Medicine and Health Sciences Commons^™

Hydropathic Interactions And Protein Structure: Utilizing The Hint Force Field In Structure Prediction And Protein‐Protein Docking., Mostafa H. Ahmed

Theses and Dissertations

Protein structure predication is a field of computational molecular modeling with an enormous potential for improvement. Side-chain geometry prediction is a critical component of this process that is crucial for computational protein structure predication as well as crystallographers in refining experimentally determined protein crystal structures. The cornerstone of side-chain geometry prediction are side-chain rotamer libraries, usually obtained through exhaustive statistical analysis of existing protein structures. Little is known, however, about the driving forces leading to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines extracted from the PDB reveals their …

Examining The Effect Of Race On The Relationship Between Posttraumatic Stress Disorder And Metabolic Syndrome In Women, Leia Harper

Theses and Dissertations

Posttraumatic stress disorder (PTSD) is a psychiatric condition affecting approximately 8% of the adult U.S. population with rates twice as high in women than men. Increasingly, evidence has suggested a close relationship between PTSD and increased risk of metabolic diseases. However, the literature on PTSD and metabolic disease risk factors has been limited by the lack of investigation of the potential influence of race on this relation. The current study examined the possible effect of race on the relation between PTSD and metabolic risk. Data for this study were provided from sample of that included 50 African American women and …

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 …

Mda-9/Syntenin: From Glioblastoma Pathogenesis To Targeted Therapy, Timothy P. Kegelman

Theses and Dissertations

The most common malignant glioma, glioblastoma multiforme (GBM), remains an intractable tumor despite advances in therapy. Its proclivity to infiltrate surrounding brain tissue contributes greatly to its treatment failure and the grim prognosis of patients. Radiation is a staple in modern therapeutic regimens, though cells surviving radiation become more aggressive and invasive. Consequently, it is imperative to define further the cellular mechanisms that control GBM invasion and identify promising novel therapeutic targets. Melanoma differentiation associated gene-9 (MDA-9/Syntenin) is a highly conserved PDZ domain-containing scaffolding protein that promotes invasion and metastasis in human melanoma models. We show that MDA-9/Syntenin is robustly …

The Roles Of Krüppel-Like Factor 1 (Klf1) In The Human Fetal Erythroid Compartment., Safa Mohamad

Theses and Dissertations

Erythroid Krüppel-like factor (EKLF or KLF1) is a transcription factor with roles in embryonic and adult erythropoiesis. KLF1 knockout mouse embryos die due to severe anemia. Dominant human mutations in KLF1 can cause hereditary persistence of fetal hemoglobin. We show that KLF1 positively regulates β-globin and Bcl11A gene expression using KLF1 knockdown in in vitro-differentiated CD34+ human umbilical cord blood cells. -globin expression appears dependent on KLF1; it is increased with modest KLF1 knockdown but not in cells with low KLF1. KLF2 mRNA amounts are usually increased in KLF1 knockdown. KLF1 knockdown in CD34+ cells results in reduced colony forming …

Synthetic, Sulfated, Lignin-Based Anticoagulants, Akul Mehta

Theses and Dissertations

Chemoenzymatically synthesized low molecular weight lignin polymers have been previously found to be potent inhibitors of a number of serine proteases via allosteric mechanisms targeting heparin binding sites. Herein, we describe the creation of synthetic sulfated β-O4 lignin (SbO4L) polymer, which is more homogenous compared to previous lignins with respect to its inter-monomeric linkage. SbO4L is a selective inhibitor of thrombin and plasmin. SbO4L was found to act via a unique mechanism targeting thrombin exosite 2 in a manner similar to platelet glycoprotein Ibα (GPIbα). Advanced hemostasis and thrombosis assays demonstrated that SbO4L acts via a dual mechanism: as an …

The Effect Of Obesity On Il-1Β, Il-1ra, And Leptin Following Acute Mental Stress, Heather Caslin

Theses and Dissertations

Research regarding the development of cardiovascular disease (CVD) is important because CVD is the leading cause of death in the United States (US) and many countries abroad. Risk factors, such as obesity and psychological stress, should be studied in order to understand contributing factors for CVD and the cellular mechanisms which link risk factors with the development of disease. Specifically, the combined influence of multiple risk factors on inflammation is of interest because many individuals have more than one risk factor, which additively increases an individual’s risk for CVD. Obesity is already characterized by disordered inflammation, which suggests that the …

Study Of Surface Modification Of Tungsten Nanostructures For Superhydrophobic Applications, Richard Alletru

Theses and Dissertations

In this work, we studied the impact of the modification of the structure of tungsten surfaces through physical vapor deposition (magnetron sputtering), electrochemical (anodization and electropolishing), and thermal (annealing) processes on the wettability of the designed surfaces. We observed static contact angle values ranging from around 10° to above 150° showing the importance of the techniques used to produce the surfaces. We noticed that the annealing process tends to increase the wettability, transforming hydrophobic surfaces into hydrophilic surfaces. We also observed that electropolishing affects the wettability in such a way that the contact angles of pre-chemically treated tungsten foils tend …

Differential Effects Of Endocannabinoid Catabolic Inhibitors On Opioid Withdrawal In Mice, Thomas Gamage

Theses and Dissertations

The effects of cannabinoids in reducing somatic signs of opioid withdrawal have been known for some time. In morphine dependent rodents, opioid withdrawal following precipitation with the mu opioid antagonist naloxone elicits robust withdrawal behaviors including jumps, paw flutters, head shakes, diarrhea and weight loss. Delta-9-tetrahydrocannabinol has been shown to reduce this opioid withdrawal in mice via activation of the cannabinoid type-1 (CB1) receptor and recently it has been shown that inhibition of the catabolic enzymes for endocannabinoids also reduce somatic signs of opioid withdrawal. Specifically, inhibition the enzyme fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid …

Outcomes Of An Emotion Word Intervention For Children With Social Communication Impairments, Rebecca Cloward Mansfield

Theses and Dissertations

Children with social communication disorders have been found to exhibit deficits in emotional intelligence, including the ability to identify emotions attributed to facial expressions. The purpose of this thesis was to examine the efficacy of a social communication intervention program designed to increase the accuracy of emotion based word use in three elementary school-aged participants with social communication disorders. The participants took part in a multiple-baseline, 20-session treatment including story enactment, journaling procedures, and supplementary activities. The story enactment portion of the intervention centered on Mercer Mayer's A Boy, A Dog, and A Frog (1967) wordless picture book series. Participants' …

Relationship Between The Experience Of Perceived And Physician Diagnosed Arthritis And The Presence Of Dsm-Iv Criteria-Based Major Depression (Mdd) Among Older, Ryan Neil Schmidt

Theses and Dissertations

BACKGROUND: The purpose of this study was to explore both positive screened MDD and the perception of being depressed (P) and the likelihood of either increasing if the patient suffered from arthritis (P/E), either perceived or evaluated by a physician. The study explored the univariate, bivariate, and multivariate relationships between MDD and depression (P) to better describe influencing characteristics and their prevalence, as related to MDD and depression (P).

METHODS: The study examined a cross section of patients 65 years and older (n=8,205) within the National Epidemiologic Survey on Alcohol Abuse and Alcoholism (NESARC) [2001-02] sponsored by the National Institute …

Exploring Factors That Influence The Choice To Retire From Driving In Older Adults, Debra J. Jenkins

Theses and Dissertations

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Tobramycin Disposition In The Lung Following Airway Administration, Min Li

Theses and Dissertations

Tobramycin disposition following airway administration was evaluated by meta-analysis of human data in the literature and, experimentally, using a realistic ex vivo model, the isolated perfused rat lung preparation (IPRL). Pulmonary bioavailability of inhaled tobramycin in published studies was re-evaluated separately for CF and healthy adults, with the drug’s intrinsic pharmacokinetic (PK) parameters obtained from intravenous (IV) studies in the literature. While large variations in tobramycin’s clearance precluded accurate assessment of its bioavailability, the results were indicative of substantial pulmonary absorption, in spite of its hydrophilic and poly cationic properties. To explore its disposition kinetics and mechanisms following airway administration, …

Clostridium Difficile Infection Occurrence In Academic Health Centers: Do Organizational Factors Matter?, Amy Pakyz

Theses and Dissertations

Healthcare-associated infections occur commonly in hospitals and have a major impact on patient well-being. The occurrence of the healthcare-associated infection, Clostridium difficile, has been occurring more frequently among hospitalized patients due to an epidemic strain, and is an important cause of antibiotic-associated diarrhea and colitis. This study examined the impact of several organizational factors on the occurrence of C. difficile infection (CDI) in hospitals using an institutional theory perspective. Administrative claims were utilized from University HealthSystem Consortium hospitals to obtain hospital-level data for the calendar year 2011. Data were available for 89 hospitals. Hospital-level analyses, negative binomial regression models, were …

Transcriptional Crosstalk Between Helper Bacteriophages And Staphylococcal Aureus Pathogenicity Islands, Kristin Lane

Theses and Dissertations

Acquisition of a superantigen pathogenicity island (SaPI) significantly increases virulence in Staphylococcus aureus. Horizontal transfer of SaPIs occurs at high frequency and depends upon a helper bacteriophage, either through direct infection or SOS-mediated induction of a lysogen. SaPIs hijack the packaging machinery of the helper phage, leading to the formation of SaPI-containing transducing particles that can introduce the pathogenicity island into neighboring SaPI-negative cells. All SaPIs contain a conserved core of genes, some of which are co-transcribed as an operon and encode functions involved in helper exploitation. The goal of this study was to more fully understand the intricate relationships …

Effects Of Thoracic Spinal Manipulative Therapy On Thoracic Spine And Shoulder Kinematics, Thoracic Spine Flexion/Extension Excursion, And Pressure Pain Sensitivity In Patients With Subacromial Pain Syndrome, Joseph Kardouni

Theses and Dissertations

EFFECTS OF THORACIC SPINAL MANIPULATIVE THERAPY ON THORACIC SPINE AND SHOULDER KINEMATICS, THORACIC SPINE FLEXION/EXTENSION EXCURSION, AND PRESSURE PAIN SENSITIVITY IN PATIENTS WITH SUBACROMIAL PAIN SYNDROME By Joseph R. Kardouni, Ph.D., PT A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, at Virginia Commonwealth University. Virginia Commonwealth University, 2013. Major Director: Lori A. Michener, PhD, PT, ATC, Professor, Department of Physical Therapy In patients with shoulder pain, the use of manual therapy directed at the spine and shoulder have been reported to provide superior outcomes to exercise based interventions or usual care without …

Hybrid Pet/Mri Nanoparticle Development And Multi-Modal Imaging, David Hoffman

Theses and Dissertations

The development of hybrid PET/MRI imaging systems needs to be paralleled with the development of a hybrid intrinsic PET/MRI probes. The aim of this work was to develop and validate a novel radio-superparamagnetic nanoparticle (r-SPNP) for hybrid PET/MRI imaging. This was achieved with the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) that intrinsically incorporated 59Fe and manganese iron oxide nanoparticles (MIONs) that intrinsically incorporated 52Mn. Both [59Fe]-SPIONs and [52Mn]-MIONs were produced through thermal decomposition synthesis. The physiochemical characteristics of the r-SPNPs were assessed with TEM, DLS, and zeta-potential measurements, as well as in imaging phantom studies. The [59Fe]-SPIONs were evaluated …

Brain Mapping Of The Mismatch Negativity Response To Vowel Variances Of Natural And Synthetic Phonemes, Lyndsy Marie Smith

Theses and Dissertations

The mismatch negativity (MMN) is a specific event-related potential (ERP) component used frequently in the observation of auditory processing. The MMN is elicited by a deviant stimulus randomly presented in the presence of repeating stimuli. The current study utilized the MMN response in order to determine the temporal (timing) and linguistic processing of natural and synthetic vowel stimuli. It was hypothesized that a significant MMN response would be elicited by natural and synthetic vowel stimuli. Brain mapping of the MMN response was hypothesized to yield temporal resolution information, which would provide detail regarding the sequential processing differences between natural and …

Sirt6 And Premature Aging Of Hutchinson-Gilford Progeria Syndrome Fibroblasts., Helal Endisha

Theses and Dissertations

The genetic disease Hutchinson-Gilford Progeria Syndrome (HGPS) arises from a de novo single nucleotide mutation (1824CàT) in the LMNA gene. As a result, the mutated lamin A protein (progerin) remains farnesylated and permanently attached to the nuclear membrane. Progerin accumulates and deforms the nuclear membrane leading to an array of cellular abnormalities driving the cells to enter a state of permanent cell-cycle arrest early on in replicative age i.e. premature cellular senescence. Cellular senescence has been extensively studied as one of the contributing factors to aging in HGPS patients and other age-related diseases. There has also been evidence to show …

Analysis Of Plasminogen Binding To Treponema Denticola, A Key Periopathogen, Brittney Tegels

Theses and Dissertations

Periodontitis is a chronic inflammatory disease that affects over 116 million adults in the United States. A shift in the normal microflora occurs as periodontal disease develops resulting in a larger number of Gram-negative anaerobes and spirochetes. An increase in the oral spirochete, Treponema denticola, is highly correlated with periodontal disease progression and severity. The ability of this periopathogen to thrive in the subgingival crevice is dependent on complement evasion mechanisms. Earlier analyses demonstrated that the primary mechanism of T. denticola serum resistance is binding of the human complement regulatory protein, Factor H (FH), to the factor H-binding protein (FhbB). …

Identification Of Human Pgc-1Α-B Isoforms Using A Novel Pgc-1Α-B Specific Antibody, Shannon Hedrick

Theses and Dissertations

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is known as the master regulator of mitochondrial biogenesis. PGC-1α holds this role by acting as a transcriptional coactivator for an array of transcription factors and nuclear hormone receptors, such as NRF-1/2 and ERRα/γ, whose downstream targets function in mitochondrial biogenesis and oxidative phosphorylation. PGC-1α is regulated both at the transcriptional and post-translational level in several signaling pathways, including p38 MAPK and AMPK. This regulation affects which transcription factor binding events can occur in a given tissue, and thus affects regulation of PGC-1α target genes. PGC-1α is downregulated in many neurodegenerative disorders as …

Beta 2 Nicotinic Acetylcholine Receptor Contributions To Anxiety-Like Behavior, Shawn Anderson

Theses and Dissertations

Nicotine is a major psychoactive ingredient in tobacco that is thought to promote smoking behavior via nicotinic acetylcholine receptors (nAChRs) in the brain. Given reports that people smoke to relieve anxiety and that anxiety precipitates relapse, the overarching goal of this dissertation research is to assess beta 2 subunit containing nAChR (beta2*nAChR) contributions to anxiety-like behavior. Nicotine’s activity at beta2*nAChRs is concentration-dependent, with high concentrations facilitating activation followed by rapid desensitization and low concentrations preferentially desensitizing beta2*nAChRs; hence, activation or inhibition of beta2*nAChRs may support smoking behavior. Rodent studies reveal that nicotine affects anxiety-like behavior dose-dependently: low doses promote anxiolysis- …

A Boot Camp Approach To Remediating Interdental /S/ In A School-Aged Child, Melanie Ellen Peris

Theses and Dissertations

The relationship between speech articulation therapy dose (frequency, intensity, duration) and treatment outcomes are poorly understood. Identifying optimal therapy doses for specific articulation disorders is essential to providing efficient clinical care. Recent research indicates that intensive speech therapy doses-known as boot camps-may promote rapid improvement and generalization for certain speech disorders. Therefore the present investigation examined the effects of a boot camp speech therapy approach to remediate interdental /s/ production in an 8-year-old male. The boot camp included two days of speech therapy involving visual, tactile, and auditory feedback approaches. Therapy was administered 5.5 hours per day across morning and …

Alcohol And Medication Use In Community-Dwelling Older Adults: Understanding The Effect Of Alcohol And Central Nervous System-Acting Medications On The Risk For Falls, Maitreyee Mohanty

Theses and Dissertations

Introduction: Aging, comorbid conditions, and use of medications render older adults more susceptible to alcohol-disease or alcohol-drug interactions that may lead to harmful outcomes. In this dissertation project the risk profile of alcohol and medications use among older adults was investigated. Considering the rise in CNS-acting medication use and the adverse effect profile linked to CNS-acting medications, it was also of interest to find if older adults were at risk of falling due to interactions between alcohol and CNS-acting medication. Objectives: The objectives were as follows: 1) to determine the prevalence, pattern and factors associated with at-risk drinking, 2) to …

Behavioral And Genomic Characterization Of Scheduled Ethanol Deprivation, Jonathan Warner

Theses and Dissertations

Alcoholism is a persistent substance abuse disorder that is associated with negative health, social, and economic outcomes. Treatment strategies for alcohol use disorders are limited, and only three drugs have been approved by the FDA for treatment. Although behavioral therapy and drug combination strategies improve abstinence outcomes, the majority of those in treatment will not achieve long-term abstinence. Therefore, better treatment strategies are needed. While much progress has been made toward understanding the neurobiology of alcoholism, this knowledge has not been effectively translated into treatment strategies. Animal models of alcohol drinking have been crucial to this research effort, but until …

A Measure Of Nephrology Nurse Perceptions Toward Advance Care Planning: Validation Of The Nephrn Perceptions Toward Advance Care Planning Instrument, Mary S. Haras

Theses and Dissertations

This dissertation is a report of a three-phase quantitative research study that included the development and testing of an instrument to examine the perceptions of nephrology nurses toward advance care planning for persons with chronic kidney disease. Phase 1 began with the identification of the dimensions of advance care planning and creation of an item pool for the instrument. The instrument was distributed to five content experts for evaluation and comments of inclusiveness to measure perceptions toward advance care planning. In Phase 2 the item pool was pilot tested in a convenience sample of 50 nephrology nurses. Exploratory factor analysis …

Analyzing The Functions Of Human Polynucleotide Phosphorylase (Hpnpaseold-35), Upneet K. Sokhi

Theses and Dissertations

RNA degradation plays a fundamental role in maintaining cellular homeostasis, along with being a part of normal regulatory mechanisms, whether it occurs as a surveillance mechanism eliminating aberrant mRNAs or during RNA processing to generate mature transcripts. 3’-5’ exoribonucleases are essential mediators of RNA decay pathways, and one such evolutionarily conserved enzyme is polynucleotide phosphorylase (PNPase). The human homologue of this fascinating enzymatic protein (hPNPaseold-35) was cloned a decade ago in the context of terminal differentiation and senescence through a novel ‘overlapping pathway screening’ approach. Since then, significant insights have been garnered about this exoribonuclease and its repertoire of expanding …

Understanding Turnover Propensity Via Affective Beliefs, Adam Bradshaw

Theses and Dissertations

Three latent variable models examined relationships among neuroticism, situation-specific affective beliefs, and turnover propensity and were evaluated with Structural Equation Modeling to determine model fit. Results provided additional insight into how affective belief systems relate to turnover propensity reinforcing and expanding upon previous research by Binning, Bradshaw, LeBreton, and Scheier (2010) as the Correlated Antecedents and the Mediated Antecedents Models fit the data as proposed. Neuroticism and situation-specific affective beliefs continue to play distinguishable roles in explaining turnover propensity. Research by Binning et al. (2010) and the present study make it increasingly clear that understanding how affective belief systems relate …

A Molecular Mechanism Regulating The Timing Of Corticogeniculate Innervation, Justin Brooks

Theses and Dissertations

Visual system development requires the formation of precise circuitry in the dorsal lateral geniculate nucleus (dLGN) of the thalamus. Although much work has examined the molecular mechanisms by which retinal axons target and form synapses in dLGN, much less is known about the mechanisms that coordinate the formation of non-retinal inputs in dLGN. These non-retinal inputs represent ~90% of the terminals that form in dLGN. Interestingly, recently reports show that the targeting and formation of retinal and non-retinal inputs are temporally orchestrated. dLGN relay neurons are first innervated by retinal axons, and it is only after retinogeniculate synapses form that …

Personal Characteristics And Learning Preference In End-Of-Life Decision Making Of Chronically Ill Community Dwelling Elders, Leigh Ann Bonney

Theses and Dissertations

Leigh Ann Bonney, RN, MSN; Susan Kossman, RN, PhD; MyoungJin Kim, PhD; Wendy Woith, PhD, Caroline Mallory, PhD

Illinois State University, Mennonite College of Nursing

Personal Characteristics and Learning Preference in End-of-Life Decision Making of

Chronically Ill Community Dwelling Elders

Purpose and Background: Clear decision-making (DM) about end-of-life [EOL] contributes to a good death This requires knowledge of life-sustaining treatment with lack of knowledge contributing to feelings of decisional conflict Decision aids can increase knowledge, but elders' preferred learning methods are unknown. Identifying characteristics associated with preferred learning method and decisional conflict can help nurses tailor information to assist in …