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Reactive Oxygen Species Production In Head Regeneration Of Planaria From Cadmium Exposure, Natalie Gonzalez

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Exposure to cadmium, a pervasive neurotoxic chemical found in our environment, poses significant health risks, disrupting various physiological systems and fostering carcinogenesis. Commonly found in everyday items like cigarettes, batteries, and plastics, cadmium disrupts the equilibrium between reactive oxygen species (ROS) production and cellular repair mechanisms, culminating in oxidative stress and potential cell damage. In toxicological and pharmaceutical research, planarians offer valuable insight for understanding how exposure to chemicals akin to human scenarios can alter biological systems. This experiment addresses the effect cadmium chloride (CdCl₂) has on planarian regeneration and whether antioxidants can mitigate those adverse outcomes. Our …

Bridging Perspectives Through Dialogic Exchanges: Intercultural Communication In Disability Support Services, Danielle Jerolds

Research Papers

This research report delves into the complexities of the disabled student body accessing accommodations and seeking needs to be met specifically pertaining to disability support services (DSS) as a campus resource. It employs fictional dialogues and composite characters to vividly illustrate the interactions between students, parents, and DSS staff, highlighting the challenges in communication and accommodation. An intercultural communication perspective is used to pave the way to think about difference, specifically how it pertains to disability as an identity categorization. The paper contrasts the social and medical models of disability, emphasizing the need for a nuanced understanding of these perspectives. …

Animals In The Courtroom, Challie Facemire, Clayton Kinsey

Journal of Law and Policy

Law centers on the experience of the human species. Yet, emerging scholarly and public conversations advocate for bringing animals into spaces once assumed to be human, a growing field known as animal studies. This Article is the first to experiment with how to integrate the more-than-human experience into the courtroom. It specifically reimagines canonical legal cases from the perspective of the animals involved in them. Through the perspective of the animals at issue, it examines cases in which animal interests were considered by human advocates and decided by human judges. This novel technique of de-centering the human requires developing a …

Risk Evaluation In Occupational Safety And Health Research: Results From A Benchmarking Exercise Of Federal And Academic Irbs, Sarah A Felknor, Jessica M K Streit, Angela M Morley, John D Piacentino

Faculty, Staff and Student Publications

OBJECTIVE: Research involving working populations can pose unique ethical and risk evaluation challenges. The purpose of this benchmarking project was to assess how federal agencies and academic institutions approach the interpretation and application of key risk evaluation concepts in research involving workers in their places of employment.

METHODS: Key informant interviews were conducted to ascertain current practices related to assessing soundness of research design, determining risk reasonableness and research relatedness of risks, and evaluating the risk of noninvasive clinical tests in occupational settings.

RESULTS: There were noteworthy commonalities among the approaches described to review and address critical aspects of risk …

The Role Of Anti-Viral Immune Response On The Therapeutic Efficacy Of Oncolytic Virotherapy For High-Grade Gliomas, Dong Ho Shin Phd

Dissertations and Theses (Open Access)

Currently, there is no effective treatment for high-grade gliomas that are resistant to conventional treatments and immune checkpoint blockade therapies. Oncolytic viruses offer a new treatment modality by selectively replicating in cancer cells and inducing anti-tumor immunity. Among these viruses, the oncolytic adenovirus Delta-24-RGD has shown safety and efficacy in clinical trials for high-grade gliomas. Strategies to improve the efficacy of oncolytic virotherapy have aimed to heighten the immunogenicity of oncolytic viruses, either by incorporating immune-stimulating transgenes or by combining treatments with immune checkpoint blockades. However, such strategies may inadvertently trigger heightened immune responses to viral antigens, which may not …

Identification Of The Phosphatase Nudt5 As A Target For The Treatment Of Triple Negative Breast Cancer, Jing Qian

Dissertations and Theses (Open Access)

Abstract

Background: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression, as well as the lack of overexpression of the human epidermal growth factor receptor 2 (HER2). Unlike ER-positive and HER2-positive tumors that can be treated with hormone therapy or HER2-targeted treatment, respectively, triple-negative breast cancer (TNBC) poses a challenge with limited treatment alternatives for affected women. The currently FDA-approved systemic regimens for TNBC patients remain as conventional chemotherapy and PARP inhibitors (only applicable for a subset of BRCA-mutated TNBC patients). Consequently, our …

Investigating The Role Of The Gut Microbiota On Immune Checkpoint Inhibitor-Mediated Colitis, Taylor Halsey, Robert Jenq

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs) have been revolutionary in the fight against cancer by recruiting the host immune system as an agent for attack on malignant cells. Unfortunately, immune-related adverse events (irAEs), including ICI-mediated colitis (IMC), are common side effects that result from immune cell mediated damage on healthy tissues. Recent studies have highlighted a role for the gut microbiota in modulating ICI-mediated anti-tumor responses, but less is known regarding how the gut microbiota may impact on irAEs. Considering that the gastrointestinal tract harbors thousands of unique microbial species, many of which are known to modulate the immune system, microbes and …

Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu

Dissertations and Theses (Open Access)

PTDSS1 (Phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with increased expression of cytolytic function related genes in CD8⁺ T cells and increased frequency of an iNOS⁺ myeloid subset. A gene signature derived from the iNOS⁺ myeloid …

Mapping The Neural Circuits That Underlie Metabolic Vs. Emotional Regulation Of Food-Seeking Behavior, Xu Zhang

Dissertations and Theses (Open Access)

Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food …

Cord Blood-Derived Invariant Natural Killer T Cells As A Platform For Allogeneic Chimeric Antigen Receptor Cell Therapy, Maison Grefe

Dissertations and Theses (Open Access)

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematopoietic malignancies achieving >50% complete response rates in numerous refractory/relapsed B cell malignancies. However, there are challenges that hinder CAR-T efficacy and bar the broader use of this therapy in patients. One approach to address these challenges is to create a safe allogeneic CAR cell product by using cells that do not cause graft versus host disease (GvHD). Invariant natural killer T (iNKT) cells are an ideal candidate as they are restricted to the monomorphic CD1d protein in contrast to HLA restricted αβ-T cells and therefore are safe in …

Retinoid X Receptor As A Mediator Of Post Stroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Macrophages, Shun-Ming Ting

Dissertations and Theses (Open Access)

After stroke, microglia (MG) and blood-derived macrophages, together (MF), clear dead cells and cellular debris in the infarcted brain through phagocytosis. However, the phagocytic capability of MF declines with age. Age-related changes in MF phenotype also include overactive inflammatory responses to stroke-induced brain injury, altogether resulting in poor recovery after stroke. Retinoid-X-receptor (RXR) is a pleiotropic transcription factor. Our studies suggest that RXRa enhances MF phagocytic functions, reduces inflammatory responses, and improves post-stroke recovery. To establish phenotypes of aging MF, MG were MACS-sorted from the brains of young adults (2-4 months old) and aged (18-20 months old) mice for transcriptomic …

Histone Lysine Methyltransferase Nsd3 Governs Transcriptional Programs That Drive Pancreatic Neuroendocrine Tumors (Pannets), Mary Esmeralda Fuentes

Dissertations and Theses (Open Access)

Pancreatic Neuroendocrine Tumors (PanNETs) are the most common and lethal neuroendocrine malignancies where treatments used in advanced patients have limited efficacy, adverse side effects, and acquire resistance. Thus, there is a critical need to uncover novel precision therapeutics for PanNET patients. Additionally, pre-clinical models that more accurately represent disease are an urgent necessity for translational studies.

This dissertation directly addresses these challenges by identifying histone lysine methyltransferase (KMT) NSD3 as a critical oncogenic driver of PanNETs through di-methylation of histone H3K36 (H3K36me2).

The findings shown in this body of work indicate that H3K36 methylation by NSD3 functions as a transcriptional …

Rna Knockdown Of The Immune Checkpoint Vista Promotes Tumor Regression, Brittany Morrow, Brittany A. Morrow

Dissertations and Theses (Open Access)

Blockade of negative immune regulators for example CTLA-4, and PD-1/PD-L1 has proven to be a clinically effective strategy to enhance tumor specific immune responses. Recently discovered novel immunoglobulin superfamily ligand V-domain Ig suppressor of T-cell Activation (VISTA) is a new target for immunotherapy. VISTA expression is specifically upregulated on tumor infiltrating myeloid cells such as dendritic cells (DCs), tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs). In addition, VISTA expression is increased on tumor-infiltrating regulatory T cells (Tregs) compared to those in the periphery. VISTA has been shown to suppress effector T cells through multiple mechanisms, primarily by …

Epiregulin As A Novel Target For Antibody-Drug Conjugate Development For The Treatment Of Colorectal Cancer, Joan Jacob

Dissertations and Theses (Open Access)

Antibody-drug conjugates (ADCs) are a fast-growing class of molecularly targeted therapies with 13 currently approved and over a 100 in clinical trials. ADCs consist of a monoclonal antibody (mAb) conjugated to a potent cytotoxic payload to selectively target tumor antigens highly expressed on the cell surface. ADC development has been limited in colorectal cancer (CRC) by the lack of novel and effective therapeutic targets. Epiregulin (EREG), is an epidermal growth factor receptor (EGFR) ligand that is highly expressed in CRCs of different subtypes and mutational statuses with low expression in normal tissues. Here, we have characterized the role of EREG …

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations and Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Interrogating Therapeutic Resistance To Oncogenic Krasg12c-Based Therapies In Colorectal Cancer, Oluwadara Coker

Dissertations and Theses (Open Access)

Colorectal cancer is the second leading cause of cancer-related deaths and the third most common cancer in the United States. Although KRAS is mutated in 50% of patients with metastatic CRC (mCRC), it has historically been a challenging therapeutic target. The recent approval of novel covalent inhibitors selective for KRASG12C mutation have entered the clinic, which has not only marked a major milestone in cancer drug discovery but has also intensified efforts to directly target other KRAS mutations that have also successfully entered the clinic. However, treatment-associated resistance mechanisms have long threatened to attenuate clinical benefit through either adaptive or …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations and Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

Syntaxin-3 Mediates Baseline And Stimulated Mucin Secretion, Brianne Wharton

Dissertations and Theses (Open Access)

There are two rates at which airway epithelial cells secrete mucin. The low baseline rate accounts for ciliary clearance, and the high stimulated rate obstructs airways in protection from helminths or in obstructive pulmonary diseases. The exocytosis of mucins occurs via the four-helix SNARE complex. The SNARE proteins contributing helices are the vesicle-SNARE VAMP, and the target-SNAREs SNAP and Syntaxin. Coiling of the complex fuses the granule and plasma membranes to release mucins into the extracellular space. The VAMP and SNAP isoforms mediating baseline and stimulated secretion are known, but the Syntaxin (Stx) isoform remains unknown.

Three candidate exocytic Stx, …

Molecular Basis Of Cell Membrane Adaption Against Daptomycin In Enterococcus Faecalis, April Nguyen

Dissertations and Theses (Open Access)

Daptomycin is a last-resort lipopeptide antibiotic that disrupts cell membrane (CM) and peptidoglycan homeostasis (Grein et al., 2020a; Müller et al., 2016a). Enterococcus faecalis has developed a sophisticated mechanism to avoid daptomycin killing by redistributing CM anionic phospholipids away from the septum. The CM changes are orchestrated by a three-component regulatory system, designated LiaFSR, with a possible contribution of cardiolipin synthase (Cls) (Cesar A Arias et al., 2011a; Khan et al., 2019b; Palmer et al., 2011a; Panesso et al., 2015a; Reyes et al., 2015a). However, the mechanism by which LiaFSR controls the cell membrane response and the role of Cls …

Dissecting The Relationship Between Mucin 5ac And The Lung/Gut Microbiome In The Pathogenesis Of K-Ras Mutant Lung Cancer, Maria T. Grimaldo

Dissertations and Theses (Open Access)

Non-small cell lung cancer, including its most common subtype, lung adenocarcinoma (LUAD), is the leading cause of cancer-related deaths worldwide. In LUAD patients, KRAS mutations are the most common oncogenic driver alteration. Given KRAS is upstream to many signaling pathways involved in cell survival and cytokine production, interventions against KRAS-mutant lung cancers are prone to develop acquired resistance. Thus, there is a need to develop alternate targeting strategies and test combination therapies for improved intervention. Previously, we have found that KRAS-mutant LUAD (KM-LUAD) patients whose tumors harbor high expression of Mucin 5 AC (MUC5AC), a main airway secretory mucin, have …

Using Pre-Trained Models For Vision-Language Understanding Tasks, Rui Cao

Dissertations and Theses Collection (Open Access)

In recent years, remarkable progress has been made in Artificial Intelligence (AI), with an increasing focus on integrating AI systems into people’s daily lives. In the context of our diverse world, research attention has shifted towards applying AI to multimodal understanding tasks. This thesis specifically addresses two key modalities, namely, vision and language, and explores Vision-Language Understanding (VLU).

In the past, addressing VLU tasks involved training distinct models from scratch using task-specific data. However, limited by the amount of training data, models may easily overfit the training data and fail to generalize. A recent breakthrough is the development of Pre-trained …

Chemical-Mediated Mate Attraction In Clover Root Curculio (Sitona Hispidulus F.), A Belowground Pest Of Forage Crops, Kristin Leutgeb

Undergraduate Honors Capstone Projects

Curculionid beetles are well known for their production of semiochemicals, including contact (e.g. cuticular hydrocarbons) and volatile pheromones that mediate conspecific attraction and mating. Clover root curculio (CRC; Sitona hispidulus) in particular is an emergent, soil-borne pest of significant concern to producers of alfalfa and other leguminous crops in the United States. Producers have few control options for CRC and a greater understanding of chemical-mediated attraction in this species can potentially improve the sustainability of its management. To examine which chemical cues are important for affecting the behavior of CRC and whether there are sex-based differences in response, I …

An In Vitro Investigation Of Urothelial Cell Function In Response To Hypoxia And Pressure In Relation To Bladder Outlet Obstruction, Britney Hudson

All Dissertations

Bladder outlet obstruction (BOO) is a prevalent urological condition and can be characterized by the presence of lower urinary tract symptoms (LUTS), such as hesitancy, weak stream, and nocturia. The main cause of BOO is a partial blockage of the urethra, which results in elevated voiding pressure, high storage pressure, and tissue ischemia, which are thought to be the triggers of bladder inflammation and subsequent fibrosis. Often patients do not seek treatment until the conditions get severe. Thus, it would be ideal to have an early diagnostic tool to detect changes in the bladder due to BOO. Extracellular vesicles (EVs) …

Toxicokinetics And Toxicodynamics Of Radium-226 In An Estuarine Sentinel Species Geukensia Demissa, Sarah Donaher

All Dissertations

The historical use of radioluminescent objects, most notably those containing radium-226 (²²⁶Ra)-based paint, has contributed to contemporary environmental contamination of radioactive material, often near naval installations or other military-associated coastal sites. The risk to both human and environmental health from this small-scale, discrete radioactive material is challenging to predict due to large uncertainties in the source terms, bioavailability, and toxicity of these objects. The objective of this study was to provide information on the accumulation and toxicity of acute ²²⁶Ra exposure in a sentinel species to improve risk assessments for small-scale, coastal radiological contamination. The sentinel species …

A Rhetorical-Sociological Understanding Of Emotion, Amy Boone

All Dissertations

This project presents a rhetorical-sociological understanding of emotion while foregrounding the place and role of language. Born from Sara Ahmed’s work in The Cultural Politics of Emotion, it presents a simplified equation (contact + orientation = emotion) as both a prescriptive and descriptive formula for making sense of human emotional experience. Starting with an exploration of the difficult-to-understand affect system, this dissertation identifies both rhetoric and affect as energies which cannot be understood apart from their traces, the things they move, produce, and become. As a way to get at these often-invisible forces, two trace studies are conducted which explore …

Additive Manufacturing With Bioresorbable Polymers: Process-Structure-Property Relationships For Biomimetic Tissue Scaffolds, Clayton Joseph Culbreath

All Dissertations

Tissue engineering has a base requirement of scaffold structures to support cell growth, proliferation, and regeneration. However, attempts to use artificial scaffold structures have often fallen short of clinical needs to justify the change away from the established, biologic-based current standard of care. Based on the limited number of successful tissue scaffolds produced by material extrusion modes of additive manufacturing, fused filament 3d printing and electrospinning, critical design specifications for a tissue scaffold are six minimum requirements: 1) biocompatibility, 2) porosity, 3) mechanical properties, 4) bioresorbable medical grade materials, 5) bioactivity, and 6) appropriately scaled production methods compliant with medical …

Exploring Novel Nutrient Acquisition Mechanisms For Maintaining Energy Metabolism In Toxoplasma Gondii, Melanie Key

All Dissertations

Toxoplasma gondii is an infectious intracellular parasite that establishes infection within various mammalian hosts, including humans. Toxoplasma infects approximately one-third of the global population, making it an impactful pathogen of study. T. gondii is the causative agent of toxoplasmosis, an opportunistic infection that causes severe illness or fatality in immunocompromised individuals or pregnant women. The parasite possesses a very effective invasion strategy, allowing it to cross different tissue types to disseminate infection across the placental and blood-brain barrier. Although there are a few treatments for acute toxoplasmosis, these drugs can produce adverse side effects. These options are not effective against …

An Exploration Of The Efficacy Of Virtual Agents Within Smartphone Mental Health Applications, Stephanie Six

All Dissertations

The prevalence of depression in the U.S. has increased over the past decade, leading to an all-time-high during the COVID-19 pandemic (WHO, 2022). With this increase, the number of mental health applications (MHealth apps) on virtual e-stores increases in tandem. Despite this expanding number of MHealth apps, few demonstrate a foundation in empirical research. One design factor that may influence usability and effectiveness is the inclusion of virtual agents. Three studies were conducted to investigate users’ preferences for a variety of characteristics associated with virtual agents. In Experiment 1, users completed a single-session, three-stage CBT-based interaction with virtual characters and …

Evolution And Biogeography Of High Appalachian Rove Beetles (Staphylinidae), Adam Haberski

All Dissertations

The southern Appalachian Mountains are a region of great species richness and a center of endemism in many taxa, including flightless arthropods. High elevation refugia have facilitated the persistence of ancient lineages (paleoendemism) and in situ speciation (neoendemism), but their ubiquity, timing, and relative importance is unknown. Congruent patterns among co-distributed, but independent taxa might illuminate common drivers of Appalachian endemism. In this dissertation, I investigated the influence of allopatric speciation, geography, and paleoclimate events on the diversification of endemic species in two genera of rove beetles (Coleoptera, Staphylinidae), Lathrobium Gravenhorst and Ischnosoma Stephens, using an integrative morphological and molecular …

Tin-Silver As A Novel Biodegradable Metallic Biomaterial, Charley Goodwin

All Dissertations

The Essure device is a non-hormonal, minimally-invasive, permanent female sterilization implant, removed from the market due to an increase in adverse events, hypothesized to be caused by corrosion of the Sn-Ag component of the implant. The goals of this dissertation were to first develop implant retrieval methods for Essure devices and surrounding tissue, documenting signs of degradation and metallic degradation products, then to characterize the electrochemical behavior of Sn-Ag in biologically representative environments and finally, to assess the biological interaction of Sn-Ag. Retrieval analyses developed successful methods, qualifying the degree of corrosion, primarily of the Sn-Ag component and finding Sn …