10 research outputs found

    Evaluating LAANC Compliance and Air Traffic Collision Hazards Posed by Small Unmanned Aircraft Operations in Controlled Airspace

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    On July 23, 2019, the Federal Aviation Administration (FAA) expanded the Low Altitude Authorization and Notification Capability (LAANC)—the system that processes airspace approvals for sUAS operators in controlled airspace—to include recreational operations. Under LAANC, sUAS operators submit flight request information to one of 14 LAANC Service Suppliers via a mobile or online application. Flight request data is checked against UAS Facility Maps, NOTAMs, and Temporary Flight Restrictions to ensure compliance. Small UAS operators then receive a digital, automated authorization in near-real time. As of May 23, 2019, 591 airports across the United States are included in the LAANC system. Researchers sought to collect and evaluate sUAS operational activity in controlled airspace using UAS detection equipment. Detected sUAS flight data was compared against airspace information, temporary flight restrictions, UAS Facility Maps, and LAANC approval data to assess sUAS operator compliance and behavior patterns. Small UAS detections and LAANC authorization data was further compared against air traffic data to identify potential UAS flight interference and collision hazards with air traffic

    Measurable versions of the LS category on laminations

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    We give two new versions of the LS category for the set-up of measurable laminations defined by Berm\'udez. Both of these versions must be considered as "tangential categories". The first one, simply called (LS) category, is the direct analogue for measurable laminations of the tangential category of (topological) laminations introduced by Colman Vale and Mac\'ias Virg\'os. For the measurable lamination that underlies any lamination, our measurable tangential category is a lower bound of the tangential category. The second version, called the measured category, depends on the choice of a transverse invariant measure. We show that both of these "tangential categories" satisfy appropriate versions of some well known properties of the classical category: the homotopy invariance, a dimensional upper bound, a cohomological lower bound (cup length), and an upper bound given by the critical points of a smooth function.Comment: 22 page

    All major cholesterol-dependent cytolysins use glycans as cellular receptors

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    Cholesterol-dependent cytolysins (CDCs) form pores in cholesterol-rich membranes, but cholesterol alone is insufficient to explain their cell and host tropism. Here, we show that all eight major CDCs have high-affinity lectin activity that identifies glycans as candidate cellular receptors. Streptolysin O, vaginolysin, and perfringolysin O bind multiple glycans, while pneumolysin, lectinolysin, and listeriolysin O recognize a single glycan class. Addition of exogenous carbohydrate receptors for each CDC inhibits toxin activity. We present a structure for suilysin domain 4 in complex with two distinct glycan receptors, P1 antigen and αGal/Galili. We report a wide range of binding affinities for cholesterol and for the cholesterol analog pregnenolone sulfate and show that CDCs bind glycans and cholesterol independently. Intermedilysin binds to the sialyl-TF O-glycan on its erythrocyte receptor, CD59. Removing sialyl-TF from CD59 reduces intermedilysin binding. Glycan-lectin interactions underpin the cellular tropism of CDCs and provide molecular targets to block their cytotoxic activity.Lucy K. Shewell, Christopher J. Day, Freda E.-C. Jen, Thomas Haselhorst, John M. Atack, Josephine F. Reijneveld, Arun Everest-Dass, David B. A. James, Kristina M. Boguslawski, Stephan Brouwer, Christine M. Gillen, Zhenyao Luo, Bostjan Kobe, Victor Nizet, Mark von Itzstein, Mark J. Walker, Adrienne W. Paton, James C. Paton, Victor J. Torres, Michael P. Jenning

    Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy

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    OBJECTIVE: To examine the relationships between blood CD4 natural regulatory T (Treg) cells, plasma HIV RNA level, CD4 T-cell count and immune activation in untreated HIV-infected patients and immunodeficient patients beginning antiretroviral therapy (ART), using a novel phenotype to define Treg cells (CD25CD127CD4). Data were compared with established Treg cell markers (FoxP3, CTLA-4 and GITR). METHODS: Twenty-nine untreated HIV-infected patients with CD4 T-cell counts of 400/μl were compared in a cross-sectional study and 12 patients beginning combination ART with < 100 CD4 T cells/μl were followed for 1 year on therapy. Three- and four-colour flow cytometry was used to quantitate proportions of Treg cells. RESULTS: In control donors and patients with high CD4 T-cell counts, 28-89% (median 60%) of CD25CD127CD4 cells were FoxP3, but < 10% expressed GITR or CTLA-4. Immunodeficient patients also had CD4-negative lymphocytes with the phenotype FoxP3CD127. Proportions of CD25CD127 cells and activated (HLA-DR) cells in the CD4 T-cell population were increased in patients with low CD4 T cell counts. The proportion of CD25CD127CD4 T cells correlated positively with plasma HIV RNA level and CD4 T-cell activation, but inversely with CD4 T-cell count. Longitudinal studies of 12 patients receiving ART in two distinct cohorts (Western Australia and Malaysia) showed that the proportion of CD25CD127CD4 cells decreased slightly over time, but remained above levels seen in non-HIV controls. CONCLUSIONS: Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high after 1 year on ART

    Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis

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    Objectives: A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia. Methods: Peripheral blood mononuclear cells were collected at weeks 0, 6, 12, 24 and 48 of ART from five patients experiencing IRD [two with cryptococcal and three with Mycobacterium tuberculosis (Mtb) disease], eight non-IRD controls who had begun ART with CD4 T-cell counts of <100 cells/μL and 17 healthy controls. Leukocytes producing interferon-gamma (IFNγ) were quantified by enzyme-linked immunospot assay after stimulation with purified protein derivative (PPD), early secretory antigenic target-6 (ESAT-6), Cryptococcus neoformans or Cytomegalovirus antigens. Plasma immunoglobulin (IgG) antibodies reactive with these antigens were assessed by enzyme-linked immunosorbent assay. Proportions of activated (HLA-DR hi) and regulatory (CD25 CD127 lo and CTLA-4 +) CD4 T-cells were quantified by flow cytometry. Results: Plasma HIV RNA declined andCD4 T-cell counts rose within 8-27 weeks on ART. Mtb IRD patients displayed elevated IFNγ responses and/or plasma IgG to PPD, but none responded to ESAT-6. Cryptococcal IRD occurred in patients with low baseline CD4 T-cell counts and involved clear IFNγ and antibody responses to cryptococcal antigen. Proportions of activated and regulatory CD4 T-cells declined on ART, but remained higher in patients than in healthy controls. At the time of IRD, proportions of activated CD4 T-cells and regulatory CD4 T-cells were generally elevated relative to other patients. Conclusions: Cryptococcal and Mtb IRD generally coincide with peaks in the proportion of activated T-cells, pathogen-specific IFNγ responses and reactive plasma IgG. IRD does not reflect a paucity of regulatory CD4 T-cells

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