strain 195 maintained in pure cultures, but can be prevented by CO-metabolizing anaerobes that coexist with D. mccartyi, resulting in an unusual syntrophic association. We also found that this pathway incorporates exogenous formate to support serine biosynthesis. This study of the incomplete Wood-Ljungdahl pathway in D. mccartyi indicates a unique bacterial C1 metabolism that is critical for D. mccartyi growth and interactions in dechlorinating communities and may play a role in other anaerobic communities.Biological SciencesIndustrial BiotechnologyAcetate-CoA LigaseAcetatesAcetyl Coenzyme AAerobiosisBacteriaAnaerobicCarbonCarbon IsotopesCarbon MonoxideCoculture TechniquesComputational BiologyGenesBacterialHalogenationHydrocarbonsHalogenatedMetabolic Networks and PathwaysMethionineMethylenetetrahydrofolate Reductase (NADPH2)PyruvatesSerinereductive dechlorinationC-13 isotope analysisacetyl-CoA synthase13C isotope analysisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/348352w2articleProceedings of the National Academy of Sciences of the United States of America, vol 111, iss 176419 - 6424oai:escholarship.org:ark:/13030/qt2fn852wd2024-03-14T17:22:26Zqt2fn852wdUnderstanding pollen tube growth dynamics using the Unscented Kalman FilterTambo, Asongu LBhanu, BirUng, NolanThakoor, NinadLuo, NanYang, Zhenbiao2016-03-01In the process of pollination, a pollen tube grows from a pollen grain that has fallen on the stigma of a flower. This tube grows towards the ovary of the flower where it will deliver male reproductive material. Knowledge of the dynamics of pollen tube growth will provide a basis for understanding more complex cells that exhibit similar growth behavior. Current pollen tube growth models are a collection of differential equations that represent the level of understanding that biologists have concerning apical growth. Due to their complex nature, these models are not used to verify observed behavior in living cells as seen under a microscope. We present a model that can be used to describe the behavior of growing pollen tube cells in actual experiments. We propose biologically relevant functions based on knowledge of the growth process to explain the dynamics of model parameters. Our model uses an affine transformation to propagate the tip of the cell and statistical parameter estimation to measure necessary parameters during growth. Using experimental videos of pollen tube growth, we show that our model can adapt to various growth scenarios while extracting growth parameters from the videos.Information and Computing SciencesPollen tubesApical growthTip growthMathematical model of tip growthArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCognitive SciencesArtificial Intelligence & Image ProcessingInformation and computing sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2fn852wdarticleoai:escholarship.org:ark:/13030/qt60p5k0f22024-03-14T04:51:24Zqt60p5k0f2Reducing Microfluidic Very Large Scale Integration (mVLSI) Chip Area by Seam CarvingCrites, BrianKong, KarenBrisk, PhilipBehjat, LalehHan, JieVelev, Miroslav NChen, Deming2017-05-10This paper introduces a technique based on seam carving to reduce the area of microuidic very large scale integration (mVLSI) chips. Seam carving repeatedly identifies small slices of the device that can be safely removed (carved) and patched without adversely affecting device functionality. Using non-linear seam carving we achieve an average improvement of 4:28x in area utilization and an average reduction in uid routing channel length of 53%.EngineeringElectrical EngineeringMicrofluidicsSeam CarvingmVLSIapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/60p5k0f2articleoai:escholarship.org:ark:/13030/qt3jn831t62024-03-12T15:01:03Zqt3jn831t6Proteomes of Micro- and Nanosized Carriers Engineered from Red Blood Cells.Lee, Chi-HuaTang, JackHendricks, NathanAnvari, Bahman2023-03-03Red blood cell (RBC)-derived systems offer a potential platform for delivery of biomedical cargos. Although the importance of specific proteins associated with the biodistribution and pharmacokinetics of these particles has been recognized, it remains to be explored whether some of the key transmembrane and cytoskeletal proteins responsible for immune-modulatory effects and mechanical integrity of the particles are retained. Herein, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and quantitative tandem mass tag mass spectrometry in conjunction with bioinformatics analysis, we have examined the proteomes of micro- and nanosized erythrocyte ghosts doped with indocyanine green and compared them with those of RBCs. We identified a total of 884 proteins in each set of RBCs, micro-, and nanosized particles, of which 8 and 45 proteins were expressed at significantly different relative abundances when comparing micro-sized particles vs RBCs and nanosized particles vs RBCs, respectively. We found greater differences in relative abundances of some mechano-modulatory proteins, such as band 3 and protein 4.2, and immunomodulatory proteins like CD44, CD47, and CD55 in nanosized particles as compared to RBCs. Our findings highlight that the methods utilized in fabricating RBC-based systems can induce substantial effects on their proteomes. Mass spectrometry data are available at ProteomeXchange with the identifier PXD038780.bioinformaticsdrug deliveryerythrocytetandem mass spectrometryProteomeTissue DistributionErythrocytesErythrocyte MembraneTandem Mass Spectrometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3jn831t6articleJournal of Proteome Research, vol 22, iss 3oai:escholarship.org:ark:/13030/qt2c58x6wk2024-03-12T14:26:15Zqt2c58x6wkCarboxymethyl cellulose-alginate interpenetrating hydroxy ethyl methacrylate crosslinked polyvinyl alcohol reinforced hybrid hydrogel templates with improved biological performance for cardiac tissue engineering.Sedighim, SharonaChen, YiqingXu, ChangluMohindra, RohitAgrawal, DevendraThankam, FinoshLiu, Huinan2023-03-01Cardiac tissue engineering is an emerging approach for cardiac regeneration utilizing the inherent healing responses elicited by the surviving heart using biomaterial templates. In this study, we aimed to develop hydrogel scaffolds for cardiac tissue regeneration following myocardial infarction (MI). Two superabsorbent hydrogels, CAHA2A and CAHA2AP, were developed employing interpenetration chemistry. CAHA2A was constituted with alginate, carboxymethyl cellulose, (hydroxyethyl) methacrylate, and acrylic acid, where CAHA2AP was prepared by interpenetrated CAHA2A with polyvinyl alcohol. Both hydrogels displayed superior physiochemical characteristics, as determined by attenuated total reflection infrared spectroscopy spectral analysis, differential scanning calorimetry measurements, tensile testing, contact angle, water profiling, dye release, and conductivity. In vitro degradation of the hydrogels displayed acceptable weight composure and pH changes. Both hydrogels were hemocompatible, and biocompatible as evidenced by direct contact and MTT assays. The hydrogels promoted anterograde and retrograde migration as determined by the z-stack analysis using H9c2 cells grown with both gels. Additionally, the coculture of the hydrogels with swine epicardial adipose tissue cells and cardiac fibroblasts resulted in synchronous growth without any toxicity. Also, both hydrogels facilitated the production of extracellular matrix by the H9c2 cells. Overall, the findings support an appreciable in vitro performance of both hydrogels for cardiac tissue engineering applications.IPN hydrogelsbiocompatibilitycardiac tissue engineeringmyocardial Infarctionsuperabsorbent hydrogelAnimalsSwineTissue EngineeringPolyvinyl AlcoholCarboxymethylcellulose SodiumHydrogelsAlginatesMethacrylatesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2c58x6wkarticleBiotechnology and Bioengineering, vol 120, iss 3oai:escholarship.org:ark:/13030/qt5t93w0gb2024-03-12T03:49:18Zqt5t93w0gbPrompting Fab Yeast Surface Display Efficiency by ER Retention and Molecular Chaperon Co-expressionMei, MengLi, JunhongWang, ShengchenLee, Ki BaekIverson, Brent LZhang, GuiminGe, XinYi, Li2019-01-01For antibody discovery and engineering, yeast surface display (YSD) of antigen-binding fragments (Fabs) and coupled fluorescence activated cell sorting (FACS) provide intact paratopic conformations and quantitative analysis at the monoclonal level, and thus holding great promises for numerous applications. Using anti-TNFα mAbs Infliximab, Adalimumab, and its variants as model Fabs, this study systematically characterized complementary approaches for the optimization of Fab YSD. Results suggested that by using divergent promoter GAL1-GAL10 and endoplasmic reticulum (ER) signal peptides for co-expression of light chain and heavy chain-Aga2 fusion, assembled Fabs were functionally displayed on yeast cell surface with sigmoidal binding responses toward TNFα. Co-expression of a Hsp70 family molecular chaperone Kar2p and/or protein-disulfide isomerase (Pdi1p) significantly improved efficiency of functional display (defined as the ratio of cells displaying functional Fab over cells displaying assembled Fab). Moreover, fusing ER retention sequences (ERSs) with light chain also enhanced Fab display quality at the expense of display quantity, and the degree of improvements was correlated with the strength of ERSs and was more significant for Infliximab than Adalimumab. The feasibility of affinity maturation was further demonstrated by isolating a high affinity Fab clone from 1:103 or 1:105 spiked libraries.Biochemistry and Cell BiologyBiological SciencesBiotechnologyyeast surface displayFabdivergent promotorER retention sequencemolecular chaperoneOther Biological SciencesBiomedical EngineeringMedical BiotechnologyIndustrial biotechnologyMedical biotechnologyBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5t93w0gbarticleoai:escholarship.org:ark:/13030/qt1p2749j62024-03-08T17:44:04Zqt1p2749j6Computational analysis reveals increased blood deposition following repeated mild traumatic brain injuryDonovan, VirginiaBianchi, AnthonyHartman, RichardBhanu, BirCarson, Monica JObenaus, Andre2012-01-01Mild traumatic brain injury (mTBI) has become an increasing public health concern as subsequent injuries can exacerbate existing neuropathology and result in neurological deficits. This study investigated the temporal development of cortical lesions using magnetic resonance imaging (MRI) to assess two mTBIs delivered to opposite cortical hemispheres. The controlled cortical impact model was used to produce an initial mTBI on the right cortex followed by a second injury induced on the left cortex at 3 (rmTBI 3d) or 7 (rmTBI 7d) days later. Histogram analysis was combined with a novel semi-automated computational approach to perform a voxel-wise examination of extravascular blood and edema volumes within the lesion. Examination of lesion volume 1d post last injury revealed increased tissue abnormalities within rmTBI 7d animals compared to other groups, particularly at the site of the second impact. Histogram analysis of lesion T2 values suggested increased edematous tissue within the rmTBI 3d group and elevated blood deposition in the rm TBI 7d animals. Further quantification of lesion composition for blood and edema containing voxels supported our histogram findings, with increased edema at the site of second impact in rmTBI 3d animals and elevated blood deposition in the rmTBI 7d group at the site of the first injury. Histological measurements revealed spatial overlap of regions containing blood deposition and microglial activation within the cortices of all animals. In conclusion, our findings suggest that there is a window of tissue vulnerability where a second distant mTBI, induced 7d after an initial injury, exacerbates tissue abnormalities consistent with hemorrhagic progression.Biomedical and Clinical SciencesNeurosciencesTraumatic Head and Spine InjuryBrain DisordersPhysical Injury - Accidents and Adverse EffectsTraumatic Brain Injury (TBI)Biomedical ImagingAetiology2.1 Biological and endogenous factorsNeurologicalEdemaHemorrhagic progressionHistogramT2Quantitative magnetic resonance imagingDTIdiffusion tensor imagingFAfractional anisotropyHPChemorrhagic progression of the contusionMDmean diffusivityBiological psychologyClinical and health psychologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1p2749j6articleNeuroImage Clinical, vol 1, iss 118 - 28oai:escholarship.org:ark:/13030/qt3pq1005g2024-03-08T17:43:59Zqt3pq1005gDynamic Low-Level Context for the Detection of Mild Traumatic Brain InjuryBianchi, AnthonyBhanu, BirObenaus, Andre2015-01-01Mild traumatic brain injury (mTBI) appears as low contrast lesions in magnetic resonance (MR) imaging. Standard automated detection approaches cannot detect the subtle changes caused by the lesions. The use of context has become integral for the detection of low contrast objects in images. Context is any information that can be used for object detection but is not directly due to the physical appearance of an object in an image. In this paper, new low-level static and dynamic context features are proposed and integrated into a discriminative voxel-level classifier to improve the detection of mTBI lesions. Visual features, including multiple texture measures, are used to give an initial estimate of a lesion. From the initial estimate novel proximity and directional distance, contextual features are calculated and used as features for another classifier. This feature takes advantage of spatial information given by the initial lesion estimate using only the visual features. Dynamic context is captured by the proposed posterior marginal edge distance context feature, which measures the distance from a hard estimate of the lesion at a previous time point. The approach is validated on a temporal mTBI rat model dataset and shown to have improved dice score and convergence compared to other state-of-the-art approaches. Analysis of feature importance and versatility of the approach on other datasets are also provided.Information and Computing SciencesComputer Vision and Multimedia ComputationBrain DisordersBasic Behavioral and Social ScienceBiomedical ImagingPhysical Injury - Accidents and Adverse EffectsNeurosciencesTraumatic Head and Spine InjuryBehavioral and Social ScienceTraumatic Brain Injury (TBI)4.2 Evaluation of markers and technologiesDetectionscreening and diagnosisAlgorithmsAnimalsBrainBrain InjuriesImage EnhancementImage InterpretationComputer-AssistedImagingThree-DimensionalMagnetic Resonance ImagingPattern RecognitionAutomatedRatsRatsSprague-DawleyReproducibility of ResultsSensitivity and SpecificityDynamic contextlow contrastmagnetic resonance imagingtraumatic brain injuryArtificial Intelligence and Image ProcessingBiomedical EngineeringElectrical and Electronic EngineeringBiomedical engineeringElectronicssensors and digital hardwareComputer vision and multimedia computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3pq1005garticleIEEE Transactions on Biomedical Engineering, vol 62, iss 1145 - 153oai:escholarship.org:ark:/13030/qt4jt6z4z82024-03-08T17:43:55Zqt4jt6z4z8Automated detection of brain abnormalities in neonatal hypoxia ischemic injury from MR imagesGhosh, NirmalyaSun, YuBhanu, BirAshwal, StephenObenaus, Andre2014-10-01We compared the efficacy of three automated brain injury detection methods, namely symmetry-integrated region growing (SIRG), hierarchical region splitting (HRS) and modified watershed segmentation (MWS) in human and animal magnetic resonance imaging (MRI) datasets for the detection of hypoxic ischemic injuries (HIIs). Diffusion weighted imaging (DWI, 1.5T) data from neonatal arterial ischemic stroke (AIS) patients, as well as T2-weighted imaging (T2WI, 11.7T, 4.7T) at seven different time-points (1, 4, 7, 10, 17, 24 and 31 days post HII) in rat-pup model of hypoxic ischemic injury were used to assess the temporal efficacy of our computational approaches. Sensitivity, specificity, and similarity were used as performance metrics based on manual ('gold standard') injury detection to quantify comparisons. When compared to the manual gold standard, automated injury location results from SIRG performed the best in 62% of the data, while 29% for HRS and 9% for MWS. Injury severity detection revealed that SIRG performed the best in 67% cases while 33% for HRS. Prior information is required by HRS and MWS, but not by SIRG. However, SIRG is sensitive to parameter-tuning, while HRS and MWS are not. Among these methods, SIRG performs the best in detecting lesion volumes; HRS is the most robust, while MWS lags behind in both respects.PaediatricsBiomedical and Clinical SciencesBioengineeringNeurosciencesBrain DisordersPhysical Injury - Accidents and Adverse EffectsStrokeBiomedical ImagingAlgorithmsAnimalsAnimalsNewbornHumansHypoxia-IschemiaBrainImage InterpretationComputer-AssistedInfantNewbornInfantNewbornDiseasesMagnetic Resonance ImagingRatsReproducibility of ResultsSensitivity and SpecificityHypoxia ischemic injuryHierarchical region splittingWatershedSymmetryArterial ischemic strokeEngineeringMedical and Health SciencesNuclear Medicine & Medical ImagingBiomedical and clinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4jt6z4z8articleMedical Image Analysis, vol 18, iss 71059 - 1069oai:escholarship.org:ark:/13030/qt0h2107mr2024-03-04T16:48:56Zqt0h2107mrAn alpha-helical lid guides the target DNA toward catalysis in CRISPR-Cas12a.Saha, AakashAhsan, MohdArantes, PabloSchmitz, MichaelChanez, ChristelleJinek, MartinPalermo, Giulia2024-02-17CRISPR-Cas12a is a powerful RNA-guided genome-editing system that generates double-strand DNA breaks using its single RuvC nuclease domain by a sequential mechanism in which initial cleavage of the non-target strand is followed by target strand cleavage. How the spatially distant DNA target strand traverses toward the RuvC catalytic core is presently not understood. Here, continuous tens of microsecond-long molecular dynamics and free-energy simulations reveal that an α-helical lid, located within the RuvC domain, plays a pivotal role in the traversal of the DNA target strand by anchoring the crRNA:target strand duplex and guiding the target strand toward the RuvC core, as also corroborated by DNA cleavage experiments. In this mechanism, the REC2 domain pushes the crRNA:target strand duplex toward the core of the enzyme, while the Nuc domain aids the bending and accommodation of the target strand within the RuvC core by bending inward. Understanding of this critical process underlying Cas12a activity will enrich fundamental knowledge and facilitate further engineering strategies for genome editing.CRISPR-Cas SystemsRNAGuideCRISPR-Cas SystemsDNAGene EditingCatalysisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0h2107mrarticleNature Communications, vol 15, iss 1oai:escholarship.org:ark:/13030/qt51x477qw2024-03-01T00:19:23Zqt51x477qwIdentification of Candidate Genes Controlling Red Seed Coat Color in Cowpea (Vigna unguiculata [L.] Walp)Herniter, Ira AMuñoz-Amatriaín, MaríaLo, SassoumGuo, Yi-NingLonardi, StefanoClose, Timothy J2024-02-09Seed coat color is an important consumer-related trait of the cowpea (Vigna unguiculata [L.] Walp.) and has been a subject of study for over a century. Utilizing newly available resources, including mapping populations, a high-density genotyping platform, and several genome assemblies, the red seed coat color has been mapped to two loci, Red-1 (R-1) and Red-2 (R-2), on Vu03 and Vu07, respectively. A gene model (Vigun03g118700) encoding a dihydroflavonol 4-reductase, a homolog of anthocyanidin reductase 1, which catalyzes the biosynthesis of epicatechin from cyanidin, has been identified as a candidate gene for R-1. Possible causative variants have also been identified for Vigun03g118700. A gene model on Vu07 (Vigun07g118500), with predicted nucleolar function and high relative expression in the developing seed, has been identified as a candidate for R-2. The observed red color is believed to be the result of a buildup of cyanidins in the seed coat.AgriculturalVeterinary and Food SciencesGeneticsAgriculturalveterinary and food sciencesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/51x477qwarticleHorticulturae, vol 10, iss 2161oai:escholarship.org:ark:/13030/qt4826v25z2024-02-27T15:50:35Zqt4826v25zBioaerosols are the dominant source of warm-temperature immersion-mode INPs and drive uncertainties in INP predictability.Cornwell, GavinMcCluskey, ChristinaHill, ThomasLevin, EzraRothfuss, NicholasTai, Sheng-LunBurrows, SusannahDeMott, PaulKreidenweis, SoniaPrather, KimberlyPetters, Markus2023-09-15Ice-nucleating particles (INPs) are rare atmospheric aerosols that initiate primary ice formation, but accurately simulating their concentrations and variability in large-scale climate models remains a challenge. Doing so requires both simulating major particle sources and parameterizing their ice nucleation (IN) efficiency. Validating and improving model predictions of INP concentrations requires measuring their concentrations delineated by particle type. We present a method to speciate INP concentrations into contributions from dust, sea spray aerosol (SSA), and bioaerosol. Field campaign data from Bodega Bay, California, showed that bioaerosols were the primary source of INPs between -12° and -20°C, while dust was a minor source and SSA had little impact. We found that recent parameterizations for dust and SSA accurately predicted ambient INP concentrations. However, the model did not skillfully simulate bioaerosol INPs, suggesting a need for further research to identify major factors controlling their emissions and INP efficiency for improved representation in models.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4826v25zarticleScience Advances, vol 9, iss 37oai:escholarship.org:ark:/13030/qt0m54638w2024-02-26T08:17:21Zqt0m54638wMultiple levers for overcoming the recalcitrance of lignocellulosic biomass.Holwerda, EvertWorthen, RobertKothari, NinadLasky, RonaldDavison, BrianFu, ChunxiangWang, Zeng-YuDixon, RichardBiswal, AjayaMohnen, DebraNelson, RichardBaxter, HollyMazarei, MitraStewart, CMuchero, WellingtonTuskan, GeraldCai, CharlesGjersing, EricaDavis, MarkHimmel, MichaelGilna, PaulLynd, LeeWyman, Charles2019-01-01BACKGROUND: The recalcitrance of cellulosic biomass is widely recognized as a key barrier to cost-effective biological processing to fuels and chemicals, but the relative impacts of physical, chemical and genetic interventions to improve biomass processing singly and in combination have yet to be evaluated systematically. Solubilization of plant cell walls can be enhanced by non-biological augmentation including physical cotreatment and thermochemical pretreatment, the choice of biocatalyst, the choice of plant feedstock, genetic engineering of plants, and choosing feedstocks that are less recalcitrant natural variants. A two-tiered combinatoric investigation of lignocellulosic biomass deconstruction was undertaken with three biocatalysts (Clostridium thermocellum, Caldicellulosiruptor bescii, Novozymes Cellic® Ctec2 and Htec2), three transgenic switchgrass plant lines (COMT, MYB4, GAUT4) and their respective nontransgenic controls, two Populus natural variants, and augmentation of biological attack using either mechanical cotreatment or cosolvent-enhanced lignocellulosic fractionation (CELF) pretreatment. RESULTS: In the absence of augmentation and under the conditions tested, increased total carbohydrate solubilization (TCS) was observed for 8 of the 9 combinations of switchgrass modifications and biocatalysts tested, and statistically significant for five of the combinations. Our results indicate that recalcitrance is not a trait determined by the feedstock only, but instead is coequally determined by the choice of biocatalyst. TCS with C. thermocellum was significantly higher than with the other two biocatalysts. Both CELF pretreatment and cotreatment via continuous ball milling enabled TCS in excess of 90%. CONCLUSION: Based on our results as well as literature studies, it appears that some form of non-biological augmentation will likely be necessary for the foreseeable future to achieve high TCS for most cellulosic feedstocks. However, our results show that this need not necessarily involve thermochemical processing, and need not necessarily occur prior to biological conversion. Under the conditions tested, the relative magnitude of TCS increase was augmentation > biocatalyst choice > plant choice > plant modification > plant natural variants. In the presence of augmentation, plant modification, plant natural variation, and plant choice exhibited a small, statistically non-significant impact on TCS.Biomass deconstructionCELFCaldicellulosiruptor besciiClostridium thermocellumCotreatmentFungal cellulasePopulus natural variantsRecalcitranceTransgenic switchgrassapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0m54638warticleoai:escholarship.org:ark:/13030/qt9tp855xw2024-02-24T12:29:22Zqt9tp855xwReverse metabolomics for the discovery of chemical structures from humansGentry, Emily CCollins, Stephanie LPanitchpakdi, MorganBelda-Ferre, PedroStewart, Allison KCarrillo Terrazas, MarvicLu, Hsueh-hanZuffa, SimoneYan, TingtingAvila-Pacheco, JulianPlichta, Damian RAron, Allegra TWang, MingxunJarmusch, Alan KHao, FuhuaSyrkin-Nikolau, MashetteVlamakis, HeraAnanthakrishnan, Ashwin NBoland, Brigid SHemperly, AmyVande Casteele, NielsGonzalez, Frank JClish, Clary BXavier, Ramnik JChu, HiutungBaker, Erin SPatterson, Andrew DKnight, RobSiegel, DionicioDorrestein, Pieter C2024-02-08Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.Medical Biochemistry and MetabolomicsAnalytical ChemistryBiomedical and Clinical SciencesChemical SciencesInflammatory Bowel DiseaseDigestive DiseasesCrohn's DiseasePreventionAnimalsHumansBifidobacteriumBile Acids and SaltsCD4-Positive T-LymphocytesClostridiumCohort StudiesCrohn DiseaseEnterococcusEstersFatty AcidsInflammatory Bowel DiseasesMetabolomicsPhenotypePregnane X ReceptorReproducibility of ResultsTandem Mass SpectrometryAmidesGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9tp855xwarticleNature, vol 626, iss 7998419 - 426oai:escholarship.org:ark:/13030/qt4f93s20w2024-02-24T04:43:47Zqt4f93s20wAccurate inference of isoforms from multiple sample RNA-Seq dataTasnim, MasrubaMa, ShiningYang, Ei-WenJiang, TaoLi, Wei2015-12-01BackgroundRNA-Seq based transcriptome assembly has become a fundamental technique for studying expressed mRNAs (i.e., transcripts or isoforms) in a cell using high-throughput sequencing technologies, and is serving as a basis to analyze the structural and quantitative differences of expressed isoforms between samples. However, the current transcriptome assembly algorithms are not specifically designed to handle large amounts of errors that are inherent in real RNA-Seq datasets, especially those involving multiple samples, making downstream differential analysis applications difficult. On the other hand, multiple sample RNA-Seq datasets may provide more information than single sample datasets that can be utilized to improve the performance of transcriptome assembly and abundance estimation, but such information remains overlooked by the existing assembly tools.ResultsWe formulate a computational framework of transcriptome assembly that is capable of handling noisy RNA-Seq reads and multiple sample RNA-Seq datasets efficiently. We show that finding an optimal solution under this framework is an NP-hard problem. Instead, we develop an efficient heuristic algorithm, called Iterative Shortest Path (ISP), based on linear programming (LP) and integer linear programming (ILP). Our preliminary experimental results on both simulated and real datasets and comparison with the existing assembly tools demonstrate that (i) the ISP algorithm is able to assemble transcriptomes with a greatly increased precision while keeping the same level of sensitivity, especially when many samples are involved, and (ii) its assembly results help improve downstream differential analysis. The source code of ISP is freely available at http://alumni.cs.ucr.edu/~liw/isp.html.Biological SciencesBioinformatics and Computational BiologyGeneticsNetworking and Information Technology R&D (NITRD)BioengineeringHuman GenomeGeneric health relevanceAlgorithmsAlternative SplicingAnimalsComputational BiologyComputer SimulationGene Expression ProfilingHumansInternetModelsGeneticProtein IsoformsReproducibility of ResultsSequence AnalysisRNASoftwareTranscriptomeInformation and Computing SciencesMedical and Health SciencesBioinformaticsBiological sciencesBiomedical and clinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4f93s20warticleBMC Genomics, vol 16, iss Suppl 2s15oai:escholarship.org:ark:/13030/qt69s100082024-02-23T15:19:42Zqt69s10008On-Site Fluorescent Detection of Sepsis-Inducing Bacteria using a Graphene-Oxide CRISPR-Cas12a (GO-CRISPR) System.Kasputis, TomHe, YawenCi, QiaoqiaoChen, Juhong2024-02-13Sepsis is an extremely dangerous medical condition that emanates from the bodys response to a pre-existing infection. Early detection of sepsis-inducing bacterial infections can greatly enhance the treatment process and potentially prevent the onset of sepsis. However, current point-of-care (POC) sensors are often complex and costly or lack the ideal sensitivity for effective bacterial detection. Therefore, it is crucial to develop rapid and sensitive biosensors for the on-site detection of sepsis-inducing bacteria. Herein, we developed a graphene oxide CRISPR-Cas12a (GO-CRISPR) biosensor for the detection of sepsis-inducing bacteria in human serum. In this strategy, single-stranded (ssDNA) FAM probes were quenched with single-layer graphene oxide (GO). Target-activated Cas12a trans-cleavage was utilized for the degradation of the ssDNA probes, detaching the short ssDNA probes from GO and recovering the fluorescent signals. Under optimal conditions, we employed our GO-CRISPR system for the detection of Salmonella Typhimurium (S. Typhimurium) with a detection sensitivity of as low as 3 × 103 CFU/mL in human serum, as well as a good detection specificity toward other competing bacteria. In addition, the GO-CRISPR biosensor exhibited excellent sensitivity to the detection of S. Typhimurium in spiked human serum. The GO-CRISPR system offers superior rapidity for the detection of sepsis-inducing bacteria and has the potential to enhance the early detection of bacterial infections in resource-limited settings, expediting the response for patients at risk of sepsis.HumansGraphiteCRISPR-Cas SystemsSepsisBacteriaColoring AgentsBacterial InfectionsOxidesBiosensing Techniquesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/69s10008articleAnalytical Chemistry, vol 96, iss 6oai:escholarship.org:ark:/13030/qt6mb3p4352024-02-19T10:28:14Zqt6mb3p435R*-Grove: Balanced Spatial Partitioning for Large-Scale DatasetsVu, TinEldawy, Ahmed2020-01-01The rapid growth of big spatial data urged the research community to develop several big spatial data systems. Regardless of their architecture, one of the fundamental requirements of all these systems is to spatially partition the data efficiently across machines. The core challenges of big spatial partitioning are building high spatial quality partitions while simultaneously taking advantages of distributed processing models by providing load balanced partitions. Previous works on big spatial partitioning are to reuse existing index search trees as-is, e.g., the R-tree family, STR, Kd-tree, and Quad-tree, by building a temporary tree for a sample of the input and use its leaf nodes as partition boundaries. However, we show in this paper that none of those techniques has addressed the mentioned challenges completely. This paper proposes a novel partitioning method, termed R*-Grove, which can partition very large spatial datasets into high quality partitions with excellent load balance and block utilization. This appealing property allows R*-Grove to outperform existing techniques in spatial query processing. R*-Grove can be easily integrated into any big data platforms such as Apache Spark or Apache Hadoop. Our experiments show that R*-Grove outperforms the existing partitioning techniques for big spatial data systems. With all the proposed work publicly available as open source, we envision that R*-Grove will be adopted by the community to better serve big spatial data research.Data Management and Data ScienceDistributed Computing and Systems SoftwareInformation and Computing SciencesClinical ResearchNetworking and Information Technology R&D (NITRD)big spatial datapartitioningR*-Groveindex optimizationquery processingcs.DBcs.DCcs.DSData management and data scienceInformation systemsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6mb3p435articleoai:escholarship.org:ark:/13030/qt6xs5w1rf2024-02-16T19:11:50Zqt6xs5w1rfThe Role of Nanofluids in Renewable Energy Engineering.Bhatti, MuhammadVafai, KambizAbdelsalam, Sara2023-09-29The phenomenon of nanofluid flows is intrinsically characterized by several scales and intricate physical processes [...].application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6xs5w1rfarticleNanomaterials, vol 13, iss 19oai:escholarship.org:ark:/13030/qt8bt9c13m2024-02-16T18:22:29Zqt8bt9c13mStrain energy density as a Gaussian process and its utilization in stochastic finite element analysis: application to planar soft tissues.Aggarwal, AnkushJensen, BjørnPant, SanjayLee, Chung-Hao2023-02-01Data-based approaches are promising alternatives to the traditional analytical constitutive models for solid mechanics. Herein, we propose a Gaussian process (GP) based constitutive modeling framework, specifically focusing on planar, hyperelastic and incompressible soft tissues. The strain energy density of soft tissues is modeled as a GP, which can be regressed to experimental stress-strain data obtained from biaxial experiments. Moreover, the GP model can be weakly constrained to be convex. A key advantage of a GP-based model is that, in addition to the mean value, it provides a probability density (i.e. associated uncertainty) for the strain energy density. To simulate the effect of this uncertainty, a non-intrusive stochastic finite element analysis (SFEA) framework is proposed. The proposed framework is verified against an artificial dataset based on the Gasser-Ogden-Holzapfel model and applied to a real experimental dataset of a porcine aortic valve leaflet tissue. Results show that the proposed framework can be trained with limited experimental data and fits the data better than several existing models. The SFEA framework provides a straightforward way of using the experimental data and quantifying the resulting uncertainty in simulation-based predictions.Constitutive modelingGaussian processesmachine learningnonlinear elasticitystochastic finite element analysistissue biomechanicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8bt9c13marticleoai:escholarship.org:ark:/13030/qt87n7314f2024-02-16T03:49:30Zqt87n7314fNeuroimaging, wearable sensors, and blood-based biomarkers reveal hyperacute changes in the brain after sub-concussive impactsGrijalva, CarissaMullins, Veronica AMichael, Bryce RHale, DallinWu, LyndiaToosizadeh, NimaChilton, Floyd HLaksari, Kaveh2023-12-01Impacts in mixed martial arts (MMA) have been studied mainly in regard to the long-term effects of concussions. However, repetitive sub-concussive head impacts at the hyperacute phase (minutes after impact), are not understood. The head experiences rapid acceleration similar to a concussion, but without clinical symptoms. We utilize portable neuroimaging technology - transcranial Doppler (TCD) ultrasound and functional near infrared spectroscopy (fNIRS) - to estimate the extent of pre- and post-differences following contact and non-contact sparring sessions in nine MMA athletes. In addition, the extent of changes in neurofilament light (NfL) protein biomarker concentrations, and neurocognitive/balance parameters were determined following impacts. Athletes were instrumented with sensor-based mouth guards to record head kinematics. TCD and fNIRS results demonstrated significantly increased blood flow velocity (p = 0.01) as well as prefrontal (p = 0.01) and motor cortex (p = 0.04) oxygenation, only following the contact sparring sessions. This increase after contact was correlated with the cumulative angular acceleration experienced during impacts (p = 0.01). In addition, the NfL biomarker demonstrated positive correlations with angular acceleration (p = 0.03), and maximum principal and fiber strain (p = 0.01). On average athletes experienced 23.9 ± 2.9 g peak linear acceleration, 10.29 ± 1.1 rad/s peak angular velocity, and 1,502.3 ± 532.3 rad/s2 angular acceleration. Balance parameters were significantly increased following contact sparring for medial-lateral (ML) center of mass (COM) sway, and ML ankle angle (p = 0.01), illustrating worsened balance. These combined results reveal significant changes in brain hemodynamics and neurophysiological parameters that occur immediately after sub-concussive impacts and suggest that the physical impact to the head plays an important role in these changes.Health SciencesSports Science and ExerciseClinical ResearchBrain DisordersNeurosciencesTraumatic Brain Injury (TBI)Physical Injury - Accidents and Adverse EffectsTraumatic Head and Spine InjuryDetectionscreening and diagnosis4.1 Discovery and preclinical testing of markers and technologiesFunctional near-infrared spectroscopyHyperacuteSub-concussive impactsTranscranial Doppler ultrasoundapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/87n7314farticleoai:escholarship.org:ark:/13030/qt1dr6q4x62024-02-13T19:15:15Zqt1dr6q4x6Validating genome-wide CRISPR-Cas9 function improves screening in the oleaginous yeast Yarrowia lipolyticaSchwartz, CoryCheng, Jan-FangEvans, RobertSchwartz, Christopher AWagner, James MAnglin, ScottBeitz, AdamPan, WeihuaLonardi, StefanoBlenner, MarkAlper, Hal SYoshikuni, YasuoWheeldon, Ian2019-09-01Genome-wide mutational screens are central to understanding the genetic underpinnings of evolved and engineered phenotypes. The widespread adoption of CRISPR-Cas9 genome editing has enabled such screens in many organisms, but identifying functional sgRNAs still remains a challenge. Here, we developed a methodology to quantify the cutting efficiency of each sgRNA in a genome-scale library, and in doing so improve screens in the biotechnologically important yeast Yarrowia lipolytica. Screening in the presence and absence of native DNA repair enabled high-throughput quantification of sgRNA function leading to the identification of high efficiency sgRNAs that cover 94% of genes. Library validation enhanced the classification of essential genes by identifying inactive guides that create false negatives and mask the effects of successful disruptions. Quantification of guide effectiveness also creates a dataset from which determinants of CRISPR-Cas9 can be identified. Finally, application of the library identified novel mutations for metabolic engineering of high lipid accumulation.Biological SciencesIndustrial BiotechnologyClinical ResearchBiotechnologyHuman GenomeGeneticsGeneric health relevanceCRISPR-Cas SystemsGene EditingGene LibraryGenesFungalYarrowiaBiochemistry and cell biologyIndustrial biotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1dr6q4x6articleoai:escholarship.org:ark:/13030/qt7q78r66n2024-02-08T23:27:22Zqt7q78r66nTherapeutic targeting of tumor hypoxia and necrosis with antibody α-radioconjugatesLopez, TylerRamirez, AaronBenitez, ChrisMustafa, ZahidPham, HenrySanchez, RamonGe, Xin2018-09-17Background: Proteases are one of the largest pharmaceutical targets for drug developments. Their dysregulations result in a wide variety of diseases. Because proteolytic networks usually consist of protease family members that share high structural and catalytic homology, distinguishing them using small molecule inhibitors is often challenging. To achieve specific inhibition, this study described a novel approach for the generation of protease inhibitory antibodies. As a proof of concept, we aimed to convert a matrix metalloproteinase (MMP)-14 specific inhibitor to MMP-9 specific inhibitory antibodies with high selectivity. Methods: An error-prone single-chain Fv (scFv) library of an MMP-14 inhibitor 3A2 was generated for yeast surface display. A dual-color competitive FACS was developed for selection on MMP-9 catalytic domain (cdMMP-9) and counter-selection on cdMMP-14 simultaneously, which were fused/conjugated with different fluorophores. Isolated MMP-9 inhibitory scFvs were biochemically characterized by inhibition assays on MMP-2/-9/-12/-14, proteolytic stability tests, inhibition mode determination, competitive ELISA with TIMP-2 (a native inhibitor of MMPs), and paratope mutagenesis assays. Results: We converted an MMP-14 specific inhibitor 3A2 into a panel of MMP-9 specific inhibitory antibodies with dramatic selectivity shifts of 690-4,500 folds. Isolated scFvs inhibited cdMMP-9 at nM potency with high selectivity over MMP-2/-12/-14 and exhibited decent proteolytic stability. Biochemical characterizations revealed that these scFvs were competitive inhibitors binding to cdMMP-9 near its reaction cleft via their CDR-H3s. Conclusions: This study developed a novel approach able to convert the selectivity of inhibitory antibodies among closely related protease family members. This methodology can be directly applied for mAbs inhibiting many proteases of biomedical importance.Biochemistry and Cell BiologyChemical SciencesBiological SciencesBiotechnology5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsFACSMMPinhibitory antibodyproteaseselectivityapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7q78r66narticleAntibody Therapeutics, vol 1, iss 275 - 83oai:escholarship.org:ark:/13030/qt48z9h9nq2024-02-08T19:01:12Zqt48z9h9nqDevelopment of a novel loading device for studying magnesium degradation under compressive load for implant applicationsTian, QiaomuMendeza, Jose AntonioRivera-Castaneda, LauraMahmood, OmarShowalter, AdamAng, ElizabethKazmi, SarahLiu, Huinan2018-04-01Medical implants play a key role in treating bone fractures. Permanent implants are currently used for immobilization of fractures and bearing physiological loads during bone healing. After bone has healed, these implants, if not removed, often cause complications in the long run; and secondary surgeries for removing them pose additional discomfort and expenses for patients. Magnesium (Mg)-based bioresorbable implants, can potentially eliminate the need for additional surgeries by degrading safely over time in the human body. When studying the degradation behaviors of Mg-based implants in vitro, it is important to simulate physiological conditions in vivo closely, including loading. Considering that implants often carry physiological loads in vivo and mechanical stresses affect the degradation rate of Mg, a novel loading device was designed and manufactured for studying Mg degradation under load over a long period of time in a simulated body fluid in vitro. Degradation of Mg rods were investigated by immersing in a revised simulated body fluid (rSBF) for two weeks while a consistent compressive load was applied using the loading device. The results showed that the loading device provided a consistent load of 500 ± 45 N during the two weeks of immersion. Mg rods showed a significant faster degradation rate under the applied load, as demonstrated by a higher mass loss of the sample, a higher pH increase and Mg2+ ion release in the rSBF.EngineeringBiomedical EngineeringBioengineeringAssistive TechnologyBiotechnologyMusculoskeletalBiomaterialsMagnesium-based biodegradable metalsCorrosionDegradationLoading deviceLoad bearing bioresorbable implantscorrosiondegradationload bearing bioresorbable implantsloading devicemagnesium-based biodegradable metalsPhysical SciencesChemical SciencesMaterialsChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/48z9h9nqarticleoai:escholarship.org:ark:/13030/qt7gr0t0g92024-02-06T22:20:19Zqt7gr0t0g9Investigation of Arrays of Two-Dimensional High-$T_\text{C}$ SQUIDs for Optimization of Electrical PropertiesCho, Ethan YZhou, Yuchao WKhapaev, Mikhail MCybart, Shane A2019-08-01In this work, we investigate two-dimensional arrays of High-T C superconducting quantum interference devices (SQUIDs) for optimization of their electrical transport characteristics. Specifically, we look at devices with different electrode configurations in between the series segments to gain insight into how the array spacing, in the direction of the bias current, affects the voltage magnetic field characteristics. Our results suggest that for spacing dimensions greater than the penetration depth interactions are minimal. Furthermore, comparisons of voltage field characteristics reveal higher modulation voltages and narrower peaks with as the numbers of SQUIDs in the parallel direction increases from 1 to 6. For larger numbers of SQUIDs in parallel greater than 6 little change is observed. These results suggest a pathway to SQUID array scaling for very large numbers of SQUIDs within in a small area.EngineeringPhysical SciencesCondensed Matter PhysicsSQUIDinductancelarge scaleElectrical and Electronic EngineeringMaterials EngineeringGeneral PhysicsElectrical engineeringCondensed matter physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7gr0t0g9articleIEEE Transactions on Applied Superconductivity, vol 29, iss 51 - 4oai:escholarship.org:ark:/13030/qt41j296sh2024-02-03T18:34:13Zqt41j296shSynthesis of Formate from CO2 Gas Catalyzed by an O2‑Tolerant NAD-Dependent Formate Dehydrogenase and Glucose DehydrogenaseYu, XuejunNiks, DimitriGe, XinLiu, HaizhouHille, RussMulchandani, Ashok2019-04-09Direct biocatalytic conversion of CO2 to formic acid is an attractive means of reversibly storing energy in chemical bonds. Formate dehydrogenases (FDHs) are a heterogeneous group of enzymes that catalyze the oxidation of formic acid to carbon dioxide, generating two protons and two electrons. Several FDHs have recently been reported to catalyze the reverse reaction, i.e., the reduction of carbon dioxide to formic acid, under appropriate conditions. The main challenges with these enzymes are relatively low rates of CO2 reduction and high oxygen sensitivity. Our earlier studies (Yu et al. (2017) J. Biol. Chem. 292, 16872-16879) have shown that the FdsABG formate dehydrogenase from Cupriavidus necator is able to effectively catalyze the reduction of CO2, using NADH as a source of reducing equivalents, with a good oxygen tolerance. On the basis of this result, we have developed a highly thermodynamically efficient and cost-effective biocatalytic process for the transformation of CO2 to formic acid using FdsABG. We have cloned the full-length soluble formate dehydrogenase (FdsABG) from C. necator and expressed it in Escherichia coli with a His-tag fused to the N terminus of the FdsG subunit; this overexpression system has greatly simplified the FdsABG purification process. Importantly, we have also combined this recombinant C. necator FdsABG with another enzyme, glucose dehydrogenase, for continuous regeneration of NADH for CO2 reduction and demonstrated that the combined system is highly effective in reducing CO2 to formate. The results indicate that this system shows significant promise for the future development of an enzyme-based system for the industrial reduction of CO2.Biological SciencesChemical SciencesIndustrial BiotechnologyBacterial ProteinsCarbon DioxideCatalysisCupriavidus necatorEscherichia coliFormate DehydrogenasesFormatesGlucose 1-DehydrogenaseIndustrial MicrobiologyKineticsNADOxidation-ReductionOxygenRecombinant ProteinsMedicinal and Biomolecular ChemistryBiochemistry and Cell BiologyMedical Biochemistry and MetabolomicsBiochemistry & Molecular BiologyBiochemistry and cell biologyMedical biochemistry and metabolomicsMedicinal and biomolecular chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/41j296sharticleBiochemistry, vol 58, iss 141861 - 1868oai:escholarship.org:ark:/13030/qt9dn7n8122024-02-03T18:14:47Zqt9dn7n812Fine-tuned local coordination environment of Pt single atoms on ceria controls catalytic reactivity.Tan, WeiXie, ShaohuaLe, DuyDiao, WeijianWang, MeiyuLow, Ke-BinAustin, DaveHong, SampyoGao, FeiDong, LinMa, LuEhrlich, StevenRahman, TalatLiu, Fudong2022-11-18Constructing single atom catalysts with fine-tuned coordination environments can be a promising strategy to achieve satisfactory catalytic performance. Herein, via a simple calcination temperature-control strategy, CeO2 supported Pt single atom catalysts with precisely controlled coordination environments are successfully fabricated. The joint experimental and theoretical analysis reveals that the Pt single atoms on Pt1/CeO2 prepared at 550 °C (Pt/CeO2-550) are mainly located at the edge sites of CeO2 with a Pt-O coordination number of ca. 5, while those prepared at 800 °C (Pt/CeO2-800) are predominantly located at distorted Ce substitution sites on CeO2 terrace with a Pt-O coordination number of ca. 4. Pt/CeO2-550 and Pt/CeO2-800 with different Pt1-CeO2 coordination environments exhibit a reversal of activity trend in CO oxidation and NH3 oxidation due to their different privileges in reactants activation and H2O desorption, suggesting that the catalytic performance of Pt single atom catalysts in different target reactions can be maximized by optimizing their local coordination structures.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9dn7n812articleNature Communications, vol 13, iss 1oai:escholarship.org:ark:/13030/qt9603g18f2024-02-03T18:10:49Zqt9603g18fStrikingly distinctive NH3-SCR behavior over Cu-SSZ-13 in the presence of NO2.Shan, YulongHe, GuangzhiDu, JinpengSun, YuLiu, ZhongqiFu, YuLiu, FudongShi, XiaoyanYu, YunboHe, Hong2022-08-08Commercial Cu-exchanged small-pore SSZ-13 (Cu-SSZ-13) zeolite catalysts are highly active for the standard selective catalytic reduction (SCR) of NO with NH3. However, their activity is unexpectedly inhibited in the presence of NO2 at low temperatures. This is strikingly distinct from the NO2-accelerated NOx conversion over other typical SCR catalyst systems. Here, we combine kinetic experiments, in situ X-ray absorption spectroscopy, and density functional theory (DFT) calculations to obtain direct evidence that under reaction conditions, strong oxidation by NO2 forces Cu ions to exist mainly as CuII species (fw-Cu2+ and NH3-solvated CuII with high CNs), which impedes the mobility of Cu species. The SCR reaction occurring at these CuII sites with weak mobility shows a higher energy barrier than that of the standard SCR reaction on dynamic binuclear sites. Moreover, the NO2-involved SCR reaction tends to occur at the Brønsted acid sites (BASs) rather than the CuII sites. This work clearly explains the strikingly distinctive selective catalytic behavior in this zeolite system.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9603g18farticleNature Communications, vol 13, iss 1oai:escholarship.org:ark:/13030/qt07c9089p2024-02-03T16:01:49Zqt07c9089pUnveiling the RNA-mediated allosteric activation discloses functional hotspots in CRISPR-Cas13a.Sinha, SouvikMolina Vargas, AdrianArantes, PabloPatel, AmunOConnell, MitchellPalermo, Giulia2024-01-25Cas13a is a recent addition to the CRISPR-Cas toolkit that exclusively targets RNA, which makes it a promising tool for RNA detection. It utilizes a CRISPR RNA (crRNA) to target RNA sequences and trigger a composite active site formed by two Higher Eukaryotes and Prokaryotes Nucleotide (HEPN) domains, cleaving any solvent-exposed RNA. In this system, an intriguing form of allosteric communication controls the RNA cleavage activity, yet its molecular details are unknown. Here, multiple-microsecond molecular dynamics simulations are combined with graph theory to decipher this intricate activation mechanism. We show that the binding of a target RNA acts as an allosteric effector, by amplifying the communication signals over the dynamical noise through interactions of the crRNA at the buried HEPN1-2 interface. By introducing a novel Signal-to-Noise Ratio (SNR) of communication efficiency, we reveal critical allosteric residues-R377, N378, and R973-that rearrange their interactions upon target RNA binding. Alanine mutation of these residues is shown to select target RNA over an extended complementary sequence beyond guide-target duplex for RNA cleavage, establishing the functional significance of these hotspots. Collectively our findings offer a fundamental understanding of the Cas13a mechanism of action and pave new avenues for the development of highly selective RNA-based cleavage and detection tools.Allosteric RegulationCRISPR-Cas SystemsMutationRNARNAGuideCRISPR-Cas SystemsCRISPR-Associated Proteinsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/07c9089particleNucleic Acids Research, vol 52, iss 2oai:escholarship.org:ark:/13030/qt1f80z7rt2024-02-03T13:29:45Zqt1f80z7rtOverview of ICARUSA Curated, Open Access, Online Repository for Atmospheric Simulation Chamber DataNguyen, Tran BBates, Kelvin HBuenconsejo, Reina SCharan, Sophia MCavanna, Eric ECocker, David RDay, Douglas ADeVault, Marla PDonahue, Neil MFinewax, ZacharyHabib, Luke FHandschy, Anne VRuiz, Lea HildebrandtHou, Chung-Yi SJimenez, Jose LJoo, TaekyuKlodt, Alexandra LKong, WeimengLe, ChenMasoud, Catherine GMayernik, Matthew SNg, Nga LNienhouse, Eric JNizkorodov, Sergey AOrlando, John JPost, Jeroen JSturm, Patrick OThrasher, Bridget LTyndall, Geoffrey SSeinfeld, John HWorley, Steven JZhang, XuanZiemann, Paul J2023-06-15Atmospheric simulation chambers continue to be indispensable tools for research in the atmospheric sciences. Insights from chamber studies are integrated into atmospheric chemical transport models, which are used for science-informed policy decisions. However, a centralized data management and access infrastructure for their scientific products had not been available in the United States and many parts of the world. ICARUS (Integrated Chamber Atmospheric data Repository for Unified Science) is an open access, searchable, web-based infrastructure for storing, sharing, discovering, and utilizing atmospheric chamber data [https://icarus.ucdavis.edu]. ICARUS has two parts: a data intake portal and a search and discovery portal. Data in ICARUS are curated, uniform, interactive, indexed on popular search engines, mirrored by other repositories, version-tracked, vocabulary-controlled, and citable. ICARUS hosts both legacy data and new data in compliance with open access data mandates. Targeted data discovery is available based on key experimental parameters, including organic reactants and mixtures that are managed using the PubChem chemical database, oxidant information, nitrogen oxide (NOx) content, alkylperoxy radical (RO2) fate, seed particle information, environmental conditions, and reaction categories. A discipline-specific repository such as ICARUS with high amounts of metadata works to support the evaluation and revision of atmospheric model mechanisms, intercomparison of data and models, and the development of new model frameworks that can have more predictive power in the current and future atmosphere. The open accessibility and interactive nature of ICARUS data may also be useful for teaching, data mining, and training machine learning models.Earth SciencesChemical SciencesPhysical Sciencesatmospheric chamberdatabasedatarepositorydata scienceatmospheric chemistryand physicsChemical sciencesEarth sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1f80z7rtarticleACS Earth and Space Chemistry, vol 7, iss 61235 - 1246oai:escholarship.org:ark:/13030/qt8mj7p92t2024-02-02T18:09:34Zqt8mj7p92tA Bayesian constitutive model selection framework for biaxial mechanical testing of planar soft tissues: Application to porcine aortic valves.Aggarwal, AnkushHudson, LukeLaurence, DevinPant, SanjayLee, Chung-Hao2023-02-01A variety of constitutive models have been developed for soft tissue mechanics. However, there is no established criterion to select a suitable model for a specific application. Although the model that best fits the experimental data can be deemed the most suitable model, this practice often can be insufficient given the inter-sample variability of experimental observations. Herein, we present a Bayesian approach to calculate the relative probabilities of constitutive models based on biaxial mechanical testing of tissue samples. Forty-six samples of porcine aortic valve tissue were tested using a biaxial stretching setup. For each sample, seven ratios of stresses along and perpendicular to the fiber direction were applied. The probabilities of eight invariant-based constitutive models were calculated based on the experimental data using the proposed model selection framework. The calculated probabilities showed that, out of the considered models and based on the information available through the utilized experimental dataset, the May-Newman model was the most probable model for the porcine aortic valve data. When the samples were further grouped into different cusp types, the May-Newman model remained the most probable for the left- and right-coronary cusps, whereas for non-coronary cusps two models were found to be equally probable: the Lee-Sacks model and the May-Newman model. This difference between cusp types was found to be associated with the first principal component analysis (PCA) mode, where this modes amplitudes of the non-coronary and right-coronary cusps were found to be significantly different. Our results show that a PCA-based statistical model can capture significant variations in the mechanical properties of soft tissues. The presented framework is applicable to other tissue types, and has the potential to provide a structured and rational way of making simulations population-based.Aortic valveBayesianBiomechanicsConstitutive modelModel selectionSoft-tissueSwineAnimalsAortic ValveBayes TheoremHeart Valve ProsthesisMechanical TestsModelsStatisticalBiomechanical PhenomenaStressMechanicalapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8mj7p92tarticleoai:escholarship.org:ark:/13030/qt13b1n0j12024-02-02T15:36:26Zqt13b1n0j1Bacterial Antifouling Characteristics of Helicene-Graphene Films.Liu, ShuhaoBae, MichaelHao, LiOh, JunWhite, AndrewMin, YounjinCisneros-Zevallos, LuisAkbulut, Mustafa2021-01-03Herein, we describe interfacially-assembled [7]helicene films that were deposited on graphene monolayer using the Langmuir-Schaefer deposition by utilizing the interactions of nonplanar (helicene) and planar (graphene) π-π interactions as functional antifouling coatings. Bacterial adhesion of Staphylococcus aureus on helicene-graphene films was noticeably lower than that on bare graphene, up to 96.8% reductions in bacterial adhesion. The promising bacterial antifouling characteristics of helicene films was attributed to the unique molecular geometry of helicene, i.e., nano-helix, which can hinder the nanoscale bacterial docking processes on a surface. We envision that helicene-graphene films may eventually be used as protective coatings against bacterial antifouling on the electronic components of clinical and biomedical devices.Langmuir-SchaeferS. aureusbacterial antifoulinghelicenethin filmapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/13b1n0j1articleNanomaterials, vol 11, iss 1oai:escholarship.org:ark:/13030/qt51c8p1tp2024-02-02T15:31:03Zqt51c8p1tpMetagenomic and Metatranscriptomic Analyses Reveal the Structure and Dynamics of a Dechlorinating Community Containing Dehalococcoides mccartyi and Corrinoid-Providing Microorganisms under Cobalamin-Limited ConditionsMen, YujieYu, KeBælum, JacobGao, YingTremblay, JulienPrestat, EmmanuelStenuit, BenTringe, Susannah GJansson, JanetZhang, TongAlvarez-Cohen, LisaLiu, Shuang-Jiang2017-04-15The aim of this study is to obtain a systems-level understanding of the interactions between Dehalococcoides and corrinoid-supplying microorganisms by analyzing community structures and functional compositions, activities, and dynamics in trichloroethene (TCE)-dechlorinating enrichments. Metagenomes and metatranscriptomes of the dechlorinating enrichments with and without exogenous cobalamin were compared. Seven putative draft genomes were binned from the metagenomes. At an early stage (2 days), more transcripts of genes in the Veillonellaceae bin-genome were detected in the metatranscriptome of the enrichment without exogenous cobalamin than in the one with the addition of cobalamin. Among these genes, sporulation-related genes exhibited the highest differential expression when cobalamin was not added, suggesting a possible release route of corrinoids from corrinoid producers. Other differentially expressed genes include those involved in energy conservation and nutrient transport (including cobalt transport). The most highly expressed corrinoid de novo biosynthesis pathway was also assigned to the Veillonellaceae bin-genome. Targeted quantitative PCR (qPCR) analyses confirmed higher transcript abundances of those corrinoid biosynthesis genes in the enrichment without exogenous cobalamin than in the enrichment with cobalamin. Furthermore, the corrinoid salvaging and modification pathway of Dehalococcoides was upregulated in response to the cobalamin stress. This study provides important insights into the microbial interactions and roles played by members of dechlorinating communities under cobalamin-limited conditions.IMPORTANCE The key chloroethene-dechlorinating bacterium Dehalococcoides mccartyi is a cobalamin auxotroph, thus acquiring corrinoids from other community members. Therefore, it is important to investigate the microbe-microbe interactions between Dehalococcoides and the corrinoid-providing microorganisms in a community. This study provides systems-level information, i.e., taxonomic and functional compositions and dynamics of the supportive microorganisms in dechlorinating communities under different cobalamin conditions. The findings shed light on the important roles of Veillonellaceae species in the communities compared to other coexisting community members in producing and providing corrinoids for Dehalococcoides species under cobalamin-limited conditions.MicrobiologyBiological SciencesBioinformatics and Computational BiologyGeneticsBiotechnologyBacteriaBiodegradationEnvironmentalBiosynthetic PathwaysChloroflexiCorrinoidsGene Expression ProfilingGenomeBacterialHalogenationMetagenomicsMicrobial ConsortiaTrichloroethyleneVeillonellaceaeVitamin B 12Dehalococcoidesreductive dechlorinationcorrinoidmetagenomemetatranscriptomeMedical microbiologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/51c8p1tparticleApplied and Environmental Microbiology, vol 83, iss 8e03508 - e03516oai:escholarship.org:ark:/13030/qt9cc3t6xz2024-02-02T14:59:46Zqt9cc3t6xzTwo-dimensional gold nanostructures with high activity for selective oxidation of carbon-hydrogen bonds.Wang, LiangZhu, YihanWang, Jian-QiangLiu, FudongHuang, JianfengMeng, XiangjuBasset, Jean-MarieHan, YuXiao, Feng-Shou2015-04-22Efficient synthesis of stable two-dimensional (2D) noble metal catalysts is a challenging topic. Here we report the facile synthesis of 2D gold nanosheets via a wet chemistry method, by using layered double hydroxide as the template. Detailed characterization with electron microscopy and X-ray photoelectron spectroscopy demonstrates that the nanosheets are negatively charged and [001] oriented with thicknesses varying from single to a few atomic layers. X-ray absorption spectroscopy reveals unusually low gold-gold coordination numbers. These gold nanosheets exhibit high catalytic activity and stability in the solvent-free selective oxidation of carbon-hydrogen bonds with molecular oxygen.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9cc3t6xzarticleoai:escholarship.org:ark:/13030/qt31q6c5kg2024-02-02T02:09:08Zqt31q6c5kgEnd to end stroke triage using cerebrovascular morphology and machine learningDeshpande, AditiElliott, JordanJiang, BinTahsili-Fahadan, PouyaKidwell, ChelseaWintermark, MaxLaksari, Kaveh2023-01-01BackgroundRapid and accurate triage of acute ischemic stroke (AIS) is essential for early revascularization and improved patient outcomes. Response to acute reperfusion therapies varies significantly based on patient-specific cerebrovascular anatomy that governs cerebral blood flow. We present an end-to-end machine learning approach for automatic stroke triage.MethodsEmploying a validated convolutional neural network (CNN) segmentation model for image processing, we extract each patient's cerebrovasculature and its morphological features from baseline non-invasive angiography scans. These features are used to detect occlusion's presence and the site automatically, and for the first time, to estimate collateral circulation without manual intervention. We then use the extracted cerebrovascular features along with commonly used clinical and imaging parameters to predict the 90 days functional outcome for each patient.ResultsThe CNN model achieved a segmentation accuracy of 94% based on the Dice similarity coefficient (DSC). The automatic stroke detection algorithm had a sensitivity and specificity of 92% and 94%, respectively. The models for occlusion site detection and automatic collateral grading reached 96% and 87.2% accuracy, respectively. Incorporating the automatically extracted cerebrovascular features significantly improved the 90 days outcome prediction accuracy from 0.63 to 0.83.ConclusionThe fast, automatic, and comprehensive model presented here can improve stroke diagnosis, aid collateral assessment, and enhance prognostication for treatment decisions, using cerebrovascular morphology.Biomedical and Clinical SciencesClinical SciencesStrokeBrain DisordersNeurosciencesDetectionscreening and diagnosis4.2 Evaluation of markers and technologiesstrokeCNN-convolutional neural networkstroke outcomecollateral circulationsegmentationmachine learningcerebrovascular diseaseCNN—convolutional neural networkPsychologyClinical sciencesBiological psychologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/31q6c5kgarticleoai:escholarship.org:ark:/13030/qt3gs718kb2024-02-01T22:48:38Zqt3gs718kbMolecular Orientations Change Reaction Kinetics and Mechanism: A Review on Catalytic Alcohol Oxidation in Gas Phase and Liquid Phase on Size-Controlled Pt NanoparticlesLiu, FudongWang, HailiangSapi, AndrasTatsumi, HironoriZherebetskyy, DanyloHan, Hui-LingCarl, Lindsay MSomorjai, Gabor A2018-01-01Catalytic oxidation of alcohols is an essential process for energy conversion, production of fine chemicals and pharmaceutical intermediates. Although it has been broadly utilized in industry, the basic understanding for catalytic alcohol oxidations at a molecular level, especially under both gas and liquid phases, is still lacking. In this paper, we systematically summarized our work on catalytic alcohol oxidation over size-controlled Pt nanoparticles. The studied alcohols included methanol, ethanol, 1-propanol, 2-propanol, and 2-butanol. The turnover rates of different alcohols on Pt nanoparticles and also the apparent activation energy in gas and liquid phase reactions were compared. The Pt nanoparticle size dependence of reaction rates and product selectivity was also carefully examined. Water showed very distinct effects for gas and liquid phase alcohol oxidations, either as an inhibitor or as a promoter depending on alcohol type and reaction phase. A deep understanding of different alcohol molecular orientations on Pt surface in gas and liquid phase reactions was established using sum-frequency generation spectroscopy analysis for in situ alcohol oxidations, as well as density functional theory calculation. This approach can not only explain the entirely different behaviors of alcohol oxidations in gas and liquid phases, but can also provide guidance for future catalyst/process design.Chemical SciencesPhysical ChemistrySubstance MisuseAlcoholismAlcohol Use and Healthcatalytic alcohol oxidationgas phaseliquid phasePt nanoparticlessum-frequency generation spectroscopysurface molecular orientationdensity functional theory calculationPhysical Chemistry (incl. Structural)Physical chemistryChemical engineeringNanotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3gs718kbarticleCatalysts, vol 8, iss 6226oai:escholarship.org:ark:/13030/qt3568c68g2024-02-01T22:48:34Zqt3568c68gAlcohol Oxidation at Platinum–Gas and Platinum–Liquid Interfaces: The Effect of Platinum Nanoparticle Size, Water Coadsorption, and Alcohol ConcentrationTatsumi, HironoriLiu, FudongHan, Hui-LingCarl, Lindsay MSapi, AndrasSomorjai, Gabor A2017-04-06Alcohol oxidation reaction over platinum nanoparticles with size ranging from 2 to 8 nm deposited on mesoporous silica MCF-17 was studied in the gas and liquid phases. Among methanol, ethanol, 2- propanol, and 2-butanol oxidations, the turnover frequency increased as the nanoparticle size became large in both reaction phases. The activation energy in the gas phase was higher than that in the liquid phase. Water coadsorption decreased the turnover rate of all the gas and liquid phase oxidations except for the gas-phase 2-butanol case, while a certain amount of water promoted 2-propanol oxidation in the liquid phase. Sum frequency generation vibrational spectroscopy study and DFT calculation revealed that the alcohol molecules pack horizontally on the metal surface in low concentration and stand up in high concentration, which affects the dissociation of β-hydrogen of the alcohol as the critical step in alcohol oxidation. (Graph Presented).Chemical SciencesPhysical ChemistryAlcoholismAlcohol Use and HealthSubstance MisuseEngineeringTechnologyChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3568c68garticleThe Journal of Physical Chemistry C, vol 121, iss 137365 - 7371oai:escholarship.org:ark:/13030/qt0v30z0px2024-02-01T22:04:33Zqt0v30z0pxThermal desorption of dimethyl methylphosphonate from MoO3Head, Ashley RTang, XinHicks, ZacharyWang, LinjieBleuel, HannesHoldren, ScottTrotochaud, LenaYu, YiKyhl, LineKarslıoǧlu, OsmanFears, KenanOwrutsky, JeffreyZachariah, MichaelBowen, Kit HBluhm, Hendrik2017-04-03Organophosphonates are used as chemical warfare agents, pesticides, and corrosion inhibitors. New materials for the sorption, detection, and decomposition of these compounds are urgently needed. To facilitate materials and application innovation, a better understanding of the interactions between organophosphonates and surfaces is required. To this end, we have used diffuse reflectance infrared Fourier transform spectroscopy to investigate the adsorption geometry of dimethyl methylphosphonate (DMMP) on MoO3, a material used in chemical warfare agent filtration devices. We further applied ambient pressure X-ray photoelectron spectroscopy and temperature programmed desorption to study the adsorption and desorption of DMMP. While DMMP adsorbs intact on MoO3, desorption depends on coverage and partial pressure. At low coverages under UHV conditions, the intact adsorption is reversible. Decomposition occurs with higher coverages, as evidenced by PCHx and POx decomposition products on the MoO3 surface. Heating under mTorr partial pressures of DMMP results in product accumulation.EngineeringChemical SciencesPhysical ChemistryAmbient pressure X-ray photoelectron spectroscopychemical warfare agent simulantsurface sciencediffuse reflectance infrared Fourier transform spectroscopyorganophosphonatetemperature programmed desorptionapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0v30z0pxarticleCatalysis Structure & Reactivity, vol 3, iss 1-2112 - 118oai:escholarship.org:ark:/13030/qt7cb542512024-02-01T20:26:35Zqt7cb54251Local Observation Based Reactive Temporal Logic Planning of Human-Robot SystemsZhou, ZhangliWang, ShaochenChen, ZiyangCai, MingyuWang, HaoLi, ZhijunKan, Zhen2023-01-01EngineeringControl EngineeringMechatronics and RoboticsElectrical EngineeringMechanical EngineeringEye Disease and Disorders of VisionReactive planninglinear temporal logichuman-robot collaborationintelligent manufacturingElectrical and Electronic EngineeringManufacturing EngineeringIndustrial Engineering & AutomationControl engineeringmechatronics and roboticsElectrical engineeringMechanical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7cb54251articleIEEE Transactions on Automation Science and Engineering, vol PP, iss 991 - 13oai:escholarship.org:ark:/13030/qt02p805kr2024-02-01T20:25:20Zqt02p805krVision-Based Reactive Temporal Logic Motion Planning for Quadruped Robots in Unstructured Dynamic EnvironmentsZhou, ZhangliChen, ZiyangCai, MingyuLi, ZhijunKan, ZhenSu, Chun-Yi2023-01-01Data Management and Data ScienceInformation and Computing SciencesArtificial IntelligenceComputer visionformal methods in automation and roboticslinear temporal logiconline motion planningquadruped robotEngineeringElectrical & Electronic EngineeringInformation and computing sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/02p805krarticleIEEE Transactions on Industrial Electronics, vol PP, iss 991 - 10oai:escholarship.org:ark:/13030/qt9p81c5tf2024-02-01T20:04:02Zqt9p81c5tfCrowdLocBhandari, RaviRaman, BhaskaranRamakrishnan, KKChander, DeepthiAggarwal, NaveenBansal, DivyaChoudhary, MahimaMoond, NishaBansal, AneeshChaudhary, Megha2018-02-28Determining the location of a mobile user is central to several crowd-sensing applications. Using a Global Positioning System is not only power-hungry, but also unavailable in many locations. While there has been work on cellular-based localization, we consider an unexplored opportunity
to improve location accuracy by combining cellular information across multiple mobile devices located near each other.
For instance, this opportunity may arise in the context of public transport units having multiple travelers.
Based on theoretical analysis and an extensive experimental study on several public transportation routes in two cities, we show that combining cellular information across nearby phones considerably improves location accuracy. Combining information across phones is especially useful when a phone has to use another phone’s fingerprint database, in a fingerprinting-based localization scheme. Both the median and 90 percentile errors reduce significantly. The location accuracy also improves irrespective of whether we combine information across phones connected to the same or different cellular operators.
Sharing information across phones can raise privacy concerns. To address this, we have developed an id-free broadcast mechanism, using audio as a medium, to share information among mobile phones. We show that such communication can work effectively on smartphones, even in real-life, noisy-road conditions.EngineeringElectronicsSensors and Digital HardwareCancerGeneric health relevanceLocalizationGSMandroidcellular fingerprintingaudio communicationsDistributed ComputingElectrical and Electronic EngineeringCommunications TechnologiesNetworking & TelecommunicationsElectronicssensors and digital hardwareapplication/pdfCC-BY-NC-SAeScholarship, University of Californiahttps://escholarship.org/uc/item/9p81c5tfarticleACM Transactions on Sensor Networks, vol 14, iss 11 - 36oai:escholarship.org:ark:/13030/qt2jc2p0k22024-02-01T20:01:29Zqt2jc2p0k2BaroSenseDimri, AnujSingh, HarsimranAggarwal, NaveenRaman, BhaskaranRamakrishnan, KKBansal, Divya2020-02-29Traffic congestion on urban roadways is a serious problem requiring novel ways to detect and mitigate it. Determining the routes that lead to the traffic congestion segment is also vital in devising mitigation strategies. Further, crowdsourcing this information allows for use of these strategies quickly and in places where infrastructure is not available. In this work, we present an unconventional method, using the barometer sensor of mobile phones to (a) detect road traffic congestion and (b) estimate the paths that lead to the congested road segment. We make the observation that roads are not completely flat and very often, altitude varies along the road. The barometer sensor chips are sensitive enough to measure these variations and consume very little energy of the mobile phone, compared to other sensors such as the GPS or accelerometer. We devise a feature set to map the rate of change of this altitude as the user moves into activities characterized as “still” and “motion,” which are further used by the traffic congestion detection algorithm (RoadSphygmo) to classify the group of users as being in “moving,” “congestion,” or “stuck” states. To estimate the paths that lead to the congested road segment, we compare the user’s barometer sensor readings with a pre-stored road signature of barometer values using Dynamic Time Warping (DTW). We show that by using correlation of barometer sensor values, we can determine if users are in the same vehicle. We crowdsource this information from multiple mobile phones and use majority voting technique to improve the accuracy of traffic congestion detection and path estimation. We find a significant increase in the accuracies using crowdsourced information as compared to individual mobile phones. Further, we show that we can use barometer sensor for other applications such as bus occupancy, boarding/deboarding of a vehicle, and so on. The validation of the state determined by RoadSphygmo is done by comparing it with average GPS speed calculated during the same time period. The path estimation is validated over different intersections and considering various cases of commuter travel. The results obtained are promising and show that the traffic state determination and the estimation of the path taken by the commuter can achieve high accuracy.Civil EngineeringEngineeringActivity recognitionbarometer sensorcrowdsourcingpath estimationsmartphonestraffic congestion detectionDistributed ComputingElectrical and Electronic EngineeringCommunications TechnologiesNetworking & TelecommunicationsElectronicssensors and digital hardwareapplication/pdfCC-BY-NC-SAeScholarship, University of Californiahttps://escholarship.org/uc/item/2jc2p0k2articleACM Transactions on Sensor Networks, vol 16, iss 11 - 24oai:escholarship.org:ark:/13030/qt9w6426j22024-02-01T19:58:37Zqt9w6426j2Name Space Analysis: Verification of Named Data Network Data PlanesJahanian, MohammadRamakrishnan, KK2021-04-01Theory Of ComputationInformation and Computing SciencesToolsAerospace electronicsTransfer functionsData modelsAnalytical modelsTopologyReal-time systemsNamed data networksnetwork verificationDistributed ComputingElectrical and Electronic EngineeringCommunications TechnologiesNetworking & TelecommunicationsCommunications engineeringDistributed computing and systems softwareapplication/pdfCC-BY-NC-SAeScholarship, University of Californiahttps://escholarship.org/uc/item/9w6426j2articleIEEE/ACM Transactions on Networking, vol 29, iss 2848 - 861oai:escholarship.org:ark:/13030/qt3sh2z8f02024-02-01T19:56:01Zqt3sh2z8f0MiddleNet: A Unified, High-Performance NFV and Middlebox Framework with eBPF and DPDKQi, ShixiongZeng, ZitengMonis, LeslieRamakrishnan, KK2023-01-01Data Management and Data ScienceInformation and Computing SciencesMiddleboxesNFVDPDKeBPFservice function chainsDistributed ComputingElectrical and Electronic EngineeringCommunications TechnologiesNetworking & TelecommunicationsCommunications engineeringCybersecurity and privacyDistributed computing and systems softwareapplication/pdfCC-BY-NC-SAeScholarship, University of Californiahttps://escholarship.org/uc/item/3sh2z8f0articleIEEE Transactions on Network and Service Management, vol PP, iss 991 - 1oai:escholarship.org:ark:/13030/qt1hz8m21t2024-01-29T15:44:29Zqt1hz8m21tA Comparative Study of Ex-Vivo Murine Pulmonary Mechanics Under Positive- and Negative-Pressure Ventilation.Quiros, KNelson, TUlu, ADominguez, EBiddle, TLo, DNordgren, TEskandari, Mona2024-01-29Increased ventilator use during the COVID-19 pandemic resurrected persistent questions regarding mechanical ventilation including the difference between physiological and artificial breathing induced by ventilators (i.e., positive- versus negative-pressure ventilation, PPV vs NPV). To address this controversy, we compare murine specimens subjected to PPV and NPV in ex vivo quasi-static loading and quantify pulmonary mechanics via measures of quasi-static and dynamic compliances, transpulmonary pressure, and energetics when varying inflation frequency and volume. Each investigated mechanical parameter yields instance(s) of significant variability between ventilation modes. Most notably, inflation compliance, percent relaxation, and peak pressure are found to be consistently dependent on the ventilation mode. Maximum inflation volume and frequency note varied dependencies contingent on the ventilation mode. Contradictory to limited previous clinical investigations of oxygenation and end-inspiratory measures, the mechanics-focused comprehensive findings presented here indicate lung properties are dependent on loading mode, and importantly, these dependencies differ between smaller versus larger mammalian species despite identical custom-designed PPV/NPV ventilator usage. Results indicate that past contradictory findings regarding ventilation mode comparisons in the field may be linked to the chosen animal model. Understanding the differing fundamental mechanics between PPV and NPV may provide insights for improving ventilation strategies and design to prevent associated lung injuries.ComplianceHysteresisMouse lungNegative-pressurePositive-pressurePulmonary mechanicsViscoelasticityapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1hz8m21tarticleJournal of bioengineering, vol 52, iss 2oai:escholarship.org:ark:/13030/qt86n1p4qm2024-01-28T20:45:51Zqt86n1p4qmImpact of various high fat diets on gene expression and the microbiome across the mouse intestinesMartinez-Lomeli, JoseDeol, PoonamjotDeans, Jonathan RJiang, TaoRuegger, PaulBorneman, JamesSladek, Frances M2023-01-01High fat diets (HFDs) have been linked to several diseases including obesity, diabetes, fatty liver, inflammatory bowel disease (IBD) and colon cancer. In this study, we examined the impact on intestinal gene expression of three isocaloric HFDs that differed only in their fatty acid composition-coconut oil (saturated fats), conventional soybean oil (polyunsaturated fats) and a genetically modified soybean oil (monounsaturated fats). Four functionally distinct segments of the mouse intestinal tract were analyzed using RNA-seq-duodenum, jejunum, terminal ileum and proximal colon. We found considerable dysregulation of genes in multiple tissues with the different diets, including those encoding nuclear receptors and genes involved in xenobiotic and drug metabolism, epithelial barrier function, IBD and colon cancer as well as genes associated with the microbiome and COVID-19. Network analysis shows that genes involved in metabolism tend to be upregulated by the HFDs while genes related to the immune system are downregulated; neurotransmitter signaling was also dysregulated by the HFDs. Genomic sequencing also revealed a microbiome altered by the HFDs. This study highlights the potential impact of different HFDs on gut health with implications for the organism as a whole and will serve as a reference for gene expression along the length of the intestines.Biological SciencesBioinformatics and Computational BiologyGeneticsDigestive DiseasesPreventionHuman GenomeCancerObesityAutoimmune DiseaseColo-Rectal CancerInflammatory Bowel DiseaseNutritionAetiology2.1 Biological and endogenous factorsOral and gastrointestinalAnimalsMiceDietHigh-FatSoybean OilDietary FatsMicrobiotaFatty AcidsIleumGene ExpressionColonic NeoplasmsInflammatory Bowel Diseasesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/86n1p4qmarticleScientific Reports, vol 13, iss 122758oai:escholarship.org:ark:/13030/qt3j5082692024-01-24T18:46:17Zqt3j508269Gold Nanoparticle Enabled Localized Surface Plasmon Resonance on Unique Gold Nanomushroom Structures for On-Chip CRISPR-Cas13a Sensing.Waitkus, JacobLiu, LiPuttaswamy, SrinivasuChung, TaerinVargas, AdrianDollery, StephenOConnell, MitchellCai, HaogangTobin, GregoryBhalla, NikhilDu, KeChang, Yu2023-01-05A novel localized surface plasmon resonance (LSPR) system based on the coupling of gold nanomushrooms (AuNMs) and gold nanoparticles (AuNPs) is developed to enable a significant plasmonic resonant shift. The AuNP size, surface chemistry, and concentration are characterized to maximize the LSPR effect. A 31 nm redshift is achieved when the AuNMs are saturated by the AuNPs. This giant redshift also increases the full width of the spectrum and is explained by the 3D finite-difference time-domain (FDTD) calculation. In addition, this LSPR substrate is packaged in a microfluidic cell and integrated with a CRISPR-Cas13a RNA detection assay for the detection of the SARS-CoV-2 RNA targets. Once activated by the target, the AuNPs are cleaved from linker probes and randomly deposited on the AuNM substrate, demonstrating a large redshift. The novel LSPR chip using AuNP as an indicator is simple, specific, isothermal, and label-free; and thus, provides a new opportunity to achieve the next generation multiplexing and sensitive molecular diagnostic system.CRISPR-Cas13aSARS-CoV-2finite difference time domaingold nanomushroomgold nanoparticlelocalized surface plasmon resonance (LSPR)microfluidicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3j508269articleAdvanced Materials Interfaces, vol 10, iss 1oai:escholarship.org:ark:/13030/qt02z063sp2024-01-20T18:23:57Zqt02z063spA Mid-Density Single-Nucleotide Polymorphism Panel for Molecular Applications in Cowpea (Vigna unguiculata (L.) Walp).Close, TimothyBoukar, OusmaneOngom, PatrickFatokun, ChristianTogola, AbouGarcia-Oliveira, AnaNg, EngKilian, AndrzejLonardi, Stefano2024-01-01Molecular markers are increasingly being deployed to accelerate genetic gain in crop plants. The objective of this study was to assess the potential of a mid-density genotyping panel for molecular applications in cowpea breeding. A core set of 2,602 targeted diversity array technology (DArTag) single-nucleotide polymorphisms (SNPs) was designed from an existing 51,128 Cowpea iSelect Consortium Array. The panels usefulness was assessed using 376 genotypes from different populations of known genetic backgrounds. The panel was informative, with over 78% of SNPs exceeding a minor allele frequency of 0.20. The panel decoded three stratifications in the constituted population, as was expected. Linkage disequilibrium (LD) decay was correctly depicted as slower in a biparental subset than in other populations. A known flower and seed coat color gene region was located on chromosome Vu07, suggesting that the mid-density panel may be used to hypothesize genomic regions underlying target traits in cowpea. Unexpected heterozygosity was detected in some lines and highly among F1 progenies, divulging the panels potential application in germplasm purity and hybridity verification. The study unveils the potential of an excellent genomic resource that can be tapped to enhance the development of improved cowpea cultivars.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/02z063sparticleoai:escholarship.org:ark:/13030/qt3z94w04c2024-01-19T21:01:00Zqt3z94w04cBeyond Conventional Density Functional Theory: Advanced Quantum Dynamical Methods for Understanding Degradation of Per- and Polyfluoroalkyl Substances.Biswas, SohagWong, Bryan2024-01-12Computational chemistry methods, such as density functional theory (DFT), have now become more common in environmental research, particularly for simulating the degradation of per- and polyfluoroalkyl substances (PFAS). However, the vast majority of PFAS computational studies have focused on conventional DFT approaches that only probe static, time-independent properties of PFAS near stationary points on the potential energy surface. To demonstrate the rich mechanistic information that can be obtained from time-dependent quantum dynamics calculations, we highlight recent studies using these advanced techniques for probing PFAS systems. We briefly discuss recent applications ranging from ab initio molecular dynamics to DFT-based metadynamics and real-time time-dependent DFT for probing PFAS degradation in various reactive environments. These quantum dynamical approaches provide critical mechanistic information that cannot be gleaned from conventional DFT calculations. We conclude with a perspective of promising research directions and recommend that these advanced quantum dynamics simulations be more widely used by the environmental research community to directly probe PFAS degradation dynamics and other environmental processes.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3z94w04carticleACS ES&T engineering, vol 4, iss 1oai:escholarship.org:ark:/13030/qt5pf943f32024-01-19T18:11:15Zqt5pf943f3A Global Analysis of Alternative Splicing of Dichocarpum Medicinal Plants, Ranunculales.Hao, Da-ChengChen, HaoXiao, Pei-GenJiang, Tao2022-07-05Background: The multiple isoforms are often generated from a single gene via Alternative Splicing (AS) in plants, and the functional diversity of the plant genome is significantly increased. Despite well-studied gene functions, the specific functions of isoforms are little known, therefore, the accurate prediction of isoform functions is exceedingly wanted. Methods: Here we perform the first global analysis of AS of Dichocarpum, a medicinal genus of Ranunculales, by utilizing full-length transcriptome datasets of five Chinese endemic Dichocarpum taxa. Multiple software were used to identify AS events, the gene function was annotated based on seven databases, and the protein-coding sequence of each AS isoform was translated into an amino acid sequence. The self-developed software DIFFUSE was used to predict the functions of AS isoforms. Results: Among 8,485 genes with AS events, the genes with two isoforms were the most (6,038), followed by those with three isoforms and four isoforms. Retained intron (RI, 551) was predominant among 1,037 AS events, and alternative 3 splice sites and alternative 5 splice sites were second. The software DIFFUSE was effective in predicting functions of Dichocarpum isoforms, which have not been unearthed. When compared with the sequence alignment-based database annotations, DIFFUSE performed better in differentiating isoform functions. The DIFFUSE predictions on the terms GO:0003677 (DNA binding) and GO: 0010333 (terpene synthase activity) agreed with the biological features of transcript isoforms. Conclusion: Numerous AS events were for the first time identified from full-length transcriptome datasets of five Dichocarpum taxa, and functions of AS isoforms were successfully predicted by the self-developed software DIFFUSE. The global analysis of Dichocarpum AS events and predicting isoform functions can help understand the metabolic regulations of medicinal taxa and their pharmaceutical explorations.Alternative splicingDNA sequenceDichocarpumdeep learninggene expression profileisoform functionapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5pf943f3articleCurrent Genomics, vol 23, iss 3oai:escholarship.org:ark:/13030/qt9nt0p7cp2024-01-02T17:55:40Zqt9nt0p7cpMapping and exploitation of signals of opportunityKassas, Zaher M, Ph.D.Morales, JoshuaKhalife, Joe2016-04-22This paper was presented at the Southern California Robotics Symposium, Apr. 22, 2016, San Diego, CAapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9nt0p7cparticleoai:escholarship.org:ark:/13030/qt4dq3h3hc2024-01-02T17:55:28Zqt4dq3h3hcNavigation with cellular CDMA signalsKassas, Zaher M, Ph.D.Khalife, JoeShamaei, Kimia2016-04-22This paper was presented at the Southern California Robotics Symposium, Apr. 22, 2016, San Diego, CABCOEapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4dq3h3hcarticleoai:escholarship.org:ark:/13030/qt1g18r8dn2024-01-02T17:55:12Zqt1g18r8dnVehicular navigation with cellular CDMA signalsKassas, Zaher, Ph.D.Khalife, JoeShamaei, Kimia2016-02-11This poster was presented at the University of California Center on Economic Competitiveness in Transportation Conference, Feb. 11-12, 2016, Riverside, CABCOEapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1g18r8dnarticleoai:escholarship.org:ark:/13030/qt1ck543092023-12-27T15:37:47Zqt1ck54309Disruption of electrostatic contacts in the HNH nuclease from a thermophilic Cas9 rewires allosteric motions and enhances high-temperature DNA cleavage.Belato, HelenNorbrun, CarmelissaLuo, JinpingPindi, ChinmaiSinha, SouvikDOrdine, AlexandraJogl, GerwaldLisi, GeorgePalermo, Giulia2022-12-14Allosteric signaling within multidomain proteins is a driver of communication between spatially distant functional sites. Understanding the mechanism of allosteric coupling in large multidomain proteins is the most promising route to achieving spatial and temporal control of the system. The recent explosion of CRISPR-Cas9 applications in molecular biology and medicine has created a need to understand how the atomic level protein dynamics of Cas9, which are the driving force of its allosteric crosstalk, influence its biophysical characteristics. In this study, we used a synergistic approach of nuclear magnetic resonance (NMR) and computation to pinpoint an allosteric hotspot in the HNH domain of the thermostable GeoCas9. We show that mutation of K597 to alanine disrupts a salt-bridge network, which in turn alters the structure, the timescale of allosteric motions, and the thermostability of the GeoHNH domain. This homologous lysine-to-alanine mutation in the extensively studied mesophilic S. pyogenes Cas9 similarly alters the dynamics of the SpHNH domain. We have previously demonstrated that the alteration of allostery via mutations is a source for the specificity enhancement of SpCas9 (eSpCas9). Hence, this may also be true in GeoCas9.CRISPR-Associated Protein 9CRISPR-Cas SystemsDNA CleavageStatic ElectricityTemperatureapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1ck54309articleJournal of Chemical Physics, vol 157, iss 22oai:escholarship.org:ark:/13030/qt67v8h5zf2023-12-25T22:36:07Zqt67v8h5zfComparing synopsis techniques for approximate spatial data analysisSiddique, ABEldawy, AhmedHristidis, Vagelis2019-07-01The increasing amount of spatial data calls for new scalable query processing techniques. One of the techniques that are getting attention is
data synopsis
, which summarizes the data using samples or histograms and computes an approximate answer based on the synopsis. This general technique is used in selectivity estimation, clustering, partitioning, load balancing, and visualization, among others. This paper experimentally studies four spatial data synopsis techniques for three common data analysis problems, namely, selectivity estimation, k-means clustering, and spatial partitioning. We run an extensive experimental evaluation on both real and synthetic datasets of up to 2.7 billion records to study the trade-offs between the synopsis methods and their applicability in big spatial data analysis. For each of the three problems, we compare with baseline techniques that operate on the whole dataset and evaluate the synopsis generation time, the time for computing an approximate answer on the synopsis, and the accuracy of the result. We present our observations about when each synopsis technique performs best.Data Management and Data ScienceInformation and Computing SciencesComputation Theory and MathematicsInformation SystemsLibrary and Information StudiesData management and data sciencepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/67v8h5zfarticleProceedings of the VLDB Endowment, vol 12, iss 111583 - 1596oai:escholarship.org:ark:/13030/qt7340v9dj2023-12-24T23:56:18Zqt7340v9djDirect observation of confined acoustic phonon polarization branches in free-standing semiconductor nanowires.Kargar, FariborzDebnath, BishwajitKakko, Joona-PekkoSäynätjoki, AnttiLipsanen, HarriNika, DenisLake, RogerBalandin, Alexander2016-11-10Similar to electron waves, the phonon states in semiconductors can undergo changes induced by external boundaries. However, despite strong scientific and practical importance, conclusive experimental evidence of confined acoustic phonon polarization branches in individual free-standing nanostructures is lacking. Here we report results of Brillouin-Mandelstam light scattering spectroscopy, which reveal multiple (up to ten) confined acoustic phonon polarization branches in GaAs nanowires with a diameter as large as 128 nm, at a length scale that exceeds the grey phonon mean-free path in this material by almost an order-of-magnitude. The dispersion modification and energy scaling with diameter in individual nanowires are in excellent agreement with theory. The phonon confinement effects result in a decrease in the phonon group velocity along the nanowire axis and changes in the phonon density of states. The obtained results can lead to more efficient nanoscale control of acoustic phonons, with benefits for nanoelectronic, thermoelectric and spintronic devices.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7340v9djarticleoai:escholarship.org:ark:/13030/qt69b6566w2023-12-19T15:32:46Zqt69b6566wProtocol for the generation of Symbiodiniaceae mutants using UV mutagenesis.Russo, JosephXiang, TingtingJinkerson, Robert2023-10-03Genetic approaches are limited in the dinoflagellate family, Symbiodiniaceae, causing a bottleneck in the discovery of useful mutants toward the goal of preventing future coral bleaching events. In this protocol, we demonstrate the application of UV exposure, coupled with downstream phenotypic screening and mutant isolation, to form a UV mutagenesis pipeline. This pipeline provides an avenue to generate Symbiodiniaceae mutants to help link genotype to phenotype, as well as address previously unanswered questions surrounding relationships with host organisms, like coral. For complete details on the use and execution of this protocol, please refer to Jinkerson et al. (2022).1.Environmental sciencesGeneticsMicrobiologyModel Organismsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/69b6566warticleStar Protocols, vol 4, iss 4oai:escholarship.org:ark:/13030/qt5xj0t2r22023-12-16T15:32:46Zqt5xj0t2r2Inhibition of Hexavalent Chromium Release from Drinking Water Distribution Systems: Effects of Water Chemistry-Based Corrosion Control Strategies.Tan, ChengLiu, Haizhou2023-11-28In drinking water distribution systems, the oxidation of zerovalent chromium, Cr(0), in iron corrosion scales by chlorine residual disinfectant is the dominant reaction to form carcinogenic hexavalent chromium, Cr(VI). This study investigates inhibitive corrosion control strategies through adjustments of chemical water parameters (i.e., pH, silicate, phosphate, calcium, and alkalinity) on Cr(VI) formation through oxidation of Cr(0)(s) by free chlorine under drinking water conditions. The results show that an increase in pH, silicate, alkalinity, and calcium suppressed Cr(VI) formation that was mainly attributed to in situ surface precipitation of new Cr(III) solids on the surface of Cr(0)(s), including Cr(OH)3(s), Cr2(SiO3)3(s), CrPO4(s), Cr2(CO3)3(s), and Cr10Ca(CO3)16(s). The Cr(III) surface precipitates were much less reactive with chlorine than Cr(0)(s) and suppressed the Cr redox reactivity. The concentration of surface Cr(III) solids was inversely correlated with the rate constant of Cr(VI) formation. Adding phosphate either promoted or inhibited the Cr(VI) formation, depending on the phosphate concentration. This study provides fundamental insight into the Cr(VI) formation mechanisms via Cr(0) oxidation by chlorine and the importance of surface precipitation of Cr(III) solids with different corrosion control strategies and suggests that increasing the pH/alkalinity and addition of phosphate or silicate can be effective control strategies to minimize Cr(VI) formation.carcinogenchromiumcorrosiondrinking waterfree chlorineredox reactivityDrinking WaterCorrosionCalciumChlorineWater PollutantsChemicalChromiumOxidation-ReductionPhosphatesSilicatesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5xj0t2r2articleEnvironmental Science & Technology, vol 57, iss 47oai:escholarship.org:ark:/13030/qt0hv063rr2023-12-15T02:15:51Zqt0hv063rrAerobic Biotransformation and Defluorination of Fluoroalkylether Substances (ether PFAS): Substrate Specificity, Pathways, and ApplicationsJin, BosenZhu, YiwenZhao, WeiyangLiu, ZekunChe, ShunChen, KunpengLin, Ying-HsuanLiu, JinyongMen, Yujie2023-09-12Fluoroalkylether substances (ether PFAS) constitute a large group of emerging PFAS with uncertain environmental fate. Among them, GenX is the well-known alternative to perfluorooctanoic acid and one of the six proposed PFAS to be regulated by the U.S. Environmental Protection Agency. This study investigated the structure-biodegradability relationship for 12 different ether PFAS with a carboxylic acid headgroup in activated sludge communities. Only polyfluorinated ethers with at least one -CH2- moiety adjacent to or a C=C bond in the proximity of the ether bond underwent active biotransformation via oxidative and hydrolytic O-dealkylation. The bioreactions at ether bonds led to the formation of unstable fluoroalcohol intermediates subject to spontaneous defluorination. We further demonstrated that this aerobic biotransformation/defluorination could complement the advanced reduction process in a treatment train system to achieve more cost-effective treatment for GenX and other recalcitrant perfluorinated ether PFAS. These findings provide essential insights into the environmental fate of ether PFAS, the design of biodegradable alternative PFAS, and the development of cost-effective ether PFAS treatment strategies.EngineeringEnvironmental Engineeringether PFASstructural specificityGenXaerobic biotransformationdefluorinationPFAS treatment trainEnvironmental Science and ManagementEnvironmental BiotechnologyChemical engineeringPollution and contaminationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0hv063rrarticleEnvironmental Science & Technology Letters, vol 10, iss 9755 - 761oai:escholarship.org:ark:/13030/qt79c880vf2023-12-15T01:22:17Zqt79c880vfTowards Environmentally Equitable AI via Geographical Load BalancingLi, PengfeiYang, JianyiWierman, AdamRen, Shaolei2023-06-20Fueled by the soaring popularity of large language and foundation models, the
accelerated growth of artificial intelligence (AI) models' enormous
environmental footprint has come under increased scrutiny. While many
approaches have been proposed to make AI more energy-efficient and
environmentally friendly, environmental inequity -- the fact that AI's
environmental footprint can be disproportionately higher in certain regions
than in others -- has emerged, raising social-ecological justice concerns. This
paper takes a first step toward addressing AI's environmental inequity by
balancing its regional negative environmental impact. Concretely, we focus on
the carbon and water footprints of AI model inference and propose equity-aware
geographical load balancing (GLB) to explicitly address AI's environmental
impacts on the most disadvantaged regions. We run trace-based simulations by
considering a set of 10 geographically-distributed data centers that serve
inference requests for a large language AI model. The results demonstrate that
existing GLB approaches may amplify environmental inequity while our proposed
equity-aware GLB can significantly reduce the regional disparity in terms of
carbon and water footprints.cs.AIcs.CYapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/79c880vfarticleoai:escholarship.org:ark:/13030/qt41x242j62023-12-15T01:05:16Zqt41x242j6Cryogenic characteristics of graphene composites—evolution from thermal conductors to thermal insulatorsNataj, Zahra EbrahimXu, YoumingWright, DylanBrown, Jonas OGarg, JivteshChen, XiKargar, FariborzBalandin, Alexander A2023-01-01The development of cryogenic semiconductor electronics and superconducting quantum computing requires composite materials that can provide both thermal conduction and thermal insulation. We demonstrated that at cryogenic temperatures, the thermal conductivity of graphene composites can be both higher and lower than that of the reference pristine epoxy, depending on the graphene filler loading and temperature. There exists a well-defined cross-over temperature-above it, the thermal conductivity of composites increases with the addition of graphene; below it, the thermal conductivity decreases with the addition of graphene. The counter-intuitive trend was explained by the specificity of heat conduction at low temperatures: graphene fillers can serve as, both, the scattering centers for phonons in the matrix material and as the conduits of heat. We offer a physical model that explains the experimental trends by the increasing effect of the thermal boundary resistance at cryogenic temperatures and the anomalous thermal percolation threshold, which becomes temperature dependent. The obtained results suggest the possibility of using graphene composites for, both, removing the heat and thermally insulating components at cryogenic temperatures-a capability important for quantum computing and cryogenically cooled conventional electronics.EngineeringElectronicsSensors and Digital HardwarePhysical SciencesCondensed Matter Physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/41x242j6articleNature Communications, vol 14, iss 13190oai:escholarship.org:ark:/13030/qt69g4f9f02023-12-14T22:45:53Zqt69g4f9f0A Magneto‐Responsive Hydrogel System for the Dynamic Mechano‐Modulation of Stem Cell NicheGoodrich, RobynTai, YouyiYe, ZuyangYin, YadongNam, Jin2023-03-01Abstract:
The biophysical microenvironment of cells dynamically evolves during embryonic development, leading to defined tissue specification. A versatile and highly adaptive magneto‐responsive hydrogel system composed of magnetic nanorods (MNRs) and a stress‐responsive polymeric matrix is developed to dynamically regulate the physical stem cell niche. The anisotropic magnetic/shape factor of nanorods is utilized to maximize the strains on the polymeric network, thus regulating the hydrogel modulus in a physiologically relevant range under a minimal magnitude of the applied magnetic fields below 4.5 mT. More significantly, the pre‐alignment of MNRs induces greater collective strains on the polymeric network, resulting in a superior stiffening range, over a 500% increase as compared to that with randomly oriented nanorods. The pre‐alignment of nanorods also enables a fast and reversible response under a magnetic field of the opposite polarity as well as spatially controlled heterogeneity of modulus within the hydrogel by applying anisotropic magnetic fields. The mechano‐modulative capability of this system is validated by a mechanotransduction model with human‐induced pluripotent stem cells where the locally controlled hydrogel modulus regulates the activation of mechano‐sensitive signaling mediators and subsequent stem cell differentiation. Therefore, this magneto‐responsive hydrogel system provides a platform to investigate various cellular behaviors under dynamic mechanical microenvironments.EngineeringBiomedical EngineeringBioengineeringStem Cell ResearchRegenerative Medicinedynamic modulus controlshydrogelsmagnetic nanorodsmechanotransductionsstem cell differentiationsPhysical SciencesChemical SciencesMaterialsChemical sciencesPhysical sciencesapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/69g4f9f0articleAdvanced Functional Materials, vol 33, iss 122211288oai:escholarship.org:ark:/13030/qt3r84x9zv2023-12-14T22:14:55Zqt3r84x9zvImplementation of real‐time TDDFT for periodic systems in the open‐source PySCF software packageHanasaki, KotaAli, Zulfikhar AChoi, MinDel Ben, MauroWong, Bryan M2023-04-05We present a new implementation of real-time time-dependent density functional theory (RT-TDDFT) for calculating excited-state dynamics of periodic systems in the open-source Python-based PySCF software package. Our implementation uses Gaussian basis functions in a velocity gauge formalism and can be applied to periodic surfaces, condensed-phase, and molecular systems. As representative benchmark applications, we present optical absorption calculations of various molecular and bulk systems and a real-time simulation of field-induced dynamics of a (ZnO)4 molecular cluster on a periodic graphene sheet. We present representative calculations on optical response of solids to infinitesimal external fields as well as real-time charge-transfer dynamics induced by strong pulsed laser fields. Due to the widespread use of the Python language, our RT-TDDFT implementation can be easily modified and provides a new capability in the PySCF code for real-time excited-state calculations of chemical and material systems.Chemical SciencesPhysical Chemistryelectron dynamicselectron transferGaussian basisperiodic systemsphotophysicsreal-time time-dependent density functional theoryPhysical Chemistry (incl. Structural)Theoretical and Computational ChemistryNanotechnologyChemical PhysicsPhysical chemistryTheoretical and computational chemistryapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/3r84x9zvarticleJournal of Computational Chemistry, vol 44, iss 9980 - 987oai:escholarship.org:ark:/13030/qt6kk414v42023-12-14T21:16:17Zqt6kk414v4Bidding strategy for wireless charging roads with energy storage in real-time electricity marketsShi, JieYu, NanpengGao, H Oliver2022-12-01Civil EngineeringEngineeringAffordable and Clean EnergyElectric vehicleEnergy storage systemWireless charging roadPoint queue modelElectricity marketDemand bidOptimal power flowModel predictive controlLocational marginal price forecastingEconomicsEnergyBuilt environment and designapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6kk414v4articleoai:escholarship.org:ark:/13030/qt9qv1x5sf2023-12-14T18:27:58Zqt9qv1x5sfVelocity-Gauge Real-Time Time-Dependent Density Functional Tight-Binding for Large-Scale Condensed Matter Systems.Del Ben, MauroSait Okyay, MahmutChoi, MinIbrahim, KhaledWong, BryanXu, Qiang2023-11-28We present a new velocity-gauge real-time, time-dependent density functional tight-binding (VG-rtTDDFTB) implementation in the open-source DFTB+ software package (https://dftbplus.org) for probing electronic excitations in large, condensed matter systems. Our VG-rtTDDFTB approach enables real-time electron dynamics simulations of large, periodic, condensed matter systems containing thousands of atoms with a favorable computational scaling as a function of system size. We provide computational details and benchmark calculations to demonstrate its accuracy and computational parallelizability on a variety of large material systems. As a representative example, we calculate laser-induced electron dynamics in a 512-atom amorphous silicon supercell to highlight the large periodic systems that can be examined with our implementation. Taken together, our VG-rtTDDFTB approach enables new electron dynamics simulations of complex systems that require large periodic supercells, such as crystal defects, complex surfaces, nanowires, and amorphous materials.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9qv1x5sfarticleJournal of Chemical Theory and Computation, vol 19, iss 22oai:escholarship.org:ark:/13030/qt0pq9p5jk2023-12-14T12:50:26Zqt0pq9p5jkIsotopic Signatures of Methane Emissions From Dairy Farms in California’s San Joaquin ValleyCarranza, ValerieBiggs, BrennaMeyer, DeanneTownsend‐Small, AmyThiruvenkatachari, Ranga RajanVenkatram, AkulaFischer, Marc LHopkins, Francesca M2022-01-01In this study, we present seasonal atmospheric measurements of δ13CCH4 from dairy farms in the San Joaquin Valley of California. We used δ13CCH4 to characterize emissions from enteric fermentation by measuring downwind of cattle housing (e.g., freestall barns, corrals) and from manure management areas (e.g., anaerobic manure lagoons) with a mobile platform equipped with cavity ring-down spectrometers. Across seasons, the δ13CCH4 from enteric fermentation source areas ranged from −69.7 ± 0.6 per mil (‰) to −51.6 ± 0.1‰ while the δ13CCH4 from manure lagoons ranged from −49.5 ± 0.1‰ to −40.5 ± 0.2‰. Measurements of δ13CCH4 of enteric CH4 suggest a greater than 10‰ difference between cattle production groups in accordance with diet. Isotopic signatures of CH4 were used to characterize enteric and manure CH4 from downwind plume sampling of dairies. Our findings show that δ13CCH4 measurements could improve the attribution of CH4 emissions from dairy sources at scales ranging from individual facilities to regions and help constrain the relative contributions from these different sources of emissions to the CH4 budget.Earth SciencesAtmospheric SciencesClimate Actionmethanegreenhouse gas emissionscarbon isotopesdairysource apportionmentGeophysicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0pq9p5jkarticleJournal of Geophysical Research Biogeosciences, vol 127, iss 1oai:escholarship.org:ark:/13030/qt4h04r9x62023-12-14T12:22:19Zqt4h04r9x6A Unique Sulfotransferase-Involving Strigolactone Biosynthetic Route in SorghumWu, ShengLi, Yanran2021-01-01LOW GERMINATION STIMULANT 1 (LGS1) plays an important role in strigolactones (SLs) biosynthesis and Striga resistance in sorghum, but the catalytic function remains unclear. Using the recently developed SL-producing microbial consortia, we examined the activities of sorghum MORE AXILLARY GROWTH1 (MAX1) analogs and LGS1. Surprisingly, SbMAX1a (cytochrome P450 711A enzyme in sorghum) synthesized 18-hydroxy-carlactonoic acid (18-hydroxy-CLA) directly from carlactone (CL) through four-step oxidations. The further oxidated product orobanchol (OB) was also detected in the microbial consortium. Further addition of LGS1 led to the synthesis of both 5-deoxystrigol (5DS) and 4-deoxyorobanchol (4DO). Further biochemical characterization found that LGS1 functions after SbMAX1a by converting 18-hydroxy-CLA to 5DS and 4DO possibly through a sulfonation-mediated pathway. The unique functions of SbMAX1 and LGS1 imply a previously unknown synthetic route toward SLs.Biochemistry and Cell BiologyBiological Sciencesstrigolactonessorghumsulfotransferasebiosynthesissynthetic biologyPlant BiologyCrop and pasture productionPlant biologypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4h04r9x6articleoai:escholarship.org:ark:/13030/qt53g5f6qk2023-12-14T11:35:51Zqt53g5f6qkModel-free voltage control of active distribution system with PVs using surrogate model-based deep reinforcement learningCao, DiZhao, JunboHu, WeihaoDing, FeiYu, NanpengHuang, QiChen, Zhe2022-01-01EngineeringElectrical EngineeringBasic Behavioral and Social ScienceBehavioral and Social ScienceVoltage regulationActive distribution networkModel-freeDeep reinforcement learningSolar PVsOptimizationEconomicsEnergyBuilt environment and designapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/53g5f6qkarticleoai:escholarship.org:ark:/13030/qt7pg368c52023-12-14T09:37:13Zqt7pg368c5Mixing of 3-term progressions in Quasirandom GroupsBhangale, AmeyHarsha, PrahladhRoy, Sourya2021-09-26In this note, we show the mixing of three-term progressions $(x, xg, xg^2)$
in every finite quasirandom groups, fully answering a question of Gowers. More
precisely, we show that for any $D$-quasirandom group $G$ and any three sets
$A_1, A_2, A_3 \subset G$, we have \[ \left|\Pr_{x,y\sim G}\left[ x \in A_1, xy
\in A_2, xy^2 \in A_3\right] - \prod_{i=1}^3 \Pr_{x\sim G}\left[x \in
A_i\right] \right| \leq \left(\frac{2}{\sqrt{D}}\right)^{\frac{1}{4}}.\] Prior
to this, Tao answered this question when the underlying quasirandom group is
$\mathrm{SL}_{d}(\mathbb{F}_q)$. Subsequently, Peluse extended the result to
all nonabelian finite $\textit{simple}$ groups. In this work, we show that a
slight modification of Peluse's argument is sufficient to fully resolve Gower's
quasirandom conjecture for 3-term progressions. Surprisingly, unlike the proofs
of Tao and Peluse, our proof is elementary and only uses basic facts from
nonabelian Fourier analysis.math.COcs.DMmath.GRapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7pg368c5articleoai:escholarship.org:ark:/13030/qt4h02911g2023-12-14T09:34:04Zqt4h02911gRational design strategies for functional reconstitution of plant cytochrome P450s in microbial systemsZhou, AnqiZhou, KangLi, Yanran2021-04-01Plant natural products (NPs) are of pharmaceutical and agricultural significance, yet the low abundance is largely impeding the broad investigation and utilization. Microbial bioproduction is a promising alternative sourcing to plant NPs. Cytochrome P450s (CYPs) play an essential role in plant secondary metabolism, and functional reconstitution of plant CYPs in the microbial system is one of the major challenges in establishing efficient microbial plant NP bioproduction. In this review, we briefly summarized the recent progress in rational engineering strategies for enhanced activity of plant CYPs in Escherichia coli and Saccharomyces cerevisiae, two commonly used microbial hosts. We believe that in-depth foundational investigations on the native microenvironment of plant CYPs are necessary to adapt the microbial systems for more efficient functional reconstitution of plant CYPs.Biological SciencesIndustrial BiotechnologyCytochrome P-450 Enzyme SystemEscherichia coliPlantsSaccharomyces cerevisiaeSecondary MetabolismBiochemistry and Cell BiologyMicrobiologyPlant BiologyPlant Biology & BotanyPlant biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4h02911garticleoai:escholarship.org:ark:/13030/qt3hc6j2tq2023-12-14T08:43:57Zqt3hc6j2tqEstablishment of strigolactone-producing bacterium-yeast consortiumWu, ShengMa, XiaoqiangZhou, AnqiValenzuela, AlexZhou, KangLi, Yanran2021-09-17Strigolactones (SLs) are a class of phytohormones playing diverse roles in plant growth and development, yet the limited access to SLs is largely impeding SL-based foundational investigations and applications. Here, we developed Escherichia coli–Saccharomyces cerevisiae consortia to establish a microbial biosynthetic platform for the synthesis of various SLs, including carlactone, carlactonoic acid, 5-deoxystrigol (5DS; 6.65 ± 1.71 μg/liter), 4-deoxyorobanchol (3.46 ± 0.28 μg/liter), and orobanchol (OB; 19.36 ± 5.20 μg/liter). The SL-producing platform enabled us to conduct functional identification of CYP722Cs from various plants as either OB or 5DS synthase. It also allowed us to quantitatively compare known variants of plant SL biosynthetic enzymes in the microbial system. The titer of 5DS was further enhanced through pathway engineering to 47.3 μg/liter. This work provides a unique platform for investigating SL biosynthesis and evolution and lays the foundation for developing SL microbial production process.Biological SciencesIndustrial BiotechnologyEmerging Infectious Diseasesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3hc6j2tqarticleScience Advances, vol 7, iss 38eabh4048oai:escholarship.org:ark:/13030/qt0481538f2023-12-13T21:39:16Zqt0481538fHeterostructured materials: superior properties from hetero-zone interactionZhu, YuntianAmeyama, KeiAnderson, Peter MBeyerlein, Irene JGao, HuajianKim, Hyoung SeopLavernia, EnriqueMathaudhu, SuveenMughrabi, HaelRitchie, Robert OTsuji, NobuhiroZhang, XiangyiWu, Xiaolei2021-01-02Heterostructured materials are an emerging class of materials with superior performances that are unattainable by their conventional homogeneous counterparts. They consist of heterogeneous zones with dramatic (>100%) variations in mechanical and/or physical properties. The interaction in these hetero-zones produces a synergistic effect where the integrated property exceeds the prediction by the rule-of-mixtures. The heterostructured materials field explores heterostructures to control defect distributions, long-range internal stresses, and nonlinear inter-zone interactions for unprecedented performances. This paper is aimed to provide perspectives on this novel field, describe the state-of-the-art of heterostructured materials, and identify and discuss key issues that deserve additional studies.EngineeringMaterials EngineeringResources Engineering and Extractive MetallurgyHeterostructured materialssynergyheterostructureshetero-deformation induced (HDI) hardeningback stressforward stressMaterials engineeringResources engineering and extractive metallurgyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0481538farticleMaterials Research Letters, vol 9, iss 11 - 31oai:escholarship.org:ark:/13030/qt1xp973j12023-12-13T17:44:34Zqt1xp973j1Yeast as a promising heterologous host for steroid bioproductionXu, ShanhuiLi, Yanran2020-10-01With the rapid development of synthetic biology and metabolic engineering technologies, yeast has been generally considered as promising hosts for the bioproduction of secondary metabolites. Sterols are essential components of cell membrane, and are the precursors for the biosynthesis of steroid hormones, signaling molecules, and defense molecules in the higher eukaryotes, which are of pharmaceutical and agricultural significance. In this mini-review, we summarize the recent engineering efforts of using yeast to synthesize various steroids, and discuss the structural diversity that the current steroid-producing yeast can achieve, the challenge and the potential of using yeast as the bioproduction platform of various steroids from higher eukaryotes.Biochemistry and Cell BiologyBiological SciencesIndustrial BiotechnologyQuality EducationMetabolic EngineeringSaccharomyces cerevisiaeSterolsSynthetic BiologyYeastSteroidsBiotransformationDe novo synthesisMetabolic engineeringFood SciencesBiotechnologyBiochemistry and cell biologyIndustrial biotechnologyMicrobiologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1xp973j1articleJournal of Industrial Microbiology & Biotechnology, vol 47, iss 9-10829 - 843oai:escholarship.org:ark:/13030/qt4nz890c42023-12-13T17:37:43Zqt4nz890c4Structure: Function Studies of the Cytosolic, Mo- and NAD+-Dependent Formate Dehydrogenase from Cupriavidus necatorHille, RussYoung, TynanNiks, DimitriHakopian, SheronTam, Timothy KYu, XuejunMulchandani, AshokBlaha, Gregor M2020-01-01Here, we report recent progress our laboratories have made in understanding the maturation and reaction mechanism of the cytosolic and NAD+-dependent formate dehydrogenase from Cupriavidus necator. Our recent work has established that the enzyme is fully capable of catalyzing the reverse of the physiological reaction, namely, the reduction of CO2 to formate using NADH as a source of reducing equivalents. The steady-state kinetic parameters in the forward and reverse directions are consistent with the expected Haldane relationship. The addition of an NADH-regenerating system consisting of glucose and glucose dehydrogenase increases the yield of formate approximately 10-fold. This work points to possible ways of optimizing the reverse of the enzyme's physiological reaction with commercial potential as an effective means of CO2 remediation. New insight into the maturation of the enzyme comes from the recently reported structure of the FdhD sulfurase. In E. coli, FdhD transfers a catalytically essential sulfur to the maturing molybdenum cofactor prior to insertion into the apoenzyme of formate dehydrogenase FdhF, which has high sequence similarity to the molybdenum-containing domain of the C. necator FdsA. The FdhD structure suggests that the molybdenum cofactor may first be transferred from the sulfurase to the C-terminal cap domain of apo formate dehydrogenase, rather than being transferred directly to the body of the apoenzyme. Closing of the cap domain over the body of the enzymes delivers the Mo-cofactor into the active site, completing the maturation of formate dehydrogenase. The structural and kinetic characterization of the NADH reduction of the FdsBG subcomplex of the enzyme provides further insights in reversing of the formate dehydrogenase reaction. Most notably, we observe the transient formation of a neutral semiquinone FMNH, a species that has not been observed previously with holoenzyme. After initial reduction of the FMN of FdsB byNADHto the hydroquinone (with a kred of 680 s-1 and Kd of 190 μM), one electron is rapidly transferred to the Fe2S2 cluster of FdsG, leaving FMNH. The Fe4S4 cluster of FdsB does not become reduced in the process. These results provide insight into the function not only of the C. necator formate dehydrogenase but also of other members of the NADH dehydrogenase superfamily of enzymes to which it belongs.Inorganic ChemistryChemical Sciences1.1 Normal biological development and functioningUnderpinning researchnicotinamide adenine dinucleotideelectron transferenzyme kineticsenzyme structureformate dehydrogenasecarbon assimilationInorganic chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4nz890c4articleInorganics, vol 8, iss 741oai:escholarship.org:ark:/13030/qt4qq703wb2023-12-13T16:36:08Zqt4qq703wbFlame Synthesis of NanomaterialsJUNG, HEEJUNGLiu, YidingHe, LeYin, Yadong2019-10-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4qq703wbchapteroai:escholarship.org:ark:/13030/qt09s363w32023-12-13T15:33:53Zqt09s363w3Frequency-domain hot-wire sensor and 3D model for thermal conductivity measurements of reactive and corrosive materials at high temperaturesWingert, MCZhao, AZKodera, YObrey, SJGaray, JE2020-05-01High temperature solids and liquids are becoming increasingly important in next-generation energy and manufacturing systems that seek higher efficiencies and lower emissions. Accurate measurements of thermal conductivity at high temperatures are required for the modeling and design of these systems, but commonly employed time-domain measurements can have errors from convection, corrosion, and ambient temperature fluctuations. Here, we describe the development of a frequency-domain hot-wire technique capable of accurately measuring the thermal conductivity of solid and molten compounds from room temperature up to 800 °C. By operating in the frequency-domain, we can lock into the harmonic thermal response of the material and reject the influence of ambient temperature fluctuations, and we can keep the probed volume below 1 µl to minimize convection. The design of the microfabricated hot-wire sensor, electrical systems, and insulating wire coating to protect against corrosion is covered in detail. Furthermore, we discuss the development of a full three-dimensional multilayer thermal model that accounts for both radial conduction into the sample and axial conduction along the wire and the effect of wire coatings. The 3D, multilayer model facilitates the measurement of small sample volumes important for material development. A sensitivity analysis and an error propagation calculation of the frequency-domain thermal model are performed to demonstrate what factors are most important for thermal conductivity measurements. Finally, we show thermal conductivity measurements including model data fitting on gas (argon), solid (sulfur), and molten substances over a range of temperatures.Manufacturing EngineeringEngineeringAffordable and Clean EnergyPhysical SciencesChemical SciencesApplied PhysicsChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/09s363w3articleReview of Scientific Instruments, vol 91, iss 5054904oai:escholarship.org:ark:/13030/qt2ww782t62023-12-13T10:13:09Zqt2ww782t6UCR-STARGhosh, SaheliVu, TinEskandari, Mehrad AminEldawy, Ahmed2019-12-17This article describes the UCR Spatio-temporal Active Repository (UCR-STAR). UCR-STAR is a visual catalog for big spatial datasets. Rather than a boring tabular listing of datasets, it provides an interactive map interface that allows users to explore these datasets to assess their coverage, quality, and distribution. This article describes both the functionality of UCR-STAR as well as the underlying system architecture. We believe that this article can help the research community by explaining how to realize research ideas into a workable product.Creative Arts and WritingInformation and Computing SciencesScreen and Digital MediapubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2ww782t6articleSIGSPATIAL Special, vol 11, iss 234 - 40oai:escholarship.org:ark:/13030/qt9b9490r62023-12-13T08:07:48Zqt9b9490r6Intravital Vascular Phototheranostics and Real-Time Circulation Dynamics of Micro- and Nanosized Erythrocyte-Derived CarriersJia, WangcunBurns, Joshua MVillantay, BettyTang, Jack CVankayala, RavirajLertsakdadet, BenChoi, BernardNelson, J StuartAnvari, Bahman2020-01-08Erythrocyte-based carriers can serve as theranostic platforms for delivery of imaging and therapeutic payloads. Engineering these carriers at micro- or nanoscales makes them potentially useful for broad clinical applications ranging from vascular diseases to tumor theranostics. Longevity of these carriers in circulation is important in delivering a sufficient amount of their payloads to the target. We have investigated the circulation dynamics of micro (∼4.95 μm diameter) and nano (∼91 nm diameter) erythrocyte-derived carriers in real time using near-infrared fluorescence imaging, and evaluated the effectiveness of such carrier systems in mediating photothermolysis of cutaneous vasculature in mice. Fluorescence emission half-lives of micro- and nanosized carriers in response to a single intravenous injection were ∼49 and ∼15 min, respectively. A single injection of microsized carriers resulted in a 3-fold increase in signal-to-noise ratio that remained nearly persistent over 1 h of imaging time. Our results also suggest that a second injection of the carriers 7 days later can induce a transient inflammatory response, as manifested by the apparent leakage of the carriers into the perivascular tissue. The administration of the carriers into the mice vasculature reduced the threshold laser fluence to induce photothermolysis of blood vessels from >65 to 20 J/cm2. We discuss the importance of membrane physicochemical and mechanical characteristics in engineering erythrocyte-derived carriers and considerations for their clinical translation.EngineeringBioengineeringNanotechnologyAnimalsDrug CarriersErythrocytesMaleMiceNanostructuresNeoplasmsOptical ImagingSkinTheranostic Nanomedicinecancererythrocyte engineeringdelivery systemslaser dermatologic surgerynear-infrared imagingphototherapyport wine stainChemical SciencesNanoscience & NanotechnologyChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9b9490r6articleACS Applied Materials & Interfaces, vol 12, iss 1275 - 287oai:escholarship.org:ark:/13030/qt6h45p9v72023-12-13T05:44:52Zqt6h45p9v7Error-correcting Bacon-Shor code with continuous measurement of noncommuting operatorsAtalaya, JuanKorotkov, Alexander NWhaley, K Birgitta2020-08-01We analyze the continuous operation of the nine-qubit error-correcting Bacon-Shor code with all noncommuting gauge operators measured at the same time. The error syndromes are continuously monitored using cross correlations of sets of three measurement signals. We calculate the logical error rates due to X, Y, and Z errors in the physical qubits and compare the continuous implementation with the discrete operation of the code. We find that both modes of operation exhibit similar performances when the measurement strength from continuous measurements is sufficiently strong. We also estimate the value of the crossover error rate of the physical qubits, below which continuous error correction gives smaller logical error rates. Continuous operation has the advantage of passive monitoring of errors and avoids the need for additional circuits involving ancilla qubits.Quantum PhysicsPhysical Sciencesquant-phcond-mat.otherChemical sciencesMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6h45p9v7articlePhysical Review A, vol 102, iss 2022415oai:escholarship.org:ark:/13030/qt0m90d01t2023-12-13T03:23:24Zqt0m90d01tUltrafast laser welding of ceramicsPenilla, EHDevia-Cruz, LFWieg, ATMartinez-Torres, PCuando-Espitia, NSellappan, PKodera, YAguilar, GGaray, JE2019-08-23Welding of ceramics is a key missing component in modern manufacturing. Current methods cannot join ceramics in proximity to temperature-sensitive materials like polymers and electronic components. We introduce an ultrafast pulsed laser welding approach that relies on focusing light on interfaces to ensure an optical interaction volume in ceramics to stimulate nonlinear absorption processes, causing localized melting rather than ablation. The key is the interplay between linear and nonlinear optical properties and laser energy-material coupling. The welded ceramic assemblies hold high vacuum and have shear strengths comparable to metal-to-ceramic diffusion bonds. Laser welding can make ceramics integral components in devices for harsh environments as well as in optoelectronic and/or electronic packages needing visible-radio frequency transparency.Manufacturing EngineeringEngineeringChemical SciencesGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0m90d01tarticleScience, vol 365, iss 6455803 - 808oai:escholarship.org:ark:/13030/qt4kv4b6q82023-12-13T00:34:15Zqt4kv4b6q8Correction to “High Hydroquinone Emissions from Burning Manzanita”Jen, Coty NLiang, YutongHatch, Lindsay EKreisberg, Nathan MStamatis, ChristosKristensen, KasperBattles, John JStephens, Scott LYork, Robert ABarsanti, Kelley CGoldstein, Allen H2019-06-11An addition to the Acknowledgments of our paper is required. It is as follows: This research used resources of the Advanced Light Source, which is a DOE Office of Science User Facility under Contract No. DE-AC02-05CH11231.Chemical EngineeringEngineeringEnvironmental SciencesPollution and ContaminationEnvironmental Science and ManagementEnvironmental EngineeringEnvironmental BiotechnologyChemical engineeringPollution and contaminationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4kv4b6q8articleEnvironmental Science & Technology Letters, vol 6, iss 6378 - 378oai:escholarship.org:ark:/13030/qt6n51r5232023-12-13T00:27:58Zqt6n51r523Characterization of ageing resistant transparent nanocrystalline yttria‐stabilized zirconia implantsDavoodzadeh, NamiCano‐Velázquez, Mildred SHalaney, David LSabzeghabae, ArianaUahengo, GottliebGaray, Javier EAguilar, Guillermo2020-04-01The "Window to the Brain" is a transparent cranial implant under development, based on nanocrystalline yttria-stabilized zirconia (nc-YSZ) transparent ceramic material. Previous work has demonstrated the feasibility of this material to facilitate brain imaging over time, but the long-term stability of the material over decades in the body is unknown. In this study, the low-temperature degradation (LTD) of nc-YSZ of 3, 6, and 8 mol % yttria is compared before and after accelerated ageing treatments following ISO standards for assessing the ageing resistance of zirconia ceramics. After 100 hr of accelerated ageing (equivalent to many decades of ageing in the body), the samples do not show any signs of phase transformation to monoclinic by X-ray diffraction and micro-Raman spectroscopy. Moreover, the mechanical hardness of the samples did not decrease, and changes in optical transmittance from 500 to 1000 nm due to ageing treatments was minimal (below 3% for all samples), and unlikely to be due to phase transformation of surface crystals to monoclinic. These results indicate the nc-YSZ has excellent ageing resistance and can withstand long-term implantation conditions without exhibiting LTD.EngineeringMaterials EngineeringBiomedical EngineeringCeramicsCrystallizationHardnessHot TemperatureHumansMaterials TestingNanoparticlesPhase TransitionPressureProstheses and ImplantsSkullSurface PropertiesX-Ray DiffractionYttriumZirconiumageing resistanceimplantlow-temperature degradationtransparent nanocrystalline yttria-stabilized zirconiazirconia ceramicBiomedical engineeringMaterials engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6n51r523articleJournal of Biomedical Materials Research Part B Applied Biomaterials, vol 108, iss 3709 - 716oai:escholarship.org:ark:/13030/qt71d160492023-12-13T00:11:56Zqt71d16049A high-spin ground-state donor-acceptor conjugated polymerLondon, AEChen, HSabuj, MATropp, JSaghayezhian, MEedugurala, NZhang, BALiu, YGu, XWong, BMRai, NBowman, MKAzoulay, JD2019-05-03Interest in high-spin organic materials is driven by opportunities to enable far-reaching fundamental science and develop technologies that integrate light element spin, magnetic, and quantum functionalities. Although extensively studied, the intrinsic instability of these materials complicates synthesis and precludes an understanding of how fundamental properties associated with the nature of the chemical bond and electron pairing in organic materials systems manifest in practical applications. Here, we demonstrate a conjugated polymer semiconductor, based on alternating cyclopentadithiophene and thiadiazoloquinoxaline units, that is a ground-state triplet in its neutral form. Electron paramagnetic resonance and magnetic susceptibility measurements are consistent with a high-to-low spin energy gap of 9.30 × 10-3 kcal mol-1. The strongly correlated electronic structure, very narrow bandgap, intramolecular ferromagnetic coupling, high electrical conductivity, solution processability, and robust stability open access to a broad variety of technologically relevant applications once thought of as beyond the current scope of organic semiconductors.Macromolecular and Materials ChemistryChemical SciencesEngineeringPhysical SciencesMaterials EngineeringpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/71d16049articleScience Advances, vol 5, iss 5eaav2336oai:escholarship.org:ark:/13030/qt7rx5m1d92023-12-12T23:42:24Zqt7rx5m1d9The invisible dance of CRISPR-Cas9Palermo, GiuliaRicci, Clarisse GMcCammon, J Andrew2019-04-01Since the discovery of the DNA double helix, the main molecular repository of genetic information, scientists have been struggling to find ways to efficiently manipulate genes. The ability to mark, modify, or regulate specific sequences of DNA in a controlled fashion is of key importance because of the ways that gene editing could be used to improve human life. For example, genetic therapies are being developed to permanently cure cancer and other life-threatening diseases.Mathematical SciencesPhysical SciencesCancerGeneticsGeneric health relevanceGeneral PhysicsMathematical sciencesPhysical sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7rx5m1d9articlePhysics Today, vol 72, iss 430 - 36oai:escholarship.org:ark:/13030/qt1h2325d92023-12-12T23:26:22Zqt1h2325d9DeepPASTA: deep neural network based polyadenylation site analysisArefeen, AshrafulXiao, XinshuJiang, TaoBirol, Inanc2019-11-01MotivationAlternative polyadenylation (polyA) sites near the 3' end of a pre-mRNA create multiple mRNA transcripts with different 3' untranslated regions (3' UTRs). The sequence elements of a 3' UTR are essential for many biological activities such as mRNA stability, sub-cellular localization, protein translation, protein binding and translation efficiency. Moreover, numerous studies in the literature have reported the correlation between diseases and the shortening (or lengthening) of 3' UTRs. As alternative polyA sites are common in mammalian genes, several machine learning tools have been published for predicting polyA sites from sequence data. These tools either consider limited sequence features or use relatively old algorithms for polyA site prediction. Moreover, none of the previous tools consider RNA secondary structures as a feature to predict polyA sites.ResultsIn this paper, we propose a new deep learning model, called DeepPASTA, for predicting polyA sites from both sequence and RNA secondary structure data. The model is then extended to predict tissue-specific polyA sites. Moreover, the tool can predict the most dominant (i.e. frequently used) polyA site of a gene in a specific tissue and relative dominance when two polyA sites of the same gene are given. Our extensive experiments demonstrate that DeepPASTA signisficantly outperforms the existing tools for polyA site prediction and tissue-specific relative and absolute dominant polyA site prediction.Availability and implementationhttps://github.com/arefeen/DeepPASTA.Supplementary informationSupplementary data are available at Bioinformatics online.Biochemistry and Cell BiologyBioinformatics and Computational BiologyBiological SciencesGeneticsUnderpinning research1.1 Normal biological development and functioningGeneric health relevance3' Untranslated RegionsAnimalsNeural NetworksComputerPoly APolyadenylationRNAMessengerMathematical SciencesInformation and Computing SciencesBioinformaticsBiological sciencesInformation and computing sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1h2325d9articleBioinformatics, vol 35, iss 224577 - 4585oai:escholarship.org:ark:/13030/qt1r50c3qh2023-12-12T22:21:32Zqt1r50c3qhMeasurement of Magnetic Nanoparticles Using High Transition Temperature Superconducting Quantum Interference DevicesWang, JiLi, HaoCho, Ethan YLeFebvere, Jay CCybart, Shane A2019-01-01Physical SciencesCondensed Matter PhysicsNanotechnologyBioengineeringSQUIDnanoparticlesmagnetometerElectrical and Electronic EngineeringMaterials EngineeringGeneral PhysicsElectrical engineeringCondensed matter physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1r50c3qharticleIEEE Transactions on Applied Superconductivity, vol 29, iss 51 - 4oai:escholarship.org:ark:/13030/qt8c79x5062023-12-12T22:20:10Zqt8c79x506Inductance Investigation of YBa2Cu3O7−δ Nano-Slit SQUIDs Fabricated With a Focused Helium Ion BeamLi, HaoCho, Ethan YCai, HanWang, Yan-TingMcCoy, Stephen JCybart, Shane A2019-01-01Focused helium ion beam material modification is ideally suited for the fabrication of YBa2Cu3O7-δ (YBCO) Josephson junctions and superconducting feature sizes down to the nanoscale. We report the fabrication and measurement of YBCO nano-slit SQUIDs and study how scaling the dimensions of the SQUID body and electrodes influences the electrical properties. Sixteen nano-slit SQUIDs with different width and length were fabricated from a single-layer 25-nm-thick YBCO film. The experimental results yield an estimation of the sheet inductance to be ∼4 pH/□ and a penetration depth of ∼180 nm. The temperature dependence of the inductance agree well with an impurity scattering model, indicating that the TC of the film was ∼82 K, and the ratio between geometric inductance and kinetic inductance at 0 K was ∼0.8. These results provide solid basis for the design of high-performance, high-TC micro-SQUID magnetometers.Physical SciencesEngineeringNanotechnologyCondensed Matter PhysicsNano-slit SQUIDfocused helium ion beaminductanceYBCO thin filmElectrical and Electronic EngineeringMaterials EngineeringGeneral PhysicsElectrical engineeringCondensed matter physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8c79x506articleIEEE Transactions on Applied Superconductivity, vol 29, iss 51 - 4oai:escholarship.org:ark:/13030/qt4fj8w0th2023-12-12T22:08:30Zqt4fj8w0thNanoscale integration of oxides and metals in bulk 3D composites: leveraging SrFe12O19/Co interfaces for magnetic exchange couplingVolodchenkov, ADKodera, YGaray, JE2019-06-01EngineeringMaterials EngineeringChemical SciencesMaterialsChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4fj8w0tharticleJournal of Materials Science, vol 54, iss 118276 - 8288oai:escholarship.org:ark:/13030/qt7ft8k6j62023-12-12T21:39:04Zqt7ft8k6j6Deciphering Off-Target Effects in CRISPR-Cas9 through Accelerated Molecular Dynamics.Ricci, CGChen, JSMiao, YJinek, MDoudna, JAMcCammon, JAPalermo, G2019-04-01CRISPR-Cas9 is the state-of-the-art technology for editing and manipulating nucleic acids. However, the occurrence of off-target mutations can limit its applicability. Here, all-atom enhanced molecular dynamics (MD) simulations-using Gaussian accelerated MD (GaMD)-are used to decipher the mechanism of off-target binding at the molecular level. GaMD reveals that base pair mismatches in the target DNA at distal sites with respect to the protospacer adjacent motif (PAM) can induce an extended opening of the RNA:DNA heteroduplex, which leads to newly formed interactions between the unwound DNA and the L2 loop of the catalytic HNH domain. These conserved interactions constitute a "lock" effectively decreasing the conformational freedom of the HNH domain and hampering its activation for cleavage. Remarkably, depending on their positions at PAM distal sites, DNA mismatches responsible for off-target cleavages are unable to "lock" the HNH domain, thereby leading to the unselective cleavage of DNA sequences. In consistency with the available experimental data, the ability to "lock" the catalytic HNH domain in an inactive "conformational checkpoint" is shown to be a key determinant in the onset of off-target effects. This mechanistic rationale contributes in clarifying a long lasting open issue in the CRISPR-Cas9 function and poses the foundation for designing novel and more specific Cas9 variants, which could be obtained by magnifying the "locking" interactions between HNH and the target DNA in the presence of any incorrect off-target sequence, thus preventing undesired cleavages.Chemical SciencesGenetics1.1 Normal biological development and functioningUnderpinning researchGeneric health relevanceChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7ft8k6j6articleACS central science, vol 5, iss 4651 - 662oai:escholarship.org:ark:/13030/qt9jw1x3gd2023-12-12T21:27:26Zqt9jw1x3gdDevelopment and applications of a concentrating membrane osmometer for colloid solutionsHale, Christopher SMcBride, Devin WBatarseh, RamseyHughey, JordanVang, KevinRodgers, VGJ2019-03-01The membrane concentration osmometer coupled with multiple sample preparations has been used for over a century to determine a number of colloidal properties. At the dilute region, this method has been used to determine solute molecular mass. When the solution is proteinaceous, in the intermediate region, the osmotic pressure profile provides the second virial coefficient, useful for estimating protein crystallization and salting out. At the most crowded concentrations, it provides insight into protein hydration and protein-ion interaction. One of the most critical factors in generating the osmotic pressure profile is minimizing the quantity of protein used and reducing the error in preparing samples. Here, we introduce a membrane concentrating osmometer that allows one to measure osmotic pressure over a wide concentration range from a single sample. A test study was performed using the osmotic pressure profile of self-crowded bovine serum albumin solutions. The resulting profile was in good agreement with previous data in the literature obtained from multiple sample studies. The osmotic pressure profile was further used with a free solvent-based osmotic pressure model to determine protein hydration and ion binding. These results were in excellent agreement with literature values. This concentrating osmometer has several advantages over a conventional concentration osmometer for obtaining the osmotic pressure profile for proteinaceous solutions: (1) the amount of protein required is significantly decreased, (2) the potential for experimental error in sample preparation diminishes, and (3) the time for generating the osmotic pressure profile is substantially reduced.Analytical ChemistryEngineeringChemical SciencesGeneric health relevancePhysical SciencesApplied PhysicsChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9jw1x3gdarticleReview of Scientific Instruments, vol 90, iss 3034102oai:escholarship.org:ark:/13030/qt2rq421vj2023-12-12T21:26:06Zqt2rq421vjUnderstanding the mechanistic basis of non-coding RNA through molecular dynamics simulationsPalermo, GiuliaCasalino, LorenzoMagistrato, AlessandraMcCammon, J Andrew2019-06-01Noncoding RNA (ncRNA) has a key role in regulating gene expression, mediating fundamental processes and diseases via a variety of yet unknown mechanisms. Here, we review recent applications of conventional and enhanced Molecular Dynamics (MD) simulations methods to address the mechanistic function of large biomolecular systems that are tightly involved in the ncRNA function and that are of key importance in life sciences. This compendium focuses of three biomolecular systems, namely the CRISPR-Cas9 genome editing machinery, group II intron ribozyme and the ribonucleoprotein complex of the spliceosome, which edit and process ncRNA. We show how the application of a novel accelerated MD simulations method has been key in disclosing the conformational transitions underlying RNA binding in the CRISPR-Cas9 complex, suggesting a mechanism for RNA recruitment and clarifying the conformational changes required for attaining genome editing. As well, we discuss the use of mixed quantum-classical MD simulations in deciphering the catalytic mechanism of RNA splicing as operated by group II intron ribozyme, one of the largest ncRNA structures crystallized so far. Finally, we debate the future challenges and opportunities in the field, discussing the recent application of MD simulations for unraveling the functional biophysics of the spliceosome, a multi-mega Dalton complex of proteins and small nuclear RNAs that performs RNA splicing in humans. This showcase of applications highlights the current talent of MD simulations to dissect atomic-level details of complex biomolecular systems instrumental for the design of finely engineered genome editing machines. As well, this review aims at inspiring future investigations of several other ncRNA regulatory systems, such as micro and small interfering RNAs, which achieve their function and specificity using RNA-based recognition and targeting strategies.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeBiotechnologyUnderpinning research1.1 Normal biological development and functioningGeneric health relevanceCRISPR-Cas SystemsGene EditingHumansMolecular Dynamics SimulationNucleic Acid ConformationProteinsRNA SplicingRNAUntranslatedCRISPR-Cas9RNA splicingGenome editingGroup II intronSpliceosomeBiochemistry and Cell BiologyZoologyBiophysicsBiochemistry and cell biologypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2rq421vjarticleJournal of Structural Biology, vol 206, iss 3267 - 279oai:escholarship.org:ark:/13030/qt4bk998vs2023-12-12T18:34:33Zqt4bk998vsMeasurements of I/SVOCs in biomass-burning smoke using solid-phase extraction disks and two-dimensional gas chromatographyHatch, Lindsay ERivas-Ubach, AlbertJen, Coty NLipton, MaryGoldstein, Allen HBarsanti, Kelley C2018-01-01Biomass-burning organic-aerosol (OA) emissions are known to exhibit semi-volatile behavior that impacts OA loading during plume transport. Because such semi-volatile behavior depends in part on OA composition, improved speciation of intermediate and semi-volatile organic compounds (I/SVOCs) emitted during fires is needed to assess the competing effects of primary OA volatilization and secondary OA production. In this study, 18 laboratory fires were sampled in which a range of fuel types were burned. Emitted I/SVOCs were collected onto Teflon filters and solid-phase extraction (SPE) disks to qualitatively characterize particulate and gaseous I/SVOCs, respectively. Derivatized filter extracts were analyzed using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS). Quality control tests were performed using biomass-burning relevant standards and demonstrate the utility of SPE disks for untargeted analysis of air samples. The observed chromatographic profiles of I/SVOCs in coniferous fuel-derived smoke samples were well correlated with each other, but poorly correlated with other fuel types (e.g., herbaceous and chaparral fuels). Emissions of benzenediol isomers were also shown to be fuel dependent. The combined Teflon and SPE filter data captured differences in gas-particle partitioning of the benzenediol isomers, with hydroquinone having a significantly higher particle-phase fraction than catechol due to its lower volatility. Additionally, the speciated volatility distribution of I/SVOCs in smoke from a rotten-log fire was estimated to evaluate the composition of potentially volatilized primary OA, which was entirely attributed to oxygenated (or other heteroatomic) compounds. The isomer-dependent partitioning and the speciated volatility distributions both suggest the need for better understanding of gas-phase and heterogenous reaction pathways of biomass-burning-derived I/SVOCs in order to represent the atmospheric chemistry of smoke in models.Earth SciencesAtmospheric SciencesClimate ActionAstronomical and Space SciencesMeteorology & Atmospheric SciencesAtmospheric sciencesClimate change scienceapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4bk998vsarticleAtmospheric Chemistry and Physics, vol 18, iss 2417801 - 17817oai:escholarship.org:ark:/13030/qt9x56g9t82023-12-12T17:24:39Zqt9x56g9t8A NEW LOOK AT SECRECY CAPACITY OF MIMOME USING ARTIFICIAL NOISE FROM ALICE AND BOB WITHOUT KNOWLEDGE OF EVE’S CSISohrabi, RezaHua, Yingbo2018-11-29This study investigates a secure wireless communication
scheme which combines two of the most effective strategies
to combat (passive) eavesdropping, namely mixing information
with artificial noise at the transmitter and jamming from a
full-duplex receiver. All nodes are assumed to possess multiple
antennas, which is known as a MIMOME network. The channel
state information (CSI) of Eve is known to Eve but not to
Alice and Bob. While such setup has been investigated in related
works, new and important insights are revealed in this work. We
investigate the design of optimal jamming parameters to achieve
higher secrecy, and in particular we focus on two important cases
corresponding to Bob using either a simple jamming or a smart
jamming. Furthermore, simulations are presented to highlight
the effectiveness of the proposed strategies.Theory Of ComputationInformation and Computing SciencesCommunications EngineeringEngineeringSecrecy capacityphysical layer securityfull-duplexMIMOMEjammingartificial noiseapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9x56g9t8articleoai:escholarship.org:ark:/13030/qt4kf9b0kg2023-12-12T16:39:06Zqt4kf9b0kgDeep Analysis of Mitochondria and Cell Health Using Machine LearningZahedi, AtenaOn, VincentPhandthong, RattapolChaili, AngelaRemark, GuadalupeBhanu, BirTalbot, Prue2018-01-01There is a critical need for better analytical methods to study mitochondria in normal and diseased states. Mitochondrial image analysis is typically done on still images using slow manual methods or automated methods of limited types of features. MitoMo integrated software overcomes these bottlenecks by automating rapid unbiased quantitative analysis of mitochondrial morphology, texture, motion, and morphogenesis and advances machine-learning classification to predict cell health by combining features. Our pixel-based approach for motion analysis evaluates the magnitude and direction of motion of: (1) molecules within mitochondria, (2) individual mitochondria, and (3) distinct morphological classes of mitochondria. MitoMo allows analysis of mitochondrial morphogenesis in time-lapse videos to study early progression of cellular stress. Biological applications are presented including: (1) establishing normal phenotypes of mitochondria in different cell types; (2) quantifying stress-induced mitochondrial hyperfusion in cells treated with an environmental toxicant, (3) tracking morphogenesis in mitochondria undergoing swelling, and (4) evaluating early changes in cell health when morphological abnormalities are not apparent. MitoMo unlocks new information on mitochondrial phenotypes and dynamics by enabling deep analysis of mitochondrial features in any cell type and can be applied to a broad spectrum of research problems in cell biology, drug testing, toxicology, and medicine.Biochemistry and Cell BiologyBiological SciencesGeneric health relevanceA549 CellsComputational BiologyHumansMachine LearningMitochondriaMovementPhenotypeSeleniumStressPhysiologicalSupervised Machine Learningapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4kf9b0kgarticleScientific Reports, vol 8, iss 116354oai:escholarship.org:ark:/13030/qt3sc8b1z52023-12-12T16:28:02Zqt3sc8b1z5Effect of phase homogeneity and grain size on ferroelectric properties of 0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3 (BXT) lead-free ceramicsDupuy, ADKodera, YCarman, GPGaray, JE2019-01-01EngineeringMaterials EngineeringSpark plasma sinteringCAPADBZT-BCTCondensed Matter PhysicsMechanical EngineeringMaterialsMaterials engineeringMechanical engineeringCondensed matter physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3sc8b1z5articleoai:escholarship.org:ark:/13030/qt237215162023-12-12T16:23:15Zqt23721516Direct-coupled micro-magnetometer with Y-Ba-Cu-O nano-slit SQUID fabricated with a focused helium ion beamCho, Ethan YLi, HaoLeFebvre, Jay CZhou, Yuchao WDynes, RCCybart, Shane A2018-10-15Direct write patterning of high-transition temperature (high-T C) superconducting oxide thin films with a focused helium ion beam is a formidable approach for the scaling of high-T C circuit feature sizes down to the nanoscale. In this letter, we report using this technique to create a sensitive micro superconducting quantum interference device (SQUID) magnetometer with a sensing area of about 100 × 100 μm2. The device is fabricated from a single 35-nm thick YBa2Cu3O7- δ film. A flux concentrating pick-up loop is directly coupled to a 10 nm × 20 μm nano-slit SQUID. The SQUID is defined entirely by helium ion irradiation from a gas field ion source. The irradiation converts the superconductor to an insulator, and no material is milled away or etched. In this manner, a very narrow non-superconducting nano-slit is created entirely within the plane of the film. The narrow slit dimension allows for maximization of the coupling to the field concentrator. Electrical measurements reveal a large 0.35 mV modulation with a magnetic field. We measure a white noise level of 2 μΦ0/Hz1∕2. The field noise of the magnetometer is 4 pT/Hz1∕2 at 4.2 K.Physical SciencesEngineeringNanotechnologyCondensed Matter PhysicsTechnologyApplied PhysicsPhysical sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/23721516articleApplied Physics Letters, vol 113, iss 16162602oai:escholarship.org:ark:/13030/qt5jm3g7082023-12-12T15:05:30Zqt5jm3g708Specific phenotypic, genomic, and fitness evolutionary trajectories toward streptomycin resistance induced by pesticide co-stressors in Escherichia coli.Xing, YueKang, XiaoxiZhang, SiweiMen, Yujie2021-08-18To explore how co-occurring non-antibiotic environmental stressors affect evolutionary trajectories toward antibiotic resistance, we exposed susceptible Escherichia coli K-12 populations to environmentally relevant levels of pesticides and streptomycin for 500 generations. The coexposure substantially changed the phenotypic, genotypic, and fitness evolutionary trajectories, resulting in much stronger streptomycin resistance (>15-fold increase) of the populations. Antibiotic target modification mutations in rpsL and rsmG, which emerged and dominated at late stages of evolution, conferred the strong resistance even with less than 1% abundance, while the off-target mutations in nuoG, nuoL, glnE, and yaiW dominated at early stages only led to mild resistance (2.5-6-fold increase). Moreover, the strongly resistant mutants exhibited lower fitness costs even without the selective pressure and had lower minimal selection concentrations than the mildly resistant ones. Removal of the selective pressure did not reverse the strong resistance of coexposed populations at a later evolutionary stage. The findings suggest higher risks of the selection and propagation of strong antibiotic resistance in environments potentially impacted by antibiotics and pesticides.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5jm3g708articleISME Communications, vol 1, iss 1oai:escholarship.org:ark:/13030/qt093690m22023-12-12T14:30:07Zqt093690m2Correlators Exceeding One in Continuous Measurements of Superconducting QubitsAtalaya, JuanHacohen-Gourgy, ShaySiddiqi, IrfanKorotkov, Alexander N2019-06-07We consider the effect of phase backaction on the correlator ⟨I(t)I(t+τ)⟩ for the output signal I(t) from continuous measurement of a qubit. We demonstrate that the interplay between informational and phase backactions in the presence of Rabi oscillations can lead to the correlator becoming larger than 1, even though |⟨I⟩|≤1. The correlators can be calculated using the generalized "collapse recipe," which we validate using the quantum Bayesian formalism. The recipe can be further generalized to the case of multitime correlators and arbitrary number of detectors, measuring non-commuting qubit observables. The theory agrees well with experimental results for continuous measurement of a transmon qubit. The experimental correlator exceeds the bound of 1 for a sufficiently large angle between the amplified and informational quadratures, causing the phase backaction. The demonstrated effect can be used to calibrate the quadrature misalignment.Quantum PhysicsPhysical SciencesCondensed Matter Physicsquant-phcond-mat.mes-hallMathematical SciencesEngineeringGeneral PhysicsMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/093690m2articlePhysical Review Letters, vol 122, iss 22223603oai:escholarship.org:ark:/13030/qt77d7r16t2023-12-12T14:18:51Zqt77d7r16tA discrete element method representation of an anisotropic elastic continuumTruszkowska, AgnieszkaYu, QinGreaney, P AlexEvans, T MatthewKruzic, Jamie J2018-12-01A method for modeling cubically anisotropic elasticity within the discrete element method is presented. The discrete element method (DEM) is an approach originally intended for modeling granular materials (sand, soil, and powders); however, recent developments have usefully extended it to model stochastic mechanical processes in monolithic solids which, to date, have been assumed to be elastically isotropic. The method presented here for efficiently capturing cubic elasticity in DEM is an important prerequisite for further extending DEM to capture the influence of elastic anisotropy on the mechanical response of polycrystals, composites, etc. The system demonstrated here uses a directionally assigned stiffness in the bonds between adjacent elements and includes separate schemes for achieving anisotropy with Zener ratios greater and smaller than one. The model framework is presented along with an analysis of the accessible space of elastic properties that can be modeled and an artificial neural network interpolation scheme for mapping input parameters to model elastic behavior.EngineeringResources Engineering and Extractive MetallurgyDiscrete element methodAnisotropic elasticityGranular mechanicsMathematical SciencesPhysical SciencesMechanical Engineering & TransportsMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/77d7r16tarticleoai:escholarship.org:ark:/13030/qt9700j4xr2023-12-12T14:18:36Zqt9700j4xrOn the Trustworthiness of Memory Analysis—An Empirical Study from the Perspective of Binary ExecutionPrakash, AravindVenkataramani, EknathYin, HengLin, Zhiqiang2015-01-01Memory analysis serves as a foundation for many security applications such as memory forensics, virtual machine introspection and malware investigation. However, malware, or more specifically a kernel rootkit, can often tamper with kernel memory data, putting the trustworthiness of memory analysis under question. With the rapid deployment of cloud computing and increase of cyber attacks, there is a pressing need to systematically study and understand the problem of memory analysis. In particular, without ground truth, the quality of the memory analysis tools widely used for analyzing closed-source operating systems (like Windows) has not been thoroughly studied. Moreover, while it is widely accepted that value manipulation attacks pose a threat to memory analysis, its severity has not been explored and well understood. To answer these questions, we have devised a number of novel analysis techniques including (1) binary level ground-truth collection, and (2) value equivalence set directed field mutation. Our experimental results demonstrate not only that the existing tools are inaccurate even under a non-malicious context, but also that value manipulation attacks are practical and severe. Finally, we show that exploiting information redundancy can be a viable direction to mitigate value manipulation attacks, but checking information equivalence alone is not an ultimate solution.Distributed Computing and Systems SoftwareInformation and Computing SciencesCybersecurity and PrivacyMemory forensicsoperating systems securityinvasive softwareDKOMkernel rootkitvirtual machine introspectionComputer SoftwareData FormatDistributed ComputingStrategicDefence & Security StudiesCybersecurity and privacyDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9700j4xrarticleIEEE Transactions on Dependable and Secure Computing, vol 12, iss 5557 - 570oai:escholarship.org:ark:/13030/qt9f7614902023-12-12T13:04:53Zqt9f761490Use of a novel camelid-inspired human antibody demonstrates the importance of MMP-14 to cancer stem cell function in the metastatic processChen, Kuan-Hui EChen, ChuanLopez, TylerRadecki, Kelly CBustamante, KarissaLorenson, Mary YGe, XinWalker, Ameae M2018-06-29Matrix metalloproteinases (MMPs) are considered excellent targets for cancer therapy because of their important roles in multiple aspects of tumor growth and metastatic spread. However, not all MMPs, or even all activities of specific MMPs, promote cancer. Therefore, there is a need for highly specific inhibitors. Monoclonal antibodies provide the potential for the degree of specificity required, but the isolation of antibodies able to inhibit a specific protease with high selectivity is challenging. Proteolysis specificity lies in recognition of the substrate in or around the active site, which generally forms a concave cleft inaccessible by human IgGs. Inspired by camelid antibodies, which have convex paratopes, we have produced a recombinant human IgG, designated 3A2, which binds in the substrate cleft of MMP-14, inhibiting its activity, but not the activity of highly homologous MMPs. In the 4T1 highly metastatic, syngeneic, orthotopic model of breast cancer, IgG 3A2 markedly inhibited growth of the primary tumor, but more importantly reduced metastatic spread to the lungs and liver by 94%. Stem cells in the tumor population expressed twice as much MMP-14 mRNA as bulk tumor cells. In addition to reducing dissemination of tumor stem cells, as would be expected from inhibition of MMP-14's ability to degrade components of the extracellular matrix, IgG 3A2 also inhibited the ability of individual stem cells to proliferate and produce colonies. We conclude that it is possible to produce antibodies with sufficient specificity for development as therapeutics and that IgG 3A2 has therapeutic potential.Biomedical and Clinical SciencesOncology and CarcinogenesisImmunologyBreast CancerBiotechnologyCancerStem Cell ResearchMMP-14cancer stem cellmetastasisOncology and carcinogenesisapplication/pdfCC-BY-NCeScholarship, University of Californiahttps://escholarship.org/uc/item/9f761490articleOncotarget, vol 9, iss 5029431 - 29444oai:escholarship.org:ark:/13030/qt4693p26p2023-12-12T09:01:23Zqt4693p26pTutorial on Continuous-Time Markov ProcessesShelton, Christian RCiardo, Gianfranco2014-12-01Applied MathematicsArtificial Intelligence and Image ProcessingCognitive SciencesArtificial Intelligence & Image ProcessingArtificial intelligenceComputer vision and multimedia computationMachine learningapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4693p26particleoai:escholarship.org:ark:/13030/qt1z06s3x32023-12-12T09:00:24Zqt1z06s3x3Event Detection in Continuous Video: An Inference in Point Process ApproachQin, ZhenShelton, Christian R2017-12-01We propose a novel approach toward event detection in real-world continuous video sequences. The method: 1) is able to model arbitrary-order non-Markovian dependences in videos to mitigate local visual ambiguities; 2) conducts simultaneous event segmentation and labeling; and 3) is time-window free. The idea is to represent a video as an event stream of both high-level semantic events and low-level video observations. In training, we learn a point process model called a piecewise-constant conditional intensity model (PCIM) that is able to capture complex non-Markovian dependences in the event streams. In testing, event detection can be modeled as the inference of high-level semantic events, given low-level image observations. We develop the first inference algorithm for PCIM and show it samples exactly from the posterior distribution. We then evaluate the video event detection task on real-world video sequences. Our model not only provides competitive results on the video event segmentation and labeling task, but also provides benefits, including being interpretable and efficient.Information and Computing SciencesComputer Vision and Multimedia ComputationAgingVideo event detectionevent segmentation and labelingvideo understandingdependency modelingvideo grammarpoint processArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCognitive SciencesArtificial Intelligence & Image ProcessingComputer vision and multimedia computationGraphicsaugmented reality and gamesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1z06s3x3articleIEEE Transactions on Image Processing, vol 26, iss 125680 - 5691oai:escholarship.org:ark:/13030/qt8j34j6z92023-12-12T08:40:39Zqt8j34j6z9Quantifying sleep architecture dynamics and individual differences using big data and Bayesian networksYetton, Benjamin DMcDevitt, Elizabeth ACellini, NicolaShelton, ChristianMednick, Sara CSilvani, Alessandro2018-01-01The pattern of sleep stages across a night (sleep architecture) is influenced by biological, behavioral, and clinical variables. However, traditional measures of sleep architecture such as stage proportions, fail to capture sleep dynamics. Here we quantify the impact of individual differences on the dynamics of sleep architecture and determine which factors or set of factors best predict the next sleep stage from current stage information. We investigated the influence of age, sex, body mass index, time of day, and sleep time on static (e.g. minutes in stage, sleep efficiency) and dynamic measures of sleep architecture (e.g. transition probabilities and stage duration distributions) using a large dataset of 3202 nights from a non-clinical population. Multi-level regressions show that sex effects duration of all Non-Rapid Eye Movement (NREM) stages, and age has a curvilinear relationship for Wake After Sleep Onset (WASO) and slow wave sleep (SWS) minutes. Bayesian network modeling reveals sleep architecture depends on time of day, total sleep time, age and sex, but not BMI. Older adults, and particularly males, have shorter bouts (more fragmentation) of Stage 2, SWS, and they transition less frequently to these stages. Additionally, we showed that the next sleep stage and its duration can be optimally predicted by the prior 2 stages and age. Our results demonstrate the potential benefit of big data and Bayesian network approaches in quantifying static and dynamic architecture of normal sleep.Biomedical and Clinical SciencesCardiovascular Medicine and HaematologyPsychologySleep ResearchClinical ResearchAgingBehavioral and Social ScienceNeurosciencesBasic Behavioral and Social ScienceAge FactorsAgedBayes TheoremBody Mass IndexFemaleHumansIndividualityMaleMiddle AgedPolysomnographyProbabilityRegression AnalysisSex FactorsSleepSleep Apnea SyndromesSleep StagesTime FactorsGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8j34j6z9articlePLOS ONE, vol 13, iss 4e0194604oai:escholarship.org:ark:/13030/qt5dn3m7qz2023-12-12T08:05:48Zqt5dn3m7qzDegradation of Bioresorbable Mg–4Zn–1Sr Intramedullary Pins and Associated Biological Responses in Vitro and in VivoCipriano, Aaron FLin, JiajiaLin, AlanSallee, AmyLe, BelindaAlcaraz, Mayra Celene CortezGuan, Ren-GuoBotimer, GaryInceoğlu, SerkanLiu, Huinan2017-12-27This article reports the degradation and biological properties of as-drawn Mg-4Zn-1Sr (designated as ZSr41) and pure Mg (P-Mg) wires as bioresorbable intramedullary pins for bone repair. Specifically, their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs) and degradation in vitro, and their biological effects on peri-implant tissues and in vivo degradation in rat tibiae were studied. The as-drawn ZSr41 pins showed a significantly faster degradation than P-Mg in vitro and in vivo. The in vivo average daily degradation rates of both ZSr41 and P-Mg intramedullary pins were significantly greater than their respective in vitro degradation rates, likely because the intramedullary site of implantation is highly vascularized for removal of degradation products. Importantly, the concentrations of Mg2+, Zn2+, and Sr2+ ions in the BMSC culture in vitro and their concentrations in rat blood in vivo were all lower than their respective therapeutic dosages, i.e., in a safe range. Despite of rapid degradation with a complete resorption time of 8 weeks in vivo, the ZSr41 intramedullary pins showed a significant net bone growth because of stimulatory effects of the metallic ions released. However, proportionally released OH- ions and hydrogen gas caused adverse effects on bone marrow cells and resulted in cavities in surrounding bone. Thus, properly engineering the degradation properties of Mg-based implants is critical for harvesting the bioactivities of beneficial metallic ions, while controlling adverse reactions associated with the release of OH- ions and hydrogen gas. It is necessary to further optimize the alloy processing conditions and/or modify the surfaces, for example, applying coatings onto the surface, to reduce the degradation rate of ZSr41 wires for skeletal implant applications.EngineeringBiomedical EngineeringBioengineeringStem Cell ResearchMusculoskeletalAbsorbable ImplantsAlloysAnimalsBone Marrow CellsIonsMagnesiumRatsZincbiodegradable magnesium zinc strontium (Mg−Zn−Sr) alloybiodegradation in vitro and in vivobioresorbable intramedullary pin implant in rat tibiabone remodelingcytocompatibility and biocompatibilitymicrocomputed tomographyChemical SciencesNanoscience & NanotechnologyChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5dn3m7qzarticleACS Applied Materials & Interfaces, vol 9, iss 5144332 - 44355oai:escholarship.org:ark:/13030/qt3vr569q62023-12-12T07:56:01Zqt3vr569q6Calculated cell-specific intracellular hydrogen peroxide concentration: Relevance in cancer cell susceptibility during ascorbate therapyErudaitius, DieaniraMantooth, JacquelineHuang, AndrewSoliman, JesseDoskey, Claire MBuettner, Garry RRodgers, Victor GJ2018-05-01The high extracellular hydrogen peroxide (H2O2) concentrations generated during pharmacological ascorbate (P-AscH-) therapy has been shown to exhibit a high flux into susceptible cancer cells leading to a decrease in clonogenic survival. It is hypothesized that the intracellular H2O2 concentration for susceptibility is independent of cell type and that the variation observed in dosing is associated with differences in the cell-specific overall steady-state intracellular H2O2 concentration values. The steady-state variation in intracellular H2O2 concentration is coupled to a number of cellular specific transport and reaction factors including catalase activity and membrane permeability. Here a lumped-parameter mathematical modeling approach, assuming a catalase-dominant peroxide removal mechanism, is used to calculate intracellular H2O2 concentration for several cell lines. Experimental measurements of critical parameters pertaining to the model are obtained. The cell lines investigated are normal pancreatic cells, H6c7, the pancreatic cancer cell line, MIA PaCa-2 and the glioblastoma cell lines, LN-229, T98G, and U-87; all which vary in susceptibility. The intracellular H2O2 concentration estimates are correlated with the clonogenic surviving fraction for each cell line, in-vitro. The results showed that, despite the fact that the experimental parameters including catalase concentration and plasma membrane permeability demonstrated significant variability across cell lines, the calculated steady-state intracellular to extracellular H2O2 concentration ratio did not vary significantly across cell lines. Thus, the calculated intracellular H2O2 concentration is not unique in characterizing susceptibility. These results imply that, although intracellular H2O2 concentration plays a key role in cellular susceptibility to P-AscH- adjuvant therapy, its overall contribution in a unifying mechanism across cell types is complex.Biological SciencesBiomedical and Clinical SciencesOncology and CarcinogenesisRare DiseasesDigestive DiseasesCancerAntineoplastic AgentsAscorbic AcidCell LineTumorDrug ResistanceNeoplasmHumansHydrogen PeroxideModelsTheoreticalPharmacological ascorbate therapyHydrogen peroxidePlasma membrane permeabilityPeroxisome permeabilityCatalaseMathematical modelIntracellular hydrogen peroxide concentrationCytosolTransport properties of cellsParameter sensitivityMedicinal and Biomolecular ChemistryBiochemistry and Cell BiologyMedical Biochemistry and MetabolomicsBiochemistry & Molecular BiologyBiochemistry and cell biologyMedical biochemistry and metabolomicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3vr569q6articleoai:escholarship.org:ark:/13030/qt6kx6t4x62023-12-12T04:36:17Zqt6kx6t4x6HALWPEO'Neal, KennethBrisk, PhilipShriver, EmilyKishinevsky, Michael2017-06-18This paper presents a predictive modeling framework for GPU performance. The key innovation underlying this approach is that performance statistics collected from representative workloads running on current generation GPUs can effectively predict the performance of next-generation GPUs. This is useful when simulators are available for the next-generation device, but simulation times are exorbitant, rendering early design space exploration of microarchitectural parameters and other features infeasible. When predicting performance across three Intel GPU generations (Haswell, Broadwell, Skylake), our models achieved low out-of-sample-errors ranging from 7.45% to 8.91%, while running 30,000-45,000 times faster than cycle-Accurate simulation.EngineeringElectrical EngineeringElectronicsSensors and Digital HardwareBioengineeringGPUDirectXRender PipelinePredictive Modelingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6kx6t4x6articleoai:escholarship.org:ark:/13030/qt7tz3r3rt2023-12-12T04:36:13Zqt7tz3r3rtDiagonal Component Expansion for Flow-Layer Placement of Flow-Based Microfluidic BiochipsCrites, BrianKong, KarenBrisk, Philip2017-10-31Continuous flow-based microfluidic devices have seen a huge increase in interest because of their ability to automate and miniaturize biochemistry and biological processes, as well as their promise of creating a programmable platform for chemical and biological experimentation. The major hurdle in the adoption of these types of devices is in the design, which is largely done by hand using tools such as AutoCAD or SolidWorks, which require immense domain knowledge and are hard to scale. This paper investigates the problem of automated physical design for continuous flow-based microfluidic very large scale integration (mVLSI) biochips, starting from a netlist specification of the flow layer. After an initial planar graph embedding, vertices in the netlist are expanded into two-dimensional components, followed by fluid channel routing. A new heuristic, DIagonal Component Expansion (DICE) is introduced for the component expansion step. Compared to a baseline expansion method, DICE improves area utilization by a factor of 8.90x and reduces average fluid routing channel length by 47.4%.Fluid Mechanics and Thermal EngineeringEngineeringBiotechnologyBioengineeringmicrofluidicsplanar placementmVLSIComputer SoftwareDistributed ComputingComputer HardwareComputer Hardware & ArchitectureCommunications engineeringDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7tz3r3rtnon_textualoai:escholarship.org:ark:/13030/qt3631k30z2023-12-12T04:33:27Zqt3631k30zDesign Automation for Flow-based Microfluidic BiochipsMcDaniel, JCrites, BCurtis, CBrisk, PL2018-01-02Flow-based microfluidic biochips are presently designed, verified, and physically laid out manually. Software automation, similar to that employed for integrated circuits in the semiconductor industry, will raise productivity and reduce the cost of using biochips in scientific experiments.MicrofluidicsDesign Automationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3631k30zarticleoai:escholarship.org:ark:/13030/qt6bm273z12023-12-12T04:14:19Zqt6bm273z1Protospacer Adjacent Motif-Induced Allostery Activates CRISPR-Cas9Palermo, GiuliaRicci, Clarisse GFernando, AmendraBasak, RajshekharJinek, MartinRivalta, IvanBatista, Victor SMcCammon, J Andrew2017-11-15CRISPR-Cas9 is a genome editing technology with major impact in life sciences. In this system, the endonuclease Cas9 generates double strand breaks in DNA upon RNA-guided recognition of a complementary DNA sequence, which strictly requires the presence of a protospacer adjacent motif (PAM) next to the target site. Although PAM recognition is essential for cleavage, it is unknown whether and how PAM binding activates Cas9 for DNA cleavage at spatially distant sites. Here, we find evidence of a PAM-induced allosteric mechanism revealed by microsecond molecular dynamics simulations. PAM acts as an allosteric effector and triggers the interdependent conformational dynamics of the Cas9 catalytic domains (HNH and RuvC), responsible for concerted cleavage of the two DNA strands. Targeting such an allosteric mechanism should enable control of CRISPR-Cas9 functionality.EngineeringChemical SciencesBiotechnologyGeneticsUnderpinning research1.1 Normal biological development and functioningAllosteric RegulationCRISPR-Associated ProteinsCRISPR-Cas SystemsCatalytic DomainClustered Regularly Interspaced Short Palindromic RepeatsDNA CleavageEndonucleasesEnzyme ActivationGene EditingMolecular Dynamics SimulationGeneral ChemistryChemical sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6bm273z1articleJournal of the American Chemical Society, vol 139, iss 4516028 - 16031oai:escholarship.org:ark:/13030/qt0d94g6rs2023-12-12T01:17:34Zqt0d94g6rsSpectroscopic and Computational Investigation of Room-Temperature Decomposition of a Chemical Warfare Agent Simulant on Polycrystalline Cupric OxideTrotochaud, LenaTsyshevsky, RomanHoldren, ScottFears, KenanHead, Ashley RYu, YiKarslıoğlu, OsmanPletincx, SvenEichhorn, BryanOwrutsky, JeffreyLong, JeffreyZachariah, MichaelKuklja, Maija MBluhm, Hendrik2017-09-12Certain organophosphorus molecules are infamous due to their use as highly toxic nerve agents. The filtration materials currently in common use for protection against chemical warfare agents were designed before organophosphorus compounds were used as chemical weapons. A better understanding of the surface chemistry between simulant molecules and the individual filtration-material components is a critical precursor to the development of more effective materials for filtration, destruction, decontamination, and/or sensing of nerve agents. Here, we report on the surface adsorption and reactions of a sarin simulant molecule, dimethyl methylphosphonate (DMMP), with cupric oxide surfaces. In situ ambient pressure X-ray photoelectron and infrared spectroscopies are coupled with density functional calculations to propose mechanisms for DMMP decomposition on CuO. We find extensive room temperature decomposition of DMMP on CuO, with the majority of decomposition fragments bound to the CuO surface. We observe breaking of PO-CH3, P-OCH3, and P-CH3 bonds at room temperature. On the basis of these results, we identify specific DMMP decomposition mechanisms not seen on other metal oxides. Participation of lattice oxygen in the decomposition mechanism leads to significant changes in chemical and electronic surface environment, which are manifest in the spectroscopic and computational data. This study establishes a computational baseline for the study of highly toxic organophosphorous compounds on metal oxide surfaces.EngineeringChemical SciencesPhysical ChemistryMaterialsChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0d94g6rsarticleChemistry of Materials, vol 29, iss 177483 - 7496oai:escholarship.org:ark:/13030/qt6bv9m1h62023-12-12T00:24:51Zqt6bv9m1h6Novel Cranial Implants of Yttria‐Stabilized Zirconia as Acoustic Windows for Ultrasonic Brain TherapyGutierrez, Mario IPenilla, Elias HLeija, LorenzoVera, ArturoGaray, Javier EAguilar, Guillermo2017-11-01Therapeutic ultrasound can induce changes in tissues by means of thermal and nonthermal effects. It is proposed for treatment of some brain pathologies such as Alzheimer's, Parkinson's, Huntington's diseases, and cancer. However, cranium highly absorbs ultrasound reducing transmission efficiency. There are clinical applications of transcranial focused ultrasound and implantable ultrasound transducers proposed to address this problem. In this paper, biocompatible materials are proposed for replacing part of the cranium (cranial implants) based on low porosity polycrystalline 8 mol% yttria-stabilized-zirconia (8YSZ) ceramics as acoustic windows for brain therapy. In order to assess the viability of 8YSZ implants to effectively transmit ultrasound, various 8YSZ ceramics with different porosity are tested; their acoustic properties are measured; and the results are validated using finite element models simulating wave propagation to brain tissue through 8YSZ windows. The ultrasound attenuation is found to be linearly dependent on ceramics' porosity. Results for the nearly pore-free case indicate that 8YSZ is highly effective in transmitting ultrasound, with overall maximum transmission efficiency of ≈81%, compared to near total absorption of cranial bone. These results suggest that 8YSZ polycrystals could be suitable acoustic windows for ultrasound brain therapy at 1 MHz.EngineeringBiomedical EngineeringBiomedical ImagingBioengineeringNeurosciencesNeurologicalAnimalsBiocompatible MaterialsBrain DiseasesCattleFinite Element AnalysisMaleModelsBiologicalPorosityProstheses and ImplantsSkullUltrasonic TherapyYttriumZirconiumbiocompatible ceramicsbrain therapycranial implantsultrasoundMedicinal and Biomolecular ChemistryMedical BiotechnologyMedical biotechnologyBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6bv9m1h6articleAdvanced Healthcare Materials, vol 6, iss 211700214oai:escholarship.org:ark:/13030/qt2652p0582023-12-12T00:24:17Zqt2652p058Efficient reduction of CO2 by the molybdenum-containing formate dehydrogenase from Cupriavidus necator (Ralstonia eutropha)Yu, XuejunNiks, DimitriMulchandani, AshokHille, Russ2017-10-01The ability of the FdsABG formate dehydrogenase from Cupriavidus necator (formerly known as Ralstonia eutropha) to catalyze the reverse of the physiological reaction, the reduction of CO2 to formate utilizing NADH as electron donor, has been investigated. Contrary to previous studies of this enzyme, we demonstrate that it is in fact effective in catalyzing the reverse reaction with a kcat of 11 ± 0.4 s-1 We also quantify the stoichiometric accumulation of formic acid as the product of the reaction and demonstrate that the observed kinetic parameters for catalysis in the forward and reverse reactions are thermodynamically consistent, complying with the expected Haldane relationships. Finally, we demonstrate the reaction conditions necessary for gauging the ability of a given formate dehydrogenase or other CO2-utilizing enzyme to catalyze the reverse direction to avoid false negative results. In conjunction with our earlier studies on the reaction mechanism of this enzyme and on the basis of the present work, we conclude that all molybdenum- and tungsten-containing formate dehydrogenases and related enzymes likely operate via a simple hydride transfer mechanism and are effective in catalyzing the reversible interconversion of CO2 and formate under the appropriate experimental conditions.Biological SciencesIndustrial BiotechnologyBacterial ProteinsCarbon DioxideCatalysisCupriavidus necatorFormate DehydrogenasesKineticsMolybdenumbiofuelcarbon dioxideenzyme catalysismolybdenummultifunctional enzymeChemical SciencesMedical and Health SciencesBiochemistry & Molecular BiologyBiological sciencesBiomedical and clinical sciencesChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2652p058articleJournal of Biological Chemistry, vol 292, iss 4116872 - 16879oai:escholarship.org:ark:/13030/qt3q1706rs2023-12-11T23:15:23Zqt3q1706rsCRISPR-Cas9 conformational activation as elucidated from enhanced molecular simulationsPalermo, GiuliaMiao, YinglongWalker, Ross CJinek, MartinMcCammon, J Andrew2017-07-11CRISPR-Cas9 has become a facile genome editing technology, yet the structural and mechanistic features underlying its function are unclear. Here, we perform extensive molecular simulations in an enhanced sampling regime, using a Gaussian-accelerated molecular dynamics (GaMD) methodology, which probes displacements over hundreds of microseconds to milliseconds, to reveal the conformational dynamics of the endonuclease Cas9 during its activation toward catalysis. We disclose the conformational transition of Cas9 from its apo form to the RNA-bound form, suggesting a mechanism for RNA recruitment in which the domain relocations cause the formation of a positively charged cavity for nucleic acid binding. GaMD also reveals the conformation of a catalytically competent Cas9, which is prone for catalysis and whose experimental characterization is still limited. We show that, upon DNA binding, the conformational dynamics of the HNH domain triggers the formation of the active state, explaining how the HNH domain exerts a conformational control domain over DNA cleavage [Sternberg SH et al. (2015) Nature, 527, 110-113]. These results provide atomic-level information on the molecular mechanism of CRISPR-Cas9 that will inspire future experimental investigations aimed at fully clarifying the biophysics of this unique genome editing machinery and at developing new tools for nucleic acid manipulation based on CRISPR-Cas9.Biochemistry and Cell BiologyBiological SciencesGenetics1.1 Normal biological development and functioningUnderpinning researchGeneric health relevanceBacterial ProteinsCRISPR-Cas SystemsCrystallographyX-RayFluorescence Resonance Energy TransferGene EditingGene Expression RegulationMolecular Dynamics SimulationNormal DistributionNucleic Acid ConformationNucleic AcidsProtein DomainsProteinsRNARNAGuideKinetoplastidaStreptococcus pyogenesThermodynamicsprotein-nucleic acid interactionsgene regulationRNA dynamicsenhanced samplingfree energyprotein–nucleic acid interactionspubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3q1706rsarticleProceedings of the National Academy of Sciences of the United States of America, vol 114, iss 287260 - 7265oai:escholarship.org:ark:/13030/qt9wd146rm2023-12-11T23:11:37Zqt9wd146rmSpVM Acceleration with Latency Masking Threads on FPGAsHalstead, Robert JNajjar, Walid AHuseini, Omar2014-01-01Long memory latencies are mitigated through the use of large cache hierarchies in multi-core architectures, SIMD execution in GPU architectures and streaming of data in FPGA-based accelerators. However, none of these approaches benefits irregular applications that exhibit no locality and rely on extensive pointer de-referencing for data accesses. By masking the memory latency, multi-threaded execution has been demonstrated to deal effectively with such applications.
In the MT-FPGA model a multi-threaded engine is implemented on the FPGA accelerator specifically for the masking on the memory latency in the execution of irregular applications: following a memory access, the execution is switched to a ready thread while the suspended threads wait for the return of the requested data value from memory. The multi-threaded engine is automatically generated, from C code, by the CHAT compilation tool and is customized to the specific application.
In this paper we use the Sparse Vector Matrix application to evaluate the performance of the MT-FPGA execution and compare it to the latest GPU architectures over a wide range of benchmarks.publiceScholarship, University of Californiahttps://escholarship.org/uc/item/9wd146rmmultimediaoai:escholarship.org:ark:/13030/qt4gg465gk2023-12-11T23:11:33Zqt4gg465gkA study on parallelizing XML path filtering using acceleratorsMoussalli, RogerSalloum, MariamHalstead, RobertNajjar, WalidTsotras, Vassilis J2014-01-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4gg465gkarticleoai:escholarship.org:ark:/13030/qt89p954h82023-12-11T23:11:28Zqt89p954h8Mapping a Single Assignment Programming Language to Reconfigurable SystemsNajjar, W2017-07-05application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/89p954h8articleoai:escholarship.org:ark:/13030/qt9fx879p82023-12-11T20:28:37Zqt9fx879p8Direct expression of active human tissue inhibitors of metalloproteinases by periplasmic secretion in Escherichia coliLee, Ki BaekNam, Dong HyunNuhn, Jacob AMWang, JuanSchneider, Ian CGe, Xin2017-12-01BackgroundAs regulators of multifunctional metalloproteinases including MMP, ADAM and ADAMTS families, tissue inhibitors of metalloproteinases (TIMPs) play a pivotal role in extracellular matrix remodeling, which is involved in a wide variety of physiological processes. Since abnormal metalloproteinase activities are related to numerous diseases such as arthritis, cancer, atherosclerosis, and neurological disorders, TIMPs and their engineered mutants hold therapeutic potential and thus have been extensively studied. Traditional productions of functional TIMPs and their N-terminal inhibitory domains (N-TIMPs) rely on costly and time-consuming insect and mammalian cell systems, or tedious and inefficient refolding from denatured inclusion bodies. The later process is also associated with heterogeneous products and batch-to-batch variation.ResultsIn this study, we developed a simple approach to directly produce high yields of active TIMPs in the periplasmic space of Escherichia coli without refolding. Facilitated by disulfide isomerase (DsbC) co-expression in protease-deficient strain BL21 (DE3), N-TIMP-1/-2 and TIMP-2 which contain multiple disulfide bonds were produced without unwanted truncations. 0.2-1.4 mg purified monomeric TIMPs were typically yielded per liter of culture media. Periplasmically produced TIMPs exhibited expected inhibition potencies towards MMP-1/2/7/14, and were functional in competitive ELISA to elucidate the binding epitopes of MMP specific antibodies. In addition, prepared N-TIMPs were fully active in a cellular context, i.e. regulating cancer cell morphology and migration in 2D and 3D bioassays.ConclusionPeriplasmic expression in E. coli is an excellent strategy to recombinantly produce active TIMPs and N-TIMPs.Biochemistry and Cell BiologyBiological SciencesCloningMolecularEpitopesEscherichia coliHumansMetalloproteasesPeriplasmProtein Disulfide-IsomerasesProtein FoldingRecombinant ProteinsSolubilityTissue Inhibitor of Metalloproteinase-1Tissue Inhibitor of Metalloproteinase-2Tissue inhibitor of metalloproteinaseMatrix metalloproteinasePeriplasmic expressionDisulfide isomeraseContact guidanceMicrobiologyIndustrial BiotechnologyBiotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9fx879p8articleMicrobial Cell Factories, vol 16, iss 173oai:escholarship.org:ark:/13030/qt30t6x6jw2023-12-11T16:51:35Zqt30t6x6jwPeak Efficiency Aware Scheduling for Highly Energy Proportional ServersWong, Daniel2016-06-01Energy proportionality of data center severs have improved drastically over the past decade to the point where near ideal energy proportional servers are now common. These highly energy proportional servers exhibit the unique property where peak efficiency no longer coincides with peak utilization. In this paper, we explore the implications of this property on data center scheduling. We identified that current state of the art data center schedulers does not efficiently leverage these properties, leading to inefficient scheduling decisions. We propose Peak Efficiency Aware Scheduling (PEAS) which can achieve better-than-ideal energy proportionality at the data center level. We demonstrate that PEAS can reduce average power by 25.5% with 3.0% improvement to TCO compared to state-of-the-art scheduling policies.Distributed Computing and Systems SoftwareInformation and Computing SciencesEngineeringAffordable and Clean Energyserversenergy efficiencyschedulingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/30t6x6jwarticleoai:escholarship.org:ark:/13030/qt7rb218vr2023-12-11T15:44:48Zqt7rb218vrEnhancing Aqueous Chlorate Reduction Using Vanadium Redox Cycles and pH Control.Gao, JinyuChen, GongdeFu, QiRen, ChangxuTan, ChengWang, YinLiu, HaizhouLiu, Jinyong2023-11-17Chlorate (ClO3-) is a toxic oxyanion pollutant from industrial wastes, agricultural applications, drinking water disinfection, and wastewater treatment. Catalytic reduction of ClO3- using palladium (Pd) nanoparticle catalysts exhibited sluggish kinetics. This work demonstrates an 18-fold activity enhancement by integrating earth-abundant vanadium (V) into the common Pd/C catalyst. X-ray photoelectron spectroscopy and electrochemical studies indicated that VV and VIV precursors are reduced to VIII in the aqueous phase (rather than immobilized on the carbon support) by Pd-activated H2. The VIII/IV redox cycle is the predominant mechanism for the ClO3- reduction. Further reduction of chlorine intermediates to Cl- could proceed via VIII/IV and VIV/V redox cycles or direct reduction by Pd/C. To capture the potentially toxic V metal from the treated solution, we adjusted the pH from 3 to 8 after the reaction, which completely immobilized VIII onto Pd/C for catalyst recycling. The enhanced performance of reductive catalysis using a Group 5 metal adds to the diversity of transition metals (e.g., Cr, Mo, Re, Fe, and Ru in Groups 6-8) for water pollutant treatment via various unique mechanisms.X-ray photoelectron spectroscopy (XPS)catalystchlorateelectrochemical studypalladiumrecycleredoxvanadiumapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7rb218vrarticleoai:escholarship.org:ark:/13030/qt1mr7d9sv2023-12-11T13:55:10Zqt1mr7d9svActive-site MMP-selective antibody inhibitors discovered from convex paratope synthetic librariesNam, Dong HyunRodriguez, CarlosRemacle, Albert GStrongin, Alex YGe, Xin2016-12-27Proteases are frequent pharmacological targets, and their inhibitors are valuable drugs in multiple pathologies. The catalytic mechanism and the active-site fold, however, are largely conserved among the protease classes, making the development of the selective inhibitors exceedingly challenging. In our departure from the conventional strategies, we reviewed the structure of known camelid inhibitory antibodies, which block enzyme activities via their unusually long, convex-shaped paratopes. We synthesized the human Fab antibody library (over 1.25 × 109 individual variants) that carried the extended, 23- to 27-residue, complementarity-determining region (CDR)-H3 segments. As a proof of principle, we used the catalytic domain of matrix metalloproteinase-14 (MMP-14), a promalignant protease and a drug target in cancer, as bait. In our screens, we identified 20 binders, of which 14 performed as potent and selective inhibitors of MMP-14 rather than as broad-specificity antagonists. Specifically, Fab 3A2 bound to MMP-14 in the vicinity of the active pocket with a high 4.8 nM affinity and was similarly efficient (9.7 nM) in inhibiting the protease cleavage activity. We suggest that the convex paratope antibody libraries described here could be readily generalized to facilitate the design of the antibody inhibitors to many additional enzymes.Biochemistry and Cell BiologyBiological SciencesBiotechnologyPreventionCancer5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsAmino Acid MotifsAnimalsAntibodiesBinding SitesAntibodyCamelusCatalytic DomainComplementarity Determining RegionsEscherichia coliHumansImmunoglobulin Fab FragmentsInhibitory Concentration 50Matrix Metalloproteinase 14Matrix Metalloproteinase InhibitorsMiceMolecular ConformationPeptide LibrarySurface Plasmon Resonanceinhibitory antibodylong CDRsynthetic libraryconvex paratopeMMPapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1mr7d9svarticleProceedings of the National Academy of Sciences of the United States of America, vol 113, iss 5214970 - 14975oai:escholarship.org:ark:/13030/qt70t398kc2023-12-11T12:53:29Zqt70t398kcSelective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasisRemacle, Albert GCieplak, PiotrNam, Dong HyunShiryaev, Sergey AGe, XinStrongin, Alex Y2017-01-10The invasion-promoting MT1-MMP is a cell surface-associated collagenase with a plethora of critical cellular functions. There is a consensus that MT1-MMP is a key protease in aberrant pericellular proteolysis in migrating cancer cells and, accordingly, a promising drug target. Because of high homology in the MMP family and a limited success in the design of selective small-molecule inhibitors, it became evident that the inhibitor specificity is required for selective and successful MT1-MMP therapies. Using the human Fab antibody library (over 1.25×109 individual variants) that exhibited the extended, 23-27 residue long, VH CDR-H3 segments, we isolated a panel of the inhibitory antibody fragments, from which the 3A2 Fab outperformed others as a specific and potent, low nanomolar range, inhibitor of MT1-MMP. Here, we report the in-depth characterization of the 3A2 antibody. Our multiple in vitro and cell-based tests and assays, and extensive structural modeling of the antibody/protease interactions suggest that the antibody epitope involves the residues proximal to the protease catalytic site and that, in contrast with tissue inhibitor-2 of MMPs (TIMP-2), the 3A2 Fab inactivates the protease functionality by binding to the catalytic domain outside the active site cavity. In agreement with the studies in metastasis by others, our animal studies in acute pulmonary melanoma metastasis support a key role of MT1-MMP in metastatic process. Conversely, the selective anti-MT1-MMP monotherapy significantly alleviated melanoma metastatic burden. It is likely that further affinity maturation of the 3A2 Fab will result in the lead inhibitor and a proof-of-concept for MT1-MMP targeting in metastatic cancers.Biomedical and Clinical SciencesOncology and CarcinogenesisCancerBiotechnology2.1 Biological and endogenous factorsAetiologyAnimalsAntibodiesBlockingAntineoplastic AgentsImmunologicalBindingCompetitiveCatalytic DomainCell LineTumorCell MovementCell SurvivalCollagenDisease ModelsAnimalEnzyme ActivationFemaleHeterograftsHumansImmunoglobulin Fab FragmentsMatrix Metalloproteinase 14Matrix Metalloproteinase InhibitorsMiceModelsMolecularMolecular ConformationNeoplasm MetastasisNeoplasm StagingNeoplasmsProtein BindingProteolysisRecombinant ProteinsmetastasiscancerMT1-MMPantibodyproteinaseOncology and carcinogenesisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/70t398kcarticleOncotarget, vol 5, iss 02781 - 2799oai:escholarship.org:ark:/13030/qt3275352n2023-12-11T12:43:05Zqt3275352nStriking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular SimulationsPalermo, GiuliaMiao, YinglongWalker, Ross CJinek, MartinMcCammon, J Andrew2016-10-26The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.Chemical SciencesBiotechnologyGeneticsAetiologyUnderpinning research1.1 Normal biological development and functioning2.1 Biological and endogenous factorsChemical sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3275352narticleACS Central Science, vol 2, iss 10756 - 763oai:escholarship.org:ark:/13030/qt23v581622023-12-11T12:33:02Zqt23v58162Optimizing Hardware Design for Human Action RecognitionMa, XiaoyinBorbon, Jose RodriguezNajjar, WalidRoy-Chowdhury, Amit KIenne, PaoloNajjar, Walid AAnderson, Jason HelgeBrisk, PhilipStechele, Walter2016-08-01Human action recognition (HAR) is an important topic in computer vision having a wide range of applications: health care, assisted living, surveillance, security, gaming, etc. Despite significant amount of work having been conducted in this area in recent years, the execution speed still limits real-time applications. Moreover, it is highly desirable to have the compute-intensive feature extraction stage done right at the output of the camera to extract and transfer only action feature in multi-camera network setting and hence reduce network bandwidth requirement. In this work, we first evaluate the possibility to perform feature extraction under reduced precision fixed-point arithmetic to ease hardware resource requirements. We compared the Histogram of Oriented Gradient in 3D (HOG3D) feature extraction with state-of-the-art Convolutional Neural Networks (CNNs) methods and shown the later to be 75× slower than the former. Our experiment shows that by re-training the classifier with reduced data precision, the classification performs as well as the original double-precision floating-point. Based on this result, we implement an FPGA-based HAR feature extraction for near camera processing using fixed-point data representation and arithmetic. This implementation, using a single Xilinx Virtex 6 FPGA, achieves about 70× speedup over multicore CPU. Furthermore, a GPU implementation of HAR is introduced with 80× speedup over CPU (on an Nvidia Tesla K20). Last but not least, a power comparison is presented for the three platforms.Data Management and Data ScienceInformation and Computing SciencesComputer Vision and Multimedia Computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/23v58162articleoai:escholarship.org:ark:/13030/qt8636h7rp2023-12-11T12:32:58Zqt8636h7rpFPGA-accelerated group-by aggregation using synchronizing cachesAbsalyamov, IldarBudhkar, PrernaWindh, SkylerHalstead, Robert JNajjar, Walid ATsotras, Vassilis J2016-06-26Recent trends in hardware have dramatically dropped the price of RAM and shifted focus from systems operating on disk-resident data to in-memory solutions. In this environment high memory access latency, also known as memory wall, becomes the biggest data processing bottleneck. Traditional CPU-based architectures solved this problem by introducing large cache hierarchies. However algorithms which experience poor locality can limit the benefits of caching. In turn, hardware multithreading provides a generic solution that does not rely on algorithm-specific locality properties. In this paper we present an FPGA-accelerated implementation of in-memory group-by hash aggregation. Our design relies on hardware multithreading to efficiently mask long memory access latency by implementing a custom operation datapath on FPGA. We propose using CAMs (Content Addressable Memories) as a mechanism of synchronization and local pre-aggregation. To the best of our knowledge this is the first work, which uses CAMs as a synchronizing cache. We evaluate aggregation throughput against the state-of-the-art multithreaded software implementations and demonstrate that the FPGA-accelerated approach significantly outperforms them on large grouping key cardinalities and yields speedup up to 10x.Built Environment and DesignEngineeringInformation and Computing SciencesElectronicsSensors and Digital HardwareArchitectureapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8636h7rparticleoai:escholarship.org:ark:/13030/qt0zv2w7272023-12-11T10:48:48Zqt0zv2w727Architecture and Design Automation for Application-Specific ProcessorsBrisk, Philip2011-10-01Application-specific instruction-set processors (ASIPs) are specialized to meet the performance and energy needs of individual or small sets of applications. Of particular importance is the inclusion of custom instruction set extensions (ISEs) that accelerate the performance of the applications from which they are derived. This manuscript reviews the architectural features of ASIPs that facilitate high performance and low energy consumption, and provides an overview of compiler algorithms to automatically identify and synthesize ISEs from an application specified using a high-level language. © 2011 IEEE.Built Environment and DesignArchitectureAffordable and Clean EnergypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0zv2w727articleoai:escholarship.org:ark:/13030/qt5j56d5wt2023-12-11T10:48:45Zqt5j56d5wtAutomatic Synthesis of Microfluidic Large Scale Integration Chips from a Domain-Specific LanguageMcDaniel, JeffreyCurtis, ChristopherBrisk, Philip2013-10-01BioCoder is a domain-specific language by which chemists and biologists can express experimental protocols in a manner that is unambiguous and clearly repeatable. This paper presents a software toolchain that converts a protocol specified in a restricted subset of BioCoder to a technology-specific description of the protocol, targeting flow-based microfluidic large-scale integration (mLSI) chips. The technology-specific description can then be used to either: (1) execute the protocol on a capable chip; or (2) to derive the architecture of a new mLSI chip that can execute the protocol. © 2013 IEEE.Information and Computing SciencesSoftware EngineeringBioengineeringBiotechnologymicrofluidic Large Scale Integrationdomain-specific languagepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5j56d5wtarticleoai:escholarship.org:ark:/13030/qt3dq0d3xc2023-12-11T10:48:41Zqt3dq0d3xcPerformance and Cost Analysis of NoC-Inspired Virtual Topologies for Digital Microfluidic BiochipsGrissom, DanielMcDaniel, JeffreyBrisk, Philip2014-12-01Virtual topologies simply the process of compiling assays to execute on digital microfluidic biochips (DMFBs). This paper evaluates the performance and cost of a virtual topology inspired by networks-on-chip (NoCs). The throughput of several deadlock-free droplet routing protocols is compared on synthetic traffic patterns that are widely used to evaluate semiconductor NoCs. The cost is the number of control pins required for actuation and the number of PCB layers required to route the chip; by eliminating unused pins, the virtual topology is cheaper than a direct-addressing DMFB, especially as chip size increases.Built Environment and DesignEngineeringElectrical EngineeringElectronicsSensors and Digital HardwareArchitectureBiotechnologyDigital Microfluidic BiochipVirtual TopologyNetwork-on-ChipDroplet RoutingDeadlockpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3dq0d3xcarticleoai:escholarship.org:ark:/13030/qt4pq2c73z2023-12-11T10:48:37Zqt4pq2c73zDesign Automation for Flow-based Microfluidic BiochipsMcDaniel, JCrites, BCurtis, CBrisk, PL2016-09-24publiceScholarship, University of Californiahttps://escholarship.org/uc/item/4pq2c73zarticleoai:escholarship.org:ark:/13030/qt8q63m69f2023-12-11T09:20:29Zqt8q63m69fSharing and community curation of mass spectrometry data with Global Natural Products Social Molecular NetworkingWang, MingxunCarver, Jeremy JPhelan, Vanessa VSanchez, Laura MGarg, NehaPeng, YaoNguyen, Don DuyWatrous, JeramieKapono, Clifford ALuzzatto-Knaan, TalPorto, CarlaBouslimani, AminaMelnik, Alexey VMeehan, Michael JLiu, Wei-TingCrüsemann, MaxBoudreau, Paul DEsquenazi, EduardoSandoval-Calderón, MarioKersten, Roland DPace, Laura AQuinn, Robert ADuncan, Katherine RHsu, Cheng-ChihFloros, Dimitrios JGavilan, Ronnie GKleigrewe, KarinNorthen, TrentDutton, Rachel JParrot, DelphineCarlson, Erin EAigle, BertrandMichelsen, Charlotte FJelsbak, LarsSohlenkamp, ChristianPevzner, PavelEdlund, AnnaMcLean, JeffreyPiel, JörnMurphy, Brian TGerwick, LenaLiaw, Chih-ChuangYang, Yu-LiangHumpf, Hans-UlrichMaansson, MariaKeyzers, Robert ASims, Amy CJohnson, Andrew RSidebottom, Ashley MSedio, Brian EKlitgaard, AndreasLarson, Charles BBoya P, Cristopher ATorres-Mendoza, DanielGonzalez, David JSilva, Denise BMarques, Lucas MDemarque, Daniel PPociute, EgleO'Neill, Ellis CBriand, EnoraHelfrich, Eric JNGranatosky, Eve AGlukhov, EvgeniaRyffel, FlorianHouson, HaileyMohimani, HoseinKharbush, Jenan JZeng, YiVorholt, Julia AKurita, Kenji LCharusanti, PepMcPhail, Kerry LNielsen, Kristian FogVuong, LisaElfeki, MaryamTraxler, Matthew FEngene, NiclasKoyama, NobuhiroVining, Oliver BBaric, RalphSilva, Ricardo RMascuch, Samantha JTomasi, SophieJenkins, StefanMacherla, VenkatHoffman, ThomasAgarwal, VinayakWilliams, Philip GDai, JingquiNeupane, RamGurr, JoshuaRodríguez, Andrés MCLamsa, AnneZhang, ChenDorrestein, KathleenDuggan, Brendan MAlmaliti, JehadAllard, Pierre-MariePhapale, Prasad2016-08-01The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data.Analytical ChemistryChemical SciencesGeneric health relevanceBiological ProductsData CurationDatabase Management SystemsDatabasesChemicalInformation DisseminationInformation Storage and RetrievalInternationalityMass Spectrometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8q63m69farticleNature Biotechnology, vol 34, iss 8828 - 837oai:escholarship.org:ark:/13030/qt3005f53k2023-12-11T08:41:50Zqt3005f53kSynthesis of strontium ferrite/iron oxide exchange coupled nano-powders with improved energy product for rare earth free permanent magnet applicationsVolodchenkov, ADKodera, YGaray, JE2016-01-01We present a simple, scalable synthesis route for producing exchange coupled soft/hard magnetic composite powder that outperforms pure soft and hard phase constituents.EngineeringMaterials EngineeringChemical SciencesMacromolecular and Materials ChemistryPhysical Chemistry (incl. Structural)Macromolecular and materials chemistryPhysical chemistryMaterials engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3005f53karticleJournal of Materials Chemistry C, vol 4, iss 245593 - 5601oai:escholarship.org:ark:/13030/qt8r4783rw2023-12-11T08:39:42Zqt8r4783rwEvaluation of laser bacterial anti‐fouling of transparent nanocrystalline yttria‐stabilized‐zirconia cranial implantDamestani, YasamanDe Howitt, NatalieHalaney, David LGaray, Javier EAguilar, Guillermo2016-10-01Background and objectiveThe development and feasibility of a novel nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant has been recently established. The purpose of what we now call "window to the brain (WttB)" implant (or platform), is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically recurring basis without the need for repeated craniotomies. WttB holds the transformative potential for enhancing light-based diagnosis and treatment of a wide variety of brain pathologies including cerebral edema, traumatic brain injury, stroke, glioma, and neurodegenerative diseases. However, bacterial adhesion to the cranial implant is the leading factor for biofilm formation (fouling), infection, and treatment failure. Escherichia coli (E. coli), in particular, is the most common isolate in gram-negative bacillary meningitis after cranial surgery or trauma. The transparency of our WttB implant may provide a unique opportunity for non-invasive treatment of bacterial infection under the implant using medical lasers.Study design/materials and methodsA drop of a diluted overnight culture of BL21-293 E. coli expressing luciferase was seeded between the nc-YSZ implant and the agar plate. This was followed by immediate irradiation with selected laser. After each laser treatment the nc-YSZ was removed, and cultures were incubated for 24 hours at 37 °C. The study examined continuous wave (CW) and pulsed wave (PW) modes of near-infrared (NIR) 810 nm laser wavelength with a power output ranging from 1 to 3 W. During irradiation, the temperature distribution of nc-YSZ surface was monitored using an infrared thermal camera. Relative luminescence unit (RLU) was used to evaluate the viability of bacteria after the NIR laser treatment.ResultsAnalysis of RLU suggests that the viability of E. coli biofilm formation was reduced with NIR laser treatment when compared to the control group (P < 0.01) and loss of viability depends on both laser fluence and operation mode (CW or PW). The results demonstrate that while CW laser reduces the biofilm formation more than PW laser with the same power, the higher surface temperature of the implant generated by CW laser limits its medical efficacy. In contrast, with the right parameters, PW laser produces a more moderate photothermal effect which can be equally effective at controlling bacterial growth.ConclusionsOur results show that E. coli biofilm formation across the thickness of the nc-YSZ implant can be disrupted using NIR laser treatment. The results of this in vitro study suggest that using nc-YSZ as a cranial implant in vivo may also allow for locally selective, non-invasive, chronic treatment of bacterial layers (fouling) that might form under cranial implants, without causing adverse thermal damage to the underlying host tissue when appropriate laser parameters are used. Lasers Surg. Med. 48:782-789, 2016. © 2016 Wiley Periodicals, Inc.Biomedical and Clinical SciencesDentistryBrain Disorders5.3 Medical devicesDevelopment of treatments and therapeutic interventionsInfectionBiofilmsEscherichia coliLasersNanoparticlesNeurosurgical ProceduresProstheses and ImplantsYttriumZirconiumwindows to the braintransparent cranial implantbiofilm laser therapybioluminescent bacteriafouling controlClinical SciencesDermatology & Venereal DiseasesClinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8r4783rwarticleLasers in Surgery and Medicine, vol 48, iss 8782 - 789oai:escholarship.org:ark:/13030/qt9c04r88f2023-12-11T04:07:46Zqt9c04r88fEvaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video BioinformaticsZahedi, AtenaOn, VincentLin, Sabrina CBays, Brett COmaiye, EstherBhanu, BirTalbot, PrueRajasingh, Johnson2016-01-01There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells.Medical BiotechnologyBiomedical and Clinical SciencesRegenerative MedicineStem Cell Research - Embryonic - HumanStem Cell ResearchBioengineeringGeneric health relevanceBiomarkersCell Culture TechniquesComputational BiologyData MiningEmbryonic Stem CellsHumansPluripotent Stem CellsSoftwareVideo RecordingGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9c04r88farticlePLOS ONE, vol 11, iss 2e0148642oai:escholarship.org:ark:/13030/qt8n4793ct2023-12-11T02:32:32Zqt8n4793ctInterpretation of negative second virial coefficients from non-attractive protein solution osmotic pressure data: An alternate perspectiveMcBride, Devin WRodgers, VGJ2013-12-01A negative second virial coefficient has long been a predictor of potential protein crystallization and salting out. However, the assumption that this is due to attractive solute-solute interactions remains a source of debate. Here we reexamine the second virial coefficient from protein osmometry in terms of the free-solvent model. The free-solvent model has been shown to provide excellent predictions of the osmotic pressure of concentrated and crowded environments for aqueous protein solutions in moderate ionic strengths. The free-solvent model relies on two critical parameters, hydration and ion binding, both which can be determined independently of osmotic pressure data. Herein, the free-solvent model is mathematically represented as a virial expansion model and the second virial coefficient is expressed in terms of solute-solvent interactions, namely hydration and ion binding. Hydration and ion binding values are then used to estimate the second virial coefficient at various protein concentrations for three model proteins ovalbumin (OVA), bovine serum albumin (BSA), and hen egg lysozyme (HEL) in various monovalent salt aqueous solutions. The results show that the conditions for obtaining a negative second virial coefficient emerge when the ionic strength of the influenced region of the protein is higher than that of the bulk. This analysis suggests a plausible explanation as to why proteins are more favorable for salting out or crystallization when the solution is represented by a negative second virial coefficient.Chemical SciencesTheoretical and Computational ChemistryBioengineeringAnimalsCattleChickensMuramidaseOsmolar ConcentrationOsmotic PressureOvalbuminSaltsSerum AlbuminBovineSolutionsSecond virial coefficientProtein osmotic pressureBovine serum albuminFree-solvent modelSolute-solute interactionSolute-solvent interactionSolute–solute interactionSolute–solvent interactionPhysical SciencesBiological SciencesBiophysicsBiological sciencesChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8n4793ctarticleoai:escholarship.org:ark:/13030/qt00r7p4362023-12-11T01:56:04Zqt00r7p436Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and PhenotypeLuu, Thuy UGott, Shannon CWoo, Bryan WKRao, Masaru PLiu, Wendy F2015-12-30Controlling the interactions between macrophages and biomaterials is critical for modulating the response to implants. While it has long been thought that biomaterial surface chemistry regulates the immune response, recent studies have suggested that material geometry may in fact dominate. Our previous work demonstrated that elongation of macrophages regulates their polarization toward a pro-healing phenotype. In this work, we elucidate how surface topology might be leveraged to alter macrophage cell morphology and polarization state. Using a deep etch technique, we fabricated titanium surfaces containing micro- and nanopatterned grooves, which have been previously shown to promote cell elongation. Morphology, phenotypic markers, and cytokine secretion of murine bone marrow derived macrophages on different groove widths were analyzed. The results suggest that micro- and nanopatterned grooves influenced macrophage elongation, which peaked on substrates with 400-500 nm wide grooves. Surface grooves did not affect inflammatory activation but drove macrophages toward an anti-inflammatory, pro-healing phenotype. While secretion of TNF-alpha remained low in macrophages across all conditions, macrophages secreted significantly higher levels of anti-inflammatory cytokine, IL-10, on intermediate groove widths compared to cells on other Ti surfaces. Our findings highlight the potential of using surface topography to regulate macrophage function, and thus control the wound healing and tissue repair response to biomaterials.EngineeringBiomedical EngineeringBiotechnologyInflammatory and immune systemAnimalsBiomarkersCell ShapeCellsCulturedCytokinesMacrophagesMiceMiceInbred C57BLPhenotypeSurface Propertiesbiocompatibilitygroovemacrophage polarizationtitaniumtopographyChemical SciencesNanoscience & NanotechnologyChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/00r7p436articleACS Applied Materials & Interfaces, vol 7, iss 5128665 - 28672oai:escholarship.org:ark:/13030/qt5mh241cr2023-12-11T01:56:00Zqt5mh241crGraphene hybrids: synthesis strategies and applications in sensors and sensitized solar cellsBadhulika, SushmeeTerse-Thakoor, TruptiVillarreal, ClaudiaMulchandani, Ashok2015-01-01Graphene exhibits unique 2-D structural, chemical, and electronic properties that lead to its many potential applications. In order to expand the scope of its usage, graphene hybrids which combine the synergetic properties of graphene along with metals/metal oxides and other nanostructured materials have been synthesized and are a widely emerging field of research. This review presents an overview of the recent progress made in the field of graphene hybrid architectures with a focus on the synthesis of graphene-carbon nanotube (G-CNT), graphene-semiconductor nanomaterial (G-SNM), and graphene-metal nanomaterial (G-MNM) hybrids. It attempts to identify the bottlenecks involved and outlines future directions for development and comprehensively summarizes their applications in the field of sensing and sensitized solar cells.Chemical Sciencesgraphene hybridsgraphene-CNTsgraphene-QDssensorsenergy conversionChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5mh241crarticleoai:escholarship.org:ark:/13030/qt1bw673522023-12-11T01:37:48Zqt1bw67352Hybrid flagellin as a T cell independent vaccine scaffoldBennett, Kaila MGorham, Ronald DGusti, VeronicaTrinh, LienMorikis, DimitriosLo, David D2015-12-01BackgroundTo extend the potency of vaccines against infectious diseases, vaccines should be able to exploit multiple arms of the immune system. One component of the immune system that is under-used in vaccine design is the subset of B cells known to be capable of responding to repetitive antigenic epitopes and differentiate into plasma cells even in the absence of T cell help (T-independent, TI).ResultsTo target vaccine responses from T-independent B cells, we reengineered a bacterial Flagellin (FliC) by replacing its exposed D3 domain with a viral envelope protein from Dengue virus (DENV2). The resulting hybrid FliC protein (hFliC) was able to form stable filaments decorated with conformationally intact DENV2 envelope domains. These filaments were not only capable of inducing a T cell-dependent (TD) humoral antibody response, but also significant IgM and IgG3 antibody response in a helper T cell repertoire-restricted transgenic mouse model.ConclusionsOur results provide proof-of-principle demonstration that a reengineered hybrid FliC could be used as a platform for polymeric subunit vaccines, enhancing T cell-dependent and possibly inducing T-independent antibody responses from B-1 B cells as well.Biological SciencesVaccine RelatedBiotechnologyEmerging Infectious DiseasesImmunizationInfectious DiseasesBiodefensePreventionVaccine Related (AIDS)2.1 Biological and endogenous factorsAetiologyPrevention of disease and conditionsand promotion of well-being3.4 VaccinesInfectionGood Health and Well BeingAnimalsB-LymphocytesEpitopesFlagellinImmunoglobulin GImmunoglobulin MMiceProtein EngineeringSalmonella entericaT-LymphocytesVaccinesViral Envelope ProteinsTechnologyBiological sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1bw67352articleBMC Biotechnology, vol 15, iss 171oai:escholarship.org:ark:/13030/qt07g817kw2023-12-11T01:37:15Zqt07g817kwExtraction of Blebs in Human Embryonic Stem Cell VideosGuan, Benjamin XBhanu, BirTalbot, PrueWeng, Nikki Jo-Hao2016-01-01Blebbing is an important biological indicator in determining the health of human embryonic stem cells (hESC). Especially, areas of a bleb sequence in a video are often used to distinguish two cell blebbing behaviors in hESC: dynamic and apoptotic blebbings. This paper analyzes various segmentation methods for bleb extraction in hESC videos and introduces a bio-inspired score function to improve the performance in bleb extraction. Full bleb formation consists of bleb expansion and retraction. Blebs change their size and image properties dynamically in both processes and between frames. Therefore, adaptive parameters are needed for each segmentation method. A score function derived from the change of bleb area and orientation between consecutive frames is proposed which provides adaptive parameters for bleb extraction in videos. In comparison to manual analysis, the proposed method provides an automated fast and accurate approach for bleb sequence extraction.Information and Computing SciencesComputer Vision and Multimedia ComputationStem Cell Research - Embryonic - HumanStem Cell ResearchBiotechnologyRegenerative MedicineNetworking and Information Technology R&D (NITRD)Generic health relevanceAlgorithmsComputational BiologyHuman Embryonic Stem CellsHumansImage ProcessingComputer-AssistedMicroscopyVideoBleb extractionbioinformaticsbio-inspiredhuman embryonic stem cellMathematical SciencesBiological SciencesBioinformaticsBiological sciencesInformation and computing sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/07g817kwarticleIEEE/ACM Transactions on Computational Biology and Bioinformatics, vol 13, iss 4678 - 688oai:escholarship.org:ark:/13030/qt4c37k5nt2023-12-11T01:36:59Zqt4c37k5ntBoosting XML filtering with a scalable FPGA-based architectureMitra, AVieira, MRBakalov, PNajjar, WTsotras, VJ2009-12-01The growing amount of XML encoded data exchanged over the Internet increases the importance of XML based publish-subscribe (pub-sub) and content based routing systems. The input in such systems typically consists of a stream of XML documents and a set of user subscriptions expressed as XML queries. The pub-sub system then filters the published documents and passes them to the subscribers. Pub-sub systems are characterized by very high input ratios, therefore the processing time is critical. In this paper we propose a "pure hardware" based solution, which utilizes XPath query blocks on FPGA to solve the filtering problem. By utilizing the high throughput that an FPGA provides for parallel processing, our approach achieves drastically better throughput than the existing software or mixed (hardware/software) architectures. The XPath queries (subscriptions) are translated to regular expressions which are then mapped to FPGA devices. By introducing stacks within the FPGA we are able to express and process a wide range of path queries very efficiently, on a scalable environment. Moreover, the fact that the parser and the filter processing are performed on the same FPGA chip, eliminates expensive communication costs (that a multi-core system would need) thus enabling very fast and efficient pipelining. Our experimental evaluation reveals more than one order of magnitude improvement compared to traditional pub/sub systems.cs.ARcs.DBapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4c37k5ntarticleoai:escholarship.org:ark:/13030/qt45g314g42023-12-11T01:35:53Zqt45g314g4Background suppressing Gabor energy filteringCruz, Albert CBhanu, BirThakoor, Ninad S2015-01-01In the field of facial emotion recognition, early research advanced with the use of Gabor filters. However, these filters lack generalization and result in undesirably large feature vector size. In recent work, more attention has been given to other local appearance features. Two desired characteristics in a facial appearance feature are generalization capability, and the compactness of representation. In this paper, we propose a novel texture feature inspired by Gabor energy filters, called background suppressing Gabor energy filtering. The feature has a generalization component that removes background texture. It has a reduced feature vector size due to maximal representation and soft orientation histograms, and it is awhite box representation. We demonstrate improved performance on the non-trivial Audio/Visual Emotion Challenge 2012 grand-challenge dataset by a factor of 7.17 over the Gabor filter on the development set. We also demonstrate applicability of our approach beyond facial emotion recognition which yields improved classification rate over the Gabor filter for four bioimaging datasets by an average of 8.22%.Information and Computing SciencesGraphicsAugmented Reality and GamesHuman-Centred ComputingGabor filterBackground textureFacial emotion recognitionBioimagingArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCognitive SciencesArtificial Intelligence & Image ProcessingInformation and computing sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/45g314g4articleoai:escholarship.org:ark:/13030/qt27t2m6r82023-12-11T01:35:49Zqt27t2m6r8Visual and Contextual Modeling for the Detection of Repeated Mild Traumatic Brain InjuryBianchi, AnthonyBhanu, BirDonovan, VirginiaObenaus, Andre2014-01-01Currently, there is a lack of computational methods for the evaluation of mild traumatic brain injury (mTBI) from magnetic resonance imaging (MRI). Further, the development of automated analyses has been hindered by the subtle nature of mTBI abnormalities, which appear as low contrast MR regions. This paper proposes an approach that is able to detect mTBI lesions by combining both the high-level context and low-level visual information. The contextual model estimates the progression of the disease using subject information, such as the time since injury and the knowledge about the location of mTBI. The visual model utilizes texture features in MRI along with a probabilistic support vector machine to maximize the discrimination in unimodal MR images. These two models are fused to obtain a final estimate of the locations of the mTBI lesion. The models are tested using a novel rodent model of repeated mTBI dataset. The experimental results demonstrate that the fusion of both contextual and visual textural features outperforms other state-of-the-art approaches. Clinically, our approach has the potential to benefit both clinicians by speeding diagnosis and patients by improving clinical care.Information and Computing SciencesEngineeringBiomedical EngineeringNeurosciencesPhysical Injury - Accidents and Adverse EffectsTraumatic Brain Injury (TBI)Biomedical ImagingBehavioral and Social ScienceEye Disease and Disorders of VisionClinical ResearchBasic Behavioral and Social ScienceBrain DisordersTraumatic Head and Spine InjuryBioengineering4.2 Evaluation of markers and technologiesDetectionscreening and diagnosis4.1 Discovery and preclinical testing of markers and technologiesNeurologicalAlgorithmsAnimalsBrain InjuriesComputer SimulationHumansImage EnhancementImage InterpretationComputer-AssistedMagnetic Resonance ImagingModelsNeurologicalModelsStatisticalPattern RecognitionAutomatedRatsRecurrenceReproducibility of ResultsSensitivity and SpecificitySubtraction TechniqueBrain injurycontextual modelingmagnetic resonance imagingtextural modelingNuclear Medicine & Medical ImagingInformation and computing sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/27t2m6r8articleIEEE Transactions on Medical Imaging, vol 33, iss 111 - 22oai:escholarship.org:ark:/13030/qt0th8v0p92023-12-10T23:43:59Zqt0th8v0p9Transparent nanocrystalline yttria-stabilized-zirconia calvarium prosthesisDamestani, YasamanReynolds, Carissa LSzu, JennyHsu, Mike SKodera, YasuhiroBinder, Devin KPark, B HyleGaray, Javier ERao, Masaru PAguilar, Guillermo2013-11-01Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of cranial bone (calvaria) limits the spatial resolution and interaction depth that can be achieved, thus constraining opportunity in this regard. Herein, we report preliminary results from efforts seeking to address this limitation through use of novel transparent cranial implants made from nanocrystalline yttria-stabilized zirconia (nc-YSZ). Using optical coherence tomography (OCT) imaging of underlying brain in an acute murine model, we show that signal strength is improved when imaging through nc-YSZ implants relative to native cranium. As such, this provides initial evidence supporting the feasibility of nc-YSZ as a transparent cranial implant material. Furthermore, it represents a crucial first step towards realization of an innovative new concept we are developing, which seeks to eventually provide a clinically-viable means for optically accessing the brain, on-demand, over large areas, and on a chronically-recurring basis, without need for repeated craniectomies.From the clinical editorIn this study, transparent nanocrystalline yttria-stabilized-zirconia is used as an experimental "cranium prosthesis" material, enabling the replacement of segments of cranial bone with a material that allows for optical access to the brain on a recurrent basis using optical imaging methods such as OCT.Biological SciencesChemical SciencesBioengineeringBiomedical ImagingNeurosciencesAnimalsBone SubstitutesLightMiceNanoparticlesOptical ImagingProstheses and ImplantsSkullYttriumZirconiumOptical neuroimagingCalvarial prosthesisTechnologyNanoscience & NanotechnologyBiological sciencesChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0th8v0p9articleNanomedicine Nanotechnology Biology and Medicine, vol 9, iss 81135 - 1138oai:escholarship.org:ark:/13030/qt2fk1d2kq2023-12-10T23:43:43Zqt2fk1d2kqGenome-wide Mapping of DNA Methylation in the Human Malaria Parasite Plasmodium falciparumPonts, NadiaFu, LijuanHarris, Elena YZhang, JingChung, Duk-Won DCervantes, Michael CPrudhomme, JacquesAtanasova-Penichon, VesselaZehraoui, EnricBunnik, Evelien MRodrigues, Elisandra MLonardi, StefanoHicks, Glenn RWang, YinshengLe Roch, Karine G2013-12-01Cytosine DNA methylation is an epigenetic mark in most eukaryotic cells that regulates numerous processes, including gene expression and stress responses. We performed a genome-wide analysis of DNA methylation in the human malaria parasite Plasmodium falciparum. We mapped the positions of methylated cytosines and identified a single functional DNA methyltransferase (Plasmodium falciparum DNA methyltransferase; PfDNMT) that may mediate these genomic modifications. These analyses revealed that the malaria genome is asymmetrically methylated and shares common features with undifferentiated plant and mammalian cells. Notably, core promoters are hypomethylated, and transcript levels correlate with intraexonic methylation. Additionally, there are sharp methylation transitions at nucleosome and exon-intron boundaries. These data suggest that DNA methylation could regulate virulence gene expression and transcription elongation. Furthermore, the broad range of action of DNA methylation and the uniqueness of PfDNMT suggest that the methylation pathway is a potential target for antimalarial strategies.Biological SciencesBiomedical and Clinical SciencesGeneticsClinical SciencesMedical MicrobiologyMalariaBiotechnologyHuman GenomeRare DiseasesInfectious DiseasesVector-Borne Diseases2.2 Factors relating to the physical environmentAetiologyInfectionGood Health and Well BeingChromatographyLiquidDNA MethylationDNAProtozoanDNA-Cytosine MethylasesEpigenesisGeneticErythrocytesGenomeProtozoanHumansPlasmodium falciparumTandem Mass SpectrometryMicrobiologyImmunologyBiochemistry and cell biologyMedical microbiologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2fk1d2kqarticleCell Host & Microbe, vol 14, iss 6696 - 706oai:escholarship.org:ark:/13030/qt4s11b6cj2023-12-10T17:09:44Zqt4s11b6cjComputerized Face Recognition in Renaissance Portrait Art: A quantitative measure for identifying uncertain subjects in ancient portraitsSrinivasan, RamyaRudolph, ConradRoy-Chowdhury, Amit K2015-01-01© 2015 IEEE. This article explores the feasibility of face-recognition technologies for analyzing works of portraiture and, in the process, provides a quantitative source of evidence to art historians in answering many of their ambiguities concerning identity of the subject in some portraits and in understanding artists? styles. Works of portrait art bear the mark of visual interpretation of the artist. Moreover, the number of samples available to model these effects is often limited. Based on an understanding of artistic conventions, we show how to learn and validate features that are robust in distinguishing subjects in portraits (sitters) and that are also capable of characterizing an individual artist?s style. This can be used to learn a feature space called portrait feature space (PFS) that is representative of quantitative measures of similarities between portrait pairs known to represent same/different sitters. Through statistical hypothesis tests, we analyze uncertain portraits against known identities and explain the significance of the results from an art historian?s perspective. Results are shown on our data consisting of over 270 portraits belonging largely to the Renaissance era.Information and Computing SciencesCommunications EngineeringEngineeringComputer Vision and Multimedia ComputationArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringMechanical EngineeringNetworking & TelecommunicationsCommunications engineeringComputer vision and multimedia computationpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4s11b6cjarticleIEEE Signal Processing Magazine, vol 32, iss 485 - 94oai:escholarship.org:ark:/13030/qt2z44r0112023-12-10T13:28:51Zqt2z44r011An overview of clinical and experimental treatment modalities for port wine stainsChen, Jennifer KGhasri, PedramAguilar, Guillermovan Drooge, Anne MargreetWolkerstorfer, AlbertKelly, Kristen MHeger, Michal2012-08-01Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy.Biomedical and Clinical SciencesClinical SciencesAngiogenesis InhibitorsHumansImmunosuppressive AgentsLow-Level Light TherapyPort-Wine Stainangiogenesis inhibitorsepidermal coolinghypobaric pressureimmunomodulatorsphotodynamic therapypulsed dye lasersite-specific pharmaco-laser therapysuperficial vascular and capillary malformationsDermatology & Venereal DiseasesClinical sciencesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2z44r011articleJournal of the American Academy of Dermatology, vol 67, iss 2289 - 304.e29oai:escholarship.org:ark:/13030/qt6gv9741c2023-12-10T11:29:25Zqt6gv9741cA photon thermal diodeChen, ZhenWong, CarlatonLubner, SeanYee, ShannonMiller, JohnJang, WanyoungHardin, CoreyFong, AnthonyGaray, Javier EDames, Chris2014-01-01A thermal diode is a two-terminal nonlinear device that rectifies energy carriers (for example, photons, phonons and electrons) in the thermal domain, the heat transfer analogue to the familiar electrical diode. Effective thermal rectifiers could have an impact on diverse applications ranging from heat engines to refrigeration, thermal regulation of buildings and thermal logic. However, experimental demonstrations have lagged far behind theoretical proposals. Here we present the first experimental results for a photon thermal diode. The device is based on asymmetric scattering of ballistic energy carriers by pyramidal reflectors. Recent theoretical work has predicted that this ballistic mechanism also requires a nonlinearity in order to yield asymmetric thermal transport, a requirement of all thermal diodes arising from the second Law of Thermodynamics, and realized here using an 'inelastic thermal collimator' element. Experiments confirm both effects: with pyramids and collimator the thermal rectification is 10.9 ± 0.8%, while without the collimator no rectification is detectable (<0.3%).Physical SciencesClassical Physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6gv9741carticleNature Communications, vol 5, iss 15446oai:escholarship.org:ark:/13030/qt9006p69g2023-12-10T09:20:38Zqt9006p69gSkull-stripping with machine learning deformable organismsPrasad, GautamJoshi, Anand AFeng, AlbertToga, Arthur WThompson, Paul MTerzopoulos, Demetri2014-10-01BackgroundSegmentation methods for medical images may not generalize well to new data sets or new tasks, hampering their utility. We attempt to remedy these issues using deformable organisms to create an easily customizable segmentation plan. We validate our framework by creating a plan to locate the brain in 3D magnetic resonance images of the head (skull-stripping).New methodOur method borrows ideas from artificial life to govern a set of deformable models. We use control processes such as sensing, proactive planning, reactive behavior, and knowledge representation to segment an image. The image may have landmarks and features specific to that dataset; these may be easily incorporated into the plan. In addition, we use a machine learning method to make our segmentation more accurate.ResultsOur method had the least Hausdorff distance error, but included slightly less brain voxels (false negatives). It also had the lowest false positive error and performed on par to skull-stripping specific method on other metrics.Comparison with existing method(s)We tested our method on 838 T1-weighted images, evaluating results using distance and overlap error metrics based on expert gold standard segmentations. We evaluated the results before and after the learning step to quantify its benefit; we also compare our results to three other widely used methods: BSE, BET, and the Hybrid Watershed algorithm.ConclusionsOur framework captures diverse categories of information needed for brain segmentation and will provide a foundation for tackling a wealth of segmentation problems.Biomedical and Clinical SciencesNeurosciencesBiomedical ImagingNetworking and Information Technology R&D (NITRD)AdultAlgorithmsAlzheimer DiseaseArtificial IntelligenceBrainCognitive DysfunctionFalse Positive ReactionsHumansImage ProcessingComputer-AssistedImagingThree-DimensionalMagnetic Resonance ImagingModelsBiologicalSkullTwinsYoung AdultDeformable organismsSkull-strippingMRIAdaboostHausdorffOverlapRegistrationPsychologyCognitive SciencesNeurology & Neurosurgeryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9006p69garticleoai:escholarship.org:ark:/13030/qt90c2j5032023-12-10T08:07:03Zqt90c2j503Growth of large-area graphene films from metal-carbon meltsAmini, ShaahinGaray, JavierLiu, GuanxiongBalandin, Alexander AAbbaschian, Reza2010-11-01We have demonstrated a new method for the large-area graphene growth, which can lead to a scalable low-cost high-throughput production technology. The method is based on growing single layer or few-layer graphene films from a molten phase. The process involves dissolving carbon inside a molten metal at a specified temperature and then allowing the dissolved carbon to nucleate and grow on top of the melt at a lower temperature. The examined metals for the metal-carbon melt included copper and nickel. For the latter, the high-quality single layer graphene was grown successfully. The resulting graphene layers were subjected to detailed microscopic and Raman spectroscopic characterization. The deconvolution of the Raman 2D band was used to accurately determine the number of atomic planes in the resulting graphene layers and access their quality. The results indicate that our technology can provide bulk graphite films, few-layer graphene as well as high-quality single layer graphene on metals. Our approach can also be used for producing graphene-metal thermal interface materials for thermal management applications. © 2010 American Institute of Physics.Physical SciencesCondensed Matter Physicscond-mat.mtrl-sciMathematical SciencesEngineeringApplied PhysicsMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/90c2j503articleJournal of Applied Physics, vol 108, iss 9094321oai:escholarship.org:ark:/13030/qt6f10485v2023-12-10T07:52:26Zqt6f10485vCutaneous Effects of Cryogen Spray Cooling on In Vivo Human SkinDATRICE, NICOLERAMIREZ‐SAN‐JUAN, JULIOZHANG, RONGMESHKINPOUR, AZINAGUILAR, GUILLERMONELSON, J STUARTKELLY, KRISTEN M2006-08-01BackgroundDespite widespread clinical use of cryogen spray cooling (CSC) in conjunction with laser dermatologic surgery, in vivo cutaneous effects have not been systematically evaluated.ObjectiveThe authors characterize the in vivo cutaneous effects for Fitzpatrick skin types I through VI after CSC exposures of varying spurt durations and spurt delivery patterns (single vs. multiple spurts).Materials and methodsTwenty-seven normal human subjects were exposed to single cryogen spurts from 10 to 80 milliseconds, and multiple spurt patterns consisting of two 20-millisecond spurts, four 10-millisecond spurts, and eight 5-millisecond spurts. Subjects were evaluated by clinical observation and photography at 1 hour, 1 day, and 1, 4, 8, and 12 weeks after CSC exposure.ResultsAcute erythema and urticaria (1-24 hours) were noted in 14 of 27 and 3 of 27 subjects, respectively. Transient hyperpigmentation occurred in 4 of 27 subjects (skin types III-VI) but resolved spontaneously without medical intervention in all subjects by 8 weeks. No permanent skin changes were noted in any subjects. Skin reactions were more common with longer single-spurt durations (50 milliseconds or greater) and multiple spurt patterns.ConclusionAcute erythema, urticaria, and, less commonly, transient hyperpigmentation were observed after CSC exposure. Permanent skin injury was not observed and is unlikely.Biomedical and Clinical SciencesClinical SciencesClinical ResearchAdministrationTopicalAerosolsCryotherapyFluorocarbonsHumansLow-Level Light TherapySkinSkin PigmentationDermatology & Venereal DiseasesClinical sciencesDentistryapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6f10485varticleDermatologic Surgery, vol 32, iss 81007 - 1012oai:escholarship.org:ark:/13030/qt9g10h3802023-12-10T05:20:00Zqt9g10h380Comparing accuracy and reproducibility of sequential and Hadamard‐encoded multidelay pseudocontinuous arterial spin labeling for measuring cerebral blood flow and arterial transit time in healthy subjects: A simulation and in vivo studyGuo, JiaHoldsworth, Samantha JFan, Audrey PLebel, Marc RZun, ZunghoShankaranarayanan, AjitZaharchuk, Greg2018-04-01PurposeTo compare performance of sequential and Hadamard-encoded pseudocontinuous arterial spin labeling (PCASL).Materials and methodsMonte Carlo simulations and in vivo experiments were performed in 10 healthy subjects. Field strength and sequence: 5-delay sequential (5-del. Seq.), 7-delay Hadamard-encoded (7-del. Had.), and a single-delay (1-del.) PCASL, without and with vascular crushing at 3.0T. The errors and variations of cerebral blood flow (CBF) and arterial transit time (ATT) from simulations and the CBF and ATT estimates and variations in gray matter (GM) with different ATT ranges were compared. Pairwise t-tests with Bonferroni correction were used.ResultsThe simulations and in vivo experiments showed that 1-del. PCASL underestimated GM CBF due to insufficient postlabeling delay (PLD) (37.2 ± 8.1 vs. 47.3 ± 8.5 and 47.3 ± 9.0 ml/100g/min, P ≤ 6.5 × 10-6 ), while 5-del. Seq. and 7-del. Had. yielded comparable GM CBF (P ≥ 0.49). 5-del. Seq. was more reproducible for CBF (P = 4.7 × 10-4 ), while 7-del. Had. was more reproducible for ATT (P = 0.033). 5-del. Seq. was more prone to intravascular artifacts and yielded lower GM ATTs compared to 7-del. Had. without crushing (1.13 ± 0.18 vs. 1.23 ± 0.13 seconds, P = 2.3 × 10-3 ), but they gave comparable ATTs with crushing (P = 0.12). ATTs measured with crushing were longer than those without crushing (P ≤ 6.7 × 10-4 ), but CBF was not affected (P ≥ 0.16).ConclusionThe theoretical signal-to-noise ratio (SNR) gain through Hadamard encoding was confirmed experimentally. For 1-del., a PLD of 1.8 seconds is recommended for healthy subjects. With current parameters, 5-del. Seq. was more reproducible for CBF, and 7-del. Had. for ATT. Vascular crushing may help reduce variations in multidelay experiments without compromising tissue CBF or ATT measurements.Level of evidence1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1119-1132.Biomedical and Clinical SciencesClinical SciencesClinical ResearchBioengineeringAdultBlood Flow VelocityCerebrovascular CirculationComputer SimulationFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedReference ValuesReproducibility of ResultsSensitivity and SpecificitySignal ProcessingComputer-AssistedSpin Labelsarterial spin labelingpseudocontinuous ASLmultidelay ASLreproducibilityarterial transit timecerebral blood flowPhysical SciencesEngineeringMedical and Health SciencesNuclear Medicine & Medical ImagingClinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9g10h380articleJournal of Magnetic Resonance Imaging, vol 47, iss 41119 - 1132oai:escholarship.org:ark:/13030/qt5h4390082023-12-10T04:31:01Zqt5h439008Cytocompatibility and early inflammatory response of human endothelial cells in direct culture with Mg-Zn-Sr alloysCipriano, Aaron FSallee, AmyTayoba, MylaAlcaraz, Mayra C CortezLin, AlanGuan, Ren-GuoZhao, Zhan-YongLiu, Huinan2017-01-01Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4Zn-xSr alloys (x=0.15, 0.5, 1.0, 1.5wt%; designated as ZSr41A, B, C, and D respectively) in the direct culture with human umbilical vein endothelial cells (HUVEC) in vitro. The second objective was to investigate, for the first time, the early-stage inflammatory response in cultured HUVECs as indicated by the induction of vascular cellular adhesion molecule-1 (VCAM-1). The results showed that the 24-h in vitro degradation of the ZSr41 alloys containing a β-phase with a Zn/Sr at% ratio ∼1.5 was significantly faster than the ZSr41 alloys with Zn/Sr at% ∼1. Additionally, the adhesion density of HUVECs in the direct culture but not in direct contact with the ZSr41 alloys for up to 24h was not adversely affected by the degradation of the alloys. Importantly, neither culture media supplemented with up to 27.6mM Mg2+ ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on HUVEC responses. In contrast, the significantly higher, yet non-cytotoxic, Zn2+ ion concentration from the degradation of ZSr41D alloy was likely the cause for the initially higher VCAM-1 expression on cultured HUVECs. Lastly, analysis of the HUVEC-ZSr41 interface showed near-complete absence of cell adhesion directly on the sample surface, most likely caused by either a high local alkalinity, change in surface topography, and/or surface composition. The direct culture method used in this study was proposed as a valuable tool for studying the design aspects of Zn-containing Mg-based biomaterials in vitro, in order to engineer solutions to address current shortcomings of Mg alloys for vascular device applications.Statement of significanceMagnesium (Mg) alloys specifically designed for biodegradable implant applications have been the focus of biomedical research since the early 2000s. Physicochemical properties of Mg alloys make these metallic biomaterials excellent candidates for temporary biodegradable implants in orthopedic and cardiovascular applications. As Mg alloys continue to be investigated for biomedical applications, it is necessary to understand whether Mg-based materials or the alloying elements have the intrinsic ability to direct an immune response to improve implant integration while avoiding cell-biomaterial interactions leading to chronic inflammation and/or foreign body reactions. The present study utilized the direct culture method to investigate for the first time the in vitro transient inflammatory activation of endothelial cells induced by the degradation products of Zn-containing Mg alloys.EngineeringBiomedical EngineeringBioengineeringBiotechnologyAlloysCell AdhesionCell DeathCorrosionCulture MediaElectrochemical TechniquesHuman Umbilical Vein Endothelial CellsHumansInflammationIonsMagnesiumSolubilitySpectrometryX-Ray EmissionSurface PropertiesBiodegradable Magnesium Zinc Strontium alloyMg-Zn-Sr alloyHuman umbilical vein endothelial cellsInduction of vascular cell adhesion molecule-1Early inflammatory responseBiomedical implantsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5h439008articleoai:escholarship.org:ark:/13030/qt0mt1g0qd2023-12-10T03:22:20Zqt0mt1g0qdHybrid LSTM and Encoder–Decoder Architecture for Detection of Image ForgeriesBappy, Jawadul HSimons, CodyNataraj, LakshmananManjunath, BSRoy-Chowdhury, Amit K2019-07-01With advanced image journaling tools, one can easily alter the semantic meaning of an image by exploiting certain manipulation techniques such as copy clone, object splicing, and removal, which mislead the viewers. In contrast, the identification of these manipulations becomes a very challenging task as manipulated regions are not visually apparent. This paper proposes a high-confidence manipulation localization architecture that utilizes resampling features, long short-term memory (LSTM) cells, and an encoder-decoder network to segment out manipulated regions from non-manipulated ones. Resampling features are used to capture artifacts, such as JPEG quality loss, upsampling, downsampling, rotation, and shearing. The proposed network exploits larger receptive fields (spatial maps) and frequency-domain correlation to analyze the discriminative characteristics between the manipulated and non-manipulated regions by incorporating the encoder and LSTM network. Finally, the decoder network learns the mapping from low-resolution feature maps to pixel-wise predictions for image tamper localization. With the predicted mask provided by the final layer (softmax) of the proposed architecture, end-to-end training is performed to learn the network parameters through back-propagation using the ground-truth masks. Furthermore, a large image splicing dataset is introduced to guide the training process. The proposed method is capable of localizing image manipulations at the pixel level with high precision, which is demonstrated through rigorous experimentation on three diverse datasets.Information and Computing SciencesComputer Vision and Multimedia ComputationMental HealthBioengineeringImage forgerytamper localizationsegmentationresamplingLSTMCNNencoderdecodercs.CVArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCognitive SciencesArtificial Intelligence & Image ProcessingComputer vision and multimedia computationGraphicsaugmented reality and gamesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0mt1g0qdarticleIEEE Transactions on Image Processing, vol 28, iss 73286 - 3300oai:escholarship.org:ark:/13030/qt5xx336vj2023-12-10T01:27:57Zqt5xx336vjThermal responses of ex vivo human skin during multiple cryogen spurts and 1,450 nm laser pulsesZhang, RongRamirez‐San‐Juan, Julio CChoi, BernardJia, WangcunAguilar, GuillermoKelly, Kristen MNelson, J Stuart2006-02-01Background and objectiveAlthough cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser dermatologic surgery, concern has been expressed that CSC may induce cryo-injury. The objective of this study is to measure temperature variations at the epidermal-dermal junction in ex vivo human skin during three clinically relevant multiple cryogen spurt-laser pulse sequences (MCS-LPS).Study design/materials and methodsThe epidermis of ex vivo human skin was separated from the dermis and a thin-foil thermocouple (13 microm thickness) was inserted between the two layers. Thermocouple depth and epidermal thickness were measured using optical coherence tomography (OCT). Skin specimens were preheated to 30 degrees C before the MCS-LPS were initiated. Three MCS-LPS patterns, with total cryogen spray times of 38, 30, and 25 milliseconds respectively, were applied to the specimens in combination with laser fluences of 10 and 14 J/cm(2), while the thermocouple recorded the temperature changes at the epidermal-dermal junction.ResultsThe thermocouple effectively recorded fast temperature changes during three MCS-LPS patterns. The lowest temperatures measured corresponded to the sequences with longer pre-cooling cryogen spurts. No sub-zero temperatures were measured for any of the MCS-LPS patterns under study.ConclusionsThe three clinically relevant MCS-LPS patterns evaluated in this study do not cause sub-zero temperatures in ex vivo human skin at the epidermal-dermal junction and, therefore, are unlikely to cause significant cryogen induced epidermal injury.Biomedical and Clinical SciencesOphthalmology and OptometryInfectious DiseasesSkinAerosolsCryotherapyDermisEpidermisHumansLaser TherapySkin TemperatureThermographyepidermal-dermal junction temperaturecryogen injuryClinical SciencesDermatology & Venereal DiseasesClinical sciencesDentistryapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5xx336vjarticleLasers in Surgery and Medicine, vol 38, iss 2137 - 141oai:escholarship.org:ark:/13030/qt69b4r2392023-12-09T22:06:31Zqt69b4r239Predicting Solute Transport Through Green Stormwater Infrastructure With Unsteady Transit Time Distribution TheoryParker, EAGrant, SBCao, YRippy, MAMcGuire, KJHolden, PAFeraud, MAvasarala, SLiu, HHung, WCRugh, MJay, JPeng, JShao, SLi, D2021-02-01In this study, we explore the use of unsteady transit time distribution (TTD) theory to model solute transport in biofilters, a popular form of nature-based or “green” storm water infrastructure (GSI). TTD theory has the potential to address many unresolved challenges associated with predicting pollutant fate and transport through these systems, including unsteadiness in the water balance (time-varying inflows, outflows, and storage), unsteadiness in pollutant loading, time-dependent reactions, and scale-up to GSI networks and urban catchments. From a solution to the unsteady age conservation equation under uniform sampling, we derive an explicit expression for solute breakthrough during and after one or more storm events. The solution is calibrated and validated with breakthrough data from 17 simulated storms at a field-scale biofilter test facility in Southern California, using bromide as a conservative tracer. TTD theory closely reproduces bromide breakthrough concentrations, provided that lateral exchange with the surrounding soil is accounted for. At any given time, according to theory, more than half of the water in storage is from the most recent storm, while the rest is a mixture of penultimate and earlier storms. Thus, key management endpoints, such as the pollutant treatment credit attributable to GSI, are likely to depend on the evolving age distribution of water stored and released by these systems.HydrologyEarth Sciencesgreen storm water infrastructurelow impact developmentnitrogen removalpathogen removalpollutant fate and transport modelingtransit time distribution theoryPhysical Geography and Environmental GeoscienceCivil EngineeringEnvironmental EngineeringCivil engineeringEnvironmental engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/69b4r239articleWater Resources Research, vol 57, iss 2oai:escholarship.org:ark:/13030/qt6jg7m2zf2023-12-09T16:10:22Zqt6jg7m2zfCarbon Capture: Theoretical Guidelines for Activated Carbon-Based CO2 Adsorption Material Evaluation.Wang, YixiaoMeng, YuqingYang, YingchaoNeupane, ManishWang, LucunZhao, HaiyanQian, JinSnyder, SethGlenna, DrewJana, AsmitaXu, Qiang2023-11-30Activated carbon (AC)-based materials have shown promising performance in carbon capture, offering low cost and sustainable sourcing from abundant natural resources. Despite ACs growing as a new class of materials, theoretical guidelines for evaluating their viability in carbon capture are a crucial research gap. We address this gap by developing a hierarchical guideline, based on fundamental gas-solid interaction strength, that underpins the success and scalability of AC-based materials. The most critical performance indicator is the CO2 adsorption energy, where an optimal range (-0.41 eV) ensures efficiency between adsorption and desorption. Additionally, we consider thermal stability and defect sensitivity to ensure consistent performance under varying conditions. Further, selectivity and capacity play significant roles due to external variables such as partial pressure of CO2 and other ambient air gases (N2, H2O, O2), bridging the gap between theory and reality. We provide actionable examples by narrowing our options to methylamine- and pyridine-grafted graphene.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6jg7m2zfarticleJournal of Physical Chemistry Letters, vol 14, iss 47oai:escholarship.org:ark:/13030/qt6258h0jq2023-12-08T17:51:42Zqt6258h0jq25th Anniversary Article: Semiconductor Nanowires – Synthesis, Characterization, and ApplicationsDasgupta, Neil PSun, JianweiLiu, ChongBrittman, SarahAndrews, Sean CLim, JongwooGao, HanweiYan, RuoxueYang, Peidong2014-04-01Semiconductor nanowires (NWs) have been studied extensively for over two decades for their novel electronic, photonic, thermal, electrochemical and mechanical properties. This comprehensive review article summarizes major advances in the synthesis, characterization, and application of these materials in the past decade. Developments in the understanding of the fundamental principles of "bottom-up" growth mechanisms are presented, with an emphasis on rational control of the morphology, stoichiometry, and crystal structure of the materials. This is followed by a discussion of the application of nanowires in i) electronic, ii) sensor, iii) photonic, iv) thermoelectric, v) photovoltaic, vi) photoelectrochemical, vii) battery, viii) mechanical, and ix) biological applications. Throughout the discussion, a detailed explanation of the unique properties associated with the one-dimensional nanowire geometry will be presented, and the benefits of these properties for the various applications will be highlighted. The review concludes with a brief perspective on future research directions, and remaining barriers which must be overcome for the successful commercial application of these technologies.EngineeringChemical SciencesNanotechnologyAnimalsAnniversaries and Special EventsElectric Power SuppliesEndoscopyHumansNanowiresNeuronsOptics and PhotonicsPhotochemical ProcessesSemiconductorsnanostructurenanowiressynthesiselectronicsphotonicsenergythermoelectricphotovoltaicphotoelectrochemistryenergy storageNEMSbio-nano interfacePhysical SciencesNanoscience & NanotechnologyChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6258h0jqarticleAdvanced Materials, vol 26, iss 142137 - 2184oai:escholarship.org:ark:/13030/qt4mz1d5wg2023-12-08T13:47:33Zqt4mz1d5wgOptimized Generation of Data-Path from C Codes for FPGAsGuo, ZhiBuyukkurt, BetulNajjar, WalidVissers, Kees2005-01-01FPGAs, as computing devices, offer significant speedup over microprocessors. Furthermore, their configurability offers an advantage over traditional ASICs. However, they do not yet enjoy high-level language programmability, as microprocessors do. This has become the main obstacle for their wider acceptance by application designers. ROCCC is a compiler designed to generate circuits from C source code to execute on FPGAs, more specifically on CSoCs. It generates RTL level HDLs from frequently executing kernels in an application. In this paper, we describe ROCCC's system overview and focus on its data path generation. We compare the performance of ROCCC-generated VHDL code with that of Xilinx IPs. The synthesis result shows that ROCCC-generated circuit takes around 2x-3x area and runs at comparable clock rate.EngineeringBuilt Environment and DesignElectronicsSensors and Digital Hardwarecs.ARapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4mz1d5wgarticleoai:escholarship.org:ark:/13030/qt02v9v0kf2023-12-08T09:18:16Zqt02v9v0kfEpitope‐specific affinity maturation improved stability of potent protease inhibitory antibodiesLopez, TylerChuan, ChenRamirez, AaronChen, Kuan‐Hui ELorenson, Mary YBenitez, ChrisMustafa, ZahidPham, HenrySanchez, RamonWalker, Ameae MGe, Xin2018-11-01Targeting effectual epitopes is essential for therapeutic antibodies to accomplish their desired biological functions. This study developed a competitive dual color fluorescence-activated cell sorting (FACS) to maturate a matrix metalloprotease 14 (MMP-14) inhibitory antibody. Epitope-specific screening was achieved by selection on MMP-14 during competition with N-terminal domain of tissue inhibitor of metalloproteinase-2 (TIMP-2) (nTIMP-2), a native inhibitor of MMP-14 binding strongly to its catalytic cleft. 3A2 variants with high potency, selectivity, and improved affinity and proteolytic stability were isolated from a random mutagenesis library. Binding kinetics indicated that the affinity improvements were mainly from slower dissociation rates. In vitro degradation tests suggested the isolated variants had half lives 6-11-fold longer than the wt. Inhibition kinetics suggested they were competitive inhibitors which showed excellent selectivity toward MMP-14 over highly homologous MMP-9. Alanine scanning revealed that they bound to the vicinity of MMP-14 catalytic cleft especially residues F204 and F260, suggesting that the desired epitope was maintained during maturation. When converted to immunoglobulin G, B3 showed 5.0 nM binding affinity and 6.5 nM inhibition potency with in vivo half-life of 4.6 days in mice. In addition to protease inhibitory antibodies, the competitive FACS described here can be applied for discovery and engineering biosimilars, and in general for other circumstances where epitope-specific modulation is needed.Biochemistry and Cell BiologyBiomedical and Clinical SciencesBiological SciencesBiotechnology5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsAnimalsAntibodiesAntibody AffinityBinding SitesDrug EvaluationPreclinicalEpitopesFlow CytometryHalf-LifeImmunologic FactorsKineticsMatrix Metalloproteinase 14Matrix Metalloproteinase InhibitorsMiceMutagenesisProtein Bindingepitope specificityFACSinhibitory antibodyMMPproteolytic stabilityapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/02v9v0kfarticleBiotechnology and Bioengineering, vol 115, iss 112673 - 2682oai:escholarship.org:ark:/13030/qt6bj8q3bq2023-12-08T08:14:42Zqt6bj8q3bqRetraction Note: A photon thermal diodeChen, ZhenWong, CarlatonLubner, SeanYee, ShannonMiller, JohnJang, WanyoungHardin, CoreyFong, AnthonyGaray, Javier EDames, Chris2017-01-01This corrects the article DOI: 10.1038/ncomms6446.Numerical and Computational MathematicsEngineeringMathematical SciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6bj8q3bqarticleNature Communications, vol 8, iss 116134oai:escholarship.org:ark:/13030/qt4vh5x8fg2023-12-08T04:17:58Zqt4vh5x8fgLaser-sculptured ultrathin transition metal carbide layers for energy storage and energy harvesting applicationsZang, XiningJian, CuiyingZhu, TaishanFan, ZhengWang, WanlinWei, MinsongLi, BuxuanFollmar Diaz, MateoAshby, PaulLu, ZhengmaoChu, YaoWang, ZizhaoDing, XinruiXie, YingxiChen, JuhongHohman, J NathanSanghadasa, MohanGrossman, Jeffrey CLin, Liwei2019-01-01Ultrathin transition metal carbides with high capacity, high surface area, and high conductivity are a promising family of materials for applications from energy storage to catalysis. However, large-scale, cost-effective, and precursor-free methods to prepare ultrathin carbides are lacking. Here, we demonstrate a direct pattern method to manufacture ultrathin carbides (MoCx, WCx, and CoCx) on versatile substrates using a CO2 laser. The laser-sculptured polycrystalline carbides (macroporous, ~10-20 nm wall thickness, ~10 nm crystallinity) show high energy storage capability, hierarchical porous structure, and higher thermal resilience than MXenes and other laser-ablated carbon materials. A flexible supercapacitor made of MoCx demonstrates a wide temperature range (-50 to 300 °C). Furthermore, the sculptured microstructures endow the carbide network with enhanced visible light absorption, providing high solar energy harvesting efficiency (~72 %) for steam generation. The laser-based, scalable, resilient, and low-cost manufacturing process presents an approach for construction of carbides and their subsequent applications.EngineeringMaterials EngineeringChemical SciencesPhysical ChemistryAffordable and Clean Energyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4vh5x8fgarticleNature Communications, vol 10, iss 13112oai:escholarship.org:ark:/13030/qt01w609qc2023-12-08T04:01:20Zqt01w609qcPhysics-informed UNets for discovering hidden elasticity in heterogeneous materialsKamali, AliLaksari, Kaveh2023-12-07Soft biological tissues often have complex mechanical properties due to variation in structural components. In this paper, we develop a novel UNet-based neural network model for inversion in elasticity (El-UNet) to infer the spatial distributions of mechanical parameters from strain maps as input images, normal stress boundary conditions, and domain physics information. We show superior performance - both in terms of accuracy and computational cost - by El-UNet compared to fully-connected physics-informed neural networks in estimating unknown parameters and stress distributions for isotropic linear elasticity. We characterize different variations of El-UNet and propose a self-adaptive spatial loss weighting approach. To validate our inversion models, we performed various finite-element simulations of isotropic domains with heterogenous distributions of material parameters to generate synthetic data. El-UNet is faster and more accurate than the fully-connected physics-informed implementation in resolving the distribution of unknown fields. Among the tested models, the self-adaptive spatially weighted models had the most accurate reconstructions in equal computation times. The learned spatial weighting distribution visibly corresponded to regions that the unweighted models were resolving inaccurately. Our work demonstrates a computationally efficient inversion algorithm for elasticity imaging using convolutional neural networks and presents a potential fast framework for three-dimensional inverse elasticity problems that have proven unachievable through previously proposed methods.EngineeringMaterials EngineeringMechanical EngineeringBiomedical EngineeringBioengineeringDeep learningElasticity imagingModel-based elastographyTissue biomechanicsBiomedical engineeringMaterials engineeringMechanical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/01w609qcarticleoai:escholarship.org:ark:/13030/qt6b56x7nt2023-12-08T01:47:58Zqt6b56x7ntSequencing of 15 622 gene‐bearing BACs clarifies the gene‐dense regions of the barley genomeMuñoz-Amatriaín, MaríaLonardi, StefanoLuo, MingChengMadishetty, KavithaSvensson, Jan TMoscou, Matthew JWanamaker, SteveJiang, TaoKleinhofs, AndrisMuehlbauer, Gary JWise, Roger PStein, NilsMa, YaqinRodriguez, EdmundoKudrna, DaveBhat, Prasanna RChao, ShiaomanCondamine, PascalHeinen, ShaneResnik, JoshWing, RodWitt, Heather NAlpert, MatthewBeccuti, MarcoBozdag, SerdarCordero, FrancescaMirebrahim, HamidOunit, RachidWu, YonghuiYou, FrankZheng, JieSimková, HanaDolezel, JaroslavGrimwood, JaneSchmutz, JeremyDuma, DenisaAltschmied, LotharBlake, TomBregitzer, PhilCooper, LaurelDilbirligi, MuharremFalk, AndersFeiz, LeilaGraner, AndreasGustafson, PerryHayes, Patrick MLemaux, PeggyMammadov, JafarClose, Timothy J2015-10-01Barley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole-genome shotgun sequences with a physical and genetic framework. However, because only 6278 bacterial artificial chromosome (BACs) in the physical map were sequenced, fine structure was limited. To gain access to the gene-containing portion of the barley genome at high resolution, we identified and sequenced 15 622 BACs representing the minimal tiling path of 72 052 physical-mapped gene-bearing BACs. This generated ~1.7 Gb of genomic sequence containing an estimated 2/3 of all Morex barley genes. Exploration of these sequenced BACs revealed that although distal ends of chromosomes contain most of the gene-enriched BACs and are characterized by high recombination rates, there are also gene-dense regions with suppressed recombination. We made use of published map-anchored sequence data from Aegilops tauschii to develop a synteny viewer between barley and the ancestor of the wheat D-genome. Except for some notable inversions, there is a high level of collinearity between the two species. The software HarvEST:Barley provides facile access to BAC sequences and their annotations, along with the barley-Ae. tauschii synteny viewer. These BAC sequences constitute a resource to improve the efficiency of marker development, map-based cloning, and comparative genomics in barley and related crops. Additional knowledge about regions of the barley genome that are gene-dense but low recombination is particularly relevant.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeBiotechnologyVaccine RelatedChromosomesArtificialBacterialGenomePlantHordeumMolecular Sequence DataBarleyHordeum vulgare LBAC sequencinggene distributionrecombination frequencysyntenycentromere BACsHarvEST:BarleyAegilops tauschiiHordeum vulgare L.Biochemistry and Cell BiologyPlant BiologyPlant Biology & BotanyBiochemistry and cell biologyPlant biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6b56x7ntarticleThe Plant Journal, vol 84, iss 1216 - 227oai:escholarship.org:ark:/13030/qt16d4s4hb2023-12-07T02:07:27Zqt16d4s4hbTunable room-temperature ferromagnetism in Co-doped two-dimensional van der Waals ZnOChen, RuiLuo, FuchuanLiu, YuziSong, YuDong, YuWu, ShanCao, JinhuaYang, FuyiN’Diaye, AlphaShafer, PadraicLiu, YinLou, ShuaiHuang, JunweiChen, XiangFang, ZixuanWang, QingjunJin, DafeiCheng, RanYuan, HongtaoBirgeneau, Robert JYao, Jie2021-01-01The recent discovery of ferromagnetism in two-dimensional van der Waals crystals has provoked a surge of interest in the exploration of fundamental spin interaction in reduced dimensions. However, existing material candidates have several limitations, notably lacking intrinsic room-temperature ferromagnetic order and air stability. Here, motivated by the anomalously high Curie temperature observed in bulk diluted magnetic oxides, we demonstrate room-temperature ferromagnetism in Co-doped graphene-like Zinc Oxide, a chemically stable layered material in air, down to single atom thickness. Through the magneto-optic Kerr effect, superconducting quantum interference device and X-ray magnetic circular dichroism measurements, we observe clear evidences of spontaneous magnetization in such exotic material systems at room temperature and above. Transmission electron microscopy and atomic force microscopy results explicitly exclude the existence of metallic Co or cobalt oxides clusters. X-ray characterizations reveal that the substitutional Co atoms form Co2+ states in the graphitic lattice of ZnO. By varying the Co doping level, we observe transitions between paramagnetic, ferromagnetic and less ordered phases due to the interplay between impurity-band-exchange and super-exchange interactions. Our discovery opens another path to 2D ferromagnetism at room temperature with the advantage of exceptional tunability and robustness.Quantum PhysicsEngineeringPhysical SciencesNanotechnologyCondensed Matter Physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/16d4s4hbarticleNature Communications, vol 12, iss 13952oai:escholarship.org:ark:/13030/qt521171r62023-12-04T15:07:05Zqt521171r6Harnessing Semi-Supervised Machine Learning to Automatically Predict Bioactivities of Per- and Polyfluoroalkyl Substances (PFASs).Kwon, HyunaAli, ZulfikharWong, Bryan2023-11-14Many per- and polyfluoroalkyl substances (PFASs) pose significant health hazards due to their bioactive and persistent bioaccumulative properties. However, assessing the bioactivities of PFASs is both time-consuming and costly due to the sheer number and expense of in vivo and in vitro biological experiments. To this end, we harnessed new unsupervised/semi-supervised machine learning models to automatically predict bioactivities of PFASs in various human biological targets, including enzymes, genes, proteins, and cell lines. Our semi-supervised metric learning models were used to predict the bioactivity of PFASs found in the recent Organisation of Economic Co-operation and Development (OECD) report list, which contains 4730 PFASs used in a broad range of industries and consumers. Our work provides the first semi-supervised machine learning study of structure-activity relationships for predicting possible bioactivities in a variety of PFAS species.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/521171r6articleEnvironmental Science & Technology Letters, vol 10, iss 11oai:escholarship.org:ark:/13030/qt6m88v5142023-11-29T16:33:23Zqt6m88v514Enhancing the Combustion of Magnesium Nanoparticles via Low-Temperature Plasma-Induced Hydrogenation.Wagner, BrandonKim, MinseokChowdhury, MahbubVidales Pasos, EmmanuelHizon, KimberlyGhildiyal, PankajMangolini, LorenzoZachariah, Michael2023-10-29The hydrogenation of metal nanoparticles provides a pathway toward tuning their combustion characteristics. Metal hydrides have been employed as solid-fuel additives for rocket propellants, pyrotechnics, and explosives. Gas generation during combustion is beneficial to prevent aggregation and sintering of particles, enabling a more complete fuel utilization. Here, we discuss a novel approach for the synthesis of magnesium hydride nanoparticles based on a two-step aerosol process. Mg particles are first nucleated and grown via thermal evaporation, followed immediately by in-flight exposure to a hydrogen-rich low-temperature plasma. During the second step, atomic hydrogen generated by the plasma rapidly diffuses into the Mg lattice, forming particles with a significant fraction of MgH2. We find that hydrogenated Mg nanoparticles have an ignition temperature that is reduced by ∼200 °C when combusted with potassium perchlorate as an oxidizer, compared to the non-hydrogenated Mg material. This is due to the release of hydrogen from the fuel, jumpstarting its combustion. In addition, characterization of the plasma processes suggests that a careful balance between the dissociation of molecular hydrogen and heating of the nanoparticles must be achieved to avoid hydrogen desorption during production and achieve a significant degree of hydrogenation.combustionenergeticshydrogen treatmentignitionmagnesiummagnesium hydridenonthermal plasmaapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6m88v514articleACS Applied Materials and Interfaces, vol 15, iss 44oai:escholarship.org:ark:/13030/qt83v7089g2023-11-09T21:34:38Zqt83v7089gAdsorption behavior of associating nanoparticle-polymer systems in the vicinity of an attractive surface: Predictions from classical density functional theoryPrusty, DebaduttaGallegos, AlejandroWu, Jianzhong2023-11-01Macromolecular and Materials ChemistryChemical SciencesNanotechnologyBioengineeringClassical density functional theoryAssociating nanoparticlesSurface affinityapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/83v7089garticleJournal of Molecular Liquids, vol 390, iss Phys. Rev. Lett. 63 1989122976oai:escholarship.org:ark:/13030/qt983704t92023-11-09T19:39:54Zqt983704t9Assisting Forearm Function in Children With Movement Disorders via A Soft Wearable Robot With Equilibrium-Point ControlRealmuto, JonathanSanger, Terence D2022-01-01Wearable robots are envisioned to amplify the independence of people with movement impairments by providing daily physical assistance. For portable, comfortable, and safe devices, soft pneumatic-based robots are emerging as a potential solution. However, due to the inherent complexities, including compliance and nonlinear mechanical behavior, feedback control for facilitating human-robot interaction remains a challenge. Herein, we present the design, fabrication, and control architecture of a soft wearable robot that assists in supination and pronation of the forearm. The soft wearable robot integrates an antagonistic pair of pneumatic-based helical actuators to provide active pronation and supination torques. Our main contribution is a bio-inspired equilibrium-point control scheme for integrating proprioceptive feedback and exteroceptive input (e.g., the user's muscle activation signals) directly with the on/off valve behavior of the soft pneumatic actuators. The proposed human-robot controller is directly inspired by the equilibrium-point hypothesis of motor control, which suggests that voluntary movements arise through shifts in the equilibrium state of the antagonistic muscle pair spanning a joint. We hypothesized that the proposed method would reduce the required effort during dynamic manipulation without affecting the error. In order to evaluate our proposed method, we recruited seven pediatric participants with movement disorders to perform two dynamic interaction tasks with a haptic manipulandum. Each task required the participant to track a sinusoidal trajectory while the haptic manipulandum behaved as a Spring-Dominate system or Inertia-Dominate system. Our results reveal that the soft wearable robot, when active, reduced user effort on average by 14%. This work demonstrates the practical implementation of an equilibrium-point volitional controller for wearable robots and provides a foundational path toward versatile, low-cost, and soft wearable robots.Information and Computing SciencesHuman-Centred ComputingEngineeringControl EngineeringMechatronics and RoboticsClinical ResearchBioengineeringwearable roboticssoft roboticshuman-robot interactionreflexesequilibrium-point controlproprioceptionhuman–robot interactionArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringInformation and computing sciencesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/983704t9articleoai:escholarship.org:ark:/13030/qt47p300vb2023-11-07T17:07:07Zqt47p300vbFLUID-GPT (Fast Learning to Understand and Investigate Dynamics with a Generative Pre-Trained Transformer): Efficient Predictions of Particle Trajectories and Erosion.Yang, SteveAli, ZulfikharWong, Bryan2023-09-20The deleterious impact of erosion due to high-velocity particle impingement adversely affects a variety of engineering and industrial systems, resulting in irreversible mechanical wear of materials/components. Brute force computational fluid dynamics (CFD) calculations are commonly used to predict surface erosion by directly solving the Navier-Stokes equations for fluid and particle dynamics; however, these numerical approaches often require significant computational resources. In contrast, recent data-driven approaches using machine learning (ML) have shown immense promise for more efficient and accurate predictions to sidestep computationally demanding CFD calculations. To this end, we have developed FLUID-GPT (Fast Learning to Understand and Investigate Dynamics with a Generative Pre-Trained Transformer), a new hybrid ML architecture for accurately predicting particle trajectories and erosion on an industrial-scale steam header geometry. Our FLUID-GPT approach utilizes a Generative Pre-Trained Transformer 2 (GPT-2) with a convolutional neural network (CNN) for the first time to predict surface erosion using only information from five initial conditions: particle size, main-inlet speed, main-inlet pressure, subinlet speed, and subinlet pressure. Compared to the bidirectional long- and short-term memory (BiLSTM) ML techniques used in previous work, our FLUID-GPT model is much more accurate (a 54% decrease in the mean squared error) and efficient (70% less training time). Our work demonstrates that FLUID-GPT is an accurate and efficient ML approach for predicting time-series trajectories and their subsequent spatial erosion patterns in these complex dynamic systems.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/47p300vbarticleIndustrial and Engineering Chemistry Research, vol 62, iss 37oai:escholarship.org:ark:/13030/qt4gc5j2d82023-10-27T18:14:54Zqt4gc5j2d8Prioritised identification of structural classes of natural products from higher plants in the expedition of antimalarial drug discovery.Moyo, PhanankosiInvernizzi, LukeMianda, SephoraRudolph, WiehanAndayi, AndrewCrouch, NeilMaharaj, VineshWang, Mingxun2023-10-12The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria. Urgent measures need to be taken to curb this impending challenge. The higher plant-derived sesquiterpene, quinoline alkaloids, and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed. Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed. The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P. falciparum. To identify these novel scaffolds, we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data. Natural products were assigned to different structural classes using NPClassifier. To identify the most promising chemical scaffolds, we then correlated natural compound class with bioactivity and other data, namely (i) potency, (ii) resistance index, (iii) selectivity index and (iv) physicochemical properties. We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data. From this analysis we identified the top-ranked natural product pathway as the alkaloids. The top three ranked super classes identified were (i) pseudoalkaloids, (ii) naphthalenes and (iii) tyrosine alkaloids and the top five ranked classes (i) quassinoids (of super class triterpenoids), (ii) steroidal alkaloids (of super class pseudoalkaloids) (iii) cycloeudesmane sesquiterpenoids (of super class triterpenoids) (iv) isoquinoline alkaloids (of super class tyrosine alkaloids) and (v) naphthoquinones (of super class naphthalenes). Launched chemical space of these identified classes of compounds was, by and large, distinct from that of legacy antimalarial drugs. Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs. These molecules have the potential to be developed into new antimalarial drugs.Antiplasmodial drug resistanceCompound classesDrug developmentMalariaNatural productsPhytochemicalsPlasmodium falciparumapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4gc5j2d8articleNatural Products and Bioprospecting, vol 13, iss 1oai:escholarship.org:ark:/13030/qt71n618g82023-10-26T21:52:50Zqt71n618g8Text-Based Localization of Moments in a Video CorpusPaul, SudiptaMithun, Niluthpol ChowdhuryRoy-Chowdhury, Amit K2021-01-01Prior works on text-based video moment localization focus on temporally grounding the textual query in an untrimmed video. These works assume that the relevant video is already known and attempt to localize the moment on that relevant video only. Different from such works, we relax this assumption and address the task of localizing moments in a corpus of videos for a given sentence query. This task poses a unique challenge as the system is required to perform: 2) retrieval of the relevant video where only a segment of the video corresponds with the queried sentence, 2) temporal localization of moment in the relevant video based on sentence query. Towards overcoming this challenge, we propose Hierarchical Moment Alignment Network (HMAN) which learns an effective joint embedding space for moments and sentences. In addition to learning subtle differences between intra-video moments, HMAN focuses on distinguishing inter-video global semantic concepts based on sentence queries. Qualitative and quantitative results on three benchmark text-based video moment retrieval datasets - Charades-STA, DiDeMo, and ActivityNet Captions - demonstrate that our method achieves promising performance on the proposed task of temporal localization of moments in a corpus of videos.Data Management and Data ScienceInformation and Computing SciencesComputer Vision and Multimedia ComputationTask analysisLocation awarenessSemanticsVisualizationImage codingFeature extractionAnnotationsTemporal localizationvideo moment retrievalvideo corpusArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCognitive SciencesArtificial Intelligence & Image ProcessingComputer vision and multimedia computationGraphicsaugmented reality and gamespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/71n618g8articleoai:escholarship.org:ark:/13030/qt34n9j3nj2023-10-26T21:51:05Zqt34n9j3njDistributed Multi-agent Video Fast-forwardingLan, ShuyueWang, ZhiluRoy-Chowdhury, Amit KWei, ErminZhu, Qi2020-10-12In many intelligent systems, a network of agents collaboratively perceives
the environment for better and more efficient situation awareness. As these
agents often have limited resources, it could be greatly beneficial to identify
the content overlapping among camera views from different agents and leverage
it for reducing the processing, transmission and storage of
redundant/unimportant video frames. This paper presents a consensus-based
distributed multi-agent video fast-forwarding framework, named DMVF, that
fast-forwards multi-view video streams collaboratively and adaptively. In our
framework, each camera view is addressed by a reinforcement learning based
fast-forwarding agent, which periodically chooses from multiple strategies to
selectively process video frames and transmits the selected frames at
adjustable paces. During every adaptation period, each agent communicates with
a number of neighboring agents, evaluates the importance of the selected frames
from itself and those from its neighbors, refines such evaluation together with
other agents via a system-wide consensus algorithm, and uses such evaluation to
decide their strategy for the next period. Compared with approaches in the
literature on a real-world surveillance video dataset VideoWeb, our method
significantly improves the coverage of important frames and also reduces the
number of frames processed in the system.Data Management and Data ScienceInformation and Computing SciencesArtificial IntelligenceComputer Vision and Multimedia ComputationVideo fast-forwardingmulti-agentdistributed optimizationcs.CVapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/34n9j3njarticleoai:escholarship.org:ark:/13030/qt55d6s1vf2023-10-26T21:50:25Zqt55d6s1vfLearning Person Re-Identification Models From Videos With Weak SupervisionWang, XuepingLiu, MinRaychaudhuri, Dripta SPaul, SujoyWang, YaonanRoy-Chowdhury, Amit K2021-01-01Most person re-identification methods, being supervised techniques, suffer from the burden of massive annotation requirement. Unsupervised methods overcome this need for labeled data, but perform poorly compared to the supervised alternatives. In order to cope with this issue, we introduce the problem of learning person re-identification models from videos with weak supervision. The weak nature of the supervision arises from the requirement of video-level labels, i.e. person identities who appear in the video, in contrast to the more precise frame-level annotations. Towards this goal, we propose a multiple instance attention learning framework for person re-identification using such video-level labels. Specifically, we first cast the video person re-identification task into a multiple instance learning setting, in which person images in a video are collected into a bag. The relations between videos with similar labels can be utilized to identify persons, on top of that, we introduce a co-person attention mechanism which mines the similarity correlations between videos with person identities in common. The attention weights are obtained based on all person images instead of person tracklets in a video, making our learned model less affected by noisy annotations. Extensive experiments demonstrate the superiority of the proposed method over the related methods on two weakly labeled person re-identification datasets.Machine LearningInformation and Computing SciencesComputer Vision and Multimedia ComputationBehavioral and Social ScienceBasic Behavioral and Social ScienceVideosAnnotationsLabelingTask analysisFeature extractionTrainingReliabilityVideo person re-identificationweak supervisionco-person attention mechanismcs.CVArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCognitive SciencesArtificial Intelligence & Image ProcessingComputer vision and multimedia computationGraphicsaugmented reality and gamespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/55d6s1vfarticleoai:escholarship.org:ark:/13030/qt11h171tg2023-10-26T20:07:21Zqt11h171tgUsing Deep Learning Models to Predict Prosthetic Ankle TorquePrasanna, ChristopherRealmuto, JonathanAnderson, AnthonyRombokas, EricKlute, Glenn2023-01-01Inverse dynamics from motion capture is the most common technique for acquiring biomechanical kinetic data. However, this method is time-intensive, limited to a gait laboratory setting, and requires a large array of reflective markers to be attached to the body. A practical alternative must be developed to provide biomechanical information to high-bandwidth prosthesis control systems to enable predictive controllers. In this study, we applied deep learning to build dynamical system models capable of accurately estimating and predicting prosthetic ankle torque from inverse dynamics using only six input signals. We performed a hyperparameter optimization protocol that automatically selected the model architectures and learning parameters that resulted in the most accurate predictions. We show that the trained deep neural networks predict ankle torques one sample into the future with an average RMSE of 0.04 ± 0.02 Nm/kg, corresponding to 2.9 ± 1.6% of the ankle torque's dynamic range. Comparatively, a manually derived analytical regression model predicted ankle torques with a RMSE of 0.35 ± 0.53 Nm/kg, corresponding to 26.6 ± 40.9% of the ankle torque's dynamic range. In addition, the deep neural networks predicted ankle torque values half a gait cycle into the future with an average decrease in performance of 1.7% of the ankle torque's dynamic range when compared to the one-sample-ahead prediction. This application of deep learning provides an avenue towards the development of predictive control systems for powered limbs aimed at optimizing prosthetic ankle torque.Distributed Computing and Systems SoftwareInformation and Computing SciencesRehabilitationBioengineeringClinical ResearchAssistive TechnologyAffordable and Clean Energybiomechanicsmachine learningdeep neural networksrobotic ankle prosthesisAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/11h171tgarticleSensors, vol 23, iss 187712oai:escholarship.org:ark:/13030/qt8gb8n34b2023-10-26T19:19:42Zqt8gb8n34bBabesia BdFE1 Esterase is Required for the Anti-parasitic Activity of the ACE Inhibitor FosinoprilVydyam, PratapChoi, Jae-YeonGihaz, ShalevChand, MeenalGewirtz, MeitalThekkiniath, JoseLonardi, StefanoGennaro, Joseph CBen Mamoun, Choukri2023-10-01Effective and safe therapies for the treatment of diseases caused by intraerythrocytic parasites are impeded by the rapid emergence of drug resistance and the lack of novel drug targets. One such disease is human babesiosis, which is a rapidly emerging tick-borne illness caused by Babesia parasites. In this study, we identified fosinopril, a phosphonate-containing, FDA-approved Angiotensin Converting Enzyme (ACE) inhibitor commonly used as a prodrug for hypertension and heart failure, as a potent inhibitor of B. duncani parasite development within human erythrocytes. Cell biological and mass spectrometry analyses revealed that the conversion of fosinopril to its active diacid molecule, fosinoprilat, is essential for its antiparasitic activity. We show that this conversion is mediated by a parasite-encoded esterase, BdFE1, which is highly conserved among apicomplexan parasites. Parasites carrying the L238H mutation in the active site of BdFE1 failed to convert the prodrug to its active moiety and became resistant to the drug. Our data set the stage for the development of this class of drugs for therapy of vector-borne parasitic diseases.Medical MicrobiologyBiomedical and Clinical SciencesAntimicrobial ResistanceEmerging Infectious DiseasesBiotechnologyPreventionOrphan DrugVaccine RelatedInfectious DiseasesRare DiseasesVector-Borne DiseasesBiodefenseDevelopment of treatments and therapeutic interventions5.1 PharmaceuticalsInfectionGood Health and Well BeingBabesiaBabesia duncaniBdFE1FDA-approved drugsHuman BabesiosisParasitefosinoprilfosinoprilatChemical SciencesBiological SciencesMedical and Health SciencesBiochemistry & Molecular BiologyBiological sciencesBiomedical and clinical sciencesChemical sciencesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8gb8n34barticleoai:escholarship.org:ark:/13030/qt2hb348xr2023-10-23T06:43:01Zqt2hb348xrDevelopment of a Network of Accurate Ozone Sensing Nodes for Parallel Monitoring in a Site Relocation Study.Feenstra, BrandonPapapostolou, VasileiosDer Boghossian, BerjPolidori, AndreaCocker, David2019-12-18Recent technological advances in both air sensing technology and Internet of Things (IoT) connectivity have enabled the development and deployment of remote monitoring networks of air quality sensors. The compact size and low power requirements of both sensors and IoT data loggers allow for the development of remote sensing nodes with power and connectivity versatility. With these technological advancements, sensor networks can be developed and deployed for various ambient air monitoring applications. This paper describes the development and deployment of a monitoring network of accurate ozone (O3) sensor nodes to provide parallel monitoring in an air monitoring site relocation study. The reference O3 analyzer at the station along with a network of three O3 sensing nodes was used to evaluate the spatial and temporal variability of O3 across four Southern California communities in the San Bernardino Mountains which are currently represented by a single reference station in Crestline, CA. The motivation for developing and deploying the sensor network in the region was that the single reference station potentially needed to be relocated due to uncertainty that the lease agreement would be renewed. With the implication of siting a new reference station that is also a high O3 site, the project required the development of an accurate and precise sensing node for establishing a parallel monitoring network at potential relocation sites. The deployment methodology included a pre-deployment co-location calibration to the reference analyzer at the air monitoring station with post-deployment co-location results indicating a mean absolute error (MAE) < 2 ppb for 1-h mean O3 concentrations. Ordinary least squares regression statistics between reference and sensor nodes during post-deployment co-location testing indicate that the nodes are accurate and highly correlated to reference instrumentation with R2 values > 0.98, slope offsets < 0.02, and intercept offsets < 0.6 for hourly O3 concentrations with a mean concentration value of 39.7 ± 16.5 ppb and a maximum 1-h value of 94 ppb. Spatial variability for diurnal O3 trends was found between locations within 5 km of each other with spatial variability between sites more pronounced during nighttime hours. The parallel monitoring was successful in providing the data to develop a relocation strategy with only one relocation site providing a 95% confidence that concentrations would be higher there than at the current site.mountain community monitoringozoneparallel monitoringsensor networksensor nodesite relocation studyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2hb348xrarticleDiversity, vol 20, iss 1oai:escholarship.org:ark:/13030/qt20f8f64s2023-10-23T00:59:45Zqt20f8f64sTechnoeconomic and life-cycle analysis of single-step catalytic conversion of wet ethanol into fungible fuel blendstocks.Hannon, JohnLynd, LeeAndrade, OnofreBenavides, PaholaBeckham, GreggBiddy, MaryBrown, NathanChagas, MateusDavison, BrianFoust, ThomasJunqueira, TassiaLaser, MarkLi, ZhenglongRichard, TomTao, LingTuskan, GeraldWang, MichaelWoods, JeremyWyman, Charles2020-06-09Technoeconomic and life-cycle analyses are presented for catalytic conversion of ethanol to fungible hydrocarbon fuel blendstocks, informed by advances in catalyst and process development. Whereas prior work toward this end focused on 3-step processes featuring dehydration, oligomerization, and hydrogenation, the consolidated alcohol dehydration and oligomerization (CADO) approach described here results in 1-step conversion of wet ethanol vapor (40 wt% in water) to hydrocarbons and water over a metal-modified zeolite catalyst. A development project increased liquid hydrocarbon yields from 36% of theoretical to >80%, reduced catalyst cost by an order of magnitude, scaled up the process by 300-fold, and reduced projected costs of ethanol conversion 12-fold. Current CADO products conform most closely to gasoline blendstocks, but can be blended with jet fuel at low levels today, and could potentially be blended at higher levels in the future. Operating plus annualized capital costs for conversion of wet ethanol to fungible blendstocks are estimated at $2.00/GJ for CADO today and $1.44/GJ in the future, similar to the unit energy cost of producing anhydrous ethanol from wet ethanol ($1.46/GJ). Including the cost of ethanol from either corn or future cellulosic biomass but not production incentives, projected minimum selling prices for fungible blendstocks produced via CADO are competitive with conventional jet fuel when oil is $100 per barrel but not at $60 per barrel. However, with existing production incentives, the projected minimum blendstock selling price is competitive with oil at $60 per barrel. Life-cycle greenhouse gas emission reductions for CADO-derived hydrocarbon blendstocks closely follow those for the ethanol feedstock.ethanolheterogeneous catalysislow-carbon fungible fuel blendstocksapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/20f8f64sarticleProceedings of the National Academy of Sciences of USA, vol 117, iss 23oai:escholarship.org:ark:/13030/qt42r1s37d2023-10-22T16:45:25Zqt42r1s37dUltrafine Particle Metrics and Research Considerations: Review of the 2015 UFP Workshop.Baldauf, RichardDevlin, RobertGehr, PeterGiannelli, RobertHassett-Sipple, BethMartini, GiorgioMcDonald, JosephSacks, JasonWalker, KatherineJung, Heejung2016-10-28In February 2015, the United States Environmental Protection Agency (EPA) sponsored a workshop in Research Triangle Park, NC, USA to review the current state of the science one missions, air quality impacts, and health effects associated with exposures to ultrafine particles[1].[...].Air PollutantsAir PollutionCongresses as TopicEnvironmental MonitoringHealth PolicyHumansParticle SizeParticulate MatterPolicy MakingResearchUnited StatesUnited States Environmental Protection Agencyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/42r1s37darticleInternational Journal of Environmental Research and Public Health, vol 13, iss 11oai:escholarship.org:ark:/13030/qt0080h4932023-10-21T14:32:10Zqt0080h493Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery.Moyo, PhanankosiInvernizzi, LukeMianda, SephoraRudolph, WiehanAndayi, WarrenCrouch, NeilMaharaj, VineshWang, Mingxun2023-10-05The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 hot plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds (IC50 ≤ 1 µM) isolated from these plant orders and families are structurally unique to the legacy antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.Drug-resistanceMalariaNatural productsPhylogeneticsPlants‘Hot’ plantsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0080h493articleNatural Products and Bioprospecting, vol 13, iss 1oai:escholarship.org:ark:/13030/qt31x7t56j2023-10-10T16:43:14Zqt31x7t56jRAIM and Failure Mode Slope: Effects of Increased Number of Measurements and Number of FaultsUwineza, Jean-BernardFarrell, Jay A2023-01-01This article provides a comprehensive analysis of the impact of the increasing number of measurements and the possible increase in the number of faults in multi-constellation Global Navigation Satellite System (GNSS) Receiver Autonomous Integrity Monitoring (RAIM). Residual-based fault detection and integrity monitoring techniques are ubiquitous in linear over-determined sensing systems. An important application is RAIM, as used in multi-constellation GNSS-based positioning. This is a field in which the number of measurements, m, available per epoch is rapidly increasing due to new satellite systems and modernization. Spoofing, multipath, and non-line of sight signals could potentially affect a large number of these signals. This article fully characterizes the impact of measurement faults on the estimation (i.e., position) error, the residual, and their ratio (i.e., the failure mode slope) by analyzing the range space of the measurement matrix and its orthogonal complement. For any fault scenario affecting h measurements, the eigenvalue problem that defines the worst-case fault is expressed and analyzed in terms of these orthogonal subspaces, which enables further analysis. For h>(m-n), where n is the number of estimated variables, it is known that there always exist faults that are undetectable from the residual vector, yielding an infinite value for the failure mode slope. This article uses the range space and its complement to explain: (1) why, for fixed h and n, the failure mode slope decreases with m; (2) why, for a fixed n and m, the failure mode slope increases toward infinity as h increases; (3) why a failure mode slope can become infinite for h≤(m-n). A set of examples demonstrate the results of the paper.Information and Computing SciencesControl EngineeringMechatronics and RoboticsEngineeringnavigationfault detectionRAIMGNSSAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/31x7t56jarticleSensors, vol 23, iss 104947oai:escholarship.org:ark:/13030/qt93k4j92j2023-10-10T16:43:00Zqt93k4j92jOn the prediction of non-CG DNA methylation using machine learningSereshki, SalehLee, NathanOmirou, MichalisFasoula, DionysiaLonardi, Stefano2023-03-29DNA methylation can be detected and measured using sequencing instruments after sodium bisulfite conversion, but experiments can be expensive for large eukaryotic genomes. Sequencing nonuniformity and mapping biases can leave parts of the genome with low or no coverage, thus hampering the ability of obtaining DNA methylation levels for all cytosines. To address these limitations, several computational methods have been proposed that can predict DNA methylation from the DNA sequence around the cytosine or from the methylation level of nearby cytosines. However, most of these methods are entirely focused on CG methylation in humans and other mammals. In this work, we study, for the first time, the problem of predicting cytosine methylation for CG, CHG and CHH contexts on six plant species, either from the DNA primary sequence around the cytosine or from the methylation levels of neighboring cytosines. In this framework, we also study the cross-species prediction problem and the cross-context prediction problem (within the same species). Finally, we show that providing gene and repeat annotations allows existing classifiers to significantly improve their prediction accuracy. We introduce a new classifier called AMPS (annotation-based methylation prediction from sequence) that takes advantage of genomic annotations to achieve higher accuracy.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeBioinformatics and computational biologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/93k4j92jarticleNAR Genomics and Bioinformatics, vol 5, iss 2lqad045oai:escholarship.org:ark:/13030/qt6n23g61x2023-10-10T12:29:28Zqt6n23g61xDiseased and healthy murine local lung strains evaluated using digital image correlationNelson, TMQuiros, KAMDominguez, ECUlu, ANordgren, TMEskandari, M2023-03-01Tissue remodeling in pulmonary disease irreversibly alters lung functionality and impacts quality of life. Mechanical ventilation is amongst the few pulmonary interventions to aid respiration, but can be harmful or fatal, inducing excessive regional (i.e., local) lung strains. Previous studies have advanced understanding of diseased global-level lung response under ventilation, but do not adequately capture the critical local-level response. Here, we pair a custom-designed pressure-volume ventilator with new applications of digital image correlation, to directly assess regional strains in the fibrosis-induced ex-vivo mouse lung, analyzed via regions of interest. We discuss differences between diseased and healthy lung mechanics, such as distensibility, heterogeneity, anisotropy, alveolar recruitment, and rate dependencies. Notably, we compare local and global compliance between diseased and healthy states by assessing the evolution of pressure-strain and pressure-volume curves resulting from various ventilation volumes and rates. We find fibrotic lungs are less-distensible, with altered recruitment behaviors and regional strains, and exhibit disparate behaviors between local and global compliance. Moreover, these diseased characteristics show volume-dependence and rate trends. Ultimately, we demonstrate how fibrotic lungs may be particularly susceptible to damage when contrasted to the strain patterns of healthy counterparts, helping to advance understanding of how ventilator induced lung injury develops.EngineeringBiomedical EngineeringRare DiseasesAcute Respiratory Distress SyndromeLungAssistive TechnologyBioengineering2.1 Biological and endogenous factorsAetiologyRespiratoryMiceAnimalsQuality of LifeRespirationArtificialLung Diseasesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6n23g61xarticleScientific Reports, vol 13, iss 14564oai:escholarship.org:ark:/13030/qt0nv3x74b2023-10-10T11:31:30Zqt0nv3x74bEffects of Pulsed Radiofrequency Source on Cardiac AblationIasiello, MarcelloAndreozzi, AssuntaBianco, NicolaVafai, Kambiz2023-01-01Heart arrhythmia is caused by abnormal electrical conduction through the myocardium, which in some cases, can be treated with heat. One of the challenges is to reduce temperature peaks-by still guaranteeing an efficient treatment where desired-to avoid any healthy tissue damage or any electrical issues within the device employed. A solution might be employing pulsed heat, in which thermal dose is given to the tissue with a variation in time. In this work, pulsed heat is used to modulate induced temperature fields during radiofrequency cardiac ablation. A three-dimensional model of the myocardium, catheter and blood flow is developed. Porous media, heat conduction and Navier-Stokes equations are, respectively, employed for each of the investigated domains. For the electric field, solved via Laplace equation, it is assumed that the electrode is at a fixed voltage. Pulsed heating effects are considered with a cosine time-variable pulsed function for the fixed voltage by constraining the product between this variable and time. Different dimensionless frequencies are considered and applied for different blood flow velocity and sustained voltages. Results are presented for different pulsed conditions to establish if a reasonable ablation zone, known from the obtained temperature profiles, can be obtained without any undesired temperature peaks.EngineeringBiomedical EngineeringCardiovascularHeart Diseaseporous mediabioheatRF catheter ablationpulsating heatBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0nv3x74barticleBioengineering, vol 10, iss 2227oai:escholarship.org:ark:/13030/qt0xn3g68g2023-10-10T09:13:38Zqt0xn3g68gPreparation and Synergy of Supported Ru0 and Pd0 for Rapid Chlorate Reduction at pH 7Gao, JinyuXie, ShaohuaLiu, FudongLiu, Jinyong2023-03-07Chlorate (ClO3-) is a common water pollutant due to its gigantic scale of production, wide applications in agriculture and industry, and formation as a toxic byproduct in various water treatment processes. This work reports on the facile preparation, mechanistic elucidation, and kinetic evaluation of a bimetallic catalyst for highly active ClO3- reduction into Cl-. Under 1 atm H2 and 20 °C, PdII and RuIII were sequentially adsorbed and reduced on a powdered activated carbon support, affording Ru0-Pd0/C from scratch within only 20 min. The Pd0 particles significantly accelerated the reductive immobilization of RuIII as >55% dispersed Ru0 outside Pd0. At pH 7, Ru-Pd/C shows a substantially higher activity of ClO3- reduction (initial turnover frequency >13.9 min-1 on Ru0; rate constant at 4050 L h-1 gmetal-1) than reported catalysts (e.g., Rh/C, Ir/C, Mo-Pd/C) and the monometallic Ru/C. In particular, Ru-Pd/C accomplished the reduction of concentrated 100 mM ClO3- (turnover number > 11,970), whereas Ru/C was quickly deactivated. In the bimetallic synergy, Ru0 rapidly reduces ClO3- while Pd0 scavenges the Ru-passivating ClO2- and restores Ru0. This work demonstrates a simple and effective design for heterogeneous catalysts tailored for emerging water treatment needs.Environmental SciencesEnvironmental ManagementChemical SciencesPalladiumChloratesOxidation-ReductionHydrogen-Ion Concentrationrutheniumpalladiumin situ preparationroom temperaturechloriteX-ray photoelectron spectroscopyscanning transmission electron microscopydispersionapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0xn3g68garticleEnvironmental Science and Technology, vol 57, iss 93962 - 3970oai:escholarship.org:ark:/13030/qt9vf7t0gq2023-10-10T09:06:34Zqt9vf7t0gqThe electronic structure of genome editors from the first principlesNierzwicki, ŁukaszAhsan, MohdPalermo, Giulia2023-03-01Genome editing based on the CRISPR-Cas9 system has paved new avenues for medicine, pharmaceutics, biotechnology, and beyond. This article reports the role of first-principles (ab-initio) molecular dynamics (MD) in the CRISPR-Cas9 revolution, achieving a profound understanding of the enzymatic function and offering valuable insights for enzyme engineering. We introduce the methodologies and explain the use of ab-initio MD simulations to characterize the two-metal dependent mechanism of DNA cleavage in the RuvC domain of the Cas9 enzyme, and how a second catalytic domain, HNH, cleaves the target DNA with the aid of a single metal ion. A detailed description of how ab-initio MD is combined with free-energy methods - i.e., thermodynamic integration and metadynamics - to break and form chemical bonds is given, explaining the use of these methods to determine the chemical landscape and establish the catalytic mechanism in CRISPR-Cas9. The critical role of classical methods is also discussed, explaining theory and application of constant pH MD simulations, used to accurately predict the catalytic residues' protonation states. Overall, first-principles methods are shown to unravel the electronic structure of the Cas9 enzyme, providing valuable insights that can serve for the design of genome editing tools with improved catalytic efficiency or controllable activity.Biological SciencesChemical SciencesPhysical ChemistryBiotechnologyHuman GenomeGenetics1.1 Normal biological development and functioningUnderpinning researchGeneric health relevancemolecular dynamicsQMMMCRISPR-casRNAfree energycatalysisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9vf7t0gqarticleElectronic Structure, vol 5, iss 1014003oai:escholarship.org:ark:/13030/qt58n0b0qb2023-10-10T06:40:42Zqt58n0b0qbGPU-Enhanced DFTB Metadynamics for Efficiently Predicting Free Energies of Biochemical SystemsKumar, AnshumanArantes, Pablo RSaha, AakashPalermo, GiuliaWong, Bryan M2023-01-01Metadynamics calculations of large chemical systems with ab initio methods are computationally prohibitive due to the extensive sampling required to simulate the large degrees of freedom in these systems. To address this computational bottleneck, we utilized a GPU-enhanced density functional tight binding (DFTB) approach on a massively parallelized cloud computing platform to efficiently calculate the thermodynamics and metadynamics of biochemical systems. To first validate our approach, we calculated the free-energy surfaces of alanine dipeptide and showed that our GPU-enhanced DFTB calculations qualitatively agree with computationally-intensive hybrid DFT benchmarks, whereas classical force fields give significant errors. Most importantly, we show that our GPU-accelerated DFTB calculations are significantly faster than previous approaches by up to two orders of magnitude. To further extend our GPU-enhanced DFTB approach, we also carried out a 10 ns metadynamics simulation of remdesivir, which is prohibitively out of reach for routine DFT-based metadynamics calculations. We find that the free-energy surfaces of remdesivir obtained from DFTB and classical force fields differ significantly, where the latter overestimates the internal energy contribution of high free-energy states. Taken together, our benchmark tests, analyses, and extensions to large biochemical systems highlight the use of GPU-enhanced DFTB simulations for efficiently predicting the free-energy surfaces/thermodynamics of large biochemical systems.Chemical SciencesTheoretical and Computational ChemistryDFTBmetadynamicsGPUsfree energiesthermodynamicscloud computingMedicinal and Biomolecular ChemistryOrganic ChemistryMedicinal and biomolecular chemistryOrganic chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/58n0b0qbarticleMolecules, vol 28, iss 31277oai:escholarship.org:ark:/13030/qt7qv9j4c12023-10-10T03:36:02Zqt7qv9j4c1Accelerating Catalytic Oxyanion Reduction with Inert Metal HydroxidesGao, JinyuZhao, QiangTan, ChengXie, ShaohuaYin, YadongLiu, FudongLiu, HaizhouChen, BaoliangLiu, Jinyong2023-01-24Adding CrIII or AlIII salts into the water suspension of platinum group metal (PGM) catalysts accelerated oxyanion pollutant reduction by up to 600%. Our initial attempts of adding K2CrVIO4, K2CrVI2O7, or KCrIII(SO4)2 into Pd/C enhanced BrO3- reduction with 1 atm H2 by 6-fold. Instrument characterizations and kinetic explorations collectively confirmed the immobilization of reduced CrVI as CrIII(OH)3 on the catalyst surface. This process altered the ζ-potentials from negative to positive, thus substantially enhancing the Langmuir-Hinshelwood adsorption equilibrium constant for BrO3- onto Pd/C by 37-fold. Adding AlIII(OH)3 from alum at pH 7 achieved similar enhancements. The Cr-Pd/C and Al-Pd/C showed top-tier efficiency of catalytic performance (normalized with Pd dosage) among all the reported Pd catalysts on conventional and nanostructured support materials. The strategy of adding inert metal hydroxides works for diverse PGMs (palladium and rhodium), substrates (BrO3- and ClO3-), and support materials (carbon, alumina, and silica). This work shows a simple, inexpensive, and effective example of enhancing catalyst activity and saving PGMs for environmental applications.Inorganic ChemistryChemical SciencesAffordable and Clean Energyaluminumchromiumchloratebromatecatalyst supportzeta-potentialX-ray photoelectron spectroscopyscanning transmission electron microscopyEnvironmental Sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7qv9j4c1articleEnvironmental Science and Technology, vol 57, iss 31479 - 1486oai:escholarship.org:ark:/13030/qt8gq2j65g2023-10-10T01:53:15Zqt8gq2j65gFormation of robust bound states of interacting microwave photonsMorvan, AAndersen, TIMi, XNeill, CPetukhov, AKechedzhi, KAbanin, DAMichailidis, AAcharya, RArute, FArya, KAsfaw, AAtalaya, JBardin, JCBasso, JBengtsson, ABortoli, GBourassa, ABovaird, JBrill, LBroughton, MBuckley, BBBuell, DABurger, TBurkett, BBushnell, NChen, ZChiaro, BCollins, RConner, PCourtney, WCrook, ALCurtin, BDebroy, DMDel Toro Barba, ADemura, SDunsworth, AEppens, DErickson, CFaoro, LFarhi, EFatemi, RFlores Burgos, LForati, EFowler, AGFoxen, BGiang, WGidney, CGilboa, DGiustina, MGrajales Dau, AGross, JAHabegger, SHamilton, MCHarrigan, MPHarrington, SDHoffmann, MHong, SHuang, THuff, AHuggins, WJIsakov, SVIveland, JJeffrey, EJiang, ZJones, CJuhas, PKafri, DKhattar, TKhezri, MKieferová, MKim, SKitaev, AYKlimov, PVKlots, ARKorotkov, ANKostritsa, FKreikebaum, JMLandhuis, DLaptev, PLau, K-MLaws, LLee, JLee, KWLester, BJLill, ATLiu, WLocharla, AMalone, FMartin, OMcClean, JRMcEwen, MMeurer Costa, BMiao, KCMohseni, MMontazeri, SMount, EMruczkiewicz, WNaaman, ONeeley, M2022-12-08Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.Quantum PhysicsPhysical SciencesPhotonsMicrowavesElectronsFees and ChargesReproductionGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8gq2j65garticleNature, vol 612, iss 7939240 - 245oai:escholarship.org:ark:/13030/qt47c9p5cn2023-10-10T01:51:35Zqt47c9p5cnNPOmix: A machine learning classifier to connect mass spectrometry fragmentation data to biosynthetic gene clustersLeão, Tiago FWang, Mingxunda Silva, RicardoGurevich, AlexeyBauermeister, AnelizeGomes, Paulo Wender PBrejnrod, AskerGlukhov, EvgeniaAron, Allegra TLouwen, Joris JRKim, Hyun WooReher, RaphaelFiore, Marli Fvan der Hooft, Justin JJGerwick, LenaGerwick, William HBandeira, NunoDorrestein, Pieter CTelenti, Amalio2022-11-01Microbial specialized metabolites are an important source of and inspiration for many pharmaceuticals, biotechnological products and play key roles in ecological processes. Untargeted metabolomics using liquid chromatography coupled with tandem mass spectrometry is an efficient technique to access metabolites from fractions and even environmental crude extracts. Nevertheless, metabolomics is limited in predicting structures or bioactivities for cryptic metabolites. Efficiently linking the biosynthetic potential inferred from (meta)genomics to the specialized metabolome would accelerate drug discovery programs by allowing metabolomics to make use of genetic predictions. Here, we present a k-nearest neighbor classifier to systematically connect mass spectrometry fragmentation spectra to their corresponding biosynthetic gene clusters (independent of their chemical class). Our new pattern-based genome mining pipeline links biosynthetic genes to metabolites that they encode for, as detected via mass spectrometry from bacterial cultures or environmental microbiomes. Using paired datasets that include validated genes-mass spectral links from the Paired Omics Data Platform, we demonstrate this approach by automatically linking 18 previously known mass spectra (17 for which the biosynthesis gene clusters can be found at the MIBiG database plus palmyramide A) to their corresponding previously experimentally validated biosynthetic genes (e.g., via nuclear magnetic resonance or genetic engineering). We illustrated a computational example of how to use our Natural Products Mixed Omics (NPOmix) tool for siderophore mining that can be reproduced by the users. We conclude that NPOmix minimizes the need for culturing (it worked well on microbiomes) and facilitates specialized metabolite prioritization based on integrative omics mining.Analytical ChemistryBiological SciencesBiomedical and Clinical SciencesChemical SciencesMedical Biochemistry and MetabolomicsBiotechnologyGeneticsBioengineeringbiosynthetic gene clustersgenomicsmachine learningmass spectrometryspecialized metabolitesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/47c9p5cnarticlePNAS Nexus, vol 1, iss 5pgac257oai:escholarship.org:ark:/13030/qt6gw8n0072023-10-09T23:48:06Zqt6gw8n007Robust dual‐module velocity‐selective arterial spin labeling (dm‐VSASL) with velocity‐selective saturation and inversionGuo, Jia2023-03-01PurposeCompared to conventional arterial spin labeling (ASL) methods, velocity-selective ASL (VSASL) is more sensitive to artifacts from eddy currents, diffusion attenuation, and motion. Background suppression is typically suboptimal in VSASL, especially of CSF. As a result, the temporal SNR and quantification accuracy of VSASL are compromised, hindering its application despite its advantage of being delay-insensitive.MethodsA novel dual-module VSASL (dm-VSASL) strategy is developed to improve the SNR efficiency and the temporal SNR with a more balanced gradient configuration in the label/control image acquisition. This strategy applies for both VS saturation (VSS) and VS inversion (VSI) labeling. The dm-VSASL schemes were compared with single-module labeling and a previously developed multi-module schemes for the SNR performance, background suppression efficacy, and sensitivity to artifacts in simulation and in vivo experiments, using pulsed ASL as the reference.ResultsDm-VSASL enabled more robust labeling and efficient backgroud suppre across brain tissues, especially of CSF, resulting in significantly reduced artifacts and improved temporal SNR. Compared to single-module labeling, dm-VSASL significantly improved the temporal SNR in gray (by 90.8% and 94.9% for dm-VSS and dm-VSI, respectively; P < 0.001) and white (by 41.5% and 55.1% for dm-VSS and dm-VSI, respectively; P < 0.002) matter. Dm-VSI also improved the SNR of VSI by 5.4% (P = 0.018).ConclusionDm-VSASL can significantly improve the robustness of VS labeling, reduce artifacts, and allow efficient background suppression. When implemented with VSI, it provides the highest SNR efficiency among VSASL methods. Dm-VSASL is a powerful ASL method for robust, accurate, and delay-insensitive perfusion mapping.EngineeringBiomedical EngineeringMagnetic Resonance AngiographySpin LabelsCerebrovascular CirculationArteriesComputer SimulationBrainarterial spin labelingdiffusion attenuationeddy currentSNR efficiencyvelocity-selective inversionvelocity-selective saturationNuclear Medicine & Medical ImagingBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6gw8n007articleMagnetic Resonance in Medicine, vol 89, iss 31026 - 1040oai:escholarship.org:ark:/13030/qt6170f2h82023-10-09T21:45:43Zqt6170f2h8Principles of target DNA cleavage and the role of Mg2+ in the catalysis of CRISPR–Cas9Nierzwicki, ŁukaszEast, Kyle WBinz, Jonas MHsu, Rohaine VAhsan, MohdArantes, Pablo RSkeens, ErinPacesa, MartinJinek, MartinLisi, George PPalermo, Giulia2022-10-01At the core of the CRISPR-Cas9 genome-editing technology, the endonuclease Cas9 introduces site-specific breaks in DNA. However, precise mechanistic information to ameliorating Cas9 function is still missing. Here, multi-microsecond molecular dynamics, free-energy and multiscale simulations are combined with solution NMR and DNA cleavage experiments to resolve the catalytic mechanism of target DNA cleavage. We show that the conformation of an active HNH nuclease is tightly dependent on the catalytic Mg2+, unveiling its cardinal structural role. This activated Mg2+-bound HNH is consistently described through molecular simulations, solution NMR and DNA cleavage assays, revealing also that the protonation state of the catalytic H840 is strongly affected by active site mutations. Finally, ab-initio QM(DFT)/MM simulations and metadynamics establish the catalytic mechanism, showing that the catalysis is activated by H840 and completed by K866, rationalising DNA cleavage experiments. This information is critical to enhance the enzymatic function of CRISPR-Cas9 toward improved genome-editing.Inorganic ChemistryChemical SciencesPhysical ChemistryGeneticsUnderpinning research1.1 Normal biological development and functioningGeneric health relevanceInorganic chemistryPhysical chemistryChemical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6170f2h8articleNature Catalysis, vol 5, iss 10912 - 922oai:escholarship.org:ark:/13030/qt7zz7n6n32023-10-09T21:35:38Zqt7zz7n6n3Charge-density-wave phase transitions in quasi-2D 1T-TaS2/h-BN heterostructure devicesBrown, Jonas OTaheri, MaedehSesing, Nicholas RSalguero, Tina TKargar, FariborzBalandin, Alexander AKobayashi, Nobuhiko PTalin, A AlecDavydov, Albert VIslam, M Saif2022-01-01Physical SciencesCondensed Matter Physicscharge-density-wavesde-pinning2D van der Waals materialstransitional metal dichalcogenidesTaS2Communications engineeringElectronicssensors and digital hardwareAtomicmolecular and optical physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7zz7n6n3articleoai:escholarship.org:ark:/13030/qt0q98g82g2023-10-09T17:26:18Zqt0q98g82gErythrocyte-Derived Nanoparticles with Folate Functionalization for Near Infrared Pulsed Laser-Mediated Photo-Chemotherapy of TumorsMac, Jenny TVankayala, RavirajLee, Chi-HuaAnvari, Bahman2022-01-01Despite its common side effects and varying degrees of therapeutic success, chemotherapy remains the gold standard method for treatment of cancer. Towards developing a new therapeutic approach, we have engineered nanoparticles derived from erythrocytes that contain indocyanine green as a photo-activated agent that enables near infrared photothermal heating, and doxorubicin hydrochloride (DOX) as a chemotherapeutic drug. We hypothesize that milliseconds pulsed laser irradiation results in rapid heating and photo-triggered release of DOX, providing a dual photo-chemo therapeutic mechanism for tumor destruction. Additionally, the surface of the nanoparticles is functionalized with folate to target the folate receptor-α on tumor cells to further enhance the therapeutic efficacy. Using non-contract infrared radiometry and absorption spectroscopy, we have characterized the photothermal response and photostability of the nanoparticles to pulsed laser irradiation. Our in vitro studies show that these nanoparticles can mediate photo-chemo killing of SKOV3 ovarian cancer cells when activated by pulsed laser irradiation. We further demonstrate that this dual photo-chemo therapeutic approach is effective in reducing the volume of tumor implants in mice and elicits an apoptotic response. This treatment modality presents a promising approach in destruction of small tumor nodules.Biochemistry and Cell BiologyBiological SciencesMedicinal and Biomolecular ChemistryChemical SciencesMicrobiologyBioengineeringNanotechnologyCancer5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsAnimalsCell LineTumorDoxorubicinErythrocytesFolic AcidHyperthermiaInducedIndocyanine GreenLasersMiceNanoparticlesNeoplasmsPhototherapybiomimeticscancerdrug deliverylaser therapynanotechnologyphotothermal therapyred blood cellsOther Chemical SciencesGeneticsOther Biological SciencesChemical PhysicsBiochemistry and cell biologyMedicinal and biomolecular chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0q98g82garticleInternational Journal of Molecular Sciences, vol 23, iss 1810295oai:escholarship.org:ark:/13030/qt7px9x65b2023-10-09T12:29:57Zqt7px9x65bGEARing smart environments for pediatric motor rehabilitationKokkoni, ElenaMavroudi, EffrosyniZehfroosh, AshkanGalloway, James CVidal, RenèHeinz, JeffreyTanner, Herbert G2020-12-01BACKGROUND:There is a lack of early (infant) mobility rehabilitation approaches that incorporate natural and complex environments and have the potential to concurrently advance motor, cognitive, and social development. The Grounded Early Adaptive Rehabilitation (GEAR) system is a pediatric learning environment designed to provide motor interventions that are grounded in social theory and can be applied in early life. Within a perceptively complex and behaviorally natural setting, GEAR utilizes novel body-weight support technology and socially-assistive robots to both ease and encourage mobility in young children through play-based, child-robot interaction. This methodology article reports on the development and integration of the different system components and presents preliminary evidence on the feasibility of the system. METHODS:GEAR consists of the physical and cyber components. The physical component includes the playground equipment to enrich the environment, an open-area body weight support (BWS) device to assist children by partially counter-acting gravity, two mobile robots to engage children into motor activity through social interaction, and a synchronized camera network to monitor the sessions. The cyber component consists of the interface to collect human movement and video data, the algorithms to identify the children's actions from the video stream, and the behavioral models for the child-robot interaction that suggest the most appropriate robot action in support of given motor training goals for the child. The feasibility of both components was assessed via preliminary testing. Three very young children (with and without Down syndrome) used the system in eight sessions within a 4-week period. RESULTS:All subjects completed the 8-session protocol, participated in all tasks involving the selected objects of the enriched environment, used the BWS device and interacted with the robots in all eight sessions. Action classification algorithms to identify early child behaviors in a complex naturalistic setting were tested and validated using the video data. Decision making algorithms specific to the type of interactions seen in the GEAR system were developed to be used for robot automation. CONCLUSIONS:Preliminary results from this study support the feasibility of both the physical and cyber components of the GEAR system and demonstrate its potential for use in future studies to assess the effects on the co-development of the motor, cognitive, and social systems of very young children with mobility challenges.EngineeringBiomedical and Clinical SciencesNeurosciencesBiomedical EngineeringPediatricRehabilitationBioengineeringAssistive TechnologyClinical ResearchBehavioral and Social ScienceAlgorithmsChildPreschoolDevelopmental DisabilitiesDown SyndromeFemaleHumansInfantInterpersonal RelationsMaleMobility LimitationMotor ActivityOrthotic DevicesRoboticsBody weight supportHuman-robot interactionActivity recognitionDecision makingPediatric rehabilitationBiomedical engineeringpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7px9x65barticleJournal of NeuroEngineering and Rehabilitation, vol 17, iss 116oai:escholarship.org:ark:/13030/qt88s522sc2023-10-09T12:12:22Zqt88s522scA hybrid inorganic–biological artificial photosynthesis system for energy-efficient food productionHann, Elizabeth COvera, SeanHarland-Dunaway, MarcusNarvaez, Andrés FLe, Dang NOrozco-Cárdenas, Martha LJiao, FengJinkerson, Robert E2022-06-01Artificial photosynthesis systems are proposed as an efficient alternative route to capture CO2 to produce additional food for growing global demand. Here a two-step CO2 electrolyser system was developed to produce a highly concentrated acetate stream with a 57% carbon selectivity (CO2 to acetate), allowing its direct use for the heterotrophic cultivation of yeast, mushroom-producing fungus and a photosynthetic green alga, in the dark without inputs from biological photosynthesis. An evaluation of nine crop plants found that carbon from exogenously supplied acetate incorporates into biomass through major metabolic pathways. Coupling this approach to existing photovoltaic systems could increase solar-to-food energy conversion efficiency by about fourfold over biological photosynthesis, reducing the solar footprint required. This technology allows for a reimagination of how food can be produced in controlled environments.AgricultureLand and Farm ManagementAgriculturalVeterinary and Food SciencesFood SciencesAffordable and Clean EnergyAgricultureland and farm managementFood sciencesCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/88s522scarticleNature Food, vol 3, iss 6461 - 471oai:escholarship.org:ark:/13030/qt1cf312gx2023-10-09T12:07:25Zqt1cf312gxProactive demand-side participation: Centralized versus transactive demand-Supply coordinationOstadijafari, MohammadBedoya, Juan CarlosWang, WeiDubey, AnamikaLiu, Chen-ChingYu, Nanpeng2022-05-01EngineeringElectrical EngineeringProactive demand-side participationDemand flexibilityJoint demand-supply coordinationProsumersElectrical and Electronic EngineeringEnergyElectrical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1cf312gxarticleoai:escholarship.org:ark:/13030/qt3cn3h51g2023-10-09T11:09:04Zqt3cn3h51gSecrecy Throughput of ANECE Assisted Transmission of Information in Finite BlocklengthZabir, IshmamSwami, AnanthramHua, Yingbo2022-04-13Theory Of ComputationInformation and Computing SciencesCommunications EngineeringEngineeringFinite blocklengthphysical layer securitysecrecy throughputfull-duplexultra-reliable low-latency communicationsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3cn3h51garticleoai:escholarship.org:ark:/13030/qt89j1q95q2023-10-09T11:03:02Zqt89j1q95qNonlocal pseudopotential energy density functional for orbital-free density functional theoryXu, QiangMa, ChengMi, WenhuiWang, YanchaoMa, Yanming2022-01-01Orbital-free density functional theory (OF-DFT) is an electronic structure method with a low computational cost that scales linearly with the number of simulated atoms, making it suitable for large-scale material simulations. It is generally considered that OF-DFT strictly requires the use of local pseudopotentials, rather than orbital-dependent nonlocal pseudopotentials, for the calculation of electron-ion interaction energies, as no orbitals are available. This is unfortunate situation since the nonlocal pseudopotentials are known to give much better transferability and calculation accuracy than local ones. We report here the development of a theoretical scheme that allows the direct use of nonlocal pseudopotentials in OF-DFT. In this scheme, a nonlocal pseudopotential energy density functional is derived by the projection of nonlocal pseudopotential onto the non-interacting density matrix (instead of "orbitals") that can be approximated explicitly as a functional of electron density. Our development defies the belief that nonlocal pseudopotentials are not applicable to OF-DFT, leading to the creation for an alternate theoretical framework of OF-DFT that works superior to the traditional approach.Chemical SciencesPhysical ChemistryTheoretical and Computational Chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/89j1q95qarticleNature Communications, vol 13, iss 11385oai:escholarship.org:ark:/13030/qt2rf1260g2023-10-09T10:18:11Zqt2rf1260gExploring the Unmet Need for Technology to Promote Motor Ability in Children Younger Than 5 Years of Age: A Systematic ReviewArnold, Amanda JHaworth, Joshua LMoran, Victor OlivaresAbulhasan, AhmadSteinbuch, NoahKokkoni, Elena2020-06-01ObjectiveTo (1) identify types of technology that promote motor ability in children younger than 5 years of age, (2) report on the type of support these devices provide, and (3) evaluate their potential for use in the community (outside of the laboratory or clinic).Data sourcesA literature search of PubMed was conducted in February 2019 using specific terms, including child, rehabilitation, movement, and instrumentation.Study selectionThe search yielded 451 peer-reviewed articles, which were screened by multiple reviewers. Articles that described the use of devices for the purpose of motor rehabilitation and/or assistance (regardless of device type or body part targeted) in the age range of 0-5 years were eligible for inclusion.Data extractionIn conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, final stage data extraction consisted of full text readings where each article was reviewed twice by 3 independent reviewers.Data synthesisAbout half of the devices available (46%) for children younger than 5 years of age are orthotics and corrective casting devices. There are more facilitative (ie, power mobility devices) than inhibitive (ie, casting) technologies being used. Approximately 60% of the devices are designed for use by a single body part. Walking is the most common motor skill addressed. Although most of the devices were used to some degree outside of the laboratory or clinic, most of the devices available are considered investigative and are not available for commercial purchase.ConclusionsMany types of pediatric devices to assist movement exist, but the current scope of employed devices is limited. There is a need for developing technology that allows for, if not supports, high-dosage, early, and variable motor practice that can take place in community settings.Allied Health and Rehabilitation ScienceHealth SciencesRehabilitationAssistive TechnologyPediatricBioengineeringChildDIYDo-It-YourselfInfantMotor skillsTechnologyAllied health and rehabilitation scienceapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2rf1260garticleArchives of Rehabilitation Research and Clinical Translation, vol 2, iss 2100051oai:escholarship.org:ark:/13030/qt2j8486rk2023-10-09T09:03:42Zqt2j8486rkThe potential of plant proteins as antifungal agents for agricultural applicationsChiu, TiffanyPoucet, TheoLi, Yanran2022-12-01Fungal pathogens induce a variety of diseases in both plants and post-harvest food crops, resulting in significant crop losses for the agricultural industry. Although the usage of chemical-based fungicides is the most common way to control these diseases, they damage the environment, have the potential to harm human and animal life, and may lead to resistant fungal strains. Accordingly, there is an urgent need for diverse and effective agricultural fungicides that are environmentally- and eco-friendly. Plants have evolved various mechanisms in their innate immune system to defend against fungal pathogens, including soluble proteins secreted from plants with antifungal activities. These proteins can inhibit fungal growth and infection through a variety of mechanisms while exhibiting diverse functionality in addition to antifungal activity. In this mini review, we summarize and discuss the potential of using plant antifungal proteins for future agricultural applications from the perspective of bioengineering and biotechnology.MicrobiologyBiological SciencesInfectious DiseasesInfectionZero HungerBiochemistry and cell biologyBioinformatics and computational biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2j8486rkarticleSynthetic and Systems Biotechnology, vol 7, iss 41075 - 1083oai:escholarship.org:ark:/13030/qt00v0358t2023-10-09T08:01:55Zqt00v0358tVelocity‐selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementationQin, QinAlsop, David CBolar, Divya SHernandez‐Garcia, LuisMeakin, JamesLiu, DapengNayak, Krishna SSchmid, SophieOsch, Matthias JPWong, Eric CWoods, Joseph GZaharchuk, GregZhao, Moss YZun, ZunghoGuo, JiaGroup, the ISMRMPerfusion Study2022-10-01This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.EngineeringBiomedical EngineeringBiomedical ImagingNeurosciencesCerebrovascular CirculationMagnetic Resonance AngiographyMagnetic Resonance ImagingPerfusionSpin Labelsarterial spin labelingarterial transit delaycerebral blood flowperfusionvelocity selective arterial spin labelingvelocity selectivityISMRMPerfusion Study GroupNuclear Medicine & Medical ImagingBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/00v0358tarticleMagnetic Resonance in Medicine, vol 88, iss 41528 - 1547oai:escholarship.org:ark:/13030/qt0w8735w72023-10-09T07:49:02Zqt0w8735w7Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptorGuo, XuanmingAsthana, PallaviGurung, SusmaZhang, ShuoWong, Sheung Kin KenFallah, SamaneChow, Chi Fung WillisChe, SijiaZhai, LixiangWang, ZeningGe, XinJiang, ZhixinWu, JiayanZhang, YijingWu, XiaoyuXu, KeyangLin, Cheng YuanKwan, Hiu YeeLyu, AipingZhou, ZhongjunBian, Zhao-XiangWong, Hoi Leong Xavier2022-01-01Insulin sensitivity progressively declines with age. Currently, the mechanism underlying age-associated insulin resistance remains unknown. Here, we identify membrane-bound matrix metalloproteinase 14 (MT1-MMP/MMP14) as a central regulator of insulin sensitivity during ageing. Ageing promotes MMP14 activation in insulin-sensitive tissues, which cleaves Insulin Receptor to suppress insulin signaling. MT1-MMP inhibition restores Insulin Receptor expression, improving insulin sensitivity in aged mice. The cleavage of Insulin Receptor by MT1-MMP also contributes to obesity-induced insulin resistance and inhibition of MT1-MMP activities normalizes metabolic dysfunctions in diabetic mouse models. Conversely, overexpression of MT1-MMP in the liver reduces the level of Insulin Receptor, impairing hepatic insulin sensitivity in young mice. The soluble Insulin Receptor and circulating MT1-MMP are positively correlated in plasma from aged human subjects and non-human primates. Our findings provide mechanistic insights into regulation of insulin sensitivity during physiological ageing and highlight MT1-MMP as a promising target for therapeutic avenue against diabetes.Biochemistry and Cell BiologyBiomedical and Clinical SciencesBiological SciencesObesityPreventionDiabetesAetiology2.1 Biological and endogenous factorsMetabolic and endocrineAge FactorsAnimalsHumansInsulinInsulin ResistanceMatrix Metalloproteinase 14MiceReceptorInsulinSignal Transductionapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0w8735w7articleNature Communications, vol 13, iss 13749oai:escholarship.org:ark:/13030/qt6qk285x02023-10-09T05:54:32Zqt6qk285x0Dynamics and mechanisms of CRISPR-Cas9 through the lens of computational methodsSaha, AakashArantes, Pablo RPalermo, Giulia2022-08-01The clustered regularly interspaced short palindromic repeat (CRISPR) genome-editing revolution established the beginning of a new era in life sciences. Here, we review the role of state-of-the-art computations in the CRISPR-Cas9 revolution, from the early refinement of cryo-EM data to enhanced simulations of large-scale conformational transitions. Molecular simulations reported a mechanism for RNA binding and the formation of a catalytically competent Cas9 enzyme, in agreement with subsequent structural studies. Inspired by single-molecule experiments, molecular dynamics offered a rationale for the onset of off-target effects, while graph theory unveiled the allosteric regulation. Finally, the use of a mixed quantum-classical approach established the catalytic mechanism of DNA cleavage. Overall, molecular simulations have been instrumental in understanding the dynamics and mechanism of CRISPR-Cas9, contributing to understanding function, catalysis, allostery, and specificity.Biochemistry and Cell BiologyBiological SciencesGeneticsUnderpinning research1.1 Normal biological development and functioningGeneric health relevanceCRISPR-Associated Protein 9CRISPR-Cas SystemsDNA CleavageGene EditingMolecular Dynamics SimulationMedicinal and Biomolecular ChemistryBiophysicsBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6qk285x0articleoai:escholarship.org:ark:/13030/qt5hs4n1xt2023-10-09T03:02:46Zqt5hs4n1xtMouse lung mechanical properties under varying inflation volumes and cycling frequenciesQuiros, KAMNelson, TMSattari, SMariano, CAUlu, ADominguez, ECNordgren, TMEskandari, M2022-01-01Respiratory pathologies alter the structure of the lung and impact its mechanics. Mice are widely used in the study of lung pathologies, but there is a lack of fundamental mechanical measurements assessing the interdependent effect of varying inflation volumes and cycling frequency. In this study, the mechanical properties of five male C57BL/6J mice (29-33 weeks of age) lungs were evaluated ex vivo using our custom-designed electromechanical, continuous measure ventilation apparatus. We comprehensively quantify and analyze the effect of loading volumes (0.3, 0.5, 0.7, 0.9 ml) and breathing rates (5, 10, 20 breaths per minute) on pulmonary inflation and deflation mechanical properties. We report means of static compliance between 5.4-16.1 µl/cmH2O, deflation compliance of 5.3-22.2 µl/cmH2O, percent relaxation of 21.7-39.1%, hysteresis of 1.11-7.6 ml•cmH2O, and energy loss of 39-58% for the range of four volumes and three rates tested, along with additional measures. We conclude that inflation volume was found to significantly affect hysteresis, static compliance, starting compliance, top compliance, deflation compliance, and percent relaxation, and cycling rate was found to affect only hysteresis, energy loss, percent relaxation, static compliance and deflation compliance.Medical PhysiologyBiomedical and Clinical SciencesBioengineeringLungRespiratoryAnimalsInsufflationLung ComplianceLung Volume MeasurementsMaleMiceMiceInbred C57BLapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5hs4n1xtarticleScientific Reports, vol 12, iss 17094oai:escholarship.org:ark:/13030/qt3nv4w6ph2023-10-09T02:57:10Zqt3nv4w6phCandyCodes: simple universally unique edible identifiers for confirming the authenticity of pharmaceuticalsGrover, William H2022-01-01Counterfeit or substandard medicines adversely affect the health of millions of people and cost an estimated $200 billion USD annually. Their burden is greatest in developing countries, where the World Health Organization estimates that one in ten medical products are fake. In this work, I describe a simple addition to the existing drug manufacturing process that imparts an edible universally unique physical identifier to each pill, tablet, capsule, caplet, etc. This technique uses nonpareils (also called sprinkles and "hundreds and thousands"), tiny inexpensive multicolor candy spheres that are normally added to other candies or desserts as decorations. If nonpareils are applied at random to a pill immediately after manufacture, the specific pattern they form is unlikely to ever be repeated by random chance; this means that the pattern (or "CandyCode") can be used to uniquely identify the pill and distinguish it from all other pills. By taking a photograph of each CandyCoded pill after manufacture and recording the location and color of each nonpareil, a manufacturer can construct a database containing the CandyCodes of all known-authentic pills they produce. A consumer can then simply use a cellphone to photograph a pill and transfer its image to the manufacturer's server, which determines whether the pill's CandyCode matches a known-good CandyCode in their database (meaning that the pill is authentic) or does not have a match in the database (in which case the consumer is warned that the pill may be counterfeit and should not be consumed). To demonstrate the feasibility of using random particles as universal identifiers, I performed a series of experiments using both real CandyCodes (on commercially produced chocolate candies) and simulated CandyCodes (generated by software). I also developed a simple method for converting a CandyCode photo to a set of strings for convenient storage and retrieval in a database. Even after subjecting CandyCodes to rough handling to simulate shipping conditions, the CandyCodes were still easily verifiable using a cellphone camera. A manufacturer could produce at least [Formula: see text] CandyCoded pills-41 million for each person on Earth-and still be able to uniquely identify each CandyCode. By providing universally-unique IDs that are easy to manufacture but hard to counterfeit, require no alteration of the existing drug formulation and minimal alteration of the manufacturing process, and need only a cameraphone for verification, CandyCodes could play an important role in the fight against fraud in pharmaceuticals and many other products.Biomedical and Clinical SciencesClinical SciencesGeneric health relevanceFraudHumansTabletsWorld Health Organizationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3nv4w6pharticleScientific Reports, vol 12, iss 17452oai:escholarship.org:ark:/13030/qt1ds9g99k2023-10-09T02:44:47Zqt1ds9g99kObservations and parameterization of the effects of barrier height and source-to-barrier distance on concentrations downwind of a roadwayFrancisco, Dianna MHeist, David KVenkatram, AkulaBrouwer, Lydia HPerry, Steven G2022-04-01New results are presented from wind tunnel studies performed at the United States Environmental Protection Agency (U.S. EPA), which include cases with solid roadside barriers of varying heights and cases with varying distances between the line source (roadway) and a 6-m-tall barrier. The Source-to-Barrier Distance cases include seven lanes of traffic with each lane acting as an independent source of continuous emissions along a line (i.e., line source). A mixed-wake algorithm that accounts for barrier effects within a steady-state air dispersion model was updated based on the recent wind tunnel studies. To study the effects of a solid roadside barrier, varying barrier heights and varying distances between the line source and barrier were modeled with the U.S. EPA regulatory air dispersion model AERMOD (v. 21112) using the line-source option that includes an experimental barrier option (RLINEXT). The mixed-wake algorithm reproduced the shape of the vertical concentration profiles observed in the wind tunnel data, including the uniform concentration profile from the ground vertically to a height somewhat greater than the height of the barrier. The algorithm responded appropriately to changes in barrier height and source-to-barrier distance, producing greater reductions in ground-level concentrations for taller barriers and for shorter source-to-barrier distances. Additionally, a rule of thumb that approximates the effect of a downwind barrier was formulated by converting an estimated vertical dispersion into an additional travel distance. The wind tunnel results, the update to the mixed-wake algorithm, and a comparison of the two data sets are described in this paper.Earth SciencesEnvironmental SciencesAtmospheric SciencesEnvironmental ManagementMobile sourcesWind tunnelAERMODDispersion modelingSolid barrierdispersion modelingmobile sourcessolid barrierwind tunnelEnvironmental Science and ManagementEnvironmental EngineeringAtmospheric sciencesEnvironmental managementapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1ds9g99karticleAtmospheric Pollution Research, vol 13, iss 4101385oai:escholarship.org:ark:/13030/qt1qj7w3wn2023-10-09T01:56:58Zqt1qj7w3wnMorphological Characteristics, Hemoglobin Content, and Membrane Mechanical Properties of Red Blood Cell Delivery SystemsLu, ThompsonLee, Chi-HuaAnvari, Bahman2022-04-27Red blood cell (RBC)-based systems are under extensive development as platforms for the delivery of various biomedical agents. While the importance of the membrane biochemical characteristics in relation to circulation kinetics of RBC delivery systems has been recognized, the membrane mechanical properties of such carriers have not been extensively studied. Using optical methods in conjunction with image analysis and mechanical modeling, we have quantified the morphological and membrane mechanical characteristics of RBC-derived microparticles containing the near-infrared cargo indocyanine green (ICG). We find that these particles have a significantly lower surface area, volume, and deformability as compared to normal RBCs. The residual hemoglobin has a spatially distorted distribution in the particles. The membrane bending modulus of the particles is about twofold higher as compared to normal RBCs and exhibits greater resistance to flow. The induced increase in the viscous characteristics of the membrane is dominant over the elastic and entropic effects of ICG. Our results suggest that changes to the membrane mechanical properties are a result of impaired membrane-cytoskeleton attachment in these particles. We provide a mechanistic explanation to suggest that the compromised membrane-cytoskeleton attachment and altered membrane compositional and structural asymmetry induce curvature changes to the membrane, resulting in mechanical remodeling of the membrane. These findings highlight the importance of membrane mechanical properties as an important criterion in the design and engineering of future generations of RBC-based delivery systems to achieve prolonged circulation.Chemical EngineeringEngineeringHematologyBioengineeringCytoskeletonErythrocyte DeformabilityErythrocytesHemoglobinsViscositycell-based therapeuticscell membrane viscoelasticitydrug deliveryerythrocyte engineeringmicroparticlesChemical SciencesNanoscience & NanotechnologyChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1qj7w3wnarticleACS Applied Materials & Interfaces, vol 14, iss 1618219 - 18232oai:escholarship.org:ark:/13030/qt8vp7r1mz2023-10-08T23:42:17Zqt8vp7r1mzEmerging Methods and Applications to Decrypt Allostery in Proteins and Nucleic AcidsArantes, Pablo RPatel, Amun CPalermo, Giulia2022-09-01Many large protein-nucleic acid complexes exhibit allosteric regulation. In these systems, the propagation of the allosteric signaling is strongly coupled to conformational dynamics and catalytic function, challenging state-of-the-art analytical methods. Here, we review established and innovative approaches used to elucidate allosteric mechanisms in these complexes. Specifically, we report network models derived from graph theory and centrality analyses in combination with molecular dynamics (MD) simulations, introducing novel schemes that implement the synergistic use of graph theory with enhanced simulations methods and ab-initio MD. Accelerated MD simulations are used to construct "enhanced network models", describing the allosteric response over long timescales and capturing the relation between allostery and conformational changes. "Ab-initio network models" combine graph theory with ab-initio MD and quantum mechanics/molecular mechanics (QM/MM) simulations to describe the allosteric regulation of catalysis by following the step-by-step dynamics of biochemical reactions. This approach characterizes how the allosteric regulation changes from reactants to products and how it affects the transition state, revealing a tense-to-relaxed allosteric regulation along the chemical step. Allosteric models and applications are showcased for three paradigmatic examples of allostery in protein-nucleic acid complexes: (i) the nucleosome core particle, (ii) the CRISPR-Cas9 genome editing system and (iii) the spliceosome. These methods and applications create innovative protocols to determine allosteric mechanisms in protein-nucleic acid complexes that show tremendous promise for medicine and bioengineering.MicrobiologyBiochemistry and Cell BiologyBiological SciencesAllosteric RegulationCRISPR-Cas SystemsDNAGene EditingMolecular Dynamics SimulationNucleic Acid ConformationNucleosomesProtein ConformationProteinsSpliceosomesmolecular dynamicsgraph theoryCRISPR-Cas9nucleosome core particlespliceosomeMedicinal and Biomolecular ChemistryBiochemistry & Molecular BiologyBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8vp7r1mzarticleJournal of Molecular Biology, vol 434, iss 17167518oai:escholarship.org:ark:/13030/qt043217h42023-10-08T23:25:39Zqt043217h4Human SUMOylation Pathway Is Critical for Influenza B VirusDang, RunruiRodgers, Victor GJGarcía-Sastre, AdolfoLiao, Jiayu2022-01-01The identification and elucidation of host pathways for viral infection are critical for understanding the viral infection processes and novel therapeutics development. Here, for the first time, we discover that the human SUMOylation pathway is essential for the IBV viral life cycle. First, IBV viruses were completely inhibited by a novel SUMOylation specific inhibitor, STE025, discovered from our FRET-based high-throughput screening, and the inhibition was very potent, with IC50~ 0.1 µM in an IBV-induced cell death rescue assay; Second, we determined that the IBV M1 protein was SUMOylated, which was mediated by the SUMOylation E2 conjugation enzyme and the E3 ligase enzyme at very high affinities, of 0.20 µM and 0.22 µM, respectively; Third, the mutation of the IBV M1 SUMOylation site, K21R, completely abolished the viral particle generation, strongly suggesting the requirement of SUMOylation for the IBV life cycle. These results suggest that the blockage of the host human SUMOylation pathway is very effective for IBV inhibition. We therefore propose that the host SUMOylation pathway is a critical host factor for the IBV virus life cycle. The identification and inhibition of critical host factor(s) provide a novel strategy for future anti-viral therapeutics development, such as IBV and other viruses.Biochemistry and Cell BiologyBiological SciencesBiotechnologyEmerging Infectious DiseasesInfectious Diseases2.2 Factors relating to the physical environmentAetiology2.1 Biological and endogenous factorsInfectionCell LineHost-Pathogen InteractionsHumansInfluenza B virusInfluenzaHumanSumoylationUbiquitin-Protein LigasesViral Matrix ProteinsVirus Replicationinfluenza B virus or IBVcritical host factorSUMOylationtherapeuticsMicrobiologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/043217h4articleViruses, vol 14, iss 2314oai:escholarship.org:ark:/13030/qt4xs610m62023-10-08T21:21:06Zqt4xs610m6Siderophores provoke extracellular superoxide production by Arthrobacter strains during carbon sources‐level fluctuationNing, XueLiang, JinsongMen, YujieWang, YuhanChang, YangyangBai, YaohuiLiu, HuijuanWang, AijieZhang, TongQu, Jiuhui2022-02-01Superoxide and other reactive oxygen species (ROS) shape microbial communities and drive the transformation of metals and inorganic/organic matter. Taxonomically diverse bacteria and phytoplankton produce extracellular superoxide during laboratory cultivation. Understanding the physiological reasons for extracellular superoxide production by aerobes in the environment is a crucial question yet not fully solved. Here, we showed that iron-starving Arthrobacter sp. QXT-31 (A. QXT-31) secreted a type of siderophore [deferoxamine (DFO)], which provoked extracellular superoxide production by A. QXT-31 during carbon sources-level fluctuation. Several other siderophores also demonstrated similar effects to A. QXT-31. RNA-Seq data hinted that DFO stripped iron from iron-bearing proteins in electron transfer chain (ETC) of metabolically active A. QXT-31, resulting in electron leakage from the electron-rich (resulting from carbon sources metabolism by A. QXT-31) ETC and superoxide production. Considering that most aerobes secrete siderophore(s) and undergo carbon sources-level fluctuation, the superoxide-generation pathway is likely a common pathway by which aerobes produce extracellular superoxide in the environment, thus influencing the microbial community and cycling of elements. Our results pointed that the ubiquitous siderophore might be the potential driving force for the microbial generation of superoxide and other ROS and revealed the important role of iron physiology in microbial ROS generation.MicrobiologyBiological SciencesArthrobacterCarbonIronSiderophoresSuperoxidesEvolutionary BiologyEcologyapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/4xs610m6articleEnvironmental Microbiology, vol 24, iss 2894 - 904oai:escholarship.org:ark:/13030/qt6dz9f6rg2023-10-08T15:59:04Zqt6dz9f6rgReference-agnostic representation and visualization of pan-genomesLiang, QihuaLonardi, Stefano2021-12-01BackgroundThe pan-genome of a species is the union of the genes and non-coding sequences present in all individuals (cultivar, accessions, or strains) within that species.ResultsHere we introduce PGV, a reference-agnostic representation of the pan-genome of a species based on the notion of consensus ordering. Our experimental results demonstrate that PGV enables an intuitive, effective and interactive visualization of a pan-genome by providing a genome browser that can elucidate complex structural genomic variations.ConclusionsThe PGV software can be installed via conda or downloaded from https://github.com/ucrbioinfo/PGV . The companion PGV browser at http://pgv.cs.ucr.edu can be tested using example bed tracks available from the GitHub page.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeComputational BiologyGenomeGenomicsHumansSoftwareComparative genomicsPan-genomeGenome analysisMathematical SciencesInformation and Computing SciencesBioinformaticsBiological sciencesInformation and computing sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6dz9f6rgarticleBMC Bioinformatics, vol 22, iss 1502oai:escholarship.org:ark:/13030/qt17h254mp2023-10-08T15:28:09Zqt17h254mpElectrochemical Impedance Spectroscopy (EIS): Principles, Construction, and Biosensing ApplicationsMagar, Hend SHassan, Rabeay YAMulchandani, Ashok2021-01-01Electrochemical impedance spectroscopy (EIS) is a powerful technique used for the analysis of interfacial properties related to bio-recognition events occurring at the electrode surface, such as antibody-antigen recognition, substrate-enzyme interaction, or whole cell capturing. Thus, EIS could be exploited in several important biomedical diagnosis and environmental applications. However, the EIS is one of the most complex electrochemical methods, therefore, this review introduced the basic concepts and the theoretical background of the impedimetric technique along with the state of the art of the impedimetric biosensors and the impact of nanomaterials on the EIS performance. The use of nanomaterials such as nanoparticles, nanotubes, nanowires, and nanocomposites provided catalytic activity, enhanced sensing elements immobilization, promoted faster electron transfer, and increased reliability and accuracy of the reported EIS sensors. Thus, the EIS was used for the effective quantitative and qualitative detections of pathogens, DNA, cancer-associated biomarkers, etc. Through this review article, intensive literature review is provided to highlight the impact of nanomaterials on enhancing the analytical features of impedimetric biosensors.Data Management and Data ScienceInformation and Computing SciencesEngineeringBioengineeringNanotechnologyBiosensing TechniquesDielectric SpectroscopyElectrochemical TechniquesNanocompositesReproducibility of Resultselectrochemical impedance spectroscopyimpedimetric biosensorsnanomaterialsAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/17h254mparticleSensors, vol 21, iss 196578oai:escholarship.org:ark:/13030/qt7c93g3tb2023-10-08T15:07:20Zqt7c93g3tbModulation of piezoelectric properties in electrospun PLLA nanofibers for application-specific self-powered stem cell culture platformsTai, YouyiYang, SteveYu, SooyounBanerjee, AihikMyung, Nosang VNam, Jin2021-11-01EngineeringBiomedical EngineeringBioengineeringRegenerative MedicineNanotechnologyStem Cell ResearchPoly(l-lactic acid)ElectrospinningPiezoelectricitySelf-poweredStemcellsMacromolecular and Materials ChemistryMaterials EngineeringMacromolecular and materials chemistryMaterials engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7c93g3tbarticleoai:escholarship.org:ark:/13030/qt7zd1p2922023-10-08T10:32:57Zqt7zd1p292Modeling turbulent transport of aerosols inside rooms using eddy diffusivityVenkatram, AkulaWeil, Jeffrey2021-11-01One major approach to modeling dispersion of pollutants inside confined spaces describes the turbulent transport of material as the product of an eddy diffusivity and the local concentration gradient. This paper examines the applicability of this eddy diffusivity/gradient model by (1) describing the conditions under which this approach is an appropriate representation of turbulent transport, and (2) re-analysis of data provided in studies that have successfully applied gradient transport to describe tracer concentrations. We find that the solutions of the mass conservation equation based on gradient transport provide adequate descriptions of concentration measurements from two studies representative of two types of sources: instantaneous and continuous release of aerosols. We then provide the rationale for the empirical success of the gradient transport model. The solutions of the gradient transport model allow us to examine the relationship between the ventilation rate and the spatial and temporal behavior of the dose of material associated with aerosol releases in a room. We conclude with the associated implications on mitigation of exposure to aerosols such as airborne virus or bacteria.Earth SciencesAtmospheric SciencesBioengineeringAerosolsAir PollutionIndoorVentilationairborne transmissioneddy diffusivitygradient transportIndoor air pollutionturbulent transport in roomsEngineeringMedical and Health SciencesBuilding & ConstructionEarth sciencesHealth sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7zd1p292articleIndoor Air, vol 31, iss 61886 - 1895oai:escholarship.org:ark:/13030/qt7658g15x2023-10-08T09:56:34Zqt7658g15xAn unrecognized inertial force induced by flow curvature in microfluidicsAgarwal, SiddhanshChan, Fan KiatRallabandi, BhargavGazzola, MattiaHilgenfeldt, Sascha2021-07-20Modern inertial microfluidics routinely employs oscillatory flows around localized solid features or microbubbles for controlled, specific manipulation of particles, droplets, and cells. It is shown that theories of inertial effects that have been state of the art for decades miss major contributions and strongly underestimate forces on small suspended objects in a range of practically relevant conditions. An analytical approach is presented that derives a complete set of inertial forces and quantifies them in closed form as easy-to-use equations of motion, spanning the entire range from viscous to inviscid flows. The theory predicts additional attractive contributions toward oscillating boundaries, even for density-matched particles, a previously unexplained experimental observation. The accuracy of the theory is demonstrated against full-scale, three-dimensional direct numerical simulations throughout its range.Fluid Mechanics and Thermal EngineeringEngineeringinertial microfluidicsoscillatory flowsparticle manipulationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7658g15xarticleProceedings of the National Academy of Sciences of the United States of America, vol 118, iss 29e2103822118oai:escholarship.org:ark:/13030/qt683764pv2023-10-08T08:48:42Zqt683764pvFINER: enhancing the prediction of tissue-specific functions of isoforms by refining isoform interaction networksChen, HaoShaw, DipanBu, DongboJiang, Tao2021-04-09Annotating the functions of gene products is a mainstay in biology. A variety of databases have been established to record functional knowledge at the gene level. However, functional annotations at the isoform resolution are in great demand in many biological applications. Although critical information in biological processes such as protein-protein interactions (PPIs) is often used to study gene functions, it does not directly help differentiate the functions of isoforms, as the 'proteins' in the existing PPIs generally refer to 'genes'. On the other hand, the prediction of isoform functions and prediction of isoform-isoform interactions, though inherently intertwined, have so far been treated as independent computational problems in the literature. Here, we present FINER, a unified framework to jointly predict isoform functions and refine PPIs from the gene level to the isoform level, enabling both tasks to benefit from each other. Extensive computational experiments on human tissue-specific data demonstrate that FINER is able to gain at least 5.16% in AUC and 15.1% in AUPRC for functional prediction across multiple tissues by refining noisy PPIs, resulting in significant improvement over the state-of-the-art methods. Some in-depth analyses reveal consistency between FINER's predictions and the tissue specificity as well as subcellular localization of isoforms.Biochemistry and Cell BiologyBioinformatics and Computational BiologyBiological SciencesGeneticsUnderpinning research1.1 Normal biological development and functioningGeneric health relevanceBioinformatics and computational biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/683764pvarticleNAR Genomics and Bioinformatics, vol 3, iss 2lqab057-oai:escholarship.org:ark:/13030/qt5jw9k6k02023-10-08T07:30:58Zqt5jw9k6k0Exploring the potential of engineering polygalacturonase‐inhibiting protein as an ecological, friendly, and nontoxic pest control agentChiu, TiffanyBehari, AnitaChartron, Justin WPutman, AlexanderLi, Yanran2021-08-01In plants, polygalacturonase-inhibiting proteins (PGIPs) play critical roles for resistance to fungal disease by inhibiting the pectin-depolymerizing activity of endopolygalacturonases (PGs), one type of enzyme secreted by pathogens that compromises plant cell walls and leaves the plant susceptible to disease. Here, the interactions between PGIPs from Phaseolus vulgaris (PvPGIP1 and PvPGIP2) and PGs from Aspergillus niger (AnPG2), Botrytis cinerea (BcPG1 and BcPG2), and Fusarium moniliforme (FmPG3) were reconstituted through a yeast two hybrid (Y2H) system to investigate the inhibition efficiency of various PvPGIP1 and 2 truncations and mutants. We found that tPvPGIP2_5-8, which contains LRR5 to LRR8 and is only one-third the size of the full length peptide, exhibits the same level of interactions with AnPG and BcPGs as the full length PvPGIP2 via Y2H. The inhibitory activities of tPvPGIP2_5-8 on the growth of A. niger and B. cinerea were then examined and confirmed on pectin agar. On pectin assays, application of both full length PvPGIP2 and tPvPGIP2_5-8 clearly slows down the growth of A. niger and B. cinerea. Investigation on the sequence-function relationships of PGIP utilizing a combination of site directed mutagenesis and a variety of peptide truncations suggests that LRR5 could have the most essential structural feature for the inhibitory activities, and may be a possible target for the future engineering of PGIP with enhanced activity. This study highlights the potential of plant-derived PGIPs as a candidate for future in planta evaluation as a pest control agent.Plant BiologyBiological SciencesAspergillus nigerFungal ProteinsFusariumPest ControlBiologicalPhaseolusPlant ProteinsPolygalacturonasepest controlpolygalacturonase-inhibiting proteinBiotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5jw9k6k0articleBiotechnology and Bioengineering, vol 118, iss 83200 - 3214oai:escholarship.org:ark:/13030/qt96j0j7wr2023-10-08T06:54:31Zqt96j0j7wrNear Infrared Fluorescence Imaging of Intraperitoneal Ovarian Tumors in Mice Using Erythrocyte-Derived Optical Nanoparticles and Spatially-Modulated IlluminationBurns, Joshua MShafer, EliseVankayala, RavirajKundra, VikasAnvari, Bahman2021-01-01Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstration of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0-0.5 mm-1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demonstrate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm-1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast.Medical BiotechnologyBiomedical and Clinical SciencesOncology and CarcinogenesisRare DiseasesBioengineeringNanotechnologyOvarian CancerBiomedical ImagingCancerbiomaterialsbiomimeticsindocyanine greennanomaterialsred blood cellsOncology and carcinogenesisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/96j0j7wrarticleCancers, vol 13, iss 112544oai:escholarship.org:ark:/13030/qt3s2412wb2023-10-08T06:00:39Zqt3s2412wbRecovery trajectories and community resilience of biofilms in receiving rivers after wastewater treatment plant upgradeLin, HuiWang, QiaojuanZhou, JieWang, DonglinMen, YujieBai, YaohuiQu, Jiuhui2021-08-01Wastewater treatment plant (WWTP) upgrades can reduce both nutrient and micropollutant emissions into receiving rivers, thus modifying the composition and function of biological communities. However, how microbial communities vary and whether they can be restored to levels found in less-polluted rivers remains uncertain. Aquatic biofilms are sensitive to environmental change and respond rapidly to bottom-up pressure. Thus, we used 12 flumes configured in three experimental treatments to mimic the dynamic processes of biofilm microbial communities occurring in a wastewater-receiving river following WWTP upgrade, with rivers containing two levels of nutrients and micropollutants used as references. We compared the biofilm microbial biomass, carbon source utilization, and community composition among the three "blocks". Results showed that the metabolic patterns of the carbon sources and composition of the biofilm bacterial communities in the flumes mimicking a receiving river with WWTP upgrade recovered over time to those mimicking a less-disturbed river. The restoration of potential carboxylic acid-consuming denitrifying bacteria (i.e., Zoogloea, Comamonas, Dechloromonas, and Acinetobacter) likely played a significant role in this process. Combining quantitative analysis of the denitrification genes nirS and nosZ, we confirmed that the denitrification function of the river biofilms recovered after WWTP upgrade, consistent with our previous field investigation.MicrobiologyBiological SciencesBacteriaBiofilmsRiversWastewaterWater PurificationWastewater treatment plant upgradeCarboxylic acid-consuming bacteriaRecoveryDenitrificationChemical SciencesEnvironmental SciencesToxicologyBiological sciencesChemical sciencesEnvironmental sciencesapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/3s2412wbarticleoai:escholarship.org:ark:/13030/qt027570d32023-10-08T04:22:53Zqt027570d3Group Refractive Index of Nanocrystalline Yttria-Stabilized Zirconia Transparent Cranial ImplantsHalaney, David LKatta, NiteshFallah, HamidrezaAguilar, GuillermoMilner, Thomas E2021-01-01Transparent "Window to the Brain" (WttB) cranial implants made from a biocompatible ceramic, nanocrystalline Yttria-Stabilized Zirconia (nc-YSZ), were recently reported. These reports demonstrated chronic brain imaging across the implants in mice using optical coherence tomography (OCT) and laser speckle imaging. However, optical properties of these transparent cranial implants are neither completely characterized nor completely understood. In this study, we measure optical properties of the implant using a swept source OCT system with a spectral range of 136 nm centered at 1,300 nm to characterize the group refractive index of the nc-YSZ window, over a narrow range of temperatures at which the implant may be used during imaging or therapy (20-43°C). Group refractive index was found to be 2.1-2.2 for OCT imaging over this temperature range. Chromatic dispersion for this spectral range was observed to vary over the sample, sometimes flipping signs between normal and anomalous dispersion. These properties of nc-YSZ should be considered when designing optical systems and procedures that propagate light through the window, and when interpreting OCT brain images acquired across the window.Biomedical and Clinical SciencesDentistryNeurosciencesBioengineeringBiomedical Imagingbrainchromatic dispersioncranial implantgroup refractive indeximagingoptical coherence tomographywindow to the brainOther Biological SciencesBiomedical EngineeringMedical BiotechnologyIndustrial biotechnologyMedical biotechnologyBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/027570d3articleoai:escholarship.org:ark:/13030/qt8z25682g2023-10-08T02:19:56Zqt8z25682gCometabolism of 17α-ethynylestradiol by nitrifying bacteria depends on reducing power availability and leads to elevated nitric oxide formationSheng, QiYi, MingMen, YujieLu, Huijie2021-08-0117α-ethynylestradiol (EE2) is a priority emerging contaminant (EC) in diverse environments that can be cometabolized by ammonia oxidizing bacteria (AOB). However, its transformation kinetics and the underlying molecular mechanism are unclear. In this study, kinetic parameters, including maximum specific EE2 transformation rate, EE2 half-saturation coefficient, and EE2transformation capacity of AOBwere obtained by using the model AOB strain, Nitrosomonas europaea 19718. The relationship between EE2 cometabolism and ammonia oxidation was divided into three phases according to reducing power availability, namely "activation", "coupling", and "saturation". Specifically, there was a universal lag of EE2 transformation after ammonia oxidation was initiated, suggesting that sufficient reducing power (approximately 0.95 ± 0.06 mol NADH/L) was required to activate EE2 cometabolism. Interestingly, nitric oxide emission increased by 12 ± 2% during EE2 cometabolism, along with significantly upregulated nirK cluster genes. The findings are of importance to understanding the cometabolic behavior and mechanism of EE2 in natural and engineered environments. Maintaining relatively high and stable reducing power supply from ammonia oxidation can potentially improve the cometabolic removal of EE2 and other ECs during wastewater nitrification processes.EngineeringEnvironmental EngineeringAmmoniaBacteriaEthinyl EstradiolNitric OxideNitrificationOxidation-ReductionCometabolismalpha-ethynylestradiolReductant modelNitric oxidenirKNitrosomonas europaea17α-ethynylestradiolEnvironmental Sciencesapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/8z25682garticleoai:escholarship.org:ark:/13030/qt04k4f82m2023-10-08T01:43:17Zqt04k4f82mDispersion at the edges of near road noise barriersVenkatram, AkulaHeist, David KPerry, Steven GBrouwer, Lydia2021-02-01This paper presents an analysis of data from a wind tunnel study conducted to examine the dispersion of emissions at the edges of near-road noise barriers. The study is motivated by the concern that a barrier positioned downwind of a roadway may guide highly polluted plumes along the barrier leading to heightened concentrations as the plume spills around and downwind of the barrier end. The wind tunnel database consists of measurements of dispersion around a simulated roadway segment with various noise barrier configurations. Each roadway segment simulated in the wind tunnel had full-scale equivalent dimensions of 135 m long. Barrier segments, 135 m long with a height (H) of 6 m, were located on the downwind side of the source at a distance of 18 m from it (measured perpendicularly from the line source). Examination of the concentration patterns associated with the cases indicates that 1) vertical mixing induced by barriers persists at crosswind distances up to the edge (lateral end) of the barrier and downwind distances of x/H = 10, 2) concentration levels at all heights below z/H = 1 increase towards the edge of the barrier at downwind distances less than x/H = 7, and 3) concentration is well mixed in the vertical at the edge of the barrier, and the levels can be higher than in the middle of the barrier even when the source ends at the edge of the barrier. We have formulated a parameterization that captures the major features of these observations and can be incorporated in models such as RLINE.Earth SciencesEnvironmental SciencesAtmospheric SciencesEnvironmental ManagementNear-road air qualityDispersion modelingWind tunnelNoise barriersEdge effectsEnvironmental Science and ManagementEnvironmental EngineeringAtmospheric sciencesEnvironmental managementapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/04k4f82marticleAtmospheric Pollution Research, vol 12, iss 2367 - 374oai:escholarship.org:ark:/13030/qt7b88r1kz2023-10-08T01:32:00Zqt7b88r1kzBiotransformation of lincomycin and fluoroquinolone antibiotics by the ammonia oxidizers AOA, AOB and comammox: A comparison of removal, pathways, and mechanismsZhou, Li-JunHan, PingZhao, MengyueYu, YaochunSun, DongyaoHou, LijunLiu, MinZhao, QiangTang, XiufengKlümper, UliGu, Ji-DongMen, YujieWu, Qinglong L2021-05-01In this study, we evaluated the biotransformation mechanisms of lincomycin (LIN) and three fluoroquinolone antibiotics (FQs), ciprofloxacin (CFX), norfloxacin (NFX), and ofloxacin (OFX), which regularly enter aquatic environments through human activities, by different ammonia-oxidizing microorganisms (AOM). The organisms included a pure culture of the complete ammonia oxidizer (comammox) Nitrospira inopinata, an ammonia oxidizing archaeon (AOA) Nitrososphaera gargensis, and an ammonia-oxidizing bacterium (AOB) Nitrosomonas nitrosa Nm90. The removal of these antibiotics by the pure microbial cultures and the protein-normalized biotransformation rate constants indicated that LIN was significantly co-metabolically biotransformed by AOA and comammox, but not by AOB. CFX and NFX were significantly co-metabolized by AOA and AOB, but not by comammox. None of the tested cultures transformed OFX effectively. Generally, AOA showed the best biotransformation capability for LIN and FQs, followed by comammox and AOB. The transformation products and their related biotransformation mechanisms were also elucidated. i) The AOA performed hydroxylation, S-oxidation, and demethylation of LIN, as well as nitrosation and cleavage of the piperazine moiety of CFX and NFX; ii) the AOB utilized nitrosation to biotransform CFX and NFX; and iii) the comammox carried out hydroxylation, demethylation, and demethylthioation of LIN. Hydroxylamine, an intermediate of ammonia oxidation, chemically reacted with LIN and the selected FQs, with removals exceeding 90%. Collectively, these findings provide important fundamental insights into the roles of different ammonia oxidizers and their intermediates on LIN and FQ biotransformation in nitrifying environments including wastewater treatment systems.Environmental SciencesPollution and ContaminationAmmoniaAnti-Bacterial AgentsArchaeaBiotransformationFluoroquinolonesHumansLincomycinNitrificationNitrosomonasOxidation-ReductionPhylogenySoil MicrobiologyAmmonia oxidizersbiotransformationcomammoxcometabolismlincomycinfluoroquinolonesEnvironmental Engineeringapplication/pdfCC-BY-NC-NDeScholarship, University of Californiahttps://escholarship.org/uc/item/7b88r1kzarticleoai:escholarship.org:ark:/13030/qt7jk3t54w2023-10-07T23:14:41Zqt7jk3t54wCharacterizing RNA Pseudouridylation by Convolutional Neural NetworksHe, XuanZhang, SaiZhang, YanqingLei, ZhixinJiang, TaoZeng, Jianyang2021-10-01Pseudouridine (Ψ) is the most prevalent post-transcriptional RNA modification and is widespread in small cellular RNAs and mRNAs. However, the functions, mechanisms, and precise distribution of Ψs (especially in mRNAs) still remain largely unclear. The landscape of Ψs across the transcriptome has not yet been fully delineated. Here, we present a highly effective model based on a convolutional neural network (CNN), called PseudoUridyLation Site Estimator (PULSE), to analyze large-scale profiling data of Ψ sites and characterize the contextual sequence features of pseudouridylation. PULSE, consisting of two alternatively-stacked convolution and pooling layers followed by a fully-connected neural network, can automatically learn the hidden patterns of pseudouridylation from the local sequence information. Extensive validation tests demonstrated that PULSE can outperform other state-of-the-art prediction methods and achieve high prediction accuracy, thus enabling us to further characterize the transcriptome-wide landscape of Ψ sites. We further showed that the prediction results derived from PULSE can provide novel insights into understanding the functional roles of pseudouridylation, such as the regulations of RNA secondary structure, codon usage, translation, and RNA stability, and the connection to single nucleotide variants. The source code and final model for PULSE are available at https://github.com/mlcb-thu/PULSE.Information and Computing SciencesBiological SciencesBioinformatics and Computational BiologyMachine LearningGenetics1.1 Normal biological development and functioningUnderpinning researchGeneric health relevanceNeural NetworksComputerPseudouridineRNARNA ProcessingPost-TranscriptionalRNAMessengerPseudouridylationConvolution neural networkSequence motifTranslationRNA stabilityMathematical SciencesBioinformaticsBiological sciencesInformation and computing sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7jk3t54warticleGenomics Proteomics & Bioinformatics, vol 19, iss 5815 - 833oai:escholarship.org:ark:/13030/qt5t74h0rn2023-10-07T23:14:28Zqt5t74h0rnCodee: A Tensor Embedding Scheme for Binary Code SearchYang, JiaFu, CaiLiu, Xiao-YangYin, HengZhou, Pan2021-01-01Given a target binary function, the binary code search retrieves top-K similar functions in the repository, and similar functions represent that they are compiled from the same source codes. Searching binary code is particularly challenging due to large variations of compiler tool-chains and options and CPU architectures, as well as thousands of binary codes. Furthermore, there are some pivotal issues in current binary code search schemes, including inaccurate text-based or token-based analysis, slow graph matching, or complex deep learning processes. In this paper, we present an unsupervised tensor embedding scheme, Codee, to carry out code search efficiently and accurately at the binary function level. First, we use an NLP-based neural network to generate the semantic-aware token embedding. Second, we propose an efficient basic block embedding generation algorithm based on the network representation learning model. We learn both the semantic information of instructions and the control flow structural information to generate the basic block embedding. Then we use all basic block embeddings in a function to obtain a variable-length function feature vector. Third, we build a tensor to generate function embeddings based on the tensor singular value decomposition, which compresses the variable-length vectors into short fixed-length vectors to facilitate efficient search afterward. We further propose a dynamic tensor compression algorithm to incrementally update the function embedding database. Finally, we use the local sensitive hash method to find the top-KK similar matching functions in the repository. Compared with state-of-the-art cross-optimization-level code search schemes, such as Asm2Vec and DeepBinDiff, our scheme achieves higher average search accuracy, shorter feature vectors, and faster feature generation performance using four datasets, OpenSSL, Coreutils, libgmp and libcurl. Compared with other cross-platform and cross-optimization-level code search schemes, such as Gemini, Safe, the average recall of our method also outperforms others.Information and Computing SciencesMachine LearningFunction feature extractiontensor embeddingcode searchtSVDComputer SoftwareInformation SystemsElectrical and Electronic EngineeringSoftware EngineeringDistributed computing and systems softwareSoftware engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5t74h0rnarticleIEEE Transactions on Software Engineering, vol 48, iss 72224 - 2244oai:escholarship.org:ark:/13030/qt1h08646t2023-10-07T22:33:22Zqt1h08646tEncapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In VivoTerry, Treniece LGivens, Brittany EAdamcakova-Dodd, AndreaThorne, Peter SRodgers, Victor GJSalem, Aliasger K2021-02-01Encapsulating genetic material into biocompatible polymeric microparticles is a means to improving gene transfection while simultaneously decreasing the tendency for inflammatory responses; and can be advantageous in terms of delivering material directly to the lungs via aerosolization for applications such as vaccinations. In this study, we investigated the advantages of using polymeric microparticles carrying the luciferase reporter gene in increasing transfection efficiency in the readily transfectable HEK293 cell line and the difficult to transfect RAW264.7 cell line. The results indicated that there was a limit to the ratio of nitrogen in polyethylenimine (PEI) to phosphate in DNA (N/P ratio) beyond which further increases in transgene expression no longer, or only marginally, occurred. Microparticles encapsulating PEI:DNA nanoplexes induced cellular toxicity in a dose-dependent manner. PEGylation increased transgene expression, likely related to enhanced degradation of particles. Furthermore, intra-tracheal instillation in rats allowed us to investigate the inflammatory response in the lung as a function of PEGylation, porosity, and size. Porosity did not influence cell counts in bronchoalveolar lavage fluid in the absence of PEG, but in particles containing PEG, non-porous particles recruited fewer inflammatory cells than their porous counterparts. Finally, both 1 μm and 10 μm porous PLA-PEG particles recruited more neutrophils than 4 μm particles. Thus, we have shown that PEGylation and lack of porosity are advantageous for faster release of genetic cargo from microparticles and a reduced inflammatory response, respectively.Medical BiotechnologyBiomedical and Clinical SciencesBiotechnologyGeneticsAnimalsDNAHEK293 CellsHumansInflammationLactatesMicePolyethylene GlycolsPolyethyleneimineRAW 264.7 CellsRatsTransfectionTransgenesPEGylationPLGAPLA-PEGGene transfectionPorosityPharmacology and Pharmaceutical SciencesPharmacology & PharmacyPharmacology and pharmaceutical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1h08646tarticleAAPS PharmSciTech, vol 22, iss 269oai:escholarship.org:ark:/13030/qt41d661tf2023-10-07T21:37:02Zqt41d661tfRemoving leakage-induced correlated errors in superconducting quantum error correctionMcEwen, MKafri, DChen, ZAtalaya, JSatzinger, KJQuintana, CKlimov, PVSank, DGidney, CFowler, AGArute, FArya, KBuckley, BBurkett, BBushnell, NChiaro, BCollins, RDemura, SDunsworth, AErickson, CFoxen, BGiustina, MHuang, THong, SJeffrey, EKim, SKechedzhi, KKostritsa, FLaptev, PMegrant, AMi, XMutus, JNaaman, ONeeley, MNeill, CNiu, MPaler, ARedd, NRoushan, PWhite, TCYao, JYeh, PZalcman, AChen, YuSmelyanskiy, VNMartinis, John MNeven, HKelly, JKorotkov, ANPetukhov, AGBarends, R2021-01-01Quantum computing can become scalable through error correction, but logical error rates only decrease with system size when physical errors are sufficiently uncorrelated. During computation, unused high energy levels of the qubits can become excited, creating leakage states that are long-lived and mobile. Particularly for superconducting transmon qubits, this leakage opens a path to errors that are correlated in space and time. Here, we report a reset protocol that returns a qubit to the ground state from all relevant higher level states. We test its performance with the bit-flip stabilizer code, a simplified version of the surface code for quantum error correction. We investigate the accumulation and dynamics of leakage during error correction. Using this protocol, we find lower rates of logical errors and an improved scaling and stability of error suppression with increasing qubit number. This demonstration provides a key step on the path towards scalable quantum computing.Quantum PhysicsEngineeringElectronicsSensors and Digital HardwarePhysical SciencesAtomicMolecular and Optical Physicsquant-phapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/41d661tfarticleNature Communications, vol 12, iss 11761oai:escholarship.org:ark:/13030/qt6w07g5cd2023-10-07T21:36:21Zqt6w07g5cdDevelopment of an Interdigitated Electrode-Based Disposable Enzyme Sensor Strip for Glycated Albumin MeasurementHatada, MikaLoew, NoyaOkuda-Shimazaki, JunkoKhanwalker, MukundTsugawa, WakakoMulchandani, AshokSode, Koji2021-01-01Glycated albumin (GA) is an important glycemic control marker for diabetes mellitus. This study aimed to develop a highly sensitive disposable enzyme sensor strip for GA measurement by using an interdigitated electrode (IDE) as an electrode platform. The superior characteristics of IDE were demonstrated using one microelectrode of the IDE pair as the working electrode (WE) and the other as the counter electrode, and by measuring ferrocyanide/ferricyanide redox couple. The oxidation current was immediately reached at the steady state when the oxidation potential was applied to the WE. Then, an IDE enzyme sensor strip for GA measurement was prepared. The measurement of fructosyl lysine, the protease digestion product of GA, exhibited a high, steady current immediately after potential application, revealing the highly reproducible measurement. The sensitivity (2.8 nA µM-1) and the limit of detection (1.2 µM) obtained with IDE enzyme sensor strip were superior compared with our previously reported sensor using screen printed electrode. Two GA samples, 15 or 30% GA, corresponding to healthy and diabetic levels, respectively, were measured after protease digestion with high resolution. This study demonstrated that the application of an IDE will realize the development of highly sensitive disposable-type amperometric enzyme sensors with high reproducibility.Analytical ChemistryChemical SciencesDiabetesBioengineeringMetabolic and endocrineBiosensing TechniquesDisposable EquipmentElectrodesEnzymesGlycation End ProductsAdvancedReproducibility of ResultsSerum AlbuminGlycated Serum Albumininterdigitated electrodeglycated albuminfructosyl amino acid oxidasepoint of care testingdisposable enzyme sensordiabetes mellitusMedicinal and Biomolecular ChemistryOrganic ChemistryTheoretical and Computational ChemistryMedicinal and biomolecular chemistryOrganic chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6w07g5cdarticleMolecules, vol 26, iss 3734oai:escholarship.org:ark:/13030/qt5gf0d0q92023-10-07T20:07:42Zqt5gf0d0q9DeepLPI: a multimodal deep learning method for predicting the interactions between lncRNAs and protein isoformsShaw, DipanChen, HaoXie, MinzhuJiang, Tao2021-01-01BackgroundLong non-coding RNAs (lncRNAs) regulate diverse biological processes via interactions with proteins. Since the experimental methods to identify these interactions are expensive and time-consuming, many computational methods have been proposed. Although these computational methods have achieved promising prediction performance, they neglect the fact that a gene may encode multiple protein isoforms and different isoforms of the same gene may interact differently with the same lncRNA.ResultsIn this study, we propose a novel method, DeepLPI, for predicting the interactions between lncRNAs and protein isoforms. Our method uses sequence and structure data to extract intrinsic features and expression data to extract topological features. To combine these different data, we adopt a hybrid framework by integrating a multimodal deep learning neural network and a conditional random field. To overcome the lack of known interactions between lncRNAs and protein isoforms, we apply a multiple instance learning (MIL) approach. In our experiment concerning the human lncRNA-protein interactions in the NPInter v3.0 database, DeepLPI improved the prediction performance by 4.7% in term of AUC and 5.9% in term of AUPRC over the state-of-the-art methods. Our further correlation analyses between interactive lncRNAs and protein isoforms also illustrated that their co-expression information helped predict the interactions. Finally, we give some examples where DeepLPI was able to outperform the other methods in predicting mouse lncRNA-protein interactions and novel human lncRNA-protein interactions.ConclusionOur results demonstrated that the use of isoforms and MIL contributed significantly to the improvement of performance in predicting lncRNA and protein interactions. We believe that such an approach would find more applications in predicting other functional roles of RNAs and proteins.Biological SciencesBioinformatics and Computational BiologyGeneticsGeneric health relevanceAnimalsComputational BiologyDeep LearningMiceNeural NetworksComputerProtein IsoformsRNALong NoncodingMathematical SciencesInformation and Computing SciencesBioinformaticsBiological sciencesInformation and computing sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5gf0d0q9articleBMC Bioinformatics, vol 22, iss 124oai:escholarship.org:ark:/13030/qt1nb2s5gf2023-10-07T17:20:15Zqt1nb2s5gfCharacterization of the Viscoelastic Properties of Ovarian Cancer Cells Membranes by Optical Tweezers and Quantitative Phase ImagingLu, ThompsonAnvari, Bahman2020-01-01Ovarian cancer is the deadliest gynecological cancer in women. It is a highly metastatic disease with pelvis, regional lymph nodes, and peritoneal cavity as major sites for tumor deposits. Mechanical properties of ovarian cancer cells can play a major role in metastasis as the cells detach from the ovaries and undergo deformation during the metastatic process. Herein, we have characterized the viscoelastic properties of the plasma membrane of normal epithelial (IOSE364) and cancerous (SKOV3) ovarian cells by optical tweezers and quantitative phase imaging. Using optical tweezers, we obtained time-resolved force profiles associated with membrane tethers pulled from the cells. We used quantitative phase imaging to measure the diameter of membrane tethers, and subsequently, estimated the membrane bending modulus and membrane tension in the tether. Our results indicate that the force (190 ± 76 pN) (mean ± standard deviation) required to separate the membrane of SKOV3 cells from the cytoskeleton was significantly lower (p = 0.0004) than the force (350 ± 81 pN) for IOSE364 cells. The mean stiffness (2.8 ± 0.8 pN/μm) of membrane tethers pulled from SKOV3 cells was significantly lower (p = 0.032) than the value for IOSE 364 cells (3.7 ± 0.8 pN/μm). Mean value of the force relaxation characteristic time associated with diffusive flow of lipids was also significantly lower (p = 0.018) for SKOV3 membranes (12.9 ± 6.9 s) as compared to the value for IOSE 364 membranes (20.4 ± 6.2 s). Similarly, the mean value of the membrane bending modulus for SKOV3 cells [(0.51 ± 0.23) × 10–18 J] was significantly lower (p = 0.007) than the value for IOSE364 cells [(1.29 ± 0.32) × 10–18 J]. Overall, our results suggest that the membranes of SKOV3 cells are less resistant to mechanical deformation. Increased membrane susceptibility to mechanical deformation may be a facilitating factor in the metastatic behavior of cancerous ovarian cells. Characterization of membrane biomechanics may provide a useful diagnostic biomarker for assessment of the metastatic potential of ovarian cancer, and a target for development of therapeutics.Mathematical SciencesPhysical SciencesCancerBioengineeringBiomedical ImagingRare DiseasesOvarian Cancercell membranelabel free imagingmembrane mechanical propertiestetherlipid flowMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1nb2s5gfarticleoai:escholarship.org:ark:/13030/qt9ct1v4h22023-10-07T16:16:16Zqt9ct1v4h2Measuring dissolution profiles of single controlled-release drug pelletsBhakta, Heran CLin, Jessica MGrover, William H2020-01-01Many solid-dose oral drug products are engineered to release their active ingredients into the body at a certain rate. Techniques for measuring the dissolution or degradation of a drug product in vitro play a crucial role in predicting how a drug product will perform in vivo. However, existing techniques are often labor-intensive, time-consuming, irreproducible, require specialized analytical equipment, and provide only "snapshots" of drug dissolution every few minutes. These limitations make it difficult for pharmaceutical companies to obtain full dissolution profiles for drug products in a variety of different conditions, as recommended by the US Food and Drug Administration. Additionally, for drug dosage forms containing multiple controlled-release pellets, particles, beads, granules, etc. in a single capsule or tablet, measurements of the dissolution of the entire multi-particle capsule or tablet are incapable of detecting pellet-to-pellet variations in controlled release behavior. In this work, we demonstrate a simple and fully-automated technique for obtaining dissolution profiles from single controlled-release pellets. We accomplished this by inverting the drug dissolution problem: instead of measuring the increase in the concentration of drug compounds in the solution during dissolution (as is commonly done), we monitor the decrease in the buoyant mass of the solid controlled-release pellet as it dissolves. We weigh single controlled-release pellets in fluid using a vibrating tube sensor, a piece of glass tubing bent into a tuning-fork shape and filled with any desired fluid. An electronic circuit keeps the glass tube vibrating at its resonance frequency, which is inversely proportional to the mass of the tube and its contents. When a pellet flows through the tube, the resonance frequency briefly changes by an amount that is inversely proportional to the buoyant mass of the pellet. By passing the pellet back-and-forth through the vibrating tube sensor, we can monitor its mass as it degrades or dissolves, with high temporal resolution (measurements every few seconds) and mass resolution (700 nanogram resolution). As a proof-of-concept, we used this technique to measure the single-pellet dissolution profiles of several commercial controlled-release proton pump inhibitors in simulated stomach and intestinal contents, as well as comparing name-brand and generic formulations of the same drug. In each case, vibrating tube sensor data revealed significantly different dissolution profiles for the different drugs, and in some cases our method also revealed differences between different pellets from the same drug product. By measuring any controlled-release pellets, particles, beads, or granules in any physiologically-relevant environment in a fully-automated fashion, this method can augment and potentially replace current dissolution tests and support product development and quality assurance in the pharmaceutical industry.Medical BiotechnologyBiomedical and Clinical SciencesEngineeringBioengineeringChemistryPharmaceuticalDelayed-Action PreparationsDrug LiberationGastric JuiceHumansProton Pump InhibitorsTabletsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9ct1v4h2articleScientific Reports, vol 10, iss 119734oai:escholarship.org:ark:/13030/qt8sf3v0kn2023-10-07T15:13:46Zqt8sf3v0knBubble dynamics of laser-induced cavitation in plasmonic gold nanorod solutions and the relative effect of surface tension and viscositySabzeghabae, Ariana NushinDevia-Cruz, Luis FelipeGutierrez-Herrera, EnochCamacho-Lopez, SantiagoAguilar, Guillermo2021-02-01Laser-induced cavitation (LIC) bubbles and the shockwaves they form upon collapse are destructive to nearby solid boundaries, making them of interest for biomedical and industrial applications. Furthermore, the LIC bubbles provide spatial control that can be tuned by the bubble size, collapse time and shockwave intensity. The inclusion of plasmonic nanoparticles, such as gold nanoparticles (GNP) in the liquids where LIC bubbles are formed, can further enhance the absorption of light, allowing for bubble formation at lower laser energies. However, the effect of the physical properties of such liquids on LIC bubble dynamics remains unknown. In this study, the dynamics of LIC bubbles in water–ethanol, water-glycerol, and water-GNP solutions were investigated by simultaneous high-speed shadowgraphy and spatial transmittance modulation. The first set of experiments demonstrated that LIC bubbles induced in the GNP solutions led to more efficient cavitation formation with lower fluence compared to solutions without GNPs, thereby producing higher-intensity pressure waves. A second set of experiments was conducted to determine the surface tension of GNP solutions at room temperature and was found to be 70.62 mN/m. With this information, and the corresponding values reported in the literature for ethanol and glycerol, we aimed at discerning the role of surface tension and viscosity on the dynamics of LIC bubbles, apart from the enhanced optical absorption of the GNP solutions. We observed that the optical breakdown threshold for plasma formation was reduced by 18% in GNP solutions as compared to DI water and 10.4% compared to ethanol, and the intensity of initial shockwaves in the GNP solutions was much higher than those in DI water. This enhanced intensity of shockwaves in GNP solutions compared to DI water opens a new avenue for the enhancement of cancer cell treatment and anti-bacterial applications in the biomedical field and the enhancement of the laser ablation technique in the industrial setting.EngineeringBioengineeringNanotechnologyGold nanoparticlesShockwavesLaser-induced cavitationLaser-induced breakdownOptical PhysicsOptoelectronics & PhotonicsInformation and computing sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8sf3v0knarticleoai:escholarship.org:ark:/13030/qt22v7w14x2023-10-07T15:11:17Zqt22v7w14xDeepBinDiff: Learning Program-Wide Code Representations for Binary DiffingDuan, YueLi, XuezixiangWang, JinghanYin, Heng2020-01-01publiceScholarship, University of Californiahttps://escholarship.org/uc/item/22v7w14xarticleoai:escholarship.org:ark:/13030/qt5814j6tf2023-10-07T15:00:59Zqt5814j6tfBismuth Subcarbonate Decorated Reduced Graphene Oxide Nanocomposite for the Sensitive Stripping Voltammetry Analysis of Pb(II) and Cd(II) in WaterZhao, GuoSedki, MohammedMa, ShengcunVillarreal, ClaudiaMulchandani, AshokJassby, David2020-01-01In this paper, bismuth subcarbonate (BiO)2CO3-reduced graphene oxide nanocomposite incorporated in Nafion matrix ((BiO)2CO3-rGO-Nafion) was synthesized and further applied, for the first time, in the sensitive detection of Pb(II) and Cd(II) by square-wave anodic stripping voltammetry (SWASV). The as-synthesized nanocomposites were characterized by energy-dispersive spectroscopy (EDS), Raman spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). (BiO)2CO3 composite plays a key role in the improvement of the detection sensitivity, which can form multicomponent alloy with cadmium and lead. Additionally, the unique structure of rGO can enlarge the surface area and provide abundant active sites. Moreover, Nafion incorporation in the nanocomposite can effectively increase the adhesion and mechanical strength of the film, and further improve the preconcetration ability due to the cation-exchange capacity of its abundant sulfonate groups. As expected, the (BiO)2CO3-rGO/Nafion nanocomposite-modified glassy carbon electrode ((BiO)2CO3-rGO-Nafion/GCE) achieved low detection limits of 0.24 μg/L for Pb(II) and 0.16 μg/L for Cd(II), in the linear range of 1.0-60 μg/L, and showed some excellent performance, such as high stability, good selectivity, and sensitivity. Finally, synthetic water samples were prepared and further used to verify the practicability of the (BiO)2CO3-rGO-Nafion/GCE with satisfactory results.EngineeringMaterials Engineeringbismuth subcarbonatesquare-wave anodic stripping voltammetryreduced graphene oxideheavy metals detectionAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5814j6tfarticleSensors, vol 20, iss 216085oai:escholarship.org:ark:/13030/qt2xt6d9ts2023-10-07T14:57:06Zqt2xt6d9tsAuthor Correction: Non-Invasive Photoacoustic Imaging of In Vivo Mice with Erythrocyte Derived Optical Nanoparticles to Detect CAD/MILiu, YonggangHanley, TaylorChen, HaoLong, Steven RGambhir, Sanjiv SCheng, ZhenWu, Joseph CFakhri, Georges ElAnvari, BahmanZaman, Raiyan T2020-01-01An amendment to this paper has been published and can be accessed via a link at the top of the paper.Medical BiotechnologyEngineeringBiomedical and Clinical Sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2xt6d9tsarticleScientific Reports, vol 10, iss 119102oai:escholarship.org:ark:/13030/qt5xj7m3n22023-10-07T10:50:13Zqt5xj7m3n2Non-Carbon 2D Materials-Based Field-Effect Transistor Biosensors: Recent Advances, Challenges, and Future PerspectivesSedki, MohammedChen, YingMulchandani, Ashok2020-01-01In recent years, field-effect transistors (FETs) have been very promising for biosensor applications due to their high sensitivity, real-time applicability, scalability, and prospect of integrating measurement system on a chip. Non-carbon 2D materials, such as transition metal dichalcogenides (TMDCs), hexagonal boron nitride (h-BN), black phosphorus (BP), and metal oxides, are a group of new materials that have a huge potential in FET biosensor applications. In this work, we review the recent advances and remarkable studies of non-carbon 2D materials, in terms of their structures, preparations, properties and FET biosensor applications. We will also discuss the challenges facing non-carbon 2D materials-FET biosensors and their future perspectives.EngineeringInformation and Computing SciencesElectrical EngineeringElectronicsSensors and Digital HardwareDistributed Computing and Systems Software2D-materialsfield-effect transistortransition metal dichalcogenidesblack phosphorusphosphorenehexagonal boron nitridetransition metal oxidesbiosensorsAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5xj7m3n2articleSensors, vol 20, iss 174811oai:escholarship.org:ark:/13030/qt69r523dv2023-10-07T10:04:28Zqt69r523dvModifying Wicking Speeds in Paper-Based Microfluidic Devices by Laser-EtchingKalish, BrentTan, Mick KyleTsutsui, Hideaki2020-01-01Paper-based microfluidic devices are an attractive platform for developing low-cost, point-of-care diagnostic tools. As paper-based devices' detection chemistries become more complex, more complicated devices are required, often entailing the sequential delivery of different liquids or reagents to reaction zones. Most research into flow control has been focused on introducing delays. However, delaying the flow can be problematic due to increased evaporation leading to sample loss. We report the use of a CO2 laser to uniformly etch the surface of the paper to modify wicking speeds in paper-based microfluidic devices. This technique can produce both wicking speed increases of up to 1.1× faster and decreases of up to 0.9× slower. Wicking speeds can be further enhanced by etching both sides of the paper, resulting in wicking 1.3× faster than unetched channels. Channels with lengthwise laser-etched grooves were also compared to uniformly etched channels, with the most heavily grooved channels wicking 1.9× faster than the fastest double-sided etched channels. Furthermore, sealing both sides of the channel in packing tape results in the most heavily etched channels, single-sided, double-sided, and grooved, wicking over 13× faster than unetched channels. By selectively etching individual channels, different combinations of sequential fluid delivery can be obtained without altering any channel geometry. Laser etching is a simple process that can be integrated into the patterning of the device and requires no additional materials or chemicals, enabling greater flow control for paper-based microfluidic devices.Fluid Mechanics and Thermal EngineeringEngineeringMaterials EngineeringBiotechnologyBioengineeringpaper-based microfluidicslaser-etchingwicking speedsfaster wickingNanotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/69r523dvarticleMicromachines, vol 11, iss 8773oai:escholarship.org:ark:/13030/qt34n231d72023-10-07T06:24:59Zqt34n231d7RBC-Derived Optical Nanoparticles Remain Stable After a Freeze–Thaw CycleTang, Jack CVankayala, RavirajMac, Jenny TAnvari, Bahman2020-09-01Nanosized carriers engineered from red blood cells (RBCs) provide a means for delivering various cargos, including drugs, biologics, and imaging agents. We have engineered nanosized particles from RBCs, doped with the near-infrared (NIR) fluorochrome, indocyanine green (ICG). An important issue related to clinical translation of RBC-derived nanocarriers, including these NIR nanoparticles, is their stability postfabrication. Freezing may provide a method for long-term storage of these and other RBC-derived nanoparticles. Herein, we have investigated the physical and optical stability of these particles in response to a single freeze-thaw cycle. Nanoparticles were frozen to -20 °C, stored frozen for up to 8 weeks, and then thawed at room temperature. Our results show that the hydrodynamic diameter, zeta potential, optical density, and NIR fluorescence emission of these nanoparticles are retained following the freeze-thaw cycle. The ability of these nanoparticles in NIR fluorescence imaging of ovarian cancer cells, as well as their biodistribution in reticuloendothelial organs of healthy Swiss Webster mice after the freeze-thaw cycle is similar to that for freshly prepared nanoparticles. These results indicate that a single cycle of freezing the RBC-derived nanoparticles to -20 °C followed by thawing at room temperature is an effective method to retain the physical and optical characteristics of the nanoparticles, and their interactions with biological systems without the need for use of cryoprotectants.Medical BiotechnologyBiomedical and Clinical SciencesEngineeringNanotechnologyBioengineeringAnimalsCryoprotective AgentsErythrocytesFreezingMiceNanoparticlesTissue DistributionChemical Physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/34n231d7articleLangmuir, vol 36, iss 3410003 - 10011oai:escholarship.org:ark:/13030/qt79m5n3682023-10-07T06:24:52Zqt79m5n368ReDU: a framework to find and reanalyze public mass spectrometry dataJarmusch, Alan KWang, MingxunAceves, Christine MAdvani, Rohit SAguirre, ShadenAksenov, Alexander AAleti, GajenderAron, Allegra TBauermeister, AnelizeBolleddu, SanjanaBouslimani, AminaCaraballo Rodriguez, Andres MauricioChaar, RamaCoras, RoxanaElijah, Emmanuel OErnst, MadeleineGauglitz, Julia MGentry, Emily CHusband, MakhaiJarmusch, Scott AJones, Kenneth LKamenik, ZdenekLe Gouellec, AudreyLu, AileenMcCall, Laura-IsobelMcPhail, Kerry LMeehan, Michael JMelnik, Alexey VMenezes, Riya CMontoya Giraldo, Yessica AlejandraNguyen, Ngoc HungNothias, Louis FelixNothias-Esposito, MélissaPanitchpakdi, MorganPetras, DanielQuinn, Robert ASikora, Nicolevan der Hooft, Justin JJVargas, FernandoVrbanac, AlisonWeldon, Kelly CKnight, RobBandeira, NunoDorrestein, Pieter C2020-09-01We present ReDU ( https://redu.ucsd.edu/ ), a system for metadata capture of public mass spectrometry-based metabolomics data, with validated controlled vocabularies. Systematic capture of knowledge enables the reanalysis of public data and/or co-analysis of one's own data. ReDU enables multiple types of analyses, including finding chemicals and associated metadata, comparing the shared and different chemicals between groups of samples, and metadata-filtered, repository-scale molecular networking.Biological SciencesDatabasesChemicalMass SpectrometryMetabolomicsMetadataModelsChemicalSoftwareTechnologyMedical and Health SciencesDevelopmental BiologyBiological sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/79m5n368articleNature Methods, vol 17, iss 9901 - 904oai:escholarship.org:ark:/13030/qt3f33t5dn2023-10-07T03:27:44Zqt3f33t5dnChronic Brain Imaging Across a Transparent Nanocrystalline Yttria-Stabilized-Zirconia Cranial ImplantHalaney, David LJonak, Carrie RLiu, JunzeDavoodzadeh, NamiCano-Velázquez, Mildred SEhtiyatkar, PashaPark, HyleBinder, Devin KAguilar, Guillermo2020-01-01Repeated non-diffuse optical imaging of the brain is difficult. This is due to the fact that the cranial bone is highly scattering and thus a strong optical barrier. Repeated craniotomies increase the risk of complications and may disrupt the biological systems being imaged. We previously introduced a potential solution in the form of a transparent ceramic cranial implant called the Window to the Brain (WttB) implant. This implant is made of nanocrystalline Yttria-Stabilized Zirconia (nc-YSZ), which possesses the requisite mechanical strength to serve as a permanent optical access window in human patients. In this present study, we demonstrate repeated brain imaging of n = 5 mice using both OCT and LSI across the WttB implant over 4 weeks. The main objectives are to determine if the WttB implant allows for chronic OCT imaging, and to shed further light on the question of whether optical access provided by the WttB implant remains stable over this duration in the body. The Window to the Brain implant allowed for stable repeated imaging of the mouse brain with Optical Coherence Tomography over 28 days, without loss of signal intensity. Repeated Laser Speckle Imaging was also possible over this timeframe, but signal to noise ratio and the sharpness of vessels in the images decreased with time. This can be partially explained by elevated blood flow during the first imaging session in response to trauma from the surgery, which was also detected by OCT flow imaging. These results are promising for long-term optical access through the WttB implant, making feasible chronic in vivo studies in multiple neurological models of brain disease.Biomedical and Clinical SciencesEngineeringBiomedical EngineeringNeurosciencesBrain DisordersBiomedical ImagingBioengineeringNeurologicalcranial implantwindow to the brainbrainimagingoptical coherence tomographylaser speckle imagingOther Biological SciencesMedical BiotechnologyIndustrial biotechnologyMedical biotechnologyBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3f33t5dnarticleoai:escholarship.org:ark:/13030/qt5kk3493k2023-10-07T03:05:20Zqt5kk3493kImplantable Osmotic Transport Device Can Reduce Edema After Severe Contusion Spinal Cord InjuryHale, ChristopherYonan, JenniferBatarseh, RamseyChaar, RomanJonak, Carrie RGe, ShaokuiBinder, DevinRodgers, Victor GJ2020-01-01Recent findings from the ISCoPe study indicate that, after severe contusion to the spinal cord, edema originating in the spinal cord accumulates and compresses the tissue against the surrounding dura mater, despite decompressive laminectomy. It is hypothesized that this compression results in restricted flow of cerebrospinal fluid (CSF) in the subarachnoid space and central canal and ultimately collapses local vasculature, exacerbating ischemia and secondary injury. Here we developed a surgically mounted osmotic transport device (OTD) that rests on the dura and can osmotically remove excess fluid at the injury site. Tests were performed in 4-h studies immediately following severe (250 kD) contusion at T8 in rats using the OTD. A 3-h treatment with the OTD after 1-h post injury significantly reduced spinal cord edema compared to injured controls. A first approximation mathematical interpretation implies that this modest reduction in edema may be significant enough to relieve compression of local vasculature and restore flow of CSF in the region. In addition, we determined the progression of edema up to 28 days after insult in the rat for the same injury model. Results showed peak edema at 72 h. These preliminary results suggest that incorporating the OTD to operate continuously at the site of injury throughout the critical period of edema progression, the device may significantly improve recovery following contusion spinal cord injury.Biomedical and Clinical SciencesNeurosciencesSpinal Cord InjuryNeurodegenerativePhysical Injury - Accidents and Adverse EffectsTraumatic Head and Spine Injuryspinal cord injuryedemasevere contusionimplantable devicemembrane separationsosmotic transport deviceOther Biological SciencesBiomedical EngineeringMedical BiotechnologyIndustrial biotechnologyMedical biotechnologyBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5kk3493karticleoai:escholarship.org:ark:/13030/qt45g453tz2023-10-06T21:49:53Zqt45g453tzRepresentative subsampling of sedimenting bloodRallabandi, BhargavNunes, Janine KPerazzo, AntonioGershtein, SergeyStone, Howard A2019-07-01It is often necessary to extract a small amount of a suspension, such as blood, from a larger sample of the same material for the purposes of diagnostics, testing or imaging. A practical challenge is that the cells in blood sediment noticeably on the time scale of a few minutes, making a representative subsampling of the original sample challenging. Guided by experimental data, we develop a Kynch sedimentation model to discuss design considerations that ensure a representative subsampling of blood, from a container of constant cross-sectional area, for the entire range of physiologically relevant hematocrit over a specified time of interest. Additionally, we show that this design may be modified to exploit the sedimentation and perform subsampling to achieve either higher or lower hematocrit relative to that of the original sample. Thus, our method provides a simple tool to either concentrate or dilute small quantities of blood or other sedimenting suspensions.EngineeringMathematical SciencesPhysical SciencessedimentationbloodKrieger-DoughertyKynchcomplex fluidsKrieger–Doughertyphysics.flu-dyncond-mat.softMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/45g453tzarticleProceedings of the Royal Society A, vol 475, iss 222720190223oai:escholarship.org:ark:/13030/qt8wc9h2gs2023-10-06T21:11:14Zqt8wc9h2gsUltrafast photoinduced band splitting and carrier dynamics in chiral tellurium nanosheetsJnawali, GirirajXiang, YuanLinser, Samuel MShojaei, Iraj AbbasianWang, RuoxingQiu, GangLian, ChaoWong, Bryan MWu, WenzhuoYe, Peide DLeng, YongshengJackson, Howard ESmith, Leigh M2020-01-01Trigonal tellurium (Te) is a chiral semiconductor that lacks both mirror and inversion symmetries, resulting in complex band structures with Weyl crossings and unique spin textures. Detailed time-resolved polarized reflectance spectroscopy is used to investigate its band structure and carrier dynamics. The polarized transient spectra reveal optical transitions between the uppermost spin-split H4 and H5 and the degenerate H6 valence bands (VB) and the lowest degenerate H6 conduction band (CB) as well as a higher energy transition at the L-point. Surprisingly, the degeneracy of the H6 CB (a proposed Weyl node) is lifted and the spin-split VB gap is reduced upon photoexcitation before relaxing to equilibrium as the carriers decay. Using ab initio density functional theory (DFT) calculations, we conclude that the dynamic band structure is caused by a photoinduced shear strain in the Te film that breaks the screw symmetry of the crystal. The band-edge anisotropy is also reflected in the hot carrier decay rate, which is a factor of two slower along the c-axis than perpendicular to it. The majority of photoexcited carriers near the band-edge are seen to recombine within 30 ps while higher lying transitions observed near 1.2 eV appear to have substantially longer lifetimes, potentially due to contributions of intervalley processes in the recombination rate. These new findings shed light on the strong correlation between photoinduced carriers and electronic structure in anisotropic crystals, which opens a potential pathway for designing novel Te-based devices that take advantage of the topological structures as well as strong spin-related properties.Macromolecular and Materials ChemistryChemical SciencesPhysical SciencesCondensed Matter Physicscond-mat.mtrl-scicond-mat.mes-hallapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8wc9h2gsarticleNature Communications, vol 11, iss 13991oai:escholarship.org:ark:/13030/qt3r94g1b02023-10-06T21:06:46Zqt3r94g1b0SweepCam — Depth-Aware Lensless Imaging Using Programmable MasksHua, YiNakamura, ShigekiAsif, M SalmanSankaranarayanan, Aswin C2020-07-01Lensless cameras, while extremely useful for imaging in constrained scenarios, struggle with resolving scenes with large depth variations. To resolve this, we propose imaging with a set of mask patterns displayed on a programmable mask, and introduce a computational focusing operator that helps to resolve the depth of scene points. As a result, the proposed imager can resolve dense scenes with large depth variations, allowing for more practical applications of lensless cameras. We also present a fast reconstruction algorithm for scene at multiple depths that reduces reconstruction time by two orders of magnitude. Finally, we build a prototype to show the proposed method improves both image quality and depth resolution of lensless cameras.Information and Computing SciencesGraphicsAugmented Reality and GamesComputer Vision and Multimedia ComputationBiomedical ImagingImage reconstructionCamerasImage resolutionSemiconductor device measurementInverse problemsConvolutionLensless imagingcomputational photographyArtificial Intelligence and Image ProcessingInformation SystemsElectrical and Electronic EngineeringArtificial Intelligence & Image ProcessingComputer vision and multimedia computationMachine learningapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3r94g1b0articleIEEE Transactions on Pattern Analysis and Machine Intelligence, vol 42, iss 71606 - 1617oai:escholarship.org:ark:/13030/qt9wp333xp2023-10-06T21:00:41Zqt9wp333xpBiosynthesis of terpene compounds using the non-model yeast Yarrowia lipolytica: grand challenges and a few perspectivesWorland, Alyssa MCzajka, Jeffrey JLi, YanranWang, YechunTang, Yinjie JSu, Wei Wen2020-08-01Yarrowia lipolytica has emerged as an important non-model host for terpene production. However, three main challenges remain in industrial production using this yeast. First, considerable knowledge gaps exist in metabolic flux across multiple compartments, cofactor generation, and catabolism of non-sugar carbon sources. Second, many enzymatic steps in the complex-terpene synthesis pathway can pose rate-limitations, causing accumulation of toxic intermediates and increased metabolic burdens. Third, metabolic shifts, morphological changes, and genetic mutations are poorly characterized under industrial fermentation conditions. To overcome these challenges, systems metabolic analysis, protein engineering, novel pathway engineering, model-guided strain design, and fermentation optimization have been attempted with some successes. Further developments that address these challenges are needed to advance the Yarrowia lipolytica platform for industrial-scale production of high-value terpenes, including those with highly complex structures such as anticancer molecules withanolides and insecticidal limonoids.Biological SciencesIndustrial BiotechnologyFermentationMetabolic EngineeringTerpenesYarrowiaEngineeringTechnologyBiotechnologyAgricultural biotechnologyIndustrial biotechnologyMedical biotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9wp333xparticleoai:escholarship.org:ark:/13030/qt0vc0g86n2023-10-06T20:59:07Zqt0vc0g86nAffine particle in cell method for MAC grids and fluid simulationDing, OunanShinar, TamarSchroeder, Craig2020-05-01EngineeringMathematical SciencesPhysical SciencesAPICPICFLIPMPMHybrid Lagrangian/EulerianComputational fluid dynamicsApplied MathematicsMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0vc0g86narticleoai:escholarship.org:ark:/13030/qt5gt757972023-10-06T20:54:12Zqt5gt75797Single and binary protein electroultrafiltration using poly(vinyl-alcohol)-carbon nanotube (PVA-CNT) composite membranesYeung, RaymondZhu, XiaoboGee, TerenceGheen, BenJassby, DavidRodgers, Victor GJGhouri, Zafar2020-01-01Electrically conductive composite ultrafiltration membranes composed of carbon nanotubes have exhibited efficient fouling inhibition in wastewater treatment applications. In the current study, poly(vinyl-alcohol)-carbon nanotube membranes were applied to fed batch crossflow electroultrafiltration of dilute (0.1 g/L of each species) single and binary protein solutions of α-lactalbumin and hen egg-white lysozyme at pH 7.4, 4 mM ionic strength, and 1 psi. Electroultrafiltration using the poly(vinyl-alcohol)-carbon nanotube composite membranes yielded temporary enhancements in sieving for single protein filtration and in selectivity for binary protein separation compared to ultrafiltration using the unmodified PS-35 membranes. Assessment of membrane fouling based on permeate flux, zeta potential measurements, and scanning electron microscopy visualization of the conditioned membranes indicated significant resulting protein adsorption and aggregation which limited the duration of improvement during electroultrafiltration with an applied cathodic potential of -4.6 V (vs. Ag/AgCl). These results imply that appropriate optimization of electroultrafiltration using carbon nanotube-deposited polymeric membranes may provide substantial short-term improvements in binary protein separations.Chemical EngineeringEngineeringNanotechnologyEnvironmental EngineeringBioengineeringAdsorptionAnimalsChickensElectric ConductivityElectrodesHydrogen-Ion ConcentrationMembrane ProteinsMembranesArtificialNanotubesCarbonPolyvinyl ChlorideStatic ElectricityUltrafiltrationGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5gt75797articlePLOS ONE, vol 15, iss 4e0228973oai:escholarship.org:ark:/13030/qt9h25g7412023-10-06T19:22:49Zqt9h25g741Non-Adversarial Video Synthesis with Learned PriorsAich, AbhishekGupta, AkashPanda, RameswarHyder, RakibAsif, M SalmanRoy-Chowdhury, Amit K2020-06-13Most of the existing works in video synthesis focus on generating videos using adversarial learning. Despite their success, these methods often require input reference frame or fail to generate diverse videos from the given data distribution, with little to no uniformity in the quality of videos that can be generated. Different from these methods, we focus on the problem of generating videos from latent noise vectors, without any reference input frames. To this end, we develop a novel approach that jointly optimizes the input latent space, the weights of a recurrent neural network and a generator through non-adversarial learning. Optimizing for the input latent space along with the network weights allows us to generate videos in a controlled environment, i.e., we can faithfully generate all videos the model has seen during the learning process as well as new unseen videos. Extensive experiments on three challenging and diverse datasets well demonstrate that our proposed approach generates superior quality videos compared to the existing state-of-the-art methods.Computer Vision and Multimedia ComputationInformation and Computing SciencesGraphicsAugmented Reality and GamesMachine Learningeess.IVcs.CVapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9h25g741articleoai:escholarship.org:ark:/13030/qt18s1f4482023-10-06T15:22:42Zqt18s1f448Correction to: Multiple levers for overcoming the recalcitrance of lignocellulosic biomassHolwerda, Evert KWorthen, Robert SKothari, NinadLasky, Ronald CDavison, Brian HFu, ChunxiangWang, Zeng-YuDixon, Richard ABiswal, Ajaya KMohnen, DebraNelson, Richard SBaxter, Holly LMazarei, MitraStewart, C NealMuchero, WellingtonTuskan, Gerald ACai, Charles MGjersing, Erica EDavis, Mark FHimmel, Michael EWyman, Charles EGilna, PaulLynd, Lee R2019-12-01[This corrects the article DOI: 10.1186/s13068-019-1353-7.].Biological SciencesIndustrial BiotechnologyChemical EngineeringBiochemistry and cell biologyIndustrial biotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/18s1f448articleBiotechnology for Biofuels and Bioproducts, vol 12, iss 125oai:escholarship.org:ark:/13030/qt39x9z0tj2023-10-06T11:46:40Zqt39x9z0tjComprehensive comparison of three commercial human whole-exome capture platformsAsanXu, YuJiang, HuiTyler-Smith, ChrisXue, YaliJiang, TaoWang, JiaweiWu, MingzhiLiu, XiaoTian, GengWang, JunWang, JianYang, HuangmingZhang, Xiuqing2011-01-01BackgroundExome sequencing, which allows the global analysis of protein coding sequences in the human genome, has become an effective and affordable approach to detecting causative genetic mutations in diseases. Currently, there are several commercial human exome capture platforms; however, the relative performances of these have not been characterized sufficiently to know which is best for a particular study.ResultsWe comprehensively compared three platforms: NimbleGen's Sequence Capture Array and SeqCap EZ, and Agilent's SureSelect. We assessed their performance in a variety of ways, including number of genes covered and capture efficacy. Differences that may impact on the choice of platform were that Agilent SureSelect covered approximately 1,100 more genes, while NimbleGen provided better flanking sequence capture. Although all three platforms achieved similar capture specificity of targeted regions, the NimbleGen platforms showed better uniformity of coverage and greater genotype sensitivity at 30- to 100-fold sequencing depth. All three platforms showed similar power in exome SNP calling, including medically relevant SNPs. Compared with genotyping and whole-genome sequencing data, the three platforms achieved a similar accuracy of genotype assignment and SNP detection. Importantly, all three platforms showed similar levels of reproducibility, GC bias and reference allele bias.ConclusionsWe demonstrate key differences between the three platforms, particularly advantages of solutions over array capture and the importance of a large gene target set.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeBiotechnologyClinical ResearchGeneric health relevanceAllelesBase CompositionExomeGenetic DiseasesInbornGenomeHumanGenotypeHumansMaleMolecular Sequence AnnotationMutationOligonucleotide Array Sequence AnalysisOpen Reading FramesPolymorphismSingle NucleotideReagent KitsDiagnosticReproducibility of ResultsSensitivity and SpecificitySequence AnalysisDNAEnvironmental SciencesInformation and Computing SciencesBioinformaticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/39x9z0tjarticleGenome Biology, vol 12, iss 9r95oai:escholarship.org:ark:/13030/qt6pf0m22z2023-10-06T11:46:36Zqt6pf0m22zExome sequencing identified a missense mutation of EPS8L3 in Marie Unna hereditary hypotrichosisZhang, XinGuo, Bi-RongCai, Li-QiongJiang, TaoSun, Liang-DanCui, YongHu, Jing-ChuZhu, JunChen, GangTang, Xian-FaSun, Guang-QingTang, Hua-YangLiu, YuanLi, MinLi, Qi-BinCheng, HuiGao, MinLi, PingYang, XuZuo, Xian-BoZheng, Xiao-DongWang, Pei-GuangWang, JianWang, JunLiu, Jian-JunYang, SenLi, Ying-RuiZhang, Xue-Jun2012-12-01BackgroundMarie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant disorder characterised by coarse, wiry, twisted hair developed in early childhood and subsequent progressive hair loss. MUHH is a genetically heterogeneous disorder. No gene in 1p21.1-1q21.3 region responsible for MUHH has been identified.MethodsExome sequencing was performed on two affected subjects, who had normal vertex hair and modest alopecia, and one unaffected individual from a four-generation MUHH family of which our previous linkage study mapped the MUHH locus on chromosome 1p21.1-1q21.3.ResultsWe identified a missense mutation in EPS8L3 (NM_024526.3: exon2: c.22G->A:p.Ala8Thr) within 1p21.1-1q21.3. Sanger sequencing confirmed the cosegregation of this mutation with the disease phenotype in the family by demonstrating the presence of the heterozygous mutation in all the eight affected and absence in all the seven unaffected individuals. This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group.ConclusionsTaken together, our results suggest that EPS8L3 is a causative gene for MUHH, which was helpful for advancing us on understanding of the pathogenesis of MUHH. Our study also has further demonstrated the effectiveness of combining exome sequencing with linkage information for identifying Mendelian disease genes.Biological SciencesBiomedical and Clinical SciencesGeneticsRare DiseasesClinical ResearchHuman GenomeNeurosciencesAetiology2.1 Biological and endogenous factorsAdaptor ProteinsSignal TransducingBase SequenceDNA Mutational AnalysisExomeFemaleGenotypeHumansHypotrichosisMaleMutationMissensePedigreeMedical and Health SciencesGenetics & HeredityClinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6pf0m22zarticleJournal of Medical Genetics, vol 49, iss 12727oai:escholarship.org:ark:/13030/qt67j6t77f2023-10-06T11:46:32Zqt67j6t77fLow concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencingO'Rawe, JasonJiang, TaoSun, GuangqingWu, YiyangWang, WeiHu, JingchuBodily, PaulTian, LifengHakonarson, HakonJohnson, W EvanWei, ZhiWang, KaiLyon, Gholson J2013-01-01BackgroundTo facilitate the clinical implementation of genomic medicine by next-generation sequencing, it will be critically important to obtain accurate and consistent variant calls on personal genomes. Multiple software tools for variant calling are available, but it is unclear how comparable these tools are or what their relative merits in real-world scenarios might be.MethodsWe sequenced 15 exomes from four families using commercial kits (Illumina HiSeq 2000 platform and Agilent SureSelect version 2 capture kit), with approximately 120X mean coverage. We analyzed the raw data using near-default parameters with five different alignment and variant-calling pipelines (SOAP, BWA-GATK, BWA-SNVer, GNUMAP, and BWA-SAMtools). We additionally sequenced a single whole genome using the sequencing and analysis pipeline from Complete Genomics (CG), with 95% of the exome region being covered by 20 or more reads per base. Finally, we validated 919 single-nucleotide variations (SNVs) and 841 insertions and deletions (indels), including similar fractions of GATK-only, SOAP-only, and shared calls, on the MiSeq platform by amplicon sequencing with approximately 5000X mean coverage.ResultsSNV concordance between five Illumina pipelines across all 15 exomes was 57.4%, while 0.5 to 5.1% of variants were called as unique to each pipeline. Indel concordance was only 26.8% between three indel-calling pipelines, even after left-normalizing and intervalizing genomic coordinates by 20 base pairs. There were 11% of CG variants falling within targeted regions in exome sequencing that were not called by any of the Illumina-based exome analysis pipelines. Based on targeted amplicon sequencing on the MiSeq platform, 97.1%, 60.2%, and 99.1% of the GATK-only, SOAP-only and shared SNVs could be validated, but only 54.0%, 44.6%, and 78.1% of the GATK-only, SOAP-only and shared indels could be validated. Additionally, our analysis of two families (one with four individuals and the other with seven), demonstrated additional accuracy gained in variant discovery by having access to genetic data from a multi-generational family.ConclusionsOur results suggest that more caution should be exercised in genomic medicine settings when analyzing individual genomes, including interpreting positive and negative findings with scrutiny, especially for indels. We advocate for renewed collection and sequencing of multi-generational families to increase the overall accuracy of whole genomes.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeBiotechnologyAetiology2.1 Biological and endogenous factorsGood Health and Well BeingClinical Sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/67j6t77farticleGenome Medicine, vol 5, iss 328oai:escholarship.org:ark:/13030/qt520627dp2023-10-06T11:46:29Zqt520627dpWhole-Exome Sequencing for the Identification of Susceptibility Genes of Kashin–Beck DiseaseYang, ZhenxingXu, YuLuo, HongrongMa, XiaohongWang, QiangWang, YingchengDeng, WeiJiang, TaoSun, GuangqingHe, TingtingHu, JingchuLi, YingruiWang, JunLi, TaoHu, XunPalmer, Nicholette D2014-01-01ObjectiveTo identify and investigate the susceptibility genes of Kashin-Beck disease (KBD) in Chinese population.MethodsWhole-exome capturing and sequencing technology was used for the detection of genetic variations in 19 individuals from six families with high incidence of KBD. A total of 44 polymorphisms from 41 genes were genotyped from a total of 144 cases and 144 controls by using MassARRAY under the standard protocol from Sequenom. Association was applied on the data by using PLINK1.07.ResultsIn the sequencing stage, each sample showed approximately 70-fold coverage, thus covering more than 99% of the target regions. Among the single nucleotide polymorphisms (SNPs) used in the transmission disequilibrium test, 108 had a p-value of <0.01, whereas 1056 had a p-value of <0.05. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis indicates that these SNPs focus on three major pathways: regulation of actin cytoskeleton, focal adhesion, and metabolic pathways. In the validation stage, single locus effects revealed that two of these polymorphisms (rs7745040 and rs9275295) in the human leukocyte antigen (HLA)-DRB1 gene and one polymorphism (rs9473132) in CD2-associated protein (CD2AP) gene have a significant statistical association with KBD.ConclusionsHLA-DRB1 and CD2AP gene were identified to be among the susceptibility genes of KBD, thus supporting the role of the autoimmune response in KBD and the possibility of shared etiology between osteoarthritis, rheumatoid arthritis, and KBD.Biological SciencesBiomedical and Clinical SciencesGeneticsGenetic TestingArthritisHuman GenomeBiotechnologyAutoimmune DiseaseAetiology2.1 Biological and endogenous factorsInflammatory and immune systemAdolescentAdultAgedAsian PeopleCase-Control StudiesExomeFemaleGenetic Predisposition to DiseaseGenotyping TechniquesHumansKashin-Beck DiseaseMaleMiddle AgedPolymorphismGeneticSequence AnalysisYoung AdultGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/520627dparticlePLOS ONE, vol 9, iss 4e92298oai:escholarship.org:ark:/13030/qt76m4m1x62023-10-06T11:46:25Zqt76m4m1x6Analysis of Down syndrome failed to be diagnosed after prenatal screeningJiang, TaoDing, JieZhang, Xiao-QingZhang, Xiao-JuanZhang, BinWang, TingYu, Bin2017-06-01To analyze the characters of Down syndrome (DS) who failed to be diagnosed after prenatal screening and hope to be able to improve the programs of prenatal screening and reduce the missed diagnosis of DS. In this multicenter study, we collected the missed cases from 3 prenatal diagnosis centers and analyzed their characters. A total of 126 DS babies failed to be diagnosed after prenatal screening. Their mothers accepted the prenatal screening in second trimester. We collected the mothers' blood and detected the levels of alpha-fetoprotein (AFP) and the free beta subunit of human chorionic gonadotropin (fβhCG) by time-resolved fluoroimmunoassay. The values were also presented as multiples of the median (MoM) and determined the risk of carrying a fetus with DS by Wallace LifeCycle Elipse analysis software. Compared with normal control group, the level of fβhCG and hCG MoM were dramatically increased, while AFP and AFP MoM were decreased. The area under the receiver-operating-characteristic curve of trisomy 21 was 0.8387 for hCG-MoM and AFP-MoM testing. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.6%, 74.8%, 75.4%, and 83.6%, respectively. Meanwhile, the prediction mode was "0.39957 + 1.90897HCG-MOM -3.32713AFP-MOM". It was worthwhile noting that the risk of 65.9% DS missed diagnosis group were higher than 1/1000, 92.9% higher than 1/3000. However, 72.5% cases in normal control group were lower than 1/3000. Only 9.2% mothers would be higher than the value of risk in 1/1000. The prediction mode of hCG MoM and AFP MoM might be able to help us reduce the missed diagnosis. It is also necessary to adjust more reasonable range of noninvasive prenatal testing with further clinical researches.Reproductive MedicineBiomedical and Clinical SciencesPediatricIntellectual and Developmental Disabilities (IDD)Down SyndromePreventionBrain DisordersDetectionscreening and diagnosis4.2 Evaluation of markers and technologiesAdultArea Under CurveBiomarkersBlood Chemical AnalysisChorionic Gonadotropinbeta SubunitHumanDiagnostic ErrorsFemaleFluoroimmunoassayHumansMaternal Serum Screening TestsPregnancyPregnancy TrimesterSecondROC CurveRetrospective StudiesRiskSoftwarealpha-Fetoproteinsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/76m4m1x6articleMedicine, vol 96, iss 24e7166oai:escholarship.org:ark:/13030/qt9fq747nz2023-10-06T11:46:21Zqt9fq747nzA pathway analysis of genome-wide association study highlights novel type 2 diabetes risk pathwaysLiu, YangZhao, JingJiang, TaoYu, MeiJiang, GuohuaHu, Yang2017-10-01Genome-wide association studies (GWAS) have been widely used to identify common type 2 diabetes (T2D) variants. However, the known variants just explain less than 20% of the overall estimated genetic contribution to T2D. Pathway-based methods have been applied into T2D GWAS datasets to investigate the biological mechanisms and reported some novel T2D risk pathways. However, few pathways were shared in these studies. Here, we performed a pathway analysis using the summary results from a large-scale meta-analysis of T2D GWAS to investigate more genetic signals in T2D. Here, we selected PLNK and VEGAS to perform the gene-based test and WebGestalt to perform the pathway-based test. We identified 8 shared KEGG pathways after correction for multiple tests in both methods. We confirm previous findings, and highlight some new T2D risk pathways. We believe that our results may be helpful to study the genetic mechanisms of T2D.EpidemiologyBiological SciencesHealth SciencesGeneticsDiabetesBiotechnologyHuman GenomeAgingPrevention2.1 Biological and endogenous factorsAetiologyMetabolic and endocrineDatabasesGeneticDiabetes MellitusType 2Genetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansPolymorphismSingle NucleotideRisk FactorsSignal Transductionapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9fq747nzarticleScientific Reports, vol 7, iss 112546oai:escholarship.org:ark:/13030/qt1rf5x2kj2023-10-06T11:46:18Zqt1rf5x2kjSignificance of data analysis in the quality control of prenatal screening for Down syndromeLi, YahongZhang, XiaojuanHong, DongyangGuan, XianweiLv, ShaoleiSun, YunJiang, Tao2018-05-01Dual detection of α-fetoprotein (AFP) and free β-human chorionic gonadotropin (β-HCG) is a common screening method for Down syndrome in the second trimester and its efficacy is assessed by false-positive rate (FPR). The present study aimed to investigate the effects of the bias in median multiple of the median (mMoM) values of AFP and free β-HCG on FPR. The bias in mMoM values of AFP and free β-HCG and the bias in mMoM values under different gestational ages and weight groups were analyzed. Median equations were adjusted, and medians in LifeCycle software were replaced by local medians. Following two adjustments of the median equations, all indices including FPR, mMoM values of markers and mMoM values under different gestational ages and weight groups generally reached an ideal state. In conclusion, abnormal bias in mMoM values may prompt aberrant application of median equations, and regular monitoring of these indicators may be important for quality control in prenatal screening.Reproductive MedicineBiomedical and Clinical SciencesPediatricDown syndromeprenatal screeningquality controlapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1rf5x2kjarticleBiomedical Reports, vol 8, iss 5447 - 453oai:escholarship.org:ark:/13030/qt4rq839z52023-10-06T11:46:15Zqt4rq839z5Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson’s disease: a case reportLiu, GangMa, DingyuanCheng, JianZhang, JingjingLuo, ChunyuSun, YunHu, PingWang, YuguoJiang, TaoXu, Zhengfeng2018-12-01BackgroundWilson's disease (WD) is an autosomal recessive disorder characterized by copper accumulation. ATP7B gene mutations lead to ATP7B protein dysfunction, which in turn causes Wilson's disease.Case presentationWe describe a male case of Wilson's disease diagnosed at 10 years after routine biochemical test that showed low serum ceruloplasmin levels and Kayser-Fleischer rings in both corneas. Analysis of the ATP7B gene revealed compound heterozygous mutations in the proband, including the reported c.3517G > A mutation and a novel c.532_574del mutation. The c.532_574del mutation covered a 43-bp region in exon 2, and resulted in a frameshift mutation (p.Leu178PhefsX10). By base sequence analysis, two microhomologies (TCTCA) were observed on both deletion breakpoints in the ATP7B gene. Meanwhile, the presence of some sequence motifs associated with DNA breakage near the deletion region promoted DNA strand break.ConclusionsBy comparison, a replication-based mechanism named fork stalling and template switching/ microhomology-mediated break-induced replication (FoSTeS/MMBIR) was used to explain the formation of this novel deletion mutation.Biological SciencesBiomedical and Clinical SciencesGeneticsNeurodegenerativeAetiology2.1 Biological and endogenous factorsChildChinaCopper-Transporting ATPasesFrameshift MutationHepatolenticular DegenerationHumansMalePedigreeSequence AnalysisDNASequence DeletionCopper-transporting ATPasesATP7BFoSTeS/MMBIRNovel mutationWilson’s diseaseClinical SciencesGenetics & HeredityClinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4rq839z5articleBMC Medical Genomics, vol 19, iss 161oai:escholarship.org:ark:/13030/qt5b77v5k72023-10-06T11:46:12Zqt5b77v5k7A Novel Whole Gene Deletion of BCKDHB by Alu-Mediated Non-allelic Recombination in a Chinese Patient With Maple Syrup Urine DiseaseLiu, GangMa, DingyuanHu, PingWang, WenLuo, ChunyuWang, YanSun, YunZhang, JingjingJiang, TaoXu, Zhengfeng2018-01-01Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by mutations in the BCKDHA, BCKDHB, DBT, and DLD genes. Among the wide range of disease-causing mutations in BCKDHB, only one large deletion has been associated with MSUD. Compound heterozygous mutations in BCKDHB were identified in a Chinese patient with typical MSUD using next-generation sequencing, quantitative PCR, and array comparative genomic hybridization. One allele presented a missense mutation (c.391G > A), while the other allele had a large deletion; both were inherited from the patient's unaffected parents. The deletion breakpoints were characterized using long-range PCR and sequencing. A novel 383,556 bp deletion (chr6: g.80811266_81194921del) was determined, which encompassed the entire BCKDHB gene. The junction site of the deletion was localized within a homologous sequence in two AluYa5 elements. Hence, Alu-mediated non-allelic homologous recombination is speculated as the mutational event underlying the large deletion. In summary, this study reports a recombination mechanism in the BCKDHB gene causing a whole gene deletion in a newborn with MSUD.Biological SciencesBioinformatics and Computational BiologyGeneticsBiotechnologyHuman GenomeBrain DisordersAetiology2.1 Biological and endogenous factorsBCKDHBdried blood spotlarge deletionmaple syrup urine diseasenovel mutationClinical SciencesLawapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5b77v5k7articleFrontiers in Genetics, vol 9, iss APR145oai:escholarship.org:ark:/13030/qt7mm4922z2023-10-06T11:46:09Zqt7mm4922zA regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune responseLyu, Xiao‐MingZhu, Xiao‐WeiZhao, ManliZuo, Xian‐BoHuang, Zhong‐XiLiu, XiaoJiang, TaoYang, Xue‐XiLi, XinLong, Xiao‐BingWang, Jian‐GuoLi, Jin‐BangHan, Ming‐YuWang, ShuangLiu, Teng‐FeiZhang, BoSun, TaoCheng, ZhiQiu, Mo‐ChangDong, LeiZheng, LuZhang, Long‐ChengWang, Jia‐HongWei, Gan‐GuanYao, KaitaiWang, QianZheng, Hou‐FengLi, Xin2018-08-01The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.Biomedical and Clinical SciencesOncology and CarcinogenesisDental/Oral and Craniofacial DiseaseBiotechnologyHuman GenomePreventionGenetics2.1 Biological and endogenous factorsAetiologyAllelesCase-Control StudiesCell LineTumorDNA-Binding ProteinsFemaleGene Expression ProfilingGene Expression RegulationNeoplasticGenotypeHigh-Throughput Nucleotide SequencingHumansImmunomodulationKiller CellsNaturalLeukocytesMononuclearMaleMutationNasopharyngeal CarcinomaNeoplasm StagingPolymorphismSingle NucleotideTripartite Motif ProteinsUbiquitin-Protein LigasesTRIM26immune responsenasopharyngeal carcinomasingle-nucleotide polymorphismstargeted MHC sequencingBiochemistry and Cell BiologyOncology and carcinogenesisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7mm4922zarticleCancer Medicine, vol 7, iss 83848 - 3861oai:escholarship.org:ark:/13030/qt6g52d18t2023-10-06T11:32:06Zqt6g52d18tProgrammable Electrofluidics for Ionic Liquid Based Neuromorphic PlatformBoldman, Walker LZhang, ChengWard, Thomas ZBriggs, Dayrl PSrijanto, Bernadeta RBrisk, PhilipRack, Philip D2019-01-01Due to the limit in computing power arising from the Von Neumann bottleneck, computational devices are being developed that mimic neuro-biological processing in the brain by correlating the device characteristics with the synaptic weight of neurons. This platform combines ionic liquid gating and electrowetting for programmable placement/connectivity of the ionic liquid. In this platform, both short-term potentiation (STP) and long-term potentiation (LTP) are realized via electrostatic and electrochemical doping of the amorphous indium gallium zinc oxide (aIGZO), respectively, and pulsed bias measurements are demonstrated for lower power considerations. While compatible with resistive elements, we demonstrate a platform based on transitive amorphous indium gallium zinc oxide (aIGZO) pixel elements. Using a lithium based ionic liquid, we demonstrate both potentiation (decrease in device resistance) and depression (increase in device resistance), and propose a 2D platform array that would enable a much higher pixel count via Active Matrix electrowetting.EngineeringMaterials EngineeringNeuroscienceselectrowettingneuromorphicionic liquidbiasingdeviceplatformtransistorsTFTTFTsIGZOindium gallium zinc oxidemicrofluidicselectrochemicalelectrostaticNanotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6g52d18tarticleMicromachines, vol 10, iss 7478oai:escholarship.org:ark:/13030/qt16j0265k2023-10-06T11:25:05Zqt16j0265kA Metagenomic Analysis of Environmental and Clinical Samples Using a Secure Hybrid Cloud Solution.Ounit, RachidMason, ChrisLonardi, StefanoO'Hara, Niamh2019-12-01The number and types of studies about the human microbiome, metagenomics and personalized medicine, and clinical genomics are increasing at an unprecedented rate, leading to computational challenges. For example, the analysis of patient/clinical samples requires methods capable of (i) accurately detecting pathogenic organisms, (ii) running with high speed to allow short response-time and diagnosis, and (iii) scaling to ever growing databases of reference genomes. While cloud-computing has the potential to offer low-cost solutions to these needs, serious concerns regarding the protection of genomic data exist due to the lack of control and security in remote genomic databases. We present a novel metagenomic analysis system called "Virgile" that is capable of performing privacy-preserving queries on databases hosted in outsourced servers (e.g., public or cloud-based). This method takes as input the sequenced data produced by any modern sequencing instruments (e.g., Illumina, Pacbio, Oxford Nanopore) and outputs the microbial profile using a database of whole genome sequences (e.g., the RefSeq database from NCBI). The algorithm for the microbial profile aims to estimate without bias the abundance of microorganisms present using a genome-centric approach. Result: Using an extensive set of 65 simulated datasets, negative and positive controls, real clinical samples, and mock communities, we show that Virgile identifies and estimates the abundance of organisms present in environmental or clinical samples with high accuracy compared to state-of-the-art and popular methods available, including MetaPhlAn2 and KrakenUniq. Running at high speed, Virgile can also be run on a standard 8 GB RAM laptop. Virgile is a novel privacy-preserving abundance estimation algorithm called Virgile that can efficiently and rapidly discern the abundance and taxonomic identification of organisms present in a metagenomic sample, including those from medical environments. To the best of our knowledge, Virgile is the only metagenome analysis system leveraging cloud computing in a secure manner.BioengineeringNetworking and Information Technology R&DHuman GenomeGeneticsInfectionGeneric Health RelevanceBiological SciencesTechnologyMedical and Health SciencesBiological sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/16j0265karticleJournal of Biomolecular Techniques, vol 30, iss Suppls2oai:escholarship.org:ark:/13030/qt98t9h9vt2023-10-06T10:37:52Zqt98t9h9vtDevelopment of a Network of Accurate Ozone Sensing Nodes for Parallel Monitoring in a Site Relocation StudyFeenstra, BrandonPapapostolou, VasileiosDer Boghossian, BerjCocker, DavidPolidori, Andrea2020-01-01Recent technological advances in both air sensing technology and Internet of Things (IoT) connectivity have enabled the development and deployment of remote monitoring networks of air quality sensors. The compact size and low power requirements of both sensors and IoT data loggers allow for the development of remote sensing nodes with power and connectivity versatility. With these technological advancements, sensor networks can be developed and deployed for various ambient air monitoring applications. This paper describes the development and deployment of a monitoring network of accurate ozone (O3) sensor nodes to provide parallel monitoring in an air monitoring site relocation study. The reference O3 analyzer at the station along with a network of three O3 sensing nodes was used to evaluate the spatial and temporal variability of O3 across four Southern California communities in the San Bernardino Mountains which are currently represented by a single reference station in Crestline, CA. The motivation for developing and deploying the sensor network in the region was that the single reference station potentially needed to be relocated due to uncertainty that the lease agreement would be renewed. With the implication of siting a new reference station that is also a high O3 site, the project required the development of an accurate and precise sensing node for establishing a parallel monitoring network at potential relocation sites. The deployment methodology included a pre-deployment co-location calibration to the reference analyzer at the air monitoring station with post-deployment co-location results indicating a mean absolute error (MAE) < 2 ppb for 1-h mean O3 concentrations. Ordinary least squares regression statistics between reference and sensor nodes during post-deployment co-location testing indicate that the nodes are accurate and highly correlated to reference instrumentation with R2 values > 0.98, slope offsets < 0.02, and intercept offsets < 0.6 for hourly O3 concentrations with a mean concentration value of 39.7 ± 16.5 ppb and a maximum 1-h value of 94 ppb. Spatial variability for diurnal O3 trends was found between locations within 5 km of each other with spatial variability between sites more pronounced during nighttime hours. The parallel monitoring was successful in providing the data to develop a relocation strategy with only one relocation site providing a 95% confidence that concentrations would be higher there than at the current site.Data Management and Data ScienceDistributed Computing and Systems SoftwareInformation and Computing Sciencesozonesensor networksensor nodemountain community monitoringparallel monitoringsite relocation studyAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/98t9h9vtarticleSensors, vol 20, iss 116oai:escholarship.org:ark:/13030/qt9xk3t6fm2023-10-06T10:25:03Zqt9xk3t6fmNMR and computational methods for molecular resolution of allosteric pathways in enzyme complexesEast, Kyle WSkeens, ErinCui, Jennifer YBelato, Helen BMitchell, BrandonHsu, RohaineBatista, Victor SPalermo, GiuliaLisi, George P2020-02-01Allostery is a ubiquitous biological mechanism in which a distant binding site is coupled to and drastically alters the function of a catalytic site in a protein. Allostery provides a high level of spatial and temporal control of the integrity and activity of biomolecular assembles composed of proteins, nucleic acids, or small molecules. Understanding the physical forces that drive allosteric coupling is critical to harnessing this process for use in bioengineering, de novo protein design, and drug discovery. Current microscopic models of allostery highlight the importance of energetics, structural rearrangements, and conformational fluctuations, and in this review, we discuss the synergistic use of solution NMR spectroscopy and computational methods to probe these phenomena in allosteric systems, particularly protein-nucleic acid complexes. This combination of experimental and theoretical techniques facilitates an unparalleled detection of subtle changes to structural and dynamic equilibria in biomolecules with atomic resolution, and we provide a detailed discussion of specialized NMR experiments as well as the complementary methods that provide valuable insight into allosteric pathways in silico. Lastly, we highlight two case studies to demonstrate the adaptability of this approach to enzymes of varying size and mechanistic complexity.Biochemistry and Cell BiologyBiological SciencesBioengineering1.1 Normal biological development and functioningUnderpinning researchGeneric health relevanceAllosteryCommunity network analysisMolecular dynamicsNMRProtein dynamicsOther Physical SciencesMedical PhysiologyBiochemistry and cell biologyMedical and biological physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9xk3t6fmarticleBiophysical Reviews, vol 12, iss 1155 - 174oai:escholarship.org:ark:/13030/qt2mr9b7tn2023-10-06T09:37:30Zqt2mr9b7tnOMGS: Optical Map-Based Genome ScaffoldingPan, WeihuaJiang, TaoLonardi, StefanoCowen, Lenore J2020-04-01Due to the current limitations of sequencing technologies, de novo genome assembly is typically carried out in two stages, namely contig (sequence) assembly and scaffolding. While scaffolding is computationally easier than sequence assembly, the scaffolding problem can be challenging due to the high repetitive content of eukaryotic genomes, possible mis-joins in assembled contigs, and inaccuracies in the linkage information. Genome scaffolding tools either use paired-end/mate-pair/linked/Hi-C reads or genome-wide maps (optical, physical, or genetic) as linkage information. Optical maps (in particular Bionano Genomics maps) have been extensively used in many recent large-scale genome assembly projects (e.g., goat, apple, barley, maize, quinoa, sea bass, among others). However, the most commonly used scaffolding tools have a serious limitation: they can only deal with one optical map at a time, forcing users to alternate or iterate over multiple maps. In this article, we introduce a novel scaffolding algorithm called OMGS (Optical Map-based Genome Scaffolding) that for the first time can take advantages of multiple optical maps. OMGS solves several optimization problems to generate scaffolds with optimal contiguity and correctness. Extensive experimental results demonstrate that our tool outperforms existing methods when multiple optical maps are available and produces comparable scaffolds using a single optical map.Biological SciencesBioinformatics and Computational BiologyGeneticsHuman GenomeGeneric health relevanceAlgorithmsChromosome MappingContig MappingEukaryotaGenomeGenomicsSequence AnalysisDNASoftwarecombinatorial optimizationde novo genome assemblyoptical mapsscaffoldingMathematical SciencesInformation and Computing SciencesBioinformaticsBiological sciencesInformation and computing sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2mr9b7tnarticleJournal of Computational Biology, vol 27, iss 4519 - 533oai:escholarship.org:ark:/13030/qt1bn045q32023-10-06T08:08:16Zqt1bn045q3Understanding Open Source Serverless PlatformsLi, JunfengKulkarni, Sameer GRamakrishnan, KKLi, Dan2019-12-09Serverless computing is increasingly popular because of the promise of lower
cost and the convenience it provides to users who do not need to focus on
server management. This has resulted in the availability of a number of
proprietary and open-source serverless solutions. We seek to understand how the
performance of serverless computing depends on a number of design issues using
several popular open-source serverless platforms. We identify the
idiosyncrasies affecting performance (throughput and latency) for different
open-source serverless platforms. Further, we observe that just having either
resource-based (CPU and memory) or workload-based (request per second (RPS) or
concurrent requests) auto-scaling is inadequate to address the needs of the
serverless platforms.Distributed Computing and Systems SoftwareInformation and Computing SciencesGeneric health relevanceserverlessfunction-as-a-serviceperformancecs.PFcs.DCapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1bn045q3articleoai:escholarship.org:ark:/13030/qt6g72267f2023-10-06T07:48:14Zqt6g72267fBalanced centroidal power diagrams for redistrictingCohen-Addad, VincentKlein, Philip NYoung, Neal E2018-11-06We consider the problem of political redistricting: given the locations of people in a geographical area (e.g. a US state), the goal is to decompose the area into subareas, called districts, so that the populations of the districts are as close as possible and the districts are “compact” and “contiguous,” to use the terms referred to in most US state constitutions and/or US Supreme Court rulings. We study a method that outputs a solution in which each district is the intersection of a convex polygon with the geographical area. The average number of sides per polygon is less than six. The polygons tend to be quite compact. Every two districts differ in population by at most one (so we call the solution balanced). In fact, the solution is a centroidal power diagram: each polygon has an associated center in R 3 such that • the projection of the center onto the plane z = 0 is the centroid of the locations of people assigned to the polygon, and • for each person assigned to that polygon, the polygon’s center is closest among all centers. The polygons are convex because they are the intersections of 3D Voronoi cells with the plane. The solution is, in a well-defined sense, a locally optimal solution to the problem of choosing centers in the plane and choosing an assignment of people to those 2-d centers so as to minimize the sum of squared distances subject to the assignment being balanced. A practical problem with this approach is that, in real-world redistricting, exact locations of people are unknown. Instead, the input consists of polygons (census blocks) and associated populations. A real redistricting must not split census blocks. We therefore propose a second phase that perturbs the solution slightly so it does not split census blocks. In our experiments, the second phase achieves this while preserving perfect population balance. The district polygons are no longer convex at the fine scale because their boundaries must follow the boundaries of census blocks, but at a coarse scale they preserve the shape of the original polygons.Applied MathematicsMathematical Sciencesredistrictingcomputational geometryoptimizationgraph algorithmapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6g72267farticleoai:escholarship.org:ark:/13030/qt0982r2zv2023-10-06T07:17:24Zqt0982r2zvHigh-content screening in zebrafish identifies perfluorooctanesulfonamide as a potent developmental toxicantDasgupta, SubhamReddam, AalekhyaLiu, ZekunLiu, JinyongVolz, David C2020-01-01Per- and polyfluoroalkyl substances (PFASs) have been used for decades within industrial processes and consumer products, resulting in frequent detection within the environment. Using zebrafish embryos, we screened 38 PFASs for developmental toxicity and revealed that perfluorooctanesulfonamide (PFOSA) was the most potent developmental toxicant, resulting in elevated mortality and developmental abnormalities following exposure from 6 to 24 h post fertilization (hpf) and 6 to 72 hpf. PFOSA resulted in a concentration-dependent increase in mortality and abnormalities, with surviving embryos exhibiting a >12-h delay in development at 24 hpf. Exposures initiated at 0.75 hpf also resulted in a concentration-dependent delay in epiboly, although these effects were not driven by a specific sensitive window of development. We relied on mRNA-sequencing to identify the potential association of PFOSA-induced developmental delays with impacts on the embryonic transcriptome. Relative to stage-matched vehicle controls, these data revealed that pathways related to hepatotoxicity and lipid transport were disrupted in embryos exposed to PFOSA from 0.75 to 14 hpf and 0.75 to 24 hpf. Therefore, we measured liver area as well as neutral lipids in 128-hpf embryos exposed to vehicle (0.1% DMSO) or PFOSA from 0.75 to 24 hpf and clean water from 24 to 128 hpf, and showed that PFOSA exposure from 0.75 to 24 hpf resulted in a decrease in liver area and increase in yolk sac neutral lipids at 128 hpf. Overall, our findings show that early exposure to PFOSA adversely impacts embryogenesis, an effect that may lead to altered lipid transport and liver development.Medical BiotechnologyBiomedical and Clinical SciencesDigestive DiseasesLiver DiseasePreventionGood Health and Well BeingAnimalsEmbryoNonmammalianEmbryonic DevelopmentFluorocarbonsHazardous SubstancesRNAMessengerSulfonamidesToxicity TestsWater PollutantsChemicalZebrafishZebrafish ProteinsPFASPerfluorooctanesulfonamideEmbryonic developmentHepatotoxicityEnvironmental Sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0982r2zvarticleoai:escholarship.org:ark:/13030/qt9539t1zs2023-10-06T07:05:16Zqt9539t1zsMicrobe–microbe interactions trigger Mn(II)-oxidizing gene expressionLiang, JinsongBai, YaohuiMen, YujieQu, Jiuhui2017-01-01Manganese (Mn) is an important metal in geochemical cycles. Some microorganisms can oxidize Mn(II) to Mn oxides, which can, in turn, affect the global cycles of other elements by strong sorption and oxidation effects. Microbe-microbe interactions have important roles in a number of biological processes. However, how microbial interactions affect Mn(II) oxidation still remains unknown. Here, we investigated the interactions between two bacteria (Arthrobacter sp. and Sphingopyxis sp.) in a co-culture, which exhibited Mn(II)-oxidizing activity, although neither were able to oxidize Mn(II) in isolation. We demonstrated that the Mn(II)-oxidizing activity in co-culture was most likely induced via contact-dependent interactions. The expressed Mn(II)-oxidizing protein in the co-culture was purified and identified as a bilirubin oxidase belonging to strain Arthrobacter. Full sequencing of the bilirubin oxidase-encoding gene (boxA) was performed. The Mn(II)-oxidizing protein and the transcripts of boxA were detected in the co-culture, but not in either of the isolated cultures. This indicate that boxA was silent in Arthrobacter monoculture, and was activated in response to presence of Sphingopyxis in the co-culture. Further, transcriptomic analysis by RNA-Seq, extracellular superoxide detection and cell density quantification by flow cytometry indicate induction of boxA gene expression in Arthrobacter was co-incident with a stress response triggered by co-cultivation with Sphingopyxis. Our findings suggest the potential roles of microbial physiological responses to stress induced by other microbes in Mn(II) oxidation and extracellular superoxide production.MicrobiologyBiological SciencesGeneticsEmerging Infectious DiseasesAetiology2.1 Biological and endogenous factorsArthrobacterBacterial ProteinsGene Expression RegulationBacterialManganeseMicrobial InteractionsOxidation-ReductionSphingomonadaceaeEnvironmental SciencesTechnologyBiological sciencesEnvironmental sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9539t1zsarticleThe ISME Journal: Multidisciplinary Journal of Microbial Ecology, vol 11, iss 167 - 77oai:escholarship.org:ark:/13030/qt4933v8pv2023-10-06T07:05:13Zqt4933v8pvMicrobial residence time is a controlling parameter of the taxonomic composition and functional profile of microbial communitiesMansfeldt, CrestenAchermann, StefanMen, YujieWalser, Jean-ClaudeVillez, KrisJoss, AdrianoJohnson, David RFenner, Kathrin2019-06-01A remaining challenge within microbial ecology is to understand the determinants of richness and diversity observed in environmental microbial communities. In a range of systems, including activated sludge bioreactors, the microbial residence time (MRT) has been previously shown to shape the microbial community composition. However, the physiological and ecological mechanisms driving this influence have remained unclear. Here, this relationship is explored by analyzing an activated sludge system fed with municipal wastewater. Using a model designed in this study based on Monod-growth kinetics, longer MRTs were shown to increase the range of growth parameters that enable persistence, resulting in increased richness and diversity in the modeled community. In laboratory experiments, six sequencing batch reactors treating domestic wastewater were operated in parallel at MRTs between 1 and 15 days. The communities were characterized using both 16S ribosomal RNA and non-target messenger RNA sequencing (metatranscriptomic analysis), and model-predicted monotonic increases in richness were confirmed in both profiles. Accordingly, taxonomic Shannon diversity also increased with MRT. In contrast, the diversity in enzyme class annotations resulting from the metatranscriptomic analysis displayed a non-monotonic trend over the MRT gradient. Disproportionately high abundances of transcripts encoding for rarer enzymes occur at longer MRTs and lead to the disconnect between taxonomic and functional diversity profiles.MicrobiologyBiological SciencesLife Below WaterBacteriaBioreactorsDNABacterialMicrobiotaPhylogenyRNARibosomal16SSewageWastewaterEnvironmental SciencesTechnologyBiological sciencesEnvironmental sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4933v8pvarticleThe ISME Journal: Multidisciplinary Journal of Microbial Ecology, vol 13, iss 61589 - 1601oai:escholarship.org:ark:/13030/qt1fm9z9j82023-10-06T06:51:13Zqt1fm9z9j8In-Situ Imaging of Molten High-Entropy Alloys Using Cold NeutronsDerimow, NicholasSantodonato, Louis JMacDonald, Benjamin ELe, BryanLavernia, Enrique JAbbaschian, Reza2019-01-01Real-time neutron imaging was utilized to produce a movie-like series of radiographs for in-situ observation of the remixing of liquid state immiscibility that occurs in equiatomic CoCrCu with the addition of Ni. A previous neutron imaging study demonstrated that liquid state immiscibility can be observed in-situ for the equiatomic CoCrCu alloy. In this follow-up study, equiatomic buttons of CoCrCu were placed alongside small Ni buttons inside an alumina crucible in a high-temperature vacuum furnace. The mass of the Ni buttons was specifically selected such that when melted in the same crucible as the CoCrCu buttons, the overall composition would become equiatomic CoCrCuNi. Neutron imaging was simultaneously carried out to capture 10 radiographs in 20 °C steps from 1000 °C to 1500 °C and back down to 1000 °C. This, in turn, produced a movie-like series of radiographs that allow for the observation of the buttons melting, the transition from immiscible to miscible as Ni is alloyed into the CoCrCu system, and solidification. This novel imaging process showed the phase-separated liquids remixing into a single-phase liquid when Ni dissolves into the melt, which makes this technique crucial for understanding the liquid state behavior of these complex alloy systems. As metals are not transparent to X-ray imaging techniques at this scale, neutron imaging of melting and solidification allows for the observation of liquid state phase changes in real time. Thermodynamic calculations of the isopleth for CoCrCuNix were carried out to compare the observed results to the predictions resulting from the current Thermo-Calc TCHEA3 thermodynamic database. The calculations show a very good agreement with the experimental results, as the calculations indicate that the CoCrCuNix alloy solidifies from a single-phase liquid when x ≥ 0.275, which is close to the nominal concentration of the CoCrCuNi alloy (x = 0.25). The neutron imaging shows that the solidification of CoCrCuNi results from a single-phase liquid. This is evident as no changes in the neutron attenuation were observed during the solidification of the CoCrCuNi alloy.Information and Computing SciencesEngineeringComputer Vision and Multimedia ComputationBiomedical Engineeringhigh-entropy alloysneutron imagingHEAsmulticomponent alloysmulti-principal element alloysMPEAscomplex concentrated alloysCCAsBiomedical engineeringComputer vision and multimedia computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1fm9z9j8articleJournal of Imaging, vol 5, iss 229oai:escholarship.org:ark:/13030/qt1d84t3js2023-10-06T06:23:16Zqt1d84t3jsGas Biosensor Arrays Based on Single-Stranded DNA-Functionalized Single-Walled Carbon Nanotubes for the Detection of Volatile Organic Compound Biomarkers Released by Huanglongbing Disease-Infected Citrus TreesWang, HuiRamnani, PankajPham, TungVillarreal, Claudia ChavesYu, XuejunLiu, GangMulchandani, Ashok2019-01-01Volatile organic compounds (VOCs) released by plants are closely associated with plant metabolism and can serve as biomarkers for disease diagnosis. Huanglongbing (HLB), also known as citrus greening or yellow shoot disease, is a lethal threat to the multi-billion-dollar citrus industry. Early detection of HLB is vital for removal of susceptible citrus trees and containment of the disease. Gas sensors are applied to monitor the air quality or toxic gases owing to their low-cost fabrication, smooth operation, and possible miniaturization. Here, we report on the development, characterization, and application of electrical biosensor arrays based on single-walled carbon nanotubes (SWNTs) decorated with single-stranded DNA (ssDNA) for the detection of four VOCs-ethylhexanol, linalool, tetradecene, and phenylacetaldehyde-that serve as secondary biomarkers for detection of infected citrus trees during the asymptomatic stage. SWNTs were noncovalently functionalized with ssDNA using π-π interaction between the nucleotide and sidewall of SWNTs. The resulting ssDNA-SWNT hybrid structure and device properties were investigated using Raman spectroscopy, ultraviolet (UV) spectroscopy, and electrical measurements. To monitor changes in the four VOCs, gas biosensor arrays consisting of bare SWNTs before and after being decorated with different ssDNA were employed to determine the different concentrations of the four VOCs. The data was processed using principal component analysis (PCA) and neural net fitting (NNF).Data Management and Data ScienceInformation and Computing SciencesEngineeringNanotechnology4.1 Discovery and preclinical testing of markers and technologiesDetectionscreening and diagnosisBiomarkersBiosensing TechniquesCitrusDNAPlantDNASingle-StrandedNanotubesCarbonPlant DiseasesPrincipal Component AnalysisReproducibility of ResultsSpectrophotometryUltravioletSpectrum AnalysisRamanTreesVolatile Organic CompoundsssDNASWNTgas sensorFETvolatile organic compoundsHLBAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1d84t3jsarticleSensors, vol 19, iss 214795oai:escholarship.org:ark:/13030/qt9sm8v3zh2023-10-06T05:45:24Zqt9sm8v3zhMulti-Aspect, Robust, and Memory Exclusive Guest OS FingerprintingGu, YufeiFu, YangchunPrakash, AravindLin, ZhiqiangYin, Heng2014-01-01Precise fingerprinting of an operating system (OS) is critical to many security and forensics applications in the cloud, such as virtual machine (VM) introspection, penetration testing, guest OS administration, kernel dump analysis, and memory forensics. The existing OS fingerprinting techniques primarily inspect network packets or CPU states, and they all fall short in precision and usability. As the physical memory of a VM always exists in all these applications, in this article, we present OS-Sommelier+, a multi-aspect, memory exclusive approach for precise and robust guest OS fingerprinting in the cloud. It works as follows: given a physical memory dump of a guest OS, OS-Sommelier+ first uses a code hash based approach from kernel code aspect to determine the guest OS version. If code hash approach fails, OS-Sommelier+ then uses a kernel data signature based approach from kernel data aspect to determine the version. We have implemented a prototype system, and tested it with a number of Linux kernels. Our evaluation results show that the code hash approach is faster but can only fingerprint the known kernels, and data signature approach complements the code signature approach and can fingerprint even unknown kernels.Distributed Computing and Systems SoftwareInformation and Computing SciencesCybersecurity and PrivacyOperating system fingerprintingvirtual machine introspectionmemory forensicsDistributed ComputingInformation SystemsDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9sm8v3zharticleIEEE Transactions on Cloud Computing, vol 2, iss 4380 - 394oai:escholarship.org:ark:/13030/qt4td3k0rd2023-10-06T05:41:59Zqt4td3k0rdDevelopment of a Meso-Scale SMA-Based Torsion Actuator for Image-Guided ProceduresSheng, JunGandhi, DheerajGullapalli, RaoSimard, J MarcDesai, Jaydev P2017-02-01This paper presents the design, modeling, and control of a meso-scale torsion actuator based on shape memory alloy (SMA) for image-guided surgical procedures. Developing a miniature torsion actuator is challenging, but it opens the possibility of significantly enhancing the robot agility and maneuverability. The proposed torsion actuator is bi-directionally actuated by a pair of antagonistic SMA torsion springs through alternate Joule heating and natural cooling. The torsion actuator is integrated into a surgical robot prototype to demonstrate its working performance in the humid environment under C-Arm CT image guidance.EngineeringEngineering Practice and EducationCT imagingTorsion actuatorcontrolmaximum motion rangemeso-scale robotshape memory alloyArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringMechanical EngineeringIndustrial Engineering & AutomationControl engineeringmechatronics and roboticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4td3k0rdarticleIEEE Transactions on Robotics, vol 33, iss 1240 - 248oai:escholarship.org:ark:/13030/qt8bj4t6x52023-10-06T05:41:55Zqt8bj4t6x5MEMS-Based Flexible Force Sensor for Tri-Axial Catheter Contact Force MeasurementPandya, Hardik JSheng, JunDesai, Jaydev P2017-02-01Atrial fibrillation (AFib) is a significant healthcare problem caused by the uneven and rapid discharge of electrical signals from pulmonary veins (PVs). The technique of radiofrequency (RF) ablation can block these abnormal electrical signals by ablating myocardial sleeves inside PVs. Catheter contact force measurement during RF ablation can reduce the rate of AFib recurrence, since it helps to determine effective contact of the catheter with the tissue, thereby resulting in effective power delivery for ablation. This paper presents the development of a three-dimensional (3D) force sensor to provide the real-time measurement of tri-axial catheter contact force. The 3D force sensor consists of a plastic cubic bead and five flexible force sensors. Each flexible force sensor was made of a PEDOT:PSS strain gauge and a PDMS bump on a flexible PDMS substrate. Calibration results show that the fabricated sensor has a linear response in the force range required for RF ablation. To evaluate its working performance, the fabricated sensor was pressed against gelatin tissue by a micromanipulator and also integrated on a catheter tip to test it within deionized water flow. Both experiments simulated the ventricular environment and proved the validity of applying the 3D force sensor in RF ablation.EngineeringMaterials EngineeringElectronicsSensors and Digital HardwareBioengineeringElectrical and Electronic EngineeringManufacturing EngineeringMechanical EngineeringNanoscience & NanotechnologyElectronicssensors and digital hardwareMechanical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8bj4t6x5articleJournal of Microelectromechanical Systems, vol 26, iss 1264 - 272oai:escholarship.org:ark:/13030/qt1rd6m56z2023-10-06T05:17:23Zqt1rd6m56zControl Ambassadors [President's Message]Farrell, Jay A2014-01-01Jay A. Farrell, Editor of the Digital Object Identifier, informs about the enhanced sensing, actuation, communication, and computational capabilities that enable increasing utilization of control theory research results, improving performance and reliability, giving rise to new areas of control applications, and motivating new directions of control research. In addition to sound control-theoretic research, effective contributions in such application domains require investigators to become control ambassadors. These people are willing to invest sufficient time to learn the fundamental domain knowledge in these application areas. The author informs that the second edition of the 'Impact of Control Technology' report provides several interesting examples of increasingly capable control systems enabled by growing computational, communication, algorithmic, and analysis capabilities.Control EngineeringMechatronics and RoboticsEngineeringAutomotive EngineeringElectrical and Electronic EngineeringControl engineeringmechatronics and roboticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1rd6m56zarticleIEEE Control Systems Magazine, vol 34, iss 512 - 98oai:escholarship.org:ark:/13030/qt6ft781x12023-10-06T05:08:21Zqt6ft781x1Secrecy Analyses of a Full-Duplex MIMOME NetworkSohrabi, RezaZhu, QipingHua, Yingbo2019-01-01This paper presents secrecy analyses of a full-duplex MIMOME network which
consists of two full-duplex multi-antenna users (Alice and Bob) and an
arbitrarily located multi-antenna eavesdropper (Eve). The paper assumes that
Eve's channel state information (CSI) is completely unknown to Alice and Bob
except for a small radius of secured zone. The first part of this paper aims to
optimize the powers of jamming noises from both users. To handle Eve's CSI
being unknown to users, the focus is placed on Eve at the most harmful
location, and the large matrix theory is applied to yield a hardened secrecy
rate to work on. The performance gain of the power optimization in terms of
maximum tolerable number of antennas on Eve is shown to be significant. The
second part of this paper shows two analyses of anti-eavesdropping channel
estimation (ANECE) that can better handle Eve with any number of antennas. One
analysis assumes that Eve has a prior statistical knowledge of its CSI, which
yields lower and upper bounds on secure degrees of freedom of the system as
functions of the number (N) of antennas on Eve and the size (K) of information
packet. The second analysis assumes that Eve does not have any prior knowledge
of its CSI but performs blind detection of information, which yields an
approximate secrecy rate for the case of K being larger than N.Theory Of ComputationInformation and Computing SciencesCommunications EngineeringEngineeringPhysical layer securitysecrecy ratefull-duplex radioMIMOMEjammingartificial noiseanti-eavesdropping channel estimationeess.SPcs.ITmath.ITNetworking & TelecommunicationspubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6ft781x1articleIEEE Transactions on Signal Processing, vol 67, iss 235968 - 5982oai:escholarship.org:ark:/13030/qt5gf4x1jn2023-10-06T05:02:30Zqt5gf4x1jnSynthesis of molybdenum oxide nanoparticles by nanosecond laser ablationZamora-Romero, NoeCamacho-Lopez, Miguel AVilchis-Nestor, Alfredo RCastrejon-Sanchez, Victor HAguilar, GuillermoCamacho-Lopez, SantiagoCamacho-Lopez, Marco2020-01-01Phothermal therapy (PTT) is one of the most promising techniques to treat cancer. Finding the ideal PTT agent nanomaterial has remained a challenge and has brought the interest of several researchers. In this work, we report the synthesis of molybdenum oxide (MoOx) nanoparticles (NPs), which exhibit absorption in the biological optical window ~840 nm, by using the laser ablation of solids in liquids (LASL) technique with nanosecond (ns) pulses. A Nd:YAG laser was used to synthesize the NPs in deionized (DI) water, free of surfactants or additives, which were optically characterized by absorption spectroscopy and TEM-EDX microscopy. Semi spherical NPs with a suitable average size and shape for potential use as PTT agents were obtained by laser ablation and ablation + fragmentation. The calculated band gap is 3.1 eV, which corresponds to MoO3. Micro-Raman spectroscopy studies determined that these NPs are composed of amorphous molybdenum oxide hydrates (MoO3 · xH2O).EngineeringNanotechnologyBioengineeringPhotothermal therapyPhotothennal agentMolybdenum oxideLaser ablationNanoparticles fragmentationMacromolecular and Materials ChemistryMaterials EngineeringMaterialsMaterials engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5gf4x1jnarticleoai:escholarship.org:ark:/13030/qt6692f2xp2023-10-06T04:54:44Zqt6692f2xpContralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute StrokeThamm, ThoralfGuo, JiaRosenberg, JarrettLiang, TieMarks, Michael PChristensen, SorenDo, Huy MKemp, Stephanie MAdair, EmmaEyngorn, IrinaMlynash, MichaelJovin, Tudor GKeogh, Bart PChen, Hui JLansberg, Maarten GAlbers, Gregory WZaharchuk, Greg2019-12-01Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730.Biomedical and Clinical SciencesClinical SciencesClinical ResearchNeurosciencesBrain DisordersStrokeBiomedical ImagingDetectionscreening and diagnosis4.2 Evaluation of markers and technologiesAgedBrainBrain IschemiaCerebrovascular CirculationFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuroimagingProspective StudiesTreatment Outcomecerebrovascular circulationmagnetic resonance imagingperfusion imagingprognosisprospective studiesstrokeCardiorespiratory Medicine and HaematologyNeurology & NeurosurgeryClinical sciencesAllied health and rehabilitation scienceapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6692f2xparticleStroke, vol 50, iss 123408 - 3415oai:escholarship.org:ark:/13030/qt41z065nm2023-10-06T04:24:15Zqt41z065nmEnsemble learning of model hyperparameters and spatiotemporal data for calibration of low-cost PM2.5 sensors.Yin, Peng-YengTsai, Chih-ChunDay, Rong-FuhTung, Ching-YingBhanu, Bir2019-01-01he PM2.5 air quality index (AQI) measurements from government-built supersites are accurate but cannot provide a dense coverage of monitoring areas. Low-cost PM2.5 sensors can be used to deploy a fine-grained internet-of-things (IoT) as a complement to government facilities. Calibration of low-cost sensors by reference to high-accuracy supersites is thus essential. Moreover, the imputation for missing-value in training data may affect the calibration result, the best performance of calibration model requires hyperparameter optimization, and the affecting factors of PM2.5 concentrations such as climate, geographical landscapes and anthropogenic activities are uncertain in spatial and temporal dimensions. In this paper, an ensemble learning for imputation method selection, calibration model hyperparameterization, and spatiotemporal training data composition is proposed. Three government supersites are chosen in central Taiwan for the deployment of low-cost sensors and hourly PM2.5 measurements are collected for 60 days for conducting experiments. Three optimizers, Sobol sequence, Nelder and Meads, and particle swarm optimization (PSO), are compared for evaluating their performances with various versions of ensembles. The best calibration results are obtained by using PSO, and the improvement ratios with respect to R2, RMSE, and NME, are 4.92%, 52.96%, and 56.85%, respectively.Chemical EngineeringMathematical SciencesApplied MathematicsEngineeringensemble learninglow-cost sensorsair quality indexparticle swarm optimizationPM2.5spatiotemporal datasensor calibrationPM2.5air quality indexensemble learninglow-cost sensorsparticle swarm optimizationsensor calibratiospatiotemporal dataBiomedical EngineeringBioinformaticsChemical engineeringApplied mathematicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/41z065nmarticleMathematical Biosciences and Engineering, vol 16, iss 66858 - 6873oai:escholarship.org:ark:/13030/qt106675xj2023-10-06T04:01:03Zqt106675xjSCALE method for single-cell ATAC-seq analysis via latent feature extractionXiong, LeiXu, KuiTian, KangShao, YanqiuTang, LeiGao, GeZhang, MichaelJiang, TaoZhang, Qiangfeng Cliff2019-01-01Single-cell ATAC-seq (scATAC-seq) profiles the chromatin accessibility landscape at single cell level, thus revealing cell-to-cell variability in gene regulation. However, the high dimensionality and sparsity of scATAC-seq data often complicate the analysis. Here, we introduce a method for analyzing scATAC-seq data, called Single-Cell ATAC-seq analysis via Latent feature Extraction (SCALE). SCALE combines a deep generative framework and a probabilistic Gaussian Mixture Model to learn latent features that accurately characterize scATAC-seq data. We validate SCALE on datasets generated on different platforms with different protocols, and having different overall data qualities. SCALE substantially outperforms the other tools in all aspects of scATAC-seq data analysis, including visualization, clustering, and denoising and imputation. Importantly, SCALE also generates interpretable features that directly link to cell populations, and can potentially reveal batch effects in scATAC-seq experiments.Information and Computing SciencesBiological SciencesBioinformatics and Computational BiologyGeneticsUnderpinning research1.1 Normal biological development and functioningGeneric health relevanceAnimalsChromatin Immunoprecipitation SequencingCluster AnalysisData AnalysisDatasets as TopicHEK293 CellsHumansLeukemiaMammary NeoplasmsExperimentalMiceModelsStatisticalNormal DistributionSingle-Cell AnalysisStem Cellsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/106675xjarticleNature Communications, vol 10, iss 14576oai:escholarship.org:ark:/13030/qt26h2g0n32023-10-06T03:08:47Zqt26h2g0n3Joint Image and Depth Estimation With Mask-Based Lensless CamerasZheng, YuchengAsif, M Salman2020-01-01Mask-based lensless cameras replace the lens of a conventional camera with a custom mask. These cameras can potentially be very thin and even flexible. Recently, it has been demonstrated that such mask-based cameras can recover light intensity and depth information of a scene. Existing depth recovery algorithms either assume that the scene consists of a small number of depth planes or solve a sparse recovery problem over a large 3D volume. Both these approaches fail to recover the scenes with large depth variations. In this paper, we propose a new approach for depth estimation based on an alternating gradient descent algorithm that jointly estimates a continuous depth map and light distribution of the unknown scene from its lensless measurements. We present simulation results on image and depth reconstruction for a variety of 3D test scenes. A comparison between the proposed algorithm and other method shows that our algorithm is more robust for natural scenes with a large range of depths. We built a prototype lensless camera and present experimental results for reconstruction of intensity and depth maps of different real objects.Information and Computing SciencesGraphicsAugmented Reality and GamesEngineeringComputer Vision and Multimedia ComputationLensless imagingflatcamdepth estimationnon-convex optimizationalternating minimizationeess.IVcs.CVCommunications engineeringComputer vision and multimedia computationNumerical and computational mathematicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/26h2g0n3articleoai:escholarship.org:ark:/13030/qt2c43s7kp2023-10-06T03:08:42Zqt2c43s7kpA Dual Camera System for High Spatiotemporal Resolution Video AcquisitionCheng, MingMa, ZhanAsif, M SalmanXu, YilingLiu, HaojieBao, WenboSun, Jun2021-10-01This paper presents a dual camera system for high spatiotemporal resolution (HSTR) video acquisition, where one camera shoots a video with high spatial resolution and low frame rate (HSR-LFR) and another one captures a low spatial resolution and high frame rate (LSR-HFR) video. Our main goal is to combine videos from LSR-HFR and HSR-LFR cameras to create an HSTR video. We propose an end-to-end learning framework, AWnet, mainly consisting of a FlowNet and a FusionNet that learn an adaptive weighting function in pixel domain to combine inputs in a frame recurrent fashion. To improve the reconstruction quality for cameras used in reality, we also introduce noise regularization under the same framework. Our method has demonstrated noticeable performance gains in terms of both objective PSNR measurement in simulation with different publicly available video and light-field datasets and subjective evaluation with real data captured by dual iPhone 7 and Grasshopper3 cameras. Ablation studies are further conducted to investigate and explore various aspects, such as reference structure, camera parallax, exposure time, etc) of our system to fully understand its capability for potential applications.Information and Computing SciencesComputer Vision and Multimedia ComputationClinical ResearchCamerasSpatial resolutionSpatiotemporal phenomenaData modelsDual camera systemhigh spatiotemporal resolutionsuper-resolutionoptical flowspatial informationend-to-end learningeess.IVcs.CVArtificial Intelligence and Image ProcessingInformation SystemsElectrical and Electronic EngineeringArtificial Intelligence & Image ProcessingComputer vision and multimedia computationMachine learningapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2c43s7kparticleIEEE Transactions on Pattern Analysis and Machine Intelligence, vol 43, iss 103275 - 3291oai:escholarship.org:ark:/13030/qt98j9r13d2023-10-06T02:46:59Zqt98j9r13dA new bottom-up emissions estimation approach for aircraft sources in support of air quality modelling for community-scale assessments around airportsArunachalam, SaravananNaess, BrianSeppanen, CatherineValencia, AlejandroBrandmeyer, Jo EllenVenkatram, AkulaWeil, JeffreyIsakov, VladBarzyk, Timothy2019-01-01Transportation infrastructure (including roadway traffic, ports, and airports) is critical to the nation's economy. With a growing economy, aircraft activity is expected to grow across the world. In the US, airport-related emissions, while generally small, are not an insignificant source of air pollution and related adverse health effects. However, currently there is a lack of tools that can easily be applied to study near-source pollution and explore the benefits of improvements to air quality and exposures. Screening-level air quality modelling is a useful tool for examining urban-scale air quality impacts of airport operations. Spatially-resolved aircraft emissions are needed for the screening-level modelling. In order to create spatially-resolved aircraft emissions, we developed a bottom-up emissions estimation methodology that includes data from a global chorded inventory dataset from the aviation environmental design tool (AEDT). The initial implementation of this method was performed for Los Angeles International Airport (LAX). This paper describes a new emissions estimation methodology for aircraft emissions in support of community-scale assessments of air quality around airports and presents an illustration of its application at the Los Angeles International Airport during the LAX 2011/2012 Air Quality Source Apportionment Study.TransportationLogistics and Supply ChainsEngineeringCommerceManagementTourism and ServicesGeneric health relevanceClimate Actionair qualityexposureairportsaircraft emissionsenvironmental pollutionaviation environmental design toolAEDTLos Angeles InternationalLAXEnvironmental SciencesCommercemanagementtourism and servicesEnvironmental sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/98j9r13darticleInternational Journal of Environment and Pollution, vol 65, iss 1-343 - 58oai:escholarship.org:ark:/13030/qt5zq0b2wj2023-10-06T00:27:16Zqt5zq0b2wjFunctionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligandsHanley, TaylorYin, RongMac, Jenny TTan, WenbinAnvari, Bahman2019-08-01Over- or under-expression of erythropoietin-production human hepatocellular receptors (Eph) and their ligands are associated with various diseases. Therefore, these molecular biomarkers can potentially be used as binding targets for the delivery of therapeutic and/or imaging agents to cells characterized by such irregular expressions. We have engineered nanoparticles derived from erythrocytes and doped with the near-infrared (NIR) FDA-approved dye, indocyanine green. We refer to these nanoparticles as NIR erythrocyte-derived transducers (NETs). We functionalized the NETs with the ligand-binding domain of a particular Eph receptor, EphB1, to target the genetically modified human dermal microvascular endothelial cells (hDMVECs) with coexpression of EphB1 receptor and its ligand ephrin-B2. This cell model mimics the pathological phenotypes of lesional endothelial cells (ECs) in port wine stains (PWSs). Our quantitative fluorescence imaging results demonstrate that such functionalized NETs bind to the ephrin-B2 ligands on these hDMVECs in a dose-dependent manner that varies sigmoidally with the number density of the particles. These nanoparticles may potentially serve as agents to target PWS lesional ECs and other diseases characterized with over-expression of Eph receptors or their associated ligands to mediate phototherapy.Medical BiotechnologyBiomedical and Clinical SciencesBioengineeringNanotechnologyAnimalsBiomarkersCattleDose-Response RelationshipDrugEndothelial CellsEphrin-B2ErythrocytesHumansLigandsLightMicrocirculationMicroscopyFluorescenceNanoparticlesOptics and PhotonicsPhototherapyPort-Wine StainProtein BindingProtein DomainsScatteringRadiationSkinSpectroscopyNear-InfraredTransducersTransfectionEph receptorsnanomaterialsnear infrared fluorescence imagingport wine stainsred blood cellsOptical PhysicsBiomedical EngineeringOpthalmology and OptometryOpticsOphthalmology and optometryBiomedical engineeringAtomicmolecular and optical physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5zq0b2wjarticleJournal of Biomedical Optics, vol 24, iss 8085002 - 085002oai:escholarship.org:ark:/13030/qt58z3p0f82023-10-05T22:40:25Zqt58z3p0f8Frequency regulation service provision in data center with computational flexibilityWang, WeiAbdolrashidi, AmiraliYu, NanpengWong, Daniel2019-10-01The rapid adoption of cloud storage and computing services led to unprecedented growth of data centers in the world. As bulk energy consumers, large-scale data centers in the U.S. rack up billions in electricity costs annually. Fortunately, the operational flexibility of data centers can be leveraged to provide valuable frequency regulation services in smart grids to mitigate the indeterminacy of the renewable generation resources. Specifically, this paper aims to leverage computational flexibility provided by servers, such as dynamic voltage frequency scaling and dummy loads. This paper develops a comprehensive framework for data center's frequency regulation service provision in both hour-ahead market and real-time operations. A risk constrained hour-ahead bidding strategy along with a real-time data center power consumption control algorithm are developed to minimize electricity bills and the total response time of the requests. The introduction of dummy load, realistic bi-linear server power consumption model, and probabilistic forecast of electricity and frequency regulation service prices enable the data center to accurately follow frequency regulation signals, while reducing the financial risks associated with electricity market participation. The simulation results show that the proposed frequency regulation provision framework results not only in significant cost reduction for data centers, but also limits degradation in quality of service. Meanwhile, the stability and reliability of a power grid will be improved by the frequency regulation service provision.EngineeringElectrical EngineeringPatient SafetyAffordable and Clean EnergyData centerDeep sleep stateElectricity marketFrequency regulationEconomicsEnergyBuilt environment and designapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/58z3p0f8articleoai:escholarship.org:ark:/13030/qt19m4k5vj2023-10-05T21:56:15Zqt19m4k5vjInformation Losses in Neural Classifiers From SamplingFoggo, BrandonYu, NanpengShi, JieGao, Yuanqi2020-10-01This article considers the subject of information losses arising from the finite data sets used in the training of neural classifiers. It proves a relationship between such losses as the product of the expected total variation of the estimated neural model with the information about the feature space contained in the hidden representation of that model. It then bounds this expected total variation as a function of the size of randomly sampled data sets in a fairly general setting, and without bringing in any additional dependence on model complexity. It ultimately obtains bounds on information losses that are less sensitive to input compression and in general much smaller than existing bounds. This article then uses these bounds to explain some recent experimental findings of information compression in neural networks that cannot be explained by previous work. Finally, this article shows that not only are these bounds much smaller than existing ones, but they also correspond well with experiments.Information and Computing SciencesMachine LearningNeural networksMachine learningTrainingRandom variablesTraining dataProbability distributionLearning systemsDeep learninginformation theorylarge deviations theorymutual informationstatistical learning theorycs.LGstat.MLArtificial Intelligence & Image ProcessingArtificial intelligenceapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/19m4k5vjarticleIEEE Transactions on Neural Networks and Learning Systems, vol 31, iss 104073 - 4083oai:escholarship.org:ark:/13030/qt2kn4c2182023-10-05T21:33:07Zqt2kn4c218Enhanced near infrared optical access to the brain with a transparent cranial implant and scalp optical clearing.Cano-Velázquez, Mildred SDavoodzadeh, NamiHalaney, DavidJonak, Carrie RBinder, Devin KHernández-Cordero, JuanAguilar, Guillermo2019-07-01We report on the enhanced optical transmittance in the NIR wavelength range (900 to 2400 nm) offered by a transparent Yttria-stabilized zirconia (YSZ) implant coupled with optical clearing agents (OCAs). The enhancement in optical access to the brain is evaluated upon comparing ex-vivo transmittance measurements of mice native skull and the YSZ cranial implant with scalp and OCAs. An increase in transmittance of up to 50% and attenuation lengths of up to 2.4 mm (i.e., a five-fold increase in light penetration) are obtained with the YSZ implant and the OCAs. The use of this ceramic implant and the biocompatible optical clearing agents offer attractive features for NIR optical techniques for brain theranostics.Biomedical and Clinical SciencesDentistryDental/Oral and Craniofacial DiseaseOptical PhysicsMaterials EngineeringOphthalmology and optometryBiomedical engineeringAtomicmolecular and optical physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2kn4c218articleBiomedical Optics Express, vol 10, iss 73369 - 3379oai:escholarship.org:ark:/13030/qt5hx584w62023-10-05T21:27:24Zqt5hx584w6Reversible intercalation of methyl viologen as a dicationic charge carrier in aqueous batteriesWei, ZhixuanShin, WoochulJiang, HengWu, XianyongStickle, William FChen, GangLu, JunAlex Greaney, PDu, FeiJi, Xiulei2019-01-01The interactions between charge carriers and electrode structures represent one of the most important considerations in the search for new energy storage devices. Currently, ionic bonding dominates the battery chemistry. Here we report the reversible insertion of a large molecular dication, methyl viologen, into the crystal structure of an aromatic solid electrode, 3,4,9,10-perylenetetracarboxylic dianhydride. This is the largest insertion charge carrier when non-solvated ever reported for batteries; surprisingly, the kinetic properties of the (de)insertion of methyl viologen are excellent with 60% of capacity retained when the current rate is increased from 100 mA g-1 to 2000 mA g-1. Characterization reveals that the insertion of methyl viologen causes phase transformation of the organic host, and embodies guest-host chemical bonding. First-principles density functional theory calculations suggest strong guest-host interaction beyond the pure ionic bonding, where a large extent of covalency may exist. This study extends the boundary of battery chemistry to large molecular ions as charge carriers and also highlights the electrochemical assembly of a supramolecular system.Macromolecular and Materials ChemistryChemical SciencesPhysical ChemistryEngineeringMaterials EngineeringAffordable and Clean Energyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5hx584w6articleNature Communications, vol 10, iss 13227oai:escholarship.org:ark:/13030/qt8831m7942023-10-05T21:21:06Zqt8831m794CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatmentPatri, Abhishek SMcAlister, LauraCai, Charles MKumar, RajeevWyman, Charles E2019-12-01BackgroundPretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars. Furthermore, lignocellulosic biomass must typically be reduced in size to increase the pretreatment effectiveness and realize high sugar yields. However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.ResultsIn this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis. Sugar yields by enzymatic hydrolysis were measured over a range of enzyme loadings. In general, DSA successfully solubilized hemicellulose, while CELF removed nearly 80% of Klason lignin from switchgrass in addition to the majority of hemicellulose. Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF. However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time. Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis. CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.ConclusionsCELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA. These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels. In addition, presoaking proved much more effective for CELF than for DSA, particularly at low enzyme loadings.Biological SciencesIndustrial BiotechnologyAffordable and Clean EnergyBiomassPretreatmentSoakingEnzymatic hydrolysisDilute acidTetrahydrofuranSize reductionChemical EngineeringBiochemistry and cell biologyIndustrial biotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8831m794articleBiotechnology for Biofuels and Bioproducts, vol 12, iss 1177oai:escholarship.org:ark:/13030/qt2dk0d4mk2023-10-05T20:13:41Zqt2dk0d4mkNon-Invasive Photoacoustic Imaging of In Vivo Mice with Erythrocyte Derived Optical Nanoparticles to Detect CAD/MILiu, YonggangHanley, TaylorChen, HaoLong, Steven RGambhir, Sanjiv SCheng, ZhenWu, Joseph CFakhri, Georges ElAnvari, BahmanZaman, Raiyan T2020-01-01Coronary artery disease (CAD) causes mortality and morbidity worldwide. We used near-infrared erythrocyte-derived transducers (NETs), a contrast agent, in combination with a photoacoustic imaging system to identify the locations of atherosclerotic lesions and occlusion due to myocardial-infarction (MI). NETs (≈90 nm diameter) were fabricated from hemoglobin-depleted mice erythrocyte-ghosts and doped with Indocyanine Green (ICG). Ten weeks old male C57BL/6 mice (n = 9) underwent left anterior descending (LAD) coronary artery ligation to mimic vulnerable atherosclerotic plaques and their rupture leading to MI. 150 µL of NETs (20 µM ICG,) was IV injected via tail vein 1-hour prior to photoacoustic (PA) and fluorescence in vivo imaging by exciting NETs at 800 nm and 650 nm, respectively. These results were verified with histochemical analysis. We observed ≈256-fold higher PA signal from the accumulated NETs in the coronary artery above the ligation. Fluorescence signals were detected in LAD coronary, thymus, and liver. Similar signals were observed when the chest was cut open. Atherosclerotic lesions exhibited inflammatory cells. Liver demonstrated normal portal tract, with no parenchymal necrosis, inflammation, fibrosis, or other pathologic changes, suggesting biocompatibility of NETs. Non-invasively detecting atherosclerotic plaques and stenosis using NETs may lay a groundwork for future clinical detection and improving CAD risk assessment.Biomedical and Clinical SciencesEngineeringBiomedical EngineeringBioengineeringHeart Disease - Coronary Heart DiseaseBiomedical ImagingHeart DiseaseNanotechnologyAtherosclerosisCardiovascularGood Health and Well BeingAnimalsCoronary Artery DiseaseCoronary VesselsDisease ModelsAnimalErythrocytesMiceMyocardial InfarctionNanoparticlesOptical ImagingPhotoacoustic Techniquesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2dk0d4mkarticleScientific Reports, vol 10, iss 15983oai:escholarship.org:ark:/13030/qt93q0r6r52023-10-05T19:41:44Zqt93q0r6r5Optical Access to Arteriovenous Cerebral Microcirculation Through a Transparent Cranial ImplantDavoodzadeh, NamiCano‐Velázquez, Mildred SHalaney, David LJonak, Carrie RBinder, Devin KAguilar, Guillermo2019-12-01Background and objectiveMicrocirculation plays a critical role in physiologic processes and several disease states. Laser speckle imaging (LSI) is a full-field, real-time imaging technique capable of mapping microvessel networks and providing relative flow velocity within the vessels. In this study, we demonstrate that LSI combine with multispectral reflectance imaging (MSRI), which allows for distinction between veins and arteries in the vascular flow maps produced by LSI. We apply this combined technique to mouse cerebral vascular network in vivo, comparing imaging through the skull, to the dura mater and brain directly through a craniectomy, and through a transparent cranial "Window to the Brain" (WttB) implant.Study design/materials and methodsThe WttB implant used in this study is made of a nanocrystalline Yttria-Stabilized-Zirconia ceramic. MSRI was conducted using white-light illumination and filtering the reflected light for 560, 570, 580, 590, 600, and 610 nm. LSI was conducted using an 810 nm continuous wave near-infrared laser with incident power of 100 mW, and the reflected speckle pattern was captured by a complementary metal-oxide-semiconductor (CMOS) camera.ResultsSeven vessel branches were analyzed and comparison was made between imaging through the skull, craniectomy, and WttB implant. Through the skull, MSRI did not detect any vessels, and LSI could not image microvessels. Imaging through the WttB implant, MSRI was able to identify veins versus arteries, and LSI was able to image microvessels with only slightly higher signal-to-noise ratio and lower sharpness than imaging the brain through a craniectomy.ConclusionsThis study demonstrates the ability to perform MSRI-LSI across a transparent cranial implant, to allow for cerebral vascular networks to be mapped, including microvessels. These images contain additional information such as vein-artery separation and relative blood flow velocities, information which is of value scientifically and medically. The WttB implant provides substantial improvements over imaging through the murine cranial bone, where microvessels are not visible and MSRI cannot be performed. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.Biomedical and Clinical SciencesDentistryDental/Oral and Craniofacial DiseaseAnimalsBlood Flow VelocityBrainCeramicsMaleMiceMicrocirculationMicrovesselsOptical ImagingProstheses and ImplantsProsthesis ImplantationSkullSpectroscopyNear-InfraredYttriumZirconiumtransparent nanocrystalline yttria-stabilized-zirconiabrain imagingarteriovenous cerebral microcirculationlaser speckle imagingmultispectral reflectance imagingClinical SciencesDermatology & Venereal DiseasesClinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/93q0r6r5articleLasers in Surgery and Medicine, vol 51, iss 10920 - 932oai:escholarship.org:ark:/13030/qt1j8250zg2023-10-05T19:41:39Zqt1j8250zgPhotochemically Induced Phase Change in Monolayer Molybdenum DisulfideByrley, PeterLiu, MingYan, Ruoxue2019-01-01Monolayer transition metal dichalcogenide (TMDs) are promising candidates for two-dimensional (2D) ultrathin, flexible, low-power, and transparent electronics and optoelectronics. However, the performance of TMD-based devices is still limited by the relatively low carrier mobility and the large contact resistance between the semiconducting 2D channel material and the contact metal electrodes. Phase-engineering in monolayer TMDs showed great promise in enabling the fabrication of high-quality hetero-phase structures with controlled carrier mobilities and heterojunction materials with reduced contact resistance. However, to date, general methods to induce phase-change in monolayer TMDs either employ highly-hostile organometallic compounds, or have limited compatibility with large-scale, cost-effective device fabrication. In this paper, we report a new photochemical method to induce semiconductor to metallic phase transition in monolayer MoS2 in a benign chemical environment, through a bench-top, cost-effective solution phase process that is compatible with large-scale device fabrication. It was demonstrated that photoelectrons produced by the band-gap absorption of monolayer MoS2 have enough chemical potential to activate the phase transition in the presence of an electron-donating solvent. This novel photochemical phase-transition mechanism advances our fundamental understanding of the phase transformation in 2D transition metal dichalcogenides (TMDs), and will open new revenues in the fabrication of atomically-thick metal-semiconductor heterostructures for improved carrier mobility and reduced contact resistance in TMD-based electronic and optoelectronic devices.Chemical Sciencesphase transitionphotochemicalmolybdenum disulfidetransition metal dichacogenidein situ spectroscopic characterizationXPSRamanChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1j8250zgarticleoai:escholarship.org:ark:/13030/qt3gg7t0fk2023-10-05T18:37:55Zqt3gg7t0fkSilver content dependent thermal conductivity and thermoelectric properties of electrodeposited antimony telluride thin filmsFerrer-Argemi, LaiaYu, ZiqiKim, JiwonMyung, Nosang VLim, Jae-HongLee, Jaeho2019-01-01While electrodeposited antimony telluride thin films with silver contents demonstrated promising thermoelectric properties, their thermal conductivity and the silver content dependence remain unknown. Here, we report the thermal conductivities of Ag3.9Sb33.6Te62.5 and AgSbTe2 thin films with controlled annealing and temperature conditions and demonstrate the impact of silver content on thermal transport. After annealing at 160 °C, the room-temperature thermal conductivity of Ag3.9Sb33.6Te62.5 and AgSbTe2 thin films increases from 0.24 to 1.59 Wm-1 K-1 and from 0.17 to 0.56 Wm-1 K-1, respectively. Using phonon transport models and X-ray diffraction measurements, we attribute the thermal conductivity increases to the crystal growth and explain the thermal conductivity variations with the degree of crystallization. Unlike electrical properties reported in previous studies, the presence of silver contents has little impact on the thermal conductivity of Ag3.9Sb33.6Te62.5 and leads to a strong reduction in the thermal conductivity of AgSbTe2 thin films. By performing transient thermal conductivity measurements at 94 °C, we find the crystallization activation energy of Ag3.9Sb33.6Te62.5 and AgSbTe2 films as 1.14 eV and 1.16 eV, respectively. Their differences reveal the role of silver in inhibiting the nucleation and growth of Sb2Te3 crystals and impeding thermal transport. These findings provide guidance for optimizing doping and annealing conditions of antimony tellurides for near-room-temperature thermoelectric applications.EngineeringChemical SciencesPhysical SciencesCondensed Matter Physicsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3gg7t0fkarticleScientific Reports, vol 9, iss 19242oai:escholarship.org:ark:/13030/qt4ns8z14q2023-10-05T17:23:32Zqt4ns8z14qCell-Free Synthetic Biology Platform for Engineering Synthetic Biological Circuits and SystemsJeong, DohyunKlocke, MelissaAgarwal, SiddharthKim, JeongwonChoi, SeungdoFranco, ElisaKim, Jongmin2019-01-01Synthetic biology brings engineering disciplines to create novel biological systems for biomedical and technological applications. The substantial growth of the synthetic biology field in the past decade is poised to transform biotechnology and medicine. To streamline design processes and facilitate debugging of complex synthetic circuits, cell-free synthetic biology approaches has reached broad research communities both in academia and industry. By recapitulating gene expression systems in vitro, cell-free expression systems offer flexibility to explore beyond the confines of living cells and allow networking of synthetic and natural systems. Here, we review the capabilities of the current cell-free platforms, focusing on nucleic acid-based molecular programs and circuit construction. We survey the recent developments including cell-free transcription-translation platforms, DNA nanostructures and circuits, and novel classes of riboregulators. The links to mathematical models and the prospects of cell-free synthetic biology platforms will also be discussed.Biochemistry and Cell BiologyBiological SciencesIndustrial BiotechnologyBiotechnologyBioengineeringGeneticsNanotechnologyUnderpinning research1.1 Normal biological development and functioningGeneric health relevancesynthetic biologycell-free transcription-translationrapid prototypingartificial cellriboregulatorDNA origamimathematical modelBiological sciencesBiomedical and clinical sciencesChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4ns8z14qarticleMethods and Protocols, vol 2, iss 239oai:escholarship.org:ark:/13030/qt6sx407zf2023-10-05T15:23:58Zqt6sx407zfImpacts of cellulase deactivation at the moving air–liquid interface on cellulose conversions at low enzyme loadingsBhagia, SamarthyaWyman, Charles EKumar, Rajeev2019-12-01BackgroundWe recently confirmed that the deactivation of T. reesei cellulases at the air-liquid interface reduces microcrystalline cellulose conversion at low enzyme loadings in shaken flasks. It is one of the main causes for lowering of cellulose conversions at low enzyme loadings. However, supplementing cellulases with small quantities of surface-active additives in shaken flasks can increase cellulose conversions at low enzyme loadings. It was also shown that cellulose conversions at low enzyme loadings can be increased in unshaken flasks if the reactions are carried for a longer time. This study further explores these recent findings to better understand the impact of air-liquid interfacial phenomena on enzymatic hydrolysis of cellulose contained in Avicel, Sigmacell, α-cellulose, cotton linters, and filter paper. The impacts of solids and enzyme loadings, supplementation with nonionic surfactant Tween 20 and xylanases, and application of different types of mixing and reactor designs on cellulose hydrolysis were also evaluated.ResultsAvicel cellulose conversions at high solid loading were more than doubled by minimizing loss of cellulases to the air-liquid interface. Maximum cellulose conversions were high for surface-active supplemented shaken flasks or unshaken flasks because of low cellulase deactivation at the air-liquid interface. The nonionic surfactant Tween 20 was unable to completely prevent cellulase deactivation in shaken flasks and only reduced cellulose conversions at unreasonably high concentrations.ConclusionsHigh dynamic interfacial areas created through baffles in reactor vessels, low volumes in high-capacity vessels, or high shaking speeds severely limited cellulose conversions at low enzyme loadings. Precipitation of cellulases due to aggregation at the air-liquid interface caused their continuous deactivation in shaken flasks and severely limited solubilization of cellulose.Biological SciencesIndustrial BiotechnologyCelluloseCellulaseDeactivationHydrolysisAir-liquid interfaceGas-liquid interfaceAir–liquid interfaceGas–liquid interfaceChemical EngineeringBiochemistry and cell biologyIndustrial biotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6sx407zfarticleBiotechnology for Biofuels and Bioproducts, vol 12, iss 196oai:escholarship.org:ark:/13030/qt4d50d7jt2023-10-05T15:16:48Zqt4d50d7jtAnodal Transcranial Direct Current Stimulation to the Left Rostrolateral Prefrontal Cortex Selectively Improves Source Memory RetrievalWestphal, Andrew JChow, Tiffany ENgoy, CoreyZuo, XiaoyeLiao, VivianStorozuk, Laryssa APeters, Megan AKWu, Allan DRissman, Jesse2019-09-01Functional neuroimaging studies have consistently implicated the left rostrolateral prefrontal cortex (RLPFC) as playing a crucial role in the cognitive operations supporting episodic memory and analogical reasoning. However, the degree to which the left RLPFC causally contributes to these processes remains underspecified. We aimed to assess whether targeted anodal stimulation-thought to boost cortical excitability-of the left RLPFC with transcranial direct current stimulation (tDCS) would lead to augmentation of episodic memory retrieval and analogical reasoning task performance in comparison to cathodal stimulation or sham stimulation. Seventy-two healthy adult participants were evenly divided into three experimental groups. All participants performed a memory encoding task on Day 1, and then on Day 2, they performed continuously alternating tasks of episodic memory retrieval, analogical reasoning, and visuospatial perception across two consecutive 30-min experimental sessions. All groups received sham stimulation for the first experimental session, but the groups differed in the stimulation delivered to the left RLPFC during the second session (either sham, 1.5 mA anodal tDCS, or 1.5 mA cathodal tDCS). The experimental group that received anodal tDCS to the left RLPFC during the second session demonstrated significantly improved episodic memory source retrieval performance, relative to both their first session performance and relative to performance changes observed in the other two experimental groups. Performance on the analogical reasoning and visuospatial perception tasks did not exhibit reliable changes as a result of tDCS. As such, our results demonstrate that anodal tDCS to the left RLPFC leads to a selective and robust improvement in episodic source memory retrieval.Biomedical and Clinical SciencesBiological PsychologyCognitive and Computational PsychologyNeurosciencesPsychologyBrain DisordersClinical ResearchEvaluation of treatments and therapeutic interventions6.6 Psychological and behaviouralAdultFemaleFunctional LateralityHumansMaleMemoryEpisodicMental RecallPrefrontal CortexThinkingTranscranial Direct Current StimulationVisual PerceptionYoung AdultCognitive SciencesExperimental PsychologyBiological psychologyCognitive and computational psychologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4d50d7jtarticleJournal of Cognitive Neuroscience, vol 31, iss 91380 - 1391oai:escholarship.org:ark:/13030/qt9g7008k92023-10-05T15:15:40Zqt9g7008k9Keys to Lipid Selection in Fatty Acid Amide Hydrolase Catalysis: Structural Flexibility, Gating Residues and Multiple Binding PocketsPalermo, GiuliaBauer, IngaCampomanes, PabloCavalli, AndreaArmirotti, AndreaGirotto, StefaniaRothlisberger, UrsulaDe Vivo, MarcoLivesay, Dennis R2015-01-01The fatty acid amide hydrolase (FAAH) regulates the endocannabinoid system cleaving primarily the lipid messenger anandamide. FAAH has been well characterized over the years and, importantly, it represents a promising drug target to treat several diseases, including inflammatory-related diseases and cancer. But its enzymatic mechanism for lipid selection to specifically hydrolyze anandamide, rather than similar bioactive lipids, remains elusive. Here, we clarify this mechanism in FAAH, examining the role of the dynamic paddle, which is formed by the gating residues Phe432 and Trp531 at the boundary between two cavities that form the FAAH catalytic site (the "membrane-access" and the "acyl chain-binding" pockets). We integrate microsecond-long MD simulations of wild type and double mutant model systems (Phe432Ala and Trp531Ala) of FAAH, embedded in a realistic membrane/water environment, with mutagenesis and kinetic experiments. We comparatively analyze three fatty acid substrates with different hydrolysis rates (anandamide > oleamide > palmitoylethanolamide). Our findings identify FAAH's mechanism to selectively accommodate anandamide into a multi-pocket binding site, and to properly orient the substrate in pre-reactive conformations for efficient hydrolysis that is interceded by the dynamic paddle. Our findings therefore endorse a structural framework for a lipid selection mechanism mediated by structural flexibility and gating residues between multiple binding cavities, as found in FAAH. Based on the available structural data, this exquisite catalytic strategy for substrate specificity seems to be shared by other lipid-degrading enzymes with similar enzymatic architecture. The mechanistic insights for lipid selection might assist de-novo enzyme design or drug discovery efforts.Biochemistry and Cell BiologyChemical SciencesBiological Sciences5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsGeneric health relevanceAmidohydrolasesArachidonic AcidsBinding SitesCatalysisComputational BiologyEndocannabinoidsHumansMolecular Dynamics SimulationMutationPolyunsaturated AlkamidesProtein ConformationMathematical SciencesInformation and Computing SciencesBioinformaticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9g7008k9articlePLOS Computational Biology, vol 11, iss 6e1004231oai:escholarship.org:ark:/13030/qt72z9625c2023-10-05T15:10:03Zqt72z9625cDeep Learning Models Unveiled Functional Difference Between Cortical Gyri and SulciZhang, ShuLiu, HuanHuang, HengZhao, YuJiang, XiBowers, BrookGuo, LeiHu, XiaopingSanchez, MarLiu, Tianming2019-05-01It is largely unknown whether there is functional role difference between cortical gyral and sulcal regions. Recent advancements in neuroimaging studies demonstrate clear difference of structural connection profiles in gyral and sulcal areas, suggesting possible functional role difference in these convex and concave cortical regions. To explore and confirm such possible functional difference, we design and apply a powerful deep learning model of convolutional neural networks (CNN) that has been proven to be superior in learning discriminative and meaningful patterns on fMRI. By using the CNN model, gyral and sulcal fMRI signals are learned and predicted, and the prediction performance is adopted to demonstrate the functional difference between gyri and sulci. By using the Human Connectome Project (HCP) fMRI data and macaque brain fMRI data, an average of 83% and 90% classification accuracy has been achieved to separate gyral/sulcal HCP task fMRI signals at the population and individual subject level, respectively; 81% and 86% classification accuracy for resting state fMRI signals at the group and individual subject level, respectively. In addition, 78% classification accuracy has been achieved to separate gyral/sulcal resting state fMRI signals in macaque brains. Importantly, further analysis reveals that the discriminative features that are learned by CNNs to differentiate gyral/sulcal fMRI signals can be meaningfully interpreted, thus unveiling the fundamental functional difference between cortical gyri and sulci. That is, gyri are more global functional integration centers with simpler lower frequency signal components, while sulci are more local processing units with more complex higher frequency signal components.Information and Computing SciencesMachine LearningNeurosciencesClinical ResearchNeurologicalAdultAlgorithmsAnimalsCerebral CortexConnectomeDeep LearningFemaleHumansMacacaMagnetic Resonance ImagingMaleMiddle AgedSignal ProcessingComputer-AssistedYoung AdultCortical gyricortical sulciclassificationbrain functionconvolutional neural networkArtificial Intelligence and Image ProcessingBiomedical EngineeringElectrical and Electronic EngineeringBiomedical engineeringElectronicssensors and digital hardwareComputer vision and multimedia computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/72z9625carticleIEEE Transactions on Biomedical Engineering, vol 66, iss 51297 - 1308oai:escholarship.org:ark:/13030/qt4q35j8sf2023-10-05T15:03:49Zqt4q35j8sfSimultaneous phase‐contrast MRI and PET for noninvasive quantification of cerebral blood flow and reactivity in healthy subjects and patients with cerebrovascular diseaseIshii, YosukeThamm, ThoralfGuo, JiaKhalighi, Mohammad MehdiWardak, MirwaisHolley, DawnGandhi, HarshPark, Jun HyungShen, BinSteinberg, Gary KChin, Frederick TZaharchuk, GregFan, Audrey Peiwen2020-01-01BackgroundH2 15 O-positron emission tomography (PET) is considered the reference standard for absolute cerebral blood flow (CBF). However, this technique requires an arterial input function measured through continuous sampling of arterial blood, which is invasive and has limitations with tracer delay and dispersion.PurposeTo demonstrate a new noninvasive method to quantify absolute CBF with a PET/MRI hybrid scanner. This blood-free approach, called PC-PET, takes the spatial CBF distribution from a static H2 15 O-PET scan, and scales it to the whole-brain average CBF value measured by simultaneous phase-contrast MRI.Study typeObservational.SubjectsTwelve healthy controls (HC) and 13 patients with Moyamoya disease (MM) as a model of chronic ischemic disease.Field strength/sequences3T/2D cardiac-gated phase-contrast MRI and H2 15 O-PET.AssessmentPC-PET CBF values from whole brain (WB), gray matter (GM), and white matter (WM) in HCs were compared with literature values since 2000. CBF and cerebrovascular reactivity (CVR), which is defined as the percent CBF change between baseline and post-acetazolamide (vasodilator) scans, were measured by PC-PET in MM patients and HCs within cortical regions corresponding to major vascular territories. Statistical Tests: Linear, mixed effects models were created to compare CBF and CVR, respectively, between patients and controls, and between different degrees of stenosis.ResultsThe mean CBF values in WB, GM, and WM in HC were 42 ± 7 ml/100 g/min, 50 ± 7 ml/100 g/min, and 23 ± 3 ml/100 g/min, respectively, which agree well with literature values. Compared with normal regions (57 ± 23%), patients showed significantly decreased CVR in areas with mild/moderate stenosis (47 ± 17%, P = 0.011) and in severe/occluded areas (40 ± 16%, P = 0.016). Data Conclusion: PC-PET identifies differences in cerebrovascular reactivity between healthy controls and cerebrovascular patients. PC-PET is suitable for CBF measurement when arterial blood sampling is not accessible, and warrants comparison to fully quantitative H2 15 O-PET in future studies.Level of evidence3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;51:183-194.Biomedical and Clinical SciencesClinical SciencesBiomedical ImagingNeurosciencesBioengineeringClinical Research4.2 Evaluation of markers and technologiesDetectionscreening and diagnosisAdultBrainCerebrovascular CirculationFemaleHumansMagnetic Resonance ImagingMaleMoyamoya DiseaseMultimodal ImagingOxygen RadioisotopesPositron-Emission Tomographycerebral blood flowcerebrovascular reactivitymoyamoya diseaseperfusion imagingphase-contrast MRIpositron emission tomographyPhysical SciencesEngineeringMedical and Health SciencesNuclear Medicine & Medical ImagingClinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4q35j8sfarticleJournal of Magnetic Resonance Imaging, vol 51, iss 1183 - 194oai:escholarship.org:ark:/13030/qt62w6r0g82023-10-05T12:33:05Zqt62w6r0g8Correction to: Comprehensive benchmarking and ensemble approaches for metagenomic classifiersMcIntyre, Alexa BROunit, RachidAfshinnekoo, EbrahimPrill, Robert JHénaff, ElizabethAlexander, NoahMinot, Samuel SDanko, DavidFoox, JonathanAhsanuddin, SofiaTighe, ScottHasan, Nur ASubramanian, PooraniMoffat, KellyLevy, ShawnLonardi, StefanoGreenfield, NickColwell, Rita RRosen, Gail LMason, Christopher E2019-12-01Following publication of the original article [1], the authors would like to highlight the following two corrections.Communication and Media StudiesLanguageCommunication and CultureCreative Arts and WritingEnvironmental SciencesBiological SciencesInformation and Computing SciencesBioinformaticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/62w6r0g8articleGenome Biology, vol 20, iss 172oai:escholarship.org:ark:/13030/qt6qr6b2ph2023-10-05T12:15:58Zqt6qr6b2phIndexing Multivariate Mobile Data through Spatio-Temporal Event Detection and ClusteringRawassizadeh, RezaDobbins, ChelseaAkbari, MohammadPazzani, Michael2019-01-01Mobile and wearable devices are capable of quantifying user behaviors based on their contextual sensor data. However, few indexing and annotation mechanisms are available, due to difficulties inherent in raw multivariate data types and the relative sparsity of sensor data. These issues have slowed the development of higher level human-centric searching and querying mechanisms. Here, we propose a pipeline of three algorithms. First, we introduce a spatio-temporal event detection algorithm. Then, we introduce a clustering algorithm based on mobile contextual data. Our spatio-temporal clustering approach can be used as an annotation on raw sensor data. It improves information retrieval by reducing the search space and is based on searching only the related clusters. To further improve behavior quantification, the third algorithm identifies contrasting events withina cluster content. Two large real-world smartphone datasets have been used to evaluate our algorithms and demonstrate the utility and resource efficiency of our approach to search.Data Management and Data ScienceInformation and Computing SciencesArtificial IntelligenceComputer Vision and Multimedia ComputationNetworking and Information Technology R&D (NITRD)BioengineeringAlgorithmsCluster AnalysisHumansInformation Storage and RetrievalSmartphonespatio-temporalclusteringevent detectionmobile sensing: contrast behavior mininghuman behaviorAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6qr6b2pharticleSensors, vol 19, iss 3448oai:escholarship.org:ark:/13030/qt3q35s84n2023-10-05T12:15:39Zqt3q35s84nEnergy-Efficient Integration of Continuous Context Sensing and Prediction into SmartwatchesRawassizadeh, RezaTomitsch, MartinNourizadeh, ManouchehrMomeni, ElahehPeery, AaronUlanova, LiudmilaPazzani, Michael2015-01-01As the availability and use of wearables increases, they are becoming a promising platform for context sensing and context analysis. Smartwatches are a particularly interesting platform for this purpose, as they offer salient advantages, such as their proximity to the human body. However, they also have limitations associated with their small form factor, such as processing power and battery life, which makes it difficult to simply transfer smartphone-based context sensing and prediction models to smartwatches. In this paper, we introduce an energy-efficient, generic, integrated framework for continuous context sensing and prediction on smartwatches. Our work extends previous approaches for context sensing and prediction on wrist-mounted wearables that perform predictive analytics outside the device. We offer a generic sensing module and a novel energy-efficient, on-device prediction module that is based on a semantic abstraction approach to convert sensor data into meaningful information objects, similar to human perception of a behavior. Through six evaluations, we analyze the energy efficiency of our framework modules, identify the optimal file structure for data access and demonstrate an increase in accuracy of prediction through our semantic abstraction method. The proposed framework is hardware independent and can serve as a reference model for implementing context sensing and prediction on small wearable devices beyond smartwatches, such as body-mounted cameras.Data Management and Data ScienceInformation and Computing SciencesEngineeringAffordable and Clean Energywearablesmartwatchmobile sensingpredictionenergy efficiencylifeloggingquantified selfAnalytical ChemistryEnvironmental Science and ManagementEcologyDistributed ComputingElectrical and Electronic EngineeringElectrical engineeringElectronicssensors and digital hardwareEnvironmental managementDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3q35s84narticleSensors, vol 15, iss 922616 - 22645oai:escholarship.org:ark:/13030/qt7md3703j2023-10-05T11:48:17Zqt7md3703jCharacterizing population exposure to coal emissions sources in the United States using the HyADS modelHenneman, Lucas RFChoirat, ChristineIvey, CesunicaCummiskey, KevinZigler, Corwin M2019-04-01In anticipation of the expanding appreciation for air quality models in health outcomes studies, we develop and evaluate a reduced-complexity model for pollution transport that intentionally sacrifices some of the sophistication of full-scale chemical transport models in order to support applicability to a wider range of health studies. Specifically, we introduce the HYSPLIT average dispersion model, HyADS, which combines the HYSPLIT trajectory dispersion model with modern advances in parallel computing to estimate ZIP code level exposure to emissions from individual coal-powered electricity generating units in the United States. Importantly, the method is not designed to reproduce ambient concentrations of any particular air pollutant; rather, the primary goal is to characterize each ZIP code's exposure to these coal power plants specifically. We show adequate performance towards this goal against observed annual average air pollutant concentrations (nationwide Pearson correlations of 0.88 and 0.73 with SO 4 2 - and PM2.5, respectively) and coal-combustion impacts simulated with a full-scale chemical transport model and adjusted to observations using a hybrid direct sensitivities approach (correlation of 0.90). We proceed to provide multiple examples of HyADS's single-source applicability, including to show that 22% of the population-weighted coal exposure comes from 30 coal-powered electricity generating units.Earth SciencesAtmospheric SciencesReduced complexity modelSource impactsHYSPLITAir pollution exposurePM2.5air pollution exposuresource impactsStatisticsEnvironmental EngineeringMeteorology & Atmospheric SciencesAtmospheric sciencesClimate change scienceEnvironmental engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7md3703jarticleoai:escholarship.org:ark:/13030/qt09q091jc2023-10-05T11:17:51Zqt09q091jcYBa$_2$Cu$_3$O$_{7-\delta }$-CeO$_2$-YBa$_2$Cu$_3$O$_{7-\delta }$ Multilayers Grown by Reactive Co-Evaporation on Sapphire WafersWang, Yan-TingSemerad, RobertMcCoy, Stephen JCai, HanLeFebvre, JayGrezdo, HollyCho, Ethan YLi, HaoCybart, Shane A2019-01-01High-TC superconductor thin film heterostructures were deposited using reactive co-evaporation for dual layer electronic applications. The epitaxial structure consisted of 35-nm YBa2Cu3O7-δ(YBCO), 75-nm CeO2 , 150-nm YBCO, and 20-nm CeO2 on r-plane sapphire wafers. The critical temperature was measured to be 83.6 K and 84.8 K for the bottom and top YBCO layers, respectively. Atomic force microscopy reveals smooth surfaces with RMS roughness of the top YBCO layer to be 4.7 nm. The CeO2 insulating layer exhibited hopping conduction that freezes out at low temperature, making these structures suitable for electrical circuits with isolated ground planes.EngineeringNanotechnologyMultilayerheterostructuresYBCOCeO2reactive co-evaporationCondensed Matter PhysicsElectrical and Electronic EngineeringMaterials EngineeringGeneral PhysicsElectrical engineeringCondensed matter physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/09q091jcarticleIEEE Transactions on Applied Superconductivity, vol 29, iss 51 - 4oai:escholarship.org:ark:/13030/qt8pt3c52z2023-10-05T11:04:24Zqt8pt3c52zDeephESC 2.0: Deep Generative Multi Adversarial Networks for improving the classification of hESCTheagarajan, RajkumarBhanu, BirFernández-Hilario, Alberto2019-01-01Human embryonic stem cells (hESC), derived from the blastocysts, provide unique cellular models for numerous potential applications. They have great promise in the treatment of diseases such as Parkinson's, Huntington's, diabetes mellitus, etc. hESC are a reliable developmental model for early embryonic growth because of their ability to divide indefinitely (pluripotency), and differentiate, or functionally change, into any adult cell type. Their adaptation to toxicological studies is particularly attractive as pluripotent stem cells can be used to model various stages of prenatal development. Automated detection and classification of human embryonic stem cell in videos is of great interest among biologists for quantified analysis of various states of hESC in experimental work. Currently video annotation is done by hand, a process which is very time consuming and exhaustive. To solve this problem, this paper introduces DeephESC 2.0 an automated machine learning approach consisting of two parts: (a) Generative Multi Adversarial Networks (GMAN) for generating synthetic images of hESC, (b) a hierarchical classification system consisting of Convolution Neural Networks (CNN) and Triplet CNNs to classify phase contrast hESC images into six different classes namely: Cell clusters, Debris, Unattached cells, Attached cells, Dynamically Blebbing cells and Apoptically Blebbing cells. The approach is totally non-invasive and does not require any chemical or staining of hESC. DeephESC 2.0 is able to classify hESC images with an accuracy of 93.23% out performing state-of-the-art approaches by at least 20%. Furthermore, DeephESC 2.0 is able to generate large number of synthetic images which can be used for augmenting the dataset. Experimental results show that training DeephESC 2.0 exclusively on a large amount of synthetic images helps to improve the performance of the classifier on original images from 93.23% to 94.46%. This paper also evaluates the quality of the generated synthetic images using the Structural SIMilarity (SSIM) index, Peak Signal to Noise ratio (PSNR) and statistical p-value metrics and compares them with state-of-the-art approaches for generating synthetic images. DeephESC 2.0 saves hundreds of hours of manual labor which would otherwise be spent on manually/semi-manually annotating more and more videos.Medical BiotechnologyInformation and Computing SciencesBiomedical and Clinical SciencesMachine LearningRegenerative MedicineStem Cell Research - Embryonic - HumanStem Cell ResearchGeneric health relevanceCellsCulturedHuman Embryonic Stem CellsHumansImage ProcessingComputer-AssistedIntravital MicroscopyNeural NetworksComputerSignal-To-Noise RatioVideo RecordingGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8pt3c52zarticlePLOS ONE, vol 14, iss 3e0212849oai:escholarship.org:ark:/13030/qt85x562662023-10-05T07:47:08Zqt85x56266Protein–Protein Affinity Determination by Quantitative FRET QuenchingJiang, LingXiong, ZhehaoSong, YangLu, YanrongChen, YounanSchultz, Jerome SLi, JunLiao, Jiayu2019-01-01The molecular dissociation constant, Kd, is a well-established parameter to quantitate the affinity of protein-protein or other molecular interactions. Recently, we reported the theoretical basis and experimental procedure for Kd determination using a quantitative FRET method. Here we report a new development of Kd determination by measuring the reduction in donor fluorescence due to acceptor quenching in FRET. A new method of Kd determination was developed from the quantitative measurement of donor fluorescence quenching. The estimated Kd values of SUMO1-Ubc9 interaction based on this method are in good agreement with those determined by other technologies, including FRET acceptor emission. Thus, the acceptor-quenched approach can be used as a complement to the previously developed acceptor excitation method. The new methodology has more general applications regardless whether the acceptor is an excitable fluorophore or a quencher. Thus, these developments provide a complete methodology for protein or other molecule interaction affinity determinations in solution.Biochemistry and Cell BiologyChemical SciencesBiological SciencesFluorescenceFluorescence Resonance Energy TransferFluorescent DyesKineticsProtein Interaction Domains and MotifsProtein Interaction MappingProtein Interaction MapsSUMO-1 ProteinUbiquitin-Conjugating Enzymesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/85x56266articleScientific Reports, vol 9, iss 12050oai:escholarship.org:ark:/13030/qt9kn6v8th2023-10-05T07:23:11Zqt9kn6v8thA portable device for studying the effects of fluid flow on degradation properties of biomaterials inside cell incubatorsJiang, WensenLin, JiajiaChen, Alex HPan, JianweiLiu, Huinan2019-02-01A portable device was designed and constructed for studying the properties of biomaterials in physiologically relevant fluids under controllable flow conditions that closely simulate fluid flow inside the body. The device can fit entirely inside a cell incubator; and, thus, it can be used directly under standard cell culture conditions. An impedance-driven pump was built in the sterile flow loop to control the flow rates of fluids, which made the device small and portable for easy deployment in the incubator. To demonstrate the device functions, magnesium (Mg) as a representative biodegradable material was tested in the flow device for immersion degradation under flow versus static conditions, while the flow module was placed inside a standard cell incubator. The flow rate was controlled at 0.17 ± 0.06 ml/s for this study; and, the flow rate is adjustable through the controller module outside of incubators for simulating the flow rates in the ranges of blood flow in human artery (0.05 ∼0.43 ml/s) and vein (0.02 ∼0.08 ml/s). Degradation of Mg under flow versus static conditions was characterized by measuring the changes of sample mass and thickness, and Mg2+ ion concentrations in the immersion media. Surface chemistry and morphology of Mg after immersion under flow versus static conditions were compared. The portable impedance-driven flow device is easy to fit inside an incubator and much smaller than a peristaltic pump, providing a valuable solution for studying biomaterials and implants (e.g. vascular or ureteral stents) in body fluids under flow versus static conditions with or without cells.EngineeringBiomedical EngineeringAssistive TechnologyBioengineeringportable flow deviceimpedance-driven pumpbiomaterialsbody fluidsmagnesium (Mg) degradationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9kn6v8tharticleRegenerative Biomaterials, vol 6, iss 1rby026oai:escholarship.org:ark:/13030/qt6rt5q6ft2023-10-05T07:11:28Zqt6rt5q6ftTCAD EIC Message: February 2019Brisk, PhilipChakraborty, SumanCoelho, ClaudionorGamatie, AbdoulayeGhosh, SwaroopJiao, Xun2019-01-01Information and Computing SciencesGraphicsAugmented Reality and GamesEngineeringElectronicsSensors and Digital HardwareElectrical and Electronic EngineeringComputer HardwareComputer Hardware & ArchitectureElectronicssensors and digital hardwareGraphicsaugmented reality and gamesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6rt5q6ftarticleIEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, vol 38, iss 2197 - 198oai:escholarship.org:ark:/13030/qt3n82r6cc2023-10-05T07:11:12Zqt3n82r6ccTunable Properties of Poly-DL-Lactide-Monomethoxypolyethylene Glycol Porous Microparticles for Sustained Release of Polyethylenimine-DNA PolyplexesTerry, Treniece LGivens, Brittany ERodgers, Victor GJSalem, Aliasger K2019-01-01Direct pulmonary delivery is a promising step in developing effective gene therapies for respiratory disease. Gene therapies can be used to treat the root cause of diseases, rather than just the symptoms. However, developing effective therapies that do not cause toxicity and that successfully reach the target site at therapeutic levels is challenging. We have developed a polymer-DNA complex utilizing polyethylene imine (PEI) and DNA, which was then encapsulated into poly(lactic acid)-co-monomethoxy poly(ethylene glycol) (PLA-mPEG) microparticles via double emulsion, solvent evaporation. Then, the resultant particle size, porosity, and encapsulation efficiency were measured as a function of altering preparation parameters. Microsphere formation was confirmed from scanning electron micrographs and the aerodynamic particle diameter was measured using an aerodynamic particle sizer. Several formulations produced particles with aerodynamic diameters in the 0-5 μm range despite having larger particle diameters which is indicative of porous particles. Furthermore, these aerodynamic diameters correspond to high deposition within the airways when inhaled and the measured DNA content indicated high encapsulation efficiency. Thus, this formulation provides promise for developing inhalable gene therapies.Medical BiotechnologyBiomedical and Clinical SciencesGeneticsBioengineeringDNADelayed-Action PreparationsDrug CarriersMicrospheresParticle SizePolyestersPolyethylene GlycolsPolyethyleneiminePorosityPLAPEGpolyplexesmicrospheresPharmacology and Pharmaceutical SciencesPharmacology & PharmacyPharmacology and pharmaceutical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3n82r6ccarticleAAPS PharmSciTech, vol 20, iss 123oai:escholarship.org:ark:/13030/qt6vr296qs2023-10-05T05:12:10Zqt6vr296qsEvaluation of electrospray differential mobility analysis for virus particle analysis: Potential applications for biomanufacturingGuha, SuvajyotiPease, Leonard FBrorson, Kurt ATarlov, Michael JZachariah, Michael R2011-12-01The technique of electrospray differential mobility analysis (ES-DMA) was examined as a potential potency assay for routine virus particle analysis in biomanufacturing environments (e.g., evaluation of vaccines and gene delivery products for lot release) in the context of the International Committee of Harmonisation (ICH) Q2 guidelines. ES-DMA is a rapid particle sizing method capable of characterizing certain aspects of the structure (such as capsid proteins) and obtaining complete size distributions of viruses and virus-like particles. It was shown that ES-DMA can distinguish intact virus particles from degraded particles and measure the concentration of virus particles when calibrated with nanoparticles of known concentration. The technique has a measurement uncertainty of ≈20%, is linear over nearly 3 orders of magnitude, and has a lower limit of detection of ≈10(9)particles/mL. This quantitative assay was demonstrated for non-enveloped viruses. It is expected that ES-DMA will be a useful method for applications involving production and quality control of vaccines and gene therapy vectors for human use.Medical BiotechnologyBiomedical and Clinical SciencesGeneticsImmunizationBiotechnologyHumansParticle SizeVirionVirologyVirosomesElectrosprayDifferential mobility analyzerVirusICH Q2Gas phase electrophoretic molecular mobility analysisMicrobiologyMedical MicrobiologyMedical microbiologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6vr296qsarticleJournal of Virological Methods, vol 178, iss 1-2201 - 208oai:escholarship.org:ark:/13030/qt1597b64c2023-10-05T03:39:32Zqt1597b64cFabrication of centimeter-scale and geometrically arbitrary vascular networks using in vitro self-assemblyMorgan, Joshua TShirazi, JasmineComber, Erica MEschenburg, ChristianGleghorn, Jason P2019-01-01One of the largest challenges facing the field of tissue engineering is the incorporation of a functional vasculature, allowing effective nourishment of graft tissue beyond diffusion length scales. Here, we demonstrate a methodology for inducing the robust self-assembly of endothelial cells into stable three-dimensional perfusable networks on millimeter and centimeter length scales. Utilizing broadly accessible cell strains and reagents, we have rigorously tested a state space of cell densities (0.5-2.0 × 106 cell/mL) and collagen gel densities (2-6 mg/mL) that result in robust vascular network formation. Further, over the range of culture conditions with which we observed robust network formation, we advanced image processing algorithms and quantitative metrics to assess network connectivity, coverage, tortuosity, lumenization, and vessel diameter. These data demonstrate that decreasing collagen density produced more connected networks with higher coverage. Finally, we demonstrated that this methodology results in the formation of perfusable networks, is extensible to arbitrary geometries and centimeter scales, and results in networks that remain stable for 21 days without the need for the co-culture of supporting cells. Given the robustness and accessibility, this system is ideal for studies of tissue-scale biology, as well as future studies on the formation and remodeling of larger engineered graft tissues.EngineeringBiomedical EngineeringBioengineeringAnimalsBiocompatible MaterialsCollagenEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansNeovascularizationPhysiologicRatsTissue EngineeringTissue ScaffoldsVasculogenesisEndothelial cellSelf-assemblyPerfusionMultiscaleTissue engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1597b64carticleoai:escholarship.org:ark:/13030/qt1cx665kk2023-10-05T03:39:28Zqt1cx665kkRegional Variation in Androgen Receptor Expression and Biomechanical Properties May Contribute to Cryptorchidism Susceptibility in the LE/orl RatMorgan, Joshua TRobbins, Alan KMateson, Abigail BSawamoto, KazukiTomatsu, ShunjiGray, Dione RGleghorn, Jason PBarthold, Julia Spencer2018-01-01Background: The process of testicular descent requires androgen and insulin-like 3, hormones secreted by fetal Leydig cells. Knowledge concerning distinct and common functions of these hormones in regulating development of the fetal gubernaculum remains limited and/or conflicting. The current studies were designed to better define characteristics of androgen receptor (AR) expression, function and regulation, as well as the biomechanical properties of normal and cryptorchid gubernaculum during fetal development. Methods: We studied fetal gubernacula from Long Evans outbred (LE/wt) rats and an inbred (LE/orl) strain with an inherited form of cryptorchidism associated with an AR signaling defect. Gubernacular cells or whole organs obtained from LE/wt and LE/orl fetal gubernacula underwent AR immunostaining and quantitative image analysis. The effects of dihydrotestosterone (DHT) on AR expression, muscle fiber morphology, hyaluronan (HA) levels and glycosaminoglycan (GAG) content were measured in LE/wt gubernacula. Finally, the spatial mechanics of freshly harvested LE/wt and LE/orl fetal gubernacula were compared using micropipette aspiration. Results: AR is expressed in the nucleus of mesenchymal core, tip and cord cells of the embryonic (E) day 17 and 21 fetal gubernaculum, and is enhanced by DHT in primary cultures of gubernacular mesenchymal cells. Enhanced AR expression at the tip was observed in LE/wt but not LE/orl gubernacula. In in vitro studies of whole mount fetal gubernaculum, DHT did not alter muscle fiber morphology, HA content or GAG production. Progressive swelling with reduced cellular density of the LE/wt gubernaculum at E19-21 was associated with increased central stiffness in LE/wt but not in LE/orl fetuses. Conclusions: These data confirm nuclear AR expression in gubernacular mesenchyme with distal enhancement at the tip/cord region in LE/wt but not LE/orl rat fetuses. DHT enhanced cellular AR expression but had no major effects on muscle morphology or matrix composition in the rat fetal gubernaculum in vitro. Regional increased stiffness and decreased cell density between E19 and E21 were observed in LE/wt but not LE/orl fetal gubernacula. Developmental differences in cell-specific AR expression in LE/orl fetal gubernacula may contribute to the dysmorphism and aberrant function that underlies cryptorchidism susceptibility in this strain.Reproductive MedicineBiomedical and Clinical SciencesUrologic DiseasesPediatricgubernaculumcryptorchidismandrogensglycosaminoglycanshyaluronanmyogenesismicroaspirationbiomechanicsClinical SciencesNutrition and DieteticsClinical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1cx665kkarticleoai:escholarship.org:ark:/13030/qt2k81q16f2023-10-04T22:42:43Zqt2k81q16fLiquid Phase Separation in High-Entropy Alloys—A ReviewDerimow, NicholasAbbaschian, Reza2018-01-01It has been 14 years since the discovery of the high-entropy alloys (HEAs), an idea of alloying which has reinvigorated materials scientists to explore unconventional alloy compositions and multicomponent alloy systems. Many authors have referred to these alloys as multi-principal element alloys (MPEAs) or complex concentrated alloys (CCAs) in order to place less restrictions on what constitutes an HEA. Regardless of classification, the research is rooted in the exploration of structure-properties and processing relations in these multicomponent alloys with the aim to surpass the physical properties of conventional materials. More recent studies show that some of these alloys undergo liquid phase separation, a phenomenon largely dictated by low entropy of mixing and positive mixing enthalpy. Studies posit that positive mixing enthalpy of the binary and ternary components contribute substantially to the formation of liquid miscibility gaps. The objective of this review is to bring forth and summarize the findings of the experiments which detail liquid phase separation (LPS) in HEAs, MPEAs, and CCAs and to draw parallels between HEAs and the conventional alloy systems which undergo liquid-liquid separation. Positive mixing enthalpy if not compensated by the entropy of mixing will lead to liquid phase separation. It appears that Co, Ni, and Ti promote miscibility in HEAs/CCAs/MPEAs while Cr, V, and Nb will raise the miscibility gap temperature and increase LPS. Moreover, addition of appropriate amounts of Ni to CoCrCu eliminates immiscibility, such as in cases of dendritically solidifying CoCrCuNi, CoCrCuFeNi, and CoCrCuMnNi.Mathematical SciencesPhysical Scienceshigh-entropy alloysliquid phase separationimmiscible alloysHEAsmulticomponent alloysmiscibility gapsmulti-principal element alloysMPEAscomplex concentrated alloysCCAsFluids & PlasmasMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2k81q16farticleEntropy, vol 20, iss 11890oai:escholarship.org:ark:/13030/qt783095wr2023-10-04T21:51:05Zqt783095wrPost-Acquisition Solvent Suppression by Singular-Value DecompositionZhu, GuangSmith, DavidHua, Yingbo1997-01-01EngineeringPhysical SciencesFourier AnalysisMathematicsMuramidaseNuclear Magnetic ResonanceBiomolecularSolventsWaterBiophysicsPhysical sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/783095wrarticleJournal of Magnetic Resonance, vol 124, iss 1286 - 289oai:escholarship.org:ark:/13030/qt2hc2q5w52023-10-04T20:54:55Zqt2hc2q5w5The diamine cation is not a chemical example where density functional theory failsAli, Zulfikhar AAquino, Fredy WWong, Bryan M2018-01-01In a recent communication, Weber and co-workers presented a surprising study
on charge-localization effects in the N,N'-dimethylpiperazine (DMP+) diamine
cation to provide a stringent test of density functional theory (DFT) methods.
Within their study, the authors examined various DFT methods and concluded that
"all DFT functionals commonly used today, including hybrid functionals with
exact exchange, fail to predict a stable charge-localized state." This
surprising conclusion is based on the authors' use of a self-interaction
correction (namely, complex-valued Perdew-Zunger Self-Interaction Correction
(PZ-SIC)) to DFT, which appears to give excellent agreement with experiment and
other wavefunction-based benchmarks. Since the publication of this recent
communication, the same DMP+ molecule has been cited in numerous subsequent
studies as a prototypical example of the importance of self-interaction
corrections for accurately calculating other chemical systems. In this
correspondence, we have carried out new high-level CCSD(T) analyses on the DMP+
cation to show that DFT actually performs quite well for this system (in
contrast to their conclusion that all DFT functionals fail), whereas the PZ-SIC
approach used by Weber et al. is the outlier that is inconsistent with the
high-level CCSD(T) (coupled-cluster with single and double excitations and
perturbative triples) calculations. Our new findings and analysis for this
system are briefly discussed in this correspondence.physics.chem-phcond-mat.mtrl-sciphysics.atm-clusapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2hc2q5w5articleNature Communications, vol 9, iss 14733oai:escholarship.org:ark:/13030/qt9c57d0f42023-10-04T19:59:01Zqt9c57d0f4Massively parallel skyline computation for processing-in-memory architecturesZois, VasileiosGupta, DivyaTsotras, Vassilis JNajjar, Walid ARoy, Jean-Francois2018-11-01Processing-In-Memory (PIM) is an increasingly popular architecture aimed at addressing the 'memory wall' crisis by prioritizing the integration of processors within DRAM. It promotes low data access latency, high bandwidth, massive parallelism, and low power consumption. The skyline operator is a known primitive used to identify those multi-dimensional points offering optimal trade-offs within a given dataset. For large multidimensional dataset, calculating the skyline is extensively compute and data intensive. Although, PIM systems present opportunities to mitigate this cost, their execution model relies on all processors operating in isolation with minimal data exchange. This prohibits direct application of known skyline optimizations which are inherently sequential, creating dependencies and large intermediate results that limit the maximum parallelism, throughput, and require an expensive merging phase. In this work, we address these challenges by introducing the first skyline algorithm for PIM architectures, called DSky. It is designed to be massively parallel and throughput efficient by leveraging a novel work assignment strategy that emphasizes load balancing. Our experiments demonstrate that it outperforms the state-of-the-art algorithms for CPUs and GPUs, in most cases. DSky achieves 2× to 14× higher throughput compared to the state-of-the-art solutions on competing CPU and GPU architectures. Furthermore, we showcase DSky's good scaling properties which are intertwined with PIM's ability to allocate resources with minimal added cost. In addition, we showcase an order of magnitude better energy consumption compared to CPUs and GPUs.Distributed Computing and Systems SoftwareInformation and Computing SciencesArchitectureBuilt Environment and DesignAffordable and Clean Energyprocessing-in-memoryskyline queriespareto dominancemassive parallelismprocessing-near-memoryload balancingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9c57d0f4articleoai:escholarship.org:ark:/13030/qt86w7f1dp2023-10-04T17:59:04Zqt86w7f1dpThe Mechanosensitive Ion Channel TRPV4 is a Regulator of Lung Development and Pulmonary Vasculature StabilizationMorgan, Joshua TStewart, Wade GMcKee, Robert AGleghorn, Jason P2018-10-01Introduction –Clinical observations and animal models suggest a critical role for the dynamic regulation of transmural pressure and peristaltic airway smooth muscle contractions for proper lung development. However, it is currently unclear how such mechanical signals are transduced into molecular and transcriptional changes at the cell level. To connect these physical findings to a mechanotransduction mechanism, we identified a known mechanosensor, TRPV4, as a component of this pathway.Methods –Embryonic mouse lung explants were cultured on membranes and in submersion culture to modulate explant transmural pressure. Time-lapse imaging was used to capture active changes in lung biology, and whole-mount images were used to visualize the organization of the epithelial, smooth muscle, and vascular compartments. TRPV4 activity was modulated by pharmacological agonism and inhibition.Results –TRPV4 expression is present in the murine lung with strong localization to the epithelium and major pulmonary blood vessels. TRPV4 agonism and inhibition resulted in hyper- and hypoplastic airway branching, smooth muscle differentiation, and lung growth, respectively. Smooth muscle contractions also doubled in frequency with agonism and were reduced by 60% with inhibition demonstrating a functional role consistent with levels of smooth muscle differentiation. Activation of TRPV4 increased the vascular capillary density around the distal airways, and inhibition resulted in a near complete loss of the vasculature.Conclusions –These studies have identified TRPV4 as a potential mechanosensor involved in transducing mechanical forces on the airways to molecular and transcriptional events that regulate the morphogenesis of the three essential tissue compartments in the lung.EngineeringBiomedical EngineeringLungBioengineering1.1 Normal biological development and functioningUnderpinning researchCardiovascularRespiratoryLung morphogenesisMechanotransductionMechanics of morphogenesisAirway smooth muscleLung reciprocal signalingairway smooth musclelung morphogenesislung reciprocal signalingmechanics of morphogenesismechanotransductionBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/86w7f1dparticleCellular and Molecular Bioengineering, vol 11, iss 5309 - 320oai:escholarship.org:ark:/13030/qt9jb3c1d92023-10-04T17:03:08Zqt9jb3c1d9Synthesis and Thermoelectric Characterization of Lead Telluride Hollow NanofibersZhang, MiluoPark, Su-DongKim, JiwonNalbandian, MichaelKim, SeilChoa, YonghoLim, JaehongMyung, Nosang V2018-01-01Lead telluride (PbTe) nanofibers were fabricated by galvanic displacement of electrospun cobalt nanofibers where their composition and morphology were altered by adjusting the electrolyte composition and diameter of sacrificial cobalt nanofibers. By employing Co instead of Ni as the sacrificial material, residue-free PbTe nanofibers were synthesized. The Pb content of the PbTe nanofibers was slightly affected by the Pb2+ concentration in the electrolyte, while the average outer diameter increased with Pb2+ concentration. The surface morphology of PbTe nanofibers was strongly dependent on the diameter of sacrificial nanofibers where it altered from smooth to rough surface as the Pb2+ concentration increased. Some of thermoelectric properties [i.e., thermopower (S) and electrical conductivity(σ)] were systematically measured as a function of temperature. Energy barrier height (Eb) was found to be one of the key factors affecting the thermoelectric properties-that is, higher energy barrier heights increased the Seebeck coefficient, but lowered the electrical conductivity.Chemical SciencesAffordable and Clean Energylead tellurideelectrospinninggalvanic displacement reactionthermoelectricshollow nanofiberenergy barrier heightChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9jb3c1d9articleoai:escholarship.org:ark:/13030/qt3x9798xm2023-10-04T14:50:00Zqt3x9798xmDECAF: A Platform-Neutral Whole-System Dynamic Binary Analysis PlatformHenderson, AndrewYan, Lok KwongHu, XunchaoPrakash, AravindYin, HengMcCamant, Stephen2017-01-01Dynamic binary analysis is a prevalent and indispensable technique in program analysis. While several dynamic binary analysis tools and frameworks have been proposed, all suffer from one or more of: prohibitive performance degradation, a semantic gap between the analysis code and the program being analyzed, architecture/OS specificity, being user-mode only, and lacking APIs. We present DECAF, a virtual machine based, multi-target, whole-system dynamic binary analysis framework built on top of QEMU. DECAF provides Just-In-Time Virtual Machine Introspection and a plugin architecture with a simple-to-use event-driven programming interface. DECAF implements a new instruction-level taint tracking engine at bit granularity, which exercises fine control over the QEMU Tiny Code Generator (TCG) intermediate representation to accomplish on-the-fly optimizations while ensuring that the taint propagation is sound and highly precise. We perform a formal analysis of DECAF's taint propagation rules to verify that most instructions introduce neither false positives nor false negatives. We also present three platform-neutral plugins - Instruction Tracer, Keylogger Detector, and API Tracer, to demonstrate the ease of use and effectiveness of DECAF in writing cross-platform and system-wide analysis tools. Implementation of DECAF consists of 9,550 lines of C++ code and 10,270 lines of C code and we evaluate DECAF using CPU2006 SPEC benchmarks and show average overhead of 605 percent for system wide tainting and 12 percent for VMI.Distributed Computing and Systems SoftwareInformation and Computing SciencesSoftware EngineeringDynamic binary analysisdynamic taint analysisvirtual machine introspectionComputer SoftwareInformation SystemsElectrical and Electronic EngineeringDistributed computing and systems softwareSoftware engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3x9798xmarticleIEEE Transactions on Software Engineering, vol 43, iss 2164 - 184oai:escholarship.org:ark:/13030/qt6g3379xt2023-10-04T14:39:19Zqt6g3379xtLandQv2: A MapReduce-Based System for Processing Arable Land Quality Big DataYao, XiaochuangMokbel, Mohamed FYe, SijingLi, GuoqingAlarabi, LouaiEldawy, AhmedZhao, ZuliangZhao, LongZhu, Dehai2018-01-01Earth SciencesGeoinformaticsNetworking and Information Technology R&D (NITRD)spatial big dataparallel processingMapReducearable land qualityGISPhysical Geography and Environmental GeoscienceGeomatic EngineeringPhysical geography and environmental geoscienceGeomatic engineeringpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6g3379xtarticleISPRS International Journal of Geo-Information, vol 7, iss 7271oai:escholarship.org:ark:/13030/qt01k029n82023-10-04T14:13:30Zqt01k029n8Near-Infrared-Fluorescent Erythrocyte-Mimicking Particles: Physical and Optical CharacteristicsTang, Jack CPartono, AllenAnvari, Bahman2019-04-01Exogenous fluorescent materials activated by near-infrared (NIR) light can offer deep optical imaging with subcellular resolution, and enhanced image contrast. We have engineered NIR particles by doping hemoglobin-depleted erythrocyte ghosts (EGs) with indocyanine green (ICG). We refer to these optical particles as NIR erythrocyte-mimicking transducers (NETs). A particular feature of NETs is that their diameters can be tuned from micrometer to nanometer scale, thereby, providing a capability for broad NIR biomedical imaging applications. Herein, we investigate the effects of ICG concentration on key material properties of micrometer-sized NETs, and nanometer-sized NETs fabricated by either sonication or mechanical extrusion of EGs. The zeta potentials of NETs do not vary significantly with ICG concentration, suggesting that ICG is encapsulated within NETs regardless of particle size or ICG concentration. Loading efficiency of ICG into the NETs monotonically decreases with increasing values of ICG concentration. Based on quantitative analyses of the fluorescence emission spectra of the NETs, we determine that 20 μM ICG utilized during fabrication of NETs presents an optimal concentration that maximizes the integrated fluorescence emission for micrometer- and nanometer-sized NETs. Encapsulation of the ICG in these constructs also enhances the fluorescence stability and quantum yield of ICG. These results guide the engineering of NETs with maximal NIR emission for imaging applications such as fluorescence-guided tumor resection and real-time angiography.EngineeringNanotechnologyBiomedical ImagingBioengineeringAnimalsCattleErythrocyte MembraneFluorescent DyesIndocyanine GreenNanomedicineNanoparticlesOptical ImagingParticle SizeSpectroscopyNear-InfraredBiomedical optical imagingbiomembranesbiomimetic materialsbiophotonicsmolecular imagingnanobiotechnologynanomedicineparticle productionArtificial Intelligence and Image ProcessingBiomedical EngineeringElectrical and Electronic EngineeringBiomedical engineeringElectronicssensors and digital hardwareComputer vision and multimedia computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/01k029n8articleIEEE Transactions on Biomedical Engineering, vol 66, iss 41034 - 1044oai:escholarship.org:ark:/13030/qt8b57x2r42023-10-04T10:37:30Zqt8b57x2r4Lectin- and Saccharide-Functionalized Nano-Chemiresistor Arrays for Detection and Identification of Pathogenic Bacteria InfectionSaucedo, Nuvia MGao, YingningPham, TungMulchandani, Ashok2018-01-01Improvement upon, and expansion of, diagnostic tools for clinical infections have been increasing in recent years. The simplicity and rapidity of techniques are imperative for their adoption and widespread usage at point-of-care. The fabrication and evaluation of such a device is reported in this work. The use of a small bioreceptor array (based on lectin-carbohydrate binding) resulted in a unique response profile, which has the potential to be used for pathogen identification, as demonstrated by Principal Component Analysis (PCA). The performance of the chemiresistive device was tested with Escherichia coli K12, Enterococcus faecalis, Streptococcus mutans, and Salmonella typhi. The limits of detection, based on concanavalin A (conA) lectin as the bioreceptor, are 4.7 × 10³ cfu/mL, 25 cfu/mL, 7.4 × 10⁴ cfu/mL, and 6.3 × 10² cfu/mL. This shows that the detection of pathogenic bacteria is achieved with clinically relevant concentrations. Importantly, responses measured in spiked artificial saliva showed minimal matrix interference. Furthermore, the exploitation of the distinctive outer composition of the bacteria and selectivity of lectin-carbohydrate interactions allowed for the discrimination of bacterial infections from viral infections, which is a current and urgent need for diagnosing common clinical infections.Biochemistry and Cell BiologyBiological SciencesBiotechnologyInfectious DiseasesEmerging Infectious DiseasesPrevention4.1 Discovery and preclinical testing of markers and technologiesDetectionscreening and diagnosisInfectionGood Health and Well BeingBacteriaBacterial InfectionsBiosensing TechniquesConcanavalin AEnterococcus faecalisEscherichia coliHumansLectinsLimit of DetectionMonosaccharidesNanotubesCarbonPrincipal Component AnalysisStreptococcus mutanspathogenslectinsCNTsPCApoint-of-carelabel-free detectionAnalytical ChemistryBiochemistry and cell biologyAnalytical chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8b57x2r4articleBiosensors, vol 8, iss 363oai:escholarship.org:ark:/13030/qt7cn111242023-10-04T10:35:48Zqt7cn11124Dissecting Distinct Roles of NEDDylation E1 Ligase Heterodimer APPBP1 and UBA3 Reveals Potential Evolution Process for Activation of Ubiquitin-related PathwaysMalik-Chaudhry, Harbani KaurGaieb, ZiedSaavedra, AmandaReyes, MichaelKung, RaphaelLe, FrankMorikis, DimitriosLiao, Jiayu2018-01-01Despite the similar enzyme cascade in the Ubiquitin and Ubiquitin-like peptide(Ubl) conjugation, the involvement of single or heterodimer E1 activating enzyme has been a mystery. Here, by using a quantitative Förster Resonance Energy Transfer (FRET) technology, aided with Analysis of Electrostatic Similarities Of Proteins (AESOP) computational framework, we elucidate in detail the functional properties of each subunit of the E1 heterodimer activating-enzyme for NEDD8, UBA3 and APPBP1. In contrast to SUMO activation, which requires both subunits of its E1 heterodimer AOS1-Uba2 for its activation, NEDD8 activation requires only one of two E1 subunits, UBA3. The other subunit, APPBP1, only contributes by accelerating the activation reaction rate. This discovery implies that APPBP1 functions mainly as a scaffold protein to enhance molecular interactions and facilitate catalytic reaction. These findings for the first time reveal critical new mechanisms and a potential evolutionary pathway for Ubl activations. Furthermore, this quantitative FRET approach can be used for other general biochemical pathway analysis in a dynamic mode.Biochemistry and Cell BiologyBiological Sciences1.1 Normal biological development and functioningUnderpinning researchGeneric health relevanceEvolutionMolecularFluorescence Resonance Energy TransferHumansMolecular Dynamics SimulationNEDD8 ProteinProtein BindingProtein DomainsProtein SubunitsStatic ElectricityUbiquitin-Activating Enzymesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7cn11124articleScientific Reports, vol 8, iss 110108oai:escholarship.org:ark:/13030/qt1gh391sc2023-10-04T10:24:48Zqt1gh391scNetwork analysis of unstructured EHR data for clinical research.Bauer-Mehren, AnnaLependu, PaeaIyer, Srinivasan VHarpaz, RaveLeeper, Nicholas JShah, Nigam H2013-01-01In biomedical research, network analysis provides a conceptual framework for interpreting data from high-throughput experiments. For example, protein-protein interaction networks have been successfully used to identify candidate disease genes. Recently, advances in clinical text processing and the increasing availability of clinical data have enabled analogous analyses on data from electronic medical records. We constructed networks of diseases, drugs, medical devices and procedures using concepts recognized in clinical notes from the Stanford clinical data warehouse. We demonstrate the use of the resulting networks for clinical research informatics in two ways-cohort construction and outcomes analysis-by examining the safety of cilostazol in peripheral artery disease patients as a use case. We show that the network-based approaches can be used for constructing patient cohorts as well as for analyzing differences in outcomes by comparing with standard methods, and discuss the advantages offered by network-based approaches.Information and Computing SciencesBiological SciencesBioinformatics and Computational BiologyClinical ResearchNetworking and Information Technology R&D (NITRD)Patient SafetyBioengineeringGeneric health relevanceapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1gh391scarticleoai:escholarship.org:ark:/13030/qt7cd017bx2023-10-04T10:24:44Zqt7cd017bxLearning signals of adverse drug-drug interactions from the unstructured text of electronic health records.Iyer, Srinivasan VLependu, PaeaHarpaz, RaveBauer-Mehren, AnnaShah, Nigam H2013-01-01Drug-drug interactions (DDI) account for 30% of all adverse drug reactions, which are the fourth leading cause of death in the US. Current methods for post marketing surveillance primarily use spontaneous reporting systems for learning DDI signals and validate their signals using the structured portions of Electronic Health Records (EHRs). We demonstrate a fast, annotation-based approach, which uses standard odds ratios for identifying signals of DDIs from the textual portion of EHRs directly and which, to our knowledge, is the first effort of its kind. We developed a gold standard of 1,120 DDIs spanning 14 adverse events and 1,164 drugs. Our evaluations on this gold standard using millions of clinical notes from the Stanford Hospital confirm that identifying DDI signals from clinical text is feasible (AUROC=81.5%). We conclude that the text in EHRs contain valuable information for learning DDI signals and has enormous utility in drug surveillance and clinical decision support.Information and Computing SciencesHealth Services and SystemsInformation SystemsHealth SciencesPatient SafetyClinical ResearchGood Health and Well Beingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7cd017bxarticleoai:escholarship.org:ark:/13030/qt1q1759t02023-10-04T10:24:41Zqt1q1759t0Pharmacovigilance using Clinical Text.Lependu, PaeaIyer, Srinivasan VBauer-Mehren, AnnaHarpaz, RaveGhebremariam, Yohannes TCooke, John PShah, Nigam H2013-01-01The current state of the art in post-marketing drug surveillance utilizes voluntarily submitted reports of suspected adverse drug reactions. We present data mining methods that transform unstructured patient notes taken by doctors, nurses and other clinicians into a de-identified, temporally ordered, patient-feature matrix using standardized medical terminologies. We demonstrate how to use the resulting high-throughput data to monitor for adverse drug events based on the clinical notes in the EHR.Information and Computing SciencesHealth Services and SystemsHealth SciencesPatient SafetyGood Health and Well Beingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1q1759t0articleoai:escholarship.org:ark:/13030/qt0tp109542023-10-04T10:23:15Zqt0tp10954On the Role of Mechanics in Chronic Lung DiseaseEskandari, MonaPfaller, Martin RKuhl, Ellen2013-01-01Progressive airflow obstruction is a classical hallmark of chronic lung disease, affecting more than one fourth of the adult population. As the disease progresses, the inner layer of the airway wall grows, folds inwards, and narrows the lumen. The critical failure conditions for airway folding have been studied intensely for idealized circular cross-sections. However, the role of airway branching during this process is unknown. Here, we show that the geometry of the bronchial tree plays a crucial role in chronic airway obstruction and that critical failure conditions vary significantly along a branching airway segment. We perform systematic parametric studies for varying airway cross-sections using a computational model for mucosal thickening based on the theory of finite growth. Our simulations indicate that smaller airways are at a higher risk of narrowing than larger airways and that regions away from a branch narrow more drastically than regions close to a branch. These results agree with clinical observations and could help explain the underlying mechanisms of progressive airway obstruction. Understanding growth-induced instabilities in constrained geometries has immediate biomedical applications beyond asthma and chronic bronchitis in the diagnostics and treatment of chronic gastritis, obstructive sleep apnea and breast cancer.EngineeringChemical SciencesLungAsthmaSleep ResearchAetiology2.1 Biological and endogenous factorsRespiratorymaterial modelingbiomaterialsinstabilitybucklingfoldinggrowthremodelingfinite element methodairway wall remodelingchronic lung diseaseChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0tp10954articleMaterials, vol 6, iss 125639 - 5658oai:escholarship.org:ark:/13030/qt4118d9f42023-10-04T10:23:10Zqt4118d9f4Annotation Analysis for Testing Drug Safety Signals using Unstructured Clinical NotesLePendu, PaeaIyer, Srinivasan VFairon, CédrickShah, Nigam H2012-12-01BackgroundThe electronic surveillance for adverse drug events is largely based upon the analysis of coded data from reporting systems. Yet, the vast majority of electronic health data lies embedded within the free text of clinical notes and is not gathered into centralized repositories. With the increasing access to large volumes of electronic medical data-in particular the clinical notes-it may be possible to computationally encode and to test drug safety signals in an active manner.ResultsWe describe the application of simple annotation tools on clinical text and the mining of the resulting annotations to compute the risk of getting a myocardial infarction for patients with rheumatoid arthritis that take Vioxx. Our analysis clearly reveals elevated risks for myocardial infarction in rheumatoid arthritis patients taking Vioxx (odds ratio 2.06) before 2005.ConclusionsOur results show that it is possible to apply annotation analysis methods for testing hypotheses about drug safety using electronic medical records.Information and Computing SciencesHeart Disease - Coronary Heart DiseasePatient SafetyNetworking and Information Technology R&D (NITRD)CardiovascularArthritisAutoimmune DiseaseHeart Disease5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsInflammatory and immune systemGood Health and Well BeingOther Biological SciencesArtificial Intelligence and Image ProcessingInformation SystemsInformation and computing sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4118d9f4articleJournal of Biomedical Semantics, vol 3, iss Suppl 1s5oai:escholarship.org:ark:/13030/qt26s2v9822023-10-04T10:23:01Zqt26s2v982Patient-Specific Airway Wall Remodeling in Chronic Lung DiseaseEskandari, MonaKuschner, Ware GKuhl, Ellen2015-10-01Chronic lung disease affects more than a quarter of the adult population; yet, the mechanics of the airways are poorly understood. The pathophysiology of chronic lung disease is commonly characterized by mucosal growth and smooth muscle contraction of the airways, which initiate an inward folding of the mucosal layer and progressive airflow obstruction. Since the degree of obstruction is closely correlated with the number of folds, mucosal folding has been extensively studied in idealized circular cross sections. However, airflow obstruction has never been studied in real airway geometries; the behavior of imperfect, non-cylindrical, continuously branching airways remains unknown. Here we model the effects of chronic lung disease using the nonlinear field theories of mechanics supplemented by the theory of finite growth. We perform finite element analysis of patient-specific Y-branch segments created from magnetic resonance images. We demonstrate that the mucosal folding pattern is insensitive to the specific airway geometry, but that it critically depends on the mucosal and submucosal stiffness, thickness, and loading mechanism. Our results suggests that patient-specific airway models with inherent geometric imperfections are more sensitive to obstruction than idealized circular models. Our models help to explain the pathophysiology of airway obstruction in chronic lung disease and hold promise to improve the diagnostics and treatment of asthma, bronchitis, chronic obstructive pulmonary disease, and respiratory failure.EngineeringBiomedical EngineeringAsthmaLungRespiratoryAdultAirway RemodelingChronic DiseaseHumansLung DiseasesModelsBiologicalRespiratory MucosaChronic lung diseaseAirway remodelingBronchoconstrictionBronchitisFinite element analysisPatient-specific modelingMedical and Health SciencesBiomedical engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/26s2v982articleAnnals of Biomedical Engineering, vol 43, iss 102538 - 2551oai:escholarship.org:ark:/13030/qt756792c12023-10-04T10:22:57Zqt756792c1A formal concept analysis and semantic query expansion cooperation to refine health outcomes of interestCuré, Olivier CMaurer, HenriShah, Nigam HLe Pendu, Paea2015-12-01BackgroundElectronic Health Records (EHRs) are frequently used by clinicians and researchers to search for, extract, and analyze groups of patients by defining Health Outcome of Interests (HOI). The definition of an HOI is generally considered a complex and time consuming task for health care professionals.MethodsIn our clinical note-based pharmacovigilance research, we often operate upon potentially hundreds of ontologies at once, expand query inputs, and we also increase the search space over clinical text as well as structured data. Such a method implies to specify an initial set of seed concepts, which are based on concept unique identifiers. This paper presents a novel method based on Formal Concept Analysis (FCA) and Semantic Query Expansion (SQE) to assist the end-user in defining their seed queries and in refining the expanded search space that it encompasses.ResultsWe evaluate our method over a gold-standard corpus from the 2008 i2b2 Obesity Challenge. This experimentation emphasizes positive results for sensitivity and specificity measures. Our new approach provides better recall with high precision of the obtained results. The most promising aspect of this approach consists in the discovery of positive results not present our Obesity NLP reference set.ConclusionsTogether with a Web graphical user interface, our FCA and SQE cooperation end up being an efficient approach for refining health outcome of interest using plain terms. We consider that this approach can be extended to support other domains such as cohort building tools.Health Services and SystemsHealth SciencesBiological OntologiesElectronic Health RecordsHumansMedical InformaticsOutcome AssessmentHealth CareSemanticsInformation SystemsClinical SciencesHealth services and systemsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/756792c1articleBMC Medical Informatics and Decision Making, vol 15, iss Suppl 1s8oai:escholarship.org:ark:/13030/qt00q0x8cn2023-10-04T10:22:52Zqt00q0x8cnSystems biology and mechanics of growthEskandari, MonaKuhl, Ellen2015-11-01In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident during embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here, we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the systems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention.Biochemistry and Cell BiologyBiological SciencesGeneric health relevanceBiomechanical PhenomenaHumansIntestinal MucosaIntestinesModelsBiologicalPlant LeavesPlantsClinical SciencesOther Medical and Health SciencesBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/00q0x8cnarticleWIREs Mechanisms of Disease, vol 7, iss 6401 - 412oai:escholarship.org:ark:/13030/qt7ng8g4d92023-10-04T10:22:43Zqt7ng8g4d9Elastosis during airway wall remodeling explains multiple co-existing instability patternsEskandari, MonaJavili, AliKuhl, Ellen2016-08-01Living structures can undergo morphological changes in response to growth and alterations in microstructural properties in response to remodeling. From a biological perspective, airway wall inflammation and airway elastosis are classical hallmarks of growth and remodeling during chronic lung disease. From a mechanical point of view, growth and remodeling trigger mechanical instabilities that result in inward folding and airway obstruction. While previous analytical and computational studies have focused on identifying the critical parameters at the onset of folding, few have considered the post-buckling behavior. All prior studies assume constant microstructural properties during the folding process; yet, clinical studies now reveal progressive airway elastosis, the degeneration of elastic fibers associated with a gradual stiffening of the inner layer. Here, we explore the influence of temporally evolving material properties on the post-bifurcation behavior of the airway wall. We show that a growing and stiffening inner layer triggers an additional subsequent bifurcation after the first instability occurs. Evolving material stiffnesses provoke failure modes with multiple co-existing wavelengths, associated with the superposition of larger folds evolving on top of the initial smaller folds. This phenomenon is exclusive to material stiffening and conceptually different from the phenomenon of period doubling observed in constant-stiffness growth. Our study suggests that the clinically observed multiple wavelengths in diseased airways are a result of gradual airway wall stiffening. While our evolving material properties are inspired by the clinical phenomenon of airway elastosis, the underlying concept is broadly applicable to other types of remodeling including aneurysm formation or brain folding.Biological SciencesMathematical SciencesAirway RemodelingAsthmaBiomechanical PhenomenaComputer SimulationHumansInflammationStressMechanicalInstabilityFoldingAirwayElastosisGrowth and remodelingFinite element analysisInformation and Computing SciencesEvolutionary BiologyBiological sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7ng8g4d9articleoai:escholarship.org:ark:/13030/qt9rj8k4df2023-10-04T10:22:39Zqt9rj8k4dfCross-domain targeted ontology subsets for annotation: The case of SNOMED CORE and RxNormLópez-García, PabloLePendu, PaeaMusen, MarkIllarramendi, Arantza2014-02-01The benefits of using ontology subsets versus full ontologies are well-documented for many applications. In this study, we propose an efficient subset extraction approach for a domain using a biomedical ontology repository with mappings, a cross-ontology, and a source subset from a related domain. As a case study, we extracted a subset of drugs from RxNorm using the UMLS Metathesaurus, the NDF-RT cross-ontology, and the CORE problem list subset of SNOMED CT. The extracted subset, which we termed RxNorm/CORE, was 4% the size of the full RxNorm (0.4% when considering ingredients only). For evaluation, we used CORE and RxNorm/CORE as thesauri for the annotation of clinical documents and compared their performance to that of their respective full ontologies (i.e., SNOMED CT and RxNorm). The wide range in recall of both CORE (29-69%) and RxNorm/CORE (21-35%) suggests that more quantitative research is needed to assess the benefits of using ontology subsets as thesauri in annotation applications. Our approach to subset extraction, however, opens a door to help create other types of clinically useful domain specific subsets and acts as an alternative in scenarios where well-established subset extraction techniques might suffer from difficulties or cannot be applied.Information and Computing SciencesArtificial IntelligenceAlgorithmsBiological OntologiesHumansMedical InformaticsReproducibility of ResultsRxNormSoftwareSystematized Nomenclature of MedicineUnified Medical Language SystemVocabularyControlledOntologiesSNOMED CTNDF-RTUMLSAnnotationBiological SciencesMedical and Health SciencesBiomedical EngineeringHealth services and systemsApplied computingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9rj8k4dfarticleoai:escholarship.org:ark:/13030/qt5xp717xw2023-10-04T10:18:20Zqt5xp717xwInvestigating the role of Hedgehog/GLI1 signaling in glioblastoma cell response to temozolomideMelamed, Jilian RMorgan, Joshua TIoele, Stephen AGleghorn, Jason PSims-Mourtada, JenniferDay, Emily S2018-06-05Resistance to chemotherapy substantially hinders successful glioblastoma (GBM) treatment, contributing to an almost 100% mortality rate. Resistance to the frontline chemotherapy, temozolomide (TMZ), arises from numerous signaling pathways that are deregulated in GBM, including Hedgehog (Hh) signaling. Here, we investigate suppression of Hh signaling as an adjuvant to TMZ using U87-MG and T98G cell lines as in vitro models of GBM. We found that silencing GLI1 with siRNA reduces cell metabolic activity by up to 30% in combination with TMZ and reduces multidrug efflux activity by 2.5-fold. Additionally, pharmacological GLI inhibition modulates nuclear p53 levels and decreases MGMT expression in combination with TMZ. While we surprisingly found that silencing GLI1 does not induce apoptosis in the absence of TMZ co-treatment, we discovered silencing GLI1 without TMZ co-treatment induces senescence as evidenced by a significant 2.3-fold increase in senescence associated β-galactosidase staining, and this occurs in a loss of PTEN-dependent manner. Finally, we show that GLI inhibition increases apoptosis in glioma stem-like cells by up to 6.8-fold in combination with TMZ, and this reduces the size and number of neurospheres grown from glioma stem-like cells. In aggregate, our data warrant the continued investigation of Hh pathway inhibitors as adjuvants to TMZ chemotherapy and highlight the importance of identifying signaling pathways that determine whether co-treatment will be successful.Biomedical and Clinical SciencesOncology and CarcinogenesisStem Cell ResearchBrain DisordersRare DiseasesBrain CancerNeurosciencesCancerGLI1chemoresistanceglioblastomahedgehogtemozolomideOncology and carcinogenesisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5xp717xwarticleOncotarget, vol 9, iss 4327000 - 27015oai:escholarship.org:ark:/13030/qt13d272rr2023-10-04T06:56:06Zqt13d272rrSuper resolution for astronomical observationsLi, ZhanPeng, QingyuBhanu, BirZhang, QingfengHe, Haifeng2018-05-01Astronomical SciencesPhysical SciencesMethods: data analysisTechniques: image processingTelescopesStars: imagingAstronomical and Space SciencesAstronomy & AstrophysicsAstronomical sciencesParticle and high energy physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/13d272rrarticleAstrophysics and Space Science, vol 363, iss 592oai:escholarship.org:ark:/13030/qt55b9j37d2023-10-04T05:00:27Zqt55b9j37dTwo-time correlators for propagating squeezed microwave fields in transientsAtalaya, JuanKhezri, MostafaKorotkov, Alexander N2019-04-01We analyze two-time correlators as the most natural characteristic of a
propagating quadrature-squeezed field in the transient regime. The considered
system is a parametrically driven resonator with a time-dependent drive. Using
a semiclassical approach derived from the input-output theory, we develop a
technique for calculation of the two-time correlators, which are directly
related to fluctuations of the measured integrated signal. While in the steady
state the correlators are determined by three parameters (as for the
phase-space ellipse describing a squeezed state), four parameters are necessary
in the transient regime. The formalism can be generalized to weakly nonlinear
resonators with additional coherent drive. We focus on squeezed microwave
fields relevant to the measurement of superconducting qubits; however, our
formalism is also applicable to optical systems. The results can be readily
verified experimentally.Quantum PhysicsPhysical Sciencesquant-phcond-mat.mes-hallcond-mat.supr-conChemical sciencesMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/55b9j37darticlePhysical Review A, vol 99, iss 4043810oai:escholarship.org:ark:/13030/qt7wb390mc2023-10-04T04:03:09Zqt7wb390mcSocial Grouping for Multi-Target Tracking and Head Pose Estimation in VideoQin, ZhenShelton, Christian R2016-10-01Many computer vision tasks are more difficult when tackled without contextual information. For example, in multi-camera tracking, pedestrians may look very different in different cameras with varying pose and lighting conditions. Similarly, head direction estimation in high-angle surveillance video in which human head images are low resolution is challenging. Even humans can have trouble without contextual information. In this work, we couple novel contextual information, social grouping, with two important computer vision tasks: multi-target tracking and head pose/direction estimation in surveillance video. These three components are modeled in a probabilistic formulation and we provide effective solvers.We show that social grouping effectively helps to mitigate visual ambiguities in multi-camera tracking and head pose estimation. We further notice that in single-camera multi-target tracking, social grouping provides a natural high-order association cue that avoids existing complex algorithms for high-order track association. In experiments, we demonstrate improvements with our model over models without social grouping context and several state-of-art approaches on a number of publicly available datasets on tracking, head pose estimation, and group discovery.Information and Computing SciencesComputer Vision and Multimedia ComputationAlgorithmsHeadHumansLightingPostureVideo RecordingMulti-target trackingmulti-camera trackinghead pose estimationsocial groupingvideo analysiscontextArtificial Intelligence and Image ProcessingInformation SystemsElectrical and Electronic EngineeringArtificial Intelligence & Image ProcessingComputer vision and multimedia computationMachine learningapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7wb390mcarticleIEEE Transactions on Pattern Analysis and Machine Intelligence, vol 38, iss 102082 - 2095oai:escholarship.org:ark:/13030/qt67p026mw2023-10-04T02:51:27Zqt67p026mwStrategies for microbial synthesis of high-value phytochemicalsLi, SijinLi, YanranSmolke, Christina D2018-04-01Phytochemicals are of great pharmaceutical and agricultural importance, but often exhibit low abundance in nature. Recent demonstrations of industrial-scale production of phytochemicals in yeast have shown that microbial production of these high-value chemicals is a promising alternative to sourcing these molecules from native plant hosts. However, a number of challenges remain in the broader application of this approach, including the limited knowledge of plant secondary metabolism and the inefficient reconstitution of plant metabolic pathways in microbial hosts. In this Review, we discuss recent strategies to achieve microbial biosynthesis of complex phytochemicals, including strategies to: (1) reconstruct plant biosynthetic pathways that have not been fully elucidated by mining enzymes from native and non-native hosts or by enzyme engineering; (2) enhance plant enzyme activity, specifically cytochrome P450 activity, by improving efficiency, selectivity, expression or electron transfer; and (3) enhance overall reaction efficiency of multi-enzyme pathways by dynamic control, compartmentalization or optimization with the host's metabolism. We also highlight remaining challenges to - and future opportunities of - this approach.Chemical SciencesComplementary and Integrative HealthCytochrome P-450 Enzyme SystemEscherichia coliMetabolic EngineeringPhytochemicalsSaccharomyces cerevisiaeOrganic ChemistryChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/67p026mwarticleNature Chemistry, vol 10, iss 4395 - 404oai:escholarship.org:ark:/13030/qt4s13z9qm2023-10-04T01:44:20Zqt4s13z9qmExploiting Spatial Structure for Localizing Manipulated Image RegionsBappy, Jawadul HRoy-Chowdhury, Amit KBunk, JasonNataraj, LakshmananManjunath, BS2017-10-01Information and Computing SciencesComputer Vision and Multimedia Computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4s13z9qmarticleoai:escholarship.org:ark:/13030/qt4wp5z50r2023-09-29T23:01:36Zqt4wp5z50rRegional biaxial mechanical data of the mitral and tricuspid valve anterior leaflets.Laurence, DevinRoss, ColtonJett, SamuelJohns, CortlandEchols, AllysonBaumwart, RyanTowner, RhealLiao, JunBajona, PietroWu, YiLee, Chung-Hao2019-06-01The collective data associated with this article presents the biaxial mechanical behavior for six smaller, delimited regions of the mitral valve and tricuspid valve anterior leaflets. Each data set consists of five columns of data, specifically: (i) biaxial testing protocol ID, (ii) circumferential stretch, (iii) radial stretch, (iv) circumferential membrane tension, and (v) radial membrane tension. For further elaboration regarding methodologies or results of the biaxial mechanical characterization please refer to the companion article Laurence, 2019.Atrioventricular heart valve biomechanicsBiaxial mechanical testingRegionally-varied mechanical propertiesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4wp5z50rarticleoai:escholarship.org:ark:/13030/qt48z846nv2023-09-29T22:59:32Zqt48z846nvRegulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair.Ayoub, SalmaLee, Chung-HaoDriesbaugh, KathrynAnselmo, WandaHughes, ConnorFerrari, GiovanniGorman, RobertGorman, JosephSacks, Michael2017-10-01Mechanical stress is one of the major aetiological factors underlying soft-tissue remodelling, especially for the mitral valve (MV). It has been hypothesized that altered MV tissue stress states lead to deviations from cellular homeostasis, resulting in subsequent cellular activation and extracellular matrix (ECM) remodelling. However, a quantitative link between alterations in the organ-level in vivo state and in vitro-based mechanobiology studies has yet to be made. We thus developed an integrated experimental-computational approach to elucidate MV tissue and interstitial cell responses to varying tissue strain levels. Comprehensive results at different length scales revealed that normal responses are observed only within a defined range of tissue deformations, whereas deformations outside of this range lead to hypo- and hyper-synthetic responses, evidenced by changes in α-smooth muscle actin, type I collagen, and other ECM and cell adhesion molecule regulation. We identified MV interstitial cell deformation as a key player in leaflet tissue homeostatic regulation and, as such, used it as the metric that makes the critical link between in vitro responses to simulated equivalent in vivo behaviour. Results indicated that cell responses have a delimited range of in vivo deformations that maintain a homeostatic response, suggesting that deviations from this range may lead to deleterious tissue remodelling and failure.collagenmyofibroblastvalve interstitial cellsAnimalsBiomechanical PhenomenaCell AdhesionCell SurvivalCollagenExtracellular MatrixGene Expression RegulationHomeostasisMitral ValveModelsCardiovascularPolymerase Chain ReactionSwineTissue Culture Techniquesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/48z846nvarticleJournal of the Royal Society Interface, vol 14, iss 135oai:escholarship.org:ark:/13030/qt85p428m82023-09-29T22:57:33Zqt85p428m8An investigation of the glycosaminoglycan contribution to biaxial mechanical behaviours of porcine atrioventricular heart valve leaflets.Ross, ColtonRoss, ColtonLaurence, DevinRichardson, JacobBabu, AnjuEvans, LaurenBeyer, EanChilders, RachelWu, YiTowner, RhealFung, Kar-MingMir, ArshidBurkhart, HaroldHolzapfel, GerhardLee, Chung-Hao2019-07-26The atrioventricular heart valve (AHV) leaflets have a complex microstructure composed of four distinct layers: atrialis, ventricularis, fibrosa and spongiosa. Specifically, the spongiosa layer is primarily proteoglycans and glycosaminoglycans (GAGs). Quantification of the GAGs mechanical contribution to the overall leaflet function has been of recent focus for aortic valve leaflets, but this characterization has not been reported for the AHV leaflets. This study seeks to expand current GAG literature through novel mechanical characterizations of GAGs in AHV leaflets. For this characterization, mitral and tricuspid valve anterior leaflets (MVAL and TVAL, respectively) were: (i) tested by biaxial mechanical loading at varying loading ratios and by stress-relaxation procedures, (ii) enzymatically treated for removal of the GAGs and (iii) biaxially mechanically tested again under the same protocols as in step (i). Removal of the GAG contents from the leaflet was conducted using a 100 min enzyme treatment to achieve approximate 74.87% and 61.24% reductions of all GAGs from the MVAL and TVAL, respectively. Our main findings demonstrated that biaxial mechanical testing yielded a statistically significant difference in tissue extensibility after GAG removal and that stress-relaxation testing revealed a statistically significant smaller stress decay of the enzyme-treated tissue than untreated tissues. These novel findings illustrate the importance of GAGs in AHV leaflet behaviour, which can be employed to better inform heart valve therapeutics and computational models.atrioventricular heart valvesbiaxial mechanical testingglycosaminoglycan removalleaflet microstructurestress relaxationAnimalsAortic ValveComputer SimulationGlycosaminoglycansModelsCardiovascularStressMechanicalSwineapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/85p428m8articleJournal of the Royal Society Interface, vol 16, iss 156oai:escholarship.org:ark:/13030/qt541022tm2023-09-29T22:55:33Zqt541022tmAn investigation of the anisotropic mechanical properties and anatomical structure of porcine atrioventricular heart valves.Jett, SamuelLaurence, DevinKunkel, RobertBabu, AnjuKramer, KatherineBaumwart, RyanTowner, RhealWu, YiLee, Chung-Hao2018-11-01Valvular heart diseases are complex disorders, varying in pathophysiological mechanism and affected valve components. Understanding the effects of these diseases on valve functionality requires a thorough characterization of the mechanics and structure of the healthy heart valves. In this study, we performed biaxial mechanical experiments with extensive testing protocols to examine the mechanical behaviors of the mitral valve and tricuspid valve leaflets. We also investigated the effect of loading rate, testing temperatures, species (porcine versus ovine hearts), and age (juvenile vs adult ovine hearts) on the mechanical responses of the leaflet tissues. In addition, we evaluated the structure of chordae tendineae within each valve and performed histological analysis on each atrioventricular leaflet. We found all tissues displayed a characteristic nonlinear anisotropic mechanical response, with radial stretches on average 30.7% higher than circumferential stretches under equibiaxial physiological loading. Tissue mechanical responses showed consistent mechanical stiffening in response to increased loading rate and minor temperature dependence in all five atrioventricular heart valve leaflets. Moreover, our anatomical study revealed similar chordae quantities in the porcine mitral (30.5 ± 1.43 chords) and tricuspid valves (35.3 ± 2.45 chords) but significantly more chordae in the porcine than the ovine valves (p < 0.010). Our histological analyses quantified the relative thicknesses of the four distinct morphological layers in each leaflet. This study provides a comprehensive database of the mechanics and structure of the atrioventricular valves, which will be beneficial to development of subject-specific atrioventricular valve constitutive models and toward multi-scale biomechanical investigations of heart valve function to improve valvular disease treatments.Biaxial mechanical testingMorphological analysisSoft tissue biomechanics and microstructureThe mitral and tricuspid valvesAnimalsAnisotropyBiomechanical PhenomenaHeart AtriaHeart ValvesHeart VentriclesMaterials TestingMechanical PhenomenaSheepSwineTemperatureWeight-Bearingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/541022tmarticleoai:escholarship.org:ark:/13030/qt9x15s5wr2023-09-29T22:53:28Zqt9x15s5wrShape Memory Polyurethane with Porous Architectures for Potential Applications in Intracranial Aneurysm Treatment.Wang, JingyuKunkel, RobertLuo, JishanLi, YuhuaLiu, HongBohnstedt, BradleyLiu, YingtaoLee, Chung-Hao2019-04-05Conventional endovascular embolization of intracranial (or brain) aneurysms using helical detachable platinum coils can be time-consuming and occasionally requires retreatment due to incomplete coil packing. These shortcomings create a need for new biomedical devices and methods of achieving brain aneurysm occlusion. This paper presents a biocompatible and highly porous shape memory polymer (SMP) material with potential applications in the development of novel endovascular devices for treating complex intracranial aneurysms. The novel highly porous polyurethane SMP is synthesized as an open cell foam material with a glass transition temperature (Tg) of 39 °C using a sugar particle leaching method. Once heated above the Tg, the compressed SMP foam is able to quickly return to its original shape. An electrical resistance heating method is also employed to demonstrate a potential triggering design for the shape recovery process in future medical applications. The mechanical properties of the developed SMP foam are characterized at temperatures up to 10 °C above the respective Tg. The results from this work demonstrate that the porous SMP material developed in this study and the electrical resistance heating trigger mechanism provide a solid foundation for future design of biomedical devices to enhance the long-term therapeutic outcomes of endovascular intracranial aneurysm treatments.electrical resistance heatingglass transition temperaturemicro-CTpolyurethaneporous architectureshape memoryshape recovery activationthermo-mechanical propertiesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9x15s5wrarticlePolymers, vol 11, iss 4oai:escholarship.org:ark:/13030/qt7550s8vr2023-09-29T22:51:22Zqt7550s8vrAn investigation of layer-specific tissue biomechanics of porcine atrioventricular valve anterior leaflets.Kramer, KatherineRoss, ColtonLaurence, DevinBabu, AnjuWu, YiTowner, RhealMir, ArshidBurkhart, HaroldHolzapfel, GerhardLee, Chung-Hao2019-09-15Atrioventricular heart valves (AHVs) are composed of structurally complex and morphologically heterogeneous leaflets. The coaptation of these leaflets during the cardiac cycle facilitates unidirectional blood flow. Valve regurgitation is treated preferably by surgical repair if possible or replacement based on the disease state of the valve tissue. A comprehensive understanding of valvular morphology and mechanical properties is crucial to refining computational models, serving as a patient-specific diagnostic and surgical tool for preoperative planning. Previous studies have modeled the stress distribution throughout the leaflets thickness, but validations with layer-specific biaxial mechanical experiments are missing. In this study, we sought to fill this gap in literature by investigating the impact of microstructure constituents on mechanical behavior throughout the thickness of the AHVs anterior leaflets. Porcine mitral valve anterior leaflets (MVAL) and tricuspid valve anterior leaflets (TVAL) were micro-dissected into three layers (atrialis/spongiosa, fibrosa, and ventricular) and two layers (atrialis/spongiosa and fibrosa/ventricularis), respectively, based on their relative distributions of extracellular matrix components as quantified by histological analyses: collagen, elastin, and glycosaminoglycans. Our results suggest that (i) for both valves, the atrialis/spongiosa layer is the most extensible and anisotropic layer, possibly due to its relatively low collagen content as compared to other layers, (ii) the intact TVAL response is stiffer than the atrialis/spongiosa layer but more compliant than the fibrosa/ventricularis layer, and (iii) the MVAL fibrosa and ventricularis layers behave nearly isotropic. These novel findings emphasize the biomechanical variances throughout the AHV leaflets, and our results could better inform future AHV computational model developments. STATEMENT OF SIGNIFICANCE: This study, which is the first of its kind for atrioventricular heart valve (AHV) leaflet tissue layers, rendered a mechanical characterization of the biaxial mechanical properties and distributions of extracellular matrix components (collagen, elastin, and glycosaminoglycans) of the mitral and tricuspid valve anterior leaflet layers. The novel findings from the present study emphasize the biomechanical variances throughout the thickness of AHV leaflets, and our results indicate that the previously-adopted homogenous leaflet in the AHV biomechanical modeling may be an oversimplification of the complex leaflet anatomy. Such improvement in the understanding of valvular morphology and tissue mechanics is crucial to future refinement of AHV computational models, serving as a patient-specific diagnostic and surgical tool, at the preoperative stage, for treating valvular heart diseases.Biaxial mechanical testingExtracellular matrixMicro-dissectionMorphological analysisThe mitral and tricuspid valvesValve tissue biomechanicsAnimalsAnisotropyBiomechanical PhenomenaMitral ValveSwineTricuspid Valveapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7550s8vrarticleoai:escholarship.org:ark:/13030/qt7kz1x1tb2023-09-29T22:49:24Zqt7kz1x1tbAn investigation of regional variations in the biaxial mechanical properties and stress relaxation behaviors of porcine atrioventricular heart valve leaflets.Laurence, DevinRoss, ColtonJett, SamuelJohns, CortlandEchols, AllysonBaumwart, RyanTowner, RhealLiao, JunBajona, PietroWu, YiLee, Chung-Hao2019-01-23The facilitation of proper blood flow through the heart depends on proper function of heart valve components, and alterations to any component can lead to heart disease or failure. Comprehension of these valvular diseases is reliant on thorough characterization of healthy heart valve structures for use in computational models. Previously, computational models have treated these leaflet structures as a structurally and mechanically homogenous material, which may not be an accurate description of leaflet mechanical response. In this study, we aimed to characterize the mechanics of the heart valve leaflet as a structurally heterogenous material. Specifically, porcine mitral valve and tricuspid valve anterior leaflets were sectioned into six regions and biaxial mechanical tests with various loading ratios and stress-relaxation test were performed on each regional tissue sample. Three main findings from this study were summarized as follows: (i) the central regions of the leaflet had a more anisotropic nature than edge regions, (ii) the mitral valve anterior leaflet was more extensible in regions closer to the annulus, and (iii) there was variance in the stress-relaxation behavior among all six regions, with mitral valve leaflet tissue regions exhibiting a greater decay than the tricuspid valve regions. This study presents a novel investigation of the regional variations in the heart valve biomechanics that has not been comprehensively examined. Our results thus allow for a refinement of computational models for more accurately predicting diseased or surgically-intervened condition, where tissue heterogeneity plays an essential role in the heart valve function.Biaxial mechanical testingHeart valve biomechanicsRegional mechanical propertiesThe mitral valveThe tricuspid valveAnimalsAnisotropyBiomechanical PhenomenaHeart AtriaHeart ValvesHeart VentriclesModelsCardiovascularStressMechanicalSwineapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7kz1x1tbarticleoai:escholarship.org:ark:/13030/qt4r9688z52023-09-29T22:47:20Zqt4r9688z5Mechanics of Porcine Heart Valves Strut Chordae Tendineae Investigated as a Leaflet-Chordae-Papillary Muscle Entity.Ross, ColtonLaurence, DevinHsu, Ming-ChenBaumwart, RyanZhao, YanMir, ArshidBurkhart, HaroldHolzapfel, GerhardWu, YiLee, Chung-Hao2020-05-01Proper blood flow through the atrioventricular heart valves (AHVs) relies on the holistic function of the valve and subvalvular structures, and a failure of any component can lead to life-threatening heart disease. A comprehension of the mechanical characteristics of healthy valvular components is necessary for the refinement of heart valve computational models. In previous studies, the chordae tendineae have been mechanically characterized as individual structures, usually in a clamping-based approach, which may not accurately reflect the in vivo chordal interactions with the leaflet insertion and papillary muscles. In this study, we performed uniaxial mechanical testing of strut chordae tendineae of the AHVs under a unique tine-based leaflet-chordae-papillary muscle testing to observe the chordae mechanics while preserving the subvalvular component interactions. Results of this study provided insight to the disparity of chordae tissue stress-stretch responses between the mitral valve (MV) and the tricuspid valve (TV) under their respective emulated physiological loading. Specifically, strut chordae tendineae of the MV anterior leaflet had peak stretches of 1.09-1.16, while peak stretches of 1.08-1.11 were found for the TV anterior leaflet strut chordae. Constitutive parameters were also derived for the chordae tissue specimens using an Ogden model, which is useful for AHV computational model refinement. Results of this study are beneficial to the eventual improvement of treatment methods for valvular disease.Chordae tendineae mechanicsConstitutive modelingThe mitral valveThe tricuspid valveUniaxial mechanical testingAnimalsBiomechanical PhenomenaChordae TendineaeMitral ValvePapillary MusclesSwineTricuspid Valveapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4r9688z5articleJournal of bioengineering, vol 48, iss 5oai:escholarship.org:ark:/13030/qt6pn9k6v02023-09-29T22:45:22Zqt6pn9k6v0On the presence of affine fibril and fiber kinematics in the mitral valve anterior leaflet.Lee, Chung-HaoZhang, WillLiao, JunCarruthers, ChristopherSacks, JacobSacks, Michael2015-04-21In this study, we evaluated the hypothesis that the constituent fibers follow an affine deformation kinematic model for planar collagenous tissues. Results from two experimental datasets were utilized, taken at two scales (nanometer and micrometer), using mitral valve anterior leaflet (MVAL) tissues as the representative tissue. We simulated MVAL collagen fiber network as an ensemble of undulated fibers under a generalized two-dimensional deformation state, by representing the collagen fibrils based on a planar sinusoidally shaped geometric model. The proposed approach accounted for collagen fibril amplitude, crimp period, and rotation with applied macroscopic tissue-level deformation. When compared to the small angle x-ray scattering measurements, the model fit the data well, with an r(2) = 0.976. This important finding suggests that, at the homogenized tissue-level scale of ∼1 mm, the collagen fiber network in the MVAL deforms according to an affine kinematics model. Moreover, with respect to understanding its function, affine kinematics suggests that the constituent fibers are largely noninteracting and deform in accordance with the bulk tissue. It also suggests that the collagen fibrils are tightly bounded and deform as a single fiber-level unit. This greatly simplifies the modeling efforts at the tissue and organ levels, because affine kinematics allows a straightforward connection between the macroscopic and local fiber strains. It also suggests that the collagen and elastin fiber networks act independently of each other, with the collagen and elastin forming long fiber networks that allow for free rotations. Such freedom of rotation can greatly facilitate the observed high degree of mechanical anisotropy in the MVAL and other heart valves, which is essential to heart valve function. These apparently novel findings support modeling efforts directed toward improving our fundamental understanding of tissue biomechanics in healthy and diseased conditions.AnimalsBiomechanical PhenomenaElasticityFemaleFibrillar CollagensMitral ValveModelsCardiovascularSheepapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6pn9k6v0articleBiophysical Journal, vol 108, iss 8oai:escholarship.org:ark:/13030/qt1m6153982023-09-29T22:43:19Zqt1m615398Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis.Rego, BrunoWells, SarahLee, Chung-HaoSacks, Michael2016-12-01Little is known about how valvular tissues grow and remodel in response to altered loading. In this work, we used the pregnancy state to represent a non-pathological cardiac volume overload that distends the mitral valve (MV), using both extant and new experimental data and a modified form of our MV structural constitutive model. We determined that there was an initial period of permanent set-like deformation where no remodelling occurs, followed by a remodelling phase that resulted in near-complete restoration of homeostatic tissue-level behaviour. In addition, we observed that changes in the underlying MV interstitial cell (MVIC) geometry closely paralleled the tissue-level remodelling events, undergoing an initial passive perturbation followed by a gradual recovery to the pre-pregnant state. Collectively, these results suggest that valvular remodelling is actively mediated by average MVIC deformations (i.e. not cycle to cycle, but over a period of weeks). Moreover, tissue-level remodelling is likely to be accomplished by serial and parallel additions of fibrillar material to restore the mean homeostatic fibre stress and MVIC geometries. This finding has significant implications in efforts to understand and predict MV growth and remodelling following such events as myocardial infarction and surgical repair, which also place the valve under altered loading conditions.heart valvepregnancyremodellingstructural constitutive modelvalve interstitial cellvolume overloadAnimalsCattleFemaleMitral ValvePregnancyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1m615398articleJournal of the Royal Society Interface, vol 13, iss 125oai:escholarship.org:ark:/13030/qt2hr9d0kf2023-09-29T22:41:19Zqt2hr9d0kfBiaxial Mechanical Characterizations of Atrioventricular Heart Valves.Ross, ColtonLaurence, DevinWu, YiLee, Chung-Hao2019-04-09Extensive biaxial mechanical testing of the atrioventricular heart valve leaflets can be utilized to derive optimal parameters used in constitutive models, which provide a mathematical representation of the mechanical function of those structures. This presented biaxial mechanical testing protocol involves (i) tissue acquisition, (ii) the preparation of tissue specimens, (iii) biaxial mechanical testing, and (iv) postprocessing of the acquired data. First, tissue acquisition requires obtaining porcine or ovine hearts from a local Food and Drug Administration-approved abattoir for later dissection to retrieve the valve leaflets. Second, tissue preparation requires using tissue specimen cutters on the leaflet tissue to extract a clear zone for testing. Third, biaxial mechanical testing of the leaflet specimen requires the use of a commercial biaxial mechanical tester, which consists of force-controlled, displacement-controlled, and stress-relaxation testing protocols to characterize the leaflet tissues mechanical properties. Finally, post-processing requires the use of data image correlation techniques and force and displacement readings to summarize the tissues mechanical behaviors in response to external loading. In general, results from biaxial testing demonstrate that the leaflet tissues yield a nonlinear, anisotropic mechanical response. The presented biaxial testing procedure is advantageous to other methods since the method presented here allows for a more comprehensive characterization of the valve leaflet tissue under one unified testing scheme, as opposed to separate testing protocols on different tissue specimens. The proposed testing method has its limitations in that shear stress is potentially present in the tissue sample. However, any potential shear is presumed negligible.AnimalsAnisotropyHeart ValvesSheepStressMechanicalSwineapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2hr9d0kfarticleoai:escholarship.org:ark:/13030/qt9zk528w22023-09-29T22:39:20Zqt9zk528w2Mechanics of the Tricuspid Valve-From Clinical Diagnosis/Treatment, In-Vivo and In-Vitro Investigations, to Patient-Specific Biomechanical Modeling.Lee, Chung-HaoLaurence, DevinRoss, ColtonKramer, KatherineBabu, AnjuJohnson, EmilyHsu, Ming-ChenAggarwal, AnkushMir, ArshidBurkhart, HaroldTowner, RhealBaumwart, RyanWu, Yi2019-05-22Proper tricuspid valve (TV) function is essential to unidirectional blood flow through the right side of the heart. Alterations to the tricuspid valvular components, such as the TV annulus, may lead to functional tricuspid regurgitation (FTR), where the valve is unable to prevent undesired backflow of blood from the right ventricle into the right atrium during systole. Various treatment options are currently available for FTR; however, research for the tricuspid heart valve, functional tricuspid regurgitation, and the relevant treatment methodologies are limited due to the pervasive expectation among cardiac surgeons and cardiologists that FTR will naturally regress after repair of left-sided heart valve lesions. Recent studies have focused on (i) understanding the function of the TV and the initiation or progression of FTR using both in-vivo and in-vitro methods, (ii) quantifying the biomechanical properties of the tricuspid valve apparatus as well as its surrounding heart tissue, and (iii) performing computational modeling of the TV to provide new insight into its biomechanical and physiological function. This review paper focuses on these advances and summarizes recent research relevant to the TV within the scope of FTR. Moreover, this review also provides future perspectives and extensions critical to enhancing the current understanding of the functioning and remodeling tricuspid valve in both the healthy and pathophysiological states.biaxial mechanical characterizationcardiovascular imagingconstitutive modelingfinite element modelingfluid-structure interactionsfunctional tricuspid regurgitationgeometrical modelingin-vitro experimentsisogeometric analysis (IGA)material anisotropymechanical characterizationsub-valvular componentsthe tricuspid valveapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9zk528w2articleBioengineering, vol 6, iss 2oai:escholarship.org:ark:/13030/qt8z3216c22023-09-29T22:37:09Zqt8z3216c2Biaxial mechanical data of porcine atrioventricular valve leaflets.Jett, SamuelLaurence, DevinKunkel, RobertBabu, AnjuKramer, KatherineBaumwart, RyanTowner, RhealWu, YiLee, Chung-Hao2018-12-01This dataset contains the anisotropic tissue responses of porcine atrioventricular valve leaflets to force-controlled biaxial mechanical testing. The set includes the first Piola-Kirchhoff Stress and the specimen stretches (λ) in both circumferential and radial tissue directions (C and R, respectively) for the mitral valve anterior and posterior leaflets (MVAL and MVPL), and the tricuspid valve anterior, posterior, and septal leaflets (TVAL, TVPL, and TVSL) from six porcine hearts at five separate force-controlled biaxial loading protocols. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of this biaxial mechanical testing (Jett et al., in press) [1].application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8z3216c2articleoai:escholarship.org:ark:/13030/qt4117s42q2023-09-29T22:35:09Zqt4117s42qTricuspid Valve Regurgitation in Hypoplastic Left Heart Syndrome: Current Insights and Future Perspectives.Ross, ColtonMir, ArshidBurkhart, HaroldHolzapfel, GerhardLee, Chung-Hao2023-03-07Hypoplastic Left Heart Syndrome (HLHS) is a congenital heart defect that requires a three-stage surgical palliation to create a single ventricle system in the right side of the heart. Of patients undergoing this cardiac palliation series, 25% will develop tricuspid regurgitation (TR), which is associated with an increased mortality risk. Valvular regurgitation in this population has been extensively studied to understand indicators and mechanisms of comorbidity. In this article, we review the current state of research on TR in HLHS, including identified valvular anomalies and geometric properties as the main reasons for the poor prognosis. After this review, we present some suggestions for future TR-related studies to answer the central question: What are the predictors of TR onset during the three palliation stages? These studies involve (i) the use of engineering-based metrics to evaluate valve leaflet strains and predict tissue material properties, (ii) perform multivariate analyses to identify TR predictors, and (iii) develop predictive models, particularly using longitudinally tracked patient cohorts to foretell patient-specific trajectories. Regarded together, these ongoing and future efforts will result in the development of innovative tools that can aid in surgical timing decisions, in prophylactic surgical valve repair, and in the refinement of current intervention techniques.engineering-based analysisinverse finite element simulationspredictive modelingsurgical interventionvalve tissue biomechanicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4117s42qarticleJournal of Cardiovascular Development and Disease, vol 10, iss 3oai:escholarship.org:ark:/13030/qt90z1k96b2023-09-29T22:33:06Zqt90z1k96bLinking the region-specific tissue microstructure to the biaxial mechanical properties of the porcine left anterior descending artery.Pineda-Castillo, SergioAparicio-Ruiz, SantiagoBurns, MadisonLaurence, DevinBradshaw, ElizabethGu, TingtingHolzapfel, GerhardLee, Chung-Hao2022-09-15Coronary atherosclerosis is the main cause of death worldwide. Advancing the understanding of coronary microstructure-based mechanics is fundamental for the development of therapeutic tools and surgical procedures. Although the passive biaxial properties of the coronary arteries have been extensively explored, their regional differences and the relationship between tissue microstructure and mechanics have not been fully characterized. In this study, we characterized the passive biaxial mechanical properties and microstructural properties of the proximal, medial, and distal regions of the porcine left anterior descending artery (LADA). We also attempted to relate the biaxial stress-stretch response of the LADA and its respective birefringent responses to the polarized light for obtaining information about the load-dependent microstructural variations. We found that the LADA extensibility is reduced in the proximal-to-distal direction and that the medial region exhibits more heterogeneous mechanical behavior than the other two regions. We have also observed highly dynamic microstructural behavior where fiber families realign themselves depending on loading. In addition, we found that the microstructure of the distal region exhibited highly aligned fibers along the longitudinal axis of the artery. To verify this microstructural feature, we imaged the LADA specimens with multi-photon microscopy and observed that the adventitia microstructure transitioned from a random fiber network in the proximal region to highly aligned fibers in the distal region. Our findings could offer new perspectives for understanding coronary mechanics and aid in the development of tissue-engineered vascular grafts, which are currently limited due to their mismatch with native tissue in terms of mechanical properties and microstructural features. STATEMENT OF SIGNIFICANCE: The tissue biomechanics of coronary arteries is fundamental for the development of revascularization techniques such as coronary artery bypass. These therapeutics require a deep understanding of arterial mechanics, microstructure, and mechanobiology to prevent graft failure and reoperation. The present study characterizes the unique regional mechanical and microstructural properties of the porcine left anterior descending artery using biaxial testing, polarized-light imaging, and confocal microscopy. This comprehensive characterization provides an improved understanding of the collagen/elastin architecture in response to mechanical loads using a region-specific approach. The unique tissue properties obtained from this study will provide guidance for the selection of anastomotic sites in coronary artery bypass grafting and for the design of tissue-engineered vascular grafts.Collagen and elastin microstructureConstitutive modelingCoronary artery biomechanicsMulti-photon microscopyPlanar biaxial testingPolarized spatial frequency domain imagingAdventitiaAnimalsBiomechanical PhenomenaCollagenCoronary VesselsHeartStressMechanicalSwineapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/90z1k96barticleoai:escholarship.org:ark:/13030/qt7mj573hf2023-09-29T22:31:03Zqt7mj573hfAn investigation of the effect of freezing storage on the biaxial mechanical properties of excised porcine tricuspid valve anterior leaflets.Duginski, GraceRoss, ColtonLaurence, DevinJohns, CortlandLee, Chung-Hao2020-01-01The atrioventricular heart valve (AHV) leaflets are critical to the facilitation of proper unidirectional blood flow through the heart. Previously, studies have been conducted to understand the tissue mechanics of healthy AHV leaflets to inform the development of valve-specific computational models and replacement materials for use in diagnosing and treating valvular heart disease. Generally, these studies involved biaxial mechanical testing of the AHV leaflet tissue specimens to extract relevant mechanical properties. Most of those studies considered freezing-based storage systems based on previous findings for other connective tissues such as aortic tissue or skin. However, there remains no study that specifically examines the effects of freezing storage on the characterized mechanical properties of the AHV leaflets. In this study, we aimed to address this gap in knowledge by performing biaxial mechanical characterizations of the tricuspid valve anterior leaflet (TVAL) tissue both before and after a 48-h freezing period. Primary findings of this study include: (i) a statistically insignificant change in the tissue extensibilities, with the frozen tissues being slightly stiffer and more anisotropic than the fresh tissues; and (ii) minimal variations in the stress relaxation behaviors between the fresh and frozen tissues, with the frozen tissues demonstrating slightly lessened relaxation. The findings from this study suggested that freezing-based storage does not significantly impact the observed mechanical properties of one of the five AHV leaflets-the TVAL. The results from this study are useful for reaffirming the experimental methodologies in the previous studies, as well as informing the tissue preservation methods of future investigations of AHV leaflet mechanics.Biaxial mechanical testingFreezing storage effectsHeart valve biomechanicsStress relaxationThe tricuspid valveAnimalsBiomechanical PhenomenaCryopreservationMechanical PhenomenaSwineTricuspid Valveapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7mj573hfarticleoai:escholarship.org:ark:/13030/qt5g0879842023-09-29T22:29:05Zqt5g087984Integration of polarized spatial frequency domain imaging (pSFDI) with a biaxial mechanical testing system for quantification of load-dependent collagen architecture in soft collagenous tissues.Jett, SamuelHudson, LukeBaumwart, RyanBohnstedt, BradleyMir, ArshidBurkhart, HaroldHolzapfel, GerhardWu, YiLee, Chung-Hao2020-01-15Collagen fiber networks provide the structural strength of tissues, such as tendons, skin and arteries. Quantifying the fiber architecture in response to mechanical loads is essential towards a better understanding of the tissue-level mechanical behaviors, especially in assessing disease-driven functional changes. To enable novel investigations into these load-dependent fiber structures, a polarized spatial frequency domain imaging (pSFDI) device was developed and, for the first time, integrated with a biaxial mechanical testing system. The integrated instrument is capable of a wide-field quantification of the fiber orientation and the degree of optical anisotropy (DOA), representing the local degree of fiber alignment. The opto-mechanical instruments performance was assessed through uniaxial loading on tendon tissues with known collagen fiber microstructures. Our results revealed that the bulk fiber orientation angle of the tendon tissue changed minimally with loading (median ± 0.5*IQR of 52.7° ± 3.3° and 51.9° ± 3.3° under 0 and 3% longitudinal strains, respectively), whereas on a micro-scale, the fibers became better aligned with the direction of loading: the DOA (mean ± SD) increased from 0.149 ± 0.032 to 0.198 ± 0.056 under 0 and 3% longitudinal strains, respectively, p < 0.001. The integrated instrument was further applied to study two representative mitral valve anterior leaflet (MVAL) tissues subjected to various biaxial loads. The fiber orientations within these representative MVAL tissue specimens demonstrated noticeable heterogeneity, with the local fiber orientations dependent upon the sample, the spatial and transmural locations, and the applied loading. Our results also showed that fibers were generally better aligned under equibiaxial (DOA = 0.089 ± 0.036) and circumferentially-dominant loading (DOA = 0.086 ± 0.037) than under the radially-dominant loading (DOA = 0.077 ± 0.034), indicating circumferential predisposition. These novel findings exemplify a deeper understanding of the load-dependent collagen fiber microstructures obtained through the use of the integrated opto-mechanical instrument. STATEMENT OF SIGNIFICANCE: In this study, a novel quantitative opto-mechanical system was developed by combining a polarized Spatial Frequency Domain Imaging (pSFDI) device with a biaxial mechanical tester. The integrated system was used to quantify the load-dependent collagen fiber microstructures in representative tendon and mitral valve anterior leaflet (MVAL) tissues. Our results revealed that MVALs fiber architectures exhibited load-dependent spatial and transmural heterogeneities, suggesting further microstructural complexity than previously reported in heart valve tissues. These novel findings were possible through the systems ability to, for the first time, capture the load-dependent collagen architecture in the mitral valve anterior leaflet tissue over a wide field of view (e.g., 10 × 10 mm for the MVAL tissue specimens). Such capabilities afford unique future opportunities to improve patient outcomes through concurrent mechanical and microstructural assessments of healthy and diseased tissues in conditions such as heart valve regurgitation and calcification.Biaxial loadingCollagen fiber architectureHeart valveLoad-dependenceMicrostructurePolarization imagingQuantitative optical techniqueAnimalsBiomechanical PhenomenaCattleCollagenMechanical TestsMitral ValveOptical ImagingSwineTendonsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5g087984articleoai:escholarship.org:ark:/13030/qt6qc1d98q2023-09-29T22:27:03Zqt6qc1d98qThermomechanical data of polyurethane shape memory polymer: Considering varying compositions.Fisher, HaileyWoolard, PaytonRoss, ColtonKunkel, RobertBohnstedt, BradleyLiu, YingtaoLee, Chung-Hao2020-10-01This article presents data from the investigation of the thermal characteristics and mechanical behaviors of twelve different compositions of a polyurethane shape memory polymer (SMP). Each of the SMP compositions has a unique molar ratio of three monomers: (i) hexamethylene diisocyanate (HDI), (ii) N,N,N,N-Tetrakis(2-Hydroxypropyl)ethylenediamine (HPED), and (iii) Triethanolamine (TEA). The thermal characteristic datasets for each composition include the glass transition temperatures, as obtained from differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA), and the thermal degradation thresholds, as found from thermogravimetric analysis (TGA). The mechanical behaviors of the SMPs are represented by the failure stresses and strains, as obtained by cyclic tensile testing and failure testing, respectively. The interpretation of these measurements as well as a discussion of the potential usage of candidate SMP compositions for medical devices can be found in the companion article by Kunkel et al. (2018) [1], Synthesis and characterization of bio-compatible shape memory polymers with potential applications to endovascular embolization of intracranial aneurysms.Failure strainFailure stressGlass transition temperatureShape memory polymerThermal degradation thresholdThermomechanical propertiesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6qc1d98qarticleoai:escholarship.org:ark:/13030/qt3g71z9022023-09-29T22:25:00Zqt3g71z902Quantification of load-dependent changes in the collagen fiber architecture for the strut chordae tendineae-leaflet insertion of porcine atrioventricular heart valves.Ross, ColtonHsu, Ming-ChenBaumwart, RyanMir, ArshidBurkhart, HaroldHolzapfel, GerhardWu, YiLee, Chung-Hao2021-02-01Atrioventricular heart valves (AHVs) regulate the unidirectional flow of blood through the heart by opening and closing of the leaflets, which are supported in their functions by the chordae tendineae (CT). The leaflets and CT are primarily composed of collagen fibers that act as the load-bearing component of the tissue microstructures. At the CT-leaflet insertion, the collagen fiber architecture is complex, and has been of increasing focus in the previous literature. However, these previous studies have not been able to quantify the load-dependent changes in the tissues collagen fiber orientations and alignments. In the present study, we address this gap in knowledge by quantifying the changes in the collagen fiber architecture of the mitral and tricuspid valves strut CT-leaflet insertions in response to the applied loads by using a unique approach, which combines polarized spatial frequency domain imaging with uniaxial mechanical testing. Additionally, we characterized these microstructural changes across the same specimen without the need for tissue fixatives. We observed increases in the collagen fiber alignments in the CT-leaflet insertion with increased loading, as described through the degree of optical anisotropy. Furthermore, we used a leaflet-CT-papillary muscle entity method during uniaxial testing to quantify the chordae tendineae mechanics, including the derivation of the Ogden-type constitutive modeling parameters. The results from this study provide a valuable insight into the load-dependent behaviors of the strut CT-leaflet insertion, offering a research avenue to better understand the relationship between tissue mechanics and the microstructure, which will contribute to a deeper understanding of AHV biomechanics.Collagen fibersConstitutive modelingMitral valvePolarized spatial frequency domain imagingTricuspid valveUniaxial mechanical testingAnimalsAnisotropyBiomechanical PhenomenaBirefringenceChordae TendineaeFemaleFibrillar CollagensHeart ValvesMaleSwineTricuspid ValveWeight-Bearingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3g71z902articleBiomechanics and Modeling in Mechanobiology, vol 20, iss 1oai:escholarship.org:ark:/13030/qt41v163852023-09-29T22:23:00Zqt41v16385Mechanics and Microstructure of the Atrioventricular Heart Valve Chordae Tendineae: A Review.Ross, ColtonZheng, JunnanMa, LiangWu, YiLee, Chung-Hao2020-03-12The atrioventricular heart valves (AHVs) are responsible for directing unidirectional blood flow through the heart by properly opening and closing the valve leaflets, which are supported in their function by the chordae tendineae and the papillary muscles. Specifically, the chordae tendineae are critical to distributing forces during systolic closure from the leaflets to the papillary muscles, preventing leaflet prolapse and consequent regurgitation. Current therapies for chordae failure have issues of disease recurrence or suboptimal treatment outcomes. To improve those therapies, researchers have sought to better understand the mechanics and microstructure of the chordae tendineae of the AHVs. The intricate structures of the chordae tendineae have become of increasing interest in recent literature, and there are several key findings that have not been comprehensively summarized in one review. Therefore, in this review paper, we will provide a summary of the current state of biomechanical and microstructural characterizations of the chordae tendineae, and also discuss perspectives for future studies that will aid in a better understanding of the tissue mechanics-microstructure linking of the AHVs chordae tendineae, and thereby improve the therapeutics for heart valve diseases caused by chordae failures.collagen fiber architectureglycosaminoglycanin-vitro flow loopspolarized spatial frequency domain imagingthe mitral valvethe tricuspid valveuniaxial mechanical testingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/41v16385articleBioengineering, vol 7, iss 1oai:escholarship.org:ark:/13030/qt9xq1k3rh2023-09-29T22:20:59Zqt9xq1k3rhA pilot study on biaxial mechanical, collagen microstructural, and morphological characterizations of a resected human intracranial aneurysm tissue.Laurence, DevinHomburg, HannahYan, FengTang, QinggongFung, Kar-MingBohnstedt, BradleyHolzapfel, GerhardLee, Chung-Hao2021-02-10Intracranial aneurysms (ICAs) are focal dilatations that imply a weakening of the brain artery. Incidental rupture of an ICA is increasingly responsible for significant mortality and morbidity in the Americans aging population. Previous studies have quantified the pressure-volume characteristics, uniaxial mechanical properties, and morphological features of human aneurysms. In this pilot study, for the first time, we comprehensively quantified the mechanical, collagen fiber microstructural, and morphological properties of one resected human posterior inferior cerebellar artery aneurysm. The tissue from the dome of a right posterior inferior cerebral aneurysm was first mechanically characterized using biaxial tension and stress relaxation tests. Then, the load-dependent collagen fiber architecture of the aneurysm tissue was quantified using an in-house polarized spatial frequency domain imaging system. Finally, optical coherence tomography and histological procedures were used to quantify the tissues microstructural morphology. Mechanically, the tissue was shown to exhibit hysteresis, a nonlinear stress-strain response, and material anisotropy. Moreover, the unloaded collagen fiber architecture of the tissue was predominantly aligned with the testing Y-direction and rotated towards the X-direction under increasing equibiaxial loading. Furthermore, our histological analysis showed a considerable damage to the morphological integrity of the tissue, including lack of elastin, intimal thickening, and calcium deposition. This new unified characterization framework can be extended to better understand the mechanics-microstructure interrelationship of aneurysm tissues at different time points of the formation or growth. Such specimen-specific information is anticipated to provide valuable insight that may improve our current understanding of aneurysm growth and rupture potential.AnisotropyBiomechanical PhenomenaCollagenElastinHumansIntracranial AneurysmPilot ProjectsStressMechanicalTensile Strengthapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9xq1k3rharticleScientific Reports, vol 11, iss 1oai:escholarship.org:ark:/13030/qt9gj2r19c2023-09-29T22:18:50Zqt9gj2r19cParameterization, geometric modeling, and isogeometric analysis of tricuspid valves.Johnson, EmilyLaurence, DevinXu, FeiCrisp, CarolineMir, ArshidBurkhart, HaroldLee, Chung-HaoHsu, Ming-Chen2021-10-01Approximately 1.6 million patients in the United States are affected by tricuspid valve regurgitation, which occurs when the tricuspid valve does not close properly to prevent backward blood flow into the right atrium. Despite its critical role in proper cardiac function, the tricuspid valve has received limited research attention compared to the mitral and aortic valves on the left side of the heart. As a result, proper valvular function and the pathologies that may cause dysfunction remain poorly understood. To promote further investigations of the biomechanical behavior and response of the tricuspid valve, this work establishes a parameter-based approach that provides a template for tricuspid valve modeling and simulation. The proposed tricuspid valve parameterization presents a comprehensive description of the leaflets and the complex chordae tendineae for capturing the typical three-cusp structural deformation observed from medical data. This simulation framework develops a practical procedure for modeling tricuspid valves and offers a robust, flexible approach to analyze the performance and effectiveness of various valve configurations using isogeometric analysis. The proposed methods also establish a baseline to examine the tricuspid valves structural deformation, perform future investigations of native valve configurations under healthy and disease conditions, and optimize prosthetic valve designs.atrioventricular valvesisogeometric analysisparametric modelingtemplate-based approachtricuspid valvesvalvular heart diseaseapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9gj2r19carticleoai:escholarship.org:ark:/13030/qt5kz8k6dp2023-09-29T22:16:36Zqt5kz8k6dpShape Memory Polymer-Based Endovascular Devices: Design Criteria and Future Perspective.Pineda-Castillo, SergioStiles, ArynBohnstedt, BradleyLee, HyowonLiu, YingtaoLee, Chung-Hao2022-06-21Devices for the endovascular embolization of intracranial aneurysms (ICAs) face limitations related to suboptimal rates of lasting complete occlusion. Incomplete occlusion frequently leads to residual flow within the aneurysm sac, which subsequently causes aneurysm recurrence needing surgical re-operation. An emerging method for improving the rates of complete occlusion both immediately after implant and in the longer run can be the fabrication of patient-specific materials for ICA embolization. Shape memory polymers (SMPs) are materials with great potential for this application, owing to their versatile and tunable shape memory properties that can be tailored to a patients aneurysm geometry and flow condition. In this review, we first present the state-of-the-art endovascular devices and their limitations in providing long-term complete occlusion. Then, we present methods for the fabrication of SMPs, the most prominent actuation methods for their shape recovery, and the potential of SMPs as endovascular devices for ICA embolization. Although SMPs are a promising alternative for the patient-specific treatment of ICAs, there are still limitations that need to be addressed for their application as an effective coil-free endovascular therapy.3D printingendovascular embolizationintracranial aneurysmspersonalized aneurysm treatmentshape memory polymersapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5kz8k6dparticlePolymers, vol 14, iss 13oai:escholarship.org:ark:/13030/qt88x2q15h2023-09-29T22:14:30Zqt88x2q15hOn the role of predicted in vivo mitral valve interstitial cell deformation on its biosynthetic behavior.Ayoub, SalmaHowsmon, DanielLee, Chung-HaoSacks, Michael2021-02-01Ischemic mitral regurgitation (IMR), a frequent complication of myocardial infarction, is characterized by regurgitation of blood from the left ventricle back into the left atrium. Physical interventions via surgery or less-invasive techniques are the only available therapies for IMR, with valve repair via undersized ring annuloplasty (URA) generally preferred over valve replacement. However, recurrence of IMR after URA occurs frequently and is attributed to continued remodeling of the MV and infarct region of the left ventricle. The mitral valve interstitial cells (MVICs) that maintain the tissue integrity of the MV leaflets are highly mechanosensitive, and altered loading post-URA is thought to lead to aberrant MVIC-directed tissue remodeling. Although studies have investigated aspects of mechanically directed VIC activation and remodeling potential, there remains a substantial disconnect between organ-level biomechanics and cell-level phenomena. Herein, we utilized an extant multiscale computational model of the MV that linked MVIC to organ-level MV biomechanical behaviors to simulate changes in MVIC deformation following URA. A planar biaxial bioreactor system was then used to cyclically stretch explanted MV leaflet tissue, emulating the in vivo changes in loading following URA. This simulation-directed experimental investigation revealed that post-URA deformations resulted in decreased MVIC activation and collagen mass fraction. These results are consistent with the hypothesis that URA failures post-IMR are due, in part, to reduced MVIC-mediated maintenance of the MV leaflet tissue resulting from a reduction in physical stimuli required for leaflet tissue homeostasis. Such information can inform the development of novel URA strategies with improved durability.Biaxial bioreactorMitral valveMitral valve repairUndersized ring annuloplastyValve interstitial cellsAnimalsBioreactorsCell NucleusComputer SimulationExtracellular MatrixHomeostasisMitral ValveSheepStressMechanicalTransducersapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/88x2q15harticleBiomechanics and Modeling in Mechanobiology, vol 20, iss 1oai:escholarship.org:ark:/13030/qt22g976v22023-09-29T22:12:28Zqt22g976v2Load-dependent collagen fiber architecture data of representative bovine tendon and mitral valve anterior leaflet tissues as quantified by an integrated opto-mechanical system.Jett, SamuelHudson, LukeBaumwart, RyanBohnstedt, BradleyMir, ArshidBurkhart, HaroldHolzapfel, GerhardWu, YiLee, Chung-Hao2020-02-01The data presented in this article provide load-dependent collagen fiber architecture (CFA) of one representative bovine tendon tissue sample and two representative porcine mitral valve anterior leaflet tissues, and they are stored in a MATLAB MAT-file format. Each dataset contains: (i) the number of pixel points, (ii) the array of pixels x- and y-coordinates, (iii) the three acquired pixel intensity arrays, and (iv) the Delaunay triangulation for visualization purpose. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of the opto-mechanical characterization of the tissues CFAs (Jett et al. [1]).Collagen fiber architectureDegree of optical anisotropyHeart valveLoad-dependenceMechanical loadingMicrostructurePolarized spatial frequency domain (pSFDI) imagingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/22g976v2articleoai:escholarship.org:ark:/13030/qt20q1567b2023-09-29T22:10:24Zqt20q1567bA pilot investigation of the tricuspid valve annulus in newborns with hypoplastic left heart syndrome.Ross, ColtonTrimble, ElizabethJohnson, EmilyBaumwart, RyanJolley, MatthewMir, ArshidBurkhart, HaroldLee, Chung-Hao2022-06-01OBJECTIVE: Hypoplastic left heart syndrome (HLHS) is a congenital disease characterized by an underdevelopment of the anatomical components inside the left heart. Approximately 30% of HLHS newborns will develop tricuspid regurgitation (TR), and it is currently unknown how the valve annulus mechanics and geometry are associated with regurgitation. Thus, we present an engineering mechanics-based analysis approach to quantify the mechanics and geometry of the HLHS-afflicted tricuspid valve (TV), using 4-dimensional echocardiograms. METHODS: Infants born with hypoplastic left heart syndrome (n=8) and healthy newborns (n=4) had their tricuspid valves imaged, and the data was imported to the 3D Slicer. The annular curves were defined at five points in the cardiac cycle. The geometry and deformation (strain) of the TV annulus were calculated to elucidate the mechanics of this critical structure, and compare them between HLHS and normal neonates. RESULTS: For the annular geometry, HLHS-afflicted newborns had significantly larger annular circumferences (20-30%) and anterior-posterior diameters (35-45%) than the healthy patients. From a biomechanics perspective, the HLHS patients had significantly smaller strains in the anterior segments (-0.1±2.6%) during end diastolic and end isovolumetric relaxation (1.7±3.0%) compared to the healthy counterparts (-13.3±2.9% and 6.8±0.9%, respectively). CONCLUSIONS: The image-based analysis in this study may provide novel insights into the geometric and mechanistic differences in the TV annulus between healthy and HLHS newborns. Future longitudinal studies of the biomechanics of TV annulus and other subvalvular structures may inform our understanding of the initiation and development of TR and the design of optimal repairs in this challenging population.congenital heart defectimage segmentationmechanical strainstransthoracic echocardiographic imagingtricuspid valve geometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/20q1567barticleoai:escholarship.org:ark:/13030/qt6h64r8qn2023-09-29T22:08:16Zqt6h64r8qnA Pilot Study on Linking Tissue Mechanics with Load-Dependent Collagen Microstructures in Porcine Tricuspid Valve Leaflets.Hudson, LukeJett, SamuelKramer, KatherineLaurence, DevinRoss, ColtonTowner, RhealBaumwart, RyanLim, KiMir, ArshidBurkhart, HaroldWu, YiLee, Chung-Hao2020-06-18The tricuspid valve (TV) is composed of three leaflets that coapt during systole to prevent deoxygenated blood from re-entering the right atrium. The connection between the TV leaflets microstructure and the tissue-level mechanical responses has yet to be fully understood in the TV biomechanics society. This pilot study sought to examine the load-dependent collagen fiber architecture of the three TV leaflets, by employing a multiscale, combined experimental approach that utilizes tissue-level biaxial mechanical characterizations, micro-level collagen fiber quantification, and histological analysis. Our results showed that the three TV leaflets displayed greater extensibility in the tissues radial direction than in the circumferential direction, consistently under different applied biaxial tensions. Additionally, collagen fibers reoriented towards the direction of the larger applied load, with the largest changes in the alignment of the collagen fibers under radially-dominant loading. Moreover, collagen fibers in the belly region of the TV leaflets were found to experience greater reorientations compared to the tissue region closer to the TV annulus. Furthermore, histological examinations of the TV leaflets displayed significant regional variation in constituent mass fraction, highlighting the heterogeneous collagen microstructure. The combined experimental approach presented in this work enables the connection of tissue mechanics, collagen fiber microstructure, and morphology for the TV leaflets. This experimental methodology also provides a new research platform for future developments, such as multiscale models for the TVs, and the design of bioprosthetic heart valves that could better mimic the mechanical, microstructural, and morphological characteristics of the native tricuspid valve leaflets.biaxial mechanical testingcollagen fiber reorientationmaterial anisotropypolarized spatial frequency domain imagingspatial alignmenttricuspid regurgitationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6h64r8qnarticleBioengineering, vol 7, iss 2oai:escholarship.org:ark:/13030/qt6g50p02v2023-09-29T22:06:07Zqt6g50p02vAn in-silico benchmark for the tricuspid heart valve - Geometry, finite element mesh, Abaqus simulation, and result data set.Laurence, DevinLee, Chung-HaoJohnson, EmilyHsu, Ming-Chen2021-12-01This article provides Abaqus input files and user subroutines for performing finite element simulations of the tricuspid heart valve with an idealized geometry. Additional post-processing steps to obtain a ParaView visualization file (*.vtk) of the deformed geometry are also provided to allow the readers to use the included ParaView state file (*.pvsm) for customizable visualization and evaluation of the simulation results. We expect this first-of-its-kind in-silico benchmark dataset will facilitate user-friendly simulations considering material nonlinearity, leaflet-to-leaflet contact, and large deformations. Additionally, the information included herein can be used to rapidly evaluate other novel in-silico approaches developed for simulating cardiac valve function. The benchmark can be expanded to consider more complex features of the tricuspid valve function, such as the dynamic annulus motion or the time-varying transvalvular pressure. Interested readers are referred to the companion article (Johnson et al., 2021) for an example application of this in-silico tool for isogeometric analysis of tricuspid valves.Finite element simulationsIn-Silico benchmarkLeaflet-to-leaflet contactMaterial nonlinearityTricuspid valveapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6g50p02varticleoai:escholarship.org:ark:/13030/qt05c8c8mh2023-09-29T22:04:09Zqt05c8c8mhThe role of elastin on the mechanical properties of the anterior leaflet in porcine tricuspid valves.Salinas, SamuelFarra, YasmeenAmini Khoiy, KeyvanHouston, JamesLee, Chung-HaoBellini, ChiaraAmini, Rouzbeh2022-01-01Elastin is present in the extracellular matrix (ECM) of connective tissues, and its mechanical properties are well documented. In Marfan syndrome, however, the inability to properly code for the protein fibrillin-1 prematurely leads to the degradation and loss of elastin fiber integrity in the ECM. In this study, the role of elastin in the ECM of the anterior leaflet of the tricuspid valve was investigated by examining the biomechanical behavior of porcine leaflets before and after the application of the enzyme elastase. Five loading protocols were applied to the leaflet specimens in two groups (elastase-treated and control samples). The mechanical response following elastase application yielded a significantly stiffer material in both the radial and circumferential directions. At a physiological level of stress (85 kPa), the elastase group had an average strain of 26.21% and 6.32% in the radial and circumferential directions, respectively, at baseline prior to elastase application. Following elastase treatment, the average strain was 5.28% and 0.97% in the radial and circumferential directions, respectively. No statistically significant change was found in the control group following sham treatment with phosphate-buffered saline (PBS). Two-photon microscopy images confirmed that after the removal of elastin, the collagen fibers displayed a loss of undulation. With a significant reduction in radial compliance, the ability to withstand physiological loads may be compromised. As such, an extracellular matrix that is structurally deficient in elastin may hinder normal tricuspid valve function.AnimalsBiomechanical PhenomenaElastinExtracellular MatrixPancreatic ElastaseStressMechanicalSwineTricuspid Valveapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/05c8c8mharticlePLoS One, vol 17, iss 5oai:escholarship.org:ark:/13030/qt7vw6s35c2023-09-29T22:01:58Zqt7vw6s35cFinite Element Modeling of Residual Hearing after Cochlear Implant Surgery in Chinchillas.Castle, NicholasLiang, JunfengSmith, MatthewPetersen, BrettMatson, CaymanEldridge, TaraZhang, KeLee, Chung-HaoLiu, YingtaoDai, Chenkai2023-04-27Cochlear implant (CI) surgery is one of the most utilized treatments for severe hearing loss. However, the effects of a successful scala tympani insertion on the mechanics of hearing are not yet fully understood. This paper presents a finite element (FE) model of the chinchilla inner ear for studying the interrelationship between the mechanical function and the insertion angle of a CI electrode. This FE model includes a three-chambered cochlea and full vestibular system, accomplished using µ-MRI and µ-CT scanning technologies. This models first application found minimal loss of residual hearing due to insertion angle after CI surgery, and this indicates that it is a reliable and helpful tool for future applications in CI design, surgical planning, and stimuli setup.chinchillacochlear implantfinite elementinner earinsertion angleapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7vw6s35carticleBioengineering, vol 10, iss 5oai:escholarship.org:ark:/13030/qt80h7w6572023-09-29T21:59:55Zqt80h7w657A pilot in silico modeling-based study of the pathological effects on the biomechanical function of tricuspid valves.Laurence, DevinJohnson, EmilyHsu, Ming-ChenBaumwart, RyanMir, ArshidBurkhart, HaroldHolzapfel, GerhardWu, YiLee, Chung-Hao2020-07-01Current clinical assessment of functional tricuspid valve regurgitation relies on metrics quantified from medical imaging modalities. Although these clinical methodologies are generally successful, the lack of detailed information about the mechanical environment of the valve presents inherent challenges for assessing tricuspid valve regurgitation. In the present study, we have developed a finite element-based in silico model of one porcine tricuspid valve (TV) geometry to investigate how various pathological conditions affect the overall biomechanical function of the TV. There were three primary observations from our results. Firstly, the results of the papillary muscle (PM) displacement study scenario indicated more pronounced changes in the TV biomechanical function. Secondly, compared to uniform annulus dilation, nonuniform dilation scenario induced more evident changes in the von Mises stresses (83.8-125.3 kPa vs 65.1-84.0 kPa) and the Green-Lagrange strains (0.52-0.58 vs 0.47-0.53) for the three TV leaflets. Finally, results from the pulmonary hypertension study scenario showed opposite trends compared to the PM displacement and annulus dilation scenarios. Furthermore, various chordae rupture scenarios were simulated, and the results showed that the chordae tendineae attached to the TV anterior and septal leaflets may be more critical to proper TV function. This in silico modeling-based study has provided a deeper insight into the tricuspid valve pathologies that may be useful, with moderate extensions, for guiding clinical decisions. NOVELTY STATEMENT: The novelties of the research are summarized below: A comprehensive in silico pilot study of how isolated functional tricuspid regurgitation pathologies and ruptured chordae tendineae would alter the tricuspid valve function; An extensive analysis of the tricuspid valve function, including mechanical quantities (eg, the von Mises stress and the Green-Lagrange strain) and clinically-relevant geometry metrics (eg, the tenting area and the coaptation height); and A developed computational modeling pipeline that can be extended to evaluate patient-specific tricuspid valve geometries and enhance the current clinical diagnosis and treatment of tricuspid regurgitation.chordae tendineaecoaptation heightfinite element simulationsfunctional tricuspid regurgitationtenting areatenting heightAnimalsChordae TendineaeComputer SimulationHumansPilot ProjectsSwineTricuspid ValveTricuspid Valve Insufficiencyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/80h7w657articleInternational Journal for Numerical Methods in Biomedical Engineering, vol 36, iss 7oai:escholarship.org:ark:/13030/qt9m6533ht2023-09-29T21:30:28Zqt9m6533htOn-Demand Fully Enclosed Superhydrophobic-Optofluidic Devices Enabled by Microstereolithography.Chang, YuBao, MengdiWaitkus, JacobCai, HaogangDu, Ke2022-08-30Superhydrophobic surface-based optofluidics have been introduced to biosensors and unconventional optics with unique advantages, such as low light loss and power consumption. However, most of these platforms were made with planar-like microstructures and nanostructures, which may cause bonding issues and result in significant waveguide loss. Here, we introduce a fully enclosed superhydrophobic-based optofluidics system, enabled by a one-step microstereolithography procedure. Various microstructured cladding designs with a feature size down to 100 μm were studied and a T-type overhang design exhibits the lowest optical loss, regardless of the excitation wavelength. Surprisingly, the optical loss of superhydrophobic-based optofluidics is not solely decided by the solid area fraction at the solid/water/air interface, but also the cross-section shape and the effective cladding layer composition. We show that this fully enclosed optofluidic system can be used for CRISPR-labeled quantum dot quantification, intended for in vitro and in vivo CRISPR therapeutics.Biosensing TechniquesHydrophobic and Hydrophilic InteractionsMicrofluidic Analytical TechniquesNanostructuresOptics and Photonicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9m6533htarticleLangmuir: the ACS journal of surfaces and colloids, vol 38, iss 34oai:escholarship.org:ark:/13030/qt522955302023-09-29T14:32:47Zqt52295530Manifold learning based data-driven modeling for soft biological tissues.He, QizhiLaurence, DevinLee, Chung-HaoChen, Jiun-Shyan2021-03-05Data-driven modeling directly utilizes experimental data with machine learning techniques to predict a materials response without the necessity of using phenomenological constitutive models. Although data-driven modeling presents a promising new approach, it has yet to be extended to the modeling of large-deformation biological tissues. Herein, we extend our recent local convexity data-driven (LCDD) framework (He and Chen, 2020) to model the mechanical response of a porcine heart mitral valve posterior leaflet. The predictability of the LCDD framework by using various combinations of biaxial and pure shear training protocols are investigated, and its effectiveness is compared with a full structural, phenomenological model modified from Zhang et al. (2016) and a continuum phenomenological Fung-type model (Tong and Fung, 1976). We show that the predictivity of the proposed LCDD nonlinear solver is generally less sensitive to the type of loading protocols (biaxial and pure shear) used in the data set, while more sensitive to the insufficient coverage of the experimental data when compared to the predictivity of the two selected phenomenological models. While no pre-defined functional form in the material model is necessary in LCDD, this study reinstates the importance of having sufficiently rich data coverage in the date-driven and machine learning type of approaches. It is also shown that the proposed LCDD method is an enhancement over the earlier distance-minimization data-driven (DMDD) against noisy data. This study demonstrates that when sufficient data is available, data-driven computing can be an alternative method for modeling complex biological materials.Data-driven material modelingHyperelasticityLocal convexity data-driven methodManifold learningMitral heart valveAnimalsHeart Valve ProsthesisMachine LearningMaleMitral ValveModelsBiologicalStressMechanicalSwineapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/52295530articleoai:escholarship.org:ark:/13030/qt7hv0b87h2023-09-29T14:07:49Zqt7hv0b87hA contact formulation based on a volumetric potential: Application to isogeometric simulations of atrioventricular valves.Kamensky, DavidXu, FeiLee, Chung-HaoYan, JinhuiBazilevs, YuriHsu, Ming-Chen2018-03-01This work formulates frictionless contact between solid bodies in terms of a repulsive potential energy term and illustrates how numerical integration of the resulting forces is computationally similar to the pinball algorithm proposed and studied by Belytschko and collaborators in the 1990s. We thereby arrive at a numerical approach that has both the theoretical advantages of a potential-based formulation and the algorithmic simplicity, computational efficiency, and geometrical versatility of pinball contact. The singular nature of the contact potential requires a specialized nonlinear solver and an adaptive time stepping scheme to ensure reliable convergence of implicit dynamic calculations. We illustrate the effectiveness of this numerical method by simulating several benchmark problems and the structural mechanics of the right atrioventricular (tricuspid) heart valve. Atrioventricular valve closure involves contact between every combination of shell surfaces, edges of shells, and cables, but our formulation handles all contact scenarios in a unified manner. We take advantage of this versatility to demonstrate the effects of chordal rupture on tricuspid valve coaptation behavior.Contact problemsHeart valvesIsogeometric analysisPinball algorithmapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7hv0b87harticleoai:escholarship.org:ark:/13030/qt7s5355092023-09-29T05:15:18Zqt7s535509Synthesis of Samarium-Cobalt Sub-micron Fibers and Their Excellent Hard Magnetic PropertiesLee, JiminHwang, Tae-YeonKang, Min KyuCho, Hong-BaekKim, JongryoulMyung, Nosang VChoa, Yong-Ho2018-01-01High-throughput synthesis of Samarium-Cobalt sub-micron fibers with controlled composition and dimension was demonstrated by combining electrospinning and reduction-diffusion processes. The composition of fibers was readily varied (8 < Sm < 20 at.%) by adjusting precursor composition whereas the diameter of fibers was precisely controlled by varying electrospinning parameters (e.g., applied voltage, solution feed rate, temperature, and humidity) to reach single-domain size. X-ray diffraction patterns confirmed that single phase Sm2Co17 fibers were synthesized when the metal precursor ratio (Sm3+/(Sm3++Co2+)) was precisely controlled at 10.6%, whereas mixed phases (i.e., Co-Sm2Co17 or Sm2Co17-Sm2Co7) were observed when the ratio is deviated from the stoichiometric. Magnetic saturation (Ms ) of the synthesized fibers monotonically decreased with an increased in Sm content. In contrast, coercivity (Hci) monotonically increased with an increase in Sm content.Inorganic ChemistryChemical Sciencessamarium cobaltelectrospinningfiberpermanent magnetmagnetic propertiesChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7s535509articleoai:escholarship.org:ark:/13030/qt9mp246g62023-09-29T03:50:52Zqt9mp246g6Evaluation and development of tools to quantify the impacts of roadside vegetation barriers on near-road air quality.Isakov, VladVenkatram, AkulaBaldauf, RichardDeshmukh, ParikshitZhang, Max2017-01-01Traffic emissions are associated with the elevation of health risks of people living close to highways. Roadside vegetation barriers have the potential of reducing these risks by decreasing near-road air pollution concentrations. However, while we understand the mechanisms that determine the mitigation caused by solid barriers, we still have questions about how vegetative barriers affect dispersion. The US EPA conducted several field experiments to understand the effects of vegetation barriers on dispersion of pollutants near roadways (e.g., 2008 North Carolina study and 2014 California study) that indicate the reduction of near-road pollutant concentrations can be up to 30% due to the barrier effects. The results of these field studies are being used to develop and evaluate dispersion models that account for the effects of near-road vegetative barriers. These models can be used for evaluating the effectiveness of vegetation barriers as a potential mitigation strategy to reduce exposure to traffic-related pollutants and their associated adverse health effects. This paper presents the results of the analysis of the field studies and discusses dispersion models being used to describe the data in order to simulate the effects of near-road barriers and to develop recommendations for model improvements.EngineeringEnvironmental SciencesPollution and Contamination2.2 Factors relating to the physical environmentAetiologyGood Health and Well BeingroadwaysbarriersvegetationdispersionmodelsCommerceManagementTourism and ServicesCommercemanagementtourism and servicesEnvironmental sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9mp246g6articleInternational Journal of Environment and Pollution, vol 62, iss 2127 - 135oai:escholarship.org:ark:/13030/qt7c36j4mr2023-09-29T02:01:00Zqt7c36j4mrA microfluidic thermometer: Precise temperature measurements in microliter- and nanoliter-scale volumesMcKenzie, Brittney AGrover, William HCao, Bing-Yang2017-01-01Measuring the temperature of a sample is a fundamental need in many biological and chemical processes. When the volume of the sample is on the microliter or nanoliter scale (e.g., cells, microorganisms, precious samples, or samples in microfluidic devices), accurate measurement of the sample temperature becomes challenging. In this work, we demonstrate a technique for accurately determining the temperature of microliter volumes using a simple 3D-printed microfluidic chip. We accomplish this by first filling "microfluidic thermometer" channels on the chip with substances with precisely known freezing/melting points. We then use a thermoelectric cooler to create a stable and linear temperature gradient along these channels within a measurement region on the chip. A custom software tool (available as online Supporting Information) is then used to find the locations of solid-liquid interfaces in the thermometer channels; these locations have known temperatures equal to the freezing/melting points of the substances in the channels. The software then uses the locations of these interfaces to calculate the temperature at any desired point within the measurement region. Using this approach, the temperature of any microliter-scale on-chip sample can be measured with an uncertainty of about a quarter of a degree Celsius. As a proof-of-concept, we use this technique to measure the unknown freezing point of a 50 microliter volume of solution and demonstrate its feasibility on a 400 nanoliter sample. Additionally, this technique can be used to measure the temperature of any on-chip sample, not just near-zero-Celsius freezing points. We demonstrate this by using an oil that solidifies near room temperature (coconut oil) in a microfluidic thermometer to measure on-chip temperatures well above zero Celsius. By providing a low-cost and simple way to accurately measure temperatures in small volumes, this technique should find applications in both research and educational laboratories.Fluid Mechanics and Thermal EngineeringEngineeringBioengineeringEquipment DesignMicrofluidic Analytical TechniquesTemperatureThermometersGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7c36j4mrarticlePLOS ONE, vol 12, iss 12e0189430oai:escholarship.org:ark:/13030/qt8ck3947g2023-09-29T01:46:55Zqt8ck3947gWind Tunnel Experiments to Study Chaparral Crown Fires.Cobian-Iñiguez, JeanetteAminfar, AmirHessamChong, JoeyBurke, GloriaZuniga, AlbertinaWeise, David RPrincevac, Marko2017-01-01The present protocol presents a laboratory technique designed to study chaparral crown fire ignition and spread. Experiments were conducted in a low velocity fire wind tunnel where two distinct layers of fuel were constructed to represent surface and crown fuels in chaparral. Chamise, a common chaparral shrub, comprised the live crown layer. The dead fuel surface layer was constructed with excelsior (shredded wood). We developed a methodology to measure mass loss, temperature, and flame height for both fuel layers. Thermocouples placed in each layer estimated temperature. A video camera captured the visible flame. Post-processing of digital imagery yielded flame characteristics including height and flame tilt. A custom crown mass loss instrument developed in-house measured the evolution of the mass of the crown layer during the burn. Mass loss and temperature trends obtained using the technique matched theory and other empirical studies. In this study, we present detailed experimental procedures and information about the instrumentation used. The representative results for the fuel mass loss rate and temperature filed within the fuel bed are also included and discussed.Biochemistry and Cell BiologyBiological SciencesCaliforniaEcosystemFiresTemperatureTreesWindWoodEngineeringIssue 129Chaparralwind tunnelsurface firecrown firefuel mass lossflame heightPsychologyCognitive SciencesBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8ck3947garticleJournal of Visualized Experiments, vol 2017, iss 129oai:escholarship.org:ark:/13030/qt9dg2b36m2023-09-28T22:51:55Zqt9dg2b36mThe Effects of Serum Proteins on Magnesium Alloy Degradation in VitroJohnson, IanJiang, WensenLiu, Huinan2017-01-01Magnesium (Mg) alloys are promising materials for biodegradable implants, but their clinical translation requires improved control over their degradation rates. Proteins may be a major contributing factor to Mg alloy degradation, but are not yet fully understood. This article reports the effects of fetal bovine serum (FBS), a physiologically relevant mixture of proteins, on Mg and Mg alloy degradation. FBS had little impact on mass loss of pure Mg during immersion degradation, regardless of whether or not a native oxide layer was present on the sample surface. FBS reduced the mass loss of Mg-Yttrium (MgY) alloy with an oxidized surface during immersion degradation, but increased the mass loss for the same alloy with a metallic surface (surface oxides were removed). FBS also influenced the mode of degradation by limiting the depth of pit formation during degradation processes on commercially pure Mg with metallic or oxidized surfaces and on MgY alloy with oxidized surfaces. The results demonstrated that serum proteins had significant interactions with Mg-based biodegradable metals, and these interactions may be modified by alloy composition and processing. Therefore, proteins should be taken into account when designing experiments to assess degradation of Mg-based implants.EngineeringMaterials EngineeringAbsorbable ImplantsAlloysAnimalsBlood ProteinsCattleCorrosionHumansHydrogen-Ion ConcentrationMagnesiumMaterials TestingMicroscopyElectronScanningOxidation-ReductionSerumSurface Propertiesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9dg2b36marticleScientific Reports, vol 7, iss 114335oai:escholarship.org:ark:/13030/qt1rc0c8nd2023-09-28T22:33:44Zqt1rc0c8ndElectrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cellsBrunelle, Alexander RHorner, Christopher BLow, KarenIco, GerardoNam, Jin2018-01-01Hydrogels have shown great potential for cartilage tissue engineering applications due to their capability to encapsulate cells within biomimetic, 3-dimensional (3D) microenvironments. However, the multi-step fabrication process that is necessary to produce cell/scaffold constructs with defined dimensions, limits their off-the-shelf translational usage. In this study, we have developed a hybrid scaffolding system which combines a thermosensitive hydrogel, poly(ethylene glycol)-poly(N-isopropylacrylamide) (PEG-PNIPAAm), with a biodegradable polymer, poly(ε-caprolactone) (PCL), into a composite, electrospun microfibrous structure. A judicious optimization of material composition and electrospinning process produced a structurally self-supporting hybrid scaffold. The reverse thermosensitivity of PEG-PNIPAAm allowed its dissolution/hydration upon cell seeding within a network of PCL microfibers while maintaining the overall scaffold shape at room temperature. A subsequent temperature elevation to 37 °C induced the hydrogel's phase transition to a gel state, effectively encapsulating cells in a 3D hydrogel without the use of a mold. We demonstrated that the hybrid scaffold enhanced chondrogenic differentiation of human mesenchymal stem cells (hMSCs) based on chondrocytic gene and protein expression, which resulted in superior viscoelastic properties of the cell/scaffold constructs. The hybrid scaffold enables a facile, single-step cell seeding process to inoculate cells within a 3D hydrogel with the potential for cartilage tissue engineering.Statement of significanceHydrogels have demonstrated the excellent ability to enhance chondrogenesis of stem cells due to their hydrated fibrous nanostructure providing a cellular environment similar to native cartilage. However, the necessity for multi-step processes, including mixing of hydrogel precursor with cells and subsequent gelation in a mold to form a defined shape, limits their off-the-shelf usage. In this study, we developed a hybrid scaffold by combining a thermosensitive hydrogel with a mechanically stable polymer, which provides a facile means to inoculate cells in a 3D hydrogel with a mold-less, single step cell seeding process. We further showed that the hybrid scaffold enhanced chondrogenesis of mesenchymal stem cells, demonstrating its potential for cartilage tissue engineering.EngineeringBiomedical EngineeringStem Cell Research - Nonembryonic - Non-HumanRegenerative MedicineBioengineeringStem Cell Research5.2 Cellular and gene therapiesDevelopment of treatments and therapeutic interventionsAcrylic ResinsCell DifferentiationCell ShapeCell SurvivalChondrogenesisHumansHydrogelPolyethylene Glycol DimethacrylateMesenchymal Stem CellsPolyestersPolyethylene GlycolsTemperatureTissue EngineeringTissue ScaffoldsElectrospun scaffoldThermosensitive hydrogelPolycaprolactonePoly(ethylene glycol)-poly(N-isopropylacry lamide)Stem cell differentiationPoly(ethylene glycol)-poly(N-isopropylacrylamide)application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1rc0c8ndarticleoai:escholarship.org:ark:/13030/qt9w2556kz2023-09-28T20:54:18Zqt9w2556kzGroup Structure Preserving Pedestrian Tracking in a Multicamera Video NetworkJin, ZhixingAn, LeBhanu, Bir2017-01-01Information and Computing SciencesEngineeringComputer Vision and Multimedia ComputationGroup structuremulticamerapedestrian trackingArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringArtificial Intelligence & Image ProcessingCommunications engineeringElectronicssensors and digital hardwareComputer vision and multimedia computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9w2556kzarticleIEEE Transactions on Circuits and Systems for Video Technology, vol 27, iss 102165 - 2176oai:escholarship.org:ark:/13030/qt5702r3gf2023-09-28T20:19:03Zqt5702r3gfSix-fold over-representation of graduates from prestigious universities does not necessitate unmeritocratic selection in the faculty hiring processMiuccio, MichaelLiu, Ka-yuetLau, HakwanPeters, Megan AKLambiotte, Renaud2017-01-01To achieve faculty status, graduating doctoral students have to substantially outperform their peers, given the competitive nature of the academic job market. In an ideal, meritocratic world, factors such as prestige of degree-granting university ought not to overly influence hiring decisions. However, it has recently been reported that top-ranked universities produced about 2-6 times more faculty than did universities that were ranked lower [1], which the authors claim suggests the use of un-meritocratic factors in the hiring process: how could students from top-ranked universities be six times more productive than their peers from lower-ranked universities? Here we present a signal detection model, supported by computer simulation and simple proof-of-concept example data from psychology departments in the U.S., to demonstrate that substantially higher rates of faculty production need not require substantially (and unrealistically) higher levels of student productivity. Instead, a high hiring threshold due to keen competition is sufficient to cause small differences in average student productivity between universities to result in manifold differences in placement rates. Under this framework, the previously reported results are compatible with a purely meritocratic system. Whereas these results do not necessarily mean that the actual faculty hiring market is purely meritocratic, they highlight the difficulty in empirically demonstrating that it is not so.Education PolicySociology and PhilosophyEducationDecent Work and Economic GrowthFacultyModelsTheoreticalPersonnel SelectionProbabilityUnited StatesUniversitiesGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5702r3gfarticlePLOS ONE, vol 12, iss 10e0185900oai:escholarship.org:ark:/13030/qt5w62f5gp2023-09-28T19:19:40Zqt5w62f5gpLineage- and developmental stage-specific mechanomodulation of induced pluripotent stem cell differentiationMaldonado, MaricelaLuu, Rebeccah JIco, GerardoOspina, AlexMyung, DanielleShih, Hung PingNam, Jin2017-12-01BackgroundTo maximize the translational utility of human induced pluripotent stem cells (iPSCs), the ability to precisely modulate the differentiation of iPSCs to target phenotypes is critical. Although the effects of the physical cell niche on stem cell differentiation are well documented, current approaches to direct step-wise differentiation of iPSCs have been typically limited to the optimization of soluble factors. In this regard, we investigated how temporally varied substrate stiffness affects the step-wise differentiation of iPSCs towards various lineages/phenotypes.MethodsElectrospun nanofibrous substrates with different reduced Young's modulus were utilized to subject cells to different mechanical environments during the differentiation process towards representative phenotypes from each of three germ layer derivatives including motor neuron, pancreatic endoderm, and chondrocyte. Phenotype-specific markers of each lineage/stage were utilized to determine differentiation efficiency by reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence imaging for gene and protein expression analysis, respectively.ResultsThe results presented in this proof-of-concept study are the first to systematically demonstrate the significant role of the temporally varied mechanical microenvironment on the differentiation of stem cells. Our results demonstrate that the process of differentiation from pluripotent cells to functional end-phenotypes is mechanoresponsive in a lineage- and differentiation stage-specific manner.ConclusionsLineage/developmental stage-dependent optimization of electrospun substrate stiffness provides a unique opportunity to enhance differentiation efficiency of iPSCs for their facilitated therapeutic applications.Biochemistry and Cell BiologyBiological SciencesGeneticsStem Cell Research - Induced Pluripotent Stem CellRegenerative MedicineStem Cell ResearchUnderpinning research1.1 Normal biological development and functioningCell DifferentiationCell LineCell LineageElastic ModulusHumansInduced Pluripotent Stem CellsNanofibersPrimary Cell CultureTissue ScaffoldsInduced pluripotent stem cellsMechanobiologyDifferentiationSubstrate stiffnessTechnologyMedical and Health SciencesBiological sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5w62f5gparticleStem Cell Research & Therapy, vol 8, iss 1216oai:escholarship.org:ark:/13030/qt2k24d0632023-09-28T18:26:47Zqt2k24d063Controllable direction of liquid jets generated by thermocavitation within a droplet.Padilla-Martinez, JPRamirez-San-Juan, JCBerrospe-Rodriguez, CKorneev, NAguilar, GZaca-Moran, PRamos-Garcia, R2017-09-01A high-velocity fluid stream ejected from an orifice or nozzle is a common mechanism to produce liquid jets in inkjet printers or to produce sprays among other applications. In the present research, we show the generation of liquid jets of controllable direction produced within a sessile water droplet by thermocavitation. The jets are driven by an acoustic shock wave emitted by the collapse of a hemispherical vapor bubble at the liquid-solid/substrate interface. The generated shock wave is reflected at the liquid-air interface due to acoustic impedance mismatch generating multiple reflections inside the droplet. During each reflection, a force is exerted on the interface driving the jets. Depending on the position of the generation of the bubble within the droplet, the mechanical energy of the shock wave is focused on different regions at the liquid-air interface, ejecting cylindrical liquid jets at different angles. The ejected jet angle dependence is explained by a simple ray tracing model of the propagation of the acoustic shock wave inside the droplet.Fluid Mechanics and Thermal EngineeringEngineeringPhysical SciencesOptical PhysicsElectrical and Electronic EngineeringMechanical EngineeringOpticsElectrical engineeringAtomicmolecular and optical physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2k24d063articleApplied Optics, vol 56, iss 257167 - 7173oai:escholarship.org:ark:/13030/qt0dh2c84g2023-09-28T16:26:04Zqt0dh2c84gAutomated spatio-temporal analysis of dendritic spines and related protein dynamicsOn, VincentZahedi, AtenaEthell, Iryna MBhanu, BirMei, Lin2017-01-01Cofilin and other Actin-regulating proteins are essential in regulating the shape of dendritic spines, which are sites of neuronal communications in the brain, and their malfunctions are implicated in neurodegeneration related to aging. The analysis of cofilin motility in dendritic spines using fluorescence video-microscopy may allow for the discovery of its effects on synaptic functions. To date, the flow of cofilin has not been analyzed by automatic means. This paper presents Dendrite Protein Analysis (DendritePA), a novel automated pattern recognition software to analyze protein trafficking in neurons. Using spatiotemporal information present in multichannel fluorescence videos, the DendritePA generates a temporal maximum intensity projection that enhances the signal-to-noise ratio of important biological structures, segments and tracks dendritic spines, estimates the density of proteins in spines, and analyzes the flux of proteins through the dendrite/spine boundary. The motion of a dendritic spine is used to generate spine energy images, which are used to automatically classify the shape of common dendritic spines such as stubby, mushroom, or thin. By tracking dendritic spines over time and using their intensity profiles, the system can analyze the flux patterns of cofilin and other fluorescently stained proteins. The cofilin flux patterns are found to correlate with the dynamic changes in dendritic spine shapes. Our results also have shown that the activation of cofilin using genetic manipulations leads to immature spines while its inhibition results in an increase in mature spines.Information and Computing SciencesBiochemistry and Cell BiologyBiological SciencesAgingNeurosciences1.1 Normal biological development and functioningUnderpinning researchNeurologicalAnimalsAutomationCellsCulturedDendritic SpinesMiceNerve Tissue ProteinsSoftwareGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0dh2c84garticlePLOS ONE, vol 12, iss 8e0182958oai:escholarship.org:ark:/13030/qt13b2s96z2023-09-28T15:32:31Zqt13b2s96zLinear Transceiver Designs for MIMO Indoor Visible Light Communications Under Lighting ConstraintsWang, RuiGao, QianYou, JiayiLiu, ErwuWang, PingXu, ZhengyuanHua, Yingbo2017-01-01In this paper, we study linear transceiver designs for indoor visible light communications (VLCs) with multiple light emitting diodes (LEDs). Specifically, we investigate VLCs including white emitting diodes and VLCs including red/green/blue (RGB) LEDs. The transmitter precoding and the offset are jointly designed by considering certain key practical lighting constraints, such as optical power, non-negativeness, and color illumination. Various non-convex transceiver design problems are formulated aiming to minimize total mean-squareerror to improve transmission reliability. We show that for multi-input single-output white VLCs, the optimal precoding reduces to a simple LED selection strategy. For multi-input multioutput (MIMO) white VLCs, we prove that the optimization problem with multiple constraints can be equivalently simplified to a problem with single constraint, which enables us to propose efficient algorithms to search local optimal solutions. For MIMO RGB VLCs, by using certain useful transformations, we show that the precoding design is equivalent to covariance matrix design of transmit signals, which can be further transformed to a convex optimization problem. To develop an algorithm to find the optimal solution, we derive the optimal structure of the covariance matrix and show that the optimal solution can be obtained via a water-filling approach. Extensive simulation results are provided to verify the performance of the proposed designs.Theory Of ComputationInformation and Computing SciencesCommunications EngineeringEngineeringVisible light communicationtransceiver designconvex optimizationData FormatElectrical and Electronic EngineeringCommunications TechnologiesCommunications engineeringElectronicssensors and digital hardwareDistributed computing and systems softwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/13b2s96zarticleIEEE Transactions on Communications, vol 65, iss 62494 - 2508oai:escholarship.org:ark:/13030/qt0k16h2sx2023-09-28T15:27:28Zqt0k16h2sxPeroxiporin Expression Is an Important Factor for Cancer Cell Susceptibility to Therapeutic H2O2: Implications for Pharmacological Ascorbate TherapyErudaitius, DieaniraHuang, AndrewKazmi, SarahBuettner, Garry RRodgers, Victor GJAhmad, Aamir2017-01-01Cancer cell toxicity to therapeutic H2O2 varies widely depending on cell type. Interestingly, it has been observed that different cancer cell types have varying peroxiporin expression. We hypothesize that variation in peroxiporin expression can alter cell susceptibility to therapeutic H2O2 concentrations. Here, we silence peroxiporin aquaporin-3 (AQP3) on the pancreatic cancer cell line MIA PaCa-2 and compare clonogenic survival response to the wild-type. The results showed a significantly higher surviving fraction in the clonogenic response for siAQP3 MIA PaCa-2 cells at therapeutic H2O2 doses (P < 0.05). These results suggest that peroxiporin expression is significant in modulating the susceptibility of cancer cells to ascorbate therapy.Biological SciencesBiomedical and Clinical SciencesOncology and CarcinogenesisCancerRare DiseasesPancreatic CancerDigestive Diseases2.1 Biological and endogenous factorsAetiologyAquaporin 3Ascorbic AcidCell LineTumorCell SurvivalGene SilencingHumansHydrogen PeroxideImmunohistochemistryNeoplasmsGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0k16h2sxarticlePLOS ONE, vol 12, iss 1e0170442oai:escholarship.org:ark:/13030/qt0f21x5gr2023-09-28T13:27:25Zqt0f21x5grUnderstanding Gas Phase Modifier Interactions in Rapid Analysis by Differential Mobility-Tandem Mass SpectrometryKafle, AmolCoy, Stephen LWong, Bryan MFornace, Albert JGlick, James JVouros, Paul2014-07-01A systematic study involving the use and optimization of gas-phase modifiers in quantitative differential mobility-mass spectrometry (DMS-MS) analysis is presented using nucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes, and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 10(6) normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab initio thermochemical results, we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry, but at lower temperatures, multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects.Analytical ChemistryChemical SciencesPhysical ChemistryAminobiphenyl CompoundsAnimalsCattleDNADNA AdductsDNA DamageDeoxyguanosineGasesImidazolesIonsKineticsTandem Mass SpectrometryDifferential ion mobilityDMSFAIMSDNA adductsGas phase interactionsModifiersQuantitationIon-polar molecule clusteringMedicinal and Biomolecular ChemistryPhysical Chemistry (incl. Structural)Analytical chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0f21x5grarticleJournal of The American Society for Mass Spectrometry, vol 25, iss 71098 - 1113oai:escholarship.org:ark:/13030/qt40b0d8gx2023-09-28T13:27:22Zqt40b0d8gxAn exclusive fluoride receptor: fluoride-induced proton transfer to a quinoline-based thioureaBasaran, IsmetKhansari, Maryam EmamiPramanik, AvijitWong, Bryan MHossain, Alamgir2014-02-01A new quinoline-based tripodal thiourea has been synthesized, which exclusively binds fluoride anion in DMSO, showing no affinity for other anions including, chloride, bromide, iodide, perchlorate, nitrate and hydrogen sulfate. As investigated by 1H NMR, the receptor forms both 1:1 and 1:2 complex yielding the binding constants of 2.32(3) (in log β1 ) and 4.39(4) (in log β2 ), respectively; where quinoline groups are protonated by the fluoride-induced proton transfer from the solution to the host molecule. The 1:2 binding is due to the interactions of one fluoride with NH binding sites of urea sites and another fluoride with secondary +NH binding sites within the tripodal pocket. The formation of both 1:1 and 1:2 complexes has been confirmed by the theoretical calculations based on density functional theory (DFT).Inorganic ChemistryOrganic ChemistryChemical SciencesFluoride sensorThiourea Anion complexMolecular recognitionAcyclic receptorAnion complexThioureaMedicinal and Biomolecular ChemistryBiochemistry and cell biologyMedicinal and biomolecular chemistryOrganic chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/40b0d8gxarticleTetrahedron Letters, vol 55, iss 81467 - 1470oai:escholarship.org:ark:/13030/qt9b22n2h02023-09-28T13:27:18Zqt9b22n2h0Color Detection Using Chromophore-Nanotube Hybrid DevicesZhou, XinjianZifer, ThomasWong, Bryan MKrafcik, Karen LLéonard, FrançoisVance, Andrew L2009-03-11We present a nanoscale color detector based on a single-walled carbon nanotube functionalized with azobenzene chromophores, where the chromophores serve as photoabsorbers and the nanotube as the electronic read-out. By synthesizing chromophores with specific absorption windows in the visible spectrum and anchoring them to the nanotube surface, we demonstrate the controlled detection of visible light of low intensity in narrow ranges of wavelengths. Our measurements suggest that upon photoabsorption, the chromophores isomerize from the ground state trans configuration to the excited state cis configuration, accompanied by a large change in dipole moment, changing the electrostatic environment of the nanotube. All-electron ab initio calculations are used to study the chromophore-nanotube hybrids and show that the chromophores bind strongly to the nanotubes without disturbing the electronic structure of either species. Calculated values of the dipole moments support the notion of dipole changes as the optical detection mechanism.EngineeringChemical SciencesNanotechnologyPhysical ChemistryBioengineeringAbsorptionElectrodesLightModelsChemicalModelsStatisticalNanocompositesNanotubesNanotubesCarbonPhotochemistrySurface-Active Agentscond-mat.mtrl-sciNanoscience & Nanotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9b22n2h0articleNano Letters, vol 9, iss 31028 - 1033oai:escholarship.org:ark:/13030/qt7gg5c2h62023-09-28T13:27:15Zqt7gg5c2h6Stress Sensing in Polycaprolactone Films via an Embedded Photochromic CompoundO’Bryan, GregWong, Bryan MMcElhanon, James R2010-06-23A photochromic polymer exhibiting mechanochromic behavior is prepared by means of ring-opening polymerization (ROP) of epsilon-caprolactone by utilizing a difunctional indolinospiropyran as an initiator. The configuration of having the photochromic initiating species within the polymer backbone leads to a mechanochromic effect with deformation of polymer films leading to ring-opening of the spiro C-O bond to form the colored merocyanine. Active stress monitoring by dynamic mechanical analysis (DMA) in tension mode was used to probe the effects of UV irradiation on polymer films held under constant strain. Irradiation with UV light induces a negative change in the polymer stress of approximately 50 kPa. Finally, a model of the mechanochromic effect was performed using density functional theory (DFT) and time-dependent DFT (TDDFT) calculations. A sharp increase in the relative molecular energy and the absorption wavelength as well as a drastic decrease in the spiro-oxygen atom charge occurred at a molecular elongation of >39%.EngineeringMacromolecular and Materials ChemistryMaterials EngineeringChemical SciencesModelsChemicalPhotochemistryPolyestersPolymersPyransStressMechanicalTime FactorsUltraviolet RaysmechanochromicphotochromicspiropyranROPDFTNanoscience & NanotechnologyChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7gg5c2h6articleACS Applied Materials & Interfaces, vol 2, iss 61594 - 1600oai:escholarship.org:ark:/13030/qt7n6035g72023-09-28T13:21:15Zqt7n6035g7Sorting cells by their densityNorouzi, NazilaBhakta, Heran CGrover, William HUgaz, Victor M2017-01-01Sorting cells by their type is an important capability in biological research and medical diagnostics. However, most cell sorting techniques rely on labels or tags, which may have limited availability and specificity. Sorting different cell types by their different physical properties is an attractive alternative to labels because all cells intrinsically have these physical properties. But some physical properties, like cell size, vary significantly from cell to cell within a cell type; this makes it difficult to identify and sort cells based on their sizes alone. In this work we continuously sort different cells types by their density, a physical property with much lower cell-to-cell variation within a cell type (and therefore greater potential to discriminate different cell types) than other physical properties. We accomplish this using a 3D-printed microfluidic chip containing a horizontal flowing micron-scale density gradient. As cells flow through the chip, Earth's gravity makes each cell move vertically to the point where the cell's density matches the surrounding fluid's density. When the horizontal channel then splits, cells with different densities are routed to different outlets. As a proof of concept, we use our density sorter chip to sort polymer microbeads by their material (polyethylene and polystyrene) and blood cells by their type (white blood cells and red blood cells). The chip enriches the fraction of white blood cells in a blood sample from 0.1% (in whole blood) to nearly 98% (in the output of the chip), a 1000x enrichment. Any researcher with access to a 3D printer can easily replicate our density sorter chip and use it in their own research using the design files provided as online Supporting Information. Additionally, researchers can simulate the performance of a density sorter chip in their own applications using the Python-based simulation software that accompanies this work. The simplicity, resolution, and throughput of this technique make it suitable for isolating even rare cell types in complex biological samples, in a wide variety of different research and clinical applications.Biological SciencesIndustrial BiotechnologyGeneric health relevanceCell CountCell SeparationErythrocytesHumansLeukocytesMicrofluidic Analytical TechniquesMicrofluidicsGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7n6035g7articlePLOS ONE, vol 12, iss 7e0180520oai:escholarship.org:ark:/13030/qt67m4k5x42023-09-28T13:03:21Zqt67m4k5x4Arbitrary Precision and Complexity Tradeoffs for Gate-Level Information Flow TrackingBecker, AndrewHu, WeiTai, YuBrisk, PhilipKastner, RyanIenne, Paolo2017-06-18Hardware has become an increasingly attractive target for attackers, yet we still largely lack tools that enable us to analyze large designs for security flaws. Information flow tracking (IFT) models provide an approach to verifying a hardware design's adherence to security properties related to isolation and reachability. However, existing precise IFT models are usually too complex to actually use. Queries may fail to finish even for small designs when verifying relatively simple properties. It is possible to create less complex models, but these come at the cost of a severe loss of precision - -they frequently indicate a property fails when in fact it passes, which means verification requires extensive additional manual investigation. We present a new method to bridge the chasm between precision and complexity in a finer-grained, controlled, and disciplined manner. Our method allows using the most appropriate precision/complexity tradeoff for the design size and available computing resources, meaning it is now possible to create models that are not too complex to be usable, but which offer more precision (fewer false positives) than was previously possible.Information and Computing SciencesCybersecurity and PrivacyGood Health and Well Beingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/67m4k5x4articleoai:escholarship.org:ark:/13030/qt9gb6s4g62023-09-28T12:32:08Zqt9gb6s4g6CdS/ZnS core–shell nanocrystal photosensitizers for visible to UV upconversionGray, VictorXia, PanHuang, ZhiyuanMoses, EmilyFast, AlexanderFishman, Dmitry AVullev, Valentine IAbrahamsson, MariaMoth-Poulsen, KasperTang, Ming Lee2017-08-01Herein we report the first example of nanocrystal (NC) sensitized triplet-triplet annihilation based photon upconversion from the visible to ultraviolet (vis-to-UV). Many photocatalyzed reactions, such as water splitting, require UV photons in order to function efficiently. Upconversion is one possible means of extending the usable range of photons into the visible. Vis-to-UV upconversion is achieved with CdS/ZnS core-shell NCs as the sensitizer and 2,5-diphenyloxazole (PPO) as annihilator and emitter. The ZnS shell was crucial in order to achieve any appreciable upconversion. From time resolved photoluminescence and transient absorption measurements we conclude that the ZnS shell affects the NC and triplet energy transfer (TET) from NC to PPO in two distinct ways. Upon ZnS growth the surface traps are passivated thus increasing the TET. The shell, however, also acts as a tunneling barrier for TET, reducing the efficiency. This leads to an optimal shell thickness where the upconversion quantum yield (Φ'UC) is maximized. Here the maximum Φ'UC was determined to be 5.2 ± 0.5% for 4 monolayers of ZnS shell on CdS NCs.Chemical SciencesPhysical ChemistryAffordable and Clean EnergyChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9gb6s4g6articleChemical Science, vol 8, iss 85488 - 5496oai:escholarship.org:ark:/13030/qt3921n05g2023-09-28T11:41:18Zqt3921n05gFast Power Allocation for Secure Communication With Full-Duplex RadioChen, LeiZhu, QipingMeng, WeixiaoHua, Yingbo2017-01-01Theory Of ComputationInformation and Computing SciencesCommunications EngineeringEngineeringFull-duplexmulticarrierOFDMpower allocationsecure communicationphysical layer securityNetworking & Telecommunicationsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3921n05garticleIEEE Transactions on Signal Processing, vol 65, iss 143846 - 3861oai:escholarship.org:ark:/13030/qt3sh5b68k2023-09-28T11:35:11Zqt3sh5b68kSignature-Based Protection from Code Reuse AttacksKayaalp, MehmetSchmitt, TimothyNomani, JunaidPonomarev, DmitryAbu Ghazaleh, Nael2015-01-01Distributed Computing and Systems SoftwareInformation and Computing SciencesSoftware EngineeringCybersecurity and PrivacyProcessor architecturessupport for securitycode reuse attacksComputer SoftwareDistributed ComputingComputer HardwareComputer Hardware & ArchitectureElectronicssensors and digital hardwareDistributed computing and systems softwarepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3sh5b68karticleIEEE Transactions on Computers, vol 64, iss 2533 - 546oai:escholarship.org:ark:/13030/qt7b4425nr2023-09-28T10:17:54Zqt7b4425nrMatrix Profile II: Exploiting a Novel Algorithm and GPUs to Break the One Hundred Million Barrier for Time Series Motifs and JoinsZhu, YanZimmerman, ZacharySenobari, Nader ShakibayYeh, Chin-Chia MichaelFunning, GarethMueen, AbdullahBrisk, PhilipKeogh, EamonnBonchi, FrancescoDomingo-Ferrer, JosepBaeza-Yates, RicardoZhou, Zhi-HuaWu, Xindong2016-12-01Time series motifs have been in the literature for about fifteen years, but have only recently begun to receive significant attention in the research community. This is perhaps due to the growing realization that they implicitly offer solutions to a host of time series problems, including rule discovery, anomaly detection, density estimation, semantic segmentation, etc. Recent work has improved the scalability to the point where exact motifs can be computed on datasets with up to a million data points in tenable time. However, in some domains, for example seismology, there is an insatiable need to address even larger datasets. In this work we show that a combination of a novel algorithm and a high-performance GPU allows us to significantly improve the scalability of motif discovery. We demonstrate the scalability of our ideas by finding the full set of exact motifs on a dataset with one hundred million subsequences, by far the largest dataset ever mined for time series motifs. Furthermore, we demonstrate that our algorithm can produce actionable insights in seismology and other domains.Data Management and Data ScienceInformation and Computing SciencesTime seriesjoinsmotifsGPUsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7b4425nrarticleoai:escholarship.org:ark:/13030/qt26v8h75b2023-09-28T10:05:08Zqt26v8h75bA Magnetometer Based on a Spin Wave InterferometerBalynsky, MGutierrez, DChiang, HKozhevnikov, ADudko, GFilimonov, YBalandin, AAKhitun, A2017-01-01We describe a magnetic field sensor based on a spin wave interferometer. Its sensing element consists of a magnetic cross junction with four micro-antennas fabricated at the edges. Two of these antennas are used for spin wave excitation while two other antennas are used for detection of the inductive voltage produced by the interfering spin waves. Two waves propagating in the orthogonal arms of the cross may accumulate significantly different phase shifts depending on the magnitude and direction of the external magnetic field. This phenomenon is utilized for magnetic field sensing. The sensitivity attains its maximum under the destructive interference condition, where a small change in the external magnetic field results in a drastic increase of the inductive voltage, as well as in the change of the output phase. We report experimental data obtained for a micrometer scale Y3Fe2(FeO4)3 cross structure. The change of the inductive voltage near the destructive interference point exceeds 40 dB per 1 Oe. The phase of the output signal exhibits a π-phase shift within 1 Oe. The data are collected at room temperature. Taking into account the low thermal noise in ferrite structures, we estimate that the maximum sensitivity of the spin wave magnetometer may exceed attotesla.Data Management and Data ScienceInformation and Computing SciencesEngineeringPhysical Sciencescond-mat.otherphysics.ins-detapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/26v8h75barticleScientific Reports, vol 7, iss 111539oai:escholarship.org:ark:/13030/qt5jz4k7r52023-09-28T09:12:53Zqt5jz4k7r5Unsupervised Adaptive Re-Identification in Open World Dynamic Camera NetworksPanda, RameswarBhuiyan, AmranMurino, VittorioRoy-Chowdhury, Amit K2017-07-01Person re-identification is an open and challenging problem in computer
vision. Existing approaches have concentrated on either designing the best
feature representation or learning optimal matching metrics in a static setting
where the number of cameras are fixed in a network. Most approaches have
neglected the dynamic and open world nature of the re-identification problem,
where a new camera may be temporarily inserted into an existing system to get
additional information. To address such a novel and very practical problem, we
propose an unsupervised adaptation scheme for re-identification models in a
dynamic camera network. First, we formulate a domain perceptive
re-identification method based on geodesic flow kernel that can effectively
find the best source camera (already installed) to adapt with a newly
introduced target camera, without requiring a very expensive training phase.
Second, we introduce a transitive inference algorithm for re-identification
that can exploit the information from best source camera to improve the
accuracy across other camera pairs in a network of multiple cameras. Extensive
experiments on four benchmark datasets demonstrate that the proposed approach
significantly outperforms the state-of-the-art unsupervised learning based
alternatives whilst being extremely efficient to compute.Information and Computing SciencesArtificial IntelligenceComputer Vision and Multimedia ComputationData Management and Data ScienceMachine LearningGeneric health relevancecs.CVapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5jz4k7r5articleoai:escholarship.org:ark:/13030/qt5pf7h3p12023-09-28T09:12:50Zqt5pf7h3p1Collaborative Summarization of Topic-Related VideosPanda, RameswarRoy-Chowdhury, Amit K2017-07-01Large collections of videos are grouped into clusters by a topic keyword,
such as Eiffel Tower or Surfing, with many important visual concepts repeating
across them. Such a topically close set of videos have mutual influence on each
other, which could be used to summarize one of them by exploiting information
from others in the set. We build on this intuition to develop a novel approach
to extract a summary that simultaneously captures both important
particularities arising in the given video, as well as, generalities identified
from the set of videos. The topic-related videos provide visual context to
identify the important parts of the video being summarized. We achieve this by
developing a collaborative sparse optimization method which can be efficiently
solved by a half-quadratic minimization algorithm. Our work builds upon the
idea of collaborative techniques from information retrieval and natural
language processing, which typically use the attributes of other similar
objects to predict the attribute of a given object. Experiments on two
challenging and diverse datasets well demonstrate the efficacy of our approach
over state-of-the-art methods.Information and Computing SciencesGraphicsAugmented Reality and GamesComputer Vision and Multimedia Computationcs.CVapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5pf7h3p1articleoai:escholarship.org:ark:/13030/qt42n761112023-09-28T09:03:31Zqt42n76111Dynamic brain connectivity is a better predictor of PTSD than static connectivityJin, ChangfengJia, HaoLanka, PradyumnaRangaprakash, DLi, LingjiangLiu, TianmingHu, XiaopingDeshpande, Gopikrishna2017-09-01Using resting-state functional magnetic resonance imaging, we test the hypothesis that subjects with post-traumatic stress disorder (PTSD) are characterized by reduced temporal variability of brain connectivity compared to matched healthy controls. Specifically, we test whether PTSD is characterized by elevated static connectivity, coupled with decreased temporal variability of those connections, with the latter providing greater sensitivity toward the pathology than the former. Static functional connectivity (FC; nondirectional zero-lag correlation) and static effective connectivity (EC; directional time-lagged relationships) were obtained over the entire brain using conventional models. Dynamic FC and dynamic EC were estimated by letting the conventional models to vary as a function of time. Statistical separation and discriminability of these metrics between the groups and their ability to accurately predict the diagnostic label of a novel subject were ascertained using separate support vector machine classifiers. Our findings support our hypothesis that PTSD subjects have stronger static connectivity, but reduced temporal variability of connectivity. Further, machine learning classification accuracy obtained with dynamic FC and dynamic EC was significantly higher than that obtained with static FC and static EC, respectively. Furthermore, results also indicate that the ease with which brain regions engage or disengage with other regions may be more sensitive to underlying pathology than the strength with which they are engaged. Future studies must examine whether this is true only in the case of PTSD or is a general organizing principle in the human brain. Hum Brain Mapp 38:4479-4496, 2017. © 2017 Wiley Periodicals, Inc.Biological PsychologyPsychologyClinical ResearchPost-Traumatic Stress Disorder (PTSD)Brain DisordersMental HealthBiomedical ImagingNeurosciencesMental healthBrainBrain MappingDiagnosisComputer-AssistedDisastersEarthquakesHumansMagnetic Resonance ImagingNeural PathwaysRestStress DisordersPost-TraumaticSupport Vector Machineresting-state functional magnetic resonance imagingdynamic brain connectivityfunctional connectivityeffective connectivitypost-traumatic stress disordersupport vector machineCognitive SciencesExperimental PsychologyBiological psychologyCognitive and computational psychologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/42n76111articleHuman Brain Mapping, vol 38, iss 94479 - 4496oai:escholarship.org:ark:/13030/qt26k2d3402023-09-28T08:14:12Zqt26k2d340A comparative evaluation of genome assembly reconciliation toolsAlhakami, HindMirebrahim, HamidLonardi, Stefano2017-12-01BackgroundThe majority of eukaryotic genomes are unfinished due to the algorithmic challenges of assembling them. A variety of assembly and scaffolding tools are available, but it is not always obvious which tool or parameters to use for a specific genome size and complexity. It is, therefore, common practice to produce multiple assemblies using different assemblers and parameters, then select the best one for public release. A more compelling approach would allow one to merge multiple assemblies with the intent of producing a higher quality consensus assembly, which is the objective of assembly reconciliation.ResultsSeveral assembly reconciliation tools have been proposed in the literature, but their strengths and weaknesses have never been compared on a common dataset. We fill this need with this work, in which we report on an extensive comparative evaluation of several tools. Specifically, we evaluate contiguity, correctness, coverage, and the duplication ratio of the merged assembly compared to the individual assemblies provided as input.ConclusionsNone of the tools we tested consistently improved the quality of the input GAGE and synthetic assemblies. Our experiments show an increase in contiguity in the consensus assembly when the original assemblies already have high quality. In terms of correctness, the quality of the results depends on the specific tool, as well as on the quality and the ranking of the input assemblies. In general, the number of misassemblies ranges from being comparable to the best of the input assembly to being comparable to the worst of the input assembly.Biological SciencesBioinformatics and Computational BiologyAlgorithmsChromosome MappingContig MappingEukaryotaGenomeHigh-Throughput Nucleotide SequencingProkaryotic CellsSequence AnalysisDNASoftwareDe novo genome assemblyGenomicsAssembly reconciliationEnvironmental SciencesInformation and Computing SciencesBioinformaticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/26k2d340articleGenome Biology, vol 18, iss 193oai:escholarship.org:ark:/13030/qt7d49t9gk2023-09-28T06:01:41Zqt7d49t9gkPhysico-electrochemical Characterization of Pluripotent Stem Cells during Self-Renewal or Differentiation by a Multi-modal Monitoring SystemLow, KarenWong, Lauren YMaldonado, MaricelaManjunath, ChetasHorner, Christopher BPerez, MarkMyung, Nosang VNam, Jin2017-05-01Monitoring pluripotent stem cell behaviors (self-renewal and differentiation to specific lineages/phenotypes) is critical for a fundamental understanding of stem cell biology and their translational applications. In this study, a multi-modal stem cell monitoring system was developed to quantitatively characterize physico-electrochemical changes of the cells in real time, in relation to cellular activities during self-renewal or lineage-specific differentiation, in a non-destructive, label-free manner. The system was validated by measuring physical (mass) and electrochemical (impedance) changes in human induced pluripotent stem cells undergoing self-renewal, or subjected to mesendodermal or ectodermal differentiation, and correlating them to morphological (size, shape) and biochemical changes (gene/protein expression). An equivalent circuit model was used to further dissect the electrochemical (resistive and capacitive) contributions of distinctive cellular features. Overall, the combination of the physico-electrochemical measurements and electrical circuit modeling collectively offers a means to longitudinally quantify the states of stem cell self-renewal and differentiation.Biochemistry and Cell BiologyBiological SciencesStem Cell Research - Induced Pluripotent Stem Cell - HumanStem Cell Research - Induced Pluripotent Stem CellStem Cell ResearchRegenerative MedicineCell DifferentiationCell LineCell ProliferationHumansInduced Pluripotent Stem CellsModelsBiologicalOptical ImagingQuartz Crystal Microbalance Techniquesdifferentiationelectrochemical impedance spectroscopyequivalent circuit modelhuman induced pluripotent stem cellsquartz crystal microbalancereal-time monitoringself-renewalClinical SciencesBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7d49t9gkarticleStem Cell Reports, vol 8, iss 51329 - 1339oai:escholarship.org:ark:/13030/qt4p11s8802023-09-28T05:50:17Zqt4p11s880Silicon Derived from Glass Bottles as Anode Materials for Lithium Ion Full Cell BatteriesLi, ChanglingLiu, ChuehWang, WeiMutlu, ZaferBell, JeffreyAhmed, KaziYe, RachelOzkan, MihrimahOzkan, Cengiz S2017-01-01Every year many tons of waste glass end up in landfills without proper recycling, which aggravates the burden of waste disposal in landfill. The conversion from un-recycled glass to favorable materials is of great significance for sustainable strategies. Recently, silicon has been an exceptional anode material towards large-scale energy storage applications, due to its extraordinary lithiation capacity of 3579 mAh g-1 at ambient temperature. Compared with other quartz sources obtained from pre-leaching processes which apply toxic acids and high energy-consuming annealing, an interconnected silicon network is directly derived from glass bottles via magnesiothermic reduction. Carbon-coated glass derived-silicon (gSi@C) electrodes demonstrate excellent electrochemical performance with a capacity of ~1420 mAh g-1 at C/2 after 400 cycles. Full cells consisting of gSi@C anodes and LiCoO2 cathodes are assembled and achieve good initial cycling stability with high energy density.EngineeringMaterials EngineeringChemical SciencesPhysical ChemistryAffordable and Clean Energyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4p11s880articleScientific Reports, vol 7, iss 1917oai:escholarship.org:ark:/13030/qt2bw5w6qf2023-09-28T05:12:02Zqt2bw5w6qfModeling and Classifying Tip Dynamics of Growing Cells in VideoTambo, Asongu LBhanu, Bir2016-01-01Communications EngineeringEngineeringElectronicsSensors and Digital HardwareTip growthtip growth classificationtip growth featuresArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCommunications TechnologiesNetworking & TelecommunicationsCommunications engineeringElectronicssensors and digital hardwareComputer vision and multimedia computationapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2bw5w6qfarticleIEEE Signal Processing Letters, vol 23, iss 101369 - 1373oai:escholarship.org:ark:/13030/qt89g7p8m92023-09-28T03:14:57Zqt89g7p8m9Potassium Iodide-Functionalized Polyaniline Nanothin Film Chemiresistor for Ultrasensitive Ozone Gas SensingSrinives, SiraSarkar, TapanHernandez, RaulMulchandani, Ashok2017-01-01Polyaniline (PANI) nanostructures have been widely studied for their sensitivity to atmospheric pollutants at ambient conditions. We recently showed an effective way to electropolymerize a PANI nanothin film on prefabricated microelectrodes, and demonstrated its remarkable sensing performance to be comparable to that of a one-dimensional nanostructure, such as PANI nanowires. In this work, we report further progress in the application of the PANI nanothin film chemiresistive sensor for the detection of ozone (O₃) by modifying the film with potassium iodide (KI). The KI-PANI sensor exhibited an excellent sensitivity to O₃ (8⁻180 ppb O₃ concentration rage) with a limit of detection of 230 ppt O₃, and exquisite selectivity against active chemicals such as nitrogen dioxide (NO₂) and sulfur dioxide (SO₂). The sensing mechanism of the sensor relied on iodometric chemistry of KI and O₃, producing triiodide ( I 3 - ) that partially doped and increased electrical conductivity of the PANI film. The sensitivity and selectivity of the KI-functionalized PANI film demonstrates the potential use for KI-PANI-based O₃ sensing devices in environmental monitoring and occupational safety.Chemical Sciencesozone sensoriodometrypolyanilinegas sensorpotassium iodideEngineeringChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/89g7p8m9articlePolymers, vol 9, iss 380oai:escholarship.org:ark:/13030/qt8jj4f2rv2023-09-27T23:48:14Zqt8jj4f2rvDetection of Side Chain Rearrangements Mediating the Motions of Transmembrane Helices in Molecular Dynamics Simulations of G Protein-Coupled ReceptorsGaieb, ZiedMorikis, Dimitrios2017-01-01Structure and dynamics are essential elements of protein function. Protein structure is constantly fluctuating and undergoing conformational changes, which are captured by molecular dynamics (MD) simulations. We introduce a computational framework that provides a compact representation of the dynamic conformational space of biomolecular simulations. This method presents a systematic approach designed to reduce the large MD simulation spatiotemporal datasets into a manageable set in order to guide our understanding of how protein mechanics emerge from side chain organization and dynamic reorganization. We focus on the detection of side chain interactions that undergo rearrangements mediating global domain motions and vice versa. Side chain rearrangements are extracted from side chain interactions that undergo well-defined abrupt and persistent changes in distance time series using Gaussian mixture models, whereas global domain motions are detected using dynamic cross-correlation. Both side chain rearrangements and global domain motions represent the dynamic components of the protein MD simulation, and are both mapped into a network where they are connected based on their degree of coupling. This method allows for the study of allosteric communication in proteins by mapping out the protein dynamics into an intramolecular network to reduce the large simulation data into a manageable set of communities composed of coupled side chain rearrangements and global domain motions. This computational framework is suitable for the study of tightly packed proteins, such as G protein-coupled receptors, and we present an application on a seven microseconds MD trajectory of CC chemokine receptor 7 (CCR7) bound to its ligand CCL21.Biological SciencesBioinformatics and Computational BiologyUnderpinning research1.1 Normal biological development and functioningMolecular dynamicsChange-point detectionSide chain reorganizationHelical domain motionIntramolecular networkMembrane proteinsGPCRGPCR computational modelingGPCR allosteryNumerical and Computational MathematicsComputation Theory and MathematicsBiochemistry and cell biologyApplied computingapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8jj4f2rvarticleoai:escholarship.org:ark:/13030/qt15g2v9rn2023-09-27T20:21:47Zqt15g2v9rnThe Anatomy of American Football: Evidence from 7 Years of NFL Game DataPelechrinis, KonstantinosPapalexakis, EvangelosEriksson, Kimmo2016-01-01How much does a fumble affect the probability of winning an American football game? How balanced should your offense be in order to increase the probability of winning by 10%? These are questions for which the coaching staff of National Football League teams have a clear qualitative answer. Turnovers are costly; turn the ball over several times and you will certainly lose. Nevertheless, what does "several" mean? How "certain" is certainly? In this study, we collected play-by-play data from the past 7 NFL seasons, i.e., 2009-2015, and we build a descriptive model for the probability of winning a game. Despite the fact that our model incorporates simple box score statistics, such as total offensive yards, number of turnovers etc., its overall cross-validation accuracy is 84%. Furthermore, we combine this descriptive model with a statistical bootstrap module to build FPM (short for Football Prediction Matchup) for predicting future match-ups. The contribution of FPM is pertinent to its simplicity and transparency, which however does not sacrifice the system's performance. In particular, our evaluations indicate that our prediction engine performs on par with the current state-of-the-art systems (e.g., ESPN's FPI and Microsoft's Cortana). The latter are typically proprietary but based on their components described publicly they are significantly more complicated than FPM. Moreover, their proprietary nature does not allow for a head-to-head comparison in terms of the core elements of the systems but it should be evident that the features incorporated in FPM are able to capture a large percentage of the observed variance in NFL games.Commercial ServicesCommerceManagementTourism and ServicesAnthropometryAthletesAthletic PerformanceBody CompositionFootballHumansModelsStatisticalUnited StatesGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/15g2v9rnarticlePLOS ONE, vol 11, iss 12e0168716oai:escholarship.org:ark:/13030/qt4wp8h88w2023-09-27T18:39:44Zqt4wp8h88wBacon-Shor code with continuous measurement of noncommuting operatorsAtalaya, JuanBahrami, MohammadPryadko, Leonid PKorotkov, Alexander N2017-03-01We analyze the operation of a four-qubit Bacon-Shor code with simultaneous
continuous measurement of non-commuting gauge operators. The error syndrome in
this case is monitored via time-averaged cross-correlators of the output
signals. We find the logical error rate for several models of decoherence, and
also find the termination rate for this quantum error detecting code. The code
operation is comparable to that based on projective measurements when the
collapse timescale due to continuous measurements is an order of magnitude less
than the time period between the projective measurements. An advantage of the
continuous-measurement implementation is the absence of time-dependence in the
code operation, with passive continuous monitoring of the error syndrome.Quantum PhysicsPhysical Sciencesquant-phcond-mat.mes-hallcond-mat.supr-conChemical sciencesMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4wp8h88warticlePhysical Review A, vol 95, iss 3032317oai:escholarship.org:ark:/13030/qt4jc034vm2023-09-27T17:16:43Zqt4jc034vmDirect observation of confined acoustic phonon polarization branches in free-standing semiconductor nanowiresKargar, FariborzDebnath, BishwajitKakko, Joona-PekkoSäynätjoki, AnttiLipsanen, HarriNika, Denis LLake, Roger KBalandin, Alexander A2016-01-01Similar to electron waves, the phonon states in semiconductors can undergo changes induced by external boundaries. However, despite strong scientific and practical importance, conclusive experimental evidence of confined acoustic phonon polarization branches in individual free-standing nanostructures is lacking. Here we report results of Brillouin-Mandelstam light scattering spectroscopy, which reveal multiple (up to ten) confined acoustic phonon polarization branches in GaAs nanowires with a diameter as large as 128 nm, at a length scale that exceeds the grey phonon mean-free path in this material by almost an order-of-magnitude. The dispersion modification and energy scaling with diameter in individual nanowires are in excellent agreement with theory. The phonon confinement effects result in a decrease in the phonon group velocity along the nanowire axis and changes in the phonon density of states. The obtained results can lead to more efficient nanoscale control of acoustic phonons, with benefits for nanoelectronic, thermoelectric and spintronic devices.Physical SciencesEngineeringNanotechnologyCondensed Matter Physicscond-mat.mes-hallcond-mat.mtrl-sciapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4jc034vmarticleNature Communications, vol 7, iss 113400oai:escholarship.org:ark:/13030/qt5pg150x32023-09-27T17:12:30Zqt5pg150x3Peptide redesign for inhibition of the complement system: Targeting age-related macular degeneration.Mohan, Rohith RCabrera, Andrea PHarrison, Reed ESGorham, Ronald DJohnson, Lincoln VGhosh, KaustabhMorikis, Dimitrios2016-01-01PurposeTo redesign a complement-inhibiting peptide with the potential to become a therapeutic for dry and wet age-related macular degeneration (AMD).MethodsWe present a new potent peptide (Peptide 2) of the compstatin family. The peptide is developed by rational design, based on a mechanistic binding hypothesis, and structural and physicochemical properties derived from molecular dynamics (MD) simulation. The inhibitory activity, efficacy, and solubility of Peptide 2 are evaluated using a hemolytic assay, a human RPE cell-based assay, and ultraviolet (UV) absorption properties, respectively, and compared to the respective properties of its parent peptide (Peptide 1).ResultsThe sequence of Peptide 2 contains an arginine-serine N-terminal extension (a characteristic of parent Peptide 1) and a novel 8-polyethylene glycol (PEG) block C-terminal extension. Peptide 2 has significantly improved aqueous solubility compared to Peptide 1 and comparable complement inhibitory activity. In addition, Peptide 2 is more efficacious in inhibiting complement activation in a cell-based model that mimics the pathobiology of dry AMD.ConclusionsWe have designed a new peptide analog of compstatin that combines N-terminal polar amino acid extensions and C-terminal PEGylation extensions. This peptide demonstrates significantly improved aqueous solubility and complement inhibitory efficacy, compared to the parent peptide. The new peptide overcomes the aggregation limitation for clinical translation of previous compstatin analogs and is a candidate to become a therapeutic for the treatment of AMD.Biomedical and Clinical SciencesOphthalmology and OptometryNeurodegenerativeEye Disease and Disorders of VisionMacular Degeneration5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsAmino Acid SequenceAnimalsCell LineComplement System ProteinsHemolysisHumansInhibitory Concentration 50PeptidesPeptidesCyclicRabbitsSolubilityOpthalmology and OptometryOphthalmology & OptometryOphthalmology and optometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5pg150x3articleoai:escholarship.org:ark:/13030/qt9996h1wk2023-09-27T15:49:13Zqt9996h1wkSpin-Josephson effects in exchange coupled antiferromagnetic insulatorsLiu, YizhouYinZang, JiadongLake, Roger KBarlas, Yafis2016-09-01Physical SciencesCondensed Matter PhysicsChemical sciencesEngineeringPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9996h1wkarticlePhysical Review B, vol 94, iss 9094434oai:escholarship.org:ark:/13030/qt75b143w92023-09-27T15:13:58Zqt75b143w9TransComb: genome-guided transcriptome assembly via combing junctions in splicing graphsLiu, JuntaoYu, TingJiang, TaoLi, Guojun2016-12-01Transcriptome assemblers aim to reconstruct full-length transcripts from RNA-seq data. We present TransComb, a genome-guided assembler developed based on a junction graph, weighted by a bin-packing strategy and paired-end information. A newly designed extension method based on weighted junction graphs can accurately extract paths representing expressed transcripts, whether they have low or high expression levels. Tested on both simulated and real datasets, TransComb demonstrates significant improvements in both recall and precision over leading assemblers, including StringTie, Cufflinks, Bayesembler, and Traph. In addition, it runs much faster and requires less memory on average. TransComb is available at http://sourceforge.net/projects/transcriptomeassembly/files/ .Biological SciencesBioinformatics and Computational BiologyGeneticsNetworking and Information Technology R&D (NITRD)Human GenomeAlgorithmsGene Expression ProfilingGene Expression RegulationHumansRNASequence AnalysisRNASoftwareTranscriptomeRNA-seqTranscriptome assemblyAlternative splicingSplicing graphIsoformEnvironmental SciencesInformation and Computing SciencesBioinformaticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/75b143w9articleGenome Biology, vol 17, iss 1213oai:escholarship.org:ark:/13030/qt3zv966n72023-09-27T12:45:55Zqt3zv966n7Engineering biosynthesis of the anticancer alkaloid noscapine in yeastLi, YanranSmolke, Christina D2016-01-01Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4'-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery.Biological SciencesIndustrial BiotechnologyGeneticsBiotechnology5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsAntineoplastic AgentsBerberine AlkaloidsBioengineeringBiosynthetic PathwaysCytochrome P-450 Enzyme SystemDrug DiscoveryMethyltransferasesMultigene FamilyNoscapinePapaverPlant ProteinsSaccharomyces cerevisiaeTetrahydropapaverolineapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3zv966n7articleNature Communications, vol 7, iss 112137oai:escholarship.org:ark:/13030/qt3jh0x2hh2023-09-27T12:39:32Zqt3jh0x2hhRecent developments in microfluidic large scale integrationAraci, Ismail EmreBrisk, Philip2014-02-01In 2002, Thorsen et al. integrated thousands of micromechanical valves on a single microfluidic chip and demonstrated that the control of the fluidic networks can be simplified through multiplexors [1]. This enabled realization of highly parallel and automated fluidic processes with substantial sample economy advantage. Moreover, the fabrication of these devices by multilayer soft lithography was easy and reliable hence contributed to the power of the technology; microfluidic large scale integration (mLSI). Since then, mLSI has found use in wide variety of applications in biology and chemistry. In the meantime, efforts to improve the technology have been ongoing. These efforts mostly focus on; novel materials, components, micromechanical valve actuation methods, and chip architectures for mLSI. In this review, these technological advances are discussed and, recent examples of the mLSI applications are summarized.AgriculturalVeterinary and Food SciencesBiological SciencesBiomedical and Clinical SciencesIndustrial BiotechnologyMedical BiotechnologyAgricultural BiotechnologyBiotechnologyHuman GenomeGeneticsAnimalsAutomationLaboratoryClick ChemistryHumansMicrofluidic Analytical TechniquesMicrofluidicsEngineeringTechnologyAgricultural biotechnologyIndustrial biotechnologyMedical biotechnologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3jh0x2hharticleoai:escholarship.org:ark:/13030/qt3184q9dq2023-09-27T12:39:28Zqt3184q9dqUSING 3D INTEGRATION TECHNOLOGY TO REALIZE MULTI-CONTEXT FPGASCevrero, AlesandroAthanasopoulos, PanagiotisParandeh-Afshar, HadiBrisk, PhilipLeblebici, YusufSkerlj, MaurizioIenne, PaoloDanek, MartinKadlec, JiriNelson, Brent E2009-08-01This paper advocates the use of 3D integration technology to stack a DRAM on top of an FPGA. The DRAM will store future FPGA contexts. A configuration is read from the DRAM into a latch array on the DRAM layer while the FPGA executes; the new configuration is loaded from the latch array into the FPGA in 60ns (5 cycles). The latency between reconfigurations, 8.42μs, is dominated by the time to read data from the DRAM into the latch array. We estimate that the DRAM can cache 289 FPGA contexts. ©2009 IEEE.Built Environment and DesignEngineeringArchitectureElectronicsSensors and Digital HardwarepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3184q9dqarticleoai:escholarship.org:ark:/13030/qt6sm4k19k2023-09-27T12:39:23Zqt6sm4k19kAn EDA-Friendly Protection Scheme against Side-Channel AttacksBayrak, Ali GalipVelickovic, NikolaRegazzoni, FrancescoNovo, DavidBrisk, PhilipIenne, PaoloMacii, Enrico2013-01-01This paper introduces a generic and automated methodology to protect hardware designs from side-channel attacks in a manner that is fully compatible with commercial standard cell design flows. The paper describes a tool that artificially adds jitter to the clocks of the sequential elements of a cryptographic unit, which increases the non-determinism of signal timing, thereby making the physical device more difficult to attack. Timing constraints are then specified to commercial EDA tools, which restore the circuit functionality and efficiency while preserving the introduced randomness. The protection scheme is applied to an AES-128 hardware implementation that is synthesized using both ASIC and FPGA design flows. © 2013 EDAA.Information and Computing SciencesEngineeringCybersecurity and PrivacypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6sm4k19karticleoai:escholarship.org:ark:/13030/qt1p86p40j2023-09-27T12:39:20Zqt1p86p40jAutomatic Application of Power Analysis CountermeasuresBayrak, Ali GalipRegazzoni, FrancescoNovo, DavidBrisk, PhilipStandaert, Francois-XavierIenne, Paolo2015-01-01We introduce a compiler that automatically inserts software countermeasures to protect cryptographic algorithms against power-based side-channel attacks. The compiler first estimates which instruction instances leak the most information through side-channels. This information is obtained either by dynamic analysis, evaluating an information theoretic metric over the power traces acquired during the execution of the input program, or by static analysis. As information leakage implies a loss of security, the compiler then identifies (groups of) instruction instances to protect with a software countermeasure such as random precharging or Boolean masking. As software protection incurs significant overhead in terms of cryptosystem runtime and memory usage, the compiler protects the minimum number of instruction instances to achieve a desired level of security. The compiler is evaluated on two block ciphers, AES and Clefia; our experiments demonstrate that the compiler can automatically identify and protect the most important instruction instances. To date, these software countermeasures have been inserted manually by security experts, who are not necessarily the main cryptosystem developers. Our compiler offers significant productivity gains for cryptosystem developers who wish to protect their implementations from side-channel attacks.Information and Computing SciencesSoftware EngineeringCybersecurity and PrivacySide-channel attackspower analysis attackssoftware countermeasurescompilerComputer SoftwareDistributed ComputingComputer HardwareComputer Hardware & ArchitectureElectronicssensors and digital hardwareDistributed computing and systems softwarepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1p86p40jarticleIEEE Transactions on Computers, vol 64, iss 2329 - 341oai:escholarship.org:ark:/13030/qt686794602023-09-27T12:39:16Zqt68679460Exploiting Fast Carry-Chains of FPGAS for Designing Compressor TreesParandeh-Afshar, HadiBrisk, PhilipIenne, PaoloDanek, MartinKadlec, JiriNelson, Brent E2009-08-01Fast carry chains featuring dedicated adder circuitry is a distinctive feature of modern FPGAs. The carry chains bypass the general routing network and are embedded in the logic blocks of FPGAs for fast addition. Conventional intuition is that such carry chains can be used only for implementing carry-propagate addition; state-of-the-art FPGA synthesizers can only exploit the carry chains for these specific circuits. This paper demonstrates that the carry chains can be used to build compressor trees, i.e., multi-input addition circuits used for parallel accumulation and partial product reduction for parallel multipliers implemented in FPGA logic. The key to our technique is to program the lookup tables (LUTs) in the logic blocks to stop the propagation of carry bits along the carry chain at appropriate points. This approach improves the area of compressor trees significantly compared to previous methods that synthesized compressor trees solely on LUTs, without compromising the performance gain over trees built from ternary carry-propagate adders. ©2009 IEEE.EngineeringElectrical EngineeringElectronicsSensors and Digital HardwarepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/68679460articleoai:escholarship.org:ark:/13030/qt45j2c7mz2023-09-27T12:39:12Zqt45j2c7mzThermal-aware data flow analysisAyala, José LAtienza, DavidBrisk, Philip2009-07-26This paper suggests that the thermal state of a processor can be approximated using data flow analysis. The results of this analysis can be used to evaluate the efficacy of thermal-aware compilation strategies, or as input to thermal-aware optimizations that occur in the early stages of back-end compilation. We propose different ways how the exploitation of thermal behavior knowledge can be included in the different compilation phases. Copyright 2009 ACM.EngineeringBuilt Environment and DesignElectronicsSensors and Digital HardwareThermal ManagementCompilerpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/45j2c7mzarticleoai:escholarship.org:ark:/13030/qt2s02f0f12023-09-27T12:39:09Zqt2s02f0f1A first step towards automatic application of power analysis countermeasuresBayrak, Ali GalipRegazzoni, FrancescoBrisk, PhilipStandaert, François-XavierIenne, PaoloStok, LeonDutt, Nikil DHassoun, Soha2011-06-05In cryptography, side channel attacks, such as power analysis, attempt to uncover secret information from the physical implementation of cryptosystems rather than exploiting weaknesses in the cryptographic algorithms themselves. The design and implementation of physically secure cryptosystems is a challenge for both hardware and software designers. Measuring and evaluating the security of a system is manual and empirical, which is costly and time consuming; this work demonstrates that it is possible to automate these processes. We introduce a systematic methodology for automatic application of software countermeasures and demonstrate its effectiveness on an AES software implementation running on an 8-bit AVR microcontroller. The framework identifies the most vulnerable instructions of the implementation to power analysis attacks, and then transforms the software using a chosen countermeasure to protect the vulnerable instructions. Lastly, it evaluates the security of the system using an information-theoretic metric and a direct attack. © 2011 ACM.Information and Computing SciencesCybersecurity and PrivacyPower Analysis AttacksSoftware CountermeasureAVRAutomationpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2s02f0f1articleoai:escholarship.org:ark:/13030/qt3qf5b06j2023-09-27T12:39:05Zqt3qf5b06jA Design Flow and Evaluation Framework for DPA-Resistant Instruction Set ExtensionsRegazzoni, FrancescoCevrero, AlessandroStandaert, François-XavierBadel, StephaneKluter, TheoBrisk, PhilipLeblebici, YusufIenne, PaoloClavier, ChristopheGaj, Kris2009-01-01Power-based side channel attacks are a significant security risk, especially for embedded applications. To improve the security of such devices, protected logic styles have been proposed as an alternative to CMOS. However, they should only be used sparingly, since their area and power consumption are both significantly larger than for CMOS. We propose to augment a processor, realized in CMOS, with custom instruction set extensions, designed with security and performance as the primary objectives, that are realized in a protected logic. We have developed a design flow based on standard CAD tools that can automatically synthesize and place-and-route such hybrid designs. The flow is integrated into a simulation and evaluation environment to quantify the security achieved on a sound basis. Using MCML logic as a case study, we have explored different partitions of the PRESENT block cipher between protected and unprotected logic. This experiment illustrates the tradeoff between the type and amount of application-level functionality implemented in protected logic and the level of security achieved by the design. Our design approach and evaluation tools are generic and could be used to partition any algorithm using any protected logic style. © 2009 Springer.Information and Computing SciencesCybersecurity and PrivacyLife on LandArtificial Intelligence & Image ProcessingInformation and computing sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3qf5b06jarticleoai:escholarship.org:ark:/13030/qt3t3074pz2023-09-27T12:39:01Zqt3t3074pzGraph-coloring and treescan register allocation using repairingColombet, QuentinBoissinot, BenoitBrisk, PhilipHack, SebastianRastello, FabriceGupta, Rajesh KMooney, Vincent John2011-10-09Graph coloring and linear scan are two appealing techniques for register allocation as the underlying formalism are extremely clean and simple. This paper advocates a decoupled approach that first lowers the register pressure by spilling variables, and then performs live ranges splitting/coalescing /coloring in a separate phase; this enables the design of simpler, cleaner, and more efficient register allocators. This paper gives a new and more general approach to deal with register constraints. This approach called repairing does not require pre live range splitting and does not introduce additional spill code. It ignores register constraints during coloring/coalescing, and repairs violated constraints afterwards. We applied this method to both graph based and scan based allocators into a decoupled approach. Here, the Iterated Register Coalescer (IRC) and a scan algorithm that uses Static Single Assignment (SSA) properties, the treescan. Moreover, this paper provides a survey on existing and new techniques of bias coloring during scan approaches. Our experimental evaluation shows for the graph based approach, that we reduced the number of vertices (edges) in the interference graph by 26% (33%) without compromising the quality of the generated code. The treescan algorithm improved the compile time of the allocation process by 6:97x over IRC while providing comparable results for the quality of the generated code. Copyright © 2011 ACM.Applied MathematicsEngineeringMathematical SciencesFast register allocationColoringCoalescingSSA formRegister constraintspubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3t3074pzarticleoai:escholarship.org:ark:/13030/qt48d3z1wc2023-09-27T12:38:57Zqt48d3z1wcCounting Stream Registers: An Efficient and Effective Snoop Filter ArchitectureRanganathan, AanjhanBayrak, Ali GalipKluter, TheoBrisk, PhilipCharbon, EdoardoIenne, Paolo2012-07-01We introduce a counting stream register snoop filter, which improves the performance of existing snoop filters based on stream registers. Over time, this class of snoop filters loses the ability to filter memory addresses that have been loaded, and then evicted, from the caches that are filtered; they include cache wrap detection logic, which resets the filter whenever the contents of the cache have been completely replaced. The counting stream register snoop filter introduced here replaces the cache wrap detection logic with a direct-mapped update unit and augments each stream register with a counter, which acts as a validity checker; loading new data into the cache increments the counter, while replacements, snoopy invalidations, and evictions decrement it. A cache wrap is detected whenever the counter reaches zero. Our experimental evaluation shows that the counting stream register snoop filter architecture improves the accuracy compared to traditional stream register snoop filters for representative embedded workloads. © 2012 IEEE.Built Environment and DesignArchitecturesnoopy coherence protocolsnoop filterstream registercounting stream registerpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/48d3z1wcarticleoai:escholarship.org:ark:/13030/qt8z09m9872023-09-27T12:38:53Zqt8z09m987Virtual Ways: Efficient Coherence for Architecturally Visible Storage in Automatic Instruction Set ExtensionsKluter, TheoBurri, SamuelBrisk, PhilipCharbon, EdoardoIenne, PaoloPatt, Yale NFoglia, PierfrancescoDuesterwald, EvelynFaraboschi, PaoloMartorell, Xavier2010-01-01Customizable processors augmented with application-specific Instruction Set Extensions (ISEs) have begun to gain traction in recent years. The most effective ISEs include Architecturally Visible Storage (AVS), compiler-controlled memories accessible exclusively to the ISEs. Unfortunately, the usage of AVS memories creates a coherence problem with the data cache. A multiprocessor coherence protocol can solve the problem, however, this is an expensive solution when applied in a uniprocessor context. Instead, we can solve the problem by modifying the cache controller so that the AVS memories function as extra ways of the cache with respect to coherence, but are not generally accessible as extra ways for use under normal software execution. This solution, which we call Virtual Ways is less costly than a hardware coherence protocol, and eliminate coherence messages from the system bus, which improves energy consumption. Moreover, eliminating these messages makes Virtual Ways significantly more robust to performance degradation when there is a significant disparity in clock frequency between the processor and main memory. © 2010 Springer-Verlag.Information and Computing SciencesApplication-Specific ProcessorsMemory CoherenceInstruction Set ExtensionsVirtual WaysArtificial Intelligence & Image ProcessingInformation and computing sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8z09m987articleoai:escholarship.org:ark:/13030/qt5xq9n8tq2023-09-27T12:38:50Zqt5xq9n8tqReducing the cost of floating-point mantissa alignment and normalization in FPGAsMoctar, Yehdhih Ould MohammedGeorge, NithinParandeh-Afshar, HadiIenne, PaoloLemieux, Guy GFBrisk, PhilipCompton, KatherineHutchings, Brad L2012-02-22In floating-point datapaths synthesized on FPGAs, the shifters that perform mantissa alignment and normalization consume a disproportionate number of LUTs. Shifters are implemented using several rows of small multiplexers; unfortunately, multiplexer-based logic structures map poorly onto LUTs. FPGAs, meanwhile, contain a large number of multiplexers in the programmable routing network; these multiplexer are placed under static control of the FPGA's configuration bitstream. In this work, we modify some of the routing multiplexers in the intra-cluster routing network of a CLB in an FPGA to implement shifters for floating-point mantissa alignment and normalization; the number of CLBs required for these operations is reduced by 67%. If shifting is not required, the routing multiplexers that have been modified can be configured to operate as normal routing multiplexers, so no functionality is sacrificed. The area overhead incurred by these modifications is small, and there is no need to modify every routing multiplexer in the FPGA. Experiments show that there is no negative impact in terms of clock frequency or routability for benchmarks that do not use the dynamic multiplexers. © 2012 ACM.EngineeringElectrical EngineeringElectronicsSensors and Digital HardwareField Programmable Gate ArrayFloating-pointMantissa AlignmentNormalizationpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5xq9n8tqarticleoai:escholarship.org:ark:/13030/qt0jp9j4dj2023-09-27T12:38:46Zqt0jp9j4djParallel fpga routing based on the operator formulationMoctar, Yehdhih Ouid MohammedBrisk, Philip2014-06-01We have implemented an FPGA routing algorithm on a shared memory multi-processor using the Galois API, which offers speculative parallelism in software. The router is a parallel implementation of PathFinder, which is the basis for most commercial FPGA routers. We parallelize the maze expansion step for each net, while routing nets sequentially to limit the amount of rollback that would likely occur due to misspeculation. Our implementation relies on non-blocking priority queues, which use software transactional memory (SMT), to identify the best route for each net. Our experimental results demonstrate scalability for large benchmarks and that the amount of available parallelism depends primarily on the circuit size, not the interdependence of signals. We achieve an average speedup of approximately 3x compared to the most recently published work on parallel multi-threaded FPGA routing, and up to 6x in comparison to the single-threaded router implemented in the publicly available Versatile Place and Route (VPR) framework. Copyright 2014 ACM.Built Environment and DesignArchitectureEngineeringElectrical EngineeringField Programmable Gate ArrayRoutingRouting Resource GraphMaze ExpansionIrregular AlgorithmSoftware Transactional MemorypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0jp9j4djarticleoai:escholarship.org:ark:/13030/qt9862j8q02023-09-27T12:38:41Zqt9862j8q0Multi-Terminal PCB Escape Routing for Digital Microfluidic Biochips Using Negotiated CongestionMcDaniel, JeffreyBrisk, PhilipGrissom, DanielGarcia, Lorena2014-10-01This paper introduces a multi-terminal escape routing algorithm for the design of Printed Circuit Boards (PCBs) that control Digital Microfluidic Biochips (DMFBs). The new algorithm is based on the principle of negotiated congestion, which has been applied in the past to problems including FPGA routing and PCB escape routing for single-terminal nets. PCBs designed for Pin-constrained DMFBs, in which one control pin may drive multiple electrodes, require multi-terminal escape routing solutions. Experimental results indicate that negotiated congestion is more effective for multi-terminal escape routing than existing techniques, which are based on maze routing coupled with rip-up and re-route, yielding an overall reduction in the number of PCB layers in most the test cases that were tried.EngineeringElectronicsSensors and Digital HardwarepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9862j8q0article2014 22ND INTERNATIONAL CONFERENCE ON VERY LARGE SCALE INTEGRATION (VLSI-SOC), vol 2015-January, iss January1 - 6oai:escholarship.org:ark:/13030/qt6hs971x02023-09-27T12:38:37Zqt6hs971x0Fast online synthesis of generally programmable digital microfluidic biochipsGrissom, DanielBrisk, PhilipJerraya, AhmedCarloni, Luca PChang, NaehyuckFummi, Franco2012-10-07We introduce an online synthesis flow for digital microfluidic biochips, which will enable real-time response to errors and control flow. The objective of this flow is to facilitate fast assay synthesis while minimally compromising the quality of results. In particular, we show that a virtual topology, which constrains the allowable locations of assay operations such as mixing, dilution, sensing, etc., in lieu of traditional placement, can significantly speed up the synthesis process without significantly lengthening assay execution time. Copyright 2012 ACM.Fluid Mechanics and Thermal EngineeringEngineeringMicrofluidicsLaboratory-on-ChipElectrowetting-on-DielectricSynthesispubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6hs971x0articleoai:escholarship.org:ark:/13030/qt5038908h2023-09-27T12:38:33Zqt5038908hSimulated Annealing-Based Placement for Microfluidic Large Scale Integration (mLSI) ChipsMcDaniel, JeffreyParker, BrendanBrisk, PhilipGarcia, Lorena2014-10-01Microfluidic large-scale integration (mLSI) chips comprise hundreds or thousands of microvalves integrated into a chemically inert elastomeric substrate. The design of these chips is time-consuming, error-prone, and presently performed by hand. To enhance design automation, a routability-oriented placement algorithm based on simulated annealing is introduced. This paper investigates relevant issues including: (1) grid representation; (2) perturbation operations; (3) objective function; (4) uniform vs. heterogeneous component sizes; (5) spacing rules and their effect on routability; and (6) random vs. directed initial placement. Our results show how the above issues affect both the pre-routing estimate on the routability of the chips, the number of flow channel intersections (each of which requires the insertion of several microvalves), and total channel distance as reported by our router.EngineeringElectrical EngineeringElectronicsSensors and Digital HardwareBioengineeringMicrofluidic large scale integrationmicrolluidicsmicrovalveplacementsimulated annealingpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5038908harticle2014 22ND INTERNATIONAL CONFERENCE ON VERY LARGE SCALE INTEGRATION (VLSI-SOC), vol 2015-January, iss January1 - 6oai:escholarship.org:ark:/13030/qt4bj8g6mt2023-09-27T12:38:30Zqt4bj8g6mtExploring Speed and Energy Tradeoffs in Droplet Transport for Digital Microfluidic BiochipsFiske, JohnathanGrissom, DanielBrisk, Philip2014-01-01This paper transforms the problem of droplet routing for digital microfluidic biochips (DMFBs) from the discrete into the continuous domain, based on the observation that droplet transport velocity is a function of the actuation voltage applied to electrodes that control the devices. A new formulation of the DMFB droplet routing problem is introduced for the continuous domain, which attempts to minimize total energy consumption while meeting a timing constraint. Henceforth, DMFBs should be viewed as continuous, highly integrated cyber-physical systems that interact with and manipulate physical quantities, as opposed to inherently discrete and fully synchronized devices. © 2014 IEEE.Fluid Mechanics and Thermal EngineeringEngineeringBiotechnologypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4bj8g6mtarticleoai:escholarship.org:ark:/13030/qt2hw060xk2023-09-27T12:38:26Zqt2hw060xkARCHITECTURAL SUPPORT FOR THE ORCHESTRATION OF FINE-GRAINED MULTIPROCESSING FOR PORTABLE STREAMING APPLICATIONSBoutellier, JaniCevrero, AlessandroBrisk, PhilipIenne, Paolo2009-10-01Handheld devices are expected to start using fine-grained ASIC accelerators to meet energy-efficiency requirements of increasingly complex applications, e.g., video decoding and reconfigurable radio. To avoid overhead, static multiprocessor schedules are preferable for orchestrating fine-grained accelerators. However, as modern applications use accelerators in irregular patterns, static scheduling leads to low hardware utilization. Run-time scheduling for fine-grained accelerators solves the utilization problem, but easily produces significant overhead. We propose an efficient Accelerator Management Unit (AMU), implemented in hardware. E.g., in video decoding, the AMU takes 3 to 18 cycles to compute a macroblock decoding schedule. The CPU may perform useful work, as the AMU does independent task dispatching. Two experiments are performed, where the AMU is integrated into an FPGA-based multiprocessing prototype system. One experiment does AMU-orchestrated MPEG-4 video decoding and the other demonstrates that the AMU enables low-overhead dynamic scheduling and produces a significant performance advantage over static scheduling. ©2009 IEEE.Built Environment and DesignEngineeringInformation and Computing SciencesElectrical EngineeringComputer Vision and Multimedia ComputationArchitectureAffordable and Clean EnergySchedulingparallel processingsignal processingapplication specific integrated circuitspubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2hw060xkarticleoai:escholarship.org:ark:/13030/qt5w92h14c2023-09-27T12:38:22Zqt5w92h14cWay StealingKluter, TheoBrisk, PhilipIenne, PaoloCharbon, Edoardo2009-07-26This paper introduces Way Stealing, a simple architectural modification to a cache-based processor to increase data bandwidth to and from application-specific Instruction Set Extensions (ISEs). Way Stealing provides more bandwidth to the ISE-logic than the register file alone and does not require expensive coherence protocols, as it does not add memory elements to the processor. When enhanced withWay Stealing, ISE identification flows detect more opportunities for acceleration than prior methods; consequently, Way Stealing can accelerate applications to up to 3.7x, whilst reducing the memory sub-system energy consumption by up to 67%, despite data-cache related restrictions. Copyright 2009 ACM.Built Environment and DesignEngineeringArchitectureElectronicsSensors and Digital HardwareAffordable and Clean EnergyApplication-Specific ProcessorsInstruction Set ExtensionsWay StealingMemory CoherenceAutomatic IdentificationpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5w92h14carticleoai:escholarship.org:ark:/13030/qt91s6t09g2023-09-27T12:38:18Zqt91s6t09gRapid Online Fault Recovery for Cyber-Physical Digital Microfluidic BiochipsJaress, ChristopherBrisk, PhilipGrissom, Daniel2015-04-01Microfluidic technologies offer benefits to the biological sciences by miniaturizing and automating chemical reactions. Software-controlled laboratories-on-a-chip (LoCs) execute biological protocols (assays) specified using high-level languages. Integrated sensors and video monitoring provide a closed feedback loop between the LoC and its control software, which provide timely information about the progress of an ongoing assay and the overall health of the LoC. This paper introduces a cyber-physical control algorithm that rectifies hard and soft faults that are detected dynamically while executing an assay on a digital microfluidic biochip (DMFB), one specific LoC technology. The approach is scalable (i.e., there is no fixed limit on the number of faults that may occur), and runs efficiently in practice, thereby limiting the performance overhead incurred when a hard or soft fault occurs during assay execution.Information and Computing SciencesEngineeringSoftware EngineeringBiotechnologyDigital Microfluidic BiochipError RecoverypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/91s6t09garticleoai:escholarship.org:ark:/13030/qt693222nb2023-09-27T12:02:07Zqt693222nbROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulationMaldonado, MaricelaLuu, Rebeccah JRamos, Michael EPNam, Jin2016-09-01Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632.Biochemistry and Cell BiologyBiomedical and Clinical SciencesBiological SciencesStem Cell ResearchStem Cell Research - Induced Pluripotent Stem CellStem Cell Research - Induced Pluripotent Stem Cell - HumanRegenerative MedicineStem Cell Research - Nonembryonic - Non-Human1.1 Normal biological development and functioningUnderpinning researchAmidesCadherinsCell DifferentiationCell LineageCellsCulturedEpithelial-Mesenchymal TransitionGene ExpressionHumansInduced Pluripotent Stem CellsNanog Homeobox ProteinOctamer Transcription Factor-3Pyridinesrho-Associated KinasesPluripotent stem cellsY-27632DifferentiationMesendodermEctodermMedical and Health SciencesDevelopmental BiologyGeneticsMedical biotechnologyOncology and carcinogenesisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/693222nbarticleStem Cell Research, vol 17, iss 2222 - 227oai:escholarship.org:ark:/13030/qt1sz8f8z52023-09-27T09:42:37Zqt1sz8f8z5Parallel Algorithms for Summing Floating-Point NumbersGoodrich, Michael TEldawy, Ahmed2016-05-17The problem of exactly summing n floating-point numbers is a fundamental
problem that has many applications in large-scale simulations and computational
geometry. Unfortunately, due to the round-off error in standard floating-point
operations, this problem becomes very challenging. Moreover, all existing
solutions rely on sequential algorithms which cannot scale to the huge datasets
that need to be processed.
In this paper, we provide several efficient parallel algorithms for summing n
floating point numbers, so as to produce a faithfully rounded floating-point
representation of the sum. We present algorithms in PRAM, external-memory, and
MapReduce models, and we also provide an experimental analysis of our MapReduce
algorithms, due to their simplicity and practical efficiency.cs.DScs.DCapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1sz8f8z5articleoai:escholarship.org:ark:/13030/qt6342n1k02023-09-27T08:22:20Zqt6342n1k0rasbhari: Optimizing Spaced Seeds for Database Searching, Read Mapping and Alignment-Free Sequence ComparisonHahn, LarsLeimeister, Chris-AndréOunit, RachidLonardi, StefanoMorgenstern, BurkhardPrlic, Andreas2016-01-01Many algorithms for sequence analysis rely on word matching or word statistics. Often, these approaches can be improved if binary patterns representing match and don't-care positions are used as a filter, such that only those positions of words are considered that correspond to the match positions of the patterns. The performance of these approaches, however, depends on the underlying patterns. Herein, we show that the overlap complexity of a pattern set that was introduced by Ilie and Ilie is closely related to the variance of the number of matches between two evolutionarily related sequences with respect to this pattern set. We propose a modified hill-climbing algorithm to optimize pattern sets for database searching, read mapping and alignment-free sequence comparison of nucleic-acid sequences; our implementation of this algorithm is called rasbhari. Depending on the application at hand, rasbhari can either minimize the overlap complexity of pattern sets, maximize their sensitivity in database searching or minimize the variance of the number of pattern-based matches in alignment-free sequence comparison. We show that, for database searching, rasbhari generates pattern sets with slightly higher sensitivity than existing approaches. In our Spaced Words approach to alignment-free sequence comparison, pattern sets calculated with rasbhari led to more accurate estimates of phylogenetic distances than the randomly generated pattern sets that we previously used. Finally, we used rasbhari to generate patterns for short read classification with CLARK-S. Here too, the sensitivity of the results could be improved, compared to the default patterns of the program. We integrated rasbhari into Spaced Words; the source code of rasbhari is freely available at http://rasbhari.gobics.de/.Biological SciencesBioinformatics and Computational BiologyAlgorithmsDNADNA Mutational AnalysisData MiningDatabase Management SystemsDatabasesGeneticMachine LearningPattern RecognitionAutomatedSequence AlignmentSequence AnalysisDNASoftwareq-bio.GNcs.DSq-bio.PEMathematical SciencesInformation and Computing SciencesBioinformaticsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6342n1k0articlePLOS Computational Biology, vol 12, iss 10e1005107oai:escholarship.org:ark:/13030/qt0q52n00r2023-09-27T08:21:50Zqt0q52n00rMECs: "Building Blocks" for Creating Biological and Chemical InstrumentsHill, Douglas AAnderson, Lindsey EHill, Casey JMostaghim, AfshinRodgers, Victor GJGrover, William HEddington, David T2016-01-01The development of new biological and chemical instruments for research and diagnostic applications is often slowed by the cost, specialization, and custom nature of these instruments. New instruments are built from components that are drawn from a host of different disciplines and not designed to integrate together, and once built, an instrument typically performs a limited number of tasks and cannot be easily adapted for new applications. Consequently, the process of inventing new instruments is very inefficient, especially for researchers or clinicians in resource-limited settings. To improve this situation, we propose that a family of standardized multidisciplinary components is needed, a set of "building blocks" that perform a wide array of different tasks and are designed to integrate together. Using these components, scientists, engineers, and clinicians would be able to build custom instruments for their own unique needs quickly and easily. In this work we present the foundation of this set of components, a system we call Multifluidic Evolutionary Components (MECs). "Multifluidic" conveys the wide range of fluid volumes MECs operate upon (from nanoliters to milliliters and beyond); "multi" also reflects the multiple disciplines supported by the system (not only fluidics but also electronics, optics, and mechanics). "Evolutionary" refers to the design principles that enable the library of MEC parts to easily grow and adapt to new applications. Each MEC "building block" performs a fundamental function that is commonly found in biological or chemical instruments, functions like valving, pumping, mixing, controlling, and sensing. Each MEC also has a unique symbol linked to a physical definition, which enables instruments to be designed rapidly and efficiently using schematics. As a proof-of-concept, we use MECs to build a variety of instruments, including a fluidic routing and mixing system capable of manipulating fluid volumes over five orders of magnitude, an acid-base titration instrument suitable for use in schools, and a bioreactor suitable for maintaining and analyzing cell cultures in research and diagnostic applications. These are the first of many instruments that can be built by researchers, clinicians, and students using the MEC system.Information and Computing SciencesBiological SciencesIndustrial BiotechnologyBiotechnologyEquipment DesignHumansLab-On-A-Chip DevicesOptics and PhotonicsGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/0q52n00rarticlePLOS ONE, vol 11, iss 7e0158706oai:escholarship.org:ark:/13030/qt3g27j3fj2023-09-27T07:17:03Zqt3g27j3fjMetal-induced rapid transformation of diamond into single and multilayer graphene on wafer scaleBerman, DianaDeshmukh, Sanket ANarayanan, BadriSankaranarayanan, Subramanian KRSYan, ZhongBalandin, Alexander AZinovev, AlexanderRosenmann, DanielSumant, Anirudha V2016-01-01The degradation of intrinsic properties of graphene during the transfer process constitutes a major challenge in graphene device fabrication, stimulating the need for direct growth of graphene on dielectric substrates. Previous attempts of metal-induced transformation of diamond and silicon carbide into graphene suffers from metal contamination and inability to scale graphene growth over large area. Here, we introduce a direct approach to transform polycrystalline diamond into high-quality graphene layers on wafer scale (4 inch in diameter) using a rapid thermal annealing process facilitated by a nickel, Ni thin film catalyst on top. We show that the process can be tuned to grow single or multilayer graphene with good electronic properties. Molecular dynamics simulations elucidate the mechanism of graphene growth on polycrystalline diamond. In addition, we demonstrate the lateral growth of free-standing graphene over micron-sized pre-fabricated holes, opening exciting opportunities for future graphene/diamond-based electronics.Physical SciencesEngineeringNanotechnologyCondensed Matter Physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3g27j3fjarticleNature Communications, vol 7, iss 112099oai:escholarship.org:ark:/13030/qt26b9t4rp2023-09-27T06:22:56Zqt26b9t4rpQuantum Bayesian approach to circuit QED measurement with moderate bandwidthKorotkov, Alexander N2016-10-01We consider continuous quantum measurement of a superconducting qubit in the
circuit QED setup with a moderate bandwidth of the measurement resonator, i.e.,
when the "bad cavity" limit is not applicable. The goal is a simple description
of the quantum evolution due to measurement, i.e., the measurement back-action.
Extending the quantum Bayesian approach previously developed for the "bad
cavity" regime, we show that the evolution equations remain the same, but now
they should be applied to the entangled qubit-resonator state, instead of the
qubit state alone. The derivation uses only elementary quantum mechanics and
basic properties of coherent states, thus being accessible to non-experts.Quantum PhysicsPhysical SciencesCondensed Matter Physicsquant-phChemical sciencesMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/26b9t4rparticlePhysical Review A, vol 94, iss 4042326oai:escholarship.org:ark:/13030/qt7cv2p16j2023-09-27T05:23:12Zqt7cv2p16jMeasuring a transmon qubit in circuit QED: Dressed squeezed statesKhezri, MostafaMlinar, EricDressel, JustinKorotkov, Alexander N2016-07-01Using circuit QED, we consider the measurement of a superconducting transmon
qubit via a coupled microwave resonator. For ideally dispersive coupling,
ringing up the resonator produces coherent states with frequencies matched to
transmon energy states. Realistic coupling is not ideally dispersive, however,
so transmon-resonator energy levels hybridize into joint eigenstate ladders of
the Jaynes-Cummings type. Previous work has shown that ringing up the resonator
approximately respects this ladder structure to produce a coherent state in the
eigenbasis (a dressed coherent state). We numerically investigate the validity
of this coherent state approximation to find two primary deviations. First,
resonator ring-up leaks small stray populations into eigenstate ladders
corresponding to different transmon states. Second, within an eigenstate ladder
the transmon nonlinearity shears the coherent state as it evolves. We then show
that the next natural approximation for this sheared state in the eigenbasis is
a dressed squeezed state, and derive simple evolution equations for such states
using a hybrid phase-Fock-space description.Quantum PhysicsPhysical Sciencesquant-phChemical sciencesMathematical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7cv2p16jarticlePhysical Review A, vol 94, iss 1012347oai:escholarship.org:ark:/13030/qt4x6487jf2023-09-27T03:18:18Zqt4x6487jfDistance Verification for LDPC CodesDumer, IlyaKovalev, Alexey APryadko, Leonid P2016-07-01The problem of finding code distance has been long studied for the generic
ensembles of linear codes and led to several algorithms that substantially
reduce exponential complexity of this task. However, no asymptotic complexity
bounds are known for distance verification in other ensembles of linear codes.
Our goal is to re-design the existing generic algorithms of distance
verification and derive their complexity for LDPC codes. We obtain new
complexity bounds with provable performance expressed in terms of the
erasure-correcting thresholds of long LDPC codes. These bounds exponentially
reduce complexity estimates known for linear codes.Theory Of ComputationInformation and Computing SciencesApplied MathematicsMathematical SciencesDistance verificationcomplexity boundsLDPC codeserasure correctioncovering setscs.ITmath.ITquant-phapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4x6487jfarticleoai:escholarship.org:ark:/13030/qt90j8f0hz2023-09-27T01:59:17Zqt90j8f0hzInflammatory response to implantation of transparent nanocrystalline yttria-stabilized zirconia using a dorsal window chamber modelDamestani, YasamanGalan-Hoffman, Diego EOrtiz, DanielCabrales, PedroAguilar, Guillermo2016-10-01The long-range goal of the windows to the brain (WttB) is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically-recurring basis without the need for repeated craniotomies. To evaluate the potential of nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant for optical therapy and imaging, in vivo biocompatibility was studied using the dorsal window chamber model in comparison with control (no implant) and commercially available cranial implant materials (PEEK and PEKK). The host tissue response to implant was characterized by using transillumination and fluorescent microscopy to measure leukocyte adhesion, blood vessel diameter, blood flow rate, and vascular permeability over two weeks. The results indicated the lack of inflammatory reaction of the host tissue to nc-YSZ at the microscopic level, suggesting that nc-YSZ is a good alternative material for cranial implants.Biological SciencesChemical SciencesBioengineeringCell AdhesionHumansMaterials TestingMicroscopyElectronScanningNanoparticlesProstheses and ImplantsSkullSurface PropertiesTitaniumYttriumZirconiumWindows to the brainYttria-stabilized-zirconiaCranial implantDorsal window chamber modelTechnologyNanoscience & NanotechnologyBiological sciencesChemical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/90j8f0hzarticleNanomedicine Nanotechnology Biology and Medicine, vol 12, iss 71757 - 1763oai:escholarship.org:ark:/13030/qt16d654jj2023-09-27T01:53:06Zqt16d654jjUsing Adhesive Patterning to Construct 3D Paper Microfluidic Devices.Kalish, BrentTsutsui, Hideaki2016-01-01We demonstrate the use of patterned aerosol adhesives to construct both planar and nonplanar 3D paper microfluidic devices. By spraying an aerosol adhesive through a metal stencil, the overall amount of adhesive used in assembling paper microfluidic devices can be significantly reduced. We show on a simple 4-layer planar paper microfluidic device that the optimal adhesive application technique and device construction style depends heavily on desired performance characteristics. By moderately increasing the overall area of a device, it is possible to dramatically decrease the wicking time and increase device success rates while also reducing the amount of adhesive required to keep the device together. Such adhesive application also causes the adhesive to form semi-permanent bonds instead of permanent bonds between paper layers, enabling single-use devices to be non-destructively disassembled after use. Nonplanar 3D origami devices also benefit from the semi-permanent bonds during folding, as it reduces the likelihood that unrelated faces may accidently stick together. Like planar devices, nonplanar structures see reduced wicking times with patterned adhesive application vs uniformly applied adhesive.Biochemistry and Cell BiologyBiological SciencesBioengineeringAdhesivesAerosolsLab-On-A-Chip DevicesMicrofluidic Analytical TechniquesPaperIssue 110Paper microfluidicsnonplanarorigamiaerosol adhesivethree-dimensionalstencilpatterningPsychologyCognitive SciencesBiochemistry and cell biologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/16d654jjarticleJournal of Visualized Experiments, vol 2016, iss 110e53805oai:escholarship.org:ark:/13030/qt9cb8k4632023-09-27T01:53:03Zqt9cb8k463Electrostatic Steering Accelerates C3d:CR2 AssociationMohan, Rohith RHuber, Gary AMorikis, Dimitrios2016-08-25Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts.Chemical SciencesTheoretical and Computational ChemistryBioengineeringComplement C3dComputer SimulationModelsMolecularMutationProtein BindingReceptorsComplement 3dStatic ElectricityPhysical SciencesEngineeringChemical sciencesPhysical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9cb8k463articleThe Journal of Physical Chemistry B, vol 120, iss 338416 - 8423oai:escholarship.org:ark:/13030/qt8pd223692023-09-27T00:32:11Zqt8pd22369Quantitative Modeling of the Alternative Pathway of the Complement SystemZewde, NehemiahGorham, Ronald DDorado, AngelMorikis, DimitriosSaiz, Leonor2016-01-01The complement system is an integral part of innate immunity that detects and eliminates invading pathogens through a cascade of reactions. The destructive effects of the complement activation on host cells are inhibited through versatile regulators that are present in plasma and bound to membranes. Impairment in the capacity of these regulators to function in the proper manner results in autoimmune diseases. To better understand the delicate balance between complement activation and regulation, we have developed a comprehensive quantitative model of the alternative pathway. Our model incorporates a system of ordinary differential equations that describes the dynamics of the four steps of the alternative pathway under physiological conditions: (i) initiation (fluid phase), (ii) amplification (surfaces), (iii) termination (pathogen), and (iv) regulation (host cell and fluid phase). We have examined complement activation and regulation on different surfaces, using the cellular dimensions of a characteristic bacterium (E. coli) and host cell (human erythrocyte). In addition, we have incorporated neutrophil-secreted properdin into the model highlighting the cross talk of neutrophils with the alternative pathway in coordinating innate immunity. Our study yields a series of time-dependent response data for all alternative pathway proteins, fragments, and complexes. We demonstrate the robustness of alternative pathway on the surface of pathogens in which complement components were able to saturate the entire region in about 54 minutes, while occupying less than one percent on host cells at the same time period. Our model reveals that tight regulation of complement starts in fluid phase in which propagation of the alternative pathway was inhibited through the dismantlement of fluid phase convertases. Our model also depicts the intricate role that properdin released from neutrophils plays in initiating and propagating the alternative pathway during bacterial infection.Biochemistry and Cell BiologyBiological SciencesInfectious DiseasesUnderpinning research1.1 Normal biological development and functioningInfectionComplement PathwayAlternativeComplement System ProteinsEscherichia coliHumansImmunityInnateModelsBiologicalNeutrophilsProperdinGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8pd22369articlePLOS ONE, vol 11, iss 3e0152337oai:escholarship.org:ark:/13030/qt8rr896xg2023-09-26T23:49:21Zqt8rr896xgChannel Estimation, Carrier Recovery, and Data Detection in the Presence of Phase Noise in OFDM Relay SystemsWang, RuiMehrpouyan, HaniTao, MeixiaHua, Yingbo2016-01-01Due to its time-varying nature, oscillator phase noise can significantly degrade the performance of the channel estimation, carrier recovery, and data detection blocks in high-speed wireless communication systems. In this paper, we propose a new data-aided joint channel, carrier frequency offset (CFO) and phase noise estimator for orthogonal frequency division multiplexing (OFDM) relay systems. For the data transmission phase, we propose a new iterative receiver that tracks phase noise and detects the transmitted symbols. Additionally, we derive the hybrid Cramér-Rao lower bound for evaluating the performance of channel estimation and carrier recovery algorithms in OFDM relay networks. Extensive simulations demonstrate that the application of the proposed estimation and receiver blocks significantly improves the performance of OFDM relay networks in the presence of phase noise and CFO.Theory Of ComputationEngineeringInformation and Computing SciencesCommunications EngineeringComputer Vision and Multimedia ComputationRelayorthogonal frequency division multiplexingchannel estimationphase noiseDistributed ComputingElectrical and Electronic EngineeringCommunications TechnologiesNetworking & TelecommunicationsCommunications engineeringElectrical engineeringDistributed computing and systems softwarepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8rr896xgarticleIEEE Transactions on Wireless Communications, vol 15, iss 21186 - 1205oai:escholarship.org:ark:/13030/qt7sk0z85g2023-09-26T23:02:26Zqt7sk0z85gOrientation-Based Control of MicrofluidicsNorouzi, NazilaBhakta, Heran CGrover, William HUgaz, Victor M2016-01-01Most microfluidic chips utilize off-chip hardware (syringe pumps, computer-controlled solenoid valves, pressure regulators, etc.) to control fluid flow on-chip. This expensive, bulky, and power-consuming hardware severely limits the utility of microfluidic instruments in resource-limited or point-of-care contexts, where the cost, size, and power consumption of the instrument must be limited. In this work, we present a technique for on-chip fluid control that requires no off-chip hardware. We accomplish this by using inert compounds to change the density of one fluid in the chip. If one fluid is made 2% more dense than a second fluid, when the fluids flow together under laminar flow the interface between the fluids quickly reorients to be orthogonal to Earth's gravitational force. If the channel containing the fluids then splits into two channels, the amount of each fluid flowing into each channel is precisely determined by the angle of the channels relative to gravity. Thus, any fluid can be routed in any direction and mixed in any desired ratio on-chip simply by holding the chip at a certain angle. This approach allows for sophisticated control of on-chip fluids with no off-chip control hardware, significantly reducing the cost of microfluidic instruments in point-of-care or resource-limited settings.Fluid Mechanics and Thermal EngineeringEngineeringBiotechnologyEquipment DesignGravitationLab-On-A-Chip DevicesRotationGeneral Science & TechnologypubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7sk0z85garticlePLOS ONE, vol 11, iss 3e0149259oai:escholarship.org:ark:/13030/qt00t175bh2023-09-26T23:02:16Zqt00t175bhSemantic Concept Co-Occurrence Patterns for Image Annotation and RetrievalFeng, LinanBhanu, Bir2016-04-01Describing visual image contents by semantic concepts is an effective and straightforward way to facilitate various high level applications. Inferring semantic concepts from low-level pictorial feature analysis is challenging due to the semantic gap problem, while manually labeling concepts is unwise because of a large number of images in both online and offline collections. In this paper, we present a novel approach to automatically generate intermediate image descriptors by exploiting concept co-occurrence patterns in the pre-labeled training set that renders it possible to depict complex scene images semantically. Our work is motivated by the fact that multiple concepts that frequently co-occur across images form patterns which could provide contextual cues for individual concept inference. We discover the co-occurrence patterns as hierarchical communities by graph modularity maximization in a network with nodes and edges representing concepts and co-occurrence relationships separately. A random walk process working on the inferred concept probabilities with the discovered co-occurrence patterns is applied to acquire the refined concept signature representation. Through experiments in automatic image annotation and semantic image retrieval on several challenging datasets, we demonstrate the effectiveness of the proposed concept co-occurrence patterns as well as the concept signature representation in comparison with state-of-the-art approaches.Data Management and Data ScienceInformation and Computing SciencesComputer Vision and Multimedia ComputationCommunity detectioncontextual informationhierarchical co-occurrence patternsimage concept signatureArtificial Intelligence and Image ProcessingInformation SystemsElectrical and Electronic EngineeringArtificial Intelligence & Image ProcessingComputer vision and multimedia computationMachine learningapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/00t175bharticleIEEE Transactions on Pattern Analysis and Machine Intelligence, vol 38, iss 4785 - 799oai:escholarship.org:ark:/13030/qt4zb8t2g52023-09-26T23:02:12Zqt4zb8t2g5Segmentation of Pollen Tube Growth Videos Using Dynamic Bi-Modal Fusion and Seam CarvingTambo, Asongu LBhanu, Bir2016-05-01The growth of pollen tubes is of significant interest in plant cell biology, as it provides an understanding of internal cell dynamics that affect observable structural characteristics such as cell diameter, length, and growth rate. However, these parameters can only be measured in experimental videos if the complete shape of the cell is known. The challenge is to accurately obtain the cell boundary in noisy video images. Usually, these measurements are performed by a scientist who manually draws regions-of-interest on the images displayed on a computer screen. In this paper, a new automated technique is presented for boundary detection by fusing fluorescence and brightfield images, and a new efficient method of obtaining the final cell boundary through the process of Seam Carving is proposed. This approach takes advantage of the nature of the fusion process and also the shape of the pollen tube to efficiently search for the optimal cell boundary. In video segmentation, the first two frames are used to initialize the segmentation process by creating a search space based on a parametric model of the cell shape. Updates to the search space are performed based on the location of past segmentations and a prediction of the next segmentation.Experimental results show comparable accuracy to a previous method, but significant decrease in processing time. This has the potential for real time applications in pollen tube microscopy.Information and Computing SciencesComputer Vision and Multimedia ComputationBioengineeringAlgorithmsImage ProcessingComputer-AssistedMicroscopyFluorescenceModelsBiologicalPollen TubeVideo RecordingArtificial Intelligence and Image ProcessingElectrical and Electronic EngineeringCognitive SciencesArtificial Intelligence & Image ProcessingComputer vision and multimedia computationGraphicsaugmented reality and gamespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4zb8t2g5articleIEEE Transactions on Image Processing, vol 25, iss 51993 - 2004oai:escholarship.org:ark:/13030/qt299901q12023-09-26T22:55:58Zqt299901q1Scalable Multifunctional Ultra-thin Graphite Sponge: Free-standing, Superporous, Superhydrophobic, Oleophilic Architecture with Ferromagnetic Properties for Environmental CleaningBay, Hamed HosseiniPatino, DaisyMutlu, ZaferRomero, PaigeOzkan, MihrimahOzkan, Cengiz S2016-01-01Water decontamination and oil/water separation are principal motives in the surge to develop novel means for sustainability. In this prospect, supplying clean water for the ecosystems is as important as the recovery of the oil spills since the supplies are scarce. Inspired to design an engineering material which not only serves this purpose, but can also be altered for other applications to preserve natural resources, a facile template-free process is suggested to fabricate a superporous, superhydrophobic ultra-thin graphite sponge. Moreover, the process is designed to be inexpensive and scalable. The fabricated sponge can be used to clean up different types of oil, organic solvents, toxic and corrosive contaminants. This versatile microstructure can retain its functionality even when pulverized. The sponge is applicable for targeted sorption and collection due to its ferromagnetic properties. We hope that such a cost-effective process can be embraced and implemented widely.EngineeringMaterials Engineeringapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/299901q1articleScientific Reports, vol 6, iss 121858oai:escholarship.org:ark:/13030/qt88j5k5h52023-09-26T22:49:16Zqt88j5k5h5Exercise-driven metabolic pathways in healthy cartilageBlazek, ADNam, JGupta, RPradhan, MPerera, PWeisleder, NLHewett, TEChaudhari, AMLee, BSLeblebicioglu, BButterfield, TAAgarwal, S2016-07-01ObjectiveExercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for the potential benefits of exercise.MethodsTranscriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays. Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO)-term enrichment and Functional Annotation analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genome (KEGG) pathway mapper was used to identify the metabolic pathways regulated by exercise.ResultsMicroarray analysis revealed that exercise-induced 644 DEGs in healthy articular cartilage. The DAVID bioinformatics tool demonstrated high prevalence of functional annotation clusters with greater enrichment scores and GO-terms associated with extracellular matrix (ECM) biosynthesis/remodeling and inflammation/immune response. The KEGG database revealed that exercise regulates 147 metabolic pathways representing molecular interaction networks for Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Diseases. These pathways collectively supported the complex regulation of the beneficial effects of exercise on the cartilage.ConclusionsOverall, the findings highlight that exercise is a robust transcriptional regulator of a wide array of metabolic pathways in healthy cartilage. The major actions of exercise involve ECM biosynthesis/cartilage strengthening and attenuation of inflammatory pathways to provide prophylaxis against onset of arthritic diseases in healthy cartilage.Biomedical and Clinical SciencesHealth SciencesClinical SciencesSports Science and ExerciseBiotechnologyGeneticsArthritisHuman GenomePreventionMusculoskeletalAnimalsCartilageFemaleGene Expression ProfilingGene Expression RegulationMetabolic Networks and PathwaysOligonucleotide Array Sequence AnalysisRatsRatsSprague-DawleyTranscriptomeExerciseOsteoarthritisMetabolic pathwaysGene expressionBiomedical EngineeringHuman Movement and Sports SciencesArthritis & RheumatologyClinical sciencesSports science and exerciseapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/88j5k5h5articleOsteoarthritis and Cartilage, vol 24, iss 71210 - 1222oai:escholarship.org:ark:/13030/qt5081k3j12023-09-26T21:51:58Zqt5081k3j1Biofunctionalized Nanostructured Zirconia for Biomedical Application: A Smart Approach for Oral Cancer DetectionKumar, SuveenKumar, SaurabhTiwari, SachchidanandSrivastava, SaurabhSrivastava, ManishYadav, Birendra KumarKumar, SarojTran, Thien ToanDewan, Ajay KumarMulchandani, AshokSharma, Jai GopalMaji, SagarMalhotra, Bansi Dhar2015-08-01Results of the studies are reported relating to application of the silanized nanostructured zirconia, electrophoretically deposited onto indium tin oxide (ITO) coated glass for covalent immobilization of the monoclonal antibodies (anti-CYFRA-21-1). This biosensing platform has been utilized for a simple, efficient, noninvasive, and label-free detection of oral cancer via cyclic voltammetry technique. The results of electrochemical response studies conducted on bovine serum albumin (BSA)/anti-CYFRA-21-1/3-aminopropyl triethoxy silane (APTES)/ZrO2/ITO immunoelectrode reveal that this immunoelectrode can be used to measure CYFRA-21-1 (oral cancer biomarker) concentration in saliva samples, with a high sensitivity of 2.2 mA mL ng-1, a linear detection range of 2-16 ng mL-1, and stability of six weeks. The results of these studies have been validated via enzyme-linked immunosorbent assay.Analytical ChemistryChemical SciencesDental/Oral and Craniofacial DiseaseCancerPreventionCYFRA‐21‐1biosensorsnoninvasive detectionoral cancerzirconiaapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5081k3j1articleAdvanced Science, vol 2, iss 81500048oai:escholarship.org:ark:/13030/qt9m03t8jp2023-09-26T19:08:41Zqt9m03t8jpSchool-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5-Year Follow-Up from the Infant Development, Environment, and Lifestyle StudyEze, NwandoSmith, Lynne MLaGasse, Linda LDerauf, ChrisNewman, ElanaArria, AmeliaHuestis, Marilyn ADella Grotta, Sheri ADansereau, Lynne MNeal, CharlesLester, Barry M2016-03-01ObjectiveTo assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years and the extent to which early adversity mediated this relationship.Study designThe multicenter, longitudinal Infant Development, Environment, and Lifestyle study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5-year follow-up, 290 children with complete Child Behavior Checklist data and an early adversity index score were available for analysis (n = 146 exposed).ResultsPME was significantly associated with an increased early adversity index score (P < .001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P < .05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant.ConclusionsThough PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems.PaediatricsBiomedical and Clinical SciencesBasic Behavioral and Social ScienceDrug Abuse (NIDA only)Perinatal Period - Conditions Originating in Perinatal PeriodBehavioral and Social ScienceSubstance MisuseMethamphetaminePreventionPediatricMental healthGood Health and Well BeingAmphetamine-Related DisordersCentral Nervous System StimulantsChildChild BehaviorChildPreschoolDevelopmental DisabilitiesEnvironmentFemaleFollow-Up StudiesGas Chromatography-Mass SpectrometryHumansInfantInfantNewbornLife StyleLongitudinal StudiesMaleMothersPregnancyPrenatal Exposure Delayed EffectsHuman Movement and Sports SciencesPaediatrics and Reproductive MedicinePediatricsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9m03t8jparticleoai:escholarship.org:ark:/13030/qt4j00c6cp2023-09-26T19:03:19Zqt4j00c6cpAPPROXIMATE DATA-STRUCTURES WITH APPLICATIONSMATIAS, YVITTER, JSYOUNG, NE1994-01-01In this paper we introduce the notion of approximate data structures, in which a small amount of error is tolerated in the output. Approximate data structures trade error of approximation for faster operation, leading to theoretical and practical speedups for a wide variety of algorithms. We give approximate variants of the van Emde Boas data structure, which support the same dynamic operations as the standard van Emde Boas data structure, except that answers to queries are approximate. The variants support all operations in constant time provided the error of approximation is 1/polylog(n), and in O(log log n) time provided the error is 1/polynomial(n), for n elements in the data structure. We consider the tolerance of prototypical algorithms to approximate data structures. We study in particular Prim's minimum spanning tree algorithm, Dijkstra's single-source shortest paths algorithm, and an on-line variant of Graham's convex hull algorithm. To obtain output which approximates the desired output with the error of approximation tending to zero, Prim's algorithm requires only linear time, Dijkstra's algorithm requires O(m log log n) time, and the on-line variant of Graham's algorithm requires constant amortized time per operation.cs.DScs.CCF.2.0F.1.3publiceScholarship, University of Californiahttps://escholarship.org/uc/item/4j00c6cparticleoai:escholarship.org:ark:/13030/qt3b49p20z2023-09-26T18:55:45Zqt3b49p20zA software system for automated identification and retrieval of moth images based on wing attributesFeng, LinanBhanu, BirHeraty, John2016-03-01© 2015 Elsevier Ltd. Manually collecting, identifying, archiving and retrieving specimen images is an expensive and time-consuming work for entomologists. There is a clear need to introduce fast systems integrated with modern image processing and analysis algorithms to accelerate the process. In this paper, we describe the development of an automated moth species identification and retrieval system (SPIR) using computer vision and pattern recognition techniques. The core of the system is a probabilistic model that infers Semantically Related Visual (SRV) attributes from low-level visual features of moth images in the training set, where moth wings are segmented into information-rich patches from which the local features are extracted, and the SRV attributes are provided by human experts as ground-truth. For the large amount of unlabeled test images in the database or added into the database later on, an automated identification process is evoked to translate the detected salient regions of low-level visual features on the moth wings into meaningful semantic SRV attributes. We further propose a novel network analysis based approach to explore and utilize the co-occurrence patterns of SRV attributes as contextual cues to improve individual attribute detection accuracy. Working with a small set of labeled training images, the approach constructs a network with nodes representing the SRV attributes and weighted edges denoting the co-occurrence correlation. A fast modularity maximization algorithm is proposed to detect the co-occurrence patterns as communities in the network. A random walk process working on the discovered co-occurrence patterns is applied to refine the individual attribute detection results. The effectiveness of the proposed approach is evaluated in automated moth identification and attribute-based image retrieval. In addition, a novel image descriptor called SRV attribute signature is introduced to record the visual and semantic properties of an image and is used to compare image similarity. Experiments are performed on an existing entomology database to illustrate the capabilities of our proposed system. We observed that the system performance is improved by the SRV attribute representation and their co-occurrence patterns.Data Management and Data ScienceInformation and Computing SciencesArtificial IntelligenceComputer Vision and Multimedia ComputationBioengineeringClinical ResearchEntomological image identification and retrievalSemantically related visual attributesAttribute co-occurrence pattern detectionArtificial Intelligence and Image ProcessingInformation SystemsElectrical and Electronic EngineeringArtificial Intelligence & Image ProcessingComputer vision and multimedia computationData management and data scienceMachine learningpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3b49p20zarticleoai:escholarship.org:ark:/13030/qt6bk3p9xr2023-09-26T18:44:41Zqt6bk3p9xrReconstruction of laser-induced cavitation bubble dynamics based on a Fresnel propagation approach.Devia-Cruz, Luis FelipeCamacho-López, SantiagoCortés, Víctor RuizRamos-Muñiz, VictoriaPérez-Gutiérrez, Francisco GAguilar, Guillermo2015-12-10A single laser-induced cavitation bubble in transparent liquids has been studied through a variety of experimental techniques. High-speed video with varying frame rate up to 20×10(7) fps is the most suitable to study nonsymmetric bubbles. However, it is still expensive for most researchers and more affordable (lower) frame rates are not enough to completely reproduce bubble dynamics. This paper focuses on combining the spatial transmittance modulation (STM) technique, a single shot cavitation bubble and a very simple and inexpensive experimental technique, based on Fresnel approximation propagation theory, to reproduce a laser-induced cavitation spatial dynamics. Our results show that the proposed methodology reproduces a laser-induced cavitation event much more accurately than 75,000 fps video recording. In conclusion, we propose a novel methodology to reproduce laser-induced cavitation events that combine the STM technique with Fresnel propagation approximation theory that properly reproduces a laser-induced cavitation event including a very precise identification of the first, second, and third collapses of the cavitation bubble.EngineeringElectrical EngineeringOptical PhysicsElectrical and Electronic EngineeringMechanical EngineeringOpticsElectrical engineeringAtomicmolecular and optical physicsapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6bk3p9xrarticleApplied Optics, vol 54, iss 3510432 - 10437oai:escholarship.org:ark:/13030/qt1st0d4m22023-09-26T16:29:01Zqt1st0d4m2Tutorial on Structured Continuous-Time Markov ProcessesShelton, CRCiardo, G2014-01-01A continuous-time Markov process (CTMP) is a collection of variables indexed by a continuous quantity, time. It obeys the Markov property that the distribution over a future variable is independent of past variables given the state at the present time. We introduce continuous-time Markov process representations and algorithms for filtering, smoothing, expected sufficient statistics calculations, and model estimation, assuming no prior knowledge of continuous-time processes but some basic knowledge of probability and statistics. We begin by describing "flat" or unstructured Markov processes and then move to structured Markov processes (those arising from state spaces consisting of assignments to variables) including Kronecker, decision-diagram, and continuous-time Bayesian network representations. We provide the first connection between decision-diagrams and continuous-time Bayesian networks.Computer Vision and Multimedia ComputationInformation and Computing SciencesArtificial IntelligenceMachine LearningApplied MathematicsArtificial Intelligence and Image ProcessingCognitive SciencesArtificial Intelligence & Image ProcessingArtificial intelligenceComputer vision and multimedia computationMachine learningapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1st0d4m2articleoai:escholarship.org:ark:/13030/qt6253p8fw2023-09-26T16:27:53Zqt6253p8fwPredicting the Activity Coefficients of Free-Solvent for Concentrated Globular Protein Solutions Using Independently Determined Physical ParametersMcBride, Devin WRodgers, Victor GJRoccatano, Danilo2013-01-01The activity coefficient is largely considered an empirical parameter that was traditionally introduced to correct the non-ideality observed in thermodynamic systems such as osmotic pressure. Here, the activity coefficient of free-solvent is related to physically realistic parameters and a mathematical expression is developed to directly predict the activity coefficients of free-solvent, for aqueous protein solutions up to near-saturation concentrations. The model is based on the free-solvent model, which has previously been shown to provide excellent prediction of the osmotic pressure of concentrated and crowded globular proteins in aqueous solutions up to near-saturation concentrations. Thus, this model uses only the independently determined, physically realizable quantities: mole fraction, solvent accessible surface area, and ion binding, in its prediction. Predictions are presented for the activity coefficients of free-solvent for near-saturated protein solutions containing either bovine serum albumin or hemoglobin. As a verification step, the predictability of the model for the activity coefficient of sucrose solutions was evaluated. The predicted activity coefficients of free-solvent are compared to the calculated activity coefficients of free-solvent based on osmotic pressure data. It is observed that the predicted activity coefficients are increasingly dependent on the solute-solvent parameters as the protein concentration increases to near-saturation concentrations.EngineeringMedicinal and Biomolecular ChemistryChemical SciencesAnimalsCattleChemical PhenomenaHemoglobinsHydrogen-Ion ConcentrationSerum AlbuminBovineSheepSolutionsSolventsSucroseGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6253p8fwarticlePLOS ONE, vol 8, iss 12e81933oai:escholarship.org:ark:/13030/qt6xg1852d2023-09-26T16:24:27Zqt6xg1852dHigh-Level Language Tools for Reconfigurable ComputingWindh, SkylerMa, XiaoyinHalstead, Robert JBudhkar, PrernaLuna, ZabdielHussaini, OmarNajjar, Walid A2015-01-01In the past decade or so we have witnessed a steadily increasing interest in FPGAs as hardware accelerators: they provide an excellent mid-point between the reprogrammability of software devices (CPUs, DSPs, and GPUs) and the performance and low energy consumption of ASICs. However, the programmability of FPGA-based accelerators remains one of the biggest obstacles to their wider adoption. Developing FPGA programs requires extensive familiarity with hardware design and experience with a tedious and complex tool chain. For half a century, layers of abstractions have been developed that simplify the software development process: languages, compilers, dynamically linked libraries, operating systems, APIs, etc. Very little, if any, such abstractions exist in the development of FPGA programs. In this paper, we review the history of using FPGAs as hardware accelerators and summarize the challenges facing the raising of the programming abstraction layers. We survey five High-Level Language tools for the development of FPGA programs: Xilinx Vivado, Altera OpenCL, BluespecBSV, ROCCC, and LegUp to provide an overview of their tool flow, the optimizations they provide, and a qualitative analysis of their hardware implementations of high level code.EngineeringElectronicsSensors and Digital HardwareAffordable and Clean EnergyCompiler optimizationhigh level synthesismax filterreconfigurable computingArtificial Intelligence and Image ProcessingBiomedical EngineeringElectrical and Electronic EngineeringElectronicssensors and digital hardwareapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6xg1852darticleProceedings of the IEEE, vol 103, iss 3390 - 408oai:escholarship.org:ark:/13030/qt6m52000v2023-09-26T16:23:43Zqt6m52000vAccelerating the Dynamic Time Warping Distance Measure using Logarithmetic ArithmeticTarango, JosephKeogh, EamonnBrisk, PhilipMatthews, Michael B2014-11-01This paper describes an application-specific embedded processor with instruction set extensions (ISEs) for the Dynamic Time Warping (DTW) distance measure, which is widely used in time series similarity search. The ISEs in this paper are implemented using a form of logarithmic arithmetic that offers significant performance and power/energy advantages compared to more traditional floating-point operations.EngineeringElectrical EngineeringTime seriessimilarity searchapplication-specific processorInstruction Set extensionEuclidean DistanceDynamic Time Warpingfloating-point arithmeticlogarithmic arithmeticpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6m52000varticleoai:escholarship.org:ark:/13030/qt8cn5k4qg2023-09-26T16:23:16Zqt8cn5k4qgIntracellular Water Exchange for Measuring the Dry Mass, Water Mass and Changes in Chemical Composition of Living CellsDelgado, Francisco FeijóCermak, NathanHecht, Vivian CSon, SungminLi, YingzhongKnudsen, Scott MOlcum, SelimHiggins, John MChen, JianzhuGrover, William HManalis, Scott RPolymenis, Michael2013-01-01We present a method for direct non-optical quantification of dry mass, dry density and water mass of single living cells in suspension. Dry mass and dry density are obtained simultaneously by measuring a cell's buoyant mass sequentially in an H2O-based fluid and a D2O-based fluid. Rapid exchange of intracellular H2O for D2O renders the cell's water content neutrally buoyant in both measurements, and thus the paired measurements yield the mass and density of the cell's dry material alone. Utilizing this same property of rapid water exchange, we also demonstrate the quantification of intracellular water mass. In a population of E. coli, we paired these measurements to estimate the percent dry weight by mass and volume. We then focused on cellular dry density - the average density of all cellular biomolecules, weighted by their relative abundances. Given that densities vary across biomolecule types (RNA, DNA, protein), we investigated whether we could detect changes in biomolecular composition in bacteria, fungi, and mammalian cells. In E. coli, and S. cerevisiae, dry density increases from stationary to exponential phase, consistent with previously known increases in the RNA/protein ratio from up-regulated ribosome production. For mammalian cells, changes in growth conditions cause substantial shifts in dry density, suggesting concurrent changes in the protein, nucleic acid and lipid content of the cell.Biochemistry and Cell BiologyBiological SciencesGeneric health relevanceAnimalsBiological TransportDNADeuterium Exchange MeasurementErythrocytesEscherichia coliFibroblastsHumansLipidsMiceProteinsRNASaccharomyces cerevisiaeT-LymphocytesWaterGeneral Science & Technologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/8cn5k4qgarticlePLOS ONE, vol 8, iss 7e67590oai:escholarship.org:ark:/13030/qt6k74m6dn2023-09-26T16:00:18Zqt6k74m6dnApproximation Algorithms for the Joint Replenishment Problem with DeadlinesBienkowski, MarcinByrka, JaroslawChrobak, MarekDobbs, NeilNowicki, TomaszSviridenko, MaximSwirszcz, GrzegorzYoung, Neal E2013-01-01The Joint Replenishment Problem ((Formula presented.)) is a fundamental optimization problem in supply-chain management, concerned with optimizing the flow of goods from a supplier to retailers. Over time, in response to demands at the retailers, the supplier ships orders, via a warehouse, to the retailers. The objective is to schedule these orders to minimize the sum of ordering costs and retailers' waiting costs. We study the approximability of (Formula presented.), the version of (Formula presented.) with deadlines, where instead of waiting costs the retailers impose strict deadlines. We study the integrality gap of the standard linear-program (LP) relaxation, giving a lower bound of (Formula presented.), a stronger, computer-assisted lower bound of (Formula presented.), as well as an upper bound and approximation ratio of (Formula presented.). The best previous upper bound and approximation ratio was (Formula presented.); no lower bound was previously published. For the special case when all demand periods are of equal length, we give an upper bound of (Formula presented.), a lower bound of (Formula presented.), and show APX-hardness. © 2014 Springer Science+Business Media New York.Artificial Intelligence & Image ProcessingInformation and computing sciencespubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6k74m6dnarticleoai:escholarship.org:ark:/13030/qt2bc105n92023-09-26T16:00:00Zqt2bc105n9SHARED MEMORY HETEROGENEOUS COMPUTATION ON PCIE-SUPPORTED PLATFORMSShukla, Sambit KYang, YangBhuyan, Laxmi NBrisk, Philip2013-09-01Domain-disparity between CPU and Hardware Accelerators(HA) leads to CPU under-utilization and inter-domain data copy overheads. By exposing HA memory to OS and host MMU, these overheads can be eliminated. In this paper, we present a shared virtual memory real system design for PCIe-based HAs to enable parallel heterogeneous execution in CPU and HAs without driver overheads. We extend Linux with a custom memory manager and scheduler to manage HA memory and application-cores respectively. Our FPGA-based multi-application logic design supports simultaneous execution of multiple heterogeneous applications. We show the advantages of heterogeneous execution and analyze how our design reduces OS overhead. © 2013 IEEE.Distributed Computing and Systems SoftwareInformation and Computing SciencesArchitectureBuilt Environment and DesignpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2bc105n9articleoai:escholarship.org:ark:/13030/qt9g32205p2023-09-26T15:45:47Zqt9g32205pA generalized free-solvent model for the osmotic pressure of multi-component solutions containing protein–protein interactionsMcBride, Devin WRodgers, VGJ2014-07-01The free-solvent model has been shown to have excellent predictability of the osmotic pressure for single and binary non-interactive proteins in aqueous solutions. Here the free-solvent model is extended to be more generalized by including the contributions of intra- and inter-protein interactions to the osmotic pressure of a solution in the form of homo- and hetero-multimers. The solute-solvent interactions are considered to be unique for each homo- and hetero-multimer in solution. The effect of the various generalized free-solvent model parameters on the osmotic pressure are examined for a single protein solution with a homo-dimer, a binary protein solution with no protein-protein interactions, and a binary protein solution with a hetero-dimer. Finally, the limitations associated with the generalized free-solvent model are discussed.Biological SciencesMathematical SciencesChemical PhenomenaMathematical ConceptsModelsChemicalOsmotic PressureProtein Interaction Domains and MotifsProtein MultimerizationProteinsSolutionsSolventsFree-solvent modelOsmotic pressureMulti-component Crowded proteinIon bindingHydrationCrowded proteinMulti-componentBioinformaticsBiological sciencesMathematical sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9g32205particleMathematical Biosciences, vol 253, iss 172 - 87oai:escholarship.org:ark:/13030/qt1pz512nd2023-09-26T15:40:08Zqt1pz512ndALGORITHMIC APPROACHES TO SELECTING CONTROL CLONES IN DNA ARRAY HYBRIDIZATION EXPERIMENTSFU, QBENT, EBORNEMAN, JCHROBAK, MYOUNG, N2007-01-01We study the problem of selecting control clones in DNA array hybridization experiments. The problem arises in the OFRG method for analyzing microbial communities. The OFRG method performs classification of rRNA gene clones using binary fingerprints created from a series of hybridization experiments, where each experiment consists of hybridizing a collection of arrayed clones with a single oligonucleotide probe. This experiment produces analog signals, one for each clone, which then need to be classified, that is, converted into binary values 1 and 0 that represent hybridization and non-hybridization events. Besides the sample clones, the array contains a number of control clones needed to calibrate the classification procedure of the hybridization signals. These control clones must be selected with care to optimize the classification process. We formulate this as a combinatorial optimization problem called Balanced Covering. We prove that the problem is NP-hard and we show some results on hardness of approximation. We propose an approximation algorithm based on randomized rounding and we show that, with high probability, it approximates well the optimum. The experimental results confirm that the algorithm finds high quality control clones. The algorithm has been implemented and is publicly available as part of the software package called CloneTools.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1pz512ndarticleoai:escholarship.org:ark:/13030/qt1fc1s79g2023-09-26T15:39:40Zqt1fc1s79gMultitarget Tracking in Nonoverlapping Cameras Using a Reference SetChen, XiaojingAn, LeBhanu, Bir2015-01-01Tracking multiple targets in nonoverlapping cameras are challenging since the observations of the same targets are often separated by time and space. There might be significant appearance change of a target across camera views caused by variations in illumination conditions, poses, and camera imaging characteristics. Consequently, the same target may appear very different in two cameras. Therefore, associating tracks in different camera views directly based on their appearance similarity is difficult and prone to error. In most previous methods, the appearance similarity is computed either using color histograms or based on pretrained brightness transfer function that maps color between cameras. In this paper, a novel reference set based appearance model is proposed to improve multitarget tracking in a network of nonoverlapping cameras. Contrary to previous work, a reference set is constructed for a pair of cameras, containing subjects appearing in both camera views. For track association, instead of directly comparing the appearance of two targets in different camera views, they are compared indirectly via the reference set. Besides global color histograms, texture and shape features are extracted at different locations of a target, and AdaBoost is used to learn the discriminative power of each feature. The effectiveness of the proposed method over the state of the art on two challenging real-world multicamera video data sets is demonstrated by thorough experiments.EngineeringMulti-target trackingreference setsurveillanceOptical PhysicsElectrical and Electronic EngineeringMechanical EngineeringAnalytical Chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1fc1s79garticleIEEE Sensors Journal, vol 15, iss 52692 - 2704oai:escholarship.org:ark:/13030/qt6m7768w52023-09-26T15:39:36Zqt6m7768w5Guest Editorial Special Issue on Distributed Smart Sensing for Mobile VisionBhanu, BirLovell, BrianPrati, AndreaQureshi, Faisal2015-01-01The recent advances in hardware and software related to distributed smart sensing have opened unprecedented opportunities for building effective solutions to applications, such as object detection, tracking and recognition for surveillance, mobile medical imaging, distributed video monitoring/retrieval, gesture recognition, etc.EngineeringOptical PhysicsElectrical and Electronic EngineeringMechanical EngineeringAnalytical Chemistryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6m7768w5articleIEEE Sensors Journal, vol 15, iss 52631 - 2631oai:escholarship.org:ark:/13030/qt9p82b4892023-09-26T15:28:51Zqt9p82b489Thermally labile components of aqueous humor potently induce osteogenic potential in adipose-derived mesenchymal stem cellsMorgan, Joshua TKwon, Heung SunWood, Joshua ABorjesson, Dori LTomarev, Stanislav IMurphy, Christopher JRussell, Paul2015-06-01Adipose-derived mesenchymal stem cells (ASCs) hold promise for use in cell-based therapies. Their intrinsic anti-inflammatory properties are potentially useful for treatments of inflammatory conditions such as uveitis, while their ability to differentiate along multiple cell lineages suggests use in regenerating damaged or degenerated tissue. However, how ASCs will respond to the intraocular environment is poorly studied. We have recently reported that aqueous humor (AH), the fluid that nourishes the anterior segment of the eye, potently increases alkaline phosphatase (ALP) activity of ASCs, indicating osteogenic differentiation. Here, we expand on our previous findings to better define the nature of this response. To this end, we cultured ASCs in the presence of 0, 5, 10, and 20% AH and assayed them for ALP activity. We found ALP activity correlates with increasing AH concentrations from 5 to 20%, and that longer treatments result in increased ALP activity. By using serum free media and pretreating AH with dextran-coated charcoal, we found that serum and charcoal-adsorbable AH components augment but are not required for this response. Further, by heat-treating the AH, we established that thermally labile components are required for the osteogenic response. Finally, we showed myocilin, a protein present in AH, could induce ALP activity in ASCs. However, this was to a lesser extent than untreated 5% AH, and myocilin could only partially rescue the effect after heat treatment, documenting there were additional thermally labile constituents of AH involved in the osteogenic response. Our work adds to the understanding of the induction of ALP in ASCs following exposure to AH, providing important insight in how ASCs will be influenced by the ocular environment. In conclusion, increased osteogenic potential upon exposure to AH represents a potential challenge to developing ASC cell-based therapies directed at the eye.Biomedical and Clinical SciencesOphthalmology and OptometryStem Cell ResearchStem Cell Research - Nonembryonic - HumanRegenerative MedicineEye Disease and Disorders of VisionAetiology2.1 Biological and endogenous factorsAdipose TissueAlkaline PhosphataseAnalysis of VarianceAqueous HumorCellsCulturedCulture MediaSerum-FreeCytoskeletal ProteinsDose-Response RelationshipDrugEye ProteinsGlycoproteinsHot TemperatureHumansMesenchymal Stem CellsOsteogenesisAqueous humorMesenchymal stem cellsOsteogenic potentialMyocilinAlkaline phosphataseMedical Biochemistry and MetabolomicsNeurosciencesOpthalmology and OptometryOphthalmology & OptometryOphthalmology and optometryapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9p82b489articleoai:escholarship.org:ark:/13030/qt1nh555vb2023-09-26T15:24:57Zqt1nh555vbGuest Editorial: Theories and Methods for Advanced Wireless Relays — Issue IIHua, YingboBliss, Daniel WGazor, SaeedRong, YueSung, Youngchul2013-01-01Information and Computing SciencesCommunications EngineeringEngineeringDistributed ComputingElectrical and Electronic EngineeringCommunications TechnologiesNetworking & TelecommunicationsCommunications engineeringDistributed computing and systems softwarepubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1nh555vbarticleIEEE Journal on Selected Areas in Communications, vol 31, iss 81361 - 1367oai_dc:bcoe:500:1702:eyJmaXJzdCI6NTAwLCJpbmNsdWRlIjpbIlBVQkxJU0hFRCIsIkVNQkFSR09FRCJdLCJvcmRlciI6IlVQREFURURfREVTQyIsImxhc3RJRCI6InF0MW5oNTU1dmIiLCJsYXN0RGF0ZSI6IjIwMjMtMDktMjZUMDg6MjQ6NTctMDc6MDAifQ