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We report on measurements of sequential Υ suppression in Au+Au collisions at sNN−−−√ = 200 GeV with the STAR detector at the Relativistic Heavy Ion Collider (RHIC) through both the dielectron and dimuon decay channels. In the 0-60% centrality class, the nuclear modification factors (RAA), which quantify the level of yield suppression in heavy-ion collisions compared to p+p collisions, for Υ(1S) and Υ(2S) are 0.40±0.03 (stat.)±0.03 (sys.)±0.09 (norm.) and 0.26±0.08 (stat.)±0.02 (sys.)±0.06 (norm.), respectively, while the upper limit of the Υ(3S) RAA is 0.17 at a 95% confidence level. This provides experimental evidence that the Υ(3S) is significantly more suppressed than the Υ(1S) at RHIC. The level of suppression for Υ(1S) is comparable to that observed at the much higher collision energy at the Large Hadron Collider. These results point to the creation of a medium at RHIC whose temperature is sufficiently high to strongly suppress excited Υ states.
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y|< 0.7) in Au+Au collisions at sNN−−−√=200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5<pT<9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p+p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
We report measurements of Xi and Xi-bar hyperon absolute yields as a function of rapidity in 158 GeV/c Pb+Pb collisions. At midrapidity, dN/dy = 2.29 +/- 0.12 for Xi, and 0.52 +/- 0.05 for Xi-bar, leading to the ratio of Xi-bar/Xi = 0.23 +/- 0.03. Inverse slope parameters fitted to the measured transverse mass spectra are of the order of 300 MeV near mid-rapidity. The estimated total yield of Xi particles in Pb+Pb central interactions amounts to 7.4 +/- 1.0 per collision. Comparison to Xi production in properly scaled p+p reactions at the same energy reveals a dramatic enhancement (about one order of magnitude) of Xi production in Pb+Pb central collisions over elementary hadron interactions.
We report the first measurements of cumulants, up to 4𝑡ℎ order, of deuteron number distributions and protondeuteron 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.
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.
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. This is the only measurement of the proton-proton elastic cross section in this 𝑡 range for collision energies above the Intersecting Storage Rings (ISR) and below the Large Hadron Collider (LHC) colliders. 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). This is the first measurement below the LHC energies for which the non-constant behavior 𝐵(𝑡) is observed. The 𝑡 dependence of 𝐵 is also 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 = 540 GeV for proton–antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR 𝑡-range is 𝜎f id el = 462.1 ± 0.9(stat.) ± 1.1(syst.) ± 11.6(scale) 𝜇b.
We present the first measurements of charge-dependent correlations on angular difference variables η1 − η2 (pseudorapidity) and φ1 − φ2 (azimuth) for primary charged hadrons with transverse momentum 0.15 <= pt <= 2 GeV/c and |η| <= 1.3 from Au–Au collisions at √sNN = 130 GeV. We observe correlation structures not predicted by theory but consistent with evolution of hadron emission geometry with increasing centrality from one-dimensional fragmentation of color strings along the beam direction to an at least two-dimensional hadronization geometry along the beam and azimuth directions of a hadron-opaque bulk medium.
The differential cross section for 𝑍0 production, measured as a function of the boson’s transverse momentum (𝑝T), provides important constraints on the evolution of the transverse momentum dependent parton distribution functions (TMDs). The transverse single spin asymmetry (TSSA) of the 𝑍0 is sensitive to one of the polarized TMDs, the Sivers function, which is predicted to have the opposite sign in 𝑝 + 𝑝 → 𝑊 ∕𝑍 + 𝑋 from that which enters in semi-inclusive deep inelastic scattering. In this Letter, the STAR Collaboration reports the first measurement of the 𝑍0∕𝛾∗ differential cross section as a function of its 𝑝T in 𝑝+𝑝 collisions at a center-of-mass energy of 510 GeV, together with the 𝑍0∕𝛾∗ total cross section. We also report the measurement of 𝑍0∕𝛾∗ TSSA in transversely polarized 𝑝+𝑝 collisions at 510 GeV.
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.
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.
A linearly polarized photon can be quantized from the Lorentz-boosted electromagnetic field of a nucleus traveling at ultrarelativistic speed. When two relativistic heavy nuclei pass one another at a distance of a few nuclear radii, the photon from one nucleus may interact through a virtual quark-antiquark pair with gluons from the other nucleus, forming a short-lived vector meson (e.g., ρ0). In this experiment, the polarization was used in diffractive photoproduction to observe a unique spin interference pattern in the angular distribution of ρ0 → π+π− decays. The observed interference is a result of an overlap of two wave functions at a distance an order of magnitude larger than the ρ0 travel distance within its lifetime. The strong-interaction nuclear radii were extracted from these diffractive interactions and found to be 6.53 ± 0.06 fm (197Au) and 7.29 ± 0.08 fm (238U), larger than the nuclear charge radii. The observable is demonstrated to be sensitive to the nuclear geometry and quantum interference of nonidentical particles. Polarized photon-gluon fusion reveals quantum wave interference of non-identical particles and shape of high-energy nuclei.
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.
In high-energy heavy-ion collisions, partonic collectivity is evidenced by the constituent quark number scaling of elliptic flow anisotropy for identified hadrons. A breaking of this scaling and dominance of baryonic interactions is found for identified hadron collective flow measurements in sNN−−−√ = 3 GeV Au+Au collisions. In this paper, we report measurements of the first- and second-order azimuthal anisotropic parameters, v1 and v2, of light nuclei (d, t, 3He, 4He) produced in sNN−−−√ = 3 GeV Au+Au collisions at the STAR experiment. An atomic mass number scaling is found in the measured v1 slopes of light nuclei at mid-rapidity. For the measured v2 magnitude, a strong rapidity dependence is observed. Unlike v2 at higher collision energies, the v2 values at mid-rapidity for all light nuclei are negative and no scaling is observed with the atomic mass number. Calculations by the Jet AA Microscopic Transport Model (JAM), with baryonic mean-field plus nucleon coalescence, are in good agreement with our observations, implying baryonic interactions dominate the collective dynamics in 3 GeV Au+Au collisions at RHIC.
In high-energy heavy-ion collisions, partonic collectivity is evidenced by the constituent quark number scaling of elliptic flow anisotropy for identified hadrons. A breaking of this scaling and dominance of baryonic interactions is found for identified hadron collective flow measurements in sNN−−−√ = 3 GeV Au+Au collisions. In this paper, we report measurements of the first-order and second-order azimuthal anisotropic parameters, v1 and v2, of light nuclei (d, t, 3He, 4He) produced in sNN−−−√ = 3 GeV Au+Au collisions at the STAR experiment. An atomic mass number scaling is found in the measured v1 slopes of light nuclei at mid-rapidity. For the measured v2 magnitude, a strong rapidity dependence is observed. Unlike v2 at higher collision energies, the v2 values at mid-rapidity for all light nuclei are negative and no scaling is observed with the atomic mass number. Calculations by the Jet AA Microscopic Transport Model (JAM), with baryonic mean-field plus nucleon coalescence, are in good agreement with our observations, implying baryonic interactions dominate the collective dynamics in 3 GeV Au+Au collisions at RHIC.
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.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
Mid-rapidity transverse mass spectra and multiplicity densities of charged and neutral kaons are reported for Au + Au collisions at √sNN = 130 GeV at RHIC. The spectra are exponential in transverse mass, with an inverse slope of about 280 MeV in central collisions. The multiplicity densities for these particles scale with the negative hadron pseudo-rapidity density. The charged kaon to pion ratios are K+/π− = 0.161± 0.002(stat) ± 0.024(syst) and K−/π− = 0.146± 0.002(stat) ± 0.022(syst) for the most central collisions. The K+/π− ratio is lower than the same ratio observed at the SPS while the K−/π− is higher than the SPS result. The ratios are enhanced by about 50% relative to p + p and p¯ + p collision data at similar energies.
In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia–reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients’ outcome.
Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
This paper offers a description and account of the patterns of 'ex-situ' focus in Dagbani. We show that there are two syntactic strategies for creating 'ex-situ' focus in the language, one involving A’-movement to the left periphery, and the second involving base generation in the left periphery combined with coreference to a resumptive pronoun. Furthermore, we argue that subjects are difficult to move from Spec,TP to Spec,CP in the left-periphery because of 'anti-locality', which creates a tension when trying to focus subjects, which are required to derivationally fill the specifier of both positions. We further show that what looks to be a two-way distinction between the behaviour of subjects and non-subjects in the language is in fact a three-way distinction between subjects that are focussed to a local left-periphery, subjects that are focussed to a non-local left-periphery, and non-subjects. These distinctions arise due to there being two methods for Dagbani to resolve the antilocality problem of subject movement, and so local subjects solve the problem differently to non-local subjects.
Global change effects on biodiversity and human wellbeing call for improved long-term environmental data as a basis for science, policy and decision making, including increased interoperability, multifunctionality, and harmonization. Based on the example of two global initiatives, the International Long-Term Ecological Research (ILTER) network and the Group on Earth Observations Biodiversity Observation Network (GEO BON), we propose merging the frameworks behind these initiatives, namely ecosystem integrity and essential biodiversity variables, to serve as an improved guideline for future site-based long-term research and monitoring in terrestrial, freshwater and coastal ecosystems. We derive a list of specific recommendations of what and how to measure at a monitoring site and call for an integration of sites into co-located site networks across individual monitoring initiatives, and centered on ecosystems. This facilitates the generation of linked comprehensive ecosystem monitoring data, supports synergies in the use of costly infrastructures, fosters cross-initiative research and provides a template for collaboration beyond the ILTER and GEO BON communities.
Since its founding in 1993 the International Long-term Ecological Research Network (ILTER) has gone through pronounced development phases. The current network comprises 44 active member LTER networks representing 700 LTER Sites and ~ 80 LTSER Platforms across all continents, active in the fields of ecosystem, critical zone and socio-ecological research. The critical challenges and most important achievements of the initial phase have now become state-of-the-art in networking for excellent science. At the same time increasing integration, accelerating technology, networking of resources and a strong pull for more socially relevant scientific information have been modifying the mission and goals of ILTER. This article provides a critical review of ILTER's mission, goals, development and impacts. Major characteristics, tools, services, partnerships and selected examples of relative strengths relevant for advancing ILTER are presented. We elaborate on the tradeoffs between the needs of the scientific community and stakeholder expectations. The embedding of ILTER in an increasingly collaborative landscape of global environmental observation and ecological research networks and infrastructures is also reflected by developments of pioneering regional and national LTER networks such as SAEON in South Africa, CERN/CEOBEX in China, TERN in Australia or eLTER RI in Europe. The primary role of ILTER is currently seen as a mechanism to investigate ecosystem structure, function, and services in response to a wide range of environmental forcings using long-term, place-based research. We suggest four main fields of activities and advancements for the next decade through development/delivery of a: (1) Global multi-disciplinary community of researchers and research institutes; (2) Strategic global framework and strong partnerships in ecosystem observation and research; (3) Global Research Infrastructure (GRI); and (4) a scientific knowledge factory for societally relevant information on sustainable use of natural resources.
Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
Background & Aims: Acute‐on‐chronic liver failure (ACLF) is characterized by high short‐term mortality and systemic inflammation (SI). Recently, different cardiodynamic states were shown to independently predict outcomes in cirrhosis. The relationship between cardiodynamic states, SI, and portal hypertension and their impact on ACLF development remains unclear. The aim of this study was therefore to evaluate the interplay of cardiodynamic state and SI on fatal ACLF development in cirrhosis.
Results: At inclusion, hemodynamic measures including cardiac index (CI) and hepatic venous pressure gradient of 208 patients were measured. Patients were followed prospectively for fatal ACLF development (primary endpoint). SI was assessed by proinflammatory markers such as interleukins (ILs) 6 and 8 and soluble IL‐33 receptor (sIL‐33R). Patients were divided according to CI (<3.2; 3.2‐4.2; >4.2 L/min/m2) in hypo‐ (n = 84), normo‐ (n = 69) and hyperdynamic group (n = 55). After a median follow‐up of 3 years, the highest risk of fatal ACLF was seen in hyperdynamic (35%) and hypodynamic patients (25%) compared with normodynamic (14%) (P = .011). Hyperdynamic patients showed the highest rate of SI. The detectable level of IL‐6 was an independent predictor of fatal ACLF development.
Conclusions: Cirrhotic patients with hyperdynamic and hypodynamic circulation have a higher risk of fatal ACLF. Therefore, the cardiodynamic state is strongly associated with SI, which is an independent predictor of development of fatal ACLF.
In memory of Edward Diener: reflections on his career, contributions and the science of happiness
(2021)
Prof. Edward (Ed) Diener (1946-2021), a pioneer in positive psychology, passed away on the 27th of April 2021 at his home in Salt Lake City, Utah (Salt Lake City Tribune, 2021). As one of the most influential psychologists of the discipline, Ed Diener pushed the boundaries of our understanding of positive psychological functioning, subjective well-being, and happiness (Layous, 2020). As one of the Top 200 most cited researchers across all disciplines and fields, he will be most remembered for founding the scientific study of subjective well-being (SWB) and happiness (Bakshi, 2019). Diener developed the concept of subjective well-being by exploring the factors that influence people's life satisfaction (Diener et al., 2017a). He studied the individual causes of subjective well-being, such as close social relationships, income, meaning and purpose, personality, and societal causes, such as economic development, low corruption and crime, and a healthy environment (Diener et al., 2018). His research has discovered both universal and culture-specific causes and consequences of SWB and influenced governmental policy (Oishi et al., 1999). In respect of his memory, the purpose of this paper is threefold: (a) to reflect upon his career journey, (b) to celebrate his significant contributions to the discipline, and (c) to provide personal reflections of those who worked closely with him over the past 50 years.
Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
Highlights
• Overview on functional work performed in rodent, zebrafish and fruit fly models of ADHD and its comorbidities.
• Comprehensive search for new genetically modified mouse models to study ADHD-related and comorbid traits.
• Review of behavioral assays available in animal models to test ADHD-related and comorbid traits.
• Animal models to assess environmental effects contributing to the epigenetic mechanisms of ADHD and comorbidities.
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder resulting from the interaction between genetic and environmental risk factors. It is well known that ADHD co-occurs frequently with other psychiatric disorders due, in part, to shared genetics factors. Although many studies have contributed to delineate the genetic landscape of psychiatric disorders, their specific molecular underpinnings are still not fully understood. The use of animal models can help us to understand the role of specific genes and environmental stimuli-induced epigenetic modifications in the pathogenesis of ADHD and its comorbidities. The aim of this review is to provide an overview on the functional work performed in rodents, zebrafish and fruit fly and highlight the generated insights into the biology of ADHD, with a special focus on genetics and epigenetics. We also describe the behavioral tests that are available to study ADHD-relevant phenotypes and comorbid traits in these models. Furthermore, we have searched for new models to study ADHD and its comorbidities, which can be useful to test potential pharmacological treatments.
Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.
Surface color and predictability determine contextual modulation of V1 firing and gamma oscillations
(2019)
The integration of direct bottom-up inputs with contextual information is a core feature of neocortical circuits. In area V1, neurons may reduce their firing rates when their receptive field input can be predicted by spatial context. Gamma-synchronized (30–80 Hz) firing may provide a complementary signal to rates, reflecting stronger synchronization between neuronal populations receiving mutually predictable inputs. We show that large uniform surfaces, which have high spatial predictability, strongly suppressed firing yet induced prominent gamma synchronization in macaque V1, particularly when they were colored. Yet, chromatic mismatches between center and surround, breaking predictability, strongly reduced gamma synchronization while increasing firing rates. Differences between responses to different colors, including strong gamma-responses to red, arose from stimulus adaptation to a full-screen background, suggesting prominent differences in adaptation between M- and L-cone signaling pathways. Thus, synchrony signaled whether RF inputs were predicted from spatial context, while firing rates increased when stimuli were unpredicted from context.
A new global synthesis and biomization of long (> 40 kyr) pollen-data records is presented, and used with simulations from the HadCM3 and FAMOUS climate models to analyse the dynamics of the global terrestrial biosphere and carbon storage over the last glacial–interglacial cycle. Global modelled (BIOME4) biome distributions over time generally agree well with those inferred from pollen data. The two climate models show good agreement in global net primary productivity (NPP). NPP is strongly influenced by atmospheric carbon dioxide (CO2) concentrations through CO2 fertilization. The combined effects of modelled changes in vegetation and (via a simple model) soil carbon result in a global terrestrial carbon storage at the Last Glacial Maximum that is 210–470 Pg C less than in pre-industrial time. Without the contribution from exposed glacial continental shelves the reduction would be larger, 330–960 Pg C. Other intervals of low terrestrial carbon storage include stadial intervals at 108 and 85 kaBP, and between 60 and 65 kaBP during Marine Isotope Stage 4. Terrestrial carbon storage, determined by the balance of global NPP and decomposition, influences the stable carbon isotope composition (δ 13C) of seawater because terrestrial organic carbon is depleted in 13C. Using a simple carbon-isotope mass balance equation we find agreement in trends between modelled ocean δ 13C based on modelled land carbon storage, and palaeo-archives of ocean δ 13C, confirming that terrestrial carbon storage variations may be important drivers of ocean δ 13 C changes.
A new global synthesis and biomization of long (> 40 kyr) pollen-data records is presented and used with simulations from the HadCM3 and FAMOUS climate models and the BIOME4 vegetation model to analyse the dynamics of the global terrestrial biosphere and carbon storage over the last glacial–interglacial cycle. Simulated biome distributions using BIOME4 driven by HadCM3 and FAMOUS at the global scale over time generally agree well with those inferred from pollen data. Global average areas of grassland and dry shrubland, desert, and tundra biomes show large-scale increases during the Last Glacial Maximum, between ca. 64 and 74 ka BP and cool substages of Marine Isotope Stage 5, at the expense of the tropical forest, warm-temperate forest, and temperate forest biomes. These changes are reflected in BIOME4 simulations of global net primary productivity, showing good agreement between the two models. Such changes are likely to affect terrestrial carbon storage, which in turn influences the stable carbon isotopic composition of seawater as terrestrial carbon is depleted in 13C.
Biallelic pathogenic variants in CLPP, encoding mitochondrial matrix peptidase ClpP, cause a rare autosomal recessive condition, Perrault syndrome type 3 (PRLTS3). It is characterized by primary ovarian insufficiency and early sensorineural hearing loss, often associated with progressive neurological deficits. Mouse models showed that accumulations of (i) its main protein interactor, the substrate-selecting AAA+ ATPase ClpX, (ii) mitoribosomes, and (iii) mtDNA nucleoids are the main cellular consequences of ClpP absence. However, the sequence of these events and their validity in human remain unclear. Here, we studied global proteome profiles to define ClpP substrates among mitochondrial ClpX interactors, which accumulated consistently in ClpP-null mouse embryonal fibroblasts and brains. Validation work included novel ClpP-mutant patient fibroblast proteomics. ClpX co-accumulated in mitochondria with the nucleoid component POLDIP2, the mitochondrial poly(A) mRNA granule element LRPPRC, and tRNA processing factor GFM1 (in mouse, also GRSF1). Only in mouse did accumulated ClpX, GFM1, and GRSF1 appear in nuclear fractions. Mitoribosomal accumulation was minor. Consistent accumulations in murine and human fibroblasts also affected multimerizing factors not known as ClpX interactors, namely, OAT, ASS1, ACADVL, STOM, PRDX3, PC, MUT, ALDH2, PMPCB, UQCRC2, and ACADSB, but the impact on downstream metabolites was marginal. Our data demonstrate the primary impact of ClpXP on the assembly of proteins with nucleic acids and show nucleoid enlargement in human as a key consequence.
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors.
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.
Strong indirect evidence exists for the existence of attractive forces between nuclei making surface contact. Experimentally, the recent observations of spontaneous positron production in heavy-ion collisions can only be understood if nuclei stick together for times long compared to the collision time. We show that any such tendency for nuclei to attract implies the existence of nuclear molecules with entirely new kinds of collective modes. We present a simple model for these modes and apply it to 238U-238U.
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.
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.
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.
Protein kinases are highly tractable targets for drug discovery. However, the biological function and therapeutic potential of the majority of the 500+ human protein kinases remains unknown. We have developed physical and virtual collections of small molecule inhibitors, which we call chemogenomic sets, that are designed to inhibit the catalytic function of almost half the human protein kinases. In this manuscript we share our progress towards generation of a comprehensive kinase chemogenomic set (KCGS), release kinome profiling data of a large inhibitor set (Published Kinase Inhibitor Set 2 (PKIS2)), and outline a process through which the community can openly collaborate to create a KCGS that probes the full complement of human protein kinases.
Under certain conditions, secondary organic aerosol (SOA) particles can exist in the atmosphere in an amorphous solid or semi-solid state. To determine their relevance to processes such as ice nucleation or chemistry occurring within particles requires knowledge of the temperature and relative humidity (RH) range for SOA to exist in these states. In the CLOUD experiment at CERN, we deployed a new in-situ optical method to detect the viscosity of α-pinene SOA particles and measured their transition from the amorphous viscous to liquid state. The method is based on the depolarising properties of laboratory-produced non-spherical SOA particles and their transformation to non-depolarising spherical liquid particles during deliquescence. We found that particles formed and grown in the chamber developed an asymmetric shape through coagulation. A transition to spherical shape was observed as the RH was increased to between 35 % at −10 ◦C and 80 % at −38 ◦C, confirming previous calculations of the viscosity transition conditions. Consequently, α-pinene SOA particles exist in a viscous state over a wide range of ambient conditions, including the cirrus region of the free troposphere. This has implications for the physical, chemical and ice-nucleation properties of SOA and SOA-coated particles in the atmosphere.
Under certain conditions, secondary organic aerosol (SOA) particles can exist in the atmosphere in an amorphous solid or semi-solid state. To determine their relevance to processes such as ice nucleation or chemistry occurring within particles requires knowledge of the temperature and relative humidity (RH) range for SOA to exist in these states. In the Cosmics Leaving Outdoor Droplets (CLOUD) experiment at The European Organisation for Nuclear Research (CERN), we deployed a new in situ optical method to detect the viscous state of α-pinene SOA particles and measured their transition from the amorphous highly viscous state to states of lower viscosity. The method is based on the depolarising properties of laboratory-produced non-spherical SOA particles and their transformation to non-depolarising spherical particles at relative humidities near the deliquescence point. We found that particles formed and grown in the chamber developed an asymmetric shape through coagulation. A transition to a spherical shape was observed as the RH was increased to between 35 % at −10 °C and 80 % at −38 °C, confirming previous calculations of the viscosity-transition conditions. Consequently, α-pinene SOA particles exist in a viscous state over a wide range of ambient conditions, including the cirrus region of the free troposphere. This has implications for the physical, chemical, and ice-nucleation properties of SOA and SOA-coated particles in the atmosphere.