Digital Commons Network^™

Targeting Bcl-2 Family Members In The Cell Death Pathway To Treat Head And Neck Cancer, Erin L. Britt

Theses and Dissertations

Head and neck cancer accounts for approximately 3 percent of all cancers in the United States, and over 90% of them are head and neck squamous cell carcinoma (HNSCC). Chemotherapeutic drugs that treat HNSCC can activate BCL-2 family dependent apoptosis. Pro-apoptotic NOXA induced by adenovirus (Ad-NOXA) or fenretinide inactivates anti-apoptotic MCL-1, while ABT-263 can inactivate other anti-apoptotic BCL-2 family members such as BCL-2 and BCL-X_L. We used p53 inactive HN8 and HN12, p53 wild-type UMSCC1, and HPV-positive UMSCC47 human HNSCC cell lines and five mouse HNSCC cell lines. Cells were treated with Ad-NOXA, ABT-263, and fenretinide alone or …

Complexities Of Chronic Opioid Exposure, Maciej Gonek

Theses and Dissertations

Studies on repeated exposure to opioids have been carried out for decades yet the mechanisms for certain phenomena such as tolerance are still not fully understood. Furthermore, different medications, such as frequently prescribed benzodiazepines, or different disease states, such as HIV, have their own effects and interactions with chronic opioid exposure that are not fully understood. The overall objective of this dissertation was to investigate the complexities of chronic opioid exposure and how different disease states and medications may modulate the effects of chronic opioids. Our findings demonstrate that the administration of diazepam, at doses that are not antinociceptive or …

Patterns Of Molecular Population Genetic And Phenotypic Variation Associated With Urbanization In The Western Black Widow Spider, Lindsay Miles

Theses and Dissertations

In urban population genetic studies, the "urban fragmentation model" predicts that urbanization acts as a barrier that isolates native populations, and can lead to reduced gene flow and increased genetic drift between populations. The “urban facilitation model” predicts urban areas act as corridors to increase dispersal among urban areas, and can lead to higher genetic diversity within and lower differentiation between urban areas.

In a review of the current literature, we found that there is no consistent signature of reduced within-population genetic diversity or increased between-population genetic differentiation. Analyses that investigate the urban barriers to gene flow also found no …

Observations Of Trends And Successes Of Revascularization Therapy At Virginia Commonwealth University: A Retrospective Study, Richard W. Sedwick

Theses and Dissertations

The aim of this study was to determine the trends in protocol, success rates, and consistency in follow up of revascularization procedures in a controlled environment. Patients of the Virginia Commonwealth University School of Dentistry were identified who were offered revascularization therapy as a treatment option on immature permanent teeth from January 1, 2010 to May 31, 2017. A total of 77 patients and 78 teeth were evaluated for revascularization therapy. For patients accepting treatment, records were reviewed for outcome assessment and consistency of follow up. A total of 30 patients (31 teeth) were treated following revascularization protocols, with only …

Chromodomain Helicase Dna Binding Protein 1 (Chd1) Is Required For Orofacial Development In Xenopus, Brent Wyatt

Theses and Dissertations

Abnormalities affecting orofacial development are some of the most common, expensive, and devastating birth defects. Children born with such defects may experience difficulties with eating, breathing, and speech and in addition, these defects often require multiple surgeries to correct them. Therefore, it is critical to understand how the orofacial region develops in order to better treat and prevent these types of birth defects. Xenopus laevis has emerged as a strong model in which to examine orofacial development and was utilized here to investigate the cellular and molecular mechanisms underlying the complex development of the orofacial region. Retinoic acid is one …

Learning Together In Highland Park To Build Civic Capacity, Grace Leonard

Theses and Dissertations

This thesis examines the work of nonprofit organizations collaborating with communities to build civic capacity in North Highland Park, a neighborhood in Richmond, Virginia. Place-focused planning strategies during the twentieth century diminished civic capacity in the community and fostered isolation. Today, collaborative community work in Highland Park is incorporating the assets, resources and knowledge held in the community into strategies to improve quality of life using collaborative learning. A case study approach closely analyzes community engagement and revitalization processes in North Highland Park between 2011 and 2017. Nonprofit organizations mobilized and led a group of community-based collaborators, including nonprofit staff …

Bromodomain And Extraterminal Domain (Bet) Inhibitor Rvx-208 Ameliorates Periodontal Bone Loss, Nicholas J. Clayton

Theses and Dissertations

Periodontal disease affects 47% of Americans over 30 and is a growing global concern. Current treatments for periodontal disease focus on the mechanical elimination of periodontal biofilms. Very few treatments are available that target the rampant, unregulated host immune response that is ultimately responsible for tissue degradation. BET proteins have been shown to play critical roles in inflammatory gene regulation and are therefore potentially ideal therapeutic targets for treating periodontal disease. RVX-208 is a selective BET-inhibitor with a high affinity for Bromodomain 2 (BD2) as compared to BD1 in BET proteins. Our previous studies have shown that RVX-208 inhibits inflammatory …

Good Game, Greyory Blake

Theses and Dissertations

This thesis and its corresponding art installation, Lessons from Ziggy, attempts to deconstruct the variables prevalent within several complex systems, analyze their transformations, and propose a methodology for reasserting the soap box within the display pedestal. In this text, there are several key and specific examples of the transformation of various signifiers (i.e. media-bred fear’s transformation into a political tactic of surveillance, contemporary freneticism’s transformation into complacency, and community’s transformation into nationalism as a state weapon). In this essay, all of these concepts are contextualized within the exponential growth of new technologies. That is to say, all of these semiotic …

Glycolytic Atp Production Is Required For Innate Mast Cell Activation And Is Limited By Lactic Acid, Which Effectively Reduces Lps-Induced Cytokine Production In Mast Cells And In Vivo, Heather Caslin

Theses and Dissertations

The metabolic pathways required for adenosine triphosphate (ATP) production within the cell are well understood, however recent publications suggest that metabolic pathways are closely linked to immune cell activation and inflammatory diseases. There has been little examination of the metabolic pathways that modulate mast cell activation and the feedback regulator lactic acid. Here we examine metabolic pathways and regulation within mast cells in the context of lipopolysaccharide (LPS) and interleukin (IL-33) activation, for which there has been little to no reported studies. First, we examine the effects of lactic acid, previously considered only a by-product of glycolysis and now understood …

The Role Of A Type Lamins In Regulating Myelination, Jacqueline M. Deloyht

Theses and Dissertations

Multiple sclerosis (MS), a demyelinating disorder of the central nervous system (CNS), affects approximately 400,000 individuals in the United States, and 2.5 million people worldwide. It is a leading cause of disability in young adults. Current treatments for MS target the inflammatory aspects of the disease, but do not aid in remyelination. To address remyelination as a therapeutic strategy, it is imperative to identify mechanisms that regulate myelin formation, including epigenetic targets. In this study, we investigate the role of the LMNA, a gene encoding Lamins A and C, intermediate filaments of the nuclear lamina, in regulating oligodendrocyte development and …

A Novel, Orally Active Hydrogen Sulfide-Releasing Compound, Sg1002, Improves Left Ventricular Function With An Associated Induction Of Angiogenesis In A Murine Model Of Ischemia/Reperfusion, Om A. Evani

Theses and Dissertations

Hydrogen sulfide (H₂S) is the newest member of the gasotransmitter family and is becoming well known for its cardioprotective effects in preclinical trials. Many recent studies have shown the benefits of exogenous H₂S in the setting of acute myocardial infarction (AMI) and pressure overload-induced heart failure, but current formulations are derived from inorganic salts which have shortcomings in the precision and control of release of H₂S. The main objective of this thesis was to determine if the novel, orally active, slow-releasing compound, SG1002, can attenuate the severity of damage and adverse remodeling caused by …

Cultivating Community And Healthy Living: Urban Grocery And Garden, Amy Williams

Theses and Dissertations

Motivation

Today 49 million individuals in the US are affected by food insecurity (Whittle et. al., 2015). Low-income populations tend to depend solely on convenient stores for calorically-dense, nutrient poor sustenance, and suffer from health problems that drastically shorten or debilitate lives (Dhurandhar et al., 2016). In Richmond, Virginia there is a dramatic divide between wealthy and low-income communities in terms of the accessibility as well as the types and quality of foods available. Several communities in this city meet the characteristics of a food desert.

Problem

Grocery store chains typically avoid building in low-income communities for fear of low …

There Is Someone In This Dress, George, Michael S. Royce

Theses and Dissertations

Questions surrounding queer subjectivity—including shame, the closet, and celebration—are at the core of my interests as a painter and image maker. Mining the history of religious iconography, including annunciation paintings, scenes of the crucifixion, and other notable works of this ilk, my paintings seek to explore the intricacies of sexuality and the workings of shame and celebration at play in the life of the queer-identified.

Cellular Inhibitor Of Apoptosis Protein2 – A Critical Regulator Of Neuroinflammation, Debolina Dipankar Biswas

Theses and Dissertations

Inhibitors of apoptosis (IAPs) modulate cell death and play critical role in signal transduction that promotes inflammation. Recently, Smac mimetics, which are IAP antagonists, have attracted attention as novel cancer therapeutics. Cellular Inhibitor of Apoptosis 2 (cIAP2), a member of IAP family, positively affects both NF-κB and MAPK activation in response to many inflammatory stimuli. We observed that the lack of cIAP2 ablates LPS-induced neuroinflammation. Also, cIAP2^-/- macrophages demonstrated diminished antigen presentation potential that could contribute to ablated immunity. In addition to these functions, we have previously reported that cIAP2 also regulates the activation of Interferon Regulatory Factor 1 …

Abuse Liability Of An Electronic Cigarette In Traditional Cigarette Smokers, Sarah F. Maloney

Theses and Dissertations

Electronic cigarettes have grown in popularity across the U.S. and concerns have been raised about their abuse liability. The purpose of the current study was to evaluate and compare the abuse liability of an electronic cigarette with and without nicotine to a nicotine inhaler (the Nicotrol inhaler) and participants’ own brand of cigarettes. A total of 24 smokers attended four sessions in which the abuse liability of each product was examined using the Multiple-Choice Procedure (MCP), nicotine delivery, nicotine abstinence symptom suppression, and subjective reinforcing effects. Results revealed that the nicotine containing and non-nicotine containing electronic cigarette had a higher …

Social Soul, Norah Alshammari

Theses and Dissertations

Twitter has over 313 million users, with 500 million tweets produced each day.

Society’s growing dependence on the internet for self-expression shows no

sign of abating. However, recent research warns that social media perpetuates

loneliness, caused by reduced face-to-face interaction. My thesis analyzes and

demonstrates the important role facial expressions play in a conversation’s

progress, impacting how people process and relate to what is being said. My

work critically assesses communication problems associated with Twitter. By

isolating and documenting expressive facial reactions to a curated selection

of tweets, the exhibition creates a commentary on our contemporary digital

existence, specifically articulating …

Parent-Implemented Communication Intervention For Preschool-Aged Children With Autism, Heather M. Coleman

Theses and Dissertations

Exploring the interventions that promote expressive, verbal language for preschool-aged children with autism is essential. When a child is lacking the ability to communicate, parents express that they would like their child to speak. B.F. Skinner (1957) proposed that the mand repertoire (communicative requests) should be an initial focus of language training. Mand training has been shown to be effective for teaching children with autism to communicate. However, many studies exploring mand training utilize highly trained instructors for intervention implementation. Early childhood best practices recommend the use of family-centered interventions and teaching within the natural environment. This study followed these …

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 …

Migratory Patterns And Population Genetic Structure In A Declining Wetland-Dependent Songbird, Matthew G. Desaix

Theses and Dissertations

Understanding migratory connectivity is essential for assessing the drivers behind population dynamics and for implementing effective management in migratory species. Genetic markers provide a means to describe migratory connectivity, as well as incorporate population genetic analyses, however genetic markers can be uninformative for species with weak genetic structure. In this study, we evaluate range-wide population genetic structure and migratory connectivity in the prothonotary warbler, Protonotaria citrea, a wetland-dependent neotropical migratory songbird, using high-resolution genetic markers. We reveal regional genetic structure between sampling sites in the Mississippi River Valley and the Atlantic Seaboard with overall weak genetic differentiation among populations …

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 …

Quotations Like The Sharpest Claws, Johanna Robinson

Theses and Dissertations

Quotations like the Sharpest Claws describes a multimedia installation composed of paintings and sound that explores the theory of cognitive dissonance, a controversial psychological model that attempts to explain how we deal with inconsistency in incompatible beliefs. Imagination is given primacy as a source for truth-seeking and world-building. The uncanny and surreal are used as entry points into this topic.

The title is derived from a description of Eileen Myles’ poetry I once read in an anonymous review. Their writing was described as beyond poetry in a way that it could only be described as such when surrounded by “quotations …

Work/Death, Of Each In Their Own, Micah H. Weber

Theses and Dissertations

Writings in support of my visual thesis, including some background, and bibliographic information: Oregon/Death/Animation/Vocation and the artist as an agent of potential.

Enact In Disappearance, Stephanie Demer

Theses and Dissertations

Enact in Disappearance excavates the unseen through the medium of photography in order to chart a new strategy for knowing and communing with a complicated world.

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 …

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 …

Laminated Paint, Travis R. Austin

Theses and Dissertations

Though we may not perceive it, we are surrounded by material-in-flux. Inert materials degrade and the events that comprise our natural and social environments causally thread into a duration that unifies us in our incomprehension. Sounds reveal ever-present vibrations of the landscape: expressions of the flexuous ground on which we stand.

Escapism: Indulging In Daydreams, Tanruk Pairoj-Boriboon

Theses and Dissertations

A fantasy world, that exists only in our minds, provides us a place where we can mentally escape from everyday reality. Escapism, such as indulging in daydreams, allows us to experience comfort and makes us feel safe, eliminating feelings of insecurity and vulnerability.

This study aims to use playfulness and reverie as a tool to access and confront mental discomforts. Transforming disturbing situations into an experience of reverie; a correction of unsatisfying reality, by converting a solid component of the real world into a desirable infinite form will provide alternative viewpoints.

Throughout my work, this method has been employed to …

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 …

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 …