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

Scholarly Works (86 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2009)
Cholera toxin (CT), the causative factor responsible for the life-threatening acute diarrhea caused by Vibrio cholerae, is also well known as a potent mucosal vaccine adjuvant. However, little is known about the cellular and molecular mechanisms that mediate the mucosal adjuvant properties of CT. Recent studies have shown that Th17 cells discovered at mucosal sites have important role in generating strong immune responses that can be either protective (e.g. antimicrobial immunity) or destructive (e.g. autoimmune diseases EAE). Here, we showed that CT activates dendritic cells (DC) via cAMP-dependent mechanisms to drive the differentiation of naïve T cells into IL-17-producing Th17 cells in vitro and in vivo. Importantly, we identified an alternative pathway for Th17 differentiation that depends on the CT-induced secretion of calcitonin gene-related peptide (CGRP) by DC but is independent of IL-6. CGRP, a neuropeptide, in turn activates cAMP-dependent pathways in T cells that contribute to the generation of Th17 cells. These findings implicate Th17 induction as a contributing factor to the adjuvant effects of CT and identify novel pathways involved in T cell differentiation at mucosal sites.
    Cover page: Cholera Toxin Induces cAMP-dependent Th17 Differentiation by Dendritic Cells
    • Thesis
    • Peer Reviewed
    UC Irvine Electronic Theses and Dissertations (2021)

    This thesis presents a modeling and design exploration study of a novel twisting wing whose motion is enabled by a tensegrity mechanism. First, the aerodynamic characteristics of the twisting wing, which does not require control surfaces to modulate its shape, are compared with those of a conventional wing having a control surface. It is shown via computational fluid dynamics analyses that the twisting wing displays higher lift-to-drag ratio than the conventional wing and hence the twisting wing is more aerodynamically efficient. Subsequently,the torsional tensegrity mechanism, composed of multiple tensegrity cylindrical cells forming a column along the wingspan, is described. A finite element model of the wing incorporating this mechanism is developed. Using the model, a full factorial design of experiments study of the influence of the topological parameters of the torsional tensegrity mechanism on the twist angle, mass, and stress in the different components of the wing is performed. A wingspan of 142.24 cm and a chord length of 25.31 cm are assumed, corresponding to those of the Carl Goldberg Falcon 56 Mk II R/C unmanned aerial vehicle. For a wing of such dimensions, the maximum achievable twist angle from root to tip per unit mass without any component exceeding their allowable stress is 5.93◦/kg and delivered 13.5◦of twisting with-out violating any of the material failure stresses. This torsional deformation is sufficiently large to allow for effective modulation of the aerodynamic characteristics of the wing. The torsional tensegrity mechanism for this design consists of eight cylindrical cells and four setsof actuator wires along the circumference of each cell. Subsequently, a design of experiments study performed using the orthogonal array (a.k.a.Taguchi) method is conducted to evaluate the effects of varying design parameters such as the thicknesses of the skin and ribs,the wire diameters, number of cells and wire sets, spar diameter, and material types. The most favorable design with a maximum twist angle to mass ratio of 10.85◦/kg is presented and delivered up to 19.5◦of twisting without violating any of the material failure stresses.Finally, befitting for the actuation of the tensegrity mechanism due to their wire form, shape memory alloy (SMA) wire actuators are explored for the reconfiguration of the wing shape through thermally driven material actuation. The combination of lightweight and compact tensegrity mechanism and SMA wire actuators eliminate the need for bulky components,such as hydraulic and electric actuators, to enhance the flight performance. The torsional morphing capability enabled by SMA actuation is demonstrated experimentally through a tensegrity twisting wing prototype integrated with commercially available SMA wire actuators. An additional orthogonal array design of experiments study is performed on the wing model with incorporated SMA wire actuators, where results analogous to those obtained from artificial strains in the aforementioned studies are obtained. The most favorable design of this DOE delivered a substantial 15.85◦total twist angle without any material failure and had a mass of 2.02 kg. The obtained twist angle was comparable to the twist angle observed from the testing of the tensegrity twisting wing prototype with integrated SMA wire actuators.

      Cover page: Modeling and Design of a Tensegrity-based Morphing Wing
      • Article
      Cardiovascular Medicine (2021)
      Myocardial strain imaging using 2D-speckle-tracking echocardiography (STE) is a relatively new method for analyzing myocardial function. Myocardial strain measures the shortening of myocytes in three directions: longitudinally, circumferentially, and radially. While ejection fraction (EF) is a common measure of heart health, strain measurements are more sensitive to changes in ventricular function and thus can be used to detect subclinical cardiac abnormalities that may not be seen by EF measurements. Strain values for various chambers have implications for identifying and treating many different cardiomyopathies. Speckle-tracking echocardiography and tissue Doppler imaging (TDI) are the two primary methods for measuring strain using echocardiography. STE is more clinically relevant than TDI due to its ability to distinguish passive tethering from active contractility and its independence of ultrasound beam angle. Reliability of strain measurements from STE is not universally agreed upon due to vendor differences in strain analysis algorithms. LV GLS tends to consistently have the greatest reliability and thus the most significant clinical application. LV GCS and GRS, LA GLS, RA GLS, and RV GLS have more mixed results and have not been implemented as widely as LV GLS.
        Cover page: Reliability of 2D-Speckle-Tracking for Myocardial Strain Measurements
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2019)
        Kim H Nguyen and colleagues examine how tobacco companies applied their knowledge of flavours, colours, and child focused marketing to develop leading children’s sugar sweetened drink brands. These techniques continue to be used by drinks companies despite industry agreement not to promote unhealthy products in this way
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2020)
          Objectives. To investigate the transfer of marketing knowledge and infrastructure for targeting racial/ethnic minorities from the tobacco to the food and beverage industry in the United States.Methods. We analyzed internal industry documents between April 2018 and April 2019 from the University of California San Francisco Truth Tobacco Industry Documents Library, triangulated with other sources.Results. In the 1980s, Philip Morris Companies purchased General Foods and Kraft Foods and created Kraft General Foods. Through centralized marketing initiatives, Philip Morris Companies directly transferred expertise, personnel, and resources from its tobacco to its food subsidiaries, creating a racial/ethnic minority-targeted food and beverage marketing program modeled on its successful cigarette program. When Philip Morris Companies sold Kraft General Foods in 2007, Kraft General Foods had a fully integrated minority marketing program that combined target marketing with racial/ethnic events promotion, racial/ethnic media outreach, and corporate donations to racial/ethnic leadership groups, making it a food industry leader.Conclusions. The tobacco industry directly transferred racial/ethnic minority marketing knowledge and infrastructure to food and beverage companies. Given the substantial growth of food and beverage corporations, their targeting of vulnerable populations, and obesity-related disparities, public policy and community action is needed to address corporate target marketing.
            Cover page: Transferring Racial/Ethnic Marketing Strategies From Tobacco to Food Corporations: Philip Morris and Kraft General Foods.
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2018)
            RNA molecules can perform a myriad of functions, from the regulation of gene expression to providing the genetic blueprint for protein synthesis. Characterizing RNA expression dynamics, in a cell-specific manner, still remains a great challenge in biology. Herein we present a new set of protected alkynyl nucleosides for cell-specific metabolic labeling of RNA. We anticipate these analogs will find wide spread utility toward the goal of understanding RNA expression in complex cellular and tissue environments, even within living animals.
              Cover page: Protected pyrimidine nucleosides for cell-specific metabolic labeling of RNA
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2020)
              Objectives. To investigate the transfer of marketing knowledge and infrastructure for targeting racial/ethnic minorities from the tobacco to the food and beverage industry in the United States.Methods. We analyzed internal industry documents between April 2018 and April 2019 from the University of California San Francisco Truth Tobacco Industry Documents Library, triangulated with other sources.Results. In the 1980s, Philip Morris Companies purchased General Foods and Kraft Foods and created Kraft General Foods. Through centralized marketing initiatives, Philip Morris Companies directly transferred expertise, personnel, and resources from its tobacco to its food subsidiaries, creating a racial/ethnic minority-targeted food and beverage marketing program modeled on its successful cigarette program. When Philip Morris Companies sold Kraft General Foods in 2007, Kraft General Foods had a "fully integrated" minority marketing program that combined target marketing with racial/ethnic events promotion, racial/ethnic media outreach, and corporate donations to racial/ethnic leadership groups, making it a food industry leader.Conclusions. The tobacco industry directly transferred racial/ethnic minority marketing knowledge and infrastructure to food and beverage companies. Given the substantial growth of food and beverage corporations, their targeting of vulnerable populations, and obesity-related disparities, public policy and community action is needed to address corporate target marketing.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2023)
                Low activity has been the primary obstacle impeding the use of DNA enzymes (DNAzymes) as gene silencing agents in clinical applications. Here we describe the chemical evolution of a DNAzyme with strong catalytic activity under near physiological conditions. The enzyme achieves ~65 turnovers in 30 minutes, a feat only previously witnessed by the unmodified parent sequence under forcing conditions of elevated Mg2+ and pH. Structural constraints imposed by the chemical modifications drive catalysis toward a highly preferred UGUD motif (cut site underlined) that was validated by positive and negative predictions. Biochemical assays support an autonomous RNA cleavage mechanism independent of RNase H1 engagement. Consistent with its strong catalytic activity, the enzyme exhibits persistent allele-specific knock-down of an endogenous mRNA encoding an undruggable oncogenic KRAS target. Together, these results demonstrate that chemical evolution offers a powerful approach for discovering new chemotype combinations that can imbue DNAzymes with the physicochemical properties necessary to support therapeutic applications.
                  Cover page: Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2021)
                  Classification of heart failure is based on the left ventricular ejection fraction (EF): preserved EF, midrange EF, and reduced EF. There remains an unmet need for further heart failure phenotyping of ventricular structure-function relationships. Because of high spatiotemporal resolution, cardiac magnetic resonance (CMR) remains the reference modality for quantification of ventricular contractile function. The authors aim to highlight novel frameworks, including theranostic use of ferumoxytol, to enable more efficient evaluation of ventricular function in heart failure patients who are also frequently anemic, and to discuss emerging quantitative CMR approaches for evaluation of ventricular structure-function relationships in heart failure.
                    Cover page: Cardiac Magnetic Resonance Quantification of Structure-Function Relationships in Heart Failure.
                    • Thesis
                    • Peer Reviewed
                    UCLA Electronic Theses and Dissertations (2022)

                    Cardiovascular disease remains the global leading cause of death. Noninvasive imaging techniques to detect and quantify myocardial ischemia continue to have wide-ranging impact in clinical cardiovascular care. This body of research aims to develop several novel noninvasive quantitative cardiac magnetic resonance imaging (MRI) techniques for the detection of ischemic heart disease. We designed, manufactured, and percutaneously deployed 3D printed implants in the left anterior descending (LAD) artery of 13 swine to investigate the feasibility and efficacy of the implants to cause hypoperfusion and ischemia on MRI. This novel animal model offers a success rate comparable to that of highly invasive methods, allowing for more rapid and cost-effective translational imaging studies. In a cohort of these swine models, we found that ferumoxytol improves the diagnostic performance of T1 reactivity as a measure of myocardial ischemia. Next, we aimed to use FE-MRI to capture a hemodynamic response to myocardial hypoperfusion at rest. We derived and tested a two-compartment water exchange model for quantification of fractional myocardial blood volume (fMBV) before developing an integrated image registration and compartmental modelling platform. We demonstrated the feasibility of a two-compartment model for estimation of fMBV using steady-state MOLLI T1 mapping over multiple ferumoxytol doses. Our technical developments to our image processing pipeline advance the current state of pixelwise fMBV mapping toward a more integrated in-line approach. We ultimately found that this fMBV mapping approach can be used to distinguish between ischemic and remote myocardium in a broader study in 19 ischemic swine models. Finally, our investigation of the in-vitro and in-vivo MRI properties of three comparable iron-based contrast agents contributes may help to expand the adoption of this unique class of contrast agents. In addition to our contributions to the development of two novel imaging biomarkers of heart disease, this body of research enables a broad range of new research in quantitative cardiovascular MRI.

                      Cover page: Optimization and Validation of Ferumoxytol-Enhanced Myocardial T1 Reactivity and Myocardial Blood Volume Mapping for Detection of Myocardial Ischemia
                      Top