Digital Commons Network^™

Wild Abandon: Postwar Literature Between Ecology And Authenticity, Alexander F. Menrisky

Theses and Dissertations--English

Wild Abandon traces a literary and cultural history of late twentieth-century appeals to dissolution, the moment at which a text seems to erase its subject’s sense of selfhood in natural environs. I argue that such appeals arose in response to a prominent yet overlooked interaction between discourses of ecology and authenticity following the rise and fall of the American New Left in the 1960s and 70s. This conjunction inspired certain intellectuals and activists to celebrate the ecological concept of interconnectivity as the most authentic basis of subjectivity in political, philosophical, spiritual, and literary writings. As I argue, dissolution represents a …

Understanding The Gray: Aging Women In Victorian Culture And Fiction, Hannah T. Ruehl

Theses and Dissertations--English

My dissertation, Understanding the Gray:Aging Women in Victorian Culture and Fiction, explores the cultural construction of aging for middle-class Victorian women and how aging was experienced and then depicted within novels. Chiefly, I work from midcentury to the end of the century in order to understand the experience of aging and ways women were ascribed age due to their position in society as spinsters, mothers, and progressive women. I explore how the age of fictional women reflects and contributes to critical debates concerning how Victorian women were expected to behave. Debates over separate spheres, how women were perceived in …

Fractionation Of Lignin Derived Compounds From Thermochemically Processed Lignin Towards Antimicrobial Properties, Luke A. Dodge

Theses and Dissertations--Biosystems and Agricultural Engineering

The overuse of antibiotics in agriculture is an emerging concern, due to their potential detrimental impact to the environment. This study focuses on exploring antimicrobial properties of lignin derived compounds. Lignin is of interest as a feedstock to replacing some petroleum-based chemicals and products because it is the most abundant source of renewable aromatic compounds on the planet. Two lignin rich streams, residues from the enzymatic hydrolysis of dilute acid and alkaline pretreated corn stover, were decomposed via pyrolysis and hydrogenolysis, respectively. The resulting liquid oils were subjected to sequential extractions using a series of solvents with different polarities. Chemical …

Assessing The Spatial Accuracy And Precision Of Lidar For Remote Sensing In Agriculture, Surya Saket Dasika

Theses and Dissertations--Biosystems and Agricultural Engineering

The objective of this whole study was to evaluate a LiDAR sensor for high-resolution remote sensing in agriculture. A linear motion system was developed to precisely control the dynamics of LiDAR sensor in effort to remove uncertainty in the LiDAR position/velocity while under motion. A user control interface was developed to operate the system under different velocity profiles and log LiDAR data synchronous to the motion of the system. The LiDAR was then validated using multiple test targets with five different velocity profiles to determine the effect of sensor velocity and height above a target on measurement error. The results …

High Resolution Sensing Of Nitrate Dynamics In A Mixed-Use Appalachian Watershed: Quantifying Nitrate Fate And Transport As Influenced By A Backwater Riparian Wetland, Alexandria Kosoma Jensen

Theses and Dissertations--Biosystems and Agricultural Engineering

As harmful algal blooms begin to appear in unexpected places such as rivers in predominantly forested systems, a better understanding of the nutrient processes within these contributing watersheds is necessary. However, these systems remain understudied. Utilization of high-resolution water quality data applied to deterministic numerical modeling has shown that a 0.42% watershed area backwater riparian wetland along the Ohio River floodplain can attenuate 18.1% of nitrate discharged from local mixed-use watersheds and improves in performance during high loading times due to coinciding increased hydrological connectivity and residence times of water in these wetlands. Loading from the Fourpole Creek watershed was …

Determining Heat Production Of Black Solderi Fly Larvae, Hermetia Illucens, To Design Rearing Structures At Livestock Facilities, Travis Mceachern

Theses and Dissertations--Biosystems and Agricultural Engineering

Due to their small size and ectothermic biology, the heat production of insects and insect larvae is hard to quantify. However, knowing the amount of heat production, as well as ammonia production of insects may be beneficial for commercial production of valuable insect species. Black soldier fly larvae (BSFL) are of interest in the agricultural industry because they quickly consume organic waste and have high amounts of protein and fat in their bodies. It has been proposed that BSFL be used to manage livestock waste, while serving as a high-protein feed source for livestock animals. To efficiently rear BSFL, it …

The Role Of Pro-Inflammatory Mediators Ifnβ And Prostaglandin E2 In Suppression Of Innate Immunity To Listeria Monocytogenes, Michelle G. Pitts

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

As a foodborne pathogen, Listeria monocytogenes (Lm) encounters many barriers to invasion and dissemination in the host that may change the nature of host response. Lm has been most commonly studied using intravenous (i.v.) inoculation, however, a method that delivers a bolus of bacteria directly to the bloodstream. Thus, little is known about what systemic and local mediators are triggered during the natural course of infection and how these may impact susceptibility. Our laboratory used foodborne transmission of Lm in mice to assess whether the method of transmission and the specific organ microenvironment could affect infection-induced secretion of …

Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron

Theses and Dissertations--Neuroscience

Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. …

The Impact Of Childhood Socioeconomic Status On Adult Reactions Toward Quantity Surcharges, Wenjing Li

Theses and Dissertations--Marketing and Supply Chain

Quantity surcharges have been widespread in the marketplace for decades. However, little is known about what kinds of consumers and under what conditions they are more likely to be impacted by this pricing practice. The current research contributes to the existing literature by investigating how a person’s childhood socioeconomic status affects their reaction toward quantity surcharges during adulthood. Across four studies, we find that childhood socioeconomic status has a positive impact on the purchase of a large and surcharged package size. However, when the economic conditions are threatening, the positive effect of childhood socioeconomic status disappears. The current research also …

Three Essays On College Earnings Premium And China’S Higher Education Expansion, Chenxu Hu

Theses and Dissertations--Economics

My dissertation consists of three essays that study the college premium in China and how it has been affected by China’s higher education expansion.

In the first essay, I utilize the high education expansion as exogenous source to estimate the college premium. The rapidly changing access to college provides a rare opportunity to estimate a local treatment effect (LATE) of college education on earnings by utilizing the drastic increase in college admission rate in 1999. I also utilize the yearly admission rate as an instrumental variable for the endogenous college education. Using China Household Income Project 2013, the two IV …

Myosin-Xva Is Key Molecule In Establishing The Architecture Of Mechanosensory Stereocilia Bundles Of The Inner Ear Hair Cells, Shadan Hadi

Theses and Dissertations--Medical Sciences

Development of hair cell stereocilia bundles involves three stages: elongation, thickening, and supernumerary stereocilia retraction. Although Myo-XVa is known to be essential for stereocilia elongation, its role in retraction/thickening remains unknown. We quantified stereocilia numbers/diameters in shaker-2 mice (Myo15^sh2) that have deficiencies in “long” and “short” isoforms of myosin-XVa, and in mice lacking only the “long” myosin-XVa isoform (Myo15^ΔN). Our data showed that myosin-XVa is largely not involved in the developmental retraction of supernumerary stereocilia. In normal development, the diameters of the first (tallest)/second row stereocilia within a bundle are equal and grow simultaneously. …

Mixtures-Of-Regressions With Measurement Error, Xiaoqiong Fang

Theses and Dissertations--Statistics

Finite Mixture model has been studied for a long time, however, traditional methods assume that the variables are measured without error. Mixtures-of-regression model with measurement error imposes challenges to the statisticians, since both the mixture structure and the existence of measurement error can lead to inconsistent estimate for the regression coefficients. In order to solve the inconsistency, We propose series of methods to estimate the mixture likelihood of the mixtures-of-regressions model when there is measurement error, both in the responses and predictors. Different estimators of the parameters are derived and compared with respect to their relative efficiencies. The simulation results …

Increasing Inclusion: The Pursuit Of Racial Diversity In Three Historically White Universities In Kentucky, Michigan, And Ontario From 2000 To 2012, David J. Luke

Theses and Dissertations--Sociology

The University of Kentucky (UK) and University of Michigan (UM) present very different patterns in terms of black student enrollments and completions from 2000 to 2012 because of a structural explanation, a qualitative explanation, and a statistical explanation. Unfortunately, the patterns at the University of Western Ontario (UWO) are partial due to a lack of data.

First, the structural explanation is that UK, as a university in the state of Kentucky, was under a mandate from the U.S. Department of Education to desegregate because they were in violation of Title VI of the Civil Rights Act. The Kentucky Council on …

Biological, Behavioral, And Psychosocial Attributes Of Individuals With Copd, Andrew A. Bugajski

Theses and Dissertations--Nursing

The purpose of this dissertation was to evaluate the biological, behavioral, and psychosocial attributes of individuals diagnosed with chronic obstructive pulmonary disease (COPD). Specific aims were to: 1) explore the predictive power of spirometry measures for event-free survival in patients with heart failure and suspected COPD, focusing on the differences in survival between those with and without airflow limitation; 2) examine the psychometric properties of the Multidimensional Scale of Perceived Social Support (MSPSS) in patients with concomitant COPD and heart failure; and 3) test the efficacy of a theory-based, multidimensional, self-care educational intervention using an eHealth platform on measures of …

Social Support, Relationship Quality, And Self-Care Behaviors In Patients With Heart Failure, Majdi Mohammad Rababa

Theses and Dissertations--Nursing

The purpose of this dissertation was to examine the associations among social support, gender, relationship quality, and self-care behaviors in patients with heart failure (HF). Specific aims were to: 1) compare the psychometric properties of the 12-item and the 9-item European Heart Failure Self-Care Behavior Scale (EHFScBS) when used to measure self-care behaviors in patients with HF in the United States; 2) determine whether gender moderated the association between perceived social support and daily sodium intake in patients with HF; and 3) determine whether a patient’s gender and relationship with the primary family caregiver (spousal or non-spousal) moderated the association …

Exploring The Effect Of Chronic Inflammation On Response To Immune Checkpoint Inhibitors In Cancer, Sherif M. El-Refai

Theses and Dissertations--Pharmacy

Precision medicine has allowed for the development of monoclonal antibodies that unmask the anti-tumor immune response. These agents have provided some patients durable clinical benefit. However, PD-1 and PD-L1 inhibitor therapies are effective in a small group (10-20%) of non-small cell lung cancer (NSCLC) patients when used as single-agent therapy. The approved companion diagnostic is expression of the immune cell surface molecule, programmed death ligand 1 (PD-L1), on tumors measured by immunohistochemistry (IHC). Studies in tumor biology and immune surveillance dictate that PD-1 inhibitor efficacy should depend on the level of PD-L1 expression; however, the literature has not followed with …

Dual Lox/Cox Inhibition: A Novel Strategy To Prevent Neurovascular Leakage In Epilepsy, Brent S. Sokola

Theses and Dissertations--Pharmacy

Epilepsy affects 3.4 million patients in the USA and is characterized by recurring seizures. The blood-brain barrier is leaky in epilepsy and may contribute to seizure progression but the mechanisms which cause this leakage are not fully understood. We hypothesized that seizures trigger LOX- and COX-mediated blood-brain barrier leakage and that dual LOX/COX inhibition prevents barrier leakage in vivo. To test this hypothesis, we administered either the dual LOX/COX inhibitor licofelone or a combination of the 5-LOX inhibitor zileuton and the COX-2 inhibitor celecoxib to rats that experienced status epilepticus (SE). Serum and brain capillaries were isolated 48 hours …

Understanding The Thermodynamics And Oral Absorption Potential Of Pharmaceutical Amorphous Solid Dispersions, Nico Setiawan

Theses and Dissertations--Pharmacy

Supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs), have been used extensively to elevate the apparent solubility and oral bioavailability of poorly water-soluble drugs. However, despite the numerous examples of success in increasing solubility and oral bioavailability using ASDs, physical stability challenges remain as formulators seek to employ high drug loading for cost reduction and improved patient compliance. Therefore, stability in both the solid and solution state must be considered for ASDs to be successful. In the solid state, the drug must remain amorphous in the solid matrix throughout the shelf life of the product. Although excipients, such …

The Impact Of Bioactive Phytosterol, Stigmasterol, On Cholesterol Elimination Pathways In Mice, Hannah C. Lifsey

Theses and Dissertations--Pharmacy

Despite advances in healthcare, cardiovascular disease (CVD) remains the leading cause of death in the United States. Elevated levels of plasma cholesterol are highly predictive of CVD and stroke and are the principal driver of atherosclerosis. Unfortunately, current cholesterol lowering agents, such as statins, are not known to reverse atherosclerotic disease once it has been established. In preclinical models, agonists of nuclear receptor, LXR, have been shown to reduce and reverse atherosclerosis. Phytosterols are bioactive non-cholesterol sterols that act as LXR agonists and regulate cholesterol metabolism and transport. We hypothesize that stigmasterol would act as an LXR agonist and alter …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui

Theses and Dissertations--Pharmacy

New antibiotics with novel targets or mechanisms of action are needed to counter the steady emergence of bacterial pathogens that are resistant to antibiotics used in the clinic. MraY, a promising novel target for antibiotic development, initiates the lipid cycle for the biosynthesis of peptidoglycan cell wall, which is essential for the survival of most, if-not-all, bacteria. MraY is an enzyme that catalyzes the transfer and attachment of phospho-MurNAc-pentapeptide to a lipid carrier, undecaprenylphosphate. Muraymycins are recently discovered lipopeptidyl nucleoside antibiotics that exhibit remarkable antibiotic activity against Gram-positive as well as Gram-negative bacteria by inhibiting MraY. We conducted a thorough …

Characterization And Engineering Of Human Proteins As Therapeutic Candidates, Kyungbo Kim

Theses and Dissertations--Pharmacy

Protein engineering has been a useful tool in the fight against human diseases. Human insulin was the first recombinant DNA-derived therapeutic protein (Humulin^®) approved by the US FDA in 1982. However, many of the early protein drugs were only recombinant versions of natural proteins with no modification of their primary amino acid sequence and most of them did not make optimal drug products mainly due to their short half-life or suboptimal affinity, leading to poor therapeutic efficacy. The difficulty in the large-scale production of some therapeutic proteins was another important issue. In the past three decades, different protein …

Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook

Theses and Dissertations--Pharmacy

The extensive and sometimes incorrect and noncompliant use of various types of antimicrobial agents has accelerated the development of antimicrobial resistance (AMR). In fact, AMR has become one of the greatest global threat to human health in this era. The broad-spectrum antibiotics aminoglycosides (AGs) display excellent potency against most Gram-negative bacteria, mycobacteria, and some Gram-positive bacteria, such as Staphylococcus aureus. The AG antibiotics amikacin, gentamicin, kanamycin, and tobramycin are still commonly prescribed in the U.S.A. for the treatment of serious infections. Unfortunately, bacteria evolve to acquire resistance to AGs via four different mechanisms: i) changing in membrane permeability to …

Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang

Theses and Dissertations--Pharmacy

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved catalytic …

Using The Qbest Equation To Evaluate Ellagic Acid Safety Data: Generating A Qnoael With Confidence Levels From Disparate Literature, Cynthia Rose Dickerson

Theses and Dissertations--Pharmacy

QBEST, a novel statistical method, can be applied to the problem of estimating the No Observed Adverse Effect Level (NOAEL or QNOAEL) of a New Molecular Entity (NME) in order to anticipate a safe starting dose for beginning clinical trials. The NOAEL from QBEST (called the QNOAEL) can be calculated using multiple disparate studies in the literature and/or from the lab. The QNOAEL is similar in some ways to the Benchmark Dose Method (BMD) used widely in toxicological research, but is superior to the BMD in some ways. The QNOAEL simulation generates an intuitive curve that is comparable to the …

Synthesis And Biological Evaluation Of Novel Drug Candidates To Address Drug Resistance In Tuberculosis And Fungal Diseases, Huy Ngo

Theses and Dissertations--Pharmacy

Tuberculosis (TB) and fungal infections are two of the most lethal infectious diseases worldwide due to the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) and fungal strains that can resist the most potent antimicrobial drugs currently employed. Due to the rise of these drug resistant strains, effective treatment options for these two infections are limited. This dissertation aims at exploring novel drug scaffolds to help combat drug resistance in TB and fungal infections.

TB caused by the pathogenic Mtb is, alongside with human immunodeficiency virus acquired immunodeficiency virus (HIV), the deadliest infectious disease worldwide with approximately 2-3 billion people …

Bivariate Generalization Of The Time-To-Event Conditional Reassessment Method With A Novel Adaptive Randomization Method, Donglin Yan

Theses and Dissertations--Epidemiology and Biostatistics

Phase I clinical trials in oncology aim to evaluate the toxicity risk of new therapies and identify a safe but also effective dose for future studies. Traditional Phase I trials of chemotherapies focus on estimating the maximum tolerated dose (MTD). The rationale for finding the MTD is that better therapeutic effects are expected at higher dose levels as long as the risk of severe toxicity is acceptable. With the advent of a new generation of cancer treatments such as the molecularly targeted agents (MTAs) and immunotherapies, higher dose levels no longer guarantee increased therapeutic effects, and the focus has shifted …

Investigation Of Environmental Cadmium Sources In Eastern Kentucky, Elizabeth Maher

Theses and Dissertations--Mining Engineering

Utilizing data collected by the University of Kentucky Lung Cancer Research Initiative (LCRI), this study investigated potential mining-related sources for the elevated levels of cadmium in Harlan and Letcher counties. Statistical analyses for this study were conducted utilizing SAS. A number of linear regression models and logarithmic models were used to evaluate the significance of the data. The linear regression models consisted of both simple and multivariate types, with the simple models seeking to establish significance between the potential sources and urine cadmium levels and the multivariate models seeking both to identify any statistically significant linear relationships between source types …

Parent-Implemented Language Intervention With Young Children From Low-Ses Environments Who Have Language Impairment, Courtney Allison Hatcher

Theses and Dissertations--Rehabilitation Sciences

In this study, the author examined the effects of training four parents from low-socioeconomic environments to use Enhanced Milieu Teaching (EMT) with their young children with language impairment. The investigator used a modified Teach-Model-Coach-Review method to teach parents to use the following EMT strategies during 8-10 individualized, home-based sessions: matched turns, expansions, time delays and milieu teaching prompts. A single-case multiple-baseline design across-behaviors replicated across four parent/child dyads was used to evaluate the parents' use of the EMT strategies. Child language outcomes were also assessed using pre- and post-intervention language samples. All parents learned and demonstrated use of each language …

Vitamin D Works Through The Lipid Droplet Protein Plin2 To Augment Mitochondrial Function In Skeletal Muscle, David M. Schnell

Theses and Dissertations--Pharmacology and Nutritional Sciences

Vitamin D has been connected with increased intramyocellular lipid (IMCL) mitochondrial function in skeletal muscle. It is also shown to prevent lipotoxicity in several tissues, but this has not yet been examined in skeletal muscle. Perilipin 2 (PLIN2), a lipid droplet protein upregulated with vitamin D treatment, is integral to managing IMCL capacity and lipid oxidation in skeletal muscle. Increased lipid storage and oxidation is associated with increased tolerance to a hyperlipidic environment and resistance to lipotoxicity. Therefore, I hypothesized that vitamin D increases β-oxidation and lipid turnover though a PLIN2 mediated mechanism, thereby preventing lipotoxicity.

This hypothesis was divided …