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Open Access Publications from the University of California

Scholarly Works (7 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2023)
The role of vaccination in tackling Covid-19 and the potential consequences of a time delay in vaccination rate are discussed. This study presents a mathematical model that incorporates the rate of vaccination and parameters related to the presence and absence of time delay in the context of Covid-19. We conducted a study on the global dynamics of a Covid-19 outbreak model, which incorporates a vaccinated population and a time delay parameter. Our findings demonstrate the global stability of these models. Our observation indicates that lower vaccination rates are associated with an increase in the overall number of infected individuals. The stability of the corresponding time delay model is determined by the value of the time delay parameter. If the time delay parameter is less than the critical value at which the Hopf bifurcation occurs, the model is stable. The results are supported by numerical illustrations that have epidemiological relevance.
    • Article
    • Peer Reviewed
    2016 Publications (2016)
      Cover page: Impacts of dimethyl carbonate blends on gaseous and particulate emissions from a heavy-duty diesel engine
      • Article
      Research Reports (2017)

      Some of the most important questions in the development of sustainable transportation are identify fuels that will reduce emissions, provide diversification from fossil fuels, reduce greenhouse gas emissions, be produced from renewable sources, and that can be produced in a sustainable manner. An alternative diesel fuel that could be used for particulate matter (PM) reductions and be produced from renewable sources could represent a key advance for the transportation sector in terms of sustainability, diversification for the marketplace for the alternative fuels, emissions reductions, and reductions in greenhouse gases. Dimethyl carbonate (DMC) is a potentially new fuel that could represent an important advance in the diesel fuel area. DMC can be produced from renewable sources such as grass, manure, or trees. Preliminary tests at the University of California at Riverside have also indicated PM reductions of about 76% at only a 20% blend with diesel fuel, which is about double or triple the reductions typically found for biodiesel at a comparable blend level, and comparable to the reductions found for diesel particulate filters (DPFs). Although these preliminary results indicate the promise of DMC as a PM mass reduction strategy, it is important to more completely characterize the emissions and viability of DMC before it can be more widely used in the fuel market or for in-field demonstrations. The objective of this study was to conduct a preliminary evaluation of the viability of DMC as a transportation fuel for fleet and wider applications. This included a literature review to address questions related to air emissions, impact on vehicle system durability and parts, and any potential storage issues. This study also included some additional emissions testing to evaluate any emissions of toxic species, and to look at some optimization of blend level in terms of a full range of emissions components.

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        Cover page: Evaluating the Viability of Dimethyl Carbonate as an Alternative Fuel for the Transportation Sector
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2014)
        Influenza causes serious and sometimes fatal disease in individuals at risk due to advanced age or immunodeficiencies. Despite progress in the development of seasonal influenza vaccines, vaccine efficacy in elderly and immunocompromised individuals remains low. We recently developed a passive immunization strategy using an adeno-associated virus (AAV) vector to deliver a neutralizing anti-influenza antibody at the site of infection, the nasal airways. Here we show that young, old, and immunodeficient (severe combined immunodeficient [SCID]) mice that were treated intranasally with AAV9 vector expressing a modified version of the broadly neutralizing anti-influenza antibody FI6 were protected and exhibited no signs of disease following an intranasal challenge with the mouse-adapted H1N1 influenza strain A/Puerto Rico/8/1934(H1N1) (PR8) (Mt. Sinai strain). Nonvaccinated mice succumbed to the PR8 challenge due to severe weight loss. We propose that airway-directed AAV9 passive immunization against airborne infectious agents may be beneficial in elderly and immunocompromised patients, for whom there still exists an unmet need for effective vaccination against influenza.
          Cover page: Adeno-Associated Virus 9-Mediated Airway Expression of Antibody Protects Old and Immunodeficient Mice against Influenza Virus
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2012)
          Abstract Background Inflammatory bowel diseases are associated with increased expression of zinc-dependent Matrix Metalloproteinase 9 (MMP-9). A stark dysregulation of intestinal mucosal homeostasis has been observed in patients with chronic inflammatory bowel diseases. We therefore sought to determine the contribution of MMP-9 to the pathogenesis of Citrobacter rodentium-induced colitis and its effects on gut microbiome homeostasis. Results Wild-type and MMP-9−/− mice aged 5–6 weeks were challenged with C. rodentium by orogastric gavage and sacrificed either 10 or 30 days post-infection. Disease severity was assessed by histological analysis of colonic epithelial hyperplasia and by using an in vivo intestinal permeability assay. Changes in the inflammatory responses were measured by using qPCR, and the composition of the fecal microbiome evaluated with both qPCR and terminal restriction fragment length polymorphism. Activation and localization of MMP-9 to the apical surface of the colonic epithelium in response to C. rodentium infection was demonstrated by both zymography and immunocytochemistry. The pro-inflammatory response to infection, including colonic epithelial cell hyperplasia and barrier dysfunction, was similar, irrespective of genotype. Nonmetric multidimensional scaling of terminal restriction fragments revealed a different fecal microbiome composition and C. rodentium colonization pattern between genotypes, with MMP-9−/− having elevated levels of protective segmented filamentous bacteria and interleukin-17, and lower levels of C. rodentium. MMP-9−/− but not wild-type mice were also protected from reductions in fecal microbial diversity in response to the bacterial enteric infection. Conclusions These results demonstrate that MMP-9 expression in the colon causes alterations in the fecal microbiome and has an impact on the pathogenesis of bacterial-induced colitis in mice.
            Cover page: Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2023)
            Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial ZFTA-fusion associated and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment. Although molecular mechanisms underlying these diseases have recently been uncovered, they remain difficult to target and innovative therapeutic approaches are urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C), complemented with CTCF and H3K27ac ChIP-seq, as well as gene expression and DNA methylation analysis in primary and relapsed ependymoma tumors, to identify chromosomal conformations and regulatory mechanisms associated with aberrant gene expression. In particular, we observe the formation of new topologically associating domains ('neo-TADs') caused by structural variants, group-specific 3D chromatin loops, and the replacement of CTCF insulators by DNA hyper-methylation. Through inhibition experiments, we validate that genes implicated by these 3D genome conformations are essential for the survival of patient-derived ependymoma models in a group-specific manner. Thus, this study extends our ability to reveal tumor-dependency genes by 3D genome conformations even in tumors that lack targetable genetic alterations.
              Cover page: 3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2022)
              Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage5-8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES+KI67+ unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB.
                Cover page: Failure of human rhombic lip differentiation underlies medulloblastoma formation
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