Digital Commons Network^™

Light Controlled Drug Activation And Release, Jonathon Sheldon

Theses and Dissertations

Cancer constitutes a terrible burden on modern society. In the United States there are an estimated 1,658,370 new cancer diagnoses resulting in 589,430 deaths in 2015 alone.^[1] An estimated 41,170 of these cases will be diagnosed right here in Virginia. With new cancer patients comes the expanding demand for new treatments. As we all know, many modern chemotherapeutics cause adverse reactions to patients. This is because the toxic nature of these therapies often affects normal tissue alongside the tumors that are infesting the body. Therefore, researching novel ways to make chemotherapeutics selective for cancer, while leaving healthy tissue unscathed, …

Normalizing Tumor Vasculature Using Sepiapterin To Increase Radiosensitivity, Ninu Bruno

Theses and Dissertations

Our studies examine the role of nitric oxide synthase (NOS) in tumor vasculature. NOS is “uncoupled” in tumor cells, resulting in peroxynitrite (ONOO^-) formation in lieu of nitric oxide (NO). NO signaling is critical for vascular function, thus uncoupling of eNOS in endothelial cells may partly explain the poor vasculature found within tumors. NOS can be “recoupled” through Sepiapterin (SP) treatment of tumor cells. We examined whether SP could normalize tumor vasculature, promoting radiosensitivity. Optoacoustic tomography of flank xenografts and spontaneous tumor models demonstrate that SP significantly enhances percent oxyhemoglobin in tumors. Immunohistochemical analysis of SP-treated tumors showed …

Nitric Oxide Synthase Activity And Its Modulation In The Treatment Of Colorectal Cancer, Asim Alam

Theses and Dissertations

The American Cancer Society estimates more than 141,000 new cases of and about 50,000 deaths from colorectal cancer every year. Treatment options include surgery, radiation therapy and targeted therapies such as anti-angiogenics. However, no therapies address the key driving factor of colorectal cancer: inflammation. It is well known that chronic inflammatory conditions such as Crohn’s Disease, ulcerative colitis, diabetes, obesity and cigarette smoking all elevate the risk of developing colorectal cancer. One of the hallmarks of chronic inflammation is the elevated levels of reactive oxygen/nitrogen species (ROS/RNS). A primary source of these ROS/RNS is uncoupled Nitric Oxide Synthase (NOS). Under …

Integrated Nanoscale Imaging And Spatial Recognition Of Biomolecules On Surfaces, Congzhou Wang

Theses and Dissertations

Biomolecules on cell surfaces play critical roles in diverse biological and physiological processes. However, conventional bulk scale techniques are unable to clarify the density and distribution of specific biomolecules in situ on single, living cell surfaces at the micro or nanoscale. In this work, a single cell analysis technique based on Atomic Force Microscopy (AFM) is developed to spatially identify biomolecules and characterize nanomechanical properties on single cell surfaces. The unique advantage of these AFM-based techniques lies in the ability to operate in situ (in a non-destructive fashion) and in real time, under physiological conditions or controlled micro-environments.

First, AFM-based …

Physicochemical And Structural Analysis Of Polymers As Putative Drugs, Meghan L. Thompson

Theses and Dissertations

Sulfated low molecular weight lignins (LMWLs) have shown good activity as anticoagulants by allosterically inhibiting thrombin, as well as promising agents for treating emphysema through inhibition of elastolysis, oxidation, and inflammation. Sulfated LMWLs are chemo-enzymatically synthesized from starting monomers caffeic, ferulic, and sinapic acid into sulfated dehydropolymers known as CDS, FDS, and SDS. To further the LMWLs’ development as drugs, their structural composition and physicochemical characteristics were defined in this work. The molecular weight distribution profile of the sulfated LMWLs from size exclusion chromatography performed on a high pressure liquid chromatography system (SEC-HPLC) changed from bimodal when no surfactant is …

Conjoined Lucuma Fruit Vessels: Evolution & Context In Nasca Art, Carley Elder

Theses and Dissertations

The function of a ceramic vessel is often evaluated in relation to its form. Vessels with complex forms can be challenging to analyze from this perspective and require a different approach. One such example is an overlooked yet long-lived specialized vessel type in the form of conjoined lúcuma fruits found throughout the ancient Andes. The main object of this study is a Nasca version of this vessel type in the Virginia Museum of Fine Art. This study explores the relationship between form and iconography, rather than function. It examines how Nasca potters adopted the conjoined lúcuma form vessel and adapted …

Individuals With Fetal Alcohol Spectrum Disorder: Predictive Factors For Successful Occupational Performance, Mary Culshaw

Theses and Dissertations

As awareness and diagnoses of FASD grow in Canada, there is increased need to support these individuals across their lifespan. One study suggested the prevalence of FASD may be as high as 10 per 1000 births (May & Gossage, 2001). The impact to society is growing as well, since this population requires support across their lifespan due to cognitive and sometimes physical impairments. It was estimated that the annual cost to Canadians was $53 billion (in 2007 dollar value) to support individuals aged 0-53 years (Stade et al., 2009). There is mounting evidence identifying the cognitive and physical impairments that …

Decreased Sound Tolerance (Dst): Prevalence, Clinical Correlates, And Development Of A Dst Assessment Instrument, Therese Verkerke Cash

Theses and Dissertations

Decreased sound tolerance (DST) conditions, including misophonia and hyperacusis, are emerging clinical conditions in behavioral medicine. Misophonia involves an extreme emotional response (often anger, disgust, or annoyance) to specific sounds (such as people chewing, swallowing, tapping their foot on the floor, etc.), while hyperacusis is defined by high sensitivity to sounds below normal sound sensitivity thresholds. Although research on these DST conditions is increasing, clearly defined prevalence rates, associations with other mental health conditions, and development of assessment tools that can identify and differentiate DST symptoms are needed. Research and clinical reports also suggest that DST problems are more likely …

Examination Of Basal Neuroendocrine Levels In Oif/Oef/Ond Veterans, Sage E. Hawn

Theses and Dissertations

Abstract

EXAMINATION OF BASAL NEUROENDOCRINE LEVELS IN OIF/OEF/OND VETERANS

By Sage E. Hawn, B.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2015.

Major Director: Ananda B. Amstadter, PhD.

Associate Professor

Departments of Psychiatry, Psychology, & Human and Molecular Genetics

High rates of combat exposure exist among veterans of the recent conflicts, and are associated with debilitating mental health conditions, including posttraumatic stress disorder (PTSD). Numerous psychosocial and biologic factors are associated with PTSD, including the HPA-axis. The present study aimed to compare baseline neuroendocrine …

Conduction States Of The Human Dopamine Transporter, Krasnodara Cameron

Theses and Dissertations

Dysregulation of dopaminergic homeostasis has been established as the primary source of numerous neurological disorders including Parkinson’s and drug addiction. A tonic increase of dopamine (DA) in the nucleus accumbens is required for associating everyday events and behaviors with rewards. Yet many addictive exogenous compounds such as amphetamine (AMPH) and cocaine (COC) produce a much greater augmentation of synaptic DA levels that are linked to euphoria and a shift in behavior towards drug seeking. The protein responsible for maintaining extracellular levels of DA is the dopamine transporter (DAT). It is primarily located in the perisynaptic area at terminals of pre-synaptic …

Into The Fray, Frances Pearce

Theses and Dissertations

My sculpture and prints are about dismemberment and the destruction caused by war. To address the high cost of war, I make works that present the threat of injury, amputation, and prosthetics. I use Classical Greek art history references to address contemporary political, military, and social issues. I include images such as Amazonian women, horses, and doves. These images are coupled with references to the damage caused by conflict. While my work concerns destruction, paradoxically, my process involves additive construction. I take a mixed media approach to both my sculptures and my prints, and use a wide range of materials …

Vitamin C: A Potential Regulator Of Inflammatory Response, Bassem M. Mohammed

Theses and Dissertations

Introduction: Neutrophils (PMNs) and Macrophages are the first responders recruited consecutively to the site of injury/inflammation. PMNs’ response/fate as well as macrophage reprogramming ultimately determine the course of resolution of inflammation. Physiologic wound healing has a significant inflammatory component. An exaggerated inflammation however is self-defeating leading to delayed healing. Parenteral vitamin C (VitC) attenuated inflammation in murine sepsis models and in patients with sepsis. However information about the mechanisms by which VitC regulates these events is limited.

Methods: Humanized mice lacking VitC synthesis capability (Gulo^-/-) were used. VitC sufficient and deficient mice were challenged with sterile inflammation, or …

Chronic Behavioral And Cognitive Deficits In A Rat Survival Model Of Organophosphate Toxicity, Beverly Huang

Theses and Dissertations

Organophosphates (OPs) are a major class of pesticides and nerve agents that elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine in the central and peripheral nervous systems. Acetylcholine accumulation following extensive AChE inhibition leads to an acute cholinergic syndrome characterized by autonomic dysfunction, involuntary movements, muscle fasciculations, respiratory distress, and seizures. Despite their classification as moderate to highly toxic, OP pesticides are the most widely used class of insecticides in the U.S., and are even more commonly used worldwide. Additionally, there is a growing concern that OP nerve agents could be …

Lost In Austen: An Immersive Approach To Pride & Prejudice, Erica Hughes

Theses and Dissertations

This paper is an account of the Theatre VCU mainstage production of Pride & Prejudice, in which I played the roles of Mrs. Bennet and of the vocal coach. In order to address the various skill levels of the cast, I planned to coach the production in a manner inspired by immersion language learning programs, with the cast speaking in dialect throughout the rehearsal process so as to learn the necessary vocal skills and to grow together as a theatrical ensemble. When the director of Pride & Prejudice was not receptive to this plan, I had to compromise and adapt …

Enhanced Epithelial-To-Mesenchymal Transition Associated With Lysosome Dysfunction In Podocytes: Role Of P62/Sequestosome 1 As A Signaling Hub, Guangbi Li

Theses and Dissertations

Autophagy is of importance in the regulation of cell differentiation and senescence in podocytes, the highly differentiated glomerular epithelial cells. It is possible that derangement of autophagy under different pathological conditions activates or enhances Epithelial-to-Mesenchymal Transition (EMT) in podocytes, resulting in glomerular sclerosis. To test this hypothesis, the present study produced lysosome dysfunction by inhibition of vacuolar- type H⁺-ATPase (V-ATPase) to test whether deficiency of autophagic flux enhances EMT in podocytes. By Western blot analysis, inhibition of lysosome function by V-ATPase inhibitor or its siRNA was found to induce a significantly enhanced EMT in cultured podocytes, as shown …

“Frailty, Thy Name Is Woman”: Depictions Of Female Madness, Julianna Little

Theses and Dissertations

Concepts of mental health and normality cannot be understood apart from cultural norms and values. The most significant of cultural constructions that shape our view of madness is gender. Madness has been perceived for centuries metaphorically and symbolically as a feminine illness and continues to be gendered into the twenty-first century. Works of art and literature and psychiatric medicine influence each other as well as our understanding and perception of mental illness. Throughout history, images of mental illness in women send the message that women are weak, dangerous, and require containment. What are the cultural links between femininity and insanity, …

African Sleeping Sickness In British Uganda And Belgian Congo, 1900-1910: Ecology, Colonialism, And Tropical Medicine, Dana Bivens

Theses and Dissertations

This thesis deconstructs the social, ecological, and colonial elements of the 1900-1910 Human African Trypanosomiasis (African Sleeping Sickness) epidemic which affected British Uganda and Belgian Congo. This paper investigates the epidemic’s medical history, and the subsequent social control policies which sought to govern the actions of the indigenous population. In addition, this paper argues that the failure to understand and respect the region’s ecological conditions and local knowledge led to disease outbreaks in epidemic proportions. Retroactive policies sought to inflict western medical practices on a non-western population, which resulted in conflict and unrest in the region. In the Belgian Congo, …

Modification And Evaluation Of A Brain Computer Interface System To Detect Motor Intention, Christopher V. Hagerty-Hoff

Theses and Dissertations

It is widely understood that neurons within the brain produce electrical activity, and electroencephalography—a technique used to measure biopotentials with electrodes placed upon the scalp—has been used to observe it. Today, scientists and engineers work to interface these electrical neural signals with computers and machines through the field of Brain-Computer Interfacing (BCI). BCI systems have the potential to greatly improve the quality of life of physically handicapped individuals by replacing or assisting missing or debilitated motor functions. This research thus aims to further improve the efficacy of the BCI based assistive technologies used to aid physically disabled individuals. This study …

Characterization Of Leukocyte-Platelet Rich Fibrin, A Novel Biomaterial, Fadi K. Hasan

Theses and Dissertations

Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and are successfully used in oral surgery. Several commercial systems exist that generate various forms of platelet concentrates including Platelet-rich plasma (PRP) and Platelet-rich fibrin (PRF). The alpha- granules of entrapped platelets release a variety of peptide growth factors that promotes healing. Usually PRP is a suspension that can be injected into the site of injury or used as a gel with the addition of thrombin (PRP-gel). In contrast Choukroun’s L-PRF is a dense fibrin based biomaterial enriched with platelets and growth factors. The physical state of …

A Perception Of Change, A Change Of Perception, Christopher D. White

Theses and Dissertations

Change is a constant reminder that permanence is the ultimate illusion. It is through the creation of hyper-realistic, ceramic sculpture that I explore the relationship between nature, humans, and the phenomenon of impermanence. I seek to expose the beauty that often results from decay while, at the same time, making my viewer question their own perception of the world around them. The juxtaposition of natural and man-made features in combination with the skewing of scale, proportion, and material, creates an altered perspective – forcing the viewer to look closer. By combining both human and natural elements within my work I …

Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi

Theses and Dissertations

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …

Phenotypic Characterization Of Pnpase Knockdown In C. Elegans, Laura A. Lambert

Theses and Dissertations

The multifunctional exoribonuclease protein PNPase is implicated as a potential target for cancer therapy as well as causing mitochondrial disorders in humans, but there has yet to be a whole animal knockdown model created. In this study, C. elegans was used to investigate the effect of knocking down pnpt-1, the gene that encodes PNPase. It was discovered that pnpt-1 knockdown significantly extends lifespan via an increase in superoxide production similar to other known mitochondrial lifespan extension pathways. Additionally, mitochondrial networks, size and respiration are affected indication of other mitochondrial dysfunction..

PNPase is also known to transport small RNAs into the …

An Impossible Alternative: Orientalism And Margaret Bourke-White's "A Moneylender's House" (1947), Sharayah Cochran

Theses and Dissertations

Between 1946 and 1948, American photographer Margaret Bourke-White traveled to India while on assignments for Life magazine. Since the late 1940s, a photograph from these assignments that depicts three men sitting in an ornately decorated room has appeared in several publications and exhibitions under variations of the title A Moneylender’s House (1947). Though Bourke-White is traditionally categorized as a documentary photojournalist, her photograph exhibits motifs similar to those seen in European Orientalist paintings from the nineteenth century. Considering recent scholarship that has expanded the temporal and geographical parameters of the Orientalist photography genre, this thesis analyzes the “documentary” photograph, A …

Behavioral Responses Of Male Parasitic Wasps To Plant Cues: A Comparison Of Two Host-Plant Complex Sources Of Cotesia Congregata (Say), Megan Ayers

Theses and Dissertations

Prior exposure to plants cues can enhance assortative mating in insects. We hypothesized that, as previously reported for females, males of Cotesia congregata would display inherent responses to plant cues that could be modified by postemergence experience and further, that males originating from two different host-plant complexes (HPCs) would display different behavioral responses to these HPCs. In no-choice contact assays with a non-host plant, searching responses of males and females increased sharply at Day 2 and remained stable through Day 4. In no-choice assays with potential host plants, males searched longer on catalpa than tobacco; responses were not modified by …

Responses Of The Catalpa Sphinx, Ceratomia Catalpae, And Its Primary Parasitoid, Cotesia Congregata, To Varying Levels Of Iridoid Glycosides In Catalpa, Jessica L. Bray

Theses and Dissertations

The catalpa sphinx, Ceratomia catalpae, is a specialist on Catalpa trees, which produce iridoid glycosides (IGs). Whereas some trees are defoliated every year, others escape herbivory. Caterpillar populations are either heavily parasitized by the braconid wasp, Cotesia congregata, or remain unparasitized. We hypothesized that these patterns could be explained by variable IG concentrations among trees and insect responses to these chemicals. IG concentrations varied among trees. Percent defoliation was positively related to IG concentration. In comparisons of insect responses to relatively high or low IG concentrations, moths preferred to oviposit on trees with high IG concentrations. Caterpillars did …

The Effect Of Dexamethasone On Il-33-Mediated Mast Cell Activation, Oksana I. Chernushevich

Theses and Dissertations

Dexamethasone has been shown to inhibit IgE-mediated mast cell activation, and the present research investigated its role in suppressing IL-33-mediated mast cell activation. We have found that micromolar concentrations of Dexamethasone are capable of suppressing IL-33-mediated mast cell cytokine production, on several genetic backgrounds, and in not only bone marrow derived mast cells, but also peritoneal mast cells. Intracellular staining demonstrated that Dexamethasone significantly reduces expression of the IL-33 receptor, T1/ST2, in mast cells; however, the cytokine suppression is independent of T1/ST2 downregulation. At the same time, Dexamethasone pretreatment significantly reduced ERK phosphorylation, but our data suggests that inhibition occurs …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Identification Of Candidate Genes For Craniosynostosis, Karen Rymer

Theses and Dissertations

Craniosynostosis is a disorder characterized by the premature fusing of cranial sutures in an infant. Premature closure of these sutures can lead to detrimental consequences on the development of a child. The two broad categories of craniosynostosis are classified as syndromic and nonsyndromic. Nonsyndromic craniosynostosis involves only the fusion of one or more sutures, whereas syndromic craniosynostosis involves other abnormalities throughout the body of the affected individual. Two of the families analyzed in this study were of the syndromic nature, and known FGFR mutations were discovered. However, phenotypical features documented in association with these mutations differed from our individuals. Two …

Engineering Of Polyamidoamine Dendrimers For Cancer Therapy, Leyuan Xu

Theses and Dissertations

Dendrimers are a class of polymers with a highly branched, three-dimensional architecture comprised of an initiator core, several interior layers of repeating units, and multiple active surface terminal groups. Dendrimers have been recognized as the most versatile compositionally and structurally controlled nanoscale building blocks for drug and gene delivery. Polyamidoamine (PAMAM) dendrimers have been most investigated because of their unique structures and properties. Polycationic PAMAM dendrimers form compacted polyplexes with nucleic acids at physiological pH, holding great potential for gene delivery.

Folate receptor (FRα) is expressed at very low levels in normal tissues but expressed at high levels in cancers …

The Effects Of 7,8-Dihydroxyflavone (7,8-Dhf) On Neuroprotection And Neuroplasticity Follwing A Traumatic Brain Injury, Jennifer M. Romeika

Theses and Dissertations

Aside from preventing traumatic brain injuries (TBIs) altogether, treatment options for TBI typically focus on the secondary biochemical processes that occur in response to the primary mechanical insult. These secondary injuries can lead to apoptosis and necrosis in the days and weeks that follow a TBI. Therefore, finding a treatment that can prevent, reduce, and repair secondary damage is instrumental in the recovery of TBI patients. The flavonoid 7,8-dihydroxyflavone (7,8-DHF) has been identified as a TrkB agonist that mimics the effects of brain derived neurotrophin factor (BDNF). Upon binding to the TrkB receptor, signaling cascades are initiated that can promote …