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- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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- Aaltonen, T., et al.
(författare)
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Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
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Tidskriftsartikel (refereegranskat)abstract
- We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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- Abazov, V. M., et al.
(författare)
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Measurement of the Angular and Lifetime Parameters of the Decays B-d(0) -> J/psi K*(0) and B-s(0) -> J/psi phi
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:3, s. 032001-:102, s. 032001-
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the linear polarization amplitudes and the strong relative phases that describe the flavor-untagged decays B-d(0) --> J/psi K*(0) and B-s(0) --> J/psi phi in the transversity basis. We also measure the mean lifetime (tau) over bar (s) of the B-s(0) mass eigenstates and the lifetime ratio (tau) over bar (s)/tau(d). The analyses are based on approximately 2.8 fb(-1) of data recorded with the D0 detector. From our measurements of the angular parameters we conclude that there is no evidence for a deviation from flavor SU( 3) symmetry for these decays and that the factorization assumption is not valid for the B-d(0) --> J/psi K*(0) decay.
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- Abazov, V. M., et al.
(författare)
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Search for Large Extra Spatial Dimensions in the Dielectron and Diphoton Channels in p(p)over-bar Collisions at root s=1.96 TeV
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:5, s. 051601-:102, s. 051601-
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Tidskriftsartikel (refereegranskat)abstract
- We report on a search for large extra spatial dimensions in the dielectron and diphoton channels using a data sample of 1: 05 fb(-1) of p (p) over bar collisions at a center-of-mass energy of 1.96 TeV collected by the D0 detector at the Fermilab Tevatron Collider. The invariant mass spectrum of the data agrees well with the prediction of the standard model. We find the most restrictive 95% C. L. lower limits on the effective Planck scale between 2.1 and 1.3 TeV for 2 to 7 extra dimensions.
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- Abazov, V. M., et al.
(författare)
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Measurement of sigma(p(p)over-bar -> Z plus X)Br(Z -> tau(+)tau(-)) at root s=1.96 TeV
- 2009
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 670:4-5, s. 292-299
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the cross section for Z boson production times the branching fraction to tau lepton pairs sigma(p (p) over bar -> Z + X)Br(Z -> tau(+)tau(-)) in p (p) over bar collisions at root s = 1.96 TeV. The measurement is performed in the channel in which one tau lepton decays into a muon and neutrinos. and the other tau lepton decays hadronically or into an electron and neutrinos. The data sample corresponds to an integrated luminosity of 1.0 fb(-1) collected with the DO detector at the Fermilab Tevatron Collider. The sample contains 1511 candidate events with an estimated 20% background from jets or muons misidentified as tau leptons. We obtain sigma . Br = 240 +/- 8 (star) +/- 12 (sys) +/- 15 (lum) pb, which is consistent with the standard model prediction.
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- Abazov, V. M., et al.
(författare)
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Search for Associated W and Higgs Boson Production in p(p)over-bar Collisions at root s=1.96 TeV
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:5, s. 051803-:102, s. 051803-
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Tidskriftsartikel (refereegranskat)abstract
- We present results of a search for WH -> l nu b (b) over bar production in p (p) over bar collisions based on the analysis of 1.05 fb(-1) of data collected by the D0 experiment at the Fermilab Tevatron, using a neural network for separating the signal from backgrounds. No signal-like excess is observed, and we set 95% C. L. upper limits on the WH production cross section multiplied by the branching ratio for H -> b (b) over bar for Higgs boson masses between 100 and 150 GeV. For a mass of 115 GeV, we obtain an observed (expected) limit of 1.5 (1.4) pb, a factor of 11.4 (10.7) times larger than the standard model prediction.
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