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Graph-Based Regularization In Machine Learning: Discovering Driver Modules In Biological Networks, Xi Gao

Theses and Dissertations

Curiosity of human nature drives us to explore the origins of what makes each of us different. From ancient legends and mythology, Mendel's law, Punnett square to modern genetic research, we carry on this old but eternal question. Thanks to technological revolution, today's scientists try to answer this question using easily measurable gene expression and other profiling data. However, the exploration can easily get lost in the data of growing volume, dimension, noise and complexity. This dissertation is aimed at developing new machine learning methods that take data from different classes as input, augment them with knowledge of feature relationships, …

Impact Of E-Cigarettes On Physician Recommendations Of Tobacco Use Cessation Pharmacotherapy, Omar El Shahawy

Theses and Dissertations

Introduction: E-cigarettes have been marketed as smoking cessation aids and harm reduction strategies. Prior regional surveys found that physicians are recommending them to patients despite the lack of evidence supporting these industry claims. Yet, little is known about physicians’ beliefs regarding e-cigarettes and whether these beliefs are associated with them recommending e-cigarette use in clinical practice. Methods: This three-manuscript dissertation used a mixed-methods approach including both qualitative and quantitative research methods. The aims were to: (1) Uncover the factors associated with primary care physicians’ (PCPs) decisions to recommend e-cigarettes to their patients for tobacco use cessation; (2) Estimate the prevalence …

Mast Cells In Kainate Receptor Knockout Mice, Andrea J. Elkovich

Theses and Dissertations

Kainate receptor knockout mice have unique differences within their immune system. They exhibit an attenuated T_H2 branch, while maintaining a robust T_H1 response. Specifically, blocking the formation of functional kainate receptors affects mast cells and their related pathologies. While they seem to develop and activate normally in vivo and in vitro, KAR KO mast cells release more inflammatory mediators upon degranulation. These mice experience severe anaphylactic shock due to two compounding abnormalities. First, KAR KO mast cells release significantly more histamine in vivo upon IgE-mediated activation. Second, the animals over-respond to exogenous histamine with drastic …

Characterization Of Transfer Of The Mobile Genomic Island Encoding Methicillin Resistance Among Staphylococci, Melissa D. Ray

Theses and Dissertations

The gene encoding methicillin resistance in Staphylococcus aureus (MRSA) is carried in the chromosome on a large genomic island called SCCmec and is always inserted at the att site within orfX. SCCmec has been designated a mobile genetic element but a mechanism by which it moves among different strains and species of staphylococci has never been demonstrated. This work shows that bacteriophage 80α is capable of transducing SCCmec into a recipient cell, after which it can integrate into the bacterial chromosome via homologous recombination. More importantly, this work characterizes a conjugative mechanism of SCCmec transfer. …

Motivation, Mindfulness, And Metabolic Factors Predicting Adolescent Adherence And Attrition In A Multidisciplinary Weight Management Program, Stephen Trapp

Theses and Dissertations

Estimated rates of obesity are notably high in the United States and pose a significant public health concern. A number of deleterious physical and psychosocial conditions are associated with pediatric obesity and the cost of its treatment is considerable. Accordingly, the number of weight management treatments has increased to meet this growing public health challenge. Unfortunately, insufficient participation in weight management treatment, namely low adherence and high attrition, often impede the effectiveness of these programs. Although the barriers associated with inadequate adherence and elevated rates of attrition are documented, there is a dearth of research on the predictors of the …

Stakeholder Views On Behavioral Health Care In The Pediatric Primary Care Setting: A Qualitative Approach Towards Integration Of Care, Alexis Quinoy

Theses and Dissertations

The pediatric primary care setting has been discussed as playing a central role for the identification and treatment of behavioral and mental health disorders in youth. Although this setting is in a unique position to provide these services, there are many barriers to the integration of mental health care and pediatric primary care. The aim of this study is to examine perspectives of multiple stakeholders (i.e., patient, parent, nurse, resident, faculty, clinic director) in a pediatric primary care setting to explore barriers, behavioral and mental health needs, and facilitators to the integration and provision of mental health care for children …

Looking “Upstream”: The Role Of Basic Psychological Needs Satisfaction In Service Members’ Future Orientation, Bradley J. Antonides

Theses and Dissertations

OBJECTIVE: This study explores psychological experiences that may influence service members’ self-concepts and future orientations. As stable, optimistic, future orientations have been associated with resilience to psychological distress and suicidality (Johnson, et al., 2011), it is worthwhile to explore how service members’ attitudes toward the future might be shaped in the context of intrapersonal and interpersonal experiences. METHOD: Data were collected from service members of the Virginia National Guard (N = 192) and included a Transportation unit, an Engineer unit, an Infantry unit and a group with no specific unit affiliation or substantive military experience. The study is a …

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 …