Digital Commons Network^™

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 …

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 …

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 …

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 …

Assessing The Relative Influences Of Abiotic And Biotic Factors On A Species’ Distribution Using Pseudo-Absence And Functional Trait Data: A Case Study With The American Eel (Anguilla Rostrata), Taylor E. Woods

Theses and Dissertations

Species’ distributions are influenced by abiotic and biotic factors but direct comparison of their relative importance is difficult, particularly when working with complex, multi-species datasets. Here, we present a flexible method to compare abiotic and biotic influences at common scales. First, data representing abiotic and biotic factors are collected using a combination of geographic information system, remotely sensed, and species’ functional trait data. Next, the relative influences of each predictor variable on the occurrence of a focal species are compared. Specifically, ‘sample’ data from sites of known occurrence are compared with ‘background’ data (i.e. pseudo-absence data collected at sites where …

Assessing Baseline And Post-Discharge Risk Factors In Subjects With And Without Sleep Apnea Undergoing Endoscopy With Deep Sedation, Mercedes E. Weir

Theses and Dissertations

ABSTRACT

ASSESSING BASELINE AND POST-DISCHARGE RISK FACTORS IN SUBJECTS WITH AND WITHOUT SLEEP APNEA UNDERGOING ENDOSCOPY WITH DEEP SEDATION

Background: Outpatient procedures encompass over 60% of all surgeries in the United States, and the prevalence of obstructive sleep apnea (OSA) remains high among adult surgical ambulatory patients. Ambulatory surgery poses problems for patients with OSA because narcotics and anesthetics used during surgery can complicate the negative effects of OSA, leading to cardiac events, brain hypoxia, and even death. This study was designed to evaluate the prevalence of cardiopulmonary risk factors among post endoscopic patients with diagnosed and undiagnosed sleep apnea. …

Relationship Between Patient-Health Coach Interactions And Changes In Markers Of Glucose Homeostasis, Jason P. Nagy

Theses and Dissertations

Diabetes and insulin resistance are on the rise in the United States. Early detection and deployment of therapies has allowed for the reversal of pancreatic beta cell damage. Unfortunately, not all providers can offer the support to facilitating the required life style modifications. The introduction of clinical health consultants (CHC) as supplemental care has improved patient health for a variety of chronic diseases. Missing in the literature are studies investigating the correlation between the number of CHC interactions and improvement in biomarkers.

The study utilized a non-experimental, retrospective study design to evaluate the relationship between the use between the use …

Usefulness Of The Captia Syphilis Igg Eia Test Method And Reverse Algorithm For Detection Of Syphilis Infection In A Public Health Setting, Patricia Armour

Theses and Dissertations

Syphilis, a systemic sexually transmitted disease, is on the rise in the US, with infection rates the highest recorded since 1994 according to the CDC. Useful laboratory testing is an important diagnostic tool for determining individual syphilis infection and preventing community-wide disease spread.

The purpose of this study was to determine the usefulness of a specific automated treponemal test method, the Captia^TM Syphilis IgG EIA, and the syphilis reverse algorithm interpretation for detecting syphilis infection among patients seeking care in a public health clinic. The study employed a retrospective, nonexperimental descriptive correlational design with data collected between 2012-2013 from …

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 …

Classification Of High-Dimensional Data Based On Multiple Testing Methods, Chong Ma

Theses and Dissertations

Supervised and unsupervised classification are common topics in machine learning in both scientific and industrial fields, which usually involve three tasks: prediction, exploration, and explanation. False discovery rate (FDR) theory has a close connection to classical classification theory, which must be employed in a sophisticated way to achieve good performance in various contexts. The study aims to explore novel supervised classifiers and unsupervised classification approaches for functional data and high-dimensional data in genome study by using FDR, respectively. One work develops a novel classifier for functional data by casting the classification problem into a multiple testing task, which involves using …

Estimation Procedures For Complex Survival Models And Their Applications In Epidemiology Studies, Jie Zhou

Theses and Dissertations

In this dissertation, we aim to address three important questions in practice, which can be solved through complex survival models. The first project focuses on studying the longitudinal fitness effect on cardiovascular disease (CVD) mortality. In the second project, we study the disease-death relation between CVD and all-cause mortality and evaluate important covariate effects on the disease or death transitions. In the third project, we compare antiretroviral treatment (ART) for HIV patients and consider both treatment effect and side effect of the drugs. The first two projects are motivated by the Aerobics Center Longitudinal Study (ACLS) datasets and the third …

Orientia Tsutsugamushi Modulates Endoplasmic Reticulum Stress To Benefit Its Intracellular Growth And Targets Nlrc5 To Inhibit Major Histocompatibility Complex I Expression, Kyle G. Rodino

Theses and Dissertations

Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, afflicts one million people annually. Despite being a global health threat, little is known about O. tsutsugamushi pathogenesis. Here, we demonstrate that O. tsutsugamushi modulates the ER and ER-associated processes as mechanisms of nutritional virulence and immune evasion. To obtain amino acids to fuel replication, O. tsutsugamushi simultaneously induces ER stress and the unfolded protein response (UPR) while inhibiting ER-associated degradation (ERAD) during early infection time points. During exponential growth, the bacterium releases the ER bottleneck, resulting in generation of ERAD-derived amino acids that it parasitized for replication. …

Prevalence And Factors Of Sibling-Recurrent Dental Treatment Under General Anesthesia, Brandy N. Edmonds

Theses and Dissertations

Objective/Aims: Assess the prevalence of sibling recurrent dental general anesthesia (DGA) at VCU Pediatric Dentistry. Assess factors that contribute to sibling recurrent dental general anesthesia. Methods: The guardian of patients with siblings were provided a questionnaire to assess the prevalence and factors associated with recurrent DGA. Results: A total of 40 families with a child presenting for GA and at least one sibling were included in the study. Of these, 45% had sibling-recurrent GA treatment (20% in one sibling; 25% in 2 or more siblings). Additionally, 13% of the children currently presenting for GA had already been treated under GA, …

Using The Frog Epidermis To Uncover Desmosome Function And Regulation In The Developing Embryo, Navaneetha Krishnan Bharathan

Theses and Dissertations

The desmosome is one of the major cell adhesion junctions found in the epithelia, heart, and hair follicle. Described as a “rivet” that hold cells together, it provides these tissues with the integrity to withstand the tremendous forces they face in everyday life. Defects in this junction can lead to devastating diseases where patients are susceptible to skin infections and cardiovascular defects. Limited treatments exist for diseases of the desmosome, and strategies do not target all symptoms. Therefore, delineating the function and regulation of desmosomes is of paramount importance for the development of prevention and treatment strategies. The Xenopus laevis …

Anxiety In Menopause: A Qualitative Inquiry, Eleanor Bremer

Theses and Dissertations

Background: Anxiety is one of the mood symptoms experienced by menopausal women; however, anxiety symptoms during menopause have received little attention in the literature despite the potential impact on quality of life. Many of the tools used to evaluate and measure anxiety associated with menopause assume that menopausal anxiety shares similar criteria as anxiety disorders and this may not be entirely true. There are very few studies that have assessed anxiety in the context of menopause leaving the concept of menopausal anxiety not well defined and raising the question: Is menopausal anxiety a unique and distinctly different syndrome? The purpose …

The Progress On Mapping Ubiquitin Signaling Using Photocrosslinking Mono And Di-Ubiquitin Probes And Other Ubiquitin Moieties, Courtney N. Braxton

Theses and Dissertations

Ubiquitin (Ub) is a small, 76 amino acid, and post-translational modification (PTM) protein in eukaryotes. Modification of a substrate protein via the covalent attachment of the C-terminal glycine of Ub to the ε-amino group of lysine residues in a substrate is termed ubiquitination. Unlike, other PTM proteins, Ub can form polyUb chains at one or more of its seven lysine residues. (K6, K11, K27, K29, K33, K48, and K68). The consequence of these different polymerization sites is altered biological response with different polyUb linkages conferring different fates to target proteins. Unfortunately, the study of these chains have been limited by …

A Familiar House, William Lenard

Theses and Dissertations

The landscapes of my home in Connecticut are important to me. When I was young, I went to the woods for seclusion and comfort. While I wandered through the woods, I discovered a passion for storytelling. Now that I no longer live in New England, I miss the familiar landscapes of home. As a way to portray my sentiment, I write poetic narratives and create objects to illustrate natural landscapes.

I combine my interests of classic Americana art and literature with brutalist architecture and modern furniture to create immersive installations. I work with concrete and hardwood to materially bridge the …

Heparan Sulfate, A New Target For Platinum In Metastatic Tnbc, Samantha J. Katner

Theses and Dissertations

Abstract

Heparan Sulfate, A New Target for Platinum in Metastatic TNBC

Author: Samantha J. Katner, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Virginia Commonwealth University, 2018

Advisor: Dr. Nicholas Farrell, Professor, Chemistry Department

Heparan sulfate proteoglycans (HSPGs), composed of the linear polysaccharide heparan sulfate (HS) conjugated to a protein core, are located on the cell surface and extracellular matrix. The HS chains display varying degrees of sulfation, which constitutes the molecular recognition motif for many HS-protein interactions. HSPGs, associated growth factors, and heparanase promote tumor progression by facilitating invasion, angiogenesis, …

Determining Tidal Characteristics In A Restored Tidal Wetland Using Unmanned Aerial Vehicles And Derived Data, Victor Thornton

Theses and Dissertations

Unmanned aerial vehicle (UAV) technology was used to determine tidal extent in Kimages Creek, a restored tidal wetland located in Charles City County, Virginia. A Sensefly eBee Real-Time Kinematic UAV equipped with the Sensor Optimized for Drone Applications (SODA) camera (20-megapixel RGB sensor) was flown during a single high and low tide event in Summer 2017. Collectively, over 1,300 images were captured and processed using Pix4D. Horizontal and vertical accuracy of models created using ground control points (GCP) ranged from 0.176 m to 0.363 m. The high tide elevation model was subtracted from the low tide using the ArcMap 10.5.1 …

Identification Of Taxonomic And Functional Ichthyofaunal Zones Within The James River Basin, Virginia, Joseph L. Noel

Theses and Dissertations

Environmental gradients structure ichthyofaunal communities longitudinally along river networks via the selective filtering of species’ traits. In many instances, these environmental influences have created distinct zones of co-occurring fish species. Zonation studies have most often been conducted with taxonomic data (species x site matrices), but the increasing availability of functional trait data creates an opportunity to build more rigorous understanding of species’ co-occurrence patterns. Notably, zonation studies that use taxonomic data may not reveal the same patterns as studies based on trait data. In this study, we tested for distinct ichthyofaunal zonation in James River Basin, VA using a combination …

Use Of Surface Enhanced Raman Spectroscopy For The Detection Of Bioactive Lipids, Christopher M. Ohlhaver

Theses and Dissertations

The detection and analysis of lipids in biological matrices for clinical applications poses many challenges, but rapid and reliable detection will prove invaluable for clinical diagnosis. Herein, we report the application of drop-casted Ag nanoplatelets as surface enhanced Raman scattering (SERS) substrates for qualitative detection of 20-hydroxyeicosatetraenoic acid (20-HETE), which is a potential biomarker for diagnosis of hypertensive disorders. Biomarker peaks of 20-HETE can be reliably detected and differentiated from those of the structurally similar lipids (arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid) commonly found in human blood, even 1 pM concentrations. Additionally, one study mixed 20-HETE with three structurally …

A Qualitative Study Of The Philanthropic Behavior Of Generation X And Crowdfunding, Donna R. Lowe

Theses and Dissertations

This applied dissertation was designed to explore the connection between social triggers, virtual validation, and philanthropic behaviours of the Generation X population. Current literature largely ignores the Generation X population and no research has yet been conducted that directly links the successful funding of crowdfunding campaigns to both virtual validation and social triggers in the Generation X population.

To explore the connection between social triggers, virtual validation, and philanthropic behaviours of the Generation X population, the writer reviewed the application of retrieving psychological motivations based on non-conscious responses by way of belongingness theory, social comparison theory, and Maslow’s Hierarchy of …