2,912 research outputs found

    Beyond immune escape:a variant surface glycoprotein causes suramin resistance in Trypanosoma brucei

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    Suramin is one of the first drugs developed in a medicinal chemistry program (Bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense. Cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with T. b. brucei have linked downregulation of the endocytic pathway to suramin resistance. Here we show that forward selection for suramin resistance in T. brucei spp. cultures is fast, highly reproducible and linked to antigenic variation. Bloodstream-form trypanosomes are covered by a dense coat of variant surface glycoprotein (VSG), which protects them from their mammalian hosts' immune defenses. Each T. brucei genome contains over 2000 different VSG genes, but only one is expressed at a time. An expression switch to one particular VSG, termed VSGSur , correlated with suramin resistance. Reintroduction of the originally expressed VSG gene in resistant T. brucei restored suramin susceptibility. This is the first report of a link between antigenic variation and drug resistance in African trypanosomes

    Spectral Classification; Old and Contemporary

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    Beginning with a historical account of the spectral classification, its refinement through additional criteria is presented. The line strengths and ratios used in two dimensional classifications of each spectral class are described. A parallel classification scheme for metal-poor stars and the standards used for classification are presented. The extension of spectral classification beyond M to L and T and spectroscopic classification criteria relevant to these classes are described. Contemporary methods of classifications based upon different automated approaches are introduced.Comment: To be published in "Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars: Ed Aruna Goswami & Eswar Reddy, Springer Verlag, 2009, 17 pages, 10 figure

    Ion cyclotron wall conditioning experiments on Tore Supra in presence of the toroidal magnetic field

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    Wall conditioning techniques applicable in the presence of the high toroidal magnetic field will be required for the operation of ITER for tritium removal, isotopic ratio control and recovery to normal operation after disruptions. Recently ion cyclotron wall conditioning (ICWC) experiments have been carried out on Tore Supra in order to assess the efficiency of this technique in ITER relevant conditions. The ICRF discharges were operated in He/H-2 Mixtures at the Tore Supra nominal field (3.8 T) and a RF frequency of 48 MHz, i.e. within the ITER operational space. RF pulses of 60 s (max.) were applied using a standard Tore Supra two-strap resonant double loop antenna in ICWC mode, operated either in pi or 0-phasing with a noticeable improvement of the RF coupling in the latter case. In order to assess the efficiency of the technique for the control of isotopic ratio the wall was first preloaded using a D-2 glow discharge. After 15 minutes of ICWC in He/H-2 gas mixtures the isotopic ratio was altered from 4% to 50% at the price of an important H implantation into the walls. An overall analysis comparing plasma production and the conditioning efficiency as a function of discharge parameters is given

    Representing complex data using localized principal components with application to astronomical data

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    Often the relation between the variables constituting a multivariate data space might be characterized by one or more of the terms: ``nonlinear'', ``branched'', ``disconnected'', ``bended'', ``curved'', ``heterogeneous'', or, more general, ``complex''. In these cases, simple principal component analysis (PCA) as a tool for dimension reduction can fail badly. Of the many alternative approaches proposed so far, local approximations of PCA are among the most promising. This paper will give a short review of localized versions of PCA, focusing on local principal curves and local partitioning algorithms. Furthermore we discuss projections other than the local principal components. When performing local dimension reduction for regression or classification problems it is important to focus not only on the manifold structure of the covariates, but also on the response variable(s). Local principal components only achieve the former, whereas localized regression approaches concentrate on the latter. Local projection directions derived from the partial least squares (PLS) algorithm offer an interesting trade-off between these two objectives. We apply these methods to several real data sets. In particular, we consider simulated astrophysical data from the future Galactic survey mission Gaia.Comment: 25 pages. In "Principal Manifolds for Data Visualization and Dimension Reduction", A. Gorban, B. Kegl, D. Wunsch, and A. Zinovyev (eds), Lecture Notes in Computational Science and Engineering, Springer, 2007, pp. 180--204, http://www.springer.com/dal/home/generic/search/results?SGWID=1-40109-22-173750210-

    Wind Tunnel Testing of Powered Lift, All-Wing STOL Model

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    Short take-off and landing (STOL) systems can offer significant capabilities to warfighters and, for civil operators thriving on maximizing efficiencies they can improve airspace use while containing noise within airport environments. In order to provide data for next generation systems, a wind tunnel test of an all-wing cruise efficient, short take-off and landing (CE STOL) configuration was conducted in the National Aeronautics and Space Administration (NASA) Langley Research Center (LaRC) 14- by 22-foot Subsonic Wind Tunnel. The test s purpose was to mature the aerodynamic aspects of an integrated powered lift system within an advanced mobility configuration capable of CE STOL. The full-span model made use of steady flap blowing and a lifting centerbody to achieve high lift coefficients. The test occurred during April through June of 2007 and included objectives for advancing the state-of-the-art of powered lift testing through gathering force and moment data, on-body pressure data, and off-body flow field measurements during automatically controlled blowing conditions. Data were obtained for variations in model configuration, angles of attack and sideslip, blowing coefficient, and height above ground. The database produced by this effort is being used to advance design techniques and computational tools for developing systems with integrated powered lift technologies

    Unknowable bodies, unthinkable sexualities: lesbian and transgender legal invisibility in the Toronto women's bathhouse raid

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    Although litigation involving sexual orientation and gender identity discrimination claims has generated considerable public attention in recent years, lesbian and transgender bodies and sexualities still remain largely invisible in Anglo-American courts. While such invisibility is generally attributed to social norms that fail to recognize lesbian and transgender experiences, the capacity to 'not see' or 'not know' queer bodies and sexualities also involves wilful acts of ignorance. Drawing from R. v Hornick (2002) a Canadian case involving the police raid of a women's bathhouse, this article explores how lesbian and transgender bodies and sexualities are actively rendered invisible via legal knowledge practices, norms and rationalities. It argues that limited knowledge and limited thinking not only regulate the borders of visibility and belonging, but play an active part in shaping identities, governing conduct and producing subjectivity

    Septate uterus: nosographic overview and endoscopic treatment

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    To comment on the prevalence, diagnosis, and treatment of the septate uterus, with special reference to hysteroscopic metroplasty and its effect on reproductive outcome, we searched publications in PubMed and Embase. Original articles, meta-analysis, reviews, and opinion articles were selected. The studies suggest that the prevalence of the septate uterus is increased in women with repeated pregnancy loss and infertility. Reliable diagnosis depends on accurate assessment of the uterine fundal contour and uterine cavity by means of magnetic resonance and three-dimensional ultrasound. Pertinent published data comparing pregnancy outcome before and after hysteroscopic metroplasty indicated a marked improvement after surgery. Magnetic resonance and three-dimensional ultrasound represent the gold standard for diagnosis of septate uterus. Hysteroscopic metroplasty with its simplicity, minimal postoperative sequelae, and improved reproductive outcome is the gold standard for treatment, not only in patients with recurrent pregnancy loss and premature labor but also in patients with infertility, especially if in vitro fertilization is being contemplated
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