Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (522 results)

  • Article
  • Peer Reviewed
Biogeographia – The Journal of Integrative Biogeography, Volume 14 (1990)
    Cover page: Mantodei della Somalia
    • Article
    LBL Publications (1990)
      Cover page: Monte Carlo Simulations of Temperature-Programmed and Isothermal Desorption from Single-Crystal Surfaces
      • Article
      • Peer Reviewed
      Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 17 (1995)
      The paper introduces a general model of recovery from errors in parsing. The mechanism proposed returns selectively on the choice points, in order to identify the one that was badly resolved, and could have caused the error. Then, it selects an alternative previously discarded and finally selectively repairs the appropriate fragments between the ambiguous region and the breakdown region. Both the psycholinguistic and the computational features of the model are put in evidence.
        Cover page: Parsing and Recovery
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (1985)
        Manoalide, an unusual nonsteroidal sesterterpenoid recently isolated from sponge, antagonizes phorbol-induced inflammation but not that induced by arachidonic acid, suggesting that manoalide acts prior to the cyclooxygenase step in prostaglandin synthesis, possibly by inhibiting phospholipase A2. We have now studied the inhibitory effect of manoalide on a homogeneous preparation of phospholipase A2 from cobra venom. For a given concentration of manoalide, the inhibition of phospholipase A2 activity toward dipalmitoylphosphatidylcholine/Triton X-100 mixed micelles is time-dependent and plateaus at about 85% inhibition of the initial velocity even after extensive preincubation. Metal ions (Ca2+, Ba2+, Mn2+) increase the inhibition, while lysophosphatidylcholine and substrate micelles protect. Increasing manoalide concentration shows increasing inhibition of the initial velocity until a plateau is reached, giving a typical saturation curve with a linear double-reciprocal plot. Under typical conditions (20-min preincubation, 40 degrees C, pH 7.1), 50% inhibition is achieved at a manoalide concentration of about 2 X 10(-6) M. The data indicate that manoalide is a potent inhibitor of the cobra venom phospholipase A2. Manoalide is now shown to react irreversibly with lysine residues in the enzyme. Surprisingly, the cobra venom phospholipase normally acts poorly on phosphatidylethanolamine as substrate, but after reaction with manoalide, the enzyme is somewhat more active toward this substrate rather than being inhibited. This suggests that a lysine residue may be important in understanding the substrate specificity of phospholipase A2.
          Cover page: Cobra venom phospholipase A2 inhibition by manoalide. A novel type of phospholipase inhibitor.
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (1985)
          The activation of cobra venom phospholipase A2 by activators (containing phosphorylcholine moieties) appears to depend upon the aggregation state of the enzyme, and the presence of a lipid-water interface. The characteristics of this activation were studied by comparing the behavior of the enzyme immobilized on an agarose gel to that of the soluble enzyme. The immobilized enzyme displays only a few per cent of the soluble enzyme activity toward micellar dipalmitoyl-phosphatidylcholine (PC). However, the relative loss of activity is much less with micellar dipalmitoylphosphatidylethanolamine or soluble diheptanoyl-PC. The affinity for Ca2+ is increased about 10-fold by immobilization while the apparent pKa of the enzyme is decreased by 0.5-0.8 pH units. Activation energies are similar for the two enzyme forms and are independent of the physical state of the substrate used. Catalytic constants of the enzyme toward monomeric PC are not changed by immobilization. Yet, activators of the soluble enzyme have negligible effect on the immobilized enzyme, either in the presence or absence of an interface. Monomeric activators promote the binding of the soluble enzyme to the immobilized form. Apparently, immobilization mainly produces monomerically constrained enzyme which cannot be activated under any condition, whereas normally, activators in the presence of lipid-water interfaces induce the formation of enzyme dimers or possibly higher order aggregates.
            Cover page: Immobilized phospholipase A2 from cobra venom. Prevention of substrate interfacial and activator effects.
            • Article
            • Peer Reviewed
            Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 19 (1997)
            In incremental parsing, infinite local ambiguity occurs when the input word can be combined with the syntactic structure built so far in a infinite number of ways. A common example is left recursion (e.g. "'railway station clock" or "his sister's boyfriend's shirt"), where local information cannot tell us the depth of embedding of the left descendent chain of nodes. From the processing point of view, infinite local ambiguity causes a technical problem, which a model must solve in order to implement incrementality fully. This paper provides a general solution to the problem of infinite local ambiguity, by introducing the concept of Minimal Recursive Structure. We give two examples of parsers in which the solution is used.
              Cover page: Incremental processing and infinite local ambiguity
              • Thesis
              • Peer Reviewed
              UC Irvine Electronic Theses and Dissertations (2020)

              Tissues are highly complex ecosystems, composed of heterogenous cell populations that vary in gene expression and function due to epigenetic and genetic distinctions, stochastic events, and microenvironmental factors. In the context of cancer, characterizing intratumor heterogeneity has been crucial in understanding cancer progression, metastasis, and the development of drug resistance. In order to capture this significant heterogeneity, high-throughput single cell analysis methods like flow cytometry, mass cytometry, and single cell RNA sequencing must be employed. However, these analysis methods require that tissues first be dissociated into cellular suspensions, which currently represents a major bottleneck hindering these efforts. Conventional protocols for dissociating tissues are inefficient and antiquated, relying on many manual intensive, time-consuming and highly user-variable steps for digesting, disaggregating, and filtering tissue specimens. In areas of regenerative medicine, the reliance on proteolytic enzymes to liberate stem/progenitor cell populations from tissue results in a cellular therapeutic that no longer meets the Food and Drug Administration’s guidelines for minimal manipulation. These therapeutics thus face increased regulatory barriers hindering their application in clinical settings. However, advances in microfabricated technologies hold exciting potential in their ability to execute many standard laboratory procedures, including tissue dissociation, on-chip by offering high-throughput and precise sample manipulation. The goal of this work is to develop and integrate a suite of microfluidic device technologies to dissociate tissues at the point of care. First, we present a simple and inexpensive microfluidic device that simultaneously filters large tissue fragments and dissociates smaller aggregates into single cells, thereby improving single cell yield and purity. Next, we integrate this microfluidic filter device with upstream tissue digestion and aggregate dissociation technologies. The resulting microfluidic platform significantly improves the breakdown of diverse minced tissue specimens, including tumor samples, into high quality cell suspensions that are ready for downstream single cell analysis. We then optimize a microfluidic digestion protocol for primary immune cell isolation from spleen specimens, exploring both enzymatic and nonenzymatic methods. Lastly, we adapt our microfluidic tissue processing technologies to standardize and improve mechanical processing of human lipoaspirate for autologous therapeutics. In future work, we envision incorporating cell sorting and analysis capabilities on-chip to achieve point-of-care single cell diagnostic or therapeutic platforms.

                Cover page: Microfluidic Tissue Processing Platform for Single Cell Analysis and Therapeutic Applications
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2017)
                Cardiac arrhythmias are a major health concern and often involve poorly understood mechanisms. Mathematical modeling is able to provide insights into these mechanisms which might result in better treatment options. A key element of this modeling is a description of the electrophysiological properties of cardiac cells. A number of electrophysiological models have been developed, ranging from highly detailed and complex models, containing numerous parameters and variables, to simplified models in which variables and parameters no longer directly correspond to electrophysiological quantities. In this study, we present a systematic reduction of the complexity of the detailed model of Koivumaki et al. using the recently developed manifold boundary approximation method. We reduce the original model, containing 42 variables and 37 parameters, to a model with only 11 variables and 5 parameters and show that this reduced model can accurately reproduce the action potential shape and restitution curve of the original model. The reduced model contains only five currents and all variables and parameters can be directly linked to electrophysiological quantities. Due to its reduction in complexity, simulation times of our model are decreased more than three-fold. Furthermore, fitting the reduced model to clinical data is much more efficient, a potentially important step towards patient-specific modeling.
                  Cover page: Systematic reduction of a detailed atrial myocyte model.
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2019)
                  Spiral waves have been observed in a variety of physical, chemical, and biological systems. They play a major role in cardiac arrhythmias, including fibrillation, where the observed irregular activation patterns are generally thought to arise from the continuous breakup of multiple unstable spiral waves. Using spatially extended simulations of different electrophysiological models of cardiac tissue, we show that a single spiral wave in the presence of heterogeneities can display chaotic tip trajectories, consistent with fibrillation. We also show that the simulated spiral tip dynamics, including chaotic trajectories, can be captured by a simple particle model which only describes the dynamics of the spiral tip. This shows that spiral wave breakup, or interactions with other waves, are not necessary to initiate chaos in spiral waves.
                    Cover page: Chaotic tip trajectories of a single spiral wave in the presence of heterogeneities.
                    • Article
                    • Peer Reviewed
                    Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 27 (2005)
                      Cover page: Knowing or Not Knowing: Children's Concept of 'Having Life'
                      Top