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Cytokine 2013年第3期63卷 310-310页

作者： Elia D. Tait Wojno Mario Noti Brian S. Kim Mark C. Siracusa Paul R. Giacomin Meera G. Nair Alain J. Benitez Kathryn R. Ruymann Amanda B. Muir David A. Hill Kudakwashe R. Chikwava Amin E. Moghaddam Quentin J. Sattentau Aneesh Alex Chao Zhou Paul Menard-Katcher Masato Kubo Kazushige Obata-Ninomiya Hajime Karasuyama Michael R. Comeau David Artis Department of Microbiology University of Pennsylvania Philadelphia PA USA Institute for Immunology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Queensland Tropical Health Alliance and School of Public Health and Tropical Medicine James Cook University Cairns Australia Division of Gastroenterology Hepatology and Nutrition Children’s Hospital of Philadelphia Philadelphia PA USA Department of Pediatrics Division of Allergy and Immunology Children’s Hospital of Philadelphia Philadelphia PA USA Department of Pathology and Laboratory Medicine Children’s Hospital of Philadelphia Philadelphia PA USA The Sir William Dunn School of Pathology The University of Oxford Oxford UK Department of Electrical and Computer Engineering Lehigh University Bethlehem PA USA Center for Photonics and Nanoelectronics Lehigh University BethlehemPA USA Bioengineering Program Lehigh University Bethlehem PA USA Division of Gastroenterology Hospital of the University of Pennsylvania Philadelphia PA USA Laboratory for Signal Network Research Center for Allergy and Immunology RIKEN Yokohama Institute Yokohama Japan Division of Molecular Pathology Research Institute for Biological Science Tokyo University of Science Chiba Japan Department of Immune Regulation Tokyo Medical and Dental University Graduate School Tokyo Japan JST CREST Tokyo Medical and Dental University Graduate School Tokyo Japan Inflammation Research Amgen Inc. Seattle WA USA Department of Pathobiology School of Veterinary Medicine University of Pennsylvania Philadelphia PA USA

Eosinophilic esophagitis (EoE) is a food allergy-associated disease characterized by esophageal eosinophilia and associated inflammation. EoE has become increasingly common in industrialized countries. However, current management strategies, such as treatment with swallowed steroids and dietary restrictions, are nonspecific or negatively impact the quality of life of EoE patients. In addition, use of more specific therapies that target immunoglobulin E (IgE) and interleukin (IL)-5 have been largely unsuccessful in ameliorating EoE. Thus, there is an urgent need to identify novel, specific immunological pathways that underlie the pathogenesis of EoE that could be targeted to treat this disease. Recently, a genome-wide association study identified that EoE is associated with a gain-of-function polymorphism in the gene that encodes thymic stromal lymphopoietin (TSLP). TSLP is an IL-7 family member cytokine that promotes allergic inflammation by eliciting T helper type 2 cytokine responses, IgE production, and the expansion of a distinct population of basophils . However, whether TSLP directly promotes allergic inflammation in the esophagus and the mechanisms by which TSLP might contribute to the pathogenesis of EoE remain unknown. Here, we describe a new murine model of experimental EoE-like disease that was used to investigate the role of TSLP in allergic inflammation of the esophagus. Murine experimental EoE-like disease developed independently of IgE but was dependent on TSLP-elicited basophils. Critically, therapeutic antibody-mediated neutralization of TSLP or depletion of basophil populations ameliorated established EoE-like disease in mice. Finally, elevated TSLP levels and exaggerated basophil responses were observed in esophageal biopsies from EoE patients, and a gain-of-function polymorphism in TSLP correlated with increased basophil responses in patients with EoE. Together, these data indicate that TSLP-elicited basophil responses may play a key role in medi

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CORROSION RESISTANCE OF ALUMINUM ALLOY 5083 IN MARINE ENVIRONMENTS

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Journal of the American Society for Naval Engineers 1961年第3期73卷 545-547页

作者： AILOR, W.H. LINDBERG, R.I. William H. Ailor has been a member of the Chemical Metallurgy Section of the Metallurgical Research Division Reynolds Metals Company for six years. Educated in chemistry and chemical engineering at the University of Tampa Florida and North Carolina State College. He is Task Force chairman of the ASTM B-3/V1 1957 20-Year Test Program for the atmospheric corrosion of metals secretary of ASTM Committee B-3 and is a member of the Electrochemical Society and the National Association of Corrosion Engineers. He formerly taught diesel engineering at North Carolina State College. He is a lieutenant commander in the Naval Reserve. During World War II he served as engineering officer afloat and later as commanding officer of USS PC 616 and USS Belet (APD-109). Recalled to service in the Korean conflict he served 17 months as executive officer of the USS Robinson (DD 562). He is in the active reserve and formerly was commanding officer of Surface Division 6–42 in Jacksonville Fla. Currently he is training officer of MSTS Co. 5-1 in Richmond Va. R. I. Lindberg is a corrosion engineer in the engineering services department of Reynolds Metals Company. Author of several papers on corrosion in marine environments Mr. Lindberg is a member of the National Association of Corrosion Engineers. Prior to joining Reynolds in 1959 Mr. Lindberg was director of corrosion research for A. M. Byers Co. Pittsbugh Pa. Mr. Lindberg graduated from the University of Cincinnati in 1939 with B. S. and Ch. E. degrees. He took post graduate work at Purdue University receiving a Master of Science degree in 1942.

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Publisher Correction: PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape

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Nature immunology 2024年第6期25卷 1123页

作者： Noah Gamble Alexandra Bradu Jason A Caldwell Joshua McKeever Olubusayo Bolonduro Ebru Ermis Caroline Kaiser YeEun Kim Benjamin Parks Sandy Klemm William J Greenleaf Gerald R Crabtree Andrew S Koh Department of Pathology University of Chicago Chicago IL USA. Graduate Program in Biophysical Sciences University of Chicago Chicago IL USA. Committee on Molecular Metabolism and Nutrition University of Chicago Chicago IL USA. Committee on Genetics Genomics Systems Biology University of Chicago Chicago IL USA. Department of Human Genetics University of Chicago Chicago IL USA. Immunology Program Stanford University Stanford CA USA. Department of Genetics Stanford University Stanford CA USA. Department of Computer Science Stanford University Stanford CA USA. Department of Applied Physics Stanford University Stanford CA USA. Chan Zuckerberg Biohub San Francisco CA USA. Department of Pathology Stanford University Stanford CA USA. Department of Developmental Biology Stanford University Stanford CA USA. Department of Pathology University of Chicago Chicago IL USA. akoh@uchicago.edu. Institute for Biophysical Dynamics University of Chicago Chicago IL USA. akoh@uchicago.edu.

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Correction to: Evaluating the reach, effectiveness, adoption, implementation and maintenance of the Resistance Training for Teens program

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The international journal of behavioral nutrition and physical activity 2021年第1期18卷 154页

作者： Sarah G Kennedy Jordan J Smith Paul A Estabrooks Nicole Nathan Michael Noetel Philip J Morgan Jo Salmon Gessika C Dos Santos David R Lubans Priority Research Centre for Physical Activity and Nutrition School of Education University of Newcastle Callaghan NSW Australia. Department of Health Promotion University of Nebraska Medical Center Omaha NE USA. National Centre of Implementation Science University of Newcastle Callaghan NSW Australia. Hunter New England Population Health Hunter New England Area Health Service Newcastle NSW Australia. College of Health Medicine and Wellbeing The University of Newcastle Newcastle NSW Australia. Hunter Medical Research Institute New Lambton Heights NSW Australia. School of Health and Behavioural Sciences Australian Catholic University Sydney NSW Australia. Institute for Physical Activity and Nutrition (IPAN) Deakin University Geelong Australia. Post-Graduate Program in Physical Education Associate UEM/UEM State University of Londrina Londrina Brazil. Priority Research Centre for Physical Activity and Nutrition School of Education University of Newcastle Callaghan NSW Australia. david.lubans@newcastle.edu.au.

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Designing the Application of Security Text Messages Into Audio Files Using Data Encryption Standard (DES) Algorithms Using the End Of File (EOF) Method

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Journal of Physics: Conference Series 2019年第1期1363卷

作者： A M H Pardede Anggi Pramana Muhammad Zarlis Akbar Iskandar Rosida Tiurma Manurung S Sriadhi Citra Kurniawan Abdurrozzaq Hasibuan Nurintan Asyiah Siregar Ayu Esteka Sari Indrya Mulyaningsih Teguh Hidayat Iskandar Alam Ibrahim Tri Listyorini Edy Winarno Tulus STMIK Kaputama Binjai Sumatera Utara Indonesia Department of Computer Science Universitas Sumatera Utara Medan Indonesia Department of Informatics STMIK AKBA Makassar Indonesia Graduate Program in Scientific Psychology Universitas Kristen Maranatha Indonesia Department of Electrical Engineering Universitas Negeri Medan Indonesia Department of Electrical Engineering Sekolah Tinggi Teknik Malang Indonesia Faculty of Engineering Universitas Islam Sumatera Utara Medan Indonesia Department of Management STIE Labuhanbatu Sumatera Utara Indonesia Department of Management STIE Sakti Alam Kerinci Jambi Indonesia Department of Indonesian Language Teaching Institut Agama Islam Negeri Syekh Nurjati Cirebon Indonesia Department of Informatics Engineering Universitas Muhammadiyah Sorong Sorong Indonesia Department of English Education Universitas Muhammadiyah Sorong Sorong Indonesia Department of Informatics Universitas Muria Kudus Indonesia Faculty of Information Technology Universitas Stikubank Semarang Indonesia Department of Mathematics Universitas Sumatera Utara Medan Indonesia

There are several ways to deal with security issues of confidential data sent via the internet, including using cryptographic techniques and steganography. Steganography is the science and art of concealing information / messages in a media in such a way that its existence is not detected by other parties who are not entitled to the information. Instead, cryptography disguises the meaning of a message, but does not hide that there is a message because the file looks suspicious. The Steganography technique used here was End Of File (EOF). The EOF technique described how to add data or files at the end of the image file. For this technique, the size of data or files that will be hidden could be larger than the size of the image file. The hidden data will be inserted at the end of the file so that it will not affect the image. This steganography application is also equipped with a cryptographic function Data Encryption Standard (DES) at the time of insertion of data that functions as a generator code and encrypts data, so that the security of a data in the file is more protected and protected from those who are not entitled to know the data.

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Engineering chirality at wafer scale with ordered carbon nanotube architectures

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Nature communications 2023年第1期14卷 7380页

作者： Jacques Doumani Minhan Lou Oliver Dewey Nina Hong Jichao Fan Andrey Baydin Keshav Zahn Yohei Yomogida Kazuhiro Yanagi Matteo Pasquali Riichiro Saito Junichiro Kono Weilu Gao Department of Electrical and Computer Engineering Rice University Houston TX USA. Applied Physics Graduate Program Smalley-Curl Institute Rice University Houston TX USA. Department of Electrical and Computer Engineering The University of Utah Salt Lake City UT USA. Carbon Hub Rice University Houston TX USA. Department of Chemical and Biomolecular Engineering Rice University Houston TX USA. J.A. Woollam Co. Inc. Lincoln NE USA. Smalley-Curl Institute Rice University Houston TX USA. Department of Physics Tokyo Metropolitan University Tokyo Japan. Department of Chemistry Rice University Houston TX USA. Department of Materials Science and NanoEngineering Rice University Houston TX USA. Department of Physics Tohoku University Sendai Japan. Department of Physics National Taiwan Normal University Taipei Taiwan. Department of Physics and Astronomy Rice University Houston TX USA. Department of Electrical and Computer Engineering The University of Utah Salt Lake City UT USA. weilu.gao@utah.edu. Carbon Hub Rice University Houston TX USA. weilu.gao@utah.edu.

Creating artificial matter with controllable chirality in a simple and scalable manner brings new opportunities to diverse areas. Here we show two such methods based on controlled vacuum filtration - twist stacking and mechanical rotation - for fabricating wafer-scale chiral architectures of ordered carbon nanotubes (CNTs) with tunable and large circular dichroism (CD). By controlling the stacking angle and handedness in the twist-stacking approach, we maximize the CD response and achieve a high deep-ultraviolet ellipticity of 40 ± 1 mdeg nm. Our theoretical simulations using the transfer matrix method reproduce the experimentally observed CD spectra and further predict that an optimized film of twist-stacked CNTs can exhibit an ellipticity as high as 150 mdeg nm, corresponding to a g factor of 0.22. Furthermore, the mechanical rotation method not only accelerates the fabrication of twisted structures but also produces both chiralities simultaneously in a single sample, in a single run, and in a controllable manner. The created wafer-scale objects represent an alternative type of synthetic chiral matter consisting of ordered quantum wires whose macroscopic properties are governed by nanoscopic electronic signatures and can be used to explore chiral phenomena and develop chiral photonic and optoelectronic devices.

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The generation challenge programme platform: Semantic standards and workbench for crop science

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International Journal of Plant Genomics 2008年第1期2008卷 369601页

作者： Bruskiewich, Richard Senger, Martin Davenport, Guy Ruiz, Manuel Rouard, Mathieu Hazekamp, Tom Takeya, Masaru Doi, Koji Satoh, Kouji Costa, Marcos Simon, Reinhard Balaji, Jayashree Akintunde, Akinnola Mauleon, Ramil Wanchana, Samart Shah, Trushar Anacleto, Mylah Portugal, Arllet Ulat, Victor Jun Thongjuea, Supat Braak, Kyle Ritter, Sebastian Dereeper, Alexis Skofic, Milko Rojas, Edwin Martins, Natalia Pappas, Georgios Alamban, Ryan Almodiel, Roque Barboza, Lord Hendrix Detras, Jeffrey Manansala, Kevin Mendoza, Michael Jonathan Morales, Jeffrey Peralta, Barry Valerio, Rowena Zhang, Yi Gregorio, Sergio Hermocilla, Joseph Echavez, Michael Yap, Jan Michael Farmer, Andrew Schiltz, Gary Lee, Jennifer Casstevens, Terry Jaiswal, Pankaj Meintjes, Ayton Wilkinson, Mark Good, Benjamin Wagner, James Morris, Jane Marshall, David Collins, Anthony Kikuchi, Shoshi Metz, Thomas McLaren, Graham Van Hintum, Theo Crop Research Informatics Laboratory International Rice Research Institute (IRRI) DAPO Box 7777 Metro Manila Philippines Crop Research Informatics Laboratory International Maize and Wheat Improvement Center (CIMMYT) DF 06600 Mexico Apdo. Postal 6-641 Mexico Centre International de Recherche Agronomique Pour le Développement (CIRAD) 34398 Montpellier Cedex 5 Avenue Agropolis France Bioversity International 00057 Maccarese (Fiumicino) Rome Via dei Tre Denari 472/a Italy National Institute for Agrobiological Sciences (NIAS) Tsukuba Ibaraki 305-8602 Kannondai 2-1-2 Japan Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA) Brasilia DF 70770-900 Parque Estaçao Biologia Final W5 Norte Brazil Centro Internacional de la Papa (CIP) Lima 12 Avenida La Molina 1895 La Molina Peru International Crops Research Institute for the Semi-Arid Tropics Patancheru Andhra Pradesh 502324 India International Center for Agricultural Research in the Dry Areas Aleppo P.O. Box 5466 Syrian Arab Republic National Center for Genetic Engineering and Biotechnology 113 Thailand Science Park Klong Luang Pathumthani 12120 Phahonyothin Road Klong 1 Thailand Institute of Computer Science College of Arts and Sciences University of the Philippines Los Banos Laguna 4031 Philippines Department of Computer Science University of the Philippines Melchor Hall Diliman Quezon City 1101 Philippines National Center for Genome Resources Santa Fe NM 87505 2935 Rodeo Park Drive East United States Scottish Crop Research Institute Invergowrie Dundee DD2 5DA United Kingdom Department of Plant Breeding Cornell University Ithaca NY 14853 United States African Centre for Gene Technologies Lynnwood Ridge 0040 P.O. Box 75011 South Africa Department of Medical Genetics Faculty of Medicine University of British Columbia Vancouver BC V6T 1Z3 Canada School of Computing Science Simon Fraser Universtiy Burnaby BC V5A 1S6 8888 University Drive Canada Bioinformatics Graduate Program Genome Sciences Centre BC

The Generation Challenge programme (GCP) is a global crop research consortium directed toward crop improvement through the application of comparative biology and genetic resources characterization to plant breeding. A key consortium research activity is the development of a GCP crop bioinformatics platform to support GCP research. This platform includes the following: (i) shared, public platform-independent domain models, ontology, and data formats to enable interoperability of data and analysis flows within the platform;(ii) web service and registry technologies to identify, share, and integrate information across diverse, globally dispersed data sources, as well as to access high-performance computational (HPC) facilities for computationally intensive, high-throughput analyses of project data;(iii) platform-specific middleware reference implementations of the domain model integrating a suite of public (largely open-access/-source) databases and software tools into a workbench to facilitate biodiversity analysis, comparative analysis of crop genomic data, and plant breeding decision making.

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TOI-2458 b: A mini-Neptune consistent with in situ hot Jupiter formation

arXiv

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arXiv 2024年

作者： Šubjak, Jan Gandolfi, Davide Goffo, Elisa Rapetti, David Jankowski, Dawid Mizuki, Toshiyuki Dai, Fei Serrano, Luisa M. Wilson, Thomas G. Goździewski, Krzysztof Nowak, Grzegorz Jenkins, Jon M. Twicken, Joseph D. Winn, Joshua N. Bieryla, Allyson Ciardi, David R. Cochran, William D. Collins, Karen A. Deeg, Hans J. Garcia, Rafael A. Guenther, Eike W. Hatzes, Artie P. Kabath, Petr Korth, Judith Latham, David W. Livingston, John H. Lund, Michael B. Mathur, Savita Narita, Norio Orell-Miquel, Jaume Palle, Enric Persson, Carina M. Redfield, Seth Schwarz, Richard P. Watanabe, David Ziegler, Carl Astronomical Institute Czech Academy of Sciences Fričova 298 Ondřejov251 65 Czech Republic Center for Astrophysics | Harvard & Smithsonian 60 Garden Street CambridgeMA02138 United States Dipartimento di Fisica Universita degli Studi di Torino via Pietro Giuria 1 TorinoI-10125 Italy Thuringer Landessternwarte Tautenburg Sternwarte 5 Tautenburg07778 Germany NASA Ames Research Center Moffett FieldCA94035 United States Research Institute for Advanced Computer Science Universities Space Research Association WashingtonDC20024 United States Institute of Astronomy Faculty of Physics Astronomy and Informatics Nicolaus Copernicus University Grudziadzka 5 Toruń87-100 Poland Astrobiology Center of NINS 2-21-1 Osawa Mitaka Tokyo181-8588 Japan National Astronomical Observatory of Japan 2-21-2 Osawa Mitaka Tokyo181-8588 Japan Institute for Astronomy University of Hawai'i 2680 Woodlawn Drive HonoluluHI96822 United States Department of Physics University of Warwick Gibbet Hill Road CoventryCV4 7AL United Kingdom SETI Institute Mountain ViewCA94043 United States Department of Astrophysical Sciences Princeton University PrincetonNJ08544 United States NASA Exoplanet Science Institute-Caltech/IPAC PasadenaCA91125 United States McDonald Observatory The University of Texas AustinTX United States Center for Planetary Systems Habitability The University of Texas AustinTX United States C. Via Lactea S/N Tenerife La LagunaE-38205 Spain Dept. de Astrofisica Tenerife La LagunaE-38206 Spain Universite Paris-Saclay Universite Paris Cite CEA CNRS AIM Gif-sur-Yvette91191 France Lund Observatory Division of Astrophysics Department of Physics Lund University Box 118 Lund22100 Sweden Astronomical Science Program Graduate University for Advanced Studies SOKENDAI 2-21-1 Osawa Mitaka Tokyo181-8588 Japan Komaba Institute for Science The University of Tokyo 3-8-1 Komaba Meguro Tokyo153-8902 Japan Chalmers University of Technology Departmen

We report on the discovery and spectroscopic confirmation of TOI-2458 b, a transiting mini-Neptune around an F-type star leaving the mainsequence with a mass of M*= 1.05 ± 0.03Mo, a radius of R*= 1.31 ± 0.03 Ro, an effective temperature of Teff = 6005 ± 50 K, and a metallicity of -0.10 ± 0.05 dex. By combining TESS photometry with high-resolution spectra acquired with the HARPS spectrograph, we found that the transiting planet has an orbital period of ∼3.74 days, a mass of Mp = 13.31±0.99M⊕ and a radius of Rp = 2.83±0.20 R⊕. The host star TOI-2458 shows a short activity cycle of ∼54 days revealed in the HARPS S-index and Hα times series. We took the opportunity to investigate other F stars showing activity cycle periods comparable to that of TOI-2458 and found that they have shorter rotation periods than would be expected based on the gyrochronology predictions. In addition, we determined TOI-2458's stellar inclination angle to be i*= 10.6+13.3 -10.6 degrees. We discuss that both phenomena (fast stellar rotation and planet orbit inclination) could be explained by in situ formation of a hot Jupiter interior to TOI-2458 b. It is plausible that this hot Jupiter was recently engulfed by the star. Analysis of HARPS spectra has identified the presence of another planet with a period of P = 16.55 ± 0.06 days and a minimum mass of Mp sin i = 10.22 ± 1.90M⊕. Using dynamical stability analysis, we constrained the mass of this planet to the range Mc (10, 25)M⊕. © 2024, CC BY.

关键词： Stars

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ARCTIC TRAFFICABILITY program - A REVIEW

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NAVAL ENGINEERS JOURNAL 1984年第3期96卷 169-175页

作者： VOELKER, R GLEN, IF SEIBOLD, F BAYLY, I Richard Voelker:is Vice President of ARCTEC Incorporated a firm specializing in cold regions technology. He has been responsible for the management of thePolarClass Traffic-ability Program since its inception and annually participates in the field data collection in the Arctic. His prior experience includes positions with the U.S. Coast Guard in the icebreaker design project the Military Sealift Command and at Newport News Shipbuilding. He is a graduate of N. Y.S. Maritime College and has a MS degree from the University of Michigan. I.F. Glen:received his professional degrees in naval architecture from the Royal Naval Engineering College Manadon Plymouth and RN College Greenwich London entering the Royal Corps of Naval Constructors in 1967. After serving as a Constructor Lieutenant in the Royal Navy's Far East Fleet for a short period he joined the Polaris submarine project team in Bath England in 1968. In 1971 he was seconded to the Canadian Department of National Defense in Ottawa as a Constructor Lieutenant Commander under NATO exchange arrangements where he had responsibilities initially for conventional submarines and latterly for computer aided conceptual design. He ventured to Bath England in 1974 and joined Forward Design Group. In 1975 he took a position as a civilian engineer in the Canadian Defense Department and was Head of Hull Systems Engineering from 1977 to 1979. He joined ARCTEC CANADA LIMITED in 1980 and in addition to managing ice model testing projects and full scale trials has specialized in structural response of ships to ice impact. He headed ARCTEC's Kanata Laboratory from 1981 to 1983 when he was promoted to president. Frederick Seibold:is a research program manager with the Maritime Administration's Office of Advanced Ship Development and Technology. He is responsible for the marine science program which includes research in the areas of ship powering structures and propeller performance and Arctic technology. Mr. Seibold has been employed by Mar Ad since 1961 having hel

This paper describes a multiyear program to make an operational assessment on the feasibility of a year-round Arctic marine transportation system to serve Alaska. Specifically, the three objectives were to: collect meteorological and ice data along potential marine routes; instrument the hull and propulsion machinery to improve design critera for ice-worthy ships; and demonstrate that ships can operate in midwinter Alaskan Arctic ice conditions. The U.S. Coast Guard's Polar class icebreakers were used to make the operational assessment by annually extending the route northward and by operating throughout the winter season. This paper reviews some of the operational and technical achievements to date, as well as plans for future Arctic deployments.

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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries (vol 55, pg 89, 2023)

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NATURE GENETICS 2023年第3期55卷 519-520页

作者： Fernandez-Rozadilla, Ceres Timofeeva, Maria Chen, Zhishan Law, Philip Thomas, Minta Schmit, Stephanie Diez-Obrero, Virginia Hsu, Li Fernandez-Tajes, Juan Palles, Claire Sherwood, Kitty Briggs, Sarah Svinti, Victoria Donnelly, Kevin Farrington, Susan Blackmur, James Vaughan-Shaw, Peter Shu, Xiao-ou Long, Jirong Cai, Qiuyin Guo, Xingyi Lu, Yingchang Broderick, Peter Studd, James Huyghe, Jeroen Harrison, Tabitha Conti, David Dampier, Christopher Devall, Mathew Schumacher, Fredrick Melas, Marilena Rennert, Gad Obon-Santacana, Mireia Martin-Sanchez, Vicente Moratalla-Navarro, Ferran Oh, Jae Hwan Kim, Jeongseon Jee, Sun Ha Jung, Keum Ji Kweon, Sun-Seog Shin, Min-Ho Shin, Aesun Ahn, Yoon-Ok Kim, Dong-Hyun Oze, Isao Wen, Wanqing Matsuo, Keitaro Matsuda, Koichi Tanikawa, Chizu Ren, Zefang Gao, Yu-Tang Jia, Wei-Hua Hopper, John Jenkins, Mark Win, Aung Ko Pai, Rish Figueiredo, Jane Haile, Robert Gallinger, Steven Woods, Michael Newcomb, Polly Duggan, David Cheadle, Jeremy Kaplan, Richard Maughan, Timothy Kerr, Rachel Kerr, David Kirac, Iva Bohm, Jan Mecklin, Lukka-Pekka Jousilahti, Pekka Knekt, Paul Aaltonen, Lauri Rissanen, Harri Pukkala, Eero Eriksson, Johan Cajuso, Tatiana Hanninen, Ulrika Kondelin, Johanna Palin, Kimmo Tanskanen, Tomas Renkonen-Sinisalo, Laura Zanke, Brent Mannisto, Satu Albanes, Demetrius Weinstein, Stephanie Ruiz-Narvaez, Edward Palmer, Julie Buchanan, Daniel Platz, Elizabeth Visvanathan, Kala Ulrich, Cornelia Siegel, Erin Brezina, Stefanie Gsur, Andrea Campbell, Peter Chang-Claude, Jenny Hoffmeister, Michael Brenner, Hermann Slattery, Martha Potter, John Tsilidis, Konstantinos Schulze, Matthias Gunter, Marc Murphy, Neil Castells, Antoni Castellvi-Bel, Sergi Moreira, Leticia Arndt, Volker Shcherbina, Anna Stern, Mariana Pardamean, Bens Bishop, Timothy Giles, Graham Southey, Melissa Idos, Gregory McDonnell, Kevin Abu-Ful, Zomoroda Greenson, Joel Shulman, Katerina Lejbkowicz, Flavio Offit, Kenneth Su, Yu-Ru Steinfelder, Robert Keku, Temitope van Guelpen, Bethany Hudson, Thomas Hampel, Heather Pearlman, Edinburgh Cancer Research Centre Institute of Genomics and Cancer University of Edinburgh Edinburgh UK Genomic Medicine Group Instituto de Investigacion Sanitaria de Santiago Santiago de Compostela Spain Colon Cancer Genetics Group Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK Danish Institute for Advanced Study Department of Public Health University of Southern Denmark Odense Denmark Division of Epidemiology Department of Medicine Vanderbilt-Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University Medical Center Nashville TN USA Division of Genetics and Epidemiology Institute of Cancer Research London UK Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA Genomic Medicine Institute Cleveland Clinic Cleveland OH USA Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland OH USA Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute Barcelona Spain Oncology Data Analytics Program Catalan Institute of Oncology Barcelona Spain Consortium for Biomedical Research in Epidemiology and Public Health Madrid Madrid Spain Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain Department of Biostatistics School of Public Health University of Washington Seattle WA USA Institute of Cancer and Genomic Sciences College of Medical and Dental Sciences University of Birmingham Birmingham UK Department of Public Health Richard Doll Building University of Oxford Oxford UK Department of Biomedical Informatics Vanderbilt University School of Medicine Nashville TN USA Department of Preventive Medicine USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA Center for Public Health Genomics Department of Public Health Sciences University of Virginia Charlottesville VA USA Department of Populat

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

关键词： Colorectal cancer Epigenomics Genome-wide association studies Transcriptomics

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