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Open Access Publications from the University of California

Scholarly Works (22 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2011)
Advancements in the field of optical sensors have resulted in an innovative class of microoptical sensors exhibiting detection capability comparable to those sophisticated analytical laboratory instrumentations. An emerging trend is to integrate these optical sensors/detecting methods into analytical tools with the ability to perform multifunctional tasks (i.e sample filtration, detection, and signal processing etc.) all in one platform. Porous silicon possesses many fascinating features making it an attractive candidate as a spectrally encoded material that is suitable as an identifier/barcode for multi-analyte bioassays and a spatially controlled structure that is applicable as a chromatography matrix for biomolecule separation. Its high surface to volume ratio and readily tailored surface chemistry also provide additional control for enhancing selectivity. Combining its optical and physical properties together with tailored surface moieties, porous silicon material can be treated as a multifunctional material allowing simultaneous separation and detection, capable of the multiplexed, low-level biodetection necessary to accommodate complex biological mixtures such as urine, whole blood, or serum used for disease diagnosis. This thesis begins with an overview on current separation techniques and progress in the field of optical sensors and nanomaterials. The second half of the introduction discusses recent development in porous silicon material with the focus on biosensing and molecular filtration applications. The objective of this thesis is to explore porous silicon as a multifunctional material with the ability to separate, process, and detect biomolecules at low concentration and in real-time with minimal sample preparation. Interrogation of porous silicon material as a multifunctional nanostructure involved three major aspects: 1) manipulation of its optical and spectral information for encoding and signal processing applications, 2) examination of the effect of its physical properties on molecular transport within its porous structure, 3) investigation of analyte-pore surface interaction for enhanced selectivity or better separation based on analyte surface moieties. The last chapter of this thesis provides an example of exploiting porous silicon as a multifunctional matrix that is capable of capturing and concentrating analyte while processing the signal, providing a new strategy for bioanalytics
    Cover page: Separation, process and detection of biomolecules using silicon-based optical nanostructures
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2013)

    Multiple drugs is much more effective in a cancer treatment than single drugs; however, it is challenging to find a reliable model that describes the relationship between drugs and the cell activities, as well as to construct efficient designs for reducing the number of drug combinations needed to be tested. We analyze data that consists of cellular ATP-levels on lung cancer cells and normal cells with 3 inhibitor drugs, AG490, U0126 and I-3'-M, each at 8 dosage levels. We construct models with different number of predictors and methods as well as different subsets of the full data. We find that large dataset does not guarantee the accuracy of a model's prediction, but an appropriate design and a good model building method are the keys. Square root transformation on the response gives a model prediction surpassing the performance among all other models we built. A second order model constructed with a 27-run factorial design performs remarkably well for both cancer cells and normal cells. It is in general much harder to model or predict cancer cells than normal cells.

      Cover page: Modeling Multiple Drugs on Lung Cancer and Normal Cells using Regression
      • Thesis
      • Peer Reviewed
      UC San Diego Electronic Theses and Dissertations (2018)

      Base isolation is an effective technology for reducing seismic damage to both structural and nonstructural components, as well as to building contents, allowing buildings to remain functional during and in the aftermath of a rare and strong intensity earthquake. This makes it an ideal seismic response modification system for hospitals and buildings of high importance. Despite the enhanced seismic resiliency of buildings incorporating base isolation, many countries have been slow to adopt it in building designs prior to experiencing the devastating effects of a major earthquake, often embracing the technology as an outcome. The goal of the research in this dissertation is to advance the understanding of base isolation, in order to diminish some of the barriers that impede its widespread use.

      This dissertation uses data collected from a shake table experiment of a full-scale five-story building outfitted with nonstructural components and systems to analyze the structural response of the building in both base isolated and fixed base configurations. By simulating a realistic environment, this project documents the destructive effects of an earthquake with and without base isolation, ultimately demonstrating the technology’s effectiveness in minimizing structural demands.

      Another test that was conducted addressed the specific response of an isolator in realistic earthquake conditions. One of the barriers that prevents the use of base isolation in certain scenarios is because of gaps in knowledge due to lack of testing. To address this, a comprehensive multiaxial testing program of a high damping rubber bearing was performed, fully characterizing the bearing in six degrees of freedom, to understand the impact of realistic loading conditions on the isolator response.

      Finally, base isolation is often implemented in buildings specifically to protect nonstructural components and ensure functionality of the building after an earthquake. Despite this, current design codes do not specifically address nonstructural components within base isolated buildings. This dissertation proposes a framework for designing inertia-sensitive nonstructural components within base isolated buildings. The framework is demonstrated through a case study using experimental structural response data in conjunction with simulated nonstructural responses generated by relative displacement floor response spectra for inelastic response.

        Cover page: Enhanced Seismic Resiliency for Buildings via Base Isolation
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2023)
        Following a stressful life event, there is considerable variation in how individuals respond and adapt. Multiple models of risk and resilience show that adverse childhood experiences may be associated with an individuals response to stress later in life. While there is considerable support that early adversity can sensitize the stress response system and lead to adverse outcomes later in life, there is mounting evidence that in adolescence and young adulthood, certain biological predispositions to stress may be associated with resilience in the context of subsequent stressors. In this study, we evaluated how individual differences in vagally mediated heart rate variability moderated the relationship between childhood maltreatment and grief among a sample of individuals experiencing a stressful life event (i.e., spousal bereavement) over time. Data were collected at approximately 3, 4.5, and 6.5 months after the death of a spouse (n = 130). Heart rate variability moderated the relationship between childhood maltreatment and grief symptoms over time (b = -0.03, p < .001), such that among individuals with more severe experiences of childhood maltreatment, those with higher heart rate variability had a faster recovery from grief than those with low heart rate variability. This research highlights an overall pattern of resilience among older adults following spousal bereavement, as well as the relationships between childhood maltreatment, heart rate variability, and differential responses to grief following the loss of a spouse. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
          Cover page: Resilience to stress across the lifespan: Childhood maltreatment, heart rate variability, and bereavement.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2015)
          Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15-0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26-0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis.
            Cover page: Predictors of Survival in Sinonasal Adenocarcinoma
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2012)
            Abstract Background B cell lymphoma 2 (Bcl-2) proteins are the central regulators of apoptosis. The two bcl-2 genes in Drosophila modulate the response to stress-induced cell death, but not developmental cell death. Because null mutants are viable, Drosophila provides an optimum model system to investigate alternate functions of Bcl-2 proteins. In this report, we explore the role of one bcl-2 gene in nutrient stress responses. Results We report that starvation of Drosophila larvae lacking the bcl-2 gene, buffy, decreases survival rate by more than twofold relative to wild-type larvae. The buffy null mutant reacted to starvation with the expected responses such as inhibition of target of rapamycin (Tor) signaling, autophagy initiation and mobilization of stored lipids. However, the autophagic response to starvation initiated faster in larvae lacking buffy and was inhibited by ectopic buffy. We demonstrate that unusually high basal Tor signaling, indicated by more phosphorylated S6K, was detected in the buffy mutant and that removal of a genomic copy of S6K, but not inactivation of Tor by rapamycin, reverted the precocious autophagy phenotype. Instead, Tor inactivation also required loss of a positive nutrient signal to trigger autophagy and loss of both was sufficient to activate autophagy in the buffy mutant even in the presence of enforced phosphoinositide 3-kinase (PI3K) signaling. Prior to starvation, the fed buffy mutant stored less lipid and glycogen, had high lactate levels and maintained a reduced pool of cellular ATP. These observations, together with the inability of buffy mutant larvae to adapt to nutrient restriction, indicate altered energy metabolism in the absence of buffy. Conclusions All animals in their natural habitats are faced with periods of reduced nutrient availability. This study demonstrates that buffy is required for adaptation to both starvation and nutrient restriction. Thus, Buffy is a Bcl-2 protein that plays an important non-apoptotic role to promote survival of the whole organism in a stressful situation.
              Cover page: Drosophila larvae lacking the bcl-2 gene, buffy, are sensitive to nutrient stress, maintain increased basal Tor signaling and exhibit characteristics of altered basal energy metabolism
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2018)

              Importance

              Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial.

              Objective

              To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry.

              Design, setting, and participants

              In this observational cohort study, 25 216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB).

              Exposures

              Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT.

              Main outcomes and measures

              Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation.

              Results

              We identified 25 216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18 968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25 216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation.

              Conclusions and relevance

              Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.
                Cover page: Association of Survival With Shorter Time to Radiation Therapy After Surgery for US Patients With Head and Neck Cancer.
                • Article
                • Peer Reviewed
                Clinical Practice and Cases in Emergency Medicine, Volume 8, Issue 4 (2024)

                Introduction: Achenbach syndrome is a rare, benign condition characterized by painful discoloration of
                a finger. Recognition of this syndrome prevents unnecessary costly workup and risky interventions.

                Case Report: A healthy, 54-year-old female was transferred to our emergency department (ED) from a
                community ED for vascular evaluation of discoloration and numbness to her finger. After extensive
                workup, medical intervention, and consultation with multiple specialists, she was diagnosed with
                Achenbach syndrome.

                Conclusion: Emergency physicians may practice good healthcare stewardship and limit invasive,
                potentially harmful, and expensive workup by reassuring patients of the benign nature of this condition.

                  Cover page: Achenbach Syndrome: A Case ReportCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2020)
                  Brain endothelial cells (BECs) are key constituents of the blood-brain barrier (BBB), protecting the brain from pathogens and restricting access of circulatory factors. Yet, because circulatory proteins have prominent age-related effects on adult neurogenesis, neuroinflammation, and cognitive function in mice, we wondered whether BECs receive and potentially relay signals between the blood and brain. Using single-cell RNA sequencing of hippocampal BECs, we discover that capillary BECs-compared with arterial and venous BECs-undergo the greatest transcriptional changes in normal aging, upregulating innate immunity and oxidative stress response pathways. Short-term infusions of aged plasma into young mice recapitulate key aspects of this aging transcriptome, and remarkably, infusions of young plasma into aged mice exert rejuvenation effects on the capillary transcriptome. Together, these findings suggest that the transcriptional age of BECs is exquisitely sensitive to age-related circulatory cues and pinpoint the BBB itself as a promising therapeutic target to treat brain disease.
                    Cover page: Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues.
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2022)
                    The negative emotions generated following stressful life events can increase ones risk of depressive symptoms and promote higher levels of perceived stress. The process model of emotion regulation can help distinguish between adaptive and maladaptive emotion regulation strategies to determine who may be at the greatest risk of worse psychological health across the lifespan. Heart rate variability (HRV) may affect these relationships as it indexes aspects of self-regulation, including emotion and behavioral regulation, that enable an individual to dynamically adapt to the changing demands of both internal and external environments. In this study, we expected individual differences in resting vagally mediated HRV to moderate the influence of emotion regulatory strategies among our sample of 267 adults. We found support for the hypothesis that higher vagally mediated HRV buffers against the typical adverse effects of expressive suppression when evaluating depressive symptoms and found weak support when considering perceived stress. There was no evidence for an interaction between cognitive reappraisal and vagally mediated HRV but there was a significant, negative association between cognitive reappraisal and depressive symptoms and perceived stress. Future work may determine if intervening on either emotion regulation strategies or HRV may change these within-persons over time.
                      Cover page: Emotion Regulation, Parasympathetic Function, and Psychological Well-Being.
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