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Guidelines for Modeling and Reporting Health Effects of Climate Change Mitigation Actions 期刊论文
Environmental Health Perspectives, 2020
作者:  Jeremy J. Hess;  Nikhil Ranadive;  Chris Boyer;  Lukasz Aleksandrowicz;  Susan C. Anenberg;  Kristin Aunan;  Kristine Belesova;  Michelle L. Bell;  Sam Bickersteth;  Kathryn Bowen;  Marci Burden;  Diarmid Campbell-Lendrum;  Elizabeth Carlton;  Guéladio Cissé;  Francois Cohen;  Hancheng Dai;  Alan David Dangour;  Purnamita Dasgupta;  Howard Frumkin;  Peng Gong;  Robert J. Gould;  Andy Haines;  Simon Hales;  Ian Hamilton;  Tomoko Hasegawa;  Masahiro Hashizume;  Yasushi Honda;  Daniel E. Horton;  Alexandra Karambelas;  Ho Kim;  Satbyul Estella Kim;  Patrick L. Kinney;  Inza Kone;  Kim Knowlton;  Jos Lelieveld;  Vijay S. Limaye;  Qiyong Liu;  Lina Madaniyazi;  Micaela Elvira Martinez;  Denise L. Mauzerall;  James Milner;  Tara Neville;  Mark Nieuwenhuijsen;  Shonali Pachauri;  Frederica Perera;  Helen Pineo;  Justin V. Remais;  Rebecca K. Saari;  Jon Sampedro;  Pauline Scheelbeek;  Joel Schwartz;  Drew Shindell;  Priya Shyamsundar;  Timothy J. Taylor;  Cathryn Tonne;  Detlef Van Vuuren;  Can Wang;  Nicholas Watts;  J. Jason West;  Paul Wilkinson;  Stephen A. Wood;  James Woodcock;  Alistair Woodward;  Yang Xie;  Ying Zhang;  Kristie L. Ebi
收藏  |  浏览/下载:17/0  |  提交时间:2020/11/20
Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I 期刊论文
NATURE, 2020, 581 (7806) : 100-+
作者:  Waszak, Sebastian M.;  Robinson, Giles W.;  Gudenas, Brian L.;  Smith, Kyle S.;  Forget, Antoine;  Kojic, Marija;  Garcia-Lopez, Jesus;  Hadley, Jennifer;  Hamilton, Kayla V.;  Indersie, Emilie;  Buchhalter, Ivo;  Kerssemakers, Jules;  Jager, Natalie;  Sharma, Tanvi;  Rausch, Tobias;  Kool, Marcel;  Sturm, Dominik;  Jones, David T. W.;  Vasilyeva, Aksana;  Tatevossian, Ruth G.;  Neale, Geoffrey;  Lombard, Berangere;  Loew, Damarys;  Nakitandwe, Joy;  Rusch, Michael;  Bowers, Daniel C.;  Bendel, Anne;  Partap, Sonia;  Chintagumpala, Murali;  Crawford, John;  Gottardo, Nicholas G.;  Smith, Amy;  Dufour, Christelle;  Rutkowski, Stefan;  Eggen, Tone;  Wesenberg, Finn;  Kjaerheim, Kristina;  Feychting, Maria;  Lannering, Birgitta;  Schuz, Joachim;  Johansen, Christoffer;  Andersen, Tina V.;  Roosli, Martin;  Kuehni, Claudia E.;  Grotzer, Michael;  Remke, Marc;  Puget, Stephanie;  Pajtler, Kristian W.;  Milde, Till;  Witt, Olaf;  Ryzhova, Marina;  Korshunov, Andrey;  Orr, Brent A.;  Ellison, David W.;  Brugieres, Laurence;  Lichter, Peter;  Nichols, Kim E.;  Gajjar, Amar;  Wainwright, Brandon J.;  Ayrault, Olivier;  Korbel, Jan O.;  Northcott, Paul A.;  Pfister, Stefan M.
收藏  |  浏览/下载:37/0  |  提交时间:2020/07/03

Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy(1-3). However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB4, mutations that cause loss of MHC-I are rarely found(5) despite the frequent downregulation of MHC-I expression(6-8). Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8(+) T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.


Inhibition of the autophagy-lysosome system upregulates surface expression of MHC class I proteins and enhances antigen presentation, and evokes a potent anti-tumour immune response that is mediated by CD8(+) T cells.


  
Electrical manipulation of a topological antiferromagnetic state 期刊论文
NATURE, 2020, 580 (7805) : 608-+
作者:  Chabon, Jacob J.;  Hamilton, Emily G.;  Kurtz, David M.;  Esfahani, Mohammad S.;  Moding, Everett J.;  Stehr, Henning;  Schroers-Martin, Joseph;  Nabet, Barzin Y.;  Chen, Binbin;  Chaudhuri, Aadel A.;  Liu, Chih Long;  Hui, Angela B.;  Jin, Michael C.;  Azad, Tej D.;  Almanza, Diego;  Jeon, Young-Jun;  Nesselbush, Monica C.;  Keh, Lyron Co Ting;  Bonilla, Rene F.;  Yoo, Christopher H.;  Ko, Ryan B.;  Chen, Emily L.;  Merriott, David J.;  Massion, Pierre P.;  Mansfield, Aaron S.;  Jen, Jin;  Ren, Hong Z.;  Lin, Steven H.;  Costantino, Christina L.;  Burr, Risa;  Tibshirani, Robert;  Gambhir, Sanjiv S.;  Berry, Gerald J.;  Jensen, Kristin C.;  West, Robert B.;  Neal, Joel W.;  Wakelee, Heather A.;  Loo, Billy W., Jr.;  Kunder, Christian A.;  Leung, Ann N.;  Lui, Natalie S.;  Berry, Mark F.;  Shrager, Joseph B.;  Nair, Viswam S.;  Haber, Daniel A.;  Sequist, Lecia V.;  Alizadeh, Ash A.;  Diehn, Maximilian
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

Room-temperature electrical switching of a topological antiferromagnetic state in polycrystalline Mn3Sn thin films is demonstrated using the same protocol as that used for conventional ferromagnetic metals.


Electrical manipulation of phenomena generated by nontrivial band topology is essential for the development of next-generation technology using topological protection. A Weyl semimetal is a three-dimensional gapless system that hosts Weyl fermions as low-energy quasiparticles(1-4). It has various exotic properties, such as a large anomalous Hall effect (AHE) and chiral anomaly, which are robust owing to the topologically protected Weyl nodes(1-16). To manipulate such phenomena, a magnetic version of Weyl semimetals would be useful for controlling the locations of Weyl nodes in the Brillouin zone. Moreover, electrical manipulation of antiferromagnetic Weyl metals would facilitate the use of antiferromagnetic spintronics to realize high-density devices with ultrafast operation(17,18). However, electrical control of a Weyl metal has not yet been reported. Here we demonstrate the electrical switching of a topological antiferromagnetic state and its detection by the AHE at room temperature in a polycrystalline thin film(19) of the antiferromagnetic Weyl metal Mn3Sn9,10,12,20, which exhibits zero-field AHE. Using bilayer devices composed of Mn3Sn and nonmagnetic metals, we find that an electrical current density of about 10(10) to 10(11) amperes per square metre induces magnetic switching in the nonmagnetic metals, with a large change in Hall voltage. In addition, the current polarity along the bias field and the sign of the spin Hall angle of the nonmagnetic metals-positive for Pt (ref. (21)), close to 0 for Cu and negative for W (ref. (22))-determines the sign of the Hall voltage. Notably, the electrical switching in the antiferromagnet is achieved with the same protocol as that used for ferromagnetic metals(23,24). Our results may lead to further scientific and technological advances in topological magnetism and antiferromagnetic spintronics.


  
Evaluation of global simulations of aerosol particle and cloud condensation nuclei number, with implications for cloud droplet formation 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2019, 19 (13) : 8591-8617
作者:  Fanourgakis, George S.;  Kanakidou, Maria;  Nenes, Athanasios;  Bauer, Susanne E.;  Bergman, Tommi;  Carslaw, Ken S.;  Grini, Alf;  Hamilton, Douglas S.;  Johnson, Jill S.;  Karydis, Vlassis A.;  Kirkevag, Alf;  Kodros, John K.;  Lohmann, Ulrike;  Luo, Gan;  Makkonen, Risto;  Matsui, Hitoshi;  Neubauer, David;  Pierce, Jeffrey R.;  Schmale, Julia;  Stier, Philip;  Tsigaridis, Kostas;  van Noije, Twan;  Wang, Hailong;  Watson-Parris, Duncan;  Westervelt, Daniel M.;  Yang, Yang;  Yoshioka, Masaru;  Daskalakis, Nikos;  Decesari, Stefano;  Gysel-Beer, Martin;  Kalivitis, Nikos;  Liu, Xiaohong;  Mahowald, Natalie M.;  Myriokefalitakis, Stelios;  Schrodner, Roland;  Sfakianaki, Maria;  Tsimpidi, Alexandra P.;  Wu, Mingxuan;  Yu, Fangqun
收藏  |  浏览/下载:20/0  |  提交时间:2019/11/27
Regeneration of fat cells from myofibroblasts during wound healing 期刊论文
SCIENCE, 2017, 355 (6326) : 748-+
作者:  Plikus, Maksim V.;  Guerrero-Juarez, Christian F.;  Ito, Mayumi;  Li, Yun Rose;  Dedhia, Priya H.;  Zheng, Ying;  Shao, Mengle;  Gay, Denise L.;  Ramos, Raul;  Hsi, Tsai-Ching;  Oh, Ji Won;  Wang, Xiaojie;  Ramirez, Amanda;  Konopelski, Sara E.;  Elzein, Arijh;  Wang, Anne;  Supapannachart, Rarinthip June;  Lee, Hye-Lim;  Lim, Chae Ho;  Nace, Arben;  Guo, Amy;  Treffeisen, Elsa;  Andl, Thomas;  Ramirez, Ricardo N.;  Murad, Rabi;  Offermanns, Stefan;  Metzger, Daniel;  Chambon, Pierre;  Widgerow, Alan D.;  Tuan, Tai-Lan;  Mortazavi, Ali;  Gupta, Rana K.;  Hamilton, Bruce A.;  Millar, Sarah E.;  Seale, Patrick;  Pear, Warren S.;  Lazar, Mitchell A.;  Cotsarelis, George
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
NATO's Northeastern Flank — Emerging Opportunities for Engagement: An Overview 科技报告
来源:Rand Corporation. 出版年: 2016
作者:  Christopher S. Chivvis;  Raphael S. Cohen;  Bryan Frederick;  Daniel S. Hamilton;  F. Stephen Larrabee;  Bonny Lin
收藏  |  浏览/下载:10/0  |  提交时间:2019/04/05
Finland  Russia  Sweden  Security Cooperation  Lithuania  Hungary  Estonia  Czech Republic  Slovakia  U.S.-European Relations  Poland  North Atlantic Treaty Organization  Peacekeeping and Stability Operations  Latvia  
Armed and Dangerous? UAVs and U.S. Security 科技报告
来源:Rand Corporation. 出版年: 2014
作者:  Lynn E. Davis;  Michael J. McNerney;  James S. Chow;  Thomas Hamilton;  Sarah Harting;  Daniel Byman
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/05
Global Security  RAND-initiated  Arms Proliferation and Control  Threat Assessment  United States  Unmanned Aerial Vehicles  Military Technology