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International evaluation of an AI system for breast cancer screening 期刊论文
NATURE, 2020, 577 (7788) : 89-+
作者:  McKinney, Scott Mayer;  Sieniek, Marcin;  Godbole, Varun;  Godwin, Jonathan;  Antropova, Natasha;  Ashrafian, Hutan;  Back, Trevor;  Chesus, Mary;  Corrado, Greg C.;  Darzi, Ara;  Etemadi, Mozziyar;  Garcia-Vicente, Florencia;  Gilbert, Fiona J.;  Halling-Brown, Mark;  Hassabis, Demis;  Jansen, Sunny;  Karthikesalingam, Alan;  Kelly, Christopher J.;  King, Dominic;  Ledsam, Joseph R.;  Melnick, David;  Mostofi, Hormuz;  Peng, Lily;  Reicher, Joshua Jay;  Romera-Paredes, Bernardino;  Sidebottom, Richard;  Suleyman, Mustafa;  Tse, Daniel;  Young, Kenneth C.;  De Fauw, Jeffrey;  Shetty, Shravya
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful(1). Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives(2). Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening.


  
A metabolic pathway for bile acid dehydroxylation by the gut microbiome 期刊论文
NATURE, 2020
作者:  Zhong, Miao;  Tran, Kevin;  Min, Yimeng;  Wang, Chuanhao;  Wang, Ziyun;  Dinh, Cao-Thang;  De Luna, Phil;  Yu, Zongqian;  Rasouli, Armin Sedighian;  Brodersen, Peter;  Sun, Song;  Voznyy, Oleksandr;  Tan, Chih-Shan;  Askerka, Mikhail;  Che, Fanglin;  Liu, Min;  Seifitokaldani, Ali;  Pang, Yuanjie;  Lo, Shen-Chuan;  Ip, Alexander;  Ulissi, Zachary;  Sargent, Edward H.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

The biosynthetic pathway that produces the secondary bile acids DCA and LCA in human gut microbes has been fully characterized, engineered into another bacterial host, and used to confer DCA production in germ-free mice-an important proof-of-principle for the engineering of gut microbial pathways.


The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 mu M and are known to block the growth ofClostridium difficile(1), promote hepatocellular carcinoma(2)and modulate host metabolism via the G-protein-coupled receptor TGR5 (ref.(3)). More broadly, DCA, LCA and their derivatives are major components of the recirculating pool of bile acids(4)  the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Nonetheless, despite the clear impact of DCA and LCA on host physiology, an incomplete knowledge of their biosynthetic genes and a lack of genetic tools to enable modification of their native microbial producers limit our ability to modulate secondary bile acid levels in the host. Here we complete the pathway to DCA and LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the eight-step conversion of cholic acid to DCA. We then engineer the pathway intoClostridium sporogenes, conferring production of DCA and LCA on a nonproducing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool.


  
Short-range order and its impact on the CrCoNi medium-entropy alloy 期刊论文
NATURE, 2020, 581 (7808) : 283-+
作者:  Tan, Hwei-Ee;  Sisti, Alexander C.;  Jin, Hao;  Vignovich, Martin;  Villavicencio, Miguel;  Tsang, Katherine S.;  Goffer, Yossef;  Zuker, Charles S.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Traditional metallic alloys are mixtures of elements in which the atoms of minority species tend to be distributed randomly if they are below their solubility limit, or to form secondary phases if they are above it. The concept of multiple-principal-element alloys has recently expanded this view, as these materials are single-phase solid solutions of generally equiatomic mixtures of metallic elements. This group of materials has received much interest owing to their enhanced mechanical properties(1-5). They are usually called medium-entropy alloys in ternary systems and high-entropy alloys in quaternary or quinary systems, alluding to their high degree of configurational entropy. However, the question has remained as to how random these solid solutions actually are, with the influence of short-range order being suggested in computational simulations but not seen experimentally(6,7). Here we report the observation, using energy-filtered transmission electron microscopy, of structural features attributable to short-range order in the CrCoNi medium-entropy alloy. Increasing amounts of such order give rise to both higher stacking-fault energy and hardness. These findings suggest that the degree of local ordering at the nanometre scale can be tailored through thermomechanical processing, providing a new avenue for tuning the mechanical properties of medium- and high-entropy alloys.


Metal alloys consisting of three or more major elemental components show enhanced mechanical properties, which are now shown to be correlated with short-range order observed with electron microscopy.


  
CARBON IN THE TIME OF COVID-19 期刊论文
NATURE, 2020, 582 (7811) : 158-159
作者:  Henderson, Caspar
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

Near-real-time data on carbon emissions reveal the sectors, countries and events that had the most impact, but it is unclear how long the dip will last.


Near-real-time data on carbon emissions reveal the sectors, countries and events that had the most impact, but it is unclear how long the dip will last.


  
A pause in Southern Hemisphere circulation trends due to the Montreal Protocol 期刊论文
NATURE, 2020, 579 (7800) : 544-548
作者:  Imai, Yu;  Meyer, Kirsten J.;  Iinishi, Akira;  Favre-Godal, Quentin;  Green, Robert;  Manuse, Sylvie;  Caboni, Mariaelena;  Mori, Miho;  Niles, Samantha;  Ghiglieri, Meghan;  Honrao, Chandrashekhar;  Ma, Xiaoyu;  Guo, Jason J.;  Makriyannis, Alexandros;  Linares-Otoya, Luis;  Boehringer, Nils;  Wuisan, Zerlina G.;  Kaur, Hundeep;  Wu, Runrun;  Mateus, Andre
收藏  |  浏览/下载:20/0  |  提交时间:2020/05/13

Observations show robust near-surface trends in Southern Hemisphere tropospheric circulation towards the end of the twentieth century, including a poleward shift in the mid-latitude jet(1,2), a positive trend in the Southern Annular Mode(1,3-6) and an expansion of the Hadley cell(7,8). It has been established that these trends were driven by ozone depletion in the Antarctic stratosphere due to emissions of ozone-depleting substances(9-11). Here we show that these widely reported circulation trends paused, or slightly reversed, around the year 2000. Using a pattern-based detection and attribution analysis of atmospheric zonal wind, we show that the pause in circulation trends is forced by human activities, and has not occurred owing only to internal or natural variability of the climate system. Furthermore, we demonstrate that stratospheric ozone recovery, resulting from the Montreal Protocol, is the key driver of the pause. Because pre-2000 circulation trends have affected precipitation(12-14), and potentially ocean circulation and salinity(15-17), we anticipate that a pause in these trends will have wider impacts on the Earth system. Signatures of the effects of the Montreal Protocol and the associated stratospheric ozone recovery might therefore manifest, or have already manifested, in other aspects of the Earth system.


  
Highly porous nature of a primitive asteroid revealed by thermal imaging 期刊论文
NATURE, 2020, 579 (7800) : 518-522
作者:  Quinn, Robert A.;  Melnik, Alexey, V;  Vrbanac, Alison;  Fu, Ting;  Patras, Kathryn A.;  Christy, Mitchell P.;  Bodai, Zsolt;  Belda-Ferre, Pedro;  Tripathi, Anupriya;  Chung, Lawton K.;  Downes, Michael;  Welch, Ryan D.;  Quinn, Melissa;  Humphrey, Greg;  Panitchpakdi, Morgan;  Weldon, Kelly C.;  Aksenov, Alexander;  da Silva, Ricardo;  Avila-Pacheco, Julian;  Clish, Clary;  Bae, Sena;  Mallick, Himel;  Franzosa, Eric A.;  Lloyd-Price, Jason;  Bussell, Robert;  Thron, Taren;  Nelson, Andrew T.;  Wang, Mingxun;  Leszczynski, Eric;  Vargas, Fernando;  Gauglitz, Julia M.;  Meehan, Michael J.;  Gentry, Emily;  Arthur, Timothy D.;  Komor, Alexis C.;  Poulsen, Orit;  Boland, Brigid S.;  Chang, John T.;  Sandborn, William J.;  Lim, Meerana;  Garg, Neha;  Lumeng, Julie C.;  Xavier, Ramnik J.;  Kazmierczak, Barbara, I;  Jain, Ruchi;  Egan, Marie;  Rhee, Kyung E.;  Ferguson, David;  Raffatellu, Manuela;  Vlamakis, Hera;  Haddad, Gabriel G.;  Siegel, Dionicio;  Huttenhower, Curtis;  Mazmanian, Sarkis K.;  Evans, Ronald M.;  Nizet, Victor;  Knight, Rob;  Dorrestein, Pieter C.
收藏  |  浏览/下载:49/0  |  提交时间:2020/05/13

Carbonaceous (C-type) asteroids(1) are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites(2,3) and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth'  s atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)(4) onboard the spacecraft Hayabusa2(5), indicating that the asteroid'  s boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m(-2) s(-0.5) K-1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites(6) and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect(7,8). We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites(6). These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity(9) of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies(10).


Thermal imaging data obtained from the spacecraft Hayabusa2 reveal that the carbonaceous asteroid 162173 Ryugu is an object of unusually high porosity.


  
Performance-limiting nanoscale trap clusters at grain junctions in halide perovskites 期刊论文
NATURE, 2020, 580 (7803) : 360-+
作者:  van den Brink, Susanne C.;  Alemany, Anna;  van Batenburg, Vincent;  Moris, Naomi;  Blotenburg, Marloes;  Vivie, Judith;  Baillie-Johnson, Peter;  Nichols, Jennifer;  Sonnen, Katharina F.;  Arias, Alfonso;  van Oudenaarden, Alexander
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

Halide perovskite materials have promising performance characteristics for low-cost optoelectronic applications. Photovoltaic devices fabricated from perovskite absorbers have reached power conversion efficiencies above 25 per cent in single-junction devices and 28 per cent in tandem devices(1,2). This strong performance (albeit below the practical limits of about 30 per cent and 35 per cent, respectively(3)) is surprising in thin films processed from solution at low-temperature, a method that generally produces abundant crystalline defects(4). Although point defects often induce only shallow electronic states in the perovskite bandgap that do not affect performance(5), perovskite devices still have many states deep within the bandgap that trap charge carriers and cause them to recombine non-radiatively. These deep trap states thus induce local variations in photoluminescence and limit the device performance(6). The origin and distribution of these trap states are unknown, but they have been associated with light-induced halide segregation in mixed-halide perovskite compositions(7) and with local strain(8), both of which make devices less stable(9). Here we use photoemission electron microscopy to image the trap distribution in state-of-the-art halide perovskite films. Instead of a relatively uniform distribution within regions of poor photoluminescence efficiency, we observe discrete, nanoscale trap clusters. By correlating microscopy measurements with scanning electron analytical techniques, we find that these trap clusters appear at the interfaces between crystallographically and compositionally distinct entities. Finally, by generating time-resolved photoemission sequences of the photo-excited carrier trapping process(10,11), we reveal a hole-trapping character with the kinetics limited by diffusion of holes to the local trap clusters. Our approach shows that managing structure and composition on the nanoscale will be essential for optimal performance of halide perovskite devices.


  
Preindustrial (CH4)-C-14 indicates greater anthropogenic fossil CH4 emissions 期刊论文
NATURE, 2020, 578 (7795) : 409-+
作者:  Keener, Megan;  Hunt, Camden;  Carroll, Timothy G.;  Kampel, Vladimir;  Dobrovetsky, Roman;  Hayton, Trevor W.;  Menard, Gabriel
收藏  |  浏览/下载:25/0  |  提交时间:2020/05/13

Atmospheric methane (CH4) is a potent greenhouse gas, and its mole fraction has more than doubled since the preindustrial era(1). Fossil fuel extraction and use are among the largest anthropogenic sources of CH4 emissions, but the precise magnitude of these contributions is a subject of debate(2,3). Carbon-14 in CH4 ((CH4)-C-14) can be used to distinguish between fossil (C-14-free) CH4 emissions and contemporaneous biogenic sources  however, poorly constrained direct (CH4)-C-14 emissions from nuclear reactors have complicated this approach since the middle of the 20th century(4,5). Moreover, the partitioning of total fossil CH4 emissions (presently 172 to 195 teragrams CH4 per year)(2,3) between anthropogenic and natural geological sources (such as seeps and mud volcanoes) is under debate  emission inventories suggest that the latter account for about 40 to 60 teragrams CH4 per year(6,7). Geological emissions were less than 15.4 teragrams CH4 per year at the end of the Pleistocene, about 11,600 years ago(8), but that period is an imperfect analogue for present-day emissions owing to the large terrestrial ice sheet cover, lower sea level and extensive permafrost. Here we use preindustrial-era ice core (CH4)-C-14 measurements to show that natural geological CH4 emissions to the atmosphere were about 1.6 teragrams CH4 per year, with a maximum of 5.4 teragrams CH4 per year (95 per cent confidence limit)-an order of magnitude lower than the currently used estimates. This result indicates that anthropogenic fossil CH4 emissions are underestimated by about 38 to 58 teragrams CH4 per year, or about 25 to 40 per cent of recent estimates. Our record highlights the human impact on the atmosphere and climate, provides a firm target for inventories of the global CH4 budget, and will help to inform strategies for targeted emission reductions(9,10).


Isotopic evidence from ice cores indicates that preindustrial-era geological methane emissions were lower than previously thought, suggesting that present-day emissions of methane from fossil fuels are underestimated.


  
Premature mortality related to United States cross-state air pollution 期刊论文
NATURE, 2020, 578 (7794) : 261-+
作者:  Helmink, Beth A.;  Reddy, Sangeetha M.;  Gao, Jianjun;  Zhang, Shaojun;  Basar, Rafet;  Thakur, Rohit;  Yizhak, Keren;  Sade-Feldman, Moshe;  Blando, Jorge;  Han, Guangchun;  Gopalakrishnan, Vancheswaran;  Xi, Yuanxin;  Zhao, Hao;  Amaria, Rodabe N.;  Tawbi, Hussein A.;  Cogdill, Alex P.;  Liu, Wenbin;  LeBleu, Valerie S.;  Kugeratski, Fernanda G.;  Patel, Sapna;  Davies, Michael A.;  Hwu, Patrick;  Lee, Jeffrey E.;  Gershenwald, Jeffrey E.;  Lucci, Anthony;  Arora, Reetakshi;  Woodman, Scott;  Keung, Emily Z.;  Gaudreau, Pierre-Olivier;  Reuben, Alexandre;  Spencer, Christine N.;  Burton, Elizabeth M.;  Haydu, Lauren E.;  Lazar, Alexander J.;  Zapassodi, Roberta;  Hudgens, Courtney W.;  Ledesma, Deborah A.;  Ong, SuFey;  Bailey, Michael;  Warren, Sarah;  Rao, Disha;  Krijgsman, Oscar;  Rozeman, Elisa A.;  Peeper, Daniel;  Blank, Christian U.;  Schumacher, Ton N.;  Butterfield, Lisa H.;  Zelazowska, Monika A.;  McBride, Kevin M.;  Kalluri, Raghu;  Allison, James;  Petitprez, Florent;  Fridman, Wolf Herman;  Sautes-Fridman, Catherine;  Hacohen, Nir;  Rezvani, Katayoun;  Sharma, Padmanee;  Tetzlaff, Michael T.;  Wang, Linghua;  Wargo, Jennifer A.
收藏  |  浏览/下载:37/0  |  提交时间:2020/05/13

Outdoor air pollution adversely affects human health and is estimated to be responsible for five to ten per cent of the total annual premature mortality in the contiguous United States(1-3). Combustion emissions from a variety of sources, such as power generation or road traffic, make a large contribution to harmful air pollutants such as ozone and fine particulate matter (PM2.5)(4). Efforts to mitigate air pollution have focused mainly on the relationship between local emission sources and local air quality(2). Air quality can also be affected by distant emission sources, however, including emissions from neighbouring federal states(5,6). This cross-state exchange of pollution poses additional regulatory challenges. Here we quantify the exchange of air pollution among the contiguous United States, and assess its impact on premature mortality that is linked to increased human exposure to PM2.5 and ozone from seven emission sectors for 2005 to 2018. On average, we find that 41 to 53 per cent of air-quality-related premature mortality resulting from a state'  s emissions occurs outside that state. We also find variations in the cross-state contributions of different emission sectors and chemical species to premature mortality, and changes in these variations over time. Emissions from electric power generation have the greatest cross-state impacts as a fraction of their total impacts, whereas commercial/residential emissions have the smallest. However, reductions in emissions from electric power generation since 2005 have meant that, by 2018, cross-state premature mortality associated with the commercial/residential sector was twice that associated with power generation. In terms of the chemical species emitted, nitrogen oxides and sulfur dioxide emissions caused the most cross-state premature deaths in 2005, but by 2018 primary PM2.5 emissions led to cross-state premature deaths equal to three times those associated with sulfur dioxide emissions. These reported shifts in emission sectors and emission species that contribute to premature mortality may help to guide improvements to air quality in the contiguous United States.


  
Reply to: Why fossil fuel producer subsidies matter 期刊论文
NATURE, 2020, 578 (7793) : E5-E7
作者:  Wang, Peng;  Zheng, Yuanlin;  Chen, Xianfeng;  Huang, Changming;  Kartashov, Yaroslav V.;  Torner, Lluis;  Konotop, Vladimir V.;  Ye, Fangwei
收藏  |  浏览/下载:24/0  |  提交时间:2020/05/13