Digital Commons Network^™

Application Of Marginal Structural Models In Pharmacoepidemiologic Studies, Shibing Yang

Theses and Dissertations

Background: Inverse-probability-of-treatment-weighted estimation (IPTW) of marginal structural models was proposed to adjust for time-varying confounders that are influenced by prior treatment use. It is unknown whether pharmacoepidemiologic studies that applied IPTW conformed to the recommendations proposed by methodological studies. In addition, no previous study has compared the performance of different analytic strategies adopted in IPTW analyses. Objectives: This project aims 1) to review the reporting practice of pharmacoepidemiologic studies that applied IPTW, 2) to compare the validity and precision of several approaches to constructing weight, 3) to use IPTW to estimate the effectiveness of glucosamine and chondroitin in treating osteoarthritis. …

Pursuing The Roles Of Non-Invasive Biomarkers In Chronic Renal Allograft Dysfunction, Mba Uzoma U. Mba

Theses and Dissertations

Kidney failure affects over 600,000 people in the United States with over 100,000 new cases of kidney failure diagnosed every year. Chronic allograft dysfunction (CAD), a disease state highlighted by a decreased eGFR and a histo-pathological diagnosis interstitial fibrosis and renal tubular atrophy, has emerged as one of the leading causes of kidney transplantation. Gene expression analysis can identify reproducible patterns of disease in ribonucleic acid (RNA) expression and may provide insights into the quality of kidney donations heretofore overlooked by current clinical analytical methods. Additionally, genetic expression profiles can be obtained from patient blood or urine samples, diminishing the …

Identification Of Micro-Rnas And Their Messenger Rna Targets In Prostate Cancer And Biological Fluids, Kanika Sharma

Theses and Dissertations

Prostate cancer is the second most common cancer in the United States that affects men today. To better treat this disease accurate biomarkers and successful therapeutic treatments are needed. A novel approach to understand the mechanisms behind prostate cancer tumor formation lies in identifying dysregulated micro-RNAs (miRNAs), which are a class of small (18-24 nucleotides) non-coding RNAs that regulate gene expression posttranscriptionally by either inhibiting protein synthesis or signaling messenger-RNA for degradation. Multiple miRNAs were discovered in our highly tumorigenic and metastatic prostate cancer progression model M12 cell line compared to its weakly tumorigenic P69 parental cell line. Various analyses …

Characterization Of Putative Porphyromonas Gingivalis Rna-Binding Proteins, Holly Dwyer

Theses and Dissertations

Porphyromonas gingivalis (P. gingivalis) is a gram-negative, anaerobic bacterium recognized as a major player in progression of periodontal disease. P. gingivalis survives in the oral cavity while being exposed to dynamic environmental conditions such as pH, temperature, nutrient availability and host immune responses such as oxygen tension and nitrosative stress. Survival and pathogenesis of P. gingivalis in the oral cavity require mechanisms to regulate gene expression in response to the extracellular signals. Little is known about the regulatory mechanisms of P. gingivalis in the oral cavity, so it is important to investigate and characterize these regulatory mechanisms. Adaptation to environmental …

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 …

Regulation And Mechanistic Functions Of Caspase-9 Rna Splicing, Ngoc T. Vu

Theses and Dissertations

Caspase-9 has two splice variants, pro-apoptotic caspase-9a and anti-apoptotic caspase-9b, and dysregulation of caspase-9 splice variant ratio or expression of caspase-9b isoform has been linked to augmentation of the anchorage-independent growth and tumorigenic capacity of non-small cell lung cancer (NSCLC) cells. This study focuses on cell signaling pathway(s) regulating the alternative splicing of caspase-9 pre-mRNA and mechanistic roles of caspase-9b in a certain oncogenic/survival pathway. In regards to the former, we have identified hnRNP U as a novel splice-enhancer associated with exon 3 of caspase-9 (C9/E3). Moreover, hnRNP U binds specifically to C9/E3 at an RNA cis-element previously reported …

The Effect Of Fluvastatin On Mast Cell Function: Genotype Dependence, Elizabeth M. Kolawole

Theses and Dissertations

Fluvastatin, the HMG-CoA reductase inhibitor known for its role in the treatment of hypercholesterolemia and cardiovascular disease, has more recently been shown to play a role in the immune response. Given the critical role that mast cells play in allergy and inflammatory diseases such as asthma, which effects one third of America’s population, we assessed the effect of fluvastatin on mast cell and basophils function. We demonstrate that fluvastatin downregulated IgE-mediated cytokine production. Additionally, in vivo studies showed that fluvastatin suppressed IgE-mediated anaphylaxis. Interestingly, the effects of fluvastatin showed dependence on genetic background, as C57BL/6 mast cells were sensitive, while …

Quantitative Mass Spectrometric Investigations Of Protein Biomarkers: Serum Thymidine Kinase 1 And Human Osteopontin, Morse Faria

Theses and Dissertations

Mass spectrometry is being increasingly used in biomarker research mainly due to its ability to achieve high selectivity coupled with high sensitivity. This dissertation focuses on quantitative mass spectrometric investigations of two protein biomarkers i.e. serum thymidine kinase 1 (TK1) and human osteopontin (OPN).

First part of this research was focused on developing a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for measuring the activity of TK1 in serum by monitoring the conversion of a TK1 specific exogenous substrate, 3’-deoxy-3’-fluorothymidine (FLT), to its mono-phosphorylated form 3’-deoxy-3’-fluorothymidine monophosphate (FLT-MP). A method to quantify FLT-MP on LC-MS/MS was developed and …

A Study Of A Professional Development Initiative To Increase Cultural Competency, Jennifer C. Coleman

Theses and Dissertations

Abstract

A STUDY OF A PROFESSIONAL DEVELOPMENT INITIATIVE TO INCREASE

CULTURAL COMPETENCY

By Jennifer Crowe Coleman, Ph.D.

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

Virginia Commonwealth University, 2014

Major Director: Charol Shakeshaft, Ph.D.

Professor, Department of Educational Leadership

School of Education

While there are broad, societal forces that contribute to achievement gaps, the professional development of teachers is one way educational leaders have sought to improve schools, improve teacher performance, and increase teacher knowledge and skills. Given the achievement and cultural gaps that exist between teachers and …

Structural And Functional Characterization Of The Mbd2-Nurd Co-Repressor Complex, Megha Desai

Theses and Dissertations

The MBD2-NuRD co-repressor complex is an epigenetic regulator of the developmental silencing of embryonic and fetal β-type globin genes in adult erythroid cells as well as aberrant methylation-dependent silencing of tumor suppressor genes in neoplastic diseases. Biochemical characterization of the MBD2-NuRD complex in chicken erythroid cells identified RbAp46/48, HDAC1/2, MTA1/2/3, p66α/β, Mi2α/β and MBD2 to comprise this multi-protein complex.

In the work presented in Chapter 2, we have pursued biophysical and molecular studies to describe a previously uncharacterized domain of human MBD2 (MBD2_IDR). Biophysical analyses show that MBD2_IDR is an intrinsically disordered region (IDR). Despite this inherent …

Aquatic Priming Effects In The York River Estuary And Implications For Dissolved Organic Carbon Mineralization, Thomas M. Dunlap

Theses and Dissertations

The priming effect (PE), characterized as the enhanced microbial processing of bio-recalcitrant organic matter with the addition of labile substrates, has been hypothesized to moderate carbon (C) cycling in aquatic systems. In this study, aquatic PEs were evaluated through bacterial respiration and dissolved organic C consumption in incubations of water collected from three locations along the York River estuary. Incubations from White’s Landing on the Pamunkey River, a tidal freshwater tributary of the York, and from Croaker Landing in the middle of the estuary, displayed positive PEs when amended with labile C. In contrast, amended incubations from Gloucester Point, near …

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …

3d Reconstruction Of Ryr1 And Structural Validation Under Different Levels Of Noise, Joshua J. Lobo

Theses and Dissertations

Ryanodine receptors (RyR) are intracellular channels that are intricately involved in Ca2+ release. These channels large membrane proteins~2.26MDa in size. In this multi-goal project firstly we successfully studied the gating mechanics of the RyR1 in the presence of Mg2+. We used single particle reconstruction and image processing techniques to obtain the 3D structure of the RyR1 with Mg2+. The 3D structure in the presence of Mg2+ and an ATP analog is the closest representation of human physiological conditions. The open and closed state structures of RyR1 are known. However, the physiologically closed state has not been studied before. Understanding this …

Family Needs, Caregiver Burden, And Mental Health: Caregivers Of Individuals With Various Neurological Conditions From Colombia And Mexico, Megan Elizabeth Sutter

Theses and Dissertations

This cross-sectional study examined differences in family needs (informational, social, financial, health, and household support), caregiver mental health (depression, satisfaction with life, vitality, social functioning, and emotional role limitations), and caregiver burden (personal life, guilt, and psychological) among caregivers of individuals with traumatic brain injury, spinal cord injury, multiple sclerosis, and dementia from cities in Colombia and Mexico (N = 343). The study also examined the connections among family needs, caregiver mental health, and caregiver burden in the combined sample of caregivers of individuals with neurological conditions. Many significant differences were identified among groups, and implications are discussed. Family …

Exploring The Asymmetric Environment Of Various Chiral Catalysts Using A Modified Ion-Trap Mass Spectrometer: Towards The Development Of A Rapid Chiral Catalyst Screening Method, Cary M. Davis

Theses and Dissertations

Since the tragedy of the drug Thalidomide® in the late 1950 to early 1960’s, chirality has been recognized as an important aspect that must be controlled in the drug development process in the pharmaceutical industry. Since then, there has been a considerable movement towards single enantiomer drugs. This demand has presented many challenges for the synthetic organic chemist. Chiral catalysts offer one solution to this problem, as they afford the unique ability to preferentially synthesize one enantiomer. Unfortunately, the design of new chiral catalysts is often empirical, with luck and trial and error necessary due to factors that govern enantioselectivity. …

Analysis And Modeling Of The Roles Of Actin-Myosin Interactions In Bladder Smooth Muscle Biomechanics, Seyed Omid Komariza

Theses and Dissertations

Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length …

Statistical Modeling Of Interfractional Tissue Deformation And Its Application In Radiation Therapy Planning, Douglas J. Vile

Theses and Dissertations

In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying …

The Creatures We “Assessinate”: Mental Testing As Science Fiction In Chicago Public High Schools In 1909, Clayton Funk

Journal of Social Theory in Art Education

This article tracks the development of what educators and psychologists, in 1909, termed “mental testing” in relation to art education in Chicago Public Schools (CPS). According to CPS Superintendent Edwin G. Cooley (1857-1923) American civilization was in trouble due to the influx of Southern and Eastern European immigrants in Chicago. He and other educators sought to ward off the social collapse they feared with the efficiency of science. As part of what Sol Cohen termed the “medicalization of education,” Chicago’s Department of Child Study tested students for mental capacity and those considered less intelligence were placed in technical classes, while …

The Journal Of Social Theory In Art Education

Journal of Social Theory in Art Education

No abstract provided.

The Effect Of Damaged Bases On The End Joining Of Dna Double Strand Break Ends, Duaa Bafail

Theses and Dissertations

DNA double strand breaks (DSBs ) are extremely toxic to cells because they can lead to genomic rearrangements and even cell death. Two main pathways can repair DSBs: the homologous recombination repair (HRR) pathway and the non-homologous end-joining (NHEJ) pathway. NHEJ is the primary repair pathway in mammalian cells. HRR repairs single strand breaks (SSBs) or DSBs, mostly during late S phase and G2 phase of the cell cycle, by using an undamaged copy of the DNA sequence, and is therefore largely error-free, while the NHEJ pathway repairs DSBs without the requirement for sequence homology, may be error-free or error-prone, …

The Role Of Authoritative Parenting In Type 1 Diabetes Adolescent Outcomes, Zach Radcliff

Theses and Dissertations

Due to psychosocial and hormonal changes, adolescents with Type 1 Diabetes (T1D) are at risk for poorer regimen adherence, quality of life (QOL), and glycemic control (HbA1c). Authoritative parenting (AP) supports youth development during the transition into adolescence. To date, the mechanisms behind authoritative parenting and better HbA1c are yet to be examined. Parent-youth dyads completed measures of authoritative parenting, adherence, and QOL. As hypothesized, more authoritative parenting related to higher socioeconomic status (SES; β = -.13, p = .04) rather than ethnicity. Further, more authoritative parenting related to better glycemic control via the mechanisms of higher youth QOL (β …

The Group Iva Cytosolic Phospholipase A2/C1p Interaction And Its Role In Eicosanoid Synthesis And Inflammation, Jennifer A. Mietla

Theses and Dissertations

In the presented study, we demonstrate that the interaction of group IVA cytosolic phospholipase A2 and ceramide-1-phosphate is crucial for production of eicosanoid synthesis in inflammation. Inflammation is a critical component of many disease states including anaphylaxis, cancer, cardiovascular disease, rheumatoid arthritis, diabetes and asthma. Eicosanoids are well established mediators of inflammation, and the initial rate limiting step in the production of eicosanoids is the liberation of arachidonic acid (AA) from membrane phospholipids by a phospholipase A2 (PLA2). The major phospholipase involved in this liberation of AA during the inflammatory response is group IVA cytosolic phospholipase A2 (cPLA2α). Previous studies …

Expanding Understanding Of Public Policy As A Complex And Pluri-Disciplinary System: Illustrating Possibilities Of Epistemic Pluralism, Cynthia Cors

Theses and Dissertations

Science, and especially the social sciences, has developed as distinct territories, each with its own vocabulary and language-game (Wittgenstein, 1945/1958). Yet understanding and explaining science as a complex and pluri-disciplinary system has important practitioner-oriented as well as research-oriented and other benefits, benefits that can be enhanced through the use of cloud-based technologies. Understanding and explaining public policy in particular as complex can inform and transform the way problems are approached. This is particularly important for an action subject like public policy and administration that can be considered as having been influenced by many disciplines. Public administration (PA) through multiple perspectives, …

Characterization Of Individual Charged Au25(Sg)18 Clusters And Their Enhancement Of Single Molecule Mass Spectrometry, Christopher Angevine

Theses and Dissertations

Metallic quantum clusters are stable structures that can exhibit many useful magnetic, chemical, and optical properties. Developing clusters for specific applications requires accurate methods for characterizing their physical and chemical properties. Most cluster characterization methods are ensemble-based measurements that can only measure the average values of the cluster properties. Single cluster measurements improve upon this by yielding information about the distribution of cluster parameters. This investigation describes the initial results on a new approach to detecting and characterizing individual gold nanoclusters (Au25(SG)18) in an aqueous solution with nanopore-based resistive pulse sensing. We also present a new application where the clusters …

Developing C. Elegans As A Model To Study Type 2 Diabetes Mellitus, Jheesoo Ahn

Theses and Dissertations

Caenorhabditis elegans has been studied as a model organism in various areas of biomedical research because it shares many conserved functions at molecular and genetic levels with humans. Specifically, it is an ideal organism to study heterogeneous metabolic syndromes such as Type 2 Diabetes Mellitus (T2DM) as C. elegans can be used to delineate molecular pathways that are at the core of its problems. A growing number of populations worldwide are faced with chronic T2DM, which also manifests several complications, such as blindness, neuropathy and cardiovascular diseases. Currently, metformin is the first-line drug of choice administered to treat T2DM. While …

The Study Of Au(Iii) Compounds And Their Interaction With Zinc Finger Proteins, Sarah Spell

Theses and Dissertations

Gold compounds have been used in medicine dating back as early as 2500 BC. Over the years gold(I) and gold(III) compounds have been used and designed to target rheumatoid arthritis, cancer, and viral diseases. New drug targets have been found for gold compounds that give insight into their mechanisms of action. Here we focus on the synthesis of Au(III) compounds designed to selectively target zinc finger (ZF) proteins. ZF proteins exhibit a variety of functions, including transcription, DNA repair, and apoptosis. Displacement of the central zinc ion, along with mutation of coordinated amino acids can result in a loss of …

Understanding Ligand Binding, Selectivity And Functions On The G Protein-Coupled Receptors: A Molecular Modeling Approach, Saheem Zaidi

Theses and Dissertations

The assessment of target protein molecular structure provides a distinct advantage in the rational drug design process. The increasing number of available G protein-coupled receptor crystal structures has enabled utilization of a varied number of computational approaches for understanding the ligand-receptor interactions, ligand selectivity and even receptor response upon ligand binding. The following dissertation examines the results from three different projects with varied objectives – i) structural modeling of human C-C chemokine receptor type 5 (CCR5) and assessment of the ligand binding pocket of the receptor, ii) assessment of the selectivity profile of naltrexone derivatives on the three opioid receptors …

Annual Higher Ground Women's Leadership Conference 2014, The Grace E. Harris Leadership Institute At Virginia Commonwealth University

The Grace E. Harris Leadership Institute Publications

No abstract provided.

Virginia Dental Journal (Vol. 91, No. 4, 2014)

Virginia Dental Journal

No abstract provided.

Investigating The Effects Of Applied Electric Fields On Microglial Cell Behaviour, Eman Bani

Theses and Dissertations

As surveyors of the central nervous system (CNS), microglial cells play an integral part in the inflammatory response following traumatic injuries. Thus, they have been implicated in the limited capability of neurons to regenerate in the CNS. Additionally, the roles of endogenous electric fields in the regenerative process of neurons in the mammalian peripheral nervous system (PNS) or amphibian CNS have long been studied. Further, previous studies in our lab have shown that physiological electric fields are capable of directing behaviours in astrocytes and schwann cells. Therefore in this study, a BV-2 microglia cell line was utilized to investigate whether …