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| 2. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 3. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 4. |
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| 5. |
- 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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| 6. |
- Aaltonen, T., et al.
(författare)
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Tevatron Run II combination of the effective leptonic electroweak mixing angle
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:11
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Tidskriftsartikel (refereegranskat)abstract
- Drell-Yan lepton pairs produced in the process p (p) over bar -> l(+)l(-) + X through an intermediate gamma*/Z boson have an asymmetry in their angular distribution related to the spontaneous symmetry breaking of the electroweak force and the associated mixing of its neutral gauge bosons. The CDF and D0 experiments have measured the effective-leptonic electroweak mixing parameter sin(2) theta(lept)(eff) using electron and muon pairs selected from the full Tevatron proton-antiproton data sets collected in 2001-2011, corresponding to 9-10 fb(-1) of integrated luminosity. The combination of these measurements yields the most precise result from hadron colliders, sin(2)theta(lept)(eff) = 0.23148 +/- 0.00033. This result is consistent with, and approaches in precision, the best measurements from electron-positron colliders. The standard model inference of the on-shell electroweak mixing parameter sin(2) theta(W), or equivalently the W-boson mass M-W, using the ZFITTER software package yields sin(2) theta(W) = 0.22324 +/- 0.00033 or equivalently, M-W = 80.367 +/- 0.017 GeV/c(2).
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| 7. |
- Aaltonen, T., et al.
(författare)
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Combination of CDF and D0 W-Boson mass measurements
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:5, s. 052018-
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Tidskriftsartikel (refereegranskat)abstract
- We summarize and combine direct measurements of the mass of the W boson in root s = 1.96 TeV proton-antiproton collision data collected by CDF and D0 experiments at the Fermilab Tevatron Collider. Earlier measurements from CDF and D0 are combined with the two latest, more precise measurements: a CDF measurement in the electron and muon channels using data corresponding to 2.2 fb(-1) of integrated luminosity, and a D0 measurement in the electron channel using data corresponding to 4.3 fb(-1) of integrated luminosity. The resulting Tevatron average for the mass of the W boson is M-W = 80387 +/- 16 MeV. Including measurements obtained in electron-positron collisions at LEP yields the most precise value of M-W = 80385 +/- 15 MeV.
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| 8. |
- Aaltonen, T., et al.
(författare)
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Combination of measurements of the top-quark pair production cross section from the Tevatron Collider
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:7
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Tidskriftsartikel (refereegranskat)abstract
- We combine six measurements of the inclusive top-quark pair (t(sic)) production cross section (sigma(t)(sic)) from data collected with the CDF and D0 detectors at the Fermilab Tevatron with proton-antiproton collisions at root s = 1.96 TeV. The data correspond to integrated luminosities of up to 8.8 fb(-1). We obtain a value of sigma tt = 7.60 +/- 0.41 pb for a top-quark mass of m(t) = 172.5 GeV. The contributions to the uncertainty are 0.20 pb from statistical sources, 0.29 pb from systematic sources, and 0.21 pb from the uncertainty on the integrated luminosity. The result is in good agreement with the standard model expectation of 7.35(-0.33)(+0.28) pb at next-to-next-to-leading order and next-to-next-to leading logarithms in perturbative QCD.
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| 9. |
- Aaltonen, T., et al.
(författare)
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Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron
- 2018
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 120:4
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Tidskriftsartikel (refereegranskat)abstract
- The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of root s = 1.96 TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is A(FB)(t (t) over bar) = 0.128 +/- 0.025. The combined inclusive and differential asymmetries are consistent with recent standard model predictions.
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| 10. |
- Aaltonen, T., et al.
(författare)
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Evidence for a Particle Produced in Association with Weak Bosons and Decaying to a Bottom-Antibottom Quark Pair in Higgs Boson Searches at the Tevatron
- 2012
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 109:7, s. 071804-
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Tidskriftsartikel (refereegranskat)abstract
- We combine searches by the CDF and D0 Collaborations for the associated production of a Higgs boson with a W or Z boson and subsequent decay of the Higgs boson to a bottom-antibottom quark pair. The data, originating from Fermilab Tevatron p (p) over bar collisions at root s = 1.96 TeV, correspond to integrated luminosities of up to 9.7 fb(-1). The searches are conducted for a Higgs boson with mass in the range 100-150 GeV/c(2). We observe an excess of events in the data compared with the background predictions, which is most significant in the mass range between 120 and 135 GeV/c(2). The largest local significance is 3.3 standard deviations, corresponding to a global significance of 3.1 standard deviations. We interpret this as evidence for the presence of a new particle consistent with the standard model Higgs boson, which is produced in association with a weak vector boson and decays to a bottom-antibottom quark pair.
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