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Open Access Publications from the University of California

Scholarly Works (25 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2009)
The proper functioning of all nervous systems requires efficient communication among neurons. Neurotransmitters provide the fundamental basis for neural communication. Establishing the expression of the appropriate neurotransmitters in different populations of neurons is a critical challenge for neural development. This is a complicated process that involves multiple mechanisms, including intrinsic genetic coding, early neuronal activity and signal transduction cascades driven by neuronal targets. Embryonic Xenopus spinal neurons generate spontaneous transient elevations of intracellular calcium. Different classes of neurons exhibit this calcium spike activity in distinct patterns, and altering this activity modulates transmitter expression. However neurotransmitter expression is sensitive to this neuronal spike activity only during an early period of development. Both calcium spiking activity and the sensitivity of activity-dependent transmitter specification decrease and disappear as embryos mature. I showed that spinal transection causes neurons to resume calcium spike activity, and that enhancing this activity leads to increased expression of the inhibitory transmitter GABA. These results indicate a potential reopening of the sensitive period that exists earlier in development. Using a neuron-muscle co-culture system, I showed that muscle, as a neuronal target, plays important role in regulating transmitter expression. Muscle contact refines transmitter expression in cultured neurons by reducing the expression of non-cholinergic transmitters, GABA, glycine and glutamate, while leaving choline acetyltransferase (ChAT) expression unaltered. Trophic factors that are normally released at synapses and delivered retrogradely along axons appear to be sufficient to induce such changes. Further investigation revealed that muscle electrical activity is required for muscle-dependent suppression of non-cholinergic transmitter expression. In addition, muscle contact also suppresses neuronal spontaneous calcium activity and abolishes activity-dependent transmitter specification at early embryonic stages
    Cover page: Neuronal class-specific patterns of calcium activity and target dependence of neurotransmitter expression in the developing spinal cord
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2017)

    Maximin distance designs as an important class of space-filling designs are widely used in computer experiments, yet their constructions are challenging. In this thesis, we develop an efficient procedure to generate maximin Latin hypercube designs, as well as maximin multi-level fractional factorial designs, from existing orthogonal or nearly orthogonal arrays via level permutation and expansion. We show that the distance distributions of the generated designs are closely connected with the distance distributions and generalized word-length patterns of the initial designs. Examples are presented to show that our method outperforms many current prevailing methods. In addition, based on number theory and finite fields, we propose three algebraic methods to construct maximin distance Latin squares, as special Latin hypercube designs. We develop lower bounds on their minimum distances. The resulting Latin squares and related Latin hypercube designs have larger minimum distances than existing ones, and are especially appealing for high-dimensional applications. We show an application of space-filling designs in a combinatorial drug experiment on lung cancer. We compare four types of designs: a 512-run 8-level full factorial design, 80-run random sub-designs, 27-run random sub-designs and a 27-run space-filling three-level sub-design under four types of models: Kriging models, neural networks, linear models and Hill-based nonlinear models. We find that it is the best to adopt space-filling designs fitting Kriging models.

      Cover page: Constructions and Applications of Space-Filling Designs
      • Thesis
      • Peer Reviewed
      UCLA Electronic Theses and Dissertations (2015)

      Maximin distance designs as an important class of space-filling designs are widely used today, yet their constructions are challenging. In this article, we develop a 3-step procedure which can efficiently generate maximin distance Latin hypercube designs and maximin distance fractional factorial designs. This new method selects existing efficient low-level designs to generate high-level maximin distance designs via level expansion. The generated maximin distance designs are of flexible run and factor sizes and also have robust pairwise correlations. To justify this method, we derive the relationships of the distance distributions between the initial low-level designs and the generated high-level designs. We also prove the relationships between the generalized word length patterns of the initial low-level designs and the distance distributions of the generated high-level designs. Examples are presented to show that this new method outperforms many current prevailing methods in generating maximin distance designs.

        Cover page: Construction of Maximin Distance Designs via Level Expansion
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2021)
        Circadian disruption may play a role in carcinogenesis. Recent research suggests that light at night (LAN), a circadian disruptor, may be a risk factor for cancer. Moreover, LAN has been linked to obesity and diabetes, two risk factors for pancreatic ductal adenocarcinoma (PDAC). Here we examine the relationship between LAN and PDAC in an epidemiologic study of 464,371 participants from the NIH-AARP Diet and Health Study. LAN was estimated from satellite imagery at baseline (1996), and incident primary PDAC cases were ascertained from state cancer registries. Cox proportional hazards models were used to estimate HRs and two-sided 95% confidence intervals (CI) for the association between quintiles of LAN and PDAC in the overall population stratified by sex. Over up to 16.2 years of follow-up, a total of 2,502 incident PDAC were identified in the cohort. Higher estimated LAN exposure was associated with an elevated PDAC risk. Compared with those living in areas in the lowest LAN quintile, those in areas in the highest quintile had a 27% increase PDAC risk [HR (95% CI), 1.24 (1.03-1.49)], with similar risk for men [1.21 (0.96-1.53)] and women [1.28 (0.94-1.75)]. In addition, stronger associations were observed in normal and overweight groups compared with the obese group (P interaction = 0.03). Our results support the hypothesis that LAN and circadian disruption may be risk factors for PDAC. SIGNIFICANCE: Our study suggests that higher LAN is a risk factor for pancreatic cancer, contributing to the growing literature that demonstrates the potentially adverse health effects of light pollution.
          Cover page: Light at Night and Risk of Pancreatic Cancer in the NIH-AARP Diet and Health Study.
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2021)
          BACKGROUND: Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone-dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. METHODS: This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. RESULTS: Among 464,371 participants, a positive association was found between LAN and thyroid cancer risk. Specifically, in comparison with the lowest quintile of LAN, the highest quintile was associated with a 55% increase in risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.18-2.02). The association was primarily driven by papillary thyroid cancer and was stronger in women (HR, 1.81; 95% CI, 1.26-2.60) than men (HR, 1.29; 95% CI, 0.86-1.94). In women, the association was stronger for localized cancer, whereas in men, the association was stronger for a more advanced stage. Results were consistent across different tumor sizes. CONCLUSIONS: LAN was positively associated with thyroid cancer risk. Future studies are needed to confirm this association and identify underlying biological mechanisms.
            Cover page: Associations between artificial light at night and risk for thyroid cancer: A large US cohort study.
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2023)
            PURPOSE: Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. METHODS: We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. RESULTS: We observed no association for endometrial cancer overall (HRQ1vsQ5 0.92; 95% CI 0.78-1.08; p trend = 0.67) or endometrioid adenocarcinoma (HRQ1vsQ5 1.01; 95% CI 0.82-1.24; p trend = 0.36). Although body mass index and menopause hormone therapy were both associated with risk, there was no evidence of interaction with LAN (p interactions = 0.52 and 0.50, respectively). CONCLUSION: Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by the inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light.
              Cover page: Outdoor light at night and risk of endometrial cancer in the NIH-AARP diet and health study.
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2019)
                Cover page: 0286 Cross-Sectional and Longitudinal Relationships between Rest-Activity Rhythms and Metabolic Biomarkers in Older Men: The Osteoporotic Fractures in Men Sleep Study
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2020)
                BACKGROUND: Research has suggested that artificial light at night (LAN) may disrupt circadian rhythms, sleep, and contribute to the development of obesity. However, almost all previous studies are cross-sectional, thus, there is a need for prospective investigations of the association between LAN and obesity risk. The goal of our current study was to examine the association between baseline LAN and the development of obesity over follow-up in a large cohort of American adults. METHODS: The study included a sample of 239,781 men and women (aged 50-71) from the NIH-AARP Diet and Health Study who were not obese at baseline (1995-1996). We used multiple logistic regression to examine whether LAN at baseline was associated with the odds of developing obesity at follow-up (2004-2006). Outdoor LAN exposure was estimated from satellite imagery and obesity was measured based on self-reported weight and height. RESULTS: We found that higher outdoor LAN at baseline was associated with higher odds of developing obesity over 10 years. Compared with the lowest quintile of LAN, the highest quintile was associated with 12% and 19% higher odds of developing obesity at follow-up in men (OR (95% CI) = 1.12 (1.00, 1.250)) and women (1.19 (1.04, 1.36)), respectively. CONCLUSIONS: Our findings suggest that high LAN exposure could predict a higher risk of developing obesity in middle-to-older aged American adults.
                  Cover page: A large prospective investigation of outdoor light at night and obesity in the NIH-AARP Diet and Health Study.
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2020)
                  INTRODUCTION: Artificial light at night (ALAN) can disrupt circadian rhythms and cause sleep disturbances. Several previous epidemiological studies have reported an association between higher levels of outdoor ALAN and shorter sleep duration. However, it remains unclear how this association may differ by individual- and neighborhood-level socioeconomic status, and whether ALAN may also be associated with longer sleep duration. METHODS: We assessed the cross-sectional relationship between outdoor ALAN and self-reported sleep duration in 333,365 middle- to older-aged men and women in the NIH-AARP Diet and Health Study. Study participants reported baseline addresses, which were geocoded and linked with outdoor ALAN exposure measured by satellite imagery data obtained from the U.S. Defense Meteorological Satellite Programs Operational Linescan System. We used multinomial logistic regression to estimate the multinomial odds ratio (MOR) and 95% confidence intervals (CI) for the likelihood of reporting very short (<5 h), short (<7 h) and long (≥9 h) sleep relative to reporting 7-8 h of sleep across quintiles of LAN. We also conducted subgroup analyses by individual-level education and census tract-level poverty levels. RESULTS: We found that higher levels of ALAN were associated with both very short and short sleep. When compared to the lowest quintile, the highest quintile of ALAN was associated with 16% and 25% increases in the likelihood of reporting short sleep in women (MORQ1 vs Q5, (95% CI), 1.16 (1.10, 1.22)) and men (1.25 (1.19, 1.31)), respectively. Moreover, we found that higher ALAN was associated with a decrease in the likelihood of reporting long sleep in men (0.79 (0.71, 0.89)). We also found that the associations between ALAN and short sleep were larger in neighborhoods with higher levels of poverty. CONCLUSIONS: The burden of short sleep may be higher among residents in areas with higher levels of outdoor LAN, and this association is likely stronger in poorer neighborhoods. Future studies should investigate the potential benefits of reducing light intensity in high ALAN areas in improve sleep health.
                    Cover page: Cross-sectional association between outdoor artificial light at night and sleep duration in middle-to-older aged adults: The NIH-AARP Diet and Health Study.
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2020)

                    Objective

                    Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes, yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men.

                    Research design and methods

                    Baseline rest-activity rhythms were derived from actigraphy with use of extended cosine model analysis. With subjects fasting, glucose, insulin, and HOMA of insulin resistance (HOMA-IR) were measured from blood at baseline and after ∼3.5 years. Type 2 diabetes was defined based on self-report, medication use, and fasting glucose.

                    Results

                    In the cross-sectional analysis (n = 2,450), lower 24-h amplitude-to-mesor ratio (i.e., mean activity-adjusted rhythm amplitude) and reduced overall rhythmicity were associated with higher fasting insulin and HOMA-IR (all P trend < 0.0001), indicating increased insulin resistance. The odds of baseline type 2 diabetes were significantly higher among those in the lowest quartile of amplitude (Q1) (odds ratio [OR]Q1 vs. Q4 1.63 [95% CI 1.14, 2.30]) and late acrophase group (ORlate vs. normal 1.46 [95% CI 1.04, 2.04]). In the prospective analysis (n = 861), multiple rest-activity characteristics predicted a two- to threefold increase in type 2 diabetes risk, including a lower amplitude (ORQ1 vs. Q4 3.81 [95% CI 1.45, 10.00]) and amplitude-to-mesor ratio (OR 2.79 [95% CI 1.10, 7.07]), reduced overall rhythmicity (OR 3.49 [95% CI 1.34, 9.10]), and a late acrophase (OR 2.44 [1.09, 5.47]).

                    Conclusions

                    Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident type 2 diabetes.
                      Cover page: Cross-sectional and Prospective Associations of Rest-Activity Rhythms With Metabolic Markers and Type 2 Diabetes in Older Men
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