Showing papers by "Paul Sabatier University published in 2019"
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TL;DR: In this article, the Event Horizon Telescope was used to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87.
Abstract: When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 +/- 3 mu as, which is circular and encompasses a central depression in brightness with a flux ratio greater than or similar to 10: 1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M = (6.5 +/- 0.7) x 10(9) M-circle dot. Our radio-wave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible.
2,589 citations
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Mike A. Nalls1, Cornelis Blauwendraat1, Costanza L. Vallerga2, Karl Heilbron +245 more•Institutions (23)
TL;DR: These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified.
Abstract: Summary Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources).
1,152 citations
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TL;DR: Two loci close to NKX6.3/MIR486 and RBSG4 are identified in the Canadian discovery cohort and replicated in the DiOGenes cohort and taken forward for Bayesian fine-mapping and functional assessment in flies.
Abstract: Hundreds of genetic variants have been associated with Body Mass Index (BMI) through genome-wide association studies (GWAS) using observational cohorts. However, the genetic contribution to efficient weight loss in response to dietary intervention remains unknown. We perform a GWAS in two large low-caloric diet intervention cohorts of obese participants. Two loci close to NKX6.3/MIR486 and RBSG4 are identified in the Canadian discovery cohort (n = 1166) and replicated in the DiOGenes cohort (n = 789). Modulation of HGTX (NKX6.3 ortholog) levels in Drosophila melanogaster leads to significantly altered triglyceride levels. Additional tissue-specific experiments demonstrate an action through the oenocytes, fly hepatocyte-like cells that regulate lipid metabolism. Our results identify genetic variants associated with the efficacy of weight loss in obese subjects and identify a role for NKX6.3 in lipid metabolism, and thereby possibly weight control. Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.
1,085 citations
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TL;DR: The Event Horizon Telescope (EHT) as mentioned in this paper is a very long baseline interferometry (VLBI) array that comprises millimeter and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth.
Abstract: The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ~1.3 mm, EHT angular resolution (λ/D) is ~25 μas, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s^(−1), exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87.
756 citations
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Paul Sabatier University1, Memorial Sloan Kettering Cancer Center2, university of lille3, University of Paris-Sud4, Aix-Marseille University5, Radboud University Nijmegen6, Stanford University7, Ben-Gurion University of the Negev8, University of Bern9, University of Colorado Boulder10, The Royal Marsden NHS Foundation Trust11, University of California, Irvine12, University Hospital of Basel13, University of Turin14, University of Zurich15, University of Grenoble16, University of Duisburg-Essen17
TL;DR: In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2) and the lack of response in the ALK group was notable.
719 citations
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TL;DR: In this article, the best practices for measuring and reporting metrics such as capacitance, capacity, coulombic and energy efficiencies, electrochemical impedance, and the energy and power densities of capacitive and pseudocapacitive materials are discussed.
Abstract: Due to the tremendous importance of electrochemical energy storage, numerous new materials and electrode architectures for batteries and supercapacitors have emerged in recent years. Correctly characterizing these systems requires considerable time, effort, and experience to ensure proper metrics are reported. Many new nanomaterials show electrochemical behavior somewhere in between conventional double‐layer capacitor and battery electrode materials, making their characterization a non‐straightforward task. It is understandable that some researchers may be misinformed about how to rigorously characterize their materials and devices, which can result in inflation of their reported data. This is not uncommon considering the current state of the field nearly requires record breaking performance for publication in high‐impact journals. Incorrect characterization and data reporting misleads both the materials and device development communities, and it is the shared responsibility of the community to follow rigorous reporting methodologies to ensure published results are reliable to ensure constructive progress. This tutorial aims to clarify the main causes of inaccurate data reporting and to give examples of how researchers should proceed. The best practices for measuring and reporting metrics such as capacitance, capacity, coulombic and energy efficiencies, electrochemical impedance, and the energy and power densities of capacitive and pseudocapacitive materials are discussed.
642 citations
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TL;DR: This multicentre randomised, non-comparative, open-label, phase 2 trial aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma.
Abstract: Summary Background There is no recommended therapy for malignant pleural mesothelioma that has progressed after first-line pemetrexed and platinum-based chemotherapy. Disease control has been less than 30% in all previous studies of second-line drugs. Preliminary results have suggested that anti-programmed cell death 1 (PD-1) monoclonal antibody could be efficacious in these patients. We thus aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma. Methods This multicentre randomised, non-comparative, open-label, phase 2 trial was done at 21 hospitals in France. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1, histologically proven malignant pleural mesothelioma progressing after first-line or second-line pemetrexed and platinum-based treatments, measurable disease by CT, and life expectancy greater than 12 weeks. Patients were randomly allocated (1:1) to receive intravenous nivolumab (3 mg/kg bodyweight) every 2 weeks, or intravenous nivolumab (3 mg/kg every 2 weeks) plus intravenous ipilimumab (1 mg/kg every 6 weeks), given until progression or unacceptable toxicity. Central randomisation was stratified by histology (epithelioid vs non-epithelioid), treatment line (second line vs third line), and chemosensitivity to previous treatment (progression ≥3 months vs Findings Between March 24 and August 25, 2016, 125 eligible patients were recruited and assigned to either nivolumab (n=63) or nivolumab plus ipilimumab (n=62). In the first 108 eligible patients, 12-week disease control was achieved by 24 (44%; 95% CI 31–58) of 54 patients in the nivolumab group and 27 (50%; 37–63) of 54 patients in the nivolumab plus ipilimumab group. In the intention-to-treat population, 12-week disease control was achieved by 25 (40%; 28–52) of 63 patients in the nivolumab group and 32 (52%; 39–64) of 62 patients in the combination group. Nine (14%) of 63 patients in the nivolumab group and 16 (26%) of 61 patients in the combination group had grade 3–4 toxicities. The most frequent grade 3 adverse events were asthenia (one [2%] in the nivolumab group vs three [5%] in the combination group), asymptomatic increase in aspartate aminotransferase or alanine aminotransferase (none vs four [7%] of each), and asymptomatic lipase increase (two [3%] vs one [2%]). No patients had toxicities leading to death in the nivolumab group, whereas three (5%) of 62 in the combination group did (one fulminant hepatitis, one encephalitis, and one acute kidney failure). Interpretation Anti-PD-1 nivolumab monotherapy or nivolumab plus anti-CTLA-4 ipilimumab combination therapy both showed promising activity in relapsed patients with malignant pleural mesothelioma, without unexpected toxicity. These regimens require confirmation in larger clinical trials. Funding French Cooperative Thoracic Intergroup.
314 citations
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TL;DR: In this paper, the authors show how simply changing the solvent of an electrolyte system can drastically influence the pseudocapacitive charge storage of the two-dimensional titanium carbide, Ti3C2 (a representative member of the MXene family).
Abstract: Pseudocapacitive energy storage in supercapacitor electrodes differs significantly from the electrical double-layer mechanism of porous carbon materials, which requires a change from conventional thinking when choosing appropriate electrolytes. Here we show how simply changing the solvent of an electrolyte system can drastically influence the pseudocapacitive charge storage of the two-dimensional titanium carbide, Ti3C2 (a representative member of the MXene family). Measurements of the charge stored by Ti3C2 in lithium-containing electrolytes with nitrile-, carbonate- and sulfoxide-based solvents show that the use of a carbonate solvent doubles the charge stored by Ti3C2 when compared with the other solvent systems. We find that the chemical nature of the electrolyte solvent has a profound effect on the arrangement of molecules/ions in Ti3C2, which correlates directly to the total charge being stored. Having nearly completely desolvated lithium ions in Ti3C2 for the carbonate-based electrolyte leads to high volumetric capacitance at high charge–discharge rates, demonstrating the importance of considering all aspects of an electrochemical system during development.
313 citations
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Wageningen University and Research Centre1, University of Puerto Rico2, National Autonomous University of Mexico3, Colby College4, National Institute of Amazonian Research5, University of São Paulo6, Federal University of Pernambuco7, University of Alberta8, Paul Sabatier University9, International Institute of Minnesota10, University of Colorado Boulder11, University of Connecticut12, Smithsonian Tropical Research Institute13, Tulane University14, University of Stirling15, Clemson University16, Comisión Nacional para el Conocimiento y Uso de la Biodiversidad17, Universidade Federal de Minas Gerais18, Centro Agronómico Tropical de Investigación y Enseñanza19, Alexander von Humboldt Biological Resources Research Institute20, The Catholic University of America21, Colorado Mesa University22, State University of New York at Purchase23, University of Haifa24, University of Wisconsin-Madison25, Universidade Federal do Rio Grande do Sul26, Universidade Federal de Viçosa27, Costa Rica Institute of Technology28, University of Minnesota29, Pedagogical and Technological University of Colombia30, University of California, Santa Barbara31, Museu Paraense Emílio Goeldi32, University of California, Berkeley33, Columbia University34, New York Botanical Garden35, Yale-NUS College36, National University of Singapore37, Puerto Rico Department of Agriculture38, University of Amsterdam39, Louisiana State University40, University of Puerto Rico, Río Piedras41
TL;DR: This work assesses how tree species richness and composition recover during secondary succession across gradients in environmental conditions and anthropogenic disturbance in an unprecedented multisite analysis for the Neotropics.
Abstract: Old-growth tropical forests harbor an immense diversity of tree species but are rapidly being cleared, while secondary forests that regrow on abandoned agricultural lands increase in extent. We assess how tree species richness and composition recover during secondary succession across gradients in environmental conditions and anthropogenic disturbance in an unprecedented multisite analysis for the Neotropics. Secondary forests recover remarkably fast in species richness but slowly in species composition. Secondary forests take a median time of five decades to recover the species richness of old-growth forest (80% recovery after 20 years) based on rarefaction analysis. Full recovery of species composition takes centuries (only 34% recovery after 20 years). A dual strategy that maintains both old-growth forests and species-rich secondary forests is therefore crucial for biodiversity conservation in human-modified tropical landscapes.
273 citations
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University of Leeds1, University of Edinburgh2, University College London3, University of Exeter4, Imperial College London5, National University of Saint Anthony the Abbot in Cuzco6, Universidad Autónoma Gabriel René Moreno7, National Institute of Amazonian Research8, Universidade do Estado de Mato Grosso9, Universidade Federal do Acre10, University of Los Andes11, University of Washington12, Environmental Change Institute13, Centre national de la recherche scientifique14, Lancaster University15, Museu Paraense Emílio Goeldi16, University of Lorraine17, Universidad Nacional de la Amazonía Peruana18, Smithsonian Institution19, University of Montpellier20, James Cook University21, Wageningen University and Research Centre22, Agro ParisTech23, University of Amsterdam24, Naturalis25, Federal University of Western Pará26, State University of Campinas27, National Institute for Space Research28, Florida International University29, University of São Paulo30, Tropenbos International31, Amazon.com32, Federal University of Pará33, Michigan Technological University34, University of Texas at Austin35, Polytechnic University of Valencia36, Venezuelan Institute for Scientific Research37, Royal Museum for Central Africa38, Tecnológico de Antioquia39, George Mason University40, Universidad del Tolima41, National University of Colombia42, Paul Sabatier University43, Georgetown University44, University of La Serena45, Forestry Commission46, Federal University of Alagoas47, Duke University48, Van Hall Larenstein University of Applied Sciences49, University of Nottingham50
TL;DR: A slow shift to a more dry‐affiliated Amazonia is underway, with changes in compositional dynamics consistent with climate‐change drivers, but yet to significantly impact whole‐community composition.
Abstract: Most of the planet's diversity is concentrated in the tropics, which includes many regions undergoing rapid climate change. Yet, while climate‐induced biodiversity changes are widely documented elsewhere, few studies have addressed this issue for lowland tropical ecosystems. Here we investigate whether the floristic and functional composition of intact lowland Amazonian forests have been changing by evaluating records from 106 long‐term inventory plots spanning 30 years. We analyse three traits that have been hypothesized to respond to different environmental drivers (increase in moisture stress and atmospheric CO2 concentrations): maximum tree size, biogeographic water‐deficit affiliation and wood density. Tree communities have become increasingly dominated by large‐statured taxa, but to date there has been no detectable change in mean wood density or water deficit affiliation at the community level, despite most forest plots having experienced an intensification of the dry season. However, among newly recruited trees, dry‐affiliated genera have become more abundant, while the mortality of wet‐affiliated genera has increased in those plots where the dry season has intensified most. Thus, a slow shift to a more dry‐affiliated Amazonia is underway, with changes in compositional dynamics (recruits and mortality) consistent with climate‐change drivers, but yet to significantly impact whole‐community composition. The Amazon observational record suggests that the increase in atmospheric CO2 is driving a shift within tree communities to large‐statured species and that climate changes to date will impact forest composition, but long generation times of tropical trees mean that biodiversity change is lagging behind climate change.
263 citations
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TL;DR: An overview of current knowledge of the antimicrobial activity of phenolic-rich plant extracts and of the promises and limits of their exploitation for the preservation of perishable foods is provided.
Abstract: The growing demand for natural food preservatives in the last decade has promoted investigations on their application for preserving perishable foods. In this context, the present review is focused on discussing the prospective application of plant extracts containing phenolics or isolated plant phenolics as natural antimicrobials in foods. Plant essential oils are outside the scope of this review since utilization of their antimicrobial activity for food preservation has been extensively reviewed.; Results: Although the exact antimicrobial mechanisms of action of phenolic compounds are not yet fully understood, it is commonly acknowledged that they have diverse sites of action at the cellular level. Antimicrobial phenolics can be added directly to the formulation of perishable food products or incorporated into food-contact materials to release them in the immediate zone of perishable foods. Edible coatings or active food packaging materials can thus be used as carriers of plant bioactive compounds.; Conclusion: These materials could be an interesting delivery system to improve the stability of phenolics in foods and to improve the shelf life of perishable foods. This review will thus provide an overview of current knowledge of the antimicrobial activity of phenolic-rich plant extracts and of the promises and limits of their exploitation for the preservation of perishable foods. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.
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École Normale Supérieure1, University of Grenoble2, University of California, Riverside3, Macquarie University4, Bangor University5, Australian Antarctic Division6, University of Canterbury7, University of Essex8, University of Milan9, University of Colorado Boulder10, Cooperative Institute for Research in Environmental Sciences11, University of Lausanne12, Norwegian University of Science and Technology13, University of Copenhagen14, Curtin University15, Commonwealth Scientific and Industrial Research Organisation16, Kansas State University17, University of Oslo18, Paul Sabatier University19, University of Paris20, University of Geneva21, University of Tartu22, Aarhus University23, University of Cambridge24, Wellcome Trust Sanger Institute25
TL;DR: This book is dedicated to the victims of the Paris terror attacks of 22 July 1997, which claimed the lives of 129 people and injured more than 200 others.
Abstract: Zinger, Lucie; Bonin, Aurélie; Alsos, Inger G; Bálint, Miklós; Bik, Holly; Boyer, Frédéric; Chariton, Anthony A; Creer, Simon; Coissac, Eric; Deagle, Bruce E; De Barba, Marta; Dickie, Ian A; Dumbrell, Alex J; Ficetola, Gentile Francesco; Fierer, Noah; Fumagalli, Luca; Gilbert, M Thomas P; Jarman, Simon; Jumpponen, Ari; Kauserud, Håvard; Orlando, Ludovic; Pansu, Johan; Pawlowski, Jan; Tedersoo, Leho; Thomsen, Philip Francis; Willerslev, Eske; Taberlet, Pierre
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Nanyang Technological University1, Swiss Federal Institute of Aquatic Science and Technology2, Aalborg University3, University of Duisburg-Essen4, Paul Sabatier University5, Karlsruhe Institute of Technology6, Delft University of Technology7, University of Florence8, Polytechnic University of Milan9, University of Notre Dame10, Helmholtz Centre for Environmental Research - UFZ11, University of Toulouse12, University of Science and Technology of China13
TL;DR: A multidisciplinary roadmap for addressing this EPS identity crisis is proposed, which involves improved EPS extraction and characterization methodologies, cross-referencing between model biofilms and full-scale biofilm systems, and functional description of isolated EPS with in situ techniques coupled with genomics, proteomics and glycomics.
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TL;DR: In this paper, the existence and uniqueness of the normalized Kahler-Ricci flow on non-singular Fano manifolds with log terminal singularities has been proved.
Abstract: We prove the existence and uniqueness of Kahler-Einstein metrics on Q-Fano varieties with log terminal singularities (and more generally on log Fano pairs) whose Mabuchi functional is proper. We study analogues of the works of Perelman on the convergence of the normalized Kahler-Ricci flow, and of Keller, Rubinstein on its discrete version, Ricci iteration. In the special case of (non-singular) Fano manifolds, our results on Ricci iteration yield smooth convergence without any additional condition, improving on previous results. Our result for the Kahler-Ricci flow provides weak convergence independently of Perelman's celebrated estimates.
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Paul Sabatier University1, University of Copenhagen2, Abdul Wali Khan University Mardan3, University of Cambridge4, Stanford University5, King Saud University6, University of Barcelona7, Hartwick College8, McDonald Institute for Archaeological Research9, Deutsches Archäologisches Institut10, Autonomous University of Madrid11, University of Oslo12, National University of Mongolia13, University of Vienna14, University of Mainz15, Tarbiat Modares University16, Spanish National Research Council17, University of Lisbon18, Ludwig Maximilian University of Munich19, University of Tehran20, Facultad de Filosofía y Letras21, Pablo de Olavide University22, Royal Belgian Institute of Natural Sciences23, Agricultural University of Iceland24, University of Potsdam25, Russian Academy of Sciences26, University of Gothenburg27, Pompeu Fabra University28, Samara State University29, Tallinn University30, Humboldt University of Berlin31, Leibniz Association32, ISCTE – University Institute of Lisbon33, University of Oxford34, Centre national de la recherche scientifique35, Istanbul University36, Tbilisi State University37, University of Bordeaux38, Indian Council of Agricultural Research39, University of Edinburgh40, Martin Luther University of Halle-Wittenberg41, University of California, Santa Cruz42, University of Kashan43, University of California, Irvine44, University of Nottingham45, University of Exeter46, Max Planck Society47, University of Zagreb48, Karagandy State University49, University of Southampton50, Al-Farabi University51, deCODE genetics52, Université Paris-Saclay53
TL;DR: This extensive dataset allows us to assess the modern legacy of past equestrian civilizations and finds that two extinct horse lineages existed during early domestication, and the development of modern breeding impacted genetic diversity more dramatically than the previous millennia of human management.
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TL;DR: The iBox system showed accuracy when assessed at different times of evaluation post-transplant, was validated in different clinical scenarios, and outperformed previous risk prediction scores as well as a risk score based solely on functional parameters including estimated glomerular filtration rate and proteinuria.
Abstract: Objective To develop and validate an integrative system to predict long term kidney allograft failure. Design International cohort study. Setting Three cohorts including kidney transplant recipients from 10 academic medical centres from Europe and the United States. Participants Derivation cohort: 4000 consecutive kidney recipients prospectively recruited in four French centres between 2005 and 2014. Validation cohorts: 2129 kidney recipients from three centres in Europe and 1428 from three centres in North America, recruited between 2002 and 2014. Additional validation in three randomised controlled trials (NCT01079143, EudraCT 2007-003213-13, and NCT01873157). Main outcome measure Allograft failure (return to dialysis or pre-emptive retransplantation). 32 candidate prognostic factors for kidney allograft survival were assessed. Results Among the 7557 kidney transplant recipients included, 1067 (14.1%) allografts failed after a median post-transplant follow-up time of 7.12 (interquartile range 3.51-8.77) years. In the derivation cohort, eight functional, histological, and immunological prognostic factors were independently associated with allograft failure and were then combined into a risk prediction score (iBox). This score showed accurate calibration and discrimination (C index 0.81, 95% confidence interval 0.79 to 0.83). The performance of the iBox was also confirmed in the validation cohorts from Europe (C index 0.81, 0.78 to 0.84) and the US (0.80, 0.76 to 0.84). The iBox system showed accuracy when assessed at different times of evaluation post-transplant, was validated in different clinical scenarios including type of immunosuppressive regimen used and response to rejection therapy, and outperformed previous risk prediction scores as well as a risk score based solely on functional parameters including estimated glomerular filtration rate and proteinuria. Finally, the accuracy of the iBox risk score in predicting long term allograft loss was confirmed in the three randomised controlled trials. Conclusion An integrative, accurate, and readily implementable risk prediction score for kidney allograft failure has been developed, which shows generalisability across centres worldwide and common clinical scenarios. The iBox risk prediction score may help to guide monitoring of patients and further improve the design and development of a valid and early surrogate endpoint for clinical trials. Trial registration Clinicaltrials.gov NCT03474003.
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TL;DR: In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC, and stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis.
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TL;DR: Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis, and safety analyses were done in the safety population.
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University of Sheffield1, Paul Sabatier University2, University of Toulouse3, Technical University of Denmark4, University of Edinburgh5, University of Montpellier6, Polytechnic University of Milan7, University of Bordeaux8, German Aerospace Center9, European Space Research and Technology Centre10, Jet Propulsion Laboratory11, University of Virginia12, University of Tasmania13, Hobart Corporation14, Chalmers University of Technology15
TL;DR: The European Space Agency's 7th Earth Explorer mission, BIOMASS, is to determine the worldwide distribution of forest above-ground biomass (AGB) in order to reduce the major uncertainties in calculations of carbon stocks and fluxes associated with the terrestrial biosphere, including carbon fluxe associated with Land Use Change, forest degradation and forest regrowth as mentioned in this paper.
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TL;DR: For patients with KRAS-mutant NSCLC (all mutational subtypes), the efficacy of ICI is similar to that for patients with other types of NSCLCs, and this finding is especially true when PD-L1 expression is high (PD-L 1 expression ≥50%).
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Hunan University1, Nanjing Tech University2, Nanyang Technological University3, Xi'an Jiaotong University4, Sichuan University5, Centre national de la recherche scientifique6, Paul Sabatier University7, Beijing University of Chemical Technology8, University of Twente9, Xiamen University10, Zhengzhou University11
TL;DR: In this article, a roadmap for two-dimensional materials for energy storage and conversion is presented, which includes graphite, black phosporus, MXenes, covalent organic frameworks (COFs), 2D oxides, 2D chalcogenides, and others.
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TL;DR: In this article, a simple parameterization model based on the spectral invariant theory was proposed to estimate the probability for SIF photons to escape from the canopy, which was found to be related to the anisotropic spectral reflectance, canopy interception of the upward solar radiation, and leaf absorption.
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TL;DR: A comprehensive review of the literature on reinforcement learning-based routing protocols is provided, structured in a way that shows how network characteristics and requirements were gradually considered over time.
Abstract: Reinforcement learning (RL), which is a class of machine learning, provides a framework by which a system can learn from its previous interactions with its environment to efficiently select its actions in the future. RL has been used in a number of application fields, including game playing, robotics and control, networks, and telecommunications, for building autonomous systems that improve themselves with experience. It is commonly accepted that RL is suitable for solving optimization problems related to distributed systems in general and to routing in networks in particular. RL also has reasonable overhead—in terms of control packets, memory and computation—compared to other optimization techniques used to solve the same problems. Since the mid-1990s, over 60 protocols have been proposed, with major or minor contributions in the field of optimal route selection to convey packets in different types of communication networks under various user QoS requirements. This paper provides a comprehensive review of the literature on the topic. The review is structured in a way that shows how network characteristics and requirements were gradually considered over time. Classification criteria are proposed to present and qualitatively compare existing RL-based routing protocols.
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Nanjing University of Information Science and Technology1, International Sleep Products Association2, Université Paris-Saclay3, Paul Sabatier University4, University of Copenhagen5, California Institute of Technology6, Ludwig Maximilian University of Munich7, Ghent University8, University of Oklahoma9, National University of Defense Technology10, Boston University11, University of Valencia12, University of Toulouse13, Lund University14, Spanish National Research Council15
TL;DR: Low-frequency L-band passive microwave observations are used to compute a direct and spatially explicit quantification of annual aboveground carbon (AGC) fluxes and show that the tropical net AGC budget was approximately in balance during 2010 to 2017.
Abstract: Changes in terrestrial tropical carbon stocks have an important role in the global carbon budget. However, current observational tools do not allow accurate and large-scale monitoring of the spatial distribution and dynamics of carbon stocks'. Here, we used low-frequency L-band passive microwave observations to compute a direct and spatially explicit quantification of annual aboveground carbon (AGC) fluxes and show that the tropical net AGC budget was approximately in balance during 2010 to 2017, the net budget being composed of gross losses of -2.86 PgC yr(-1) offset by gross gains of -2.97 PgC yr(-1) between continents. Large interannual and spatial fluctuations of tropical AGC were quantified during the wet 2011 La Nina year and throughout the extreme dry and warm 2015-2016 El Nino episode. These interannual fluctuations, controlled predominantly by semiarid biomes, were shown to be closely related to independent global atmospheric CO2 growth-rate anomalies (Pearson's r = 0.86), highlighting the pivotal role of tropical AGC in the global carbon budget.
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TL;DR: SMP buoyancy is significantly decreased compared to the large microplastics (LMP, 1-5 mm) and consequently more susceptible to vertical transport, and it is demonstrated that SMP were 300 to 70 000 times more abundant than LMP.
Abstract: Estimates of cumulative plastic inputs into the oceans are expressed in hundred million tons, whereas the total mass of microplastics afloat at sea is 3 orders of magnitude below this. This large gap is evidence of our ignorance about the fate of plastics, as well as transformations and sinks in the oceans. One of the current challenges consists of identifying and quantifying plastic particles at the microscale, the small microplastics (SMP, 25–1000 μm). The aim of the present study is to investigate SMP concentration in count and in mass at the sea surface in the North Atlantic subtropical gyre during the sea campaign Expedition 7th Continent. After isolation, SMP were characterized by micro-Fourier-transform infrared spectroscopy. Microplastic distribution was modeled by a wind-driven vertical mixing correction model taking into account individual particle properties (dimension, shape and density). We demonstrate that SMP buoyancy is significantly decreased compared to the large microplastics (LMP, 1–5 mm) and consequently more susceptible to vertical transport. The uncorrected LMP concentration in count was between 13 000 and 174 000 pieces km–2, and was between 5 and 170 times more abundant for SMP. With a wind-driven vertical mixing correction, we estimated that SMP were 300 to 70 000 times more abundant than LMP. When discussing this in terms of weight after correction, LMP concentrations were between 50 and 1000 g km–2, and SMP concentrations were between 5 and 14 000 g km–2.
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TL;DR: Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy and no unexpected safety concerns were observed.
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National Institutes of Health1, University of Queensland2, UCL Institute of Neurology3, Queen Mary University of London4, Van Andel Institute5, Baylor College of Medicine6, University of Maryland, Baltimore7, German Center for Neurodegenerative Diseases8, University of Tübingen9, Montreal Neurological Institute and Hospital10, McGill University11, Oslo University Hospital12, Oulu University Hospital13, University of Oulu14, Michael J. Fox Foundation15, University of Illinois at Urbana–Champaign16, Johns Hopkins University17, University of Murcia18, Paul Sabatier University19, University of Paris20, University of Helsinki21, University of Oslo22, Boston Children's Hospital23
TL;DR: These data provide the most comprehensive understanding of the genetic architecture of PD to date by revealing many additional PD risk loci, providing a biological context for these risk factors, and demonstrating that a considerable genetic component of this disease remains unidentified.
Abstract: We performed the largest genome-wide association study of PD to date, involving the analysis of 7.8M SNPs in 37.7K cases, 18.6K UK Biobank proxy-cases, and 1.4M controls. We identified 90 independent genome-wide significant signals across 78 loci, including 38 independent risk signals in 37 novel loci. These variants explained 26-36% of the heritable risk of PD. Tests of causality within a Mendelian randomization framework identified putatively causal genes for 70 risk signals. Tissue expression enrichment analysis suggested that signatures of PD loci were heavily brain-enriched, consistent with specific neuronal cell types being implicated from single cell expression data. We found significant genetic correlations with brain volumes, smoking status, and educational attainment. In sum, these data provide the most comprehensive understanding of the genetic architecture of PD to date by revealing many additional PD risk loci, providing a biological context for these risk factors, and demonstrating that a considerable genetic component of this disease remains unidentified.
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TL;DR: There are signs of late response not sufficient to justify the development of crizotinib in patients with ROS1-translocated tumours, but the continued targeting of c-MET with innovative therapies appears justified.
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Wageningen University and Research Centre1, Federal University of Pernambuco2, University of Florida3, Centro Agronómico Tropical de Investigación y Enseñanza4, National Autonomous University of Mexico5, Colby College6, National Institute of Amazonian Research7, Thomas Jefferson University8, University of São Paulo9, Paul Sabatier University10, University of Connecticut11, University of the Sunshine Coast12, State University of Campinas13, University of Göttingen14, Tulane University15, University of Stirling16, Smithsonian Tropical Research Institute17, Clemson University18, University of Alberta19, University of Arizona20, Universidade Federal de Minas Gerais21, Colorado Mesa University22, University of Haifa23, College of the Atlantic24, University of Wisconsin-Madison25, Universidade Federal de Viçosa26, Universidade Federal do Rio Grande do Sul27, Aarhus University28, Uppsala University29, Pedagogical and Technological University of Colombia30, Consejo Nacional de Ciencia y Tecnología31, University of British Columbia32, University of Maryland, College Park33, New York Botanical Garden34, Columbia University35, Yale-NUS College36, National University of Singapore37, Puerto Rico Department of Agriculture38, Museu Paraense Emílio Goeldi39, Louisiana State University40, University of Puerto Rico41, Macquarie University42
TL;DR: Forest recovery is analyzed using 1,403 plots that differ in age since agricultural abandonment from 50 sites across the Neotropics to analyse changes in community composition using species-specific stem wood density (WD), which is a key trait for plant growth, survival and forest carbon storage.
Abstract: Tropical forests are converted at an alarming rate for agricultural use and pastureland, but also regrow naturally through secondary succession. For successful forest restoration, it is essential to understand the mechanisms of secondary succession. These mechanisms may vary across forest types, but analyses across broad spatial scales are lacking. Here, we analyse forest recovery using 1,403 plots that differ in age since agricultural abandonment from 50 sites across the Neotropics. We analyse changes in community composition using species-specific stem wood density (WD), which is a key trait for plant growth, survival and forest carbon storage. In wet forest, succession proceeds from low towards high community WD (acquisitive towards conservative trait values), in line with standard successional theory. However, in dry forest, succession proceeds from high towards low community WD (conservative towards acquisitive trait values), probably because high WD reflects drought tolerance in harsh early successional environments. Dry season intensity drives WD recovery by influencing the start and trajectory of succession, resulting in convergence of the community WD over time as vegetation cover builds up. These ecological insights can be used to improve species selection for reforestation. Reforestation species selected to establish a first protective canopy layer should, among other criteria, ideally have a similar WD to the early successional communities that dominate under the prevailing macroclimatic conditions.
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University of Copenhagen1, Max Planck Society2, University of Florence3, Georgian National Museum4, University of Luxembourg5, University of North Texas6, University of Minnesota7, Harvard University8, University of York9, Swedish Museum of Natural History10, Stockholm University11, Sabah Wildlife Department12, University of California, Santa Cruz13, University of Venda14, Catalan Institution for Research and Advanced Studies15, Weimar Institute16, Tbilisi State University17, Paul Sabatier University18, Norwegian University of Science and Technology19
TL;DR: It is demonstrated that sequencing the proteome of Early Pleistocene dental enamel overcomes the limitations of phylogenetic inference based on ancient collagen or DNA, and resolves the phylogeny of Eurasian Rhinocerotidae.
Abstract: The sequencing of ancient DNA has enabled the reconstruction of speciation, migration and admixture events for extinct taxa1. However, the irreversible post-mortem degradation2 of ancient DNA has so far limited its recovery—outside permafrost areas—to specimens that are not older than approximately 0.5 million years (Myr)3. By contrast, tandem mass spectrometry has enabled the sequencing of approximately 1.5-Myr-old collagen type I4, and suggested the presence of protein residues in fossils of the Cretaceous period5—although with limited phylogenetic use6. In the absence of molecular evidence, the speciation of several extinct species of the Early and Middle Pleistocene epoch remains contentious. Here we address the phylogenetic relationships of the Eurasian Rhinocerotidae of the Pleistocene epoch7–9, using the proteome of dental enamel from a Stephanorhinus tooth that is approximately 1.77-Myr old, recovered from the archaeological site of Dmanisi (South Caucasus, Georgia)10. Molecular phylogenetic analyses place this Stephanorhinus as a sister group to the clade formed by the woolly rhinoceros (Coelodonta antiquitatis) and Merck’s rhinoceros (Stephanorhinus kirchbergensis). We show that Coelodonta evolved from an early Stephanorhinus lineage, and that this latter genus includes at least two distinct evolutionary lines. The genus Stephanorhinus is therefore currently paraphyletic, and its systematic revision is needed. We demonstrate that sequencing the proteome of Early Pleistocene dental enamel overcomes the limitations of phylogenetic inference based on ancient collagen or DNA. Our approach also provides additional information about the sex and taxonomic assignment of other specimens from Dmanisi. Our findings reveal that proteomic investigation of ancient dental enamel—which is the hardest tissue in vertebrates11, and is highly abundant in the fossil record—can push the reconstruction of molecular evolution further back into the Early Pleistocene epoch, beyond the currently known limits of ancient DNA preservation. Palaeoproteomic analysis of dental enamel from an Early Pleistocene Stephanorhinus resolves the phylogeny of Eurasian Rhinocerotidae, by enabling the reconstruction of molecular evolution beyond the limits of ancient DNA preservation.