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Scrollar Invariants Of Tropical Chains Of Loops, Kalila Joelle Sawyer

Theses and Dissertations--Mathematics

We define scrollar invariants of tropical curves with a fixed divisor of rank 1. We examine the behavior of scrollar invariants under specialization, and compute these invariants for a much-studied family of tropical curves. Our examples highlight many parallels between the classical and tropical theories, but also point to some substantive distinctions.

Orthogonal Recurrent Neural Networks And Batch Normalization In Deep Neural Networks, Kyle Eric Helfrich

Theses and Dissertations--Mathematics

Despite the recent success of various machine learning techniques, there are still numerous obstacles that must be overcome. One obstacle is known as the vanishing/exploding gradient problem. This problem refers to gradients that either become zero or unbounded. This is a well known problem that commonly occurs in Recurrent Neural Networks (RNNs). In this work we describe how this problem can be mitigated, establish three different architectures that are designed to avoid this issue, and derive update schemes for each architecture. Another portion of this work focuses on the often used technique of batch normalization. Although found to be successful …

An Examination Of Single-Sex Secondary Agricultural Education Classrooms: The Effects Of Teacher Expectancy, Brett Morris Wasden

Theses and Dissertations--Community & Leadership Development

The effectiveness of single-sex classrooms in the United States remains unclear. To address this issue, the purpose of this quasi-experiment was to examine single-sex classrooms in secondary agricultural education classrooms in Kentucky. Data were collected through quantitative pretests and posttests from student participants (n = 168) and teacher participants (n = 8). The findings indicated that student participants in single-sex classrooms had higher academic performance, better attendance, and an increased gain in interest in the agriculture, food, and natural resources career pathway. Students participants in coeducational classrooms had less discipline referrals. Teacher participants’ expectation were related to student …

Quantifying Nitrogen Fate In Karst Agroecosystem Streams Of Central Kentucky: Development And Application Of Numerical Modeling And Insight From High-Resolution Sensors, Nolan Lewis Bunnell

Theses and Dissertations--Biosystems and Agricultural Engineering

In-stream fate of nutrients in karst agroecosystems remains poorly understood, despite the known impact of karst on water resources at local to global scales. In the Inner-Bluegrass region of central Kentucky, heterogeneity of karst maturity, flow pathways, and nutrient sources adds to the complexity of quantifying nutrient dynamics, thus requiring novel monitoring and modeling approaches. The significance of these streams is recognized given spring/surface water confluences have been identified as hotspots for biogeochemical transformations. In slow-moving streams high in dissolved inorganic nutrients (particularly dissolved inorganic nitrogen (DIN) and dissolved reactive phosphorus (DRP)), benthic and floating aquatic macrophytes are recognized to …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Involvement Of The Sigma-1 Receptor In Methamphetamine-Mediated Changes To Astrocyte Structure And Function, Richik Neogi

Theses and Dissertations--Medical Sciences

Methamphetamine is a highly addictive psychostimulant drug. There are currently no FDA-approved pharmacological treatments for methamphetamine addiction. Pharmacologically, (+)-methamphetamine is a dopamine releasing agent and dopamine transporter substrate that redistributes dopamine from intracellular vesicles via the vesicular monoamine transporter 2 (VMAT2) and reverses the direction of dopamine transport in the dopamine transporter. Methamphetamine, cocaine, and other drugs of abuse are also sigma-1 receptor ligands, and previous studies have demonstrated the role of the sigma-1 receptor in modulating the behavioral and cellular effects of these drugs. However, almost all these studies were conducted in cell culture systems or with emphasis on …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Predicting Positive Attitudes Toward Immigrants With Altruism, Kati Elizabeth Stafford

Theses and Dissertations--Political Science

Immigration is one of the most salient and divisive issues in the US and a host of other countries, with public opinion polarized and elites deadlocked on the issue. One limitation of research on immigration attitudes is the tendency for scholars to focus exclusively on dark motivations driving hostility toward immigrants rather than those leading to compassion and support for immigrants. Using 2016 American National Election Studies (ANES) data, I examine the relationship between attitudes towards immigration and several Big Five personality traits, focusing on Altruism. I find that personality traits, especially those related to Altruism, are crucial determinants of …

Cancer Phylogenetic Analysis Based On Rna-Seq Data, Tingting Zhai

Theses and Dissertations--Statistics

Studying tumor evolution is a major task to understand the biological mechanism of carcinogenesis, develop new cancer therapies, and prevent drug resistance. We focus on two important questions in tumor evolution. The first question is to quantify intra-tumor heterogeneity, where multiple subclones of tumor cells with distinct transcriptomic profiles. Another question is to estimate the temporal order of alteration of key cancer pathways during tumor evolution. We present a new statistical method to 1) reconstruct the evolutionary history and population frequency of the subclonal lineages of tumor cells and 2) infer temporal order of pathway alterations in tumor evolution for …

Semiparametric And Nonparametric Methods For Comparing Biomarker Levels Between Groups, Yuntong Li

Theses and Dissertations--Statistics

Comparing the distribution of biomarker measurements between two groups under either an unpaired or paired design is a common goal in many biomarker studies. However, analyzing biomarker data is sometimes challenging because the data may not be normally distributed and contain a large fraction of zero values or missing values. Although several statistical methods have been proposed, they either require data normality assumption, or are inefficient. We proposed a novel two-part semiparametric method for data under an unpaired setting and a nonparametric method for data under a paired setting. The semiparametric method considers a two-part model, a logistic regression for …

Associations Between Psychosocial Stressors, Genes, And Cardiovascular Disease In At-Risk Adults, Kaitlin Voigts Key

Theses and Dissertations--Nursing

Psychosocial stressors have a significant adverse impact on cardiovascular health. While better medical treatments and increased emphasis on healthy lifestyle have improved cardiovascular health for many in the United States over the past 50 years, there are persistent inequities in cardiovascular disease (CVD) rates, with the highest rates among populations burdened by chronic exposure to psychosocial stressors such as discrimination and anxiety, among others. Genetic factors may interact with these stressors further influencing the rates of CVD in these populations. The purpose of this dissertation is to examine associations among psychosocial stressors and other CVD risk factors, and the influence …

Establishing Exclusive Breastfeeding And The Influence Of Hospital Support, Martha Monroe

Theses and Dissertations--Nursing

Maternal-child health authorities recommend that infants breastfeed exclusively for the first six months of life. Currently, 25% of infants in the United States do so. Breastfeeding specific care that mothers receive from their postpartum nurses and lactation specialists is integral to successfully initiating exclusive breastfeeding. Due to the time sensitive nature of establishing milk supply, interrupting the process of lactogenesis with supplementation puts infants at high risk for early termination of breastfeeding. The purpose of this dissertation is to examine the relationship of breastfeeding care received during the postpartum hospital stay, defined as the first 48-72 hours of life, and …

Meaningful Measurement Matters: Defining Potentially Inappropriate Medication Use To Target Cognitive Outcomes, Ashley I. Martinez

Theses and Dissertations--Pharmacy

Preventable and unintended consequences of medication use occur in more than 25% of ambulatory and hospitalized patients, and nearly half of long-term care patients. Unfortunately, many medications used to treat common health conditions in older adults (such as anxiety, behavioral disturbances, incontinence, insomnia, depression, and pain) have also been linked to cognitive impairment and decline. Recently, substantial efforts to investigate medications and medication classes that may be associated with cognitive impairment and decline in older adults have been undertaken. Unfortunately, studies have used a wide variety of different tools to define “potentially inappropriate medication” (PIM) use, and no published literature …

Relationship Between Initial Prescription Opioid Exposure Length And Future Opioid Use Disorder Diagnosis In Opioid Naive Adolescents, Eric Lindahl

Theses and Dissertations--Pharmacy

Objectives: The long-term risks associated with the use of short-term prescription opioids in opioid naïve adolescents in not well characterized. The purpose of this study was to explore the potential association between the days’ supply of the initial prescription opioid exposure and the rates of diagnosed OUD in the subsequent 3-year period. Methods: We conducted a retrospective cohort study using a nationwide database of commercially-insured adolescents aged 12-17 at the time of the index opioid fill. A multivariable Cox Proportional Hazard regression model was developed to analyze the association of interest while accounting for known risk factors for the development …

Population Pharmacokinetic Modeling And Genetic Association Analysis In Infants With Neonatal Abstinence Syndrome Receiving Morphine Or Clonidine, Fei Tang

Theses and Dissertations--Pharmacy

Neonatal abstinence syndrome, or NAS, is a postnatal opioid withdrawal syndrome occurring in 55% to 94% of neonates as a result of in utero exposure to opioids. It has emerged as a significant public health issue, as its incidence more than quadrupled in the past decade. There is significant variability in disease severity and treatment outcomes in neonates with NAS due to patient-specific factors and treatment- or site-specific factors. To understand what contributes to variability in length of hospital stay and other outcomes in neonates with NAS, we assessed population pharmacokinetics (PK) of clonidine and morphine, and we investigated potential …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

Novel Small Molecule Antifungals For Invasive Fungal Infections, Emily Dennis

Theses and Dissertations--Pharmacy

Human fungal pathogens cause a range of diseases from benign skin conditions (i.e., ringworm) to thrush, mucosal membrane infections, and life-threatening systemic infections including bloodstream infections (i.e., aspergillosis and candidiasis) and Cryptococcal meningitis. These systemic infections occur most often in immunocompromised individuals and have high mortality rates. Current antifungal agents used in the clinic belong to three main classes: the polyenes (e.g., amphotericin B (AmB)), the echinocandins (e.g., caspofungin (CFG)), and the azoles (e.g., fluconazole (FLC)). In addition, the antimetabolite pyrimidine analogue flucytosine is used in combination with AmB. The …

Characterization And Engineering Of Interrupted Adenylation Domains, Taylor A. Lundy

Theses and Dissertations--Pharmacy

Nature has historically served as a prolific source of biologically active molecules produced by plants, fungi, and bacteria termed natural products (NPs). These NPs often serve as therapeutic leads due to their structural diversity and unique mechanisms of action. However, many need modifications to make them more effective or safer for human use. This can be a daunting and complicated task to do via traditional organic chemistry because of their complexity, copious stereocenters, and a multitude of reactive functional groups. For this reason, enzymatic modification of these NP during their biosynthesis is an appealing option. One major class of NPs …

Investigating Whether Ecological Models Of Community-Oriented Variables Improve Prediction Of Childhood Resilience Over A Set Of Personal Characteristic Variables Such As Impulse Control, Emotional Regulation, Relational Motivation, And Self-Reliance, Vinod Kumar Srivastava

Theses and Dissertations--Social Work

Children experiencing trauma and entering child protective services have been continuously increasing. Problems associated with childhood trauma, such as neurodevelopmental disorder, trauma and stress-related disorders, personality disorders, substance use disorder, externalizing and internalizing disorders, academic problems, relational difficulties, and delinquent behaviors, have been found increasing despite advances in trauma and translational research. Children’s trauma is mostly interpersonal in nature and nested in their immediate environment. There is a need for a change in focus from helping children to overcome challenges and adversities to strengthening the resilience-building process by utilizing functional strengths in the environment to achieve sustainable outcomes. This study’s …

Embodying Inequality: Three Papers On The Role Of Gender And Discrimination In The Lives Of Women, Stefana I. Moldovan

Theses and Dissertations--Social Work

Women experience different forms of discrimination throughout their lives such as unfair treatment in interpersonal interactions in the public spheres and in the private sphere, as prescribed by societal gender roles, women can also experience inequality and discrimination as a disproportionate share of household work and caregiving, limited participation in decision making, unequal access and share of financial resources and leisure, and as well as in cases, of emotional, and physical, or sexual abuse. Limited research explored the potential joint effect of these forms of discrimination. The questions explored in this dissertation were: (1) How does gendered intra-household inequality, experienced …

Electrophoresis In Heterogeneous Hydrogels And Applications In Surface Patterning, Ning Ge

Theses and Dissertations--Mechanical and Aerospace Engineering

The creation of chemical micropatterns on surfaces makes it possible to add unique chemical functionality to surfaces, modifying properties such as wettability, or even adding the ability to selectively bind other molecules. The creation of biochemical surface patterning in particular is useful in a variety of fields including tissue engineering and highthroughput drug screening. There are many existing surface patterning techniques which focus on precise control over the patterned geometry, even down to submicron scale features, but they do not allow local control over chemical concentration. So the results are high resolution patterns with binary concentration. There are also existing …

Bacterial Cell Wall Characterization Via Atomic Force And Confocal Microscopy, Joree Sandin

Theses and Dissertations--Mechanical and Aerospace Engineering

Poor oral hygiene is a severe global health issue, with about 44% of the Earth’s population suffering from untreated tooth decay, accounting for over $100 billion dollars spent on dental services per year in the United States, alone. Manual treatments, such as brushing, flossing, or swishing with antiseptic rinse are the main ways to alleviate harmful bacteria that cause these oral health problems. Streptococcus mutans (S. mutans) is a group of highly antibiotic, Gram-positive bacteria that heavily contribute to oral cavities, plaque build-up, and potential loosening or loss of dental implants if a biofilm develops. Currently, the mechanism …

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Molecular Features, Epidemiological Risk Factors, And Evidence-Based Clinical Recommendations, Ryan Decoster

Theses and Dissertations--Clinical and Translational Science

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that can form around textured-surface breast implants. In this dissertation, the cellular and molecular mechanisms of BIA-ALCL are reviewed with a focus on the role of oncogenic JAK-STAT3 signaling in BIA-ALCL tumorigenesis and progression. Herein, the epidemiology of BIA-ALCL is systematically studied to better define the risk of BIA-ALCL and to determine the oncologic safety of smooth surface devices relative to BIA-ALCL formation. Next, a systematic review is conducted which critically appraises current clinical guidelines in order to establish an evidence base to better inform …

Transcriptomic And Cellular Response To Mechanical Overload And The Underlying Role Of Macrophages In Extracellular Matrix Remodeling, Bailey D. Peck

Theses and Dissertations--Rehabilitation Sciences

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. Upon mechanical loading, including resistance exercise, which alter muscle fiber contractile activity, size, orientation and connectivity, remodeling processes must occur that involve both ECM deposition and degradation. ECM remodeling involves many cell types in muscle, but the focus of our research was directed towards macrophages, which participate in the early immune response to damage and loading. We have consistently demonstrated a significant increase in skeletal muscle macrophage abundance using pan macrophage markers (CD11b/CD68) and anti-inflammatory markers (CD206/CD163) following exercise training in …

The Effects Of Dietary Nitrate And Vitamin C On Endothelial Function And Oxidative Stress Biomarkers, Reem Basaqr

Theses and Dissertations--Pharmacology and Nutritional Sciences

Background: Endothelial dysfunction is associated with a decline in the vasodilator nitric oxide (NO) and presents alongside other cardiovascular risk factors in the early stages of atherosclerosis. Independently, inorganic nitrate and vitamin C supplementation have shown promise in providing some restoration of NO bioavailability, reduced oxidative stress, and improvements in endothelial function. Some preliminary evidence has suggested that vitamin C may augment the reduction of nitrite to further liberate NO and improve cardiovascular health. However, co-supplementation has not been adequately studied. Our objective was to compare the effect of inorganic nitrate in the form of concentrated beetroot juice (CBJ) with …

Functional Impact Of Angiotensinogen Specific Domains On Angiotensin Ii-Mediated Functions, Chia-Hua Wu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Angiotensinogen (AGT) is the only substrate for all angiotensin peptides in the renin angiotensin system (RAS). Cleavage of AGT by renin is a rate-limiting step of angiotensin peptides productions in the RAS and regulates angiotensin peptides-associated pathophysiological functions. Only ten N-terminal residues are cleaved by renin and the functions of remaining part of AGT protein, which is called des(angiotensin I)AGT, remain unclear. Despite of pivotal roles of AGT in the RAS, studies related to how AGT is metabolized and how des(angiotensin I)AGT regulates AGT functions or AngII-mediated functions are limited.

Renin cleavage of AGT shows species specificity. It has been …

Divergence In Neuronal Calcium Dysregulation In Brain Aging And Animal Models Of Ad, Adam Ghoweri

Theses and Dissertations--Pharmacology and Nutritional Sciences

Neuronal calcium dysregulation first garnered attention during the mid-1980’s as a key factor in brain aging, which led to the formulation of the Ca²⁺ hypothesis of brain aging and dementia. Indeed, many Ca²⁺-dependent cellular processes that change with age, including an increase in the afterhyperpolarization, a decrease in long-term potentiation, an increased susceptibility to long-term depression, and a reduction in short-term synaptic plasticity, have been identified. It was later determined that increased intracellular Ca²⁺ with age was due to increased Ca²⁺ channel density, elevated release from intracellular Ca²⁺ stores, and decreased Ca²⁺ buffering …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Striated Muscle Specific Ribosomal Protein L3-Like: Effect Of Knockout On Cardiac Function And Protein Translation, Laura P. Brown

Theses and Dissertations--Physiology

Ribosomes are the molecular machinery of the cell that catalyzes synthesis of peptides from amino acids. The eukaryotic ribosome is made up of four strands of ribosomal RNA (rRNA) and ~80 ribosomal proteins. While many tissues routinely exhibit variations of ribosomal protein stoichiometry, tissue specific ribosomal proteins are rare. The ribosomal protein with the highest tissue specificity of any ribosomal protein is found in striated muscle, ribosomal protein L3-like (RPL3L). Other than its tissue specificity, association with atrial fibrillation, and chromosomal location, there is little known about the function of RPL3L. However, its ubiquitously expressed paralog, RPL3, has been well …