924 research outputs found

    Producing Godspell: An exploration of the concept musical

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    In this thesis I will explore my direction of the production of Godspell produced January 16 through 18,2009, in the Johnson Commons Ballroom on The University of Mississippi campus. Godspell is a concept musical based on the Book of Matthew from The Bible. This paper explores the use of different methods of directing, the use of integrated choreography, and the means it takes to produce a musical. In it I will discover which methods were successful and which failed to meet my expectations. It will conclude with a detailed analysis of methods explored, problems encountered, and goals accomphshed, ultimately resulting in three successful performances of Godspell in January 2009

    The Star Formation History of the WLM Dwarf Irregular Galaxy

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    https://scholarworks.seattleu.edu/fss-2019/1002/thumbnail.jp

    Community Study, Wilmington Metropolitan Area

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    The purpose of this Community Study is to provide essential information for the pastors and lay leaders of the Seventh-day Adventist churches in the Wilmington metropolitan area and the steering committee of the Wilmington Area Adventist Community Services Agency. It is designed to assess community needs, potential partnerships, and opportunities for humanitarian ministry, as well as provide basic information about demographics.https://digitalcommons.andrews.edu/hrsa/1004/thumbnail.jp

    Do Somatic Mitochondrial DNA Mutations Contribute to Parkinson's Disease?

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    A great deal of evidence supports a role for mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD), although the origin of the mitochondrial dysfunction in PD remains unclear. Expression of mitochondrial DNA (mtDNA) from PD patients in “cybrid” cell lines recapitulates the mitochondrial defect, implicating a role for mtDNA mutations, but the specific mutations responsible for the mitochondrial dysfunction in PD have been difficult to identify. Somatic mtDNA point mutations and deletions accumulate with age and reach high levels in substantia nigra (SN) neurons. Mutations in mitochondrial DNA polymerase γ (POLG) that lead to the accumulation of mtDNA mutations are associated with a premature aging phenotype in “mutator” mice, although overt parkinsonism has not been reported in these mice, and with parkinsonism in humans. Together these data support, but do not yet prove, the hypothesis that the accumulation of somatic mtDNA mutations in SN neurons contribute to the pathogenesis of PD

    Reducing Catheter Associated Urinary Tract Infections (CAUTI) by Decreasing Use of Indwelling Catheters

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    Background: Catheter Associated Urinary Tract Infections (CAUTI) are considered a preventable hospital-acquired infection [2]. Centers for Medicaid and Medicare no longer reimburse hospitals for preventable CAUTIs [2]. A concerted effort to decrease our indwelling urinary catheter (IUC) rate has led to a decrease in the number of infections related to these catheters at Maine Medical Center (MMC) in Portland, Maine. Starting in 2012 as a result of The Joint Commission National Patient Safety Goal, the inter-professional CAUTI committee focus has been on decreasing utilization of IUC[1]. After an initial large decrease in utilization, the rates have flattened. The effort over the past year has been focused on breaking this plateau and lowering IUC use. As a result, MMC has decreased its CAUTI rate below the national bench mark

    The role of dimerisation in the activation of platelets by the collagen receptor GPVI

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    Cardiovascular disease is the leading cause of death globally and platelets have emerged as key markers for disease pathophysiology. Cardiovascular disorders caused by pathological thrombosis are divided into two underlying causes’ namely, arterial thrombosis and thrombo-inflammation. Current antiplatelet treatments however have a high risk of causing excessive bleeding and are largely ineffective against thrombo-inflammation. Therefore there is a need to develop new antiplatelet treatments including targeting the receptor tyrosine kinase, glycoprotein VI (GPVI). GPVI has emerged as a promising therapeutic target due to it having a key role in arterial thrombosis (at site of plaque rupture) and a number of thrombo-inflammatory disorders (including ischaemic stroke) but a minimal role in haemostasis. This glycoprotein is a critical signalling receptor responsible for collagen-induced platelet responses and a receptor for additional endogenous ligands including fibrin(ogen). GPVI is also a receptor for snake venom toxins and charged surfaces. GPVI has two immunoglobulin (Ig) domains (D1 & D2), a single transmembrane helix and a mucin rich stalk. It has been proposed that GPVI is expressed as a dimer through association via its D2 domains, that collagen binds to a unique epitope in dimeric GPVI, that the number of GPVI dimers increases upon platelet activation and that dimerisation of GPVI is inhibited by elevation of cyclic adenosine monophosphate (cAMP). In this thesis, I confirm that elevation of cAMP reduces dimerisation but show this has a minimal effect on collagen signalling. Furthermore, through functional studies on transfected cells expressing GPVI mutants I provide evidence that dimerisation is not critical for activation of the collagen receptor. In addition, I show using super-resolution single molecule microscopy, fluorescence correlation spectroscopy (FCS) and bioluminescence resonance energy transfer (BRET) that GPVI is expressed as a mixture of monomers and dimers in transfected cell lines but is predominately monomeric, and that collagen increases the degree of dimerisation/oligomerisation. The results suggest that a dimer-specific conformation is not critical for collagen binding and receptor activation but supports collagen signalling through an increase in avidity. The results are discussed in the context of GPVI as a novel target in thrombosis

    Signal transduction and activator of transcription-3 (STAT3) in patients with colorectal cancer: associations with the phenotypic features of the tumour and host

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    Purpose: In patients with colorectal cancer (CRC), a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL-6/JAK/STAT3 pathway. The present study examines the relationship between tumour total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses and survival in patients undergoing resection of stage I-III CRC. Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumour cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density and Klintrup-Mäkinen grade) and systemic inflammatory responses and cancer-specific survival were examined. Results: 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r=0.363, P<0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r=0.130, P=0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P=0.012), CD8+ (P=0.003) and FOXP3+ T-lymphocytes (P=0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P=0.004). The combination of nuclear STAT3/pSTAT3 stratified five-year survival from 81% to 62% (P=0.012), however was not associated with survival independent of venous invasion, tumour perforation or tumour budding. Conclusion In patients undergoing CRC resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Up-regulation of tumour STAT3 may be an important mechanism whereby the tumour deregulates local and systemic inflammatory responses
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