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Journal ArticleDOI
07 Aug 2015-Science
TL;DR: A pathway is proposed, called the plasmon-induced interfacial charge-transfer transition (PICTT), that enables the decay of a plAsmon by directly exciting an electron from the metal to a strongly coupled acceptor.
Abstract: Plasmon-induced hot-electron transfer from metal nanostructures is a potential new paradigm for solar energy conversion; however, the reported efficiencies of devices based on this concept are often low because of the loss of hot electrons via ultrafast electron-electron scattering. We propose a pathway, called the plasmon-induced interfacial charge-transfer transition (PICTT), that enables the decay of a plasmon by directly exciting an electron from the metal to a strongly coupled acceptor. We demonstrated this concept in cadmium selenide nanorods with gold tips, in which the gold plasmon was strongly damped by cadmium selenide through interfacial electron transfer. The quantum efficiency of the PICTT process was high (>24%), independent of excitation photon energy over a ~1-electron volt range, and dependent on the excitation polarization.

885 citations


Journal ArticleDOI
TL;DR: The clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma are reviewed and a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma is outlined.
Abstract: Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints. These changes in the treatment landscape have dramatically improved patient outcomes, with the median overall survival of patients with advanced-stage melanoma increasing from approximately 9 months before 2011 to at least 2 years - and probably longer for those with BRAF-V600-mutant disease. Herein, we review the clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma. Mechanisms of resistance and biomarkers of response to BRAF-targeted treatments and immunotherapies are discussed, and the contrasting clinical benefits and limitations of these therapies are explored. We summarize the state of the field and outline a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma.

885 citations


Proceedings ArticleDOI
05 Jun 2016
TL;DR: This work simulates dialogues between two virtual agents, using policy gradient methods to reward sequences that display three useful conversational properties: informativity, non-repetitive turns, coherence, and ease of answering.
Abstract: Recent neural models of dialogue generation offer great promise for generating responses for conversational agents, but tend to be shortsighted, predicting utterances one at a time while ignoring their influence on future outcomes. Modeling the future direction of a dialogue is crucial to generating coherent, interesting dialogues, a need which led traditional NLP models of dialogue to draw on reinforcement learning. In this paper, we show how to integrate these goals, applying deep reinforcement learning to model future reward in chatbot dialogue. The model simulates dialogues between two virtual agents, using policy gradient methods to reward sequences that display three useful conversational properties: informativity, coherence, and ease of answering (related to forward-looking function). We evaluate our model on diversity, length as well as with human judges, showing that the proposed algorithm generates more interactive responses and manages to foster a more sustained conversation in dialogue simulation. This work marks a first step towards learning a neural conversational model based on the long-term success of dialogues.

885 citations


Posted Content
TL;DR: TWNs are introduced - neural networks with weights constrained to +1, 0 and -1, which have stronger expressive abilities than the recently proposed binary precision counterparts and are thus more effective than the latter.
Abstract: We introduce ternary weight networks (TWNs) - neural networks with weights constrained to +1, 0 and -1. The Euclidian distance between full (float or double) precision weights and the ternary weights along with a scaling factor is minimized. Besides, a threshold-based ternary function is optimized to get an approximated solution which can be fast and easily computed. TWNs have stronger expressive abilities than the recently proposed binary precision counterparts and are thus more effective than the latter. Meanwhile, TWNs achieve up to 16$\times$ or 32$\times$ model compression rate and need fewer multiplications compared with the full precision counterparts. Benchmarks on MNIST, CIFAR-10, and large scale ImageNet datasets show that the performance of TWNs is only slightly worse than the full precision counterparts but outperforms the analogous binary precision counterparts a lot.

884 citations


Journal ArticleDOI
13 Nov 2020-Science
TL;DR: It is shown that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity and serves as a host factor for Sars-Cov-2 infection and may potentially provide a therapeutic target for COVID-19.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses the viral spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.

884 citations


Proceedings ArticleDOI
08 Feb 2016
TL;DR: It is demonstrated that the proposed model is a generalization of several well-known collaborative filtering models but with more flexible components, and that CDAE consistently outperforms state-of-the-art top-N recommendation methods on a variety of common evaluation metrics.
Abstract: Most real-world recommender services measure their performance based on the top-N results shown to the end users. Thus, advances in top-N recommendation have far-ranging consequences in practical applications. In this paper, we present a novel method, called Collaborative Denoising Auto-Encoder (CDAE), for top-N recommendation that utilizes the idea of Denoising Auto-Encoders. We demonstrate that the proposed model is a generalization of several well-known collaborative filtering models but with more flexible components. Thorough experiments are conducted to understand the performance of CDAE under various component settings. Furthermore, experimental results on several public datasets demonstrate that CDAE consistently outperforms state-of-the-art top-N recommendation methods on a variety of common evaluation metrics.

884 citations


Journal ArticleDOI
TL;DR: The study significantly adds to the understanding of mental health symptoms and their role in addictive use of modern technology, and suggests that the concept of Internet use disorder (i.e., "Internet addiction") as a unified construct is not warranted.
Abstract: Over the last decade, research into "addictive technological behaviors" has substantially increased. Research has also demonstrated strong associations between addictive use of technology and comorbid psychiatric disorders. In the present study, 23,533 adults (mean age 35.8 years, ranging from 16 to 88 years) participated in an online cross-sectional survey examining whether demographic variables, symptoms of attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, and depression could explain variance in addictive use (i.e., compulsive and excessive use associated with negative outcomes) of two types of modern online technologies: social media and video games. Correlations between symptoms of addictive technology use and mental disorder symptoms were all positive and significant, including the weak interrelationship between the two addictive technological behaviors. Age appeared to be inversely related to the addictive use of these technologies. Being male was significantly associated with addictive use of video games, whereas being female was significantly associated with addictive use of social media. Being single was positively related to both addictive social networking and video gaming. Hierarchical regression analyses showed that demographic factors explained between 11 and 12% of the variance in addictive technology use. The mental health variables explained between 7 and 15% of the variance. The study significantly adds to our understanding of mental health symptoms and their role in addictive use of modern technology, and suggests that the concept of Internet use disorder (i.e., "Internet addiction") as a unified construct is not warranted.

884 citations


Proceedings ArticleDOI
14 Oct 2017
TL;DR: DeepXplore efficiently finds thousands of incorrect corner case behaviors in state-of-the-art DL models with thousands of neurons trained on five popular datasets including ImageNet and Udacity self-driving challenge data.
Abstract: Deep learning (DL) systems are increasingly deployed in safety- and security-critical domains including self-driving cars and malware detection, where the correctness and predictability of a system's behavior for corner case inputs are of great importance Existing DL testing depends heavily on manually labeled data and therefore often fails to expose erroneous behaviors for rare inputs We design, implement, and evaluate DeepXplore, the first whitebox framework for systematically testing real-world DL systems First, we introduce neuron coverage for systematically measuring the parts of a DL system exercised by test inputs Next, we leverage multiple DL systems with similar functionality as cross-referencing oracles to avoid manual checking Finally, we demonstrate how finding inputs for DL systems that both trigger many differential behaviors and achieve high neuron coverage can be represented as a joint optimization problem and solved efficiently using gradient-based search techniques DeepXplore efficiently finds thousands of incorrect corner case behaviors (eg, self-driving cars crashing into guard rails and malware masquerading as benign software) in state-of-the-art DL models with thousands of neurons trained on five popular datasets including ImageNet and Udacity self-driving challenge data For all tested DL models, on average, DeepXplore generated one test input demonstrating incorrect behavior within one second while running only on a commodity laptop We further show that the test inputs generated by DeepXplore can also be used to retrain the corresponding DL model to improve the model's accuracy by up to 3%

884 citations


Journal ArticleDOI
TL;DR: In this article, a review of microgrid drivers, real-world applications, challenges, and future prospects is presented, along with a multi-disciplinary portrait of today's micro-grid drivers.
Abstract: Microgrids are now emerging from lab benches and pilot demonstration sites into commercial markets, driven by technological improvements, falling costs, a proven track record, and growing recognition of their benefits. They are being used to improve reliability and resilience of electrical grids, to manage the addition of distributed clean energy resources like wind and solar photovoltaic (PV) generation to reduce fossil fuel emissions, and to provide electricity in areas not served by centralized electrical infrastructure. This review article (1) explains what a microgrid is, and (2) provides a multi-disciplinary portrait of today's microgrid drivers, real-world applications, challenges, and future prospects.

884 citations


Proceedings Article
27 Jun 2018
TL;DR: QT-Opt as mentioned in this paper is a scalable self-supervised vision-based reinforcement learning framework that can leverage over 580k real-world grasp attempts to train a deep neural network Q-function with over 1.2M parameters.
Abstract: In this paper, we study the problem of learning vision-based dynamic manipulation skills using a scalable reinforcement learning approach. We study this problem in the context of grasping, a longstanding challenge in robotic manipulation. In contrast to static learning behaviors that choose a grasp point and then execute the desired grasp, our method enables closed-loop vision-based control, whereby the robot continuously updates its grasp strategy based on the most recent observations to optimize long-horizon grasp success. To that end, we introduce QT-Opt, a scalable self-supervised vision-based reinforcement learning framework that can leverage over 580k real-world grasp attempts to train a deep neural network Q-function with over 1.2M parameters to perform closed-loop, real-world grasping that generalizes to 96% grasp success on unseen objects. Aside from attaining a very high success rate, our method exhibits behaviors that are quite distinct from more standard grasping systems: using only RGB vision-based perception from an over-the-shoulder camera, our method automatically learns regrasping strategies, probes objects to find the most effective grasps, learns to reposition objects and perform other non-prehensile pre-grasp manipulations, and responds dynamically to disturbances and perturbations.

884 citations


Journal ArticleDOI
TL;DR: An engineering strategy for stabilization of soluble S proteins in the prefusion conformation is described, which results in greatly increased expression, conformational homogeneity, and elicitation of potent antibody responses, and an engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV.
Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.

Journal ArticleDOI
Corinne Le Quéré1, Robbie M. Andrew, Pierre Friedlingstein2, Stephen Sitch2, Julia Pongratz3, Andrew C. Manning1, Jan Ivar Korsbakken, Glen P. Peters, Josep G. Canadell4, Robert B. Jackson5, Thomas A. Boden6, Pieter P. Tans7, Oliver Andrews1, Vivek K. Arora, Dorothee C. E. Bakker1, Leticia Barbero8, Leticia Barbero9, Meike Becker10, Meike Becker11, Richard Betts2, Richard Betts12, Laurent Bopp13, Frédéric Chevallier14, Louise Chini15, Philippe Ciais14, Catherine E Cosca7, Jessica N. Cross7, Kim I. Currie16, Thomas Gasser17, Ian Harris1, Judith Hauck18, Vanessa Haverd4, Richard A. Houghton19, Christopher W. Hunt20, George C. Hurtt15, Tatiana Ilyina3, Atul K. Jain21, Etsushi Kato, Markus Kautz22, Ralph F. Keeling23, Kees Klein Goldewijk24, Kees Klein Goldewijk25, Arne Körtzinger26, Peter Landschützer3, Nathalie Lefèvre27, Andrew Lenton28, Andrew Lenton29, Sebastian Lienert30, Sebastian Lienert31, Ivan D. Lima19, Danica Lombardozzi32, Nicolas Metzl27, Frank J. Millero33, Pedro M. S. Monteiro34, David R. Munro35, Julia E. M. S. Nabel3, Shin-Ichiro Nakaoka36, Yukihiro Nojiri36, X. Antonio Padin37, Anna Peregon14, Benjamin Pfeil10, Benjamin Pfeil11, Denis Pierrot8, Denis Pierrot9, Benjamin Poulter38, Benjamin Poulter39, Gregor Rehder40, Janet J. Reimer41, Christian Rödenbeck3, Jörg Schwinger11, Roland Séférian14, Ingunn Skjelvan11, Benjamin D. Stocker, Hanqin Tian42, Bronte Tilbrook29, Bronte Tilbrook28, Francesco N. Tubiello43, Ingrid T. van der Laan-Luijkx44, Guido R. van der Werf45, Steven van Heuven46, Nicolas Viovy14, Nicolas Vuichard14, Anthony P. Walker6, Andrew J. Watson2, Andy Wiltshire12, Sönke Zaehle3, Dan Zhu14 
University of East Anglia1, University of Exeter2, Max Planck Society3, Commonwealth Scientific and Industrial Research Organisation4, Stanford University5, Oak Ridge National Laboratory6, National Oceanic and Atmospheric Administration7, Atlantic Oceanographic and Meteorological Laboratory8, Cooperative Institute for Marine and Atmospheric Studies9, Geophysical Institute, University of Bergen10, Bjerknes Centre for Climate Research11, Met Office12, École Normale Supérieure13, Centre national de la recherche scientifique14, University of Maryland, College Park15, National Institute of Water and Atmospheric Research16, International Institute for Applied Systems Analysis17, Alfred Wegener Institute for Polar and Marine Research18, Woods Hole Oceanographic Institution19, University of New Hampshire20, University of Illinois at Urbana–Champaign21, Karlsruhe Institute of Technology22, University of California, San Diego23, Utrecht University24, Netherlands Environmental Assessment Agency25, Leibniz Institute of Marine Sciences26, University of Paris27, Cooperative Research Centre28, Hobart Corporation29, University of Bern30, Oeschger Centre for Climate Change Research31, National Center for Atmospheric Research32, University of Miami33, Council of Scientific and Industrial Research34, Institute of Arctic and Alpine Research35, National Institute for Environmental Studies36, Spanish National Research Council37, Montana State University38, Goddard Space Flight Center39, Leibniz Institute for Baltic Sea Research40, University of Delaware41, Auburn University42, Food and Agriculture Organization43, Wageningen University and Research Centre44, VU University Amsterdam45, University of Groningen46
TL;DR: In this paper, the authors quantify the five major components of the global carbon budget and their uncertainties, and the resulting carbon budget imbalance (BIM) is a measure of imperfect data and understanding of the contemporary carbon cycle.
Abstract: Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the "global carbon budget" – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on land-cover change data and bookkeeping models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2007–2016), EFF was 9.4 ± 0.5 GtC yr−1, ELUC 1.3 ± 0.7 GtC yr−1, GATM 4.7 ± 0.1 GtC yr−1, SOCEAN 2.4 ± 0.5 GtC yr−1, and SLAND 3.0 ± 0.8 GtC yr−1, with a budget imbalance BIM of 0.6 GtC yr−1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr−1. Also for 2016, ELUC was 1.3 ± 0.7 GtC yr−1, GATM was 6.1 ± 0.2 GtC yr−1, SOCEAN was 2.6 ± 0.5 GtC yr−1, and SLAND was 2.7 ± 1.0 GtC yr−1, with a small BIM of −0.3 GtC. GATM continued to be higher in 2016 compared to the past decade (2007–2016), reflecting in part the high fossil emissions and the small SLAND consistent with El Nino conditions. The global atmospheric CO2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6–9 months indicate a renewed growth in EFF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set (Le Quere et al., 2016, 2015b, a, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2017 (GCP, 2017).

Journal ArticleDOI
TL;DR: In this paper, the authors extend the literature on how managerial traits relate to corporate choices by documenting that firms run by female CEOs have lower leverage, less volatile earnings, and a higher chance of survival than otherwise similar firms running by male CEOs, and that transitions from male to female CEOs are associated with economically and statistically significant reductions in corporate risk-taking.

Journal ArticleDOI
TL;DR: The history of dressings from its earliest inception to the current status is traced and the advantage and limitations of the dressing materials are discussed.
Abstract: Wound healing is a dynamic and complex process which requires suitable environment to promote healing process. With the advancement in technology, more than 3000 products have been developed to treat different types of wounds by targeting various aspects of healing process. The present review traces the history of dressings from its earliest inception to the current status and also discusses the advantage and limitations of the dressing materials.

Journal ArticleDOI
10 Mar 2016-Nature
TL;DR: These repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.
Abstract: Observations of repeated fast radio bursts, having dispersion measures and sky positions consistent with those of FRB 121102, show that the signals do not originate in a single cataclysmic event and may come from a young, highly magnetized, extragalactic neutron star. Fast radio bursts (FRBs) are transient radio pulses that last a few milliseconds. They are thought to be extragalactic, and are of unknown physical origin. Many FRB models have proposed the cause to be one-time-only cataclysmic events. Follow-up monitoring of detected bursts did not reveal repeat bursts, consistent with such models. However, this paper reports ten additional bursts from the direction of FRB 121102, demonstrating that its source survived the energetic events that caused the bursts. Although there may be multiple physical origins for the burst, the repeating bursts seen from FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star. Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances1,2,3,4,5,6,7,8. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections9. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events10. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst4. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star11,12.

Journal ArticleDOI
Juanita A. Haagsma1, Nicholas Graetz1, Ian Bolliger1, Mohsen Naghavi1, Hideki Higashi1, Erin C Mullany1, Semaw Ferede Abera2, Jerry Puthenpurakal Abraham3, Koranteng Adofo4, Ubai Alsharif5, Emmanuel A. Ameh6, Walid Ammar, Carl Abelardo T. Antonio7, Lope H Barrero8, Tolesa Bekele9, Dipan Bose10, Alexandra Brazinova, Ferrán Catalá-López, Lalit Dandona1, Rakhi Dandona11, Paul I. Dargan12, Diego De Leo13, Louisa Degenhardt14, Sarah Derrett15, Samath D Dharmaratne16, Tim Driscoll17, Leilei Duan18, Sergey Petrovich Ermakov19, Farshad Farzadfar20, Valery L. Feigin21, Richard C. Franklin22, Belinda J. Gabbe23, Richard A. Gosselin24, Nima Hafezi-Nejad20, Randah R. Hamadeh25, Martha Híjar, Guoqing Hu26, Sudha Jayaraman27, Guohong Jiang, Yousef Khader28, Ejaz Ahmad Khan29, Sanjay Krishnaswami30, Chanda Kulkarni, Fiona Lecky31, Ricky Leung32, Raimundas Lunevicius33, Ronan A Lyons34, Marek Majdan, Amanda J. Mason-Jones35, Richard Matzopoulos36, Peter A. Meaney37, Wubegzier Mekonnen38, Ted R. Miller39, Charles Mock40, Rosana E. Norman41, Ricardo Orozco, Suzanne Polinder, Farshad Pourmalek42, Vafa Rahimi-Movaghar20, Amany H. Refaat43, David Rojas-Rueda, Nobhojit Roy44, David C. Schwebel45, Amira Shaheen46, Saeid Shahraz47, Vegard Skirbekk48, Kjetil Søreide49, Sergey Soshnikov, Dan J. Stein50, Bryan L. Sykes51, Karen M. Tabb52, Awoke Misganaw Temesgen, Eric Y. Tenkorang53, Alice Theadom21, Bach Xuan Tran54, Bach Xuan Tran55, Tommi Vasankari, Monica S. Vavilala40, Vasiliy Victorovich Vlassov56, Solomon Meseret Woldeyohannes57, Paul S. F. Yip58, Naohiro Yonemoto, Mustafa Z. Younis59, Chuanhua Yu60, Christopher J L Murray1, Theo Vos1 
Institute for Health Metrics and Evaluation1, College of Health Sciences, Bahrain2, Harvard University3, Kwame Nkrumah University of Science and Technology4, Charité5, Ahmadu Bello University6, University of the Philippines Manila7, Pontifical Xavierian University8, Madawalabu University9, World Bank10, Public Health Foundation of India11, Guy's and St Thomas' NHS Foundation Trust12, Griffith University13, University of New South Wales14, Massey University15, University of Peradeniya16, University of Sydney17, Chinese Center for Disease Control and Prevention18, Russian Academy of Sciences19, Tehran University of Medical Sciences20, Auckland University of Technology21, James Cook University22, Monash University23, University of California, San Francisco24, Arabian Gulf University25, Central South University26, Virginia Commonwealth University27, Jordan University of Science and Technology28, Health Services Academy29, Oregon Health & Science University30, University of Sheffield31, University at Albany, SUNY32, Aintree University Hospitals NHS Foundation Trust33, Swansea University34, University of York35, South African Medical Research Council36, Children's Hospital of Philadelphia37, Addis Ababa University38, Curtin University39, University of Washington40, Queensland University of Technology41, University of British Columbia42, Suez Canal University43, Karolinska Institutet44, University of Alabama at Birmingham45, An-Najah National University46, Tufts Medical Center47, Norwegian Institute of Public Health48, Stavanger University Hospital49, University of Cape Town50, University of California, Irvine51, University of Illinois at Urbana–Champaign52, St. John's University53, Johns Hopkins University54, Hanoi Medical University55, National Research University – Higher School of Economics56, University of Gondar57, University of Hong Kong58, Jackson State University59, Wuhan University60
TL;DR: An overview of injury estimates from the 2013 update of GBD is provided, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country.
Abstract: Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Journal ArticleDOI
TL;DR: It is found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds ofospitalisation in patients with rheumatic disease.
Abstract: Objectives COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. Methods Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. Results A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. Conclusions We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

Journal ArticleDOI
TL;DR: In this article, the first experimental evidence for negative magneto-resistance generated by the chiral anomaly in a newly predicted time-reversal invariant Weyl semi-metal material TaAs was reported.
Abstract: Weyl semi-metal is the three dimensional analog of graphene. According to the quantum field theory, the appearance of Weyl points near the Fermi level will cause novel transport phenomena related to chiral anomaly. In the present paper, we report the first experimental evidence for the long-anticipated negative magneto-resistance generated by the chiral anomaly in a newly predicted time-reversal invariant Weyl semi-metal material TaAs. Clear Shubnikov de Haas oscillations (SdH) have been detected starting from very weak magnetic field. Analysis of the SdH peaks gives the Berry phase accumulated along the cyclotron orbits to be {\pi}, indicating the existence of Weyl points.

Journal ArticleDOI
TL;DR: The PD-1 pathway plays an essential role in maintaining immunologic self-tolerance, however, cancers can subvert the role of this pathway and blind the immune system to their presence.
Abstract: The PD-1 pathway plays an essential role in maintaining immunologic self-tolerance. However, cancers can subvert the role of this pathway and blind the immune system to their presence. The molecular details of the pathway are discussed.

Journal ArticleDOI
TL;DR: To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants.
Abstract: For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-e-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material for further experiments. Titanium implants with 600 µm pore size were evaluated and found to be a good implant material for bone, as primary osteoblasts showed a vitality and proliferation onto the implants comparable to well bottom (WB). Pure porous titanium implants and PCL coated porous titanium implants were compared using Live Cell Imaging (LCI) with Green fluorescent protein (GFP)-osteoblasts. Cell count and cell covered area did not differ between the implants after seven days. To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants. An angiogenesis assay was performed to establish an in vitro method for evaluating the impact of metallic implants on angiogenesis to reduce and refine animal experiments in future. Incorporated concentrations of proangiogenic factors were probably too low, as they did not lead to any effect. Magnesium implants did not yield evaluable results, as they led to pH increase and subsequent cell death.

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TL;DR: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma, and no maximum tolerated dose was identified in part 1.
Abstract: BACKGROUND Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1–2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. RESULTS No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytope nia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.)

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Jens Kattge1, Gerhard Bönisch2, Sandra Díaz3, Sandra Lavorel  +751 moreInstitutions (314)
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

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TL;DR: The Bitcoin protocol as mentioned in this paper is an online communication protocol that facilitates the use of virtual currency, including electronic payments, and allows for irreversible transactions, a prescribed path of money creation over time, and a public transaction history.
Abstract: Bitcoin is an online communication protocol that facilitates the use of a virtual currency, including electronic payments. Bitcoin's rules were designed by engineers with no apparent influence from lawyers or regulators. Bitcoin is built on a transaction log that is distributed across a network of participating computers. It includes mechanisms to reward honest participation, to bootstrap acceptance by early adopters, and to guard against concentrations of power. Bitcoin's design allows for irreversible transactions, a prescribed path of money creation over time, and a public transaction history. Anyone can create a Bitcoin account, without charge and without any centralized vetting procedure—or even a requirement to provide a real name. Collectively, these rules yield a system that is understood to be more flexible, more private, and less amenable to regulatory oversight than other forms of payment—though as we discuss, all these benefits face important limits. Bitcoin is of interest to economis...

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TL;DR: This review focuses on the epidemiology, pathogenesis and clinical characteristics among SARS‐coronaviruses (CoV), MERS‐CoV and other HCoV infections.
Abstract: Human coronaviruses (HCoVs) have been considered to be relatively harmless respiratory pathogens in the past. However, after the outbreak of the severe acute respiratory syndrome (SARS) and emergence of the Middle East respiratory syndrome (MERS), HCoVs have received worldwide attention as important pathogens in respiratory tract infection. This review focuses on the epidemiology, pathogenesis and clinical characteristics among SARS-coronaviruses (CoV), MERS-CoV and other HCoV infections.

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TL;DR: Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.

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24 Jun 2016-Science
TL;DR: The observation of a many-body localization transition between thermal and localized phases for bosons in a two-dimensional disordered optical lattice is reported, highlighting the power of quantum simulation to solve problems that are currently inaccessible to classical computing techniques.
Abstract: A fundamental assumption in statistical physics is that generic closed quantum many-body systems thermalize under their own dynamics. Recently, the emergence of many-body localized systems has questioned this concept and challenged our understanding of the connection between statistical physics and quantum mechanics. Here we report on the observation of a many-body localization transition between thermal and localized phases for bosons in a two-dimensional disordered optical lattice. With our single-site–resolved measurements, we track the relaxation dynamics of an initially prepared out-of-equilibrium density pattern and find strong evidence for a diverging length scale when approaching the localization transition. Our experiments represent a demonstration and in-depth characterization of many-body localization in a regime not accessible with state-of-the-art simulations on classical computers.

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TL;DR: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation and responded to pharmacokinetics and objective response according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
Abstract: Background No therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non–small-cell lung cancers (NSCLCs) and in 1 to 3% of colorect...

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TL;DR: A minimum set of common outcome measures for studies of COVID-19, which includes a measure of viral burden, patient survival, and patient progression through the health-care system by use of the WHO Clinical Progression Scale are urged.
Abstract: Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.

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18 Nov 2016-Science
TL;DR: The bioengineering of an accelerated response to natural shading events in Nicotiana (tobacco) is described, resulting in increased leaf carbon dioxide uptake and plant dry matter productivity by about 15% in fluctuating light.
Abstract: Crop leaves in full sunlight dissipate damaging excess absorbed light energy as heat. When sunlit leaves are shaded by clouds or other leaves, this protective dissipation continues for many minutes and reduces photosynthesis. Calculations have shown that this could cost field crops up to 20% of their potential yield. Here, we describe the bioengineering of an accelerated response to natural shading events in Nicotiana (tobacco), resulting in increased leaf carbon dioxide uptake and plant dry matter productivity by about 15% in fluctuating light. Because the photoprotective mechanism that has been altered is common to all flowering plants and crops, the findings provide proof of concept for a route to obtaining a sustainable increase in productivity for food crops and a much-needed yield jump.