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- Mishra, A., et al.
(author)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Journal article (peer-reviewed)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.
(author)
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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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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
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Journal article (peer-reviewed)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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- Blokland, G. A. M., et al.
(author)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Journal article (peer-reviewed)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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- Abazov, V. M., et al.
(author)
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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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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:3, s. 032001-:102, s. 032001-
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Journal article (peer-reviewed)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.
(author)
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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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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:5, s. 051601-:102, s. 051601-
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Journal article (peer-reviewed)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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12. |
- Abazov, V. M., et al.
(author)
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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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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 670:4-5, s. 292-299
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Journal article (peer-reviewed)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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13. |
- Abazov, V. M., et al.
(author)
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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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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:5, s. 051803-:102, s. 051803-
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Journal article (peer-reviewed)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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14. |
- Abazov, V. M., et al.
(author)
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Search for pair production of second generation scalar leptoquarks
- 2009
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 671:2, s. 224-232
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Journal article (peer-reviewed)abstract
- We report on a search for the pair production of second generation scalar leptoquarks (LQ) in p (p) over bar collisions at the center of mass energy root s- = 1.96 TeV using a data set corresponding to an integrated luminosity of 1.0 fb(-1) collected with the D empty set experiment at the Fermilab Tevatron Collider. Topologies arising from the LQ (LQ) over bar -> mu q nu q and LQ (LQ) over bar -> mu q mu q decay modes are investigated. No excess of data over the standard model prediction is observed and upper limits on the leptoquark pair production cross section are derived at the 95% C.L. as a function of the leptoquark mass and the branching fraction beta for the decay LQ -> mu q. These are interpreted as lower limits on the leptoquark mass as a function of beta. For beta = 1 (0.5), scalar second generation leptoquarks with masses up to 316 GeV (270 GeV) are excluded.
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15. |
- Abazov, V. M., et al.
(author)
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Evidence for the Decay B-s(0)->(DsDs(*))-D-(*) and a Measurement of Delta Gamma(CP)(s)/Gamma(s)
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:9, s. 091801-
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Journal article (peer-reviewed)abstract
- We search for the semi-inclusive process B-s(0)->(DsDs(*))-D-(*) using 2.8 fb(-1) of pp collisions at s=1.96 TeV recorded by the D0 detector operating at the Fermilab Tevatron Collider. We observe 26.6 +/- 8.4 signal events with a significance above background of 3.2 standard deviations yielding a branching ratio of B(B-s(0)->(DsDs(*))-D-(*))=0.035 +/- 0.010(stat.)+/- 0.011(syst.). Under certain theoretical assumptions, these double-charm final states saturate CP-even eigenstates in the B-s(0) decays resulting in a width difference of Delta Gamma(CP)(s)/Gamma(s)=0.072 +/- 0.021(stat.)+/- 0.022(syst.).
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16. |
- Abazov, V. M., et al.
(author)
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Observation of ZZ Production in p(p)over-bar Collisions at root s=1.96 TeV
- 2008
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 101:17, s. 171803-:101, s. 171803-
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Journal article (peer-reviewed)abstract
- We present an observation for ZZ -> l(+) l(-) l'(+) l'(-) (l, l' =e or mu) production in p (p) over bar collisions at a center-of-mass energy of root s = 1.96 TeV. Using 1.7 fb(-1) of data collected by the D0 experiment at the Fermilab Tevatron Collider, we observe three candidate events with an expected background of 0.14(-0.02)(+0.03) events. The significance of this observation is 5.3 standard deviations. The combination of D0 results in this channel, as well as in ZZ -> l(+) l(-) v (v) over bar yields a significance of 5.7 standard deviations and a combined cross section of sigma(ZZ) = 1.60 +/- 0.63(stat)(-0.17)(+0.16)(syst) pb.
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17. |
- Abazov, V. M., et al.
(author)
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Search for Anomalous Top-Quark Couplings with the D0 Detector
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:9, s. 092002-
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Journal article (peer-reviewed)abstract
- Anomalous Wtb couplings modify the angular correlations of the top-quark decay products and change the single top-quark production cross section. We present limits on anomalous top-quark couplings by combining information from W boson helicity measurements in top-quark decays and anomalous coupling searches in the single top-quark final state. We set limits on right-handed vector couplings as well as left-handed and right-handed tensor couplings based on about 1 fb(-1) of data collected by the D0 experiment.
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18. |
- Abazov, V. M., et al.
(author)
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Search for large extra dimensions via single photon plus missing energy final states at root s=1.96 TeV
- 2008
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 101:1, s. 011601-:101, s. 011601-
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Journal article (peer-reviewed)abstract
- We report on a search for large extra dimensions in a data sample of approximately 1 fb(-1) of p (p) over bar collisions at root s=1.96 TeV. We investigate Kaluza-Klein graviton production with a photon and missing transverse energy in the final state. At the 95% C.L. we set limits on the fundamental mass scale M-D from 884 to 778 GeV for two to eight extra dimensions.
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19. |
- Abazov, V. M., et al.
(author)
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Search for Neutral Higgs Bosons at High tan beta in the b(h/H/A) -> b tau(+)tau(-) Channel
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:5, s. 051804-:102, s. 051804-
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Journal article (peer-reviewed)abstract
- The first search in p (p) over bar collisions at root s = 1.96 TeV for the production of neutral Higgs bosons in association with bottom quarks and decaying in two tau leptons is presented. The cross section for this process is enhanced in many extensions of the standard model, such as its minimal supersymmetric extension (MSSM) at large tan beta. The data, corresponding to an integrated luminosity of 328 pb(-1), were collected with the D0 detector at the Fermilab Tevatron Collider. An upper limit is set on the production cross section of neutral Higgs bosons in the mass range of 90 to 150 GeV, and this limit is used to exclude part of the MSSM parameter space.
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20. |
- Franceschini, N., et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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21. |
- Abazov, M, et al.
(author)
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Search for Long-Lived Charged Massive Particles with the D0 Detector
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:16, s. 161802-
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Journal article (peer-reviewed)abstract
- We search for long-lived charged massive particles using 1.1 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron pp Collider. Time-of-flight information is used to search for pair produced long-lived tau sleptons, gauginolike charginos, and Higgsino-like charginos. We find no evidence of a signal and set 95% C.L. cross section upper limits for staus, which vary from 0.31 to 0.04 pb for stau masses between 60 and 300 GeV. We also set lower mass limits of 206 GeV (171 GeV) for pair produced charged gauginos (Higgsinos).
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22. |
- Abazov, M, et al.
(author)
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Search for the Standard Model Higgs Boson in the Missing Energy and Acoplanar b-Jet Topology at root s=1.96 TeV
- 2008
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 101:25, s. 251802-
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Journal article (peer-reviewed)abstract
- We report a search for the standard model Higgs boson in the missing energy and acoplanar b-jet topology, using an integrated luminosity of 0.93 fb(-1) recorded by the D0 detector at the Fermilab Tevatron p (p) over bar Collider. The analysis includes signal contributions from p (p) over bar -> ZH -> v (v) over barb (b) over bar, as well as from WH production in which the charged lepton from the W boson decay is undetected. Neural networks are used to separate signal from background. In the absence of a signal, we set limits on sigma(p (p) over bar -> VH) x B(H -> b (b) over bar) at the 95% C.L. of 2.6-2.3 pb, for Higgs boson masses in the range 105-135 GeV, where V W, Z. The corresponding expected limits range from 2.8 to 2.0 pb.
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23. |
- Abazov, V. M., et al.
(author)
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Measurement of the top quark mass in final states with two leptons
- 2009
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In: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998 .- 1550-2368. ; 80, s. 092006-
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Journal article (peer-reviewed)abstract
- We present measurements of the top quark mass (m(t)) in tt candidate events with two final state leptons using 1 fb(-1) of data collected by the D0 experiment. Our data sample is selected by requiring two fully identified leptons or by relaxing one lepton requirement to an isolated track if at least one jet is tagged as a b jet. The top quark mass is extracted after reconstructing the event kinematics under the tt hypothesis using two methods. In the first method, we integrate over expected neutrino rapidity distributions, and in the second we calculate a weight for the possible top quark masses based on the observed particle momenta and the known parton distribution functions. We analyze 83 candidate events in the data and obtain m(t)=176.2 +/- 4.8(stat)+/- 2.1(sys) GeV and m(t)=173.2 +/- 4.9(stat)+/- 2.0(sys) GeV for the two methods, respectively. Accounting for correlations between the two methods, we combine the measurements to obtain m(t)=174.7 +/- 4.4(stat)+/- 2.0(sys) GeV.
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24. |
- Abazov, V. M., et al.
(author)
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Search for CP violation in B-s(0) -> mu(+) D-s(-) X decays in p(p)over-bar collisions at root s=1.96 TeV
- 2010
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In: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998 .- 1550-2368. ; 82:1, s. 012003-
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Journal article (peer-reviewed)abstract
- We have performed a search for CP violation in a sample of B-s(0) -> mu+Ds-X decays corresponding to 5 fb(-1) of proton-antiproton collisions collected by the D0 detector in Run II at the Fermilab Tevatron Collider. New physics in B-s(0) mixing could contribute a significant CP violating weak phase, which would be observed as a difference in the decay-time distribution for B-s(0) -> (B) over bar (0)(s) oscillated states versus that for (B) over bar (0)(s) -> B-s(0). A fit to the decay-time distributions of the B-s(0)/(B) over bar (0)(s) candidates yields the flavor-specific asymmetry as a(fs)(s) = [-1.7 +/- 9.1(stat)(-1.5)(+1.4)(syst) x 10(-3), which excludes CP violation due to new physics within the experimental sensitivity.
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25. |
- Abazov, M, et al.
(author)
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Measurement of differential Z/gamma* plus jet plus X cross sections in p(p)over-bar collisions at root S=1.96 TeV
- 2008
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 669:5, s. 278-286
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Journal article (peer-reviewed)abstract
- We present new measurements of differential cross sections for Z/gamma* (-> mu mu) + jet + X production in a 1 fb(-1) data sample collected with the DO detector in p (p) over bar collisions at root s = 1.96 TeV. Results include the first measurements differential in the Z/gamma* transverse momentum and rapidity, as well as new measurements differential in the leading jet transverse momentum and rapidity. Next-to-leading order perturbative QCD predictions are compared to the measurements, and reasonable agreement is observed, except in the region of low Z/gamma* transverse momentum. Predictions from two event generators based on matrix elements and parton showers, and one pure parton shower event generator are also compared to the measurements. These show significant overall normalization differences to the data and have varied success in describing the shape of the distributions.
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