778 research outputs found

    Ares I-X Flight Data Evaluation: Executive Overview

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    NASA's Constellation Program (CxP) successfully launched the Ares I-X flight test vehicle on October 28, 2009. The Ares I-X flight was a developmental flight test to demonstrate that this very large, long, and slender vehicle could be controlled successfully. The flight offered a unique opportunity for early engineering data to influence the design and development of the Ares I crew launch vehicle. As the primary customer for flight data from the Ares I-X mission, the Ares Projects Office (APO) established a set of 33 flight evaluation tasks to correlate flight results with prospective design assumptions and models. The flight evaluation tasks used Ares I-X data to partially validate tools and methodologies in technical disciplines that will ultimately influence the design and development of Ares I and future launch vehicles. Included within these tasks were direct comparisons of flight data with preflight predictions and post-flight assessments utilizing models and processes being applied to design and develop Ares I. The benefits of early development flight testing were made evident by results from these flight evaluation tasks. This overview provides summary information from assessment of the Ares I-X flight test data and represents a small subset of the detailed technical results. The Ares Projects Office published a 1,600-plus-page detailed technical report that documents the full set of results. This detailed report is subject to the International Traffic in Arms Regulations (ITAR) and is available in the Ares Projects Office archives files

    High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease.

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    BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis

    Conventional and Dense Gas Techniques for the Production of Liposomes: A Review

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    The aim of this review paper is to compare the potential of various techniques developed for production of homogenous, stable liposomes. Traditional techniques, such as Bangham, detergent depletion, ether/ethanol injection, reverse-phase evaporation and emulsion methods, were compared with the recent advanced techniques developed for liposome formation. The major hurdles for scaling up the traditional methods are the consumption of large quantities of volatile organic solvent, the stability and homogeneity of the liposomal product, as well as the lengthy multiple steps involved. The new methods have been designed to alleviate the current issues for liposome formulation. Dense gas liposome techniques are still in their infancy, however they have remarkable advantages in reducing the use of organic solvents, providing fast, single-stage production and producing stable, uniform liposomes. Techniques such as the membrane contactor and heating methods are also promising as they eliminate the use of organic solvent, however high temperature is still required for processing

    HTLV-1 clonality during chronic infection and BLV clonality during primary infection

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    peer reviewedaudience: researcherHTLV-1 clonality during chronic infection and BLV clonality during primary infection Nicolas A Gillet1,2*, Carol Hlela1, Tine Verdonck3, Eduardo Gotuzzo3, Daniel Clark3, Sabrina Rodriguez2, Nirav Malani4, Anat Melamed1, Niall Gormley5, Richard Carter5, David Bentley5, Charles Berry6, Frederic D Bushman4, Graham P Taylor7, Luc Willems2, Charles R M Bangham1 1Department of Immunology, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. 2Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liège (ULg), Liège, 4000, Belgium. 3Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. 4Department of Microbiology, University of Pennsylvania School of Medicine, Pennsylvania, Philadelphia, PA, 19104, USA. 5Illumina, Chesterford Research Park, Essex, Little Chesterford, CB10 1XL, UK. 6University of California, California, La Jolla San Diego, CA, 92093-0901, USA. 7Department of Genitourinary Medicine and Communicable Diseases, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. HTLV-1 persists by driving clonal proliferation of infected T-lymphocytes. A high proviral load predisposes to the inflammatory and malignant diseases associated with HTLV-1. Yet the reasons for the remarkable variation within and between individuals in the abundance of HTLV-1-infected clones remain unknown. We demonstrate that negative selection dominates during chronic infection, favouring establishment of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. We postulated that this selection occurred mainly during the primary infection. We are testing this hypothesis in an animal model by studying the BLV clonality during the primary infection in cows. By measuring the proviral load, the anti-BLV immune response and the BLV clonality we aim to quantify the impact of the immune response on the rate of infectious spread and on the selection of proviruses inserted in a particular genomic environment. Co-infection with Strongyloides stercoralis or Staphylococcus appears to be another risk factor for the development of HTLV-1 associated diseases. We observed that HTLV-1 clonality is altered by co-infection with these pathogens with an increase of both the number and the abundance of the infected T-cell clones. The genomic characteristics of the proviral integration sites in the most abundant clones differ significantly between co-infected individuals and those with HTLV-1 alone, implying the existence of different selection forces in co-infected patients. The rate of appearance of new clones in patients co-infected with Strongyloides stercoralis is higher than in patients with HTLV-1 alone. By comparing skin lesions and blood samples from patients with Infective Dermatitis associated with HTLV-1 (IDH), we observed a significant proportion of distinct infected clones between the two compartments. The skin lesions seem to be a site for HTLV-1 infectious spread

    T-Cell Epitope Prediction: Rescaling Can Mask Biological Variation between MHC Molecules

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    Theoretical methods for predicting CD8+ T-cell epitopes are an important tool in vaccine design and for enhancing our understanding of the cellular immune system. The most popular methods currently available produce binding affinity predictions across a range of MHC molecules. In comparing results between these MHC molecules, it is common practice to apply a normalization procedure known as rescaling, to correct for possible discrepancies between the allelic predictors. Using two of the most popular prediction software packages, NetCTL and NetMHC, we tested the hypothesis that rescaling removes genuine biological variation from the predicted affinities when comparing predictions across a number of MHC molecules. We found that removing the condition of rescaling improved the prediction software's performance both qualitatively, in terms of ranking epitopes, and quantitatively, in the accuracy of their binding affinity predictions. We suggest that there is biologically significant variation among class 1 MHC molecules and find that retention of this variation leads to significantly more accurate epitope prediction
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