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Elucidating The Role Of Gsk3 In Synaptic And Cognitive Deficits In Fragile X Syndrome, Aimee Vinson Franklin Jan 2014

Elucidating The Role Of Gsk3 In Synaptic And Cognitive Deficits In Fragile X Syndrome, Aimee Vinson Franklin

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Fragile X Syndrome (FX) is the most common inherited form of mental retarda-tion. Prominent characteristics of FX are mimicked in a mouse model with deleted fmr1 including hyperactivity, anxiety, developmental delay and social deficits. Additionally, FX mice display deficits in n-methyl-d-aspartate receptor (NMDAR) dependent long-term potentiation (LTP) at medial perforant path synapses onto dentate granule cells (MPP-DGC synapses). Because LTP is a cellular correlate of learning and memory, defi-cits in LTP at this synapse are thought to underlie impairments in pattern separation, a form of learning and memory dependent on proper DG function. Identifying the patho-logical mechanisms that cause impaired …

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Stress And Myostatin In Salmoninae, Nicholas Galt Jan 2014

Stress And Myostatin In Salmoninae, Nicholas Galt

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The relationship between the muscle growth inhibitor, myostatin, and the stress response has been extensively studied in mammals, and myostatin is now known to partially mediate the degradative effects of stress in skeletal muscle. In fish, this relationship has not yet been clearly described. Herein, the effects of two stress mimetics, cortisol treatment and crowding, on myostatin-1a, -1b, and -2a expression in rainbow trout (Oncorhynchus mykiss), cutthroat trout (Oncorhynchus clarki), Chinook salmon (Oncorhynchus tshawytscha), brook trout (Salvelinus fontinalis), and Atlantic salmon (Salmo salar) are described. In study I, no clear effects on myostatin mRNA expression were detected in rainbow trout …

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Tumorgraft Models As A Platform For Molecular Characterization And Drug Evaluation In Pancreaticobiliary Malignancies, Patrick Lee Garcia Jan 2014

Tumorgraft Models As A Platform For Molecular Characterization And Drug Evaluation In Pancreaticobiliary Malignancies, Patrick Lee Garcia

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arribada nesting behavior. The first chapter addresses the potential effects of a nest’s

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Using Mce4 Sirna Molecular Beacons For Detection And Eradication Of Mycobacterial Infection In Macrophages, Remo George Jan 2014

Using Mce4 Sirna Molecular Beacons For Detection And Eradication Of Mycobacterial Infection In Macrophages, Remo George

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temperatures. The third chapter represents the most comprehensive evaluation to date of

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Characterization Of Murine And Human Breast Cancer Stem Cells In Vitro And In Vivo, Carnella Lee Jan 2014

Characterization Of Murine And Human Breast Cancer Stem Cells In Vitro And In Vivo, Carnella Lee

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Breast cancer stem cells (BCa-SC) are considered as a rare population of cells which cause resistance to chemotherapy in breast cancer (BCa). This population is characterized in humans and mice by CD24- CD44+ ALDH1+ phenotype and expresses mesenchymal properties that differ from the normal epithelial CD24+ CD44+ phenotype expressed in the majority of BCa cells. It has been widely accepted that tumor growth is sustained by BCa-SC that are similar to normal stem cells in which they have the ability to self-renew and differentiate. However, unlike their normal counterparts, BCa-SC are rare cells within tumors with the ability to self-renew …

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Osteomimmunology Of Bone Fracture Healing And Cell And Gene Therapy Approaches For Nonunion Bone Defects, Seth G. Levy Jan 2014

Osteomimmunology Of Bone Fracture Healing And Cell And Gene Therapy Approaches For Nonunion Bone Defects, Seth G. Levy

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Despite the body's ability to repair bone fractures under normal circumstances, up to 10% of the 7.9 million fractures suffered in the United States each year do not achieve bony union. Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis are known to work in concert to control many stages of this process, but when one is impaired it leads to failure of bone healing, referred to as a nonunion. Such nonunion fractures often result from critical-size defects that will not completely heal over the natural lifetime of the animal. Based on this …

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Engineering Fibroblast-Remodeled Electrospun Matrices For Full-Thickness Skin Regeneration, Paul Bonvallet Jan 2014

Engineering Fibroblast-Remodeled Electrospun Matrices For Full-Thickness Skin Regeneration, Paul Bonvallet

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Skin is often severely damaged, resulting in the need for surgical intervention. There are many limitations to current therapies, therefore a synthetic skin graft would be invaluable for skin regeneration. The focus of the current study is on developing engineered scaffolds with embedded dermal fibroblasts that can be remodeled into native skin tissue upon implantation. To achieve this goal we created electrospun scaffolds composed of collagen I and polycaprolactone (PCL), and then introduced pores to allow fibroblast infiltration. In initial experiments performed to optimize pore size and collagen to PCL concentration, we determined that a 160 µm pore diameter, and …

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Assessing The Active Kinome Of Influenza Virus Infected A549 Cells, Colm Atkins Jan 2014

Assessing The Active Kinome Of Influenza Virus Infected A549 Cells, Colm Atkins

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Influenza A Virus is a respiratory pathogen of the family Orthomyxoviridae and causes significant worldwide morbidity and mortality during seasonal epidemics and periodic pandemics. As with all viruses, influenza's limited coding capacity requires the use of host proteins and processes in its replication and release cycle. Phosphorylation, mediated by cellular kinases and phosphatases, represents a significant mechanism of post-translational modification of cellular products, and is responsible for regulating the activi-ty, lifespan and localization of many lipids and proteins in host-cells. Several cellular kinases have been associated with various steps of the Influenza lifecycle, including PKC-ßII (viral entry), PKR (host defense), …

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Il-8 Is Necessary And Sufficient For X-Ray Radiation Enhanced Endothelial Adhesion., Stephen Kyle Babitz Jan 2014

Il-8 Is Necessary And Sufficient For X-Ray Radiation Enhanced Endothelial Adhesion., Stephen Kyle Babitz

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Ionizing radiation (IR) is a potent inflammatory stimulus to the human body. In the vasculature, inflammation is a major contributing factor for atherosclerosis. In addition, radiation from several sources has been linked with increased risk for multiple cardiovascular complications. A key compnent of radiation associated inflammation is an increase in the adhesiveness of the endothelium which leads to a pathogenic accumulation of leukocytes in the vascular wall. This is one of the initial steps in vascular inflammation and leads to a number of adverse complications such as heart disease and stroke. The molecular mechanisms behind radiaton enhanced endothelial adhesion have …

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Targeted Delivery Of Osteoinductive Peptides To Bone Graft Utilizing A Calcium Binding Domain To Enhance The Regenerative Potential, Jennifer Leigh Bain Jan 2014

Targeted Delivery Of Osteoinductive Peptides To Bone Graft Utilizing A Calcium Binding Domain To Enhance The Regenerative Potential, Jennifer Leigh Bain

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Bone grafting procedures are common practice. Autogenous bone is considered optimal, however, complications associated with bone harvesting often lead clinicians to use off-the-shelf materials that have limited osteoinductivity. Alternatively, bioactive factors passively adsorbed onto various carriers are available. These materials, while effective, are expensive to produce, require supraphysiological doses, and have adverse side effects due to dissemination from the graft site. This dissertation aims to reintroduce osteoinductive factors to bone grafts to enhance regenerative capacity. Specifically, we utilized negatively-charged calcium-binding domains (polyglutamate) to anchor two osteoinductive peptides bone graft materials including an allograft, xenograft, alloplast, and bone cement. The peptides …

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Internet Use And Mental Health/Well-Being In Old Age: Exploring The Roles Of Social Integration And Social Support, Ronald William Berkowsky Jan 2014

Internet Use And Mental Health/Well-Being In Old Age: Exploring The Roles Of Social Integration And Social Support, Ronald William Berkowsky

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The escalating pressures put on the US healthcare system, due in part to the growing needs of the expanding older adult population, has motivated research dedicated to more fully understanding the mental health and mental well-being needs of this population and ways to address these needs and alleviate the pressure on the healthcare system. An increasing area of interest is in examining the role information and communication technologies (ICTs), such as Internet-connected computers and smartphones, in the health of older adults. Research has shown that ICTs can successfully be used to help treat, manage, and cope with mental health/well-being issues, …

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Ap2 Clock Mutant Mice: Baseline Characteristics And Novel Responses To A Lipopolysaccharide Challenge, Tana Birky Jan 2014

Ap2 Clock Mutant Mice: Baseline Characteristics And Novel Responses To A Lipopolysaccharide Challenge, Tana Birky

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Circadian rhythms are the daily biological changes present within most organisms that occur in a predictable, approximately 24 hour pattern, even in the absence of external stimuli. These rhythms occur both at a global and cellular level, and although the molecular mechanics are highly conserved, their functions may vary depending on the tissues in which they are expressed. These functions include various aspects of metabolic processes such as satiety signaling and cellular proliferation. In order to explore the specific functions of circadian rhythms within adipocytes, a mouse model with Clock disruption driven by the fatty acid-binding protein 2 (aP2) promoter …

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Predictors Of Outcomes In Patients With Ventricular Assist Devices, Amelia Katharine Boehme Jan 2014

Predictors Of Outcomes In Patients With Ventricular Assist Devices, Amelia Katharine Boehme

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Ventricular assist devices (VAD) are used as a bridge to transplant and to increase the quality of life in advanced heart failure patients. The use of the VAD is not without risks itself, with an increased risk of thromboembolism, hemorrhage and death. Therefore, we aimed to (1) evaluate predictors of thromboembolism; (2) design a score to predict hemorrhages in VAD patients; and (3) evaluate the change in kidney function post-VAD implant and to investigate the relationship between kidney function and mortality in VAD patients using data collected from the University of Alabama at Birmingham Mechanical Circulatory Support Clinic. Over the …

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Promoting Worksite Stair Use By Launching The "Stepping Up" Campaign, Lynne A. Obiaka Jan 2014

Promoting Worksite Stair Use By Launching The "Stepping Up" Campaign, Lynne A. Obiaka

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Background: Obesity and overweight contribute to worksite absenteeism and decreased productivity. Encouraging employees to frequent the stairs is one approach towards increasing worksite physical activity. Methods: An explanatory, mixed methods research design was used to explore the impact of a health communications campaign entitled "Stepping Up" on worksite stair use in health department employees. The campaign included octagonal shaped posters similar to traffic signs, email prompts and printed materials. A pretest and posttest were administered before and after the intervention to assess stair use frequencies and identify predictors. A Wilcoxon signed-rank test for related samples, Spearman correlations and multiple rank …

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Effects Of Early Life Exposure To Methylmercury On Predator Response In Daphnia Pulex, Megan Lisa Steed Jan 2014

Effects Of Early Life Exposure To Methylmercury On Predator Response In Daphnia Pulex, Megan Lisa Steed

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Knowledge of the health effects of toxic chemicals is largely based on single chemical models rather than a multi-factor model, which more accurately captures realworld exposures. This study investigated how methylmercury affects Daphnia pulex in the presence of predatory stress chemical. A kairomone is an infochemical released by an animal that can be detected by another animal. Daphnia pulex detects kairomone released by Danio rerio resulting in the induction of morphological and life history changes. Danio rerio were kept in COMBO media for 24 hours at a density of 2 fish per liter. Daphnids were then housed in kairomone-containing COMBO …

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Translocation Of Shed Syndecan-1 To The Nucleus: A Novel Mechanism Of Tumor-Host Crosstalk, Mark Stewart Jan 2014

Translocation Of Shed Syndecan-1 To The Nucleus: A Novel Mechanism Of Tumor-Host Crosstalk, Mark Stewart

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Multiple myeloma is a hematological malignancy of plasma cells that disseminates throughout the body. Crosstalk between myeloma and host cells is critical to the establishment of a microenvironment conducive to tumor growth and progression. An important mediator of this crosstalk is syndecan-1, a heparan sulfate proteoglycan. Syndecan-1 is proteolytically shed from the surface of myeloma cells and is abundant in the bone marrow microenvironment and serum of myeloma patients. Shed syndecan-1 facilitates tumor-host crosstalk within the microenvironment to drive tumor growth, angiogenesis, and metastasis. We now report for the first time that shed syndecan-1 can be taken up by a …

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The Conservation Of The Western Pacific Leatherback Sea Turtle (Dermochelys Coriacea) At Bird's Head Peninsula, Papua Barat, Indonesia, Ricardo F. Tapilatu Jan 2014

The Conservation Of The Western Pacific Leatherback Sea Turtle (Dermochelys Coriacea) At Bird's Head Peninsula, Papua Barat, Indonesia, Ricardo F. Tapilatu

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Leatherbacks declined significantly worldwide during the 20th century and continue to decline in the Pacific and Indian oceans. In the Pacific Ocean, nesting numbers on beaches in Malaysia and the Pacific coast of Mexico and Costa Rica have collapsed. The nesting beaches at Bird's Head Papua Barat, Indonesia, represent the last stronghold for leatherback nesting in the western Pacific. The studies in this dissertation provide basic information that is critical to our understanding of the biology, ecology, and conservation of the western Pacific leatherback. (1) Year-round nesting surveys were conducted from 2005 to 2011 at both Jamursba Medi and Wermon …

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Statistical Analysis In Genomic Studies, Guodong Wu Jan 2014

Statistical Analysis In Genomic Studies, Guodong Wu

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Next-generation sequencing (NGS) technologies reveal unprecedented insights about genome, transcriptome, and epigenome. However, existing quantification and statistical methods are not well prepared for the coming deluge of NGS data. In this dissertation, we propose to develop powerful new statistical methods in three aspects. First, we propose a Hidden Markov Model (HMM) in Bayesian framework to quantify methylation levels at base-pair resolution by NGS. Second, in the context of exome-based studies, we develop a general simulation framework that distributes total genetic effects hierarchically into pathways, genes, and individual variants, allowing the extensive evaluation of existing pathway-based methods. Finally, we develop a …

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Usp16 And Histone H2a Deubiquitination In Mouse Embryonic Stem Cell Function, Wei Yang Jan 2014

Usp16 And Histone H2a Deubiquitination In Mouse Embryonic Stem Cell Function, Wei Yang

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In eukaryotic cells, genomic DNA is packaged into a chromatin structure by association with histone and non-histone proteins. Posttranslational modifications of histones play important roles in the regulation of chromatin structure and function. Ubiquitination of histone H2A (ubH2A) represents a predominate modification, occurring on ~10% of total cellular H2A. While H2A ubiquitination is primarily conferred by Polycomb Repressive Complex 1 (PRC1), H2A deubiquitination has been attributed to multiple H2A deubiquitinases. Our laboratory previously reported the purification and functional characterization of a H2A-specific deubiquitinase, USP16 (initially named as Ubp-M) in human cells. However, whether USP16 represents a general and important regulator …

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The Roles Of Mammalian Tribbles Homolog 3 (Trib3) In Coordinating Energy Metabolism And Development Of Insulin Resistance, Wei Zhang Jan 2014

The Roles Of Mammalian Tribbles Homolog 3 (Trib3) In Coordinating Energy Metabolism And Development Of Insulin Resistance, Wei Zhang

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Insulin resistance in diabetics comprises of a reversible component treatable with intensive glycemic control and a non-reversible component present in pre-diabetes that may lead to the development of overt diabetes. The reversible component is induced and exacerbated by hyperglycemia in both uncontrolled type 1 and type 2 diabetes, a process known as glucose-induced insulin resistance (GIIR) or glucose toxicity. The tribbles homolog 3 (TRIB3) has been identified as a pseudokinase that inhibits Akt activity by physically blocking its phosphorylation site. Expression of TRIB3 has been associated with various signals such as endoplasmic reticulum (ER) stress and nutrient availability in pancreatic …

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Multiple Human Itgam Variants Alter Mac-1, Fcgamma Receptor And Tlr Functions On Neutrophils, Yebin Zhou Jan 2014

Multiple Human Itgam Variants Alter Mac-1, Fcgamma Receptor And Tlr Functions On Neutrophils, Yebin Zhou

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Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the non-synonymous SNPs rs1143679, rs1143678 and rs1143683) are associated with SLE. ITGAM encodes the protein CD11b, a subunit of the ß2 integrin Mac-1. The purpose of this work was to determine the effects of ITGAM genetic variation on the biological functions of neutrophil Mac-1. Neutrophils from ITGAM genotyped and sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement coated erythrocytes, serum treated zymosan, heat treated zymosan and IgG coated erythrocytes. The adhesion capacity of ITGAM variants, in …

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A Low-Power Multichannel Telemetry System For High-Speed Wireless Neural Recordings, Yang-Guo Li Jan 2014

A Low-Power Multichannel Telemetry System For High-Speed Wireless Neural Recordings, Yang-Guo Li

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The advances in microelectronics and wireless communication are going to change our lifestyles and benefit our healthcare system in the foreseeable future. New conception named "Ubiquitous Healthcare" has been proposed. It envisions a continuous, real-time, remote monitoring on the health conditions of people through the wireless communication network. Traditional biosignal monitoring devices need wire-connections for the recording, which may cause skin rupture and body infection. The physical connections also limited the number of the integrated recording channels. A low-power implantable multichannel telemetry system which can be implanted in the body and transmit recordings wirelessly can solve the problem of the …

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Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino Jan 2014

Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino

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The purpose of these dissertation studies was to 1) determine whether influenza infection alters CFTR activity in polarized epithelium; 2) measure CFTR expression and activity in cells co-expressing influenza M2 protein; and 3) examine the role of M2 on the alteration of CFTR during viral infection. We determined that infection of polarized primary epithelial cells with influenza decreases CFTR expression and activity. In addition, individual cells infected with influenza had decreased CFTR conductance as measured by whole-cell patch clamp. We also found that the influenza ion channel, matrix protein 2 (M2), alone reduced CFTR expression and activity. M2 is expressed …

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Interaction Between A Low-Iron Diet And Early-Life Methylmercury Exposure In Daphnia Pulex, Sherri Hudson Jan 2014

Interaction Between A Low-Iron Diet And Early-Life Methylmercury Exposure In Daphnia Pulex, Sherri Hudson

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Methylmercury (MeHg) is a known neurotoxicant and bioaccumulates in fish, with exposure to humans in utero being of highest concern. Iron deficiency (ID) accounts for approximately 50% of anemia cases. Anemia is estimated to affect 1.62 billion people worldwide, and is particularly problematic during pregnancy and early life. Previous studies have shown that ID exacerbates toxicity associated with exposure to metals, including lead, manganese, and cadmium. The overall purpose of this thesis research is to investigate the interaction between a low-iron (Fe) diet and early-life exposure to MeHg in Daphnia pulex. I hypothesized when D. pulex are fed a low-Fe …

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Relationship Between Diabetes And Indoor Air Pollution: An Exploratory Analysis, Sandeep Mishra Jan 2014

Relationship Between Diabetes And Indoor Air Pollution: An Exploratory Analysis, Sandeep Mishra

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India has the second highest number of people with diabetes. The high prevalence of diabetes in India cannot be explained on the basis of established risk factors like obesity. The role of air pollution in diabetes has recently received attention. Studies have indicated the possibility that air pollution generated by traffic might be associated with increased risk of diabetes. Published literature lacks studies that assess the relationship between indoor air pollution and diabetes, although indoor air pollution can lead to higher levels of pollutants in house compared to traffic pollution. The current study determined the relationship between indoor air pollution …

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Osteoblast And Odontoblast Specific Regulatory Actions Of Runx2 For The Development Of Mineralized Tissues, Mitra Darice Adhami Jan 2014

Osteoblast And Odontoblast Specific Regulatory Actions Of Runx2 For The Development Of Mineralized Tissues, Mitra Darice Adhami

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The Runx2 transcription factor is necessary for commitment and differentiation of mesenchymal cells into the chondroblasts, osteoblasts and odontoblasts. Runx2 induces the expression of several key genes involved in mineralization of both the bone and dentin matrices. Global Runx2-null mice are completely void of mineralized tissue and do not express osteoblast markers, indicating that Runx2 is required for commitment to the osteoblast lineage. Tooth development in Runx2-null mice is arrested in the bell stage, prior to the differentiation of odontoblasts. Thus, Runx2 is essential for development of osteoblast and odontoblast lineages. However, the functional requirements of Runx2 after commitment to …

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Formaldehyde Exposure In Pregnant Women And Its Relationship To Fetal Growth, Azita Amiri Jan 2014

Formaldehyde Exposure In Pregnant Women And Its Relationship To Fetal Growth, Azita Amiri

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Formaldehyde exposure during pregnancy has been linked to adverse pregnancy outcomes such as poor fetal growth, although few studies have examined formaldehyde exposure during pregnancy and its relationship to fetal growth. The purpose of this study was to determine the level of formaldehyde exposure during pregnancy and examine the relationship between formaldehyde exposure and fetal growth. Formaldehyde exposure was examined, using vapor monitor badge and urine formic acid, in 140 women in their second trimester of pregnancy. One time urine samples were collected during a routine prenatal visit, and women wore the vapor badges for 24 hours. Fetal growth was …

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Modulating The Cxcl12/Cxcr4 Axis In The Pulmonary Vasculature By Adenoviral Vector-Mediated Delivery Of Soluble Cxcr4 (Scxcr4): A Prophylactic Approach To The Prevention Of Cancer Metastasis To The Lung, Anand Chandrasekaran Annan Jan 2014

Modulating The Cxcl12/Cxcr4 Axis In The Pulmonary Vasculature By Adenoviral Vector-Mediated Delivery Of Soluble Cxcr4 (Scxcr4): A Prophylactic Approach To The Prevention Of Cancer Metastasis To The Lung, Anand Chandrasekaran Annan

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The results also indicate that in situ nests were cooler than egg corral nests but still

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Fatigue Testing Of Straight And Angled Abutments In A High Torque Dental Implant System, Rana M. Atieh Jan 2014

Fatigue Testing Of Straight And Angled Abutments In A High Torque Dental Implant System, Rana M. Atieh

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Root form dental implants are a common solution used today to replace missing teeth. However current designs still suffer from a number of limitations. Angled abutments are used for incisors, where maximum human bite forces are normally < 200N, while straight abutments are used for molars subjected to higher forces > 200 N. The aim of this study was to evaluate the mechanical performance of a novel dental implant system by fatigue testing straight and 15-degree angled abutments. It was hypothesized that the novel thread design will dissipate the load evenly throughout the implant allowing the system to withstand normal chewing forces. Implants with 4.2mm diameter were tested according to ISO 14801 in specimen …

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Francisella Tularensis Lvs Invasion Of Primary Murine Macrophages And Mtor Signaling, Michael Warren Edwards Jan 2014

Francisella Tularensis Lvs Invasion Of Primary Murine Macrophages And Mtor Signaling, Michael Warren Edwards

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Francisella tularensis is an intracellular pathogen and the etiologic agent of tularemia. Because virulent strains cause morbidity and lethality in human, the attenuated live vaccine strain (LVS) has been used to study F. tularensis pathogenesis in murine models, since the disease in mice resembles human tularemia. Despite growing knowledge about host responses to Francisella infection, there is scarce information on the cell signaling events involved in Francisella host cell entry and in early immune re-sponses. Therefore, the purpose of this dissertation was to assess the involvement of the mammalian target of rapamycin (mTOR) in these processes. First, we evaluated the …

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