Computational Bayesian Methods Applied to Complex Problems in Bio and Astro Statistics

In this dissertation we apply computational Bayesian methods to three distinct problems. In the first chapter, we address the issue of unrealistic covariance matrices used to estimate collision probabilities. We model covariance matrices with a Bayesian Normal-Inverse-Wishart model, which we fit with Gibbs sampling. In the second chapter, we are interested in determining the sample sizes necessary to achieve a particular interval width and establish non-inferiority in the analysis of prevalences using two fallible tests. To this end, we use a third order asymptotic approximation. In the third chapter, we wish to synthesize evidence across multiple domains in measurements taken longitudinally across time, featuring a substantial amount of structurally missing data, and fit the model with Hamiltonian Monte Carlo in a simulation to analyze how estimates of a parameter of interest change across sample sizes

Effects of Chronic Cd Exposure via the Diet or Water on Internal Organ-Specific Distribution and Subsequent Gill Cd Uptake Kinetics in Juvenile Rainbow Trout (\u3cem\u3eOncorhynchus mykiss\u3c/em\u3e)

New regulatory approaches to metal toxicity (e.g., biotic ligand model [BLM]) focus on gill metal binding and tissue specific accumulation of waterborne metals; the dietary route of exposure and dietary/waterborne interactions are not considered, nor are the consequences of chronic exposure by either route. Therefore, we studied the effect of the same gill Cd load (∼μ2.5 mg/g), achieved by a chronic, 30-d exposure to Cd either via the diet (1,500 mg/kg) or the water (2 μg/L), on tissue-specific Cd distribution and subsequent uptake of waterborne Cd in juvenile rainbow trout (Oncorhynchus mykiss). These two exposure regimes resulted in a branchial Cd load that had been taken up across either apical gill membranes (waterborne Cd) or basolateral gill membranes (through the bloodstream for dietary Cd). The BLM characteristics of the gills (i.e., short-term Cd uptake kinetics) were altered: affinity (log KCd-Gill [95% confidence level]) decreased from 7.05 (6.75–8.76) for control to 6.54 (6.32–7.03) for waterborne Cd and 5.92 (5.83–6.51) for dietary Cd, whereas binding capacity (Bmax) increased from 3.12 (2.14–4.09) to 4.80 (3.16–6.43) and 5.50 (2.86–8.17) nmol·g-1 for control, waterborne, and dietary Cd, respectively. Fish exposed to dietary Cd accumulated a much greater overall chronic Cd body burden relative to fish exposed to waterborne Cd or control fish. The carcass accumulated the greatest percentage of total body Cd in control and waterborne-exposed fish, whereas the intestinal tissue accumulated the greatest percentage in dietary-exposed fish. Tissue-specific Cd burdens were highest in the kidney in both dietary and waterborne treatments. We conclude that chronic Cd exposure alters Cd uptake dynamics, and that the route of Cd exposure, whether waterborne or dietary, results in differences of internal Cd accumulation and branchial Cd uptake characteristics. These factors should be considered in future BLM development

Protective Effects of Calcium Against Chronic Waterborne Cadmium Exposure to Juvenile Rainbow Trout

Juvenile rainbow trout (Oncorhynchus mykiss [Walbaum]) on 1% daily ration were exposed to 0 (control) or 2 μg of cadmium as Cd(NO3)2·4H2O per liter added to four different calcium (Ca) concentrations: 260 (background), 470 (low), 770 (medium), or 1200 (high) μM of Ca added as Cd(NO3)2·4H2O in synthetic soft water for 30 d. Mortality was highest (;80%) in the background 1 Cd treatment. Approximately 40% mortality was observed in the low 1 Cd exposure; mortality was 10% or less for all other treatments. No growth effects were seen for any of the exposures. Kidneys accumulated the greatest concentration of Cd during the 30 d, followed by gills and livers. Accumulation of Cd in gills, kidney, and liver decreased at higher water Ca concentrations. No differences in whole-body or plasma Ca concentrations were found. Swimming performance was impaired in the low + Cd-exposed fish. Influx of Ca2+ into whole bodies decreased as water Ca concentrations increased; influx of Ca2+ into background + Cd–treated fish was significantly reduced compared to that in control fish. Experiments that measured uptake of new Cd into gills showed that the affinity of gills for Cd (KCd-gill) and the number of binding sites for Cd decreased as water Ca concentrations increased. Acute accumulation of new Cd into gills and number of gill Cd-binding sites increased with chronic Cd exposure, whereas the affinity of gills for Cd decreased with chronic Cd exposure. Longer-term gill binding (72 h) showed reduced uptake of new Cd at higher water Ca levels and increased uptake with chronic Cd exposure. Complications were found in applying the biotic ligand model to fish that were chronically exposed to Cd because of discrepancies in the maximum number of gill Cd-binding sites among different studies

Physiological Effects of Chronic Copper Exposure to Rainbow Trout (\u3cem\u3eOncorhynchus Mykiss\u3c/em\u3e) in Hard and Soft Water: Evaluation of Chronic Indicators

Effects of chronic copper exposure on a suite of indicators were examined: acute toxicity, acclimation, growth, sprint performance, whole-body electrolytes, tissue residues, and gill copper binding characteristics. Juvenile rainbow trout were exposed for 30 d to waterborne copper in hard water (hardness = 120 μg/L as CaCO3, pH = 8.0, Cu = 20 and 60 μg/L) and soft water (hardness = 20 μg/L as CaCO3, pH = 7.2, Cu = 1 and 2 μg/L). Significant acclimation to the metal occurred only in fish exposed to 60 mg/L, as seen by an approx. twofold increase in 96-h LC50 (153 vs 91 μg Cu/L). Chronic copper exposure had little or no effect on survival, growth, or swimming performance in either water hardness, nor was there any initial whole-body electrolyte loss (Na+ and Cl-). The present data suggest that the availability of food (3% wet body weight/day, distributed as three 1% meals) prevented growth inhibition and initial ion losses that usually result from Cu exposure. Elevated metal burdens in the gills and livers of exposed fish were measures of chronic copper exposure but not of effect. Initial gill binding experiments revealed the necessity of using radiolabeled Cu (64Cu) to detect newly accumulated Cu against gill background levels. Using this method, we verified the presence of saturable Cu-binding sites in the gills of juvenile rainbow trout and were able to make estimates of copperbinding affinity (log Kgill=Cu) and capacity (Bmax). Furthermore, we showed that both chronic exposure to Cu and to low water calcium had important effects on the Cu-binding characteristics of the gills

Costs of Chronic Waterborne Zinc Exposure and the Consequences of Zinc Acclimation on the Gill/Zinc Interactions of Rainbow Trout in Hard and Soft Water

Juvenile rainbow trout were exposed to zinc in both moderately hard water (hardness 5 120 mg CaCO3/L, pH = 8.0, Zn = 150 μg/L or 450 μg/L) and soft water (hardness = 20 mg CaCO3/L, pH = 7.2, Zn = 50 μg/L or 120 μg/L) for 30 d. Only the 450 mg/L zinc–exposed fish experienced significant mortality (24% in the first 2 d). Zinc exposure caused no effect on growth rate, but growth affected tissue zinc levels. Whole body zinc levels were elevated, but gills and liver showed no consistent increases relative to controls over the 30-d. Therefore, tissue zinc residues were not a good indicator of chronic zinc exposure. After the 30-d exposure, physiological function tests were performed. Zinc was 5.4 times more toxic in soft water (control 96 h LC50s in hard and soft water were 869 μg/L and 162 μg/L, respectively). All zinc-exposed trout had acclimated to the metal, as seen by an increase in the LC50 of 2.2 to 3.9 times over that seen in control fish. Physiological costs related to acclimation appeared to be few. Zinc exposure had no effect on whole body Ca2+ or Na+ levels, on resting or routine metabolic rates, or on fixed velocity sprint performance. However, critical swimming speed (UCrit) was significantly reduced in zinc-exposed fish, an effect that persisted in zinc-free water. Using radioisotopic techniques to distinguish new zinc incorporation, the gills were found to possess two zinc pools: a fast turnover pool (T1/2 = 3–4 h) and a slow turnover pool (T1/2 = days to months). The fast pool was much larger in soft water than in hard water, but at most it accounted for \u3c3.5% of the zinc content of the gills. The size of the slow pool was unknown, but its loading rate was faster in soft water. Chronic zinc exposure was found to increase the size of the fast pool and to increase the loading rate of the slow pool

Evolution: Mimicry meets the mitochondrion

AbstractA recent molecular study of the evolution of mimicry in tropical butterflies of the genus Heliconius proves that the mimics adapted to previously diverged ‘model’ species, but does not clearly distinguish between opposing views of how the model species diverged

A global fit of top quark effective theory to data

In this paper we present a global fit of beyond the Standard Model (BSM) dimension six operators relevant to the top quark sector to currently available data. Experimental measurements include parton-level top-pair and single top production from the LHC and the Tevatron. Higher order QCD corrections are modelled using differential and global K-factors, and we use novel fast-fitting techniques developed in the context of Monte Carlo event generator tuning to perform the fit. This allows us to provide new, fully correlated and model-independent bounds on new physics effects in the top sector from the most current direct hadron-collider measurements in light of the involved theoretical and experimental systematics. As a by-product, our analysis constitutes a proof-of-principle that fast fitting of theory to data is possible in the top quark sector, and paves the way for a more detailed analysis including top quark decays, detector corrections and precision observables.Comment: Additional references and preprint code added. Minor error in generation of plots fixed, no conclusions affecte