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Open Access Publications from the University of California

Scholarly Works (26 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2024)

The advancement of new exposure assessment techniques has facilitated the development of several wildland fire smoke datasets employing varied smoke estimation methods. Exposure to wildland fire smoke can increase respiratory health risks, particularly among vulnerable groups such as the elderly. This study compares estimates of wildland fire smoke fine particulate matter (“smoke PM2.5”) in California from 2008 to 2018 across three datasets and quantifies differences in the attributable respiratory health burden among elderly populations from utilizing different smoke datasets. Smoke estimates from Childs and Casey, which rely on similar input datasets, were more similar than those from CMAQ in terms of correlation, spatial distributions, and temporal trends. Approximately 1,300-5,400 respiratory morbidity impacts among the elderly are attributable to smoke PM2.5 in California during the study period. Using different smoke datasets and dose-response values yielded discrepancies in health impact estimates, with larger discrepancies between CMAQ with Childs and Casey. Differences in smoke PM2.5 and health impact estimates can affect future wildland fire policies that rely on these estimates to address health burdens.

    Cover page: Wildland fire smoke and respiratory health outcomes among elderly populations in California: comparison of exposure and health impact estimates
    • Thesis
    • Peer Reviewed
    UC Irvine Electronic Theses and Dissertations (2017)

    ABSTRACT OF THE THESIS

    Exhibiting Asian Objects in the Norton Simon Museum:

    The Orientalization of the Asian Art Galleries

    By

    Jenny Hong Mai Nguyen

    Master of Arts in Art History

    University of California, Irvine, 2017

    Professor Margaret M. Miles, Chair

    The purpose of my thesis is to analyze how the label, "Asian Art Collection," misrepresents and misinterprets the cultural objects displayed in the Norton Simon Museum. After Norton Simon's death in 1993, the museum underwent a five million dollar renovation, which included adding gallery space for Simon's Asian art collection. Designed by Frank Gehry with the assistance of Dr. Pratapaditya Pal, the overall design and aesthetic of the galleries suggests the idea of a sacred temple space, which generalizes Asia to be a timeless and oriental place. While the collection itself contains mostly religious objects, it fails to represent all Asian cultures and countries as indicated by the collection title. Using James Clifford's art-culture system, I question whether these cultural objects are considered art and analyze the value the museum assigned to these objects and how this value is reflected in how they are displayed. The Norton Simon Museum fails to educate the community it serves by not presenting a diverse and inclusive collection of objects from Asia.

      Cover page: Exhibiting Cultural Objects from Asia in the Norton Simon Museum: The Orientalization of the Asian Art Galleries
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2018)
      Neutralizing antibodies (NAb) interfering with glycoprotein complex-mediated virus entry into host cells are thought to contribute to the protection against herpesvirus infection. However, using herpesvirus glycoprotein complexes as vaccine antigens can be complicated by the necessity of expressing multiple subunits simultaneously to allow efficient complex assembly and formation of conformational NAb epitopes. By using a novel bacterial artificial chromosome (BAC) clone of the clinically deployable Modified Vaccinia Ankara (MVA) vector and exploiting ribosomal skipping mediated by 2A peptides, MVA vectors were generated that expressed self-processing subunits of the human cytomegalovirus (HCMV) pentamer complex (PC) composed of gH, gL, UL128, UL130, and UL131A. These MVA vectors expressed 2A-linked HCMV PC subunits that were efficiently cleaved and transported to the cell surface as protein complexes forming conformational neutralizing epitopes. In addition, vaccination of mice by only two immunizations with these MVA vectors resulted in potent HCMV NAb responses that remained stable over a period of at least six months. This method of eliciting NAb by 2A-linked, self-processing HCMV PC subunits could contribute to develop a HCMV vaccine candidate and may serve as a template to facilitate the development of subunit vaccine strategies against other herpesviruses.
        Cover page: Exploiting 2A peptides to elicit potent neutralizing antibodies by a multi-subunit herpesvirus glycoprotein complex
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2024)
        PURPOSE: The impact of digital health on medically underserved patients is unclear. This study aimed to determine the early impact of a digital innovation to grow quality care through an interprofessional care team (DIG IT) on the blood pressure (BP) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of medically underserved patients. METHODS: This was a 3-month, prospective intervention study that included patients aged 40 years or more with BP of 140/90 mmHg or higher who received care from DIG IT from August through December 2021. Sociodemographic and clinical outcomes of DIG IT were compared with historical controls (controls) whose data were randomly extracted by the University of California Data Warehouse and matched 1:1 based on age, ethnicity, and baseline BP of the DIG IT arm. Multiple linear regression was performed to adjust for potential confounding factors. RESULTS: A total of 140 patients (70 DIG IT, 70 controls) were included. Both arms were similar with an average age (SD) of 62.8 (9.7) years. The population was dominated by Latinx (79.3%) persons, with baseline mean BP of 163/81 mmHg, and mean ASCVD risk score of 23.9%. The mean (SD) reduction in systolic BP at 3 months in the DIG IT arm was twice that of the controls (30.8 [17.3] mmHg vs 15.2 [21.2] mmHg; P <.001). The mean (SD) ASCVD risk score reduction in the DIG IT arm was also twice that of the controls (6.4% [7.4%] vs 3.1% [5.1%]; P = .003). CONCLUSIONS: The DIG IT was more effective than controls (receiving usual care). Twofold improvement in the BP readings and ASCVD scores in medically underserved patients were achieved with DIG IT.
          Cover page: Digital Innovation to Grow Quality Care Through an Interprofessional Care Team (DIG IT) Among Underserved Patients With Hypertension.
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2020)

          Background

          Evasion from programmed cell death is a hallmark of cancer and can be achieved in cancer cells by overexpression of inhibitor of apoptosis proteins (IAPs). Second mitochondria-derived activator of caspases (SMAC) directly bind to IAPs and promote apoptosis; thus, SMAC mimetics have been investigated in a variety of cancer types. particularly in diseases with high inflammation and NFĸB activation. Given that elevated TNFα levels and NFĸB activation is a characteristic feature of myeloproliferative neoplasms (MPN), we investigated the effect of the SMAC mimetic LCL-161 on MPN cell survival in vitro and disease development in vivo.

          Methods

          To investigate the effect of the SMAC mimetic LCL-161 in vitro, we utilized murine and human cell lines to perform cell viability assays as well as primary bone marrow from mice or humans with JAK2V617F-driven MPN to interrogate myeloid colony formation. To elucidate the effect of the SMAC mimetic LCL-161 in vivo, we treated a JAK2V617F-driven mouse model of MPN with LCL-161 then assessed blood counts, splenomegaly, and myelofibrosis.

          Results

          We found that JAK2V617F-mutated cells are hypersensitive to the SMAC mimetic LCL-161 in the absence of exogenous TNFα. JAK2 kinase activity and NFĸB activation is required for JAK2V617F-mediated sensitivity to LCL-161, as JAK or NFĸB inhibitors diminished the differential sensitivity of JAK2V617F mutant cells to IAP inhibition. Finally, LCL-161 reduces splenomegaly and may reduce fibrosis in a mouse model of JAK2V617F-driven MPN.

          Conclusion

          LCL-161 may be therapeutically useful in MPN, in particular when exogenous TNFα signaling is blocked. NFĸB activation is a characteristic feature of JAK2V617F mutant cells and this sensitizes them to SMAC mimetic induced killing even in the absence of TNFα. However, when exogenous TNFα is added, NFĸB is activated in both mutant and wild-type cells, abolishing the differential sensitivity. Moreover, JAK kinase activity is required for the differential sensitivity of JAK2V617F mutant cells, suggesting that the addition of JAK2 inhibitors to SMAC mimetics would detract from the ability of SMAC mimetics to selectively target JAK2V617F mutant cells. Instead, combination therapy with other agents that reduce inflammatory cytokines but preserve JAK2 signaling in mutant cells may be a more beneficial combination therapy in MPN.
            Cover page: The SMAC mimetic LCL-161 selectively targets JAK2V617F mutant cells
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2024)
            California faces several serious direct and indirect climate exposures that can adversely affect public health, some of which are already occurring. The public health burden now and in the future will depend on atmospheric greenhouse gas concentrations, underlying population vulnerabilities, and adaptation efforts. Here, we present a structured review of recent literature to examine the leading climate risks to public health in California, including extreme heat, extreme precipitation, wildfires, air pollution, and infectious diseases. Comparisons among different climate-health pathways are difficult due to inconsistencies in study design regarding spatial and temporal scales and health outcomes examined. We find, however, that the current public health burden likely affects thousands of Californians each year, depending on the exposure pathway and health outcome. Further, while more evidence exists for direct and indirect proximal health effects that are the focus of this review, distal pathways (e.g., impacts of drought on nutrition) are more uncertain but could add to this burden. We find that climate adaptation measures can provide significant health benefits, particularly in disadvantaged communities. We conclude with priority recommendations for future analyses and solution-driven policy actions.
              Creative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2020)
              Human cytomegalovirus (CMV) is a ubiquitous pathogen that causes significant morbidity in some vulnerable populations. Individualized adoptive transfer of ex vivo expanded CMV-specific CD8+ T cells has provided proof-of-concept that immunotherapy can be highly effective, but a chimeric antigen receptor (CAR) approach would provide a feasible method for broad application. We created 8 novel CARs using anti-CMV neutralizing antibody sequences, which were transduced via lentiviral vector into primary CD8+ T cells. All CARs were expressed. Activity against CMV-infected target cells was assessed by release of cytokines (interferon-γ and tumor necrosis factor-α), upregulation of surface CD107a, proliferation, cytolysis of infected cells, and suppression of viral replication. While some CARs showed varying functional activity across these assays, 1 CAR based on antibody 21E9 was consistently superior in all measures. These results support development of a CMV-specific CAR for therapeutic use against CMV and potentially other applications harnessing CMV-driven immunotherapies.
                Cover page: Chimeric Antigen Receptors Targeting Human Cytomegalovirus
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2022)

                Background

                Polycyclic aromatic hydrocarbon (PAH) exposures from tobacco smoke, automobile exhaust, grilled or smoked meat and other sources are widespread and are a public health concern, as many are classified as probable carcinogens and suspected endocrine-disrupting chemicals. PAH exposures can be quantified using urinary biomarkers.

                Methods

                Seven urinary metabolites of naphthalene, fluorene, phenanthrene, and pyrene were measured in two samples collected from girls aged 6-16 years from the San Francisco Bay Area. We used Spearman correlation coefficients (SCC) to assess correlations among metabolite concentrations (corrected for specific gravity) separately in first (n = 359) and last (N = 349) samples, and to assess consistency of measurements in samples collected up to 72 months apart. Using multivariable linear regression, we assessed variation in mean metabolites across categories of participant characteristics and potential outdoor, indoor, and dietary sources of PAH exposures.

                Results

                The detection rate of PAH metabolites was high (4 metabolites in ≥98% of first samples; 5 metabolites in ≥95% of last samples). Correlations were moderate to strong between fluorene, phenanthrene and pyrene metabolites (SCC 0.43-0.82), but weaker between naphthalene and the other metabolites (SCC 0.18-0.36). SCC between metabolites in first and last samples ranged from 0.15 to 0.49. When classifying metabolite concentrations into tertiles based on single samples (first or last samples) vs. the average of the two samples, agreement was moderate to substantial (weighted kappa statistics 0.52-0.65). For specific metabolites, concentrations varied by age, race/ethnicity, and body mass index percentile, as well as by outdoor sources (season of sample collection, street traffic), indoor sources (heating with gas, cigarette smoke), and dietary sources (frequent use of grill, consumption of smoked meat or fish) of PAH exposures.

                Conclusions

                Urinary PAH exposure was widespread in girls aged 6-16 years and associated with several sources of exposure. Tertile classification of a single urine sample provides reliable PAH exposure ranking.
                  Cover page: Predictors of urinary polycyclic aromatic hydrocarbon metabolites in girls from the San Francisco Bay Area
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2015)
                  The aim of the study was to examine functional brain activity in response to unpleasant images in individuals with the 7-repeat (7R) allele compared to individuals with the 4-repeat (4R) allele of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3). Based on the response ready hypothesis, individuals with the DRD4-4R/7R genotype were expected to show greater functional brain activity in response to unpleasant compared to neutral stimuli in specific regions of the frontal, temporal, parietal and limbic lobes, which form the networks involved in attentional, emotional, and preparatory responses. Functional Magnetic Resonance Imaging activity was studied in 26 young adults (13 with the DRD4-4R/7R genotype and 13 with the DRD4-4R/4R genotype). Participants were asked to look at and subjectively rate unpleasant and neutral images. Results showed increased brain activity in response to unpleasant images compared to neutral images in the right temporal lobe in participants with the DRD4-4R/7R genotype versus participants with the DRD4-4R/4R genotype. The increase in right temporal lobe activity in individuals with DRD4-4R/7R suggests greater involvement in processing negative emotional stimuli. Intriguingly, no differences were found between the two genotypes in the subjective ratings of the images. The findings corroborate the response ready hypothesis, which suggests that individuals with the 7R allele are more responsive to negative emotional stimuli compared to individuals with the 4R allele of the DRD4 gene.
                    Cover page: Increased brain activity to unpleasant stimuli in individuals with the 7R allele of the DRD4 geneCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed

                    Background

                    Many patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma.

                    Results

                    TMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6-methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals.

                    Conclusion

                    Our results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC.
                      Cover page: Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo
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