Showing papers by "Nagoya University published in 2020"
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23 Feb 2020
TL;DR: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper, where a brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
Abstract: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
3,111 citations
Queen's University Belfast1, University of St Andrews2, Aix-Marseille University3, Historic England4, University of Sheffield5, University of Oxford6, Alfred Wegener Institute for Polar and Marine Research7, University of Minnesota8, Xi'an Jiaotong University9, Nanjing Normal University10, University of Hohenheim11, University of Kiel12, University of California, Santa Cruz13, Lawrence Livermore National Laboratory14, ETH Zurich15, University of Waikato16, Woods Hole Oceanographic Institution17, Heidelberg University18, Cornell University19, Lund University20, University of New South Wales21, University of Arizona22, University of Groningen23, University of Bristol24, University of Glasgow25, University of California, Irvine26, University of Bern27, Aarhus University28, Nagoya University29, Swiss Federal Institute for Forest, Snow and Landscape Research30, National Museum of Japanese History31, University of Bologna32
TL;DR: In this article, the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP.
Abstract: Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
2,800 citations
National Yang-Ming University1, The Chinese University of Hong Kong2, Mahidol University3, University of Tokyo4, Seoul National University Bundang Hospital5, Peking Union Medical College Hospital6, Kyung Hee University7, Nagoya University8, Seoul National University9, Taipei Veterans General Hospital10, Ajou University11, Tan Tock Seng Hospital12, Osaka University13, University of Tsukuba14, Chinese Ministry of Health15
TL;DR: The Asian Working Group for Sarcopenia 2019 introduces "possible sarcopenia," defined by either low muscle strength or low physical performance only, specifically for use in primary health care or community-based health promotion, to enable earlier lifestyle interventions.
2,287 citations
F. Kyle Satterstrom1, F. Kyle Satterstrom2, Jack A. Kosmicki, Jiebiao Wang3 +198 more•Institutions (53)
TL;DR: The largest exome sequencing study of autism spectrum disorder (ASD) to date, using an enhanced analytical framework to integrate de novo and case-control rare variation, identifies 102 risk genes at a false discovery rate of 0.1 or less, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
1,169 citations
TL;DR: It is shown that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity and serves as a host factor for Sars-Cov-2 infection and may potentially provide a therapeutic target for COVID-19.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses the viral spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.
884 citations
TL;DR: The technical aspect of automated driving is surveyed, with an overview of available datasets and tools for ADS development and many state-of-the-art algorithms implemented and compared on their own platform in a real-world driving setting.
Abstract: Automated driving systems (ADSs) promise a safe, comfortable and efficient driving experience. However, fatalities involving vehicles equipped with ADSs are on the rise. The full potential of ADSs cannot be realized unless the robustness of state-of-the-art is improved further. This paper discusses unsolved problems and surveys the technical aspect of automated driving. Studies regarding present challenges, high-level system architectures, emerging methodologies and core functions including localization, mapping, perception, planning, and human machine interfaces, were thoroughly reviewed. Furthermore, many state-of-the-art algorithms were implemented and compared on our own platform in a real-world driving setting. The paper concludes with an overview of available datasets and tools for ADS development.
851 citations
TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon is reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice approach.
801 citations
TL;DR: Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type.
Abstract: Background The efficacy and safety of the anti–programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those of platinum-based chemotherapy, as first-line trea...
773 citations
TL;DR: The FLUXNET2015 dataset provides ecosystem-scale data on CO 2 , water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe, and is detailed in this paper.
Abstract: The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.
681 citations
University of Glasgow1, University of Birmingham2, Karolinska University Hospital3, Linköping University4, University of Mainz5, Nagoya University6, The Chinese University of Hong Kong7, Rabin Medical Center8, Tel Aviv University9, McGill University Health Centre10, Kyoto Prefectural University of Medicine11, University Hospitals Birmingham NHS Foundation Trust12, Inova Fairfax Hospital13, Newcastle University14, Newcastle upon Tyne Hospitals NHS Foundation Trust15
TL;DR: Biopsy-confirmed fibrosis is found to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in Patients with reported NASH.
498 citations
Columbia University1, University of Bologna2, Istituto Nazionale di Fisica Nucleare3, University of Mainz4, University of Münster5, University of Coimbra6, University of Turin7, University of Amsterdam8, New York University Abu Dhabi9, University of Zurich10, Rensselaer Polytechnic Institute11, Weizmann Institute of Science12, Max Planck Society13, Purdue University14, University of Freiburg15, University of L'Aquila16, University of Tokyo17, Nagoya University18, Konan University19, University of California, San Diego20, University of Chicago21, Rice University22, University of California, Los Angeles23
TL;DR: In this article, the XENON1T data was used for searches for new physics with low-energy electronic recoil data recorded with the Xenon1T detector, which enabled one of the most sensitive searches for solar axions, an enhanced neutrino magnetic moment using solar neutrinos, and bosonic dark matter.
Abstract: We report results from searches for new physics with low-energy electronic recoil data recorded with the XENON1T detector. With an exposure of 0.65 tonne-years and an unprecedentedly low background rate of 76±2stat events/(tonne×year×keV) between 1 and 30 keV, the data enable one of the most sensitive searches for solar axions, an enhanced neutrino magnetic moment using solar neutrinos, and bosonic dark matter. An excess over known backgrounds is observed at low energies and most prominent between 2 and 3 keV.
The solar axion model has a 3.4σ significance, and a three-dimensional 90% confidence surface is reported for axion couplings to electrons, photons, and nucleons. This surface is inscribed in the cuboid defined by gae<3.8×10-12, gaeganeff<4.8×10-18, and gaegaγ<7.7×10-22 GeV-1, and excludes either gae=0 or gaegaγ=gaeganeff=0. The neutrino magnetic moment signal is similarly favored over background at 3.2σ, and a confidence interval of μν∈(1.4,2.9)×10-11 μB (90% C.L.) is reported. Both results are in strong tension with stellar constraints. The excess can also be explained by β decays of tritium at 3.2σ significance with a corresponding tritium concentration in xenon of (6.2±2.0)×10-25 mol/mol. Such a trace amount can neither be confirmed nor excluded with current knowledge of its production and reduction mechanisms. The significances of the solar axion and neutrino magnetic moment hypotheses are decreased to 2.0σ and 0.9σ, respectively, if an unconstrained tritium component is included in the fitting. With respect to bosonic dark matter, the excess favors a monoenergetic peak at (2.3±0.2) keV (68% C.L.) with a 3.0σ global (4.0σ local) significance over background.
This analysis sets the most restrictive direct constraints to date on pseudoscalar and vector bosonic dark matter for most masses between 1 and 210 keV/c2. We also consider the possibility that Ar37 may be present in the detector, yielding a 2.82 keV peak from electron capture. Contrary to tritium, the Ar37 concentration can be tightly constrained and is found to be negligible.
TL;DR: Substantial precision is reached to discriminate between the measurement of the anomalous magnetic moment of the muon and the predictions of dispersive methods, which favours the experimentally measured value over those obtained using the dispersion relation.
Abstract: We compute the leading order hadronic vacuum polarization (LO-HVP) contribution to the anomalous magnetic moment of the muon, $(g_\mu-2)$, using lattice QCD Calculations are performed with four flavors of 4-stout-improved staggered quarks, at physical quark masses and at six values of the lattice spacing down to 0064~fm All strong isospin breaking and electromagnetic effects are accounted for to leading order The infinite-volume limit is taken thanks to simulations performed in volumes of sizes up to 11~fm Our result for the LO-HVP contribution to $(g_\mu-2)$ has a total uncertainty of 08\% Compared to the result of the dispersive approach for this contribution, ours significantly reduces the tension between the standard model prediction for $(g_\mu-2)$ and its measurement
Icahn School of Medicine at Mount Sinai1, California Institute of Technology2, Kobe University3, Nagoya University4, University of Minnesota5, University of Virginia6, Beth Israel Deaconess Medical Center7, Vanderbilt University8, Brigham and Women's Hospital9, University of Texas Health Science Center at San Antonio10, Northwestern University11, Washington University in St. Louis12, Broad Institute13
TL;DR: It is suggested that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease.
Abstract: Microglia, the brain’s resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival1. Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures. Suppression of neuronal activation by microglia occurs in a highly region-specific fashion and depends on the ability of microglia to sense and catabolize extracellular ATP, which is released upon neuronal activation by neurons and astrocytes. ATP triggers the recruitment of microglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then converted into adenosine by CD73, which is expressed on microglia as well as other brain cells. Microglial sensing of ATP, the ensuing microglia-dependent production of adenosine, and the adenosine-mediated suppression of neuronal responses via the adenosine receptor A1R are essential for the regulation of neuronal activity and animal behaviour. Our findings suggest that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease. Microglia, the brain’s immune cells, suppress neuronal activity in response to synaptic ATP release and alter behavioural responses in mice.
TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon has been reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach.
Abstract: We review the present status of the Standard Model calculation of the anomalous magnetic moment of the muon. This is performed in a perturbative expansion in the fine-structure constant $\alpha$ and is broken down into pure QED, electroweak, and hadronic contributions. The pure QED contribution is by far the largest and has been evaluated up to and including $\mathcal{O}(\alpha^5)$ with negligible numerical uncertainty. The electroweak contribution is suppressed by $(m_\mu/M_W)^2$ and only shows up at the level of the seventh significant digit. It has been evaluated up to two loops and is known to better than one percent. Hadronic contributions are the most difficult to calculate and are responsible for almost all of the theoretical uncertainty. The leading hadronic contribution appears at $\mathcal{O}(\alpha^2)$ and is due to hadronic vacuum polarization, whereas at $\mathcal{O}(\alpha^3)$ the hadronic light-by-light scattering contribution appears. Given the low characteristic scale of this observable, these contributions have to be calculated with nonperturbative methods, in particular, dispersion relations and the lattice approach to QCD. The largest part of this review is dedicated to a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach. The final result reads $a_\mu^\text{SM}=116\,591\,810(43)\times 10^{-11}$ and is smaller than the Brookhaven measurement by 3.7$\sigma$. The experimental uncertainty will soon be reduced by up to a factor four by the new experiment currently running at Fermilab, and also by the future J-PARC experiment. This and the prospects to further reduce the theoretical uncertainty in the near future-which are also discussed here-make this quantity one of the most promising places to look for evidence of new physics.
Tsinghua University1, Centre national de la recherche scientifique2, Pennsylvania State University3, University of California, Irvine4, California Institute of Technology5, Nanjing University of Information Science and Technology6, Chinese Academy of Sciences7, Nagoya University8, Kunming University of Science and Technology9, University of Paris10, Paris Dauphine University11, National Institute for Environmental Studies12, Beijing Institute of Technology13, Shandong University14, Beijing Normal University15, Nanjing University16, Xiamen University17, University of California, Berkeley18, Potsdam Institute for Climate Impact Research19
TL;DR: The key result is an abrupt 8.8% decrease in global CO2 emissions in the first half of 2020 compared to the same period in 2019, larger than during previous economic downturns or World War II.
Abstract: The COVID-19 pandemic is impacting human activities, and in turn energy use and carbon dioxide (CO2) emissions. Here we present daily estimates of country-level CO2 emissions for different sectors based on near-real-time activity data. The key result is an abrupt 8.8% decrease in global CO2 emissions (-1551 Mt CO2) in the first half of 2020 compared to the same period in 2019. The magnitude of this decrease is larger than during previous economic downturns or World War II. The timing of emissions decreases corresponds to lockdown measures in each country. By July 1st, the pandemic's effects on global emissions diminished as lockdown restrictions relaxed and some economic activities restarted, especially in China and several European countries, but substantial differences persist between countries, with continuing emission declines in the U.S. where coronavirus cases are still increasing substantially.
TL;DR: Cryo-electron microscopy reveals the structures of α-synuclein filaments from the brains of individuals with multiple system atrophy, which has implications for understanding the mechanisms of aggregate propagation and neurodegeneration in the human brain.
Abstract: Synucleinopathies, which include multiple system atrophy (MSA), Parkinson’s disease, Parkinson’s disease with dementia and dementia with Lewy bodies (DLB), are human neurodegenerative diseases1. Existing treatments are at best symptomatic. These diseases are characterized by the presence of, and believed to be caused by the formation of, filamentous inclusions of α-synuclein in brain cells2,3. However, the structures of α-synuclein filaments from the human brain are unknown. Here, using cryo-electron microscopy, we show that α-synuclein inclusions from the brains of individuals with MSA are made of two types of filament, each of which consists of two different protofilaments. In each type of filament, non-proteinaceous molecules are present at the interface of the two protofilaments. Using two-dimensional class averaging, we show that α-synuclein filaments from the brains of individuals with MSA differ from those of individuals with DLB, which suggests that distinct conformers or strains characterize specific synucleinopathies. As is the case with tau assemblies4–9, the structures of α-synuclein filaments extracted from the brains of individuals with MSA differ from those formed in vitro using recombinant proteins, which has implications for understanding the mechanisms of aggregate propagation and neurodegeneration in the human brain. These findings have diagnostic and potential therapeutic relevance, especially because of the unmet clinical need to be able to image filamentous α-synuclein inclusions in the human brain. Cryo-electron microscopy reveals the structures of α-synuclein filaments from the brains of individuals with multiple system atrophy.
TL;DR: A biomarker based on PD-1 positivity of effector and regulatory T cells in the tumor microenvironment that accurately predicts the effectiveness of checkpoint blockade in patients is developed.
Abstract: Immune checkpoint blockade has provided a paradigm shift in cancer therapy, but the success of this approach is very variable; therefore, biomarkers predictive of clinical efficacy are urgently required. Here, we show that the frequency of PD-1+CD8+ T cells relative to that of PD-1+ regulatory T (Treg) cells in the tumor microenvironment can predict the clinical efficacy of programmed cell death protein 1 (PD-1) blockade therapies and is superior to other predictors, including PD ligand 1 (PD-L1) expression or tumor mutational burden. PD-1 expression by CD8+ T cells and Treg cells negatively impacts effector and immunosuppressive functions, respectively. PD-1 blockade induces both recovery of dysfunctional PD-1+CD8+ T cells and enhanced PD-1+ Treg cell–mediated immunosuppression. A profound reactivation of effector PD-1+CD8+ T cells rather than PD-1+ Treg cells by PD-1 blockade is necessary for tumor regression. These findings provide a promising predictive biomarker for PD-1 blockade therapies. Checkpoint blockade is effective in only a subset of patients; therefore, biomarkers that can predict efficacy would be clinically highly valuable. Nishkawa and colleagues develop a biomarker based on PD-1 positivity of effector and regulatory T cells in the tumor microenvironment that accurately predicts the effectiveness of checkpoint blockade in patients.
Kindai University1, Kurume University2, Hiroshima University3, Yamaguchi University4, Nagoya City University5, Kawasaki Medical School6, Nagoya University7, Jichi Medical University8, Kyoto Prefectural University of Medicine9, Kagoshima University10, Fujita Health University11, Nagasaki University12, Chiba University13, Kyorin University14, Memorial Hospital of South Bend15, University of Liverpool16
TL;DR: TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC, and Adverse events were consistent with those of previous TACE combination trials.
Abstract: Objective This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE. Design Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2–3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing. Results Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities. Conclusion TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials. Trial registration number NCT01217034.
University of Reading1, Leipzig University2, Imperial College London3, Max Planck Society4, University of Oxford5, University of Paris6, University of Leeds7, University of Bordeaux8, École Normale Supérieure9, National Oceanic and Atmospheric Administration10, University of Cologne11, National Center for Atmospheric Research12, University of Exeter13, Met Office14, ETH Zurich15, Stockholm University16, University of Oslo17, Carnegie Institution for Science18, Goethe University Frankfurt19, Nagoya University20, Hokkaido University21, Norwegian Meteorological Institute22, Brookhaven National Laboratory23, Lille University of Science and Technology24, University of Tartu25, Langley Research Center26
TL;DR: A new range of aerosol radiative forcing over the industrial era is provided based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations, to constrain the forcing from aerosol‐radiation interactions.
Abstract: Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth’s radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable and arguable lines of evidence, including modelling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of −1.60 to −0.65 W m−2, or −2.0 to −0.4 W m−2 with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted towards more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds.
Newcastle University1, Mayo Clinic2, University of Strasbourg3, Nagoya University4, University of Cambridge5, McGill University6, King's College London7, University of Exeter8, University of Chieti-Pescara9, University of Miami10, University of California, San Diego11, Northwestern University12, Harvard University13, Columbia University14, Osaka University15, Cleveland Clinic16, University of Sydney17, Sunnybrook Health Sciences Centre18, University of Washington19, University College London20, University of Toronto21
TL;DR: This work proposes operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for Use in clinical practice and are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease.
Abstract: The prodromal phase of dementia with Lewy bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.
TL;DR: In this article, a search for the electroweak production of charginos and sleptons decaying into final states with two electrons or muons is presented, based on 139.fb$^{-1}$ of proton-proton collisions recorded by the ATLAS detector at the Large Hadron Collider at
Abstract: A search for the electroweak production of charginos and sleptons decaying into final states with two electrons or muons is presented. The analysis is based on 139 fb$^{-1}$ of proton–proton collisions recorded by the ATLAS detector at the Large Hadron Collider at $\sqrt{s}=13$ $\text {TeV}$. Three R-parity-conserving scenarios where the lightest neutralino is the lightest supersymmetric particle are considered: the production of chargino pairs with decays via either W bosons or sleptons, and the direct production of slepton pairs. The analysis is optimised for the first of these scenarios, but the results are also interpreted in the others. No significant deviations from the Standard Model expectations are observed and limits at 95% confidence level are set on the masses of relevant supersymmetric particles in each of the scenarios. For a massless lightest neutralino, masses up to 420 $\text {Ge}\text {V}$ are excluded for the production of the lightest-chargino pairs assuming W-boson-mediated decays and up to 1 $\text {TeV}$ for slepton-mediated decays, whereas for slepton-pair production masses up to 700 $\text {Ge}\text {V}$ are excluded assuming three generations of mass-degenerate sleptons.
Broad Institute1, Harvard University2, Kyushu University3, Chiba University4, University of Tokyo5, Osaka University6, University of North Carolina at Chapel Hill7, Japanese Foundation for Cancer Research8, Tokyo Medical and Dental University9, Tohoku University10, National Cancer Research Institute11, Fujita Health University12, Hiroshima University13, Shiga University of Medical Science14, University of Tokushima15, Kyoto University16, Iwate Medical University17, Nagoya University18, Nippon Medical School19, Nihon University20, Juntendo University21, University of Hyogo22, Saga University23, University of Manchester24
TL;DR: A large-scale genome-wide association study in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.
Abstract: The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10-9). East Asian-specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.
TL;DR: This work constitutes the most precise measurements of R(D) and R (D^{*}) performed to date as well as the first result for R( D) based on a semileptonic tagging method.
Abstract: The experimental results on the ratios of branching fractions $\mathcal{R}(D) = {\cal B}(\bar{B} \to D \tau^- \bar{
u}_{\tau})/{\cal B}(\bar{B} \to D \ell^- \bar{
u}_{\ell})$ and $\mathcal{R}(D^*) = {\cal B}(\bar{B} \to D^* \tau^- \bar{
u}_{\tau})/{\cal B}(\bar{B} \to D^* \ell^- \bar{
u}_{\ell})$, where $\ell$ denotes an electron or a muon, show a long-standing discrepancy with the Standard Model predictions, and might hint to a violation of lepton flavor universality. We report a new simultaneous measurement of $\mathcal{R}(D)$ and $\mathcal{R}(D^*)$, based on a data sample containing $772 \times 10^6$ $B\bar{B}$ events recorded at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB $e^+ e^-$ collider. In this analysis the tag-side $B$ meson is reconstructed in a semileptonic decay mode and the signal-side $\tau$ is reconstructed in a purely leptonic decay. The measured values are $\mathcal{R}(D)= 0.307 \pm 0.037 \pm 0.016$ and $\mathcal{R}(D^*) = 0.283 \pm 0.018 \pm 0.014$, where the first uncertainties are statistical and the second are systematic. These results are in agreement with the Standard Model predictions within $0.2$, $1.1$ and $0.8$ standard deviations for $\mathcal{R}(D)$, $\mathcal{R}(D^*)$ and their combination, respectively. This work constitutes the most precise measurements of $\mathcal{R}(D)$ and $\mathcal{R}(D^*)$ performed to date as well as the first result for $\mathcal{R}(D)$ based on a semileptonic tagging method.
École Polytechnique Fédérale de Lausanne1, University at Buffalo2, ETH Zurich3, Uppsala University4, Hebrew University of Jerusalem5, Katholieke Universiteit Leuven6, University of Bologna7, University of Siena8, Aix-Marseille University9, National University of Singapore10, Lund University11, Stockholm University12, University of Oslo13, Nagoya University14, Imperial College London15, Autonomous University of Madrid16, University of Nantes17, University of Liège18
TL;DR: This article provides a comprehensive overview of the main features of the MOLCAS/OpenMolcas code, specifically reviewing the use of the code in previously reported chemical applications as well as more recent applications including the calculation of magnetic properties from optimized density matrix renormalization group wave functions.
Abstract: MOLCAS/OpenMolcas is an ab initio electronic structure program providing a large set of computational methods from Hartree-Fock and density functional theory to various implementations of multiconfigurational theory. This article provides a comprehensive overview of the main features of the code, specifically reviewing the use of the code in previously reported chemical applications as well as more recent applications including the calculation of magnetic properties from optimized density matrix renormalization group wave functions.
University of Toronto1, Mayo Clinic2, The Royal Marsden NHS Foundation Trust3, Claude Bernard University Lyon 14, Curie Institute5, Emory University6, Netherlands Cancer Institute7, University of Padua8, University College London9, Princess Margaret Cancer Centre10, Memorial Sloan Kettering Cancer Center11, University of Erlangen-Nuremberg12, Heidelberg University13, Institute of Cancer Research14, University of Texas MD Anderson Cancer Center15, University of Southern California16, Nagoya University17, Ohio State University18, Harvard University19, University of Colorado Boulder20, University of Münster21, Maine Medical Center22, European Medicines Agency23
TL;DR: An evidence-based, joint global consensus guideline approach to the management of Desmoid tumor focussing on molecular genetics, indications for an active treatment, and available systemic therapeutic options is presented.
University of Massachusetts Amherst1, University of North Carolina at Chapel Hill2, University of Oxford3, The Chinese University of Hong Kong4, Kyoto University5, Seoul National University Hospital6, Vanderbilt University Medical Center7, National University of Singapore8, Academia Sinica9, Nagoya University10, University of California, Los Angeles11, Los Angeles Biomedical Research Institute12, Hallym University13, University of Texas Health Science Center at Houston14, University of Michigan15, Wake Forest University16, Genentech17, London North West Healthcare NHS Trust18, Imperial College London19, University of Liverpool20, University of Manchester21, Kyushu University22, Peking Union Medical College23, National Taiwan University24, University of Minnesota25, Chinese National Human Genome Center26, National Defense Medical Center27, Tri-Service General Hospital28, National Yang-Ming University29, Taipei Veterans General Hospital30, Jichi Medical University31, Heidelberg University32, University of Tokyo33, Osaka University34, University of the Ryukyus35, Agency for Science, Technology and Research36, Ehime University37, Yonsei University38, Samsung Medical Center39, University of San Carlos40, Peking University41, Macau University of Science and Technology42, China Medical University (Taiwan)43, Shanghai Jiao Tong University44, Kurume University45, University of Pittsburgh46, Capital Medical University47, New Generation University College48, Seoul National University49
TL;DR: A meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2abetes in both East Asian and European populations.
Abstract: Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.
National Institute of Informatics1, University of Edinburgh2, Institut Eurécom3, University of Lorraine4, University of Eastern Finland5, NEC6, Aalto University7, Academia Sinica8, Trinity College, Dublin9, Google10, Nagoya University11, University of Avignon12, University of Science and Technology of China13
TL;DR: The ASVspoof challenge as mentioned in this paper was created to foster research on anti-spoofing and to provide common platforms for the assessment and comparison of spoofing countermeasures, and the first edition focused on replay spoofing attacks and countermeasures.
Columbia University1, Stockholm University2, University of Bologna3, University of Mainz4, University of Münster5, University of Coimbra6, University of Turin7, University of Amsterdam8, New York University Abu Dhabi9, University of Zurich10, Rensselaer Polytechnic Institute11, Weizmann Institute of Science12, Max Planck Society13, Purdue University14, University of Freiburg15, University of Nantes16, University of L'Aquila17, University of Paris18, University of Chicago19, Institute for the Physics and Mathematics of the Universe20, Nagoya University21, Université Paris-Saclay22, Kobe University23, University of California, San Diego24, Rice University25, Karlsruhe Institute of Technology26, University of California, Los Angeles27
TL;DR: In this paper, the authors predict the experimental background and project the sensitivity of XENONnT to the detection of weakly interacting massive particles (WIMPs) in a 4 t fiducial mass.
Abstract: XENONnT is a dark matter direct detection experiment, utilizing 5.9 t of instrumented liquid xenon, located at the INFN Laboratori Nazionali del Gran Sasso. In this work, we predict the experimental background and project the sensitivity of XENONnT to the detection of weakly interacting massive particles (WIMPs). The expected average differential background rate in the energy region of interest, corresponding to (1, 13) keV and (4, 50) keV for electronic and nuclear recoils, amounts to 12.3 ± 0.6 (keV t y)-1 and (2.2± 0.5)× 10−3 (keV t y)-1, respectively, in a 4 t fiducial mass. We compute unified confidence intervals using the profile construction method, in order to ensure proper coverage. With the exposure goal of 20 t y, the expected sensitivity to spin-independent WIMP-nucleon interactions reaches a cross-section of 1.4×10−48 cm2 for a 50 GeV/c2 mass WIMP at 90% confidence level, more than one order of magnitude beyond the current best limit, set by XENON1T . In addition, we show that for a 50 GeV/c2 WIMP with cross-sections above 2.6×10−48 cm2 (5.0×10−48 cm2) the median XENONnT discovery significance exceeds 3σ (5σ). The expected sensitivity to the spin-dependent WIMP coupling to neutrons (protons) reaches 2.2×10−43 cm2 (6.0×10−42 cm2).
TL;DR: It is shown that α-synuclein filaments from the brains of patients with MSA and DLB are different, suggesting that distinct conformers (or strains) characterise synucleinopathies, with implications for understanding the mechanisms of aggregate propagation and neurodegeneration in human brain.
Abstract: Synucleinopathies are human neurodegenerative diseases that include multiple system atrophy (MSA), Parkinson9s disease, Parkinson9s disease dementia (PDD) and dementia with Lewy bodies (DLB). Existing treatments are at best symptomatic. These diseases are characterised by the presence in brain cells of filamentous inclusions of α-synuclein, the formation of which is believed to cause disease. However, the structures of α-synuclein filaments from human brain are not known. Here we show, using electron cryo-microscopy, that α-synuclein inclusions from MSA are made of two types of filaments, each of which consists of two different protofilaments. Non-proteinaceous molecules are present at the protofilament interfaces. By two-dimensional class averaging, we show that α-synuclein filaments from the brains of patients with MSA and DLB are different, suggesting that distinct conformers (or strains) characterise synucleinopathies. As was the case of tau assemblies, the structures of α-synuclein filaments extracted from the brains of individuals with MSA differ from those formed in vitro using recombinant proteins, with implications for understanding the mechanisms of aggregate propagation and neurodegeneration in human brain. These findings have diagnostic and potential therapeutic relevance, especially in view of the unmet clinical need to be able to image filamentous α-synuclein inclusions in human brain.
Kobe University1, Japan Aerospace Exploration Agency2, Chiba Institute of Technology3, Kōchi University4, Toho University5, Centre national de la recherche scientifique6, University of Bern7, Tokyo University of Science8, University of Tokyo9, Rikkyo University10, Spanish National Research Council11, National Institute of Advanced Industrial Science and Technology12, University of Aizu13, Nagoya University14, Graduate University for Advanced Studies15, University of Liverpool16
TL;DR: An impact experiment on Ryugu is described using Hayabusa2’s Small Carry-on Impactor, which produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit, and implications for Ryugu's surface age are discussed.
Abstract: The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.