Digital Commons Network^™

The Definition Of Youth, Jessta Noel

Theses and Dissertations

The purpose of this project was to write my own theatrical production which would solely include me as the actor. I drew upon my experience of childhood growing up in Atlanta, GA as well as the stories passed on in my family.

Non-Native Speaker Attentional Capacity And The Processing Of English Phrasal Verb Constructions, Aubrey Dillard

Theses and Dissertations

The effect of syntactic and semantic complexity on attention and processing in second language acquisition (SLA) has long been of interest to both practitioners and researchers of SLA. Theoretical models of attention in SLA (Schmidt 1990, Tomlin and Villa 1994, Robinson 1995) have spurred a great deal of empirical research in the field, and VanPatten's (1994, 2004, 2007) work on the effect of attention to form and meaning on comprehension of input has been very influential in the field. From a language processing viewpoint, Clahsen and Felser (2006, 2009) have hypothesized that the different ways in which native and nonnative …

John Pecham On Life And Mind, Caleb G. Colley

Theses and Dissertations

No abstract provided.

Modified Seed Growth Of Iron Oxide Nanoparticles In Benzyl Alcohol: Magnetic Nanoparticles For Radio Frequency Hyperthermia Treatment Of Cancer, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for precise control of nanoparticle properties. This thesis presents an investigation of parameters in the benzyl alcohol synthesis of iron oxide nanoparticles. A modified seed growth method was designed for obtaining optimal nanoparticle properties for magnetic fluid hyperthermia. With a one or two addition process, iron oxide nanoparticles were produced with crystallite sizes ranging from 5-20 nm using only benzyl alcohol and iron precursor. The effects of reaction environment, temperature, concentration, and modified seed growth parameters were investigated to obtain precise control over properties …

Using Structural Analysis To Investigate The Function Of Suppressor Of Ikk-Epsilon (Sike), Sean W. Mckinley

Theses and Dissertations

The innate immune system provides the body’s first line of defense against pathogenic challenge through pathogen recognition and initiation of the immune response. Among the various cellular mechanisms of pathogen recognition in mammals, Toll-like receptor 3 (TLR3) recognizes viral dsRNA. Stimulation of TLR3 signaling pathway leads to transcription of pro-inflammatory cytokines and type-1 Interferons. Suppressor of IKKε (SIKE) interacts with two kinases in the signaling pathway, IKKε and TANK binding kinase 1 (TBK1), inhibiting the transcription of type I interferons. Recently, the Bell Laboratory discovered that SIKE blocks TBK1-mediated activation of type I interferons by acting as a high affinity, …

An Evolutionary Perspective On Infectious And Chronic Disease, John Eberth

Theses and Dissertations

The integration of evolutionary biology with traditional medicine can elucidate novel mechanisms of contemporary disease. Whereas the goal of traditional medicine is to treat and cure the proximate causes, evolutionary biology aims to understand the driving forces behind why humans are susceptible to disease. To form the basis of this hypothesis we postulate that modern man's current genetic information was programmed at a time, and in an environment, that is not relevant to today's human populations. The discordance between these genes of our ancestors and the environment of contemporary humans is thought to be a major reason for the increase …

Characterization Of The Hippocampal Acetylcholine System In A Rodent Model Of Fetal Alcohol Syndrome, Amy Elizabeth Perkins

Theses and Dissertations

Fetal alcohol spectrum disorders (FASD) are a major public health concern, as it is estimated that 2-5% of children are exposed to alcohol at some point during prenatal development. FASD have been shown to cause damage to multiple brain regions, but research shows that the hippocampus is especially sensitive to alcohol exposure. This damage to the hippocampus explains, in part, deficits in learning and memory that are hallmark symptoms of FASD. The acetylcholine neurotransmitter system plays a major role in learning and memory, and the hippocampus is one of its main targets. This experiment used a rodent model of Fetal …

Novel Therapeutic Strategies For Pancreatic Cancer, Bridget A. Quinn

Theses and Dissertations

Pancreatic cancer is a devastating disease that leaves patients with a very poor prognosis and few therapeutic options. Many of the treatment options available are the same that have been used for almost 2 decades. There is a dire need for both novel treatments for this disease as well as novel strategies of treatment. This body of work will introduce and provide evidence in support of a novel combination therapy for pancreatic cancer treatment, a novel strategy of modifying currently used chemotherapeutics for pancreatic cancer therapy, and a novel transgenic preclinical mouse model of pancreatic cancer. Sabutoclax, an antagonist of …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

The Role Of Microrna In Staphylococcal Enterotoxin B-Induced Inflammation And Acute Lung Injury, Roshni Rao

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a potent activator of the Vβ8+T-cells leading to the proliferation of nearly 30% of the T-cell pool. As a consequence, excessive amounts of cytokine mediators are released leading to extensive tissue damage and sometimes toxic shock and death. Due to the ease with which SEB can be aerosolized anddisseminated, it is considered a biological weapon. In the current study, we investigated the pro-inflammatory effects of SEB in two mouse models of acute inflammatory lung injury. Specifically, while inflammatory cues are known to elicit changes in key transcriptional factors and gene expression, we explored for the …

The Troublesome Document, Stanley Wolukau-Wanambwa

Theses and Dissertations

An essay concerning the development of documentary photography, its relationship to political norms, conventions of realism in visual culture, and the form of the photographic book.

An Analysis Of Fatty Acid Metabolism’S Role In The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans, Richard Raabe

Theses and Dissertations

An individual’s naïve level of response (LR) to ethanol is predictive of their lifetime likelihood to abuse alcohol. LR is heavily genetically influenced, suggesting that the genes responsible for LR may also be central to the development of abuse disorders. Our laboratory uses the model organism C. elegans to investigate the genetic influences on responses to acute ethanol exposure. We recently found that changes in TAG levels can alter LR. From this result we investigated the role of long-chain polyunsaturated fatty acids (LC-PUFAs) as well enzymes involved in lipid modifications of proteins. We found that LC-PUFAs are necessary for acute …

Group Via Calcium-Independent Phospholipase A2 Regulates Bcl-Xl Protein Levels In Mice Lung, Sang-Jin Nam

Theses and Dissertations

With previous indication of the Group VIA phospholipase A2 (iPLA2β) enzyme regulating ER-stress induced apoptosis in β-cells by regulating the anti-apoptotic protein Bcl-xL via alternative splicing, our lab postulated iPLA2β to be utilizing a similar mechanism to regulate apoptosis in mice lung. Our previous lab work has shown implications of lung function compromise in iPLA2β-/- mice, and we speculated the cause to be due altered lung architecture stemming from the attenuation of apoptosis. The western blot analysis in this study suggested that iPLA2β is involved in the regulation of Bcl-xL, but the mRNA ratios of the splice variants suggested that …

Evolution And Divergence Of The Structural And Physical Properties Of Dna Binding By Methyl-Cytosine Binding Domain Family Members 2 And 3, Jason Cramer

Theses and Dissertations

The studies presented in this dissertation, Evolution And Divergence Of The Structural And Physical Properties Of DNA Binding By Methyl-Cytosine Binding Domain Family Members 2 And 3, pertain primarily to two key epigenetic regulators involved with the biological interpretation of methylated DNA marks. We provide insights into the emergence and evolution of the MBD2 and MBD3 and how those molecular entities influence heritable changes in gene activity. We further provide details regarding the mystery surrounding MBD3 function and the MBD2-mediated capacity of primitive animals to carry out methylation-specific epigenetic mechanisms. In chapter two, we describe the DNA binding properties of …

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic (Pk) Properties Using Quantitative Structure Pharmacokinetic Relationships (Qspkr) And Interspecies Pharmacokinetic Allometric Scaling (Pk-As) Approaches For Four Different Pharmacological Classes Of Compounds, Gopichand Gottipati

Theses and Dissertations

This research developed and validated QSPKR models for predicting in-vivo human, systemic biologically relevant PK properties (i.e., reflecting the disposition of the unbound drug) of four, preselected, pharmacological classes of drugs, namely, benzodiazepines (BZD), neuromuscular blocking agents (NMB), triptans (TRP) and class III antiarrhythmic agents (AAR), as well as PK allometric scaling (PK-AS) models for BZD and NMB, using pertinent human and animal systemic PK information (fu, CLtot, Vdss and fe) from published literature. Overall, lipophilicity (logD7.4) and molecular weight (MW) were found to be the most important and statistically significant molecular properties, affecting biologically relevant systemic PK properties, and …

Present With An Uncertain Future: Dispositional Mindfulness, Covariation Bias, And Event-Related Potential Responses To Emotional Stimuli In Uncertain Contexts, Robert J. Goodman

Theses and Dissertations

Uncertainty represents a robust threat that can amplify aversive experiences and exaggerate negative expectations about uncertain future outcomes. Mindfulness – an open and receptive attention to present moment experiences -- has been shown to facilitate adaptive regulation when faced with a variety of distinct emotional threats. Reduced experiential avoidance and equanimity in the face of unpleasant emotional experiences have been theorized as central to these emotional regulatory benefits. The present study explored whether dispositional mindfulness would promote adaptive responses to uncertainty during the anticipation of, and after exposure to emotional stimuli, as indicated by self-reports and neural (event-related potential) markers …

Mitochondrial Gene Expression In Human Mononuclear Cells, Monika Ruchala

Theses and Dissertations

MITOCHONDRIAL GENE EXPRESSION IN HUMAN MONONUCLEAR CELLS By Monika D. Ruchała, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2014. Director: Dr. James P. Bennett Jr, M.D., Ph.D., Bemiss Professor Departments of Neurology, Psychiatry and Physiology and Biophysics Adult neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), have been intensively studied in recent years in pursuit of mechanisms responsible for origin and progression. One emerging theme is mitochondrial energetic deficiency as a mechanism of neuronal death. Recent descriptions of protocols to generate induced pluripotent stems …

Evaluation Of The Allometric Exponents In Prediction Of Human Drug Clearance, Da Zhang

Theses and Dissertations

Background. Allometric scaling (AS) is widely used in predicting human clearance (CL) based on animal data. Substantial prediction errors have been commonly observed and various modifications to AS have not provided a broad reliable improvement. In this study, an extensive data set was assembled including animal and human systemic CL and physiochemical properties. The allometric exponents were calculated based on multiple species AS and single-species AS methods. The correlations between the allometic exponents and physiochemical properties were evaluated in an attempt to find covariates that may explain the inter-compound variability in the allometric exponents. Lastly, the statistical approaches in analyzing …

Modeling Acute Changes In Bladder Wall Tension, Shape And Compliance During Filling, Firdaweke Habteyes

Theses and Dissertations

The bladder wall consists primarily of detrusor smooth muscle. Tension-sensitive nerves in the bladder wall are responsible for providing bladder fullness information that is interpreted as urgency. Bladder wall tension, and therefore nerve output, is a function of bladder volume, shape and material properties. Studies have shown that the bladder wall exhibits acutely regulated detrusor compliance. In addition, bladder shape throughout filling depends on intra-abdominal forces and material properties of the bladder wall, such as regulated detrusor compliance. This thesis focused on modeling the potential influence of acute changes in bladder compliance, shape and bladder wall tension during filling. Laplace’s …

Reversed-Phase Ion-Pairing Ultra Performance Liquid Chromatography-Mass Spectrometry In Characterization Of Glycosaminoglycans, Alhumaidi Alabbas

Theses and Dissertations

Glycosaminoglycans (GAGs) are a family of linear bio-polysaccharides, which are heterogeneously modified with negatively charged sulfate and carboxylate groups. They are located on every cell surface, extracellular matrix or intracellular space in the body. GAGs are composed of alternating units of an amino sugars (glucosamine or galactosamine) and hexuronic acid/hexose (iduronic acid, glucoronic acid/ or galactose), which are linked by glycosidic bonds with different geometries. In recent years, GAGs have attracted considerable interest. GAGs play vital roles in fundamental biological processes, such as hemostasis, angiogenesis, cell signaling, growth and differentiation. Thus, GAGs contribute to a number of diseases such as …

Fabrication Of Nanoporous Gold And Biological Applications, Badharinadh Uppalapati

Theses and Dissertations

FABRICATION OF NANOPOROUS GOLD AND BIOLOGICAL APPLICATIONS By Badharinadh Uppalapati A Dissertation submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2014 Major Director: Maryanne M. Collinson, Professor, Department of Chemistry Fabrication of nanoporous gold electrodes by dealloying Au:Ag alloys has attracted much attention in sensing applications. In the first part of this work, the electrochemical response of the redox active molecule, potassium ferricyanide, in a solution of bovine serum albumin in buffer, serum or blood was studied using nanoporous gold and comparisons made to planar gold. Nanoporous …

Novel 3d Head And Neck Cancer Model To Evaluate Chemotherapeutic Efficacy, Kelly Morgan

Theses and Dissertations

HNSCC accounts for 7 percent of all new cancer occurrences. Despite currently available treatments, there continues to be a high mortality and recurrence rate in HNSCC. Well over 50 percent of all cancer patients receive chemotherapy as a standard treatment. However, only 5 percent of these cases have been shown to help with treatment of the disease. Formerly, two options were available for drug testing: in vivo animal models, and in vitro two-dimensional models. While in vivo models remain the most representative, their use is burdened by high costs, time constraints, and ethical concerns. 2D models are simple to use …

Evaluation Of The Physiological Effects Of Reduced Hydroxocobalamin On Acute Carbon Monoxide Toxicity, Alden Newcomb

Theses and Dissertations

Carbon monoxide (CO) poisoning represents a global health threat responsible for hundreds of thousands of hospital visits and tens of thousands of deaths annually. Oxygen therapy is the only current approved treatment for CO poisoning. Previous work published in the 1970’s and research conducted in the VCURES lab group has indicated that a reduced form of vitamin B12, hydroxocobalamin (B12r), can potentially serve as an antidote for CO poisoning by converting CO bound to hemoglobin to carbon dioxide (CO2) and mitigating the deleterious neurological effects of CO poisoning. For the first time in documented literature we successfully used a Clark-type …

Modulation Of Cns Neurotransmitter Levels And Associated Behaviors In Organic Anion Transporter 1 (Slc22a6) And Organic Anion Transporter 3 (Slc22a8) Knockout Mice, Christine Farthing

Theses and Dissertations

According to the World Health Organization, mental disorders represent the leading cause of disability in the US generating ~58 billion dollars in medical costs annually. Additionally, among the US population, ~40 million adults suffer from an anxiety disorder and ~14 million suffer from a major depressive disorder. The association between the persistence of these neurobehavioral conditions and central nervous system (CNS) levels of biogenic amines and metabolites has been studied for half a century. Further, a number of drugs interfering with neurotransmission/metabolism are used clinically for treatment of these disorders. Recently, some members of the solute carrier (SLC) superfamily, the …

Transformational Directing: An Analysis On How Leadership Affects The Creative Process, James Clayton Winters

Theses and Dissertations

Leadership is often ascribed as a quality one either possess or doesn’t. We often hear phrases like “She is born leader” or “All eyes are on you”, these are thrown around without discretion in the classroom, conference rooms, social gatherings, and business meetings. This work contends that leadership and in particular leadership that grows and transforms its participants is less an inherent character trait, than an outlook and set of core principles that lead to transformation. Through the application of current and developing business leadership theory and its effect on creativity and a cross analysis of “Best in Class” theatre …

Investigating The Role Of The Synaptic Transcriptome In Ethanol-Responsive Behaviors, Megan A. O'Brien

Theses and Dissertations

Alcoholism is a complex neurological disorder characterized by loss of control in limiting intake, compulsion to seek and imbibe ethanol, and chronic craving and relapse. It is suggested that the characteristic behaviors associated with the escalation of drug use are caused by long-term molecular adaptations precipitated by the drug’s continual administration. These lasting activity-dependent changes that underlie addiction-associated behavior are thought, in part, to depend on new protein synthesis and remodeling at the synapses. It is well established that mRNA can be transported to neuronal distal processes, where it can undergo localized translation that is regulated in a spatially restricted …

Structural Studies Of Interferon Regulatory Factor 4: A Molecular Perspective Of Its Regulatory Mechanism, Soumya Govinda Remesh

Theses and Dissertations

Interferon (IFN) regulatory factor family member 4 (IRF4) is a transcription factor that serves specific roles in transcriptional regulation of IFN responsive genes and is indispensable in B- & T-cell differentiation. IRF4 like the other members of the family has two major domains- the N-terminal DNA binding domain (DBD) essential for its recognition and binding to the Interferon Stimulated Response Element DNA sequence and a C-terminal Interferon activation domain (IAD) thought to maintain IRF4 in an auto-inhibited inactive state and is also critical in its activation. A putative unstructured linker connects the DBD and IAD. Activation in most members of …

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …

Studies Of The Middle Class, Scott S. Stanard

Theses and Dissertations

I create oil paintings and drypoints that bring attention to scenes of American middle class life. I present crowds of people engaged in community activities and festivals. This enables me to depict a cross section of the residents of a given region. I also create a counterpoint to these peopled gatherings by painting and drawing the exteriors of middle class homes. In my work, I attempt to imbue a sense of intrigue and pathos.

I work from candid photos that I take of people and their living spaces. In these photos, I modify and delete elements to optimize narrative and …

Regulation Of Pancreatic Α And Β Cell Function By The Bile Acid Receptor Tgr5, Divya Prasanna Kumar

Theses and Dissertations

The discovery that bile acids act as endogenous ligands of the membrane receptor TGR5 and the nuclear receptor FXR increased their significance as regulators of cholesterol, glucose and energy metabolism. Activation of TGR5, expressed on enteroendocrine L cells, by bile acids caused secretion of GLP-1, which stimulates insulin secretion from pancreatic β cells. Expression of TGR5 on pancreatic islet cells and the direct effect of bile acids on the endocrine functions of pancreas, however, are not fully understood. The aim of this study was to identify expression of TGR5 in pancreatic islet cells and determine the effect of bile acids …