Digital Commons Network^™

Temporal And Spatial Characterization Of Macondo 252 Signatures In Gulf Of Mexico Shelf And Slope Sediments, Olivia P. Woodruff

Theses and Dissertations--Earth and Environmental Sciences

The long-term fate of hydrocarbons in the Gulf of Mexico (GOMx) following the 2010 Deepwater Horizon oil spill has yet to be fully characterized. Elemental (% C and % N), stable isotopes (δ¹³C_organic), and polycyclic aromatic hydrocarbon (PAH) molecular signatures were investigated in shelf and slope sediments collected in October 2010 and 2011 to gain insight into processes affecting the distribution and fate of spilled Macondo oil. Particulate organic carbon (POC) ranged between 1.55 and 2.22 wt. % in 2010 and 0.55 and 2.06 % in 2011 while the corresponding δ¹³C_organic ranges were …

Analysis Of The Role Of Two Autophagy Pathway Related Genes, Becn1 And Tsc1, In Murine Mammary Gland Development And Differentiation, Amber N. Hale

Theses and Dissertations--Biology

The mammary gland is a dynamic organ that undergoes the majority of its development in the postnatal period in four stages; mature virgin, pregnancy, lactation, and involution. Every stage relies on tightly regulated cellular proliferation, programmed cell death, and tissue remodeling mechanisms. Misregulation of autophagy, an intracellular catabolic process to maintain energy stores, has long been associated with mammary tumorigenesis and other pathologies. We hypothesize that appropriate regulation and execution of autophagy are necessary for proper development of the mammary ductal tree and maintenance of the secretory epithelia during late pregnancy and lactation. To test this hypothesis we examined the …

A Petrographic Characterization Of The Leatherwood Coal Bed In Eastern Kentucky, Michelle N. Johnston

Theses and Dissertations--Earth and Environmental Sciences

The Eastern Kentucky Coal Field is located in the central portion of the Appalachian Basin. The Pennsylvanian Breathitt Formation in this region is characterized by numerous sequences of bituminous coal-bearing sedimentary rocks. These coals have distinct maceral compositions due to variations in depositional environments. Coal characterization is an important method for determining conditions that influenced peat accumulation and overall depositional settings of mires.

This study focuses on the characterization of the maceral composition of the Middle Pennsylvanian-age Leatherwood coal bed. It utilizes petrographical, palynological, and geochemical analyses to describe specific depositional environments and associated peat accumulation conditions.

Petrographic analyses indicate …

The Nature And Origin Of Cyclicity In The Cleveland Member Of The Ohio Shale (Upper Devonian), Northeastern Kentucky, U.S.A., Alice C. O'Bryan

Theses and Dissertations--Earth and Environmental Sciences

The Cleveland Shale displays a characteristic and distinctive pattern of promontories and recessed intervals on weathered outcrops, which appears to represent cyclicity. This weathering pattern can be observed in other shales, both within and outside the Appalachian Basin; so determining the nature of these cycles may be critical for understanding the origin of, not only the Cleveland Shale, but also of black shales in general. Cyclicity in the Cleveland was examined on a decimeter-to-meter scale using lithologic characterization, gamma-ray stratigraphy and x-ray fluorescence, and on a millimeter-to-centimeter scale using organic petrography. Lithologic characterization and gamma-ray stratigraphy revealed Milankovitch-band fourth- and …

Renal Humoral, Genetic And Genomic Mechanisms Underlying Spontaneous Hypertension, Jason A. Collett

Theses and Dissertations--Biology

In spite of significant progress in our knowledge of mechanisms that control blood pressure, our understanding of the pathogenesis of hypertension, its genetics, and population efforts to control blood pressure, hypertension remains the leading risk factor for mortality worldwide. It’s estimated that 1 out of every 3 adults has hypertension. Hypertension is a major risk factor for cardiovascular disease and stroke, and is considered a primary or contributing cause of death to more than 2.4 million US deaths each year. Although spontaneous hypertension has been the subject of substantial research, many critical questions remain unanswered.

To investigate mechanisms underlying spontaneous …

Strong Angels Of Comfort: Middle Class Managing Daughters In Victorian Literature, Emily A. Dotson

Theses and Dissertations--English

This dissertation joins a vibrant conversation in the social sciences about the challenging nature of care labor as well as feminist discussions about the role of the daughter in Victorian culture.

It explores the literary presence of the middle class managing daughter in the Victorian home.

Collectively, the novels in this study articulate social anxieties about the unclear and unstable role of daughters in the family, the physically and emotionally challenging work they, and all women, do, and the struggle for daughters to find a place in a family hierarchy, which is often structured not by effort or affection, but …

Knowing And Being Known: Sexual Delinquency, Stardom, And Adolescent Girlhood In Midcentury American Film, Michael Todd Hendricks

Theses and Dissertations--English

Sexual delinquency marked midcentury cinematic representations of adolescent girls in 1940s, 50, and early 60s. Drawing from the history of adolescence and the context of midcentury female juvenile delinquency, I argue that studios and teen girl stars struggled for decades with publicity, censorship, and social expectations regarding the sexual license of teenage girls. Until the late 1950s, exploitation films and B movies exploited teen sex and pregnancy while mainstream Hollywood ignored those issues, struggling to promote teen girl stars by tightly controlling their private lives but depriving fan magazines of the gossip and scandals that normally fueled the machinery of …

Biomechanical Effects Of Trees And Soil Thickness In The Cumberland Plateau, Michael Shouse

Theses and Dissertations--Geography

Previous research in the Ouachita Mountains, Arkansas suggests that, on relatively thin soils overlying bedrock, individual trees locally thicken the regolith by root penetration into bedrock. However, that work was conducted mainly in areas of strongly dipping and contorted rock, where joints and bedding planes susceptible to root penetration are more common and accessible. This project extended this concept to the Cumberland Plateau, Kentucky, with flat, level-bedded sedimentary rocks. Spatial variability of soil thickness was quantified at three nested spatial scales, and statistical relationships with other potential influences of thickness were examined. In addition, soil depth beneath trees was compared …

Effectiveness Of A Farm Field Trip, Bonnie S. Sigmon

Theses and Dissertations--Community & Leadership Development

The annual Sigmon Farm Tour was started in 1992 as an agricultural education program where students could experience being on a farm with the goal of increasing the agricultural literacy levels of the participants. Every year the entire 4th grade student population of Rockcastle County spends the day touring the farm and participating in experiential mini lessons given by the cooperating farm service and health agencies. The program has continued for 20+ years without an evaluation as to whether it is achieving its objectives. This evaluation will also exhibit the programs strengths and weakness so it can continue to improve. …

Sequential Co-Culture Of Anaerobic Bacteria On Switchgrass In A Continuous Flow-Through Reactor For Biofuel Production, Noelia M. Elia

Theses and Dissertations--Biosystems and Agricultural Engineering

Solid substrate cultivation (SSC) using lignocellulosic non-food feedstock, such as switchgrass, is an alternative for advanced biofuel production. Acetone-Butanol-Ethanol (ABE) fermentation in two stages using a sequential culture of microorganisms from the class Clostridia is an approach proposed to increase the butanol production.

The goal was to test the efficacy of a sequential culture on high solid substrate cultivation in batch and continuous cultivation, and to evaluate conditions to optimize butanol production using switchgrass as substrate.

Initial batch experiments were used to determine particle size effect, choice of solvent producer and pretreatment evaluation: The effect of particle size on gas …

Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh

Theses and Dissertations--Neuroscience

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca²⁺ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …

Modulation Of Vaccine-Induced Responses By Anthelmintic Treatment In Ponies, Emily Rubinson

Theses and Dissertations--Medical Sciences

Vaccines and anthelmintics induce an inflammatory response in equids. Since they are commonly given concurrently, it is practical to study any interaction between them. This study evaluated whether IVM and PYR would modulate the acute phase inflammatory response, the systemic gene expression of pro-inflammatory cytokines, and vaccine-specific titers induced by WNV, EHV, and KLH vaccines. Naturally-infected, yearling ponies were sorted by gender, then fecal epgs. They were randomly assigned to three treatment groups: IVM, PYR, and control. All ponies received vaccinations intramuscularly on days 0 and 29. Whole blood, serum, and plasma samples were collected 1, 3, and 14 days …

Immunotherapy In Combination With Behavioral Enrichment In A Canine Model Of Aging, Paulina R. Davis

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is characterized by cognitive decline and hallmark neuropathology, including β-amyloid (Aβ). Therapeutic strategies for AD are focusing on reducing Aβ. Canines develop Aβ neuropathology and cognitive decline with age similar to AD patients. In previous studies, immunization with Aβ1-42 (VAC) in aged canines decreased brain Aβ but did not improve cognition. Behavioral enrichment (ENR) improved cognition without reducing brain Aβ. We hypothesized that VAC combined with ENR would provide cognitive benefits and reduce Aβ neuropathology, as compared individual VAC and ENR treatments. Aged beagles were placed into groups: control, VAC with fibrillar Aβ1-42, ENR, and combination treatment …

A Brief Elevation Of Serum Amyloid A Is Sufficient To Increase Atherosclerosis, Joel C. Thompson

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease is now the leading cause of death worldwide. Serum amyloid A (SAA), a positive acute phase reactant, along with C-reactive protein is used clinically as a marker of cardiovascular disease risk. However, recent data has shed light on a possible causal role of SAA in the development of atherosclerosis, the most pervasive form of cardiovascular disease. Several inflammatory diseases such as diabetes and obesity are known to confer increased risk of developing cardiovascular disease. Individuals with these diseases all have modest but persistent elevation of SAA. To determine if SAA caused the development of atherosclerosis, apoe^-/-chow …

Immobilizing Mutation In An Unconventional Myosin15a Affects Not Only The Structure Of Mechanosensory Stereocilia In The Inner Ear Hair Cells But Also Their Ionic Conductances, Diana Syam

Theses and Dissertations--Medical Sciences

In the inner and outer hair cells (OHCs) of the inner ear, an unconventional myosin 15a localizes at the tips of mechanosensory stereocilia and plays an important role in forming and maintaining their normal structure. A missense mutation makes the motor domain of myosin 15a dysfunctional and is responsible for the congenital deafness DFNB3 in humans and deafness and vestibular defects in Shaker-2 (Sh2) mouse model. All hair cells of homozygous Shaker-2 mice (Myo15^sh2/sh2) have abnormally short stereocilia, but, only stereocilia of Myo15^sh2/sh2OHCs start to degenerate after the first few days of postnatal development …

Contaminated Chi-Square Modeling And Its Application In Microarray Data Analysis, Feng Zhou

Theses and Dissertations--Statistics

Mixture modeling has numerous applications. One particular interest is microarray data analysis. My dissertation research is focused on the Contaminated Chi-Square (CCS) Modeling and its application in microarray. A moment-based method and two likelihood-based methods including Modified Likelihood Ratio Test (MLRT) and Expectation-Maximization (EM) Test are developed for testing the omnibus null hypothesis of no contamination of a central chi-square distribution by a non-central Chi-Square distribution. When the omnibus null hypothesis is rejected, we further developed the moment-based test and the EM test for testing an extra component to the Contaminated Chi-Square (CCS+EC) Model. The moment-based approach is easy and …

Genetic Association Testing Of Copy Number Variation, Yinglei Li

Theses and Dissertations--Statistics

Copy-number variation (CNV) has been implicated in many complex diseases. It is of great interest to detect and locate such regions through genetic association testings. However, the association testings are complicated by the fact that CNVs usually span multiple markers and thus such markers are correlated to each other. To overcome the difficulty, it is desirable to pool information across the markers. In this thesis, we propose a kernel-based method for aggregation of marker-level tests, in which first we obtain a bunch of p-values through association tests for every marker and then the association test involving CNV is based on …

Natural Phenomena As Potential Influence On Social And Political Behavior: The Earth’S Magnetic Field, Jackie R. East

Theses and Dissertations--Political Science

Researchers use natural phenomena in a number of disciplines to help explain human behavioral outcomes. Research regarding the potential effects of magnetic fields on animal and human behavior indicates that fields could influence outcomes of interest to social scientists. Tests so far have been limited in scope. This work is a preliminary evaluation of whether the earth’s magnetic field influences human behavior it examines the baseline relationship exhibited between geomagnetic readings and a host of social and political outcomes. The emphasis on breadth of topical coverage in these statistical trials, rather than on depth of development for any one model, …

Beyond Peroxisome: Abcd2 Modifies Pparα Signaling And Identifies A Subclass Of Peroxisomes In Mouse Adipose Tissue, Xiaoxi Liu

Theses and Dissertations--Pharmacy

ABCD2 (D2) has been proposed as a peroxisomal long-chain acyl-CoA transporter that is essential for very long chain fatty acid metabolism. In the livers of mice, D2 is highly induced by fenofibrate, a PPARα ligand that has been widely used as a lipid lowering agent in the treatment of hypertriglyceridemia. To determine if D2 is a modifier of fibrate responses, wild-type and D2 deficient mice were treated with fenofibrate for 14 days. The absence of D2 altered expression of gene clusters associated with lipid metabolism, including PPARα signaling. Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Synthesis And Biological Evaluation Of Novel Resveratrol And Combretastatin A4 Derivatives As Potent Anti-Cancer Agents, Nikhil Reddy Madadi

Theses and Dissertations--Pharmacy

Resveratrol has been reported as a potential anticancer agent but cannot be used as an antitumor drug due to its chemical and metabolic instability. We have designed and synthesized 184 novel compounds related to resveratrol in an attempt to produce more potent and drug-like molecules. We have identified a tetrazole analog of resveratrol, ST-145(a) as a lead anticancer agent from the resveratrol analog series of compounds with a GI₅₀ value of less than 10nM against almost all the human cancer cell lines in the National Cancer Institute’s screening panel.

In a separate study, we tested the hypothesis that the …

Human Butyrylcholinesterase Mutants For Cocaine Detoxification, Shurong Hou

Theses and Dissertations--Pharmacy

Cocaine is one of the most reinforcing drugs of abuse and has caused serious medical and social problems. There is no FDA-approved medication specific for cocaine. It is of a high priority to develop an effective therapeutic treatment for cocaine abuse. Human butyrylcholinesterase (BChE) has been recognized as a promising candidate of enzyme therapy to metabolize cocaine into biologically inactive metabolites and prevent it from reaching central nervous system (CNS). However, the catalytic activity of wide-type human BChE against cocaine is not sufficiently high for treatment of cocaine abuse. Dr. Zhan’s lab has successfully designed and discovered a series of …

Mechanisms Of Cyclooxygenase-2-Dependent Human Aortic Smooth Muscle Cell Phenotypic Modulation, Oreoluwa O. Adedoyin

Theses and Dissertations--Pharmacy

Abdominal aortic aneurysm (AAA) is a disease of the aorta characterized by pathological remodeling and progressive weakening of the vessel resulting in the increased risk of rupture and sudden death. In a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, progression of AAAs is associated with reduced differentiation of smooth muscle cells (SMCs) at the site of lesion development. In the mouse model, the effectiveness of cyclooxygenase-2 (COX-2) inhibition for attenuating AAA progression is associated with maintenance of a differentiated SMC phenotype. However, the safety of COX-2 inhibitors is currently in question due to the increased …

Investigating Structure And Protein-Protein Interactions Of Key Post-Type Ii Pks Tailoring Enzymes, Theresa E. Downey

Theses and Dissertations--Pharmacy

Type II polyketide synthase (PKS) produced natural products have proven to be an excellent source of pharmacologically relevant molecules due to their rich biological activities and chemical scaffolds. Type II-PKS manufactured polyketides share similar polycyclic aromatic backbones leaving their diversity to stem from various chemical additions and alterations facilitated by post-PKS tailoring enzymes. Evidence suggests that post-PKS tailoring enzymes form complexes in order to facilitate the highly orchestrated process of biosynthesis. Thus, protein-protein interactions between these enzymes must play crucial roles in their structures and functions. Despite the importance of these interactions little has been done to study them. In …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Estimating Passive Material Properties And Fiber Orientation In A Myocardial Infarction Through An Optimization Scheme Using Mri And Fe Simulation, Dimitri Mojsejenko

Theses and Dissertations--Mechanical and Aerospace Engineering

Myocardial infarctions induce a maladaptive ventricular remodeling process that independently contributes to heart failure. In order to develop effective treatments, it is necessary to understand the way and extent to which the heart undergoes remodeling over the course of healing. There have been few studies to produce any data on the in-vivo material properties of infarcts, and much less on the properties over the time course of healing. In this paper, the in-vivo passive material properties of an infarcted porcine model were estimated through a combined use of magnetic resonance imaging, catheterization, finite element modeling, and a genetic algorithm optimization …

Heat Transfer Characteristics In Wildland Fuelbeds, Justin English

Theses and Dissertations--Mechanical and Aerospace Engineering

The fundamental physics governing wildland fire spread are still largely misunderstood. This thesis was motivated by the need to better understand the role of radiative and convective heat transfer in the ignition and spread of wildland fires. The focus of this work incorporated the use of infrared thermographic imaging techniques to investigate fuel particle response from three different heating sources: convective dominated heating from an air torch, radiative dominated heating from a crib fire, and an advancing flame front in a laboratory wind tunnel test. The series of experiments demonstrated the uniqueness and valuable characteristics of infrared thermography to reveal …

From Geology To Art History: Ceramist Alexandre Brongniart’S Overlooked Contribution To The Developing Science Of Art History In The Early Nineteenth Century, Julia A. Carr-Trebelhorn

Theses and Dissertations--Art and Visual Studies

Alexandre Brongniart was known for his work as an important geologist and as an administrator at the Sèvres Porcelain Manufactory, but his roles as art historian and museologist are overlooked. Brongniart created a holistic methodology taken directly from science and applied it to ceramic art of all cultures and eras. He had a uniquely modern perspective on time, world culture, and archeology. Brongniart wrote about the art of Asia and the Americas on an equal status with that of the Classical West at least fifty years before it became a mainstream idea. Brongniart integrated scientific principle and practice into the …

The Relationship Of Somatosensory Perception And Fine-Force Control In The Adult Human Orofacial System, Nicole M. Etter

Theses and Dissertations--Rehabilitation Sciences

The orofacial area stands apart from other body systems in that it possesses a unique performance anatomy whereby oral musculature inserts directly into the underlying cutaneous skin, allowing for the generation of complex three-dimensional deformations of the orofacial system. This anatomical substrate provides for the tight temporal synchrony between self-generated cutaneous somatosensation and oromotor control during functional behaviors in this region and provides the necessary feedback needed to learn and maintain skilled orofacial behaviors.

The Directions into Velocity of Articulators (DIVA) model highlights the importance of the bidirectional relationship between sensation and production in the orofacial region in children learning …