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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.
Feeding exclusively on blood, vampire bats represent the only obligate sanguivorous lineage among mammals. To uncover genomic changes associated with adaptations to this unique dietary specialization, we generated a new haplotype-resolved reference-quality genome of the common vampire bat (Desmodus rotundus) and screened 26 bat species for genes that were specifically lost in the vampire bat lineage. We discovered previously-unknown gene losses that relate to metabolic and physiological changes, such as reduced insulin secretion (FFAR1, SLC30A8), limited glycogen stores (PPP1R3E), and a distinct gastric physiology (CTSE). Other gene losses likely reflect the biased nutrient composition (ERN2, CTRL) and distinct pathogen diversity of blood (RNASE7). Interestingly, the loss of REP15 likely helped vampire bats to adapt to high dietary iron levels by enhancing iron excretion and the loss of the 24S-hydroxycholesterol metabolizing enzyme CYP39A1 could contribute to their exceptional cognitive abilities. Finally, losses of key cone phototransduction genes (PDE6H, PDE6C) suggest that these strictly-nocturnal bats completely lack cone-based vision. These findings enhance our understanding of vampire bat biology and the genomic underpinnings of adaptations to sanguivory.
SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.
The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo–electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines.
We report measurements of the longitudinal double-spin asymmetry, ALL, for inclusive jet and dijet production in polarized proton-proton collisions at midrapidity and center-of-mass energy s√ = 510 GeV, using the high luminosity data sample collected by the STAR experiment in 2013. These measurements complement and improve the precision of previous STAR measurements at the same center-of-mass energy that probe the polarized gluon distribution function at partonic momentum fraction 0.015 ≲x≲ 0.25. The dijet asymmetries are separated into four jet-pair topologies, which provide further constraints on the x dependence of the polarized gluon distribution function. These measurements are in agreement with previous STAR measurements and with predictions from current next-to-leading order global analyses. They provide more precise data at low dijet invariant mass that will better constraint the shape of the polarized gluon distribution function of the proton.
We present measurements of the differential cross sections of inclusive J/ψ meson production as a function of transverse momentum (pJ/ψT) using the μ+μ− and e+e− decay channels in proton+proton collisions at center-of-mass energies of 510 and 500 GeV, respectively, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The measurement from the μ+μ− channel is for 0 <pJ/ψT< 9 GeV/c and rapidity range |yJ/ψ|< 0.4, and that from the e+e− channel is for 4 <pJ/ψT< 20 GeV/c and |yJ/ψ|< 1.0. The ψ(2S) to J/ψ ratio is also measured for 4 <pmesonT< 12 GeV/c through the e+e− decay channel. Model calculations, which incorporate different approaches toward the J/ψ production mechanism, are compared with experimental results and show reasonable agreement within uncertainties.
We report on the first measurements of J/ψ production at very low transverse momentum (pT< 0.2 GeV/c) in hadronic Au+Au collisions at √sNN = 200 GeV and U+U collisions at √sNN = 193 GeV. Remarkably, the inferred nuclear modification factor of J/ψ at mid-rapidity in Au+Au (U+U) collisions reaches about 24 (52) for pT< 0.05 GeV/c in the 60-80% collision centrality class. This noteworthy enhancement cannot be explained by hadronic production accompanied by cold and hot medium effects. In addition, the dN/dt distribution of J/ψ for the very low pT range is presented for the first time. The distribution is consistent with that expected from the Au nucleus and shows a hint of interference. Comparison of the measurements to theoretical calculations of coherent production shows that the excess yield can be described reasonably well and reveals a partial disruption of coherent production in semi-central collisions, perhaps due to the violent hadronic interactions. Incorporating theoretical calculations, the results strongly suggest that the dramatic enhancement of J/ψ yield observed at extremely low pT originates from coherent photon-nucleus interactions. In particular, coherently produced J/ψ's in violent hadronic collisions may provide a novel probe of the quark-gluon-plasma.
We report on the first measurements of J/ψ production at very low transverse momentum (pT< 0.2 GeV/c) in hadronic Au+Au collisions at √sNN = 200 GeV and U+U collisions at √sNN = 193 GeV. Remarkably, the inferred nuclear modification factor of J/ψ at mid-rapidity in Au+Au (U+U) collisions reaches about 24 (52) for pT< 0.05 GeV/c in the 60-80% collision centrality class. This noteworthy enhancement cannot be explained by hadronic production accompanied by cold and hot medium effects. In addition, the dN/dt distribution of J/ψ for the very low pT range is presented for the first time. The distribution is consistent with that expected from the Au nucleus and shows a hint of interference. Comparison of the measurements to theoretical calculations of coherent production shows that the excess yield can be described reasonably well and reveals a partial disruption of coherent production in semi-central collisions, perhaps due to the violent hadronic interactions. Incorporating theoretical calculations, the results strongly suggest that the dramatic enhancement of J/ψ yield observed at extremely low pT originates from coherent photon-nucleus interactions. In particular, coherently produced J/ψ's in violent hadronic collisions may provide a novel probe of the quark-gluon-plasma.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546~GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546 GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546 GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at mid-rapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.
Jet-hadron correlations with respect to the event plane in √sNN = 200 GeV Au+Au collisions in STAR
(2024)
Angular distributions of charged particles relative to jet axes are studied in sNN−−−√ = 200 GeV Au+Au collisions as a function of the jet orientation with respect to the event plane. This differential study tests the expected path-length dependence of energy loss experienced by a hard-scattered parton as it traverses the hot and dense medium formed in heavy-ion collisions. A second-order event plane is used in the analysis as an experimental estimate of the reaction plane formed by the collision impact parameter and the beam direction. Charged-particle jets with 15<pT,jet< 20 and 20<pT,jet< 40 GeV/c were reconstructed with the anti-kT algorithm with radius parameter setting of (R=0.4) in the 20-50\% centrality bin to maximize the initial-state eccentricity of the interaction region. The reaction plane fit method is implemented to remove the flow-modulated background with better precision than prior methods. Yields and widths of jet-associated charged-hadron distributions are extracted in three angular bins between the jet axis and the event plane. The event-plane (EP) dependence is further quantified by ratios of the associated yields in different EP bins. No dependence on orientation of the jet axis with respect to the event plane is seen within the uncertainties in the kinematic regime studied. This finding is consistent with a similar experimental observation by ALICE in sNN−−−√ = 2.76 TeV Pb+Pb collision data.
Jet-hadron correlations with respect to the event plane in √sNN = 200 GeV Au+Au collisions in STAR
(2024)
Angular distributions of charged particles relative to jet axes are studied in sNN−−−√ = 200 GeV Au+Au collisions as a function of the jet orientation with respect to the event plane. This differential study tests the expected path-length dependence of energy loss experienced by a hard-scattered parton as it traverses the hot and dense medium formed in heavy-ion collisions. A second-order event plane is used in the analysis as an experimental estimate of the reaction plane formed by the collision impact parameter and the beam direction. Charged-particle jets with 15<pT,jet< 20 and 20<pT,jet< 40 GeV/c were reconstructed with the anti-kT algorithm with radius parameter setting of (R=0.4) in the 20-50\% centrality bin to maximize the initial-state eccentricity of the interaction region. The reaction plane fit method is implemented to remove the flow-modulated background with better precision than prior methods. Yields and widths of jet-associated charged-hadron distributions are extracted in three angular bins between the jet axis and the event plane. The event-plane (EP) dependence is further quantified by ratios of the associated yields in different EP bins. No dependence on orientation of the jet axis with respect to the event plane is seen within the uncertainties in the kinematic regime studied. This finding is consistent with a similar experimental observation by ALICE in sNN−−−√ = 2.76 TeV Pb+Pb collision data.
We report the first measurements of cumulants, up to 4th order, of deuteron number distributions and proton-deuteron correlations in Au+Au collisions recorded by the STAR experiment in phase-I of Beam Energy Scan (BES) program at the Relativistic Heavy Ion Collider. Deuteron cumulants, their ratios, and proton-deuteron mixed cumulants are presented for different collision centralities covering a range of center-of-mass energy per nucleon pair sNN−−−−√~=~7.7 to 200~GeV. It is found that the cumulant ratios at lower collision energies favor a canonical ensemble over a grand canonical ensemble in thermal models. An anti-correlation between proton and deuteron multiplicity is observed across all collision energies and centralities, consistent with the expectation from global baryon number conservation. The UrQMD model coupled with a phase-space coalescence mechanism qualitatively reproduces the collision-energy dependence of cumulant ratios and proton-deuteron correlations.
12 hepatics and 32 mosses are reported new to Uganda, 1 moss being also new to Africa, and 1 liverwort new to mainland Africa. Ectropothecium plumigerum (Broth.) Hedenäs is a new combination (basionym: Isopterygium plumigerum Broth.) with a new synonym Taxicaulis plumirameus Müll.Hal. nom. nud., and Taxiphyllum maniae (Renauld & Paris) M. Fleisch. is a new synonym of Taxiphyllum taxirameum (Mitt.) M.Fleisch. Three mosses are removed from the Uganda list.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m3 and is operated in a 0.5 T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
The polarization of Λ and Λ¯ hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at √sNN = 200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild pT dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagree with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and pT dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.