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Early-childhood linear growth faltering in low- and middle-income countries (

NATURE 2023年第7985期623卷 E2-E2页

作者： Benjamin-Chung, Jade Mertens, Andrew Colford, John M., Jr. Hubbard, Alan E. van der Laan, Mark J. Coyle, Jeremy Sofrygin, Oleg Cai, Wilson Nguyen, Anna Pokpongkiat, Nolan N. Djajadi, Stephanie Seth, Anmol Jilek, Wendy Jung, Esther Chung, Esther O. Rosete, Sonali Hejazi, Nima Malenica, Ivana Li, Haodong Hafen, Ryan Subramoney, Vishak Haggstrom, Jonas Norman, Thea Brown, Kenneth H. Christian, Parul Arnold, Benjamin F. Department of Epidemiology & Population Health Stanford University Stanford CA USA Division of Epidemiology & Biostatistics University of California Berkeley Berkeley CA USA Chan Zuckerberg Biohub San Francisco CA USA Hafen Consulting LLC West Richland WA USA DVPL Tech Dubai United Arab Emirates Cytel Inc. Waltham MA USA Quantitative Sciences Bill & Melinda Gates Foundation Seattle WA USA Department of Nutrition University of California Davis Davis CA USA Center for Human Nutrition Department of International Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA Francis I. Proctor Foundation University of California San Francisco San Francisco CA USA Department of Ophthalmology University of California San Francisco San Francisco CA USA Department of Public Health and Primary Care Ghent University Ghent Belgium Department of Nutrition University of North Carolina at Chapel Hill Chapel Hill NC USA International Centre for Diarrhoeal Disease Research Bangladesh Dhaka Bangladesh Department of Pediatrics and Child Health The Aga Khan University Karachi Pakistan University of Virginia Charlottesville VA USA JiVitA Project John Hopkins Bangladesh Rangpur Bangladesh Center for Child Adolescent and Maternal Health Research Department of Medicine and Health Technology Tampere University Tampere Finland Tampere University Hospital Tampere Finland World Health Organization Geneva Switzerland Center of Data and Knowledge Integration for Health Fundação Oswaldo Cruz Salvador Brazil UNICEF New York NY USA HIV/AIDS & Global Health Research Programme University of Venda Thohoyandou South Africa Indian Institute of Technology New Delhi India Centre for Health Research and Development Society for Applied Studies New Delhi India Sunder Lal Jain Hospital New Delhi India Centre of Excellence in Women & Child Health Institute for Global Health & Development The Aga Khan University Karachi Pakistan Johns Hopkins University Bl

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GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

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Nature genetics 2023年第9期55卷 1471-1482页

作者： Remi Stevelink Dorothee Kasteleijn-Nolst Trenite Bobby P. C. Koeleman Dick Lindhout Anja C. M. Sonsma Ciarán Campbell Gianpiero L. Cavalleri Norman Delanty Hany El-Naggar Austin Lacey Peter Widdess-Walsh Colin P. Doherty Siwei Chen Claire Churchhouse Mark J. Daly Yen-Chen A. Feng Daniel P. Howrigan Mitja I. Kurki Benjamin M. Neale Aarno Palotie Wei Zhou Namrata Gupta Henrike O. Heyne Bassel Abou-Khalil Kevin F. Haas R. S. Taneja Oluyomi M. Adesoji Michael Nothnagel Peter Nürnberg Thomas Sander Zaid Afawi Ilan Blatt Amos D. Korczyn Elisabetta Amadori Ganna Balagura Antonella Riva Marcello Scala Paolo Scudieri Pasquale Striano Federico Zara Michele Iacomino Francesca Madia Alison Anderson Patrick Kwan Terence J. O’Brien Slavé Petrovski K. Meng Tan Marian Todaro Joseph Anderson Danielle M. Andrade Quratulain Zulfiqar Ali Grazia Annesi Pauls Auce Andreja Avbersek Simona Balestrini Vera Braatz Claudia B. Catarino Krishna Chinthapalli Jennifer Jamnadas-Khoda Dalia Kasperavičiūte Costin Leu Josemir W. Sander Sanjay M. Sisodiya Sara Zagaglia Melanie Bahlo Karen L. Oliver Mark D. Baker Beata Fonferko-Shadrach William O. Pickrell Carmen Barba Claudia Bianchini Viola Doccini Renzo Guerrini Davide Mei Martino Montomoli Elena Parrini Annalisa Vetro Karen Barboza Fabrice Bartolomei Thomas Bast Bernhard J. Steinhoff Larry Baum Stacey S. Cherny Pak Sham Tobias Baumgartner Christian E. Elger Kerstin Hallmann Wolfram S. Kunz Rainer Surges Randi von Wrede Gábor Zsurka Betül Baykan Nerses Bebek Yeşim Kesim Albert J. Becker Susanne Schoch Felicitas Becker Caitlin A. Bennett Samuel F. Berkovic Stephanie L. Leech Brigid M. Regan Ingrid E. Scheffer Bianca Berghuis Ahmad Beydoun Wassim Nasreddine Francesca Bisulli Lidia Di Vito Lorenzo Ferri Tania Giangregorio Laura Licchetta Raffaella Minardi Barbara Mostacci Carlotta Stipa Paolo Tinuper Lorenzo Muccioli Federica Pondrelli Dheeraj R. Bobbili Emadeldin Hassanin Roland Krause Zied Landoulsi Patrick May Ingo Borggraefe Christian Bosselmann Christian Hengsbach Josua Kegele Stephen Lauxmann Department of Genetics University Medical Center Utrecht Utrecht The Netherlands Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands School of Pharmacy and Biomolecular Sciences The Royal College of Surgeons in Ireland Dublin Ireland The FutureNeuro Research Centre Dublin Ireland Department of Neurology Beaumont Hospital Dublin Ireland Department of Neurology St. James’s Hospital Dublin Ireland Analytic and Translational Genetics Unit Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston MA USA Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Stanley Center for Psychiatric Research Broad Institute of Harvard and M.I.T Cambridge MA USA Institute for Molecular Medicine Finland (FIMM) University of Helsinki Helsinki Finland Psychiatric & Neurodevelopmental Genetics Unit Department of Psychiatry Massachusetts General Hospital and Harvard Medical School Boston MA USA Division of Biostatistics Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei Taiwan Hasso Plattner Institute Digital Health Center University of Potsdam Potsdam Germany Hasso Plattner Institute Mount Sinai School of Medicine New York City NY USA Department of Neurology Vanderbilt University Medical Center Nashville TN USA Cologne Center for Genomics (CCG) University of Cologne Faculty of Medicine and University Hospital Cologne Cologne Germany University Hospital Cologne Cologne Germany Department of Neurology Charité Universitaetsmedizin Berlin Campus Virchow-Clinic Berlin Germany Tel-Aviv University Sackler Faculty of Medicine Ramat Aviv Israel Department of Neurology Sheba Medical Center Ramat Gan Israel Department of Neurosciences Rehabilitation Ophthalmology Genetics Maternal and Child Health University of Genova Genova Italy IRCCS Istituto Giannina Gaslini Genova Italy Department of Medicine University of Melbour

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.

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TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A (vol 603, pg 131, 2022)

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NATURE 2024年第8020期631卷 E7-E7页

作者： Brown, Anna-Leigh Wilkins, Oscar G. Keuss, Matthew J. Hill, Sarah E. Zanovello, Matteo Lee, Weaverly Colleen Bampton, Alexander Lee, Flora C. Y. Masino, Laura Qi, Yue A. Bryce-Smith, Sam Gatt, Ariana Hallegger, Martina Fagegaltier, Delphine Phatnani, Hemali Phatnani, Hemali Newcombe, Jia Gustavsson, Emil K. Seddighi, Sahba Reyes, Joel F. Coon, Steven L. Ramos, Daniel Schiavo, Giampietro Fisher, Elizabeth M. C. Raj, Towfique Secrier, Maria Lashley, Tammaryn Ule, Jernej Buratti, Emanuele Humphrey, Jack Ward, Michael E. Fratta, Pietro UCL Queen Square Motor Neuron Disease Centre Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology UCL London UK The Francis Crick Institute London UK UK Dementia Research Institute University College London London UK Department of Molecular Biology and Nanobiotechnology National Institute of Chemistry Ljubljana Slovenia National Institute of Neurological Disorders and Stroke NIH Bethesda MD USA Medical Scientist Training Program Johns Hopkins University School of Medicine Baltimore MD USA Center for Alzheimer’s and Related Dementias National Institutes of Health Bethesda MD USA Queen Square Brain Bank UCL Queen Square Institute of Neurology University College London London UK Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology University College London London UK Great Ormond Street Institute of Child Health Genetics and Genomic Medicine University College London London UK Center for Genomics of Neurodegenerative Disease New York Genome Center (NYGC) New York NY USA NeuroResource Department of Neuroinflammation UCL Queen Square Institute of Neurology London UK Molecular Genomics Core Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH Bethesda MD USA Nash Family Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York NY USA Ronald M. Loeb Center for Alzheimer’s Disease Icahn School of Medicine at Mount Sinai New York NY USA Department of Pathology Fishberg Department of Neuroscience Icahn School of Medicine at Mount Sinai New York NY USA Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai New York NY USA Estelle and Daniel Maggin Department of Neurology Icahn School of Medicine at Mount Sinai New York NY USA Department of Genetics Evolution and Environment UCL Genetics Institute University College London London UK Mole

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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

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Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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Cosmic-Ray Boron Flux Measured from 8.4 GeV/n to 3.8 TeV/n with the Calorimetric Electron Telescope on the International Space Station

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Physical Review Letters 2022年第25期129卷 251103-251103页

作者： O. Adriani Y. Akaike K. Asano Y. Asaoka E. Berti G. Bigongiari W. R. Binns M. Bongi P. Brogi A. Bruno J. H. Buckley N. Cannady G. Castellini C. Checchia M. L. Cherry G. Collazuol G. A. de Nolfo K. Ebisawa A. W. Ficklin H. Fuke S. Gonzi T. G. Guzik T. Hams K. Hibino M. Ichimura K. Ioka W. Ishizaki M. H. Israel K. Kasahara J. Kataoka R. Kataoka Y. Katayose C. Kato N. Kawanaka Y. Kawakubo K. Kobayashi K. Kohri H. S. Krawczynski J. F. Krizmanic P. Maestro P. S. Marrocchesi A. M. Messineo J. W. Mitchell S. Miyake A. A. Moiseev M. Mori N. Mori H. M. Motz K. Munakata S. Nakahira J. Nishimura S. Okuno J. F. Ormes S. Ozawa L. Pacini P. Papini B. F. Rauch S. B. Ricciarini K. Sakai T. Sakamoto M. Sasaki Y. Shimizu A. Shiomi P. Spillantini F. Stolzi S. Sugita A. Sulaj M. Takita T. Tamura T. Terasawa S. Torii Y. Tsunesada Y. Uchihori E. Vannuccini J. P. Wefel K. Yamaoka S. Yanagita A. Yoshida K. Yoshida W. V. Zober Department of Physics Department of Physics University of Florence Via Sansone 1–50019 Sesto Fiorentino Italy INFN Sezione di Florence Via Sansone 1–50019 Sesto Fiorentino Italy Waseda Research Institute for Science and Engineering Waseda University 17 Kikuicho Shinjuku Tokyo 162-0044 Japan JEM Utilization Center Human Spaceflight Technology Directorate Japan Aerospace Exploration Agency 2-1-1 Sengen Tsukuba Ibaraki 305-8505 Japan Institute for Cosmic Ray Research The University of Tokyo 5-1-5 Kashiwa-no-Ha Kashiwa Chiba 277-8582 Japan Department of Physical Sciences Earth and Environment University of Siena via Roma 56 53100 Siena Italy INFN Sezione di Pisa Polo Fibonacci Largo B. Pontecorvo 3–56127 Pisa Italy Department of Physics and McDonnell Center for the Space Sciences Washington University One Brookings Drive St. Louis Missouri 63130-4899 USA Heliospheric Physics Laboratory NASA/GSFC Greenbelt Maryland 20771 USA Center for Space Sciences and Technology University of Maryland Baltimore County 1000 Hilltop Circle Baltimore Maryland 21250 USA Astroparticle Physics Laboratory NASA/GSFC Greenbelt Maryland 20771 USA Center for Research and Exploration in Space Sciences and Technology NASA/GSFC Greenbelt Maryland 20771 USA Institute of Applied Physics (IFAC) National Research Council (CNR) Via Madonna del Piano 10 50019 Sesto Fiorentino Italy Department of Physics and Astronomy Louisiana State University 202 Nicholson Hall Baton Rouge Louisiana 70803 USA Department of Physics and Astronomy University of Padova Via Marzolo 8 35131 Padova Italy INFN Sezione di Padova Via Marzolo 8 35131 Padova Italy Institute of Space and Astronautical Science Japan Aerospace Exploration Agency 3-1-1 Yoshinodai Chuo Sagamihara Kanagawa 252-5210 Japan Kanagawa University 3-27-1 Rokkakubashi Kanagawa Yokohama Kanagawa 221-8686 Japan Faculty of Science and Technology Graduate School of Science and Technology Hirosaki University 3 Bunkyo Hiros

We present the measurement of the energy dependence of the boron flux in cosmic rays and its ratio to the carbon flux in an energy interval from 8.4 GeV/n to 3.8 TeV/n based on the data collected by the Calorimetric Electron Telescope (CALET) during ∼6.4 yr of operation on the International Space Station. An update of the energy spectrum of carbon is also presented with an increase in statistics over our previous measurement. The observed boron flux shows a spectral hardening at the same transition energy E0∼200 GeV/n of the C spectrum, though B and C fluxes have different energy dependences. The spectral index of the B spectrum is found to be γ=−3.047±0.024 in the interval 25

关键词： Cosmic ray & astroparticle detectors Cosmic ray acceleration Cosmic ray composition & spectra Cosmic ray propagation Cosmic ray sources Cosmic rays & astroparticles

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Direct Measurement of the Nickel Spectrum in Cosmic Rays in the Energy Range from 8.8 GeV/n to 240 GeV/n with CALET on the International Space Station

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Physical Review Letters 2022年第13期128卷 131103-131103页

作者： O. Adriani Y. Akaike K. Asano Y. Asaoka E. Berti G. Bigongiari W. R. Binns M. Bongi P. Brogi A. Bruno J. H. Buckley N. Cannady G. Castellini C. Checchia M. L. Cherry G. Collazuol K. Ebisawa A. W. Ficklin H. Fuke S. Gonzi T. G. Guzik T. Hams K. Hibino M. Ichimura K. Ioka W. Ishizaki M. H. Israel K. Kasahara J. Kataoka R. Kataoka Y. Katayose C. Kato N. Kawanaka Y. Kawakubo K. Kobayashi K. Kohri H. S. Krawczynski J. F. Krizmanic P. Maestro P. S. Marrocchesi A. M. Messineo J. W. Mitchell S. Miyake A. A. Moiseev M. Mori N. Mori H. M. Motz K. Munakata S. Nakahira J. Nishimura G. A. de Nolfo S. Okuno J. F. Ormes N. Ospina S. Ozawa L. Pacini P. Papini B. F. Rauch S. B. Ricciarini K. Sakai T. Sakamoto M. Sasaki Y. Shimizu A. Shiomi P. Spillantini F. Stolzi S. Sugita A. Sulaj M. Takita T. Tamura T. Terasawa S. Torii Y. Tsunesada Y. Uchihori E. Vannuccini J. P. Wefel K. Yamaoka S. Yanagita A. Yoshida K. Yoshida W. V. Zober Department of Physics University of Florence Via Sansone 1 - 50019 Sesto Fiorentino Italy INFN Sezione di Florence Via Sansone 1 - 50019 Sesto Fiorentino Italy Waseda Research Institute for Science and Engineering Waseda University 17 Kikuicho Shinjuku Tokyo 162-0044 Japan JEM Utilization Center Human Spaceflight Technology Directorate Japan Aerospace Exploration Agency 2-1-1 Sengen Tsukuba Ibaraki 305-8505 Japan Institute for Cosmic Ray Research The University of Tokyo 5-1-5 Kashiwa-no-Ha Kashiwa Chiba 277-8582 Japan Department of Physical Sciences Earth and Environment University of Siena via Roma 56 53100 Siena Italy INFN Sezione di Pisa Polo Fibonacci Largo B. Pontecorvo 3 - 56127 Pisa Italy Department of Physics and McDonnell Center for the Space Sciences Washington University One Brookings Drive St. Louis Missouri 63130-4899 USA Heliospheric Physics Laboratory NASA/GSFC Greenbelt Maryland 20771 USA Center for Space Sciences and Technology University of Maryland Baltimore County 1000 Hilltop Circle Baltimore Maryland 21250 USA Astroparticle Physics Laboratory NASA/GSFC Greenbelt Maryland 20771 USA Center for Research and Exploration in Space Sciences and Technology NASA/GSFC Greenbelt Maryland 20771 USA Institute of Applied Physics (IFAC) National Research Council (CNR) Via Madonna del Piano 10 50019 Sesto Fiorentino Italy Department of Physics and Astronomy Louisiana State University 202 Nicholson Hall Baton Rouge Louisiana 70803 USA Department of Physics and Astronomy University of Padova Via Marzolo 8 35131 Padova Italy INFN Sezione di Padova Via Marzolo 8 35131 Padova Italy Institute of Space and Astronautical Science Japan Aerospace Exploration Agency 3-1-1 Yoshinodai Chuo Sagamihara Kanagawa 252-5210 Japan Kanagawa University 3-27-1 Rokkakubashi Kanagawa Yokohama Kanagawa 221-8686 Japan Faculty of Science and Technology Graduate School of Science and Technology Hirosaki University 3 Bunkyo Hirosaki Aomori 036-856

The relative abundance of cosmic ray nickel nuclei with respect to iron is by far larger than for all other transiron elements; therefore it provides a favorable opportunity for a low background measurement of its spectrum. Since nickel, as well as iron, is one of the most stable nuclei, the nickel energy spectrum and its relative abundance with respect to iron provide important information to estimate the abundances at the cosmic ray source and to model the Galactic propagation of heavy nuclei. However, only a few direct measurements of cosmic-ray nickel at energy larger than ∼3 GeV/n are available at present in the literature, and they are affected by strong limitations in both energy reach and statistics. In this Letter, we present a measurement of the differential energy spectrum of nickel in the energy range from 8.8 to 240 GeV/n, carried out with unprecedented precision by the Calorimetric Electron Telescope (CALET) in operation on the International Space Station since 2015. The CALET instrument can identify individual nuclear species via a measurement of their electric charge with a dynamic range extending far beyond iron (up to atomic number Z=40). The particle’s energy is measured by a homogeneous calorimeter (1.2 proton interaction lengths, 27 radiation lengths) preceded by a thin imaging section (3 radiation lengths) providing tracking and energy sampling. This Letter follows our previous measurement of the iron spectrum [O. Adriani et al. (CALET Collaboration), Phys. Rev. Lett. 126, 241101 (2021).], and it extends our investigation on the energy dependence of the spectral index of heavy elements. It reports the analysis of nickel data collected from November 2015 to May 2021 and a detailed assessment of the systematic uncertainties. In the region from 20 to 240 GeV/n our present data are compatible within the errors with a single power law with spectral index −2.51±0.07.

关键词： Cosmic ray acceleration Cosmic ray composition & spectra Cosmic ray propagation Cosmic ray sources Cosmic rays & astroparticles

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Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

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Nature genetics 2023年第10期55卷 1778-1779页

作者： Nick Shrine Abril G Izquierdo Jing Chen Richard Packer Robert J Hall Anna L Guyatt Chiara Batini Rebecca J Thompson Chandan Pavuluri Vidhi Malik Brian D Hobbs Matthew Moll Wonji Kim Ruth Tal-Singer Per Bakke Katherine A Fawcett Catherine John Kayesha Coley Noemi Nicole Piga Alfred Pozarickij Kuang Lin Iona Y Millwood Zhengming Chen Liming Li Sara R A Wijnant Lies Lahousse Guy Brusselle Andre G Uitterlinden Ani Manichaikul Elizabeth C Oelsner Stephen S Rich R Graham Barr Shona M Kerr Veronique Vitart Michael R Brown Matthias Wielscher Medea Imboden Ayoung Jeong Traci M Bartz Sina A Gharib Claudia Flexeder Stefan Karrasch Christian Gieger Annette Peters Beate Stubbe Xiaowei Hu Victor E Ortega Deborah A Meyers Eugene R Bleecker Stacey B Gabriel Namrata Gupta Albert Vernon Smith Jian'an Luan Jing-Hua Zhao Ailin F Hansen Arnulf Langhammer Cristen Willer Laxmi Bhatta David Porteous Blair H Smith Archie Campbell Tamar Sofer Jiwon Lee Martha L Daviglus Bing Yu Elise Lim Hanfei Xu George T O'Connor Gaurav Thareja Omar M E Albagha Karsten Suhre Raquel Granell Tariq O Faquih Pieter S Hiemstra Annelies M Slats Benjamin H Mullin Jennie Hui Alan James John Beilby Karina Patasova Pirro Hysi Jukka T Koskela Annah B Wyss Jianping Jin Sinjini Sikdar Mikyeong Lee Sebastian May-Wilson Nicola Pirastu Katherine A Kentistou Peter K Joshi Paul R H J Timmers Alexander T Williams Robert C Free Xueyang Wang John L Morrison Frank D Gilliland Zhanghua Chen Carol A Wang Rachel E Foong Sarah E Harris Adele Taylor Paul Redmond James P Cook Anubha Mahajan Lars Lind Teemu Palviainen Terho Lehtimäki Olli T Raitakari Jaakko Kaprio Taina Rantanen Kirsi H Pietiläinen Simon R Cox Craig E Pennell Graham L Hall W James Gauderman Chris Brightling James F Wilson Tuula Vasankari Tarja Laitinen Veikko Salomaa Dennis O Mook-Kanamori Nicholas J Timpson Eleftheria Zeggini Josée Dupuis Caroline Hayward Ben Brumpton Claudia Langenberg Stefan Weiss Georg Homuth Carsten Oliver Schmidt Nicole Probst-Hensch Marjo-Riitta Jarvelin Alanna C Morrison Ozren Polasek Igor Department of Population Health Sciences University of Leicester Leicester UK. nick.shrine@leicester.ac.uk. Department of Population Health Sciences University of Leicester Leicester UK. Division of Respiratory Medicine and NIHR Nottingham Biomedical Research Centre University of Nottingham Nottingham UK. Leicester National Institute for Health and Care Research Biomedical Research Centre Glenfield Hospital Leicester UK. Channing Division of Network Medicine Division of Pulmonary and Critical Care Medicine Department of Medicine Brigham and Women's Hospital Boston MA USA. Harvard Medical School Boston MA USA. COPD Foundation Washington DC USA. Department of Clinical Science Unversity of Bergen Bergen Norway. Nuffield Department of Population Health University of Oxford Oxford UK. MRC Population Health Research Unit University of Oxford Oxford UK. Department of Epidemiology and Biostatistics School of Public Health Peking University Health Science Center Beijing China. Department of Respiratory Diseases Ghent Universital Hospital Ghent Belgium. Department of Bioanalysis Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium. Department of Epidemiology Eramus Medical Center Rotterdam The Netherlands. Department of Internal Medicine Eramus Medical Center Rotterdam The Netherlands. Center for Public Health Genomics University of Virginia Charlottesville VA USA. Department of Medicine Columbia University Medical Center New York NY USA. Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK. Human Genetics Center Department of Epidemiology Human Genetics and Environmental Sciences School of Public Health The University of Texas Health Science Center at Houston Houston TX USA. MRC Centre for Environment and Health Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK. Department of Epidemiology and Public Health Swiss Tropical

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The “i Competency Dictionary” Framework for IT Engineering Education

The “i Competency Dictionary” Framework for IT Engineering...

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IEEE World Engineering Education Conference (EDUNINE)

作者： Eiji Hayashiguchi Osamu Endou John Impagliazzo Information-technology Promotion Agency Japan (IPA) IT Human Resource Development Tokyo Japan School of Engineering and Applied Science Hofstra University Hempstead New York USA

Information technology (IT) engineering education in Japan has a major issue in linking IT education in universities with IT industry requirements. The IT world is changing very rapidly now and the academia-industry linkage is becoming difficult and divergent. In this paper, the authors describe the “i Competency Dictionary” (iCD) framework developed and announced by Information-technology Promotion Agency (IPA), a Japanese government organization in 2015. IPA developed this iCD framework for IT user organizations and IT vendor companies for their human resource development. Since its announcement, iCD has been expanding very rapidly within Japanese IT industries and the framework is becoming a reference in many IT organizations outside Japan. In the meantime, universities and educational organizations are starting to use iCD to develop and evaluate their curricula since it contains rich industry requirements reflecting today's rapid IT changes. The authors believe that iCD can contribute much to educational areas and they illustrate examples of the iCD successes in academic circles.

关键词： Task analysis Standards organizations Dictionaries Companies Industries

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Polygenic risk score and lung adenocarcinoma risk among never-smokers by EGFR mutation status-a brief report

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Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2024年第4期20卷 521-530页

作者： Batel Blechter Chao Agnes Hsiung Xiaoyu Wang Haoyu Zhang Wei Jie Seow Jianxin Shi Nilanjan Chatterjee Hee Nam Kim Maria Pik Wong Yun-Chul Hong Jason Yy Wong Juncheng Dai H Dean Hosgood Zhaoming Wang I-Shou Chang Jiyeon Choi Jiucun Wang Minsun Song Wei Hu Wei Zheng Jin Hee Kim Baosen Zhou Demetrius Albanes Min-Ho Shin Lap Ping Chung She-Juan An Hong Zheng Yasushi Yatabe Xu-Chao Zhang Young Tae Kim Xiao-Ou Shu Young-Chul Kim Roel C H Vermeulen Bryan A Bassig Jiang Chang James Chung Man Ho Bu-Tian Ji Michiaki Kubo Yataro Daigo Yukihide Momozawa Yoichiro Kamatani Takayuki Honda Hideo Kunitoh Shun-Ichi Watanabe Yohei Miyagi Haruhiko Nakayama Shingo Matsumoto Masahiro Tsuboi Koichi Goto Zhihua Yin Atsushi Takahashi Akiteru Goto Yoshihiro Minamiya Kimihiro Shimizu Kazumi Tanaka Tangchun Wu Fusheng Wei Jian Su Yeul Hong Kim In-Jae Oh Victor Ho Fun Lee Wu-Chou Su Yuh-Min Chen Gee-Chen Chang Kuan-Yu Chen Ming-Shyan Huang Hsien-Chih Lin Adeline Seow Jae Yong Park Sun-Seog Kweon Chien-Jen Chen Yu-Tang Gao Chen Wu Biyun Qian Daru Lu Jianjun Liu Hyo-Sung Jeon Chin-Fu Hsiao Jae Sook Sung Ying-Huang Tsai Yoo Jin Jung Huan Guo Zhibin Hu Tzu-Yu Chen Laurie Burdett Meredith Yeager Amy Hutchinson Sonja I Berndt Wei Wu Junwen Wang Jin Eun Choi Kyong Hwa Park Sook Whan Sung Li Liu Chang Hyun Kang Chung-Hsing Chen Jun Xu Peng Guan Wen Tan Chih-Liang Wang Alan Dart Loon Sihoe Ying Chen Yi Young Choi Jun Suk Kim Ho-Il Yoon Qiuyin Cai In Kyu Park Ping Xu Qincheng He Chih-Yi Chen Junjie Wu Wei-Yen Lim Kun-Chieh Chen John K C Chan Jihua Li Hongyan Chen Chong-Jen Yu Li Jin Joseph F Fraumeni Jie Liu Maria Teresa Landi Taiki Yamaji Yang Yang Belynda Hicks Kathleen Wyatt Shengchao A Li Hongxia Ma Bao Song Zhehai Wang Sensen Cheng Xuelian Li Yangwu Ren Motoki Iwasaki Junjie Zhu Gening Jiang Ke Fei Guoping Wu Li-Hsin Chien Fang-Yu Tsai Jinming Yu Victoria L Stevens Pan-Chyr Yang Dongxin Lin Kexin Chen Yi-Long Wu Keitaro Matsuo Nathaniel Rothman Kouya Shiraishi Hongbing Shen Stephen J Chanock Takashi Kohno Qing Lan Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA. Institute of Population Health Sciences National Health Research Institutes Zhunan Taiwan. Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD USA Saw Swee Hock School of Public Health National University of Singapore and National University Health System Singapore Singapore Department of Medicine Yong Loo Lin School of Medicine National University of Singapore and National University Health System Singapore Singapore. Department of Oncology School of Medicine Johns Hopkins University Baltimore MD USA Department of Biostatistics Johns Hopkins Bloomberg School of Public Health Baltimore MD USA. Department of Preventive Medicine Chonnam National University Medical School Gwangju Republic of Korea. Department of Pathology Queen Mary Hospital Hong Kong Hong Kong. Department of Preventive Medicine Seoul National University College of Medicine Seoul Republic of Korea. Epidemiology and Community Health Branch National Heart Lung and Blood Institute Bethesda MD USA. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Epidemiology and Population Health Albert Einstein College of Medicine New York USA. Department of Computational Biology St. Jude Children's Research Hospital Memphis TN USA. National Institute of Cancer Research National Health Research Institutes Zhunan Taiwan. Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai China State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Shanghai China. Department of Statistics & Research Institute of Natural Sciences Sookmyung Women's University Seoul 04310 Korea. Division of Epidemiology Department of Medicine Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center Nashville TN USA. Department of Environmental Health

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the epidermal growth factor receptor (EGFR) gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4,544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared to EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (OR=8.63, 95% CI:5.67, 13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (OR=3.50, 95% CI: 2.44, 5.00) (p-heterogeneity=3.66x10). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.

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Observation of Spectral Structures in the Flux of Cosmic-Ray Protons from 50 GeV to 60 TeV with the Calorimetric Electron Telescope on the International Space Station

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Physical Review Letters 2022年第10期129卷 101102-101102页

作者： O. Adriani Y. Akaike K. Asano Y. Asaoka E. Berti G. Bigongiari W. R. Binns M. Bongi P. Brogi A. Bruno J. H. Buckley N. Cannady G. Castellini C. Checchia M. L. Cherry G. Collazuol K. Ebisawa A. W. Ficklin H. Fuke S. Gonzi T. G. Guzik T. Hams K. Hibino M. Ichimura K. Ioka W. Ishizaki M. H. Israel K. Kasahara J. Kataoka R. Kataoka Y. Katayose C. Kato N. Kawanaka Y. Kawakubo K. Kobayashi K. Kohri H. S. Krawczynski J. F. Krizmanic P. Maestro P. S. Marrocchesi A. M. Messineo J. W. Mitchell S. Miyake A. A. Moiseev M. Mori N. Mori H. M. Motz K. Munakata S. Nakahira J. Nishimura G. A. de Nolfo S. Okuno J. F. Ormes S. Ozawa L. Pacini P. Papini B. F. Rauch S. B. Ricciarini K. Sakai T. Sakamoto M. Sasaki Y. Shimizu A. Shiomi P. Spillantini F. Stolzi S. Sugita A. Sulaj M. Takita T. Tamura T. Terasawa S. Torii Y. Tsunesada Y. Uchihori E. Vannuccini J. P. Wefel K. Yamaoka S. Yanagita A. Yoshida K. Yoshida W. V. Zober Department of Physics University of Florence Via Sansone 1—50019 Sesto Fiorentino Italy INFN Sezione di Florence Via Sansone 1—50019 Sesto Fiorentino Italy Waseda Research Institute for Science and Engineering Waseda University 17 Kikuicho Shinjuku Tokyo 162-0044 Japan JEM Utilization Center Human Spaceflight Technology Directorate Japan Aerospace Exploration Agency 2-1-1 Sengen Tsukuba Ibaraki 305-8505 Japan Institute for Cosmic Ray Research The University of Tokyo 5-1-5 Kashiwa-no-Ha Kashiwa Chiba 277-8582 Japan Department of Physical Sciences Earth and Environment University of Siena via Roma 56 53100 Siena Italy INFN Sezione di Pisa Polo Fibonacci Largo B. Pontecorvo 3—56127 Pisa Italy Department of Physics and McDonnell Center for the Space Sciences Washington University One Brookings Drive St. Louis Missouri 63130-4899 USA Heliospheric Physics Laboratory NASA/GSFC Greenbelt Maryland 20771 USA Center for Space Sciences and Technology University of Maryland Baltimore County 1000 Hilltop Circle Baltimore Maryland 21250 USA Astroparticle Physics Laboratory NASA/GSFC Greenbelt Maryland 20771 USA Center for Research and Exploration in Space Sciences and Technology NASA/GSFC Greenbelt Maryland 20771 USA Institute of Applied Physics (IFAC) National Research Council (CNR) Via Madonna del Piano 10 50019 Sesto Fiorentino Italy Department of Physics and Astronomy Louisiana State University 202 Nicholson Hall Baton Rouge Louisiana 70803 USA Department of Physics and Astronomy University of Padova Via Marzolo 8 35131 Padova Italy INFN Sezione di Padova Via Marzolo 8 35131 Padova Italy Institute of Space and Astronautical Science Japan Aerospace Exploration Agency 3-1-1 Yoshinodai Chuo Sagamihara Kanagawa 252-5210 Japan Kanagawa University 3-27-1 Rokkakubashi Kanagawa Yokohama Kanagawa 221-8686 Japan Faculty of Science and Technology Graduate School of Science and Technology Hirosaki University 3 Bunkyo Hirosaki Aomori 036-8561 Jap

A precise measurement of the cosmic-ray proton spectrum with the Calorimetric Electron Telescope (CALET) is presented in the energy interval from 50 GeV to 60 TeV, and the observation of a softening of the spectrum above 10 TeV is reported. The analysis is based on the data collected during ∼6.2 years of smooth operations aboard the International Space Station and covers a broader energy range with respect to the previous proton flux measurement by CALET, with an increase of the available statistics by a factor of ∼2.2. Above a few hundred GeV we confirm our previous observation of a progressive spectral hardening with a higher significance (more than 20 sigma). In the multi-TeV region we observe a second spectral feature with a softening around 10 TeV and a spectral index change from −2.6 to −2.9 consistently, within the errors, with the shape of the spectrum reported by DAMPE. We apply a simultaneous fit of the proton differential spectrum which well reproduces the gradual change of the spectral index encompassing the lower energy power-law regime and the two spectral features observed at higher energies.

关键词： Cosmic ray acceleration Cosmic ray composition & spectra Cosmic ray propagation Cosmic ray sources Cosmic rays & astroparticles

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