Digital Commons Network^™

K-Nearest Neighbors Density-Based Clustering, Avory C. Bryant

Theses and Dissertations

Traditional density-based clustering approaches rely on a distance-based parameter to define data connectivity and density. However, an appropriate value of this parameter can be difficult to determine as it is highly dependent on the underlying distribution of the data. In particular, distribution parameters affect the scale of inter-group distances (e.g., variance); this dependence leads to a well-known inability to simultaneously detect clusters at varying levels of density. In this work, connectivity and density are defined according to the rank-order induced by the distance metric (i.e., invariant to the expected scale of the distances). Connectivity by k-nearest neighbors and density by …

Continuous Preparation And Application Of Novel Heterogeneous Catalysis, Michael B. Burkholder

Theses and Dissertations

Transition metal heterogeneous catalysts are widely used across many chemical industries to reduce waste and emissions and reduce production time while increasing rate. The prevalence of these materials results from the complex relationship between metal nanoparticles and supports affecting final catalytic performance. Rational catalyst synthesis describes the ability to precisely engineer structures through controlled preparation. Novel materials and continuous processing represent a promising approach for rational catalyst synthesis.

The application of these catalysts in continuous, multiphase processes, such as cross-coupling reactions, oxidation chemistry, and nitroreduction processes, are paramount to developing new commercial routes for high-value products. Pd/G catalysts synthesized by …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Exploring The Dopamine Transporter Utilizing A Two-Pronged Approach With Novel Cathinone Analogs And Mutant Dopamine Transporters, Charles B. Jones Iii

Theses and Dissertations

The dopamine transporter (DAT) is responsible for the removal of the neurotransmitter from the synaptic gap and a therapeutic target for a multitude of drugs. While the ortholog Drosophila melanogaster dopamine transporter (dDAT) and human serotonin transporter (hSERT) have resolved structures, the human dopamine transporter (hDAT) does not. A 3-D computational homology model of hDAT was constructed for the study of molecular interactions with agents within the central binding site (S1) of the transporter.

Synthetic cathiones are a class of abused stimulant drugs that primarily target DAT. Greater than 150 cathinones have been identified on the clandestine market but there …

Characterization Of Cytochrome P450 3a4 Structure And Ligand Binding Mechanism In Anionic Nanodiscs, David T. Sweeney

Theses and Dissertations

The Cytochromes P450 superfamily are ubiquitous throughout life and are present in some viruses. Humans encode for 57 of these enzymes that are involved in the metabolism of ~90% of all chemicals. These membrane-bound monooxygenase enzymes utilize a heme protoporphyrin at their active site to activate molecular oxygen and oxidize their substrates through an intermediate deemed nature's most powerful oxidizer. They are a powerful system at our disposal yet understanding of their structure and ligand binding mechanisms in the presence of a lipid bilayer remains poorly understood. The focus of this work is on Cytochrome P450 3A4 (CYP3A4). We set …

Development Of Sam-Based Chemical Probes For Methyltransferases, Daniel V. Mongeluzi

Theses and Dissertations

Fig.1. SAM analog for the profiling of MTase activity. A. Chemical structure of probe 1; B. General scheme of the labeling and capture strategy.

A

B

Methylation is a fundamental mechanism used in the biological system to modify the structure and function of biomolecules such as proteins, DNA, RNA, and metabolites.¹ Methyl groups are installed by a large and diverse class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases), which transfer the sulfonium methyl group of SAM to either carbon, nitrogen, oxygen, or other heteroatoms on biomolecules.² Dysregulated MTase activity contributes to numerous diseases, including cancer, metabolic disorders, neurodegenerative diseases. …

Prognostic Modeling Of Recovery Following Stem Cell Transplantation, Brielle A. Forsthoffer

Theses and Dissertations

Predicting the trajectory of lymphoid recovery following myeloablative hematopoietic stem cell transplantation (SCT) can help guide subsequent therapeutic decisions, since poor recovery has been associated with graft-versus-host disease (GVHD), relapse and mortality. Previous attempts at classifying patients depended on absolute criteria being set prior to modeling absolute lymphocyte counts (ALCs) over time. Having an empirical clinical decision support tool for objectively determining the trajectory an individual might take during their recovery would be advantageous. We propose using growth-based trajectory modeling (GBTM) and growth mixture modeling (GMM), which utilize machine learning algorithms to empirically identify latent groupings of data. Due to …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

Intentions To Use Telerehabilitation For Communication And Treatment For Vision Impairments, Eric E. Hicks

Theses and Dissertations

BACKGROUND: Approximately 8.1 million people in the United States 18 and older have difficulty performing one or more daily activities because of vision impairment or blindness (Erickson, Lee, & von Schrader, 2020; Taylor, 2018). If the impairments caused by vision loss are not addressed, they can result in financial difficulties, suffering, disability, loss of productivity, and decreased quality of life (National Center for Chronic Disease Prevention and Health Promotion, 2011). Currently, in-person low vision rehabilitation services are the gold standard for teaching people how to adapt to and compensate for these deficits, however, the access and utilization of these services …

Therapeutic Modalities For Preventing Osteoarthritis Following Trauma To The Knee, Kayla M. Scott

Theses and Dissertations

Over 32.5 million adults in the United States and 300 million worldwide have osteoarthritis (OA). To date, there are no disease-modifying therapeutics, only strategies to slow OA progression through pain management, regenerative medicine approaches, and ultimately joint replacement.

On a microscale, a phenotypic shift of the normally quiescent articular chondrocytes leads to aberrant expression of pro-inflammatory and catabolic pathways, which are hypothesized to contribute to OA progression. Of note, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and WNT/β-catenin signaling are key players disrupting cartilage homeostasis and driving inflammatory pathway activation. These pathways become dysregulated and form a positive feedback loop, increasing …

In Vitro Evaluation Of High Flow Gas And Aerosol Drug Delivery Using Anatomically Biorelevant Infant And Child Airway Replicas, John Wilkins Jr

Theses and Dissertations

Respiratory care has greatly evolved from the use of an iron lung to treat patients with polio to now having at home continuous positive airway pressure (CPAP) machines for sleep apnea. Additionally, advances have been made in drug delivery as common delivery methods, such as spray and nebulizer devices, are used extensively for treatment of various pulmonary diseases and in some cases even used to deliver vaccines. More recently, 3D printing has allowed for anatomically-accurate physical airway models to be developed to better understand the countless number of therapies involving regional aerosol deposition as well as physical effects of therapies …

Ligand Effects On Electronic, Magnetic, And Catalytic Properties Of Clusters And Cluster Assemblies, Dinesh Bista 9288522

Theses and Dissertations

Ligands commonly protect metallic clusters against reacting with outside reactants. However, ligands can also be used to control the redox properties enabling the formation of super donors/acceptors that can donate/accept multiple electrons. This thesis focuses on how the ligands can be used to control the electronic and magnetic features of clusters and ligand stabilized cluster-based assemblies, leading to nano pn junctions with directed transport, the possibility of light-harvesting, and catalysts for cross-coupling reactions. The thesis addresses three distinct classes of clusters and their applications. The first class of cluster “metal chalcogen clusters” is the central idea of the thesis focused …

Prediction Of Mrna Abundance In Firmicutes: Steps Towards A Universal Model Of Prokaryotic Gene Expression, Jesse J. Raynor

Theses and Dissertations

Measurements of gene expression find use in many areas related to the characterization of prokaryotes. For example, metabolic modeling is commonly employed to assist in the design of engineered microbes by helping to elucidate the organism’s extant metabolic processes. With insights generated from the modeling procedure, targeted genetic modifications can be introduced to the organism to bring about some desired effect. Metabolic models based upon the “flux balance analysis” method (or FBA) can be made more accurate by integrating gene expression data, such as that from RNAseq experiments. For various reasons, gene expression data is not always available for every …

Sleep-Related Problems, Sleep-Related Distress, And Sleep-Related Functional Status Among Adult Inpatients Receiving Palliative Care, Lisa C. Sievers

Theses and Dissertations

Palliative care patients may be at a higher risk for sleep-related problems and their negative effects compared to the general population, yet limited sleep research has been done with this population. The purpose of this dissertation was to determine prevalence rates for excessive sleepiness, insomnia, restless legs syndrome (RLS), and high risk for sleep apnea (HRSA); examine relationships between the aforementioned sleep-related problems, sleep-related distress (SD), and sleep-related functional status (SFS); and to determine which sleep-related problem measures along with age and gender predicted SD and SFS among a sample of adult palliative care inpatients. Secondary aims were to understand …

A Deep Learning U-Net For Detecting And Segmenting Liver Tumors, Vidhya Cardozo

Theses and Dissertations

Visualization of liver tumors on simulation CT scans is challenging even with contrast-enhancement, due to the sensitivity of the contrast enhancement to the timing of the CT acquisition. Image registration to magnetic resonance imaging (MRI) can be helpful for delineation, but differences in patient position, liver shape and volume, and the lack of anatomical landmarks between the two image sets makes the task difficult. This study develops a U-Net based neural network for automated liver and tumor segmentation for purposes of radiotherapy treatment planning. Non-contrast simulation based abdominal CT axial scans of 52 patients with primary liver tumors were utilized. …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Development Of Unnatural Amino Acid Mutagenesis Technologies To Control Enzyme Activity And Synthesis Of Chemically Reactive Ubiquitin Probes, Jenny Cheung

Theses and Dissertations

Most of the work vital for the survival of the cell are performed by proteins. The primary sequence of proteins is composed of 20 canonical amino acids. However, these 20 amino acids do not offer the full range of functionalities needed for proteins to do their job. Often times, post-translational modifications (PTM’s) occur to add the required functional group. This interaction between all the different proteins in the proteome in addition to PTM’s create a complex system that scientists are still trying to unravel to this day. Many different tools had been developed for this purpose, and one such tool …

Health Outcomes And Utilization Associated With Renal Diseases In Patients With Cancer In The United States, Mitisha Dedhia

Theses and Dissertations

Background: Adverse events and impairments associated with cancer and its treatments causes worse outcomes. Increased incidence of renal diseases among cancer patients is of particular concern. Objective: To determine the risk factors for renal disease in cancer patients and compare healthcare costs, utilization and health-related quality of life (HRQoL) of cancer patients with a renal disease and cancer patients without renal diseases. Methods: Medical Expenditure Panel Survey files from 2009 – 2018 for cancer patients was used for this study. Multiple logistic regression, generalized linear model, Poisson regression and multiple linear regression for analyses after adjusting for demographic, socioeconomic and …

Patient Blood Management Programs And Their Association With Patient And Organizational Outcomes, Sandra L. Lamm

Theses and Dissertations

Blood transfusions are the most common hospital procedure. However, many transfusions may be unnecessary. These unnecessary transfusion may expose patients to the potential risks of transfusion without improving patient outcomes Patient blood management (PBM) programs emphasize conserving a patient’s own blood resources and only transfusing the minimum amount needed. This study examined the organizational and environmental factors associated with a hospital having a PBM program, or having processes based on PBM, and their impact on organizational and patient outcomes potentially affected by blood transfusions.

A PBM survey was created for this study and used to gather information on hospitals having …

Examining The Impact Of Entrepreneurship Training On Entrepreneurial Mindset And Economic Well-Being, Sombo Muzata

Theses and Dissertations

This study used a mixed methods research design to examine the impact of entrepreneurship training on entrepreneurial mindset and economic well-being using the RVA Works Entrepreneurship Training Program as a case study. With human capital theory as a theoretical framework, a combination of 55 interviews and 36 surveys were used to answer the research questions. The study found that entrepreneurship training positively impacts an entrepreneurial mindset. The impact of the training on entrepreneurial mindset differed by participants age and educational level. Study participants applied their entrepreneurial mindset to their businesses, jobs, and other aspects of life. Participation in the program’s …

Physiological And Subjective Effects Of Protonated Nicotine Liquids In Tobacco Users, Alisha Eversole

Theses and Dissertations

Electronic cigarettes (ECIGs) produce an aerosol by heating a liquid that often contains nicotine. The nicotine can be protonated, potentially making the aerosol easier to inhale than freebase nicotine. This study’s purpose was to determine, in inhaled tobacco product users, the effects of three concentrations of protonated nicotine aerosolized at two different power settings (in watts).

Twenty-two participants completed six sessions that varied by liquid nicotine concentration (10, 15, or 30 mg/ml protonated nicotine) and device power (15 or 30 W). Participants took 10 puffs from each product and then used each product for 60 minutes ad libitum. Plasma …

Formulation, Characterization And Pharmacokinetic Modelling Of Excipient Enhanced Growth Spray-Dried Inhalation Powders, Serena Bonasera

Theses and Dissertations

The overall aim of this research project was to evaluate effects of spray drying parameters and storage conditions on solid-state characteristics and aerosol performance of excipient enhanced growth (EEG) powders and to formulate a stable and highly dispersible tobramycin EEG powder to be delivered to pediatric cystic fibrosis subjects using a novel positive pressure dry powder inhaler.

Micrometer-sized albuterol sulfate EEG powders were produced using a medium-sized nebulizer and optimized spray drying conditions. Using trileucine as the dispersion enhancer improved the aerosol performance but showed increased moisture absorption compared to the L-leucine formulation.

The optimized spray drying conditions were then …

Starting Earnings Of Bachelor’S And Advanced Degree Graduates By Field Of Study: Using Multi-Level Modeling To Estimate The Effects And Early Labor Market Consequences Of Vertical And Horizontal Dimensions Of Higher Education, Qiao Liang

Theses and Dissertations

This study was conducted to better understand early labor market outcomes of higher education and the importance of the vertical and horizontal dimensions of higher education. Using College Scorecard’s institution and field of study levels data and a multilevel modeling approach, it estimated and ranked typical starting earnings associated with a large spectrum of bachelor’s and advanced degree programs, and discussed patterns, variations, and irregularities observed in the ranked earnings. This study also calculated advanced degree effects on the typical starting earnings associated with bachelor’s and advanced degree programs, and set precedence to systematically compare the effects of major, department, …

Breaking The Cycle: A Longitudinal Study Of Factors That Disrupt Peer Selection And Influence Processes Among Urban Youth, Kelly E. Oconnor

Theses and Dissertations

Having friends who engage in problem behavior (i.e., aggression, substance use, delinquency) has consistently been linked to adolescents’ own engagement in problem behavior. There are, however, several key gaps in the literature on peer influence. Few studies have considered the influence of friends’ prosocial behavior and there has been limited research to identify promotive factors that influence urban youths’ affiliation with peers who engage in problem and prosocial behavior across early adolescence, a time of heightened susceptibility to peer influence. The purpose of this study was to identify modifiable promotive factors that reduce adolescents’ problem behavior by decreasing exposure to …

Alcohol Use Subgroups Among Rural Middle School Students: The Impact Of Community Violence Exposure, Courtney B. Dunn

Theses and Dissertations

A substantial portion of early adolescents initiate alcohol use. This represents a significant public health concern due to its association with a variety of adverse consequences. Although person-centered analytic approaches such as latent class analysis have been used to describe heterogeneity in adolescents’ alcohol use, most prior studies have focused on high school or older samples. This may obscure patterns of alcohol use that emerge during early adolescence. The current study identified and described subgroups of adolescents based on their alcohol use in a racially diverse sample of rural middle school students. Because research and theory indicate that exposure to …

Bayesian Techniques For Relating Genetic Polymorphisms To Diffusion Tensor Images Of Cocaine Users, Tmader Alballa

Theses and Dissertations

Past investigations utilizing Diffusion Tensor Imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes. We proposed three Bayesian techniques in order to explore the relationship between Fractional Anisotropy (FA), genetic data, and years of cocaine use (YCU). CUD participants exhibit abnormality in different areas of the brain versus non-drug using controls, which is measured by DTI. This dissertation is motivated by a neuroimaging genetic study in cocaine dependence, which found that there were relationships between several genes such as GAD and 5-HT₂R and CUD subjects.

In the first chapter, there is background on the …

Surface Characterization Of Accident Tolerant Fuel Claddings Candidates After Prolonged Exposure To Steam Oxidation, Connor F. Donlan

Theses and Dissertations

Accident Tolerant Fuel Claddings are designed to improve fuel performance and safety in abnormal reactor conditions. The development of these cladding materials has become a top priority for the nuclear community, with incidents such as the Three Mile Island accident and the Fukashima Dai-chi accident. The development of these claddings has resulted in 2 subsections: coating current claddings or replacing cladding materials with new materials. The claddings studied in this thesis are a Zircaloy-4 cladding coated with chromium through physical vapor deposition, Zircaloy-4, and a FeCrAl alloy, C26M. This thesis assessed the surface chemistry, roughness, and wettability after extended exposure …

Repair In An Economy Of Trauma: How Identifying Traumas As The Basis For Teacher Artmaking Contributes To Resiliency In Managing Traumatic Stress, Danielle R. Houdek

Theses and Dissertations

REPAIR IN AN ECONOMY OF TRAUMA:

HOW IDENTIFYING TRAUMAS AS THE BASIS FOR TEACHER ARTMAKING CONTRIBUTES TO RESILIENCY IN MANAGING TRAUMATIC STRESS

By Danielle Raddin Houdek, BFA, MAE

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Art Education at Virginia Commonwealth University.

Virginia Commonwealth University, 2021.

Major Director: Dr. Sara Wilson-McKay

Associate Professor, Department of Art Education, School of the Arts

Objective: Through this research project, the impact that secondary traumatic stress has on art educators and how artmaking contributes to resiliency in managing secondary traumatic stress was examined. The research question is: …

Gender Equity Implications Of Nonprofit Youth Programs: Education Outcomes Of Three African American-Led Nonprofits, Yali Pang

Theses and Dissertations

Significant racial and gender differences in school performance have been a great concern in the past decades, and especially the significant differences in education performance between both Black youth and other racial groups and between Black males and Black females. Nonprofit youth programs are increasingly considered a promising intervention that can effectively improve Black youth development and education outcomes. While there is a growing body of literature evaluating the outcomes of nonprofit youth programs, little is known about gender differences in the outcomes, and specifically whether these nonprofit programs are equally effective for both Black males and females. This study …

Identification Of Four Residues Within The Tm4 Of The 5-Ht2a Receptor Necessary For 5-Ht2a·Mglu2 Heteromerization, John Mcginn

Theses and Dissertations

While the etiology is unknown, serotonin and glutamate G protein-coupled receptors (GPCR) neurotransmission dysfunctionality is characteristic of schizophrenia. Previous findings demonstrated that the serotonin 5-hydroxytryptamine 2A (5-HT_2A) receptor and the metabotropic glutamate 2 (mGlu2) receptor assemble into a heteromeric complex; however, little is known of the complete structural interface of the heteromer. Through a mutational-based approach, previous research identified Transmembrane domain 4 (TM4) as being responsible for mediating heteromerization in mGlu2 before determining the particular amino acids responsible for the interface. A similar technique was used in this investigation to determine which component of 5-HT_2A is responsible …