17 research outputs found

    A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers

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    The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis

    Measurement of the track reconstruction efficiency at LHCb

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    The determination of track reconstruction efficiencies at LHCb using J/psi -> mu(+)mu(-) decays is presented. Efficiencies above 95% are found for the data taking periods in 2010, 2011, and 2012. The ratio of the track reconstruction efficiency of muons in data and simulation is compatible with unity and measured with an uncertainty of 0.8% for data taking in 2010, and at a precision of 0.4% for data taking in 2011 and 2012. For hadrons an additional 1.4% uncertainty due to material interactions is assumed. This result is crucial for accurate cross section and branching fraction measurements in LHCb

    Identification of beauty and charm quark jets at LHCb

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    Identification of jets originating from beauty and charm quarks is important for measuring Standard Model processes and for searching for new physics. The performance of algorithms developed to select b- and c-quark jets is measured using data recorded by LHCb from proton-proton collisions at root s = 7TeV in 2011 and at root s = 8TeV in 2012. The efficiency for identifying a b (c) jet is about 65%(25%) with a probability for misidentifying a light-parton jet of 0.3% for jets with transverse momentum pT > 20GeV and pseudorapidity 2 : 2 < eta < 4.2. The dependence of the performance on the pT and eta of the jet is also measured

    Measurement of CP violation and constraints on the CKM angle gamma in B-+/- -> DK +/- with D -> K-s(0)pi(+)pi(-) decays

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    A model-dependent amplitude analysis of B-+/- -> DK +/- with D -> K-s(0)pi(+)pi(-) decays is performed using proton proton collision data, corresponding to an integrated luminosity of 1 fb(-1), recorded by LHCb at a centre-of-mass energy of 7 TeV in 2011. Values of the CP violation observables x +/- and y +/-, which are sensitive to the CKM angle gamma, are measured to be x- = +0.027 +/- 0.0441(-0.008)(+0.010) +/- 0.001, y- = +0.013 +/- 0.0481(-0.007)(+0.009) +/- 0.003, x+ = -0.084 +/- 0.045 +/- 0.009 +/- 0.005, y+ = -0.032 +/- 0.048(-0.009)(+0.010) +/- 0.008, where the first uncertainty is statistical, the second systematic and the third arises from the uncertainty of the D -> K-S(0)pi(+)pi(-) amplitude model. The value of gamma is determined to be (84(-42)(+49))degrees including all sources of uncertainty. Neutral D meson mixing is found to have negligible effect. (C) 2014 The Authors. Published by Elsevier B.V

    Observation of the decay (B)over-bar(s)(0) -> psi(2S)K+pi(-)

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    The decay (B) over bar (0)(s) -> psi(2S)K+pi(-) is observed using a data set corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. The branching fraction relative to the B-0 -> psi(2S)K+pi(-) decay mode is measured to be B((B) over bar (0)(s) -> psi(2S)K+pi(-))/B(B-0 -> psi(2S)K+pi(-)) = 5.38 +/- 0.36 (stat) +/- 0.22 (syst) +/- 0.31 (f(s)/f(d)) %, where f(s)/f(d) indicates the uncertainty due to the ratio of probabilities for a b quark to hadronise into a B-s(0) or B-0 meson. Using an amplitude analysis, the fraction of decays proceeding via an intermediate K*(892)(0) meson is measured to be 0.645 +/- 0.049 (stat) +/- 0.049 (syst) and its longitudinal polarisation fraction is 0.524 +/- 0.056 (stat) +/- 0.029 (syst). The relative branching fraction for this component is determined to be B((B) over bar (0)(s) -> psi(2S)K*(892)(0))/B(B-0 -> psi(2S)K*(892)(0)) = 5.58 +/- 0.57 (stat) +/- 0.40 (syst) +/- 0.32 (f(s)/f(d)) %. In addition, the mass splitting between the B-s(0) and B-0 mesons is measured as M(B-s(0)) - M(B-0) = 87.45 +/- 0.44 (stat) +/- 0.09 (syst) MeV/c(2). (C) 2015 CERN for the benefit of the LHCb Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY licens

    Measurement of the lifetime of the B-c(+) meson using the B-c(+) -> J/psi pi(+) decay mode

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    The difference in total widths between the B-c(+) and B+ mesons is measured using a data sample corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton-proton collisions at the LHC. Through the study of the time evolution of B-c(+) -> J/psi pi(+) and B+ -> J/psi K+ decays, the width difference is measured to be Delta Gamma = Gamma(Bc+) - Gamma(Bc+) = 4.46 +/- 0.14 +/- 0.07 mm(-1) c, where the first uncertainty is statistical and the second systematic. The known lifetime of the B+ meson is used to convert this to a precise measurement of the B-c(+) clifetime, tau(Bc+) = 513.4 +/- 11.0 +/- 5.7 fs, where the first uncertainty is statistical and the second is systematic. (C) 2015 The Authors. Published by Elsevier B.V

    Measurement of the (B)over-bar(0)-B-0 and (B)over-bars(0)-B-s(0) production asymmetries in pp collisions at root s=7 TeV

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    The (B) over bar (0)-B-0 and (B) over bar (0)(s)-B-s(0) production asymmetries, A(P)(B-0) and A(P)(B-s(0)), are measured by means of a time-dependent analysis of B-0 -> J/Psi K-*0, B-0 -> D-pi(+) and B-s(0) -> D-s(-)pi(+) decays, using a data sample corresponding to an integrated luminosity of 1.0 fb(-1), collected by LHCb in pp collisions at a centre-of-mass energy of 7 TeV. The measurements are performed as a function of transverse momentum and pseudorapidity of the B-0 and B-s(0) mesons within the LHCb acceptance. The production asymmetries, integrated over p(T) and eta in the range 4 < p(T) < 30 GeV/c and 2.5 < eta < 4.5, are determined to be A(P)(B-0) = (-0.35 +/- 0.76 +/- 0.28)% and A(P)(B-s(0)) = (1.09 +/- 2.61 +/- 0.66)%, where the first uncertainties are statistical and the second systematic. (C) 2014 The Authors. Published by Elsevier B.V

    Observation of the B0→ρ0ρ0 decay from an amplitude analysis of B0→(π+π−)(π+π−) decays

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    Proton-proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb(-1), are analysed to search for the charmless B-0 -> rho(0)rho(0) decay. More than 600 B-0 -> (pi(+)pi(-))(pi(+)pi(-)) signal decays are selected and used to perform an amplitude, analysis, under the assumption of no CP violation in the decay, from which the B-0 -> rho(0)rho(0) decay is observed for the first time with 7.1 standard deviations significance. The fraction of B-0 -> rho(0)rho(0) decays yielding a longitudinally polarised final state is measured to be f(L) = 0.745(-0.058)(+0.048)(stat) +/- 0.034(syst). The B-0 -> rho(0)rho(0) branching fraction, using the B-0 -> phi K*(892)(0) decay as reference, is also reported as B(B-0 -> rho(0)rho(0)) = (0.94 +/- 0.17(stat) +/- 0.09(syst) +/- 0.06(BF)) x 10(-6). (C) 2015 CERN for the benefit of the LHCb Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY licens

    LHCb detector performance

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    The LHCb detector is a forward spectrometer at the Large Hadron Collider (LHC) at CERN. The experiment is designed for precision measurements of CP violation and rare decays of beauty and charm hadrons. In this paper the performance of the various LHCb sub-detectors and the trigger system are described, using data taken from 2010 to 2012. It is shown that the design criteria of the experiment have been met. The excellent performance of the detector has allowed the LHCb collaboration to publish a wide range of physics results, demonstrating LHCb's unique role, both as a heavy flavour experiment and as a general purpose detector in the forward region

    Measurement of the CP-violating phase phi(s) in (B)over-bar(s)(0) -> J / psi pi(+)pi(-) decays

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    The mixing-induced CP-violating phase phi(s) in B-s(0) and (B) over bar (0)(s) decays is measured using the J / psi pi(+)pi(-) final state in data, taken from 3 fb(-1) of integrated luminosity, collected with the LHCb detector in 7 and 8 TeV centre-of-mass pp collisions at the LHC. A time-dependent flavour-tagged amplitude analysis, allowing for direct CP violation, yields a value for the phase phi(s) = 70 +/- 68 +/- 8 mrad. This result is consistent with the Standard Model expectation and previous measurements. (C) 2014 The Authors. Published by Elsevier B.V
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