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The Effect Of Intermittent Theta Burst Stimulation On Biceps Corticomotor Excitability In Non-Impaired Individuals And Individuals With Tetraplegia, Blaize Majdic

Theses and Dissertations

Neuromodulation of the primary motor cortex (M1) in pair with physical therapy may be a promising method for improving motor outcomes after spinal cord injury (SCI). Increased excitability of the corticospinal motor pathways (i.e. corticomotor excitability) has shown to be associated with improved motor learning and skill acquisition. Intermittent theta burst stimulation (iTBS) is a form of non-invasive brain stimulation which can increase corticomotor excitability, as measured by an increase in the amplitude of motor evoked potentials (MEPs). However, the ability for iTBS to increase the corticomotor excitability of proximal muscles such as the biceps, and muscles affected by spinal …

Understanding The Contributions Of Discrepant Parent-Adolescent Views Of Parenting Practices And Peer Deviance To Adolescent Problem Behavior: A Cross-Lagged Polynomial Regression Approach, Mallory Stephenson

Theses and Dissertations

The present study used autoregressive cross-lagged models to examine the processes through which peer deviance and discrepant parent-adolescent views of monitoring-related communication, involvement, and positive parenting influence one another and contribute to physical and relational aggression, substance use, and delinquency. Participants included 535 adolescents (64% male) who were identified as prone to aggression and socially influential by their sixth-grade teachers during the 2001-2002 and 2002-2003 school years; participants self-identified as African American (69%), Hispanic (14%), White (9%), Multiracial (5%), or another race (3%). Contrary to expectations, parent-adolescent reporting discrepancies were not related to peer deviance, physical aggression, substance use, and …

Exploring The Use Of Pulsed Erbium Lasers To Retrieve A Zirconia Crown From A Zirconia Implant Abutment, Ahmed Elkharashi

Theses and Dissertations

Removal of zirconia crowns, commonly used as cement-retained implant fixed restorations, can be challenging. Conventional methods of crown removal are time consuming and often leave irreparable damage to the crown, which can be costly to patients and practitioners. This research explored the use of two different types of pulsed erbium lasers, erbium-doped yttrium aluminum garnet laser (Er:YAG) and erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG), as non-invasive tools to retrieve cemented zirconia crowns from zirconia implant abutments. Times needed to remove the crowns were recorded and analyzed using ANOVA (��=0.05). No statistical differences between the debond times of each …

Role Of Nurd In Acute Leukemia Cell Survival, Javeria Aijaz

Theses and Dissertations

Depletion of the ATPase component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, CHD4, reduces acute myeloid leukemia (AML) cell survival. This study identified other NuRD components, as potential therapeutic targets for disrupting protein-protein interactions within NuRD. In addition to AML, we established that T-cell Acute Lymphoblastic Leukemia (T-ALL) cell lines responded similarly to CHD4 depletion.

Greater than 90% depletion of either MBD2 or MBD3 (the mutually exclusive two DNA binding NuRD paralogues) – was unremarkable, but complete depletion of MBD3 increased apoptosis and genotoxic sensitivity. Combined depletion of MBD-NuRD proteins augmented apoptosis observed with complete MBD3 depletion - indicating …

Teacher Approaches To Women’S History, Gender, And Feminism In Secondary Social Studies, Kimberly R. Bowman

Theses and Dissertations

While several scholars have worked to reimagine social studies curriculum from a feminist perspective, there are few studies that look at how teachers understand and experience gender equity work (Bohan, 2017; Engebretson, 2018). This study seeks to bridge that gap between theory and practice in order to progress toward a more gender-equitable social studies education. Utilizing a hermeneutic circle design to facilitate dialogue across participants, I conducted one-on-one, semi-structured interviews with seven secondary social studies teacher participants and collected participant-provided curriculum materials. Using techniques from constructivist grounded theory, I analyzed how teachers made sense of their experiences trying to include …

Characterization Of The Tsc/Dyrk1a Interaction, Supriya Joshi

Theses and Dissertations

The Tuberous sclerosis complex (TSC) includes TSC1, TSC2 and the TBC1D7 subunits that together function as a principal inhibitor of the mTOR protein kinase complex 1 (mTORC1). mTORC1 is a master regulator of cell growth and proliferation that responds to signaling cues such as growth factors and nutrient availability. Proteomic studies in our lab revealed an interaction between the TSC subunits and DYRK1A, a ubiquitous protein kinase encoded by a gene located in the Down syndrome (DS) region on human chr21. In this study, we sought to validate the interaction of the TSC components with DYRK1A and to determine the …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

Phenotype Extraction: Estimation And Biometrical Genetic Analysis Of Individual Dynamics, Kevin L. Mckee

Theses and Dissertations

Within-person data can exhibit a virtually limitless variety of statistical patterns, but it can be difficult to distinguish meaningful features from statistical artifacts. Studies of complex traits have previously used genetic signals like twin-based heritability to distinguish between the two. This dissertation is a collection of studies applying state-space modeling to conceptualize and estimate novel phenotypic constructs for use in psychiatric research and further biometrical genetic analysis. The aims are to: (1) relate control theoretic concepts to health-related phenotypes; (2) design statistical models that formally define those phenotypes; (3) estimate individual phenotypic values from time series data; (4) consider hierarchical …

Senescent Trees Stabilize Aboveground Wood Net Primary Production Immediately After Disturbance, Maxim S. Grigri

Theses and Dissertations

In the United States, forests sequester 17% of national carbon (C) emissions annually (UGCRP, 2018), however shifting forest disturbances threaten the stability of this essential C sink. Unlike the high severity, stand-replacing disturbances that were widespread a century ago, today’s eastern temperate forests experience frequent low-to-moderate severity disturbances from invasive pests and pathogens with mixed effects on net primary production (NPP). Carbon cycling stability after disturbance has been reported, however, the mechanisms underlying immediate NPP stability or decline are not well understood. Through weekly measurements of production in a landscape scale experiment, we show that the sustained growth of senescent …

Dna Analysis And The Postmortem Submersion Interval From The Microbiome Of Waterlogged Sus Scrofa Skeletal Remains, Claire Cartozzo

Theses and Dissertations

Following water-related deaths, soft tissue on victims’ remains may be entirely absent after a temperature dependent period of time. Due to their physical and chemical components, which protect them from environmental deterioration and biological attack, bones preserve DNA for longer periods of time. Therefore, the ability to both identify an individual and estimate the postmortem submersion interval (PMSI) may depend on DNA obtained from skeletal remains. The goals of the dissertation were to examine differences in both the degradation of skeletal DNA and the microbiome inhabiting bone in freshwater aquatic environments (e.g., Henley Lake and the James River). At each …

Characteristics Of Alveolar Bone Marrow Cells From Patients Undergoing Dental Extractions Or Dental Implant Therapy, Meng H. Lee

Theses and Dissertations

Alveolar bone marrow stromal cells (aBMSCs) play important roles in craniofacial wound healing. To establish an easy, efficient and reliable method to harvest aBMSCs, we compared three different methods: extraction socket aspiration, osteotomy aspiration and bone core digestion. Samples of aBMSC were collected from two groups of subjects. Group 1 (dental extraction): after dental extraction, 22.5-gauge needles were used to collect 0.5-1cc marrow aspirate. Group 2 (dental implant): during implant surgeries, bone core and 0.5-1cc marrow aspirate were obtained from the osteotomy. Samples were cultured in petri dishes and attached cells were expanded. The population doubling time (PDT), surface markers, …

Associations Between Stress, Racial Discrimination, And Cytokine Levels In Black Americans, Takia Williams

Theses and Dissertations

Inflammation is a common pathophysiological pathway for a number of chronic diseases and is influenced by exposure to stress. Although there are racial disparities in health outcomes, relatively little is known about factors that may influence the inflammatory response in Black American individuals. This study examined whether racial discrimination and other forms of stress are associated with the balance of pro- and anti- inflammatory cytokines in Black American adults. Data from 22 participants were drawn from a larger study of Black American children (ages 5-12) and their primary caregivers drawn from low income neighborhoods in Richmond, Virginia. Caregivers reported demographics, …

Development Of Near-Real Time Material Detection And Analysis By Coupling Electrochemical & Optical Spectroscopy Methods For Molten Salt Systems, Hunter Andrews

Theses and Dissertations

For both pyroprocessing and molten salt reactors (MSRs), it is desirable from a process control and nuclear safeguards perspective to monitor the species in the molten salts for material accountancy. Many traditional monitoring techniques, even simple salt sample retrieval, are time exhaustive or rendered useless for these systems due to the high thermal loads, high radiation zones, and corrosive nature of molten salts. Therefore, the main motivation for this work is the need for an online monitoring system for a molten salt system that is robust enough to handle the extreme environment yet deliver quantifiable salt concentrations. The intent of …

Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji

Theses and Dissertations

Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology.

Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of …

Psychometric Developments Of The Ace-Iq: Understanding The Trauma History Of Latine Immigrants, Jorli K. Swingen Dr.

Theses and Dissertations

Adverse childhood experiences (ACEs) have a profound effect on an individual’s physical and mental health. The World Health Organization has recently updated the ACE questionnaire so it could be used with international populations. The Adverse Childhood Experiences-International Questionnaire (ACE-IQ), has not been translated to Spanish or used with Latine immigrants.

This study translated the ACE-IQ into Spanish, evaluated the psychometric properties of the questionnaire, and collected data on 184 four adult English Language Learners in Chesterfield County, VA.

There is evidence of internal consistency for the ACE-IQ as a whole (α = .908) and within subscales. Three factors were identified …

Modulation Of Ferroportin In Oral Cancer, Ashley N. Hemingway

Theses and Dissertations

Iron plays a critical role in life sustaining functions for the cell. Dysregulation of these processes can be an issue with maintaining homeostatic conditions. Various cancer types have been observed to show malfunction in the maintenance of their iron homeostasis, in particular with the iron export protein—ferroportin. Ferroportin is the sole iron exporter known. Its structure and mechanism have not fully been elucidated yet, but its modulation has been associated with a poorer prognosis in cancers like breast, leukemia, prostrate, ovarian, colorectal, etc. Decreased iron exportation by ferroportin may lead to an increased labile iron pool allowing the cell to …

Design, Synthesis, And Biological Evaluation Of Mu Opioid Receptor Selective Antagonists Bearing Pyrazole And Imidazole Side Chains, Pornprom Klongkumnuankarn

Theses and Dissertations

Opioid Use Disorder (OUD) is one of the major national threats to human health and economic system. Since the opiate substances produce their pharmacological effects mainly at the Mu Opioid Receptor (MOR), the development of potent MOR selective antagonists is imperative. By application of the message-address concept, the novel selective MOR antagonist, NAP was synthesized in our group. The molecular modeling studies of NAP revealed that its MOR selectivity was determined by interactions between the C(6) side chain and the non-conserved residues of the receptor. To enrich our understanding of Structure-Activity Relationship (SAR) of the opioid ligands as well as …

The Design Of A New Vaginal Applicator For Direction Modulated Brachytherapy (Dmbt) Using Geant4 Monte Carlo Simulation Code, Moeen Meftahi

Theses and Dissertations

Purpose: Anisotropy of the 192Ir source causes a lack of dose coverage at the apex in HDR vaginal cylinder brachytherapy (VC BT). In this study, we took advantage of the GEANT4 Monte Carlo (MC) simulation code to design a new DMBT vaginal applicator so that it maintains the dose coverage of the current vaginal cylinder at periphery everywhere while improving the apex coverage. In addition, since current treatment planning systems (TPS) considers the whole environment as water according to TG43 formalism, based on the capability of the MC in the calculation of dose in the material, the effect of inhomogeneity …

Robert Catherine, Sarah Nelson Rupp

Theses and Dissertations

Robert Catherine is an experimental augmented reality novel engaged in the speculative realist question: What is the point to anything if everything?

A perverted and downwardly mobile Richmond millennial man quarantined because of the Coronavirus writes a series of creative non-fiction essays for his girlfriend about suicide, panic attacks, ADHD, DNA testing, capitalism, depression, and sexual repression.

Heparan Sulfate. A Ligand For Coordination Compounds., Eric Ginsburg

Theses and Dissertations

Heparan sulfate (HS), a type of glycosaminoglycan (GAG), has been identified as a ligand for interactions with polynuclear platinum complexes (PPCs). HS is involved in numerous biological processes, and often considered to be extracellular DNA. PPCs interact with HS through the formation of a “sulfate clamp”, where multiple anionic sulfate groups cluster around the cationic PPC. The masking of HS results in the inhibition of enzymatic activity, protein-HS interactions, and other biological processes. PPCs use HS proteoglycans as an method of cellular internalization. By targeting sulfated-GAGs, PPCs can offer precision medicine not currently observed with the FDA approved platinum therapies. …

Effects Of (R,S)-Ketamine And (2r,6r)-Hydroxynorketamine: A Preclinical Study, Remington Rice

Theses and Dissertations

In 2017, 7.1% of US adults were diagnosed with depression, and 50% of patients received medication to treat their depression. Depression can cause severe interruptions in an individual's cognitive functioning and behaviors like sleeping, eating, working, and socializing. Unfortunately, approximately 40% of patients do not respond to treatment with monoaminergic medications (e.g. Prozac) and therapeutic effects may be delayed 2-8 weeks. Due to these therapeutic shortcomings, faster acting and more efficacious treatments are needed. Recent preclinical findings indicate potential for glutamatergic drugs like (R,S)-ketamine and (2R,6R) hydroxynorketamine to produce more rapid and longer-acting therapeutic effects. The antidepressant effectiveness of (R,S)-ketamine …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

Interspecific Gene Flow Potentiates Adaptive Evolution In A Hybrid Zone Formed Between Pinus Strobiformis And Pinus Flexilis, Mitra Menon

Theses and Dissertations

Species range margins are often characterised by high degrees of habitat fragmentation resulting in low genetic diversity and higher gene flow from populations at the core of the species range. Interspecific gene flow from a closely related species with abutting range margins can increase standing genetic diversity and generate novel allelic combinations thereby alleviating limits to adaptive evolution in range margin populations. Hybridization driven interspecific gene flow has played a key role in the demographic history of several conifer due to their life history characteristics such as weak crossability barriers and long generation times. Nevertheless, demonstrating whether introgression is adaptive …

E-Liquid Exposure Causes Multiple Cardiovascular Defects In Xenopus Laevis Embryos, James E. Black Iii

Theses and Dissertations

Over the past several years vaping has become part of the cultural zeitgeist in the United States, with ECIG usage amongst those of reproductive age rising more and more. Due to a lack of regulation and research concerning their long term effects, public opinion trends toward the idea that they are somehow safer than their traditional counterparts. As cases of lung injury and ECIG related death are beginning to be reported more and more, it is clear that the misinformation about their safety is unfounded. Congenital heart defects (CHDs) are some of the most common birth defects currently in the …

Amixicile As A Novel Antimicrobial Treatment For Periodontitis: A Pilot Study In The Non-Human Primate, Macaca Mulatta, Denver J. Lyons

Theses and Dissertations

Periodontitis is an inflammatory disease with a bacterial etiology in a susceptible host. Given the bacterial etiology, a selective antimicrobial agent with minimal side effects could be a useful adjunct to traditional therapy. Amixicile is a novel antimicrobial that targets the pyruvate: ferredoxin oxidoreductase (PFOR) which is an enzyme that is critical for anaerobic bacterial metabolism. It has been found to have no effect on commensal, aerobic microbes and has little to no side-effects thus far in animal models. In this study, two nonhuman primates of the Macaca mulatta species with naturally occurring mild chronic periodontitis were studied before and …

Symmetry Algebras Of The Canonical Lie Group Geodesic Equations In Dimension Five, Hassan Almusawa

Theses and Dissertations

Nowadays, there is much interest in constructing exact analytical solutions of differential equations using Lie symmetry methods. Lie devised the method in the 1880s. These methods were substantially developed utilizing modern mathematical language in the 1960s and 1970s by several different groups of authors such as L.V. Ovsiannikov, G. Bluman, and P. J. Olver, and have since been implemented as a software package for symbolic computation on commonly used platforms such as Mathematica and MAPLE.

In this work, we first develop an algorithmic scheme using the MAPLE platform to perform a Lie symmetry algebra identification and validate it on nonlinear …

Identifying And Addressing Barriers To Accessing Treatment For Substance Use Disorders Among Opioid-Misusing Individuals Following Implementation Of The Affordable Care Act, Mirinda A. Gormley

Theses and Dissertations

BACKGROUND: This project utilized opioid-misusing adults to investigate the association between type of opioid misuse and perceived readiness, financial, structural, and stigma-related barriers to accessing SUD treatment; identified classes of PSU and the association between patterns of PSU and perceived barriers, and evaluated effectiveness of an out-of-hospital opioid-treatment connection program.

METHODS: Respondents from 2015-2018 NSDUH included insured adults reporting past year opioid misuse. Multivariate logistic regression assessed relationship between type of opioid misuse and perceived barriers to SUD treatment. LCA identified patterns of PSU, and multivariate logistic regression assessed association between PSU classes and perceived barriers. EMS ePCRs for nonfatal …

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

Pharmacology Of Fentanyl-Related Substances In Mice Reveals Potential Therapeutics With Improved Protective Indices, Neil B. Varshneya

Theses and Dissertations

Fentanyl-related substances constitute a class of compounds that were originally developed in the latter half of the 20th century as combination analgesic-anesthetic agents. Today, many of these compounds have emerged in the recreational drug marketplace as adulterants to heroin, counterfeit prescription pills, and even as standalone products designed to circumvent drug control laws. The objective of this dissertation was to identify the structural determinants of fentanyl analogs that could affect the potency and efficacy for eliciting their therapeutic and toxic effects to identify candidates of potential therapeutic interest. To accomplish this objective, thirty-eight fentanyl-related substances, in addition to the MOR …