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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Article
UC Merced Undergraduate Research Journal, Volume 4, Issue 2 (2013)
Abstract is available in the article.
    Cover page: A Molecular Characterization of Recombinant HIV-1 Fusin Inhibitors
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2019)

    Despite significant surveillance and vaccine development efforts, Influenza A viruses remain a significant challenge to human health. A critical aspect of routine surveillance concerns strain specificity towards sialylated glycan structures on the cell surface and avoidance of host decoy structures on secreted mucins. Although methods of assessing glycan-binding phenotype, such as glycan microarray technology, have generated significant advances in our understanding of these interactions, the inherent complexity of this multivalent recognition event and the glycocalyx itself necessitate additional methods that better recapitulate the full molecular context of viral binding. Here in, I present multivalent glycopolymers displaying sialoglycans to better recapitulate native IAV receptor binding events in a chemically-controlled manner. This biologically inspired chemical approach facilitates the collection of quantitative whole-virus binding to our multivalent scaffolds presented either on glass slide/bead arrays or in soluble form, which can be combined to assess viral binding preference across varying geometric parameters including glycan density, valency, and scaffold length. In addition, I report the utilization of lipid bearing sialoglycopolymers to remodel the glycocalyx of mammalian cells as a tool to investigate viral recognition of sialylated glycan structures on living cell surfaces. In this bottom-up approach, we can readily control the glycan structure installation and Influenza receptor display on the cell membrane. Importantly, these glycomaterials appear able to restore viral adhesion to sialic acid deficient cells. By combining existing technologies with this method, we aim to better uncover structural features that enhance influenza’s primary recognition of host cells.

      Cover page: Development of biomimetic glycopolymer scaffolds to probe the role of sialoglycan display on influenza A host recognition
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2016)
      The initial engagement of host cells by pathogens is often mediated by glycan structures presented on the cell surface. Various components of the glycocalyx can be targeted by pathogens for adhesion to facilitate infection. Glycans also play integral roles in the modulation of the host immune response to infection. Therefore, understanding the parameters that define glycan interactions with both pathogens and the various components of the host immune system can aid in the development of strategies to prevent, interrupt, or manage infection. Glycomaterials provide a unique and powerful tool with which to interrogate the compositional and functional complexity of the glycocalyx. The objective of this review is to highlight some key contributions from this area of research in deciphering the mechanisms of pathogenesis and the associated host response.
        Cover page: Glycomaterials for probing host–pathogen interactions and the immune response
        • Article
        • Peer Reviewed
        Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 41 (2019)
        Measuring cognitive workload is a persistent challenge in cog-nitive science. Cognitive architectures may offer a prin-cipledway to measure, define, and understand workload and its be-havioral and physiological consequences in terms ofunder-lying cognitive dynamics. Previous research has shown thatmodel-based workload relates to subjective workloadjudg-ments in simple tasks. Our goal was to further validate model-based workload measurement with known physiolog-ical work-load indicators in a complex task characterized by varying de-grees of workload levels. Participants completedan unmannedvehicle management task while their physiology was recorded.Correlations between model-based workloadand physiologi-cal metrics generally trended in the predicted direction, andthe engagement index showed the strongest andmost consis-tent relationship to model workload. The results provide pre-liminary validation for model-based workloadmeasurement.
          Cover page: A Cognitive Modeling Approach for Predicting Behavioral and PhysiologicalWorkload Indicators
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2015)
          Influenza viruses bind to mucosal glycans to gain entry into a host organism and initiate infection. The target glycans are often displayed in multivalent arrangements on proteins; however, how glycan presentation influences viral specificity is poorly understood. Here, we report a microarray platform approximating native glycan display to facilitate such studies.
            Cover page: Determination of receptor specificities for whole influenza viruses using multivalent glycan arrays
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2014)

            Objective

            This study explored the automatic and controlled processes that may influence performance on an implicit measure across cognitive-behavioral group therapy for panic disorder.

            Method

            The Quadruple Process model was applied to error scores from an Implicit Association Test evaluating associations between the concepts Me (vs. Not Me) + Calm (vs. Panicked) to evaluate four distinct processes: Association Activation, Detection, Guessing, and Overcoming Bias. Parameter estimates were calculated in the panic group (n = 28) across each treatment session where the IAT was administered, and at matched times when the IAT was completed in the healthy control group (n = 31).

            Results

            Association Activation for Me + Calm became stronger over treatment for participants in the panic group, demonstrating that it is possible to change automatically activated associations in memory (vs. simply overriding those associations) in a clinical sample via therapy. As well, the Guessing bias toward the calm category increased over treatment for participants in the panic group.

            Conclusions

            This research evaluates key tenets about the role of automatic processing in cognitive models of anxiety, and emphasizes the viability of changing the actual activation of automatic associations in the context of treatment, versus only changing a person's ability to use reflective processing to overcome biased automatic processing.
              Cover page: Applying the Quadruple Process model to evaluate change in implicit attitudinal responses during therapy for panic disorder
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2016)
              Current drugs against the influenza A virus (IAV) act by inhibiting viral neuraminidase (NA) enzymes responsible for the release of budding virions from sialoglycans on infected cells. Here, we describe an approach focused on a search for inhibitors that reinforce the protective functions of mucosal barriers that trap viruses en route to the target cells. We have generated mimetics of sialo-glycoproteins that insert into the viral envelope to provide a well-defined mucus-like environment encapsulating the virus. By introducing this barrier, which the virus must breach using its NA enzymes to infect a host cell, into a screening platform, we have been able to identify compounds that provide significant protection against IAV infection. This approach may facilitate the discovery of potent new IAV prophylactics among compounds with NA activities too weak to emerge from traditional drug screens.
                Cover page: Synthetic Mucus Nanobarriers for Identification of Glycan-Dependent Primary Influenza A Infection Inhibitors
                • Article
                • Peer Reviewed
                Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 37 (2015)
                Adaptive Control of Thought-Rational (ACT-R) and the Linear Ballistic Accumulator (LBA) were compared in a model mimicry simulation of the Psychomotor Vigilance Task (PVT), a simple, reaction time (RT) task requiring sustained attention. The models use different formalisms to capture the full response profile of the PVT. The parameters were varied systematically to illustrate the ranges of the models’ predictions, to assess the models’ estimation properties, and to determine which parameters in the models correspond with each other. Both models produced skewed RT distributions typical of empirical data, including false starts and lapses. The simulation study demonstrated that both models and their parameters are recoverable. Lastly, isolated parameters in the LBA model captured the effects of varying parameters in the ACT-R model, but the reverse was not always true. These interesting correspondences across different modeling formalisms suggest the possibility of integrating ACT-R and the LBA in future work
                  Cover page: ACT-R and LBA Model Mimicry Reveals Similarity Across Modeling Formalisms
                  • Article
                  • Peer Reviewed
                  Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 39 (2017)
                  We developed a cognitive-pharmacokinetic computational(CPC) model to understand how pharmacoactive substances,such as caffeine and toluene, modulate cognition. In this in-tegrated model, dynamic physiological mechanisms are sim-ulated to predict concentrations of the solvent toluene in thebrain, which modulates specific cognitive systems in a dose-response fashion over multiple hours. We used our CPC modelto reanalyze the results from prior research that documented anincrease in reaction time following exposure to toluene in sev-eral laboratory tasks with no change in accuracy. Our analysisprovides tentative evidence that toluene affects motor execu-tion, rather than attention or declarative memory.
                    Cover page: A Cognitive-Pharmacokinetic Computational Model of the Effect of Toluene onPerformance
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2016)
                    Influenza A viruses (IAVs) utilize sialylated host glycans as ligands for binding and infection. The glycan-binding preference of IAV hemagglutinin (HA) is an important determinant of host specificity. Propagation of IAV in embryonated chicken eggs and cultured mammalian cells yields viruses with amino acid substitutions in the HA that can alter the binding specificity. Therefore, it is important to determine the binding specificity of IAV directly in primary samples since it reflects the actual tropism of virus in nature. We developed a novel platform for analysis of IAV binding specificity in samples that contain very low virus titers. This platform consists of a high-density flexible glycan display on magnetic beads, which promotes multivalent interactions with the viral HA. Glycan-bound virus is detected by quantifying the viral neuraminidase activity via a fluorogenic reporter, 2'-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid. This method eliminates the need for labeling the virus and significantly enhances the sensitivity of detection.
                      Cover page: Capture and characterization of influenza A virus from primary samples using glycan bead arrays.
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