Digital Commons Network^™

The Role Of The Nucleosome Remodeling Factor Nurf In Inhibiting T And Natural Killer Cell Mediated Antitumor Immunity By Suppressing Tumor Antigenicity And Natural Cytotoxicity Receptor Co-Ligands, Kimberly Mayes

Theses and Dissertations

Tumor immunoediting is a dynamic process in which the immune response attacks tumor cells by detecting danger signals and tumor antigens. In order to survive, tumor cells develop mechanisms to avoid detection or destruction by the immune system. To counteract this, several strategies are being developed to enhance the antitumor immune response, including the depletion of immunosuppressive cells, enhancing the activation of antitumor immune cells and increasing tumor cell immunogenicity. These therapies have seen limited success individually, however, and it is likely that combination therapy with novel targets will be necessary to see reproducible beneficial responses. Epigenetic modifications are attractive …

Design, Synthesis, And Biological Screening Of Selective Mu Opioid Receptor Ligands As Potential Treatments For Opioid Addiction, Samuel Obeng

Theses and Dissertations

Today, more Americans die each year because of drug overdoses than are killed in motor vehicle accidents. In fact, in 2015, more than 33,000 individuals died due to an overdose of heroin or prescription opioids. Sadly, 40-60 % of patients on current opioid addiction treatment medications relapse. Studies have shown that the addiction/abuse liability of opioids are abolished in mu opioid receptor (MOR) knock-out mice; this indicates that the addiction and abuse liability of opioids are mainly mediated through MOR. Utilizing the “message-address concept”, the our laboratory reported a novel non-peptide, reversible MOR selective ligand 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α (isoquinoline-3-carboxamido)morphinan (NAQ). Molecular modeling …

Diabetes-Induced Expression And Regulation Of Glp-1 Levels By Bile Acid Receptors (Tgr5 & Fxr), Joseph R. Spengler

Theses and Dissertations

Diabetes Mellitus has continued to drastically affect the health of the world and many complications can prove fatal. As long as this metabolic disease persist, research discoveries will need to continue to be made so that patient outcomes and healthcare are dramatically enhanced. In recent years, GLP-1 has been the topic of conversation for diabetes research, due to its promising effects in promoting insulin sensitivity. Furthermore, bile acids and their receptors (TGR5 & FXR) have shown promise in their actions in the regulation of GLP-1, and thus glucose homeostasis. Here we have shown the detection and increased expression of TGR5 …

Walking In Beauty: Responsive And Responsible Health And Healing Among Virginia American Indian People, Amy J. Prorock-Ernest

Theses and Dissertations

Little is systematically known about the collective health and well-being of Virginia American Indian people. This study sought to explore the meaning of health and healing among Virginia American Indian people in the context of a reservation-based, non-federally funded health clinic. Using an emergent approach to qualitative research grounded in a constructivist inquiry paradigm and guided by Indigenous research principles, a total of 24 in-depth, semi-structured interviews were conducted with 17 American Indian service-users of the Clinic. Through an inductive thematic analysis of participant stories, a framework for understanding responsive and responsible health and healing was derived. The framework includes …

Alpha6 Beta2 Subunit Containing Nicotinic Acetylcholine Receptor Contributions To Abuse-Related Effects Of Nicotine And Alcohol, Alexandra M. Stafford

Theses and Dissertations

Pharmacotherapies for tobacco and alcohol cessation are only modestly successful, so it is important to better understand mechanisms underlying their use and abuse. The overarching goal of this research is to assess a6b2 subunit containing nicotinic acetylcholine receptor (a6b2*nAChR; *denotes possible assembly with other subunits) contributions to abuse-related effects of nicotine and alcohol. In the absence of a6b2*nAChR-selective agonists, a6b2*nAChR gain-of-function (a6L9’S) mice provide a tool for selective activation of a6b2*nAChRs. Using the a6L9’S mice together with nicotine doses sub-threshold for stimulation of native nAChRs, these studies tested the hypothesis that activation of a6b2*nAChRs is sufficient to promote neurochemical and …

Ethanol Reversal Of Oxycodone Tolerances, Joanna C. Jacob

Theses and Dissertations

Oxycodone is a semi-synthetic opioid originally developed as a safer alternative to morphine. It is commonly prescribed for its pain-relieving effects, but has recently been implicated as a major underlying cause of the current opioid epidemic due to its clinical limitations that include tolerance, dependence and a high abuse liability. Simultaneous consumption of opioids and ethanol has been shown to increase the risk of overdose and death from opioids in opioid-tolerant individuals. We hypothesized that ethanol reversed opioid tolerance and previous studies showed that ethanol reversed morphine tolerance. This dissertation investigated whether ethanol reversed tolerance to other opioids in mice, …

Interleukin-18 As A Therapeutic Target In Western-Diet Induced Cardiomyopathy, Pratyush Narayan

Theses and Dissertations

Background: Heart Failure (HF) is characterized by impaired cardiac function with symptoms of dyspnea, fatigue and exercise intolerance. Western diet (WD), a diet high in saturated fats and sugars, causes systemic increase in IL-18, a cytokine elevated in HF, which induces abnormal myocardial structure and diastolic dysfunction. IL-18 binding protein(IL-18BP) binds IL-18, preventing the binding to the IL-18-receptor. We investigated a therapeutic intervention using recombinant-murine IL-18BP to improve the WD-induced cardiomyopathy in C57BL/6J mice.

Methods: Echocardiography with pulse-wave Doppler and tissue imaging was performed to assess cardiac function. Oral glucose tolerance test was performed to assess metabolic parameters and IL-18 …

Gomds - Grumpy Old Men Doing Shakespeare; The Comedy Of Errors As Metaphor For Life, Aging, And Building Community, Elizabeth B. Pedersen

Theses and Dissertations

This thesis explores the process of building community over time, through collaboration, to rehearse and produce a portable production of Shakespeare's The Comedy of Errors, looking at the elements of time, trust and age with an ensemble of ten men, all actors over the age of 55. The building of trust over time was vital to the production process and the actors had the time to embody their roles and the language of the play. We look at the questions “why this play,” “why all men?” and “why theatre?” and investigate the physical nature of the play and its …

Effects Of Hydraulic Dredging And Vessel Operation On Atlantic Sturgeon Behavior In A Large Coastal River, Michael R. Barber

Theses and Dissertations

The tidal James River, a focus of VCU's Atlantic Sturgeon program, supports both commercial shipping and hydraulic dredging. These anthropogenic threats present documented but preventable sources of mortality to the endangered species. Using three separate VEMCO Positioning System (VPS) receiver arrays, spatial data of previously-tagged fish were collected. ArcGIS and Programita software were used to analyze fish spatial distributions in the presence and absence of potential threats, using additional data including automatic identification system (AIS) vessel locations, vessel passages compiled using camera footage, and dredge records provided by the US Army Corps of Engineers. The data showed a change in …

(Re)Mediating The Spirit: Evangelical Christian Young Adult Media, Tamara Watkins

Theses and Dissertations

"We are in the world, but not of the world," a maxim frequently spoken in evangelical Christian culture, provides insight into how these individuals view their relationship with secular culture. They presume to share the same temporal plane with secular culture, but do not participate in it. In this dissertation, I explore whether the division between evangelical Christian culture and secular culture is as clear as this aphorism implies. To facilitate this investigation, I examine media Christian content creators created for an American evangelical Christian young adult audience in the early twenty-first century, specifically focusing on novel-length fiction, comics and …

The Dual Faces Of Misery, Arden Moscati

Theses and Dissertations

Major Depression (MD) and Generalized Anxiety Disorder (GAD) are psychiatric disorders that arise from dysfunction of the core human capacities for emotion. Sapience is inextricably bound up with the potential for feelings of regret, worry and concern. When these emotions lead to clinically significant impairment or distress, they may result in one or both of the disorders of MD and GAD. The occurrence of MD and GAD in the same person, known as comorbidity, is remarkably high; substantially higher than would be expected by chance.

MD and GAD have been studied since the mid-20^th century, resulting in a substantial …

Zebrafish (Danio Rerio) As A Model For Orofacial Research, Kevin A. Ghaffari

Theses and Dissertations

Across species, the face and more specifically the mouth, serves as an essential facet of everyday life. Amongst humans the mouth serves as a tool for the ingestion of food, a marker for facial recognition and a medium for communication. In order for the mouth to properly form, a series of precise growth and fusion events are needed. In order to insure that these events are orchestrated properly is a wide array of signals, transcription factors and epigenetic regulators. Due to the needed precision of these events, congenital birth defects of the face such as cleft lip and cleft palate …

The Monstrous Self: Negotiating The Boundary Of The Abject, Katya Yakubov

Theses and Dissertations

Through the lens of the horror film and the fairy tale, this thesis explores the notion of the grotesque as a boundary phenomenon—a negotiation of what is self and what is other. As such, it locates the function that the monstrous and the grotesque have in the formation of a personal and social identity. In asking why we take pleasure in the perverse, I explore how permutations of guilt, victimhood, and desire can be actively rewritten, in order to construct a stable sense of self.

The Fractured Memory Of A Mind’S Eye, Russell G. White

Theses and Dissertations

The work I create is informed by questioning reality/identity, the fractalizing planes

of existence our essence occupies, and the artifacts of memory experience navigating

through space time. While existing in this realm of oversaturated media and neon

glow, I question the effects of pervasive data systems overloading or programming the

mental software we possess. My work includes humor as a means of exploring these

conventions while also displaying psychedelic surrealist imagery to help break away

from the conscious prison this existence births our concept apparatuses within.

Construction Of An Album For Oneself, Maria Tinaut

Theses and Dissertations

My work focuses on the construction and validation of images assembled from fragments of found photographs, generating new narratives that hover between “reality” and fiction. Archive and Fiction: Construction of the past and the self is the result of two years of artwork exploring my family archives and my relationship to my family through them. I understand the family as a place of identity in continuous change, serving as a container of history and memory. Conceiving of my family albums as material allows me to approach my family history as a visitor. Mediated memory and constructed memory intertwine in the …

A Dull Soldier And A Keen Guest: Stumbling Through The Falstaffiad One Drink At A Time, Emma Givens

Theses and Dissertations

Theatre history has long interwoven with the production, consumption, and peddling of alcohol. While the seedier aspects of our past generally go unremembered, we can find traces of them in the culture of the times. If we read Shakespeare through the lens of drinking culture, what can we discover about the play and what can that tell us about how to produce his works today? By looking at the rules and customs surrounding alehouses during the English Renaissance I have analyzed the three plays contained within the Falstaffiad (1 Henry IV, 2 Henry IV, and Merry Wives …

Spooky Action At A Distance, Jonathan A. Rehwoldt

Theses and Dissertations

The question posed is “Can I experience remote human intimacy?” This is only posed after a network of computer code, images and entities have worked through the studio apparatus. These objects only materialize after khaos, the gap, the chasm has been recognized and a remote position has been realized. The work is about examining this constellation of objects and processes in their aspiration to answer the stated question in the affirmative. The resulting presentation is an experience of the failures and illuminations of both the material and the work.

Nature Nurtures, Moriah Rhodes

Theses and Dissertations

Richmond, Virginia is defined by our connection to the James River. The James River Park system stretches over 550 acres of natural beauty. The park is broken into 14 different sections from the Huguenot Bridge in the west to a half mile beyond the I-95 Bridge in the east. The James River includes water features that appeal to the young and curious to the most experienced river-adventurer. The James River Park System boasts idyllic shorelines, peaceful meadows, and miles of challenging hiking and biking trails that appeal to the community and guests alike. Every year thousands of people come to …

Wiped Clean, Elizabeth H. Hunter

Theses and Dissertations

It seems that all forms of pain, quotidian and monumental, are catalogued in the same muted and inaccessible space in our memory. In my installation Wiped Clean, I question whether human capacity to externalize physical trauma is aided by a the physical design of our institutions. I examine the architectures and structural mechanisms that mediate traumatic and intimate experiences with our bodies, and explore the potential of self-formation within these conditions.

Biochemical Analysis Of Putative Single-Stranded Nucleic Acid Binding Proteins In Porphyromonas Gingivalis, Steve H. Kokorelis

Theses and Dissertations

Proteins that bind to both DNA and RNA embody the ability to perform multiple functions by a single gene product. These nucleic acid binding proteins in prokaryotes can play a vital role in many cellular processes, including replication, transcription, gene expression, recombination, and repair, to name a few. Nucleic acid binding proteins have unique functional characteristics that stem from their structural attributes that have evolved in a widely-conserved manner. In Escherichia coli (E. coli), the highly-conserved histone-like protein, HU, which predominates as a heterodimer of HUα and HUβ, has been found to bind to both dsDNA and ssDNA. …

The Role Of Mindfulness In The Regulation Of Behavior Among Those Prone To Negative Urgency, Alexandra M. Martelli

Theses and Dissertations

Negative emotions can be challenging to regulate, and for some individuals can lead to failures of behavior regulation. The present study is an initial effort to explore the role that mindfulness may play in fostering effective behavior regulation among those prone to high negative urgency (NU). Eighty undergraduate students were recruited based on their high or low scores of NU. First, participants completed a self-report measure of mindfulness (Mindful Attention Awareness Scale; MAAS), an Emotional Go/No Go task in an fMRI scanner, and then reported alcohol consumption. Results showed that those with high in NU had low levels of mindfulness …

Niche Conservatism Or Divergence: Insights Into The Evolutionary Histories Of Pinus Taeda, Pinus Rigida, And Pinus Pungens, Constance E. Bolte

Theses and Dissertations

Environmentally related selective pressures and community interactions are well-documented drivers for niche differentiation, as natural selection acts on adaptive traits best fit for survival. Here, we investigated niche evolution between and within Pinus taeda, Pinus rigida, and Pinus pungens and sought to identify which climate variables contributed to species divergence. We also sought to describe niche differentiation across genetic groupings previously identified for P. taeda and P. rigida. Ecological niche models were produced using Maximum Entropy followed by statistical testing based on a measure of niche overlap, Schoener’s D. Both niche conservatism and niche divergence were …

Combining Noxa-Inducing Drugs With Abt-263 To Efficiently Increase Cell Death In Head And Neck Squamous Cell Carcinoma (Hnscc), Sung Woo Kim

Theses and Dissertations

Head and neck cancer is the sixth leading cancer worldwide. Head and neck squamous cell carcinoma (HNSCC) accounts for more than 90% of incident cases. Despite intense, multimodality treatment regimens for HNSCC including surgery, chemotherapy, and radiation, little progress has been made over the past 30 years in improving overall survival rates. Tumor cell death induced by both conventional and targeted chemotherapy is often mediated by the BCL-2 family-dependent mitochondrial apoptotic pathway. However, initiators of this apoptotic pathway, such as p53, are more than 50% of the time mutated or deleted in HNSCC rendering the disease refractory to treatment. To …

Theatrical Texts And Contexts: Poe And Hawthorne’S Fictional Women, Savannah M. Singletary

Theses and Dissertations

Edgar Allen Poe and Nathaniel Hawthorne are arguably two of the most highly read and heavily debated nineteenth-century antebellum authors in America. Their writings fascinate readers, while their character depictions, particularly their characterizations of fictional women, prompt intense academic debate. This thesis examines the previously less-studied historical developments surrounding Poe and Hawthorne in the antebellum era that shaped their approach to writing fiction. In particular, this study scrutinizes the effects of the development of a newly popular art form, ballet, the ascendency of female authorship, and the impact of American theatrical reform upon antebellum authors’ authorial faculties, especially Hawthorne and …

Po2 Dependence Of Oxygen Consumption In Skeletal Muscle Of Diabetic And Non-Diabetic Rats, Alexander C. Liles

Theses and Dissertations

Abstract

PO₂ DEPENDENCE OF OXYGEN CONSUMPTION IN SKELETAL MUSCLE OF DIABETIC AND NON-DIABETIC RATS

By: Alexander C. Liles

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at the Medical College of Virginia Campus, Virginia Commonwealth University

Virginia Commonwealth University, 2017

Advisor: Roland N. Pittman, Ph.D.

Department of Physiology and Biophysics

Type 2 diabetes mellitus (T2DM) is a major medical problem around the world, affecting nearly 6% of the world’s population. This study was an attempt to better understand physiological changes the disease may cause to the microcirculation and more specifically, to …

A Range-Wide Assessment Of Migratory Connectivity For The Prothonotary Warbler Using Stable Hydrogen Isotopes, Jessica Reese

Theses and Dissertations

Populations of many species of migratory birds are declining, and an understanding of how populations are linked between the breeding and nonbreeding grounds is necessary in order to determine drivers of declines. While all current tracking technologies to study the movements of small songbirds are limited by their coarse resolution, tracking birds by measuring stable isotopes in keratin offers an advantage because it requires only a single capture and is cost-effective, which leads to robust sample sizes. While this tracking method is accurate, stable hydrogen isotope values measured in feathers (δ²H_f) are known to be variable …

Sub For More, Chelsea Lee

Theses and Dissertations

This written thesis unpacks the thoughts and motivations behind the decisions I have made in my artistic practice that have ultimately culminated in my M.F.A. Thesis Exhibition: Sub for More. By merging images of my own work as well as internet sourced images of the culture that drives my work, I have created a platform to begin to understand my experience during graduate school. This text examines and explores my belief in the inherent power in pop culture, my obsession with fame, celebrity, and my self-identity as a participant in current pop-culture.

The Institute Of New Feelings: Plastic Identities And Imperfect Surfaces, Weijian Zhou

Theses and Dissertations

Digital media are moldable spaces where an image is simultaneously a thought. This instance and flexibility enables digital existences to be malleable, transformative, situational, and unstable. They are plastic images. Video games generate digital bodies that are a fusion of subjectivities and cybernetic simulations, in a perceivable and ambiguous process. Such bodies are extensions of ourselves, being girlish, imperfect, unfinished and happening—digesting and emitting clusters of feelings, regardless of our biological gender and age. The performative experience of play is progressively departing from spectacle, gambling and competition, and increasingly shifting towards an emotional journey of alternate realities, spreading subjectivities into …

Chemical Probes For Protein Α-N-Terminal Methylation, Brianna D. Mackie

Theses and Dissertations

While protein α-N-terminal methylation has been known for nearly four decades since it was first uncovered on bacteria ribosomal proteins L33, the function of this modification is still not entirely understood. Recent discoveries have demonstrated α-N-terminal methylation is essential to stabilize the interactions between regulator of chromosome condensation 1 (RCC1) and chromatin during mitosis, to localize and enhance the interaction of centromere proteins (CENPs) with chromatin, and to facilitate the recruitment of DNA damage-binding protein 2 (DDB2) to DNA damage foci. Identification of N-terminal methyltransferase 1 (NTMT1) unveiled the eukaryotic methylation writer for protein α-N-termini. In addition, NTMT2 that shares …

The Odcombian Climber: How Thomas Coryate Employed Media For Social Advantage, Julian T. Neuhauser

Theses and Dissertations

Thomas Coryate (1577?-1617), the writer, traveler and social climber, embraced various media in order to achieve social gains. This thesis surveys the content and materiality of writings by and about Coryate to investigate the nature of his sociability. The study begins by drawing on John Hoskyns’ (1566–1638) poem, “Convivium philosophicum,” to explore how Coryate used oral and social performance to create a unique form of sociability through which mockery is transmuted into praise. This thesis then addresses how Coryate’s sociability factored into the conflation of aspects of manuscript and print media in the production of the “Panegyricke Verses” that were …