45 research outputs found

    Multiplicity of young brown dwarfs in Cha I

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    How frequent are brown dwarf binaries? Do brown dwarfs have planets? Are current theoretical pre-main-sequence evolutionary tracks valid down to the substellar regime? - Any detection of a companion to a brown dwarf takes us one step forward towards answering these basic questions of star formation. We report here on a search for spectroscopic and visual companions to young brown dwarfs in the Cha I star forming cloud. Based on spectra taken with UVES at the VLT, we found significant radial velocity (RV) variations for five bona-fide and candidate brown dwarfs in Cha I. They can be caused by either a (substellar or planetary) companion or stellar activity. A companion causing the detected RV variations would have about a few Jupiter masses. We are planning further UVES observations in order to explore the nature of the detected RV variations. We also found that the RV dispersion is only ~ 2km/s indicating that there is probably no run-away brown dwarf among them. Additionally a search for companions by direct imaging with the HST and SOFI (NTT) has yielded to the detection of a few companion candidates in larger orbits.Comment: Conference proceeding "Origins of stars and planets: The VLT view", ESO, Garching, April 24-27 200

    Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

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    Background: The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings: Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions: The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens

    Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study

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    A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment

    Exchange of functional domains between a bacterial conjugative relaxase and the integrase of the human adeno-associated virus

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    Endonucleases of the HUH family are specialized in processing single-stranded DNA in a variety of evolutionarily highly conserved biological processes related to mobile genetic elements. They share a structurally defined catalytic domain for site-specific nicking and strand-transfer reactions, which is often linked to the activities of additional functional domains, contributing to their overall versatility. To assess if these HUH domains could be interchanged, we created a chimeric protein from two distantly related HUH endonucleases, containing the N-terminal HUH domain of the bacterial conjugative relaxase TrwC and the C-terminal DNA helicase domain of the human adeno-associated virus (AAV) replicase and site-specific integrase. The purified chimeric protein retained oligomerization properties and DNA helicase activities similar to Rep68, while its DNA binding specificity and cleaving-joining activity at oriT was similar to TrwC. Interestingly, the chimeric protein could catalyse site-specific integration in bacteria with an efficiency comparable to that of TrwC, while the HUH domain of TrwC alone was unable to catalyze this reaction, implying that the Rep68 C-terminal helicase domain is complementing the TrwC HUH domain to achieve site-specific integration into TrwC targets in bacteria. Our results illustrate how HUH domains could have acquired through evolution other domains in order to attain new roles, contributing to the functional flexibility observed in this protein superfamily.This work was supported by the Medical Research Council (MRC) grant MR/N022890/1 to EH and grant 1001764 to RML; National Institutes of Health (NIH) grant RO1-GM09285 to CRE; Spanish Ministry of Economy and competitiveness (MINECO) grant BIO2013-46414-P to ML and AFM is supported by a Doc.Mobility fellowship from the Swiss National Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Gaia Data Release 1: Open cluster astrometry: Performance, limitations, and future prospects

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    Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs

    Modeling risk factors and confounding effects in stroke

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    Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

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    To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

    Gaia Data Release 1: Testing parallaxes with local Cepheids and RR Lyrae stars

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    Context. Parallaxes for 331 classical Cepheids, 31 Type II Cepheids, and 364 RR Lyrae stars in common between Gaia and the Hipparcos and Tycho-2 catalogues are published in Gaia Data Release 1 (DR1) as part of the Tycho-Gaia Astrometric Solution (TGAS). Aims. In order to test these first parallax measurements of the primary standard candles of the cosmological distance ladder, which involve astrometry collected by Gaia during the initial 14 months of science operation, we compared them with literature estimates and derived new period-luminosity (PL), period-Wesenheit (PW) relations for classical and Type II Cepheids and infrared PL, PL-metallicity (PLZ), and optical luminosity-metallicity (M V -[Fe/H]) relations for the RR Lyrae stars, with zero points based on TGAS. Methods. Classical Cepheids were carefully selected in order to discard known or suspected binary systems. The final sample comprises 102 fundamental mode pulsators with periods ranging from 1.68 to 51.66 days (of which 33 with σ Ω /Ω < 0.5). The Type II Cepheids include a total of 26 W Virginis and BL Herculis stars spanning the period range from 1.16 to 30.00 days (of which only 7 with σ Ω /Ω < 0.5). The RR Lyrae stars include 200 sources with pulsation period ranging from 0.27 to 0.80 days (of which 112 with σ Ω /Ω < 0.5). The new relations were computed using multi-band (V,I,J,K s ) photometry and spectroscopic metal abundances available in the literature, and by applying three alternative approaches: (i) linear least-squares fitting of the absolute magnitudes inferred from direct transformation of the TGAS parallaxes; (ii) adopting astrometry-based luminosities; and (iii) using a Bayesian fitting approach. The last two methods work in parallax space where parallaxes are used directly, thus maintaining symmetrical errors and allowing negative parallaxes to be used. The TGAS-based PL,PW,PLZ, and M V - [Fe/H] relations are discussed by comparing the distance to the Large Magellanic Cloud provided by different types of pulsating stars and alternative fitting methods. Results. Good agreement is found from direct comparison of the parallaxes of RR Lyrae stars for which both TGAS and HST measurements are available. Similarly, very good agreement is found between the TGAS values and the parallaxes inferred from the absolute magnitudes of Cepheids and RR Lyrae stars analysed with the Baade-Wesselink method. TGAS values also compare favourably with the parallaxes inferred by theoretical model fitting of the multi-band light curves for two of the three classical Cepheids and one RR Lyrae star, which were analysed with this technique in our samples. The K-band PL relations show the significant improvement of the TGAS parallaxes for Cepheids and RR Lyrae stars with respect to the Hipparcos measurements. This is particularly true for the RR Lyrae stars for which improvement in quality and statistics is impressive. Conclusions. TGAS parallaxes bring a significant added value to the previous Hipparcos estimates. The relations presented in this paper represent the first Gaia-calibrated relations and form a work-in-progress milestone report in the wait for Gaia-only parallaxes of which a first solution will become available with Gaia Data Release 2 (DR2) in 2018.This work has made use of results from the European Space Agency (ESA) space mission Gaia, the data from which were processed by the Gaia Data Processing and Analysis Consortium (DPAC). Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. The Gaia mission website is http://www.cosmos.esa.int/gaia. The authors are current or past members of the ESA and Airbus DS Gaia mission teams and of the Gaia DPAC. This research has made use of the SIMBAD database, operated at CDS, Strasbourg, France. We thank the referee, Pierre Kervella, for his detailed comments and suggestions that have helped to improve the paper analysis and presentation. This work has financially been supported by: the Agenzia Spaziale Italiana (ASI) through grants I/037/08/0, I/058/10/0, 2014-025-R.0, and 2014-025-R.1.2015 to INAF and contracts I/008/10/0 and 2013/030/I.0 to ALTEC S.p.A.; the Algerian Centre de Recherche en Astronomie, Astrophysique et GĂ©ophysique of Bouzareah Observatory; the Austrian FWF Hertha Firnberg Programme through grants T359, P20046, and P23737; the BELgian federal Science Policy Office (BELSPO) through various PROgramme de DĂ©veloppement d’ExpĂ©riences scientifiques (PRODEX) grants; the Brazil-France exchange programmes FAPESP-COFECUB and CAPES-COFECUB; the Chinese National Science Foundation through grant NSFC 11573054; the Czech-Republic Ministry of Education, Youth, and Sports through grant LG 15010; the Danish Ministry of Science; the Estonian Ministry of Education and Research through grant IUT40-1; the European Commission’s Sixth Framework Programme through the European Leadership in Space Astrometry (ELSA) Marie Curie Research Training Network (MRTN-CT-2006-033481), through Marie Curie project PIOF-GA-2009-255267 (SAS-RRL), and through a Marie Curie Transfer-of-Knowledge (ToK) fellowship (MTKD-CT-2004-014188); the European Commission’s Seventh Framework Programme through grant FP7-606740 (FP7-SPACE-2013-1) for the Gaia European Network for Improved data User Services (GENIUS) and through grant 264895 for the Gaia Research for European Astronomy Training (GREAT-ITN) network; the European Research Council (ERC) through grant 320360 and through the European Union’s Horizon 2020 research and innovation programme through grant agreement 670519 (Mixing and Angular Momentum tranSport of massIvE stars – MAMSIE); the European Science Foundation (ESF), in the framework of the Gaia Research for European Astronomy Training Research Network Programme (GREAT-ESF); the European Space Agency in the framework of the Gaia project; the European Space Agency Plan for European Cooperating States (PECS) programme through grants for Slovenia; the Czech Space Office through ESA PECS contract 98058; the Academy of Finland; the Magnus Ehrnrooth Foundation; the French Centre National de la Recherche Scientifique (CNRS) through action “DĂ©fi MASTODONS”; the French Centre National d’Études Spatiales (CNES); the French L’Agence Nationale de la Recherche (ANR) “investissements d’avenir” Initiatives D’EXcellence (IDEX) programme PSL∗ through grant ANR-10-IDEX-0001-02; the RĂ©gion Aquitaine; the UniversitĂ© de Bordeaux; the French Utinam Institute of the UniversitĂ© de Franche-ComtĂ©, supported by the RĂ©gion de Franche-ComtĂ© and the Institut des Sciences de l’Univers (INSU); the German Aerospace Agency (Deutsches Zentrum fĂŒr Luft- und Raumfahrt e.V., DLR) through grants 50QG0501, 50QG0601, 50QG0602, 50QG0701, 50QG0901, 50QG1001, 50QG1101, 50QG140, 50QG1401, 50QG1402, and 50QG1404; the Hungarian Academy of Sciences through LendĂŒlet Programme LP2014-17; the Hungarian National Research, Development, and Innovation Office through grants NKFIH K-115709, K-119517 and PD-116175; the Israel Ministry of Science and Technology through grant 3-9082; the Italian Istituto Nazionale di Astrofisica (INAF); the Netherlands Organisation for Scientific Research (NWO) through grant NWO-M-614.061.414 and through a VICI grant to A. Helmi; the Netherlands Research School forAstronomy (NOVA); the Polish National Science Centre through HARMONIA grant 2015/18/M/ST9/00544; the Portugese Fundação para a CiĂȘncia e a Tecnologia (FCT) through grants PTDC/CTE-SPA/118692/2010, PDCTE/CTE-AST/81711/2003, and SFRH/BPD/74697/2010; the Strategic Programmes PEst-OE/AMB/UI4006/2011 for SIM, UID/FIS/00099/2013 for CENTRA, and UID/EEA/00066/2013 for UNINOVA; the Slovenian Research Agency; the Spanish Ministry of Economy MINECO-FEDER through grants AyA2014-55216, AyA2011-24052, ESP2013-48318-C2-R, and ESP2014-55996-C2-R and MDM-2014-0369 of ICCUB (Unidad de Excelencia MarĂ­a de Maeztu); the Swedish National Space Board (SNSB/Rymdstyrelsen); the Swiss State Secretariat for Education, Research, and Innovation through the ESA PRODEX programme; the Swiss Mesures d’Accompagnement; the Swiss ActivitĂ©s Nationales ComplĂ©mentaires; the Swiss National Science Foundation, including an Early Postdoc.Mobility fellowship; the United Kingdom Rutherford Appleton Laboratory; the United Kingdom Science and Technology Facilities Council (STFC) through grants PP/C506756/1 and ST/I00047X/1; and the United Kingdom Space Agency (UKSA) through grants ST/K000578/1 and ST/N000978/1
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