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The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta Jan 2012

The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta

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Several studies have established the importance of epigenetic regulation of gene transcription in the brain during memory consolidation. Epigenetic mechanisms involve modifying the DNA or the associated histone proteins to determine the transcriptional outcome of a gene. The work encompassed in this dissertation serves as an initial investigation for the role of histone lysine methylation mechanisms in regulating gene activation and suppression in the medial temporal lobe that includes entorhinal cortex (EC), hippocampus, and amygdala during memory consolidation. To this end, we found that di-methylation of histone H3 at lysine 9 (H3K9me2) which promotes gene suppression was specific to associative …


The Effects Of Psychological Stress, Depressive Symptoms, And Cortisol On Body Mass And Central Adiposity In 10-To12-Year-Old Children, Hong-Thuy Lam Jan 2012

The Effects Of Psychological Stress, Depressive Symptoms, And Cortisol On Body Mass And Central Adiposity In 10-To12-Year-Old Children, Hong-Thuy Lam

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The percentage of children with elevated body mass and central adiposity has tripled in the U.S. over the past thirty years. While physical factors, such as decreased physical activity and poor nutrition, have been noted to influence elevated body mass and central adiposity in school-aged children, less is known about psychological factors, such as psychological stress and depressive symptoms, especially in 10-to12-year-old children. Further, it has been suggested that cortisol, a biomarker of psychological stress, plays a role in the underlying mechanism that links psychological stress and depressive symptoms to increased body mass and central adiposity, but this has not …


The Influence Of Growth Factors Applied During Socket Conversion, On The Incidence Of Spontaneous Early Dental Implant Exposure, Michael Anh Minh Nguyen Jan 2012

The Influence Of Growth Factors Applied During Socket Conversion, On The Incidence Of Spontaneous Early Dental Implant Exposure, Michael Anh Minh Nguyen

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Spontaneous early exposure of a dental implant's cover screw can result in a nidus for plaque accumulation, which may result in inflammation, damage to the peri-implant mucosa, and possible peri-implant bone loss. This study aims to investigate the effect of the addition of growth factors, specifically recombinant human platelet-derived growth factor, and platelet-rich plasma, at the time of socket conversion, on the incidence of early implant exposures. This retrospective study utilized data from a study involving a total of 80 implants that were placed in 4 different types of sites (Groups 1,2,3, and 4). Group 1 sites were extraction sites …


Association Between Cc Chemokine Ligand 3-Like-1 (Ccl3l1) Gene Copy Number And Rheumatoid Arthritis In African Americans, Mawuli Kwame Nyaku Jan 2012

Association Between Cc Chemokine Ligand 3-Like-1 (Ccl3l1) Gene Copy Number And Rheumatoid Arthritis In African Americans, Mawuli Kwame Nyaku

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Gene copy number of the CC Chemokine ligand 3-Like-1 (CCL3L1) located on chromosome 17 position q12 varies between ethnicities. Previously, gene copy number of CCL3L1 greater than the ethnic median copy has been associated with an increased risk of Rheumatoid Arthritis. Three later studies found no association between CCL3L1 and RA. All studies were conducted in non-African Americans and an objective of this study was to determine this association in an African American cohort. CCL3L1 shares significant homology with three other genes within the same cluster; CC Chemokine ligand 3 (CCL3), CC Chemokine ligand 3-Like-2 (CCL3L2) and CC Chemokine ligand …


Soy And Breast Cancer, Mandeep K. Virk-Baker Jan 2012

Soy And Breast Cancer, Mandeep K. Virk-Baker

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The incidence of breast cancer is lower in Asia as compared to Western countries. However, the breast cancer risk among Asian immigrants living in Western countries reaches nearly as high as the Western country, suggesting environmental factors (e.g. diet and lifestyle) may be important for this geographical disparity. One dietary change of Asian immigrants is a reduction in soy consumption. Soy is rich in isoflavones, which compete with estrogen for receptor (ER) binding, and may protect against breast cancer. S-(-)equol, a metabolite of the soy isoflavone daidzein (DZ) has a higher bioavailability and greater affinity for ER than DZ. The …


The Hypometabolic Actions Of Hydrogen Sulfide In Mammalian Systems, Asaf Stein Jan 2012

The Hypometabolic Actions Of Hydrogen Sulfide In Mammalian Systems, Asaf Stein

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In recent years, hydrogen sulfide (H2S) has been identified as a ubiquitous cell signaling molecule. In addition to its diverse physiological roles, H2S has emerged as a possible drug therapy, with a wide range of applications. Along with cytoprotective effects in pathological states such as ischemia-reperfusion injury, H2S has been shown to decrease aerobic metabolism in a reversible manner. This dissertation is focused on exploring H2S-induced hypometabolism and the implications therein for human health and disease. We have shown that rats exposed to 80 ppm H2S gas in combination with low oxygen (10.5% O2) for 6 hr exhibit decreases in …


Modulation Of Autoimmune Diabetes By B Cells Specific For N-Acetyl-D-Glucosamine, Brian L. Dizon Jan 2012

Modulation Of Autoimmune Diabetes By B Cells Specific For N-Acetyl-D-Glucosamine, Brian L. Dizon

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Type I diabetes (T1D) is an autoimmune disease in which ß cells are destroyed by the immune system; however, role of infections in type I diabetes (T1D) pathogenesis is unclear. Reports suggesting that childhood Group A Streptococcal (GAS) infections protected against T1D prompted us to study how antibodies to N-acetyl-D-glucosamine (GlcNAc), which are induced by GAS infection, influenced T1D development. We found that GlcNAc-specific antibodies reacted with ß cell secretory granules, and neonatal NOD mice immunized with GAS or given GAS-immune sera were protected from spontaneous diabetes. Monoclonal GlcNAc-specific IgM blocked activation and effector responses to islet antigens by diabetogenic …


Adaptation To A Simulated Central Scotoma With Visual Search Tasks, Dave Walsh Jan 2012

Adaptation To A Simulated Central Scotoma With Visual Search Tasks, Dave Walsh

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This study characterized the perceptual and oculomotor adaptation to a simulated central scotoma in normally-sighted subjects and characterized the effects of two different scotoma profiles on the adaptation process. Twelve normally-sighted subjects, 6 for each type of scotoma profile, prac-ticed a search task (finding an "O" target among "C" distracters) for 11 blocks (162 trials per block). Search reaction time (RT) and eye movement data were collected. A head-mounted eye tracker was used to simulate two 10 deg circular central scotomas (CS), one with a sharp change from seeing to unseeing (S-CS) and the other with a gradual transition (G-CS). …


Suppression Of A Nonsense Mutation In A Mouse Model Of Hurler Syndrome, Dan Wang Jan 2012

Suppression Of A Nonsense Mutation In A Mouse Model Of Hurler Syndrome, Dan Wang

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Nonsense suppression therapy utilizes compounds that suppress translation termination at disease-causing premature termination codons (PTCs) to restore full-length, functional protein synthesis. This approach may provide a treatment for many diseases caused by nonsense mutations including Hurler syndrome (mucopolysaccharidosis type I - Hurler, MPS I-H). MPS I-H is a lysosomal storage disease caused by severe &alpha-L-iduronidase deficiency and subsequent lysosomal glycosaminoglycan (GAG) accumulation. In this work, we investigated the effectiveness of nonsense suppression therapy as a treatment for MPS I-H. We first generated a targeted knock-in mouse model that carries the Idua-W392X nonsense mutation homologous to the human IDUA-W402X mutation frequently …


Siderophore-Mediated Iron Acquisition In Mycobacterium Tuberculosis, Ryan Wells Jan 2012

Siderophore-Mediated Iron Acquisition In Mycobacterium Tuberculosis, Ryan Wells

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Mycobacterium tuberculosis is a dangerous human pathogen that has the capacity to adapt to and survive within the harsh phagosomal environment of macrophages. One obstacle that must be overcome by pathogens is to acquire iron, an essential component and cofactor of proteins required for vital cellular processes. M. tuberculosis meets its iron demands in the face of an array of sequestration strategies of the host by synthesizing and secreting two siderophores called mycobactin and carboxymycobactin. Siderophores are low molecular weight high affinity iron binding compounds that steal iron away from host stores and have been shown to be important for …


Fcrl5 Exerts Binary And Compartment-Specific Influence On Innate-Like B Cell Receptor Signaling, Zilu Zhu Jan 2012

Fcrl5 Exerts Binary And Compartment-Specific Influence On Innate-Like B Cell Receptor Signaling, Zilu Zhu

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Innate-like splenic marginal zone (MZ) and peritoneal cavity (PEC)-derived B1 B lymphocytes are the major contributors to primary humoral responses and play an important role in connecting innate and adaptive immunity, but are known to significantly differ in their B cell receptor (BCR) signaling characteristics. In mice, FCRL5 is discretely expressed by innate-like MZ and B1 B cells and is furthermore equipped with cytoplasmic ITAM-like and ITIM elements, suggesting diverse signaling potential for it. Our results showed that FCRL5 markedly inhibited BCR-mediated activation in MZ B cells, but not in PEC B1 B cells. To characterize its signaling function, a …


A Role Of Angiogenin In Models Of Parkinson's Disease, Trent Steidinger Jan 2012

A Role Of Angiogenin In Models Of Parkinson's Disease, Trent Steidinger

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Parkinson's Disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Gene multiplication of alpha-synuclein causes an autosomal dominant inheritance pattern of PD. A mouse model overexpressing alpha-synuclein demonstrates some of the phenotype seen in PD. In a microarray of these mice, a downregulation of angiogenin was observed prior to symptom onset, demonstrating a potential link of angiogenin to pathology in this model. Angiogenin has also been associated with the onset of Amyotrophic Lateral Sclerosis (ALS), and is neuroprotective in models of ALS through activation of the Akt …


Electrophysiological Investigation Of Rabbit Retinal Ganglion Cells, Przemyslaw Nowak Jan 2012

Electrophysiological Investigation Of Rabbit Retinal Ganglion Cells, Przemyslaw Nowak

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The retina is the first stage of the visual system, responsible for transducing light into the neural signal and for subsequent processing of this signal before sending it to the higher visual centers in the brain. The output to the higher visual centers is mediated by retinal ganglion cells, which not only relay the signal, but also substantially contribute to its processing. Depending on what computations they perform, they are subdivided into different types. These cells have been extensively studied in various spices, one prominent example being the rabbit. In rabbits, one characteristic type comprises On-Off directionally selective retinal ganglion …


The Antecedents And Consequences Of Public Hospital Privatization, Zo Harivololona Ramamonjiarivelo Jan 2012

The Antecedents And Consequences Of Public Hospital Privatization, Zo Harivololona Ramamonjiarivelo

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ABSTRACT The purpose of this study was to explore the antecedents and consequences of public hospital privatization with special attention to financial distress and financial performance. A national sample of public hospitals using secondary longitudinal data from 1997 to 2009 was used in this study. Data set from the American Hospital Association, the Area Resource File, the Medicare Cost Report and the Local Area Unemployment Statistics were merged to test the hypotheses pertaining to each research question. Based on the resource dependence theory, both environmental variables and organizational variables were included in the analyses. This study adopted the Altman Z-score …


Molar Distalization To Resolve Class Ii Malocclusion: A Cephalometric Study Utilizing The Carriere Distalizer, Careybeth Hayes Rivers Jan 2012

Molar Distalization To Resolve Class Ii Malocclusion: A Cephalometric Study Utilizing The Carriere Distalizer, Careybeth Hayes Rivers

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Objective: The purpose of this study is to determine the short-term skeletal and dental effects that occur as a result of Class II malocclusion correction utilizing the Carrière Distalizer as compared to best-matched controls. Methods: This is a retrospective cohort cephalometric study using lateral cephalometric films of 25 (14 male, 11 female, average age 13y 6m) class II patients consecutively treated with the Carrière Distalizer compared with 36 (19 male, 17 female, 13y 2m) untreated class II control subjects from a historical database best-matched based upon age, sex and skeletal classifications. Pretreatment and posttreatment lateral head films were analyzed with …


Effect Of Different Percentages Of Silica Nanofibers Filler Loads On Mechanical And Physical Properties Of Flowable And Hybrid Composite Resins, Qinyue Cai Jan 2012

Effect Of Different Percentages Of Silica Nanofibers Filler Loads On Mechanical And Physical Properties Of Flowable And Hybrid Composite Resins, Qinyue Cai

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Dental composites are used for a variety of applications in dentistry today. Dental composites are composed of a resin matrix containing a blend of Bis-GMA (bis-phenol A-glycidyldimethacrylate) or urethane dimethacrylate (UDMA) along with TEGDMA (tetraethylglycidylmethacrylate). Exhaustive researches has been conducted in recent years to improve physical and mechanical properties of resin-based dental composites, since the existing resin-filler systems may not be suitable for long term applications in large as well as high stress restorations. Nanofillers reinforced composite resins have shown promising results. Silica-based nanoparticles and clusters are blended with larger-sized fillers and are available commercially for restoring large posterior restorations. …


Effects Of Stress On Growth Hormone Receptor Signaling, Ryan Marshall Corrick Jan 2012

Effects Of Stress On Growth Hormone Receptor Signaling, Ryan Marshall Corrick

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Growth hormone (GH) regulates body composition via stimulation of protein synthesis and catabolism of adipose tissue, generally promoting maintenance of lean body mass. Following severe injury, GH resistance contributes to muscle protein wasting, adversely impacting morbidity and mortality. In this dissertation research, we sought to determine the mechanisms of GH resistance following injury. To accomplish this, we evaluated GH signaling in a mouse model of severe injury. In the first section of this thesis, we demonstrate severe impairments in hepatic GH signaling occurring in association with an apparent, hemorrhage-dependent cleavage of the GH receptor (GHR). In the second section, we …


Modulation Of Wzy-Dependent Capsule Production In Streptococcus Pneumoniae By The Phosphotyrosine-Specific Phosphatase Cpsb, Kimball Aaron Geno Jan 2012

Modulation Of Wzy-Dependent Capsule Production In Streptococcus Pneumoniae By The Phosphotyrosine-Specific Phosphatase Cpsb, Kimball Aaron Geno

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Biosynthesis of capsule polysaccharide in the Gram-positive pathogen Streptococcus pneumoniae is regulated in part through the action of a phosphoregulatory system comprised of the products of the capsule biosynthetic operon genes cpsBCD. CpsC and CpsD together comprise an autophosphorylating tyrosine kinase whose homologs are implicated in chain length regulation in other systems in both Gram-positive and Gram-negative organisms. CpsB is the cognate phosphatase for the system. Unlike Gram-negative organisms, which use a low molecular weight phosphotyrosine phosphatase in phosphoregulation of capsule synthesis, Gram-positive organisms utilize a polymerase and histidinol phosphatase (PHP) superfamily phosphatase. Deletion of cpsB has resulted in conflicting …


Career Satisfaction Of Physicians Employed By Health Systems, Edward L. Heath Jan 2012

Career Satisfaction Of Physicians Employed By Health Systems, Edward L. Heath

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CAREER SATISFACTION OF PHYSICIANS EMPLOYED BY HEALTH SYSTEMS EDWARD L HEATH, JR ADMINISTRATION-HEALTH SERVICES ABSTRACT Background:Higher career satisfaction has been shown to result in better patient outcomes, higher patient satisfaction and less turnover among physicians. The purpose of this study is to examine the relationship between physician employment and career satisfaction. Methods:Data from the Center for Studying Health System Change (HSC) 2008 Health Tracking Physician Survey was used in the study. The study is a cross sectional, quantitative study of the relationship between physician employment and career satisfaction. A total of 4,720 respondents responded to the survey, with a weighted …


Diagnostic Classifications For Bipedal Locomotion, Lois Deming Hedman Jan 2012

Diagnostic Classifications For Bipedal Locomotion, Lois Deming Hedman

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Background: Analysis of and intervention for movement dysfunction, especially walking dysfunction, is the central expertise of physical therapists (PTs). PTs are called to establish a diagnosis prior to making patient management decisions yet no valid classification system for walking exists. Objectives: The purpose of this study was to determine if locomotor experts could arrive at consensus on the validity, mutual exclusivity and understandability of diagnostic classifications for bipedal locomotion. Methods: An electronic mail Delphi survey methodology was utilized. Experts were recruited purposefully through research and clinical leaders in the PT profession. Identified experts were then asked for their recommendations in …


Histomorphometry And Quantitative Analysis Of Longer-Term Implant Interfaces, Dave Darko Kojic Jan 2012

Histomorphometry And Quantitative Analysis Of Longer-Term Implant Interfaces, Dave Darko Kojic

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Objective: This investigation was to evaluate (>10 year) bone response around custom (HA plasma coated) dental implants and HA particulate. Materials and Methods: Three individual post mortem mandibular COI Implants with surrounding bone were processed at six transverse locations to obtain non-decalcified ground sections (20-80µm)(n=36) and stained initially with methylene blue/basic fuchsin. Slides were evaluated to select (n= 8) slides for regions of interest along the perimeter of the implant, using optical microscopy (Olympus BX51 microscope) with a Retiga EXi color digital camera (Olympus, Center Valley, PA) and Bioquant VR software (R&M Biometrics, Nashville, TN) at an original magnification …


Finding A Cure For Venezuelan Equine Encephalitis Virus (Veev) Infection: The Search For The Antiviral Genes And Vaccine Development., Svetlana Atasheva Jan 2012

Finding A Cure For Venezuelan Equine Encephalitis Virus (Veev) Infection: The Search For The Antiviral Genes And Vaccine Development., Svetlana Atasheva

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Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus that causes a severe and often fatal disease in equids and humans. To date, despite a continuous public health threat, no vaccines or antiviral drugs against VEEV infection have been developed for human use. In this study we took advantage of accumulated knowledge of capsid protein function in viral replication, assembly and virus-host interactions. Besides being an integral part of the virion, capsid protein is the major determinant of VEEV pathogenesis. This protein is cytotoxic and induces cellular transcriptional shutoff as a countermeasure to the cellular antiviral response. We introduced targeted …


Characterizing The Transcriptional Complexity Of Pkhd1/Pkhd1, Ravindra Boddu Jan 2012

Characterizing The Transcriptional Complexity Of Pkhd1/Pkhd1, Ravindra Boddu

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Mutations in PKHD1 gene cause autosomal recessive polycystic kidney disease. Our previous studies have shown that human PKHD1 and its mouse orthologue, Pkhd1, undergo an extensive pattern of alternative splicing. Pkhd1 is primarily expressed in renal and biliary tubular structures. Translation products of these alternative spliced transcripts are predicted to generate isoforms expressed in plasma membrane, primary cilium and cytoplasm. We have characterized the cyli mouse model of ARPKD and identified a frameshift mutation, c.7589delGGinsT, in Pkhd1 exon 48. In this thesis we have characterized the mouse Pkhd1cyli/cyli model (liver restricted phenotype) and evaluated the transcriptome in terms of alternative …


Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson Jan 2012

Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson

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Pneumonia caused by the fungal pathogen Pneumocystis continues to be the leading cause of morbidity and mortality in AIDS patients. In addition, there are a number of other non-HIV-associated diseases that render an individual susceptible to Pneumocystis infection, including chronic obstructive pulmonary disease. Innate immune mechanisms are important for controlling Pneumocystis lung infection. As alveolar macrophages serve the front lines of lung host defense, our goal was to elucidate their responses during lung Pneumocystis infection. Here, we established a role for Src family kinases in the lung immune response to Pneumocystis, which uncovered a role for alternatively activated alveolar macrophages. …


Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily Jan 2012

Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily

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TARGETING MITOCHONDRIAL FUNCTION IN DIABETIC NEPHROPATHY The incidence of diabetes has increased to epidemic proportions over the last 50 years, due to a complex interaction of lifestyle and dietary factors. Changes in physical activity, caloric intake, and the composition of foods consumed over the last century are thought to interact with metabolic syndrome prone subpopulations leading ultimately to diabetes. It is widely accepted that chronic hyperglycemia in the blood characterizes the diabetic condition. Since the discovery of insulin therapy in the first half of the 20th century, diabetics have extended their lifespan considerably, but at the cost of increased morbitity …


Stress And Job Performance: The Roles Of Salivary Cortisol And Social Support, Tracy Shamburger Jan 2012

Stress And Job Performance: The Roles Of Salivary Cortisol And Social Support, Tracy Shamburger

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Perceived stress may negatively affect job performance. Perceived stress is known to alter physiological responses, including cortisol response. Cortisol affects working memory and may explain how stress affects performance. Aeromedical crewmembers transport wounded soldiers in the austere aeromedical environment. The demands of the Aeromedical Evacuation (AE) may lead to stress and impact job performance. The AE training mission simulates real world operational missions and this setting was used to examine the effects of perceived stress on job performance among aeromedical crewmembers at different time points during the mission (Time 1- baseline, Time 2 - pre-flight, Time 3 - in-flight, Time …


The Role Of St6gal-I Sialylation In Fas (Cd95) Death Receptor Function And Tumorigenesis, Amanda F. Swindall Jan 2012

The Role Of St6gal-I Sialylation In Fas (Cd95) Death Receptor Function And Tumorigenesis, Amanda F. Swindall

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The golgi glycosyltransferase, ST6Gal-I, adds a negatively-charged sialic acid in an alpha-2-6 linkage to N-linked glycans. ST6Gal-I is upregulated in many cancers, and is associated with increased metastasis and poor patient prognosis. ST6Gal-I expression has been shown to be driven by oncogenic-ras signaling. However, mechanistic details of the role ST6Gal-I plays in tumor initiation and progression are not well defined. Historically, studies have focused on contributions of ST6Gal-I to the malignant cell phenotypes of migration and invasion. Emerging evidence including studies contained in this dissertation have begun to elucidate a role for ST6Gal-I as a regulator of apoptotic signaling by …


Three Dimensional Comparison Of Facial Morphology Of A Caucasian American Population And A Native Brazilian Population, William N. Turner Jan 2012

Three Dimensional Comparison Of Facial Morphology Of A Caucasian American Population And A Native Brazilian Population, William N. Turner

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The aim of this study was to assess the use of 3-dimensional facial averages in determining facial morphologic differences in a Caucasian North American population and a native Brazilian population. Methods and Materials: Three-dimensional images were acquired through a commercially available stereo-photogrammetric camera system (The 3dMDfaceTM system). A total of 200 images from two population groups (Caucasian American and Native Brazilian) were taken. Each image was acquired as a facial mesh and orientated along a triangulated axis. All facial images were overlaid and superimposed, using Rapid Form 6 software to create a composite facial average of one man and one …


Schizophrenia And Vergence Eye Movements, Mark S. Bolding Jan 2012

Schizophrenia And Vergence Eye Movements, Mark S. Bolding

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Background: Compared to healthy controls (HC), patients with schizophrenia (SZ) have lower smooth pursuit gain and have been reported as having a higher prevalence of convergence insufficiency. To date, however, there have been no reports on vergence tracking gain in such patients. Therefore, we investigated both static and dynamic vergence behavior in healthy controls and patients with schizophrenia. Methods: Eye movements were recorded in multiple tasks including antisaccades, triangular waveform smooth pursuit at multiple frequencies, and triangular waveform vergence tracking of a real target at multiple frequencies. Eye position data were collected at 500 Hz using a binocular video eye …


Mycobacterial Iron Acquisition Systems, Christopher M. Jones Jan 2012

Mycobacterial Iron Acquisition Systems, Christopher M. Jones

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Iron is an essential nutrient for the vast majority of organisms; yet, the availability of iron is limited to microorganisms due to the insolubility of ferric hydroxides and to pathogens by iron withholding strategies of their hosts. Many bacteria produce small, high-affinity iron chelators called siderophores to scavenge iron from the environment. In addition, many bacterial pathogens have evolved mechanisms to steal host iron contained in heme, hemoglobin, or transferrin. Mycobacteria are unique genera of bacteria represented by the notorious pathogens Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis (TB) and leprosy, respectively. Tuberculosis remains a global health …