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Variable Selection For High-Dimensional Data With Interaction Effects: Methods, Applications, And Inferences, Leiyue Li

Theses and Dissertations--Statistics

For high-dimensional data where the number of variables greatly exceeds the number of observations, selecting important variables while maintaining the required heredity conditions can be challenging. This dissertation is structured into three interconnected parts. In the first part, we propose a variable selection method by implementing a well-known optimization technique, the Genetic Algorithm. An R package was developed to simplify the implementation and usage of the proposed method. We then propose another variable selection method by extending the study from the Genetic Algorithm to a different but related optimization technique, Simulated Annealing. We consider three different hierarchical structures in both …

Design Of Kappa Opioid Receptor Agonists For Potential Treatment Of Multiple Sclerosis, Lindsay Kornberger

Theses and Dissertations--Pharmacy

Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system characterized by demyelination and neuroinflammation. There is currently no cure for MS. There is a critically unmet need for the development of pharmacotherapies that can induce remyelination promoting both repair and recovery. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating pharmacotherapies. KOR activation has been shown to promote functional recovery and remyelination preclinically. However, typical KOR agonists like U50,488 have limitations such as sedation and dysphoria limiting their use. This necessitates further development of new KOR agonists that maintain …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Transfer Learning-Enhanced Transformer For Virtual Sensing Applications In Resistance Spot Welding, Ethan York

Theses and Dissertations--Mechanical and Aerospace Engineering

Resistance spot welding is a crucial manufacturing process used across a wide range of industries for permanently joining metal components. Characterized by its applications in the automotive industry, resistance spot welding is valued for its speed, efficiency, and relatively low cost to set up and maintain. The process involves running a pulse of electrical current through two metal sheets to liquify the material and create a permanent bond. The process complexity necessitates precise control over various parameters to ensure acceptable results, emphasizing the importance of quality control. Because there are no low-cost and non-invasive techniques to inspect welds, strategies utilizing …

Multiscale Fiber Remodeling In The Heart Using A Finite Element Framework, Mohammad Mehri

Theses and Dissertations--Mechanical and Aerospace Engineering

The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI) or hypertrophic cardiomyopathy (HCM), this organization can become disrupted, leading to alteration in pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and …

Characterization Of Heterogeneous Material Architectures Through X-Ray Computed Micro-Tomography, Cameron Brewer

Theses and Dissertations--Mechanical and Aerospace Engineering

Low-density carbon-phenolic composites, such as phenolic impregnated carbon ablator (PICA), possess meso-, micro-, and nano-pores making the structure of the resin difficult to characterize. X-ray Computed Tomography (XRCT) is a widely ac- cepted method for characterizing the carbon fiber preform, yet this technique is often insufficient for visualizing the resin because of its minimal attenuation of the incident x-ray beam. Phase Contrast Retrieval (PCR) reconstruction considers not only the linear attenuation coefficient, but also the refractive indices of the constituent materials. This research leverages phase contrast tomography to characterize the meso- and micro-structure of the porous resin phase with a …

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

Evaluation Of The Cellular And Physiologic Impact Of Mitomycin C On Colon Cancer, Hannah Mcdonald

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) has more than doubled the overall and disease-free survival in patients with peritoneal metastases (PM) due to colorectal cancer (CRC) over the past two decades. Although MMC is the most used HIPEC drug for PM due to CRC, dosing protocols vary dramatically between and within institutions across the world. Additionally, little is known about the impact of hyperthermia and MMC on intracellular pathways for CRC. The aim of this work is to determine the optimal dosing strategy in the clinical application of MMC and hyperthermia for treatment of …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

Exenatide As Chronopharmacotherapy For T2dm Associated Complications: Targeting Nondipping Blood Pressure And Sleep Insufficiency, Aaron Chacon

Theses and Dissertations--Pharmacology and Nutritional Sciences

Although largely impacted by age, race and ethnicity, and socioeconomic factors, Type 2 Diabetes Mellitus (T2DM) is primarily driven by obesity, currently affecting ~30 million in the U.S and ~463 million globally. T2DM carries numerous complications, including high prevalence of hypertension and nondipping blood pressure (BP), sleep insufficiency and fragmentation. Nondipping BP is an inadequate drop in BP (≤ 10%) during sleeping hours compared with waking hours. Lending to this, sleep disturbance acts as both precursor and consequence of metabolic dysregulation, greatly impacting circadian rhythmicity. To model these conditions, we utilized diabetic (db/db) mice. These mice carry a point mutation …

Mitigating Risks For Dementia In Apoe4 Mice: Efficacy Of Prebiotic Inulin, Probiotics, And Fecal Microbiota Transplants, Ya-Hsuan Chang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Apolipoprotein E4 allele (APOE4) carriers show early metabolic changes, heightening the genetic risk of late-onset Alzheimer's Disease (AD), characterized by amyloid-β and tau tangle plaques and neurodegeneration. Its development is influenced by age, environment, and genetics, with Mild Cognitive Impairment (MCI) often preceding AD, providing a crucial window for early intervention. Factors in AD progression include sex differences and gut microbiome imbalances, with women disproportionately affected and APOE4 carriers showing early metabolic and cognitive changes. This study explores the potential of prebiotic inulin, probiotic Bifidobacterium animalis, and fecal microbiota transplants (FMT) from healthy donors to mitigate AD …

Cell-Based Cardiac Repair And The Natural Cardiac Healing In Regenerative Adult Mammal, Hsuan Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heart failure (HF) following myocardial infarction (MI) remains a significant global health concern, with the initial ischemic injury often leading to microvascular damage and infarct expansion, exacerbating the overall cardiac impairment. Despite extensive research, there are currently no effective therapies to limit myocardial damage post-MI, resulting in a substantial number of patients progressing to HF. Stem cell therapy has emerged as a promising approach to modulate cardiac injury and promote healing. However, clinical trials have shown only modest success, underscoring the need for improved strategies to enhance efficacy. Additionally, the lack of significant ventricular regeneration highlights the necessity of targeting …

The Delineation Of Platelet Pathology In Cardiometabolic Disease, Chi Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a multifactorial disease with many comorbidities leading to multiorgan dysfunction. Current studies point towards dysregulation of platelet signaling as a driver for increased risk of cardiovascular disease and stroke. The exact mechanisms remain elusive due to the complex interplay of factors involved, warranting the need to further understand how platelets are affected. Our preliminary data evaluating changes in platelet and coagulation parameters from bariatric patients showed that obesity did not affect platelet count or clotting time as demonstrated in INR values. However, female patients had increased bleeding events before surgery that were decreased after surgery. Due to limitations …

Characterization Of Bowel Dysfunction After Spinal Cord Injury In Mice, Olivia Wireman

Theses and Dissertations--Physiology

Most individuals who suffer a spinal cord injury (SCI) will experience some form of bowel dysfunction. Trauma to the spinal cord can result in severe constipation and/or incontinence, otherwise known as neurogenic bowel. Constipation requires extensive bowel routines typically involving the help of another person. Still, many living with SCI are hospitalized due to bowel complications such as fecal impaction. While neurogenic bowel has been well characterized in the clinic, pre-clinical models of neurogenic bowel after SCI are still in development. Most pre-clinical studies in bowel dysfunction after SCI are published in rat models. Studies existing in mice, to our …

Maternal-Adolescent Communication About Sex And Risky Sexual Behaviors: A Cross-Cultural Comparison Of Czech, Spanish, And Taiwanese Youth, Mckinley Hall

Theses and Dissertations--Family Sciences

This present study aimed to test the relationship between perceived maternal-adolescent communication about sex and risky sexual behaviors, while also considering the links between perceived maternal-adolescent closeness and maternal-adolescent conflict with risky sexual behaviors, across three culturally distinct countries, namely the Czech Republic (N=878, mean age of 17.93), Spain (N =1024, mean age of 18.79), and Taiwan (N =1443, mean age of 16.48). Samples of adolescents from each country were used and statistical analyses were conducted to test the hypothesized relationships. Based on path analysis carried out on each sample, the results revealed that Czech adolescents reported the highest levels …

Indoor Pests And Human Health: Characterizing Contaminants And Improving Mitigation, Johnalyn Gordon

Theses and Dissertations--Entomology

Much of the United States population spends the majority of their time indoors and within the home. Not only are indoor arthropod pests an unsightly nuisance in our homes, but they can have serious impacts on human health, especially with chronic exposure. In addition to negative health impacts, costs associated with these medical impacts can be tremendous. For these reasons, it is critical to develop comprehensive strategies for pest reduction and mitigation of associated health impacts. The work outlined in this dissertation represent examination of the distribution of a hypothesized bed bug allergen within the indoor environment, identification of a …

Addressing The Trade-Offs Of Pest Protective Row Covers For Integrated Pest Management In Vegetable Production, Kathleen Fiske

Theses and Dissertations--Entomology

The success of many integrated pest management (IPM) strategies is limited by trade-offs with economic, cultural, and environmental factors. While some IPM strategies reduce pests, they may harm pollinators, reduce the efficiency of weed or disease management, or may increase costs relative to revenue. Pest protective row covers, in the form of fine-mesh netting (referred to as mesotunnels), are an effective alternative to pesticide use, but they are not without their challenges. While row covers exclude insect pests and the pathogens they vector, it is unknown how well non-vectored diseases can be managed underneath the row cover. The exclusion of …

Practical Challenges In Delivering Dsrna For Woody Plant Protection, Zachary Bragg

Theses and Dissertations--Entomology

Unprecedented weather events associated with climate change, coupled with extensive anthropogenic stresses, have reduced the effectiveness of traditional forest pest management approaches, which can no longer keep pace with invasive species overwhelming naïve landscapes and native pests experiencing eruptive and expansive outbreaks. Double-stranded RNA-(dsRNA) mediated gene silencing, a type of RNA interference (RNAi), has been coopted for use as a biopesticide against a multitude of agricultural and horticultural pests and could serve as a powerful tool for woody plant protection. While effective initiation of gene silencing and subsequent mortality have been demonstrated in multiple tree pests, effective and efficient methods …

Increased Social Support And Maintained Weight Loss Among Post Metabolic And Bariatric Surgery Patients Following A Support And Nutrition-Based Program, Sydney Mae Mcintosh

Theses and Dissertations--Nutrition and Food Systems

Obesity, a prevalent health condition nationwide, has now been recognized as a diagnosable chronic health disease. With that prevalence we have seen a rise in obesity-related comorbidities which can be attributed to excess weight. Therefore, to combat obesity and related comorbidities, metabolic and bariatric surgery is becoming a more accepted and utilized treatment for individuals with obesity. Metabolic and bariatric surgery is the most effective and safest treatment for weight loss in individuals with obesity. However, metabolic, and bariatric surgery is a restrictive and/or malabsorptive procedure that requires significant lifestyle changes before and after the procedure. Patients who undergo metabolic …

Links Between Perceived Mother-Adolescent And Father-Adolescent Conflict And Low Self-Control: A Cross-National Comparative Study, Tory Thomas

Theses and Dissertations--Family Sciences

The influence of parent-adolescent relationships and adolescent adjustment have been well-documented. Self-control has emerged as a key probabilistic construct in understanding adjustment, well-being, and life success. The present study tests the links between adolescent perceptions of maternal and paternal conflict and self-control. In addition, to understand the extent to which cultural developmental context impacts these associations, the study will employ a cross-cultural comparative lens to test whether cultural context moderates these links. Self-report data were collected from N = 4,924 adolescents (Mage = 16.97 years, 54.08% female) across four countries (China, Czech Republic, Turkey, and the United States). In by …

Consequences Of Abiotic And Anthropogenic Stressors In The Antarctic Midge, Belgica Antarctica, Jack J. Devlin

Theses and Dissertations--Entomology

The ability to tolerate stress is key to maintaining fitness in extreme environments such as the polar regions. Subject to a myriad of extreme year-round abiotic conditions, invertebrates inhabiting the terrestrial ecosystems of Antarctica provide an excellent system to investigate adaptations to stress. Understanding the response of these species to abiotic and novel stressors is crucial in a world with rapidly occurring climate change and increasing anthropogenic activity. In this dissertation, I investigated physiological and molecular responses to naturally occurring and human-derived stresses in the midge Belgica antarctica, which is Antarctica’s only endemic insect.

In my first research chapter, I …

Nutrient Profile Assessment Of A Meal Program Impact On Older Adults' Diet Quality And Food Security Status, Millicent Yaa Gyasiwaa Ms

Theses and Dissertations--Nutrition and Food Systems

The rise in food insecurity globally has ignited institutions and organizations to implement policies and programs to reduce the burden on vulnerable people including older adults and people living in underserved areas. Though programs such as congregate, home-delivered meals, and pantries have been initiated to contribute to reducing food insecurity the nutrient content of these meals including recovered meals and their effect on food security status, food quality, and health has not been widely studied. The current study, Meals on Wings (MOW), assessed the nutrient profile of the free meals offered 4 times per week for 3 months, from May …

Sex Differences In Pediatric Hypertension: Obesity, Stress, And The Renin-Angiotensin System, Allyson Dyar

Theses and Dissertations--Nutrition and Food Systems

Pediatric hypertension, linked to long-term cardiovascular risks, shows increasing prevalence and varying patterns between boys and girls. This study explores sex-based differences in hypertension among 251 children aged 6-18 from Kentucky Children’s Hospital. Using 24-hour ambulatory blood pressure monitoring (ABPM) and assessing plasma renin, aldosterone, and cortisol, we examined blood pressure severity by sex. Girls showed a higher incidence of severe hypertension and elevated cortisol levels, whereas boys had higher mean systolic blood pressure. Aldosterone was associated with night systolic blood pressure in girls, while night diastolic blood pressure was linked to aldosterone in both sexes and renin in girls. …

Examining Anxious Attachment And Its Effects On Sexual Behaviors In Adulthood, Justin Graham

Theses and Dissertations--Family Sciences

The current study aimed to investigate the relationship between anxious attachment and adult sexual behaviors. The study utilized pairfam, a nationally representative German sample, as a secondary data set for its quantitative analysis. Participants responded to two anxious attachment scales and questions regarding sexual desire, sexual confidence, and age at first sexual experiences. Analyzing data from 5561 individuals, averaging 29.27 years old, a path analysis was conducted to assess variable effects. Findings indicate that higher anxious attachment correlates with reduced sexual confidence and earlier onset of sexual intercourse. Future studies should investigate additional attachment scales and include a more diverse …

The Relationships Between Maternal And Paternal Inconsistent Parenting And Cyberbullying Victimization, Anxiety And Depressive Symptoms Among Adolescents, Lynn Maamari

Theses and Dissertations--Family Sciences

The present research investigated the associations between maternal and paternal inconsistent parenting and cyberbullying victimization, anxiety, and depression. It also tested the extent to which these relationships were moderated by sex. It was expected that inconsistent maternal and paternal parenting would be positively associated with cyberbullying victimization, anxiety, and depressive symptoms. It was also expected that the links between maternal and paternal inconsistent parenting and cyberbullying victimization, anxiety as well as depression symptoms would not be moderated by sex. Data were collected from 500 14–18-year-old Czech teenagers, with a mean age of 14.4 years; 54% of the participants were female. …

Evaluation Of Ten Alternative Treatments For The Management Of Harlequin Bug (Murgantia Histrionica) On Brassica Crops, Sarah Clark

Theses and Dissertations--Entomology

This thesis investigates the efficacy of exclusion netting and selected biopesticides in controlling the common brassica pest harlequin bug (Murgantia histrionica); it assesses the phytotoxic effects caused by selected essential oil products; and it evaluates whether selected treatments caused mortality in common beneficial insects. This is one of the first studies to investigate the potential pest controlling properties of commercially produced bokashi fermented composting products as well as their effect on natural enemies.

During both the first and second year of the study, none of the commercially produced essential oil products or bokashi products were effective in controlling …

Assessing Endophyte Frequency Distributions And The Effect Of Epichloë Brachyelytri In The Chemotypic And Genotypic Diversity Of Brachyelytrum Erectum, Rachel Ann Sneed

Theses and Dissertations--Plant Pathology

Seed-transmissible epichloid fungal endophytes are best known for their roles as defensive mutualists in cool-season grasses. Historically, the discovery of fungal endophytes was driven by investigations of plant toxicity to livestock, followed by extensive study of their alkaloids and protection against insects and nematodes. Epichloae can produce four classes of alkaloids: ergot alkaloids, lolines (saturated aminopyrrolizidines), indole–diterpenes, and peramine. It is increasingly evident that these hereditary symbionts have much more diverse chemical profiles both in individual populations and between them. To this end, differences in chemotypic profiles of these symbionts may translate to different evolutionary and environmental advantages across plant …

Role Of Autophagy-Related Genes In Lipid Transport For Efficient Replication Of Tombusviruses, Yuanrong Kang

Theses and Dissertations--Plant Pathology

Tombusviruses are positive-strand RNA viruses, which utilize numerous co-opted host factors and massive de-novo synthesized membrane resources to modify host membranes and form large viral replication organelles (VROs). Among plenty of host cellular processes, autophagy emerges as a potential membrane resource for VROs formation due to its ability to de-novo generate the double membrane structures, known as autophagosomes. Besides, as an important host defense pathway, autophagy is also a target for tombusviruses to prevent its antiviral activities. In this study, I identify the role of key autophagy related genes, Atg11, Atg8, and Atg2, which are involved in autophagosome formation, and …

Systemic Signaling In Plants: Role Of Cuticle, Salicylic Acid, Rna, And Vitamins, Huazhen Liu

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is a form of broad-spectrum resistance induced in response to local infection that protects uninfected parts against subsequent secondary infections. Several diverse chemical signals contributing to SAR have been isolated and characterized, including glycerol-3-phosphate (G3P) and pipecolic acid (Pip), both of which play an important role in human and plant disease physiologies. In addition to these, salicylic acid (SA) also regulates SAR and normal transport of SA and G3P is required for de novo biosynthesis of Pip in the distal leaves. Pip is catabolized via multiple pathways, and this in turn regulates vitamin homeostasis. A normal …