Interferon Gamma Signaling In Ovarian Cancer Cells, Bijaya Gaire

Theses and Dissertations

Interferon gamma (IFNγ) is a pleiotropic cytokine that can have, depending on the cellular and molecular context, both anti-tumor and pro-tumorigenic functions. IFNγ expression can be induced in cancer cells in response to radiation therapy or immune checkpoint blockade used in cancer treatment. We have previously shown that IFNγ induces expression of the Bcl3 proto-oncogene in ovarian cancer (OC) cells, resulting in their increased proliferation and migration, but the mechanisms are unknown. Here, I demonstrate that the IFNγ-induced Bcl3 expression is dependent on JAK1 and STAT1 signaling, and on p65 NFkB. Furthermore, my data show that the IFNγ-induced Bcl3 expression …

Cytotoxicity Of Copper (Ii) Octanoate On Mouse Hippocampal Astrocytes, Ali A. Shohatee

Theses and Dissertations

Copper, as an essential trace element, is crucial for various biological processes but has also been utilized as a constituent of various pesticides for decades. Copper (II) octanoate is a pesticide utilized as a fungicide and is approved for use in the production of certified organic foods. Previous studies have implicated copper as an inducer of oxidative stress and activator of the Nrf2-ARE pathway. Nrf2 is essential in regulating the transcription of various genes to alleviate toxicity such as those involved in glutathione synthesis and detoxification. Due to the limited toxicological data, this study into the potential induction of oxidative …

The Role Of Child Maltreatment On Personality From Adolescence To Young Adulthood, Morgan T. Cohen

Theses and Dissertations

Historically, a defining feature of personality characteristics has been their stability and consistency across time. However, research over the past decade has established patterns of personality change across the lifespan, with the most mean-level trait change occurring between 20 to 40 years old (Roberts & Mroczek, 2009), making young adulthood a fruitful developmental period to study personality change. There are several factors that can influence personality trait change and some literature has suggested that major life events such as childhood adversity can impact the stability and change of personality traits across time. The present study uses two waves of data …

Animal Instinct: Radical Black Feminism And The Virtue Of The Demonic, Amity S. Nathaniel

Theses and Dissertations

The impossible strive towards “human” has dominated much of Black feminist studies, but there are scholars such as Sylvia Wynter, Zakiyyah Iman Jackson, Alex Weheliye, and Octavia Butler who've re-configured the concept of humanity in their work by embracing different species and technologies that could provide liberation for Black women. My dissertation explores these new spaces, using Wynter’s “demonic ground” theory as a backbone, to conceptualize Black post-humanism, animality, and the embracing of the “demonic” as radical tools of empowerment. My dissertation aims to establish the consistent and perpetual violence that Black women—from past to present—have endured by living on …

Regulation Of P53 By Trpm6 And Trpm7, Thomas Whitbread

Theses and Dissertations

TRPM6 and TRPM7 are two divalent metal cation channels that also possess a serine/threonine kinase domain. They both play critical roles in cellular and organismal metal homeostasis, and are necessary for proper embryonic development and human health. They may function independently in homomeric units, or act together as heterotetramers that display unique characteristics compared to the homomeric channels. These channel-kinases have increasingly been linked to cancer, displaying altered expression levels in a variety of human cancers and contributing to disease progression. Prior work has shown that TRPM6 and TRPM7 can participate in cancer-related signaling pathways. Here, the potential for TRPM6 …

Evaluating How Acidic Solutions Affect The Microhardness Of Bioceramic Sealers, Colton Fischer

Theses and Dissertations

Introduction: With growing use of bioceramic sealers (BCS) in root canal therapy, there have been challenges when retreating BCS cases. Weak acids may be effective in removing BCS and their efficacy as a solvent can be measured by their influence on the microhardness of BCS. Microhardness can be used as an indirect measurement of material hardness. The purpose of this study was to investigate the microhardness of BCS when placed in contact with various acidic solutions to assess their potential use as a solvent for retreatment procedures.

Methods: EndoSequence BC Sealer (Brasseler USA) was injected into four 10 × 3mm …

Exploring The Impact Of Covid-19 On Adults With Intellectual And Developmental Disabilities In The United States, Sarah Lineberry

Theses and Dissertations

Like most disasters, the COVID-19 pandemic has disproportionately impacted people from historically marginalized communities. People with intellectual and developmental disabilities (IDD) have faced higher rates of infection, hospitalization, and death compared to people without disabilities, as well as significant disruptions to the services that support them to participate in the community. A relative lack of research about the experiences of people with IDD may have contributed to this risk and continues to limit our understanding of the impacts of COVID-19. This three-paper dissertation is guided by the theory of epistemic injustice (Fricker, 2007) to understand the impacts of COVID-19 on …

Bet Inhibition As A Strategy For Enhancing The Response To Estrogen Antagonism/Cdk4-6 Inhibition In Er Positive Breast Cancer, Ahmed M. Elshazly

Theses and Dissertations

Breast cancer is the most commonly occurring malignancy in females, accounting for the second most common cause of cancer-related deaths. ER+ breast cancer constitutes approximately 70% of all breast cancer cases. The standard care of therapy comprises endocrine antagonists together with adjuvant therapy; however, the recovery from the therapy-suppressive state is associated with further drug resistance together with increasing tumor aggressiveness and with possible metastasis. Autophagy induction has been shown to be associated with various therapeutic modalities, with different functions, including cytotoxic, cytoprotective, cytostatic as well as non-protective forms. The triggering of autophagy may be responsible for resistance development and …

Effects Of Hiv-1 Tat And Opiates On Gene Regulation Of Oligodendrocyte Lineage Cells: Identification Of Myrf As A Novel Target, Kelly M. Flounlacker

Theses and Dissertations

HIV-associated neurocognitive disorders remain pervasive even with increased efficacy/use of antiretroviral therapies. Opioid use/abuse among HIV+ individuals is documented to exacerbate deficits. White matter (WM) alterations (myelin pallor, volume/structural) detected by diffusion tensor imaging, are common observations in HIV+ individuals. Using transgenic mice expressing HIV-1 Tat, we examined effects of 2-6 weeks of Tat/morphine exposure on WM using genomic/biochemical methods. RNA sequencing of striatal tissue after 2-weeks revealed robust changes in mRNAs associated with oligodendrocyte populations/myelin integrity, including Transferrin, Ndrg1, and myelin regulatory factor (Myrf/Mrf), an oligodendrocyte-specific transcription factor involved in differentiation/maturation. Immunoblots conducted after 6-weeks exposure in …

Quantifying Insect Emergence In Tidal Freshwaters And The Importance Of Aquatic Prey In Wetland-Dependent Songbird Diet, Samantha L. Rogers

Theses and Dissertations

Insectivorous birds and their arthropod prey are experiencing widespread population declines, driven largely by anthropogenic disturbance and climate change. For wetland-dependent insectivores that consume a mixture of terrestrial and aquatic insects, understanding the availability, consumption, and nutritional qualities of aquatic diet subsidies is important for conservation. I use prothonotary warblers (Protonotaria citrea) as a model species throughout this work, because their breeding season aligns with aquatic insect emergence and they include aquatic insects when provisioning nestlings. In the first chapter, I estimate aquatic insect emergence from tidal freshwaters, which are understudied compared to nontidal systems. Using continuous field …

How Stromal Interactions Play A Role In The Quest For Human Papillomavirus Specific Cancer Therapeutics, Alexis-Leigh A. Fakunmoju

Theses and Dissertations

High-risk human papillomaviruses (HPV), like HPV16 and HPV18, are associated with malignant cancer growth within the oropharynx and cervix. Globally, HPV-induced cancers, including oropharyngeal and cervical cancers, contribute 5% to the overwhelming burden of all cancers. HPV is highly transmissible by sexual contact via micro abrasions to the mucosa. Once exposure occurs, the virus begins replication and creates an intimate relationship with the host’s cellular proteins. While most HPV is cleared quickly by our immune system, persistent infections, or infections in immune compromised individuals, are susceptible to transformation and tumor progression. Early detection measures like PAP smears and preventable measures …

Radiation Shielding Effectiveness Of Hafnium Diboride (Hfb2) Reinforced Epoxy Composites For Enhanced Radiation Protection And Safety, Furkan Erdogan

Theses and Dissertations

This thesis investigates the radiation shielding effectiveness of hafnium diboride (HfB2) reinforced epoxy composites, with the aim of enhancing radiation protection and safety in various applications. The study focuses on the development and characterization of HfB2-epoxy composites with varying weight percentages of HfB2 nanoparticles, as well as on the evaluation of their shielding effectiveness against gamma rays and thermal neutrons. The radiation shielding performance of the composites is assessed using gamma-ray spectroscopy and neutron counting, and the neutron attenuation efficacy is compared with that of 5% borated high-dense polyethylene. The results indicate that the HfB2-epoxy composites exhibit promising radiation shielding …

Prospective Investigation Of Insomnia Symptoms And Sleep Duration As Risk Factors For Stroke Incidence And All-Cause Mortality In U.S Adult, Wendemi Sawadogo

Theses and Dissertations

Background and Objectives: Stroke is the second leading cause of death in the world. In the United States, on average, someone has a stroke every 40 seconds and someone dies as a result of stroke every 3.5 minutes. Identifying modifiable risk factors of stroke is therefore a public health priority. The purpose of this study was to investigate the extent to which insomnia symptoms and sleep duration contribute to stroke incidence, all-cause mortality, and explore potential causal pathways.

Methods: The Health and Retirement Study (HRS) and the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were …

Association Of Interpersonal Trauma And Polygenic Risk Scores With Depressive Symptoms In College Students, Rowan K. O'Hara

Theses and Dissertations

Major depression is considered a complex trait influenced by both polygenic risk factors and environmental exposures, such as childhood trauma. This study applied statistical genetic methods to calculate aggregate genetic risk for major depression to predict depressive symptoms scores in a college student sample. Data were from the Spit for Science (S4S) study in which college students from a large urban university self-reported interpersonal trauma (IPT) exposure prior to college and depressive symptoms from the past month (N = 7502; ancestry group: 20% African [AFR], 12% Admixed Americas [AMR], 10% East Asian [EAS], 49% European [EUR], 8% South Asian [SAS]). …

Enhancing Neuromorphic Computing With Advanced Spiking Neural Network Architectures, Paolo Gabriel Alejandro Cachi Delgado

Theses and Dissertations

This dissertation proposes ways to address current limitations of neuromorphic computing to create energy-efficient and adaptable systems for AI applications. It does so by designing novel spiking neural networks architectures that improve their performance. Specifically, the two proposed architectures address the issues of training complexity, hyperparameter selection, computational flexibility, and scarcity of neuromorphic training data. The first architecture uses auxiliary learning to improve training performance and data usage, while the second architecture leverages neuromodulation capability of spiking neurons to improve multitasking classification performance. The proposed architectures are tested on Intel's Loihi2 neuromorphic chip using several neuromorphic datasets, such as NMIST, …

Quantifying Fibronectin Mechanical Properties Using Antibody-Mediated Optical Tweezing (Amot), Caleb Dalton

Theses and Dissertations

Despite decades of investigations into fibronectin (FN) fibrillogenesis, fibril mechanics remain unclear. One of the most important roles for FN fibrils is in the arena of cellular mechanotransduction. Numerous studies have demonstrated that cells sense and respond to the mechanical properties of their surroundings; since FN fibrils are a major constituent of the ECM that links cells to their surroundings, mechanotransduction cannot be fully understood without understanding the mechanical properties of FN fibrils. In this proposal, a novel biomechanical assay is developed to probe isolated FN fibrils and quantify their response to specific loading conditions. This will be accomplished by …

“It's Just Not Enough”: Examining The Experiences Of School-Based Sexual Health Education And Conversation Engagement With Trusted Adults Among Black Boys In Richmond, Va, Sharyn A. Dougherty

Theses and Dissertations

The Centers for Disease Control and Prevention estimate that youth make up a quarter of the sexually active population, yet account for half of the 20 million new sexually transmitted infections in the United States.In 2021, youth age 15-19 living in Virginia’s central region, which includes the Richmond Metropolitan area, had the second highest number of chlamydia cases and fourth highest number of gonorrhea cases among all age groups, with the highest rates among Black youth. The aim of this study is to explore the experiences of Black youth in Richmond, VA with school-based sexual health education (SHE) and their …

Integrating Historically Marginalized Students’ Funds Of Knowledge For Culturally Responsive Teaching And Learning, Martinique Ann Sealy

Theses and Dissertations

The United States historically has not always recognized the unique knowledge, or Funds of Knowledge (FoK; Moll et. al, 1992) that Black (and other historically marginalized) students’ have as assets to classroom learning and much of today’s mainstream curriculum represents White cultural norms as the basis (Sjursen, 2021). Because of this reality, marginalized students must navigate mainstream cultural norms alongside their own culture to be successful in the classroom. This three-paper dissertation includes 1. a systematic literature review of Black U.S. k-8 students language and identity in relation to achievement, 2. a qualitative case study centered on middle school urban …

The Effect Of Strain And Drug Combinations On Ketamine's Locomotor Activating Effects In Rats, Caroline K. Flagler

Theses and Dissertations

Rationale: Initially developed as an anesthetic, ketamine is now used to treat a variety of disorders, including treatment resistant depression (TRD). While ketamine appears to be a breakthrough therapy for TRD, it has many use-limiting side effects, including abuse liability, psychotomimetic effects, and sedation. Utilizing ketamine in combination with other medications, such as the monoaminergic antidepressant desipramine (DSP), opioid antagonist naltrexone (NTX), and the NMDA receptor partial agonist D-cycloserine (DCS) may reduce side-effects resulting from ketamine therapy.

Objectives: The goal of this project was to study ketamine’s adverse effects using locomotor activation in an open field as a behavioral correlate …

Role Of The Ormdls In Keratinocytes, Souad Hatmi

Theses and Dissertations

The epidermis, the outermost layer of the skin, serves as a vital barrier protecting the body from environmental stressors, pathogens, and dehydration. Keratinocytes, the predominant cell type in the epidermis, play a central role in maintaining skin integrity and barrier function. In normal human skin, keratinocytes move from the basal layer to the stratum corneum, the top layer of the epidermis. In their travel, keratinocytes undergo a process of terminal differentiation, loss their ability to proliferate, secrete sphingolipids into the extracellular space, and gradually loss their nucleus and organelles. Sphingolipids, particularly ceramides, are key components of the intercellular lipid lamellae …

Computational Modeling Of Temporal Eeg Responses To Cyclic Binary Visual Stimulus Patterns, Connor M. Delaney

Theses and Dissertations

The human visual system serves as the basis for many modern computer vision and machine learning approaches. While detailed biophysical models of certain aspects of the visual system exist, little work has been done to develop an end-to-end model from the visual stimulus to the signals generated at the visual cortex measured via the scalp electroencephalogram (EEG). The creation of such a model would not only provide a better understanding of the visual processing pathways but would also facilitate the design and evaluation of more robust visual stimuli for brain-computer interfaces (BCIs). A novel experiment was designed and conducted where …

Evaluating The Influence Of Concurrently Available Non-Drug Reinforcers On Drug Reinforcement Using Sophisticated Preclinical Models Of Substance Use Disorder, Madison M. Marcus

Theses and Dissertations

The maladaptive allocation of behavior towards cocaine and away from other concurrently available non-drug reinforcers (e.g., family, health, work, etc.) is a key characteristic of cocaine use disorder (CUD) that is embedded into multiple diagnostic criteria for CUD. Accordingly, basic research conducted in a drug-vs-food “choice” context has improved our fundamental knowledge of the behavioral and neurobiological mechanisms of drug reinforcement. However, to date, these preclinical studies have only been conducted with food as the alternative reinforcer. The extent to which other non-drug reinforcers compete with cocaine-taking behavior is unknown. The studies in this dissertation establish two sophisticated discrete-trial cocaine-vs-alternative …

Quantitative And Molecular Genetic Analyses Of Brain Structure, Substance Use, And Posttraumatic Stress Phenotypes: Data From Children, Adolescents And Adults, Daniel Bustamante

Theses and Dissertations

Abstract

QUANTITATIVE AND MOLECULAR GENETIC ANALYSES OF BRAIN-IMAGING, SUBSTANCE USE, AND POSTTRAUMATIC STRESS PHENOTYPES: DATA FROM CHILDREN, ADOLESCENTS AND ADULTS

By Daniel Bustamante, B.S., B.A.

Doctoral dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Integrative Life Sciences – Behavioral and Statistical Genetics at Virginia Commonwealth University.

Virginia Commonwealth University, 2023.

Dissertation directors: Michael C. Neale, Ph.D., Banks Distinguished Professor of Psychiatry & Human and Molecular Genetics; and, Ananda B. Amstadter, Ph.D., Professor of Psychiatry, Psychology, & Human and Molecular Genetics.

Substance use (SU) and posttraumatic stress disorder (PTSD) phenotypes are comorbid, share …

Novel Strategies In Head And Neck Tumor Therapy; Contribution Of Senescence In Therapy Response, And Resistance Development After Cisplatin Treatment, Fereshteh Ahmadinejad

Theses and Dissertations

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local, and distant metastasis and disease relapse as well as cisplatin-induced resistance are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild- type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further established a cisplatin-resistant cell line from HN30 parental cell line that underwent brief senescence …

Advancing Our Understanding On The Role Of Bromodomain Phd-Finger Transcription Factor (Bptf) In Cancer Through The Analysis Of Publicly Available Databases., Preksha Jerajani

Theses and Dissertations

The initiation and progression of cancer are significantly influenced by genetic factors, and despite ongoing research, a definite cure for this disease remains elusive. Over time, researchers have explored various genes as potential targets for treating various types of cancer, and numerous innovative therapies continue to be developed. General chemotherapies face their own challenges like recurrence, while cancer specific drugs face the challenge of metastasis. Therefore, therapeutic strategies have slowly started to shift towards comprehending the pathways and corresponding genes that may be implicated in multiple types of cancer, with the aim of identifying more effective targets for drug development. …

Examining The Unique Experiences Of Underrepresented Minority Stem Faculty: How Discrimination, Microaggression, And Allyship Relate To Sense Of Relatedness, Motivation, And Perceived Success, Mojdeh J. Mardani

Theses and Dissertations

Results from empirical studies reveal underrepresented minority, URM, university faculty experience biases, discrimination, and affiliated stress that can impact multiple aspects of their work such as research performance (Fisher et al., 2019; O’Meara et al., 2020; Stolzenberg et al., 2019; Stupnisky et al., 2015), isolation, and lessened relatedness to colleagues (Zambrana et al., 2017; 2021), which may affect their motivation to conduct research. This dissertation is a collection of three separate but complementary research studies examining the effects of various forms of discrimination and the role of allyship in shaping the motivation of URM faculty members to engage in research, …

Application Of Artificial Treatment Wetland Systems In The English Coulee, Michael Anthony Rosati

Theses and Dissertations

Artificial treatment wetlands are commonly used for treating urban stormwater runoffand surface waters affected by agricultural runoff. While this method is well-established, its effectiveness can vary based on environmental, design, and hydraulic factors. In Grand Forks, ND, the English Coulee, a hydraulically altered class III stream, is currently experiencing elevated nutrient pollution, specifically nitrates and phosphates. Implementing a floating treatment wetland (FTW) system in the English Coulee is a potential solution. This paper analyzes the feasibility and requirements for a 4.64 ha FTW to achieve a minimum of 50% nutrient removal, utilizing comprehensive modeling approaches. Through HEC-HMS and HECRAS simulations, …

Quantification Of Rigidity And Synthesis Of Cyclobutane Bisimide Building Blocks, Joseph Earl Mcgilligan Robertson

Theses and Dissertations

The quantification of a molecule’s conformational rigidity was achieved via development of a new measure called the Rigidity Factor, Rg_f. This value is a unit interval wherein molecules with corresponding Rg_f values closer to 1 are rigid and values closer to 0 are more flexible. The value is determined as a ratio between the molecule’s Van der Waals volume, V_W, and it’s Van der Waals potential volume, VWpot. The V_Wpot was defined as the minimum total volume occupied by a rotamer ensemble of the molecule which has been aligned according to the RMSD for …

Machine Learning And Data Mining To Validate The Prognostics And Predictive Breast Cancer Biomarkers On A Large Racially Diverse Population, Kalli Scheafer

Theses and Dissertations

Breast cancer biomarkers have great potential in providing clinicians more individualized information about the composition and outcomes of a patient’s breast cancer. However, many breast cancer biomarkers have not been evaluated on a large scale or in groups of patients with diverse characteristics, leading to difficulty in their translation to having an impact on patients. In this study, we compile a large, pooled breast cancer patient data cohort and evaluate breast cancer biomarkers on patients with diverse characteristics. Biomarkers are found to have varying expression patterns within the different breast cancer subtypes, validating the need to evaluate biomarkers on patient …

Exploring Zinc Amido-Oxazolinate Complexes As Catalysts For Ring Opening Polymerization (Rop) And Ring Opening Co-Polymerization (Rocop), Muneer Shaik

Theses and Dissertations

This research aims to explore the potential of zinc amido-oxazolinate complexes as catalysts for ring opening polymerization (ROP) and ring opening copolymerization (ROCOP). ROP is a method for synthesizing polymers by opening cyclic monomers, while ROCOP involves using two different monomers to create a copolymer. The ROP of lactones is a well-established method for the synthesis of polyesters, whereas the ROCOP of epoxides and cyclic anhydrides is a more recent development. Zinc amido-oxazolinate complexes are a promising class of catalysts due to their tunable electronic properties and high reactivity. The catalytic activity of these complexes can be tuned by modifying …