Doctor of Philosophy, The Ohio State University, 2022, Chemistry

Carr-Purcell-Meiboom-Gill (CPMG) echo train acquisition is commonly used in solid-state NMR to enhance its measurements' sensitivity when the lifetime of the signal is shortened by inhomo- geneous broadenings. The sensitivity gain that it provides depends on the echo train's coherence lifetime; thus, it's crucial to understand the factors that influence this lifetime to achieve the best sensitivity enhancements. Detailed in this thesis is an extensive investigation of 29Si's echo train coherence lifetime in silicate glasses. The origin of the 29Si echo train coherence lifetime decays was found to be dominated by residual dipolar couplings to alkali cation nuclei. Not only does this knowledge aid in improving the sensitivity of 29Si and facilitate the application of J coupling measurements, but it also has been used to show differences in the echo train coherence lifetimes between Q3 and Q4 sites indicate the presence of phase separation in alkali silicate glasses. This document also describes how the echo train coherence lifetime of the symmetric central (±1/2 → ∓1/2) transition of half-integer quadrupolar nuclei can be extended through the use of highly selective (low power) radio frequency pulses. For instance, I have shown that the echo train coherence lifetime of 17O in α-quartz can be extended by two orders of magnitude through the use of highly selective (low power) radio frequency pulses. This translates into enormous sensitivity gains for echo train acquisition schemes such as CPMG. By combining satellite population transfer schemes with a low power (2.73 kHz) CPMG on 17O in α-quartz, I have obtained over a 1000-fold sensitivity enhancement compared to a spectrum from a free induction decay acquired at a more typical rf field strength of 32.5 kHz. Additionally, I have determined higher power echo trains result in anisotropic lineshape distortions due to a disproportionate excitation of the crystallites' satellite transitions. A technical challenge with thi (open full item for complete abstract)

Committee: Philip Grandinetti (Advisor); Rafael Brüschweiler (Committee Member); James Coe (Committee Member) Subjects: Physical Chemistry

Master of Science (MS), Wright State University, 2017, Physiology and Neuroscience

The carotid bodies (CB), the primary peripheral chemoreceptors, respond to changes in blood gases with neurotransmitter release, thereby increasing carotid sinus nerve firing frequency and ultimately correcting the pattern of breathing. It has previously been demonstrated that acute application of the adipokine leptin caused perturbations of intracellular calcium and membrane ion movement in isolated CB Type I cells (Pye et al, 2015) and augmented the response of the intact CB to hypoxia (Pye et al, 2016). This study's aim was to examine, in-vivo, if elevated leptin modulated CB function and breathing. Rats were fed high-fat chow or control chow for 16-weeks. High-fat fed (HFF) animals gained significantly more weight compared to control fed (CF) animals (n=18; p<.001; 512.56 g ± 14.70 g vs. 444.11 g ± 7.09 g). HFF animals also had significantly higher serum leptin levels compared to CF (n=18; p<.0001; 3.05 ng/mL ± 0.24 ng/mL vs. 1.29 ng/mL ± 0.12 ng/mL). Whole-body plethysmography was used to test the acute hypoxic ventilatory response (HVR) in unrestrained, conscious animals. HFF animals had an attenuated 2nd-phase of the HVR when compared to CF (n=18; p<.05; 710.1 ± 41.9 mL kg-1 min-1 vs. 855.4 ± 44.05 mL kg-1 min-1). CB Type I cells were isolated and intracellular calcium measured; no significant differences in the cellular hypoxic responses between groups were observed. These data show differences in the 2nd-phase of the HVR caused by high fat feeding are unlikely to be caused by an action of leptin on the Type I cells. However the possibility remains that leptin may have in-vivo postsynaptic effects on the carotid sinus nerve; this remains to be investigated.

Committee: Christopher Wyatt Ph.D. (Advisor); Eric Bennett Ph.D. (Other); David Ladle Ph.D. (Committee Member); Mark Rich M.D./Ph.D. (Committee Member); Robert Fyffe Ph.D. (Other) Subjects: Biology; Cellular Biology; Neurosciences; Physiology

Doctor of Philosophy (PhD), University of Toledo, 2012, College of Medicine

Hypertension, affecting over one billion people worldwide, is one of the leading risk factors for heart attack and stroke. Kidney cross-transplantation studies between hypertensive and normotensive people and strains of rats provide the most compelling evidence for the fundamental role of the kidney in the pathogenesis of hypertension. Recently, there is growing evidence supporting Arthur Guyton's hypothesis that a common characteristic feature of hypertension is impaired renal sodium excretion. However, the exact molecular mechanism responsible for the impaired renal sodium excretion is not clearly defined. The overall aim of this dissertation is to improve our understanding of Na/K-ATPase and sodium proton exchanger 3 (NHE3) trafficking regulation and determine molecular mechanisms of renal proximal tubular sodium handling, which might contribute to the impaired sodium excretion associated with hypertension and results may help to develop effective therapy for hypertension. Renal proximal tubules (RPTs) responsible for 65-70% of filtered sodium and water reabsorption have profound effects on renal and body fluid balance associated with hypertension. Studies from our lab were the first to demonstrate that in renal proximal tubular cells, binding of cardiotonic steroids (CTS) such as ouabain to Na/K-ATPase stimulates Na/K-ATPase signaling cascade and induces the redistribution of basolateral Na/K-ATPase and apical NHE3, leading to a net increase in urinary sodium excretion. The first manuscript entitled “Ouabain-stimulated trafficking regulation of the Na/K-ATPase and NHE3 in renal proximal tubule cells” improves our understanding of Na/K-ATPase and NHE3 trafficking regulation. Three renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19 originated from LLC-PK1 cells in which the pig alpha1 was replaced by ouabain-resistant rat alpha1) were employed to compare ouabain-induced regulation of the alpha1 subunit and NHE3 as well as transcellular 22 (open full item for complete abstract)

Committee: Joseph Shapiro MD (Committee Chair); Jiang Liu PhD (Committee Member); Nader Abraham, PhD (Committee Member); Deepak Malhotra MD, PhD (Committee Member); Bina Joe PhD (Committee Member); Zijian Xie PhD (Committee Member) Subjects: Biomedical Research; Medicine