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New measurements of directed flow for charged hadrons, characterized by the Fourier coefficient v1, are presented for transverse momenta pT, and centrality intervals in Au+Au collisions recorded by the STAR experiment for the center-of-mass energy range √sN N = 7.7–200 GeV. The measurements underscore the importance of momentum conservation, and the characteristic dependencies on √sN N , centrality and pT are consistent with the expectations of geometric fluctuations generated in the initial stages of the collision, acting in concert with a hydrodynamic-like expansion. The centrality and pT dependencies of veven 1 , as well as an observed similarity between its excitation function and that for v3, could serve as constraints for initial-state models. The veven 1 excitation function could also provide an important supplement to the flow measurements employed for precision extraction of the temperature dependence of the specific shear viscosity.
We present the first systematic comparison of the charged-particle pseudorapidity densities for three widely different collision systems, pp, pPb, and PbPb, at the top energy of the Large Hadron Collider (√sNN=5.02TeV) measured over a wide pseudorapidity range (−3.5<η<5), the widest possible among the four experiments at that facility. The systematic uncertainties are minimised since the measurements are recorded by the same experimental apparatus (ALICE). The distributions for pPb and PbPb collisions are determined as a function of the centrality of the collisions, while results from pp collisions are reported for inelastic events with at least one charged particle at midrapidity. The charged-particle pseudorapidity densities are, under simple and robust assumptions, transformed to charged-particle rapidity densities. This allows for the calculation and the presentation of the evolution of the width of the rapidity distributions and of a lower bound on the Bjorken energy density, as a function of the number of participants in all three collision systems. We find a decreasing width of the particle production, and roughly a smooth ten fold increase in the energy density, as the system size grows, which is consistent with a gradually higher dense phase of matter.
The production of prompt Λc+ baryons at midrapidity (|y|<0.5) was measured in central (0–10%) and mid-central (30–50%) Pb–Pb collisions at the center-of-mass energy per nucleon–nucleon pair √sNN=5.02 TeV with the ALICE detector. The results are more precise, more differential in centrality, and reach much lower transverse momentum (pT=1 GeV/c) with respect to previous measurements performed by the ALICE, STAR, and CMS Collaborations in nucleus–nucleus collisions, allowing for an extrapolation down to pT=0. The pT-differential Λc+/D0 ratio is enhanced with respect to the pp measurement for 4<pT<8 GeV/c by 3.7 standard deviations (σ), while the pT-integrated ratios are compatible within 1σ. The observed trend is similar to that observed in the strange sector for the Λ/KS0 ratio. Model calculations including coalescence or statistical hadronization for charm-hadron formation are compared with the data.
The production of prompt D0, Ds+, and Λc+ hadrons, and their ratios, Ds+/D0 and Λc+/D0, are measured in proton–proton collisions at √s=13 TeV at midrapidity (|y|<0.5) with the ALICE detector at the LHC. The measurements are performed as a function of the charm-hadron transverse momentum (pT) in intervals of charged-particle multiplicity, measured with two multiplicity estimators covering different pseudorapidity regions. While the strange to non-strange Ds+/D0 ratio indicates no significant multiplicity dependence, the baryon-to-meson pT-differential Λc+/D0 ratio shows a multiplicity-dependent enhancement, with a significance of 5.3σ for 1<pT<12 GeV/c, comparing the highest multiplicity interval with respect to the lowest one. The measurements are compared with a theoretical model that explains the multiplicity dependence by a canonical treatment of quantum charges in the statistical hadronisation approach, and with predictions from event generators that implement colour reconnection mechanisms beyond the leading colour approximation to model the hadronisation process. The Λc+/D0 ratios as a function of pT present a similar shape and magnitude as the Λ/KS0 ratios in comparable multiplicity intervals, suggesting a potential common mechanism for light- and charm-hadron formation, with analogous multiplicity dependence. The pT-integrated ratios, extrapolated down to pT=0, do not show a significant dependence on multiplicity within the uncertainties.
The production of muons from heavy-flavour hadron decays in p–Pb collisions at t √sNN=5.02 TeV was studied for 2<pT<16 GeV/c with the ALICE detector at the CERN LHC. The measurement was performed at forward (p-going direction) and backward (Pb-going direction) rapidity, in the ranges of rapidity in the centre-of-mass system (cms) 2.03<ycms<3.53 and −4.46<ycms<−2.96, respectively. The production cross sections and nuclear modification factors are presented as a function of transverse momentum (pT). At forward rapidity, the nuclear modification factor is compatible with unity while at backward rapidity, in the interval 2.5<pT<3.5 GeV/c, it is above unity by more than 2σ. The ratio of the forward-to-backward production cross sections is also measured in the overlapping interval 2.96<|ycms|<3.53 and is smaller than unity by 3.7σ in 2.5<pT<3.5 GeV/c. The data are described by model calculations including cold nuclear matter effects.
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.
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
Although there is much interest in the future retail price of gasoline among consumers, industry analysts, and policymakers, it is widely believed that changes in the price of gasoline are essentially unforecastable given publicly available information. We explore a range of new forecasting approaches for the retail price of gasoline and compare their accuracy with the no-change forecast. Our key finding is that substantial reductions in the mean-squared prediction error (MSPE) of gasoline price forecasts are feasible in real time at horizons up to two years, as are substantial increases in directional accuracy. The most accurate individual model is a VAR(1) model for real retail gasoline and Brent crude oil prices. Even greater reductions in MSPEs are possible by constructing a pooled forecast that assigns equal weight to five of the most successful forecasting models. Pooled forecasts have lower MSPE than the EIA gasoline price forecasts and the gasoline price expectations in the Michigan Survey of Consumers. We also show that as much as 39% of the decline in gas prices between June and December 2014 was predictable.
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
Members of the ATP‐binding cassette (ABC) transporter superfamily translocate a broad spectrum of chemically diverse substrates. While their eponymous ATP‐binding cassette in the nucleotide‐binding domains (NBDs) is highly conserved, their transmembrane domains (TMDs) forming the translocation pathway exhibit distinct folds and topologies, suggesting that during evolution the ancient motor domains were combined with different transmembrane mechanical systems to orchestrate a variety of cellular processes. In recent years, it has become increasingly evident that the distinct TMD folds are best suited to categorize the multitude of ABC transporters. We therefore propose a new ABC transporter classification that is based on structural homology in the TMDs:
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (~ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.