Digital Commons Network^™

Streptococcus Sanguinis: The Good, The Bad, And The Metal-Binding Lipoprotein, Cody Murgas

Theses and Dissertations

Streptococcus sanguinis is an opportunistic bacterium living beneficially in the human mouth. When S. sanguinis gains access to the bloodstream, it can result in colonization on damaged tissue and generate heart valve vegetations that can develop into infective endocarditis. It has been suggested that Mn and Fe are cofactors in the pathogenic capacity of this bacterium, and that these redox active metals are imported by the metal binding lipoprotein S. sanguinis adhesin B (SsaB). The SsaB lipoprotein is an integral part of SsaACB, an ATP-binding cassette (ABC) transport system in S. sanguinis. When SsaB is deleted, the resulting strain displays …

Identifying Inhibitors Of Gain-Of-Function P53-Driven Transcriptional Activation For Cancer Therapy, Megan Thompson

Theses and Dissertations

TP53 is the most commonly mutated tumor suppressor gene and is mutated in 50% of all cancers and up to 70% of lung cancers. When p53 is mutated, it loses its tumor suppressor function and can also gain new oncogenic functions, such as increased cell proliferation, tumorigenicity and chemoresistance. Previous studies have shown that cancer cells containing gain-of-function (GOF) p53 mutations depend on its transactivation function for cell proliferation and tumor formation. We hypothesized that small molecule inhibitors impeding GOF p53-mediated transactivation should selectively inhibit GOF p53-induced oncogenesis. In this study, we employed a novel detection system to screen chemical …

The Algorithmic Mashrabiya: Reimagining The Traditional Islamic Screen, Ahmed Nour

Theses and Dissertations

Traditionally, a mashrabiya was an ornate wooden structure attached to the side of an Arabian building or house, with small, intricately patterned openings to provide both ventilation and privacy for the people inside. The patterns, following the geometric rules of Islamic ornament, lent a distinctive appearance to buildings in the region. A mashrabiya converted the house into a safe, private sanctuary, providing a magical scene inside, characterized by linear sun rays, filtered points of light and shadow. Over time, as building technology changed and the number of skilled craftsmen dwindled, the traditional mashrabiya has all but vanished. The aim of …

Kaleidoscope Wellness | Destigmatizing Mental Health For Teens By Design, Rhode L. Baptiste

Theses and Dissertations

Motivation

Mental health is a global public health crisis. (Marcus et. al, 2012; WHO, 2020). Although there is a growing acceptance of the complexities surrounding mental illness, care delivery for adolescents with mental health concerns remains highly stigmatized, which contributes to delays in care (Hoisington et. al, 2019; Burns & Birrell, 2014). Half of all mental illnesses can be detected prior to the age of 14 (National Alliance for Mental Health, 2020). While research exploring how the physical health care environment impacts health and well-being for patients has evolved immensely over the past two decades, research on how facility design …

Identification Of Compounds Causing Cellular Autofluorescence In Touch Samples, Elora C. Wall

Master of Science in Forensic Science Directed Research Projects

As DNA analysis has advanced and produced tests with higher sensitivities, attention has turned toward obtaining DNA profiles from cells left with fingermarks. Recent studies have reported that cells deposited within fingermarks can exhibit differences in autofluorescence emission in the ‘red’ region of the visible spectrum (e.g., between 650-670 nm), which can be used to differentiate contributor cell population and separate them before DNA profiles. Interestingly, this emission was not consistent to the individual day-to-day and likely not a genetically-controlled attribute of the contributor. Instead, this emission signature results from extended exposure of the skin to certain materials such as …

The Same Flight, Laura Bender

Mighty Pen Project Anthology & Archive

After 9/11, a navy chaplain prepares for war.

Articles, stories, and other compositions in this archive were written by participants in the Mighty Pen Project. The program, developed by author David L. Robbins, and in partnership with Virginia Commonwealth University and the Virginia War Memorial in Richmond, Virginia, offers veterans and their family members a customized twelve-week writing class, free of charge. The program encourages, supports, and assists participants in sharing their stories and experiences of military experience so both writer and audience may benefit.

Ordination, Laura Bender

Mighty Pen Project Anthology & Archive

A chaplain reflects on her path to service, to God and to the military.

Articles, stories, and other compositions in this archive were written by participants in the Mighty Pen Project. The program, developed by author David L. Robbins, and in partnership with Virginia Commonwealth University and the Virginia War Memorial in Richmond, Virginia, offers veterans and their family members a customized twelve-week writing class, free of charge. The program encourages, supports, and assists participants in sharing their stories and experiences of military experience so both writer and audience may benefit.

Improving Patient-Specific Assessments Of Regional Aortic Mechanics Via Quantitative Magnetic Resonance Imaging With Early Applications In Patients At Elevated Risk For Thoracic Aortopathy, Patrick A. Jones

Theses and Dissertations

Unstable aortic aneurysms and dissections are serious cardiovascular conditions associated with high mortality. The current gold standards for assessment of stability, however, rely on simple geometric measurements, like cross-sectional area or increased diameter between follow-up scans, and fail to incorporate information about underlying aortic mechanics. Displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) has been used previously to determine heterogeneous circumferential strain patterns in the aortas of healthy volunteers. Here, I introduce technical improvements to DENSE aortic analysis and early pilot application in patients at higher risk for the development of aortopathies. Modifications to the DENSE aortic postprocessing …

Movement, Home Ranges, And Population Estimates Of Spotted Turtles (Clemmys Guttata) During A Rainy Breeding Season In Virginia, Lauren J. Jurczak

Theses and Dissertations

Spotted turtles (Clemmys guttata) use a complex of wetland and terrestrial habitats for survival and reproduction. Precipitation expands and creates larger and more numerous ephemeral pools available to spotted turtles on the landscape. In this study, I investigated the effects of precipitation on movement patterns and ephemeral pool usage by spotted turtles in southeastern Virginia. I conducted a 4-month capture-mark-recapture study alongside a telemetry study to estimate population size and to quantify movement of spotted turtles across the landscape during the breading season. A change point analysis was used to detect discrete changes in turtle behavior and whether …

Human Organic Anion Transporters 1 And 3: Structural Elements Impacting Transporter-Substrate Binding Interactions, Julie Nguyen

Theses and Dissertations

Organic anion transporters (OATs) are known to interact with a wide variety of negatively charged drugs and can impact their clinical safety and efficacy profiles. The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have recognized and highlighted the importance of evaluating the potential interactions with transporters, specifically hOAT1 and hOAT3, during the development of new drug entities. Little is known about OAT-drug interactions as they are difficult to discern on a molecular level in the absence of any solved crystal structures for OATs. Therefore, in a previous study, in silico homology models of hOAT1 and hOAT3 …

Modeling Vegetation Effects On Barrier Island Evolution, Eric W. Schoen

Theses and Dissertations

Barrier islands play a significant role in protecting coastlines and harboring coastal habitats. In an effort to study and better understand the evolution of barrier island systems, a cellular model capturing various meteorological and environmental processes is proposed. Erosion due to wind, gravity, and marine processes are coupled with plant population effects. We demonstrate the inhibition of plant cover on sediment mobility, island migration, and erosion in the presence of sea level rise.

Cloaca Palace, Connor Marie Stankard

Theses and Dissertations

In this thesis, I trace the compulsive fear of holes, known as trypophobia, from an uncontrollable obsession to a pleasurable preoccupation. The body’s physical porousness makes us receptive to our surroundings, allowing external matter in and destabilizing the boundaries of self and other. Matter invades us, encoding itself into our DNA and transforming humans into chimeric creatures.

Through paintings and multi-media installations, I encourage viewers to reflect on their own bodies as a series of holes, vulnerable receptors to the world. I use the figure of a woman to personify a human hole which has been infected by the outside, …

Heavy Hold: A Physical Score, Alexandra Velozo

Theses and Dissertations

This document is a collection of essays, stories, and fictional interviews that are in conversation with my performance, teaching, and sculpture practice. My research and work considers chronic illness, disability, the historic cultural connection between swamplands and illness, the medical industrial complex, medical theater, the medical gaze, disabled performers, metatactile space, sensory learning, and access.

Mechanistic Insights Of Mitochondrial Reactive Oxygen Species In Alzheimer's Disease Models, Jakob C. Green

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disease that results in impaired cognition, disorientation, confusion, poor judgement, and behavioral changes. The mitochondrial cascade hypothesis (MCH), which postulates that accumulating oxidative stress and mitochondrial dysfunction plays an integral role in the development of the disease, potentially upstream, in conjunction with or independent of Aβ and tau. The literature supports the critical role of mitochondrial dysfunction in the progression and development of AD, but is inconclusive about what precise role, as initiator or delegate, it performs. Regardless, the impact that oxidative stress and mitochondrial dysfunction have on AD deserves further study and investigation. …

Successional Changes In Carbon Storage Are Sustained In A Temperate Forest Across Different Initiating Disturbances, Cameron Clay

Theses and Dissertations

Managing forests for carbon (C) sequestration requires an understanding of how disturbance history shapes C pools and fluxes over successional time. At the University of Michigan Biological Station, we examined how two stand establishing disturbances influenced C pools and fluxes over 100+ years of succession, comparing these secondary forests with “legacy” late-successional stands encompassing ages and compositions that would be present in the absence of region-wide stand-replacing disturbance. Our work utilized measurements taken between 2014 and 2020 from separate experimental forest chronosequences initiated following clear-cut harvesting only or clear-cut harvesting and fire, along with three >130-yr-old late successional stands comprising …

Using Deep Learning-Based Framework For Child Speech Emotion Recognition, Gerald N. Onwujekwe

Theses and Dissertations

Biological languages of the body through which human emotion can be detected abound including heart rate, facial expressions, movement of the eyelids and dilation of the eyes, body postures, skin conductance, and even the speech we make. Speech emotion recognition research started some three decades ago, and the popular Interspeech Emotion Challenge has helped to propagate this research area. However, most speech recognition research is focused on adults and there is very little research on child speech. This dissertation is a description of the development and evaluation of a child speech emotion recognition framework. The higher-level components of the framework …

Local Delivery Of Tumor Associated Macrophage Immunotherapy For The Treatment Of Metastases To The Lungs, Sulaiman Alhudaithi

Theses and Dissertations

Metastases are the leading cause of cancer-related deaths, and the lungs are one of the primary sites of metastases from several malignancies. Existing therapies fail to entirely eradicate tumors that disseminate and reside in lungs; therefore, patient prognosis significantly worsens. Conventional therapies utilized to treat lung tumors such as chemotherapy are administered systemically and typically exhibit poor lung biodistribution profiles, leading to many undesirable off target effects and suboptimal drug concentration in the tumor, which may promote resistance, further compromising the quality of life of secondary lung cancer patients. Immune cells that infiltrate the tumor microenvironment (TME) play a central …

A Novel Sulfated Trimer Of Quercetin For Pulmonary Delivery To Treat The Emphysematous Lung, Abhinav Mohan

Theses and Dissertations

Emphysema, a major manifestation of chronic obstructive pulmonary disease (COPD), affects millions of patients in the United States; yet, no present treatment is able to directly modify the disease process. In the recent past, a pathobiologic hypothesis surrounding the deficiency of vascular endothelial growth factor (VEGF), has surfaced as a cause of the alveolar structural destruction and loss in emphysema. Additionally, sirtuin 1 (SIRT1), a regulator of anti-oxidative proteins and cellular homeostasis, has been found to be reduced in the lungs of emphysematous patients. Given these disturbances, this research hypothesized that such pathobiologic deficiencies can be inhibited with a sulfated …

The Mechanisms And Consequences Of Shrub Encroachment On The Virginia Barrier Islands, Lauren K. Wood

Theses and Dissertations

Shrub encroachment is a global phenomenon driven by direct and indirect anthropogenic influence which alters plant communities and ecosystem function. Many studies have investigated drivers and consequences of woody plant establishment, but mesic landscapes are underrepresented in the literature. My objective was to assess the mechanisms of Morella cerifera encroachment into coastal mesic grassland, the potential for self-reinforcement, and consequences on community composition, nutrients, and landscape productivity. I studied temperature and water microclimate modification by Morella cerifera presence and removal to understand ecosystem engineering and community composition changes. Additionally, I examined the influence of shrubs on surrounding grassland species traits …

E-Cigarette Use And Perceptions Among Adolescents With Attention-Deficit/Hyperactivity Disorder: The Role Of Parental Messages About Tobacco, Mayra S. Ramos

Theses and Dissertations

Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of using e-cigarettes compared to their neurotypical peers. Parent-adolescent communication about tobacco use and number of ADHD symptoms can influence adolescents’ perceptions of e-cigarettes and their e-cigarette use. Adolescents with ADHD (n = 80) completed questionnaires assessing parental messages about tobacco use; e-cigarette harm perceptions; susceptibility to use e-cigarettes; and e-cigarette use. Parents reported on messages about tobacco use, adolescent’s ADHD symptomatology, and completed demographic questionnaires. Twenty-percent of adolescents reported e-cigarette ever use. Adolescent girls were significantly more likely to report higher e-cigarette harm perceptions than boys. Parents reported providing messages …

A Computational Model Relating Tissue Oxygen Consumption To Oxygen Delivery In A Krogh Cylinder Model Of Skeletal Muscle, Raghad A. Alqahtani

Theses and Dissertations

Oxygen transport from a capillary to skeletal muscle tissue is a complex process that involves convective and diffusive mechanisms to deliver adequate oxygen to meet tissue metabolic activities. Typically, oxygen uptake in tissue is set by oxygen demand, which is set by metabolic activity. The relationship between the oxygen consumption (VO₂) of an isolated perfused tissue and the rate of delivery of oxygen (QO₂) to the tissue has been a subject of interest to many investigators over the past century. Experiments have shown that there is a critical value of QO₂ below which tissue VO …

Identifying Genes Downstream Of Mef2 That Influence Ethanol Sedation In Drosophila Melanogaster, Ananya Talikoti

Theses and Dissertations

Alcohol use disorder is a global public health issue that affects millions across the world. It can result in negative physical and mental health outcomes, and currently treatment options are limited and rates of relapse are high. Identifying genes that affect aspects of ethanol behaviors in model organisms, such as Drosophila melanogaster, can serve to eventually develop more robust therapeutic interventions for those experiencing alcohol dependence. Previous studies have identified a relationship between a person's initial sensitivity to alcohol and their abuse potential for the drug in later life. Therefore, we can study sedation behaviors in Drosophila melanogaster to …

Evaluating The Effects Of Electronic Nicotine Delivery Systems On Smoking Reduction, Negative Mood, And Stress Among Smokers With Mental Illness, Cosima Hoetger

Theses and Dissertations

Introduction: Smokers with mental illness (MI) are disproportionately affected by negative health outcomes. Electronic nicotine delivery systems (ENDS) may represent a harm reduction tool for those who reduce and/or replace their cigarettes with ENDS. Little previous research has examined how smokers with MI respond to ENDS. This analysis aimed to address this research gap using secondary data from a randomized controlled trial of ENDS varying in nicotine delivery among smokers with and without current MI. The aims were to test 1) the effects of MI status, condition, and time on changes in smoking behavior and negative mood and stress measures, …

Mobile-Based Contingency Management To Promote Daily Self-Monitoring Of Pain Severity And Related Measures In An Online Sample Of Individuals With Chronic Pain, Kathryn Polak`

Theses and Dissertations

Between 11% and 40% of the US population experience chronic pain. One promising pain management solution is remote self-monitoring. Unfortunately, low rates of adherence have impeded the use of remote self-monitoring among chronic pain patients. One robust strategy for improving adherence is contingency management (CM). This project pilot tested a fully-automated CM app (DynamiCare Rewards) programmed with an escalating variable-ratio reinforcement schedule for promoting daily self-monitoring of pain symptom severity, related variables (e.g., sleep), and prescription opioid use over a 28-day period in a sample of individuals with chronic pain. A pilot RCT compared participants randomized to CM (n …

Urate Genetic Assessment In Asian And Pacific Islander Subgroups Of Pregnant Women: Implications For Personalized Medicine And Means To Reduce Health Disparities, Ali Alghubayshi

Theses and Dissertations

Gout is one of the most common rheumatic conditions and appears to have a higher prevalence in certain populations. Risk factors for gout and its precursor, hyperuricemia, are also significant risk factors for preeclampsia, major pregnancy-related morbidity. A retrospective cross-sectional study was conducted on 1059 pregnant women from different populations whom 100% reported their ethnicities from the Asian, Native Hawaiian, and Pacific Islander populations. Numerous uric acid (UA) genes and clinical conditions were addressed, and all study details were reviewed and exempted by the University of Hawaii human Studies Program (Protocol Number: 2018-00225). In this project, we hypothesized that UA …

Rheological Analysis Of The Mechanical Properties Of Murine Lungs Over The Lifespan, Olajumoke Olufunke Harrison

Theses and Dissertations

To study the effects of aging in murine lungs, we characterized C57Bl6j mice from neonatal to 24-month-old mice. Samples were divided into two groups: Young Mice (YM) and Middle Age/Old Age Mice (MOM). The YM group included the neonatal and 6-10week. The MOM group included 7- and 22–24-month-old mice. Rheological testing was performed using a TA Instruments DHR-2 Rheometer to collect the mechanics of each mice sample. Utilizing a 20-mm parallel plate fixture, a gap of 0.8-1.0-mm, and a temperature setting of 25C, we conducted a frequency sweep. Samples were the decellularized over a four-day process then lyophilized for mass …

Cryogenic Electron-Microscopy (Cryo-Em) Analysis Of Mscs, Ynai, Connexin 26 And Bioinformatic Analysis Of Cysteine And Serine In Experimental Protein Structures, Claudio Catalano

Theses and Dissertations

Functional insights into macromolecules lie in the arrangement of their molecular structures. Investigating the atomic framework of a biomolecule could unwind its biochemical mechanism, providing aid to many relevant biological questions, thus facilitating drug discovery processes. Two approaches have been used to gain knowledge at the atomic level of a protein function: experimental and computational methodologies.

From an experimental perspective, membrane proteins (MPs) were investigated. Such proteins represent ~20% of the human proteome, and ~60% of them are drug targets since they are exposed to the surface of cells and are responsible for a wide range of fundamental functions like …

Continuous Manufacturing Of Pharmaceuticals Using Novel Platforms, Sarah S. Aboelela

Theses and Dissertations

Pharmaceuticals have been synonymously manufactured in a centralized, batch mode with less attention to process and formulation understanding. However, due to rising drug costs, shortages, and robustness issues, in addition to the alarming lack of flexibility and agility, regulatory agencies have pushed towards switching to continuous processes. They believed in continuous manufacturing, providing cleaner, flexible, and more efficient processes. Hence, it was foreseen to reduce development and manufacturing costs, time, and environmental impact and ensured drug product quality. Over the last two decades, continuous manufacturing quality, environmental, and economic advantages have been evident through many case studies and approved products …

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 …

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 …