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Comparisons Between The Nod And Nor Mouse: Insight Into Diabetes Pathogenesis And Protection, Joseph Guy Daft Jan 2014

Comparisons Between The Nod And Nor Mouse: Insight Into Diabetes Pathogenesis And Protection, Joseph Guy Daft

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Type 1 Diabetes (T1D) is defined as the selective immune destruction of insulin producing beta cells within the islet. A new emphasis has been put on the role of the gastrointestinal (GI) tract in T1D; however, there is much more to learn about this relationship. Distinct differences have been observed in the intestinal permeability, barrier function, commensal microbiota, and mucosal innate and adaptive immunity of patients and animals with T1D, when compared to healthy controls. The non-obese diabetic (NOD) mouse and the BioBreeding diabetes prone (BBdp) rat are commonly used to models to study T1D in humans. Most murine studies …

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Imaging Biomarkers For Prediction Of Treatment Response In Schizophrenia, Jennifer Ann Hadley Jan 2014

Imaging Biomarkers For Prediction Of Treatment Response In Schizophrenia, Jennifer Ann Hadley

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Schizophrenia affects approximately 1% of the population and is one of the top five causes of disability worldwide. Patient response to any particular drug is variable and currently unpredictable. Our overall goal is to identify imaging biomarkers that will distinguish patients with schizophrenia who will respond to an antipsychotic drug from those who will not. When considering potential biomarkers, it is important to note that schizophrenia is known to involve altered neuronal connections, thought to reflect pathologically relevant changes associated with the disease. We propose to utilize functional connectivity as a biomarker for treatment response to antipsychotic drugs in schizophrenia. …

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The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers Jan 2014

The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers

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In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. Neutrophils play a critical role in controlling bacterial and fungal infections by multiple mechanisms including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). …

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Autism And Work: The Impact Of Comorbidity On Employment, Karen Harris Jan 2014

Autism And Work: The Impact Of Comorbidity On Employment, Karen Harris

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included sex ratio predictions for every nest in the main egg corral for 2007 and 2008.

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Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher Jan 2014

Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher

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Streptococcus pneumoniae (pneumococcus) is one of the leading causes of bacterial meningitis world-wide. The classic paradigm in the establishment of bacterial meningitis is that in the absence of physical trauma, infection in the peripheral blood is needed to cause invasion of the central nervous system (CNS). Our previous studies have shown that pneumococci, a frequent colonizer of the nasopharynx, can cause bacterial meningitis through a nonhematogenous route by which bacteria appear to travel along the olfactory nerves, through the cribriform plate to the olfactory bulbs and into the rest of the CNS. However, with the frequency of nasopharyngeal colonization and …

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The Role Of Gene Fragmentation And Loss In Poxvirus Evolution, Eneida Hatcher Jan 2014

The Role Of Gene Fragmentation And Loss In Poxvirus Evolution, Eneida Hatcher

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temperatures were near pivotal. The second chapter addresses the effects of fluctuating

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Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven Jan 2014

Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven

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The first aim of my thesis was to identify the protein composition of the protein aggregates, called Rosenthal fibers, which are the defining feature of Alexander disease (AxD). AxD is a rare neurodegenerative disease caused by mutations in the astrocyte specific protein, glial fibrillary acidic protein (GFAP). GFAP is a type III intermediate filament protein that is overexpressed in AxD. A guiding hypothesis of this project was that sequestration of vital cell proteins in the aggregates contributed to disease. The results of my research do not support this hypothesis, but do provide an in depth characterization of the protein composition …

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Sex Differences In Ss-Adrenergic Responsiveness Of Isolated Rabbit Hearts, Gregory Hoeker Jan 2014

Sex Differences In Ss-Adrenergic Responsiveness Of Isolated Rabbit Hearts, Gregory Hoeker

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Stimulation of adrenergic receptors by catecholamines is the predominant regulatory mechanism for cardiovascular performance. Many cardiovascular diseases involve changes in ß-adrenergic signaling that often lead to decreased cardiac performance, cardiac arrhythmias, and/or sudden cardiac death. This has made ß-adrenergic receptors (ß-ARs) a significant therapeutic target in cardiovascular disease. Sex differences in ß-adrenergic responsiveness have been associated with cardioprotection in females, conferring a survival benefit in female patients with heart failure (HF). The heart contains three distinct ß-ARs: ß1-, ß2-, and ß3-AR. It is not known how each ß-AR subtype contributes to the sex differences in ß-responsiveness, let alone how this …

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Role Of Immunoregulatory Cytokines Il-12 And Il-23 In Skin Cancer, Tahseen H. Nasti Jan 2014

Role Of Immunoregulatory Cytokines Il-12 And Il-23 In Skin Cancer, Tahseen H. Nasti

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The incidence of new cases of skin cancer, which includes non-melanoma epithelial tumors and melanoma, has increased dramatically over the last few decades. Approximately 75% of all skin cancer-related deaths is due to melanoma, which is one of the most aggressive and difficult cancers to treat. The initiating events and mechanisms that influence melanoma development are not fully known, due in part to a paucity of animal models amenable to identifying new oncogenic mutations, and investigating mechanisms of immunosurveillance. Transgenic mouse models often harbor an activating mutation in a known oncogene in all somatic cells, and its widespread expression from …

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Immunoprotection Versus Immunopathogenesis Associated With Aspergillus Fumigatus Exposure, Lauren Lilly Jan 2013

Immunoprotection Versus Immunopathogenesis Associated With Aspergillus Fumigatus Exposure, Lauren Lilly

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Opportunistic fungus Aspergillus fumigatus can cause a wide range of disorders depending on the immunological state of the host. In individuals lacking a robust innate immune response, invasive aspergillosis (IA) within the lungs can occur. In contrast, patients with a hyperreactive immune response can develop an allergic disorder called Allergic Bronchopulmonary Aspergillosis (ABPA). Using mouse models, we investigated contributing factors of host defense in IA and fungal asthma induced by Aspergillus fumigatus. The connection between fungi and the development of allergic disease has long been of interest. Previously, we have shown that beta-glucan receptor, dectin-1, is required for clearance during …

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Intramural Electrical Uncoupling During Long-Duration Ventricular Fibrillation In Rabbit, Trenika A. Madden Jan 2013

Intramural Electrical Uncoupling During Long-Duration Ventricular Fibrillation In Rabbit, Trenika A. Madden

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Ventricular fibrillation is a lethal cardiac arrhythmia which alters electrophysiological properties of the myocardium while concurrently inducing global ischemia and is associated with high mortality rates. Studies on the organization of long-duration ventricular fibrillation (LDVF) have shown that an endocardial to epicardial (i.e. transmural) activation rate gradient exists during ventricular fibrillation in canine and human myocardium; however, the underlying mechanism is unknown. This study tested the hypothesis that the activation rate gradient reflects heterogeneous changes in tissue electrical resistivity resulting in differential transmural electrical uncoupling of the ventricular myocardium. LDVF (>5min) was electrically induced in anesthetized, open-chest rabbits using …

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Rhodopsin Trafficking And Retinal Function, Nicholas Joseph Reish Jan 2013

Rhodopsin Trafficking And Retinal Function, Nicholas Joseph Reish

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The health and maintenance of rod photoreceptors depends on the high-fidelity vectorial transport of rhodopsin from its site of synthesis in the inner segment to its final resting place in the outer segment disks. Multiple molecular interactions play a role in this process, including the interaction of the small GTPase rab11a with rhodopsin that was first described in vertebrates in amphibians. We found that the interaction of the small GTPase rab11a and rhodopsin is conserved in mammalian retina. This interaction is direct, is abrogated by human disease-causing truncation mutations in rhodopsin, and does not depend on the nucleotide binding status …

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A Collaborative Social Computing Model For Transdisciplinary Problem Solving, Jerry Allen Higgs Jan 2013

A Collaborative Social Computing Model For Transdisciplinary Problem Solving, Jerry Allen Higgs

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The capacity to address and solve today's complex problems is becoming exceedingly more difficult because of the transdisciplinary nature of our current system of knowledge. Innovative solutions are no longer the by-products of centralized offices and laboratories. In fact, crafting solutions for truly complex problems requires a collaborative sharing of knowledge that transcends the artificial boundaries of departmentalized offices and research facilities. For decades, segmented information systems built on distributed platforms have kept transdisciplinary problem solving fragmented, without the ability to effectively share knowledge or data. This segmentation has stifled the progress of research reaching beyond the traditional boundaries of …

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The Fireball Brothers: A Novel, Michael David Hornbuckle Jan 2013

The Fireball Brothers: A Novel, Michael David Hornbuckle

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The Fireball Brothers is a novel about two teenage brothers who, while swimming near their Alabama farm in 1959, come near a "fireball" that has fallen from the sky. From then on, the two brothers are joined at the shoulder. Because they can no longer do regular work to support the family farm, their father takes them on the road as travelling musicians. While travelling, they meet fellow travelers, snakeoil salesmen, freakshows, and beatniks. A reporter named Munford Coldwater takes an interest in the family and tries to help them while documenting their journeys. Taken as a whole, the novel …

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Estimation And Forecasting Of Air Handling Condensate Recovery Using Multiple Regression Analysis And Time-Series Autoregressive Models, Atul Nandkumar Kajale Jan 2013

Estimation And Forecasting Of Air Handling Condensate Recovery Using Multiple Regression Analysis And Time-Series Autoregressive Models, Atul Nandkumar Kajale

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According to the U.S. Drought Monitor (University of Nebraska at Lincoln, 2011), the majority of the Southeastern states are classified as being in a state of moderate, severe, extreme, and or exceptional drought. The northern part of Alabama including Jefferson County falls into the "abnormal" drought category. Due to the prevailing drought conditions in the Southeastern U.S. in the recent past, it is necessary to conserve water resources by using them as efficiently and responsibly as possible. The increasing population, socioeconomic developments, and industrialization could have significant impacts on the way we consume water today. There will be an imbalance …

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Predictors Of Falls Among Older Adults, Jaspreet Kaur Jan 2013

Predictors Of Falls Among Older Adults, Jaspreet Kaur

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With an aging population, more attention has to be focused on the needs of older adults, especially regarding medical and psychological concerns. Thirty-three percent of older adults fall each year, and falling is one of the leading causes of accidental death nationwide. The objective of this study was to identify predictors of falls among sedentary community-dwelling older adults (age 65+). The study employed a secondary data analysis of measures collected in the Physical and Cognitive Exercise Study (PACES). Logistic regression analysis was used to evaluate whether individual or composite measures of vision, cognition, and physical functioning were associated with an …

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Gabaergic Dysfunction In Huntington Disease, Sarah Elizabeth Dougherty Jan 2013

Gabaergic Dysfunction In Huntington Disease, Sarah Elizabeth Dougherty

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GABAergic neurons are responsible for regulation of neuronal signaling through inhibition. Alterations in the delicate balance of excitation and inhibition have been observed in many neurological disorders, including neurodegenerative diseases. Huntington disease (HD) is an autosomal dominant neurodegenerative disorder that is characterized by motor, psychiatric, and cognitive disturbances. As the hallmark movement pathology of HD is hyperkinesis it is intriguing to postulate that alterations in inhibition, and by extension within GABAergic cell networks, could be part of the pathogenesis of this disorder. In order to elucidate the role of GABAergic cell populations in HD we have used behavioral paradigms, molecular …

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Straight Through The Middle: Notes From My Journey, Nancy Rutland Glaub Jan 2013

Straight Through The Middle: Notes From My Journey, Nancy Rutland Glaub

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This memoir is primarily a collection of creative nonfiction essays. It includes one fictional short story for adults, "Rise," and one fictional story written for children, "The Memory Keepers." The essays and stories were produced following the death of my son; they explore the process of grieving his loss and rediscovering purpose and meaning in my life through story, faith, and community.

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Investigation Of Nanodiamonds With Si-V Defect Centers For Applications In Fluorescence-Based Sensing And Drug Delivery, Sonal Singh Jan 2013

Investigation Of Nanodiamonds With Si-V Defect Centers For Applications In Fluorescence-Based Sensing And Drug Delivery, Sonal Singh

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Fluorescent Nanodiamond (FND) offers a promising platform for many therapeutic applications involving drug and gene delivery, optical agents for bioimaging and labeling, and molecular detection. This is due to the potential to incorporate photostable luminescent vacancy-related defects into sub-10 nm diamond crystals which are biologically compatible and easy to functionalize. Moreover, the development of future nanoscale devices and arrays based on nanodiamonds (NDs) will require precise spatial control. Hence, the direct placement and manipulation (control of size, shape and chemical functionality) of brightly fluorescent sub-10 nm NDs offers potential for highly localized /specific imaging and sensing, while also providing the …

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The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall Jan 2013

The Phenotypic Expression Of Usp14 Deficiency Is Dependent Upon Genetic Background, Andrea Gail Marshall

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The ubiquitin proteasome system (UPS) plays a critical role in regulating a diversity of cellular processes that are essential to neuronal function, such as synaptic transmission, axon guidance, and neurite outgrowth. Dysfunctions of the UPS are linked with many neurodegenerative disorders, including motor neuron diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), although it is not known how UPS dysfunction contributes to disease pathology. The proteasome, an approximate 2.5 megadalton protein complex comprised of a 20S core particle and 19S regulatory particle, is the site of ubiquitin-mediated proteolysis in the cell. Recent studies have linked ubiquitin specific …

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In Vitro Prevascularization Of 3d Tissue Constructs, Lauren Marshall Jan 2013

In Vitro Prevascularization Of 3d Tissue Constructs, Lauren Marshall

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There is a need for more effective therapies to combat breast cancer. One reason for the inefficiency of therapeutics is that testing technologies currently employed in drug discovery and development are not reliable when transitioning drugs into human clinical trials. To supplement the currently used in vitro cell culture studies and in vivo animal studies, an in vitro three-dimensional breast tumor system has been suggested with integration of human cells, hydrogel biomaterials, 3D architecture, and endothelialized microchannels. Therefore, the objective of the thesis project, as an initial step in fabrication of the supplemental system for drug testing, is to fabricate …

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Cd5 Regulation Of T Helper Cell Differentiation And Cytokine Signaling, Donald J. Mcguire Jan 2013

Cd5 Regulation Of T Helper Cell Differentiation And Cytokine Signaling, Donald J. Mcguire

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CD5 is expressed on T and B1a cells and is an important regulator of cell survival and activation. Engagement of CD5 promotes cell survival through the activation of the serine threonine kinase CK2. Mice with genetic abrogation of CD5 binding to CK2 (CD5∆CK2bd) exhibited reduced severity of experimental autoimmune encephalomyelitis that was associated with increased activation induced cell death. In addition to inhibiting cell death, CD5 activation of CK2 significantly enhances Th17 differentiation. Loss of CD5-CK2 signaling reduces the generation of Th17 cells despite an unexpected increase in pSTAT3 levels. The mechanisms of CD5's enhancement of Th17 differentiation have not …

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Effects Of Nicotine On The Human Visual System: 1) Color Perception; 2) Processing At The Cortical Level, Naser T. Naser Jan 2013

Effects Of Nicotine On The Human Visual System: 1) Color Perception; 2) Processing At The Cortical Level, Naser T. Naser

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The visual system is sensitive to various types of chemical substances, including nicotine. Nicotinic acetylcholine receptors (nAChRs) are found in the nervous system, including the retina. These receptors play a role in modulating signals within the visual system. It has been shown that smoking affects color vision, and visual evoked potentials (VEPs). But few studies have been devoted to understanding the effects of nicotine alone. The purpose of this research was to examine the effects of oral administration of nicotine in human adults, who are non-smokers, on color vision, and visual cortical processing. Previous studies on adult smokers revealed that …

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An Investigation Of The Sublethal Effects Of Carbon Dioxide On The Common Sea Urchin Lytechinus Variegatus And The Carbonate Chemistry Of Its Nearshore Habitat, Roberta Challener Jan 2013

An Investigation Of The Sublethal Effects Of Carbon Dioxide On The Common Sea Urchin Lytechinus Variegatus And The Carbonate Chemistry Of Its Nearshore Habitat, Roberta Challener

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Increases in CO2 concentrations, whether from accumulation of metabolic waste under intensive culturing conditions or from increases in atmospheric levels, lead to decreases in seawater pH and carbonate saturation states. Lytechinus variegatus survive chronic exposure to hypercapnic conditions (pH 7.4 -7.8, partial pressure of CO2 (pCO2) 1738-4290 μatm) in synthetic seawater, yet aspects of growth and development are affected. Rates of embryonic and larval development were delayed and larval size and arm length reduced under high pCO2 conditions. Fecal production rates were higher and ash absorption efficiency (%) was lower in individuals exposed to hypercapnic conditions, suggesting that the ability …

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Identification Of Claudin-1 As An Entry Factor In Dengue Infection And Development Of A High Throughput Screening Assay For Antivirals Against Dengue Virus, Pulin Che Jan 2013

Identification Of Claudin-1 As An Entry Factor In Dengue Infection And Development Of A High Throughput Screening Assay For Antivirals Against Dengue Virus, Pulin Che

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Dengue virus (DENV) has become a huge public health concern around the world with no vaccine or antivirals available. More than one-third of the world's population is living in areas at risk of infection. To conquer the dengue disease, a better understanding of virus-host interactions and development of the appropriate therapeutic treatments are required. In this dissertation, we first broadly reviewed the factors involved in dengue viral entry and the role of tight junctions as a pathogen target. Second, we developed, optimized and validated a high throughput screening (HTS) assay for anti-dengue virus drug screening. Taking advantage of using live …

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Identification Of Staphylococcus Aureus Sortase A Inhibitors As Potential Antibacterial Agents, Bala Chandra Chenna Jan 2013

Identification Of Staphylococcus Aureus Sortase A Inhibitors As Potential Antibacterial Agents, Bala Chandra Chenna

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Staphylococcus aureus (S. aureus) is the causative organism for a wide range of infectious diseases from superficial skin infections to dangerous bacteremias. Six pathogens named ESKAPE pathogens are responsible for majority of antibiotic resistant bacterial infections. MRSA is the single most prevalent ESKAPE pathogen. Many of the nosocomial MRSA strains are multi-drug resistant, and even methicillin-sensitive strains can be deadly. S. aureus has recently taken on a new role in causing an escalating number of community-acquired infections in non-hospitalized persons without predisposing risk factors. Due to the increase in the number of infections caused by multi-drug resistant S. aureus and …

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Comparisons Between Electrophysiologic Assessments Of Visual Function And Histological Findings Of Cone Photoreceptors In Light-Damaged Albino Rats, Molly Clark Jan 2013

Comparisons Between Electrophysiologic Assessments Of Visual Function And Histological Findings Of Cone Photoreceptors In Light-Damaged Albino Rats, Molly Clark

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The purpose of this project was to investigate the etiology of decreased cone-driven vision in the light damage model of retinal degenerations. Experimental albino rats underwent moderate, low-intensity light damage for 10 days. Electroretinography was utilized to assess physiologic function of the rod- and cone-driven retinal function in the experimental and control (sibling) rats. Immunohistochemical staining for cone arrestin antibody identified cone photoreceptors, allowing quantification of cone density and comparison to the decline in functional vision. In this experiment the light-damaged rats showed decreased rod- and cone-driven function with partial recovery of responses 30 days later. Outer nuclear layer thickness …

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Selection And Evolution Of Pneumococci In Response To Conjugate Vaccines, Christina M. Croney Jan 2013

Selection And Evolution Of Pneumococci In Response To Conjugate Vaccines, Christina M. Croney

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Pneumococcal conjugate vaccines (PCVs) containing subsets of the >90 capsular polysaccharide antigens have been successful as a means of decreasing invasive and non-invasive pneumococcal disease worldwide. However, this success is limited to the specif-ic capsular serotypes against which PCVs are formulated and studies have reported the increase of nonvaccine serotypes. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media and was released without efficacy data. In this study we set out to 1) determine potential efficacy for invasive and noninvasive pneumococcal disease and 2) …

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Utilizing A Hydroxyapatite-Binding Domain To Deliver Bone Regenerative Molecules To Hydroxyapatite And Allograft Bone To Enhance Osteogenesis, Bonnie Kathleen Culpepper Jan 2013

Utilizing A Hydroxyapatite-Binding Domain To Deliver Bone Regenerative Molecules To Hydroxyapatite And Allograft Bone To Enhance Osteogenesis, Bonnie Kathleen Culpepper

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Hydroxyapatite (HA) makes up the mineral component of bone, and synthetic HA is commonly used to coat metal implants for use in dentistry and orthopedics. Additionally, allograft and synthetic HA are common alternatives to autograft bone, to circumvent the complications associated with a second surgery site. While both HA and allograft are known to be osteoconductive, osteoinductivity is limited. In this work, we developed methods for anchoring osteoinductive factors onto multiple types of HA biomaterials and human allograft bone, with the goal of enhancing their osteoregenerative potential. Specifically, a HA-binding domain, heptaglutamate (E7), modeled on bone-binding domains within native proteins, …

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Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo Jan 2013

Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo

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Mutations in the AP3-ß1 gene are known to cause Hermansky-Pudlak syndrome type 2 (HPS2) in humans and canine cyclic hematopoiesis (CH) in gray collie dogs. HPS2 patients have severe congenital neutropenia (SCN), and dogs have cyclic neutropenia (CN). The mechanism behind neutropenia is uncertain. Pearl mice have an AP3-ß1 mutation, but whether they actually have neutropenia has not yet been evaluated. This dissertation presents a discussion of the evaluation of neutropenia in pearl mice, hematopoietic progenitor cell mobilization defect in pearl mice and finally an evaluation of methods of dog-to-mouse xenotransplantation to establish a xenotransplant model of the dog hematopoietic …

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