Digital Commons Network^™

Investigating The Impact Of Chronic Inflammatory Pain On Ethanol Consumption In Mouse Models., Joshua L. Hunt

Theses and Dissertations

Chronic pain affects nearly 20% of Americans annually and for many alcohol provides a convenient and legally acquired palliative. Population-based studies have suggested a link between increased alcohol use and reduced pain, but chronic or excessive alcohol use potentiates the risk to develop alcohol dependence and neuropathy. However, sex differences in chronic pain and alcohol abuse are still not well understood. In the present study, we investigated whether chronic inflammatory pain using the inflammatory agent Complete Freund’s Adjuvant (CFA) model could alter ethanol consumption in male and female C57BL/6J mice. We observed that only CFA-treated male mice increased their ethanol …

Memory Impairments Due To Binge Ethanol Are Impacted By Age And Sex, Maria Alexis M. Bent

Theses and Dissertations

Ethanol is the most consumed drug among adolescents, which can cause long-term effects on memory and changes in gene and protein expression. While both adolescents and adults engage in binge drinking, the neurological and behavioral effects differ, with adolescents showing fewer adverse physiological effects but greater memory deficits than adults. Sex differences related to ethanol occur with women showing higher BEC than men and similar cognitive deficits despite fewer years of ethanol consumption. During adolescence the mPFC and dHPC undergo maturation development with both brain regions playing a role in spatial and recognition memory. Proteins critically involved in memory and …

Exploring The Role Of Senescence In Disuse-Induced Bone Loss And Therapeutic Strategies For Prevention, Steven J. Meas

Theses and Dissertations

Both age-related and disuse-related bone loss result in decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. Disuse induces physiological changes in bone similar to those seen with aging. This study compared age- and disuse-related bone loss using C57BL/6J mice of various ages that were hind-limb unloaded (HLU). In male and female mice, HLU induced a bone phenotype between those of 6-month-old and 22-month-old control mice. Gene analysis suggested that HLU leads to mitochondrial dysfunction, while aging primarily downregulates cell cycle processes. Although, the specific response to HLU appeared to be dependent on age. The study identified …

Modeling The Radiation Shielding Effectiveness Of Hafnium Diboride Reinforced Epoxy Composites Using Mcnp, Randolph Snook

Theses and Dissertations

This thesis uses MCNP simulations to evaluate the performance of a radiation shielding material consisting of Hafnium Diboride (HfB₂) powder in an epoxy matrix. Comparing the results to previously measured data against both gamma and neutron sources, suitability for other applications can be confirmed. The model simulated the epoxy material with different weight percentages of HfB₂ and thicknesses. It was compared to other shielding materials such as pure epoxy and 5% Borated High Density Polyethylene (HDPE-B). The HfB₂-epoxy composite was tested against a wide energy range gamma spectrum from a ¹⁵²Eu source, and neutrons …

Enhancing Chemotherapeutic Efficacy Of Doxorubicin Through Combination Therapy With Rapamycin And Sildenafil, While Providing Cardioprotection In Breast Cancer Models, Rebecca Mathew

Theses and Dissertations

Doxorubicin (DOX) is a common chemo-drug for breast cancer, but it causes severe cardiotoxicity. This study explores combining Sildenafil (Sild) and Rapamycin (Rapa), which inhibit phosphodiesterase-5 (PDE5) and mTOR, respectively, to boost DOX’s anticancer, but provide cardioprotection. Triple negative human (MDA-MB-231) and murine (4T1) breast cancer cells were treated with DOX (1 µM) with/without Rapa (100 nM) and Sild (10 µM) for 24-72 hours to analyze cell death, cell viability assays and protein expression. Human epidermal growth factor receptor 2-positive breast cancer (SKBr3) spheroids were treated with the same concentrations of DOX and/or AG825 (5µM) with/without Rapa and/or Sild for …

The Regulation Of Laryngeal Cancer Cell Phenotype And Proliferation By 24r,25-Dihydroxyvitamin D3 Is Correlated With Erα Isoform Expression, Cydney Dennis

Theses and Dissertations

Laryngeal cancer is the most common type of head and neck cancer and is associated with poor prognosis due to common delayed diagnoses. The sex disparities associated with laryngeal cancer are constantly growing, as the risk of malignancy in males is continually increasing compared to women. Due to the high chance of late-stage diagnosis requiring aggressive treatments, there is a high demand for less aggressive treatment options and early-stage diagnostic markers. The apparent sex disposition of the larynx, the correlation between sex hormones, and the risk of malignancy in aging men suggest that estrogen may play a role in laryngeal …

Behavioral Effects Of Adolescent Social Isolation Stress And/Or Binge Drinking And The Role Of The Vhip --> Mpfc Circuit, Jyoti Lodha

Theses and Dissertations

Adolescence is characterized by heightened social interaction and risk-taking behavior. Disruptions to cortical development by binge ethanol or social isolation can lead to attention, social, and cognitive deficits later in life, and increase risk for alcohol use disorders. During adolescence, proper development of a monosynaptic connection from the ventral hippocampus (vHip) to the medial prefrontal cortex (mPFC) is critical to proper social and working memory. We ask whether these factors affect neurobiological factors such as gene expression and the role of the vHipmPFC circuit in these behaviors. Social stress was modeled by social isolation (aSI) during adolescence. We expect aSI …

The Role Of Mirna-17-92 Following Myocardial Ischemia/ Reperfusion Under Normal And Diabetic Conditions, Virginia Villani Zwiren

Theses and Dissertations

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. The risk of developing CVD is increased two-to-four-fold in patients with diabetes, and, following a myocardial infarction, patients with diabetes often have worse outcomes. Dysregulation of individual or clusters of microRNAs is linked to the pathogenesis of heart diseases and its risk factors, such as diabetes, hypertension, atherosclerosis, myocardial ischemia/reperfusion (I/R) injury, and heart failure. Our study identified that the microRNA-17-92 cluster (miR-17-92) is suppressed in diabetic hearts with CVD. The purpose of the present study is to define how miR-17-92 attenuates injurious signaling in the post ischemic heart …

Exploring Serotonin 1b Autoreceptor Mediated Regulation Of Serotonin Transporter In Female Mice, Sanyukta Jalihalkar

Theses and Dissertations

Rationale: Serotonin (5-HT) is a crucial neurotransmitter involved in regulating various physiological processes. Dysregulation of the serotonergic system has been implicated in several neuropsychiatric disorders. Though numerous 5-HT receptors exist, the 5-HT transporter (SERT) is responsible for 5-HT clearance in the brain and periphery. 5-HT_1Bautoreceptors regulate 5-HT release and interact with glycogen synthase kinase-3β (GSK3β), which can modulate SERT function via specific Ser44/48 phosphorylation sites. While these findings suggest a potential interplay between 5-HT_1Band GSK3β-mediated SERT phosphorylation in regulating extracellular 5-HT, the primary causal molecular link remains unknown.

Objectives: To investigate if 5-HT_1B activation by …

Exploration Of Dopaminergic And Serotonergic Pathways Utilizing Pleiotropic Agents, Charles B. Jones Iii

Theses and Dissertations

2-(Benzoyl)piperidines (BPs) are at a crossroads of therapy and abuse. These compounds are a hybrid between the ADHD medication methylphenidate and abused stimulant cathinones. Here we use computational molecular modeling, synthesis, mutagenesis, and epifluorescence microscopy to further improve the understanding of and potential treatments for several neuropsychiatric disorders. Utilizing the BP scaffold and controlling chirality and aryl substitution, these agents were examined at DAT and SERT. From these investigations it has now been established that R isomer BPs are favored for DAT while S isomer BPs are favored for SERT. Aryl-substitution can greatly affect the selectivity of these agents with …

Muscle-Nerve Signaling And Its Role In Myogenesis, Synaptogenesis, And Regeneration, James T. Redden

Theses and Dissertations

Despite only comprising 0.1% of the myofiber surface area, a healthy motor endplate is densely packed with acetylcholine receptors (AChRs) responsible for mediating activity between the connected motor neuron and skeletal muscle via the neurotransmitter, acetylcholine. Loss of the endplate, known as fragmentation, is caused by car crashes, deep lacerations, and other traumatic injuries to the innervating nerve or direct injuries to the limb muscle(s) with intramuscular denervation as a common comorbidity. In both cases, endplate fragmentation begins within a week of injury proceeding muscle atrophy causing decreased mobility, paralysis, and quality of life. Endplate fragmentation of intact muscle fibers …

Mild Traumatic Brain Injury In Yucatan Minipigs: Assessing Changes In Approachability And Mechanical Nociception Following Diffuse Central Fluid Percussion Injury, Mark D. Pavlichenko

Theses and Dissertations

Traumatic brain injury (TBI) is a major healthcare concern affecting millions. Symptoms of TBI include sensory sensitivity and social changes that may persist long-term. Due to similarities in cytoarchitecture, metabolism, and inflammation, higher order minipig models are advantageous for translational TBI research, however, there remains a shortage of information regarding their behavioral and sensory sequelae following injury. Therefore, in this study, we assessed changes in sociability and somatosensation in adult male and female Yucatan minipigs for up to one-week following a sham or central fluid percussion injury (cFPI). Specifically, the voluntary human approach task (VHAT) and the forced human approach …

Potential Treatments For Epileptiform Activity In Microgyral Cortex, Eliot R. Niessen

Theses and Dissertations

In this study, the effects of several drug treatments on epileptiform activity in the freeze lesion (FL) mouse model of epilepsy have been evaluated and compared. The FL model replicates the histopathology and epileptiform activity that occurs in humans with the developmental cortical malformation of polymicrogyria (PMG). While Gabapentin is already used in a clinical setting to treat seizures, there are other alternatives that have not been fully tested. Rapamycin, for instance, has been shown to reduce seizures in other models of epilepsy. It is an inhibitor of the mammalian target of rapamycin (mTOR) pathway, which regulates the function of …

T Cell Polarization Regulates The Inflammatory Response And Tissue Regeneration At The Peri-Implant Interface, Derek Avery

Theses and Dissertations

Unresolved healing and localized chronic inflammation are common occurrences after biomaterial implantation, resulting in unfavorable clinical outcomes such as implant failure or fibrous encapsulation. T cells are adaptive immune cells found in lymph nodes, thymus, spleen, bone marrow, and around biomaterials, significantly impacting the degree of inflammation and wound healing. T cells are vital for inflammatory cytokine production and modulation of innate immune cells, including neutrophils and macrophages. T cells can be differentiated into two primary subsets, CD4⁺ and CD8⁺ T cells, playing distinctive roles in various pathologies and disease states. While T cells have been characterized well …

Genetic And Transcriptomic Investigations Of Progressive Ethanol Consumption In The Diversity Outbred Mouse, Zachary Tatom

Theses and Dissertations

As a complex genetic disorder, alcohol use disorder (AUD) is thought to be influenced by many genes each contributing only a small effect to the overall disease liability. Dozens of genes have been implicated as potentially affecting risk for AUD and alcohol consumption. However, understanding the full genetic architecture of AUD – what genes are involved, to what extent, and how these genes are regulated – remains a challenging step in identifying novel treatments. Gene expression studies in humans have attempted to augment GWAS of alcohol consumption but are often confounded by environmental factors; the difficulty of collecting tissue from …

Multi-Magnetic Material Transcranial Magnetic Stimulation Coils Development And Electric Field Measurement & Modeling Using Machine Learning, Mohannad Tashli

Theses and Dissertations

Transcranial Magnetic Stimulation (TMS) is a safe, effective, and non-invasive therapy for treating several psychiatric and neurological disorders. TMS is Food and Drug Administration (FDA) approved treatment and is commonly applied to patients who do not respond to medications for the treatment of clinical depression, smoking cessation, obsessive-compulsive disorder and migraine. Recently, there has been an increase in the development of electromagnetic neuromodulation techniques targeted at enhancing the effectiveness of TMS devices for the treatment of mental diseases. In TMS stimulation, focality is an important factor which determines the specificity of the pulses induced in different brain tissues. The electromagnetic …

Evaluation Of Alternative Methods For Dna Recovery Of Compromised Skeletal Remains, Ciara N. Rhodes

Theses and Dissertations

Skeletal remains frequently serve as the sole source of genetic material available for developing a profile in cases concerning unidentified human remains or mass casualties. Nevertheless, as unidentified skeletal remains age and are exposed to uncontrolled environmental conditions, the success rates of conventional methods of bone analysis diminish significantly. The physical and mechanical processing of skeletal remains into fine powder for DNA isolation and downstream analysis can substantially impact the quality and quantity of recoverable genetic information. This concern may be exacerbated when dealing with degraded forensic skeletal remains. Few studies have explored whether pulverization of bone samples contributes to …

Utilizing Hemoglobin Binding Kinetics And X-Ray Crystallography In Sickle Cell Disease Drug Development, Ahmed Alghamdi

Theses and Dissertations

ABSTRACT

UTILIZING HEMOGLOBIN BINDING KINETICS AND X-RAY CRYSTALLOGRAPHY IN SICKLE CELL DISEASE DRUG DEVELOPMENT

By Ahmed Alghamdi, M.Sc. in Medicinal Chemistry

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Medicinal Chemistry at Virginia Commonwealth University.

Virginia Commonwealth University, 2024.

Director: Dr. Martin K. Safo Professor, Department of Medicinal Chemistry

Introduction: Sickle Cell Disease (SCD) is characterized by severe hemolytic anemia, recurrent painful crises, and chronic organ damage, posing significant challenges to patients' quality of life and longevity. While current FDA-approved therapies offer symptomatic relief, they do not address the underlying molecular …

Roleplaying Builds Character: Avatar Performance In Dungeons & Dragons As An Art-Form For Self-Development., Maria F. Pagola Garcia

Theses and Dissertations

This paper examines the impact of the performance and embodiment of Dungeons & Dragons characters on their player’s self-development and self-confidence. Focusing on the game’s 5th edition, this narrative inquiry study is concerned with the applications of D&D as an artistic tool to build both community in formal and informal spaces of art education and individual players’ self-development through the avatars being portrayed during game time.

Ten adult participants ranging from age 23-28 were selected using a mix of direct recruitment and voluntary response. They filled out a digital survey introducing themselves and their main D&D characters, then a 45-minute …

Impact Of Environmental, Social, And Governance Disclosure On Firm Performance: A Case Of Listed Manufacturing Firms In Nigeria, Abdulbaki Ubandawaki

Theses and Dissertations

The traditional goal of companies is to maximize shareholders’ wealth. However, to achieve this objective, many complementary goals must be pursued alongside the traditional ones. To achieve corporate goals, businesses need to interact with the environment. The continual interaction of the corporation with the environment has definitely come with its costs and benefits, and the global interest in promoting sustainable development has made corporate ESG reporting a crucial issue. The aim of the study is to investigate the relationship between ESG reporting and firm performance among listed manufacturing firms in Nigeria. The data was collected from annual and standalone sustainability …

Characterization Of Tonneau1 Recruiting Motif Proteins And Ton2 Signaling Functions, Tyler Falk

Theses and Dissertations

Plants cells are fixed in place. As a result they have to carefully divide in order to function properly. Plants use a number of complex microtubule arrays to ensure proper division and orientation including the preprophase band (PPB) and the phragmoplast. The PPB orients the cell prior to division and marks the cortical division site, which is where the phragmoplast is guided to. The phragmoplast is a dynamic microtubule array that builds the cell plate which later becomes the cell wall that divides daughter cells. Proteins involved with PPB formation include Tonneau1 (TON1) and Tonneau2 (TON2) which localize to and …

Terror And Time: Analyzing Homegrown Terrorism In The United States, Kyser Daniels-Baessler

Theses and Dissertations

The events of September 11th, 2001, prompted a global reckoning with the threat of international terrorism, leading to intensified awareness and policy responses worldwide. However, amidst this heightened global focus, the United States has faced a concerning rise in politically motivated violence on its soil. Against this backdrop, this thesis delves into the phenomenon of homegrown terrorism within the United States from 2000 to 2020. By employing advanced geospatial techniques, this study seeks to pinpoint areas nationwide with elevated rates of homegrown terrorist incidents. Moreover, it endeavors to uncover potential temporal correlations between these acts of violence and significant events, …

Assessing The Needs Of Elementary School Students From Low Socioeconomic Environments Displaying Poor Performance In Reading, Reynaldo Flores

Theses and Dissertations

This dissertation was designed to provide current information on the low reading level of students in Grade 4 who are from families of low socioeconomic status (SES). While it was known that SES is crucial to student learning which gave rise to initiates to address the problem, low SES students in elementary school continue to struggle to read at grade level. The Every Student Succeeds Act (ESSA) is used to measure performance index framework in reading along with mathematics, writing, science, and social studies to address and correct deficiencies. The data for the ESSA was drawn from the State of …

A Phenomenological Study Of Online Physical Education On Former Students’ Activity Levels And Fitness Concepts Knowledge, Jerry Veshio

Theses and Dissertations

This applied dissertation was designed to provide an understanding of the perspectives of former online physical education high school students and how participation in the course affected their ability to be active post-high school and their knowledge of fitness concepts. A phenomenological design was used to guide the study’s investigation. Participants in the study were interviewed about their experiences in online physical education while in high school and how that experience currently influences their physical activity levels. Additionally, respondents described the positives and negatives of their experience in the course, specifically as it relates to the course materials, assessments, instructor …

A Study On Reducing Motor Stereotypy With Response Interruption And Redirection Using Functionally Matched And Unmatched Stimuli, Alana Fallucca

Theses and Dissertations

This applied dissertation was designed to expand the scope of existing literature on the use of response interruption and redirection intervention with functionally matched and unmatched stimuli to reduce motor stereotypy in children with autism. While response interruption and redirection is an effective, evidence-based strategy for the reduction of vocal and motor stereotypy, it requires interruption of each instance of stereotypic behavior and implementation of an alternative behavior. This process can be laborious, implementation of which depends upon the frequency of stereotypy. To mitigate the intervention difficulties with response interruption and redirection implementation, a single-step functionally matched stimulus that is …

Victim Advocates' Experiences In The Provision Of Domestic Violence Services For Jewish Women, Michael Sue Jenefsky

Theses and Dissertations

Domestic violence is a serious, dangerous global epidemic and does not discriminate. Domestic violence has no limitations happening in all communities, religions, and cultures. There are many types of abuse, and it is not always physical; however, the underlying threat of violence is perceived by victims. Abusers use manipulative and coercive tactics to gain and maintain power and control of victims. It is deliberate and a choice. Feelings of shame, guilt, blame, failure, helplessness, and being trapped with no means to escape are prevalent among victims. Jewish women have specific feelings and fears that are associated with halakha, Jewish law, …

Faculty Experiences Incorporating Universal Design For Learning In Online Course Design At Historically Black Colleges And Universities, Chinyere Yvette James

Theses and Dissertations

Historically Black colleges and universities (HBCUs) contributed to over 20% of all bachelor’s degrees earned by African American students. Since the 2019 pandemic, HBCUs have provided more online course offerings to their students. The continued success of HBCUs depends on their ability to grow with technology. This study examined the lived experiences of faculty applying universal design for learning (UDL) principles in online courses at HBCUs. This study was conducted to gain insight into the impact UDL had on retention rates, learning experience, and implementation. Online courses at HBCUs are underdeveloped, which poses a problem for continued growth and success …

Examination Of The Differences And Similarities In The Classification Of Multiple Homicide Perpetrators, Lucy M. Papp

Theses and Dissertations

The applied dissertation compares the lifestyle and behavioral characteristics of mass, serial, and spree murderers. Historically, studies have focused on serial murder according to the perpetrator's typology or indicators at the crime scene. The current topics of research lack a comparison of these classifications. While the classification and described typologies are essential for academic and investigative purposes, understanding the impactful lifestyle factors of these perpetrators may also serve as an essential factor in predictive analysis, victimology, and the motive behind their heinous crimes.

The researcher collected data on the classifications for each type of multiple homicide perpetrator: mass, serial, and …

Investigating Teacher’S Perceptions Of Equitable Author Choices In Secondary High School Classrooms, Joy Price

Theses and Dissertations

The purpose of this qualitative study was to explore how English teachers can incorporate diverse authors into instruction. The following research questions guided the study:

1. What do teachers describe as the pros/cons of integrating diverse perspectives into teachers’ instruction, in the form of literature by diverse authors?

2. In what ways and how can incorporating literature by diverse authors benefit students?

3. What challenges may teachers face when integrating diverse literature perspectives into instruction?

4. What might enable teachers to integrate diverse literature perspectives into instruction.

The researcher developed designed and field tested a questionnaire for teachers to take …

Strategies Teachers Use To Encourage Student Reading Motivation And Engagement In The High School Setting: A Generic Qualitative Study, Shelia Tate

Theses and Dissertations

This applied dissertation was designed to provide an understanding of the practices and strategies used by Title 1 high school teachers to promote student reading motivation and engagement. Engaging students in the curriculum and motivating them to read is essential to a successful classroom experience. As districts move to a more prescribed curriculum with provided scope and sequence, teachers look for ways to engage their students and provide relevant resources to meet their students' needs creatively.

The researcher interviewed teachers to explore their beliefs, strategies, and practices for fostering student reading motivation and classroom engagement in high school. The guiding …