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 …

Modeling Fluid Motion Over Fibrous Surfaces, Delli Ganesh Venkateshan

Theses and Dissertations

The ultimate goal of this project has been to develop a computational model for quantifying the interactions between of a body of fluid and a fibrous surface. To achieve this goal, one has to develop a model to create virtual structures that resemble the morphology of a fibrous surface (Objective-1) as well as a model that can simulate the flow of a fluid over these virtual surfaces (Objective-2). To achieve the first objective, we treated fibers as an array of beads interconnected through viscoelastic elements (springs and dampers). The uniqueness of our algorithm lies in its ability to simulate the …

Oncogene Induced Dna Replication In Lung Injury Repair And Carcinogenesis, Shilpa Singh

Theses and Dissertations

Deregulation of genome duplication is a common theme in cancer cells. Although multitude of pathways has been discovered and implicated in the ability of oncogenes or loss of function tumor suppressors to induce oncogenesis, most of the pathways ultimately converge in deregulated genome duplication or uncoupling of DNA replication and segregation in cancer cells. It is important to determine how known oncogenes deregulate genome duplication, and if prevention of deregulated genome duplication could be a feasible target to thwart uncontrolled proliferation of cancer cells. Conventional paradigm ascribes the cell proliferative function of the human oncoprotein mouse double minute2 (MDM2) primarily …

An Innovative Use Of Technology And Associative Learning To Assess Prone Motor Learning And Design Interventions To Enhance Motor Development In Infants, Tanya Tripathi

Theses and Dissertations

Since the introduction of the American Academy of Pediatrics Back to Sleep Campaign infants have not met the recommendation to “incorporate supervised, awake “prone play” in their infant’s daily routine to support motor development and minimize the risk of plagiocephaly”. Interventions are needed to increase infants’ tolerance for prone position and prone playtime to reduce the risk of plagiocephaly and motor delays. Associative learning is the ability to understand causal relationship between events. Operant conditioning is a form of associative learning that occurs by associating a behavior with positive or negative consequences. Operant conditions has been utilized to encourage behaviors …

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 …

Candor & Ebb: Searching For My Truth Through Solo Performance, Andrew Ross Wynn

Theses and Dissertations

This thesis is an examination of autobiographical solo performance. It explores the use of personal trauma and illness in the dramatic form. In addition to investigating how other solo performing artists utilize their medical conditions in their work, this thesis gives some historical context to the author’s own process and development. The thesis culminates in the author’s solo performance script and a desire for its audience to find solace and compassion through the experience of witnessing it being performed.

A Personal Approach To Landscape: Empathy, Sentiment, And The Environment's Representation In Tumultuous Times, Lauren Hensens

Theses and Dissertations

My work approaches the multitude of personal experience within the landscape, considering its cultural representation, aiming to give the environment agency within these tumultuous times. The following text is a personal narrative, realizing the many lenses through which a landscape can be experienced, including analyses of artists, writers, and musicians who have represented landscape through their own individuality.

Inquiry-Based Methods In The International Baccalaureate Primary Years Program Art Room, Andrew Bell

Theses and Dissertations

The International Baccalaureate Primary Years Program [IB PYP] is a student-driven, inquiry-based elementary school level educational program that has grown rapidly in the United States since its creation in 1997. This study explores how IB PYP art teachers define and implement inquiry-based instructional methods in their art rooms through a nation-wide, online survey of art teachers, coordinators, and administrators. The Survey consists of 22 questions which ask respondents to describe their classroom practices and provide examples of how they make use of inquiry-based methods in the art room. The responses to this survey were then value coded for four different …

Scan & Scansion: An Urban Residency For Poets & Artists Working In Collaboration, Heather A. Overby

Theses and Dissertations

Scansion is the act of discerning a poem’s meter and measure to discover its overall meaning. To achieve beauty in poetry, just as in interior design, content must continually be in conversation with form. And, just as a building must be scaled against the human figure to determine its final shape, a poem is scaled against human breath, the breadth of our sounds.

Scan & Scansion is a Richmond-based residency with a six-month term providing a work, living and exhibition space to poets and artists who wish to work collaboratively across disciplines. As the program is essentially about applied poetics …

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 …

Influence Of Cultural Strengths On The Relationships Among Acculturative Stress, Racism, And Mental And Physical Health In Latino Immigrants, Annahir N. Cariello

Theses and Dissertations

The Latino immigrant population in the United States has grown rapidly, now standing at over 56 million people. Due to this increase in Latino immigrants, investigation of their mental and physical health is crucial. Few studies have investigated conjointly both physical and mental health in Latino immigrant adults. Daily discrimination and acculturative stress have been found to affect the mental and physical health of Latino immigrants. Cultural strengths including social support, religiosity, and enculturation have been linked to Latino immigrant health. In the minority stress model, cultural strengths have been theorized to moderate relationships between discrimination and health. The purpose …

Black Lives Examined: Black Nonfiction And The Praxis Of Survival In The Post-Civil Rights Era, Ariel D. Lawrence

Theses and Dissertations

The subject of my thesis project is black nonfiction, namely the essay, memoir, and autobiography, written by black authors about and during the Post-Civil Rights Era. The central goals of this work are to briefly investigate the role of genre analysis within the various subsets of nonfiction and also to exemplify the ways that black writers have taken key genre models and evolved them. Secondly, I aim to understand the historical, political, and cultural contributions of the Post-Civil Rights Era, which I mark as hitting its stride in 1968. It is not my desire to create a definitive historical framework …

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.

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, …

Performative Design, Lenita Ann Eldhose

Theses and Dissertations

The field of design is one that holds the power to empower, bridge gaps, inform, evolve and revolutionize human thoughts. To gain a higher understanding of the correlation of anthropometrics and ergonomics in an embodied space relative to the discipline of dance connecting one’s mind and body. The need for a space that instills a sense of freedom for artists to experience and execute their art and to reside alongside their mentors and traveling artists. The need for a space that can bring the diverse cultures that live in and around Richmond together through an expressive form of art. Providing …

Role Of Sphingosine-1-Phosphate Receptors In Cytokine And Chemokine Production By Glia, Jean Moon

Theses and Dissertations

About 1 in 10 newly diagnosed HIV cases in the United States are attributed to injection drug abuse. Opiate abuse exacerbates HIV disease progression in the central nervous system by disrupting glial function and significantly augmenting glial-derived pro-inflammatory mediators. Astroglia and microglia exposed to viral proteins, such as transactivator of transcription (Tat), become activated leading to release of a large number of cytokines and chemokines and a positive loop of neuro-inflammation. Despite effective antiretroviral therapy, persistent inflammation and immune activation affect HIV-infected individuals. A potential alternative target is sphingosine 1-phosphate receptor 1 (S1PR1) which is known to play a role …

Placental Eicosanoids And Sphingolipids In Preeclampsia, Daniel T. Reep

Theses and Dissertations

Placental dysfunction is implicated in the pathogenesis of preeclampsia. Chemical signals between the placenta and maternal circulation are a suspect cause of endothelial dysfunction and maternal hypertension. This study examined select lipid mediators of inflammation produced by the placenta. Patients were recruited from Virginia Commonwealth University’s pregnancy clinics and placentas were collected at delivery. Forty-eight-hour explant cultures of villous placental tissue were used to model lipid production. Electrospray ionization mass spectrometry was used to quantify concentrations of free lipids in the culture media. Bicinchoninic acid assays were performed to quantify protein in each culture for normalization of lipid data. After …

Fibronectin Mechanics And Signaling In Tgf-Β1-Induced Epithelial To Mesenchymal Transition, Lauren Griggs

Theses and Dissertations

Epithelial to Mesenchymal Transition (EMT) is a dynamic process by which a distinct change in the phenotype and function of epithelial cells render them as mesenchymal cells. Characteristics of mesenchymal cells include the ability to invade, increased migratory kinetics and heightened resistance to apoptosis. Therefore, there is a strong need to fully understand the mechanism for the induction of EMT in pathological conditions such as carcinoma progression. Recent advances highlight two pivotal contributors, soluble growth factor (gf) signals, and mechanical signals, in the process. However, to date, no clear mechanism exists linking the two in epithelial transdifferentiation. Transforming Growth Factor-β1 …

Motion-Induced Artifact Mitigation And Image Enhancement Strategies For Four-Dimensional Fan-Beam And Cone-Beam Computed Tomography, Matthew J. Riblett

Theses and Dissertations

Four dimensional imaging has become part of the standard of care for diagnosing and treating non-small cell lung cancer. In radiotherapy applications 4D fan-beam computed tomography (4D-CT) and 4D cone-beam computed tomography (4D-CBCT) are two advanced imaging modalities that afford clinical practitioners knowledge of the underlying kinematics and structural dynamics of diseased tissues and provide insight into the effects of regular organ motion and the nature of tissue deformation over time. While these imaging techniques can facilitate the use of more targeted radiotherapies, issues surrounding image quality and accuracy currently limit the utility of these images clinically.

The purpose of …

Developing A Cyberterrorism Policy: Incorporating Individual Values, Osama Bassam J. Rabie

Theses and Dissertations

Preventing cyberterrorism is becoming a necessity for individuals, organizations, and governments. However, current policies focus on technical and managerial aspects without asking for experts and non-experts values and preferences for preventing cyberterrorism. This study employs value focused thinking and public value forum to bare strategic measures and alternatives for complex policy decisions for preventing cyberterrorism. The strategic measures and alternatives are per socio-technical process.

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Validation Of Virginia's Juvenile Risk Assessment Instrument, Jessica P. Schneider

Theses and Dissertations

Utilizing a validated risk assessment tool to predict future offending is recommended as best practices in corrections by a number of professional organizations (Latessa & Lovins, 2010). Guided by the risk-needs-responsivity model, risk assessment tools have evolved to help inform criminal justice practitioners by identifying offenders most in need of intervention or supervision, guiding the case plan to optimize outcomes (Bonta & Andrews, 2007). The Virginia Department of Juvenile Justice (DJJ) utilizes the Youth Assessment and Screening Instrument (YASI) at all stages of contact with youthful offenders, including intake, probation, commitment, and parole (DJJ, 2016). However, risk assessment instruments do …

Women In Music: Letting A Long Story Be Long Contemplating Women’S Sonic, Musical, And Spiritual Experiences In Prehistory, Deborah J. Saidel

Theses and Dissertations

Situated within deep history, this study explores the auditory and spiritual lives of Paleolithic women. It considers their personal agency in mediating the spiritual power of sound and how doing so contributes to a multifaceted musicality. The theoretical framework involves a wide spectrum of topics, from ways of rethinking the writing of history and reckoning with time, to sound studies and the study of acoustics in ancient sites, to a critical examination through a feminist lens of normative disciplinary scholarship in anthropology and archaeology, religious studies, and musicology. I explore potential audio-visual-lithic relationships for their implications for deepening an understanding …

Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks

Theses and Dissertations

Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14⁺⁺CD16^-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14⁺⁺CD16⁺) and non-classical (CD14^LowCD16⁺⁺) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …

Trna Profiling Of Mesenchymal Stem Cell Exosome, Khin Mimi San

Theses and Dissertations

Background: Exosomes have great potential in regenerative medicine through the

transfer of their bioactive cargos, such as RNA. tRF RNA and tiRNA are tRNAderived

non-coding RNA. Here, we sought to identify the tRF/tiRNA profile in human

mesenchymal stem cell (hMSC) exosomes. Methods: Bone marrow hMSCs were

cultured with/without osteogenic differentiation medium and exosomes were

harvested. RNA was extracted from: 1) control cells (Cell-NT); 2) control exosomes

(EXO-NT); 3) differentiated cells (Cell-OM); 4) exosomes produced by differentiated

cells (EXO-OM). RNA was sequenced to profile the small RNA with a focus on

tRF/tiRNA. Results: tRF/tiRNA was highly enriched in hMSC exosomes. Less …

Genomic Instability In Severe Congenital Neutropenia, A Leukemia Predisposition Syndrome, Adya Sapra

Theses and Dissertations

Severe congenital neutropenia (SCN) is a rare blood disorder characterized by abnormally low levels of circulating neutrophils. Mutations in multiple genes like neutrophil elastase gene (ELANE) and granulocyte colony stimulating factor receptor (CSF3R) may cause SCN. The treatment of choice for SCN is the administration of granulocyte-colony stimulating factor (G-CSF) which elevates the neutrophil count and hence improves the survival and quality of life. Long term survivorship on G-CSF is however linked to development of MDS (myelodysplastic syndrome)/AML (acute myeloid leukemia). About 70% of MDS/AML patients acquire nonsense mutations affecting the cytoplasmic domain of CSF3R. …

From Blacker The Berry To Darker The Flesh: Gendered Racial Microaggressions, Ethnic Identity, And Black Women’S Sexual Behaviors, Chelsie E. Dunn

Theses and Dissertations

Race- and gender-related contextual factors influence Black women’s sexual behaviors, attitudes, and outcomes. Contextual factors of Black women’s sexual behaviors include stereotypes, microaggressions, ethnic identity, and self-concept. Little to no research has examined race- and gender-specific microaggressions (i.e., gendered racial microaggressions; GRM) impact on Black women's sexual health. Responsively, using an intersectional approach, this study hypothesized that ethnic identity’s influence on the relationship between GRM and sexual behavior (i.e., condom use, lifetime sexual partners) is conditional on self-conceptualization moderated effect on ethnic identity and sexual behavior. Participants included 124 unmarried Black women, recruited from mTurk, a southeastern university and community. …

Embedded In These Walls, Trish J. Gibson

Theses and Dissertations

Embedded In These Walls uses photographic imagery, archival ephemera, and written text to examine a specific history of generational trauma through the lens of a singular family of a southern tradition to point to a larger systemic breakdown of accountability and truthfulness regarding abuse

Secondary Student Information Literacy Self-Efficacy Vs. Performance, Jen Spisak

Theses and Dissertations

The amount of information in the world has grown exponentially in the last generation. Students often believe that growing up as digital natives means they have advanced information literacy skills. However, school librarians are not seeing evidence of this in their schools. The purpose of this study was to determine if secondary students overestimate their information literacy (IL) abilities, if relationships exist between IL self-efficacy and performance, and if grade level or self-efficacy level changes those relationships. To accomplish this, data were collected from two middle schools and three high schools from a total of 397 students in grades 6, …

Integrating Obesity And Eating Disorder Prevention: A Pilot And Feasibility Trial Of Inspire, Courtney C. Simpson

Theses and Dissertations

Obesity and eating disorders are pervasive concerns among young adult women, and profoundly impact physical and psychological functioning. Weight-related disorders are typically chronic conditions; their treatment is often complex and frequently ineffective. Moreover, Black and Latina women have disproportionately high rates of obesity, and experience rates of eating disorders comparable to those of their White peers; yet, they are less likely to be referred to appropriate treatment. Given the intractability of weight-related concerns and their detrimental consequences, attempts to prevent unhealthy eating attitudes and behaviors are essential. To date, few prevention programs have significantly reduced both obesity risk and eating …