Digital Commons Network^™

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Ultrasound—Re:Viewing Bodies, Minjee Jeon

Theses and Dissertations

A medical evaluation of physical impairment imposes the additional burden of “labeling” the patient with the condition. The binary nature of the normal versus abnormal label emphasizes difference and can lead to trauma. Understanding differences, however, can lead to the generation of new forms and thus, more sensitive differentiation and representation. Tension is created by exploring different bodily forms—a dialectic between form and essence. I am designing a space that visualizes and illuminates difference as a source of trauma and amplifying the tension by comparing figures that represent varying degrees of normalcy. This forms a critique of idealized form and …

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti

Theses and Dissertations

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate …

Consuming Digital Debris In The Plasticene, Stephen R. Parks

Theses and Dissertations

Claims of customization and control by socio-technical industries are altering the role of consumer and producer. These narratives are often misleading attempts to engage consumers with new forms of technology. By addressing capitalist intent, material, and the reproduction limits of 3-D printed objects’, I observe the aspirational promise of becoming a producer of my own belongings through new networks of production. I am interested in gaining a better understanding of the data consumed that perpetuates hyper-consumptive tendencies for new technological apparatuses. My role as a designer focuses on the resolution of not only the surface of the object through 3-D …

Advances In Dual-Energy Computed Tomography Imaging Of Radiological Properties, Dong Han

Theses and Dissertations

Dual-energy computed tomography (DECT) has shown great potential in the reduction of uncertainties of proton ranges and low energy photon cross section estimation used in radiation therapy planning. The work presented herein investigated three contributions for advancing DECT applications. 1) A linear and separable two-parameter DECT, the basis vector model (BVM) was used to estimate proton stopping power. Compared to other nonlinear two-parameter models in the literature, the BVM model shows a comparable accuracy achieved for typical human tissues. This model outperforms other nonlinear models in estimations of linear attenuation coefficients. This is the first study to clearly illustrate the …

Rational Design Of Allosteric Modulators Of Hemoglobin As Dual Acting Antisickling Agents, Piyusha P. Pagare

Theses and Dissertations

Intracellular polymerization of deoxygenated sickle hemoglobin (Hb S) remains the principal cause of the pathophysiology associated with sickle cell disease (SCD). Naturally occurring and synthetic allosteric effectors of hemoglobin (AEH) have been investigated as potential therapeutic agents for the treatment of SCD. Several aromatic aldehydes, including vanillin, have been studied previously as AEHs for their antisickling activities. Specifically, these compounds form Schiff- base adduct with Hb to stabilize the oxygenated (R) state, increase Hb affinity for O2 and concomitantly prevent the hypoxia-induced primary pathophysiology of Hb S polymerization and RBC sickling, in turn, ameliorating several of the cascading secondary adverse …

The Development Of Novel Inhibitors Of The Nlrp3 Inflammasome, Jacob W. Fulp

Theses and Dissertations

Inflammasomes are intracellular multimeric protein complexes that regulate inflammation by controlling the maturation of cytokines, interleukin-1β (IL-1β) and interleukin-18 (IL-18). Additionally, activation of these inflammasome complexes has been implicated in an inflammatory form of death known as proptosis. Of the known inflammasomes, the NOD-like receptor family pyrin domain containing 3 (NLPP3) inflammasome, is the most elucidated. Under physiological conditions, NLRP3-mediated inflammation promotes healing and the elimination of cellular debris and pathogens. However, the dysregulation of IL-1β, IL-18 and pyroptosis are instrumental in the development of multiple pathologies. Furthermore, studies suggest that the NLRP3 inflammasome mediates detrimental neuroinflammation and …

Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna

Theses and Dissertations

Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:

Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (c_p(t)) and sputum (c_s(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from c_p(t) …

The Break, Ian Gerson

Theses and Dissertations

The Break is a personal investigation into problems and possibilities of representing my specific transgender identity.

Trans as a tactic to speak about a state of forever becoming, forever in between, outside of and in opposition to dominant social norms of being.

Trans as a model for a different way of viewing and being in the world.

Can we form a different kind of horizontal shared power though a collective refusal to play into existing structures from which we have been excluded? What are the potentials for modeling other ways of being, other ways of (dis)engaging, other ways to be …

Nuclear Rupture In Progeria Expressing Cells, Kranthidhar Bathula

Theses and Dissertations

Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this …

Enhancing Adherence To Prescribed Opioids Using A Mobile-Base Application: A Pilot Study Of Feasibility In Chronic Non-Cancer Pain, Daniel M. Sop

Theses and Dissertations

In this study we present feasibility of a mobile monitoring and reporting system that would provide an accurate unbiased screening tool to systematically analyze opioid adherence in Sickle cell disease patients. In addition, the software simultaneously measures pain. The Mobile Applications Rating Scale: a new and validated tool for assessing the quality of health mobile apps for engagement, functionality, aesthetics, information quality, subjective quality, relevance and overall impact was administered post usage to evaluate the application.

A total of 28 patients were recruited to review and test the software at one sitting. The majority of the population found the application …

Psychick Order, Corissa Duffey

Theses and Dissertations

Preserving Psychick Order is an investigation into the subliminal, of a body processing trauma and transition. I explore how my mind and body filter memory, fear, and the impact of the past into the present. Since childhood, making dolls has been a way for me to express complex feelings, especially as they relate to dynamics between biological and found family. By tenderly modeling dolls after my own transforming physical features and mental processes, I make connections between the effects of my mind on my body and vice versa. I like to describe the resulting forms as queer monsters trying to …

Engineering Surface Properties To Modulate Inflammation And Stem Cell Recruitment Through Macrophage Activation, Kelly M. Hotchkiss

Theses and Dissertations

Biomaterials are becoming the most commonly used therapeutic method for treatment of lost or damaged tissue in the body. Metallic materials are chosen for high strength orthopaedic and dental applications. Titanium (Ti) implants are highly successful in young, healthy patients with the ability to fully integrate to surrounding tissue. However the main population requiring these corrective treatments will not be healthy or young, therefore further research into material modifications have been started to improve outcomes in compromised patients. The body’s immune system will generate a response to any implanted material, and control the final outcome. Among the first and most …

Adolescent Emotion Expression, Emotion Regulation, And Decision-Making In Social Context, Tennisha N. Riley

Theses and Dissertations

Adolescents engage in risk behaviors at an alarming rate, and particularly when they are with peers. Despite efforts to develop prevention and intervention programs, rates of risk-taking among adolescents is still relatively high. Adolescents continue to engage in physical fights and aggressive behavior, use substances such as alcohol and illicit drugs, and make decisions that impact driving and motor vehicle incidents. The regulation of emotions plays a significant role in adolescents’ decisions to engage in such risk behaviors.Examining adolescents’ emotion expression and regulation is therefore critical to identifying ways to support positive development.

This dissertation project explored important regulatory mechanisms …

Edgelands, Anne Bujold

Theses and Dissertations

Animal imagery has been part of the human effort to understand our place in the world since the beginning of recorded history. Through examining the role and use of animal imagery in the creation of cultural signals, I have developed a framework for my practice. Edgelands employs representations of feral animals as symbols for the “misfit” to emphasize the value of those who do not fit in. My experience as a woman in the field of metal work informs my material choice and process, subverting ironwork motifs and the purpose of gates and boundaries. Edgelands overlaps a series of material …

Stat3 In The Regulation Of Brown Adipocyte Differentiation, Marc Cantwell

Theses and Dissertations

Thermogenic fat is a promising target for new therapies in diabetes and obesity. Understanding how thermogenic fat develops is important to develop rational strategies to treat obesity. Previously, we have shown that Tyk2 and STAT3, part of the JAK-STAT pathway, are necessary for proper development of classical brown fat. Using primary preadipocytes isolated from newborn mice we demonstrate that STAT3 is required for differentiation and robust expression of Uncoupling Protein 1. We also confirm that STAT3 is necessary during the early induction stage of differentiation and is dispensable during the later terminal differentiation stage. Without STAT3, the brown preadipocytes have …

High-Throughput Prediction And Analysis Of Drug-Protein Interactions In The Druggable Human Proteome, Chen Wang

Theses and Dissertations

Drugs exert their (therapeutic) effects via molecular-level interactions with proteins and other biomolecules. Computational prediction of drug-protein interactions plays a significant role in the effort to improve our current and limited knowledge of these interactions. The use of the putative drug-protein interactions could facilitate the discovery of novel applications of drugs, assist in cataloging their targets, and help to explain the details of medicinal efficacy and side-effects of drugs. We investigate current studies related to the computational prediction of drug-protein interactions and categorize them into protein structure-based and similarity-based methods. We evaluate three representative structure-based predictors and develop a Protein-Drug …

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …

Big Networks: Analysis And Optimal Control, Hung The Nguyen

Theses and Dissertations

The study of networks has seen a tremendous breed of researches due to the explosive spectrum of practical problems that involve networks as the access point. Those problems widely range from detecting functionally correlated proteins in biology to finding people to give discounts and gain maximum popularity of a product in economics. Thus, understanding and further being able to manipulate/control the development and evolution of the networks become critical tasks for network scientists. Despite the vast research effort putting towards these studies, the present state-of-the-arts largely either lack of high quality solutions or require excessive amount of time in real-world …

Advanced Imaging Analysis For Predicting Tumor Response And Improving Contour Delineation Uncertainty, Rebecca N. Mahon

Theses and Dissertations

ADVANCED IMAGING ANALYSIS FOR PREDICTING TUMOR RESPONSE AND IMPROVING CONTOUR DELINEATION UNCERTAINTY

By Rebecca Nichole Mahon, MS

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2018

Major Director: Dr. Elisabeth Weiss,

Professor,

Department of Radiation Oncology

Radiomics, an advanced form of imaging analysis, is a growing field of interest in medicine. Radiomics seeks to extract quantitative information from images through use of computer vision techniques to assist in improving treatment. Early prediction of treatment response is one way of improving overall patient care. This work …

If This Be Sin: Gladys Bentley And The Performance Of Identity, Moira Mahoney Church

Theses and Dissertations

Known for her improvisational risqué lyrics and tailored white tuxedo, Gladys Bentley was one of the most notorious figures of the 1930s. Situated in the pansy and lesbian craze of the 1920s and 30s, Bentley’s career was part of a broader trend that favored gender-queer performers due to their exotic appeal. Despite being more transgressive than most, Bentley has ultimately faded from society’s collective memory.

Linking Microbial Phylogenetic And Functional Gene Diversity To Microbial Mat Ecosystem Function Following Environmental Disturbance, Eva Christine Preisner

Theses and Dissertations

The ability of ecosystems to adapt to environmental perturbations depends on the duration and intensity of change and the overall biological diversity of the system. In this study, a microbial mat ecosystem located on San Salvador Island, the Bahamas was used as a model to examine how environmental disturbance affects microbial community resistance, their protein synthesis potential (PSP), ecosystem function as measured by biogeochemical cycling, community stability, and resilience. This ecosystem experienced a large shift in salinity (230 to 65 g kg-1) during 2011–2012 following the landfall of Hurricane Irene on San Salvador Island. High throughput sequencing and analysis of …

The Impact Of False Positive Mammography Results On Breast Cancer Screening Intention Among Black Women, Deeonna E. Farr

Theses and Dissertations

Extensive research indicates that false-positive mammograms (FPM) have been associated with negative psychosocial and cancer-related beliefs, but only a handful of studies examine Black women’s reactions to this experience. Additionally, these studies do not investigate how organizational and provider-level factors in concert with individual patient characteristics shape Black women’s experiences and reactions to FPM results. The purpose of this study was to determine the impact of organizational, provider, and individual-level factors on the processes and outcomes associated with FPM results in Black women. This study had two specific aims:

1) To describe, using a mixed methods approach, the organizational and …

Role Of Mammary Microenvironment In Promoting Left-Right Differences In Tumor Progression, Metastasis, And Therapeutic Response, Huda Issa Atiya

Theses and Dissertations

Metastasis is the main cause of death in breast cancer patients; however, there are currently no treatments available to treat or prevent metastasis. This is in part because regulators of metastasis are not yet fully understood. Over the past century researchers began to study metastasis regulators by different hypotheses, such as the seed and soil hypothesis which focuses on studying the role of cancer cells, the seeds, and the tissue microenvironment, the soil, in regulating metastasis. Although lots of studies have focused on the microenvironment of metastatic sites and their roles in regulating metastasis, limited studies have focused on the …

Sleep, Shiftwork Adaptation, Autonomic Dysfunction, And Metabolic Syndrome, Torrance Torrance

Theses and Dissertations

Background: Sleep is considered a physiological necessity and its disruption is associated with a wide variety of adverse mental and physical health outcomes including increased incidence of obesity, cancer, hypertension, cardiovascular disease, type 2 diabetes mellitus, stroke, depression, post-traumatic stress disorder (PTSD), work-related and vehicle accidents, and aberration of the autonomic nervous system.

Methods: Three studies were conducted from three separate populations. The first study examined the latent trajectories of self-reported sleep quality in active duty Army soldiers over a 3-year period using data from the Global Assessment 2.0 survey and Repeated Measures Latent Class Analysis (RMCLA) procedures. Generalized Estimating …

Regulation Of Cytoplasmic Dynein By Lis1 And Adenomatous Polyposis Coli, Timothy Joshua Hines

Theses and Dissertations

Cytoplasmic dynein 1 (dynein) is a microtubule motor that plays a role in mitosis, cell migration, and minus-end directed microtubule-based transport. The lissencephaly protein, Lis1, and its binding partner, Ndel1, are critical regulators of cytoplasmic dynein (Niethammer et al., 2000). In humans, haploinsufficiency of Lis1 leads to lissencephaly, a devastating developmental neurological disorder characterized by severe brain malformation, leading to cognitive and motor defects, and progressively worsening seizures (Dobyns et al., 1993). While Lis1 is known to play a role in regulating dynein-dependent functions such as neuronal migration and mitotic spindle orientation during development, the protein is still highly expressed …

A Comprehensive Reengineering Of The Hospital Emergency Triage System, Nicholas D. Boltin

Theses and Dissertations

Hospital emergency triage and specifically Mass Casualty Incidents (MCIs) are of major concern with regard to treatment and patient outcomes. Traditional emergency department triage models are oversimplified and often lead to over/under triaging of patients. Furthermore, triage models do not account for the full spectrum of different types of MCIs which often results in misclassification. In this thesis, we begin by looking at traditional triage models currently being used in hospital systems and identify several shortcomings of using these models within the context of a chemical related MCI. I will then move to describe a new approach to creating a …

Iron Transport Machinery: A Potential Therapeutic Target In Escherichia Coli, Clorissa L. Washington – Hughes

Theses and Dissertations

Iron metabolism is an integral part of life for most organisms. Despite its essentiality, iron can also become toxic. There are many aspects to maintaining iron balance within the cell. The aim of this work is to provide insight into the function of several components involved in bacterial iron homeostasis. This work is significant for the development of novel antibiotics for treating resistant or pathogenic bacteria. Herein, it is shown that nickel can disrupt normal bacterial iron metabolism and that bacterial resistance can be affected by expression of iron acquisition genes. Once iron is obtained by the cell, it can …

Designed Polymer Brush Interfaces For Plutonium Separations And Polyethylene Nanocomposites, Julia G. Pribyl

Theses and Dissertations

Modification of surfaces with polymer brushes has become an important area of research for developing materials with a variety of advanced properties. Flat or continuous surfaces modified with polymer brushes can serve as surfaces where chemical reactions or separations take place, and discrete nanoparticles covered in a polymer brush can disperse within a miscible surrounding polymer, generating a composite which retains the processability of the polymer but becomes endowed with the properties of the filler as well. Presented herein are new synthetic approaches to modify both continuous surfaces as well as discrete particles with polymer brushes for complex applications. In …

Black Men, Red Coats: The Carolina Corps, Race, And Society In The Revolutionary British Atlantic, Gary Sellick

Theses and Dissertations

The Carolina Corps were both a product and driver of British military zeal during the Age of Revolution. Created in South Carolina in the final years of the American Revolutionary War, the unit was the only black fighting force that survived the conflict on the British side. Evacuated at the end of the conflict as free men, the Carolina Corps straddled the boundaries of military–civil society in the highly racialized eighteenth century British Caribbean. Although former slaves, the men of the Corps were nonetheless crucial to the defense of the region. This gave the men opportunities and legal standing that …