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Investigation Of Phenylephrine Sulfation And Inhibition Using A Novel Hilic Assay Method, Heta N. Shah

Theses and Dissertations

Phenylephrine (PE) is the most commonly used over-the-counter nasal decongestant. The problem associated with phenylephrine is that it undergoes extensive first pass metabolism in the intestinal gut wall leading to its poor and variable oral bioavailability.

This research project aims at developing strategies in order to increase the oral bioavailability of PE by co-administration of GRAS compounds. A HILIC assay method was developed to detect the parent drug, phenylephrine (PE) and its sulfate metabolite (PES).The enzyme kinetic studies were done with phenolic dietary or GRAS compounds using LS180 human intestinal cell model, recombinant SULT enzymes and human intestinal cytosol (HIC). …

Mirnas As Biomarkers For Prostate Cancer Progression, Gene C. Clark

Theses and Dissertations

Prostate cancer is one of the most challenging global medical issues today. In 2011, prostate cancer was the most diagnosed malignancy in the United States, making up 29% of new cancer cases. In that year it was the second leading cause of cancer related deaths among men in the USA and the second most common cause of cancer related death overall from the EU. The prostate remains, however, an under studied organ, making insights into the anatomy and biology of prostate cancer difficult to achieve. After 30 years, PSA screening of men of the appropriate age is still the first …

Automating The Process Of Fabricating Uniform-Sized Cell Spheroids For Three-Dimensional Bioprinting, Ganesh Sosale

Theses and Dissertations

Although researchers have been able to print small, simple, and avascular tissues, they have been unsuccessful in creating large, complex and vascularized organs. Printing large and complex three-dimensional tissues or organs involves utilizing a large quantity of cellular spheroids and layer-by-layer addition of spheroids. In this study, an in-house cell spheroid fabrication system was developed to produce cell spheroids with human liver cells (hepG2), human endothelial cells (hEC), human neural stem cells (hNSC), and induced pluripotent stem cells (iPSC). It offers the ability of fabricating uniform-sized spheroids repeatedly, which is essential when large and complex structures need to be produced. …

Multi-Platform Arabinoxylan Scaffolds As Potential Wound Dressing Materials, Donald C. Aduba Jr

Theses and Dissertations

Biopolymers are becoming more attractive as advanced wound dressings because of their naturally derived origin, abundance, low cost and high compatibility with the wound environment. Arabinoxylan (AX) is a class of polysaccharide polymers derived from cereal grains that are primarily used in food products and cosmetic additives. Its application as a wound dressing material has yet to be realized. In this two-pronged project, arabinoxylan ferulate (AXF) was fabricated into electrospun fibers and gel foams to be evaluated as platforms for wound dressing materials. In the first study, AXF was electrospun with varying amounts of gelatin. In the second study, AXF …

Dispersal: A Multidisciplinary Investigation Of Plant Life, Alexandra E. Arzt

Theses and Dissertations

Using plants as a basis for exploring the interstices between the human and nonhuman, this thesis investigates ideas of awareness, intelligence, deep time, animism, and the fluctuating human perception of the agency of Nature. It outlines environmental art practices since the 1950s involving vegetal life. In addition, the paper provides a critical analysis of plant perception of Jakob von Uexküll’s work and theories of vital materialism and “critical plant studies” while noting recent studies in plant neurobiology. In my work, plants become active participants via their movement, seeding, and smell. This study takes the form of imitation, purposeful symbiosis, anthropomorphism, …

The Synthesis Of Solid Supported Palladium Nanoparticles: Effective Catalysts For Batch And Continuous Cross Coupling Reactions, Kendra W. Brinkley

Theses and Dissertations

Catalysis is one of the pillars of the chemical industry. While the use of catalyst is typically recognized in the automobile industry, their impact is more widespread as; catalysts are used in the synthesis of 80% of the US commercial chemicals. Despite the improved selectivity provided by catalyst, process inefficiencies still threaten the sustainability of a number of synthesis methods, especially in the pharmaceutical industry. Recyclable solid supported catalysts offer a unique opportunity to address these inefficiencies. Such systems coupled with continuous synthesis techniques, have the potential to significantly reduce the waste to desired product ratio (E-factor) of the production …

Physical And Biological Constraints On The Abundance Of Cyanobacteria In The James River Estuary, Brendan C. Trache

Theses and Dissertations

The tidal-fresh James River experiences recurring blooms of toxin-producing cyanobacteria, including Microcystis aeruginosa. However, cyanobacteria cell densities in the James are relatively low. Our purpose was to identify key factors suppressing cyanobacteria growth in the face of eutrophication. A mesocosm experiment was designed to test the effects of light, mixing and grazing on cyanobacteria abundance, with nutrients held constant. We predicted that toxic cyanobacteria would be most abundant under stagnant conditions, with enhanced light, with no bivalve grazers present. Abundances of indicator gene copies and phytoplankton counts supported this hypothesis. However, chlorophyll-a, phycocyanin, and the toxin microcystin were all …

Emergent Non-Consumptive Predator Effects Alter Habitat Colonization By Dipteran Prey, Ethan G. Staats

Theses and Dissertations

When ovipositing, prey organisms avoid habitat patches containing predator cues because predators consume, and negatively affect the fitness of their prey. Richness of predator species often enhances the strength of consumptive predator effects, but little is known about how multiple predators combined affect prey non-consumptively. We quantified dipteran colonization in aquatic mesocosms in response to varied predator richness. Multiple predator species combined reduced oviposition by Culex mosquitoes, chironomid midges, and the general colonizing dipteran community more than predicted by the effects of the independent predator species. Previous research which quantifies effects of multiple predators on prey as prey abundance, but …

Measurements And Modeling Of Hydrocarbon Mixture Fluid Properties Under Extreme Temperature And Pressure Conditions, Babatunde A. Bamgbade

Theses and Dissertations

Knowledge of thermodynamic fluid properties, such as density and phase behavior, is important for the design, operation, and safety of several processes including drilling, extraction, transportation, and separation that are required in the petroleum. The knowledge is even more critical at extreme temperature and pressure conditions as the search for more crude oil reserves lead to harsher conditions. Currently, there is dearth of experimental data at these conditions and as such, the predictive capability of the existing modeling tools are unproven. The objective of this research is to develop a fundamental understanding of the impact of molecular architecture on fluid …

Prothonotary Warbler Nestling Diet And Growth In Response To Variation In Aquatic And Terrestrial Food Availability, Jenna C. Dodson

Theses and Dissertations

Food supply has been suggested as the main determinant of reproductive success in birds. Riparian species can take advantage of seasonal pulses of both terrestrial and aquatic prey, though aquatic resources are often overlooked in studies of diet and reproductive ecology. This study investigates the flux of both aquatic (mayfly) and terrestrial (caterpillar) prey resources and nestling diet of the Prothonotary Warbler throughout the breeding season in two eastern Virginia sites. One site had significantly higher aquatic prey (mayfly) availability. Nestling diet was generally reflective of prey availability, and nestlings grew faster at the site with high aquatic prey availability. …

Relational Coordination: An Exploration Of Nursing Units, An Emergency Department And In-Patient Transfers, Mary Coffey

Theses and Dissertations

Emergency department (ED) crowding is a patient safety concern that has been increasing for more than a decade. Increased visits have resulted in ED crowding, longer wait times, ambulance diversions, and boarding of admitted patients (Hing & Bhuiya, 2012). Numerous factors affect ED crowding. Once various extraneous issues are resolved and a bed is available for a patient, it becomes the responsibility of nurses across unit boundaries to coordinate the patient transfer. This study applies Relational Coordination Theory (RCT) as a framework to provide nurses insight into the relational aspects of their work in the transfer of ED patients to …

Spatio-Temporal Modeling Of Anatomic Motion For Radiation Therapy, Elizabeth Zachariah

Theses and Dissertations

In radiation therapy, it is imperative to deliver high doses of radiation to the tumor while reducing radiation to the healthy tissue. Respiratory motion is the most significant source of errors during treatment. Therefore, it is essential to accurately model respiratory motion for precise and effective radiation delivery. Many approaches exist to account for respiratory motion, such as controlled breath hold and respiratory gating, and they have been relatively successful. They still present many drawbacks. Thus, research has been expanded to tumor tracking.

The overall goal of 4D-CT is to predict tumor motion in real time, and this work attempts …

An Examination Of Weight, Weight Bias, And Health Care Utilization And Attitudes Among Emerging Adults, Jessica M. Mccauley

Theses and Dissertations

Individuals with overweight/obesity have been found to exhibit more negative attitudes toward health care and disproportionate rates of health care delay and avoidance, compared to their healthy weight peers. The present study sought to examine potential mechanisms through which weight status influences health care utilization and attitudes. Six hundred and thirty-three students completed a questionnaire measuring weight status, perceived weight bias, patient-provider relationship, and health care utilization and attitudes. Although the majority of the paths in the proposed theoretical mediation model were supported by the present findings, there was no support for the anticipated link between perceived weight bias and …

Enhancement Of The Placental Transmission Of Lopinavir Using A Transporter Targeted Prodrug Strategy, Meng Wang

Theses and Dissertations

Lopinavir (LPV) is a potent protease inhibitor specific for HIV-1. However, LPV has poor placental penetration due to substrate activity for efflux transporter by P-glycoprotein (P-gp). Since fatty acid transporters are highly expressed in the placenta during pregnancy, we designed fatty acid ester prodrug of lopinavir as substrates of fatty acid transporter in order to improve their uptake into placenta. Seven dicarboxylic acid esters of lopinavir have been made in our lab. The structures were characterized by ¹H-NMR, ¹³C-NMR, LC-MS/MS, HRMS, IR and melting points. After making the prodrugs, an LC-MS/MS method with high specificity and sensitivity, as …

The Role Of Srsf3 In Control Of Alternative Splicing Of Cpeb2 In Triple Negative Breast Cancer, Brian P. Griffin

Theses and Dissertations

In the presented study, we identified that SRSF3 controls the alternative splicing of CPEB2 and consequently promotes a metastatic phenotype in triple negative breast cancer (TNBC). TNBC causes thousands of deaths annually, frequently due to a lack of effective treatments and a high rate of metastasis in patients. Alternative splicing has been found to be dysregulated in numerous cancers, while splicing factors such as SRSF3 are variably expressed. In this study we performed a siRNA panel to screen potential splicing factors, then used specific siRNA to study the effect of its knockdown on cellular function. These results showed that SRSF3 …

Nourish-C: Implementing A Family Based Weight Loss Intervention In A Church Community, Jacqueline Woods

Theses and Dissertations

Increasing rates of obesity across all race, ethnic, gender, and age groups over the past thirty years have generated significant public health concern. Black children face disproportionately higher risk for overweight and obesity compared with their White peers. Substantial evidence suggests that parent involvement improves pediatric obesity treatment outcomes. Moreover, churches are feasible and culturally congruent places to host health promotion interventions within the Black community. The current study examined the feasibility of disseminating an existing pediatric obesity intervention, NOURISH, in Black church communities. Twenty-five families participated in baseline assessment of the NOURISH-C. Five churches hosted the intervention and eight …

Characterizarion Of The Regulation And Function Of Neisseria Gonorrhoeae Tonb-Dependent Transporters: Tdfg, Tdfh And Tdfj, Sophonie Jean

Theses and Dissertations

The obligate human pathogen Neisseria gonorrhoeae successfully overcomes host strategies to limit essential nutrients, termed “nutritional immunity” by expression of TonB-dependent transporters (TdTs): outer membrane receptors that facilitate nutrient transport in an energy-dependent manner. N. gonorrhoeae encodes eight TdTs, five of which facilitate utilization of iron or iron-chelates from host derived proteins including transferrin, lactoferrin and hemoglobin, in addition to siderophores from neighboring bacteria. The transferrin utilization system was previously shown to be critical for establishing infection in human males; demonstrating the possible contributions of TdTs to gonococcal pathogenesis. As such, studies describing the biological function and contribution to pathogenesis …

Generation And Delivery Of Charged Aerosols To Infant Airways, Landon T. Holbrook

Theses and Dissertations

The administration of pharmaceutical aerosols to infants on mechanical ventilation needs to be improved by increasing the efficiency of delivery devices and creating better ways of evaluating potential therapies. Aerosolized medicines such as surfactants have been administered to ventilated infants with mixed results, but studies have shown improvement in respiratory function with a much lower dose than with liquid instillation through an endotracheal tube (ETT). An aerosolized medicine must be transported through the ventilation tubing and deposit in the lungs to have the desired therapeutic response.

This work has taken a systematic approach to (i) develop new devices for the …

Effects Of Brain-Derived Neurotrophic Factor And Its Signaling Pathway On Sensory Neuronal Activation During Colitis, Fiza Hashmi

Theses and Dissertations

Visceral hypersensitivity is the heightened response to sensory stimuli. Visceral sensations are transmitted through primary afferent neurons in the dorsal root ganglion (DRG) and the sensitization of the neural pathway leads to modification in spinal ascending and descending neurons. The aim of this investigation is to determine the effects of brain-derived neurotrophic factor (BDNF) and its signaling pathway on sensory neuronal activation during colitis. In order to evaluate this, levels of calcitonin-gene related peptide (CGRP), a neuropeptide marker for nociceptive transmission, and phosphorylated cAMP-response element binding protein (pCREB), a molecular switch in neuronal plasticity, were studied in response to BDNF …

A Study To Evaluate Non-Uniform Phase Maps In Shape Memory Alloys Using Finite Element Method, Naren Motte

Theses and Dissertations

The unique thermo-mechanical behavior of Shape Memory Alloys (SMAs), such as their ability to recover the original shape upon heating or being able to tolerate large deformations without undergoing plastic transformations, makes them a good choice for actuators.

This work studies their application in the aerospace and defense industries where SMA components can serve as release mechanisms for gates of enclosures that have to be deployed remotely. This work provides a novel approach in evaluating the stress and heat induced change of phase in a SMA, in terms of the transformation strain tensor. In particular, the FEA tool

ANSYS has …

Xlf-Dependent Nonhomologous End Joining Of Complex Dna Double-Strand Breaks With Proximal Thymine Glycol And Screening For Xrcc4-Xlf Interaction Inhibitors, Mohammed Al Mohaini

Theses and Dissertations

DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol (Tg) at the first (Tg1) , second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3’ terminus was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate …

Micro- And Macro-Scale Modeling Of Filter Aging: Effects Of Particle Poly-Dispersity And Fiber Cross-Sectional Shape, Ahmed M. Saleh

Theses and Dissertations

The goal of this study is to further advance the state of the art in developing self-sufficient methods to predict the performance of an aerosol filter. The simulation methods developed in this study are based on first principles and consequently, they do not rely on empirical correction factors. These simulation methods can be used to predict the instantaneous collection efficiency and pressure drop of a filter under dust-loading conditions. In the current study, 3-D micro- and macroscale CFD models are developed to simulate the service life of flat-sheet and pleated filters. These CFD micro- and macroscale models are also used …

Domination Numbers Of Semi-Strong Products Of Graphs, Stephen R. Cheney

Theses and Dissertations

This thesis examines the domination number of the semi-strong product of two graphs G and H where both G and H are simple and connected graphs. The product has an edge set that is the union of the edge set of the direct product of G and H together with the cardinality of V(H), copies of G. Unlike the other more common products (Cartesian, direct and strong), the semi-strong product is neither commutative nor associative.

The semi-strong product is not supermultiplicative, so it does not satisfy a Vizing like conjecture. It is also not submultiplicative so it shares these two …

Exploring Stakeholders' Perceptions Of The Evaluation Of Early Fieldwork Experience In An Undergraduate Teacher Preparation Program, Amber R. Peacock

Theses and Dissertations

This study is a qualitative meta-evaluation of the early field experience (EFE) program at a small, private, undergraduate teacher preparation program in Virginia focusing on the perceptions of preservice teachers, cooperating teachers and course instructors about the EFE evaluation objectives, evaluation experience, and resulting data usage. The EFE evaluation protocol at the study site is explored using a participatory-oriented evaluation model that solicited the perceptions of stakeholders. Analysis of EFE evaluation documents and semi-structured interviews with the stakeholders were conducted to explore the extent to which (1) official EFE objectives are congruent with the EFE evaluation, (2) the intended evaluation …

The Characterization Of A Putative Virulence Factor Expressed By Sneathia Amnii, Amy Sanford

Theses and Dissertations

Preterm birth, defined at birth before 37 weeks gestation, affects millions of newborns worldwide every year. Preterm birth is a leading cause of infant morbidity and mortality. One major cause of preterm birth is preterm premature rupture of membranes (PPROM), which can be triggered by bacterial infection and inflammation. A bacterial species that has been implicated in preterm birth and other obstetric complications is Sneathia amnii. The goals of this study were to observe cytopathogenic effects caused by S. amnii strain Sn35 and identify putative virulence factors causing those effects. Sn35 was able to adhere to, invade, and damage/kill …

Expression And Pharmacological Modulation Of Pain-Depressed Behavior In Rats, Michael D. Leitl

Theses and Dissertations

Pain is often associated with depression of behavior and mood, and relief of pain-related depression is a common goal of treatment. This goal of this dissertation was to conduct preclinical research experiments designed to address a set of three inter-related aims that examine the expression, mechanisms and treatment of pain-related depression of Intracranial Self-Stimulation (ICSS) in rats. First, studies evaluated the hypothesis that acute acid-induced depression of ICSS was mediated by a kappa opioid receptor mediated decrease in mesolimbic dopamine release in the nucleus accumbens. Results support a role for depressed mesolimbic dopamine release in pain-related depression of ICSS; however, …

Depletion Of The Chromatin Remodeler Chd4 Sensitizes Aml Blasts To Genotoxic Agents And Reduces Tumor Formation, Justin Sperlazza

Theses and Dissertations

Chromodomain Helicase DNA-Binding Protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double stranded break (DSB) repair. Here, we show that depletion of CHD4 in Acute Myeloid Leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the …

Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal

Theses and Dissertations

New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …

Investigating The Role Of The Nucleosome Remodeling Factor Nurf As A Regulator Of Gene Expression, Aiman S. Alhazmi

Theses and Dissertations

The nucleosome remodeling factor (NURF) is an evolutionary conserved ATP-dependent chromatin remodeling factor. It was first isolated from Drosophila as a complex with enzymatic activity that once recruited to nucleosome, it slides the nucleosome to provide accessibility for transcription factors. Since then, numerous works from animal models and cell lines show the role of NURF as a regulator of gene expression. NURF interacts with H3K4me3 and sequence specific transcription factors that recruit the complex to promoter regions. Whether this is the only mechanism by which NURF regulates gene expression is not known. However, other ATP-dependent chromatin remodeling complexes are known …

A Novel Antimicrobial Drug Discovery Approach For The Periodontal Pathogen Porphyromonas Gingivalis, Victoria N. Stone

Theses and Dissertations

The human body is colonized by more than 100 trillion microbes which make up an essential part of the body and plays a significant role in health. We now know the over use and misuse of broad-spectrum antibiotics can disrupt this microbiome contributing to the onset of disease and runs the risk of promoting antibiotic resistance. With antibiotic research still on the decline, new strategies are greatly needed to combat emerging pathogens while maintaining a healthy microbiome. We therefore set out to present a novel species-selective antimicrobial drug discovery strategy.

Disruption of the homeostasis within the oral cavity can trigger …