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 …

Leaf To Canopy Functional Resilience: Plant Physiological And Carbon Cycling Stability Following Disturbances, Lisa T. Haber

Theses and Dissertations

Ecological disturbances impact core ecosystem functions, including production and biogeochemical cycling, by precipitating changes in biodiversity, physical environmental variables, vegetation structure, and functional trait distributions. As disturbance patterns intensify and abruptly transition to novel regimes under global change, future trajectories of ecosystem functions, including carbon (C) uptake and storage, are uncertain. A more complete understanding of the mechanisms underpinning ecosystem stability (or ability to return to baseline functioning) following disturbance is needed to forecast future C cycling.

Replicated ecosystem-scale disturbance experiments, particularly when coupled with modeling, are required to rigorously test hypothesized trajectories of ecosystem structural and functional change following …

The Relationship Between Outcomes Associated With Patient Blood Management Programs And Transfusion Safety Officers, Gary Morral

Theses and Dissertations

BACKGROUND: Patient Blood Management (PBM) has become the standard of care for transfusion services in hospitals. Transfusion Safety Officers (TSOs) have been identified by some as being a crucial part of a successful PBM program; however, no studies have been done to show their effectiveness, or if there is even a relationship between having a TSO and outcomes associated with PBM programs. The purpose of this study was to describe and test the relationship between having a TSO and six outcomes associated with PBM programs including blood product wastage (red blood cells, plasma, and platelets), hospital lengths of stay, rates …

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 …

Mathematical Analysis Of Eukaryotic Pericentromere, Puranjan Ghimire

Theses and Dissertations

The centromere is crucial for chromosomal stability and their proper segregation during cell division in eukaryotes. Surrounding the centromere are pericentromeres, made of repetitive DNA elements called pericentromeric repeats, varying from 10 in fission yeast to thousands in humans. These repeats form densely packed heterochromatin, where genes are usually silenced. The silencing mechanism across different pericentromeric repeats remains unclear.

Despite variations in sequence and length, pericentromeric repeats are conserved across eukaryotes, indicating their functional importance. This dissertation presents mathematical models to quantify gene silencing in fission yeast and humans. In fission yeast, my model predicts that silencing occurs only with …

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 …

A Complexity Aware Overlay Architecture For High Integrity Fpga Based Systems, Richard Dwight Hite Jr

Theses and Dissertations

Cyber-Physical systems are becoming more and more prevalent in our society and are simultaneously becoming more complex due to evolving technological capabilities in both hardware and software. This complexity exacerbates verification and validation activities thereby negatively impacting important system attributes like design assurance, system reliability, development costs and trust. These facts necessitate the need for computing architectures that constrain complexity for the sake of assurance. Traditional software and hardware development for safety-critical systems have been demonstrated in previous safety-critical systems and the established development methodologies are well understood. However, both technologies have their strengths and limitations. Processor-based technology (SW based …

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 …

Effects Of Flooding And Plant Community Arrangement On Freshwater Wetland Greenhouse Gas Emissions And Plant Growth, Walker A. Trainum

Theses and Dissertations

Climate change threatens the status quo of tidal freshwater wetlands by altering their hydrology and species makeup. Increases in water level within freshwater wetlands are well studied, but with the inclusion of saltwater intrusion; while common for some tidal wetlands affected by sea level rise, it is not universal. For wetlands that will experience flooding apart from increases in salinity, adequate study is lacking. For these wetlands, the effect of increasing water level is largely unknown. Thus, the aim of this study was to use an outdoor mesocosm experiment to isolate effects of flooding and communities of differing species makeups …

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 …

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 …

Mathematical Modeling Of Phage-Bacteria Population Dynamics, John Lawrence D. Palacios

Theses and Dissertations

Bacteriophages are viruses that infect and replicate within bacteria. Lytic phages cause the bacterial cell to burst, killing the bacteria. These types of phages can be used to treat patients with antibiotic-resistant bacterial infections. As a step in developing successful treatment protocols, we aim to understand the population dynamics of phages and bacteria using an in vitro model. We model the dynamics using the Campbell model, which consists of a delay differential equation (DDE), as a base model. We extended the model by including the emergence of phage resistance. We then compared the DDE model with a parallel ordinary differential …

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 …

Longitudinal Analysis Of Maternal Depression, Physical Work Demand, And Working Hours Before, During, And After Pregnancy On Offspring Blood Pressure Trajectories, Medhin Tsegaye Haile

Theses and Dissertations

Overall Abstract

Background: Pediatric high blood pressure (BP) is a growing global concern, with 1 in 7 adolescents in the U.S. experiencing elevated BP or hypertension. Maternal lifestyle factors, including depressive symptoms, physically demanding work, and work hours during pregnancy, may influence offspring BP trajectories. However, prior studies often focus on single time points or specific age groups, limiting understanding of long-term effects. This study investigates the associations between maternal depressive symptoms, physically demanding work-related factors, and work hours before, during, and after pregnancy with offspring systolic blood pressure (SBP) trajectories from early childhood to adolescence.

Methods: We utilized …

Cellular Metabolism Is A Viable Therapeutic Target For Radiation-Induced Pulmonary Fibrosis, Josly Pierre-Louis Odoom

Theses and Dissertations

Herein, we provide evidence for cellular metabolic reprogramming as a driver of radiation-induced pulmonary fibrosis (RIPF). We are the first to identify a distinct metabolic signature for RIPF in a cohort of patients with radiographic sequela. We also used a RIPF mouse model to detect the metabolic pathways that enrich during pathogenesis. Our previous work highlighted the importance of lactate, a derivative of the glycolysis end-product pyruvate. Consequently, we took a special interest in the effects of radiation on the glycolysis pathway. We learned that radiation accelerates and reprograms glycolysis to an anabolic state in a pyruvate kinase M2 (PKM2)-dependent …

Long-Wave Modeling Of Viscous Film Dynamics Inside A Tube With Time-Dependent Radius, Robert E. Hicks

Theses and Dissertations

Lung fluid dynamics is a well studied topic and relevant in the field of research surrounding patients with Chronic Obstructive Pulmonary Disease (COPD) and cystic fibrosis. However, the literature on the mathematical description of the net pulmonary fluid transport in the case of constricting and expanding airways is scarce. In this paper we aim to address how breathing contributes to airways clearance in patients with pulmonary diseases such as COPD and CF in which cilia do not function properly. We begin with the flow of a fluid-filled tube with rigid walls of fixed radius and the effects of gravity being …

Examining Parent Behavior And Adolescent Outcomes In A Pediatric Obesity Intervention, Madison W. Weinstock

Theses and Dissertations

Pediatric obesity is a major public health concern that affects over 14.4 million children and adolescents in the United States. Multiple short- and long-term health complications are associated with obesity. Therefore, effective treatment methods are needed in order to ameliorate the effects of said complications, particularly among adolescents. This dissertation investigated potential associations between parent eating behaviors and the outcomes of adolescents enrolled in a pediatric weight loss trial (TEENS+; PI: Bean, R21HD084930). The TEENS+ intervention offered a comprehensive behavioral weight intervention for parent-adolescent dyads. Given the well-established importance of parents in the development of an adolescent’s health behavior, this …

Life After Discharge: Predicting Longitudinal Trajectories Of Community Integration And Global Functioning In Black Individual With Traumatic Brain Injury, Chimdindu Ohayagha

Theses and Dissertations

The onset of traumatic brain injury (TBI) begins a chronic health pathway that contributes to various impairments and comorbidities across the lifespan. Common consequences of TBI include mental health issues, cognitive impairments, and reduced functional independence, all of which impact how an individual integrates into their community. Community integration is a primary goal for rehabilitation after TBI. Studies show that racially/ethnically minoritized individuals have a higher incidence of TBI, higher rates of mortality, and report poorer functional and community integration outcomes. Limited studies have explored longitudinal outcomes of community integration in a Black-only sample of individuals with TBI. Additionally, no …

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 …

The Patient Experience Of Language Discordance And Interpreter Services In The Emergency Department, Keri L. Baker

Theses and Dissertations

Background: Clear communication is critical to the interaction of a patient and medical provider. For non-English speaking patients, language discordance, described as the lack of proficiency in a shared language, with the medical team results in a poor patient experience and poor patient outcomes. The predominant solution to language discordance is the use of interpreter services, however these services are underused in the emergency department (ED). Studies examining underuse of interpreter services have primarily focused on the clinician and little is known about the patient’s influence on the use of interpreter services.

Methods: Semi-structured interviews were conducted with 12 Spanish-speaking …

Mechanistic Analysis Of Four-Way Dna Junctions And Cytokine-Binding Aptamers For Therapeutic Interventions, Roaa S. Mahmoud

Theses and Dissertations

DNA is inherently dynamic and topologically diverse and can fold into many different structures. Besides the canonical Watson-Crick structure, other higher-order structures such as G-quadruplexes (G4), i-motifs (iM), and four-way DNA junctions are possible. Although these high-order DNA structures are known to form transiently, they are important due to the crucial roles they play in many cellular processes including DNA replication, recombination, and repair. Among these DNA structures, 4-way junctions (also known as Holliday junctions, HJ) which are formed during the repair of double-strand DNA breaks (DSBs) and interact with proteins have garnered significant attention due to their central role …

Redesign, Evaluation, And Validation Of A Commercially Viable High-Resolution Melt Based Mixture Screening Tool, Chastyn Smith

Theses and Dissertations

Analysis of evidentiary samples containing DNA from multiple contributors (“mixtures”) is a time intensive process for a forensic analyst and one where the contributor nature of a sample is not revealed until the end of the traditional forensic workflow. Often, at this stage, retesting or additional testing of mixture samples may not be possible, particularly if the DNA collection device did not preserve the DNA well enough; consequently leaving only trace amounts of a contributor’s DNA present. Thus, a new collection device that would allow for the increased preservation/integrity of evidentiary samples as well as a method that would allow …

Polyvictimization In Context: Identifying Patterns Of Peer, Dating, And Community Violence Among Black Early Adolescents, Carine Leslie

Theses and Dissertations

Early adolescents exposed to multiple forms of victimization (“polyvictimization”) may experience a number of detrimental psychosocial outcomes. Some person-centered research has identified victimization subgroups among adolescents but have not examined the overlap of peer, dating, and community victimization among Black early adolescents living in economically disadvantaged urban communities. Thus, this study empirically identifies victimization profiles in a sample of Black early adolescents to ascertain the patterns and correlates of polyvictimization. The present study aimed to (a) identify subgroups of Black early adolescents based on their frequency of peer, dating, and community victimization using latent profile analyses, and (b) evaluate the …

An Ecocritical Approach To Fyodor Abramov's Story "What Do The Horses Cry About", Badegül Can Emir

Khazar Journal of Humanities and Social Sciences

Human's destructive behaviors toward the environment also harm animals. Fyodor Abramov's story, “What Do The Horses Cry About”. focuses on this issue. While this story reflects the world through the eyes of an animal, it reveals people's changing behaviors towards animals. The study tries to read the changing attitude of man toward nature in the modern age on the axis of Fyodor Abramov's story called “What Do The Horses Cry About”. On the other hand, it tries to understand how the relationship between the human and other living things has penetrated the fiction of the story. It shall be emphasized …

Facilitative And Competitive Interactions Among Dune Grass Species In Monoculture And Polyculture Communities, Anne M. Sciolino

Theses and Dissertations

Coastal dunes are natural barriers between land and sea and are imperative to the protection and preservation of inland ecosystems and human infrastructure. However, due to global warming, seal level rise, and coastal development, coastal dunes are under constant threat of destruction. Restoration efforts have been implemented to rebuild the protective function of dunes through the planting of dune building grasses. Dune grasses build and maintain these vital sand dunes. However, little is known about facilitative and competitive relationships among the grasses. In order to maximize restoration efforts, research is needed to better understand the biotic interactions among restorative grass …

Correlates Of Coffee And Energy Drink Use Among Individuals With Severe Alcohol Use Disorder, Enkelejda Ngjelina

Theses and Dissertations

Research on caffeine consumption among college students and young adults has primarily focused on caffeinated energy drinks (EDs) and their combination with alcohol, demonstrating a strong association with heavy and problematic alcohol use. However, little attention has been directed toward older adults. Furthermore, studies have shown that regular ED consumers are more likely to meet the criteria for alcohol dependence compared to their peers. Despite this association, little is known about ED consumption among individuals with Alcohol Use Disorder (AUD), particularly those undergoing treatment, and even less is understood about other caffeine sources such as coffee. This study aimed to …