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The process e+e−→ϕη is studied at 22 center-of-mass energy points (√s) between 2.00 and 3.08 GeV using 715 pb−1 of data collected with the BESIII detector. The measured Born cross section of e+e−→ϕη is found to be consistent with BABAR measurements, but with improved precision. A resonant structure around 2.175 GeV is observed with a significance of 6.9σ with mass (2163.5±6.2±3.0) MeV/c2 and width (31.1+21.1−11.6±1.1) MeV, where the first uncertainties are statistical and the second are systematic.
By analyzing 6.32 fb − 1 of e+ e− annihilation data collected at the center-of-mass energies between 4.178 and 4.226 GeV with the BESIII detector, we determine the branching fraction of the leptonic decay D + s → τ + ντ, with τ+ → π + π0¯ντ, to be B D + s → τ + ν τ = (5.29 ± 0.25 stat ± 0.20 syst) %. We estimate the product of the Cabibbo-Kobayashi-Maskawa matrix element |Vcs|and the D + s decay constant f D + s to be f D + s|Vcs| = (244.8 ± 5.8 stat ± 4.8syst) MeV, using the known values of the τ + and D + s masses as well as the D + s lifetime, together with our branching fraction measurement. Combining the value of |Vcs| obtained from a global fit in the standard model and f D + s from lattice quantum chromodynamics, we obtain f D + s = (251.6 ± 5.9 stat ± 4.9syst) MeV and |Vcs| = 0.980 ± 0.023 stat ± 0.019 syst. Using the branching fraction of B D + s → μ + νμ = (5.35±0.21)×10−3, we obtain the ratio of the branching fractions B D + s → τ + ντ/B D +s → μ+νμ = 9.89±0.71, which is consistent with the standard model prediction of lepton flavor universality.
The Born cross sections of the e+e− → D*+D*− and e+e− → D*+D− processes are measured using e+e− collision data collected with the BESIII experiment at center-of-mass energies from 4.085 to 4.600 GeV, corresponding to an integrated luminosity of 15.7 fb−1. The results are consistent with and more precise than the previous measurements by the Belle, Babar and CLEO collaborations. The measurements are essential for understanding the nature of vector charmonium and charmonium-like states.
We report a measurement of the observed cross sections of e+ e− → J/ψX based on 3.21 fb − 1 of data accumulated at energies from 3.645 to 3.891 GeV with the BESIII detector operated at the BEPCII collider. In analysis of the cross sections, we measured the decay branching fractions of B(ψ(3686) → J/ψX) = (64.4 ± 0.6 ± 1.6)% and B(ψ(3770) → J/ψX) = (0.5 ± 0.2 ± 0.1)% for the first time. The energy-dependent line shape of these cross sections cannot be well described by two Breit-Wigner (BW) amplitudes of the expected decays ψ (3686) → J/ψX and ψ(3770) → J/ψX. Instead, it can be better described with one more BW amplitude of the decay R(3760)→ J/ψX. Under this assumption, we extracted the R (3760) mass M R (3760 ) = 3766.2 ± 3.8 ± 0.4 MeV/c2, total width Γ tot R ( 3760 ) = 22.2 ± 5.9 ± 1.4 MeV, and product of leptonic width and decay branching fraction
ΓeeR(3760) B[R(3760) → J/ψX] = (79.4 ± 85.5 ± 11.7) eV. The significance of the R(3760) is 5.3σ. The first uncertainties of these measured quantities are from fits to the cross sections and second systematic.
The first measurements of dielectron production at midrapidity (|ηc|<0.8) in proton-proton and proton-lead collisions at sNN−−−√ = 5.02 TeV at the LHC are presented. The dielectron cross section is measured with the ALICE detector as a function of the invariant mass mee and the pair transverse momentum pT,ee in the ranges mee < 3.5 GeV/c2 and pT,ee < 8.0 GeV/c2, in both collision systems. In proton-proton collisions, the charm and beauty cross sections are determined at midrapidity from a fit to the data with two different event generators. This complements the existing dielectron measurements performed at s√ = 7 and 13 TeV. The slope of the s√ dependence of the three measurements is described by FONLL calculations. The dielectron cross section measured in proton-lead collisions is in agreement, within the current precision, with the expected dielectron production without any nuclear matter effects for e+e− pairs from open heavy-flavor hadron decays. For the first time at LHC energies, the dielectron production in proton-lead and proton-proton collisions are directly compared at the same sNN−−−√ via the dielectron nuclear modification factor RpPb. The measurements are compared to model calculations including cold nuclear matter effects, or additional sources of dielectrons from thermal radiation.
The first measurements of dielectron production at midrapidity (|ηc|<0.8) in proton-proton and proton-lead collisions at sNN−−−√ = 5.02 TeV at the LHC are presented. The dielectron cross section is measured with the ALICE detector as a function of the invariant mass mee and the pair transverse momentum pT,ee in the ranges mee < 3.5 GeV/c2 and pT,ee < 8.0 GeV/c2, in both collision systems. In proton-proton collisions, the charm and beauty cross sections are determined at midrapidity from a fit to the data with two different event generators. This complements the existing dielectron measurements performed at s√ = 7 and 13 TeV. The slope of the s√ dependence of the three measurements is described by FONLL calculations. The dielectron cross section measured in proton-lead collisions is in agreement, within the current precision, with the expected dielectron production without any nuclear matter effects for e+e− pairs from open heavy-flavor hadron decays. For the first time at LHC energies, the dielectron production in proton-lead and proton-proton collisions are directly compared at the same sNN−−−√ via the dielectron nuclear modification factor RpPb. The measurements are compared to model calculations including cold nuclear matter effects, or additional sources of dielectrons from thermal radiation.
The first measurements of dielectron production at midrapidity (|ηc|<0.8) in proton-proton and proton-lead collisions at sNN−−−√ = 5.02 TeV at the LHC are presented. The dielectron cross section is measured with the ALICE detector as a function of the invariant mass mT,ee and the pair transverse momentum pT,ee in the ranges mT,ee < 3.5 GeV/c2 and mT,ee < 8.0 GeV/c2, in both collision systems. In proton-proton collisions, the charm and beauty cross sections are determined at midrapidity from a fit to the data with two different event generators. This complements the existing dielectron measurements performed at s√ = 7 and 13 TeV. The slope of the s√ dependence of the three measurements is described by FONLL calculations. The dielectron cross section measured in proton-lead collisions is in agreement, within the current precision, with the expected dielectron production without any nuclear matter effects for e+e− pairs from open heavy-flavor hadron decays. For the first time at LHC energies, the dielectron production in proton-lead and proton-proton collisions are directly compared at the same sNN−−−√ via the dielectron nuclear modification factor RpPb. The measurements are compared to model calculations including cold nuclear matter effects, or additional sources of dielectrons from thermal radiation.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies from 4.178 to 4.600 GeV, we study the process eþe− → π0Xð3872Þγ and search for Zcð4020Þ0 → Xð3872Þγ. We find no significant signal and set upper limits on σðeþe− → π0Xð3872ÞγÞ · BðXð3872Þ → πþπ−J=ψÞ and σðeþe− → π0Zcð4020Þ0Þ · BðZcð4020Þ0 → Xð3872ÞγÞ · BðXð3872Þ → πþπ−J=ψÞ for each energy point at 90% confidence level, which is of the order of several tenths pb.
We measure the inclusive semielectronic decay branching fraction of the D+s meson. A double-tag technique is applied to e+e− annihilation data collected by the BESIII experiment at the BEPCII collider, operating in the center-of-mass energy range 4.178–4.230 GeV. We select positrons fromD+s→Xe+νe with momenta greater than 200 MeV/c and determine the laboratory momentum spectrum, accounting for the effects of detector efficiency and resolution. The total positron yield and semielectronic branching fraction are determined by extrapolating this spectrum below the momentum cutoff. We measure the D+s semielectronic branching fraction to be(6.30±0.13(stat.)±0.09(syst.)±0.04(ext.))%, showing no evidence for unobserved exclusive semielectronic modes. We combine this result with external data taken from literature to determine the ratio of the D+s and D0 semielectronic widths, Γ(D+s→Xe+νe)Γ(D0→Xe+νe)=0.790±0.016(stat.)±0.011(syst.)±0.016(ext.). Our results are consistent with and more precise than previous measurements.
The electromagnetic process is studied with the initial-state-radiation technique using 7.5 fb−1 of data collected by the BESIII experiment at seven energy points from 3.773 to 4.600 GeV. The Born cross section and the effective form factor of the proton are measured from the production threshold to 3.0 GeV/ using the invariant-mass spectrum. The ratio of electric and magnetic form factors of the proton is determined from the analysis of the proton-helicity angular distribution.
Relative fractions and phases of the intermediate decays are determined. With the detection efficiency estimated by the results of the amplitude analysis, the branching fraction of Dþ s → K−Kþπþπ0 decay is measured to be ð5.42 0.10stat 0.17systÞ%.
Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts
(2014)
Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.
Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.
Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.
Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively.
Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
Klaus Heinrich im Gespräch mit Wolfram Ette und Volkmar Billig zur Frage, in welcher Weise gerade die Städte eine gattungsgeschichtliche Utopie zu formulieren in der Lage sein könnten, die alle Konflikte, Brüche und Unvereinbarkeiten, die das Leben der Menschen bestimmen, ausstellen? Sind Ruinen, Brachflächen und die in die Stadt einwachsende Natur ein Indiz für ökonomischen Niedergang und stadtplanerisches Versagen oder drückt sich daran, wenn auch vielleicht ungewollt, eine realistische Korrektur eines falschen stadtplanerischen Rationalismus aus? - Religionswissenschaft thematisiert, Klaus Heinrich zufolge, "das Verdrängte der Philosophie". Neben den Religionen hat sie daher auch die Künste zu Bundesgenossen - und eben die Psychoanalyse, die selbst einen Gegenentwurf zum Rationalismus der europäischen Aufklärung praktiziert.
Rationale: Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. S olitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions.
Aim: The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with S olitaire revascularization devices reduces degree of disability 3 months post stroke.
Design: The study is a global multicenter, two‐arm, prospective, randomized, open, blinded end‐point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled.
Procedures:Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the S olitaire device within six‐hours of symptom onset.
Study Outcomes: The primary end‐point is 90‐day global disability, assessed with the modified R ankin S cale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in N ational I nstitutes of H ealth S troke S cale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure.
Analysis:Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified R ankin S cale (R ankin shift) and proportions of subjects achieving functional independence (mRS 0–2).
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
The differential charged jet cross sections, jet fragmentation distributions, and jet shapes are measured in minimum bias proton-proton collisions at centre-of-mass energy s√=7 TeV using the ALICE detector at the LHC. Jets are reconstructed from charged particle momenta in the mid-rapidity region using the sequential recombination kT and anti-kT as well as the SISCone jet finding algorithms with several resolution parameters in the range R=0.2 to 0.6. Differential jet production cross sections measured with the three jet finders are in agreement in the transverse momentum (pT) interval 20<pjet,chT<100 GeV/c. They are also consistent with prior measurements carried out at the LHC by the ATLAS collaboration. The jet charged particle multiplicity rises monotonically with increasing jet pT, in qualitative agreement with prior observations at lower energies. The transverse profiles of leading jets are investigated using radial momentum density distributions as well as distributions of the average radius containing 80% (⟨R80⟩) of the reconstructed jet pT. The fragmentation of leading jets with R=0.4 using scaled pT spectra of the jet constituents is studied. The measurements are compared to model calculations from event generators (PYTHIA, PHOJET, HERWIG). The measured radial density distributions and ⟨R80⟩ distributions are well described by the PYTHIA model (tune Perugia-2011). The fragmentation distributions are better described by HERWIG.
The ALICE collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y|<0.8 and transverse momentum 1<pT<10 GeV/c, in pp collisions at s√= 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD calculations agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e=3.47±0.40(stat)+1.12−1.33(sys)±0.07(norm)μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) predictions to obtain the total bb¯ production cross section, σbb¯=130±15.1(stat)+42.1−49.8(sys)+3.4−3.1(extr)±2.5(norm)±4.4(BR)μb.
The ALICE collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y|<0.8 and transverse momentum 1<pT<10 GeV/c, in pp collisions at s√= 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD calculations agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e=3.47±0.40(stat)+1.12−1.33(sys)±0.07(norm)μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) predictions to obtain the total bb¯ production cross section, σbb¯=130±15.1(stat)+42.1−49.8(sys)+3.4−3.1(extr)±2.5(norm)±4.4(BR)μb.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
Mitochondrial complex I, the largest and most complicated proton pump of the respiratory chain, links the electron transfer from NADH to ubiquinone to the pumping of four protons from the matrix into the intermembrane space. In humans, defects in complex I are involved in a wide range of degenerative disorders. Recent progress in the X-ray structural analysis of prokaryotic and eukaryotic complex I confirmed that the redox reactions are confined entirely to the hydrophilic peripheral arm of the L-shaped molecule and take place at a remarkable distance from the membrane domain. While this clearly implies that the proton pumping within the membrane arm of complex I is driven indirectly via long-range conformational coupling, the molecular mechanism and the number, identity, and localization of the pump-sites remains unclear. Here, we report that upon deletion of the gene for a small accessory subunit of the Yarrowia complex I, a stable subcomplex (nb8m delta) is formed that lacks the distal part of the membrane domain as revealed by single particle analysis. The analysis of the subunit composition of holo and subcomplex by three complementary proteomic approaches revealed that two (ND4 and ND5) of the three subunits with homology to bacterial Mrp-type Na+/H+ antiporters that have been discussed as prime candidates for harbouring the proton pumps were missing in nb8m delta. Nevertheless, nb8m delta still pumps protons at half the stoichiometry of the complete enzyme. Our results provide evidence that the membrane arm of complex I harbours two functionally distinct pump modules that are connected in series by the long helical transmission element recently identified by X-ray structural analysis.