| 1. |
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Adare, A., et al.
(author)
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Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
- 2015
-
In: Physical Review Letters. - 1079-7114. ; 115:14
-
Journal article (peer-reviewed)abstract
- We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
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| 9. |
- Adare, A., et al.
(author)
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Medium Modification of Jet Fragmentation in Au plus Au Collisions at root S-NN=200 GeV Measured in Direct Photon-Hadron Correlations
- 2013
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In: Physical Review Letters. - 1079-7114. ; 111:3
-
Journal article (peer-reviewed)abstract
- The jet fragmentation function is measured with direct photon-hadron correlations in p + p and Au + Au collisions at root S-NN = 200 GeV. The P-T of the photon is an excellent approximation to the initial P-T of the jet and the ratio Z(T) = P-T(h)/P-T(gamma) is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au + Au collisions while a photon isolation cut is applied in p + p. I-AA, the ratio of hadron yield opposite the photon in Au + Au to that in p + p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high Z(T). The associated hadron yield at low Z(T) is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.
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| 10. |
- Adare, A., et al.
(author)
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Search for dark photons from neutral meson decays in p plus p and d plus Au collisions at root s(NN)=200 GeV
- 2015
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:3
-
Journal article (peer-reviewed)abstract
- The standard model (SM) of particle physics is spectacularly successful, yet the measured value of the muon anomalous magnetic moment (g - 2)mu deviates from SM calculations by 3.6 sigma. Several theoretical models attribute this to the existence of a "dark photon," an additional U(1) gauge boson, which is weakly coupled to ordinary photons. The PHENIX experiment at the Relativistic Heavy Ion Collider has searched for a dark photon, U, in pi(0), eta -> gamma e(+)e(-) decays and obtained upper limits of O(2 x 10(-6)) on U-gamma mixing at 90% C.L. for the mass range 30 < m(U) < 90 MeV/c(2). Combined with other experimental limits, the remaining region in the U-gamma mixing parameter space that can explain the (g - 2)(mu) deviation from its SM value is nearly completely excluded at the 90% confidence level, with only a small region of 29 < m(U) < 32 MeV/c(2) remaining.
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| 11. |
- Adare, A., et al.
(author)
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Measurement of higher cumulants of net-charge multiplicity distributions in Au plus Au collisions at root s(NN)=7.7-200 GeV
- 2016
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 93:1
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Journal article (peer-reviewed)abstract
- We report the measurement of cumulants (C-n,n = 1, ..., 4) of the net-charge distributions measured within pseudorapidity (vertical bar eta vertical bar < 0.35) in Au + Au collisions at root s(NN) = 7.7-200 GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g., C-1/C-2, C-3/C-1) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of C-1/C-2 and C-3/C-1 can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy. The extracted baryon chemical potentials are in excellent agreement with a thermal-statistical analysis model.
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| 12. |
- Adare, A., et al.
(author)
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Centrality dependence of low-momentum direct-photon production in Au plus Au collisions at root s(NN)=200 GeV
- 2015
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:6
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Journal article (peer-reviewed)abstract
- The PHENIX experiment at RHIC has measured the centrality dependence of the direct photon yield from Au + Au collisions at root s(NN) = 200 GeV down to pT = 0.4 GeV/c. Photons are detected via photon conversions to e(+)e(-) pairs and an improved technique is applied that minimizes the systematic uncertainties that usually limit direct photon measurements, in particular at low pT. We find an excess of direct photons above the N-coll-scaled yield measured in p + p collisions. This excess yield is well described by an exponential distribution with an inverse slope of about 240 MeV/c in the pT range 0.6-2.0 GeV/c. While the shape of the pT distribution is independent of centrality within the experimental uncertainties, the yield increases rapidly with increasing centrality, scaling approximately with N-part(alpha), where alpha = 1.38 +/- 0.03(stat) +/- 0.07(syst).
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| 13. |
- Adare, A., et al.
(author)
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Low-mass vector-meson production at forward rapidity in p plus p collisions at root s=200 GeV
- 2014
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In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:5
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Journal article (peer-reviewed)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has measured low-mass vector-meson ,omega, rho, and phi, production through the dimuon decay channel at forward rapidity (1.2 < vertical bar y vertical bar < 2.2) in p + p collisions at root s = 200 GeV. The differential cross sections for these mesons are measured as a function of both p(T) and rapidity. We also report the integrated differential cross sections over 1 < p(T) < 7 GeV/c and 1.2 < vertical bar y vertical bar < 2.2: d sigma/dy(omega + rho rho -> mu mu) = 80 +/- 6(stat) +/- 12(syst)nb and d sigma/dy(phi -> mu mu) = 27 +/- 3(stat) +/- 4(syst)nb. These results are compared with midrapidity measurements and calculations.
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| 14. |
- Adare, A., et al.
(author)
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phi meson production in d plus Au collisions at root s(NN)=200 GeV
- 2015
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:4
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Journal article (peer-reviewed)abstract
- The PHENIX Collaboration has measured phi meson production in d + Au collisions at root s(NN) = 200 GeV using the dimuon and dielectron decay channels. The phi meson is measured in the forward (backward) d-going (Au-going) direction, 1.2 < y < 2.2 (-2.2 < y < -1.2) in the transverse-momentum (pT) range from 1-7 GeV/c and at midrapidity vertical bar y vertical bar < 0.35 in the p(T) range below 7 GeV/c. The phi meson invariant yields and nuclear-modification factors as a function of p(T), rapidity, and centrality are reported. An enhancement of phi meson production is observed in the Au-going direction, while suppression is seen in the d-going direction, and no modification is observed at midrapidity relative to the yield in p + p collisions scaled by the number of binary collisions. Similar behavior was previously observed for inclusive charged hadrons and open heavy flavor, indicating similar cold-nuclear-matter effects.
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| 15. |
- Adare, A., et al.
(author)
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Measurement of gamma(1S+2S+3S) production in p plus p and Au plus Au collisions at root sNN=200 GeV
- 2015
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:2
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Journal article (peer-reviewed)abstract
- Measurements of bottomonium production in heavy-ion and p + p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three states, (1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au + Au and p + p collisions at root sNN = 200 GeV. The (1S + 2S + 3S) -> e(+)e(-) differential cross section at midrapidity was found to be B(ee)d sigma/dy = 108 +/- 38 (stat) +/- 15 (syst) +/- 11 (luminosity) pb in p + p collisions. The nuclear modification factor in the 30% most central Au + Au collisions indicates a suppression of the total. state yield relative to the extrapolation from p + p collision data. The suppression is consistent with measurements made by STAR at RHIC and at higher energies by the CMS experiment at the Large Hadron Collider.
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| 16. |
- Adare, A., et al.
(author)
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Systematic study of charged-pion and kaon femtoscopy in Au plus Au collisions at root s(NN)=200 GeV
- 2015
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:3
-
Journal article (peer-reviewed)abstract
- We present a systematic study of charged-pion and kaon interferometry in Au + Au collisions at root s(NN) = 200 GeV. The kaon mean source radii are found to be larger than pion radii in the outward and longitudinal directions for the same transverse mass; this difference increases for more central collisions. The azimuthal-angle dependence of the radii was measured with respect to the second-order event plane and similar oscillations of the source radii were found for pions and kaons. Hydrodynamic models qualitatively describe the similar oscillations of the mean source radii for pions and kaons, but they do not fully describe the transverse-mass dependence of the oscillations.
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| 17. |
- Adare, A., et al.
(author)
-
gamma (1S+2S+3S) production in d plus Au and p plus p collisions at root s(NN)=200 GeV and cold-nuclear-matter effects
- 2013
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 87:4
-
Journal article (peer-reviewed)abstract
- The three gamma states, gamma (1S + 2S + 3S), are measured in d + Au and p + p collisions at root s(NN) = 200 GeV and rapidities 1.2 < vertical bar y vertical bar < 2.2 by the PHENIX experiment at the Relativistic Heavy Ion Collider. Cross sections for the inclusive gamma (1S + 2S + 3S) production are obtained. The inclusive yields per binary collision for d + Au collisions relative to those in p + p collisions (R-dAu) are found to be 0.62 +/- 0.26 (stat) +/- 0.13 (syst) in the gold-going direction and 0.91 +/- 0.33 (stat) +/- 0.16 (syst) in the deuteron-going direction. The measured results are compared to a nuclear-shadowing model, EPS09 [Eskola et al., J. High Energy Phys. 04 (2009) 065], combined with a final-state breakup cross section, sigma(br), and compared to lower energy p + A results. We also compare the results to the PHENIX J/psi results [Adare et al., Phys. Rev. Lett. 107, 142301 (2011)]. The rapidity dependence of the observed gamma suppression is consistent with lower energy p + A measurements. DOI: 10.1103/PhysRevC.87.044909
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| 18. |
- Adare, A., et al.
(author)
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Cold-Nuclear-Matter Effects on Heavy-Quark Production at Forward and Backward Rapidity in d + Au Collisions at root s(NN) = GeV
- 2014
-
In: Physical Review Letters. - 1079-7114. ; 112:25
-
Journal article (peer-reviewed)abstract
- The PHENIX experiment has measured open heavy-flavor production via semileptonic decay over the transverse momentum range 1 < p(T) < 6 GeV/c at forward and backward rapidity (1.4 < vertical bar y vertical bar < 2.0) in d + Au and p + p collisions at root s(NN) = 200 GeV. In central d + Au collisions, relative to the yield in p + p collisions scaled by the number of binary nucleon-nucleon collisions, a suppression is observed at forward rapidity (in the d-going direction) and an enhancement at backward rapidity (in the Au-going direction). Predictions using nuclear-modified-parton-distribution functions, even with additional nuclear-p(T) broadening, cannot simultaneously reproduce the data at both rapidity ranges, which implies that these models are incomplete and suggests the possible importance of final-state interactions in the asymmetric d + Au collision system. These results can be used to probe cold-nuclear-matter effects, which may significantly affect heavy-quark production, in addition to helping constrain the magnitude of charmonia-breakup effects in nuclear matter.
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| 19. |
- Adare, A, et al.
(author)
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Measurement of Long-Range Angular Correlation and Quadrupole Anisotropy of Pions and (Anti)Protons in Central d+Au Collisions at sqrt[s_{NN}]=200 GeV.
- 2015
-
In: Physical Review Letters. - 1079-7114. ; 114:19
-
Journal article (peer-reviewed)abstract
- We present azimuthal angular correlations between charged hadrons and energy deposited in calorimeter towers in central d+Au and minimum bias p+p collisions at sqrt[s_{NN}]=200 GeV. The charged hadron is measured at midrapidity |η|<0.35, and the energy is measured at large rapidity (-3.7<η<-3.1, Au-going direction). An enhanced near-side angular correlation across |Δη|>2.75 is observed in d+Au collisions. Using the event plane method applied to the Au-going energy distribution, we extract the anisotropy strength v_{2} for inclusive charged hadrons at midrapidity up to p_{T}=4.5 GeV/c. We also present the measurement of v_{2} for identified π^{±} and (anti)protons in central d+Au collisions, and observe a mass-ordering pattern similar to that seen in heavy-ion collisions. These results are compared with viscous hydrodynamic calculations and measurements from p+Pb at sqrt[s_{NN}]=5.02 TeV. The magnitude of the mass ordering in d+Au is found to be smaller than that in p+Pb collisions, which may indicate smaller radial flow in lower energy d+Au collisions.
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| 20. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)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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| 21. |
- Wang, QBS, et al.
(author)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)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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| 22. |
- Adare, A., et al.
(author)
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Charged-pion cross sections and double-helicity asymmetries in polarized p plus p collisions at root s=200 GeV
- 2015
-
In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 91:3
-
Journal article (peer-reviewed)abstract
- We present midrapidity charged-pion invariant cross sections, the ratio of the pi(-) to pi(+) cross sections and the charge-separated double-spin asymmetries in polarized p + p collisions at root s = p + 200 GeV. While the cross section measurements are consistent within the errors of next-to-leading-order (NLO) perturbative quantum chromodynamics predictions (pQCD), the same calculations overestimate the ratio of the charged-pion cross sections. This discrepancy arises from the cancellation of the substantial systematic errors associated with the NLO-pQCD predictions in the ratio and highlights the constraints these data will place on flavor-dependent pion fragmentation functions. The charge-separated pion asymmetries presented here sample an x range of similar to 0.03-0.16 and provide unique information on the sign of the gluon-helicity distribution.
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| 23. |
- Adare, A., et al.
(author)
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Cross Section and Parity-Violating Spin Asymmetries of W-+/- Boson Production in Polarized p plus p Collisions at root s=500 Gev
- 2011
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In: Physical Review Letters. - 1079-7114. ; 106:6
-
Journal article (peer-reviewed)abstract
- Large parity-violating longitudinal single-spin asymmetries A(L)(e+) = 0.86(-0.14)(+0.30) and Ae(L)(e-) = 0.88(-0.71)(+0.12) are observed for inclusive high transverse momentum electrons and positrons in polarized p + p collisions at a center-of-mass energy of root s = 500 GeV with the PHENIX detector at RHIC. These e(+/-) come mainly from the decay of W-+/- and Z(0) bosons, and their asymmetries directly demonstrate parity violation in the couplings of the W-+/- to the light quarks. The observed electron and positron yields were used to estimate W-+/- boson production cross sections for the e(+/-) channels of sigma(pp -> W+X) X BR(W+ -> e(+) nu(e)) = 144.1 +/- 21.2(stat)(-10.3)(+3.4)(syst) +/- 21.6(norm) pb, and sigma(pp -> W-X) X BR(W- -> e(-) (nu) over bar (e)) = 3.17 +/- 12.1(stat)(-8.2)(+10.1)(syst) +/- 4.8(norm) pb.
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| 24. |
- Adare, A., et al.
(author)
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Double-spin asymmetry of electrons from heavy-flavor decays in p plus p collisions at root s=200 GeV
- 2013
-
In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:1
-
Journal article (peer-reviewed)abstract
- We report on the first measurement of the double-spin asymmetry, A(LL), of electrons from the decays of hadrons containing heavy flavor in longitudinally polarized p + p collisions at root s = 200 GeV for p(T) = 0.5 to 3.0 GeV/c. The asymmetry was measured at midrapidity (vertical bar eta vertical bar < 0.35) with the PHENIX detector at the Relativistic Heavy Ion Collider. The measured asymmetries are consistent with zero within the statistical errors. We obtained a constraint for the polarized gluon distribution in the proton of vertical bar Delta g/g(log(10)(x) = -1.6(-0.4)(+0.5), mu = m(T)(c)vertical bar(2) < 0.030 (1 sigma) based on a leading-order perturbative quantum chromodynamics model, using the measured asymmetry. DOI: 10.1103/PhysRevD.87.012011
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| 25. |
- Adare, A., et al.
(author)
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Inclusive cross section and double-helicity asymmetry for pi(0) production at midrapidity in p plus p collisions at root s=510 GeV
- 2016
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In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 93:1
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Journal article (peer-reviewed)abstract
- PHENIX measurements are presented for the cross section and double-helicity asymmetry (A(LL)) in inclusive pi(0) production at midrapidity from p + p collisions at root s = 510 GeV from data taken in 2012 and 2013 at the Relativistic Heavy Ion Collider. The next-to-leading-order perturbative-quantum-chromodynamics theory calculation is in excellent agreement with the presented cross section results. The calculation utilized parton-to-pion fragmentation functions from the recent DSS14 global analysis, which prefer a smaller gluon-to-pion fragmentation function. The pi(0)A(LL) results follow an increasingly positive asymmetry trend with p(T) and root s with respect to the predictions and are in excellent agreement with the latest global analysis results. This analysis incorporated earlier results on pi(0) and jet A(LL) and suggested a positive contribution of gluon polarization to the spin of the proton Delta G for the gluon momentum fraction range x > 0.05. The data presented here extend to a currently unexplored region, down to x similar to 0.01, and thus provide additional constraints on the value of Delta G.
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| 26. |
- Adare, A., et al.
(author)
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Inclusive double-helicity asymmetries in neutral-pion and eta-meson production in + collisions at root s=200 GeV
- 2014
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In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:1
-
Journal article (peer-reviewed)abstract
- Results are presented from data recorded in 2009 by the PHENIX experiment at the Relativistic Heavy Ion Collider for the double-longitudinal spin asymmetry, A(LL), for pi(0) and eta production in root s = 200 GeV polarized p + p collisions. Comparison of the pi(0) results with different theory expectations based on fits of other published data showed a preference for small positive values of gluon polarization, Delta G, in the proton in the probed Bjorken x range. The effect of adding the new 2009 pi(0) data to a recent global analysis of polarized scattering data is also shown, resulting in a best fit Delta G(DSSV)([0.05,0.2]) = 0.06(-0.15)(+0.11) in the range 0.05 < x < 0.2, with the uncertainty at Delta chi(2) = 9 when considering only statistical experimental uncertainties. Shifting the PHENIX data points by their systematic uncertainty leads to a variation of the best-fit value of Delta G(DSSV)([0.05,0.2]) between 0.02 and 0.12, demonstrating the need for full treatment of the experimental systematic uncertainties in future global analyses.
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| 27. |
- Adare, A., et al.
(author)
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Nuclear matter effects on J/psi production in asymmetric Cu plus Au collisions at root S-NN=200 GeV
- 2014
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:6
-
Journal article (peer-reviewed)abstract
- We report on J/psi production from asymmetric Cu + Au heavy-ion collisions at root S-NN = 200 GeV at the Relativistic Heavy Ion Collider at both forward (Cu-going direction) and backward (Au-going direction) rapidities. The nuclear modification of J/psi yields in Cu + Au collisions in the Au-going direction is found to be comparable to that inAu + Au collisions when plotted as a function of the number of participating nucleons. In the Cu-going direction, J/psi production shows a stronger suppression. This difference is comparable in magnitude and has the same sign as the difference expected from shadowing effects due to stronger low-x gluon suppression in the larger Au nucleus.
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| 28. |
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| 29. |
- Adare, A., et al.
(author)
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Evolution of pi(0) Suppression in Au plus Au Collisions from root s(NN)=39 to 200 GeV
- 2012
-
In: Physical Review Letters. - 1079-7114. ; 109:15
-
Journal article (peer-reviewed)abstract
- Neutral-pion pi(0) spectra were measured at midrapidity (vertical bar y vertical bar < 0.35) in Au + Au collisions at root s(NN) = 39 and 62.4 GeV and compared with earlier measurements at 200 GeV in a transverse-momentum range of 1 < p(T) < 10 GeV/c. The high-p(T) tail is well described by a power law in all cases, and the powers decrease significantly with decreasing center-of-mass energy. The change of powers is very similar to that observed in the corresponding spectra for p + p collisions. The nuclear modification factors (RAA) show significant suppression, with a distinct energy, centrality, and p(T) dependence. Above p(T) = 7 GeV/c, R-AA is similar for root sNN = 62.4 and 200 GeV at all centralities. Perturbative-quantum-chromodynamics calculations that describe R-AA well at 200 GeV fail to describe the 39 GeV data, raising the possibility that, for the same p(T) region, the relative importance of initial-state effects and soft processes increases at lower energies. The p(T) range where pi(0) spectra in central Au + Au collisions have the same power as in p + p collisions is approximate to 5 and 7 GeV/c for root sNN = 200 and 62.4 GeV, respectively. For the root sNN = 39 GeV data, it is not clear whether such a region is reached, and the x(T) dependence of the x(T)-scaling power-law exponent is very different from that observed in the root sNN = 62 and 200 GeV data, providing further evidence that initial-state effects and soft processes mask the in-medium suppression of hardscattered partons to higher p(T) as the collision energy decreases.
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| 30. |
- Adare, A., et al.
(author)
-
Heavy-quark production and elliptic flow in Au plus Au collisions at root(NN)-N-S=62.4 GeV
- 2015
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:4
-
Journal article (peer-reviewed)abstract
- We present measurements of electrons and positrons from the semileptonic decays of heavy-flavor hadrons at midrapidity (vertical bar gamma vertical bar < 0.35) in Au + Au collisions at root(NN)-N-S = 62.4 GeV. The data were collected in 2010 by the PHENIX experiment that included the new hadron-blind detector. The invariant yield of electrons from heavy-flavor decays is measured as a function of transverse momentum in the range 1 < p(T)(e) < 5 GeV/c. The invariant yield per binary collision is slightly enhanced above the p + p reference in Au + Au 0%-20%, 20%-40%, and 40%-60% centralities at a comparable level. At this low beam energy this may be a result of the interplay between initial-state Cronin effects, final-state flow, and energy loss in medium. The v(2) of electrons from heavy-flavor decays is nonzero when averaged between 1.3 < p(T)(e) < 2.5 GeV/c for 0%-40% centrality collisions at root(NN)-N-S = 62.4 GeV. For 20%-40% centrality collisions, the v(2) at root(NN)-N-S = 62.4 GeV is smaller than that for heavy-flavor decays at root(NN)-N-S = 200 GeV. The v2 of the electrons from heavy-flavor decay at the lower beam energy is also smaller than v(2) for pions. Both results indicate that the heavy quarks interact with the medium formed in these collisions, but they may not be at the same level of thermalization with the medium as observed at root(NN)-N-S = 200 GeV.
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| 31. |
- Adare, A., et al.
(author)
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J/psi suppression at forward rapidity in Au plus Au collisions at root s(NN)=39 and 62.4 GeV
- 2012
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 86:6
-
Journal article (peer-reviewed)abstract
- We present measurements of the J/psi invariant yields in root s(NN) = 39 and 62.4 GeV Au + Au collisions at forward rapidity (1.2 < vertical bar y vertical bar < 2.2). Invariant yields are presented as a function of both collision centrality and transverse momentum. Nuclear modifications are obtained for central relative to peripheral Au + Au collisions (R-CP) and for various centrality selections in Au + Au relative to scaled p + p cross sections obtained from other measurements (R-AA). The observed suppression patterns at 39 and 62.4 GeV are quite similar to those previously measured at 200 GeV. This similar suppression presents a challenge to theoretical models that contain various competing mechanisms with different energy dependencies, some of which cause suppression and others enhancement. DOI: 10.1103/PhysRevC.86.064901
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| 32. |
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| 33. |
- Meech, K. J., et al.
(author)
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EPOXI: Comet 103P/Hartley 2 Observations from a Worldwide Campaign
- 2011
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In: Astrophysical Journal Letters. - London : IOP. - 2041-8213 .- 2041-8205. ; 734:L1, s. 1-9
-
Journal article (peer-reviewed)abstract
- Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4?hr. Starting in 2010 August the period changed from 16.6?hr to near 19?hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
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| 34. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 35. |
- Kaptoge, S., et al.
(author)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
-
Journal article (peer-reviewed)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 36. |
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| 37. |
- Adolphi, C., et al.
(author)
-
Exclusive omega meson muoproduction on transversely polarised protons
- 2017
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In: Nuclear Physics B. - : ELSEVIER SCIENCE BV. - 0550-3213 .- 1873-1562. ; 915, s. 454-475
-
Journal article (peer-reviewed)abstract
- Exclusive production of omega mesons was studied at the COMPASS experiment by scattering 160GeV/c muons off transversely polarised protons. Five single-spin and three double-spin azimuthal asymmetries were measured in the range of photon virtuality 1(GeV/c)(2) < Q(2) < 10(GeV/c)(2), Bjorken scaling variable 0.003 < xBj < 0.3 and transverse momentum squared of the omega meson 0.05(GeV/c)(2) < p(T)(2) < 0.5(GeV/c)(2). The measured asymmetries are sensitive to the nucleon helicity-flip Generalised Parton Distributions (GPD) Et hat are related to the orbital angular momentum of quarks, the chiral-odd GPDs H-T that are related to the transversity Parton Distribution Functions, and the sign of the pi omega transition form factor. The results are compared to recent calculations of a GPD-based model.
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| 38. |
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| 39. |
- Adolph, C., et al.
(author)
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Leading-order determination of the gluon polarisation from semi-inclusive deep inelastic scattering data
- 2017
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In: European Physical Journal C. - : SPRINGER. - 1434-6044 .- 1434-6052. ; 77:4
-
Journal article (peer-reviewed)abstract
- Using a novel analysis technique, the gluon polarisation in the nucleon is re-evaluated using the longitudinal double-spin asymmetry measured in the cross section of semi-inclusive single-hadron muoproduction with photon virtuality Q(2) > 1 ( GeV/c)(2). The data were obtained by the COMPASS experiment at CERN using a 160 GeV/c polarised muon beam impinging on a polarised (LiD)-Li-6 target. By analysing the full range in hadron transverse momentum p(T), the different pT-dependences of the underlying processes are separated using a neural-network approach. In the absence of pQCD calculations at next-to-leading order in the selected kinematic domain, the gluon polarisation Delta g/g is evaluated at leading order in pQCD at a hard scale of mu(2) = < Q(2) > = 3( GeV/c)(2). It is determined in three intervals of the nucleon momentum fraction carried by gluons, x(g), covering the range 0.04< x(g)< 0.28 and does not exhibit a significant dependence on xg. The average over the three intervals, < Delta g/g > = 0.113 +/- 0.038(stat) +/- 0.036( syst) at < x(g) > approximate to 0.10, suggests that the gluon polarisation is positive in the measured x(g) range.
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| 40. |
- Adolph, C., et al.
(author)
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Multiplicities of charged pions and charged hadrons from deep-inelastic scattering of muons off an isoscalar target
- 2017
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In: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 764, s. 1-10
-
Journal article (peer-reviewed)abstract
- Multiplicities of charged pions and charged hadrons produced in deep-inelastic scattering were measured in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y and the relative hadron energy z. Data were obtained by the COMPASS Collaboration using a 160 GeV muon beam and an isoscalar target ((LiD)-Li-6). They cover the kinematic domain in the photon virtuality Q(2) > 1 (GeV/c) 2, 0.004 < x < 0.4, 0.2 < z < 0.85 and 0.1 < y < 0.7. In addition, a leading-order pQCD analysis was performed using the pion multiplicity results to extract quark fragmentation functions.
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| 41. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 42. |
- Patrignani, C., et al.
(author)
-
REVIEW OF PARTICLE PHYSICS : Particle Data Group
- 2016
-
In: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 40:10
-
Journal article (peer-reviewed)abstract
- The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including new reviews on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group (http://pdg.lbl.gov). The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available.
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| 43. |
- Adolph, C., et al.
(author)
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Resonance production and pi pi S-wave in pi(-) + p -> pi(-) pi(-) pi(+) + p(recoil) at 190 GeV/c
- 2017
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In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 95:3
-
Journal article (peer-reviewed)abstract
- The COMPASS collaboration has collected the currently largest data set on diffractively produced pi(-) pi(-) pi(+) final states using a negative pion beam of 190 GeV/c momentum impinging on a stationary proton target. This data set allows for a systematic partial-wave analysis in 100 bins of three-pion mass, 0.5 < m(3 pi) < 2.5 GeV/c(2), and in 11 bins of the reduced four-momentum transfer squared, 0.1 < t' < 1.0 (GeV/c)(2). This two-dimensional analysis offers sensitivity to genuine one-step resonance production, i.e. the production of a state followed by its decay, as well as to more complex dynamical effects in nonresonant 3 pi production. In this paper, we present detailed studies on selected 3p partial waves with J(PC) = 0(-+) ,1(++) ,2(-+) ,2(++) ,and 4(++). In these waves, we observe the well-known groundstate mesons as well as a new narrow axial-vector meson a(1)(1420) decaying into f(0) (980)pi. In addition, we present the results of a novel method to extract the amplitude of the pi(-)pi(+) subsystem with I(G)J(PC) = 0(+)0(++) in various partial waves from the pi(-)pi(-)pi(+) data. Evidence is found for correlation of the f (0)(980) and f(0)(1500) appearing as intermediate pi(-)pi(+) isobars in the decay of the known pi(1800) and pi(2)(1880).
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| 44. |
- Adolph, C., et al.
(author)
-
Interplay among transversity induced asymmetries in hadron leptoproduction
- 2016
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 753, s. 406-411
-
Journal article (peer-reviewed)abstract
- In the fragmentation of a transversely polarized quark several left-right asymmetries are possible for the hadrons in the jet. When only one unpolarized hadron is selected, it exhibits an azimuthal modulation known as the Collins effect. When a pair of oppositely charged hadrons is observed, three asymmetries can be considered, a di-hadron asymmetry and two single hadron asymmetries. In lepton deep inelastic scattering on transversely polarized nucleons all these asymmetries are coupled with the transversity distribution. From the high statistics COMPASS data on oppositely charged hadron-pair production we have investigated for the first time the dependence of these three asymmetries on the difference of the azimuthal angles of the two hadrons. The similarity of transversity induced single and di-hadron asymmetries is discussed. A new analysis of the data allows quantitative relationships to be established among them, providing for the first time strong experimental indication that the underlying fragmentation mechanisms are all driven by a common physical process.
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| 45. |
- Adolph, C., et al.
(author)
-
The spin structure function g(1)(p) of the proton and a test of the Bjorken sum rule
- 2016
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 753, s. 18-28
-
Journal article (peer-reviewed)abstract
- New results for the double spin asymmetry A(1)(p) and the proton longitudinal spin structure function g(1)(p) are presented. They were obtained by the COMPASS Collaboration using polarised 200 GeV muons scattered off a longitudinally polarised NH3 target. The data were collected in 2011 and complement those recorded in 2007 at 160 GeV, in particular at lower values of x. They improve the statistical precision of g(1)(p)(x) by about a factor of two in the region x less than or similar to 0.02. A next-to-leading order QCD fit to the g(1) world data is performed. It leads to a new determination of the quark spin contribution to the nucleon spin, Delta Sigma, ranging from 0.26 to 0.36, and to a re-evaluation of the first moment of g(1)(p). The uncertainty of Delta Sigma is mostly due to the large uncertainty in the present determinations of the gluon helicity distribution. A new evaluation of the Bjorken sum rule based on the COMPASS results for the non-singlet structure function g(1)(NS) (x, Q(2)) yields as ratio of the axial and vector coupling constants vertical bar gA/gV vertical bar = 1.22 +/- 0.05 (stat.) +/- 0.10 (syst.), which validates the sum rule to an accuracy of about 9%.
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| 46. |
- Olive, K. A., et al.
(author)
-
REVIEW OF PARTICLE PHYSICS Particle Data Group
- 2014
-
In: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 38:9
-
Research review (peer-reviewed)abstract
- The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.
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| 47. |
- Amare, A. T., et al.
(author)
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Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
- 2021
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 2457-2470
-
Journal article (peer-reviewed)abstract
- Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi(+)Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
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| 48. |
- Cearns, M., et al.
(author)
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- 2022
-
In: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 220:4, s. 219-228
-
Journal article (peer-reviewed)abstract
- Background Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. Aims To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder. Method This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi(+)Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework. Results The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data. Conclusions Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
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| 49. |
- Le Clerc, S., et al.
(author)
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HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
- 2021
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 x 10(-3); FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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| 50. |
- Reinbold, C. S., et al.
(author)
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Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder
- 2018
-
In: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
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