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Open Access Publications from the University of California

Scholarly Works (51 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2019)

Latinas, their families, and their communities carry rich incredible resources and practices that can be leveraged to learn in STEM. Despite this strength in diversity, national reports describe that Latinas are not successful in their STEM academic achievement. The purpose of this study is to ameliorate this disconnect and understand the cultural resources and practices, including language, that Mexican American girls leverage to engage in STEM learning. Drawing on social practice theory and employing a critical ethnographic case study, I ask how do Mexican-American girls generate identity resources, during identity work, across different settings of home, school, and afterschool? Multiple sources of data were collected in an afterschool STEM program for 5th graders. Analysis of the identity development of the 4 case study girls revealed two patterns: (a) the relative nature of identity work, and (b) the importance of having a productive role to engage deeply in STEM activities. Based on these findings, I made three claims. First, having a role becomes opportunities to generate identity resources. Second, building relationships through dichos and convivir generate relational identity resources. Third, recognition work is complex and relative when taking on different perspectives of people. Three implications for future research are discussed.

    Creative Commons 'BY-NC-ND' version 4.0 license
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2016)

    Solute uptake and release govern the efficacy of hydrogels in controlled drug delivery, tissue engineering, and chromatographic separations. In soft contact lenses, uptake and release of wetting, packaging, and care-solution agents is extensively employed to improve on-eye lens performance. Key physical parameters are the equilibrium solute partition coefficient and the solute diffusion coefficient in the gel that dictate the amounts and rates of uptake/release, respectively. To investigate the mechanisms of solute uptake and release in hydrogels, this work experimentally and theoretically determines equilibrium partition and diffusion coefficients of prototypical macromolecules and drugs in hydrogels over a wide range of water contents.

    A hydrogel is a crosslinked polymer network with water-filled voids arranged in an unstructured three-dimensional mesh. Solutes (e.g., drugs, sugars, proteins, polymers) typically partition into and diffuse through the water-filled mesh but are excluded from mesh voids smaller than solute size. Consequently, solute size and the distribution of mesh sizes in the hydrogel-polymer network are vital to understand solute uptake and release. Solutes may also exhibit specific interactions with and, accordingly, adsorb to hydrogel polymer chains by hydrogen bonding or counterion binding. Specific solute adsorption to hydrogel-polymer strands results in larger partition coefficients and diminished effective diffusion rates.

    To elucidate size effects on aqueous-solute transport rates, diffusion coefficients of large macromolecules in hydrogels with relatively small mesh sizes are investigated experimentally and theoretically. Two photon-confocal microscopy measures transient uptake and release concentration profiles of fluorescently labeled dextrans of varying molecular weight, and fluorescently labeled cationic avidin protein. Dextrans are highly water-soluble polysaccharides. Consequently, they exhibit negligible specific interactions with the hydrogel polymer network. Hydrogel uptake and release follow Fick’s second law with almost identical diffusion coefficients in the uptake and release directions. To interpret our data, we implement a Large Pore Effective Medium (LPEM) model taking into account hydrodynamic drag, steric obstruction, and the distribution of mesh sizes available for solute transport. All necessary parameters are measured independently. In all cases, a priori- predicted diffusion coefficients by LPEM theory display excellent agreement with experiment. In contrast to the nonspecific interacting dextrans, cationic avidin protein exhibits near irreversible adsorption with incomplete loading even after 6 days and incomplete release even after two weeks. Avidin protein uptake and release rates clearly highlight the significance of solute-specific adsorption in understanding solute transport rates in hydrogels.

    Despite its importance, little attention has been given to how solute-specific interactions affect solute uptake in and release from hydrogels. We measure and theoretically predict partition and diffusion coefficients for prototypical water-soluble drugs in hydrogels where solute-specific binding is pronounced. Hydrogel composition is varied by adjusting the ratio of monomer constituents, 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA). Partition and diffusion coefficients are obtained through two-photon confocal microscopy and UV/Vis-absorption spectrophotometry upon back extraction. The studied prototypical drugs all exhibit specific adsorption to nonionic MAA and HEMA moieties characterized by greater-than-unity partition coefficients and smaller effective diffusion rates. Conversely, none of the prototypical drugs displayed specific interactions with anionic MAA moieties. To predict equilibrium partition coefficients, we express the partition coefficient as a product of the hydrogel water content and individual enhancement factors for size-exclusion, nonspecific electrostatic interactions, and specific adsorption. Again, all necessary parameters are obtained independently. To predict effective diffusion coefficients, we extend LPEM for specific-solute adsorption and impose local equilibrium. As with the non-interacting dextran solutes, predicted partition and diffusion coefficients are in good agreement with experiment. A framework is now available to predict solute partitioning and diffusion in solute-hydrogel systems that exhibit specific interactions.

    The developed theories for solute partitioning are further extended for direct application to silicone-hydrogel contact-lens materials. Silicone hydrogels (SiHy) are microphase-separated materials with silicone domains for oxygen transport and hydrophilic-polymer domains for aqueous-solute transport. Equilibrium silicone-hydrogel water and solute uptake are measured and predicted with an extended partitioning theory assuming that water and aqueous solutes reside only in the hydrophilic-polymer phase, whereas oleophilic solutes partition primarily into the silicone microphase. Excellent agreement is found between theory and experiment. Significantly, our development provides estimation of partitioning properties in silicone hydrogels based solely on synthesis formulation chemistry.

    Finally, we deduce compositional properties of a laminated soft contact lens, DAILIES TOTAL 1® (delefilcon A) through measurement of fluorescent solute partition coefficients. Measured partition coefficients and solute-partitioning theory establish (1) the silicone-hydrogel core of the laminated lens is structurally similar to that of a non-laminated commercial SiHy soft contact lens, O2OPTIXTM, (2) the laminated-lens surface-gel layers are ~10 µm in thickness, (3) the laminated-lens surface-gel layers are of higher water content than the core, and (4) the surface-gel layers of the laminated lens are anionic, whereas the core is nonionic. Importantly, with solute-uptake properties known, our proposed solute-partitioning theory provides a means to elucidate hydrogel physico-chemical properties.

      Cover page: Solute Partitioning and Hindered Diffusion in Hydrogels
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2018)
      Genome editing methods have commonly relied on the initial introduction of double-stranded DNA breaks (DSBs), resulting in stochastic insertions, deletions, and translocations at the target genomic locus. To achieve gene correction, these methods typically require the introduction of exogenous DNA repair templates and low-efficiency homologous recombination processes. In this review, we describe alternative, mechanistically motivated strategies to perform chemistry on the genome of unmodified cells without introducing DSBs. One such strategy, base editing, uses chemical and biological insights to directly and permanently convert one target base pair to another. Despite its recent introduction, base editing has already enabled a number of new capabilities and applications in the genome editing community. We summarize these advances here and discuss the new possibilities that this method has unveiled, concluding with a brief analysis of future prospects for genome and transcriptome editing without double-stranded DNA cleavage.
        Cover page: Editing the Genome Without Double-Stranded DNA Breaks
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2006)

        SUMMARY Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola cause bacterial blight and bacterial leaf streak of rice (Oryza sativa), which constrain production of this staple crop in much of Asia and parts of Africa. Tremendous progress has been made in characterizing the diseases and breeding for resistance. X. oryzae pv. oryzae causes bacterial blight by invading the vascular tissue, while X. oryzae pv. oryzicola causes bacterial leaf streak by colonizing the parenchyma. In rice there are 29 major genes for resistance to bacterial blight, but so far only a few quantitative resistance loci for bacterial leaf streak. Over 30 races of X. oryzae pv. oryzae have been reported. Both pathogens exhibit genetic variation among isolates. Mechanisms of pathogenesis and resistance have begun to be elucidated. Members of the AvrBs3/PthA family of transcription activator-like effectors play a major role in the virulence of X. oryzae pv. oryzae and possibly X. oryzae pv. oryzicola. Cloning of six rice resistance genes for bacterial blight and one from maize effective against bacterial leaf streak has uncovered a diversity of structure and function, some shared by genes involved in defence in animals. This article reviews research that spans a century. It also presents a perspective on challenges for sustainable control, and opportunities that interactions of X. oryzae pathovars with rice present as models for understanding fundamental aspects of bacterial pathogenesis of plants and plant disease resistance, as well as other aspects of plant and microbial biology, with implications also for animal innate immunity.

          Cover page: Xanthomonas oryzae pathovars: model pathogens of a model crop.
          • Article
          • Peer Reviewed
          UC Santa Cruz Previously Published Works (2020)
          Two foundational concepts in biology education are 1) offspring are not identical to their parents, and 2) organisms undergo changes throughout their lives. These concepts are included in both international and U.S. curricular standards. Research in psychology has shown that children often have difficulty understanding these concepts, as they are inconsistent with their intuitive theories of the biological world. Additionally, prior research suggests that diagrams are commonly used in instruction and that their features influence student learning. Given this prior work, we explored the characteristics of life cycle diagrams and discuss possible implications for student learning. We examined 75 life cycle diagrams from books, including five biology or general science textbooks and 25 specialized trade books focusing on biology for children. We also examined 633 life cycle diagrams from a publicly available online database of science diagrams. Most diagrams failed to show any within-species variability. Additionally, many diagrams had perceptually rich backgrounds, which prior research suggests might hinder learning. We discuss how the design characteristics of diagrams may reinforce students intuitive theories of biology, which might make it difficult for students to understand key biological concepts in the future.
            Cover page: Representing Variability: The Case of Life Cycle Diagrams.
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2014)
              Cover page: Solute-Uptake Characterization of Water-Gradient Laminated Soft Contact Lenses
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2009)
              Cyanine dyes have been shown to undergo reversible photoswitching, where the fluorophore can be switched between a fluorescent state and a dark state upon illumination at different wavelengths. The photochemical mechanism by which switching occurs has yet to be elucidated. In this study, we have determined the mechanism of photoswitching by characterizing the kinetics of dark state formation and the spectral and structural properties of the dark state. The rate of switching to the dark state depends on the concentration of the primary thiol in the solution and the solution pH in a manner quantitatively consistent with the formation of an encounter complex between the cyanine dye and ionized thiol prior to their conjugation. Mass spectrometry suggests that the photoconversion product is a thiol-cyanine adduct in which covalent attachment of the thiol to the polymethine bridge disrupts the original conjugated pi-electron system of the dye.
                Cover page: Photoswitching Mechanism of Cyanine Dyes
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2011)

                Purpose

                To evaluate the safety and efficacy of two different methods of proximal cystic artery embolization in patients undergoing yttrium-90 radioembolization.

                Materials and methods

                Forty-six patients had cystic artery embolization performed immediately before yttrium-90 radioembolization, either by using Gelfoam pledgets (n = 35) or coils (n = 11). Clinical symptomatology during the admission and angiographic findings at 1-month follow-up were retrospectively reviewed. Rates of collateralization or recanalization of the cystic artery were compared, as well as the frequency of postprocedural abdominal pain and need for cholecystectomy.

                Results

                Technical success was achieved in all patients, and there were no procedural complications related to cystic artery embolization. Of the 11 coil-embolized patients, 5 (45%) demonstrated collateralization of the cystic artery at 1 month, and 1 (9%) demonstrated recanalization of the cystic artery. Of the 35 Gelfoam-embolized cases, 2 (6%) had collateralized at 1 month, and 14 (40%) had recanalized. Two patients (one from each group) had self-limited right upper quadrant pain after the procedure, and one patient in the coil embolization group required cholecystectomy.

                Conclusion

                Proximal cystic artery embolization is safe and feasible and may be performed during liver-directed embolotherapy to minimize the exposure of the gallbladder to particulate, chemoembolic, or radioembolic agents.
                  Cover page: Prophylactic Embolization of the Cystic Artery Before Radioembolization: Feasibility, Safety, and Outcomes
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2022)
                  CRISPR-Cas-based genome editing technologies could, in principle, be used to treat a wide variety of inherited diseases, including genetic disorders of vision. Programmable CRISPR-Cas nucleases are effective tools for gene disruption, but they are poorly suited for precisely correcting pathogenic mutations in most therapeutic settings. Recently developed precision genome editing agents, including base editors and prime editors, have enabled precise gene correction and disease rescue in multiple preclinical models of genetic disorders. Additionally, new delivery technologies that transiently deliver precision genome editing agents in vivo offer minimized off-target editing and improved safety profiles. These improvements to precision genome editing and delivery technologies are expected to revolutionize the treatment of genetic disorders of vision and other diseases. In this Perspective, we describe current preclinical and clinical genome editing approaches for treating inherited retinal degenerative diseases, and we discuss important considerations that should be addressed as these approaches are translated into clinical practice.
                    Cover page: Precision genome editing in the eye
                    • Article
                    • Peer Reviewed
                    UC Berkeley Previously Published Works (2013)
                    The RNA-programmable Cas9 endonuclease cleaves double-stranded DNA at sites complementary to a 20-base-pair guide RNA. The Cas9 system has been used to modify genomes in multiple cells and organisms, demonstrating its potential as a facile genome-engineering tool. We used in vitro selection and high-throughput sequencing to determine the propensity of eight guide-RNA:Cas9 complexes to cleave each of 10(12) potential off-target DNA sequences. The selection results predicted five off-target sites in the human genome that were confirmed to undergo genome cleavage in HEK293T cells upon expression of one of two guide-RNA:Cas9 complexes. In contrast to previous models, our results show that guide-RNA:Cas9 specificity extends past a 7- to 12-base-pair seed sequence. Our results also suggest a tradeoff between activity and specificity both in vitro and in cells as a shorter, less-active guide RNA is more specific than a longer, more-active guide RNA. High concentrations of guide-RNA:Cas9 complexes can cleave off-target sites containing mutations near or within the PAM that are not cleaved when enzyme concentrations are limiting.
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