TY - JOUR AB - In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field. AU - Klionsky, Daniel J. AU - Abdel-Aziz, Amal Kamal AU - Abdelfatah, Sara AU - Abdellatif, Mahmoud AU - Abdoli, Asghar AU - Abel, Steffen AU - Abeliovich, Hagai AU - Abildgaard, Marie H. AU - Abudu, Yakubu Princely AU - Acevedo-Arozena, Abraham AU - Adamopoulos, Iannis E. AU - Adeli, Khosrow AU - Adolph, Timon E. AU - Adornetto, Annagrazia AU - Aflaki, Elma AU - Agam, Galila AU - Agarwal, Anupam AU - Aggarwal, Bharat B. AU - Agnello, Maria AU - Agostinis, Patrizia AU - Agrewala, Javed N. AU - Agrotis, Alexander AU - Aguilar, Patricia V. AU - Ahmad, S. Tariq AU - Ahmed, Zubair M. AU - Ahumada-Castro, Ulises AU - Aits, Sonja AU - Aizawa, Shu AU - Akkoc, Yunus AU - Akoumianaki, Tonia AU - Akpinar, Hafize Aysin AU - Al-Abd, Ahmed M. AU - Al-Akra, Lina AU - Al-Gharaibeh, Abeer AU - Alaoui-Jamali, Moulay A. AU - Alberti, Simon AU - Alcocer-Gómez, Elísabet AU - Alessandri, Cristiano AU - Ali, Muhammad AU - Alim Al-Bari, M. Abdul AU - Aliwaini, Saeb AU - Alizadeh, Javad AU - Almacellas, Eugènia AU - Almasan, Alexandru AU - Alonso, Alicia AU - Alonso, Guillermo D. AU - Altan-Bonnet, Nihal AU - Altieri, Dario C. AU - Álvarez, Élida M.C. AU - Alves, Sara AU - Alves Da Costa, Cristine AU - Alzaharna, Mazen M. AU - Amadio, Marialaura AU - Amantini, Consuelo AU - Amaral, Cristina AU - Ambrosio, Susanna AU - Amer, Amal O. AU - Ammanathan, Veena AU - An, Zhenyi AU - Andersen, Stig U. AU - Andrabi, Shaida A. AU - Andrade-Silva, Magaiver AU - Andres, Allen M. AU - Angelini, Sabrina AU - Ann, David AU - Anozie, Uche C. AU - Ansari, Mohammad Y. AU - Antas, Pedro AU - Antebi, Adam AU - Antón, Zuriñe AU - Anwar, Tahira AU - Apetoh, Lionel AU - Apostolova, Nadezda AU - Araki, Toshiyuki AU - Araki, Yasuhiro AU - Arasaki, Kohei AU - Araújo, Wagner L. AU - Araya, Jun AU - Arden, Catherine AU - Arévalo, Maria Angeles AU - Arguelles, Sandro AU - Arias, Esperanza AU - Arikkath, Jyothi AU - Arimoto, Hirokazu AU - Ariosa, Aileen R. AU - Armstrong-James, Darius AU - Arnauné-Pelloquin, Laetitia AU - Aroca, Angeles AU - Arroyo, Daniela S. AU - Arsov, Ivica AU - Artero, Rubén AU - Asaro, Dalia Maria Lucia AU - Aschner, Michael AU - Ashrafizadeh, Milad AU - Ashur-Fabian, Osnat AU - Atanasov, Atanas G. AU - Au, Alicia K. AU - Auberger, Patrick AU - Auner, Holger W. AU - Aurelian, Laure AU - Autelli, Riccardo AU - Avagliano, Laura AU - Ávalos, Yenniffer AU - Aveic, Sanja AU - Aveleira, Célia Alexandra AU - Avin-Wittenberg, Tamar AU - Aydin, Yucel AU - Ayton, Scott AU - Ayyadevara, Srinivas AU - Azzopardi, Maria AU - Baba, Misuzu AU - Backer, Jonathan M. AU - Backues, Steven K. AU - Bae, Dong Hun AU - Bae, Ok Nam AU - Bae, Soo Han AU - Baehrecke, Eric H. AU - Baek, Ahruem AU - Baek, Seung Hoon AU - Baek, Sung Hee AU - Bagetta, Giacinto AU - Bagniewska-Zadworna, Agnieszka AU - Bai, Hua AU - Bai, Jie AU - Bai, Xiyuan AU - Bai, Yidong AU - Bairagi, Nandadulal AU - Baksi, Shounak AU - Balbi, Teresa AU - Baldari, Cosima T. AU - Balduini, Walter AU - Ballabio, Andrea AU - Ballester, Maria AU - Balazadeh, Salma AU - Balzan, Rena AU - Bandopadhyay, Rina AU - Banerjee, Sreeparna AU - Banerjee, Sulagna AU - Bánréti, Ágnes AU - Bao, Yan AU - Baptista, Mauricio S. AU - Baracca, Alessandra AU - Barbati, Cristiana AU - Bargiela, Ariadna AU - Barilà, Daniela AU - Barlow, Peter G. AU - Barmada, Sami J. AU - Barreiro, Esther AU - Barreto, George E. AU - Bartek, Jiri AU - Bartel, Bonnie AU - Bartolome, Alberto AU - Barve, Gaurav R. AU - Basagoudanavar, Suresh H. AU - Bassham, Diane C. AU - Bast, Robert C. AU - Basu, Alakananda AU - Batoko, Henri AU - Batten, Isabella AU - Baulieu, Etienne E. AU - Baumgarner, Bradley L. AU - Bayry, Jagadeesh AU - Beale, Rupert AU - Beau, Isabelle AU - Beaumatin, Florian AU - Bechara, Luiz R.G. AU - Beck, George R. AU - Beers, Michael F. AU - Begun, Jakob AU - Behrends, Christian AU - Behrens, Georg M.N. AU - Bei, Roberto AU - Bejarano, Eloy AU - Bel, Shai AU - Behl, Christian AU - Belaid, Amine AU - Belgareh-Touzé, Naïma AU - Bellarosa, Cristina AU - Belleudi, Francesca AU - Belló Pérez, Melissa AU - Bello-Morales, Raquel AU - Beltran, Jackeline Soares De Oliveira AU - Beltran, Sebastián AU - Benbrook, Doris Mangiaracina AU - Bendorius, Mykolas AU - Benitez, Bruno A. AU - Benito-Cuesta, Irene AU - Bensalem, Julien AU - Berchtold, Martin W. AU - Berezowska, Sabina AU - Bergamaschi, Daniele AU - Bergami, Matteo AU - Bergmann, Andreas AU - Berliocchi, Laura AU - Berlioz-Torrent, Clarisse AU - Bernard, Amélie AU - Berthoux, Lionel AU - Besirli, Cagri G. AU - Besteiro, Sebastien AU - Betin, Virginie M. AU - Beyaert, Rudi AU - Bezbradica, Jelena S. AU - Bhaskar, Kiran AU - Bhatia-Kissova, Ingrid AU - Bhattacharya, Resham AU - Bhattacharya, Sujoy AU - Bhattacharyya, Shalmoli AU - Bhuiyan, Md Shenuarin AU - Bhutia, Sujit Kumar AU - Bi, Lanrong AU - Bi, Xiaolin AU - Biden, Trevor J. AU - Bijian, Krikor AU - Billes, Viktor A. AU - Binart, Nadine AU - Bincoletto, Claudia AU - Birgisdottir, Asa B. AU - Bjorkoy, Geir AU - Blanco, Gonzalo AU - Blas-Garcia, Ana AU - Blasiak, Janusz AU - Blomgran, Robert AU - Blomgren, Klas AU - Blum, Janice S. AU - Boada-Romero, Emilio AU - Boban, Mirta AU - Boesze-Battaglia, Kathleen AU - Boeuf, Philippe AU - Boland, Barry AU - Bomont, Pascale AU - Bonaldo, Paolo AU - Bonam, Srinivasa Reddy AU - Bonfili, Laura AU - Bonifacino, Juan S. AU - Boone, Brian A. AU - Bootman, Martin D. AU - Bordi, Matteo AU - Borner, Christoph AU - Bornhauser, Beat C. AU - Borthakur, Gautam AU - Bosch, Jürgen AU - Bose, Santanu AU - Botana, Luis M. AU - Botas, Juan AU - Boulanger, Chantal M. AU - Boulton, Michael E. AU - Bourdenx, Mathieu AU - Bourgeois, Benjamin AU - Bourke, Nollaig M. AU - Bousquet, Guilhem AU - Boya, Patricia AU - Bozhkov, Peter V. AU - Bozi, Luiz H.M. AU - Bozkurt, Tolga O. AU - Brackney, Doug E. AU - Brandts, Christian H. AU - Braun, Ralf J. AU - Braus, Gerhard H. AU - Bravo-Sagua, Roberto AU - Bravo-San Pedro, José M. AU - Brest, Patrick AU - Bringer, Marie Agnès AU - Briones-Herrera, Alfredo AU - Broaddus, V. Courtney AU - Brodersen, Peter AU - Brodsky, Jeffrey L. AU - Brody, Steven L. AU - Bronson, Paola G. AU - Bronstein, Jeff M. AU - Brown, Carolyn N. AU - Brown, Rhoderick E. AU - Brum, Patricia C. AU - Brumell, John H. AU - Brunetti-Pierri, Nicola AU - Bruno, Daniele AU - Bryson-Richardson, Robert J. AU - Bucci, Cecilia AU - Buchrieser, Carmen AU - Bueno, Marta AU - Buitrago-Molina, Laura Elisa AU - Buraschi, Simone AU - Buch, Shilpa AU - Buchan, J. Ross AU - Buckingham, Erin M. AU - Budak, Hikmet AU - Budini, Mauricio AU - Bultynck, Geert AU - Burada, Florin AU - Burgoyne, Joseph R. AU - Burón, M. Isabel AU - Bustos, Victor AU - Büttner, Sabrina AU - Butturini, Elena AU - Byrd, Aaron AU - Cabas, Isabel AU - Cabrera-Benitez, Sandra AU - Cadwell, Ken AU - Cai, Jingjing AU - Cai, Lu AU - Cai, Qian AU - Cairó, Montserrat AU - Calbet, Jose A. AU - Caldwell, Guy A. AU - Caldwell, Kim A. AU - Call, Jarrod A. AU - Calvani, Riccardo AU - Calvo, Ana C. AU - Calvo-Rubio Barrera, Miguel AU - Camara, Niels O.S. AU - Camonis, Jacques H. AU - Camougrand, Nadine AU - Campanella, Michelangelo AU - Campbell, Edward M. AU - Campbell-Valois, François Xavier AU - Campello, Silvia AU - Campesi, Ilaria AU - Campos, Juliane C. AU - Camuzard, Olivier AU - Cancino, Jorge AU - Candido De Almeida, Danilo AU - Canesi, Laura AU - Caniggia, Isabella AU - Canonico, Barbara AU - Cantí, Carles AU - Cao, Bin AU - Caraglia, Michele AU - Caramés, Beatriz AU - Carchman, Evie H. AU - Cardenal-Muñoz, Elena AU - Cardenas, Cesar AU - Cardenas, Luis AU - Cardoso, Sandra M. AU - Carew, Jennifer S. AU - Carle, Georges F. AU - Carleton, Gillian AU - Carloni, Silvia AU - Carmona-Gutierrez, Didac AU - Carneiro, Leticia A. AU - Carnevali, Oliana AU - Carosi, Julian M. AU - Carra, Serena AU - Carrier, Alice AU - Carrier, Lucie AU - Carroll, Bernadette AU - Carter, A. Brent AU - Carvalho, Andreia Neves AU - Casanova, Magali AU - Casas, Caty AU - Casas, Josefina AU - Cassioli, Chiara AU - Castillo, Eliseo F. AU - Castillo, Karen AU - Castillo-Lluva, Sonia AU - Castoldi, Francesca AU - Castori, Marco AU - Castro, Ariel F. AU - Castro-Caldas, Margarida AU - Castro-Hernandez, Javier AU - Castro-Obregon, Susana AU - Catz, Sergio D. AU - Cavadas, Claudia AU - Cavaliere, Federica AU - Cavallini, Gabriella AU - Cavinato, Maria AU - Cayuela, Maria L. AU - Cebollada Rica, Paula AU - Cecarini, Valentina AU - Cecconi, Francesco AU - Cechowska-Pasko, Marzanna AU - Cenci, Simone AU - Ceperuelo-Mallafré, Victòria AU - Cerqueira, João J. AU - Cerutti, Janete M. AU - Cervia, Davide AU - Cetintas, Vildan Bozok AU - Cetrullo, Silvia AU - Chae, Han Jung AU - Chagin, Andrei S. AU - Chai, Chee Yin AU - Chakrabarti, Gopal AU - Chakrabarti, Oishee AU - Chakraborty, Tapas AU - Chakraborty, Trinad AU - Chami, Mounia AU - Chamilos, Georgios AU - Chan, David W. AU - Chan, Edmond Y.W. AU - Chan, Edward D. AU - Chan, H. Y.Edwin AU - Chan, Helen H. AU - Chan, Hung AU - Chan, Matthew T.V. AU - Chan, Yau Sang AU - Chandra, Partha K. AU - Chang, Chih Peng AU - Chang, Chunmei AU - Chang, Hao Chun AU - Chang, Kai AU - Chao, Jie AU - Chapman, Tracey AU - Charlet-Berguerand, Nicolas AU - Chatterjee, Samrat AU - Chaube, Shail K. AU - Chaudhary, Anu AU - Chauhan, Santosh AU - Chaum, Edward AU - Checler, Frédéric AU - Cheetham, Michael E. AU - Chen, Chang Shi AU - Chen, Guang Chao AU - Chen, Jian Fu AU - Chen, Liam L. AU - Chen, Leilei AU - Chen, Lin AU - Chen, Mingliang AU - Chen, Mu Kuan AU - Chen, Ning AU - Chen, Quan AU - Chen, Ruey Hwa AU - Chen, Shi AU - Chen, Wei AU - Chen, Weiqiang AU - Chen, Xin Ming AU - Chen, Xiong Wen AU - Chen, Xu AU - Chen, Yan AU - Chen, Ye Guang AU - Chen, Yingyu AU - Chen, Yongqiang AU - Chen, Yu Jen AU - Chen, Yue Qin AU - Chen, Zhefan Stephen AU - Chen, Zhi AU - Chen, Zhi Hua AU - Chen, Zhijian J. AU - Chen, Zhixiang AU - Cheng, Hanhua AU - Cheng, Jun AU - Cheng, Shi Yuan AU - Cheng, Wei AU - Cheng, Xiaodong AU - Cheng, Xiu Tang AU - Cheng, Yiyun AU - Cheng, Zhiyong AU - Chen, Zhong AU - Cheong, Heesun AU - Cheong, Jit Kong AU - Chernyak, Boris V. AU - Cherry, Sara AU - Cheung, Chi Fai Randy AU - Cheung, Chun Hei Antonio AU - Cheung, King Ho AU - Chevet, Eric AU - Chi, Richard J. AU - Chiang, Alan Kwok Shing AU - Chiaradonna, Ferdinando AU - Chiarelli, Roberto AU - Chiariello, Mario AU - Chica, Nathalia AU - Chiocca, Susanna AU - Chiong, Mario AU - Chiou, Shih Hwa AU - Chiramel, Abhilash I. AU - Chiurchiù, Valerio AU - Cho, Dong Hyung AU - Choe, Seong Kyu AU - Choi, Augustine M.K. AU - Choi, Mary E. AU - Choudhury, Kamalika Roy AU - Chow, Norman S. AU - Chu, Charleen T. AU - Chua, Jason P. AU - Chua, John Jia En AU - Chung, Hyewon AU - Chung, Kin Pan AU - Chung, Seockhoon AU - Chung, So Hyang AU - Chung, Yuen Li AU - Cianfanelli, Valentina AU - Ciechomska, Iwona A. AU - Cifuentes, Mariana AU - Cinque, Laura AU - Cirak, Sebahattin AU - Cirone, Mara AU - Clague, Michael J. AU - Clarke, Robert AU - Clementi, Emilio AU - Coccia, Eliana M. AU - Codogno, Patrice AU - Cohen, Ehud AU - Cohen, Mickael M. AU - Colasanti, Tania AU - Colasuonno, Fiorella AU - Colbert, Robert A. AU - Colell, Anna AU - Čolić, Miodrag AU - Coll, Nuria S. AU - Collins, Mark O. AU - Colombo, María I. AU - Colón-Ramos, Daniel A. AU - Combaret, Lydie AU - Comincini, Sergio AU - Cominetti, Márcia R. AU - Consiglio, Antonella AU - Conte, Andrea AU - Conti, Fabrizio AU - Contu, Viorica Raluca AU - Cookson, Mark R. AU - Coombs, Kevin M. AU - Coppens, Isabelle AU - Corasaniti, Maria Tiziana AU - Corkery, Dale P. AU - Cordes, Nils AU - Cortese, Katia AU - Costa, Maria Do Carmo AU - Costantino, Sarah AU - Costelli, Paola AU - Coto-Montes, Ana AU - Crack, Peter J. AU - Crespo, Jose L. AU - Criollo, Alfredo AU - Crippa, Valeria AU - Cristofani, Riccardo AU - Csizmadia, Tamas AU - Cuadrado, Antonio AU - Cui, Bing AU - Cui, Jun AU - Cui, Yixian AU - Cui, Yong AU - Culetto, Emmanuel AU - Cumino, Andrea C. AU - Cybulsky, Andrey V. AU - Czaja, Mark J. AU - Czuczwar, Stanislaw J. AU - D’Adamo, Stefania AU - D’Amelio, Marcello AU - D’Arcangelo, Daniela AU - D’Lugos, Andrew C. AU - D’Orazi, Gabriella AU - Da Silva, James A. AU - Dafsari, Hormos Salimi AU - Dagda, Ruben K. AU - Dagdas, Yasin AU - Daglia, Maria AU - Dai, Xiaoxia AU - Dai, Yun AU - Dai, Yuyuan AU - Dal Col, Jessica AU - Dalhaimer, Paul AU - Dalla Valle, Luisa AU - Dallenga, Tobias AU - Dalmasso, Guillaume AU - Damme, Markus AU - Dando, Ilaria AU - Dantuma, Nico P. AU - Darling, April L. AU - Das, Hiranmoy AU - Dasarathy, Srinivasan AU - Dasari, Santosh K. AU - Dash, Srikanta AU - Daumke, Oliver AU - Dauphinee, Adrian N. AU - Davies, Jeffrey S. AU - Dávila, Valeria A. AU - Davis, Roger J. AU - Davis, Tanja AU - Dayalan Naidu, Sharadha AU - De Amicis, Francesca AU - De Bosscher, Karolien AU - De Felice, Francesca AU - De Franceschi, Lucia AU - De Leonibus, Chiara AU - De Mattos Barbosa, Mayara G. AU - De Meyer, Guido R.Y. AU - De Milito, Angelo AU - De Nunzio, Cosimo AU - De Palma, Clara AU - De Santi, Mauro AU - De Virgilio, Claudio AU - De Zio, Daniela AU - Debnath, Jayanta AU - Debosch, Brian J. AU - Decuypere, Jean Paul AU - Deehan, Mark A. AU - Deflorian, Gianluca AU - Degregori, James AU - Dehay, Benjamin AU - Del Rio, Gabriel AU - Delaney, Joe R. AU - Delbridge, Lea M.D. AU - Delorme-Axford, Elizabeth AU - Delpino, M. Victoria AU - Demarchi, Francesca AU - Dembitz, Vilma AU - Demers, Nicholas D. AU - Deng, Hongbin AU - Deng, Zhiqiang AU - Dengjel, Joern AU - Dent, Paul AU - Denton, Donna AU - Depamphilis, Melvin L. AU - Der, Channing J. AU - Deretic, Vojo AU - Descoteaux, Albert AU - Devis, Laura AU - Devkota, Sushil AU - Devuyst, Olivier AU - Dewson, Grant AU - Dharmasivam, Mahendiran AU - Dhiman, Rohan AU - Di Bernardo, Diego AU - Di Cristina, Manlio AU - Di Domenico, Fabio AU - Di Fazio, Pietro AU - Di Fonzo, Alessio AU - Di Guardo, Giovanni AU - Di Guglielmo, Gianni M. AU - Di Leo, Luca AU - Di Malta, Chiara AU - Di Nardo, Alessia AU - Di Rienzo, Martina AU - Di Sano, Federica AU - Diallinas, George AU - Diao, Jiajie AU - Diaz-Araya, Guillermo AU - Díaz-Laviada, Inés AU - Dickinson, Jared M. AU - Diederich, Marc AU - Dieudé, Mélanie AU - Dikic, Ivan AU - Ding, Shiping AU - Ding, Wen Xing AU - Dini, Luciana AU - Dinić, Jelena AU - Dinic, Miroslav AU - Dinkova-Kostova, Albena T. AU - Dionne, Marc S. AU - Distler, Jörg H.W. AU - Diwan, Abhinav AU - Dixon, Ian M.C. AU - Djavaheri-Mergny, Mojgan AU - Dobrinski, Ina AU - Dobrovinskaya, Oxana AU - Dobrowolski, Radek AU - Dobson, Renwick C.J. AU - Đokić, Jelena AU - Dokmeci Emre, Serap AU - Donadelli, Massimo AU - Dong, Bo AU - Dong, Xiaonan AU - Dong, Zhiwu AU - Dorn, Gerald W. AU - Dotsch, Volker AU - Dou, Huan AU - Dou, Juan AU - Dowaidar, Moataz AU - Dridi, Sami AU - Drucker, Liat AU - Du, Ailian AU - Du, Caigan AU - Du, Guangwei AU - Du, Hai Ning AU - Du, Li Lin AU - Du Toit, André AU - Duan, Shao Bin AU - Duan, Xiaoqiong AU - Duarte, Sónia P. AU - Dubrovska, Anna AU - Dunlop, Elaine A. AU - Dupont, Nicolas AU - Durán, Raúl V. AU - Dwarakanath, Bilikere S. AU - Dyshlovoy, Sergey A. AU - Ebrahimi-Fakhari, Darius AU - Eckhart, Leopold AU - Edelstein, Charles L. AU - Efferth, Thomas AU - Eftekharpour, Eftekhar AU - Eichinger, Ludwig AU - Eid, Nabil AU - Eisenberg, Tobias AU - Eissa, N. Tony AU - Eissa, Sanaa AU - Ejarque, Miriam AU - El Andaloussi, Abdeljabar AU - El-Hage, Nazira AU - El-Naggar, Shahenda AU - Eleuteri, Anna Maria AU - El-Shafey, Eman S. AU - Elgendy, Mohamed AU - Eliopoulos, Aristides G. AU - Elizalde, María M. AU - Elks, Philip M. AU - Elsasser, Hans Peter AU - Elsherbiny, Eslam S. AU - Emerling, Brooke M. AU - Emre, N. C.Tolga AU - Eng, Christina H. AU - Engedal, Nikolai AU - Engelbrecht, Anna Mart AU - Engelsen, Agnete S.T. AU - Enserink, Jorrit M. AU - Escalante, Ricardo AU - Esclatine, Audrey AU - Escobar-Henriques, Mafalda AU - Eskelinen, Eeva Liisa AU - Espert, Lucile AU - Eusebio, Makandjou Ola AU - Fabrias, Gemma AU - Fabrizi, Cinzia AU - Facchiano, Antonio AU - Facchiano, Francesco AU - Fadeel, Bengt AU - Fader, Claudio AU - Faesen, Alex C. AU - Fairlie, W. Douglas AU - Falcó, Alberto AU - Falkenburger, Bjorn H. AU - Fan, Daping AU - Fan, Jie AU - Fan, Yanbo AU - Fang, Evandro F. AU - Fang, Yanshan AU - Fang, Yognqi AU - Fanto, Manolis AU - Farfel-Becker, Tamar AU - Faure, Mathias AU - Fazeli, Gholamreza AU - Fedele, Anthony O. AU - Feldman, Arthur M. AU - Feng, Du AU - Feng, Jiachun AU - Feng, Lifeng AU - Feng, Yibin AU - Feng, Yuchen AU - Feng, Wei AU - Fenz Araujo, Thais AU - Ferguson, Thomas A. AU - Fernández, Álvaro F. AU - Fernandez-Checa, Jose C. AU - Fernández-Veledo, Sonia AU - Fernie, Alisdair R. AU - Ferrante, Anthony W. AU - Ferraresi, Alessandra AU - Ferrari, Merari F. AU - Ferreira, Julio C.B. AU - Ferro-Novick, Susan AU - Figueras, Antonio AU - Filadi, Riccardo AU - Filigheddu, Nicoletta AU - Filippi-Chiela, Eduardo AU - Filomeni, Giuseppe AU - Fimia, Gian Maria AU - Fineschi, Vittorio AU - Finetti, Francesca AU - Finkbeiner, Steven AU - Fisher, Edward A. AU - Fisher, Paul B. AU - Flamigni, Flavio AU - Fliesler, Steven J. AU - Flo, Trude H. AU - Florance, Ida AU - Florey, Oliver AU - Florio, Tullio AU - Fodor, Erika AU - Follo, Carlo AU - Fon, Edward A. AU - Forlino, Antonella AU - Fornai, Francesco AU - Fortini, Paola AU - Fracassi, Anna AU - Fraldi, Alessandro AU - Franco, Brunella AU - Franco, Rodrigo AU - Franconi, Flavia AU - Frankel, Lisa B. AU - Friedman, Scott L. AU - Fröhlich, Leopold F. AU - Frühbeck, Gema AU - Fuentes, Jose M. AU - Fujiki, Yukio AU - Fujita, Naonobu AU - Fujiwara, Yuuki AU - Fukuda, Mitsunori AU - Fulda, Simone AU - Furic, Luc AU - Furuya, Norihiko AU - Fusco, Carmela AU - Gack, Michaela U. AU - Gaffke, Lidia AU - Galadari, Sehamuddin AU - Galasso, Alessia AU - Galindo, Maria F. AU - Gallolu Kankanamalage, Sachith AU - Galluzzi, Lorenzo AU - Galy, Vincent AU - Gammoh, Noor AU - Gan, Boyi AU - Ganley, Ian G. AU - Gao, Feng AU - Gao, Hui AU - Gao, Minghui AU - Gao, Ping AU - Gao, Shou Jiang AU - Gao, Wentao AU - Gao, Xiaobo AU - Garcera, Ana AU - Garcia, Maria Noé AU - Garcia, Verónica E. AU - García-Del Portillo, Francisco AU - Garcia-Escudero, Vega AU - Garcia-Garcia, Aracely AU - Garcia-Macia, Marina AU - García-Moreno, Diana AU - Garcia-Ruiz, Carmen AU - García-Sanz, Patricia AU - Garg, Abhishek D. AU - Gargini, Ricardo AU - Garofalo, Tina AU - Garry, Robert F. AU - Gassen, Nils C. AU - Gatica, Damian AU - Ge, Liang AU - Ge, Wanzhong AU - Geiss-Friedlander, Ruth AU - Gelfi, Cecilia AU - Genschik, Pascal AU - Gentle, Ian E. AU - Gerbino, Valeria AU - Gerhardt, Christoph AU - Germain, Kyla AU - Germain, Marc AU - Gewirtz, David A. AU - Ghasemipour Afshar, Elham AU - Ghavami, Saeid AU - Ghigo, Alessandra AU - Ghosh, Manosij AU - Giamas, Georgios AU - Giampietri, Claudia AU - Giatromanolaki, Alexandra AU - Gibson, Gary E. AU - Gibson, Spencer B. AU - Ginet, Vanessa AU - Giniger, Edward AU - Giorgi, Carlotta AU - Girao, Henrique AU - Girardin, Stephen E. AU - Giridharan, Mridhula AU - Giuliano, Sandy AU - Giulivi, Cecilia AU - Giuriato, Sylvie AU - Giustiniani, Julien AU - Gluschko, Alexander AU - Goder, Veit AU - Goginashvili, Alexander AU - Golab, Jakub AU - Goldstone, David C. AU - Golebiewska, Anna AU - Gomes, Luciana R. AU - Gomez, Rodrigo AU - Gómez-Sánchez, Rubén AU - Gomez-Puerto, Maria Catalina AU - Gomez-Sintes, Raquel AU - Gong, Qingqiu AU - Goni, Felix M. AU - González-Gallego, Javier AU - Gonzalez-Hernandez, Tomas AU - Gonzalez-Polo, Rosa A. AU - Gonzalez-Reyes, Jose A. AU - González-Rodríguez, Patricia AU - Goping, Ing Swie AU - Gorbatyuk, Marina S. AU - Gorbunov, Nikolai V. AU - Görgülü, Kıvanç AU - Gorojod, Roxana M. AU - Gorski, Sharon M. AU - Goruppi, Sandro AU - Gotor, Cecilia AU - Gottlieb, Roberta A. AU - Gozes, Illana AU - Gozuacik, Devrim AU - Graef, Martin AU - Gräler, Markus H. AU - Granatiero, Veronica AU - Grasso, Daniel AU - Gray, Joshua P. AU - Green, Douglas R. AU - Greenhough, Alexander AU - Gregory, Stephen L. AU - Griffin, Edward F. AU - Grinstaff, Mark W. AU - Gros, Frederic AU - Grose, Charles AU - Gross, Angelina S. AU - Gruber, Florian AU - Grumati, Paolo AU - Grune, Tilman AU - Gu, Xueyan AU - Guan, Jun Lin AU - Guardia, Carlos M. AU - Guda, Kishore AU - Guerra, Flora AU - Guerri, Consuelo AU - Guha, Prasun AU - Guillén, Carlos AU - Gujar, Shashi AU - Gukovskaya, Anna AU - Gukovsky, Ilya AU - Gunst, Jan AU - Günther, Andreas AU - Guntur, Anyonya R. AU - Guo, Chuanyong AU - Guo, Chun AU - Guo, Hongqing AU - Guo, Lian Wang AU - Guo, Ming AU - Gupta, Pawan AU - Gupta, Shashi Kumar AU - Gupta, Swapnil AU - Gupta, Veer Bala AU - Gupta, Vivek AU - Gustafsson, Asa B. AU - Gutterman, David D. AU - H.B, Ranjitha AU - Haapasalo, Annakaisa AU - Haber, James E. AU - Hać, Aleksandra AU - Hadano, Shinji AU - Hafrén, Anders J. AU - Haidar, Mansour AU - Hall, Belinda S. AU - Halldén, Gunnel AU - Hamacher-Brady, Anne AU - Hamann, Andrea AU - Hamasaki, Maho AU - Han, Weidong AU - Hansen, Malene AU - Hanson, Phyllis I. . AU - Hao, Zijian AU - Harada, Masaru AU - Harhaji-Trajkovic, Ljubica AU - Hariharan, Nirmala AU - Haroon, Nigil AU - Harris, James AU - Hasegawa, Takafumi AU - Hasima Nagoor, Noor AU - Haspel, Jeffrey A. AU - Haucke, Volker AU - Hawkins, Wayne D. AU - Hay, Bruce A. AU - Haynes, Cole M. AU - Hayrabedyan, Soren B. AU - Hays, Thomas S. AU - He, Congcong AU - He, Qin AU - He, Rong Rong AU - He, You Wen AU - He, Yu Ying AU - Heakal, Yasser AU - Heberle, Alexander M. AU - Hejtmancik, J. Fielding AU - Helgason, Gudmundur Vignir AU - Henkel, Vanessa AU - Herb, Marc AU - Hergovich, Alexander AU - Herman-Antosiewicz, Anna AU - Hernández, Agustín AU - Hernandez, Carlos AU - Hernandez-Diaz, Sergio AU - Hernandez-Gea, Virginia AU - Herpin, Amaury AU - Herreros, Judit AU - Hervás, Javier H. AU - Hesselson, Daniel AU - Hetz, Claudio AU - Heussler, Volker T. AU - Higuchi, Yujiro AU - Hilfiker, Sabine AU - Hill, Joseph A. AU - Hlavacek, William S. AU - Ho, Emmanuel A. AU - Ho, Idy H.T. AU - Ho, Philip Wing Lok AU - Ho, Shu Leong AU - Ho, Wan Yun AU - Hobbs, G. Aaron AU - Hochstrasser, Mark AU - Hoet, Peter H.M. AU - Hofius, Daniel AU - Hofman, Paul AU - Höhn, Annika AU - Holmberg, Carina I. AU - Hombrebueno, Jose R. AU - Yi-Ren Hong, Chang Won Hong AU - Hooper, Lora V. AU - Hoppe, Thorsten AU - Horos, Rastislav AU - Hoshida, Yujin AU - Hsin, I. Lun AU - Hsu, Hsin Yun AU - Hu, Bing AU - Hu, Dong AU - Hu, Li Fang AU - Hu, Ming Chang AU - Hu, Ronggui AU - Hu, Wei AU - Hu, Yu Chen AU - Hu, Zhuo Wei AU - Hua, Fang AU - Hua, Jinlian AU - Hua, Yingqi AU - Huan, Chongmin AU - Huang, Canhua AU - Huang, Chuanshu AU - Huang, Chuanxin AU - Huang, Chunling AU - Huang, Haishan AU - Huang, Kun AU - Huang, Michael L.H. AU - Huang, Rui AU - Huang, Shan AU - Huang, Tianzhi AU - Huang, Xing AU - Huang, Yuxiang Jack AU - Huber, Tobias B. AU - Hubert, Virginie AU - Hubner, Christian A. AU - Hughes, Stephanie M. AU - Hughes, William E. AU - Humbert, Magali AU - Hummer, Gerhard AU - Hurley, James H. AU - Hussain, Sabah AU - Hussain, Salik AU - Hussey, Patrick J. AU - Hutabarat, Martina AU - Hwang, Hui Yun AU - Hwang, Seungmin AU - Ieni, Antonio AU - Ikeda, Fumiyo AU - Imagawa, Yusuke AU - Imai, Yuzuru AU - Imbriano, Carol AU - Imoto, Masaya AU - Inman, Denise M. AU - Inoki, Ken AU - Iovanna, Juan AU - Iozzo, Renato V. AU - Ippolito, Giuseppe AU - Irazoqui, Javier E. AU - Iribarren, Pablo AU - Ishaq, Mohd AU - Ishikawa, Makoto AU - Ishimwe, Nestor AU - Isidoro, Ciro AU - Ismail, Nahed AU - Issazadeh-Navikas, Shohreh AU - Itakura, Eisuke AU - Ito, Daisuke AU - Ivankovic, Davor AU - Ivanova, Saška AU - Iyer, Anand Krishnan V. AU - Izquierdo, José M. AU - Izumi, Masanori AU - Jäättelä, Marja AU - Jabir, Majid Sakhi AU - Jackson, William T. AU - Jacobo-Herrera, Nadia AU - Jacomin, Anne Claire AU - Jacquin, Elise AU - Jadiya, Pooja AU - Jaeschke, Hartmut AU - Jagannath, Chinnaswamy AU - Jakobi, Arjen J. AU - Jakobsson, Johan AU - Janji, Bassam AU - Jansen-Dürr, Pidder AU - Jansson, Patric J. AU - Jantsch, Jonathan AU - Januszewski, Sławomir AU - Jassey, Alagie AU - Jean, Steve AU - Jeltsch-David, Hélène AU - Jendelova, Pavla AU - Jenny, Andreas AU - Jensen, Thomas E. AU - Jessen, Niels AU - Jewell, Jenna L. AU - Ji, Jing AU - Jia, Lijun AU - Jia, Rui AU - Jiang, Liwen AU - Jiang, Qing AU - Jiang, Richeng AU - Jiang, Teng AU - Jiang, Xuejun AU - Jiang, Yu AU - Jimenez-Sanchez, Maria AU - Jin, Eun Jung AU - Jin, Fengyan AU - Jin, Hongchuan AU - Jin, Li AU - Jin, Luqi AU - Jin, Meiyan AU - Jin, Si AU - Jo, Eun Kyeong AU - Joffre, Carine AU - Johansen, Terje AU - Johnson, Gail V.W. AU - Johnston, Simon A. AU - Jokitalo, Eija AU - Jolly, Mohit Kumar AU - Joosten, Leo A.B. AU - Jordan, Joaquin AU - Joseph, Bertrand AU - Ju, Dianwen AU - Ju, Jeong Sun AU - Ju, Jingfang AU - Juárez, Esmeralda AU - Judith, Delphine AU - Juhász, Gábor AU - Jun, Youngsoo AU - Jung, Chang Hwa AU - Jung, Sung Chul AU - Jung, Yong Keun AU - Jungbluth, Heinz AU - Jungverdorben, Johannes AU - Just, Steffen AU - Kaarniranta, Kai AU - Kaasik, Allen AU - Kabuta, Tomohiro AU - Kaganovich, Daniel AU - Kahana, Alon AU - Kain, Renate AU - Kajimura, Shinjo AU - Kalamvoki, Maria AU - Kalia, Manjula AU - Kalinowski, Danuta S. AU - Kaludercic, Nina AU - Kalvari, Ioanna AU - Kaminska, Joanna AU - Kaminskyy, Vitaliy O. AU - Kanamori, Hiromitsu AU - Kanasaki, Keizo AU - Kang, Chanhee AU - Kang, Rui AU - Kang, Sang Sun AU - Kaniyappan, Senthilvelrajan AU - Kanki, Tomotake AU - Kanneganti, Thirumala Devi AU - Kanthasamy, Anumantha G. AU - Kanthasamy, Arthi AU - Kantorow, Marc AU - Kapuy, Orsolya AU - Karamouzis, Michalis V. AU - Karim, Md Razaul AU - Karmakar, Parimal AU - Katare, Rajesh G. AU - Kato, Masaru AU - Kaufmann, Stefan H.E. AU - Kauppinen, Anu AU - Kaushal, Gur P. AU - Kaushik, Susmita AU - Kawasaki, Kiyoshi AU - Kazan, Kemal AU - Ke, Po Yuan AU - Keating, Damien J. AU - Keber, Ursula AU - Kehrl, John H. AU - Keller, Kate E. AU - Keller, Christian W. AU - Kemper, Jongsook Kim AU - Kenific, Candia M. AU - Kepp, Oliver AU - Kermorgant, Stephanie AU - Kern, Andreas AU - Ketteler, Robin AU - Keulers, Tom G. AU - Khalfin, Boris AU - Khalil, Hany AU - Khambu, Bilon AU - Khan, Shahid Y. AU - Khandelwal, Vinoth Kumar Megraj AU - Khandia, Rekha AU - Kho, Widuri AU - Khobrekar, Noopur V. AU - Khuansuwan, Sataree AU - Khundadze, Mukhran AU - Killackey, Samuel A. AU - Kim, Dasol AU - Kim, Deok Ryong AU - Kim, Do Hyung AU - Kim, Dong Eun AU - Kim, Eun Young AU - Kim, Eun Kyoung AU - Kim, Hak Rim AU - Kim, Hee Sik AU - Hyung-Ryong Kim, Unknown AU - Kim, Jeong Hun AU - Kim, Jin Kyung AU - Kim, Jin Hoi AU - Kim, Joungmok AU - Kim, Ju Hwan AU - Kim, Keun Il AU - Kim, Peter K. AU - Kim, Seong Jun AU - Kimball, Scot R. AU - Kimchi, Adi AU - Kimmelman, Alec C. AU - Kimura, Tomonori AU - King, Matthew A. AU - Kinghorn, Kerri J. AU - Kinsey, Conan G. AU - Kirkin, Vladimir AU - Kirshenbaum, Lorrie A. AU - Kiselev, Sergey L. AU - Kishi, Shuji AU - Kitamoto, Katsuhiko AU - Kitaoka, Yasushi AU - Kitazato, Kaio AU - Kitsis, Richard N. AU - Kittler, Josef T. AU - Kjaerulff, Ole AU - Klein, Peter S. AU - Klopstock, Thomas AU - Klucken, Jochen AU - Knævelsrud, Helene AU - Knorr, Roland L. AU - Ko, Ben C.B. AU - Ko, Fred AU - Ko, Jiunn Liang AU - Kobayashi, Hotaka AU - Kobayashi, Satoru AU - Koch, Ina AU - Koch, Jan C. AU - Koenig, Ulrich AU - Kögel, Donat AU - Koh, Young Ho AU - Koike, Masato AU - Kohlwein, Sepp D. AU - Kocaturk, Nur M. AU - Komatsu, Masaaki AU - König, Jeannette AU - Kono, Toru AU - Kopp, Benjamin T. AU - Korcsmaros, Tamas AU - Korkmaz, Gözde AU - Korolchuk, Viktor I. AU - Korsnes, Mónica Suárez AU - Koskela, Ali AU - Kota, Janaiah AU - Kotake, Yaichiro AU - Kotler, Monica L. AU - Kou, Yanjun AU - Koukourakis, Michael I. AU - Koustas, Evangelos AU - Kovacs, Attila L. AU - Kovács, Tibor AU - Koya, Daisuke AU - Kozako, Tomohiro AU - Kraft, Claudine AU - Krainc, Dimitri AU - Krämer, Helmut AU - Krasnodembskaya, Anna D. AU - Kretz-Remy, Carole AU - Kroemer, Guido AU - Ktistakis, Nicholas T. AU - Kuchitsu, Kazuyuki AU - Kuenen, Sabine AU - Kuerschner, Lars AU - Kukar, Thomas AU - Kumar, Ajay AU - Kumar, Ashok AU - Kumar, Deepak AU - Kumar, Dhiraj AU - Kumar, Sharad AU - Kume, Shinji AU - Kumsta, Caroline AU - Kundu, Chanakya N. AU - Kundu, Mondira AU - Kunnumakkara, Ajaikumar B. AU - Kurgan, Lukasz AU - Kutateladze, Tatiana G. AU - Kutlu, Ozlem AU - Kwak, Seong Ae AU - Kwon, Ho Jeong AU - Kwon, Taeg Kyu AU - Kwon, Yong Tae AU - Kyrmizi, Irene AU - La Spada, Albert AU - Labonté, Patrick AU - Ladoire, Sylvain AU - Laface, Ilaria AU - Lafont, Frank AU - Lagace, Diane C. AU - Lahiri, Vikramjit AU - Lai, Zhibing AU - Laird, Angela S. AU - Lakkaraju, Aparna AU - Lamark, Trond AU - Lan, Sheng Hui AU - Landajuela, Ane AU - Lane, Darius J.R. AU - Lane, Jon D. AU - Lang, Charles H. AU - Lange, Carsten AU - Langel, Ülo AU - Langer, Rupert AU - Lapaquette, Pierre AU - Laporte, Jocelyn AU - Larusso, Nicholas F. AU - Lastres-Becker, Isabel AU - Lau, Wilson Chun Yu AU - Laurie, Gordon W. AU - Lavandero, Sergio AU - Law, Betty Yuen Kwan AU - Law, Helen Ka Wai AU - Layfield, Rob AU - Le, Weidong AU - Le Stunff, Herve AU - Leary, Alexandre Y. AU - Lebrun, Jean Jacques AU - Leck, Lionel Y.W. AU - Leduc-Gaudet, Jean Philippe AU - Lee, Changwook AU - Lee, Chung Pei AU - Lee, Da Hye AU - Lee, Edward B. AU - Lee, Erinna F. AU - Lee, Gyun Min AU - Lee, He Jin AU - Lee, Heung Kyu AU - Lee, Jae Man AU - Lee, Jason S. AU - Lee, Jin A. AU - Lee, Joo Yong AU - Lee, Jun Hee AU - Lee, Michael AU - Lee, Min Goo AU - Lee, Min Jae AU - Lee, Myung Shik AU - Lee, Sang Yoon AU - Lee, Seung Jae AU - Lee, Stella Y. AU - Lee, Sung Bae AU - Lee, Won Hee AU - Lee, Ying Ray AU - Lee, Yong Ho AU - Lee, Youngil AU - Lefebvre, Christophe AU - Legouis, Renaud AU - Lei, Yu L. AU - Lei, Yuchen AU - Leikin, Sergey AU - Leitinger, Gerd AU - Lemus, Leticia AU - Leng, Shuilong AU - Lenoir, Olivia AU - Lenz, Guido AU - Lenz, Heinz Josef AU - Lenzi, Paola AU - León, Yolanda AU - Leopoldino, Andréia M. AU - Leschczyk, Christoph AU - Leskelä, Stina AU - Letellier, Elisabeth AU - Leung, Chi Ting AU - Leung, Po Sing AU - Leventhal, Jeremy S. AU - Levine, Beth AU - Lewis, Patrick A. AU - Ley, Klaus AU - Li, Bin AU - Li, Da Qiang AU - Li, Jianming AU - Li, Jing AU - Li, Jiong AU - Li, Ke AU - Li, Liwu AU - Li, Mei AU - Li, Min AU - Li, Min AU - Li, Ming AU - Li, Mingchuan AU - Li, Pin Lan AU - Li, Ming Qing AU - Li, Qing AU - Li, Sheng AU - Li, Tiangang AU - Li, Wei AU - Li, Wenming AU - Li, Xue AU - Li, Yi Ping AU - Li, Yuan AU - Li, Zhiqiang AU - Li, Zhiyong AU - Li, Zhiyuan AU - Lian, Jiqin AU - Liang, Chengyu AU - Liang, Qiangrong AU - Liang, Weicheng AU - Liang, Yongheng AU - Liang, Yong Tian AU - Liao, Guanghong AU - Liao, Lujian AU - Liao, Mingzhi AU - Liao, Yung Feng AU - Librizzi, Mariangela AU - Lie, Pearl P.Y. AU - Lilly, Mary A. AU - Lim, Hyunjung J. AU - Lima, Thania R.R. AU - Limana, Federica AU - Lin, Chao AU - Lin, Chih Wen AU - Lin, Dar Shong AU - Lin, Fu Cheng AU - Lin, Jiandie D. AU - Lin, Kurt M. AU - Lin, Kwang Huei AU - Lin, Liang Tzung AU - Lin, Pei Hui AU - Lin, Qiong AU - Lin, Shaofeng AU - Lin, Su Ju AU - Lin, Wenyu AU - Lin, Xueying AU - Lin, Yao Xin AU - Lin, Yee Shin AU - Linden, Rafael AU - Lindner, Paula AU - Ling, Shuo Chien AU - Lingor, Paul AU - Linnemann, Amelia K. AU - Liou, Yih Cherng AU - Lipinski, Marta M. AU - Lipovšek, Saška AU - Lira, Vitor A. AU - Lisiak, Natalia AU - Liton, Paloma B. AU - Liu, Chao AU - Liu, Ching Hsuan AU - Liu, Chun Feng AU - Liu, Cui Hua AU - Liu, Fang AU - Liu, Hao AU - Liu, Hsiao Sheng AU - Liu, Hua Feng AU - Liu, Huifang AU - Liu, Jia AU - Liu, Jing AU - Liu, Julia AU - Liu, Leyuan AU - Liu, Longhua AU - Liu, Meilian AU - Liu, Qin AU - Liu, Wei AU - Liu, Wende AU - Liu, Xiao Hong AU - Liu, Xiaodong AU - Liu, Xingguo AU - Liu, Xu AU - Liu, Xuedong AU - Liu, Yanfen AU - Liu, Yang AU - Liu, Yang AU - Liu, Yueyang AU - Liu, Yule AU - Livingston, J. Andrew AU - Lizard, Gerard AU - Lizcano, Jose M. AU - Ljubojevic-Holzer, Senka AU - Lleonart, Matilde E. AU - Llobet-Navàs, David AU - Llorente, Alicia AU - Lo, Chih Hung AU - Lobato-Márquez, Damián AU - Long, Qi AU - Long, Yun Chau AU - Loos, Ben AU - Loos, Julia A. AU - López, Manuela G. AU - López-Doménech, Guillermo AU - López-Guerrero, José Antonio AU - López-Jiménez, Ana T. AU - López-Pérez, Óscar AU - López-Valero, Israel AU - Lorenowicz, Magdalena J. AU - Lorente, Mar AU - Lorincz, Peter AU - Lossi, Laura AU - Lotersztajn, Sophie AU - Lovat, Penny E. AU - Lovell, Jonathan F. AU - Lovy, Alenka AU - Lőw, Péter AU - Lu, Guang AU - Lu, Haocheng AU - Lu, Jia Hong AU - Lu, Jin Jian AU - Lu, Mengji AU - Lu, Shuyan AU - Luciani, Alessandro AU - Lucocq, John M. AU - Ludovico, Paula AU - Luftig, Micah A. AU - Luhr, Morten AU - Luis-Ravelo, Diego AU - Lum, Julian J. AU - Luna-Dulcey, Liany AU - Lund, Anders H. AU - Lund, Viktor K. AU - Lünemann, Jan D. AU - Lüningschrör, Patrick AU - Luo, Honglin AU - Luo, Rongcan AU - Luo, Shouqing AU - Luo, Zhi AU - Luparello, Claudio AU - Lüscher, Bernhard AU - Luu, Luan AU - Lyakhovich, Alex AU - Lyamzaev, Konstantin G. AU - Lystad, Alf Håkon AU - Lytvynchuk, Lyubomyr AU - Ma, Alvin C. AU - Ma, Changle AU - Ma, Mengxiao AU - Ma, Ning Fang AU - Ma, Quan Hong AU - Ma, Xinliang AU - Ma, Yueyun AU - Ma, Zhenyi AU - Macdougald, Ormond A. AU - Macian, Fernando AU - Macintosh, Gustavo C. AU - Mackeigan, Jeffrey P. AU - Macleod, Kay F. AU - Maday, Sandra AU - Madeo, Frank AU - Madesh, Muniswamy AU - Madl, Tobias AU - Madrigal-Matute, Julio AU - Maeda, Akiko AU - Maejima, Yasuhiro AU - Magarinos, Marta AU - Mahavadi, Poornima AU - Maiani, Emiliano AU - Maiese, Kenneth AU - Maiti, Panchanan AU - Maiuri, Maria Chiara AU - Majello, Barbara AU - Major, Michael B. AU - Makareeva, Elena AU - Malik, Fayaz AU - Mallilankaraman, Karthik AU - Malorni, Walter AU - Maloyan, Alina AU - Mammadova, Najiba AU - Man, Gene Chi Wai AU - Manai, Federico AU - Mancias, Joseph D. AU - Mandelkow, Eva Maria AU - Mandell, Michael A. AU - Manfredi, Angelo A. AU - Manjili, Masoud H. AU - Manjithaya, Ravi AU - Manque, Patricio AU - Manshian, Bella B. AU - Manzano, Raquel AU - Manzoni, Claudia AU - Mao, Kai AU - Marchese, Cinzia AU - Marchetti, Sandrine AU - Marconi, Anna Maria AU - Marcucci, Fabrizio AU - Mardente, Stefania AU - Mareninova, Olga A. AU - Margeta, Marta AU - Mari, Muriel AU - Marinelli, Sara AU - Marinelli, Oliviero AU - Mariño, Guillermo AU - Mariotto, Sofia AU - Marshall, Richard S. AU - Marten, Mark R. AU - Martens, Sascha AU - Martin, Alexandre P.J. AU - Martin, Katie R. AU - Martin, Sara AU - Martin, Shaun AU - Martín-Segura, Adrián AU - Martín-Acebes, Miguel A. AU - Martin-Burriel, Inmaculada AU - Martin-Rincon, Marcos AU - Martin-Sanz, Paloma AU - Martina, José A. AU - Martinet, Wim AU - Martinez, Aitor AU - Martinez, Ana AU - Martinez, Jennifer AU - Martinez Velazquez, Moises AU - Martinez-Lopez, Nuria AU - Martinez-Vicente, Marta AU - Martins, Daniel O. AU - Martins, Joilson O. AU - Martins, Waleska K. AU - Martins-Marques, Tania AU - Marzetti, Emanuele AU - Masaldan, Shashank AU - Masclaux-Daubresse, Celine AU - Mashek, Douglas G. AU - Massa, Valentina AU - Massieu, Lourdes AU - Masson, Glenn R. AU - Masuelli, Laura AU - Masyuk, Anatoliy I. AU - Masyuk, Tetyana V. AU - Matarrese, Paola AU - Matheu, Ander AU - Matoba, Satoaki AU - Matsuzaki, Sachiko AU - Mattar, Pamela AU - Matte, Alessandro AU - Mattoscio, Domenico AU - Mauriz, José L. AU - Mauthe, Mario AU - Mauvezin, Caroline AU - Maverakis, Emanual AU - Maycotte, Paola AU - Mayer, Johanna AU - Mazzoccoli, Gianluigi AU - Mazzoni, Cristina AU - Mazzulli, Joseph R. AU - Mccarty, Nami AU - Mcdonald, Christine AU - Mcgill, Mitchell R. AU - Mckenna, Sharon L. AU - Mclaughlin, Beth Ann AU - Mcloughlin, Fionn AU - Mcniven, Mark A. AU - Mcwilliams, Thomas G. AU - Mechta-Grigoriou, Fatima AU - Medeiros, Tania Catarina AU - Medina, Diego L. AU - Megeney, Lynn A. AU - Megyeri, Klara AU - Mehrpour, Maryam AU - Mehta, Jawahar L. AU - Meijer, Alfred J. AU - Meijer, Annemarie H. AU - Mejlvang, Jakob AU - Meléndez, Alicia AU - Melk, Annette AU - Memisoglu, Gonen AU - Mendes, Alexandrina F. AU - Meng, Delong AU - Meng, Fei AU - Meng, Tian AU - Menna-Barreto, Rubem AU - Menon, Manoj B. AU - Mercer, Carol AU - Mercier, Anne E. AU - Mergny, Jean Louis AU - Merighi, Adalberto AU - Merkley, Seth D. AU - Merla, Giuseppe AU - Meske, Volker AU - Mestre, Ana Cecilia AU - Metur, Shree Padma AU - Meyer, Christian AU - Meyer, Hemmo AU - Mi, Wenyi AU - Mialet-Perez, Jeanne AU - Miao, Junying AU - Micale, Lucia AU - Miki, Yasuo AU - Milan, Enrico AU - Milczarek, Małgorzata AU - Miller, Dana L. AU - Miller, Samuel I. AU - Miller, Silke AU - Millward, Steven W. AU - Milosevic, Ira AU - Minina, Elena A. AU - Mirzaei, Hamed AU - Mirzaei, Hamid Reza AU - Mirzaei, Mehdi AU - Mishra, Amit AU - Mishra, Nandita AU - Mishra, Paras Kumar AU - Misirkic Marjanovic, Maja AU - Misasi, Roberta AU - Misra, Amit AU - Misso, Gabriella AU - Mitchell, Claire AU - Mitou, Geraldine AU - Miura, Tetsuji AU - Miyamoto, Shigeki AU - Miyazaki, Makoto AU - Miyazaki, Mitsunori AU - Miyazaki, Taiga AU - Miyazawa, Keisuke AU - Mizushima, Noboru AU - Mogensen, Trine H. AU - Mograbi, Baharia AU - Mohammadinejad, Reza AU - Mohamud, Yasir AU - Mohanty, Abhishek AU - Mohapatra, Sipra AU - Möhlmann, Torsten AU - Mohmmed, Asif AU - Moles, Anna AU - Moley, Kelle H. AU - Molinari, Maurizio AU - Mollace, Vincenzo AU - Møller, Andreas Buch AU - Mollereau, Bertrand AU - Mollinedo, Faustino AU - Montagna, Costanza AU - Monteiro, Mervyn J. AU - Montella, Andrea AU - Montes, L. Ruth AU - Montico, Barbara AU - Mony, Vinod K. AU - Monzio Compagnoni, Giacomo AU - Moore, Michael N. AU - Moosavi, Mohammad A. AU - Mora, Ana L. AU - Mora, Marina AU - Morales-Alamo, David AU - Moratalla, Rosario AU - Moreira, Paula I. AU - Morelli, Elena AU - Moreno, Sandra AU - Moreno-Blas, Daniel AU - Moresi, Viviana AU - Morga, Benjamin AU - Morgan, Alwena H. AU - Morin, Fabrice AU - Morishita, Hideaki AU - Moritz, Orson L. AU - Moriyama, Mariko AU - Moriyasu, Yuji AU - Morleo, Manuela AU - Morselli, Eugenia AU - Moruno-Manchon, Jose F. AU - Moscat, Jorge AU - Mostowy, Serge AU - Motori, Elisa AU - Moura, Andrea Felinto AU - Moustaid-Moussa, Naima AU - Mrakovcic, Maria AU - Muciño-Hernández, Gabriel AU - Mukherjee, Anupam AU - Mukhopadhyay, Subhadip AU - Mulcahy Levy, Jean M. AU - Mulero, Victoriano AU - Muller, Sylviane AU - Münch, Christian AU - Munjal, Ashok AU - Munoz-Canoves, Pura AU - Muñoz-Galdeano, Teresa AU - Münz, Christian AU - Murakawa, Tomokazu AU - Muratori, Claudia AU - Murphy, Brona M. AU - Murphy, J. Patrick AU - Murthy, Aditya AU - Myöhänen, Timo T. AU - Mysorekar, Indira U. AU - Mytych, Jennifer AU - Nabavi, Seyed Mohammad AU - Nabissi, Massimo AU - Nagy, Péter AU - Nah, Jihoon AU - Nahimana, Aimable AU - Nakagawa, Ichiro AU - Nakamura, Ken AU - Nakatogawa, Hitoshi AU - Nandi, Shyam S. AU - Nanjundan, Meera AU - Nanni, Monica AU - Napolitano, Gennaro AU - Nardacci, Roberta AU - Narita, Masashi AU - Nassif, Melissa AU - Nathan, Ilana AU - Natsumeda, Manabu AU - Naude, Ryno J. AU - Naumann, Christin AU - Naveiras, Olaia AU - Navid, Fatemeh AU - Nawrocki, Steffan T. AU - Nazarko, Taras Y. AU - Nazio, Francesca AU - Negoita, Florentina AU - Neill, Thomas AU - Neisch, Amanda L. AU - Neri, Luca M. AU - Netea, Mihai G. AU - Neubert, Patrick AU - Neufeld, Thomas P. AU - Neumann, Dietbert AU - Neutzner, Albert AU - Newton, Phillip T. AU - Ney, Paul A. AU - Nezis, Ioannis P. AU - Ng, Charlene C.W. AU - Ng, Tzi Bun AU - Nguyen, Hang T.T. AU - Nguyen, Long T. AU - Ni, Hong Min AU - Ní Cheallaigh, Clíona AU - Ni, Zhenhong AU - Nicolao, M. Celeste AU - Nicoli, Francesco AU - Nieto-Diaz, Manuel AU - Nilsson, Per AU - Ning, Shunbin AU - Niranjan, Rituraj AU - Nishimune, Hiroshi AU - Niso-Santano, Mireia AU - Nixon, Ralph A. AU - Nobili, Annalisa AU - Nobrega, Clevio AU - Noda, Takeshi AU - Nogueira-Recalde, Uxía AU - Nolan, Trevor M. AU - Nombela, Ivan AU - Novak, Ivana AU - Novoa, Beatriz AU - Nozawa, Takashi AU - Nukina, Nobuyuki AU - Nussbaum-Krammer, Carmen AU - Nylandsted, Jesper AU - O’Donovan, Tracey R. AU - O’Leary, Seónadh M. AU - O’Rourke, Eyleen J. AU - O’Sullivan, Mary P. AU - O’Sullivan, Timothy E. AU - Oddo, Salvatore AU - Oehme, Ina AU - Ogawa, Michinaga AU - Ogier-Denis, Eric AU - Ogmundsdottir, Margret H. AU - Ogretmen, Besim AU - Oh, Goo Taeg AU - Oh, Seon Hee AU - Oh, Young J. AU - Ohama, Takashi AU - Ohashi, Yohei AU - Ohmuraya, Masaki AU - Oikonomou, Vasileios AU - Ojha, Rani AU - Okamoto, Koji AU - Okazawa, Hitoshi AU - Oku, Masahide AU - Oliván, Sara AU - Oliveira, Jorge M.A. AU - Ollmann, Michael AU - Olzmann, James A. AU - Omari, Shakib AU - Omary, M. Bishr AU - Önal, Gizem AU - Ondrej, Martin AU - Ong, Sang Bing AU - Ong, Sang Ging AU - Onnis, Anna AU - Orellana, Juan A. AU - Orellana-Muñoz, Sara AU - Ortega-Villaizan, Maria Del Mar AU - Ortiz-Gonzalez, Xilma R. AU - Ortona, Elena AU - Osiewacz, Heinz D. AU - Osman, Abdel Hamid K. AU - Osta, Rosario AU - Otegui, Marisa S. AU - Otsu, Kinya AU - Ott, Christiane AU - Ottobrini, Luisa AU - Ou, Jing Hsiung James AU - Outeiro, Tiago F. AU - Oynebraten, Inger AU - Ozturk, Melek AU - Pagès, Gilles AU - Pahari, Susanta AU - Pajares, Marta AU - Pajvani, Utpal B. AU - Pal, Rituraj AU - Paladino, Simona AU - Pallet, Nicolas AU - Palmieri, Michela AU - Palmisano, Giuseppe AU - Palumbo, Camilla AU - Pampaloni, Francesco AU - Pan, Lifeng AU - Pan, Qingjun AU - Pan, Wenliang AU - Pan, Xin AU - Panasyuk, Ganna AU - Pandey, Rahul AU - Pandey, Udai B. AU - Pandya, Vrajesh AU - Paneni, Francesco AU - Pang, Shirley Y. AU - Panzarini, Elisa AU - Papademetrio, Daniela L. AU - Papaleo, Elena AU - Papinski, Daniel AU - Papp, Diana AU - Park, Eun Chan AU - Park, Hwan Tae AU - Park, Ji Man AU - Park, Jong In AU - Park, Joon Tae AU - Park, Junsoo AU - Park, Sang Chul AU - Park, Sang Youel AU - Parola, Abraham H. AU - Parys, Jan B. AU - Pasquier, Adrien AU - Pasquier, Benoit AU - Passos, João F. AU - Pastore, Nunzia AU - Patel, Hemal H. AU - Patschan, Daniel AU - Pattingre, Sophie AU - Pedraza-Alva, Gustavo AU - Pedraza-Chaverri, Jose AU - Pedrozo, Zully AU - Pei, Gang AU - Pei, Jianming AU - Peled-Zehavi, Hadas AU - Pellegrini, Joaquín M. AU - Pelletier, Joffrey AU - Peñalva, Miguel A. AU - Peng, Di AU - Peng, Ying AU - Penna, Fabio AU - Pennuto, Maria AU - Pentimalli, Francesca AU - Pereira, Cláudia M.F. AU - Pereira, Gustavo J.S. AU - Pereira, Lilian C. AU - Pereira De Almeida, Luis AU - Perera, Nirma D. AU - Pérez-Lara, Ángel AU - Perez-Oliva, Ana B. AU - Pérez-Pérez, María Esther AU - Periyasamy, Palsamy AU - Perl, Andras AU - Perrotta, Cristiana AU - Perrotta, Ida AU - Pestell, Richard G. AU - Petersen, Morten AU - Petrache, Irina AU - Petrovski, Goran AU - Pfirrmann, Thorsten AU - Pfister, Astrid S. AU - Philips, Jennifer A. AU - Pi, Huifeng AU - Picca, Anna AU - Pickrell, Alicia M. AU - Picot, Sandy AU - Pierantoni, Giovanna M. AU - Pierdominici, Marina AU - Pierre, Philippe AU - Pierrefite-Carle, Valérie AU - Pierzynowska, Karolina AU - Pietrocola, Federico AU - Pietruczuk, Miroslawa AU - Pignata, Claudio AU - Pimentel-Muiños, Felipe X. AU - Pinar, Mario AU - Pinheiro, Roberta O. AU - Pinkas-Kramarski, Ronit AU - Pinton, Paolo AU - Pircs, Karolina AU - Piya, Sujan AU - Pizzo, Paola AU - Plantinga, Theo S. AU - Platta, Harald W. AU - Plaza-Zabala, Ainhoa AU - Plomann, Markus AU - Plotnikov, Egor Y. AU - Plun-Favreau, Helene AU - Pluta, Ryszard AU - Pocock, Roger AU - Pöggeler, Stefanie AU - Pohl, Christian AU - Poirot, Marc AU - Poletti, Angelo AU - Ponpuak, Marisa AU - Popelka, Hana AU - Popova, Blagovesta AU - Porta, Helena AU - Porte Alcon, Soledad AU - Portilla-Fernandez, Eliana AU - Post, Martin AU - Potts, Malia B. AU - Poulton, Joanna AU - Powers, Ted AU - Prahlad, Veena AU - Prajsnar, Tomasz K. AU - Praticò, Domenico AU - Prencipe, Rosaria AU - Priault, Muriel AU - Proikas-Cezanne, Tassula AU - Promponas, Vasilis J. AU - Proud, Christopher G. AU - Puertollano, Rosa AU - Puglielli, Luigi AU - Pulinilkunnil, Thomas AU - Puri, Deepika AU - Puri, Rajat AU - Puyal, Julien AU - Qi, Xiaopeng AU - Qi, Yongmei AU - Qian, Wenbin AU - Qiang, Lei AU - Qiu, Yu AU - Quadrilatero, Joe AU - Quarleri, Jorge AU - Raben, Nina AU - Rabinowich, Hannah AU - Ragona, Debora AU - Ragusa, Michael J. AU - Rahimi, Nader AU - Rahmati, Marveh AU - Raia, Valeria AU - Raimundo, Nuno AU - Rajasekaran, Namakkal Soorappan AU - Ramachandra Rao, Sriganesh AU - Rami, Abdelhaq AU - Ramírez-Pardo, Ignacio AU - Ramsden, David B. AU - Randow, Felix AU - Rangarajan, Pundi N. AU - Ranieri, Danilo AU - Rao, Hai AU - Rao, Lang AU - Rao, Rekha AU - Rathore, Sumit AU - Ratnayaka, J. Arjuna AU - Ratovitski, Edward A. AU - Ravanan, Palaniyandi AU - Ravegnini, Gloria AU - Ray, Swapan K. AU - Razani, Babak AU - Rebecca, Vito AU - Reggiori, Fulvio AU - Régnier-Vigouroux, Anne AU - Reichert, Andreas S. AU - Reigada, David AU - Reiling, Jan H. AU - Rein, Theo AU - Reipert, Siegfried AU - Rekha, Rokeya Sultana AU - Ren, Hongmei AU - Ren, Jun AU - Ren, Weichao AU - Renault, Tristan AU - Renga, Giorgia AU - Reue, Karen AU - Rewitz, Kim AU - Ribeiro De Andrade Ramos, Bruna AU - Riazuddin, S. Amer AU - Ribeiro-Rodrigues, Teresa M. AU - Ricci, Jean Ehrland AU - Ricci, Romeo AU - Riccio, Victoria AU - Richardson, Des R. AU - Rikihisa, Yasuko AU - Risbud, Makarand V. AU - Risueño, Ruth M. AU - Ritis, Konstantinos AU - Rizza, Salvatore AU - Rizzuto, Rosario AU - Roberts, Helen C. AU - Roberts, Luke D. AU - Robinson, Katherine J. AU - Roccheri, Maria Carmela AU - Rocchi, Stephane AU - Rodney, George G. AU - Rodrigues, Tiago AU - Rodrigues Silva, Vagner Ramon AU - Rodriguez, Amaia AU - Rodriguez-Barrueco, Ruth AU - Rodriguez-Henche, Nieves AU - Rodriguez-Rocha, Humberto AU - Roelofs, Jeroen AU - Rogers, Robert S. AU - Rogov, Vladimir V. AU - Rojo, Ana I. AU - Rolka, Krzysztof AU - Romanello, Vanina AU - Romani, Luigina AU - Romano, Alessandra AU - Romano, Patricia S. AU - Romeo-Guitart, David AU - Romero, Luis C. AU - Romero, Montserrat AU - Roney, Joseph C. AU - Rongo, Christopher AU - Roperto, Sante AU - Rosenfeldt, Mathias T. AU - Rosenstiel, Philip AU - Rosenwald, Anne G. AU - Roth, Kevin A. AU - Roth, Lynn AU - Roth, Steven AU - Rouschop, Kasper M.A. AU - Roussel, Benoit D. AU - Roux, Sophie AU - Rovere-Querini, Patrizia AU - Roy, Ajit AU - Rozieres, Aurore AU - Ruano, Diego AU - Rubinsztein, David C. AU - Rubtsova, Maria P. AU - Ruckdeschel, Klaus AU - Ruckenstuhl, Christoph AU - Rudolf, Emil AU - Rudolf, Rüdiger AU - Ruggieri, Alessandra AU - Ruparelia, Avnika Ashok AU - Rusmini, Paola AU - Russell, Ryan R. AU - Russo, Gian Luigi AU - Russo, Maria AU - Russo, Rossella AU - Ryabaya, Oxana O. AU - Ryan, Kevin M. AU - Ryu, Kwon Yul AU - Sabater-Arcis, Maria AU - Sachdev, Ulka AU - Sacher, Michael AU - Sachse, Carsten AU - Sadhu, Abhishek AU - Sadoshima, Junichi AU - Safren, Nathaniel AU - Saftig, Paul AU - Sagona, Antonia P. AU - Sahay, Gaurav AU - Sahebkar, Amirhossein AU - Sahin, Mustafa AU - Sahin, Ozgur AU - Sahni, Sumit AU - Saito, Nayuta AU - Saito, Shigeru AU - Saito, Tsunenori AU - Sakai, Ryohei AU - Sakai, Yasuyoshi AU - Sakamaki, Jun Ichi AU - Saksela, Kalle AU - Salazar, Gloria AU - Salazar-Degracia, Anna AU - Salekdeh, Ghasem H. AU - Saluja, Ashok K. AU - Sampaio-Marques, Belém AU - Sanchez, Maria Cecilia AU - Sanchez-Alcazar, Jose A. AU - Sanchez-Vera, Victoria AU - Sancho-Shimizu, Vanessa AU - Sanderson, J. Thomas AU - Sandri, Marco AU - Santaguida, Stefano AU - Santambrogio, Laura AU - Santana, Magda M. AU - Santoni, Giorgio AU - Sanz, Alberto AU - Sanz, Pascual AU - Saran, Shweta AU - Sardiello, Marco AU - Sargeant, Timothy J. AU - Sarin, Apurva AU - Sarkar, Chinmoy AU - Sarkar, Sovan AU - Sarrias, Maria Rosa AU - Sarkar, Surajit AU - Sarmah, Dipanka Tanu AU - Sarparanta, Jaakko AU - Sathyanarayan, Aishwarya AU - Sathyanarayanan, Ranganayaki AU - Scaglione, K. Matthew AU - Scatozza, Francesca AU - Schaefer, Liliana AU - Schafer, Zachary T. AU - Schaible, Ulrich E. AU - Schapira, Anthony H.V. AU - Scharl, Michael AU - Schatzl, Hermann M. AU - Schein, Catherine H. AU - Scheper, Wiep AU - Scheuring, David AU - Schiaffino, Maria Vittoria AU - Schiappacassi, Monica AU - Schindl, Rainer AU - Schlattner, Uwe AU - Schmidt, Oliver AU - Schmitt, Roland AU - Schmidt, Stephen D. AU - Schmitz, Ingo AU - Schmukler, Eran AU - Schneider, Anja AU - Schneider, Bianca E. AU - Schober, Romana AU - Schoijet, Alejandra C. AU - Schott, Micah B. AU - Schramm, Michael AU - Schröder, Bernd AU - Schuh, Kai AU - Schüller, Christoph AU - Schulze, Ryan J. AU - Schürmanns, Lea AU - Schwamborn, Jens C. AU - Schwarten, Melanie AU - Scialo, Filippo AU - Sciarretta, Sebastiano AU - Scott, Melanie J. AU - Scotto, Kathleen W. AU - Scovassi, A. Ivana AU - Scrima, Andrea AU - Scrivo, Aurora AU - Sebastian, David AU - Sebti, Salwa AU - Sedej, Simon AU - Segatori, Laura AU - Segev, Nava AU - Seglen, Per O. AU - Seiliez, Iban AU - Seki, Ekihiro AU - Selleck, Scott B. AU - Sellke, Frank W. AU - Selsby, Joshua T. AU - Sendtner, Michael AU - Senturk, Serif AU - Seranova, Elena AU - Sergi, Consolato AU - Serra-Moreno, Ruth AU - Sesaki, Hiromi AU - Settembre, Carmine AU - Setty, Subba Rao Gangi AU - Sgarbi, Gianluca AU - Sha, Ou AU - Shacka, John J. AU - Shah, Javeed A. AU - Shang, Dantong AU - Shao, Changshun AU - Shao, Feng AU - Sharbati, Soroush AU - Sharkey, Lisa M. AU - Sharma, Dipali AU - Sharma, Gaurav AU - Sharma, Kulbhushan AU - Sharma, Pawan AU - Sharma, Surendra AU - Shen, Han Ming AU - Shen, Hongtao AU - Shen, Jiangang AU - Shen, Ming AU - Shen, Weili AU - Shen, Zheni AU - Sheng, Rui AU - Sheng, Zhi AU - Sheng, Zu Hang AU - Shi, Jianjian AU - Shi, Xiaobing AU - Shi, Ying Hong AU - Shiba-Fukushima, Kahori AU - Shieh, Jeng Jer AU - Shimada, Yohta AU - Shimizu, Shigeomi AU - Shimozawa, Makoto AU - Shintani, Takahiro AU - Shoemaker, Christopher J. AU - Shojaei, Shahla AU - Shoji, Ikuo AU - Shravage, Bhupendra V. AU - Shridhar, Viji AU - Shu, Chih Wen AU - Shu, Hong Bing AU - Shui, Ke AU - Shukla, Arvind K. AU - Shutt, Timothy E. AU - Sica, Valentina AU - Siddiqui, Aleem AU - Sierra, Amanda AU - Sierra-Torre, Virginia AU - Signorelli, Santiago AU - Sil, Payel AU - Silva, Bruno J.De Andrade AU - Silva, Johnatas D. AU - Silva-Pavez, Eduardo AU - Silvente-Poirot, Sandrine AU - Simmonds, Rachel E. AU - Simon, Anna Katharina AU - Simon, Hans Uwe AU - Simons, Matias AU - Singh, Anurag AU - Singh, Lalit P. AU - Singh, Rajat AU - Singh, Shivendra V. AU - Singh, Shrawan K. AU - Singh, Sudha B. AU - Singh, Sunaina AU - Singh, Surinder Pal AU - Sinha, Debasish AU - Sinha, Rohit Anthony AU - Sinha, Sangita AU - Sirko, Agnieszka AU - Sirohi, Kapil AU - Sivridis, Efthimios L. AU - Skendros, Panagiotis AU - Skirycz, Aleksandra AU - Slaninová, Iva AU - Smaili, Soraya S. AU - Smertenko, Andrei AU - Smith, Matthew D. AU - Soenen, Stefaan J. AU - Sohn, Eun Jung AU - Sok, Sophia P.M. AU - Solaini, Giancarlo AU - Soldati, Thierry AU - Soleimanpour, Scott A. AU - Soler, Rosa M. AU - Solovchenko, Alexei AU - Somarelli, Jason A. AU - Sonawane, Avinash AU - Song, Fuyong AU - Song, Hyun Kyu AU - Song, Ju Xian AU - Song, Kunhua AU - Song, Zhiyin AU - Soria, Leandro R. AU - Sorice, Maurizio AU - Soukas, Alexander A. AU - Soukup, Sandra Fausia AU - Sousa, Diana AU - Sousa, Nadia AU - Spagnuolo, Paul A. AU - Spector, Stephen A. AU - Srinivas Bharath, M. M. AU - St. Clair, Daret AU - Stagni, Venturina AU - Staiano, Leopoldo AU - Stalnecker, Clint A. AU - Stankov, Metodi V. AU - Stathopulos, Peter B. AU - Stefan, Katja AU - Stefan, Sven Marcel AU - Stefanis, Leonidas AU - Steffan, Joan S. AU - Steinkasserer, Alexander AU - Stenmark, Harald AU - Sterneckert, Jared AU - Stevens, Craig AU - Stoka, Veronika AU - Storch, Stephan AU - Stork, Björn AU - Strappazzon, Flavie AU - Strohecker, Anne Marie AU - Stupack, Dwayne G. AU - Su, Huanxing AU - Su, Ling Yan AU - Su, Longxiang AU - Suarez-Fontes, Ana M. AU - Subauste, Carlos S. AU - Subbian, Selvakumar AU - Subirada, Paula V. AU - Sudhandiran, Ganapasam AU - Sue, Carolyn M. AU - Sui, Xinbing AU - Summers, Corey AU - Sun, Guangchao AU - Sun, Jun AU - Sun, Kang AU - Sun, Meng Xiang AU - Sun, Qiming AU - Sun, Yi AU - Sun, Zhongjie AU - Sunahara, Karen K.S. AU - Sundberg, Eva AU - Susztak, Katalin AU - Sutovsky, Peter AU - Suzuki, Hidekazu AU - Sweeney, Gary AU - Symons, J. David AU - Sze, Stephen Cho Wing AU - Szewczyk, Nathaniel J. AU - Tabęcka-Łonczynska, Anna AU - Tabolacci, Claudio AU - Tacke, Frank AU - Taegtmeyer, Heinrich AU - Tafani, Marco AU - Tagaya, Mitsuo AU - Tai, Haoran AU - Tait, Stephen W.G. AU - Takahashi, Yoshinori AU - Takats, Szabolcs AU - Talwar, Priti AU - Tam, Chit AU - Tam, Shing Yau AU - Tampellini, Davide AU - Tamura, Atsushi AU - Tan, Chong Teik AU - Tan, Eng King AU - Tan, Ya Qin AU - Tanaka, Masaki AU - Tanaka, Motomasa AU - Tang, Daolin AU - Tang, Jingfeng AU - Tang, Tie Shan AU - Tanida, Isei AU - Tao, Zhipeng AU - Taouis, Mohammed AU - Tatenhorst, Lars AU - Tavernarakis, Nektarios AU - Taylor, Allen AU - Taylor, Gregory A. AU - Taylor, Joan M. AU - Tchetina, Elena AU - Tee, Andrew R. AU - Tegeder, Irmgard AU - Teis, David AU - Teixeira, Natercia AU - Teixeira-Clerc, Fatima AU - Tekirdag, Kumsal A. AU - Tencomnao, Tewin AU - Tenreiro, Sandra AU - Tepikin, Alexei V. AU - Testillano, Pilar S. AU - Tettamanti, Gianluca AU - Tharaux, Pierre Louis AU - Thedieck, Kathrin AU - Thekkinghat, Arvind A. AU - Thellung, Stefano AU - Thinwa, Josephine W. AU - Thirumalaikumar, V. P. AU - Thomas, Sufi Mary AU - Thomes, Paul G. AU - Thorburn, Andrew AU - Thukral, Lipi AU - Thum, Thomas AU - Thumm, Michael AU - Tian, Ling AU - Tichy, Ales AU - Till, Andreas AU - Timmerman, Vincent AU - Titorenko, Vladimir I. AU - Todi, Sokol V. AU - Todorova, Krassimira AU - Toivonen, Janne M. AU - Tomaipitinca, Luana AU - Tomar, Dhanendra AU - Tomas-Zapico, Cristina AU - Tomić, Sergej AU - Tong, Benjamin Chun Kit AU - Tong, Chao AU - Tong, Xin AU - Tooze, Sharon A. AU - Torgersen, Maria L. AU - Torii, Satoru AU - Torres-López, Liliana AU - Torriglia, Alicia AU - Towers, Christina G. AU - Towns, Roberto AU - Toyokuni, Shinya AU - Trajkovic, Vladimir AU - Tramontano, Donatella AU - Tran, Quynh Giao AU - Travassos, Leonardo H. AU - Trelford, Charles B. AU - Tremel, Shirley AU - Trougakos, Ioannis P. AU - Tsao, Betty P. AU - Tschan, Mario P. AU - Tse, Hung Fat AU - Tse, Tak Fu AU - Tsugawa, Hitoshi AU - Tsvetkov, Andrey S. AU - Tumbarello, David A. AU - Tumtas, Yasin AU - Tuñón, María J. AU - Turcotte, Sandra AU - Turk, Boris AU - Turk, Vito AU - Turner, Bradley J. AU - Tuxworth, Richard I. AU - Tyler, Jessica K. AU - Tyutereva, Elena V. AU - Uchiyama, Yasuo AU - Ugun-Klusek, Aslihan AU - Uhlig, Holm H. AU - Ułamek-Kozioł, Marzena AU - Ulasov, Ilya V. AU - Umekawa, Midori AU - Ungermann, Christian AU - Unno, Rei AU - Urbe, Sylvie AU - Uribe-Carretero, Elisabet AU - Üstün, Suayib AU - Uversky, Vladimir N. AU - Vaccari, Thomas AU - Vaccaro, Maria I. AU - Vahsen, Björn F. AU - Vakifahmetoglu-Norberg, Helin AU - Valdor, Rut AU - Valente, Maria J. 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AU - Viganó, Sonia AU - Vihinen, Helena AU - Vijayan, Vinoy AU - Vila, Miquel AU - Vilar, Marçal AU - Villalba, José M. AU - Villalobo, Antonio AU - Villarejo-Zori, Beatriz AU - Villarroya, Francesc AU - Villarroya, Joan AU - Vincent, Olivier AU - Vindis, Cecile AU - Viret, Christophe AU - Viscomi, Maria Teresa AU - Visnjic, Dora AU - Vitale, Ilio AU - Vocadlo, David J. AU - Voitsekhovskaja, Olga V. AU - Volonté, Cinzia AU - Volta, Mattia AU - Vomero, Marta AU - Von Haefen, Clarissa AU - Vooijs, Marc A. AU - Voos, Wolfgang AU - Vucicevic, Ljubica AU - Wade-Martins, Richard AU - Waguri, Satoshi AU - Waite, Kenrick A. AU - Wakatsuki, Shuji AU - Walker, David W. AU - Walker, Mark J. AU - Walker, Simon A. AU - Walter, Jochen AU - Wandosell, Francisco G. 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AU - Wang, Wen Tao AU - Wang, Wuyang AU - Wang, Xinnan AU - Wang, Xuejun AU - Wang, Yan AU - Wang, Yanchang AU - Wang, Yanzhuang AU - Wang, Yen Yun AU - Wang, Yihua AU - Wang, Yipeng AU - Wang, Yu AU - Wang, Yuqi AU - Wang, Zhe AU - Wang, Zhenyu AU - Wang, Zhouguang AU - Warnes, Gary AU - Warnsmann, Verena AU - Watada, Hirotaka AU - Watanabe, Eizo AU - Watchon, Maxinne AU - Wawrzyńska, Anna AU - Weaver, Timothy E. AU - Wegrzyn, Grzegorz AU - Wehman, Ann M. AU - Wei, Huafeng AU - Wei, Lei AU - Wei, Taotao AU - Wei, Yongjie AU - Weiergräber, Oliver H. AU - Weihl, Conrad C. AU - Weindl, Günther AU - Weiskirchen, Ralf AU - Wells, Alan AU - Wen, Runxia H. AU - Wen, Xin AU - Werner, Antonia AU - Weykopf, Beatrice AU - Wheatley, Sally P. AU - Whitton, J. Lindsay AU - Whitworth, Alexander J. AU - Wiktorska, Katarzyna AU - Wildenberg, Manon E. AU - Wileman, Tom AU - Wilkinson, Simon AU - Willbold, Dieter AU - Williams, Brett AU - Williams, Robin S.B. AU - Williams, Roger L. AU - Williamson, Peter R. AU - Wilson, Richard A. AU - Winner, Beate AU - Winsor, Nathaniel J. AU - Witkin, Steven S. AU - Wodrich, Harald AU - Woehlbier, Ute AU - Wollert, Thomas AU - Wong, Esther AU - Wong, Jack Ho AU - Wong, Richard W. AU - Wong, Vincent Kam Wai AU - Wong, W. Wei Lynn AU - Wu, An Guo AU - Wu, Chengbiao AU - Wu, Jian AU - Wu, Junfang AU - Wu, Kenneth K. AU - Wu, Min AU - Wu, Shan Ying AU - Wu, Shengzhou AU - Wu, Shu Yan AU - Wu, Shufang AU - Wu, William K.K. AU - Wu, Xiaohong AU - Wu, Xiaoqing AU - Wu, Yao Wen AU - Wu, Yihua AU - Xavier, Ramnik J. AU - Xia, Hongguang AU - Xia, Lixin AU - Xia, Zhengyuan AU - Xiang, Ge AU - Xiang, Jin AU - Xiang, Mingliang AU - Xiang, Wei AU - Xiao, Bin AU - Xiao, Guozhi AU - Xiao, Hengyi AU - Xiao, Hong Tao AU - Xiao, Jian AU - Xiao, Lan AU - Xiao, Shi AU - Xiao, Yin AU - Xie, Baoming AU - Xie, Chuan Ming AU - Xie, Min AU - Xie, Yuxiang AU - Xie, Zhiping AU - Xie, Zhonglin AU - Xilouri, Maria AU - Xu, Congfeng AU - Xu, En AU - Xu, Haoxing AU - Xu, Jing AU - Xu, Jin Rong AU - Xu, Liang AU - Xu, Wen Wen AU - Xu, Xiulong AU - Xue, Yu AU - Yakhine-Diop, Sokhna M.S. AU - Yamaguchi, Masamitsu AU - Yamaguchi, Osamu AU - Yamamoto, Ai AU - Yamashina, Shunhei AU - Yan, Shengmin AU - Yan, Shian Jang AU - Yan, Zhen AU - Yanagi, Yasuo AU - Yang, Chuanbin AU - Yang, Dun Sheng AU - Yang, Huan AU - Yang, Huang Tian AU - Yang, Hui AU - Yang, Jin Ming AU - Yang, Jing AU - Yang, Jingyu AU - Yang, Ling AU - Yang, Liu AU - Yang, Ming AU - Yang, Pei Ming AU - Yang, Qian AU - Yang, Seungwon AU - Yang, Shu AU - Yang, Shun Fa AU - Yang, Wannian AU - Yang, Wei Yuan AU - Yang, Xiaoyong AU - Yang, Xuesong AU - Yang, Yi AU - Yang, Ying AU - Yao, Honghong AU - Yao, Shenggen AU - Yao, Xiaoqiang AU - Yao, Yong Gang AU - Yao, Yong Ming AU - Yasui, Takahiro AU - Yazdankhah, Meysam AU - Yen, Paul M. AU - Yi, Cong AU - Yin, Xiao Ming AU - Yin, Yanhai AU - Yin, Zhangyuan AU - Yin, Ziyi AU - Ying, Meidan AU - Ying, Zheng AU - Yip, Calvin K. AU - Yiu, Stephanie Pei Tung AU - Yoo, Young H. AU - Yoshida, Kiyotsugu AU - Yoshii, Saori R. AU - Yoshimori, Tamotsu AU - Yousefi, Bahman AU - Yu, Boxuan AU - Yu, Haiyang AU - Yu, Jun AU - Yu, Jun AU - Yu, Li AU - Yu, Ming Lung AU - Yu, Seong Woon AU - Yu, Victor C. AU - Yu, W. Haung AU - Yu, Zhengping AU - Yu, Zhou AU - Yuan, Junying AU - Yuan, Ling Qing AU - Yuan, Shilin AU - Yuan, Shyng Shiou F. AU - Yuan, Yanggang AU - Yuan, Zengqiang AU - Yue, Jianbo AU - Yue, Zhenyu AU - Yun, Jeanho AU - Yung, Raymond L. AU - Zacks, David N. AU - Zaffagnini, Gabriele AU - Zambelli, Vanessa O. AU - Zanella, Isabella AU - Zang, Qun S. AU - Zanivan, Sara AU - Zappavigna, Silvia AU - Zaragoza, Pilar AU - Zarbalis, Konstantinos S. AU - Zarebkohan, Amir AU - Zarrouk, Amira AU - Zeitlin, Scott O. AU - Zeng, Jialiu AU - Zeng, Ju Deng AU - Žerovnik, Eva AU - Zhan, Lixuan AU - Zhang, Bin AU - Zhang, Donna D. AU - Zhang, Hanlin AU - Zhang, Hong AU - Zhang, Hong AU - Zhang, Honghe AU - Zhang, Huafeng AU - Zhang, Huaye AU - Zhang, Hui AU - Zhang, Hui Ling AU - Zhang, Jianbin AU - Zhang, Jianhua AU - Zhang, Jing Pu AU - Zhang, Kalin Y.B. AU - Zhang, Leshuai W. AU - Zhang, Lin AU - Zhang, Lisheng AU - Zhang, Lu AU - Zhang, Luoying AU - Zhang, Menghuan AU - Zhang, Peng AU - Zhang, Sheng AU - Zhang, Wei AU - Zhang, Xiangnan AU - Zhang, Xiao Wei AU - Zhang, Xiaolei AU - Zhang, Xiaoyan AU - Zhang, Xin AU - Zhang, Xinxin AU - Zhang, Xu Dong AU - Zhang, Yang AU - Zhang, Yanjin AU - Zhang, Yi AU - Zhang, Ying Dong AU - Zhang, Yingmei AU - Zhang, Yuan Yuan AU - Zhang, Yuchen AU - Zhang, Zhe AU - Zhang, Zhengguang AU - Zhang, Zhibing AU - Zhang, Zhihai AU - Zhang, Zhiyong AU - Zhang, Zili AU - Zhao, Haobin AU - Zhao, Lei AU - Zhao, Shuang AU - Zhao, Tongbiao AU - Zhao, Xiao Fan AU - Zhao, Ying AU - Zhao, Yongchao AU - Zhao, Yongliang AU - Zhao, Yuting AU - Zheng, Guoping AU - Zheng, Kai AU - Zheng, Ling AU - Zheng, Shizhong AU - Zheng, Xi Long AU - Zheng, Yi AU - Zheng, Zu Guo AU - Zhivotovsky, Boris AU - Zhong, Qing AU - Zhou, Ao AU - Zhou, Ben AU - Zhou, Cefan AU - Zhou, Gang AU - Zhou, Hao AU - Zhou, Hong AU - Zhou, Hongbo AU - Zhou, Jie AU - Zhou, Jing AU - Zhou, Jing AU - Zhou, Jiyong AU - Zhou, Kailiang AU - Zhou, Rongjia AU - Zhou, Xu Jie AU - Zhou, Yanshuang AU - Zhou, Yinghong AU - Zhou, Yubin AU - Zhou, Zheng Yu AU - Zhou, Zhou AU - Zhu, Binglin AU - Zhu, Changlian AU - Zhu, Guo Qing AU - Zhu, Haining AU - Zhu, Hongxin AU - Zhu, Hua AU - Zhu, Wei Guo AU - Zhu, Yanping AU - Zhu, Yushan AU - Zhuang, Haixia AU - Zhuang, Xiaohong AU - Zientara-Rytter, Katarzyna AU - Zimmermann, Christine M. AU - Ziviani, Elena AU - Zoladek, Teresa AU - Zong, Wei Xing AU - Zorov, Dmitry B. AU - Zorzano, Antonio AU - Zou, Weiping AU - Zou, Zhen AU - Zou, Zhengzhi AU - Zuryn, Steven AU - Zwerschke, Werner AU - Brand-Saberi, Beate AU - Dong, X. Charlie AU - Kenchappa, Chandra Shekar AU - Li, Zuguo AU - Lin, Yong AU - Oshima, Shigeru AU - Rong, Yueguang AU - Sluimer, Judith C. AU - Stallings, Christina L. AU - Tong, Chun Kit ID - 9298 IS - 1 JF - Autophagy SN - 1554-8627 TI - Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) VL - 17 ER - TY - JOUR AB - We develop a version of Ekedahl’s geometric sieve for integral quadratic forms of rank at least five. As one ranges over the zeros of such quadratic forms, we use the sieve to compute the density of coprime values of polynomials, and furthermore, to address a question about local solubility in families of varieties parameterised by the zeros. AU - Browning, Timothy D AU - Heath-Brown, Roger ID - 8742 IS - 1 JF - Forum Mathematicum SN - 0933-7741 TI - The geometric sieve for quadrics VL - 33 ER - TY - THES AB - Many security definitions come in two flavors: a stronger “adaptive” flavor, where the adversary can arbitrarily make various choices during the course of the attack, and a weaker “selective” flavor where the adversary must commit to some or all of their choices a-priori. For example, in the context of identity-based encryption, selective security requires the adversary to decide on the identity of the attacked party at the very beginning of the game whereas adaptive security allows the attacker to first see the master public key and some secret keys before making this choice. Often, it appears to be much easier to achieve selective security than it is to achieve adaptive security. A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption [Pan07][FJP15], constrained PRFs [FKPR14], and Yao’s garbled circuits [JW16]. Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework (published at Crypto ’17 [JKK+17a]) that connects all of these works and allows us to present them in a unified and simplified fashion. Having the framework in place, we show how to achieve adaptive security for proxy re-encryption schemes (published at PKC ’19 [FKKP19]) and provide the first adaptive security proofs for continuous group key agreement protocols (published at S&P ’21 [KPW+21]). Questioning optimality of our framework, we then show that currently used proof techniques cannot lead to significantly better security guarantees for "graph-building" games (published at TCC ’21 [KKPW21a]). These games cover generalized selective decryption, as well as the security of prominent constructions for constrained PRFs, continuous group key agreement, and proxy re-encryption. Finally, we revisit the adaptive security of Yao’s garbled circuits and extend the analysis of Jafargholi and Wichs in two directions: While they prove adaptive security only for a modified construction with increased online complexity, we provide the first positive results for the original construction by Yao (published at TCC ’21 [KKP21a]). On the negative side, we prove that the results of Jafargholi and Wichs are essentially optimal by showing that no black-box reduction can provide a significantly better security bound (published at Crypto ’21 [KKPW21c]). AU - Klein, Karen ID - 10035 SN - 2663-337X TI - On the adaptive security of graph-based games ER - TY - CONF AB - The security of cryptographic primitives and protocols against adversaries that are allowed to make adaptive choices (e.g., which parties to corrupt or which queries to make) is notoriously difficult to establish. A broad theoretical framework was introduced by Jafargholi et al. [Crypto’17] for this purpose. In this paper we initiate the study of lower bounds on loss in adaptive security for certain cryptographic protocols considered in the framework. We prove lower bounds that almost match the upper bounds (proven using the framework) for proxy re-encryption, prefix-constrained PRFs and generalized selective decryption, a security game that captures the security of certain group messaging and broadcast encryption schemes. Those primitives have in common that their security game involves an underlying graph that can be adaptively built by the adversary. Some of our lower bounds only apply to a restricted class of black-box reductions which we term “oblivious” (the existing upper bounds are of this restricted type), some apply to the broader but still restricted class of non-rewinding reductions, while our lower bound for proxy re-encryption applies to all black-box reductions. The fact that some of our lower bounds seem to crucially rely on obliviousness or at least a non-rewinding reduction hints to the exciting possibility that the existing upper bounds can be improved by using more sophisticated reductions. Our main conceptual contribution is a two-player multi-stage game called the Builder-Pebbler Game. We can translate bounds on the winning probabilities for various instantiations of this game into cryptographic lower bounds for the above-mentioned primitives using oracle separation techniques. AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Pietrzak, Krzysztof Z AU - Walter, Michael ID - 10410 SN - 0302-9743 T2 - 19th International Conference TI - The cost of adaptivity in security games on graphs VL - 13043 ER - TY - CONF AB - The security of cryptographic primitives and protocols against adversaries that are allowed to make adaptive choices (e.g., which parties to corrupt or which queries to make) is notoriously difficult to establish. A broad theoretical framework was introduced by Jafargholi et al. [Crypto’17] for this purpose. In this paper we initiate the study of lower bounds on loss in adaptive security for certain cryptographic protocols considered in the framework. We prove lower bounds that almost match the upper bounds (proven using the framework) for proxy re-encryption, prefix-constrained PRFs and generalized selective decryption, a security game that captures the security of certain group messaging and broadcast encryption schemes. Those primitives have in common that their security game involves an underlying graph that can be adaptively built by the adversary. Some of our lower bounds only apply to a restricted class of black-box reductions which we term “oblivious” (the existing upper bounds are of this restricted type), some apply to the broader but still restricted class of non-rewinding reductions, while our lower bound for proxy re-encryption applies to all black-box reductions. The fact that some of our lower bounds seem to crucially rely on obliviousness or at least a non-rewinding reduction hints to the exciting possibility that the existing upper bounds can be improved by using more sophisticated reductions. Our main conceptual contribution is a two-player multi-stage game called the Builder-Pebbler Game. We can translate bounds on the winning probabilities for various instantiations of this game into cryptographic lower bounds for the above-mentioned primitives using oracle separation techniques. AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Pietrzak, Krzysztof Z AU - Walter, Michael ID - 10048 T2 - 19th Theory of Cryptography Conference 2021 TI - The cost of adaptivity in security games on graphs ER - TY - JOUR AB - We prove an adiabatic theorem for the Landau–Pekar equations. This allows us to derive new results on the accuracy of their use as effective equations for the time evolution generated by the Fröhlich Hamiltonian with large coupling constant α. In particular, we show that the time evolution of Pekar product states with coherent phonon field and the electron being trapped by the phonons is well approximated by the Landau–Pekar equations until times short compared to α2. AU - Leopold, Nikolai K AU - Rademacher, Simone Anna Elvira AU - Schlein, Benjamin AU - Seiringer, Robert ID - 10738 IS - 7 JF - Analysis and PDE SN - 2157-5045 TI - The Landau–Pekar equations: Adiabatic theorem and accuracy VL - 14 ER - TY - THES AB - The scalability of concurrent data structures and distributed algorithms strongly depends on reducing the contention for shared resources and the costs of synchronization and communication. We show how such cost reductions can be attained by relaxing the strict consistency conditions required by sequential implementations. In the first part of the thesis, we consider relaxation in the context of concurrent data structures. Specifically, in data structures such as priority queues, imposing strong semantics renders scalability impossible, since a correct implementation of the remove operation should return only the element with highest priority. Intuitively, attempting to invoke remove operations concurrently creates a race condition. This bottleneck can be circumvented by relaxing semantics of the affected data structure, thus allowing removal of the elements which are no longer required to have the highest priority. We prove that the randomized implementations of relaxed data structures provide provable guarantees on the priority of the removed elements even under concurrency. Additionally, we show that in some cases the relaxed data structures can be used to scale the classical algorithms which are usually implemented with the exact ones. In the second part, we study parallel variants of the stochastic gradient descent (SGD) algorithm, which distribute computation among the multiple processors, thus reducing the running time. Unfortunately, in order for standard parallel SGD to succeed, each processor has to maintain a local copy of the necessary model parameter, which is identical to the local copies of other processors; the overheads from this perfect consistency in terms of communication and synchronization can negate the speedup gained by distributing the computation. We show that the consistency conditions required by SGD can be relaxed, allowing the algorithm to be more flexible in terms of tolerating quantized communication, asynchrony, or even crash faults, while its convergence remains asymptotically the same. AU - Nadiradze, Giorgi ID - 10429 SN - 2663-337X TI - On achieving scalability through relaxation ER - TY - CONF AB - Decentralized optimization is emerging as a viable alternative for scalable distributed machine learning, but also introduces new challenges in terms of synchronization costs. To this end, several communication-reduction techniques, such as non-blocking communication, quantization, and local steps, have been explored in the decentralized setting. Due to the complexity of analyzing optimization in such a relaxed setting, this line of work often assumes \emph{global} communication rounds, which require additional synchronization. In this paper, we consider decentralized optimization in the simpler, but harder to analyze, \emph{asynchronous gossip} model, in which communication occurs in discrete, randomly chosen pairings among nodes. Perhaps surprisingly, we show that a variant of SGD called \emph{SwarmSGD} still converges in this setting, even if \emph{non-blocking communication}, \emph{quantization}, and \emph{local steps} are all applied \emph{in conjunction}, and even if the node data distributions and underlying graph topology are both \emph{heterogenous}. Our analysis is based on a new connection with multi-dimensional load-balancing processes. We implement this algorithm and deploy it in a super-computing environment, showing that it can outperform previous decentralized methods in terms of end-to-end training time, and that it can even rival carefully-tuned large-batch SGD for certain tasks. AU - Nadiradze, Giorgi AU - Sabour, Amirmojtaba AU - Davies, Peter AU - Li, Shigang AU - Alistarh, Dan-Adrian ID - 10435 T2 - 35th Conference on Neural Information Processing Systems TI - Asynchronous decentralized SGD with quantized and local updates ER - TY - CONF AB - We study the problem of estimating a rank-$1$ signal in the presence of rotationally invariant noise-a class of perturbations more general than Gaussian noise. Principal Component Analysis (PCA) provides a natural estimator, and sharp results on its performance have been obtained in the high-dimensional regime. Recently, an Approximate Message Passing (AMP) algorithm has been proposed as an alternative estimator with the potential to improve the accuracy of PCA. However, the existing analysis of AMP requires an initialization that is both correlated with the signal and independent of the noise, which is often unrealistic in practice. In this work, we combine the two methods, and propose to initialize AMP with PCA. Our main result is a rigorous asymptotic characterization of the performance of this estimator. Both the AMP algorithm and its analysis differ from those previously derived in the Gaussian setting: at every iteration, our AMP algorithm requires a specific term to account for PCA initialization, while in the Gaussian case, PCA initialization affects only the first iteration of AMP. The proof is based on a two-phase artificial AMP that first approximates the PCA estimator and then mimics the true AMP. Our numerical simulations show an excellent agreement between AMP results and theoretical predictions, and suggest an interesting open direction on achieving Bayes-optimal performance. AU - Mondelli, Marco AU - Venkataramanan, Ramji ID - 10593 SN - 1049-5258 T2 - 35th Conference on Neural Information Processing Systems TI - PCA initialization for approximate message passing in rotationally invariant models VL - 35 ER - TY - CONF AB - The question of how and why the phenomenon of mode connectivity occurs in training deep neural networks has gained remarkable attention in the research community. From a theoretical perspective, two possible explanations have been proposed: (i) the loss function has connected sublevel sets, and (ii) the solutions found by stochastic gradient descent are dropout stable. While these explanations provide insights into the phenomenon, their assumptions are not always satisfied in practice. In particular, the first approach requires the network to have one layer with order of N neurons (N being the number of training samples), while the second one requires the loss to be almost invariant after removing half of the neurons at each layer (up to some rescaling of the remaining ones). In this work, we improve both conditions by exploiting the quality of the features at every intermediate layer together with a milder over-parameterization condition. More specifically, we show that: (i) under generic assumptions on the features of intermediate layers, it suffices that the last two hidden layers have order of N−−√ neurons, and (ii) if subsets of features at each layer are linearly separable, then no over-parameterization is needed to show the connectivity. Our experiments confirm that the proposed condition ensures the connectivity of solutions found by stochastic gradient descent, even in settings where the previous requirements do not hold. AU - Nguyen, Quynh AU - Bréchet, Pierre AU - Mondelli, Marco ID - 10594 SN - 1049-5258 T2 - 35th Conference on Neural Information Processing Systems TI - When are solutions connected in deep networks? VL - 35 ER - TY - JOUR AB - The quantum bits (qubits) on which superconducting quantum computers are based have energy scales corresponding to photons with GHz frequencies. The energy of photons in the gigahertz domain is too low to allow transmission through the noisy room-temperature environment, where the signal would be lost in thermal noise. Optical photons, on the other hand, have much higher energies, and signals can be detected using highly efficient single-photon detectors. Transduction from microwave to optical frequencies is therefore a potential enabling technology for quantum devices. However, in such a device the optical pump can be a source of thermal noise and thus degrade the fidelity; the similarity of input microwave state to the output optical state. In order to investigate the magnitude of this effect we model the sub-Kelvin thermal behavior of an electro-optic transducer based on a lithium niobate whispering gallery mode resonator. We find that there is an optimum power level for a continuous pump, whilst pulsed operation of the pump increases the fidelity of the conversion. AU - Mobassem, Sonia AU - Lambert, Nicholas J. AU - Rueda Sanchez, Alfredo R AU - Fink, Johannes M AU - Leuchs, Gerd AU - Schwefel, Harald G.L. ID - 9815 IS - 4 JF - Quantum Science and Technology TI - Thermal noise in electro-optic devices at cryogenic temperatures VL - 6 ER - TY - GEN AB - Redox mediators could catalyse otherwise slow and energy-inefficient cycling of Li-S and Li-O 2 batteries by shuttling electrons/holes between the electrode and the solid insulating storage materials. For mediators to work efficiently they need to oxidize the solid with fast kinetics yet the lowest possible overpotential. Here, we found that when the redox potentials of mediators are tuned via, e.g., Li + concentration in the electrolyte, they exhibit distinct threshold potentials, where the kinetics accelerate several-fold within a range as small as 10 mV. This phenomenon is independent of types of mediators and electrolyte. The acceleration originates from the overpotentials required to activate fast Li + /e – extraction and the following chemical step at specific abundant surface facets. Efficient redox catalysis at insulating solids requires therefore carefully considering the surface conditions of the storage materials and electrolyte-dependent redox potentials, which may be tuned by salt concentrations or solvents. AU - Cao, Deqing AU - Shen, Xiaoxiao AU - Wang, Aiping AU - Yu, Fengjiao AU - Wu, Yuping AU - Shi, Siqi AU - Freunberger, Stefan Alexander AU - Chen, Yuhui ID - 9978 KW - Catalysis KW - Energy engineering KW - Materials theory and modeling T2 - Research Square TI - Sharp kinetic acceleration potentials during mediated redox catalysis of insulators ER - TY - JOUR AB - P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict at the blood–brain barrier (BBB) the brain distribution of the majority of currently known molecularly targeted anticancer drugs. To improve brain delivery of dual ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques with PET. Tolerability of the erlotinib/tariquidar combination was assessed in human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3). Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar alone led to less pronounced VT,brain increases in both species. Treatment of cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly targeted anticancer drugs for a more effective treatment of brain tumors. AU - Tournier, N AU - Goutal, S AU - Mairinger, S AU - Lozano, IH AU - Filip, T AU - Sauberer, M AU - Caillé, F AU - Breuil, L AU - Stanek, J AU - Freeman, AF AU - Novarino, Gaia AU - Truillet, C AU - Wanek, T AU - Langer, O ID - 8730 IS - 7 JF - Journal of Cerebral Blood Flow and Metabolism SN - 0271-678x TI - Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib VL - 41 ER - TY - JOUR AB - A primary roadblock to our understanding of speciation is that it usually occurs over a timeframe that is too long to study from start to finish. The idea of a speciation continuum provides something of a solution to this problem; rather than observing the entire process, we can simply reconstruct it from the multitude of speciation events that surround us. But what do we really mean when we talk about the speciation continuum, and can it really help us understand speciation? We explored these questions using a literature review and online survey of speciation researchers. Although most researchers were familiar with the concept and thought it was useful, our survey revealed extensive disagreement about what the speciation continuum actually tells us. This is due partly to the lack of a clear definition. Here, we provide an explicit definition that is compatible with the Biological Species Concept. That is, the speciation continuum is a continuum of reproductive isolation. After outlining the logic of the definition in light of alternatives, we explain why attempts to reconstruct the speciation process from present‐day populations will ultimately fail. We then outline how we think the speciation continuum concept can continue to act as a foundation for understanding the continuum of reproductive isolation that surrounds us. AU - Stankowski, Sean AU - Ravinet, Mark ID - 9383 IS - 6 JF - Evolution SN - 0014-3820 TI - Defining the speciation continuum VL - 75 ER - TY - JOUR AB - Growth regulation tailors development in plants to their environment. A prominent example of this is the response to gravity, in which shoots bend up and roots bend down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phosphoproteomics in Arabidopsis thaliana, we advance understanding of how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on rapid regulation of apoplastic pH, a causative determinant of growth. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+ influx, causing apoplast alkalinization. Simultaneous activation of these two counteracting mechanisms poises roots for rapid, fine-tuned growth modulation in navigating complex soil environments. AU - Li, Lanxin AU - Verstraeten, Inge AU - Roosjen, Mark AU - Takahashi, Koji AU - Rodriguez Solovey, Lesia AU - Merrin, Jack AU - Chen, Jian AU - Shabala, Lana AU - Smet, Wouter AU - Ren, Hong AU - Vanneste, Steffen AU - Shabala, Sergey AU - De Rybel, Bert AU - Weijers, Dolf AU - Kinoshita, Toshinori AU - Gray, William M. AU - Friml, Jiří ID - 10223 IS - 7884 JF - Nature KW - Multidisciplinary SN - 00280836 TI - Cell surface and intracellular auxin signalling for H+ fluxes in root growth VL - 599 ER - TY - JOUR AB - When B cells encounter membrane-bound antigens, the formation and coalescence of B cell antigen receptor (BCR) microclusters amplifies BCR signaling. The ability of B cells to probe the surface of antigen-presenting cells (APCs) and respond to APC-bound antigens requires remodeling of the actin cytoskeleton. Initial BCR signaling stimulates actin-related protein (Arp) 2/3 complex-dependent actin polymerization, which drives B cell spreading as well as the centripetal movement and coalescence of BCR microclusters at the B cell-APC synapse. Sustained actin polymerization depends on concomitant actin filament depolymerization, which enables the recycling of actin monomers and Arp2/3 complexes. Cofilin-mediated severing of actin filaments is a rate-limiting step in the morphological changes that occur during immune synapse formation. Hence, regulators of cofilin activity such as WD repeat-containing protein 1 (Wdr1), LIM domain kinase (LIMK), and coactosin-like 1 (Cotl1) may also be essential for actin-dependent processes in B cells. Wdr1 enhances cofilin-mediated actin disassembly. Conversely, Cotl1 competes with cofilin for binding to actin and LIMK phosphorylates cofilin and prevents it from binding to actin filaments. We now show that Wdr1 and LIMK have distinct roles in BCR-induced assembly of the peripheral actin structures that drive B cell spreading, and that cofilin, Wdr1, and LIMK all contribute to the actin-dependent amplification of BCR signaling at the immune synapse. Depleting Cotl1 had no effect on these processes. Thus, the Wdr1-LIMK-cofilin axis is critical for BCR-induced actin remodeling and for B cell responses to APC-bound antigens. AU - Bolger-Munro, Madison AU - Choi, Kate AU - Cheung, Faith AU - Liu, Yi Tian AU - Dang-Lawson, May AU - Deretic, Nikola AU - Keane, Connor AU - Gold, Michael R. ID - 9379 JF - Frontiers in Cell and Developmental Biology KW - B cell KW - actin KW - immune synapse KW - cell spreading KW - cofilin KW - WDR1 (AIP1) KW - LIM domain kinase KW - B cell receptor (BCR) TI - The Wdr1-LIMK-Cofilin axis controls B cell antigen receptor-induced actin remodeling and signaling at the immune synapse VL - 9 ER - TY - JOUR AB - A central goal in systems neuroscience is to understand the functions performed by neural circuits. Previous top-down models addressed this question by comparing the behaviour of an ideal model circuit, optimised to perform a given function, with neural recordings. However, this requires guessing in advance what function is being performed, which may not be possible for many neural systems. To address this, we propose an inverse reinforcement learning (RL) framework for inferring the function performed by a neural network from data. We assume that the responses of each neuron in a network are optimised so as to drive the network towards ‘rewarded’ states, that are desirable for performing a given function. We then show how one can use inverse RL to infer the reward function optimised by the network from observing its responses. This inferred reward function can be used to predict how the neural network should adapt its dynamics to perform the same function when the external environment or network structure changes. This could lead to theoretical predictions about how neural network dynamics adapt to deal with cell death and/or varying sensory stimulus statistics. AU - Chalk, Matthew J AU - Tkačik, Gašper AU - Marre, Olivier ID - 9362 IS - 4 JF - PLoS ONE TI - Inferring the function performed by a recurrent neural network VL - 16 ER - TY - JOUR AB - Size control is a fundamental question in biology, showing incremental complexity in plants, whose cells possess a rigid cell wall. The phytohormone auxin is a vital growth regulator with central importance for differential growth control. Our results indicate that auxin-reliant growth programs affect the molecular complexity of xyloglucans, the major type of cell wall hemicellulose in eudicots. Auxin-dependent induction and repression of growth coincide with reduced and enhanced molecular complexity of xyloglucans, respectively. In agreement with a proposed function in growth control, genetic interference with xyloglucan side decorations distinctly modulates auxin-dependent differential growth rates. Our work proposes that auxin-dependent growth programs have a spatially defined effect on xyloglucan’s molecular structure, which in turn affects cell wall mechanics and specifies differential, gravitropic hypocotyl growth. AU - Velasquez, Silvia Melina AU - Guo, Xiaoyuan AU - Gallemi, Marçal AU - Aryal, Bibek AU - Venhuizen, Peter AU - Barbez, Elke AU - Dünser, Kai Alexander AU - Darino, Martin AU - Pӗnčík, Aleš AU - Novák, Ondřej AU - Kalyna, Maria AU - Mouille, Gregory AU - Benková, Eva AU - Bhalerao, Rishikesh P. AU - Mravec, Jozef AU - Kleine-Vehn, Jürgen ID - 9986 IS - 17 JF - International Journal of Molecular Sciences KW - auxin KW - growth KW - cell wall KW - xyloglucans KW - hypocotyls KW - gravitropism SN - 1661-6596 TI - Xyloglucan remodeling defines auxin-dependent differential tissue expansion in plants VL - 22 ER - TY - JOUR AB - Transposable elements exist widely throughout plant genomes and play important roles in plant evolution. Auxin is an important regulator that is traditionally associated with root development and drought stress adaptation. The DEEPER ROOTING 1 (DRO1) gene is a key component of rice drought avoidance. Here, we identified a transposon that acts as an autonomous auxin‐responsive promoter and its presence at specific genome positions conveys physiological adaptations related to drought avoidance. Rice varieties with high and auxin‐mediated transcription of DRO1 in the root tip show deeper and longer root phenotypes and are thus better adapted to drought. The INDITTO2 transposon contains an auxin response element and displays auxin‐responsive promoter activity; it is thus able to convey auxin regulation of transcription to genes in its proximity. In the rice Acuce, which displays DRO1‐mediated drought adaptation, the INDITTO2 transposon was found to be inserted at the promoter region of the DRO1 locus. Transgenesis‐based insertion of the INDITTO2 transposon into the DRO1 promoter of the non‐adapted rice variety Nipponbare was sufficient to promote its drought avoidance. Our data identify an example of how transposons can act as promoters and convey hormonal regulation to nearby loci, improving plant fitness in response to different abiotic stresses. AU - Zhao, Y AU - Wu, L AU - Fu, Q AU - Wang, D AU - Li, J AU - Yao, B AU - Yu, S AU - Jiang, L AU - Qian, J AU - Zhou, X AU - Han, L AU - Zhao, S AU - Ma, C AU - Zhang, Y AU - Luo, C AU - Dong, Q AU - Li, S AU - Zhang, L AU - Jiang, X AU - Li, Y AU - Luo, H AU - Li, K AU - Yang, J AU - Luo, Q AU - Li, L AU - Peng, S AU - Huang, H AU - Zuo, Z AU - Liu, C AU - Wang, L AU - Li, C AU - He, X AU - Friml, Jiří AU - Du, Y ID - 9189 IS - 6 JF - Plant, Cell & Environment SN - 0140-7791 TI - INDITTO2 transposon conveys auxin-mediated DRO1 transcription for rice drought avoidance VL - 44 ER - TY - GEN AB - This paper establishes new connections between many-body quantum systems, One-body Reduced Density Matrices Functional Theory (1RDMFT) and Optimal Transport (OT), by interpreting the problem of computing the ground-state energy of a finite dimensional composite quantum system at positive temperature as a non-commutative entropy regularized Optimal Transport problem. We develop a new approach to fully characterize the dual-primal solutions in such non-commutative setting. The mathematical formalism is particularly relevant in quantum chemistry: numerical realizations of the many-electron ground state energy can be computed via a non-commutative version of Sinkhorn algorithm. Our approach allows to prove convergence and robustness of this algorithm, which, to our best knowledge, were unknown even in the two marginal case. Our methods are based on careful a priori estimates in the dual problem, which we believe to be of independent interest. Finally, the above results are extended in 1RDMFT setting, where bosonic or fermionic symmetry conditions are enforced on the problem. AU - Feliciangeli, Dario AU - Gerolin, Augusto AU - Portinale, Lorenzo ID - 9792 T2 - arXiv TI - A non-commutative entropic optimal transport approach to quantum composite systems at positive temperature ER - TY - JOUR AB - Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency. AU - Maes, Margaret E AU - Wögenstein, Gabriele M. AU - Colombo, Gloria AU - Casado Polanco, Raquel AU - Siegert, Sandra ID - 10655 JF - Molecular Therapy - Methods and Clinical Development TI - Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment VL - 23 ER - TY - JOUR AB - Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally and it degrades the ECM for several weeks. Here, we provide two minimally invasive and transient protocols for microglia-enabled PNN disassembly in mouse cortex: repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes. For complete details on the use and execution of this protocol, please refer to Venturino et al. (2021). AU - Venturino, Alessandro AU - Siegert, Sandra ID - 10565 IS - 4 JF - STAR Protocols TI - Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain VL - 2 ER - TY - JOUR AB - Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021). AU - Amberg, Nicole AU - Hippenmeyer, Simon ID - 10321 IS - 4 JF - STAR Protocols TI - Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers VL - 2 ER - TY - JOUR AB - A precise quantitative description of the ultrastructural characteristics underlying biological mechanisms is often key to their understanding. This is particularly true for dynamic extra- and intracellular filamentous assemblies, playing a role in cell motility, cell integrity, cytokinesis, tissue formation and maintenance. For example, genetic manipulation or modulation of actin regulatory proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural architecture of actin filament-rich cell peripheral structures, such as lamellipodia or filopodia. However, the observed ultrastructural effects often remain subtle and require sufficiently large datasets for appropriate quantitative analysis. The acquisition of such large datasets has been enabled by recent advances in high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates the development of complementary approaches to maximize the extraction of relevant biological information. We have developed a computational toolbox for the semi-automatic quantification of segmented and vectorized filamentous networks from pre-processed cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple experimental conditions. GUI-based components simplify the processing of data and allow users to obtain a large number of ultrastructural parameters describing filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing cryo-ET data of untreated and chemically perturbed branched actin filament networks and that of parallel actin filament arrays. In principle, the computational toolbox presented here is applicable for data analysis comprising any type of filaments in regular (i.e. parallel) or random arrangement. We show that it can ease the identification of key differences between experimental groups and facilitate the in-depth analysis of ultrastructural data in a time-efficient manner. AU - Dimchev, Georgi A AU - Amiri, Behnam AU - Fäßler, Florian AU - Falcke, Martin AU - Schur, Florian KM ID - 10290 IS - 4 JF - Journal of Structural Biology KW - Structural Biology SN - 1047-8477 TI - Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data VL - 213 ER - TY - CONF AB - Payment channel networks are a promising approach to improve the scalability of cryptocurrencies: they allow to perform transactions in a peer-to-peer fashion, along multihop routes in the network, without requiring consensus on the blockchain. However, during the discovery of cost-efficient routes for the transaction, critical information may be revealed about the transacting entities. This paper initiates the study of privacy-preserving route discovery mechanisms for payment channel networks. In particular, we present LightPIR, an approach which allows a client to learn the shortest (or cheapest in terms of fees) path between two nodes without revealing any information about the endpoints of the transaction to the servers. The two main observations which allow for an efficient solution in LightPIR are that: (1) surprisingly, hub labelling algorithms – which were developed to preprocess “street network like” graphs so one can later efficiently compute shortest paths – also perform well for the graphs underlying payment channel networks, and that (2) hub labelling algorithms can be conveniently combined with private information retrieval. LightPIR relies on a simple hub labeling heuristic on top of existing hub labeling algorithms which leverages the specific topological features of cryptocurrency networks to further minimize storage and bandwidth overheads. In a case study considering the Lightning network, we show that our approach is an order of magnitude more efficient compared to a privacy-preserving baseline based on using private information retrieval on a database that stores all pairs shortest paths. AU - Pietrzak, Krzysztof Z AU - Salem, Iosif AU - Schmid, Stefan AU - Yeo, Michelle X ID - 9969 SN - 978-1-6654-4501-6 TI - LightPIR: Privacy-preserving route discovery for payment channel networks ER - TY - CONF AB - We present a new approach to proving non-termination of non-deterministic integer programs. Our technique is rather simple but efficient. It relies on a purely syntactic reversal of the program's transition system followed by a constraint-based invariant synthesis with constraints coming from both the original and the reversed transition system. The latter task is performed by a simple call to an off-the-shelf SMT-solver, which allows us to leverage the latest advances in SMT-solving. Moreover, our method offers a combination of features not present (as a whole) in previous approaches: it handles programs with non-determinism, provides relative completeness guarantees and supports programs with polynomial arithmetic. The experiments performed with our prototype tool RevTerm show that our approach, despite its simplicity and stronger theoretical guarantees, is at least on par with the state-of-the-art tools, often achieving a non-trivial improvement under a proper configuration of its parameters. AU - Chatterjee, Krishnendu AU - Goharshady, Ehsan Kafshdar AU - Novotný, Petr AU - Zikelic, Dorde ID - 9644 SN - 9781450383912 T2 - Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation TI - Proving non-termination by program reversal ER - TY - JOUR AB - The quantum approximate optimization algorithm (QAOA) is a prospective near-term quantum algorithm due to its modest circuit depth and promising benchmarks. However, an external parameter optimization required in the QAOA could become a performance bottleneck. This motivates studies of the optimization landscape and search for heuristic ways of parameter initialization. In this work we visualize the optimization landscape of the QAOA applied to the MaxCut problem on random graphs, demonstrating that random initialization of the QAOA is prone to converging to local minima with suboptimal performance. We introduce the initialization of QAOA parameters based on the Trotterized quantum annealing (TQA) protocol, parameterized by the Trotter time step. We find that the TQA initialization allows to circumvent the issue of false minima for a broad range of time steps, yielding the same performance as the best result out of an exponentially scaling number of random initializations. Moreover, we demonstrate that the optimal value of the time step coincides with the point of proliferation of Trotter errors in quantum annealing. Our results suggest practical ways of initializing QAOA protocols on near-term quantum devices and reveal new connections between QAOA and quantum annealing. AU - Sack, Stefan AU - Serbyn, Maksym ID - 9760 JF - Quantum TI - Quantum annealing initialization of the quantum approximate optimization algorithm VL - 5 ER - TY - CONF AB - We consider the almost-sure (a.s.) termination problem for probabilistic programs, which are a stochastic extension of classical imperative programs. Lexicographic ranking functions provide a sound and practical approach for termination of non-probabilistic programs, and their extension to probabilistic programs is achieved via lexicographic ranking supermartingales (LexRSMs). However, LexRSMs introduced in the previous work have a limitation that impedes their automation: all of their components have to be non-negative in all reachable states. This might result in LexRSM not existing even for simple terminating programs. Our contributions are twofold: First, we introduce a generalization of LexRSMs which allows for some components to be negative. This standard feature of non-probabilistic termination proofs was hitherto not known to be sound in the probabilistic setting, as the soundness proof requires a careful analysis of the underlying stochastic process. Second, we present polynomial-time algorithms using our generalized LexRSMs for proving a.s. termination in broad classes of linear-arithmetic programs. AU - Chatterjee, Krishnendu AU - Goharshady, Ehsan Kafshdar AU - Novotný, Petr AU - Zárevúcky, Jiří AU - Zikelic, Dorde ID - 10414 SN - 0302-9743 T2 - 24th International Symposium on Formal Methods TI - On lexicographic proof rules for probabilistic termination VL - 13047 ER - TY - JOUR AB - Research on two-dimensional (2D) materials has been explosively increasing in last seventeen years in varying subjects including condensed matter physics, electronic engineering, materials science, and chemistry since the mechanical exfoliation of graphene in 2004. Starting from graphene, 2D materials now have become a big family with numerous members and diverse categories. The unique structural features and physicochemical properties of 2D materials make them one class of the most appealing candidates for a wide range of potential applications. In particular, we have seen some major breakthroughs made in the field of 2D materials in last five years not only in developing novel synthetic methods and exploring new structures/properties but also in identifying innovative applications and pushing forward commercialisation. In this review, we provide a critical summary on the recent progress made in the field of 2D materials with a particular focus on last five years. After a brief background introduction, we first discuss the major synthetic methods for 2D materials, including the mechanical exfoliation, liquid exfoliation, vapor phase deposition, and wet-chemical synthesis as well as phase engineering of 2D materials belonging to the field of phase engineering of nanomaterials (PEN). We then introduce the superconducting/optical/magnetic properties and chirality of 2D materials along with newly emerging magic angle 2D superlattices. Following that, the promising applications of 2D materials in electronics, optoelectronics, catalysis, energy storage, solar cells, biomedicine, sensors, environments, etc. are described sequentially. Thereafter, we present the theoretic calculations and simulations of 2D materials. Finally, after concluding the current progress, we provide some personal discussions on the existing challenges and future outlooks in this rapidly developing field. AU - Chang, Cheng AU - Chen, Wei AU - Chen, Ye AU - Chen, Yonghua AU - Chen, Yu AU - Ding, Feng AU - Fan, Chunhai AU - Fan, Hong Jin AU - Fan, Zhanxi AU - Gong, Cheng AU - Gong, Yongji AU - He, Qiyuan AU - Hong, Xun AU - Hu, Sheng AU - Hu, Weida AU - Huang, Wei AU - Huang, Yuan AU - Ji, Wei AU - Li, Dehui AU - Li, Lain Jong AU - Li, Qiang AU - Lin, Li AU - Ling, Chongyi AU - Liu, Minghua AU - Liu, Nan AU - Liu, Zhuang AU - Loh, Kian Ping AU - Ma, Jianmin AU - Miao, Feng AU - Peng, Hailin AU - Shao, Mingfei AU - Song, Li AU - Su, Shao AU - Sun, Shuo AU - Tan, Chaoliang AU - Tang, Zhiyong AU - Wang, Dingsheng AU - Wang, Huan AU - Wang, Jinlan AU - Wang, Xin AU - Wang, Xinran AU - Wee, Andrew T.S. AU - Wei, Zhongming AU - Wu, Yuen AU - Wu, Zhong Shuai AU - Xiong, Jie AU - Xiong, Qihua AU - Xu, Weigao AU - Yin, Peng AU - Zeng, Haibo AU - Zeng, Zhiyuan AU - Zhai, Tianyou AU - Zhang, Han AU - Zhang, Hui AU - Zhang, Qichun AU - Zhang, Tierui AU - Zhang, Xiang AU - Zhao, Li Dong AU - Zhao, Meiting AU - Zhao, Weijie AU - Zhao, Yunxuan AU - Zhou, Kai Ge AU - Zhou, Xing AU - Zhou, Yu AU - Zhu, Hongwei AU - Zhang, Hua AU - Liu, Zhongfan ID - 14800 IS - 12 JF - Acta Physico-Chimica Sinica SN - 1001-4861 TI - Recent progress on two-dimensional materials VL - 37 ER - TY - CONF AB - Neural-network classifiers achieve high accuracy when predicting the class of an input that they were trained to identify. Maintaining this accuracy in dynamic environments, where inputs frequently fall outside the fixed set of initially known classes, remains a challenge. The typical approach is to detect inputs from novel classes and retrain the classifier on an augmented dataset. However, not only the classifier but also the detection mechanism needs to adapt in order to distinguish between newly learned and yet unknown input classes. To address this challenge, we introduce an algorithmic framework for active monitoring of a neural network. A monitor wrapped in our framework operates in parallel with the neural network and interacts with a human user via a series of interpretable labeling queries for incremental adaptation. In addition, we propose an adaptive quantitative monitor to improve precision. An experimental evaluation on a diverse set of benchmarks with varying numbers of classes confirms the benefits of our active monitoring framework in dynamic scenarios. AU - Lukina, Anna AU - Schilling, Christian AU - Henzinger, Thomas A ID - 10206 KW - monitoring KW - neural networks KW - novelty detection SN - 0302-9743 T2 - 21st International Conference on Runtime Verification TI - Into the unknown: active monitoring of neural networks VL - 12974 ER - TY - JOUR AB - We consider the Fröhlich Hamiltonian with large coupling constant α. For initial data of Pekar product form with coherent phonon field and with the electron minimizing the corresponding energy, we provide a norm approximation of the evolution, valid up to times of order α2. The approximation is given in terms of a Pekar product state, evolved through the Landau-Pekar equations, corrected by a Bogoliubov dynamics taking quantum fluctuations into account. This allows us to show that the Landau-Pekar equations approximately describe the evolution of the electron- and one-phonon reduced density matrices under the Fröhlich dynamics up to times of order α2. AU - Leopold, Nikolai K AU - Mitrouskas, David Johannes AU - Rademacher, Simone Anna Elvira AU - Schlein, Benjamin AU - Seiringer, Robert ID - 14889 IS - 4 JF - Pure and Applied Analysis SN - 2578-5893 TI - Landau–Pekar equations and quantum fluctuations for the dynamics of a strongly coupled polaron VL - 3 ER - TY - JOUR AB - We consider a system of N interacting bosons in the mean-field scaling regime and construct corrections to the Bogoliubov dynamics that approximate the true N-body dynamics in norm to arbitrary precision. The N-independent corrections are given in terms of the solutions of the Bogoliubov and Hartree equations and satisfy a generalized form of Wick's theorem. We determine the n-point correlation functions of the excitations around the condensate, as well as the reduced densities of the N-body system, to arbitrary accuracy, given only the knowledge of the two-point functions of a quasi-free state and the solution of the Hartree equation. In this way, the complex problem of computing all n-point correlation functions for an interacting N-body system is essentially reduced to the problem of solving the Hartree equation and the PDEs for the Bogoliubov two-point functions. AU - Bossmann, Lea AU - Petrat, Sören P AU - Pickl, Peter AU - Soffer, Avy ID - 14890 IS - 4 JF - Pure and Applied Analysis SN - 2578-5893 TI - Beyond Bogoliubov dynamics VL - 3 ER - TY - JOUR AB - We consider random n×n matrices X with independent and centered entries and a general variance profile. We show that the spectral radius of X converges with very high probability to the square root of the spectral radius of the variance matrix of X when n tends to infinity. We also establish the optimal rate of convergence, that is a new result even for general i.i.d. matrices beyond the explicitly solvable Gaussian cases. The main ingredient is the proof of the local inhomogeneous circular law [arXiv:1612.07776] at the spectral edge. AU - Alt, Johannes AU - Erdös, László AU - Krüger, Torben H ID - 15013 IS - 2 JF - Probability and Mathematical Physics SN - 2690-0998 TI - Spectral radius of random matrices with independent entries VL - 2 ER - TY - JOUR AB - Clathrin-mediated endocytosis is the major route of entry of cargos into cells and thus underpins many physiological processes. During endocytosis, an area of flat membrane is remodeled by proteins to create a spherical vesicle against intracellular forces. The protein machinery which mediates this membrane bending in plants is unknown. However, it is known that plant endocytosis is actin independent, thus indicating that plants utilize a unique mechanism to mediate membrane bending against high-turgor pressure compared to other model systems. Here, we investigate the TPLATE complex, a plant-specific endocytosis protein complex. It has been thought to function as a classical adaptor functioning underneath the clathrin coat. However, by using biochemical and advanced live microscopy approaches, we found that TPLATE is peripherally associated with clathrin-coated vesicles and localizes at the rim of endocytosis events. As this localization is more fitting to the protein machinery involved in membrane bending during endocytosis, we examined cells in which the TPLATE complex was disrupted and found that the clathrin structures present as flat patches. This suggests a requirement of the TPLATE complex for membrane bending during plant clathrin–mediated endocytosis. Next, we used in vitro biophysical assays to confirm that the TPLATE complex possesses protein domains with intrinsic membrane remodeling activity. These results redefine the role of the TPLATE complex and implicate it as a key component of the evolutionarily distinct plant endocytosis mechanism, which mediates endocytic membrane bending against the high-turgor pressure in plant cells. AU - Johnson, Alexander J AU - Dahhan, Dana A AU - Gnyliukh, Nataliia AU - Kaufmann, Walter AU - Zheden, Vanessa AU - Costanzo, Tommaso AU - Mahou, Pierre AU - Hrtyan, Mónika AU - Wang, Jie AU - Aguilera Servin, Juan L AU - van Damme, Daniël AU - Beaurepaire, Emmanuel AU - Loose, Martin AU - Bednarek, Sebastian Y AU - Friml, Jiří ID - 9887 IS - 51 JF - Proceedings of the National Academy of Sciences TI - The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis VL - 118 ER - TY - GEN AB - Raw data generated from the publication - The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis by Johnson et al., 2021 In PNAS AU - Johnson, Alexander J ID - 14988 TI - Raw data from Johnson et al, PNAS, 2021 ER - TY - GEN AB - Superconductor-semiconductor hybrids are platforms for realizing effective p-wave superconductivity. Spin-orbit coupling, combined with the proximity effect, causes the two-dimensional semiconductor to inherit p±ip intraband pairing, and application of magnetic field can then result in transitions to the normal state, partial Bogoliubov Fermi surfaces, or topological phases with Majorana modes. Experimentally probing the hybrid superconductor-semiconductor interface is challenging due to the shunting effect of the conventional superconductor. Consequently, the nature of induced pairing remains an open question. Here, we use the circuit quantum electrodynamics architecture to probe induced superconductivity in a two dimensional Al-InAs hybrid system. We observe a strong suppression of superfluid density and enhanced dissipation driven by magnetic field, which cannot be accounted for by the depairing theory of an s-wave superconductor. These observations are explained by a picture of independent intraband p±ip superconductors giving way to partial Bogoliubov Fermi surfaces, and allow for the first characterization of key properties of the hybrid superconducting system. AU - Phan, Duc T AU - Senior, Jorden L AU - Ghazaryan, Areg AU - Hatefipour, M. AU - Strickland, W. M. AU - Shabani, J. AU - Serbyn, Maksym AU - Higginbotham, Andrew P ID - 10029 T2 - arXiv TI - Breakdown of induced p±ip pairing in a superconductor-semiconductor hybrid ER - TY - DATA AB - This .zip File contains the transport data for figures presented in the main text and supplementary material of "Enhancement of Proximity Induced Superconductivity in Planar Germanium" by K. Aggarwal, et. al. The measurements were done using Labber Software and the data is stored in the hdf5 file format. The files can be opened using either the Labber Log Browser (https://labber.org/overview/) or Labber Python API (http://labber.org/online-doc/api/LogFile.html). AU - Katsaros, Georgios ID - 9291 TI - Raw transport data for: Enhancement of proximity induced superconductivity in planar germanium ER - TY - DATA AU - Higginbotham, Andrew P ID - 9636 TI - Data for "Breakdown of induced p ± ip pairing in a superconductor-semiconductor hybrid" ER - TY - JOUR AB - A semiconducting nanowire fully wrapped by a superconducting shell has been proposed as a platform for obtaining Majorana modes at small magnetic fields. In this study, we demonstrate that the appearance of subgap states in such structures is actually governed by the junction region in tunneling spectroscopy measurements and not the full-shell nanowire itself. Short tunneling regions never show subgap states, whereas longer junctions always do. This can be understood in terms of quantum dots forming in the junction and hosting Andreev levels in the Yu-Shiba-Rusinov regime. The intricate magnetic field dependence of the Andreev levels, through both the Zeeman and Little-Parks effects, may result in robust zero-bias peaks—features that could be easily misinterpreted as originating from Majorana zero modes but are unrelated to topological superconductivity. AU - Valentini, Marco AU - Peñaranda, Fernando AU - Hofmann, Andrea C AU - Brauns, Matthias AU - Hauschild, Robert AU - Krogstrup, Peter AU - San-Jose, Pablo AU - Prada, Elsa AU - Aguado, Ramón AU - Katsaros, Georgios ID - 8910 IS - 6550 JF - Science SN - 00368075 TI - Nontopological zero-bias peaks in full-shell nanowires induced by flux-tunable Andreev states VL - 373 ER - TY - DATA AB - This .zip File contains the data for figures presented in the main text and supplementary material of "A singlet triplet hole spin qubit in planar Ge" by D. Jirovec, et. al. The measurements were done using Labber Software and the data is stored in the hdf5 file format. The files can be opened using either the Labber Log Browser (https://labber.org/overview/) or Labber Python API (http://labber.org/online-doc/api/LogFile.html). A single file is acquired with QCodes and features the corresponding data type. XRD data are in .dat format and a code to open the data is provided. The code for simulations is as well provided in Python. AU - Jirovec, Daniel ID - 9323 TI - Research data for "A singlet-triplet hole spin qubit planar Ge" ER - TY - DATA AB - This .zip File contains the transport data for "Non-topological zero bias peaks in full-shell nanowires induced by flux tunable Andreev states" by M. Valentini, et. al. The measurements were done using Labber Software and the data is stored in the hdf5 file format. Instructions of how to read the data are in "Notebook_Valentini.pdf". AU - Valentini, Marco ID - 9389 TI - Research data for "Non-topological zero bias peaks in full-shell nanowires induced by flux tunable Andreev states" ER - TY - JOUR AB - Hole gases in planar germanium can have high mobilities in combination with strong spin-orbit interaction and electrically tunable g factors, and are therefore emerging as a promising platform for creating hybrid superconductor-semiconductor devices. A key challenge towards hybrid Ge-based quantum technologies is the design of high-quality interfaces and superconducting contacts that are robust against magnetic fields. In this work, by combining the assets of aluminum, which provides good contact to the Ge, and niobium, which has a significant superconducting gap, we demonstrate highly transparent low-disordered JoFETs with relatively large ICRN products that are capable of withstanding high magnetic fields. We furthermore demonstrate the ability of phase-biasing individual JoFETs, opening up an avenue to explore topological superconductivity in planar Ge. The persistence of superconductivity in the reported hybrid devices beyond 1.8 T paves the way towards integrating spin qubits and proximity-induced superconductivity on the same chip. AU - Aggarwal, Kushagra AU - Hofmann, Andrea C AU - Jirovec, Daniel AU - Prieto Gonzalez, Ivan AU - Sammak, Amir AU - Botifoll, Marc AU - Martí-Sánchez, Sara AU - Veldhorst, Menno AU - Arbiol, Jordi AU - Scappucci, Giordano AU - Danon, Jeroen AU - Katsaros, Georgios ID - 10559 IS - 2 JF - Physical Review Research KW - general engineering SN - 2643-1564 TI - Enhancement of proximity-induced superconductivity in a planar Ge hole gas VL - 3 ER - TY - JOUR AB - While sexual reproduction is widespread among many taxa, asexual lineages have repeatedly evolved from sexual ancestors. Despite extensive research on the evolution of sex, it is still unclear whether this switch represents a major transition requiring major molecular reorganization, and how convergent the changes involved are. In this study, we investigated the phylogenetic relationship and patterns of gene expression of sexual and asexual lineages of Eurasian Artemia brine shrimp, to assess how gene expression patterns are affected by the transition to asexuality. We find only a few genes that are consistently associated with the evolution of asexuality, suggesting that this shift may not require an extensive overhauling of the meiotic machinery. While genes with sex-biased expression have high rates of expression divergence within Eurasian Artemia, neither female- nor male-biased genes appear to show unusual evolutionary patterns after sexuality is lost, contrary to theoretical expectations. AU - Huylmans, Ann K AU - Macon, Ariana AU - Hontoria, Francisco AU - Vicoso, Beatriz ID - 10166 IS - 1959 JF - Proceedings of the Royal Society B: Biological Sciences KW - asexual reproduction KW - parthenogenesis KW - sex-biased genes KW - sexual conflict KW - automixis KW - crustaceans SN - 0962-8452 TI - Transitions to asexuality and evolution of gene expression in Artemia brine shrimp VL - 288 ER - TY - DATA AB - Here are the research data underlying the publication " Effects of fine-scale population structure on inbreeding in a long-term study of snapdragons (Antirrhinum majus)." Further information are summed up in the README document. AU - Surendranadh, Parvathy AU - Arathoon, Louise S AU - Baskett, Carina AU - Field, David AU - Pickup, Melinda AU - Barton, Nicholas H ID - 9192 TI - Effects of fine-scale population structure on the distribution of heterozygosity in a long-term study of Antirrhinum majus ER - TY - DATA AU - Vicoso, Beatriz ID - 9949 TI - Data from Hyulmans et al 2021, "Transitions to asexuality and evolution of gene expression in Artemia brine shrimp" ER - TY - JOUR AB - Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems. AU - Kavcic, Bor AU - Tkačik, Gašper AU - Bollenbach, Tobias ID - 8997 JF - PLOS Computational Biology KW - Modelling and Simulation KW - Genetics KW - Molecular Biology KW - Antibiotics KW - Drug interactions SN - 1553-7358 TI - Minimal biophysical model of combined antibiotic action VL - 17 ER - TY - JOUR AB - Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs. AU - Nagy-Staron, Anna A AU - Tomasek, Kathrin AU - Caruso Carter, Caroline AU - Sonnleitner, Elisabeth AU - Kavcic, Bor AU - Paixão, Tiago AU - Guet, Calin C ID - 9283 JF - eLife KW - Genetics and Molecular Biology SN - 2050-084X TI - Local genetic context shapes the function of a gene regulatory network VL - 10 ER - TY - JOUR AB - We introduce a novel technique to automatically decompose an input object’s volume into a set of parts that can be represented by two opposite height fields. Such decomposition enables the manufacturing of individual parts using two-piece reusable rigid molds. Our decomposition strategy relies on a new energy formulation that utilizes a pre-computed signal on the mesh volume representing the accessibility for a predefined set of extraction directions. Thanks to this novel formulation, our method allows for efficient optimization of a fabrication-aware partitioning of volumes in a completely automatic way. We demonstrate the efficacy of our approach by generating valid volume partitionings for a wide range of complex objects and physically reproducing several of them. AU - Alderighi, Thomas AU - Malomo, Luigi AU - Bickel, Bernd AU - Cignoni, Paolo AU - Pietroni, Nico ID - 10184 IS - 6 JF - ACM Transactions on Graphics SN - 0730-0301 TI - Volume decomposition for two-piece rigid casting VL - 40 ER - TY - JOUR AB - The Massively Parallel Computation (MPC) model is an emerging model that distills core aspects of distributed and parallel computation, developed as a tool to solve combinatorial (typically graph) problems in systems of many machines with limited space. Recent work has focused on the regime in which machines have sublinear (in n, the number of nodes in the input graph) space, with randomized algorithms presented for the fundamental problems of Maximal Matching and Maximal Independent Set. However, there have been no prior corresponding deterministic algorithms. A major challenge underlying the sublinear space setting is that the local space of each machine might be too small to store all edges incident to a single node. This poses a considerable obstacle compared to classical models in which each node is assumed to know and have easy access to its incident edges. To overcome this barrier, we introduce a new graph sparsification technique that deterministically computes a low-degree subgraph, with the additional property that solving the problem on this subgraph provides significant progress towards solving the problem for the original input graph. Using this framework to derandomize the well-known algorithm of Luby [SICOMP’86], we obtain O(log Δ + log log n)-round deterministic MPC algorithms for solving the problems of Maximal Matching and Maximal Independent Set with O(nɛ) space on each machine for any constant ɛ > 0. These algorithms also run in O(log Δ) rounds in the closely related model of CONGESTED CLIQUE, improving upon the state-of-the-art bound of O(log 2Δ) rounds by Censor-Hillel et al. [DISC’17]. AU - Czumaj, Artur AU - Davies, Peter AU - Parter, Merav ID - 9541 IS - 2 JF - ACM Transactions on Algorithms SN - 1549-6325 TI - Graph sparsification for derandomizing massively parallel computation with low space VL - 17 ER - TY - JOUR AB - We investigate the effect of coupling between translational and internal degrees of freedom of composite quantum particles on their localization in a random potential. We show that entanglement between the two degrees of freedom weakens localization due to the upper bound imposed on the inverse participation ratio by purity of a quantum state. We perform numerical calculations for a two-particle system bound by a harmonic force in a 1D disordered lattice and a rigid rotor in a 2D disordered lattice. We illustrate that the coupling has a dramatic effect on localization properties, even with a small number of internal states participating in quantum dynamics. AU - Suzuki, Fumika AU - Lemeshko, Mikhail AU - Zurek, Wojciech H. AU - Krems, Roman V. ID - 10134 IS - 16 JF - Physical Review Letters KW - General Physics and Astronomy SN - 0031-9007 TI - Anderson localization of composite particles VL - 127 ER - TY - CONF AB - We introduce a new graph problem, the token dropping game, and we show how to solve it efficiently in a distributed setting. We use the token dropping game as a tool to design an efficient distributed algorithm for stable orientations and more generally for locally optimal semi-matchings. The prior work by Czygrinow et al. (DISC 2012) finds a stable orientation in O(Δ^5) rounds in graphs of maximum degree Δ, while we improve it to O(Δ^4) and also prove a lower bound of Ω(Δ). For the more general problem of locally optimal semi-matchings, the prior upper bound is O(S^5) and our new algorithm runs in O(C · S^4) rounds, which is an improvement for C = o(S); here C and S are the maximum degrees of customers and servers, respectively. AU - Brandt, Sebastian AU - Keller, Barbara AU - Rybicki, Joel AU - Suomela, Jukka AU - Uitto, Jara ID - 9678 SN - 9781450380706 T2 - Annual ACM Symposium on Parallelism in Algorithms and Architectures TI - Efficient load-balancing through distributed token dropping ER - TY - JOUR AB - We consider the following dynamic load-balancing process: given an underlying graph G with n nodes, in each step t≥ 0, one unit of load is created, and placed at a randomly chosen graph node. In the same step, the chosen node picks a random neighbor, and the two nodes balance their loads by averaging them. We are interested in the expected gap between the minimum and maximum loads at nodes as the process progresses, and its dependence on n and on the graph structure. Variants of the above graphical balanced allocation process have been studied previously by Peres, Talwar, and Wieder [Peres et al., 2015], and by Sauerwald and Sun [Sauerwald and Sun, 2015]. These authors left as open the question of characterizing the gap in the case of cycle graphs in the dynamic case, where weights are created during the algorithm’s execution. For this case, the only known upper bound is of 𝒪(n log n), following from a majorization argument due to [Peres et al., 2015], which analyzes a related graphical allocation process. In this paper, we provide an upper bound of 𝒪 (√n log n) on the expected gap of the above process for cycles of length n. We introduce a new potential analysis technique, which enables us to bound the difference in load between k-hop neighbors on the cycle, for any k ≤ n/2. We complement this with a "gap covering" argument, which bounds the maximum value of the gap by bounding its value across all possible subsets of a certain structure, and recursively bounding the gaps within each subset. We provide analytical and experimental evidence that our upper bound on the gap is tight up to a logarithmic factor. AU - Alistarh, Dan-Adrian AU - Nadiradze, Giorgi AU - Sabour, Amirmojtaba ID - 8286 JF - Algorithmica SN - 0178-4617 TI - Dynamic averaging load balancing on cycles ER - TY - THES AB - This thesis is the result of the research carried out by the author during his PhD at IST Austria between 2017 and 2021. It mainly focuses on the Fröhlich polaron model, specifically to its regime of strong coupling. This model, which is rigorously introduced and discussed in the introduction, has been of great interest in condensed matter physics and field theory for more than eighty years. It is used to describe an electron interacting with the atoms of a solid material (the strength of this interaction is modeled by the presence of a coupling constant α in the Hamiltonian of the system). The particular regime examined here, which is mathematically described by considering the limit α →∞, displays many interesting features related to the emergence of classical behavior, which allows for a simplified effective description of the system under analysis. The properties, the range of validity and a quantitative analysis of the precision of such classical approximations are the main object of the present work. We specify our investigation to the study of the ground state energy of the system, its dynamics and its effective mass. For each of these problems, we provide in the introduction an overview of the previously known results and a detailed account of the original contributions by the author. AU - Feliciangeli, Dario ID - 9733 SN - 2663-337X TI - The polaron at strong coupling ER - TY - JOUR AB - As the size and complexity of models and datasets grow, so does the need for communication-efficient variants of stochastic gradient descent that can be deployed to perform parallel model training. One popular communication-compression method for data-parallel SGD is QSGD (Alistarh et al., 2017), which quantizes and encodes gradients to reduce communication costs. The baseline variant of QSGD provides strong theoretical guarantees, however, for practical purposes, the authors proposed a heuristic variant which we call QSGDinf, which demonstrated impressive empirical gains for distributed training of large neural networks. In this paper, we build on this work to propose a new gradient quantization scheme, and show that it has both stronger theoretical guarantees than QSGD, and matches and exceeds the empirical performance of the QSGDinf heuristic and of other compression methods. AU - Ramezani-Kebrya, Ali AU - Faghri, Fartash AU - Markov, Ilya AU - Aksenov, Vitalii AU - Alistarh, Dan-Adrian AU - Roy, Daniel M. ID - 9571 IS - 114 JF - Journal of Machine Learning Research SN - 15324435 TI - NUQSGD: Provably communication-efficient data-parallel SGD via nonuniform quantization VL - 22 ER - TY - JOUR AB - The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis. AU - Takeo, Yukari H. AU - Shuster, S. Andrew AU - Jiang, Linnie AU - Hu, Miley AU - Luginbuhl, David J. AU - Rülicke, Thomas AU - Contreras, Ximena AU - Hippenmeyer, Simon AU - Wagner, Mark J. AU - Ganguli, Surya AU - Luo, Liqun ID - 8544 IS - 4 JF - Neuron TI - GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells VL - 109 ER - TY - GEN AB - We provide a definition of the effective mass for the classical polaron described by the Landau-Pekar equations. It is based on a novel variational principle, minimizing the energy functional over states with given (initial) velocity. The resulting formula for the polaron's effective mass agrees with the prediction by Landau and Pekar. AU - Feliciangeli, Dario AU - Rademacher, Simone Anna Elvira AU - Seiringer, Robert ID - 9791 T2 - arXiv TI - The effective mass problem for the Landau-Pekar equations ER - TY - JOUR AB - Normative theories and statistical inference provide complementary approaches for the study of biological systems. A normative theory postulates that organisms have adapted to efficiently solve essential tasks, and proceeds to mathematically work out testable consequences of such optimality; parameters that maximize the hypothesized organismal function can be derived ab initio, without reference to experimental data. In contrast, statistical inference focuses on efficient utilization of data to learn model parameters, without reference to any a priori notion of biological function, utility, or fitness. Traditionally, these two approaches were developed independently and applied separately. Here we unify them in a coherent Bayesian framework that embeds a normative theory into a family of maximum-entropy “optimization priors.” This family defines a smooth interpolation between a data-rich inference regime (characteristic of “bottom-up” statistical models), and a data-limited ab inito prediction regime (characteristic of “top-down” normative theory). We demonstrate the applicability of our framework using data from the visual cortex, and argue that the flexibility it affords is essential to address a number of fundamental challenges relating to inference and prediction in complex, high-dimensional biological problems. AU - Mlynarski, Wiktor F AU - Hledik, Michal AU - Sokolowski, Thomas R AU - Tkačik, Gašper ID - 7553 IS - 7 JF - Neuron TI - Statistical analysis and optimality of neural systems VL - 109 ER - TY - CONF AB - We consider the problem of estimating a signal from measurements obtained via a generalized linear model. We focus on estimators based on approximate message passing (AMP), a family of iterative algorithms with many appealing features: the performance of AMP in the high-dimensional limit can be succinctly characterized under suitable model assumptions; AMP can also be tailored to the empirical distribution of the signal entries, and for a wide class of estimation problems, AMP is conjectured to be optimal among all polynomial-time algorithms. However, a major issue of AMP is that in many models (such as phase retrieval), it requires an initialization correlated with the ground-truth signal and independent from the measurement matrix. Assuming that such an initialization is available is typically not realistic. In this paper, we solve this problem by proposing an AMP algorithm initialized with a spectral estimator. With such an initialization, the standard AMP analysis fails since the spectral estimator depends in a complicated way on the design matrix. Our main contribution is a rigorous characterization of the performance of AMP with spectral initialization in the high-dimensional limit. The key technical idea is to define and analyze a two-phase artificial AMP algorithm that first produces the spectral estimator, and then closely approximates the iterates of the true AMP. We also provide numerical results that demonstrate the validity of the proposed approach. AU - Mondelli, Marco AU - Venkataramanan, Ramji ED - Banerjee, Arindam ED - Fukumizu, Kenji ID - 10598 SN - 2640-3498 T2 - Proceedings of The 24th International Conference on Artificial Intelligence and Statistics TI - Approximate message passing with spectral initialization for generalized linear models VL - 130 ER - TY - JOUR AB - This paper aims to obtain a strong convergence result for a Douglas–Rachford splitting method with inertial extrapolation step for finding a zero of the sum of two set-valued maximal monotone operators without any further assumption of uniform monotonicity on any of the involved maximal monotone operators. Furthermore, our proposed method is easy to implement and the inertial factor in our proposed method is a natural choice. Our method of proof is of independent interest. Finally, some numerical implementations are given to confirm the theoretical analysis. AU - Shehu, Yekini AU - Dong, Qiao-Li AU - Liu, Lu-Lu AU - Yao, Jen-Chih ID - 8196 JF - Optimization and Engineering SN - 1389-4420 TI - New strong convergence method for the sum of two maximal monotone operators VL - 22 ER - TY - JOUR AB - In the worldwide endeavor for disruptive quantum technologies, germanium is emerging as a versatile material to realize devices capable of encoding, processing, or transmitting quantum information. These devices leverage special properties of the germanium valence-band states, commonly known as holes, such as their inherently strong spin-orbit coupling and the ability to host superconducting pairing correlations. In this Review, we initially introduce the physics of holes in low-dimensional germanium structures with key insights from a theoretical perspective. We then examine the material science progress underpinning germanium-based planar heterostructures and nanowires. We review the most significant experimental results demonstrating key building blocks for quantum technology, such as an electrically driven universal quantum gate set with spin qubits in quantum dots and superconductor-semiconductor devices for hybrid quantum systems. We conclude by identifying the most promising prospects toward scalable quantum information processing. AU - Scappucci, Giordano AU - Kloeffel, Christoph AU - Zwanenburg, Floris A. AU - Loss, Daniel AU - Myronov, Maksym AU - Zhang, Jian-Jun AU - Franceschi, Silvano De AU - Katsaros, Georgios AU - Veldhorst, Menno ID - 8911 JF - Nature Reviews Materials TI - The germanium quantum information route VL - 6 ER - TY - JOUR AB - Canonical parametrisations of classical confocal coordinate systems are introduced and exploited to construct non-planar analogues of incircular (IC) nets on individual quadrics and systems of confocal quadrics. Intimate connections with classical deformations of quadrics that are isometric along asymptotic lines and circular cross-sections of quadrics are revealed. The existence of octahedral webs of surfaces of Blaschke type generated by asymptotic and characteristic lines that are diagonally related to lines of curvature is proved theoretically and established constructively. Appropriate samplings (grids) of these webs lead to three-dimensional extensions of non-planar IC nets. Three-dimensional octahedral grids composed of planes and spatially extending (checkerboard) IC-nets are shown to arise in connection with systems of confocal quadrics in Minkowski space. In this context, the Laguerre geometric notion of conical octahedral grids of planes is introduced. The latter generalise the octahedral grids derived from systems of confocal quadrics in Minkowski space. An explicit construction of conical octahedral grids is presented. The results are accompanied by various illustrations which are based on the explicit formulae provided by the theory. AU - Akopyan, Arseniy AU - Bobenko, Alexander I. AU - Schief, Wolfgang K. AU - Techter, Jan ID - 8338 JF - Discrete and Computational Geometry SN - 0179-5376 TI - On mutually diagonal nets on (confocal) quadrics and 3-dimensional webs VL - 66 ER - TY - JOUR AB - We design fast deterministic algorithms for distance computation in the Congested Clique model. Our key contributions include: A (2+ϵ)-approximation for all-pairs shortest paths in O(log2n/ϵ) rounds on unweighted undirected graphs. With a small additional additive factor, this also applies for weighted graphs. This is the first sub-polynomial constant-factor approximation for APSP in this model. A (1+ϵ)-approximation for multi-source shortest paths from O(n−−√) sources in O(log2n/ϵ) rounds on weighted undirected graphs. This is the first sub-polynomial algorithm obtaining this approximation for a set of sources of polynomial size. Our main techniques are new distance tools that are obtained via improved algorithms for sparse matrix multiplication, which we leverage to construct efficient hopsets and shortest paths. Furthermore, our techniques extend to additional distance problems for which we improve upon the state-of-the-art, including diameter approximation, and an exact single-source shortest paths algorithm for weighted undirected graphs in O~(n1/6) rounds. AU - Censor-Hillel, Keren AU - Dory, Michal AU - Korhonen, Janne AU - Leitersdorf, Dean ID - 7939 JF - Distributed Computing SN - 0178-2770 TI - Fast approximate shortest paths in the congested clique VL - 34 ER - TY - JOUR AB - We consider the following setting: suppose that we are given a manifold M in Rd with positive reach. Moreover assume that we have an embedded simplical complex A without boundary, whose vertex set lies on the manifold, is sufficiently dense and such that all simplices in A have sufficient quality. We prove that if, locally, interiors of the projection of the simplices onto the tangent space do not intersect, then A is a triangulation of the manifold, that is, they are homeomorphic. AU - Boissonnat, Jean-Daniel AU - Dyer, Ramsay AU - Ghosh, Arijit AU - Lieutier, Andre AU - Wintraecken, Mathijs ID - 8248 JF - Discrete and Computational Geometry SN - 0179-5376 TI - Local conditions for triangulating submanifolds of Euclidean space VL - 66 ER - TY - JOUR AB - All vertebrates have a spinal cord with dimensions and shape specific to their species. Yet how species‐specific organ size and shape are achieved is a fundamental unresolved question in biology. The formation and sculpting of organs begins during embryonic development. As it develops, the spinal cord extends in anterior–posterior direction in synchrony with the overall growth of the body. The dorsoventral (DV) and apicobasal lengths of the spinal cord neuroepithelium also change, while at the same time a characteristic pattern of neural progenitor subtypes along the DV axis is established and elaborated. At the basis of these changes in tissue size and shape are biophysical determinants, such as the change in cell number, cell size and shape, and anisotropic tissue growth. These processes are controlled by global tissue‐scale regulators, such as morphogen signaling gradients as well as mechanical forces. Current challenges in the field are to uncover how these tissue‐scale regulatory mechanisms are translated to the cellular and molecular level, and how regulation of distinct cellular processes gives rise to an overall defined size. Addressing these questions will help not only to achieve a better understanding of how size is controlled, but also of how tissue size is coordinated with the specification of pattern. AU - Kuzmicz-Kowalska, Katarzyna AU - Kicheva, Anna ID - 7883 JF - Wiley Interdisciplinary Reviews: Developmental Biology SN - 17597684 TI - Regulation of size and scale in vertebrate spinal cord development ER - TY - JOUR AB - We investigate a sheaf-theoretic interpretation of stratification learning from geometric and topological perspectives. Our main result is the construction of stratification learning algorithms framed in terms of a sheaf on a partially ordered set with the Alexandroff topology. We prove that the resulting decomposition is the unique minimal stratification for which the strata are homogeneous and the given sheaf is constructible. In particular, when we choose to work with the local homology sheaf, our algorithm gives an alternative to the local homology transfer algorithm given in Bendich et al. (Proceedings of the 23rd Annual ACM-SIAM Symposium on Discrete Algorithms, pp. 1355–1370, ACM, New York, 2012), and the cohomology stratification algorithm given in Nanda (Found. Comput. Math. 20(2), 195–222, 2020). Additionally, we give examples of stratifications based on the geometric techniques of Breiding et al. (Rev. Mat. Complut. 31(3), 545–593, 2018), illustrating how the sheaf-theoretic approach can be used to study stratifications from both topological and geometric perspectives. This approach also points toward future applications of sheaf theory in the study of topological data analysis by illustrating the utility of the language of sheaf theory in generalizing existing algorithms. AU - Brown, Adam AU - Wang, Bei ID - 7905 JF - Discrete and Computational Geometry SN - 0179-5376 TI - Sheaf-theoretic stratification learning from geometric and topological perspectives VL - 65 ER - TY - JOUR AB - We consider large non-Hermitian real or complex random matrices X with independent, identically distributed centred entries. We prove that their local eigenvalue statistics near the spectral edge, the unit circle, coincide with those of the Ginibre ensemble, i.e. when the matrix elements of X are Gaussian. This result is the non-Hermitian counterpart of the universality of the Tracy–Widom distribution at the spectral edges of the Wigner ensemble. AU - Cipolloni, Giorgio AU - Erdös, László AU - Schröder, Dominik J ID - 8601 JF - Probability Theory and Related Fields SN - 01788051 TI - Edge universality for non-Hermitian random matrices ER - TY - JOUR AB - In this paper, we introduce a relaxed CQ method with alternated inertial step for solving split feasibility problems. We give convergence of the sequence generated by our method under some suitable assumptions. Some numerical implementations from sparse signal and image deblurring are reported to show the efficiency of our method. AU - Shehu, Yekini AU - Gibali, Aviv ID - 7925 JF - Optimization Letters SN - 1862-4472 TI - New inertial relaxed method for solving split feasibilities VL - 15 ER - TY - JOUR AB - Eukaryotic DNA-binding proteins operate in the context of chromatin, where nucleosomes are the elementary building blocks. Nucleosomal DNA is wrapped around a histone core, thereby rendering a large fraction of the DNA surface inaccessible to DNA-binding proteins. Nevertheless, first responders in DNA repair and sequence-specific transcription factors bind DNA target sites obstructed by chromatin. While early studies examined protein binding to histone-free DNA, it is only now beginning to emerge how DNA sequences are interrogated on nucleosomes. These readout strategies range from the release of nucleosomal DNA from histones, to rotational/translation register shifts of the DNA motif, and nucleosome-specific DNA binding modes that differ from those observed on naked DNA. Since DNA motif engagement on nucleosomes strongly depends on position and orientation, we argue that motif location and nucleosome positioning co-determine protein access to DNA in transcription and DNA repair. AU - Michael, Alicia AU - Thomä, Nicolas H. ID - 15151 IS - 14 JF - Cell KW - General Biochemistry KW - Genetics and Molecular Biology SN - 0092-8674 TI - Reading the chromatinized genome VL - 184 ER - TY - JOUR AB - Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system. AU - Vandael, David H AU - Okamoto, Yuji AU - Borges Merjane, Carolina AU - Vargas Barroso, Victor M AU - Suter, Benjamin AU - Jonas, Peter M ID - 9438 IS - 6 JF - Nature Protocols SN - 17542189 TI - Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses VL - 16 ER - TY - THES AB - Blood – this is what animals use to heal wounds fast and efficient. Plants do not have blood circulation and their cells cannot move. However, plants have evolved remarkable capacities to regenerate tissues and organs preventing further damage. In my PhD research, I studied the wound healing in the Arabidopsis root. I used a UV laser to ablate single cells in the root tip and observed the consequent wound healing. Interestingly, the inner adjacent cells induced a division plane switch and subsequently adopted the cell type of the killed cell to replace it. We termed this form of wound healing “restorative divisions”. This initial observation triggered the questions of my PhD studies: How and why do cells orient their division planes, how do they feel the wound and why does this happen only in inner adjacent cells. For answering these questions, I used a quite simple experimental setup: 5 day - old seedlings were stained with propidium iodide to visualize cell walls and dead cells; ablation was carried out using a special laser cutter and a confocal microscope. Adaptation of the novel vertical microscope system made it possible to observe wounds in real time. This revealed that restorative divisions occur at increased frequency compared to normal divisions. Additionally, the major plant hormone auxin accumulates in wound adjacent cells and drives the expression of the wound-stress responsive transcription factor ERF115. Using this as a marker gene for wound responses, we found that an important part of wound signalling is the sensing of the collapse of the ablated cell. The collapse causes a radical pressure drop, which results in strong tissue deformations. These deformations manifest in an invasion of the now free spot specifically by the inner adjacent cells within seconds, probably because of higher pressure of the inner tissues. Long-term imaging revealed that those deformed cells continuously expand towards the wound hole and that this is crucial for the restorative division. These wound-expanding cells exhibit an abnormal, biphasic polarity of microtubule arrays before the division. Experiments inhibiting cell expansion suggest that it is the biphasic stretching that induces those MT arrays. Adapting the micromanipulator aspiration system from animal scientists at our institute confirmed the hypothesis that stretching influences microtubule stability. In conclusion, this shows that microtubules react to tissue deformation and this facilitates the observed division plane switch. This puts mechanical cues and tensions at the most prominent position for explaining the growth and wound healing properties of plants. Hence, it shines light onto the importance of understanding mechanical signal transduction. AU - Hörmayer, Lukas ID - 9992 SN - 2663-337X TI - Wound healing in the Arabidopsis root meristem ER - TY - JOUR AB - Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks. AU - Guzmán, José AU - Schlögl, Alois AU - Espinoza Martinez, Claudia AU - Zhang, Xiaomin AU - Suter, Benjamin AU - Jonas, Peter M ID - 10816 IS - 12 JF - Nature Computational Science KW - general medicine SN - 2662-8457 TI - How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network VL - 1 ER - TY - COMP AB - Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks. AU - Guzmán, José AU - Schlögl, Alois AU - Espinoza Martinez, Claudia AU - Zhang, Xiaomin AU - Suter, Benjamin AU - Jonas, Peter M ID - 10110 TI - How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network ER - TY - GEN AB - Although much is known about how single neurons in the hippocampus represent an animal’s position, how cell-cell interactions contribute to spatial coding remains poorly understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured cell-to-cell interactions whose statistics depend on familiar vs. novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the signal-to-noise ratio of their spatial inputs. Moreover, the topology of the interactions facilitates linear decodability, making the information easy to read out by downstream circuits. These findings suggest that the efficient coding hypothesis is not applicable only to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain. AU - Nardin, Michele AU - Csicsvari, Jozsef L AU - Tkačik, Gašper AU - Savin, Cristina ID - 10077 T2 - bioRxiv TI - The structure of hippocampal CA1 interactions optimizes spatial coding across experience ER - TY - JOUR AB - Aprotic alkali metal–O2 batteries face two major obstacles to their chemistry occurring efficiently, the insulating nature of the formed alkali superoxides/peroxides and parasitic reactions that are caused by the highly reactive singlet oxygen (1O2). Redox mediators are recognized to be key for improving rechargeability. However, it is unclear how they affect 1O2 formation, which hinders strategies for their improvement. Here we clarify the mechanism of mediated peroxide and superoxide oxidation and thus explain how redox mediators either enhance or suppress 1O2 formation. We show that charging commences with peroxide oxidation to a superoxide intermediate and that redox potentials above ~3.5 V versus Li/Li+ drive 1O2 evolution from superoxide oxidation, while disproportionation always generates some 1O2. We find that 1O2 suppression requires oxidation to be faster than the generation of 1O2 from disproportionation. Oxidation rates decrease with growing driving force following Marcus inverted-region behaviour, establishing a region of maximum rate. AU - Petit, Yann K. AU - Mourad, Eléonore AU - Prehal, Christian AU - Leypold, Christian AU - Windischbacher, Andreas AU - Mijailovic, Daniel AU - Slugovc, Christian AU - Borisov, Sergey M. AU - Zojer, Egbert AU - Brutti, Sergio AU - Fontaine, Olivier AU - Freunberger, Stefan Alexander ID - 9250 IS - 5 JF - Nature Chemistry KW - General Chemistry KW - General Chemical Engineering SN - 1755-4330 TI - Mechanism of mediated alkali peroxide oxidation and triplet versus singlet oxygen formation VL - 13 ER - TY - THES AB - Cytoplasmic reorganizations are essential for morphogenesis. In large cells like oocytes, these reorganizations become crucial in patterning the oocyte for later stages of embryonic development. Ascidians oocytes reorganize their cytoplasm (ooplasm) in a spectacular manner. Ooplasmic reorganization is initiated at fertilization with the contraction of the actomyosin cortex along the animal-vegetal axis of the oocyte, driving the accumulation of cortical endoplasmic reticulum (cER), maternal mRNAs associated to it and a mitochondria-rich subcortical layer – the myoplasm – in a region of the vegetal pole termed contraction pole (CP). Here we have used the species Phallusia mammillata to investigate the changes in cell shape that accompany these reorganizations and the mechanochemical mechanisms underlining CP formation. We report that the length of the animal-vegetal (AV) axis oscillates upon fertilization: it first undergoes a cycle of fast elongation-lengthening followed by a slow expansion of mainly the vegetal pole (VP) of the cell. We show that the fast oscillation corresponds to a dynamic polarization of the actin cortex as a result of a fertilization-induced increase in cortical tension in the oocyte that triggers a rupture of the cortex at the animal pole and the establishment of vegetal-directed cortical flows. These flows are responsible for the vegetal accumulation of actin causing the VP to flatten. We find that the slow expansion of the VP, leading to CP formation, correlates with a relaxation of the vegetal cortex and that the myoplasm plays a role in the expansion. We show that the myoplasm is a solid-like layer that buckles under compression forces arising from the contracting actin cortex at the VP. Straightening of the myoplasm when actin flows stops, facilitates the expansion of the VP and the CP. Altogether, our results present a previously unrecognized role for the myoplasm in ascidian ooplasmic segregation. AU - Caballero Mancebo, Silvia ID - 9623 SN - 2663-337X TI - Fertilization-induced deformations are controlled by the actin cortex and a mitochondria-rich subcortical layer in ascidian oocytes ER - TY - JOUR AB - Cytoplasm is a gel-like crowded environment composed of various macromolecules, organelles, cytoskeletal networks, and cytosol. The structure of the cytoplasm is highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules are restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the crowded nature of the cytoplasm at the microscopic scale, large-scale reorganization of the cytoplasm is essential for important cellular functions, such as cell division and polarization. How such mesoscale reorganization of the cytoplasm is achieved, especially for large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, is only beginning to be understood. In this review, we will discuss recent advances in elucidating the molecular, cellular, and biophysical mechanisms by which the cytoskeleton drives cytoplasmic reorganization across different scales, structures, and species. AU - Shamipour, Shayan AU - Caballero Mancebo, Silvia AU - Heisenberg, Carl-Philipp J ID - 9006 IS - 2 JF - Developmental Cell SN - 15345807 TI - Cytoplasm's got moves VL - 56 ER - TY - JOUR AB - De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs. AU - Morandell, Jasmin AU - Schwarz, Lena A AU - Basilico, Bernadette AU - Tasciyan, Saren AU - Dimchev, Georgi A AU - Nicolas, Armel AU - Sommer, Christoph M AU - Kreuzinger, Caroline AU - Dotter, Christoph AU - Knaus, Lisa AU - Dobler, Zoe AU - Cacci, Emanuele AU - Schur, Florian KM AU - Danzl, Johann G AU - Novarino, Gaia ID - 9429 IS - 1 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology TI - Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development VL - 12 ER - TY - THES AB - Quantum information and computation has become a vast field paved with opportunities for researchers and investors. As large multinational companies and international funds are heavily investing in quantum technologies it is still a question which platform is best suited for the task of realizing a scalable quantum processor. In this work we investigate hole spins in Ge quantum wells. These hold great promise as they possess several favorable properties: a small effective mass, a strong spin-orbit coupling, long relaxation time and an inherent immunity to hyperfine noise. All these characteristics helped Ge hole spin qubits to evolve from a single qubit to a fully entangled four qubit processor in only 3 years. Here, we investigated a qubit approach leveraging the large out-of-plane g-factors of heavy hole states in Ge quantum dots. We found this qubit to be reproducibly operable at extremely low magnetic field and at large speeds while maintaining coherence. This was possible because large differences of g-factors in adjacent dots can be achieved in the out-of-plane direction. In the in-plane direction the small g-factors, on the other hand, can be altered very effectively by the confinement potentials. Here, we found that this can even lead to a sign change of the g-factors. The resulting g-factor difference alters the dynamics of the system drastically and produces effects typically attributed to a spin-orbit induced spin-flip term. The investigations carried out in this thesis give further insights into the possibilities of holes in Ge and reveal new physical properties that need to be considered when designing future spin qubit experiments. AU - Jirovec, Daniel ID - 10058 KW - qubits KW - quantum computing KW - holes SN - 2663-337X TI - Singlet-Triplet qubits and spin-orbit interaction in 2-dimensional Ge hole gases ER - TY - JOUR AB - Spin qubits are considered to be among the most promising candidates for building a quantum processor. Group IV hole spin qubits have moved into the focus of interest due to the ease of operation and compatibility with Si technology. In addition, Ge offers the option for monolithic superconductor-semiconductor integration. Here we demonstrate a hole spin qubit operating at fields below 10 mT, the critical field of Al, by exploiting the large out-of-plane hole g-factors in planar Ge and by encoding the qubit into the singlet-triplet states of a double quantum dot. We observe electrically controlled X and Z-rotations with tunable frequencies exceeding 100 MHz and dephasing times of 1μs which we extend beyond 15μs with echo techniques. These results show that Ge hole singlet triplet qubits outperform their electronic Si and GaAs based counterparts in speed and coherence, respectively. In addition, they are on par with Ge single spin qubits, but can be operated at much lower fields underlining their potential for on chip integration with superconducting technologies. AU - Jirovec, Daniel AU - Hofmann, Andrea C AU - Ballabio, Andrea AU - Mutter, Philipp M. AU - Tavani, Giulio AU - Botifoll, Marc AU - Crippa, Alessandro AU - Kukucka, Josip AU - Sagi, Oliver AU - Martins, Frederico AU - Saez Mollejo, Jaime AU - Prieto Gonzalez, Ivan AU - Borovkov, Maksim AU - Arbiol, Jordi AU - Chrastina, Daniel AU - Isella, Giovanni AU - Katsaros, Georgios ID - 8909 IS - 8 JF - Nature Materials SN - 1476-1122 TI - A singlet triplet hole spin qubit in planar Ge VL - 20 ER - TY - THES AB - Accumulation of interstitial fluid (IF) between embryonic cells is a common phenomenon in vertebrate embryogenesis. Unlike other model systems, where these accumulations coalesce into a large central cavity – the blastocoel, in zebrafish, IF is more uniformly distributed between the deep cells (DC) before the onset of gastrulation. This is likely due to the presence of a large extraembryonic structure – the yolk cell (YC) at the position where the blastocoel typically forms in other model organisms. IF has long been speculated to play a role in tissue morphogenesis during embryogenesis, but direct evidence supporting such function is still sparse. Here we show that the relocalization of IF to the interface between the YC and DC/epiblast is critical for axial mesendoderm (ME) cell protrusion formation and migration along this interface, a key process in embryonic axis formation. We further demonstrate that axial ME cell migration and IF relocalization engage in a positive feedback loop, where axial ME migration triggers IF accumulation ahead of the advancing axial ME tissue by mechanically compressing the overlying epiblast cell layer. Upon compression, locally induced flow relocalizes the IF through the porous epiblast tissue resulting in an IF accumulation ahead of the leading axial ME. This IF accumulation, in turn, promotes cell protrusion formation and migration of the leading axial ME cells, thereby facilitating axial ME extension. Our findings reveal a central role of dynamic IF relocalization in orchestrating germ layer morphogenesis during gastrulation. AU - Huljev, Karla ID - 9397 SN - 2663-337X TI - Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation ER - TY - GEN AB - The potential of Si and SiGe-based devices for the scaling of quantum circuits is tainted by device variability. Each device needs to be tuned to operation conditions. We give a key step towards tackling this variability with an algorithm that, without modification, is capable of tuning a 4-gate Si FinFET, a 5-gate GeSi nanowire and a 7-gate SiGe heterostructure double quantum dot device from scratch. We achieve tuning times of 30, 10, and 92 minutes, respectively. The algorithm also provides insight into the parameter space landscape for each of these devices. These results show that overarching solutions for the tuning of quantum devices are enabled by machine learning. AU - Severin, B. AU - Lennon, D. T. AU - Camenzind, L. C. AU - Vigneau, F. AU - Fedele, F. AU - Jirovec, Daniel AU - Ballabio, A. AU - Chrastina, D. AU - Isella, G. AU - Kruijf, M. de AU - Carballido, M. J. AU - Svab, S. AU - Kuhlmann, A. V. AU - Braakman, F. R. AU - Geyer, S. AU - Froning, F. N. M. AU - Moon, H. AU - Osborne, M. A. AU - Sejdinovic, D. AU - Katsaros, Georgios AU - Zumbühl, D. M. AU - Briggs, G. A. D. AU - Ares, N. ID - 10066 T2 - arXiv TI - Cross-architecture tuning of silicon and SiGe-based quantum devices using machine learning ER - TY - JOUR AB - The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation. AU - Bhandari, Pradeep AU - Vandael, David H AU - Fernández-Fernández, Diego AU - Fritzius, Thorsten AU - Kleindienst, David AU - Önal, Hüseyin C AU - Montanaro-Punzengruber, Jacqueline-Claire AU - Gassmann, Martin AU - Jonas, Peter M AU - Kulik, Akos AU - Bettler, Bernhard AU - Shigemoto, Ryuichi AU - Koppensteiner, Peter ID - 9437 JF - eLife TI - GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals VL - 10 ER - TY - THES AB - Left-right asymmetries can be considered a fundamental organizational principle of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell synaptic connection shows an input-side dependent asymmetry where the hemispheric location of the presynaptic CA3 neuron determines the synaptic properties. Left-input synapses terminating on apical dendrites in stratum radiatum have a higher density of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1 and smaller areas with less often perforated PSDs. On the other hand, left-input synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities than right-input ones. Apical and basal synapses further employ different signaling pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize synaptic membrane proteins with high sensitivity and resolution, and has been used to reveal the asymmetry at the electron microscopic level. However, it requires time-consuming manual demarcation of the synaptic surface for quantitative measurements. To facilitate the analysis of replica labeling, I first developed a software named Darea, which utilizes deep-learning to automatize this demarcation. With Darea I characterized the synaptic distribution of NMDA and AMPA receptors as well as the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I explored the role of GluN2B and its carboxy-terminus in the establishment of input-side dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were detected. We further discovered a previously unknown functional asymmetry of GluN2A, which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus plays a critical role in normal formation of input-side dependent asymmetry. AU - Kleindienst, David ID - 9562 SN - 2663-337X TI - 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning ER - TY - THES AB - In this thesis, we consider several of the most classical and fundamental problems in static analysis and formal verification, including invariant generation, reachability analysis, termination analysis of probabilistic programs, data-flow analysis, quantitative analysis of Markov chains and Markov decision processes, and the problem of data packing in cache management. We use techniques from parameterized complexity theory, polyhedral geometry, and real algebraic geometry to significantly improve the state-of-the-art, in terms of both scalability and completeness guarantees, for the mentioned problems. In some cases, our results are the first theoretical improvements for the respective problems in two or three decades. AU - Goharshady, Amir Kafshdar ID - 8934 SN - 2663-337X TI - Parameterized and algebro-geometric advances in static program analysis ER - TY - THES AB - Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response. AU - Tomasek, Kathrin ID - 10307 SN - 2663-337X TI - Pathogenic Escherichia coli hijack the host immune response ER - TY - GEN AB - A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease. AU - Tomasek, Kathrin AU - Leithner, Alexander F AU - Glatzová, Ivana AU - Lukesch, Michael S. AU - Guet, Calin C AU - Sixt, Michael K ID - 10316 T2 - bioRxiv TI - Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14 ER - TY - JOUR AB - Availability of the essential macronutrient nitrogen in soil plays a critical role in plant growth, development, and impacts agricultural productivity. Plants have evolved different strategies for sensing and responding to heterogeneous nitrogen distribution. Modulation of root system architecture, including primary root growth and branching, is among the most essential plant adaptions to ensure adequate nitrogen acquisition. However, the immediate molecular pathways coordinating the adjustment of root growth in response to distinct nitrogen sources, such as nitrate or ammonium, are poorly understood. Here, we show that growth as manifested by cell division and elongation is synchronized by coordinated auxin flux between two adjacent outer tissue layers of the root. This coordination is achieved by nitrate‐dependent dephosphorylation of the PIN2 auxin efflux carrier at a previously uncharacterized phosphorylation site, leading to subsequent PIN2 lateralization and thereby regulating auxin flow between adjacent tissues. A dynamic computer model based on our experimental data successfully recapitulates experimental observations. Our study provides mechanistic insights broadening our understanding of root growth mechanisms in dynamic environments. AU - Ötvös, Krisztina AU - Marconi, Marco AU - Vega, Andrea AU - O’Brien, Jose AU - Johnson, Alexander J AU - Abualia, Rashed AU - Antonielli, Livio AU - Montesinos López, Juan C AU - Zhang, Yuzhou AU - Tan, Shutang AU - Cuesta, Candela AU - Artner, Christina AU - Bouguyon, Eleonore AU - Gojon, Alain AU - Friml, Jiří AU - Gutiérrez, Rodrigo A. AU - Wabnik, Krzysztof T AU - Benková, Eva ID - 9010 IS - 3 JF - EMBO Journal SN - 02614189 TI - Modulation of plant root growth by nitrogen source-defined regulation of polar auxin transport VL - 40 ER - TY - JOUR AB - Nitrate commands genome-wide gene expression changes that impact metabolism, physiology, plant growth, and development. In an effort to identify new components involved in nitrate responses in plants, we analyze the Arabidopsis thaliana root phosphoproteome in response to nitrate treatments via liquid chromatography coupled to tandem mass spectrometry. 176 phosphoproteins show significant changes at 5 or 20 min after nitrate treatments. Proteins identified by 5 min include signaling components such as kinases or transcription factors. In contrast, by 20 min, proteins identified were associated with transporter activity or hormone metabolism functions, among others. The phosphorylation profile of NITRATE TRANSPORTER 1.1 (NRT1.1) mutant plants was significantly altered as compared to wild-type plants, confirming its key role in nitrate signaling pathways that involves phosphorylation changes. Integrative bioinformatics analysis highlights auxin transport as an important mechanism modulated by nitrate signaling at the post-translational level. We validated a new phosphorylation site in PIN2 and provide evidence that it functions in primary and lateral root growth responses to nitrate. AU - Vega, Andrea AU - Fredes, Isabel AU - O’Brien, José AU - Shen, Zhouxin AU - Ötvös, Krisztina AU - Abualia, Rashed AU - Benková, Eva AU - Briggs, Steven P. AU - Gutiérrez, Rodrigo A. ID - 9913 IS - 9 JF - EMBO Reports SN - 1469-221X TI - Nitrate triggered phosphoproteome changes and a PIN2 phosphosite modulating root system architecture VL - 22 ER - TY - THES AB - Nitrogen is an essential macronutrient determining plant growth, development and affecting agricultural productivity. Root, as a hub that perceives and integrates local and systemic signals on the plant’s external and endogenous nitrogen resources, communicates with other plant organs to consolidate their physiology and development in accordance with actual nitrogen balance. Over the last years, numerous studies demonstrated that these comprehensive developmental adaptations rely on the interaction between pathways controlling nitrogen homeostasis and hormonal networks acting globally in the plant body. However, molecular insights into how the information about the nitrogen status is translated through hormonal pathways into specific developmental output are lacking. In my work, I addressed so far poorly understood mechanisms underlying root-to-shoot communication that lead to a rapid re-adjustment of shoot growth and development after nitrate provision. Applying a combination of molecular, cell, and developmental biology approaches, genetics and grafting experiments as well as hormonal analytics, I identified and characterized an unknown molecular framework orchestrating shoot development with a root nitrate sensory system. AU - Abualia, Rashed ID - 10303 SN - 2663-337X TI - Role of hormones in nitrate regulated growth ER - TY - THES AB - The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration. AU - Hansen, Andi H ID - 9962 KW - Neuronal migration KW - Non-cell-autonomous KW - Cell-autonomous KW - Neurodevelopmental disease SN - 2663-337X TI - Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration ER - TY - JOUR AB - Thermalization is the inevitable fate of many complex quantum systems, whose dynamics allow them to fully explore the vast configuration space regardless of the initial state---the behaviour known as quantum ergodicity. In a quest for experimental realizations of coherent long-time dynamics, efforts have focused on ergodicity-breaking mechanisms, such as integrability and localization. The recent discovery of persistent revivals in quantum simulators based on Rydberg atoms have pointed to the existence of a new type of behaviour where the system rapidly relaxes for most initial conditions, while certain initial states give rise to non-ergodic dynamics. This collective effect has been named ”quantum many-body scarring’by analogy with a related form of weak ergodicity breaking that occurs for a single particle inside a stadium billiard potential. In this Review, we provide a pedagogical introduction to quantum many-body scars and highlight the emerging connections with the semiclassical quantization of many-body systems. We discuss the relation between scars and more general routes towards weak violations of ergodicity due to embedded algebras and non-thermal eigenstates, and highlight possible applications of scars in quantum technology. AU - Serbyn, Maksym AU - Abanin, Dmitry A. AU - Papić, Zlatko ID - 9428 IS - 6 JF - Nature Physics TI - Quantum many-body scars and weak breaking of ergodicity VL - 17 ER - TY - JOUR AB - Auxin is a major plant growth regulator, but current models on auxin perception and signaling cannot explain the whole plethora of auxin effects, in particular those associated with rapid responses. A possible candidate for a component of additional auxin perception mechanisms is the AUXIN BINDING PROTEIN 1 (ABP1), whose function in planta remains unclear. Here we combined expression analysis with gain- and loss-of-function approaches to analyze the role of ABP1 in plant development. ABP1 shows a broad expression largely overlapping with, but not regulated by, transcriptional auxin response activity. Furthermore, ABP1 activity is not essential for the transcriptional auxin signaling. Genetic in planta analysis revealed that abp1 loss-of-function mutants show largely normal development with minor defects in bolting. On the other hand, ABP1 gain-of-function alleles show a broad range of growth and developmental defects, including root and hypocotyl growth and bending, lateral root and leaf development, bolting, as well as response to heat stress. At the cellular level, ABP1 gain-of-function leads to impaired auxin effect on PIN polar distribution and affects BFA-sensitive PIN intracellular aggregation. The gain-of-function analysis suggests a broad, but still mechanistically unclear involvement of ABP1 in plant development, possibly masked in abp1 loss-of-function mutants by a functional redundancy. AU - Gelová, Zuzana AU - Gallei, Michelle C AU - Pernisová, Markéta AU - Brunoud, Géraldine AU - Zhang, Xixi AU - Glanc, Matous AU - Li, Lanxin AU - Michalko, Jaroslav AU - Pavlovicova, Zlata AU - Verstraeten, Inge AU - Han, Huibin AU - Hajny, Jakub AU - Hauschild, Robert AU - Čovanová, Milada AU - Zwiewka, Marta AU - Hörmayer, Lukas AU - Fendrych, Matyas AU - Xu, Tongda AU - Vernoux, Teva AU - Friml, Jiří ID - 8931 JF - Plant Science KW - Agronomy and Crop Science KW - Plant Science KW - Genetics KW - General Medicine SN - 0168-9452 TI - Developmental roles of auxin binding protein 1 in Arabidopsis thaliana VL - 303 ER - TY - JOUR AB - The phytohormone auxin and its directional transport through tissues are intensively studied. However, a mechanistic understanding of auxin-mediated feedback on endocytosis and polar distribution of PIN auxin transporters remains limited due to contradictory observations and interpretations. Here, we used state-of-the-art methods to reexamine the auxin effects on PIN endocytic trafficking. We used high auxin concentrations or longer treatments versus lower concentrations and shorter treatments of natural (IAA) and synthetic (NAA) auxins to distinguish between specific and nonspecific effects. Longer treatments of both auxins interfere with Brefeldin A-mediated intracellular PIN2 accumulation and also with general aggregation of endomembrane compartments. NAA treatment decreased the internalization of the endocytic tracer dye, FM4-64; however, NAA treatment also affected the number, distribution, and compartment identity of the early endosome/trans-Golgi network (EE/TGN), rendering the FM4-64 endocytic assays at high NAA concentrations unreliable. To circumvent these nonspecific effects of NAA and IAA affecting the endomembrane system, we opted for alternative approaches visualizing the endocytic events directly at the plasma membrane (PM). Using Total Internal Reflection Fluorescence (TIRF) microscopy, we saw no significant effects of IAA or NAA treatments on the incidence and dynamics of clathrin foci, implying that these treatments do not affect the overall endocytosis rate. However, both NAA and IAA at low concentrations rapidly and specifically promoted endocytosis of photo-converted PIN2 from the PM. These analyses identify a specific effect of NAA and IAA on PIN2 endocytosis, thus contributing to its polarity maintenance and furthermore illustrate that high auxin levels have nonspecific effects on trafficking and endomembrane compartments. AU - Narasimhan, Madhumitha AU - Gallei, Michelle C AU - Tan, Shutang AU - Johnson, Alexander J AU - Verstraeten, Inge AU - Li, Lanxin AU - Rodriguez Solovey, Lesia AU - Han, Huibin AU - Himschoot, E AU - Wang, R AU - Vanneste, S AU - Sánchez-Simarro, J AU - Aniento, F AU - Adamowski, Maciek AU - Friml, Jiří ID - 9287 IS - 2 JF - Plant Physiology SN - 0032-0889 TI - Systematic analysis of specific and nonspecific auxin effects on endocytosis and trafficking VL - 186 ER - TY - THES AB - Plant motions occur across a wide spectrum of timescales, ranging from seed dispersal through bursting (milliseconds) and stomatal opening (minutes) to long-term adaptation of gross architecture. Relatively fast motions include water-driven growth as exemplified by root cell expansion under abiotic/biotic stresses or during gravitropism. A showcase is a root growth inhibition in 30 seconds triggered by the phytohormone auxin. However, the cellular and molecular mechanisms are still largely unknown. This thesis covers the studies about this topic as follows. By taking advantage of microfluidics combined with live imaging, pharmaceutical tools, and transgenic lines, we examined the kinetics of and causal relationship among various auxininduced rapid cellular changes in root growth, apoplastic pH, cytosolic Ca2+, cortical microtubule (CMT) orientation, and vacuolar morphology. We revealed that CMT reorientation and vacuolar constriction are the consequence of growth itself instead of responding directly to auxin. In contrast, auxin induces apoplast alkalinization to rapidly inhibit root growth in 30 seconds. This auxin-triggered apoplast alkalinization results from rapid H+- influx that is contributed by Ca2+ inward channel CYCLIC NUCLEOTIDE-GATED CHANNEL 14 (CNGC14)-dependent Ca2+ signaling. To dissect which auxin signaling mediates the rapid apoplast alkalinization, we combined microfluidics and genetic engineering to verify that TIR1/AFB receptors conduct a non-transcriptional regulation on Ca2+ and H+ -influx. This non-canonical pathway is mostly mediated by the cytosolic portion of TIR1/AFB. On the other hand, we uncovered, using biochemical and phospho-proteomic analysis, that auxin cell surface signaling component TRANSMEMBRANE KINASE 1 (TMK1) plays a negative role during auxin-trigger apoplast alkalinization and root growth inhibition through directly activating PM H+ -ATPases. Therefore, we discovered that PM H+ -ATPases counteract instead of mediate the auxintriggered rapid H+ -influx, and that TIR1/AFB and TMK1 regulate root growth antagonistically. This opposite effect of TIR1/AFB and TMK1 is consistent during auxin-induced hypocotyl elongation, leading us to explore the relation of two signaling pathways. Assisted with biochemistry and fluorescent imaging, we verified for the first time that TIR1/AFB and TMK1 can interact with each other. The ability of TIR1/AFB binding to membrane lipid provides a basis for the interaction of plasma membrane- and cytosol-localized proteins. Besides, transgenic analysis combined with genetic engineering and biochemistry showed that vi they do function in the same pathway. Particularly, auxin-induced TMK1 increase is TIR1/AFB dependent, suggesting TIR1/AFB regulation on TMK1. Conversely, TMK1 also regulates TIR1/AFB protein levels and thus auxin canonical signaling. To follow the study of rapid growth regulation, we analyzed another rapid growth regulator, signaling peptide RALF1. We showed that RALF1 also triggers a rapid and reversible growth inhibition caused by H + influx, highly resembling but not dependent on auxin. Besides, RALF1 promotes auxin biosynthesis by increasing expression of auxin biosynthesis enzyme YUCCAs and thus induces auxin signaling in ca. 1 hour, contributing to the sustained RALF1-triggered growth inhibition. These studies collectively contribute to understanding rapid regulation on plant cell growth, novel auxin signaling pathway as well as auxin-peptide crosstalk. AU - Li, Lanxin ID - 10083 SN - 2663-337X TI - Rapid cell growth regulation in Arabidopsis ER - TY - JOUR AB - Auxin plays a dual role in growth regulation and, depending on the tissue and concentration of the hormone, it can either promote or inhibit division and expansion processes in plants. Recent studies have revealed that, beyond transcriptional reprogramming, alternative auxincontrolled mechanisms regulate root growth. Here, we explored the impact of different concentrations of the synthetic auxin NAA that establish growth-promoting and -repressing conditions on the root tip proteome and phosphoproteome, generating a unique resource. From the phosphoproteome data, we pinpointed (novel) growth regulators, such as the RALF34-THE1 module. Our results, together with previously published studies, suggest that auxin, H+-ATPases, cell wall modifications and cell wall sensing receptor-like kinases are tightly embedded in a pathway regulating cell elongation. Furthermore, our study assigned a novel role to MKK2 as a regulator of primary root growth and a (potential) regulator of auxin biosynthesis and signalling, and suggests the importance of the MKK2 Thr31 phosphorylation site for growth regulation in the Arabidopsis root tip. AU - Nikonorova, N AU - Murphy, E AU - Fonseca de Lima, CF AU - Zhu, S AU - van de Cotte, B AU - Vu, LD AU - Balcerowicz, D AU - Li, Lanxin AU - Kong, X AU - De Rop, G AU - Beeckman, T AU - Friml, Jiří AU - Vissenberg, K AU - Morris, PC AU - Ding, Z AU - De Smet, I ID - 10015 JF - Cells KW - primary root KW - (phospho)proteomics KW - auxin KW - (receptor) kinase SN - 2073-4409 TI - The Arabidopsis root tip (phospho)proteomes at growth-promoting versus growth-repressing conditions reveal novel root growth regulators VL - 10 ER - TY - GEN AB - Growth regulation tailors plant development to its environment. A showcase is response to gravity, where shoots bend up and roots down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots, while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phospho-proteomics in Arabidopsis thaliana, we advance our understanding how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on the rapid regulation of the apoplastic pH, a causative growth determinant. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+-influx, causing apoplast alkalinisation. The simultaneous activation of these two counteracting mechanisms poises the root for a rapid, fine-tuned growth modulation while navigating complex soil environment. AU - Li, Lanxin AU - Verstraeten, Inge AU - Roosjen, Mark AU - Takahashi, Koji AU - Rodriguez Solovey, Lesia AU - Merrin, Jack AU - Chen, Jian AU - Shabala, Lana AU - Smet, Wouter AU - Ren, Hong AU - Vanneste, Steffen AU - Shabala, Sergey AU - De Rybel, Bert AU - Weijers, Dolf AU - Kinoshita, Toshinori AU - Gray, William M. AU - Friml, Jiří ID - 10095 SN - 2693-5015 T2 - Research Square TI - Cell surface and intracellular auxin signalling for H+-fluxes in root growth ER - TY - THES AB - Indirect reciprocity in evolutionary game theory is a prominent mechanism for explaining the evolution of cooperation among unrelated individuals. In contrast to direct reciprocity, which is based on individuals meeting repeatedly, and conditionally cooperating by using their own experiences, indirect reciprocity is based on individuals’ reputations. If a player helps another, this increases the helper’s public standing, benefitting them in the future. This lets cooperation in the population emerge without individuals having to meet more than once. While the two modes of reciprocity are intertwined, they are difficult to compare. Thus, they are usually studied in isolation. Direct reciprocity can maintain cooperation with simple strategies, and is robust against noise even when players do not remember more than their partner’s last action. Meanwhile, indirect reciprocity requires its successful strategies, or social norms, to be more complex. Exhaustive search previously identified eight such norms, called the “leading eight”, which excel at maintaining cooperation. However, as the first result of this thesis, we show that the leading eight break down once we remove the fundamental assumption that information is synchronized and public, such that everyone agrees on reputations. Once we consider a more realistic scenario of imperfect information, where reputations are private, and individuals occasionally misinterpret or miss observations, the leading eight do not promote cooperation anymore. Instead, minor initial disagreements can proliferate, fragmenting populations into subgroups. In a next step, we consider ways to mitigate this issue. We first explore whether introducing “generosity” can stabilize cooperation when players use the leading eight strategies in noisy environments. This approach of modifying strategies to include probabilistic elements for coping with errors is known to work well in direct reciprocity. However, as we show here, it fails for the more complex norms of indirect reciprocity. Imperfect information still prevents cooperation from evolving. On the other hand, we succeeded to show in this thesis that modifying the leading eight to use “quantitative assessment”, i.e. tracking reputation scores on a scale beyond good and bad, and making overall judgments of others based on a threshold, is highly successful, even when noise increases in the environment. Cooperation can flourish when reputations are more nuanced, and players have a broader understanding what it means to be “good.” Finally, we present a single theoretical framework that unites the two modes of reciprocity despite their differences. Within this framework, we identify a novel simple and successful strategy for indirect reciprocity, which can cope with noisy environments and has an analogue in direct reciprocity. We can also analyze decision making when different sources of information are available. Our results help highlight that for sustaining cooperation, already the most simple rules of reciprocity can be sufficient. AU - Schmid, Laura ID - 10293 SN - 2663-337X TI - Evolution of cooperation via (in)direct reciprocity under imperfect information ER - TY - JOUR AB - Indirect reciprocity is a mechanism for the evolution of cooperation based on social norms. This mechanism requires that individuals in a population observe and judge each other’s behaviors. Individuals with a good reputation are more likely to receive help from others. Previous work suggests that indirect reciprocity is only effective when all relevant information is reliable and publicly available. Otherwise, individuals may disagree on how to assess others, even if they all apply the same social norm. Such disagreements can lead to a breakdown of cooperation. Here we explore whether the predominantly studied ‘leading eight’ social norms of indirect reciprocity can be made more robust by equipping them with an element of generosity. To this end, we distinguish between two kinds of generosity. According to assessment generosity, individuals occasionally assign a good reputation to group members who would usually be regarded as bad. According to action generosity, individuals occasionally cooperate with group members with whom they would usually defect. Using individual-based simulations, we show that the two kinds of generosity have a very different effect on the resulting reputation dynamics. Assessment generosity tends to add to the overall noise and allows defectors to invade. In contrast, a limited amount of action generosity can be beneficial in a few cases. However, even when action generosity is beneficial, the respective simulations do not result in full cooperation. Our results suggest that while generosity can favor cooperation when individuals use the most simple strategies of reciprocity, it is disadvantageous when individuals use more complex social norms. AU - Schmid, Laura AU - Shati, Pouya AU - Hilbe, Christian AU - Chatterjee, Krishnendu ID - 9997 IS - 1 JF - Scientific Reports KW - Multidisciplinary TI - The evolution of indirect reciprocity under action and assessment generosity VL - 11 ER - TY - JOUR AB - Direct and indirect reciprocity are key mechanisms for the evolution of cooperation. Direct reciprocity means that individuals use their own experience to decide whether to cooperate with another person. Indirect reciprocity means that they also consider the experiences of others. Although these two mechanisms are intertwined, they are typically studied in isolation. Here, we introduce a mathematical framework that allows us to explore both kinds of reciprocity simultaneously. We show that the well-known ‘generous tit-for-tat’ strategy of direct reciprocity has a natural analogue in indirect reciprocity, which we call ‘generous scoring’. Using an equilibrium analysis, we characterize under which conditions either of the two strategies can maintain cooperation. With simulations, we additionally explore which kind of reciprocity evolves when members of a population engage in social learning to adapt to their environment. Our results draw unexpected connections between direct and indirect reciprocity while highlighting important differences regarding their evolvability. AU - Schmid, Laura AU - Chatterjee, Krishnendu AU - Hilbe, Christian AU - Nowak, Martin A. ID - 9402 IS - 10 JF - Nature Human Behaviour TI - A unified framework of direct and indirect reciprocity VL - 5 ER - TY - JOUR AB - Elastic bending of initially flat slender elements allows the realization and economic fabrication of intriguing curved shapes. In this work, we derive an intuitive but rigorous geometric characterization of the design space of plane elastic rods with variable stiffness. It enables designers to determine which shapes are physically viable with active bending by visual inspection alone. Building on these insights, we propose a method for efficiently designing the geometry of a flat elastic rod that realizes a target equilibrium curve, which only requires solving a linear program. We implement this method in an interactive computational design tool that gives feedback about the feasibility of a design, and computes the geometry of the structural elements necessary to realize it within an instant. The tool also offers an iterative optimization routine that improves the fabricability of a model while modifying it as little as possible. In addition, we use our geometric characterization to derive an algorithm for analyzing and recovering the stability of elastic curves that would otherwise snap out of their unstable equilibrium shapes by buckling. We show the efficacy of our approach by designing and manufacturing several physical models that are assembled from flat elements. AU - Hafner, Christian AU - Bickel, Bernd ID - 9817 IS - 4 JF - ACM Transactions on Graphics KW - Computing methodologies KW - shape modeling KW - modeling and simulation KW - theory of computation KW - computational geometry KW - mathematics of computing KW - mathematical optimization SN - 0730-0301 TI - The design space of plane elastic curves VL - 40 ER -