Digital Commons Network^™

Exploring The Role Of The Arginine-Methylation Writer-Reader Pair Prmt5/Snd1 In Jak2-Mutant Myeloproliferative Neoplasms, Rocio Rubiano

Dissertations and Theses (Open Access)

Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible …

The Role Of An Ultraconserved Long Non-Coding Rna In B-Cell Lymphomagenesis, Swati Mohapatra

Dissertations and Theses (Open Access)

Ultraconserved regions (UCRs) are genomic segments with perfect (100%) conservation between the orthologous regions of human, rat, and mouse genomes. UCRs can be transcribed into mono-exonic long non-coding RNAs (lncRNAs) known as transcribed ultraconserved regions (T-UCRs). These regions, despite lacking protein-coding potential, are increasingly recognized for their regulatory roles in gene expression, including the modulation of non-coding RNA (ncRNA) transcripts. NcRNAs play crucial roles in cellular processes, including oncogenic transformation, with emerging evidence revealing their ability to encode small peptides known as ncRNA-encoded peptides (ncPEPs). These peptides, originating from small open reading frames (smORFs), contribute to diverse cellular functions and …

The Role Of The Circadian Clock In Disease And Tissue Function, Marvin Wirianto

Dissertations and Theses (Open Access)

The mammalian circadian clock responds to the 24-hour daily cycle and regulates tissue-specific gene expression and downstream physiology. The central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN) synchronizes the peripheral clocks in different tissues. This dissertation aims to uncover specific circadian regulatory mechanisms in the brain and skeletal muscle.

Alzheimer’s Disease (AD) is the most common type of dementia. It has previously been shown that there is a strong correlation of disease progression with circadian rhythm decline. We showed that circadian modulation by a small molecule Nobiletin (NOB) was able to mitigate AD pathogenesis. Furthermore, NOB significantly alleviated the …

Genetic Analysis Of Kmt2d Loss In Tumorigenesis Using Genetically Engineered Mouse Models, Yingda Jiang

Dissertations and Theses (Open Access)

The Cancer Genome Atlas Program (TCGA) has discovered multiple tumor suppressors that are commonly mutated across a variety of human cancers, such as chromatin regulators in COMPASS and SWI/SNF complexes. KMT2D, a histone H3K4 methyltransferase in the COMPASS complex, is frequently mutated in human lymphoma, melanoma, and epithelial carcinoma. Biochemically, KMT2D shapes the cellular enhancer landscape as the major writer of the putative enhancer mark H3K4me1. Given the critical role of cellular enhancer landscape in determining cellular lineage in embryonic development, it is unknown whether enhancer dysregulation caused by KMT2D loss leads lineage switch of tumor cells, which has …

Utilizing The In4mer Crispr/Cas12a Multiplex Knockout Platform To Investigate Synthetic Lethality In The Human Genome, Xingdi Ma

Dissertations and Theses (Open Access)

The emergence of high-throughput sequencing technologies and the development of targeted cancer therapies have significantly advanced our understanding of cancer genomics and prolonged patient survival. Despite these advances, durable response remains difficult to achieve in the clinic. The concept of synthetic lethality has gained traction as a promising opportunity to discover novel cancer-specific vulnerabilities and therapeutic targets. Unfortunately, initial technologies for combinatorial genetic perturbation in mammalian cells suffer from inefficiency and are challenging to scale. In this dissertation, I report: 1) paralog selection method to select candidate synthetic lethal paralogs; 2) our Cas12a multiplex platform “IN4MER” that provides superior sensitivity …

Vesicle-Associated Membrane Proteins In Airway Mucin Secretion, Boxuan Yang

Dissertations and Theses (Open Access)

Mucus plays a vital role in shielding the lungs against harmful substances such as particles, pathogens, and chemicals inhaled from the environment. It captures these harmful elements, and ciliary action helps to expel them from the lungs. Paradoxically, malfunctioning of mucus induces the development of various respiratory illnesses, including asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. Despite extensive research on controlling mucin production and hydration, the process of secretion is not yet fully comprehended.

Mucin undergoes regulated secretion at two rates: a low baseline rate and a high stimulated rate. Over the past 25 years, …

Evaluation Of Myogenic Differentiation Potential Of Bmd Ipscs In Vitro And The Effect Of Ubiquitination Inhibitors On Dystrophin Stability In Vivo, Muchen Liu

Dissertations and Theses (Open Access)

Background: Muscular dystrophies are heterogeneous groups of inherited diseases leading to progressive muscular weakness and degeneration. In the case of Becker muscular dystrophy (BMD), non-disrupting mutations of the DMD gene reading frame is the causative defect. By the age of 30s, about 60 to 70% of BMD patients develop cardiomyopathy, which is often lethal. Unfortunately, there is currently no cure for BMD. Meanwhile, improvement of dystrophin stability by repressing polyubiquitination is a promising strategy. The application of human iPSCs in tissue regeneration also serves as a potential therapeutic strategy. This study aims to test the efficacy of selected drugs interfering …

Plasma Proteins Associated With Plant-Based Diets: Results From The Atherosclerosis Risk In Communities (Aric) Study And Framingham Heart Study (Fhs), Hyunju Kim, Jingsha Chen, Brenton Prescott, Maura E Walker, Morgan E Grams, Bing Yu, Ramachandran S Vasan, James S Floyd, Nona Sotoodehnia, Nicholas L Smith, Dan E Arking, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background & aims: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.

Methods: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics …

Analyzing Heterogeneity In Biomarker Discriminative Performance Through Partial Time-Dependent Receiver Operating Characteristic Curve Modeling, Xinyang Jiang, Wen Li, Kang Wang, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

This study investigates the heterogeneity of a biomarker's discriminative performance for predicting subsequent time-to-event outcomes across different patient subgroups. While the area under the curve (AUC) for the time-dependent receiver operating characteristic curve is commonly used to assess biomarker performance, the partial time-dependent AUC (PAUC) provides insights that are often more pertinent for population screening and diagnostic testing. To achieve this objective, we propose a regression model tailored for PAUC and develop two distinct estimation procedures for discrete and continuous covariates, employing a pseudo-partial likelihood method. Simulation studies are conducted to assess the performance of these procedures across various scenarios. …

E-Cigarette Use Reasons And Associated E-Cigarette Use Dependence Among College Students: A Longitudinal Examination, Tzung-Shiang Ou, Anne Buu, James J Yang, Hsien-Chang Lin

Faculty, Staff and Student Publications

Objective: Previous studies have established an understanding of reasons for e-cigarette use and associated e-cigarette use patterns such as use frequency, yet the critical extension to associated e-cigarette dependence outcome remains under-researched. This study used longitudinal data to examine whether the reasons for e-cigarette use predict a higher/lower level of e-cigarette dependence.

Methods: This study recruited college students who were current e-cigarette users from Fall 2019 to Fall 2020 (four semesters) at three public universities in the Midwest and South of the U.S. Those who participated for at least two semesters were included (N = 366). Data were collected using …

In Vivo Examination Of Peripheral Drivers Of Alzheimer’S Disease, Celso Catumbela

Dissertations and Theses (Open Access)

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk …

Mapping The Single-Cell Differentiation Landscape Of Osteosarcoma, Danh D Truong, Corey Weistuch, Kevin A Murgas, Prasad Admane, Bridgette L King, Jes Chauviere Lee, Salah-E Lamhamedi-Cherradi, Jyothishmathi Swaminathan, Najat C Daw, Nancy Gordon, Vidya Gopalakrishnan, Richard G Gorlick, Neeta Somaiah, Joseph O Deasy, Antonios G Mikos, Allen Tannenbaum, Joseph Ludwig

Faculty, Staff and Student Publications

Purpose: The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival.

Experimental design: To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas.

Results: This "roadmap" served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify …

Essays On Cho: An Investigation Of Industrially Relevant Stressors In Recombinant Protein Production, Benjamin Synoground

All Dissertations

Recombinant protein therapeutics have become integral in the treatment and prevention of an increasingly broad range of diseases and conditions. The vast majority of these biopharmaceuticals are produced in Chinese hamster ovary (CHO) cells due to their well-established expression systems, scalability, and ability to produce safe, human-compatible glycoproteins. Previous research has aimed to increase productivity while maintaining or improving product quality metrics, resulting in substantial improvements in product yields over the past forty years. This progress has been largely driven by 'omics and multivariate approaches, which offer valuable mechanistic insights and identify process bottlenecks.

Within this dissertation, CHO cell stress …

Enhancing Crop Resilience: Physiological And Omics Approaches For Drought And Heat Stress Tolerance In Soybean And Peanut, Jyoti Prasad Kakati

All Dissertations

Soybean and peanut are two major crops globally grown for oil and protein. Climate change-associated factors like drought and increased temperature (heat stress) challenge the global production of soybeans and peanuts. Though the United States is the second-largest producer of soybean and the fourth-largest producer of peanuts, it still faces production constraints associated with drought and heat stresses. In the present study, we have examined the responses of soybean and peanut plants to drought and heat stresses during germination and reproductive phases. We conducted field and controlled environmental studies to elucidate the impact of drought stress on germination and seedling …

Investigating The Etiology, Epidemiology, And Ecology Of Blackberry Yellow Vein Disease In South Carolina, Wanita Dantes

All Dissertations

Blackberry production is growing in popularity in the southeastern U.S. However, blackberry growers in this region report major problems with productivity and longevity due to viruses. First, the state of knowledge on blackberry yellow vein disease (BVYD) complex, associated with mixed infections of a diverse group of viruses, is discussed. Specific viruses associated with symptom types are unknown. Therefore, the etiology of BYVD is not fully understood, which makes BYVD diagnosis challenging. My research focused on improving BYVD diagnosis, etiology, and epidemiology. Second, I developed a farm-level diagnostic protocol to improve virus disease surveillance. High throughput sequencing detected 17 known …

Fluid-Solid Coupled Analysis Of Biological Samples In A Flow Chamber Using Optical Coherence Tomography, Reece W. Fratus

All Dissertations

Forces from fluid flow on a tissue or cellular boundary can drive remodeling processes through mechanotransduction pathways. In most cases, the exact mechanisms are not understood, such as in marine biofilm development or vascular remodeling. To gain a better understanding of these interactions, the flow profile at a solid boundary and the mechanical changes of that solid can be coupled together to determine the impact of fluid flow on mechanical remodeling. To achieve this, optical coherence tomography (OCT) is used to image the fluid and solid simultaneously. Fluid seeded with particles can be imaged and run through a particle image …

Fundamental Study Of Nonlinear Electrophoresis, Joseph Armakan Bentor

All Dissertations

Classical electrophoretic theory describes the linear response of particles suspended in Newtonian fluids under weak electric fields. When the electric field exceeds this weak limit, a nonlinear response arises due to non-uniform surface conduction over the curved particles. This nonlinear behavior introduces dependencies on fluid and particle properties not considered in the classical theory, offering potential advantages for microfluidic particle manipulation. While this phenomenon has been extensively studied theoretically and numerically in Newtonian fluids, experimental investigations have been relatively limited.

Fluid rheology can significantly alter particle dynamics under applied electric fields. Rheological properties like shear-thinning and elasticity which are not …

Effect Of Long-Term Use Of Antimicrobials On Commonly Used Surfaces In Foodservice Establishments, Anuradhi Bandaranayake

All Dissertations

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Contribution Of Collagen Type I To The Mechanical Properties Of Myocardial Tissues At The Micron Level, Adam Baker

All Dissertations

Collagen is a critical component of the organization and one of the key factors contributing to the mechanical stability of the myocardium. Where cardiomyocytes actuate to contract the heart and deliver blood to the lungs and the entire body, the local collagen network must be able to support the mechanical needs of the heart by enhancing rigidity, reducing the mechanical responsibility of cells, and increasing compliance to add loading capacity during diastole. At an organ-wide level, this has been measured and modeled in many ways. At the tissue level, the mechanical properties have been evaluated using techniques such as bi-axial …

Lab To Leadership: How Do Women College Stem Students’ Classroom Experiences Inform Their Leader Identity Development?, Meredith Mcdevitt

All Dissertations

This dissertation is an exploration of leader identity development and women in science, technology, engineering, and mathematics (STEM) college academic classrooms. While there continues to be research promoting diversity in STEM professions, women remain underrepresented in STEM disciplines, leadership positions, and for this specific study, the college academic classroom. This dissertation represents an opportunity for women in STEM college students to reflect on their experiences in STEM academic spaces and communities, while self-exploring factors that shape their leader identity development. The research utilized a basic qualitative research design to understand the participant’s authentic experiences within the academic environment. Conducting semi-structured …

Exploring Acetate Metabolism: Genetically Characterizing Acetate Production And Acetate Utilization In The Fungal Pathogen Cryptococcus Neoformans, Rodrigo Catalan-Hurtado

All Dissertations

The basidiomycete Cryptococcus neoformans is an invasive opportunistic fungal pathogen and the most frequent cause of fungal meningitis resulting in approximately 112,000 deaths per year worldwide. Recently, the World Health Organization systematically prioritized fungal pathogens in which C. neoformans was among four fungal pathogens deemed critically important. Current methods of treatment are inadequate for most of the infected population; therefore, it is imperative to find novel therapeutic targets. Previous studies have shown that acetate is a major metabolite found in biopsies of C. neoformans infected mouse brain and lung tissues. Two potential pathways for acetate production have been identified. …

Assessment Of Tce And Chiral Pcb Dechlorination Rate, Congener Diversity, And Enantioselectivity In Town Creek, Sc, Usa Sediment Microcosms, Catherine P. Sumner

All Dissertations

Polychlorinated biphenyls (PCBs) and trichloroethene (TCE) are ubiquitous contaminants and are recognized as persistent organic pollutants due to their extreme chemical stability. PCBs were manufactured by chlorinating biphenyls that created 209 congeners with various structures, of which 19 are chiral and can exist as a pair of stable atropisomers. PCBs have been known to cause developmental and neurological toxicity in humans and wildlife; they can act as endocrine disrupters, carcinogens, and teratogens. Sangamo Weston Inc. was an industrial plant located near Town Creek in Pickens Country, South Carolina, that manufactured capacitors and used Aroclors 1016 and 1254 as dialectic fluids …

No Longer Unseen Or Unheard: Exploring The Connectedness Of Campus Climate With Multiracial Students’ Experiences At Historically White Institutions In The United States, Christian Barrientos

All Dissertations

This qualitative research study will illustrate the link(s) between Multiracial students and their perceptions of campus climate at historically White institutions and how that impacts their sense of belonging. Existing bodies of literature and research have focused more extensively on monoracial students of color than Multiracial students. As a result, there is a formidable gap in the literature about how Multiracial students navigate their racial identity at historically White institutions and how multiracial students perceive campus climate based on their experienced sense of belonging. The use of Kellogg and Liddell (2012) will serve as a guide for this research study. …

Opportunities To Learn In Rural South Carolina Schools: Rurality, Place, And Passion, Grig Sawyer

All Dissertations

High school principals can change the status quo of the current iniquitous disparities in the education system between South Carolina’s rural high schools and their more populated and affluent suburban schools. Using a non-standard structure and the resources in their control, these school leaders can find solutions so schools can offer rural students advanced math and science programs. Yet, there is a paucity of studies examining how small rural school principals make advanced math and science courses available to their students, particularly in rural South Carolina. Thus, studies must examine how South Carolina school leaders successfully offer advanced math and …

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

The Impact Of Reactive Oxygen Species On Bactericidal Activity And Drug Resistance In Salmonella Typhimurium Upon Chlorine And Eugenol Exposure, Mohammed Aljuwayd

Graduate Theses and Dissertations

Salmonella Typhimurium (S.T) is a foodborne pathogenic bacterium which causes salmonellosis in human beings. Chicken is the most common source of S.T contamination. In chapter I, I discuss the growth of the poultry industry, the role chickens play as Salmonella reservoirs, the spread of drug-resistant strains caused by chicken husbandry and antibiotic use, and how eugenol can be used in poultry feed to decrease Salmonella infections and improve intestinal health. In chapter Ⅱ, I summarize the role of reactive oxygen species (ROS) in bactericidal activity. In chapter Ⅲ, I describe the killing mechanism of sodium hypochlorite (NaOCl) and identify the …

Gan With Skip Patch Discriminator For Biological Electron Microscopy Image Generation, Nishith Ranjon Roy

Graduate Theses and Dissertations

GAN models have been successfully used for image generation in various sections such as real-life objects like human faces, cars, animal faces, landscapes, etc. This work focuses on biological electron microscopy (EM) image generation. Unlike other real-life objects, biological EM images are obtained through electron microscopy techniques to study biological specimens. Electron microscopy offers high resolution and magnification capabilities, making it a powerful tool for visualizing biological structures at the nanoscale. However, using GAN models for biological EM image generation poses challenges due to the complex and unique arrangements of biological structures and the sparse and asymmetrical patterns in EM …

Antiracism In Higher Education: An Integrated Psychological Perspective, Rhea E. Nesbitt

Dissertations, 2020-current

Antiracism is a complicated and important term with prominent, influential voices claiming that systemic equity and the reconfiguration of white identity are the central solutions to eradicating American racism. Within the profound sociocultural effects of the existing antiracist rhetoric, there is vagueness, conflict, and incoherence. Language serves as a fundamental aspect of human experience, facilitating individual meaning-making and comprehension. Effective communication hinges on the ability to articulate subjective experiences and justifications clearly, a challenge evident in discussions surrounding antiracism. Despite advocating for antiracism as crucial and unending work, scholars recognize significant hurdles, including unclear responsibilities for implementation and entrenched structures …

Candida Albicans Farnesol Synthesis And Secretion, Daniel J. Gutzmann

School of Biological Sciences: Dissertations, Theses, and Student Research

Candida albicans is a polymorphic fungus and opportunistic commensal found primarily in the gastrointestinal and skin of healthy individuals. Several barriers prevent C. albicans from causing disease including a healthy immune system and microbiome. When these barriers become comprised, C. albicans can transition to a pathogen and disseminate through the intestinal mucosa leading to life-threatening bloodstream and invasive infections with mortality rates of up to 64%. Morphogenic plasticity is key to this transition and impacts virulence, adaptation to different host environments, and evasion of host immune responses. One regulator of morphogenesis is farnesol. Farnesol is a secondary metabolite of …

Guiding The Management Of Acute Promyelocytic Leukemia: A Quality Improvement Project, Lauren Sheldon, Donna M. Tydings, Tara L. Sacco

Nursing Doctoral

Background: Despite successful treatment regimens and remission rates of greater than 90%, early death is a concern for patients with acute promyelocytic leukemia (APL). The challenges surrounding proper care for APL are centered on the low volume of patients, which limits healthcare professionals’ knowledge of disease management.

Objectives: The purpose of this project was to develop resources and present an educational module specific to managing patients newly diagnosed with APL. An intervention to evaluate bedside nurses’ knowledge of APL was implemented.

Methods: Thirty-four RNs were recruited for participation. A clinical practice guideline, an algorithm, and a fact sheet were developed …