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2007

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A Role For P63 In The Regulati On Of Cell Cycle Progression And Cell Death, Eric Scott Helton Jan 2007

A Role For P63 In The Regulati On Of Cell Cycle Progression And Cell Death, Eric Scott Helton

All ETDs from UAB

p63 is a member of the p53 family of transcription factors that is a critical regulator of epithelial development. Studies have shown that p63 does not appear to function as a classical tumor suppressor like p53. Instead, the expression pattern of p63 in cancers suggests that p63 retains the potential to function as either a tumor suppressor or an onco-protein. Here, we provide evidence describing the transcriptional activity of the p63 isoforms and provide mechanisms whereby p63 function is regulated in a context dependent manner. Our data shows that both the ΔNp63 and TAp63 variants retain the potential to regulate …

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Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper Jan 2007

Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper

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Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the …

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Characterization Of A Global Regulatory Pathway In Streptococcus Pneumoniae, Greer E. Kaufman Jan 2007

Characterization Of A Global Regulatory Pathway In Streptococcus Pneumoniae, Greer E. Kaufman

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Streptococcus pneumoniae is a versatile organism that adapts to many different environments in the host. S. pneumoniae can asymptomatically colonize the nasopharynx of humans. However, dissemination of the bacterium from the nasopharynx to different locations in the body can lead to invasive diseases such as pneumonia, bacteremia, and meningitis. How S. pneumoniae modulates factors that are important for survival in these niches has not been well characterized. In the studies described here, we propose that S. pneumoniae may modulate gene expression in these niches by sensing the different glu-cose concentrations via carbon catabolite control protein A (CcpA). Initially we characterized …

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Mcmv Induced Cerebellar Maldevelopment, Thadeus B. Koontz Jan 2007

Mcmv Induced Cerebellar Maldevelopment, Thadeus B. Koontz

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Congenital Human Cytomegalovirus (HCMV) infection represents a significant cause of morbidity and mortality in infants and children. While most of the systemic damage incurred by the infant in the course of the infection resolves without permanent consequence, the pathological manifestations of infection in the central nervous system (CNS) are often permanent. Children born with congenital HCMV infection may exhibit hearing loss and cognitive impairment in various degrees. These neurological disabilities are correlated with pathological findings in various permutations including infection of the inner ear, ventricular calcifications, ventriculomegaly, microgyria, lissencephaly, and cerebellar hypoplasia. To develop a therapeutic or preventive strategy, HCMV …

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Kainate Receptor Modulation Of Synaptic Transmission In Neocortex, Seena S. Mathew Jan 2007

Kainate Receptor Modulation Of Synaptic Transmission In Neocortex, Seena S. Mathew

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The actions of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) are tightly regulated to ensure effective information processing as well as prevention of excess excitatory activity, which can lead to seizures and neurological disorders such as epilepsy. Drugs which enhance the effects of GABA are used as anesthetics, sedatives and anticonvulsants. Using whole-cell patch clamp recordings from neocortical neurons, we examined the mechanisms of GABAergic modulation that occur when kainate receptors (KARs) are activated. First, we address a novel signaling mechanism for the KAR-mediated facilitation of GABAergic synaptic transmission. Our first observation involved the presence of presynaptic KARs located on the …

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Primer Selection Of E. Coli Trna Lys,3 By Human Immunodeficiency Virus Type-1, Anna Mcculley Jan 2007

Primer Selection Of E. Coli Trna Lys,3 By Human Immunodeficiency Virus Type-1, Anna Mcculley

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Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS). HIV replication includes the notable process of reverse transcription, a conversion of RNA to DNA. Reverse transcription is initiated from a primer by a viral enzyme, reverse transcriptase. The primer, tRNALys,3, is selected from the cytoplasm of an infected cell, annealed via the 3’ terminal 18-nucleotides to the viral primer binding site (PBS), and used in a subsequent infection. The mechanism of primer selection has not been determined although numerous studies have been performed. This has been hampered by the challenge of tRNALys,3 manipulation in the cell and …

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Sperm Production And Vitellogenesis As Biomarkers Of Endocrine Disruption In The Male Western Mosquitofish, Gambusia Affinis, Paul D. Melvin Jan 2007

Sperm Production And Vitellogenesis As Biomarkers Of Endocrine Disruption In The Male Western Mosquitofish, Gambusia Affinis, Paul D. Melvin

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Estrogenic compounds of anthropogenic origin enter the environment from several different sources, including domestic wastewater and agricultural runoff. Natural estrogens, synthetic estrogens, and estrogen breakdown products have been identified in wastewater treatment plant (WWTP) effluents. These compounds have direct and indirect effects on the endocrine systems of organisms living in the receiving waters. Male mosquitofish (Gambusia affinis) have been suggested as model bioindicator organisms for endocrine disruption by estrogenic compounds for a variety of reasons, including their hardiness, broad environmental tolerances (including temperature, salinity, and dissolved oxygen), widespread geographical distribution, and ease of use in the laboratory. We examined two …

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Directing Akt And Gsk3ss: Molecular Insights Into Cell Signaling And Survival, Gordon P. Meares Jan 2007

Directing Akt And Gsk3ss: Molecular Insights Into Cell Signaling And Survival, Gordon P. Meares

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Proper regulation of survival signaling is critical for all organisms. One important signaling cascade involved in the coordinated effort to control signals influencing cell fate is the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3β (GSK3β) signaling cascade. Following activation by growth factors the PI3K-Akt pathway promotes cell survival and, cell death is facilitated following inhibition of Akt. Many factors influence the function of the Akt-GSK3β signaling dyad, including phosphorylation, protein complex formation and subcellular localization. Previous work had demonstrated that the 90kDa heat shock protein, HSP90, directly binds and stabilizes Akt. Furthermore, several heat shock proteins including HSP90 and HSP105 can …

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Multiple Roles: Benefits Or Strain? An Examination Of The Effects Of Work And Mothering On Health Lifestyle Behaviors For Women Living With Hiv/Aids, Mercy W. Mwaria Jan 2007

Multiple Roles: Benefits Or Strain? An Examination Of The Effects Of Work And Mothering On Health Lifestyle Behaviors For Women Living With Hiv/Aids, Mercy W. Mwaria

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Does occupying multiple roles cause strain or does it lead to health lifestyle practices for women living with HIV/AIDS? Previous research has established a relationship between multiple role occupation and physical and mental wellbeing for women. Health lifestyle modifications for persons living with HIV/AIDS benefit health by slowing down disease progression and enhancing the body’s tolerance to drug therapies. This study extends these findings to a specific population of women living with HIV/AIDS and examines health lifestyle outcomes for this population. Using data from the HIV Cost and Services Utilization Study (HCSUS), the study draws on a subsample of women …

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Retinal Pigment Epithelial Cells And The Insulin-Like Growth Factor System In Proliferative Vitreoretinopathy, Sudipto Mukherjee Jan 2007

Retinal Pigment Epithelial Cells And The Insulin-Like Growth Factor System In Proliferative Vitreoretinopathy, Sudipto Mukherjee

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The goal of this study was to determine the influence, if any, of the insulin-like growth factors (IGFs) on retinal pigment epithelial (RPE) cell tractional force generation and the contributions of vitreous insulin-like growth factor binding proteins (IGFBPs) towards control of IGF activity. Another objective was to evaluate RPE cells as a potential source of all six high-affinity IGFBPs and to determine if IGFBP biosynthesis is modulated in concert with phenotype changes and growth factor stimuli known to be present in disease. RPE generate tractional forces in response to IGF-I and -II with IGF-I being the more potent stimulus. Differential …

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Delayed Childbearing, Pregnancy Spacing And Impact On Subsequent Pregnancy Outcomes: Missouri Resident Mothers 1978-1997, Sarah K. Nabukera Jan 2007

Delayed Childbearing, Pregnancy Spacing And Impact On Subsequent Pregnancy Outcomes: Missouri Resident Mothers 1978-1997, Sarah K. Nabukera

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Introduction The main objective of the study was to examine reproductive health issues among women delaying initiation of childbearing until age 30 or older. Specifically, it examined pregnancy spacing patterns, relationship between pregnancy spacing and subsequent perinatal outcomes as well as racial differences in spacing and adverse perinatal outcomes. Methods A retrospective cohort study was conducted using the Missouri maternally linked live birth, fetal death and infant death files 1978-1997. The study sample was limited to mothers residing in Missouri during the study period, having first pregnancy at age 20-50 years, as well as a subsequent second pregnancy. Final study …

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The Function Of Hiv-1 A-Loop On Primer Selection, Na Ni Jan 2007

The Function Of Hiv-1 A-Loop On Primer Selection, Na Ni

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Reverse transcription is the hallmark of retroviruses, such as HIV-1. A cellular tRNA bound to the primer binding site region (PBS) is used for initiation of reverse transcription. HIV-1 specially selects tRNALys3 as primer, although changing the PBS can force HIV-1 to use alternative tRNAs as a primer. However, HIV-1 reverts back to use tRNALys3 following in vitro replication. The A-loop, located upstream of PBS, interacts with the anti-codon of primer tRNA. The inclusion of A-loop modification has been shown to stabilize the utilization of some alternative tRNAs. The studies in this dissertation focus on further defining the role of …

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Association Between The Exposure To Aflatoxin And Micronutrient Status Of Hiv Infected Adults In Ghana, Francis Ayodele Obuseh Jan 2007

Association Between The Exposure To Aflatoxin And Micronutrient Status Of Hiv Infected Adults In Ghana, Francis Ayodele Obuseh

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Aflatoxins, found naturally in some foods are toxic metabolites of some Aspergillus species.They constitute the most potent hepatocarcinogens known and are also mutagenic and hepatotoxic. The preponderance of evidence indicates that aflatoxin is the major cause of hepatocellular cancer. In studies conducted in Africa, food-borne aflatoxin exposure is common (Oyelami et al. 1996; Egal et al. 2005). There is a critical need for additional information on health outcomes associated with exposure to aflatoxin in humans, especially in developing countries with a higher degree of malnutrition and likelihood of HIV infections. We sought to test the hypothesis that aflatoxin B1 and …

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Temperament, Sensation-Seeking, Sleep Patterns, And Alcohol Use During A Competitive Athletic Season: Predicting Injuries In College Athletes, Zachary H. Osborn Jan 2007

Temperament, Sensation-Seeking, Sleep Patterns, And Alcohol Use During A Competitive Athletic Season: Predicting Injuries In College Athletes, Zachary H. Osborn

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Temperament, sensation-seeking, general personality variables, sleep patterns, and alcohol use have all been shown to be related to injuries in both community-based and athlete samples. However, these variables have not been studied in concert with one another to examine how they might interact to predict injuries. One-hundred and seventy-eight athletes (both football and soccer) completed pre-season alcohol use and sleep pattern questionnaires, as well as personality measures. The results indicated that playing football predicted more total injuries. No other personality, sleep, or alcohol use variables were predictive of injuries or injury related variables. Analyses also indicated that football players suffered …

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Regulation Of Vertebrate Gastrulation By Erbb Signaling, Shuyi Nie Jan 2007

Regulation Of Vertebrate Gastrulation By Erbb Signaling, Shuyi Nie

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ErbB receptor tyrosine kinases have long been implicated in cancer formation and progression by regulating cell division, migration, and survival. ErbBs are also essential in multiple processes during invertebrate development; however, their activities during vertebrate embryogenesis are not well understood. For functional characterization of ErbB signaling during vertebrate development, frog model Xenopus laevis was used in our studies. The expression pattern and the general activities of ErbB receptors during early frog development were first analyzed and results shown that ErbBs regulate gastrulation, somite organization and head patterning. As gastrulation is the first major morphogenetic event in vertebrate development, I focused …

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Surveying The Chromosomal Supercoiling Levels In Rapidly Growing Wild Type And Gyrase Mutant Strains Of Salmonella Enterica Serovar Typhimurium With Γδ Resolvase-Mediated Recombination Assay, Zhenhua Pang Jan 2007

Surveying The Chromosomal Supercoiling Levels In Rapidly Growing Wild Type And Gyrase Mutant Strains Of Salmonella Enterica Serovar Typhimurium With Γδ Resolvase-Mediated Recombination Assay, Zhenhua Pang

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A gyrase mutant strain (gyrB652) has severe growth defect at 42°C. The survival at high temperature is dependent on DNA repair proteins. The purified mutant gyrase was assayed for supercoiling acitivity and quinolone-induced DNA cleavage activity. The results suggested that the mutant enzyme is not temperature-sensitive, but has slower kinetics than the wild type gyrase. The DNA supercoiling levels at multiple chromosomal loci in exponential phase cells were monitored with γδ resolvase-mediated recombination assay. The wild type cells showed homogenous supercoiling levels throughout most of the chromosome. But the superhelicity at dif locus was significantly lower than the other loci. …

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Insulin Dynamics In African Americans And European Americans: Mechanistic Aspects, And Association With Inflammation, Radhika P. Phadke Jan 2007

Insulin Dynamics In African Americans And European Americans: Mechanistic Aspects, And Association With Inflammation, Radhika P. Phadke

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Identification and characterization of ethnic differences in insulin dynamics, insulin sensitivity (SI), and inflammation may shed light on the greater risk for type 2 diabetes in African Americans (AA), relative to European Americans (EA). Ideally, such studies should take into account the potential confounding roles of adiposity, fat distribution, genetic background, and socioeconomic status (SES). The objectives of this study were, 1) to evaluate ethnic differences in insulin dynamics in AA and EA children and adults using robust measures of insulin secretion and clearance; 2) to identify the contributions of genetic admixture and SES to insulin dynamics; 3) to examine …

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Genetic And Epigenetic Modulation Of Telomerase Activity In Development And Disease, Sharla Marion Ostein Phipps Jan 2007

Genetic And Epigenetic Modulation Of Telomerase Activity In Development And Disease, Sharla Marion Ostein Phipps

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The end replication problem of linear chromosomes leads to the erosion of telomeric DNA with each cell division. A mechanism to counteract telomeric attrition involves the activity of the specialized ribonucleoprotein telomerase. Expression of the catalytic subunit of telomerase, hTERT, is tightly regulated and this regulation is achieved through both genetic and epigenetic mechanisms. Activators such as c- MYC and SP1 and repressors such as MAD1, Menin, and p53 mediate hTERT transcription. Epigenetic control mediated by DNA methylation and histone modifications such as methylation and acetylation can reversibly and potently regulate telomerase activity. Not only is there synergism between the …

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Enterprise Configuration Management In A Service-Oriented Architecture Environment Delivering It Services, Robert E. Raygan Jan 2007

Enterprise Configuration Management In A Service-Oriented Architecture Environment Delivering It Services, Robert E. Raygan

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Information Technology (IT) is a collaboration environment for business and engineering. The past decade has seen a reduction in business understanding of engineering principles because of the lack of trained engineers working in IT, while businesses have become increasingly dependent upon new and complex technologies. These new technologies, often still evolving, are system-of-systems environments and present significant challenges to early implementers. Service-Oriented Architecture (SOA) is one such system-of-systems that pushes the discipline of Software Configuration Management (SCM) beyond traditionally defined bounds. Evolving standards associated with SOA and the nature of SOA contribute to these challenges of governance and management: loose …

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Trafficking Of Hantaviral Nucleocapsid Proteins, Harish N. Ramanathan Jan 2007

Trafficking Of Hantaviral Nucleocapsid Proteins, Harish N. Ramanathan

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Hantaviruses are enveloped, negative-sense RNA viruses belonging to genus Hantavirus, within the family Bunyaviridae. Hantaviruses include many serious human pathogens and are classified as Old and New World based on the geographic distribution of rodent reservoirs and their ability to in induce distinct illnesses in humans. Currently there are no reservoirs known for hantaviruses other than the rodents. Human transmission of hantaviruses occurs via inhalation of aerosolized rodent excreta leading to hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Hantavirus genome consists of small (S), medium (M) and large (L) segments that encode nucleocapsid (N) protein, two …

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The Role Of Complement In Experimental Autoimmune Uveitis, Russell W. Read Jan 2007

The Role Of Complement In Experimental Autoimmune Uveitis, Russell W. Read

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The complement system has been increasingly implicated in the pathophysiology of autoimmune disease. Complement expression in the normal human eye had not been previously completely defined. We performed immunohistochemical studies for membrane complement proteins in normal human retina to provide a baseline for future studies. We found expression of the anaphylatoxin receptors, CD55, and CD59 in the inner retina and CD46 in a polarized fashion on the retinal pigment epithelium. Previous studies in uveitis have shown activated fragments of complement in human eyes with uveitis and animal models have shown an effect on disease by complement depletion with cobra venom …

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Development And Initial Validation Of A Self-Efficacy Scale For Use With Registered Dietitians Working With Overweight Youth, Christopher M. Reinold Jan 2007

Development And Initial Validation Of A Self-Efficacy Scale For Use With Registered Dietitians Working With Overweight Youth, Christopher M. Reinold

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This study developed and validated the Youth-Directed Obesity Counseling Self-efficacy (Y-DOCS) Scale to evaluate the self-efficacy of registered dietitians (RDs) working with childhood overweight. The specific purpose of this study was to create an evaluation instrument that can measure the effectiveness of continuing education (CE) that provides behavioral counseling training. Two research questions guided this investigation into measuring the self-efficacy of RD’s: (a) Is the Y-DOCS scale for dietitians a reliable instrument for assessing self-efficacy among dietitians who receive training? (b) Is the Y-DOCS scale for dietitians a valid instrument for assessing self-efficacy among dietitians who receive training? The population …

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Pathogenesis And Therapeutic Potential Of Plasmacytoid Dendritic Cells In Siv/Shiv-Infected Macaques, R Keith Reeves Jan 2007

Pathogenesis And Therapeutic Potential Of Plasmacytoid Dendritic Cells In Siv/Shiv-Infected Macaques, R Keith Reeves

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Plasmacytoid dendritic cells (pDCs) are among the first responders during acute viral infections and are the primary producers of IFN-α, a cytokine known to inhibit viral replication and to activate natural killer (NK) cells. In HIV patients pDCs are decreased in number, are dysfunctional, and can harbor HIV-1 proviruses. However, since the time of transmission is usually unknown, pDC-virus interactions immediately after exposure to HIV remain unclear. Using the SIV/SHIV-macaque model, we showed that an acute and sustained loss of blood pDCs occurred during SIVmac239 infections, and when compared to those from naïve controls, pDCs were also significantly reduced in …

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In Vivo Imaging Studies In Animal Models Of Myocardial Infarction With And Without Cell Injections, Balazs Ruzsics Jan 2007

In Vivo Imaging Studies In Animal Models Of Myocardial Infarction With And Without Cell Injections, Balazs Ruzsics

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After prolonged myocardial ischemia, myocardial infarction occurs. Several tissue changes are associated with myocardial infarction and iron labeled cell injections. In the present thesis our major aim was to develop methods to monitor these tissue changes with MRI and MDCT. In the first chapter we used transendocardial injection to deliver iron labeled allogen skeletal myoblasts one week after myocardial infarction. Our goal was to identify the cells and/or injection sites in the myocardium. We used our new Tissue Characterization Mapping method to delineate tissue edema and hemorrhage in the myocardium. The T2 weighted signal intensity enhancement, T2w SIE region was …

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Factors Influencing The Adoption Of Administrative Innovations, Tom J. Sanders Jan 2007

Factors Influencing The Adoption Of Administrative Innovations, Tom J. Sanders

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The purpose of this dissertation was to investigate the influence of selected environmental and organizational factors on the adoption of administrative innovations in order to better understand strategic adaptation by organizations. General systems theory, various organizational theories, strategic adaptation and management theories, and adoption and diffusion of innovation literature were used to develop a theoretical framework to address four primary and sixteen secondary hypotheses. The administrative innovation used for this study was the magnet hospital concept for enhancing attraction and retention of registered nurses in order to address a persistent workforce shortage in U.S. hospitals. Secondary data related to U.S. …

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Caste As A Determinant Of Utilization Of Maternal And Neonatal Healthcare Services In Maitha, Uttar Pradesh, India, Ekta Saroha Jan 2007

Caste As A Determinant Of Utilization Of Maternal And Neonatal Healthcare Services In Maitha, Uttar Pradesh, India, Ekta Saroha

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Caste among Hindus in India is a non-modifiable socio-demographic characteristic, often the basis of segregation and discrimination. Despite the provision of subsidized maternal and child healthcare services, utilization in rural Uttar Pradesh (UP), India is poor. Studies showed that upper caste (UC) women were more likely to utilize healthcare services than the lower caste (LC) women but this association is inadequately researched. We explored whether caste was a determinant of utilization of maternal healthcare (MH) and neonatal healthcare (NH) services among rural Hindu women and neonates in Maitha, UP, India. Data from the ‘Morbidity and Performance Assessment’ study for 482 …

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A Grounded Theory Study: Hispanic Adolescents' Experience Of Being Overweight, Wilma Powell Stuart Jan 2007

A Grounded Theory Study: Hispanic Adolescents' Experience Of Being Overweight, Wilma Powell Stuart

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The number of overweight adolescents worldwide has continued to increase over the past several decades. Intervention studies for weight management with overweight adolescents are challenged by high rates of attrition and have failed to achieve sustained outcomes. Hispanic adolescents have a higher risk of being overweight than their African American and White peers do. However, Hispanic overweight adolescents have been poorly represented in intervention studies with overweight adolescents. The factors that influence the Hispanic overweight adolescents’ perceptions of weight and weight loss management are not known. This qualitative study used ground theory methodology to identify the factors that influence perceptions …

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The Characterization Of The Subcellular Localization Of Bile Acid Coa: N-Acyltransferase, Nathan Allen Styles Jan 2007

The Characterization Of The Subcellular Localization Of Bile Acid Coa: N-Acyltransferase, Nathan Allen Styles

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The liver plays a central role in metabolism. It controls protein metabolism through deamination and transamination of amino acids, removal of ammonia through urea synthesis, synthesis of non-essential amino acids and synthesis of the majority of plasma proteins such as albumin. The liver regulates blood glucose levels through glyconeogenesis and glyconeolysis of glycogen, as well as gluconeogenesis from amino acids. It regulates fat metabolism through oxidation of triglycerides and fatty acids, as well as synthesis of cholesterol, lipoproteins, and phospholipids. Furthermore, the liver is the only site of formation of bile acids and their conjugates, physiologically important compounds that solubilize …

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Bacillus Anthracis Spore-Host Interactions, Melissa K. Swiecki Jan 2007

Bacillus Anthracis Spore-Host Interactions, Melissa K. Swiecki

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The use of Bacillus anthracis as a bioweapon depends on the dispersal of its spores into the environment, entrance into the body, spore uptake by human host cells, germination of the spores in the host and the pathological consequences of the virulence factors produced by the vegetative cells. Prior to 2001, very little was known about the mechanisms of spore entry into the host, including targeting cell types at airway, digestive and skin surfaces, potential spore receptors on these cells and spore encounters with cellular and humoral elements of the innate and adaptive immune systems. To this end, we have …

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Relaxation Rate-Based Magnetic Resonance Imaging Quantification Of Myocardial Infarction, Pal Suranyi Jan 2007

Relaxation Rate-Based Magnetic Resonance Imaging Quantification Of Myocardial Infarction, Pal Suranyi

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Ischemic heart disease is the leading cause of mortality in western societies. Treatment needs to be tailored for each individual, which requires accurate assessment of the underlying pathology. Magnetic Resonance Imaging (MRI) is a relatively young modality in the field of cardiovascular imaging, and boasts with the lack of harmful radiation, excellent soft tissue contrast, and high spatial-temporal resolution. The very foundation of the concept of MRI was the finding that pathology causes changes in the relaxation rates of tissues. Measurement of relaxation rates is more time consuming than generating simple signal intensity images weighted by the longitudinal or transverse …

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