37,893 research outputs found

    Contribution of the infection-associated complement regulator-acquiring surface protein 4 (ErpC) to complement resistance of Borrelia burgdorferi

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    Borrelia burgdorferi evades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance of B. burgdorferi and its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, a B. garinii strain was generated that ectopically expresses CRASP-4. CRASP-4-producing bacteria bound CFHR1, CFHR2, and CFHR5 but not CFH. In addition, transformed spirochetes deposited significant amounts of lethal complement components on their surface and were susceptible to human serum, thus indicating that CRASP-4 plays a subordinate role in complement resistance of B. burgdorferi

    Case report: Novel FHR2 variants in atypical Hemolytic Uremic Syndrome: A case study of a translational medicine approach in renal transplantation

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    Atypical hemolytic-uremic syndrome (aHUS) is a severe thrombotic microangiopathy in which kidney involvement is common. aHUS can be due to either genetic or acquired abnormalities, with most abnormalities affecting the alternative complement pathway. Several genetic factors/alterations can drive the clinical presentation, therapeutic response, and risk of recurrence, especially recurrence following kidney transplantation. We report here the case of a 22-year-old man who developed a severe form of aHUS. Renal biopsy revealed thrombotic microangiopathy and features of chronic renal damage. Despite two eculizumab infusions, the patient remained dialysis dependent. Two novel rare variants, c.109G>A (p.E37K) and c.159 C>A (p.Y53*), were identified in the factor H-related 2 (FHR2) gene, and western blot analysis revealed a significant reduction in the level of FHR2 protein in the patient's serum. Although FHR2 involvement in complement 3 glomerulopathy has been reported previously, a role for FRH2 as a complement modulator has not yet been definitively shown. In addition, no cases of aHUS in individuals with FHR2 variants have been reported. Given the role of FHRs in the complement system and the fact that this patient was a candidate for a kidney transplant, we studied the relevance of low FHR2 plasma levels through a set of functional in vitro assays. The aim of our work was to determine if low FHR2 plasma levels could influence complement control at the endothelial surface with a view to identifying a therapeutic approach tailored to this specific patient. Interestingly, we observed that low FHR2 levels in the patient's serum could induce complement activation, as well as C5b-9 deposition on human endothelial cells, and affected cell morphology. As C5b-9 deposition is a prerequisite for endothelial cell damage, these results suggest that extremely low FHR2 plasma levels increase the risk of aHUS. Given their ability to reduce C5b-9 deposition, recombinant FHR2 and eculizumab were tested in vitro and found to inhibit hemolysis and endothelial cell surface damage. Both molecules showed effective and comparable profiles. Based on these results, the patient underwent a kidney transplant, and received eculizumab as induction and maintenance therapy. Five years after transplantation, the patient remains in good general health, with stable graft function and no evidence of disease recurrence. To our knowledge, this is first reported case of an aHUS patient carrying FHR2 mutations and provides an example of a translational therapeutic approach in kidney transplantation

    Logarithmic variance profiles and the corresponding f-1 spectra of temperature fluctuations in turbulent Rayleigh-Bénard convection

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    We report experimental results for the temperature variance 2(z) and the corresponding frequency spectra P(f) in turbulent Rayleigh-Bénard convection (RBC) in a cylindrical sample of aspect ratioT= D/L = 1:00 (D = 1:12 m is the diameter and L = 1:12 m the height). The measurements were conducted in the Rayleigh-number range 1011 < Ra < 1:35 1014 and Pr ' 0:8. For Ra = 1:35x1014, 2(z) could be described well by a logarithmic dependence on the vertical position z in a range of z 1 < z < z 2 with z 1 ' 70 and z 2 = 0:1L. Here L=(2Nu) is the thickness of a thin thermal sublayer adjacent to the horizontal plate where the heat flux (denoted by the Nusselt number Nu) is carried mostly by thermal diffusion. In the log layer, we found that the temperature spectra had a significant frequency range over which P(f) f with close to 1. As Ra decreased, increased so that the log layer became thinner. At Ra = 2:05 1011, z 2 < z 1 and therefore there was no range for a log layer. Correspondingly, the temperature spectrum near the horizontal plate did not have the f1 scaling form either

    Contestations over Caprivi identities : from pre colonial times to the present

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    Includes abstract.Includes bibliographical references.This study investigated the hypothesis that Caprivi identities exist; and that they have always been contested. These identities defined as a sense of not belonging to greater South West Africa exist in two forms: i) as a spatial or geographical entity usually divided into East and West in history for administrative purposes; and, ii) as a people, such as Subia, Mafwe, Mayeyi, Mbukushu, Barakwena, Totela, Mbalangwe, and Lozi, collectively referred to as ‘Caprivians’. Through utilizing primary sources such as oral interviews and archival material as well as secondary sources, the study endeavored to establish how Caprivi identities were constructed; what the nature of its contestations are; and how ‘Caprivians’ responded to its construction. It was established that Caprivi identities were the result of administrative neglect in state formation that constructed isolation on the basis of difference – that ‘Caprivians’ are different from other groups in South West Africa, and that Caprivi was geographically remote from Windhoek and hence difficult to administer as part of South West Africa. Resultantly, only a primitive form of indirect rule existed in the area for most part of its colonial history resulting in constant change of colonial masters. Though it was pushed more to neighboring territories administratively, it was not made an integral part of such territories but made to stand separate as a geographical entity

    Prime values of f(a,b2)f(a,b^2) and f(a,p2)f(a,p^2), ff quadratic

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    We prove an asymptotic formula for primes of the shape f(a,b2)f(a,b^2) with a,ba,b integers and of the shape f(a,p2)f(a,p^2) with pp prime. Here ff is a binary quadratic form with integer coefficients, irreducible over Q\mathbb{Q} and has no local obstructions. This refines the seminal work of Friedlander and Iwaniec on primes of the form x2+y4x^2 + y^4 and Heath-Brown and Li on primes of the form a2+p4a^2 + p^4, as well as earlier work of the author with Lam and Schindler on primes of the form f(a,p)f(a,p) with ff a positive definite form.45 page

    A 2 h periodic variation in the low-mass X-ray binary Ser X-1

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    Spectroscopy of the low-mass X-ray binary Ser X-1 using the Gran Telescopio Canarias have revealed a ?2 h periodic variability that is present in the three strongest emission lines. We tentatively interpret this variability as due to orbital motion, making it the first indication of the orbital period of Ser X-1. Together with the fact that the emission lines are remarkably narrow, but still resolved, we show that a main-sequence K dwarf together with a canonical 1.4 M? neutron star gives a good description of the system. In this scenario, the most likely place for the emission lines to arise is the accretion disc, instead of a localized region in the binary (such as the irradiated surface or the stream-impact point), and their narrowness is due instead to the low inclination (?10°) of Ser X-1

    K. F. C. Rose, The Date and Author of the Satyricon. With an Introduction by J. P. Sullivan

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    Verdière Raoul. K. F. C. Rose, The Date and Author of the Satyricon. With an Introduction by J. P. Sullivan. In: L'antiquité classique, Tome 42, fasc. 1, 1973. pp. 279-280

    Also By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation

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    The desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters

    K. F. C. Rose, The date and author of the Satyricon, with an introduction by J. P. Sullivan, 1971

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    Rastier Françoise. K. F. C. Rose, The date and author of the Satyricon, with an introduction by J. P. Sullivan, 1971. In: Revue des Études Anciennes. Tome 74, 1972, n°1-4. pp. 300-303

    K. F. C. Rose, The date and author of the Satyricon, with an introduction by J. P. Sullivan, 1971

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    Rastier Françoise. K. F. C. Rose, The date and author of the Satyricon, with an introduction by J. P. Sullivan, 1971. In: Revue des Études Anciennes. Tome 74, 1972, n°1-4. pp. 300-303
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