60 research outputs found

    Proposed Improvements in Collegiate Aviation Education

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    This paper presents findings related to proposed improvements in four-year aviation education programs as indicated by nation-wide survey instruments conducted in summer of 1993. Aviation education programs directors of four-year non-engineering collegiate aviation programs were contacted to provide input as to methods of improving the quality of aviation education programs. Key information obtained was then paraphrased into a written instrument that was categorized in order of importance by the program directors. The improvement of both faculty and facilities and to provide more student internships were the most recommended improvements in this study. This paper provides multiple nationwide ranked proposed improvements in aviation education, and describes peer-suggested methods of improving student attainment of knowledge, competency, and proficiency in aviation education

    A Comparative Analysis of Proposed Improvements in Aviation Education: Nationwide Aviation Education Programs Versus Embry-Riddle Aeronautical University

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    This paper presents a comparison of findings related to a study of proposed improvements in four-year aviation education programs as indicated by nation-wide survey instruments conducted in the summer of 1993 and during a follow-on survey performed at Embry-Riddle Aeronautical University in early 1996. Aviation education program directors of four-year non-engineering collegiate aviation programs and faculty members throughout the Embry-Riddle Aeronautical University system were contacted to provide input as to methods of improving the quality of aviation education programs. Key information obtained was then paraphrased into a written instrument that was categorized in order of importance by the two different mailings. The improvement of both faculty and teaching aids and to provide more student internships were the most recommended improvements in this study. This paper provides multiple nationwideranked proposed improvements in aviation education, and describes peer-suggested methods of improving student attainment of knowledge, competency, and proficiency in aviation education

    Role of NADPH Oxidase versus Neutrophil Proteases in Antimicrobial Host Defense

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    NADPH oxidase is a crucial enzyme in mediating antimicrobial host defense and in regulating inflammation. Patients with chronic granulomatous disease, an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates (ROIs), suffer from life-threatening bacterial and fungal infections. The mechanisms by which NADPH oxidase mediate host defense are unclear. In addition to ROI generation, neutrophil NADPH oxidase activation is linked to the release of sequestered proteases that are posited to be critical effectors of host defense. To definitively determine the contribution of NADPH oxidase versus neutrophil serine proteases, we evaluated susceptibility to fungal and bacterial infection in mice with engineered disruptions of these pathways. NADPH oxidase-deficient mice (p47phox−/−) were highly susceptible to pulmonary infection with Aspergillus fumigatus. In contrast, double knockout neutrophil elastase (NE)−/−×cathepsin G (CG)−/− mice and lysosomal cysteine protease cathepsin C/dipeptidyl peptidase I (DPPI)-deficient mice that are defective in neutrophil serine protease activation demonstrated no impairment in antifungal host defense. In separate studies of systemic Burkholderia cepacia infection, uniform fatality occurred in p47phox−/− mice, whereas NE−/−×CG−/− mice cleared infection. Together, these results show a critical role for NADPH oxidase in antimicrobial host defense against A. fumigatus and B. cepacia, whereas the proteases we evaluated were dispensable. Our results indicate that NADPH oxidase dependent pathways separate from neutrophil serine protease activation are required for host defense against specific pathogens

    Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

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    Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

    Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

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    -linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1
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