Downregulation Of Mir-10a-5p As A Potential Therapeutic Target To Improve The Detrimental Effects Of Post-Stroke Social Isolation, Patrick Mooz

Dissertations and Theses (Open Access)

Introduction

Social isolation is detrimental to health. Isolation and loneliness are linked to all-cause mortality and accelerated disease progression in patients with cancer, dementia, and vascular disease. The number of individuals that live alone is increasing in our society, especially in the elderly, and loneliness and isolation represent a profound growing public health challenge. Previous studies have found that the detrimental effects of social isolation can be recapitulated in animal models. Mice that are socially isolated (SI) prior to an experimental stroke have larger infarcts and significantly worse outcomes. Importantly, animals that remain pair housed (PH) when an experimental stroke …

A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals, Safia Essien, Safia Essien

Dissertations and Theses (Open Access)

Efficient replacement of dead cells in epithelial tissue is crucial for maintaining barrier function and tissue homeostasis. Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss and maintain overall cell numbers in normal physiology and cancer. While dying cells can transmit instructive cues to neighboring cells, the molecular mechanisms that induce cell division are not well understood. Recent evidence suggests that apoptotic bodies (ABs) or apoptotic extracellular vesicles (AEVs) mediate cell-to-cell communication and carry diverse biologically active cellular cargo which can influence cell proliferation. This dissertation visualizes and characterizes AEVs in larval zebrafish and …

A Novel Ngs Assay To Detect Any Kmt2a Fusion Transcript At Low Levels, Ghayas Issa

Dissertations and Theses (Open Access)

Measurable residual disease (MRD) detection is associated with cancer relapse. Leukemias with rearrangement of the lysine methyltransferase 2 A gene (KMT2Ar) have an adverse prognosis with more than 80 possible fusion partner genes (FPG) identified. With the advent of effective targeted therapies for KMT2Ar leukemia such as menin inhibitors, there is an unmet need for sensitive assays to detect these various fusions. Standard next-generation sequencing (NGS) methods cannot accurately detect genetic alterations at low frequencies because of inherent technical errors and the need for high sequencing depth. Blocker Displacement Amplification (BDA) technology enables selective detection of such rare …

Single Cell Proteogenomics Analysis Of Aml Samples Treated With Decitabine And Venetoclax Reveals Divergent Treatment Escape Mechanisms, Yi June Kim

Dissertations and Theses (Open Access)

Venetoclax is a small molecule inhibitor targeting BCL-2. Since its approval, the combination therapy of hypomethylating agents and Venetoclax (HMA+Ven) has become a standard of care for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Nonetheless, clinical challenges persist as patients either do not respond or eventually relapse, and the underlying mechanisms of these outcomes are not yet fully understood. Prior studies have identified genetic factors (TP53 and RTK/RAS pathway mutations) and phenotypic factors (monocytic differentiation) to be associated with resistance. In this light, we hypothesized that integrative assessment of genetic and phenotypic factors could further elucidate the unknown …

Opening The Black Box Of Family-Based Treatments: An Artificial Intelligence Framework To Examine Therapeutic Alliance And Therapist Empathy, Phillippe B Cunningham, Jordon Gilmore, Sylvie Naar, Stephanie D Preston, Catherine F Eubanks, Nina Christina Hubig, Jerome Mcclendon, Samiran Ghosh, Stacy Ryan-Pettes

Faculty, Staff and Student Publications

The evidence-based treatment (EBT) movement has primarily focused on core intervention content or treatment fidelity and has largely ignored practitioner skills to manage interpersonal process issues that emerge during treatment, especially with difficult-to-treat adolescents (delinquent, substance-using, medical non-adherence) and those of color. A chief complaint of "real world" practitioners about manualized treatments is the lack of correspondence between following a manual and managing microsocial interpersonal processes (e.g. negative affect) that arise in treating "real world clients." Although family-based EBTs share core similarities (e.g. focus on family interactions, emphasis on practitioner engagement, family involvement), most of these treatments do not have …

A Double-Robust Test For High-Dimensional Gene Coexpression Networks Conditioning On Clinical Information, Maomao Ding, Ruosha Li, Jin Qin, Jing Ning

Faculty, Staff and Student Publications

It has been increasingly appealing to evaluate whether expression levels of two genes in a gene coexpression network are still dependent given samples' clinical information, in which the conditional independence test plays an essential role. For enhanced robustness regarding model assumptions, we propose a class of double-robust tests for evaluating the dependence of bivariate outcomes after controlling for known clinical information. Although the proposed test relies on the marginal density functions of bivariate outcomes given clinical information, the test remains valid as long as one of the density functions is correctly specified. Because of the closed-form variance formula, the proposed …

Analyzing Extracellular Vesicles For Disease Monitoring In Metastatic Colorectal Cancer Patients, Vahid Bahrambeigi

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Metastases are the main cause of cancer-related death, and the most frequent metastatic sites in patients with CRCs are liver and lung. To confirm the diagnosis of metastatic CRC (mCRCs) and to classify mCRCs, tumor biopsy of a suspected metastasis is often required. The consensus molecular subtype (CMS) classification which is based on gene expression profiles of CRC tumor specimens, is a predictive factor for treatment outcomes of standard chemotherapies for mCRCs. The practicality of repeated tumor biopsies for disease monitoring in mCRC patients is …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations and Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …

Oncogenic Kras And Telomere Biology In Crc Progression, Ronald Depinho

Dissertations and Theses (Open Access)

While colorectal cancer (CRC) patients diagnosed with localized stage disease (as defined by SEER) have a 5-year survival rate of 90%, this rate plunges to 14% for patients diagnosed with metastatic CRC. Consequently, there is an immediate imperative to elucidate the mechanisms that drive the transition to advanced CRC.

Human CRCs carrying oncogenic mutations in the KRAS oncogene, henceforth referred to as KRAS*, exhibit a 25% higher propensity for developing liver metastases. Similarly, in our CRC mouse model, engineered with an inducible Kras* transgene and conditional null alleles of Apc and Tp53 (referred to as iKAP), KRAS* has been …

Synthesis Of Glucomannan-Xylan Composite Biofilms: Characterization And Applications For Food Packaging, Kholoud Al-Ajlouni

Dissertations

Scientists are most concerned about the need for green alternatives for efficient food packaging polymers to replace petroleum-based packaging products. The waste of corn cobs and the roots of the konjac plant contain hemicellulose, xylan and glucomannan respectively, and can be used to produce biofilms for food packaging.

The aim of these studies is to formulate biofilms from glucomannan-xylan blends that compete with petroleum-based plastic wrap. The biofilms must be strong, smooth, transparent, have a water vapor barrier, have the required mechanical properties and be cheap. Biofilms from glucomannan were stiff, lacked mechanical properties, and absorbed moisture. Therefore, it reacts …

The Effect Of Nitroglycerin In Testicular Histopathology, Reproductive Hormones And Testicular Oxidative Stress In Adolescent Rats, Volkan Koşal, Çağlar Okulmuş, Yılmaz Koçak, Ömer Faruk Keleş, Nesrin Ceylan, Yıldıray Başbuğan

Mansoura Veterinary Medical Journal

Background: Nitroglycerin (NTG) exerts a vasodilation effect by acting on vascular smooth muscles. The exact impact of vasodilation on the testes is not fully understood. Objectives: This study aimed to investigate the effects of NTG on the testes before the onset of spermatogenesis and reproductive activity in adolescent rats. Methods: An Average of 45 days male Albino Wistar rats were used. Two groups were formed: an adolescent control group and an adolescent NTG group (10 mg/kg, 5 d). Results: At the end of the study, testicular oxidative stress (malondialdehyde /MDA, catalase/ CAT, advanced oxidation protein products /AOPP, and nitric oxide/ …

Comparing City Park Perspectives: Users Vs Organizers, Kalli Hull

Undergraduate Honors Capstone Projects

Green spaces and parks are an essential aspect of a healthy community. Incorporating parks into the landscape of a city can benefit the community. Understanding the relationship between park management and park users is important for creating the most effective use of space and accessibility. This project looks at the comprehensive viewpoints of both park managers and park users through a series of interviews and reviews of previous research and literature. Logan City, Utah is used as the location of interest for collecting and determining outcomes. This project displays the key findings of the priorities and viewpoints of both park …

Instrumentality: How We Develop Relationships With Objects And People, Nathaniel Bee

Undergraduate Honors Capstone Projects

There are many different types of relationships a person will have throughout their life, each being given varying levels of authenticity, weight, and care. One’s attention is primarily placed upon the meaningful relationships in one’s life, but often deeper consideration of one’s “lesser” relationships is neglected. Networking and professional relationships are often impersonal. Family members will often lie to each other in favor of avoiding conflict. The emotional labor of service workers often goes underappreciated and undercompensated. Careers in the political sphere revolve heavily around maintaining a positive public image, and there are well-observed disparities between politicians’ stated values and …

Assessing Chondrocyte Viability Of Articular Cartilage Using Label-Free Imaging Methods, Hongming Fan

All Dissertations

ABSTRACT

Articular cartilage covers the ends of bones, providing a protective layer that can endure forces during movement. Chondrocytes, the only cell type found in articular cartilage, produce collagen fibers and proteoglycans that maintain the extracellular matrix (ECM). Cartilage damage impairs chondrocytes and their ability to maintain tissue stability. There are various factors that can cause cell death, which can be broadly classified into two categories: programmed cell death (apoptosis) and non-programmed cell death (necrosis). The consequences of cell death can have significant impacts on the extracellular matrix (ECM). The ECM is a complex network of proteins and carbohydrates that …

Aspects Of Stochastic Geometric Mechanics In Molecular Biophysics, David Frost

All Dissertations

In confocal single-molecule FRET experiments, the joint distribution of FRET efficiency and donor lifetime distribution can reveal underlying molecular conformational dynamics via deviation from their theoretical Forster relationship. This shift is referred to as a dynamic shift. In this study, we investigate the influence of the free energy landscape in protein conformational dynamics on the dynamic shift by simulation of the associated continuum reaction coordinate Langevin dynamics, yielding a deeper understanding of the dynamic and structural information in the joint FRET efficiency and donor lifetime distribution. We develop novel Langevin models for the dye linker dynamics, including rotational dynamics, based …

An In Vitro Platform To Characterize Myocardial Wound Remodeling, Jonathan Heywood

All Dissertations

Heart Failure, sometimes called Congestive Heart Failure, is a collection of pathological disruptions in which the heart is unable to pump blood properly. It affects over 6 million people in the United States, with the cost-per-patient at approximately $30,000 and the total cost estimated to be $160 billion by 2030. There is no single cause of heart failure, as it can manifest as a varying array of diseases, disorders, and syndromes. However, many of these underlying diseases result specifically from dysregulation of mechanically active cells called cardiac fibroblasts, which play a critical role in the remodeling of the extracellular matrix …

Trash, Fragments, And Breaking Things: Toward A Grotesque Cripistemology For Disabled Life Writing, Michelle Anne Lloyd

All Dissertations

Despite the boom of memoirs of mental health post-1997 and the first advertisements for Prozac, most of them follow the same formula and come from the same places of privilege. This privilege is evident in the author bios on the books themselves and the careers of the writers. The popularity of these books within both abled and disabled realms has therefore created a script that those with mental illnesses are expected to abide by. Following in the example of Margaret Price, Katie Rose Guest Pryal, Merri Lisa Johnson, and others, I resituate mental illness as mental disability and place it …

Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica, Jin Cho

All Dissertations

Entamoeba histolytica is a water- and food-borne intestinal parasite that causes amoebiasis and liver abscess in ~100 million people each year leading to ~100,000 deaths. This amitochondriate parasite lacks many metabolic pathways including the tricarboxylic acid cycle and oxidative phosphorylation, and cannot synthesize purines, pyrimidines, or most amino acids. As a result, E. histolytica is presumed to rely on its modified pyrophosphate (PP_i)-dependent glycolytic pathway for ATP production during growth on glucose. This pathway relies on a PP_i-dependent rather than ATP-dependent phosphofructokinase (PFK) and thus has a net production of three ATP per glucose. However, in …

Physics-Based Machine Learning Methods For Control And Sensing In Fish-Like Robots, Colin Rodwell

All Dissertations

Underwater robots are important for the construction and maintenance of underwater infrastructure, underwater resource extraction, and defense. However, they currently fall far behind biological swimmers such as fish in agility, efficiency, and sensing capabilities. As a result, mimicking the capabilities of biological swimmers has become an area of significant research interest. In this work, we focus specifically on improving the control and sensing capabilities of fish-like robots.

Our control work focuses on using the Chaplygin sleigh, a two-dimensional nonholonomic system which has been used to model fish-like swimming, as part of a curriculum to train a reinforcement learning agent to …

Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang

All Dissertations

Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …

Influence Of Access To Public Parks On Mortality Among Older Adults In The United States, Jiaying Dong

All Dissertations

Research shows the health benefits of green spaces are universal, but there's a noticeable disparity in their distribution in the U.S., especially between urban and rural areas. Marginalized groups, particularly those of lower economic status or racial minorities, often have limited access to these spaces. This inequity could be more impactful on the elderly, who are more vulnerable to health issues. However, specific health benefits of green spaces for seniors are not well defined. This study examines the correlation between park access, mortality in those over 65, and income disparities across all U.S. counties.

The study employed a quantitative approach …

Interpretable Mechanistic And Machine Learning Models For Pre-Dicting Cardiac Remodeling From Biochemical And Biomechanical Features, Anamul Haque

All Dissertations

Biochemical and biomechanical signals drive cardiac remodeling, resulting in altered heart physiology and the precursor for several cardiac diseases, the leading cause of death for most racial groups in the USA. Reversing cardiac remodeling requires medication and device-assisted treatment such as Cardiac Resynchronization Therapy (CRT), but current interventions produce highly variable responses from patient to patient. Mechanistic modeling and Machine learning (ML) approaches have the functionality to aid diagnosis and therapy selection using various input features. Moreover, 'Interpretable' machine learning methods have helped make machine learning models fairer and more suited for clinical application. The overarching objective of this doctoral …

Multidimensional Chromatographic Coupling Strategies Implementing Capillary-Channeled Polymer Fiber Stationary Phases, Sarah Wysor

All Dissertations

Liquid chromatography (LC) is a widely employed technique in analytical separations due to the ease of implementing rapid analysis methods to isolate targeted analytes. While LC is commonplace, challenges often arise with complex macromolecules as it often effects isolation via only one attribute of the targeted analyte (i.e., physical, chemical). To cater to increasingly complex samples requiring multiple chromatographic workflows, two-dimensional liquid chromatography (2DLC) has emerged. Various applications, such as drug discovery, pharmaceutical manufacturing, and specialty chemical manufacturing, require highly pure final products for release to the market. Consequently, multiple chromatographic steps are necessary for isolation and purification. Within pharmaceuticals, …

Ti-6al-4v Β Phase Selective Dissolution: In Vitro Mechanism And Prediction, Michael A Kurtz

All Dissertations

Retrieval studies document Ti-6Al-4V β phase dissolution within total hip replacement systems. A gap persists in our mechanistic understanding and existing standards fail to reproduce this damage. This thesis aims to (1) elucidate the Ti-6Al-4V selective dissolution mechanism as functions of solution chemistry, electrode potential and temperature; (2) investigate the effects of adverse electrochemical conditions on additively manufactured (AM) titanium alloys and (3) apply machine learning to predict the Ti-6Al-4V dissolution state. We hypothesized that (1) cathodic activation and inflammatory species (H₂O₂) would degrade the Ti-6Al-4V oxide, promoting dissolution; (2) AM Ti-6Al-4V selective dissolution would occur …

The Use Of The South Carolina School Improvement Model - Quick Cycles In Sixth-Grade Science Classrooms, Jennifer Gnann

All Dissertations

Using data to make informed decisions about instruction strengthens a teacher’s delivery of content within the classroom. However, many teachers have not been taught how to properly use a model of rapid improvement cycles to analyze data and apply it to their classroom instruction. I modified the South Carolina School Improvement Model so that it could be used in short cycles to see how teachers used it to plan for, monitor, and adjust instruction in their classrooms.

I conducted a single case study over a six-week period in which I instructed two sixth-grade science teachers on how to use the …

Exploring Modalities Of Productivity And Critical Quality Attributes In Fed-Batch Chinese Hamster Ovary Cell Cultures, Stephanie Klaubert

All Dissertations

Chinese hamster ovary (CHO) cells are among the most commonly used mammalian cell lines for the production of recombinant therapeutic proteins due to ease of culturing and humanlike post-translational modification capabilities. However, when compared to microbial systems, CHO cell line growth and productivity is relatively low. As the demand for monoclonal antibody (mAb) treatments continues to rise, it is critical to explore modalities for improved growth and productivity in CHO cell cultures, with the goal of increased protein concentrations and maintained product quality. Though some mechanisms for improved productivity, including temperature and cell culture media formulations, are relatively well understood; …

Engineering Next-Generation Cardiovascular Therapies, Ryan Walker Barrs

All Dissertations

Cardiovascular diseases are the leading cause of death worldwide. Heart disease, in particular, accounted for 1 in every 5 deaths in the United States in 2021, representing a substantial public health burden that will require more effective treatment options to alleviate. Heart transplant surgery is currently the only option to completely restore cardiac function, but many patients die while waiting for a transplant due to a longstanding organ donor shortage. Thus, there is a dire need for accessible treatment options that can repair damaged hearts. Recent advances in tissue engineering and regenerative medicine have accelerated the development of therapies for …

Experimental And Computational Platforms For Studying Systems Mechanobiology, Brendyn Miller

All Dissertations

Mechanical stimulation through physical activity has been shown to play an important role in treating and preventing several non-communicable diseases such as hypertension, lower back pain (LBP), type-2 diabetes mellitus, and several cancers. This is accomplished through the regulation of cellular behavior and tissue remodeling within the body at both the micro- and macro-scale levels. The goal of mechanobiology research is to gain in-depth knowledge and understanding of how cells sense physical forces in conjunction with other biochemical cues and translate those factors into important biological functions that either maintain tissue homeostasis or lead to pathological states. Understanding these processes …

Cellular Mechanism Of Pentagalloyl Glucose-Mediated Prevention And Reversal Of Abdominal Aortic Aneurysms, Greg Halsey

All Dissertations

Abdominal aortic aneurysm (AAA) has been the 15th leading cause of death in persons older than 55 for the past ten years in several Western countries, with rupture resulting in an almost 100% mortality rate. AAA is a focal dilation of the aorta characterized by progressive loss of elastin and vascular smooth muscle cells (SMCs), as well as persistent inflammatory response [1]. The only treatment for AAA is surgery; however, the mortality post-procedure is still 1-4%, with a 15-30% chance of morbidity [2].

Pentagalloyl glucose (PGG) treatment is effective in the reversal of AAA. While its stabilizing interactions with extracellular …

Addressing Mercury Contamination From Artisanal Gold Mining In Colombia: Pollution Exposure, Health Risk, And Educational Efforts In The Communities Of La Toma, Colombia, Kelli Mccourt

All Dissertations

Artisanal and small-scale gold mining (ASGM) has become a primary environmental and public health concern in the region of Colombia known as Alto Cauca. The predominantly Afro-descendent communities of Yolombó and La Toma in Alto Cauca have experienced pollution linked to the use of mercury in the ASGM process. For the past decade, mercury has emerged as a contaminant of increasing concern in the communities due to its toxicity and ability to bioaccumulate and biomagnify. Likewise, mining in the region raises concerns over the leaching of metals into local waters. Given the complexity of risk and pollution in the communities, …