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Senolytics reduce coronavirus-related mortality in old mice 期刊论文
Science, 2021
作者:  Christina D. Camell;  Matthew J. Yousefzadeh;  Yi Zhu;  Larissa G. P. Langhi Prata;  Matthew A. Huggins;  Mark Pierson;  Lei Zhang;  Ryan D. O’Kelly;  Tamar Pirtskhalava;  Pengcheng Xun;  Keisuke Ejima;  Ailing Xue;  Utkarsh Tripathi;  Jair Machado Espindola-Netto;  Nino Giorgadze;  Elizabeth J. Atkinson;  Christina L. Inman;  Kurt O. Johnson;  Stephanie H. Cholensky;  Timothy W. Carlson;  Nathan K. LeBrasseur;  Sundeep Khosla;  M. Gerard O’Sullivan;  David B. Allison;  Stephen C. Jameson;  Alexander Meves;  Ming Li;  Y. S. Prakash;  Sergio E. Chiarella;  Sara E. Hamilton;  Tamara Tchkonia;  Laura J. Niedernhofer;  James L. Kirkland;  Paul D. Robbins
收藏  |  浏览/下载:15/0  |  提交时间:2021/07/27
Mapping out a future for ungulate migrations 期刊论文
Science, 2021
作者:  Matthew J. Kauffman;  Francesca Cagnacci;  Simon Chamaillé-Jammes;  Mark Hebblewhite;  J. Grant C. Hopcraft;  Jerod A. Merkle;  Thomas Mueller;  Atle Mysterud;  Wibke Peters;  Christiane Roettger;  Alethea Steingisser;  James E. Meacham;  Kasahun Abera;  Jan Adamczewski;  Ellen O. Aikens;  Hattie Bartlam-Brooks;  Emily Bennitt;  Joel Berger;  Charlotte Boyd;  Steeve D. Côté;  Lucie Debeffe;  Andrea S. Dekrout;  Nandintsetseg Dejid;  Emiliano Donadio;  Luthando Dziba;  William F. Fagan;  Claude Fischer;  Stefano Focardi;  John M. Fryxell;  Richard W. S. Fynn;  Chris Geremia;  Benito A. González;  Anne Gunn;  Elie Gurarie;  Marco Heurich;  Jodi Hilty;  Mark Hurley;  Aran Johnson;  Kyle Joly;  Petra Kaczensky;  Corinne J. Kendall;  Pavel Kochkarev;  Leonid Kolpaschikov;  Rafał Kowalczyk;  Frank van Langevelde;  Binbin V. Li;  Alex L. Lobora;  Anne Loison;  Tinaapi H. Madiri;  David Mallon;  Pascal Marchand;  Rodrigo A. Medellin;  Erling Meisingset;  Evelyn Merrill;  Arthur D. Middleton;  Kevin L. Monteith;  Malik Morjan;  Thomas A. Morrison;  Steffen Mumme;  Robin Naidoo;  Andres Novaro;  Joseph O. Ogutu;  Kirk A. Olson;  Alfred Oteng-Yeboah;  Ramiro J. A. Ovejero;  Norman Owen-Smith;  Antti Paasivaara;  Craig Packer;  Danila Panchenko;  Luca Pedrotti;  Andrew J. Plumptre;  Christer M. Rolandsen;  Sonia Said;  Albert Salemgareyev;  Aleksandr Savchenko;  Piotr Savchenko;  Hall Sawyer;  Moses Selebatso;  Matthew Skroch;  Erling Solberg;  Jared A. Stabach;  Olav Strand;  Michael J. Suitor;  Yasuyuki Tachiki;  Anne Trainor;  Arnold Tshipa;  Munir Z. Virani;  Carly Vynne;  Stephanie Ward;  George Wittemyer;  Wenjing Xu;  Steffen Zuther
收藏  |  浏览/下载:25/0  |  提交时间:2021/05/14
Combating ecosystem collapse from the tropics to the Antarctic 期刊论文
Global Change Biology, 2021
作者:  Dana M. Bergstrom;  Barbara C. Wienecke;  John van den Hoff;  Lesley Hughes;  David B. Lindenmayer;  Tracy D. Ainsworth;  Christopher M. Baker;  Lucie Bland;  David M. J. S. Bowman;  Shaun T. Brooks;  Josep G. Canadell;  Andrew J. Constable;  Katherine A. Dafforn;  Michael H. Depledge;  Catherine R. Dickson;  Norman C. Duke;  Kate J. Helmstedt;  André;  s Holz;  Craig R. Johnson;  Melodie A. McGeoch;  Jessica Melbourne‐;  Thomas;  Rachel Morgain;  Emily Nicholson;  Suzanne M. Prober;  Ben Raymond;  Euan G. Ritchie;  Sharon A. Robinson;  Katinka X. Ruthrof;  Samantha A. Setterfield;  Carla M. Sgrò;  Jonathan S. Stark;  Toby Travers;  Rowan Trebilco;  Delphi F. L. Ward;  Glenda M. Wardle;  Kristen J. Williams;  Phillip J. Zylstra;  Justine D. Shaw
收藏  |  浏览/下载:13/0  |  提交时间:2021/03/02
Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems 期刊论文
Science, 2021
作者:  Shahar Alon;  Daniel R. Goodwin;  Anubhav Sinha;  Asmamaw T. Wassie;  Fei Chen;  Evan R. Daugharthy;  Yosuke Bando;  Atsushi Kajita;  Andrew G. Xue;  Karl Marrett;  Robert Prior;  Yi Cui;  Andrew C. Payne;  Chun-Chen Yao;  Ho-Jun Suk;  Ru Wang;  Chih-Chieh Yu;  Paul Tillberg;  Paul Reginato;  Nikita Pak;  Songlei Liu;  Sukanya Punthambaker;  Eswar P. R. Iyer;  Richie E. Kohman;  Jeremy A. Miller;  Ed S. Lein;  Ana Lako;  Nicole Cullen;  Scott Rodig;  Karla Helvie;  Daniel L. Abravanel;  Nikhil Wagle;  Bruce E. Johnson;  Johanna Klughammer;  Michal Slyper;  Julia Waldman;  Judit Jané-Valbuena;  Orit Rozenblatt-Rosen;  Aviv Regev;  IMAXT Consortium19¶;  George M. Church;  Adam H. Marblestone;  Edward S. Boyden
收藏  |  浏览/下载:16/0  |  提交时间:2021/02/17
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms 期刊论文
Science, 2020
作者:  David E. Gordon;  Joseph Hiatt;  Mehdi Bouhaddou;  Veronica V. Rezelj;  Svenja Ulferts;  Hannes Braberg;  Alexander S. Jureka;  Kirsten Obernier;  Jeffrey Z. Guo;  Jyoti Batra;  Robyn M. Kaake;  Andrew R. Weckstein;  Tristan W. Owens;  Meghna Gupta;  Sergei Pourmal;  Erron W. Titus;  Merve Cakir;  Margaret Soucheray;  Michael McGregor;  Zeynep Cakir;  Gwendolyn Jang;  Matthew J. O’Meara;  Tia A. Tummino;  Ziyang Zhang;  Helene Foussard;  Ajda Rojc;  Yuan Zhou;  Dmitry Kuchenov;  Ruth Hüttenhain;  Jiewei Xu;  Manon Eckhardt;  Danielle L. Swaney;  Jacqueline M. Fabius;  Manisha Ummadi;  Beril Tutuncuoglu;  Ujjwal Rathore;  Maya Modak;  Paige Haas;  Kelsey M. Haas;  Zun Zar Chi Naing;  Ernst H. Pulido;  Ying Shi;  Inigo Barrio-Hernandez;  Danish Memon;  Eirini Petsalaki;  Alistair Dunham;  Miguel Correa Marrero;  David Burke;  Cassandra Koh;  Thomas Vallet;  Jesus A. Silvas;  Caleigh M. Azumaya;  Christian Billesbølle;  Axel F. Brilot;  Melody G. Campbell;  Amy Diallo;  Miles Sasha Dickinson;  Devan Diwanji;  Nadia Herrera;  Nick Hoppe;  Huong T. Kratochvil;  Yanxin Liu;  Gregory E. Merz;  Michelle Moritz;  Henry C. Nguyen;  Carlos Nowotny;  Cristina Puchades;  Alexandrea N. Rizo;  Ursula Schulze-Gahmen;  Amber M. Smith;  Ming Sun;  Iris D. Young;  Jianhua Zhao;  Daniel Asarnow;  Justin Biel;  Alisa Bowen;  Julian R. Braxton;  Jen Chen;  Cynthia M. Chio;  Un Seng Chio;  Ishan Deshpande;  Loan Doan;  Bryan Faust;  Sebastian Flores;  Mingliang Jin;  Kate Kim;  Victor L. Lam;  Fei Li;  Junrui Li;  Yen-Li Li;  Yang Li;  Xi Liu;  Megan Lo;  Kyle E. Lopez;  Arthur A. Melo;  Frank R. Moss;  Phuong Nguyen;  Joana Paulino;  Komal Ishwar Pawar;  Jessica K. Peters;  Thomas H. Pospiech;  Maliheh Safari;  Smriti Sangwan;  Kaitlin Schaefer;  Paul V. Thomas;  Aye C. Thwin;  Raphael Trenker;  Eric Tse;  Tsz Kin Martin Tsui;  Feng Wang;  Natalie Whitis;  Zanlin Yu;  Kaihua Zhang;  Yang Zhang;  Fengbo Zhou;  Daniel Saltzberg;  QCRG Structural Biology Consortium12†;  Anthony J. Hodder;  Amber S. Shun-Shion;  Daniel M. Williams;  Kris M. White;  Romel Rosales;  Thomas Kehrer;  Lisa Miorin;  Elena Moreno;  Arvind H. Patel;  Suzannah Rihn;  Mir M. Khalid;  Albert Vallejo-Gracia;  Parinaz Fozouni;  Camille R. Simoneau;  Theodore L. Roth;  David Wu;  Mohd Anisul Karim;  Maya Ghoussaini;  Ian Dunham;  Francesco Berardi;  Sebastian Weigang;  Maxime Chazal;  Jisoo Park;  James Logue;  Marisa McGrath;  Stuart Weston;  Robert Haupt;  C. James Hastie;  Matthew Elliott;  Fiona Brown;  Kerry A. Burness;  Elaine Reid;  Mark Dorward;  Clare Johnson;  Stuart G. Wilkinson;  Anna Geyer;  Daniel M. Giesel;  Carla Baillie;  Samantha Raggett;  Hannah Leech;  Rachel Toth;  Nicola Goodman;  Kathleen C. Keough;  Abigail L. Lind;  Zoonomia Consortium‡;  Reyna J. Klesh;  Kafi R. Hemphill;  Jared Carlson-Stevermer;  Jennifer Oki;  Kevin Holden;  Travis Maures;  Katherine S. Pollard;  Andrej Sali;  David A. Agard;  Yifan Cheng;  James S. Fraser;  Adam Frost;  Natalia Jura;  Tanja Kortemme;  Aashish Manglik;  Daniel R. Southworth;  Robert M. Stroud;  Dario R. Alessi;  Paul Davies;  Matthew B. Frieman;  Trey Ideker;  Carmen Abate;  Nolwenn Jouvenet;  Georg Kochs;  Brian Shoichet;  Melanie Ott;  Massimo Palmarini;  Kevan M. Shokat;  Adolfo García-Sastre;  Jeremy A. Rassen;  Robert Grosse;  Oren S. Rosenberg;  Kliment A. Verba;  Christopher F. Basler;  Marco Vignuzzi;  Andrew A. Peden;  Pedro Beltrao;  Nevan J. Krogan
收藏  |  浏览/下载:25/0  |  提交时间:2020/12/07
Ecological insights from three decades of animal movement tracking across a changing Arctic 期刊论文
Science, 2020
作者:  Sarah C. Davidson;  Gil Bohrer;  Eliezer Gurarie;  Scott LaPoint;  Peter J. Mahoney;  Natalie T. Boelman;  Jan U. H. Eitel;  Laura R. Prugh;  Lee A. Vierling;  Jyoti Jennewein;  Emma Grier;  Ophélie Couriot;  Allicia P. Kelly;  Arjan J. H. Meddens;  Ruth Y. Oliver;  Roland Kays;  Martin Wikelski;  Tomas Aarvak;  Joshua T. Ackerman;  José A. Alves;  Erin Bayne;  Bryan Bedrosian;  Jerrold L. Belant;  Andrew M. Berdahl;  Alicia M. Berlin;  Dominique Berteaux;  Joël Bêty;  Dmitrijs Boiko;  Travis L. Booms;  Bridget L. Borg;  Stan Boutin;  W. Sean Boyd;  Kane Brides;  Stephen Brown;  Victor N. Bulyuk;  Kurt K. Burnham;  David Cabot;  Michael Casazza;  Katherine Christie;  Erica H. Craig;  Shanti E. Davis;  Tracy Davison;  Dominic Demma;  Christopher R. DeSorbo;  Andrew Dixon;  Robert Domenech;  Götz Eichhorn;  Kyle Elliott;  Joseph R. Evenson;  Klaus-Michael Exo;  Steven H. Ferguson;  Wolfgang Fiedler;  Aaron Fisk;  Jérôme Fort;  Alastair Franke;  Mark R. Fuller;  Stefan Garthe;  Gilles Gauthier;  Grant Gilchrist;  Petr Glazov;  Carrie E. Gray;  David Grémillet;  Larry Griffin;  Michael T. Hallworth;  Autumn-Lynn Harrison;  Holly L. Hennin;  J. Mark Hipfner;  James Hodson;  James A. Johnson;  Kyle Joly;  Kimberly Jones;  Todd E. Katzner;  Jeff W. Kidd;  Elly C. Knight;  Michael N. Kochert;  Andrea Kölzsch;  Helmut Kruckenberg;  Benjamin J. Lagassé;  Sandra Lai;  Jean-François Lamarre;  Richard B. Lanctot;  Nicholas C. Larter;  A. David M. Latham;  Christopher J. Latty;  James P. Lawler;  Don-Jean Léandri-Breton;  Hansoo Lee;  Stephen B. Lewis;  Oliver P. Love;  Jesper Madsen;  Mark Maftei;  Mark L. Mallory;  Buck Mangipane;  Mikhail Y. Markovets;  Peter P. Marra;  Rebecca McGuire;  Carol L. McIntyre;  Emily A. McKinnon;  Tricia A. Miller;  Sander Moonen;  Tong Mu;  Gerhard J. D. M. Müskens;  Janet Ng;  Kerry L. Nicholson;  Ingar Jostein Øien;  Cory Overton;  Patricia A. Owen;  Allison Patterson;  Aevar Petersen;  Ivan Pokrovsky;  Luke L. Powell;  Rui Prieto;  Petra Quillfeldt;  Jennie Rausch;  Kelsey Russell;  Sarah T. Saalfeld;  Hans Schekkerman;  Joel A. Schmutz;  Philipp Schwemmer;  Dale R. Seip;  Adam Shreading;  Mónica A. Silva;  Brian W. Smith;  Fletcher Smith;  Jeff P. Smith;  Katherine R. S. Snell;  Aleksandr Sokolov;  Vasiliy Sokolov;  Diana V Solovyeva;  Mathew S. Sorum;  Grigori Tertitski;  J. F. Therrien;  Kasper Thorup;  T. Lee Tibbitts;  Ingrid Tulp;  Brian D. Uher-Koch;  Rob S. A. van Bemmelen;  Steven Van Wilgenburg;  Andrew L. Von Duyke;  Jesse L. Watson;  Bryan D. Watts;  Judy A. Williams;  Matthew T. Wilson;  James R. Wright;  Michael A. Yates;  David J. Yurkowski;  Ramūnas Žydelis;  Mark Hebblewhite
收藏  |  浏览/下载:19/0  |  提交时间:2020/11/09
Systemic racism in higher education 期刊论文
Science, 2020
作者:  Paul H. Barber;  Tyrone B. Hayes;  Tracy L. Johnson;  Leticia Márquez-Magaña;  10,234 signatories
收藏  |  浏览/下载:8/0  |  提交时间:2020/09/22
Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic 期刊论文
Science, 2020
作者:  Emily N. Chin;  Chenguang Yu;  Vincent F. Vartabedian;  Ying Jia;  Manoj Kumar;  Ana M. Gamo;  William Vernier;  Sabrina H. Ali;  Mildred Kissai;  Daniel C. Lazar;  Nhan Nguyen;  Laura E. Pereira;  Brent Benish;  Ashley K. Woods;  Sean B. Joseph;  Alan Chu;  Kristen A. Johnson;  Philipp N. Sander;  Francisco Martínez-Peña;  Eric N. Hampton;  Travis S. Young;  Dennis W. Wolan;  Arnab K. Chatterjee;  Peter G. Schultz;  H. Michael Petrassi;  John R. Teijaro;  Luke L. Lairson
收藏  |  浏览/下载:19/0  |  提交时间:2020/08/25
Pharmacologic fibroblast reprogramming into photoreceptors restores vision 期刊论文
NATURE, 2020, 581 (7806) : 83-+
作者:  Jiang, Mingkai;  Medlyn, Belinda E.;  Drake, John E.;  Duursma, Remko A.;  Anderson, Ian C.;  Barton, Craig V. M.;  Boer, Matthias M.;  Carrillo, Yolima;  Castaneda-Gomez, Laura;  Collins, Luke;  Crous, Kristine Y.;  De Kauwe, Martin G.;  dos Santos, Bruna M.;  Emmerson, Kathryn M.;  Facey, Sarah L.;  Gherlenda, Andrew N.;  Gimeno, Teresa E.;  Hasegawa, Shun;  Johnson, Scott N.;  Kannaste, Astrid;  Macdonald, Catriona A.;  Mahmud, Kashif;  Moore, Ben D.;  Nazaries, Loic;  Neilson, Elizabeth H. J.;  Nielsen, Uffe N.;  Niinemets, Ulo;  Noh, Nam Jin;  Ochoa-Hueso, Raul;  Pathare, Varsha S.;  Pendall, Elise;  Pihlblad, Johanna;  Pineiro, Juan;  Powell, Jeff R.;  Power, Sally A.;  Reich, Peter B.;  Renchon, Alexandre A.;  Riegler, Markus;  Rinnan, Riikka;  Rymer, Paul D.;  Salomon, Roberto L.;  Singh, Brajesh K.;  Smith, Benjamin;  Tjoelker, Mark G.;  Walker, Jennifer K. M.;  Wujeska-Klause, Agnieszka;  Yang, Jinyan;  Zaehle, Soenke;  Ellsworth, David S.
收藏  |  浏览/下载:46/0  |  提交时间:2020/07/03

Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision(1,2). Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss  however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-kappa B and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.


A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.


  
A giant exoplanet orbiting a very-low-mass star challenges planet formation models 期刊论文
SCIENCE, 2019, 365 (6460) : 1441-+
作者:  Morales, J. C.;  Mustill, A. J.;  Ribas, I.;  Davies, M. B.;  Reiners, A.;  Bauers, F. F.;  Kossakowski, D.;  Herrero, E.;  Rodriguez, E.;  Lopez-Gonzalez, M. J.;  Rodriguez-Lopez, C.;  Bejar, V. J. S.;  Gonzalez-Cuesta, L.;  Luque, R.;  Palle, E.;  Perger, M.;  Baroch, D.;  Johansen, A.;  Klahr, H.;  Mordasini, C.;  Anglada-Escude, G.;  Caballero, J. A.;  Cortes-Contreras, M.;  Dreizler, S.;  Lafarga, M.;  Nagel, E.;  Passegger, V. M.;  Reffert, S.;  Rosich, A.;  Schweitzer, A.;  Tal-Or, L.;  Trifonov, T.;  Zechmeister, M.;  Quirrenbach, A.;  Amado, P. J.;  Guenther, E. W.;  Hagen, H. -J.;  Henning, T.;  Jeffers, S. V.;  Kaminski, A.;  Kuester, M.;  Montes, D.;  Seifert, W.;  Abellan, F. J.;  Abril, M.;  Aceituno, J.;  Aceituno, F. J.;  Alonso-Floriano, F. J.;  Ammler-von Eiff, M.;  Antona, R.;  Arroyo-Torres, B.;  Azzaro, M.;  Barrado, D.;  Becerril-Jarque, S.;  Benitez, D.;  Berdinas, Z. M.;  Bergond, G.;  Brinkmoller, M.;  del Burgo, C.;  Burn, R.;  Calvo-Ortega, R.;  Cano, J.;  Cardenas, M. C.;  Cardona Guillen, C.;  Carro, J.;  Casa, E.;  Casanova, V.;  Casasayas-Barris, N.;  Chaturvedi, P.;  Cifuentes, C.;  Claret, A.;  Colome, J.;  Czesla, S.;  Diez-Alonso, E.;  Dorda, R.;  Emsenhuber, A.;  Fernandez, M.;  Fernandez-Martin, A.;  Ferro, I. M.;  Fuhrmeister, B.;  Galadi-Enriquez, D.;  Gallardo Cava, I.;  Garcia Vargas, M. L.;  Garcia-Piquer, A.;  Gesa, L.;  Gonzalez-Alvarez, E.;  Gonzalez Hernandez, J. I.;  Gonzalez-Peinado, R.;  Guardia, J.;  Guijarro, A.;  de Guindos, E.;  Hatzes, A. P.;  Hauschildt, P. H.;  Hedrosa, R. P.;  Hermelo, I.;  Hernandez Arabi, R.;  Hernandez Otero, F.;  Hintz, D.;  Holgado, G.;  Huber, A.;  Huke, P.;  Johnson, E. N.;  de Juan, E.;  Kehr, M.;  Kemmer, J.;  Kim, M.;  Klueter, J.;  Klutsch, A.;  Labarga, F.;  Labiche, N.;  Lalitha, S.;  Lampon, M.;  Lara, L. M.;  Launhardt, R.;  Lazaro, F. J.;  Lizon, J. -L.;  Llamas, M.;  Lodieu, N.;  Lopez del Fresno, M.;  Lopez Salas, . F.;  Lopez-Santiago, J.;  Magan Madinabeitia, H.;  Mall, U.;  Mancini, L.;  Mandel, H.;  Marfil, E.;  Marin Molina, J. . A.;  Martin, E. L.;  Martin-Fernandez, P.;  Martin-Ruiz, S.;  Martinez-Rodriguez, H.;  Marvin, C. J.;  Mirabet, E.;  Moya, A.;  Naranjo, V.;  Nelson, R. P.;  Nortmann, L.;  Nowak, G.;  Ofir, A.;  Pascua, J.;  Pavlov, A.;  Pedraz, S.;  Perez Medialdea, D.;  Perez-Calpena, A.;  Perryman, M. A. C.;  Rabaza, O.;  Ramon Ballesta, A.;  Rebolo, R.;  Redondo, P.;  Rix, H. -W.;  Rodler, F.;  Rodriguez Trinidad, A.;  Sabotta, S.;  Sadegi, S.;  Salz, M.;  Sanchez-Blanco, E.;  Sanchez Carrasco, M. A.;  Sanchez-Lopez, A.;  Sanz-Forcada, J.;  Sarkis, P.;  Sarmiento, L. F.;  Schafer, S.;  Schlecker, M.;  Schmitt, J. H. M. M.;  Schofer, P.;  Solano, E.;  Sota, A.;  Stahl, O.;  Stock, S.;  Stuber, T.;  Sturmer, J.;  Suarez, J. C.;  Tabernero, H. M.;  Tulloch, S. M.;  Veredas, G.;  Vico-Linares, J. I.;  Vilardell, F.;  Wagner, K.;  Winkler, J.;  Wolthoff, V.;  Yan, F.;  Zapatero Osorio, M. R.
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