Showing papers by "Pierre-and-Marie-Curie University published in 2014"
TL;DR: The review as discussed by the authors summarizes much of particle physics and cosmology using data from previous editions, plus 3,283 new measurements from 899 Japers, including the recently discovered Higgs boson, leptons, quarks, mesons and baryons.
Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.
7,337 citations
French Institute of Health and Medical Research1, Pierre-and-Marie-Curie University2, University of British Columbia3, UBC Hospital4, Beta5, Sahlgrenska University Hospital6, University of Virginia7, McGill University8, Brigham and Women's Hospital9, Washington University in St. Louis10, Vita-Salute San Raffaele University11, University College London12, University of Antwerp13, University of Geneva14, University of California, San Diego15, University of Kentucky16, Karolinska University Hospital17, university of lille18, University of California, San Francisco19, University of Nice Sophia Antipolis20, Brown University21, University of Paris22, Universidade Federal de Minas Gerais23, Maastricht University Medical Centre24, University of Southern California25, NewYork–Presbyterian Hospital26, VU University Amsterdam27, Lou Ruvo Brain Institute28
TL;DR: It is proposed that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease.
Abstract: In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.
2,581 citations
Tufts Medical Center1, University of Oxford2, Pierre-and-Marie-Curie University3, Erasmus University Rotterdam4, Women's College Hospital5, University of Liège6, American Physical Therapy Association7, Royal North Shore Hospital8, University of Tokyo9, University of Arizona10, Lund University11, Paris Descartes University12, University of Southern Denmark13, Coventry Health Care14
TL;DR: These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.
2,467 citations
Icahn School of Medicine at Mount Sinai1, Cleveland Clinic2, University of Alabama at Birmingham3, University of Copenhagen4, University College London5, University of Texas Health Science Center at Houston6, New York University7, University of Pennsylvania8, VU University Amsterdam9, National Multiple Sclerosis Society10, Johns Hopkins University11, Vita-Salute San Raffaele University12, University of Ottawa13, University of Rochester14, University of Basel15, University of Düsseldorf16, Pierre-and-Marie-Curie University17, Autonomous University of Barcelona18, University of Toronto19, University of British Columbia20, Sapienza University of Rome21, University of Texas Southwestern Medical Center22, University of California, San Francisco23
TL;DR: Refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression are proposed and strategies for future research to better define phenotypes are outlined.
Abstract: Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
2,180 citations
TL;DR: ForceAtlas2 is a force-directed layout close to other algorithms used for network spatialization, designed for the Gephi user experience, and proposed for the first time as a benchmark for the compromise between performance and quality.
Abstract: Gephi is a network visualization software used in various disciplines (social network analysis, biology, genomics…). One of its key features is the ability to display the spatialization process, aiming at transforming the network into a map, and ForceAtlas2 is its default layout algorithm. The latter is developed by the Gephi team as an all-around solution to Gephi users’ typical networks (scale-free, 10 to 10,000 nodes). We present here for the first time its functioning and settings. ForceAtlas2 is a force-directed layout close to other algorithms used for network spatialization. We do not claim a theoretical advance but an attempt to integrate different techniques such as the Barnes Hut simulation, degree-dependent repulsive force, and local and global adaptive temperatures. It is designed for the Gephi user experience (it is a continuous algorithm), and we explain which constraints it implies. The algorithm benefits from much feedback and is developed in order to provide many possibilities through its settings. We lay out its complete functioning for the users who need a precise understanding of its behaviour, from the formulas to graphic illustration of the result. We propose a benchmark for our compromise between performance and quality. We also explain why we integrated its various features and discuss our design choices.
2,032 citations
TL;DR: The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma, and the glucocorticoid requirement was lower.
Abstract: Background Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy–temozolomide for the treatment of newly diagnosed glioblastoma. Methods We randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival. Results A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P = 0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P = 0.049) and 33.9% and 30.1% at 2 years (P = 0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%). Conclusions The addition of bevacizumab to radiotherapy–temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. (Funded by F. Hoffmann–La Roche; ClinicalTrials.gov number, NCT00943826.)
1,996 citations
University of Chicago1, Pierre-and-Marie-Curie University2, Lawrence Berkeley National Laboratory3, University of Pennsylvania4, Argonne National Laboratory5, Fermilab6, African Institute for Mathematical Sciences7, University of Cape Town8, Texas A&M University9, University of Cambridge10, University of Portsmouth11, University of Toronto12, Wayne State University13, University of Colorado Boulder14, University of Tokyo15, California Institute of Technology16, University of Victoria17, University of California, Berkeley18, University of Illinois at Urbana–Champaign19, Autonomous University of Barcelona20, University of Chile21, Stockholm University22, University of Texas at Austin23, Princeton University24, University of Oxford25, Las Cumbres Observatory Global Telescope Network26, University of California, Santa Barbara27, Rutgers University28, University of Copenhagen29, Australian Astronomical Observatory30, Instituto Superior Técnico31, University of Utah32, Rochester Institute of Technology33, Space Telescope Science Institute34, Johns Hopkins University35, Pennsylvania State University36, University of the Western Cape37, University of Southampton38
TL;DR: In this article, the authors presented cosmological constraints from a joint analysis of type Ia supernova (SN Ia) observations obtained by the SDSS-II and SNLS collaborations.
Abstract: Aims. We present cosmological constraints from a joint analysis of type Ia supernova (SN Ia) observations obtained by the SDSS-II and SNLS collaborations. The dataset includes several low-redshift samples (z< 0.1), all three seasons from the SDSS-II (0.05
1,939 citations
German Center for Neurodegenerative Diseases1, University of Bonn2, Harvard University3, Maastricht University4, Aix-Marseille University5, Pierre-and-Marie-Curie University6, French Institute of Health and Medical Research7, University of Melbourne8, VU University Amsterdam9, New York University10, Mayo Clinic11, City University of New York12, University of New South Wales13, Indiana University14, King's College London15, University of Toulouse16
TL;DR: Research criteria for SCD in pre‐mild cognitive impairment (MCI) are presented and a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings.
Abstract: There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.
1,626 citations
Valentina Escott-Price1, Céline Bellenguez2, Li-San Wang3, Seung Hoan Choi4 +191 more•Institutions (67)
TL;DR: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimers disease.
Abstract: Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This s ...
1,518 citations
Pierre-and-Marie-Curie University1, Paris Descartes University2, French Institute of Health and Medical Research3, University of Bern4, University of Erlangen-Nuremberg5, Providence Portland Medical Center6, Radboud University Nijmegen7, Umeå University8, Karolinska Institutet9, Humanitas University10, Medical University of Graz11, Dorset County Hospital NHS Foundation Trust12, Charles University in Prague13, Cornell University14, University Health Network15, University of Toronto16, Keio University17, Yamaguchi University18, Kindai University19, Harvard University20, Royal Melbourne Hospital21, University of Melbourne22, Sapporo Medical University23, Kurume University24, Xi'an Jiaotong University25, University of Texas MD Anderson Cancer Center26, Mayo Clinic27, Grigore T. Popa University of Medicine and Pharmacy28, Oregon Health & Science University29
TL;DR: In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC or UICCTNM classification.
Abstract: The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
1,128 citations
TL;DR: The value of the ratio of branching fractions for the dilepton invariant mass squared range 1 < q(2) < 6 GeV(2)/c(4) is measured to be 0.745(-0.074)(+0.090)(stat) ± 0.036(syst).
Abstract: A measurement of the ratio of the branching fractions of the B+→K+μ+μ− and B+→K+e+e− decays is presented using proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb−1, recorded with the LHCb experiment at center-of-mass energies of 7 and 8 TeV. The value of the ratio of branching fractions for the dilepton invariant mass squared range 1
German Center for Neurodegenerative Diseases1, University of Bonn2, Harvard University3, Maastricht University4, Aix-Marseille University5, Pierre-and-Marie-Curie University6, French Institute of Health and Medical Research7, University of Melbourne8, VU University Amsterdam9, New York University10, Mayo Clinic11, City University of New York12, University of New South Wales13, Indiana University14, King's College London15, University of Toulouse16
TL;DR: In this paper, research criteria for subjective cognitive decline in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD) are presented.
Abstract: There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.
TL;DR: In this article, a single high-resolution image of the scattered light, captured with a standard camera, encodes sufficient information to image through visually opaque layers and around corners with diffraction-limited resolution.
Abstract: Optical imaging through and inside complex samples is a difficult challenge with important applications in many fields. The fundamental problem is that inhomogeneous samples such as biological tissue randomly scatter and diffuse light, preventing the formation of diffraction-limited images. Despite many recent advances, no current method can perform non-invasive imaging in real-time using diffused light. Here, we show that, owing to the ‘memory-effect’ for speckle correlations, a single high-resolution image of the scattered light, captured with a standard camera, encodes sufficient information to image through visually opaque layers and around corners with diffraction-limited resolution. We experimentally demonstrate single-shot imaging through scattering media and around corners using spatially incoherent light and various samples, from white paint to dynamic biological samples. Our single-shot lensless technique is simple, does not require wavefront-shaping nor time-gated or interferometric detection, and is realized here using a camera-phone. It has the potential to enable imaging in currently inaccessible scenarios. Diffraction-limited imaging in a variety of complex media is realized based on analysis of speckle correlations in light captured using a camera phone.
Canadian Institute for Advanced Research1, University of British Columbia2, Monterey Bay Aquarium Research Institute3, Stony Brook University4, University of California, San Diego5, Marine Biological Laboratory6, Brown University7, University of Washington8, Dalhousie University9, National Center for Genome Resources10, Alfred Wegener Institute for Polar and Marine Research11, Rutgers University12, Texas A&M University13, University of Southern California14, University of Delaware15, Victoria University of Wellington16, University of Paris-Sud17, Columbia University18, University of Oslo19, University of Hawaii at Manoa20, University of Prince Edward Island21, University of Rhode Island22, Woods Hole Oceanographic Institution23, Jacobs University Bremen24, Max Planck Society25, Smith College26, University of South Alabama27, University of Geneva28, Saint Petersburg State University29, University of Connecticut30, Laval University31, University of Guelph32, University of North Carolina at Chapel Hill33, University of New Brunswick34, University of Camerino35, University of East Anglia36, Stazione Zoologica Anton Dohrn37, University of Georgia38, University of Technology, Sydney39, University of Puerto Rico40, University of Pisa41, Centre national de la recherche scientifique42, Colorado School of Mines43, Lund University44, University of Western Ontario45, California State University46, University of Texas at Austin47, Los Alamos National Laboratory48, Pierre-and-Marie-Curie University49, University of Oklahoma50, Plymouth Marine Laboratory51, Bigelow Laboratory For Ocean Sciences52, Princeton University53
TL;DR: In this paper, the authors describe a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans and their biology, evolution, and ecology.
Abstract: Current sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans.
TL;DR: In this article, a new terminology for local/regional or relative sea-level changes ( eurybatic shifts) is proposed to distinguish them from global ( eustatic ) sea-Level changes, with the observation that all measures of sealevel change in any given location are euryBatic, even when they include a strong global signal.
Icahn School of Medicine at Mount Sinai1, Centre national de la recherche scientifique2, French Institute of Health and Medical Research3, Pierre-and-Marie-Curie University4, University of Toronto5, Trinity College, Dublin6, University of Pittsburgh7, Utrecht University8, McMaster University9, Our Lady's Children's Hospital10, University College Dublin11, University of Oxford12, University of Lisbon13, Instituto Nacional de Saúde Dr. Ricardo Jorge14, University of California, Los Angeles15, University of Miami16, Goethe University Frankfurt17, University of Pennsylvania18, Vanderbilt University19, Temple University20, University of Bologna21, Cancer Care Ontario22, University of Southern California23, University of Alberta24, University of Birmingham25, Université de Montréal26, Rush University Medical Center27, University of Coimbra28, Kaiser Permanente29, Cornell University30, Newcastle University31, University of Illinois at Chicago32, University of Minnesota33, University of Gothenburg34, Memorial University of Newfoundland35, Duke University36, University of Paris37, Centre for Mental Health38, King's College London39, University of Washington40, Nationwide Children's Hospital41, Indiana University42, Tufts University43, German Cancer Research Center44, University of Utah45, Stanford University46
TL;DR: For example, the authors analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability.
Abstract: Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
TL;DR: Because it has no unique clinical, biologic, or histologic features, reactive hemophagocytic syndrome may be difficult to distinguish from other diseases such as severe sepsis or hematologic malignancies.
Abstract: Objective
Because it has no unique clinical, biologic, or histologic features, reactive hemophagocytic syndrome may be difficult to distinguish from other diseases such as severe sepsis or hematologic malignancies. This study was undertaken to develop and validate a diagnostic score for reactive hemophagocytic syndrome.
Methods
A multicenter retrospective cohort of 312 patients who were judged by experts to have reactive hemophagocytic syndrome (n = 162), were judged by experts to not have reactive hemophagocytic syndrome (n = 104), or in whom the diagnosis of reactive hemophagocytic syndrome was undetermined (n = 46) was used to construct and validate the reactive hemophagocytic syndrome diagnostic score, called the HScore. Ten explanatory variables were evaluated for their association with the diagnosis of hemophagocytic syndrome, and logistic regression was used to calculate the weight of each criterion included in the score. Performance of the score was assessed using developmental and validation data sets.
Results
Nine variables (3 clinical [i.e., known underlying immunosuppression, high temperature, organomegaly], 5 biologic [i.e., triglyceride, ferritin, serum glutamic oxaloacetic transaminase, and fibrinogen levels, cytopenia], and 1 cytologic [i.e., hemophagocytosis features on bone marrow aspirate]) were retained in the HScore. The possible number of points assigned to each variable ranged from 0–18 for known underlying immunosuppression to 0–64 for triglyceride level. The median HScore was 230 (interquartile range [IQR] 203–257) for patients with a positive diagnosis of reactive hemophagocytic syndrome and 125 (IQR 91–150) for patients with a negative diagnosis. The probability of having hemophagocytic syndrome ranged from 99% with an HScore of ≥250.
Conclusion
The HScore can be used to estimate an individual's risk of having reactive hemophagocytic syndrome. This scoring system is freely available online (http://saintantoine.aphp.fr/score/).
TL;DR: In this article, a variable proportion of isotropically prestretched chains that can break and dissipate energy before the material fails is introduced to increase the stiffness and toughness of brittle elastomers.
Abstract: Elastomers are widely used because of their large-strain reversible deformability. Most unfilled elastomers suffer from a poor mechanical strength, which limits their use. Using sacrificial bonds, we show how brittle, unfilled elastomers can be strongly reinforced in stiffness and toughness (up to 4 megapascals and 9 kilojoules per square meter) by introducing a variable proportion of isotropically prestretched chains that can break and dissipate energy before the material fails. Chemoluminescent cross-linking molecules, which emit light as they break, map in real time where and when many of these internal bonds break ahead of a propagating crack. The simple methodology that we use to introduce sacrificial bonds, combined with the mapping of where bonds break, has the potential to stimulate the development of new classes of unfilled tough elastomers and better molecular models of the fracture of soft materials.
TL;DR: In this article, the authors reconstructed the trajectory followed, in the past 50 years, by 124 countries in terms of crop yield and total nitrogen inputs to cropland (manure, synthetic fertilizer, symbiotic fixation and atmospheric deposition).
Abstract: Nitrogen (N) is crucial for crop productivity. However, nowadays more than half of the N added to cropland is lost to the environment, wasting the resource, producing threats to air, water, soil and biodiversity, and generating greenhouse gas emissions. Based on FAO data, we have reconstructed the trajectory followed, in the past 50 years, by 124 countries in terms of crop yield and total nitrogen inputs to cropland (manure, synthetic fertilizer, symbiotic fixation and atmospheric deposition). During the last five decades, the response of agricultural systems to increased nitrogen fertilization has evolved differently in the different world countries. While some countries have improved their agro-environmental performances, in others the increased fertilization has produced low agronomical benefits and higher environmental losses. Our data also suggest that, in general, those countries using a higher proportion of N inputs from symbiotic N fixation rather than from synthetic fertilizer have a better N use efficiency.
TL;DR: The physiological regulation of autophagy by metabolic circuitries, as well as alterations of such control in disease are discussed.
Institut Gustave Roussy1, University of São Paulo2, Katholieke Universiteit Leuven3, University of Burgundy4, Sapienza University of Rome5, Istituto Superiore di Sanità6, Vrije Universiteit Brussel7, University of Manchester8, University of Michigan9, National University of Cuyo10, Pierre-and-Marie-Curie University11, New York University12, University of Salento13, University of Crete14, Charles University in Prague15, University of Erlangen-Nuremberg16, University Hospital Heidelberg17, University of Pittsburgh18, University of Helsinki19, National Institutes of Health20, University of Bonn21, Providence Portland Medical Center22, National University of Singapore23, Ghent University24, University of Milan25, University of Graz26, University of Paris-Sud27, University College London28, Tuscia University29, McMaster University30, Technische Universität München31, Medical University of Vienna32, Karolinska Institutet33, University of Nice Sophia Antipolis34, University of Turin35, QIMR Berghofer Medical Research Institute36, Université de Montréal37, Dow University of Health Sciences38, French Institute of Health and Medical Research39, University of Colorado Denver40, University of Hawaii41, Stony Brook University42, Paris Descartes University43
TL;DR: Strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative I CD inducers are outlined, based on a high-content, high-throughput platform that was recently developed.
Abstract: Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.
VU University Medical Center1, Bristol Royal Infirmary2, University of Ottawa3, University of Toronto4, Pierre-and-Marie-Curie University5, University of Leeds6, Johns Hopkins University7, University of Melbourne8, University of Amsterdam9, Royal North Shore Hospital10, Kolling Institute of Medical Research11, Veterans Health Administration12, University of Alabama at Birmingham13, Stanford University14
TL;DR: The OMERACT Filter 2.0 explicitly describes a comprehensive conceptual framework and a recommended process to develop core outcome measurement sets for rheumatology likely to be useful as a template in other areas of health care.
TL;DR: The mixing inferred from observations appears to be sufficiently strong to imply a climate sensitivity of more than 3 degrees for a doubling of carbon dioxide, significantly higher than the currently accepted lower bound of 1.5 degrees, thereby constraining model projections towards relatively severe future warming.
Abstract: Equilibrium climate sensitivity refers to the ultimate change in global mean temperature in response to a change in external forcing. Despite decades of research attempting to narrow uncertainties, equilibrium climate sensitivity estimates from climate models still span roughly 1.5 to 5 degrees Celsius for a doubling of atmospheric carbon dioxide concentration, precluding accurate projections of future climate. The spread arises largely from differences in the feedback from low clouds, for reasons not yet understood. Here we show that differences in the simulated strength of convective mixing between the lower and middle tropical troposphere explain about half of the variance in climate sensitivity estimated by 43 climate models. The apparent mechanism is that such mixing dehydrates the low-cloud layer at a rate that increases as the climate warms, and this rate of increase depends on the initial mixing strength, linking the mixing to cloud feedback. The mixing inferred from observations appears to be sufficiently strong to imply a climate sensitivity of more than 3 degrees for a doubling of carbon dioxide. This is significantly higher than the currently accepted lower bound of 1.5 degrees, thereby constraining model projections towards relatively severe future warming.
TL;DR: It is shown that strong, rapid adhesion between two hydrogels can be achieved at room temperature by spreading a droplet of a nanoparticle solution on one gel’s surface and then bringing the other gel into contact with it.
Abstract: Adhesives are made of polymers because, unlike other materials, polymers ensure good contact between surfaces by covering asperities, and retard the fracture of adhesive joints by dissipating energy under stress. But using polymers to 'glue' together polymer gels is difficult, requiring chemical reactions, heating, pH changes, ultraviolet irradiation or an electric field. Here we show that strong, rapid adhesion between two hydrogels can be achieved at room temperature by spreading a droplet of a nanoparticle solution on one gel's surface and then bringing the other gel into contact with it. The method relies on the nanoparticles' ability to adsorb onto polymer gels and to act as connectors between polymer chains, and on the ability of polymer chains to reorganize and dissipate energy under stress when adsorbed onto nanoparticles. We demonstrate this approach by pressing together pieces of hydrogels, for approximately 30 seconds, that have the same or different chemical properties or rigidities, using various solutions of silica nanoparticles, to achieve a strong bond. Furthermore, we show that carbon nanotubes and cellulose nanocrystals that do not bond hydrogels together become adhesive when their surface chemistry is modified. To illustrate the promise of the method for biological tissues, we also glued together two cut pieces of calf's liver using a solution of silica nanoparticles. As a rapid, simple and efficient way to assemble gels or tissues, this method is desirable for many emerging technological and medical applications such as microfluidics, actuation, tissue engineering and surgery.
Ames Research Center1, Search for extraterrestrial intelligence2, Aarhus University3, University of British Columbia4, Ohio State University5, University of Hawaii at Manoa6, University of Paris7, University of Amsterdam8, Max Planck Society9, Space Science Institute10, Pierre-and-Marie-Curie University11, Harvard University12, Vanderbilt University13, Yale University14, University of Sydney15, University of Birmingham16, Massachusetts Institute of Technology17, Space Telescope Science Institute18, Georgia State University19, University of Hawaii20, Spanish National Research Council21
TL;DR: In this paper, the authors presented revised properties for 196,468 stars observed by the NASA Kepler mission and used in the analysis of Quarter 1-16 (Q1-Q16) data to detect and characterize transiting planets.
Abstract: We present revised properties for 196,468 stars observed by the NASA Kepler mission and used in the analysis of Quarter 1-16 (Q1-Q16) data to detect and characterize transiting planets. The catalog is based on a compilation of literature values for atmospheric properties (temperature, surface gravity, and metallicity) derived from different observational techniques (photometry, spectroscopy, asteroseismology, and exoplanet transits), which were then homogeneously fitted to a grid of Dartmouth stellar isochrones. We use broadband photometry and asteroseismology to characterize 11,532 Kepler targets which were previously unclassified in the Kepler Input Catalog (KIC). We report the detection of oscillations in 2762 of these targets, classifying them as giant stars and increasing the number of known oscillating giant stars observed by Kepler by ~20% to a total of ~15,500 stars. Typical uncertainties in derived radii and masses are ~40% and ~20%, respectively, for stars with photometric constraints only, and 5%-15% and ~10% for stars based on spectroscopy and/or asteroseismology, although these uncertainties vary strongly with spectral type and luminosity class. A comparison with the Q1-Q12 catalog shows a systematic decrease in radii of M dwarfs, while radii for K dwarfs decrease or increase depending on the Q1-Q12 provenance (KIC or Yonsei-Yale isochrones). Radii of F-G dwarfs are on average unchanged, with the exception of newly identified giants. The Q1-Q16 star properties catalog is a first step toward an improved characterization of all Kepler targets to support planet-occurrence studies.
TL;DR: The results suggest that neural activity in vivo shows a mélange of avalanches, and not temporally separated ones, and that their global activity propagation can be approximated by the principle that one spike on average triggers a little less than one spike in the next step.
Abstract: In self-organized critical (SOC) systems avalanche size distributions follow power-laws. Power-laws have also been observed for neural activity, and so it has been proposed that SOC underlies brain organization as well. Surprisingly, for spiking activity in vivo, evidence for SOC is still lacking. Therefore we analyzed highly parallel spike recordings from awake rats and monkeys, anaesthetized cats, and also local field potentials from humans. We compared these to spiking activity from two established critical models: the Bak-Tang-Wiesenfeld model, and a stochastic branching model. We found fundamental differences between the neural and the model activity. These differences could be overcome for both models through a combination of three modifications: (1) subsampling, (2) increasing the input to the model (this way eliminating the separation of time scales, which is fundamental to SOC and its avalanche definition), and (3) making the model slightly sub-critical. The match between the neural activity and the modified models held not only for the classical avalanche size distributions and estimated branching parameters, but also for two novel measures (mean avalanche size, and frequency of single spikes), and for the dependence of all these measures on the temporal bin size. Our results suggest that neural activity in vivo shows a melange of avalanches, and not temporally separated ones, and that their global activity propagation can be approximated by the principle that one spike on average triggers a little less than one spike in the next step. This implies that neural activity does not reflect a SOC state but a slightly sub-critical regime without a separation of time scales. Potential advantages of this regime may be faster information processing, and a safety margin from super-criticality, which has been linked to epilepsy.
TL;DR: In this article, a conformal bootstrap was used to perform a precision study of the operator spectrum of the critical 3D Ising model, and it was shown that the 3d Ising spectrum minimizes the central charge c in the space of unitary solutions to crossing symmetry.
Abstract: We use the conformal bootstrap to perform a precision study of the operator spectrum of the critical 3d Ising model. We conjecture that the 3d Ising spectrum minimizes the central charge c in the space of unitary solutions to crossing symmetry. Because extremal solutions to crossing symmetry are uniquely determined, we are able to precisely reconstruct the first several Z_2 -even operator dimensions and their OPE coefficients. We observe that a sharp transition in the operator spectrum occurs at the 3d Ising dimension Δ_σ=0.518154(15), and find strong numerical evidence that operators decouple from the spectrum as one approaches the 3d Ising point. We compare this behavior to the analogous situation in 2d, where the disappearance of operators can be understood in terms of degenerate Virasoro representations.
TL;DR: SynIII as mentioned in this paper is a designer eukaryotic chromosome based on the S. cerevisiae chromosome III that includes TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites.
Abstract: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.
Manchester Academic Health Science Centre1, Harvard University2, Boston Children's Hospital3, University of Pavia4, Necker-Enfants Malades Hospital5, University of Liverpool6, University of Florence7, University of Colorado Denver8, NHS Ayrshire and Arran9, Children's Hospital at Westmead10, Royal Hospital for Sick Children11, Katholieke Universiteit Leuven12, University of Burgundy13, University of Brescia14, French Institute of Health and Medical Research15, McMaster Children's Hospital16, Paris Descartes University17, Leeds Teaching Hospitals NHS Trust18, University of São Paulo19, University of Glasgow20, University of Milan21, Great Ormond Street Hospital22, Pierre-and-Marie-Curie University23, University of Cape Town24, Southern General Hospital25, Children's National Medical Center26
TL;DR: It is demonstrated that aberrant sensing of nucleic acids can cause immune upregulation and heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state.
Abstract: The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutieres syndrome and of other undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer gain of function such that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.
TL;DR: A consensus conference was organized to better define, diagnose, and manage primary graft dysfunction (PGD), with the aim of leading to better understanding of PGD and prevention/minimization of its adverse outcomes.
Abstract: Although primary graft dysfunction (PGD) is fairly common early after cardiac transplant, standardized schemes for diagnosis and treatment remain contentious. Most major cardiac transplant centers use different definitions and parameters of cardiac function. Thus, there is difficulty comparing published reports and no agreed protocol for management. A consensus conference was organized to better define, diagnose, and manage PGD. There were 71 participants (transplant cardiologists, surgeons, immunologists and pathologists), with vast clinical and published experience in PGD, representing 42 heart transplant centers worldwide. State-of-the-art PGD presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues. Graft dysfunction will be classified into primary graft dysfunction (PGD) or secondary graft dysfunction where there is a discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications. PGD must be diagnosed within 24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD-right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe grades depending on the level of cardiac function and the extent of inotrope and mechanical support required. Agreed risk factors for PGD include donor, recipient, and surgical procedural factors. Recommended management involves minimization of risk factors, gradual increase of inotropes, and use of mechanical circulatory support as needed. Retransplantation may be indicated if risk factors are minimal. With a standardized definition of PGD, there will be more consistent recognition of this phenomenon and treatment modalities will be more comparable. This should lead to better understanding of PGD and prevention/minimization of its adverse outcomes.