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Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multi-particle cumulant methods are reported in collisions of pp at s√=13 TeV, p-Pb at sNN−−−√=5.02 TeV, Xe-Xe at sNN−−−√=5.44 TeV, and Pb-Pb at sNN−−−√=5.02 TeV recorded with the ALICE detector. These measurements are performed as a function of multiplicity in the mid-rapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p-Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus--nucleus collisions in the same multiplicity range. Using the novel subevent method, v2 measured in pp and p-Pb collisions with four-particle cumulants is found to be compatible with that from six-particle cumulants. The symmetric cumulants SC(m,n) calculated with the subevent method which evaluate the correlation strength between v2n and v2m are also presented. The presented data, which add further support to the existence of long-range multi-particle azimuthal correlations in high multiplicity pp and p-Pb collisions, can neither be described by PYTHIA8 nor by IP-Glasma+MUSIC+UrQMD model calculations, and hence provide new insights into the understanding of collective effects in small collision systems.
Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multi-particle cumulant methods are reported in collisions of pp at s√=13 TeV, p-Pb at sNN−−−√=5.02 TeV, Xe-Xe at sNN−−−√=5.44 TeV, and Pb-Pb at sNN−−−√=5.02 TeV recorded with the ALICE detector. The multiplicity dependence of vn is studied in a very wide range from 20 to 3000 particles produced in the mid-rapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p-Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus-nucleus collisions in the same multiplicity range. Using a novel subevent method, v2 measured with four-particle cumulants is found to be compatible with that from six-particle cumulants in pp and p-Pb collisions. The magnitude of the correlation between v2n and v2m, evaluated with the symmetric cumulants SC(m,n) is observed to be positive at all multiplicities for v2 and v4, while for v2 and v3 it is negative and changes sign for multiplicities below 100, which may indicate a different vn fluctuation pattern in this multiplicity range. The observed long-range multi-particle azimuthal correlations in high multiplicity pp and p-Pb collisions can neither be described by PYTHIA 8 nor by IP-Glasma+MUSIC+UrQMD model calculations, and hence provide new insights into the understanding of collective effects in small collision systems.
Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multi-particle cumulant methods are reported in collisions of pp at s√=13 TeV, p-Pb at sNN−−−√=5.02 TeV, Xe-Xe at sNN−−−√=5.44 TeV, and Pb-Pb at sNN−−−√=5.02 TeV recorded with the ALICE detector. These measurements are performed as a function of multiplicity in the mid-rapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p-Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus--nucleus collisions in the same multiplicity range. Using the novel subevent method, v2 measured in pp and p-Pb collisions with four-particle cumulants is found to be compatible with that from six-particle cumulants. The symmetric cumulants SC(m,n) calculated with the subevent method which evaluate the correlation strength between v2n and v2m are also presented. The presented data, which add further support to the existence of long-range multi-particle azimuthal correlations in high multiplicity pp and p-Pb collisions, can neither be described by PYTHIA8 nor by IP-Glasma+MUSIC+UrQMD model calculations, and hence provide new insights into the understanding of collective effects in small collision systems.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
We present the first measurements of femtoscopic correlations between the K0 S and K± particles in pp collisions at √s = 7 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding solely via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0 SK− are found to be equal within the experimental uncertainties to those for K0 SK+. Results of the present study are compared with those from identical-kaon femtoscopic studies also performed with pp collisions at √s = 7 TeV by ALICE andwith a K0 SK± measurement in Pb–Pb collisions at √sNN = 2.76 TeV. Combined with the Pb–Pb results, our pp analysis is found to be compatible with th e interpretation of the a0(980) having a tetraquark structure instead of that of a diquark.
Using a microscopic transport model together with a coalescence after-burner, we study the formation of deuterons in Au + Au central collisions at s = 200 AGeV . It is found that the deuteron transverse momentum distributions are strongly a ected by the nucleon space-momentum correlations, at the moment of freeze-out, which are mostly determined by the number of rescatterings. This feature is useful for studying collision dynamics at ultrarelativistic energies.
The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy.
The Kinase Chemogenomic Set (KCGS): an open science resource for kinase vulnerability identification
(2021)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification
(2019)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.