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Detection Of Genetic Abnormalities Using High Speed Atomic Force Microscopy, Anita J. Olsen

Theses and Dissertations

Genetic mutations in the regulatory genes responsible for cell proliferation, differentiation, and death play a significant role in cancer. Molecular diagnostic and sequencing techniques used to detect these abnormalities have limitations that need to be overcome. These issues can be addressed with the use of a novel High-Speed Atomic Force Microscope (HS-AFM) taking physical measurement of molecules labeled with a programmable nanoparticle (Cas9). This technique was used to demonstrate proof-of-concept using genetic mutations found in breast cancer and follicular lymphoma.

Current quantification methods for copy number variation (gene duplication) and gene expression analysis are based on amplification and fluorescence-based techniques …

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT_2A-dependent upregulation of histone deacetylase 2 …

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 …

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 …

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 Player’S Journey: Ludology And Narratology In Modern Gaming, Angelica Fuchs

Theses and Dissertations

This thesis examines the evolution of gaming criticism (specifically ludology and narratology) and games as a medium of expression through the use of case studies. These case studies look at some of the core aspects of four major titles (The Last of Us, Horizon Zero Dawn, various BioWare games and Journey) and survey how these games work to effectively employ a narrative while maintaining an immersive, intuitive system for the player to interact with. Through these titles, the thesis suggests that in order to gain a full scope of a game’s intentions, studies should analyze more than …

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, …

Structural And Functional Consequences Of Hiv-1 Viral Protein Tat And Morphine Co-Exposure At The Blood-Brain Barrier, Crystal R. Leibrand

Theses and Dissertations

According to UNAIDS 2016, over 37 million people worldwide were infected with human immunodeficiency virus (HIV) in 2016, with over 1.2 million people living with HIV in the United States. Of those, approximately one half will suffer from HIV-associated neurocognitive disorders (HAND), which is a spectrum of neurocognitive disorders ranging from asymptomatic neurocognitive impairment, to mild neurocognitive disorder, to HIV-associated dementia. While combination antiretroviral therapy (cART) has decreased the incidence of the most severe forms of HAND in patients with HIV, milder forms of HAND still persist. These defects can include decreased motor skills, cognitive abilities, memory, and attention. While …

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) …

Contesting The Commemorative Narrative: Planning For Richmond’S Cultural Landscape, Hannah M. Cameron

Theses and Dissertations

Abstract: New Orleans, Baltimore, and Charlottesville are reevaluating the presence of Confederate statues in their built environment. Known as the Capital of the Confederacy, Richmond’s cultural landscape is visible through the connection of two historical spaces, Monument Avenue and Shockoe Bottom. Both serve as a powerful case study for how the commemorative narrative of these spaces is contested today and how barriers that exist influence urban planning processes and outcomes.

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 …

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 …

What Lies Beneath, Meg Wachs

Theses and Dissertations

What is the very first thing you notice about a person? Appearance? What if the first thing you saw was everything that they were trying to hide? We would see every flaw but we would also see every truth. What Lies Beneath is an exploration of interior and exterior and an exposure to the dark and abject inside all of us; the parts we keep hidden and the things that build up until they have no place else to go. Rooted in an examination of the human psyche, my thesis explores the difference between the facade we project to the …

Skin-Tone And Academic Achievement Among 5-Year-Old Mexican Children, Selamawit Hailu

Theses and Dissertations

Skin-tone based social stratification has been characterized as an enduring part of the U.S. racial landscape (Hunter, 2002). Despite the plethora of research that examines the racial disparities in education (e.g., Reardon & Portilla, 2015), and an emerging literature finding that lighter skin-tones are associated with higher educational attainment among adults (Hunter, 2002) few studies have examined whether similar processes emerge during early childhood. Thus, grounded in Garcia Coll and colleagues’ (1996) integrative model, we tested whether skin-tone predicted children’s academic achievement, and whether these relations were modified by children’s ethnic-racial identification (i.e., positive ethnic-racial attitudes and centrality). Consistent with …

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 …

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 …

Evaluating The Effects Of A Flipped Classroom Compared To A Traditional Classroom On Retention Of Information And Course Engagement In A Radiation Safety Course, Stephanie A. Mchugh

Theses and Dissertations

The purpose of this study was to compare the flipped and traditional classroom pedagogies in relation to retention, critical thinking skills, and student engagement as measured by the multiple choice and short answer questions on the final exams, course evaluations, and CUCEI scores. Radiologic technologists, nuclear medicine technologists, and radiation therapists play vital roles in both diagnostic and therapeutic applications in patient care. Employers today are seeking graduates who know more, are better able to apply this knowledge, and solve more challenging problems (McLean, et al., 2016). This quasi-experimental study aimed to compare the flipped and traditional classroom pedagogies at …

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 …

Healthcare Cost Savings Through Telemedicine Use At Correctional State Facilities, Sydney Davis, Paulius Mui, Tamara Broadnax, David Collins, Vimal Mishra

Graduate Research Posters

Telemedicine offers both soft and hard return on investment, including cost savings avoidance and convenience of access to care. Incarcerated individuals represent a patient population that uniquely benefit from receiving care via telemedicine. They lack access to subspecialty care as prison facilities are located outside of urban areas, which is compounded by security risks, risk to individuals around inmates, and transportation cost to tertiary care facilities. To attend a brief in-office medical visit, an inmate requires hours of administrative support and logistical coordination, including appointment scheduling, transport arrangement and related fuel expense, and guard accompaniment - all at a financial …

Visualizing The Opioid Overdose With A Dynamic Heat Map To Identify And Predict Vulnerable Communities, Justin R. Chang, Garrett K. Wong, Chase Greco, Yadunandan Pillai, Mohammad A. Shahrezaei, Melissa H. Burton, Rob Lawrence, Alan Dow

Graduate Research Posters

Background: Opioid and heroin overdose epidemic is a public health emergency in the state of Virginia. In order to prevent overdose deaths, we need the target expertise in substance use disorders to areas with high rates of overdose. In particular, an area with an acute spike in overdoses might represent an urgent need for intervention.

Aims: The CDC urges the use of near real-time surveillance to effectively identify overdose incidence, and to coordinate community responses in the states affected by the epidemic, including Virginia. However, current opioid overdose datasets for Virginia lack adequate consistency, granularity, and temporality for …

How Personal Names Shape The Way Society Sees People As Individuals In The United States., Rand Gabriel M. Buenaventura

UROP Posters

In a world where people are disadvantaged by first impressions and implicit bias, names factor a lot into a person’s successes in life. Whether it be first names, last names, the number of middle initials, the gender and racial implications of a person’s name, and societal standards surrounding names and naming systems, there are multiple ways names shape a person’s identity. Thus, it is important to ask how personal names shape the way people are seen as individuals in the United States and contribute to their identity. Names are a trait that people are born with, usually determined before anything …

Detection And Quantification Of Glucuronidation Of Ursolic Acid (Ua) In Human Liver Microsomes (Hlms)., Kamola Tolliboeva, Philip M. Gerk

UROP Posters

No abstract provided.

Community Engagement For Health And Wellness In Aging Populations: Institute For Inclusion, Inquiry, And Innovation (Icubed), Naziirah Vines

UROP Posters

The Virginia Commonwealth University (VCU) Institute for Inclusion, Inquiry and Innovation (iCubed) is a cutting-edge institute focused on creating collaborative connections between the university and Richmond through innovative academic and research programs. iCubed consists of six transdisciplinary cores which unite faculty members and students to work with key community members to develop holistic solutions to 21st century urban challenges. One of these cores, the Health and Wellness in Aging Populations (HWAP) core, was designed to educate and assist low-income older adults in becoming self-sufficient in navigating healthcare services. The HWAP core is centered within the Richmond Health and Wellness Program, …

Influence Of Gluteus Medius Strength On Interlimb Asymmetry In Female Recreational Runners., Morgan Meyer, Olivia Moody, Kathryn Harrison, Gregory Crosswell, Bhushan Thakkar

UROP Posters

PURPOSE: Running-related injuries are most often single-sided and are partially attributed to lower limb movement and loading asymmetries.¹ Gluteus Medius (GM) plays a significant role in lower limb alignment, especially in the frontal and transverse planes by its influence on the pelvis and the femur.² Female runners are more prone to GM weakness which has been proposed to be a risk factor for overuse injuries.³ These strength deficits contribute to abnormal lower limb kinematics and kinetics during dynamic tasks like running and jumping.⁴ These changes include an increase in peak hip adduction angle (HA), hip internal …

[2017-12-08] Meeting Of The Finance, Investment And Property Committee, Virginia Commonwealth University. Board Of Visitors

VCU Board of Visitors Minutes

Official minutes of the VCU Board of Visitors and its Executive Committee.

[2017-12-08] University Resources Committee Of The Board Of Visitors, Virginia Commonwealth University. Board Of Visitors

VCU Board of Visitors Minutes

Official minutes of the VCU Board of Visitors and its Executive Committee.

[2017-12-08] Governance And Compensation Committee Of The Board Of Visitors, Virginia Commonwealth University. Board Of Visitors

VCU Board of Visitors Minutes

Official minutes of the VCU Board of Visitors and its Executive Committee.

[2017-12-08] Meeting Of The Board Of Visitors Of Virginia Commonwealth University, Virginia Commonwealth University. Board Of Visitors

VCU Board of Visitors Minutes

Official minutes of the VCU Board of Visitors and its Executive Committee.