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Practical Extensions Of The Continual Reassessment Method, Amber Salter Jan 2015

Practical Extensions Of The Continual Reassessment Method, Amber Salter

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This dissertation considers the presence of patient heterogeneity in dose finding studies using the likelihood-based time to event continual reassessment method (TITE-CRM). First, assuming group membership is known and the groups share some information regarding their maximum tolerated dose (MTD), we extend the two-group two-parameter CRM to the TITE-CRM. We examine the performance of the two-group two-parameter TITE-CRM for various scenarios where the true MTD for each group is different. We also consider the situation where the groups are truly homogeneous but a heterogeneous model is employed. Our simulations show that the method has some loss in accuracy compared to …

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Role Of Vapb/Als8 Signaling Through Lar Receptor, Jessica Lindsey Winek Schultz Jan 2015

Role Of Vapb/Als8 Signaling Through Lar Receptor, Jessica Lindsey Winek Schultz

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In humans, a P56S point mutation in the VAPB/ALS8 MSP domain is associated with amyotrophic lateral sclerosis (ALS) and late-onset spinal muscular atrophy (SMA). The N-terminal MSP domain is cleaved from the C-terminus, and secreted through an unknown, nonconventional manner. The P56S mutation inhibits secretion of the MSP domain. We use Caenorhabditis elegans to study live secretion of VPR-1, as well as to understand vMSP receptor signaling in muscle and gonad. To study the secretion mechanism of VPR-1 we created a transgenic line of C. elegans with a fluorescently tagged VPR-1. Using this model, we were able to visualize live …

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A Randomized Trial Evaluating Child Dog-Bite Prevention In Rural China Through Video-Based Testimonials, Jiabin Shen Jan 2015

A Randomized Trial Evaluating Child Dog-Bite Prevention In Rural China Through Video-Based Testimonials, Jiabin Shen

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Dog-bite injuries pose a significant threat to children around the world. School-aged children are especially at risk of injuries because of their cognitively immature tendency toward poor perception of vulnerability regarding risky behaviors. This risk is elevated further for millions of school-aged children living in rural China due to the large number of stray dogs, all potential rabies carriers. Effective intervention programs for pediatric dog-bite injuries are sparse. Most existing programs were based on public health concerns and only involve the impartment of safety knowledge to children. They produced mixed results in changing actual behaviors with dogs. Based on the …

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Gaba(A) Receptor Trafficking And Localization In Schizophrenia, Toni Marie Mueller Jan 2015

Gaba(A) Receptor Trafficking And Localization In Schizophrenia, Toni Marie Mueller

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Mechanisms underlying the complex etiology of schizophrenia have long been a subject of scientific inquiry. Early investigations focused on identifying functional deficits in dopaminergic and glutamatergic neurotransmission, but evidence for disrupted GABAergic signaling has also emerged. Recent studies from our lab have identified disrupted N-glycosylation of glutamate receptor and transporter subunits and abnormal subcellular distribution of glutamate receptor subunits, suggesting a potential functional consequence of perturbed N-glycosylation in schizophrenia. N-glycosylation is the posttranslational enzymatic attachment of an oligosaccharide precursor to a protein. This modification plays a significant role in protein processing in the ER and Golgi, and is known to …

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Detection Of Scardovia Genus From Oral Samples In Children Using Real-Time Quantitative Polymerase Chain Reaction, Jungyi Alexis Liu Jan 2014

Detection Of Scardovia Genus From Oral Samples In Children Using Real-Time Quantitative Polymerase Chain Reaction, Jungyi Alexis Liu

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Streptococcus mutans (Sm) and Streptococcus sobrinus (Ss) , are considered the major bacterium associated with dental caries. However, recent findings identify Scardovia species (Sc) is associated with early childhood caries, with or without the presence of Sm or Ss. This IRB approved study quantified the presence of Sm and Sc in saliva by real-time quantitative PCR (qPCR) in relation to caries. Saliva samples were collected from 72 preschool children in a high-caries risk community in rural Alabama. SYBR Green-based qPCR using extracted DNA and primers specific for Sm, Ss, Sc and total bacteria determined the copy number (CN/ml). Twenty two …

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Combinatorial Effects Of Corexit 9500a And Temperature Stressors On Embryo Development In The Zebrafish Danio Rerio, Erica Davis Anderson Jan 2014

Combinatorial Effects Of Corexit 9500a And Temperature Stressors On Embryo Development In The Zebrafish Danio Rerio, Erica Davis Anderson

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the Kemp’s Ridley Recovery Program during the 2005-2008 nesting seasons. This

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The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone Jan 2014

The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone

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chapters test the role of non-steady moisture or temperature on sex ratios produced by the

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Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham-Snary Jan 2014

Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham-Snary

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Obesity and cardiometabolic pathologies have reached epidemic levels worldwide over the last 30 years. Currently, the majority of research investigating possible genetic causes of obesity is focused on nuclear DNA (nDNA). While this has lead to the development of numerous animal models, it is apparent the etiology of obesity is more complex than single gene mutations. Recently it has also been suggested that mitochondrial DNA (mtDNA) mutations sustained during evolution as a consequence of our prehistoric environment may influence individual propensity and risk of disease. Contemporary human populations are no longer faced with the challenges of our ancestors such as …

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Unraveling The Mechanisms Of Skeletal Muscle Hyperplasia: Juxtaposing Divergent Growth Paradigms, Jacob Michael Froehlich Jan 2014

Unraveling The Mechanisms Of Skeletal Muscle Hyperplasia: Juxtaposing Divergent Growth Paradigms, Jacob Michael Froehlich

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During the course of vertebrate evolution, two major growth paradigms have appeared: determinate, one in which an animal's final size is largely governed by predisposed genetic potential; and indeterminate, a paradigm involving life-long, largely environmentally governed somatic growth. Of the tissues constituting an adult vertebrate, skeletal muscle comprises ≥60% of that organism's mass, making it an important factor in overall body growth. To better understand the process by which many teleost fishes grow throughout their natural lifespans, the clade Danioninae and the model rainbow trout (Oncorhynchus mykiss) were utilized in a comparative manner. Contrary to current hypotheses, fish with indeterminate …

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Urbanization And Land-Use Change In Puerto Maldonado, Peru: Categorizing The Landscape Using High-Resolution Satellite Imagery For Potential Use In Public Health Research, Laura Brianna Gast Jan 2014

Urbanization And Land-Use Change In Puerto Maldonado, Peru: Categorizing The Landscape Using High-Resolution Satellite Imagery For Potential Use In Public Health Research, Laura Brianna Gast

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Environmental change, especially rapid urbanization, has measurable effects on human health. Over 70 percent of the global population is expected to live in urban areas by 2025, and at least 1 in 3 of these individuals will live in extreme poverty. Living in a slum or shantytown exposes individuals to health and safety risks including inadequate sanitation, lack of access to clean water, air pollution, violence, over-crowding and risk of infectious disease. Remote sensing technologies are an effective tool for detection and prediction of areas with significant land use change, which enables identification of populations with the highest risk of …

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Synaptic And Circuit Mechanisms Of Glutamate Spillover Signaling, Luke Teichert Coddington Jan 2014

Synaptic And Circuit Mechanisms Of Glutamate Spillover Signaling, Luke Teichert Coddington

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Glutamate is the most prominent fast excitatory neurotransmitter released at mammalian central synapses, where point-to-point activation of receptors in postsynaptic densities is accepted to be the primary pathway for information flow through neural circuits. More controversial are the activities of synaptically-released glutamate outside the synaptic cleft of origin, as "spillover" glutamate may signal through neighboring synapses or through extrasynaptic receptors. The role of such extrasynaptic signaling in physiological neuronal communication is unproven and its inappropriate occurrence has been proposed to underlie a range of neurodegenerative conditions. Elucidation of spillover signaling mechanisms thus benefits our understanding of the brain in both …

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The Role Of Spinal Serotonergic Receptors 5-Ht1a And 5-Ht3 In Stress-Induced Urinary Bladder Hypersensitivity, Chelsea L. Crawford Jan 2014

The Role Of Spinal Serotonergic Receptors 5-Ht1a And 5-Ht3 In Stress-Induced Urinary Bladder Hypersensitivity, Chelsea L. Crawford

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Disorders in which pain originates from the urinary bladder such as interstitial cystitis (IC) are steadily increasing in prevalence. A common finding among patients with IC is the comorbidity with stress or anxiety disorders. In rats, footshock stress alone is sufficient to elicit bladder hypersensitivity. Serotonin (5-hydroxytryptamine; 5-HT) has been established as a mediator in anxiety and pain separately, but little is known about the role of 5-HT in stress-induced visceral hypersensitivity. The current set of studies addresses three main concerns: (1) the impact of spinal 5-HT1A and 5-HT3 receptor blockade with WAY-100635 (10 µg) and ondansetron (10 µg), respectively, …

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Sak Yant: The Transition From Indic Yantras To Thai "Magical" Buddhist Tattoos, Angela May Jan 2014

Sak Yant: The Transition From Indic Yantras To Thai "Magical" Buddhist Tattoos, Angela May

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Officially, Thailand is dominated by the state-sponsored Theravada Buddhist tradition, which has essentially been practiced in Thailand since 1902 when the sangha bureaucracy was established. However, within the last couple of decades a hybrid form of Thai Buddhism has emerged. The contemporary, hybridic Thai religion emphasizes Buddhism--placing it at the top of its hierarchal pyramid--even while it includes elements of Animism and Hinduism. This thesis explores the hybridization of popular religions in contemporary Thailand as reflected in the art form of Sak Yant. Thai Buddhist magical tattoos called Sak Yant are based on ancient Indic yantras that are considered powerful …

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Illuminating The Physiology And Ecology Of The Wound-Induced Macroalgal Oxidative Burst, Ruth Ellen Mcdowell Jan 2014

Illuminating The Physiology And Ecology Of The Wound-Induced Macroalgal Oxidative Burst, Ruth Ellen Mcdowell

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The role of reactive oxygen species (ROS) in the macroalgal wound response was investigated with emphasis on their occurrence, source, and ecological role. In a survey of Antarctic macroalgae, an oxidative response to wounding was common and ROS in seawater decreased the feeding rate of sympatric amphipod grazers. The macroalgal oxidative response was also sensitive to light. In contrast to the current understanding of the macroalgal oxidative burst, initial wound-induced ROS from the temperate kelp Saccharina latissima were light-dependent and arose from disrupted photosynthetic electron transport rather than from a defense-related enzyme such as an NADPH-oxidase. Furthermore, the light-dependence of …

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Modeling Of Pollutant Transport In The Nile Delta, Egypt, Mohamed Khaled Elsayed Mostafa Jan 2014

Modeling Of Pollutant Transport In The Nile Delta, Egypt, Mohamed Khaled Elsayed Mostafa

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Poor water quality is one of the biggest problems faced by most countries and especially by developing countries such as Egypt. The mismanagement of potable water resources constitutes one of the main reasons for the depletion of water. This research was carried out in the Nile River delta, a region in which toxic dumping and water quality degradation exist. The Nile delta receives pollution loads from industrial, agricultural, and domestic activities located along its path leading to the spread of water-related diseases such as hepatitis, typhoid, cholera, and kidney failure [Safe Drinking Water Foundation, 2009]. The main objective of this …

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Quantum Computation Approach To Information Theoretic Modeling And Analysis Of Systems, Luai Najim Jan 2014

Quantum Computation Approach To Information Theoretic Modeling And Analysis Of Systems, Luai Najim

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The modeling of systems has been addressed in the physical sciences from the perspective of Energy and matter. The 3rd original idea of Communication as a means of modeling systems has been established and applied. In this study, we apply the 3rd original idea of communication to systems on a quantum level. By marrying Shannon's noisy communication channel to Feynman QED and Quantum Computing, we realize a visual model for the representation of the entropy of a noisy communication channel on a quantum scale. We also use that visual representation concept to define a geometric view into the superposition of …

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Regulatory Control Of Palatogenesis And Odontogenesis By Specificity Protein 7, John Christopher Clarke Jan 2014

Regulatory Control Of Palatogenesis And Odontogenesis By Specificity Protein 7, John Christopher Clarke

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Runx2 and its downstream target Specificity Protein 7 (Sp7) are essential for skeletogenesis. In humans, mutations in Sp7 gene are associated with osteogenesis imperfecta. Unlike Runx2, the role of Sp7 in palatogenesis, tooth development or differentiation of ameloblasts and odontoblasts remains unknown. The main goal of this research was to identify the functional requirement of Sp7 transcription factor during tooth development and palatogenesis. Molecular, biochemical, and histological approaches were employed to answer this question. We established Sp7-null mice that are completely void of mineralized tissue, exhibit craniofacial dysmorphogenesis and die shortly after birth. Surprisingly, Sp7 homozygous mutants exhibited normal tooth …

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Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts Jan 2014

Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts

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Grape seed extract (GSE), a dietary supplement, has potential in the treatment and prevention of human chronic age-related diseases including cancers, cardiovascular diseases, and neurodegenerative diseases. GSE and adult hippocampal neurogenesis, independently, have enhanced learning and memory in rodents. We hypothesized that GSE enhances learning and memory, at least partially, by enhancing hippocampal neurogenesis. However, adult mice given GSE did not exhibit increased number of progenitor cells or new neurons, established markers of neurogenesis, in the dentate gyrus (DG). Also, 26-day-old pups whose mother was given GSE only while nursing had fewer new neurons in the DG compared to control …

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Utilization Of Dual Energy Computed Tomography Based Metal Artifact Reduction To Improve Radiation Treatment Planning In Patients With Implanted High-Z Materials, Evan Thomas Jan 2014

Utilization Of Dual Energy Computed Tomography Based Metal Artifact Reduction To Improve Radiation Treatment Planning In Patients With Implanted High-Z Materials, Evan Thomas

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High quality computed tomography (CT) scans are integral to the successful cancer radiation therapy treatment plan. Metal streak artifact in the CT image originates when a high density medical implant (dental, orthopedic, etc.) disproportionally attenuates the imaging beam and corrupts the imaging data. This impairs the physician's task of identifying important boundaries between tumor and healthy issue. The ability of treatment planning software to accurately compute vital radiation dosimetry metrics is also compromised. Many methods have been explored to mitigate the complications of streak artifact; however, none have been found effective and efficient for routine clinical use. This work explores …

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Targeting Tau-Mediated Nmdar Hypofunction Reverses Deficits In A Mouse Model Of Frontotemporal Dementia, Brian Andrew Warmus Jan 2014

Targeting Tau-Mediated Nmdar Hypofunction Reverses Deficits In A Mouse Model Of Frontotemporal Dementia, Brian Andrew Warmus

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Frontotemporal dementia (FTD) is a rapidly progressive and lethal disease, with no disease-modifying treatments. It is known that tau mutations cause FTD, but the underlying neurobiology is undefined. We sought to identify how tau affects the neurobiology in order to find potential treatment targets. Here, we address this question using a new mouse model expressing human tau with an FTD-associated mutation. We studied behavior, physiology, biochemistry, and neuropathology in several cohorts of mice at different ages. These mutant tau mice had abnormal repetitive behavior characteristic of FTD and synaptic deficits selectively in regions associated with FTD (ventral striatum and insula). …

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Print Vs. Pulpit: Representations Of Religion In The Harlem Renaissance, Sondra Bickham Washington Jan 2014

Print Vs. Pulpit: Representations Of Religion In The Harlem Renaissance, Sondra Bickham Washington

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At the turn of the twentieth century, African American race leaders believed that literature and other creative works could strengthen the fight against the social, economic, and political oppression facing members of their race across the country. However, when younger writers began explicitly focusing their narratives and poems on the more taboo and less religious elements of African American life such as heavy drinking, sensual dancing at jazz and blues clubs, and unmarried sexual relationships, black religious leaders often expressed opposition to their creative work. This sometimes harsh disapproval only served to create a larger gap between the religious and …

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Corrosion Prevention And Control Training In An Immersive Virtual Learning Environment, Rustin Deane Webster Jan 2014

Corrosion Prevention And Control Training In An Immersive Virtual Learning Environment, Rustin Deane Webster

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The majority of military education and training has not veered far from the days of chalk and talk instruction. Often with technological breakthroughs comes the proposal of the next revolution in multimedia instruction. Motion pictures to radios to educational television programs have all seemed to come and gone. The next wave of multimedia learning may involve more than a PowerPoint® presentation and lecture. Researchers continue to propose that Virtual Reality (VR) will find its true application and/or market in education and training. The objective of the project was to develop and provide a low-cost, scalable, and portable VR system containing …

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Understanding The Described Experiences Of Court Judges, Court Appointed Special Advocates (Casa) Volunteers, Department Of Human Resources Caseworkers, And Foster Parents, Mitsy Collier Wilbourne Jan 2014

Understanding The Described Experiences Of Court Judges, Court Appointed Special Advocates (Casa) Volunteers, Department Of Human Resources Caseworkers, And Foster Parents, Mitsy Collier Wilbourne

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UNDERSTANDING THE DESCRIBED EXPERIENCES OF COURT JUDGES, COURT APPOINTED SPECIAL ADVOCATES (CASA) VOLUNTEERS, DEPARTMENT OF HUMAN RESOURCES'CASEWORKERS, AND FOSTER PARENTS MITSY COLLIER WILBOURNE EARLY CHILDHOOD EDUCATION ABSTRACT The purpose of this study was to identify the described experiences of court judges, Court Appointed Special Advocates (CASA) volunteers, Department of Human Resources' caseworkers, and foster parents in the southeastern United States to enhance the early childhood educational needs and development of children in out-of-home care. The study was designed with cases so various perspectives were examined. Children who were neglected and abused, specifically those who must be removed from their parent's …

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Modulation Of Neocortical Gabaergic Interneurons By Voltage-Gated Ion Channels, Sidney B. Williams Jan 2014

Modulation Of Neocortical Gabaergic Interneurons By Voltage-Gated Ion Channels, Sidney B. Williams

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GABAergic interneurons provide the main source of inhibition in the neocortex and are important in regulating neocortical network activity. In the presence of the K+ channel blocker 4-AP and the glutamate receptor blockers, CNQX and D-APV, large amplitude evoked and spontaneous depolarizing responses are observed in the neocortex. These large propagating responses are blocked by GABAA receptor antagonists indicating that these events are due to synchronized activity of GABAergic interneurons. Cortical GABAergic networks are comprised of several types of interneurons, each with its own protein expression pattern, receptor profile, firing properties, synaptic targets and role in network activity. Voltage-gated ion …

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The Bear And The Tiger: Decoding Attitudes And Anxieties Towards Nature Through A.A. Milne's Winnie-The-Pooh In Post-Wwi Britain, Joanna Catherine Wilson Jan 2014

The Bear And The Tiger: Decoding Attitudes And Anxieties Towards Nature Through A.A. Milne's Winnie-The-Pooh In Post-Wwi Britain, Joanna Catherine Wilson

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This thesis aims to demonstrate how the two volumes of Winnie-the-Pooh stories, published in 1926 and 1928, and written by A.A. Milne and illustrated by E.H. Shepard, operate as a unique lens through which early twentieth-century attitudes towards nature and wildlife in Britain may be discerned, and in particular how the stuffed animal characters of Pooh the bear and Tigger the tiger represent a shift in post-war British worldviews concerning nature and domination. The initial stage of this investigation determines how the exceptionally broad demographic constituting the audience for children's fiction makes the medium a particularly expressive record of the …

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Copper Homeostasis In Mycobacteria, Jennifer L. Rowland Jan 2014

Copper Homeostasis In Mycobacteria, Jennifer L. Rowland

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Mycobacterium tuberculosis, the causative agent on tuberculosis in humans, is a globally important pathogen. In 2013, nearly 1.2 million people died from tuberculosis. Drug treatments and effective vaccines are lacking for this pathogen. A better understanding of the basic physiology of M. tuberculosis is required to improve disease outcomes. Upon inhalation into the lungs, M. tuberculosis is taken up by macrophages, in a process called phagocytosis, which normally destroys invading bacteria. As the phagosome inside the macrophage matures, bactericidal mechanisms are activated including: lowering pH, and introducing reactive oxygen and nitrogen species and hydrolytic enzymes to degrade bacterial cell walls. …

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Rhodopsin As A Model For Gpcr Trafficking And Its Role In Outer Segment Formation, Joshua D. Sammons Jan 2014

Rhodopsin As A Model For Gpcr Trafficking And Its Role In Outer Segment Formation, Joshua D. Sammons

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Rhodopsin is a prototypical G-protein coupled receptor whose biological function has been well worked out, yet little is known about the mechanism by which it is so efficiently transported to the rod outer segment (ROS) after synthesis. If rhodopsin is not efficiently transported to the ROS, rod cells will apoptose leading to cone cell apoptosis as well which results in the blinding disease retinitis pigmentosa. Work has begun to elucidate proteins responsible for transporting rhodopsin to the ROS using Xenopus laevis as a model since the photoreceptors of this amphibian are large and transgenic animals are relatively easy to prepare. …

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The Effects Of Estrogen On Learning And Memory, Carol Yvette Harden Jan 2014

The Effects Of Estrogen On Learning And Memory, Carol Yvette Harden

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Learning is the process in which new information is acquired and requires cellular modifications that occur in the hippocampus. These cellular changes can be seen through behavioral modifications which indicate memorization of the previously learned material. Increases in phosphorylation of the extracellular regulated protein kinase (ERK), a subfamily of MAPKs alters synaptic efficacy making it a correlate for learning and memory. Additionally, surges in plasma 17ß estradiol (E2) levels can increase synaptic plasticity, suggesting an importance for the role of E2 in cognition. Both human and animals studies have shown that elevated levels of estrogen correlated to an enhancement in …

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Gene Expression Signatures In Tree Shrew Retina, Rpe, And Choroid During Experimental Myopia And Recovery, Li He Jan 2014

Gene Expression Signatures In Tree Shrew Retina, Rpe, And Choroid During Experimental Myopia And Recovery, Li He

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During the development of induced myopia and recovery, the emmetropization mechanism is stimulated to modulate ocular growth. Emmetropization signals originate in the retina, are transmitted and transformed by retinal pigment epithelium (RPE) and choroid, and reach sclera to induce tissue remodeling. Induced myopia occurs in response to myopiagenic stimuli - minus lens, form deprivation, and darkness - (three GO conditions) which increase ocular elongation; recovery from lens-induced myopia (STOP) occurs when minus-lens wear is discontinued after complete compensation, slowing ocular elongation. This dissertation examined gene expression signatures in the retina, RPE, and choroid under GO and STOP conditions to examine …

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Protein O-Glcnac Modification In Diabetic Vascular Calcification, Jack Heath Jan 2014

Protein O-Glcnac Modification In Diabetic Vascular Calcification, Jack Heath

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Vascular calcification is prevalent in patients of diabetes mellitus, which represents an independent risk factor that positively correlated with morbidity and mortality in these patients. Vascular calcification is now recognized as a cell-regulated process of osteogenic differentiation of vascular smooth muscle cells (VSMC) in response to stress, such as hyperglycemia and oxidative stress. Both hyperglycemia and oxidative stress have been shown to induce protein modification by O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation), which is also elevated in diabetes. The present studies aimed to determine the effects of protein O-GlcNAcylation on vascular calcification in diabetes, and uncover the underlying molecular mechanisms. With the …

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