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Open Access Publications from the University of California

Scholarly Works (17 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2017)

This dissertation focuses on the use of supplemental energy-dissipation devices to improve the seismic performance of tall steel buildings. It is divided into two parts. Part 1 focuses on exploring cost-effective retrofit strategies to improve the seismic performance of an existing tall building. The selected building is a 35-story steel moment-resisting frame, with representative details from the early 1970s. Detailed seismic evaluations were conducted in the framework of Performance Based Earthquake Engineering (PBEE), using the scenario-based performance assessment methods. A three-dimensional numerical model capturing the mechanical properties of the most critical structural elements was generated using the program: Open System for Earthquake Engineering Simulation (OpenSees). Seismic evaluation of the selected building was done following ASCE 41-13, FEMA 351 and FEMA P-58, and two hazard levels: basic safety earthquake levels 1 and 2 (BSE-1E and BSE-2E) prescribed by ASCE 41 were used for the assessment. Results predicted that this building failed to meet the recommended performance objectives and had a variety of seismic vulnerabilities, and possible retrofits were needed.

Therefore, a two-level retrofit approach was examined that focused on achieving the collapse prevention limit state under the BSE-2E hazard level. In Level-1, the brittle column splices were fixed everywhere in the building, and the massive concrete cladding was replaced with lightweight substitute in the exterior of the building. Level-2 strategies augmented the Level-1 methods by adding different supplemental energy-dissipation devices. Devices investigated include: fluid viscous dampers (FVDs), viscous wall dampers (VWDs) and buckling restrained braces (BRBs). Among these, the scheme that used FVDs was expected to be the most promising to upgrade the seismic performance of the case-study steel moment frame, and thus was examined first. In this approach, feasible damper locations and overall effective damping ratios were evaluated through a series of preliminary studies, and then a two-phase manual design method was used to refine the distribution and mechanical properties of the dampers. Thorough assessments of the refined design were carried out and the results indicated that the proposed retrofit method of using FVDs could achieve the retrofit goal and provide a cost-effective means of improving the structural behavior and reducing economic losses in a major seismic event for this case-study building.

The study was extended to examine alternative measures to upgrade the case-study building by using either VWDs or BRBs, and compared their relative effectiveness and economy with the scheme using FVDs. The locations and effective damping ratios were kept the same for all three schemes to insure a valid comparison. Results indicated that the proposed schemes of VWDs and BRBs both failed to achieve the targeted performance goal for this structure under a BSE-2E event, and special design considerations were required.

Part 2 of the dissertation focuses on developing an automated tool to streamline the design of FVDs in tall buildings. Aided by the high-performance computers and parallel processors, a large amount of complicated nonlinear response history analysis was conducted to facilitate the automate design procedure. The optimization problem was devised in a simplified PBEE framework under one hazard level each time. Basic optimization ingredients were selected to reflect the target performance goal, and several cases using different objective functions were evaluated.

Two tall buildings: the existing steel moment frame examined before and a newly-designed mega-brace steel frame were selected to rely on the automated procedure to optimally design FVDs. In both cases, the automated procedure turned to be very efficient, help identify design parameters of dampers in selected locations and reduce a great amount of engineering efforts. With only limited number of iterations, optimal design patterns of FVDs in a tall building could be found, which were able to improve the structural performance under different hazard events. The suggested optimal design could meet retrofit goal for the existing tall building, as well as achieve enhanced performance goal for both existing and new tall buildings.

    Cover page: Enhancing Seismic Performance of Tall Buildings by Optimal Design of Supplemental Energy-Dissipation Devices
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2020)
    This study sought to determine if reducing dopamine D1 receptor (D1R) expression in the dorsal striatum (DS) via RNA-interference alters methamphetamine self-administration. A lentiviral construct containing a short hairpin RNA (shRNA) was used to knock down D1R expression (D1RshRNA). D1RshRNA in male rats increased responding for methamphetamine (i.v.) under a fixed-ratio schedule in an extended access paradigm, compared to D1R-intact rats. D1RshRNA also produced a vertical shift in a dose-response paradigm and enhanced responding for methamphetamine in a progressive-ratio schedule, generating a drug-vulnerable phenotype. D1RshRNA did not alter responding for sucrose (oral) under a fixed-ratio schedule compared to D1R-intact rats. Western blotting confirmed reduced D1R expression in methamphetamine and sucrose D1RshRNA rats. D1RshRNA reduced the expression of PSD-95 and MAPK-1 and increased the expression of dopamine transporter (DAT) in the DS from methamphetamine, but not sucrose rats. Sucrose density gradient fractionation was performed in behavior-naïve controls, D1RshRNA- and D1R-intact rats to determine the subcellular localization of D1Rs, DAT and D1R signaling proteins. D1Rs, DAT, MAPK-1 and PSD-95 predominantly localized to heavy fractions, and the membrane/lipid raft protein caveolin-1 (Cav-1) and flotillin-1 were distributed equally between buoyant and heavy fractions in controls. Methamphetamine increased localization of PSD-95, Cav-1, and flotillin-1 in D1RshRNA and D1R-intact rats to buoyant fractions. Our studies indicate that reduced D1R expression in the DS increases vulnerability to methamphetamine addiction-like behavior, and this is accompanied by striatal alterations in the expression of DAT and D1R signaling proteins and is independent of the subcellular localization of these proteins.
      Cover page: In vivo reduction of striatal D1R by RNA interference alters expression of D1R signaling-related proteins and enhances methamphetamine addiction in male rats.
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2021)
      Mitochondrial dysfunction plays a pivotal role in the Alzheimer's Disease (AD) pathology. Disrupted mitochondrial dynamics (i.e., fusion/fission balance), which are essential for normal mitochondria structure and function, are documented in AD. Caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein regulates metabolic pathways in several different cell types such as hepatocytes and cancer cells. Previously, we have shown decreased expression of Cav-1 in the hippocampus of 9-month (m) old PSAPP mice, while hippocampal overexpression of neuron-targeted Cav-1 using the synapsin promoter (i.e., SynCav1) preserved cognitive function, neuronal morphology, and synaptic ultrastructure in 9 and 12 m PSAPP mice. Considering the central role of energy production in maintaining normal neuronal and synaptic function and survival, the present study reveals that PSAPP mice exhibit disrupted mitochondrial distribution, morphometry, and respiration. In contrast, SynCav1 mitigates mitochondrial damage and loss and enhances mitochondrial respiration. Furthermore, by examining mitochondrial dynamics, we found that PSAPP mice showed a significant increase in the phosphorylation of mitochondrial dynamin-related GTPase protein (DRP1), resulting in excessive mitochondria fragmentation and dysfunction. In contrast, hippocampal delivery of SynCav1 significantly decreased p-DRP1 and augmented the level of the mitochondrial fusion protein, mitofusin1 (Mfn1) in PSAPP mice, a molecular event, which may mechanistically explain for the preserved balance of mitochondria fission/fusion and metabolic resilience in 12 m PSAPP-SynCav1 mice. Our data demonstrate the critical role for Cav-1 in maintaining normal mitochondrial morphology and function through affecting mitochondrial dynamics and explain a molecular and cellular mechanism underlying the previously reported neuroprotective and cognitive preservation induced by SynCav1 in PSAPP mouse model of AD.
        Cover page: Synapsin-Promoted Caveolin-1 Overexpression Maintains Mitochondrial Morphology and Function in PSAPP Alzheimer’s Disease Mice
        • Article
        • Peer Reviewed
        UC Riverside Previously Published Works (2020)
        Tea green leafhopper [Empoasca (Matsumurasca) onukii Matsuda] is one of the most devastating pests of tea plants (Camellia sinensis), greatly impacting tea yield and quality. A thorough understanding of the interactions between the tea green leafhopper and the tea plant would facilitate a better pest management. To gain more insights into the molecular and biochemical mechanisms behind their interactions, a combined analysis of the global transcriptome and metabolome reconfiguration of the tea plant challenged with tea green leafhoppers was performed for the first time, complemented with phytohormone analysis. Non-targeted metabolomics analysis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS), together with quantifications by ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QqQ MS), revealed a marked accumulation of various flavonoid compounds and glycosidically bound volatiles but a great reduction in the level of amino acids and glutathione upon leaf herbivory. RNA-Seq data analysis showed a clear modulation of processes related to plant defense. Genes pertaining to the biosynthesis of phenylpropanoids and flavonoids, plant-pathogen interactions, and the biosynthesis of cuticle wax were significantly up-regulated. In particular, the transcript level for a CER1 homolog involved in cuticular wax alkane formation was most drastically elevated and an increase in C29 alkane levels in tea leaf waxes was observed. The tea green leafhopper attack triggered a significant increase in salicylic acid (SA) and a minor increase in jasmonic acid (JA) in infested tea leaves. Moreover, transcription factors (TFs) constitute a large portion of differentially expressed genes, with several TFs families likely involved in SA and JA signaling being significantly induced by tea green leafhopper feeding. This study presents a valuable resource for uncovering insect-induced genes and metabolites, which can potentially be used to enhance insect resistance in tea plants.
          Cover page: Defensive Responses of Tea Plants (Camellia sinensis) Against Tea Green Leafhopper Attack: A Multi-Omics Study
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2017)
          In this report, we present a mesoporous carbon nanosphere that can target drugs to tumors and image tumor biomarkers. A single-strand DNA (P0 aptamer) aptavalve was capped on the surface of doxorubicin-loaded oxide mesoporous carbon nanospheres (Dox-OMCN-P0) through π-π stacking for real-time imaging-guided on-demand targeting drug delivery. The Dox-OMCN-P0 could not only realize the detection of MUC1 tumor marker with a wide linear range (0.1 - 10.6 μmol/L) and a low detection limit (17.5 nmol) based on different apparatuses, but also achieve in-situ targeting imaging of cellular MUC1 concentration in vitro and in vivo via "off-on" fluorescence biosensing. Much attractively, as a real-time feedback of the diagnostic/imaging outcomes, Dox-OMCN-P0 accomplished the on-demand targeting drug delivery in quantitative response to MUC1. Controllable chemotherapy with sustained release and pH-sensitiveness, together with the potential photothermal therapy, were also clearly demonstrated. This is a simple but advanced platform, which could well achieve the real-time switchable imaging of cellular mucin for targeting cancer therapy.
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2022)
            Pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3' untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.
              Cover page: A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2022)
              Mitochondria play a crucial role in Alzheimer's disease (AD) onset and progression. Traditional transgenic AD mouse models which were widely used in the past decades share a common limitation: The overexpression of APP and overproduction of amyloid-beta (Aβ) are accompanied by other APP peptide fragments, which could introduce artificial and non-clinically relevant phenotypes. Here, we performed an in-depth and time-resolved behavioral and metabolic characterization of a clinically relevant AD mouse model engineered to express normal physiological levels of APP harboring humanized Swedish (K670N/M671L), Beyreuther/Iberian (I716F), and Arctic (E693G) mutations (App NL-G-F/NL-G-F ), termed APP knock-in (APPKI) mice. Our result showed that APPKI mice exhibited fear learning deficits at 6-m age and contextual memory deficit at 12-m age. Histopathological analysis revealed mild amyloidosis (6E10) accompanied by microgliosis (Iba1) as early as 3 months, which progressed significantly together with significant astrocytosis at 6 and 12 m. We further analyzed hippocampal mitochondrial dysfunction by multiple assays, while 3-m APPKI mice brain mitochondrial function remains a similar level as WT mice. Significant mitochondrial dysfunction characterized by decreased ATP production and higher membrane potential with subsequent overproduction of reactive oxygen species (ROS) was observed in mitochondria isolated from 7-m APPKI mice hippocampal tissue. Morphologically, these mitochondria were larger in volume with a decreased level of mitochondrial fusion protein mitofusin-2 (MFN2). At 12 months, APPKI mice exhibit a significantly decreased total mitochondrial oxygen consumption rate (OCR) in isolated hippocampal mitochondria detected by high-resolution respirometry. These data indicate early mitochondrial dysfunction in the brain at pre-symptomatic age in the App NL-G-F/NL-G-mice, which may play a key role in the progression of the disease. Moreover, the identified behavioral and bioenergetic alterations in this clinically relevant AD mouse model provide a valuable tool to optimize the temporal component for therapeutic interventions to treat AD.
                Cover page: Age-Dependent Behavioral and Metabolic Assessment of AppNL−G−F/NL−G−F Knock-in (KI) Mice
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2019)
                Proper axonal growth and guidance is essential for neuron differentiation and development. Abnormal neuronal development due to genetic or epigenetic influences can contribute to neurological and mental disorders such as Down syndrome, Rett syndrome, and autism. Identification of the molecular targets that promote proper neuronal growth and differentiation may restore structural and functional neuroplasticity, thus improving functional performance in neurodevelopmental disorders. Using differentiated human neuronal progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs), the present study demonstrates that during early stage differentiation of human NPCs, neuron-targeted overexpression constitutively active Rac1 (Rac1CA) and constitutively active Cdc42 (Cdc42CA) enhance expression of P-Cav-1, T-Cav-1, and P-cofilin and increases axonal growth. Similarly, neuron-targeted over-expression of Cav-1 (termed SynCav1) increases axonal development by increasing both axon length and volume. Moreover, inhibition of Cav-1(Y14A) phosphorylation blunts Rac1/Cdc42-mediated both axonal growth and differentiation of human NPCs and SynCav1(Y14A)-treated NPCs exhibited blunted axonal growth. These results suggest that: (1) SynCav1-mediated dendritic and axonal growth in human NPCs is dependent upon P-Cav-1, (2) P-Cav-1 is necessary for proper axonal growth during early stages of neuronal differentiation, and (3) Rac1/Cdc42CA-mediated neuronal growth is in part dependent upon P-Cav-1. In conclusion, Cav-1 phosphorylation is essential for human neuronal axonal growth during early stages of neuronal differentiation.
                  Cover page: Caveolin-1 Phosphorylation Is Essential for Axonal Growth of Human Neurons Derived From iPSCs
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2024)

                  Background and purpose

                  Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes.

                  Experimental approach

                  Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation.

                  Key results

                  Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation.

                  Conclusions and implications

                  Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.
                    Cover page: Nicotine inhalant via E‐cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF–TrkB signalling in traumatic brain injury
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2024)
                      Cover page: Nicotine inhalant via E-cigarette facilitates sensorimotorfunction recovery by upregulating neuronal BDNF–TrkBsignalling in traumatic brain injury
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