Digital Commons Network^™

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 …

Listeria Monocytogenes Can Utilize Both M Cell Transcytosis And Inla-Mediated Uptake To Cross The Epithelial Barrier Of The Intestine During An Oral Infection Model Of Listeriosis, Hilary Denney

Theses and Dissertations--Medical Sciences

The invasive pathways, InlA- and InB-mediated uptake and M cell transcytosis, that Listeria monocytogenes uses to invade the intestine have mainly been studied using infection models that do not truly replicate what occurs during a natural infection. Recently, our lab has developed an oral infection model that is more physiolocally relevant to what occurs during food borne listeriosis. We have sought to evaluate the relative roles of the previously defined invasive pathways, in our oral model of infection. We have done this by utilizing an InlAmCG Lm strain that is able to bind murine E-cadherin, knockout Lm strains, ΔinlA Lm …

Dopamine And Glutamate Dysfunction In A Rodent Model Of Attention-Deficit/Hyperactivity Disorder: Implications For Future Neuropharmacology, Erin M. Miller

Theses and Dissertations--Neuroscience

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders of childhood. It is theorized to be caused by catecholamine dysfunction in the striatum (Str) and frontal cortex (FC). The spontaneously hypertensive rat (SHR) has been used as a model for ADHD because of its attention deficits, impulsiveness, and hyperactivity. Prior studies of dopamine (DA) in the Str and FC have revealed conflicting results in the SHR compared to control, indicative of a need for a better understanding of DA dynamics in this model. In addition to the DA hypothesis, studies have begun implicating glutamate in the etiology of ADHD. …

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 …

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 …

Lobelane Analogs With Various Methylene Linker Lengths And Acyclic Lobelane Analogs As Potential Pharmacotherapies To Treat Methamphetamine Abuse, Zheng Cao

Theses and Dissertations--Pharmacy

Methamphetamine interacts with vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine (DA) uptake and promotes DA release from presynaptic vesicles, increasing cytosolic DA available for methamphetamine-induced reverse transport by DA transporters. By inhibiting VMAT2, lobelane, a defunctionalized, saturated lobeline analog, decreases methamphetamine-evoked DA release and methamphetamine self-administration in rats. In this dissertation structure-activity relationships around the lobelane structure were investigated on racemic lobelane analogs with varying methylene linker lengths at central piperidine ring. Affinity for dihydrotetrabenazine (DTBZ) sites on VMAT2 and for inhibition of VMAT2 function was determined to be 0.88-63 and 0.024-4.6 µM, respectively, and positively correlated. The most potent …

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 …

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 …

Development Of Industry Oriented Cfd Code For Analysis / Design Of Face Ventilation Systems, Todor P. Petrov

Theses and Dissertations--Mining Engineering

Two of the main safety and health issues recognized during deep cut coal mining are methane and dust hazards. Advances in continuous miner technology have improved safety and productivity. However, these advances have created some environmental problems, notably more dust and methane being generated at the face during coal extraction.

Results of studies performed in the last three decades concerning the face ventilation for deep cut mining showed very complicated airflow behavior. The specifics of flow patterns developed by the face ventilation systems presents significant challenge for analytical description even for equipment-free entry. Fortunately, there are methods, such as numerical …

Computational Investigation Of Injectable Treatment Strategies For Myocardial Infarction, Hua Wang

Theses and Dissertations--Mechanical and Aerospace Engineering

Heart failure is an important medical disease and impacts millions of people throughout the world. In order to treat this problem, biomaterial injectable treatment injected into the myocardium of the failing LV are currently being developed. Through this treatment, the biomaterial material injections can reduce wall stresses during the cardiac remodeling process. By using computational techniques to analyze the effects of a treatment involving the injection of biomaterial material into the LV after MI, the material parameters of the hydrogel injections can be optimized. The results shows that the hydrogel injections could reduce the global average fiber stress and the …

Finite Element Modeling And Fabrication Of An Sma-Smp Shape Memory Composite Actuator, Mohammad Souri

Theses and Dissertations--Mechanical and Aerospace Engineering

Shape memory alloys and polymers have been extensively researched recently because of their unique ability to recover large deformations. Shape memory polymers (SMPs) are able to recover large deformations compared to shape memory alloys (SMAs), although SMAs have higher strength and are able to generate more stress during recovery.

This project focuses on procedure for fabrication and Finite Element Modeling (FEM) of a shape memory composite actuator. First, SMP was characterized to reveal its mechanical properties. Specifically, glass transition temperature, the effects of temperature and strain rate on compressive response and recovery properties of shape memory polymer were studied. Then, …

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 …

Combining Sustainable Value Stream Mapping And Simulation To Assess Manufacturing Supply Chain Network Performance, Daniel T. Sparks

Theses and Dissertations--Mechanical and Aerospace Engineering

Sustainable Value Stream Mapping (Sus-VSM) builds upon traditional VSM to capture additional sustainability aspects of the product flow, such as environmental and societal aspects. This work presents research to expand the utility of Sus-VSM to supply chain networks, develop a general approach towards improving supply chain sustainability, and examine the benefits of implementing simulation and a design of experiments (DOE) style analysis. Metrics are identified to assess economic, environmental, and societal sustainability for supply chain networks and visual symbols are developed for the Supply Chain Sus-VSM (SC Sus-VSM) to allow users to easily identify locations where sustainability can be improved. …

Assessing Candidacy For Intensive Language Therapy: A Preliminary Study, Jessica N. Bellamy

Theses and Dissertations--Communication Sciences and Disorders

The goal of the present study was to examine changes in the speech and language performance of patients with chronic, non-fluent aphasia over the course of a three-hour group speech and language treatment session, a time allotment comparable to intensive therapy practices. Nine participants, (three groups of three), with chronic, non-fluent aphasia were seen for a single group therapy session three hours in length. Therapeutic activities were designed to be as similar as possible for each group of participants. Each participant was individually assessed before (time 1), during (time 2), and after (time 3) the group treatment session. Assessments included …

Using Video Based Instruction To Teach Art To Students With Autism Spectrum Disorder, Anthony W. Woodruff

Theses and Dissertations--Art and Visual Studies

Students with Autism Spectrum Disorders often do not respond to common pedagogical strategies and traditional in vivo teaching approaches. From my observations, students diagnosed with Autism Spectrum Disorders learn best when material is presented through technology. Based on the information found in the literature review and personal observations from working with students with special needs, when students with Autism Spectrum Disorders receive video based instruction by watching recorded art lessons, they may learn to develop artistic skills and retain more art content knowledge with greater success than through traditional teaching methods. The purpose of this research study is to test …

The Relationship Between Patient Expectations, Functional Outcome, Self-Efficacy, And Rehabilitation Adherence Following Cartilage Repair Of The Knee: A Sequential Explanatory Analysis, Jenny L. Toonstra

Theses and Dissertations--Rehabilitation Sciences

Patient expectations have been shown to be a major predictor of outcomes. Furthermore, fulfilled expectations have been linked to increased patient satisfaction and rehabilitation adherence. Expectations may be influenced by a variety of factors, including patient characteristics, pre-operative function, or disease characteristics. However, it is currently unknown what factors and to what degree they may influence patient expectations prior to knee surgery. Furthermore, understanding the importance and values of those expectations for recovery using qualitative methods has not previously been conducted in this patient population.

A mixed methods design was used. Twenty-one participants scheduled to undergo cartilage repair of the …

Nucleoside Reverse Transcriptase Inhibitors Are Anti-Inflammatory And Target Dry Age-Related Macular Degeneration, Benjamin J. Fowler

Theses and Dissertations--Physiology

Age-related macular degeneration (AMD) is a principal cause of blindness in the United States and other industrialized nations. An estimated 10 million Americans are afflicted with AMD, which is comparable in scope to the 12 million living with cancer, or the 5 million with Alzheimer’s disease. The prevalence of AMD steadily increases with age, affecting 2% of the population at age 40, and one in four people by age 80. For reasons that are not fully understood, AMD is more common in lightly-pigmented and female populations. Treatment of AMD is largely an unmet need: There are no FDA approved therapies …

Attenuating Trigeminal Neuropathic Pain By Repurposing Pioglitazone And D-Cycloserine In The Novel Trigeminal Inflammatory Compression Mouse Model, Danielle N. Lyons

Theses and Dissertations--Physiology

Approximately 22% of the United States population suffers from a chronic orofacial pain condition. One such condition is known as trigeminal neuropathic pain frequently reported as continuous aching and burning pain, often accompanied by intermittent electrical shock-like sensations. Dental procedures or trauma are known causes of peripheral trigeminal nerve injury and inflammation. Patients who have this type of facial pain also suffer from emotional distress. For these reasons, trigeminal neuropathic pain needs to be studied in more detail to improve the understanding of the etiology and maintenance of this condition, as well as to develop effective treatment strategies. The first …

Trpa1 Channels In Cochlear Supporting Cells Regulate Hearing Sensitivity After Noise Exposure, Alejandra C. Velez-Ortega

Theses and Dissertations--Physiology

TRPA1 channels are sensors for noxious stimuli in a subset of nociceptive neurons. TRPA1 channels are also expressed in cells of the mammalian inner ear, but their function in this tissue remains unknown given that Trpa1^–/– mice exhibit normal hearing, balance and sensory mechanotransduction. Here we show that non-sensory (supporting) cells of the hearing organ in the cochlea detect tissue damage via the activation of TRPA1 channels and subsequently modulate cochlear amplification through active cellshape changes.

We found that cochlear supporting cells of wild type but not Trpa1^–/– mice generate inward currents and robust long-lasting Ca²⁺ responses …

Identification Of Soils On Firefighter Turnout Gear From The Philadelphia Fire Department, Tabitha N. Huston

Theses and Dissertations--Retailing and Tourism Management

The purpose of this research was to identify the composition of soils on firefighter turnout gear from the Philadelphia Fire Department and to determine which soils contain hazardous materials. The objective of the research was to identify the composition of soils remaining on the firefighter turnout gear to enable the industry to design an effective cleaning procedure for removal of soils. A pilot study was conducted on hoods from the Philadelphia fire department to evaluate the test methods that would be used to identify the composition of soils. Soils that had been identified from previous studies were targeted in the …

The Effects Of Mountaintop Removal Mining And Valley Fills On Stream Salamander Communities, Brenee' Lynn Muncy

Theses and Dissertations--Forestry and Natural Resources

Mountaintop removal mining and valley filling (MTR/VF) is a common form of land conversion in Central Appalachia and threatens the integrity of stream ecosystems. We investigated the effects of MTR/VF on stream salamander occupancy probabilities and community structure by conducting area constrained active searches for stream salamanders within intermittent streams located in mature forest (i.e., control) and those impacted by MTR/VF. During March to June of 2013, we detected five stream salamander species (Desmognathus fuscus, D. monticol, Eurycea cirrigera, Pseudotriton ruber, and Gyrinophilus porphyriticus) and found that the probability of occupancy was greatly reduced in MTR/VF streams compared …

The Roles Of Orthopaedic Pathology And Genetic Determinants In Equine Cervical Stenotic Myelopathy, Jennifer Gail Janes

Theses and Dissertations--Veterinary Science

Cervical stenotic myelopathy (CSM) is an important musculoskeletal and neurologic disease of the horse. Clinical disease occurs due to malformations of the vertebrae in the neck causing stenosis of the cervical vertebral canal and subsequent spinal cord compression. The disease is multifactorial in nature, therefore a clearer understanding of the etiology and pathogenesis of CSM will allow for improved management and therapeutic practices. This thesis examines issues of equine CSM diagnosis, skeletal tissue pathology, and inherited genetic determinants utilizing advances in biomedical imaging technologies and equine genomics. Magnetic resonance imaging (MRI) data provided a more complete assessment of the cervical …

Use Of Genomic Tools To Discover The Cause Of Champagne Dilution Coat Color In Horses And To Map The Genetic Cause Of Extreme Lordosis In American Saddlebred Horses, Deborah G. Cook

Theses and Dissertations--Veterinary Science

Champagne dilution of coat color in horses is caused by dominant gene action. Three sire families were identified as segregating for this trait. Genome wide linkage analysis using 104 microsatellite DNA markers was used to map the gene to ECA14 (LOD > 11.0). Four genes, namely SPARC, SLC36A1, SLC36A2 and SLC36A3, were selected from the region implicated by linkage and their exons sequenced. DNA sequences were compared for two homozygotes for Champagne dilution, two heterozygotes and two horses without dilution. A single base change in exon 2 of SLC36A1 was found unique to horses exhibiting Champagne dilution. This change in base …