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Acharya, Shreyasi ; Adam, Jaroslav ; Adamová, Dagmar ; Adler, Clemens ; Adolfsson, Jonatan ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahn, Sang Un ; Aiola, Salvatore ; Akindinov, Alexander ; Al-Turany, Mohammad ; Alam, Sk Noor ; Antonczyk, Dariusz ; Arend, Andreas ; Bazo Alba, José Luis ; Albuquerque, Danilo Silva de ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Alme, Johan ; Alt, Torsten ; Altenkämper, Lucas ; Altsybeev, Igor ; Prado, Caio Alves Garcia ; Andrei, Cristian ; Andreou, Dimitra ; Andrews, Harry Arthur ; Andronic, Anton ; Anguelov, Venelin ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Anwar, Rafay ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arnold, Oliver Werner ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Audurier, Benjamin ; Augustinus, Andre ; Averbeck, Ralf Peter ; Azmi, Mohd Danish ; Badalà, Angela ; Baek, Yong Wook ; Bagnasco, Stefano ; Bailhache, Raphaëlle ; Bala, Renu ; Baldisseri, Alberto ; Ball, Markus ; Baral, Rama Chandra ; Barbano, Anastasia Maria ; Barbera, Roberto ; Barile, Francesco ; Barioglio, Luca ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Ramillien Barret, Valerie ; Bartalini, Paolo ; Barth, Klaus ; Bartos, D ; Bartsch, Esther ; Basile, Maurizio ; Bastid, Nicole ; Basu, Sumit ; Bathen, Bastian ; Batigne, Guillaume ; Batyunya, Boris ; Bätzing, Paul Christoph ; Baumann, Christoph ; Bearden, Ian Gardner ; Beck, Hans ; Bedda, Cristina ; Behera, Nirbhay Kumar ; Belikov, Iouri ; Bellini, Francesca ; Bello Martinez, Hector ; Bellwied, Rene ; Espinoza Beltran, Lucina Gabriela ; Belyaev, Vladimir ; Bencédi, Gyula ; Beolè, Stefania ; Berceanu, Ionela ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berényi, Dániel ; Bertens, Redmer Alexander ; Berzano, Dario ; Betev, Latchezar ; Bhasin, Anju ; Bhat, Inayat Rasool ; Bhati, Ashok Kumar ; Bhattacharjee, Buddhadeb ; Bhom, Jihyun ; Bianchi, Antonio ; Bianchi, Livio ; Bianchi, Nicola ; Bianchin, Chiara ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Rathijit ; Biswas, Saikat ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blume, Christoph ; Boca, Gianluigi ; Bock, Friederike ; Bogdanov, Alexey A. ; Boldizsar, Laszlo ; Bombara, Marek ; Bonomi, Germano ; Bonora, Matthias ; Book, Julian ; Borel, Herve ; Borissov, Alexander ; Borri, Marcello ; Botta, Elena ; Bourjau, Christian ; Bratrud, Lars ; Braun-Munzinger, Peter ; Bregant, Marco ; Broker, Theo Alexander ; Broz, Michal ; Brücken, Erik Jens ; Bruna, Elena ; Bruno, Giuseppe Eugenio ; Bucher, Damian ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bühler, Paul ; Bunčić, Predrag ; Busch, Oliver ; Buthelezi, Edith Zinhle ; Bashir Butt, Jamila ; Buxton, Jesse Thomas ; Cabala, Jan ; Caffarri, Davide ; Caines, Helen Louise ; Caliva, Alberto ; Calvo Villar, Ernesto ; Camerini, Paolo ; Capon, Aaron Allan ; Caragheorgheopol, G ; Carena, Francesco ; Carena, Wisla ; Carnesecchi, Francesca ; Castillo Castellanos, Javier Ernesto ; Castro, Andrew John ; Casula, Ester Anna Rita ; Catanescu, V ; Ceballos Sanchez, Cesar ; Cerello, Piergiorgio ; Chandra, Sinjini ; Chang, Beomsu ; Chapeland, Sylvain ; Chartier, Marielle ; Chattopadhyay, Subhasis ; Chattopadhyay, Sukalyan ; Chauvin, Alex Henri Jean ; Chernenko, Sergey P. ; Cherney, Michael Gerard ; Cheshkov, Cvetan Valeriev ; Cheynis, Brigitte ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Cho, Soyeon ; Chochula, Peter ; Chojnacki, Marek ; Choudhury, Subikash ; Chowdhury, Tasnuva ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Chung, Suh-Urk ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Ciobanu, M ; Cleymans, Jean Willy Andre ; Colamaria, Fabio Filippo ; Colella, Domenico ; Collu, Alberto ; Colocci, Manuel ; Concas, Matteo ; Conesa Balbastre, Gustavo ; Conesa Del Valle, Zaida ; Connors, Megan Elizabeth ; Contreras Nuno, Jesus Guillermo ; Cormier, Thomas Michael ; Corrales Morales, Yasser ; Cortes Maldonado, Ismael ; Cortese, Pietro ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Costanza, Susanna ; Crkovská, Jana ; Crochet, Philippe ; Cuautle Flores, Eleazar ; Cunqueiro Mendez, Leticia ; Dahms, Torsten ; Dainese, Andrea ; Danisch, Meike Charlotte ; Danu, Andrea ; Das, Debasish ; Das, Indranil ; Das, Supriya ; Dash, Ajay Kumar ; Dash, Sadhana ; Daues, Heinz ; De, Sudipan ; De Caro, Annalisa ; De Cataldo, Giacinto ; Conti, Camila de ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; De Marco, Nora ; De Pasquale, Salvatore ; Souza, Rafael Derradi de ; Degenhardt, Hermann Franz ; Deisting, Alexander ; Deloff, Andrzej ; Deplano, Caterina ; Devismes, A ; Dhankher, Preeti ; Di Bari, Domenico ; Di Mauro, Antonio ; Di Nezza, Pasquale ; Di Ruzza, Benedetto ; Dietel, Thomas ; Dillenseger, Pascal ; Divià, Roberto ; Djuvsland, Øystein ; Dobrin, Alexandru Florin ; Domenicis Gimenez, Diogenes ; Donigus, Benjamin ; Dordic, Olja ; Doremalen, Lennart Vincent Rogier van ; Dubey, Anand Kumar ; Dubla, Andrea ; Ducroux, Laurent ; Duggal, Ashpreet Kaur ; Dupieux, Pascal ; Duta, V ; Ehlers Iii, Raymond James ; Elia, Domenico ; Emschermann, David ; Endress, Eric ; Engel, Heiko ; Epple, Eliane ; Erazmus, Barbara Ewa ; Erhardt, Filip ; Espagnon, Bruno ; Esumi, ShinIchi ; Eulisse, Giulio ; Eum, Jongsik ; Evans, David ; Evdokimov, Sergey ; Fabbietti, Laura ; Faivre, Julien ; Fantoni, Alessandra ; Fasel, Markus ; Fateev, O ; Feldkamp, Linus ; Feliciello, Alessandro ; Feofilov, Grigori A. ; Ferencei, Jozef ; Fernández Téllez, Arturo ; Ferretti, Alessandro ; Festanti, Andrea ; Feuillard, Victor Jose Gaston ; Figiel, Jan ; Figueredo, Marcel Araujo Silva ; Filchagin, Sergey ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Fleck, M ; Floris, Michele ; Foertsch, Siegfried Valentin ; Foka, Panagiota ; Fokin, Sergey ; Fragiacomo, Enrico ; 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Greiner, Leo Clifford ; Grelli, Alessandro ; Grigoraș, Costin ; Grigoryev, Vladislav ; Grigoryan, Ara ; Grigoryan, Smbat ; Grimm, Helge ; Grion, Nevio ; Gronefeld, Julius Maximilian ; Grosa, Fabrizio ; Große-Oetringhaus, Jan Fiete ; Grosso, Raffaele ; Gruber, Lukas ; Guber, Fedor ; Guernane, Rachid ; Guerzoni, Barbara ; Gulbrandsen, Kristjan Herlache ; Gunji, Taku ; Gupta, Anik ; Gupta, Ramni ; Gutfleisch, M ; Bautista Guzman, Irais ; Haake, Rüdiger ; Hadjidakis, Cynthia Marie ; Hamagaki, Hideki ; Hamar, Gergö ; Hamon, Julien Charles ; Haque, Md Rihan ; Harris, John William ; Hartig, Matthias ; Harton, Austin Vincent ; Hassan, Hadi ; Hatzifotiadou, Despina ; Hayashi, Shinichi ; Heckel, Stefan Thomas ; Hehner, Joerg ; Heide, Markus ; Hellbär, Ernst ; Helstrup, Håvard ; Herghelegiu, Andrei Ionut ; Herrera Corral, Gerardo Antonio ; Herrmann, Florian ; Herrmann, Norbert ; Hess, Benjamin Andreas ; Hetland, Kristin Fanebust ; Hillemanns, Hartmut ; Hills, Christopher ; Hippolyte, Boris ; Hladkỳ, Jan ; Hohlweger, Bernhard ; Horak, David ; Hornung, Sebastian ; Hosokawa, Ritsuya ; Hristov, Peter ; Huber, Sebastian ; Hughes, Charles ; Humanic, Thomas J. ; Hussain, Nur ; Hussain, Tahir ; Hutter, Dirk ; Hwang, Dae Sung ; Iga Buitron, Sergio Arturo ; Ilkaev, Radiy ; Inaba, Motoi ; Ippolitov, Mikhail ; Irfan, Muhammad ; Islam, Md Samsul ; Ivanov, Marian ; Ivanov, Vladimir ; Izucheev, Vladimir ; Jacak, Barbara ; Jacazio, Nicolò ; Jacobs, Peter Martin ; Jadhav, Manoj Bhanudas ; Jadlovsky, Jan ; Jaelani, Syaefudin ; Jahnke, Cristiane ; Jakubowska, Monika Joanna ; Janik, Malgorzata Anna ; Pahula Hewage, Sandun ; Jena, Chitrasen ; Jena, Satyajit ; Jercic, Marko ; Jiménez Bustamante, Raúl Tonatiuh ; Jones, Peter Graham ; Jusko, Anton ; Kalinak, Peter ; Kalweit, Alexander Philipp ; Kang, Ju Hwan ; Kaplin, Vladimir ; Kar, Somnath ; Karasu Uysal, Ayben ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karayan, Lilit ; Karczmarczyk, Przemyslaw ; Karpechev, Evgeny ; Kebschull, Udo ; Keidel, Ralf ; Keijdener, Darius Laurens D. ; Keil, Markus ; Ketzer, Bernhard ; Khabanova, Zhanna ; Khan, Palash ; Khan, Shuaib Ahmad ; Khanzadeev, Alexei ; Kharlov, Yury ; Khatun, Anisa ; Khuntia, Arvind ; Kielbowicz, Mirosław Marek ; Kileng, Bjarte ; Kim, Byungchul ; Kim, Daehyeok ; Kim, Dong Jo ; Kim, Hyeonjoong ; Kim, Jinsook ; Kim, Jiyoung ; Kim, Minjung ; Kim, Minwoo ; Kim, Se Yong ; Kim, Taesoo ; Kirsch, Stefan ; Kisel, Ivan ; Kiselev, Sergej N. ; Kisiel, Adam Ryszard ; Kislov, E ; Kiss, Gabor ; Klay, Jennifer Lynn ; Klein, Carsten ; Klein, Jochen ; Klein-Bösing, Christian ; Klein-Bösing, Melanie ; Kliemant, Michael ; Klingenmeyer, Hannah ; Klewin, Sebastian ; Kluge, Alexander ; Knichel, Michael Linus ; Knospe, Anders Garritt ; Kobdaj, Chinorat ; Varga-Kofarago, Monika ; Kohn, Martin ; Kollegger, Thorsten ; Kondratev, Valerii ; Kondratyeva, Natalia ; Kondratyuk, Evgeny ; Konevskikh, Artem ; Konno, Masahiro ; Konyushikhin, Maxim A. ; Kopcik, Michal ; Kour, Mandeep ; Kouzinopoulos, Charalampos ; Kovalenko, Oleksandr ; Kovalenko, Vladimir ; Kowalski, Marek ; Koyithatta Meethaleveedu, Greeshma ; Králik, Ivan ; Kramer, Frederick ; Kravčáková, Adela ; Krawutschke, Tobias ; Kreis, Lukas ; Krivda, Marian ; Krizek, Filip ; Krumbhorn, Dirk ; Kryshen, Evgeny ; Krzewicki, Mikolaj ; Kubera, Andrew Michael ; Kucera, Vit ; Kuhn, Christian Claude ; Kuijer, Paulus Gerardus ; Kumar, Ajay ; Kumar, Jitendra ; Kumar, Lokesh ; Kumar, Shyam ; Kundu, Sourav ; Kurashvili, Podist ; Kurepin, Alexander ; Kurepin, Alexey B. ; Kuryakin, Alexey ; Kushpil, Svetlana ; Kweon, Min Jung ; Kwon, Youngil ; La Pointe, Sarah Louise ; La Rocca, Paola ; Lagana Fernandes, Caio ; Lai, Yue Shi ; Lakomov, Igor ; Langoy, Rune ; Lapidus, Kirill ; Lara Martinez, Camilo Ernesto ; Lardeux, Antoine Xavier ; Lattuca, Alessandra ; Laudi, Elisa ; Lavicka, Roman ; Lea, Ramona ; Leardini, Lucia ; Lee, Seongjoo ; Lehas, Fatiha ; Lehmann, T ; Lehner, Jorg ; Lehner, Sebastian ; Lehrbach, Johannes ; Lemmon, Roy Crawford ; Lenti, Vito ; Leogrande, Emilia ; Leon Monzon, Ildefonso ; Lesser, F ; Lévai, Peter ; Li, Xiaomei ; Lien, Jørgen André ; Lietava, Roman ; Lim, Bong-Hwi ; Lindal, Svein ; Lindenstruth, Volker ; Lindsay, Scott William ; Lippmann, Christian ; Lisa, Michael A. ; Litichevskyi, Vladyslav ; Llope, William ; Lodato, Davide Francesco ; Lohner, Daniel ; Lønne, Per-Ivar ; Loginov, Vitaly ; Loizides, Constantinos ; Lončar, Petra ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Lowe, Andrew John ; Lu, XianGuo ; Ludolphs, W ; Lüttig, Philipp ; Luhder, Jens Robert ; Lunardon, Marcello ; Luparello, Grazia ; Lupi, Matteo ; Lutz, Tyler Harrison ; Maevskaya, Alla ; Mager, Magnus ; Magureanu, C ; Mahajan, Sanjay ; Mahmoud, Tariq ; Mahmood, Sohail Musa ; Maire, Antonin ; Majka, Richard Daniel ; Malaev, Mikhail ; Malinina, Liudmila ; Mal’Kevich, Dmitry ; Malzacher, Peter ; Mamonov, Alexander ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Margutti, Jacopo ; 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Morsch, Andreas ; Muccifora, Valeria ; Mudnic, Eugen ; Muhlheim, Daniel ; Muhuri, Sanjib ; Mukherjee, Maitreyee ; Mulligan, James Declan ; Gameiro Munhoz, Marcelo ; Munning, Konstantin ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Myers, Corey James ; Myrcha, Julian Wojciech ; Mycke, Jan Felix ; Nag, Dipanjan ; Naik, Bharati ; Nair, Rahul Ramachandran ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Narayan, Amrendra ; Naru, Muhammad Umair ; Luz, Pedro Hugo Ferreira Natal da ; Nattrass, Christine ; Rosado Navarro, Sebastian ; Nayak, Kishora ; Nayak, Ranjit ; Nayak, Tapan Kumar ; Nazarenko, Sergey ; Nedosekin, Alexander ; Oliveira, Renato Aparecido Negrao de ; Neher, Michael ; Nellen, Lukas ; Nesbo, Simon Voigt ; Ng, Fabian ; Nicassio, Maria ; Niculescu, Mihai ; Niedziela, Jeremi ; Nielsen, Borge Svane ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Nomokonov, Petr V. ; Nooren, Gerardus ; Cabanillas Noris, Juan Carlos ; Norman, Jaime ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Oeschler, Helmut ; Oh, Saehanseul ; Ohlson, Alice ; Okubo, Tsubasa ; Oláh, László ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Onderwaater, Jacobus ; Oppedisano, Chiara ; Orava, Risto ; Oravec, Matej ; Ortiz Velasquez, Antonio ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Pachmayer, Yvonne C. ; Pacik, Vojtech ; Pagano, Davide ; Pagano, Paola ; Paic, Guy ; Panebratsev, Yu ; Palni, Prabhakar ; Pan, Jinjin ; Pandey, Ashutosh Kumar ; Panebianco, Stefano Matthias ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Pareek, Pooja ; Park, Jonghan ; Park, WooJin ; Parmar, Sonia ; Passfeld, Annika ; Pathak, Surya Prakash ; Patra, Rajendra Nath ; Paul, Biswarup ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pereira, Luis Gustavo ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Pérez Lezama, Edgar ; Peskov, Vladimir ; Pestov, Yury N. ; Petráček, Vojtech ; Petris, M ; Petrov, Viacheslav ; Petrovici, Mihai A. ; Petta, Catia ; Pezzi, Rafael Peretti ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Ozelin de Lima Pimentel, Laís ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pitz, Nora ; Piyarathna, Danthasinghe ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Pluta, Jan Marian ; Pochybova, Sona ; Podesta Lerma, Pedro Luis Manuel ; Poghosyan, Martin G. ; Polishchuk, Boris ; Poljak, Nikola ; Poonsawat, Wanchaloem ; Pop, Amalia ; Poppenborg, Hendrik ; Porteboeuf, Sarah Julie ; Pozdniakov, Valeriy ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Puddu, Giovanna ; Pujahari, Prabhat Ranjan ; Punin, Valery ; Putschke, Jörn H. ; Radomski, Sylwester ; Rachevski, Alexandre ; Raha, Sibaji ; Rajput, Sonia ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Rana, Dhan Bahadur ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rascanu, Bogdan Theodor ; Rathee, Deepika ; Ratza, Viktor ; Ravasenga, Ivan ; Read, Kenneth Francis ; Redlich, Krzysztof ; Rehman, Attiq ur ; Reichelt, Patrick ; Reidt, Felix ; Reischl, A ; Ren, Xiaowen ; Renfordt, Rainer Arno Ernst ; Reolon, Anna Rita ; Reshetin, Andrey ; Reygers, Klaus ; Riabov, Viktor ; Ricci, Renato Angelo ; Richert, Tuva Ora Herenui ; Richter, Matthias Rudolph ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Ristea, Cătălin-Lucian ; Rodrı́guez Cahuantzi, Mario ; Røed, Ketil ; Rogochaya, Elena ; Rohr, David ; Röhrich, Dieter ; Rokita, Przemyslaw Stefan ; Ronchetti, Federico ; Dominguez Rosas, Edgar ; Rosnet, Philippe ; Rossi, Andrea ; Rotondi, Alberto ; Roukoutakis, Filimon ; Roy, Ankhi ; Roy, Christelle Sophie ; Roy, Pradip Kumar ; Vazquez Rueda, Omar ; Rui, Rinaldo ; Rumyantsev, Boris ; Rusanov, Ivan ; Rustamov, Anar ; Ryabinkin, Evgeny ; Ryabov, Yury ; Rybicki, Andrzej ; Saarinen, Sampo ; Sadhu, Samrangy ; Sadovskiy, Sergey ; Šafařík, Karel ; Saha, Sumit Kumar ; SahlmÜller, Baldo ; Sahoo, Baidyanath ; Sahoo, Pragati ; Sahoo, Raghunath ; Sahoo, Sarita ; Sahu, Pradip Kumar ; Saini, Jogender ; Sakai, Shingo ; Sakata, Dousatsu ; Saleh, Mohammad Ahmad ; Salzwedel, Jai ; Sambyal, Sanjeev Singh ; Samsonov, Vladimir ; Sandoval, Andres ; Sann, Hans ; Sano, Masato ; Santo, Rainer ; Sarkar, Debojit ; Sarkar, Nachiketa ; Sarma, Pranjal ; Sas, Mike Henry Petrus ; Scapparone, Eugenio ; Scarlassara, Fernando ; Schaefer, Brennan ; Scharenberg, Rolf Paul ; Scheid, Horst Sebastian ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schmidt, Marten Ole ; Schmidt, Martin ; Schmidt, Nicolas ; Schmiederer, Stefan ; Schneider, R ; Schukraft, Jürgen ; Schulze, R ; Schutz, Yves Roland ; Schwarz, Kilian Eberhard ; Schweda, Kai Oliver ; Scioli, Gilda ; Scomparin, Enrico ; Scott, Rebecca Michelle ; Sedykh, S ; Šefčík, Michal ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selyuzhenkov, Ilya ; Senosi, Kgotlaesele ; 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The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Acharya, Shreyasi ; Adam, Jaroslav ; Adamová, Dagmar ; Adler, Clemens ; Adolfsson, Jonatan ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahn, Sang Un ; Aiola, Salvatore ; Akindinov, Alexander ; Al-Turany, Mohammad ; Alam, Sk Noor ; Antonczyk, Dariusz ; Arend, Andreas ; Bazo Alba, José Luis ; Albuquerque, Danilo Silva de ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Alme, Johan ; Alt, Torsten ; Altenkämper, Lucas ; Altsybeev, Igor ; Prado, Caio Alves Garcia ; Andrei, Cristian ; Andreou, Dimitra ; Andrews, Harry Arthur ; Andronic, Anton ; Anguelov, Venelin ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Anwar, Rafay ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arnold, Oliver Werner ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Audurier, Benjamin ; Augustinus, Andre ; 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Lesser, F ; Lévai, Peter ; Li, Xiaomei ; Lien, Jørgen André ; Lietava, Roman ; Lim, Bong-Hwi ; Lindal, Svein ; Lindenstruth, Volker ; Lindsay, Scott William ; Lippmann, Christian ; Lisa, Michael A. ; Litichevskyi, Vladyslav ; Llope, William ; Lodato, Davide Francesco ; Lohner, Daniel ; Lønne, Per-Ivar ; Loginov, Vitaly ; Loizides, Constantinos ; Lončar, Petra ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Lowe, Andrew John ; Lu, XianGuo ; Ludolphs, W ; Lüttig, Philipp ; Luhder, Jens Robert ; Lunardon, Marcello ; Luparello, Grazia ; Lupi, Matteo ; Lutz, Tyler Harrison ; Maevskaya, Alla ; Mager, Magnus ; Magureanu, C ; Mahajan, Sanjay ; Mahmoud, Tariq ; Mahmood, Sohail Musa ; Maire, Antonin ; Majka, Richard Daniel ; Malaev, Mikhail ; Malinina, Liudmila ; Mal’Kevich, Dmitry ; Malzacher, Peter ; Mamonov, Alexander ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Margutti, Jacopo ; 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Morsch, Andreas ; Muccifora, Valeria ; Mudnic, Eugen ; Muhlheim, Daniel ; Muhuri, Sanjib ; Mukherjee, Maitreyee ; Mulligan, James Declan ; Gameiro Munhoz, Marcelo ; Munning, Konstantin ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Myers, Corey James ; Myrcha, Julian Wojciech ; Mycke, Jan Felix ; Nag, Dipanjan ; Naik, Bharati ; Nair, Rahul Ramachandran ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Narayan, Amrendra ; Naru, Muhammad Umair ; Luz, Pedro Hugo Ferreira Natal da ; Nattrass, Christine ; Rosado Navarro, Sebastian ; Nayak, Kishora ; Nayak, Ranjit ; Nayak, Tapan Kumar ; Nazarenko, Sergey ; Nedosekin, Alexander ; Oliveira, Renato Aparecido Negrao de ; Neher, Michael ; Nellen, Lukas ; Nesbo, Simon Voigt ; Ng, Fabian ; Nicassio, Maria ; Niculescu, Mihai ; Niedziela, Jeremi ; Nielsen, Borge Svane ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Nomokonov, Petr V. ; Nooren, Gerardus ; Cabanillas Noris, Juan Carlos ; Norman, Jaime ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Oeschler, Helmut ; Oh, Saehanseul ; Ohlson, Alice ; Okubo, Tsubasa ; Oláh, László ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Onderwaater, Jacobus ; Oppedisano, Chiara ; Orava, Risto ; Oravec, Matej ; Ortiz Velasquez, Antonio ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Pachmayer, Yvonne C. ; Pacik, Vojtech ; Pagano, Davide ; Pagano, Paola ; Paic, Guy ; Panebratsev, Yu ; Palni, Prabhakar ; Pan, Jinjin ; Pandey, Ashutosh Kumar ; Panebianco, Stefano Matthias ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Pareek, Pooja ; Park, Jonghan ; Park, WooJin ; Parmar, Sonia ; Passfeld, Annika ; Pathak, Surya Prakash ; Patra, Rajendra Nath ; Paul, Biswarup ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pereira, Luis Gustavo ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Pérez Lezama, Edgar ; Peskov, Vladimir ; Pestov, Yury N. ; Petráček, Vojtech ; Petris, M ; Petrov, Viacheslav ; Petrovici, Mihai A. ; Petta, Catia ; Pezzi, Rafael Peretti ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Ozelin de Lima Pimentel, Laís ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pitz, Nora ; Piyarathna, Danthasinghe ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Pluta, Jan Marian ; Pochybova, Sona ; Podesta Lerma, Pedro Luis Manuel ; Poghosyan, Martin G. ; Polishchuk, Boris ; Poljak, Nikola ; Poonsawat, Wanchaloem ; Pop, Amalia ; Poppenborg, Hendrik ; Porteboeuf, Sarah Julie ; Pozdniakov, Valeriy ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Puddu, Giovanna ; Pujahari, Prabhat Ranjan ; Punin, Valery ; Putschke, Jörn H. ; Radomski, Sylwester ; Rachevski, Alexandre ; Raha, Sibaji ; Rajput, Sonia ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Rana, Dhan Bahadur ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rascanu, Bogdan Theodor ; Rathee, Deepika ; Ratza, Viktor ; Ravasenga, Ivan ; Read, Kenneth Francis ; Redlich, Krzysztof ; Rehman, Attiq ur ; Reichelt, Patrick ; Reidt, Felix ; Reischl, A ; Ren, Xiaowen ; Renfordt, Rainer Arno Ernst ; Reolon, Anna Rita ; Reshetin, Andrey ; Reygers, Klaus ; Riabov, Viktor ; Ricci, Renato Angelo ; Richert, Tuva Ora Herenui ; Richter, Matthias Rudolph ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Ristea, Cătălin-Lucian ; Rodrı́guez Cahuantzi, Mario ; Røed, Ketil ; Rogochaya, Elena ; Rohr, David ; Röhrich, Dieter ; Rokita, Przemyslaw Stefan ; Ronchetti, Federico ; Dominguez Rosas, Edgar ; Rosnet, Philippe ; Rossi, Andrea ; Rotondi, Alberto ; Roukoutakis, Filimon ; Roy, Ankhi ; Roy, Christelle Sophie ; Roy, Pradip Kumar ; Vazquez Rueda, Omar ; Rui, Rinaldo ; Rumyantsev, Boris ; Rusanov, Ivan ; Rustamov, Anar ; Ryabinkin, Evgeny ; Ryabov, Yury ; Rybicki, Andrzej ; Saarinen, Sampo ; Sadhu, Samrangy ; Sadovskiy, Sergey ; Šafařík, Karel ; Saha, Sumit Kumar ; SahlmÜller, Baldo ; Sahoo, Baidyanath ; Sahoo, Pragati ; Sahoo, Raghunath ; Sahoo, Sarita ; Sahu, Pradip Kumar ; Saini, Jogender ; Sakai, Shingo ; Sakata, Dousatsu ; Saleh, Mohammad Ahmad ; Salzwedel, Jai ; Sambyal, Sanjeev Singh ; Samsonov, Vladimir ; Sandoval, Andres ; Sann, Hans ; Sano, Masato ; Santo, Rainer ; Sarkar, Debojit ; Sarkar, Nachiketa ; Sarma, Pranjal ; Sas, Mike Henry Petrus ; Scapparone, Eugenio ; Scarlassara, Fernando ; Schaefer, Brennan ; Scharenberg, Rolf Paul ; Scheid, Horst Sebastian ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schmidt, Marten Ole ; Schmidt, Martin ; Schmidt, Nicolas ; Schmiederer, Stefan ; Schneider, R ; Schukraft, Jürgen ; Schulze, R ; Schutz, Yves Roland ; Schwarz, Kilian Eberhard ; Schweda, Kai Oliver ; Scioli, Gilda ; Scomparin, Enrico ; Scott, Rebecca Michelle ; Sedykh, S ; Šefčík, Michal ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selyuzhenkov, Ilya ; Senosi, Kgotlaesele ; Senyukov, Serhiy ; Serradilla Rodriguez, Eulogio ; Sett, Priyanka ; Sevcenco, Adrian ; Shabanov, Arseniy ; Shabetai, Alexandre ; Shahoyan, Ruben ; Shaikh, Wadut ; Shangaraev, Artem ; Sharma, Anjali ; Sharma, Ankita ; Sharma, Mona ; Sharma, Monika ; Sharma, Natasha ; Sheikh, Ashik Ikbal ; Shigaki, Kenta ; Shimansky, S ; Shou, Qiye ; Shtejer Diaz, Katherin ; Shukla, P ; Sibiryak, Yury ; Sicking, Eva ; Siddhanta, Sabyasachi ; Sielewicz, Krzysztof Marek ; Siemiarczuk, Teodor ; Silaeva, Svetlana ; Silvermyr, David Olle Rickard ; Silvestre, Catherine Micaela ; Simatovic, Goran ; Simon, Reinhard S ; Simonetti, Giuseppe ; Singaraju, Rama Narayana ; Singh, Ranbir ; Singhal, Vikas ; Sarkar - Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Slupecki, Maciej ; Smirnov, Nikolai ; Smykov, L ; Snellings, Raimond ; Snellman, Tomas Wilhelm ; Solveit, Hans Kristian ; Sommer, Wolfgang ; Song, Jihye ; Song, Myunggeun ; Soramel, Francesca ; Sorensen, Soren Pontoppidan ; Sozzi, Federica ; Spiriti, Eleuterio ; Sputowska, Iwona Anna ; Srivastava, Brijesh Kumar ; Stachel, Johanna ; Stan, Ionel ; Stankus, Paul William ; Stelzer, Herbert ; Stenlund, Evert Anders ; Stiller, Johannes ; Stocco, Diego ; Stockmeyer, M.R. ; Storetvedt, Maksim Melnik ; Strmen, Peter ; Suaide, Alexandre Alarcon do Passo ; Sugitate, Toru ; Suire, Christophe Pierre ; Suleymanov, Mais Kazim Oglu ; Šuljić, Miljenko ; Sultanov, Rishat ; Šumbera, Michal ; Sumowidagdo, Suharyo ; Suzuki, Ken ; Swain, Sagarika ; Szabo, Alexander ; Szarka, Imrich ; Tabassam, Uzma ; Takahashi, Jun ; Tambave, Ganesh Jagannath ; Tanaka, Naoto ; Tarhini, Mohamad ; Tariq, Mohammad ; Tarzila, Madalina-Gabriela ; Tauro, Arturo ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terasaki, Kohei ; Terrevoli, Cristina ; Teyssier, Boris ; Thakur, Dhananjaya ; Thakur, Sanchari ; Thomas, Deepa ; Thoresen, Freja ; Tieulent, Raphael Noel ; Tikhonov, Anatoly ; Tilsner, Heinz ; Timmins, Anthony Robert ; Toia, Alberica ; Rojas Torres, Solangel ; Tripathy, Sushanta ; Trogolo, Stefano ; Trombetta, Giuseppe ; Tropp, Lukas ; Trubnikov, Victor ; Trzaska, Wladyslaw Henryk ; Trzeciak, Barbara Antonina ; Tsiledakis, Georgios ; Tsuji, Tomoya ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ullaland, Kjetil ; Umaka, Ejiro Naomi ; Uras, Antonio ; Usai, Gianluca ; Utrobicic, Antonija ; Vala, Martin ; Maarel, Jasper van der ; Hoorne, Jacobus Willem van ; Leeuwen, Marco van ; Vanat, Tomas ; Vargas, H ; Vyvre, Pierre vande ; Varga, Dezsö ; Vargas Treviño, Maria Aurora Diozcora ; Vargyas, Márton ; Varma, Raghava ; Vasileiou, Maria ; Vasiliev, Andrey ; Vauthier, Astrid ; Vazquez Doce, Oton ; Vechernin, Vladimir ; Veen, Annelies Marianne ; Velure, Arild ; Vercellin, Ermanno ; Vergara Limon, Sergio ; Vernet, Renaud ; Vértesi, Róbert ; Vicković, Linda ; Vigolo, Sonia ; Viinikainen, Jussi Samuli ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Villatoro Tello, Abraham ; Vinogradov, Alexander ; Vinogradov, Leonid ; Virgili, Tiziano ; Vislavicius, Vytautas ; Vodopyanov, Alexander ; Volkl, Martin Andreas ; Voloshin, Kirill ; Voloshin, Sergei ; Volpe, Giacomo ; Haller, Barthélémy von ; Vorobyev, Ivan ; Voscek, Dominik ; Vranić, Danilo ; Vrlakova, Janka ; Vulpescu, Bogdan ; Wagner, Boris ; Wang, Hongkai ; Wang, Mengliang ; Wang, Yifei ; Watanabe, Daisuke ; Watanabe, Kengo ; Watanabe, Yosuke ; Weber, Michael ; Weber, Steffen Georg ; Wegerle, Dominik ; Weiser, Dennis ; Wenzel, Sandro Christian ; Wessels, Johannes P. ; Westerhoff, Uwe ; Whitehead, Andile Mothegi ; Wiechula, Jens ; Wikne, Jon ; Wilk, Alexander ; Wilk, Grzegorz Andrzej ; Wilkinson, Jeremy John ; Willems, Guido Alexander ; Williams, M. Crispin S. ; Willsher, Emily ; Windelband, Bernd Stefan ; Winn, Michael ; Witt, William Edward ; Xu, C ; Yalcin, Serpil ; Yamakawa, Kosei ; Yang, Ping ; Yano, Satoshi ; Yin, Zhongbao ; Yokoyama, Hiroki ; Yoo, In-kwon ; Yoon, Jin Hee ; Yurchenko, Volodymyr ; Yurevich, Vladimir ; Zaccolo, Valentina ; Zaman, Ali ; Zampolli, Chiara ; Correia Zanoli, Henrique Jose ; Zanevski, Yuri ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zavyalov, Nikolay ; Zbroszczyk, Hanna Paulina ; Zhalov, Mikhail ; Zhang, Haitao ; Zhang, Xiaoming ; Zhang, Yonghong ; Chunhui, Zhang ; Zhang, Zuman ; Zhao, Chengxin ; Zhigareva, Natalia ; Zhou, Daicui ; Zhou, You ; Zhou, Zhuo ; Zhu, Hongsheng ; Zhu, Jianhui ; Zichichi, Antonino ; Zimmer, Stefan ; Zimmermann, Alice ; Zimmermann, Markus ; Zinovjev, Gennady M. ; Zmeskal, Johann ; Zou, Shuguang
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Hou, Liping ; Bergen, Sarah E. ; Akula, Nirmala ; Song, Jie ; Hultman, Christina M. ; Landén, Mikael ; Adli, Mazda ; Alda, Martin ; Ardau, Raffaella ; Arias, Bárbara ; Aubry, Jean-Michel ; Backlund, Lena ; Badner, Judith A. ; Barrett, Thomas B. ; Bauer, Michael ; Baune, Bernhard T. ; Bellivier, Frank ; Benabarre Hernandez, Antonio ; Bengesser, Susanne ; Berrettini, Wade H. ; Bhattacharjee, Abesh Kumar ; Biernacka, Joanna ; Birner, Armin ; Bloss, Cinnamon S. ; Brichant-Petitjean, Clara ; Bui, Elise T. ; Byerley, William ; Cervantes, Pablo ; Chillotti, Caterina ; Cichon, Sven ; Colom, Francesc ; Coryell, William ; Craig, David W. ; Cruceanu, Cristiana ; Czerski, Piotr M. ; Davis, Tony ; Dayer, Alexandre ; Degenhardt, Franziska ; Del Zompo, Maria ; DePaulo, J. Raymond ; Edenberg, Howard J. ; Étain, Bruno ; Falkai, Peter ; Foroud, Tatiana ; Forstner, Andreas Josef ; Frisén, Louise ; Frye, Mark A. ; Fullerton, Janice M. ; Gard, Sébastien ; Garnham, Julie S. ; Gershon, Elliot S. ; Goes, Fernando S. ; Greenwood, Tiffany A. ; Grigoroiu-Serbanescu, Maria ; Hauser, Joanna ; Heilbronner, Urs ; Heilmann-Heimbach, Stefanie ; Herms, Stefan ; Hipolito, Maria ; Hitturlingappa, Shashi ; Hoffmann, Per ; Hofmann, Andrea ; Jamain, Stephane ; Jiménez, Esther ; Kahn, Jean-Pierre ; Kassem, Layla ; Kelsoe, John R. ; Kittel-Schneider, Sarah ; Kliwicki, Sebastian ; Koller, Daniel L. ; König, Barbara ; Lackner, Nina ; Laje, Gonzalo ; Lang, Maren ; Lavebratt, Catharina ; Lawson, William B. ; Leboyer, Marion ; Leckband, Susan G. ; Liu, Chunyu ; Maaser, Anna ; Mahon, Pamela B. ; Maier, Wolfgang ; Maj, Mario ; Manchia, Mirko ; Martinsson, Lina ; McCarthy, Michael J. ; McElroy, Susan L. ; McInnis, Melvin G. ; McKinney, Rebecca ; Mitchell, Philip B. ; Mitjans, Marina ; Mondimore, Francis Mark ; Monteleone, Palmiero ; Mühleisen, Thomas W. ; Nievergelt, Caroline M. ; Nöthen, Markus Maria ; Novák, Tomas ; Nurnberger, John I. ; Nwulia, Evaristus A. ; Ösby, Urban ; Pfennig, Andrea ; Potash, James B. ; Propping, Peter ; Reif, Andreas ; Reininghaus, Eva ; Rice, John ; Rietschel, Marcella ; Rouleau, Guy A. ; Rybakowski, Janusz K. ; Schalling, Martin ; Scheftner, William A. ; Schofield, Peter R. ; Schork, Nicholas J. ; Schulze, Thomas Gerd ; Schumacher, Johannes ; Schweizer, Barbara W. ; Severino, Giovanni ; Shekhtman, Tatyana ; Shilling, Paul D. ; Simhandl, Christian ; Slaney, Claire M. ; Smith, Erin N. ; Squassina, Alessio ; Stamm, Thomas ; Stopkova, Pavla ; Streit, Fabian ; Strohmaier, Jana ; Szelinger, Szabolcs ; Tighe, Sarah K. ; Tortorella, Alfonso ; Turecki, Gustavo ; Vieta, Eduard ; Volkert, Julia ; Witt, Stephanie H. ; Wright, Adam ; Zandi, Peter P. ; Zhang, Peng ; Zollner, Sebastian ; McMahon, Francis J.
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
Lamm, Gerrit H. U. ; Marin, Egor ; Schellbach, Anna V. ; Stetsenko, Artem ; Alekseev, Alexey ; Bourenkov, Gleb ; Borshchevskiy, Valentin ; Asido, Marvin ; Agthe, Michael ; Engilberge, Sylvain ; Rose, Samuel L. ; Caramello, Nicolas ; Royant, Antoine ; Schneider, Thomas R. ; Bateman, Alex ; Mager, Thomas ; Moser, Tobias ; Wachtveitl, Josef ; Guskov, Albert ; Kovalev, Kirill
Microbial rhodopsins are omnipresent on Earth, however the vast majority of them remain uncharacterized. Here we describe a new rhodopsin clade from cold-adapted organisms and cold environments, such as glaciers, denoted as CryoRhodopsins (CryoRs). Our data suggest that CryoRs have photosensory activity. A distinguishing feature of the clade is the presence of a buried arginine residue close to the cytoplasmic face of its members. Combining single-particle cryo-electron microscopy and X-ray crystallography with the rhodopsin activation by light, we demonstrate that the arginine stabilizes a strongly blue-shifted intermediate of an extremely slow CryoRhodopsin photocycle. Together with extensive spectroscopic characterization, our investigations on CryoR1 and CryoR2 proteins reveal mechanisms of photoswitching in the newly identified clade and demonstrate principles of the adaptation of these rhodopsins to low temperatures.
Koromina, Maria ; Ravi, Ashvin ; Panagiotaropoulou, Georgia ; Schilder, Brian M. ; Humphrey, Jack ; Braun, Alice ; Bidgeli, Tim ; Chatzinakos, Chris ; Coombes, Brandon ; Kim, Jaeyoung ; Liu, Xiaoxi ; Terao, Chikashi ; O'Connell, Kevin S. ; Adams, Mark ; Adolfsson, Rolf ; Alda, Martin ; Alfredsson, Lars ; Andlauer, Till ; Andreassen, Ole A. ; Antoniou, Anastasia ; Baune, Bernhard T. ; Bengesser, Susanne ; Biernacka, Joanna ; Boehnke, Michael ; Bosch, Rosa ; Cairns, Murray ; Carr, Vaughan J. ; Casas Brugué, Miquel ; Catts, Stanley ; Cichon, Sven ; Corvin, Aiden ; Craddock, Nicholas ; Dafnas, Konstantinos ; Dalkner, Nina ; Dannlowski, Udo ; Degenhardt, Franziska ; Di Florio, Arianna ; Dikeos, Dimitris ; Fellendorf, Frederike Tabea ; Ferentinos, Panagiotis ; Forstner, Andreas Josef ; Forty, Liz ; Frye, Mark ; Fullerton, Janice M. ; Gawlik, Micha ; Gizer, Ian R. ; Gordon-Smith, Katherine ; Green, Melissa J. ; Grigoroiu-Serbanescu, Maria ; Guzman-Parra, José ; Hahn, Tim ; Henskens, Frans ; Hillert, Jan ; Jablensky, Assen V. ; Jones, Lisa ; Jones, Ian ; Jonsson, Lina ; Kelsoe, John R. ; Kircher, Tilo ; Kirov, George ; Kittel-Schneider, Sarah ; Kogevinas, Manolis ; Landén, Mikael ; Leboyer, Marion ; Lenger, Melanie ; Lissowska, Jolanta ; Lochner, Christine ; Loughland, Carmel ; MacIntyre, Donald ; Martin, Nicholas G. ; Maratou, Eirini ; Mathews, Carol A. ; Mayoral, Fermı́n ; McElroy, Susan L. ; McGregor, Nathaniel W. ; McIntosh, Andrew M. ; McQuillin, Andrew ; Michie, Patricia ; Milanova, Vihra ; Mitchell, Philip B. ; Moutsatsou, Paraskevi ; Mowry, Bryan ; Müller-Myhsok, Bertram ; Myers, Richard M. ; Nenadić, Igor ; Nöthen, Markus Maria ; O'Donovan, Claire ; O'Donovan, Michael ; Ophoff, Roel André ; Owen, Michael J. ; Pantelis, Christos ; Pato, Carlos ; Pato, Michele T. ; Patrinos, George P. ; Pawlak, Joanna M. ; Perlis, Roy H. ; Porichi, Evgenia ; Posthuma, Danielle ; Ramos-Quiroga, Josep Antoni ; Reif, Andreas ; Reininghaus, Eva Z. ; Ribasés, Marta ; Rietschel, Marcella ; Schall, Ulrich ; Schulze, Thomas Gerd ; Scott, Laura J. ; Scott, Rodney J. ; Serretti, Alessandro ; Shannon Weickert, Cynthia ; Smoller, Jordan W. ; Soler Artigas, Marı́a ; Stein, Dan J. ; Streit, Fabian ; Toma, Claudio ; Tooney, Paul ; Vieta, Eduard ; Vincent, John B. ; Waldman, Irwin D. ; Weickert, Thomas ; Witt, Stephanie H. ; Hong, Kyung Sue ; Ikeda, Masashi ; Iwata, Nakao ; Świątkowska, Beata ; Won, Hong-Hee ; Edenberg, Howard J. ; Ripke, Stephan ; Raj, Towfique ; Coleman, Jonathan R. I. ; Mullins, Niamh
Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Lamm, Gerrit H. U. ; Marin, Egor ; Alekseev, Alexey ; Schellbach, Anna V. ; Stetsenko, Artem ; Bourenkov, Gleb ; Borshchevskiy, Valentin ; Asido, Marvin ; Agthe, Michael ; Engilberge, Sylvain ; Rose, Samuel L. ; Caramello, Nicolas ; Royant, Antoine ; Schneider, Thomas R. ; Bateman, Alex ; Mager, Thomas ; Moser, Tobias ; Wachtveitl, Josef ; Guskov, Albert ; Kovalev, Kirill
Microbial rhodopsins are omnipresent on Earth, however the vast majority of them remain uncharacterized. Here we describe a new rhodopsin group from cold-adapted organisms and cold environments, such as glaciers, denoted as CryoRhodopsins (CryoRs). Our data suggest that CryoRs have dual functionality switching between inward transmembrane proton translocation and photosensory activity, both of which can be modulated with UV light. CryoR1 exhibits two subpopulations in the ground state, which upon light activation lead to transient photocurrents of opposing polarities. A distinguishing feature of the group is the presence of a buried arginine residue close to the cytoplasmic face of its members. Combining single-particle cryo-electron microscopy and X-ray crystallography with the rhodopsin activation by lit, we demonstrate that the arginine stabilizes a UV-absorbing intermediate of an extremely slow CryoRhodopsin photocycle. Together with extensive spectroscopic characterization, our investigations on CryoR1 and CryoR2 proteins reveal mechanisms of photoswitching in the newly identified group and demonstrate principles of the adaptation of these rhodopsins to low temperatures.Microbial rhodopsins are omnipresent on Earth, however the vast majority of them remain uncharacterized. Here we describe a new rhodopsin group from cold-adapted organisms and cold environments, such as glaciers, denoted as CryoRhodopsins (CryoRs). Our data suggest that CryoRs have dual functionality switching between inward transmembrane proton translocation and photosensory activity, both of which can be modulated with UV light. CryoR1 exhibits two subpopulations in the ground state, which upon light activation lead to transient photocurrents of opposing polarities. A distinguishing feature of the group is the presence of a buried arginine residue close to the cytoplasmic face of its members. Combining single-particle cryo-electron microscopy and X-ray crystallography with the rhodopsin activation by light, we demonstrate that the arginine stabilizes a UV-absorbing intermediate of an extremely slow CryoRhodopsin photocycle. Together with extensive spectroscopic characterization, our investigations on CryoR1 and CryoR2 proteins reveal mechanisms of photoswitching in the newly identified group and demonstrate principles of the adaptation of these rhodopsins to low temperatures.
Rothenburger, Tamara ; McLaughlin, Katie-May ; Herold, Tobias ; Schneider, Constanze ; Oellerich, Thomas ; Rothweiler, Florian ; Feber, Andrew ; Fenton, Tim R. ; Wass, Mark N. ; Keppler, Oliver Till ; Michaelis, Martin ; Cinatl, Jindrich
The nucleoside analogue nelarabine, the prodrug of arabinosylguanine (AraG), has been known for decades to be effective against acute lymphoblastic leukaemias of T-cell (T-ALL), but not of B-cell (B-ALL) origin. The mechanisms underlying this lineage-specific drug sensitivity have remained elusive. Data from pharmacogenomics studies and from a panel of ALL cell lines revealed an inverse correlation of SAMHD1 expression and nelarabine sensitivity. SAMHD1 can hydrolyse and thus inactivate triphosphorylated nucleoside analogues. Transcriptomic and protein expression profiling of cell lines and patient-derived leukaemic blasts revealed lower SAMHD1 abundance in T-ALL than in B-ALL. Mechanistically, SAMHD1 promoter methylation strongly correlated with suppressed SAMHD1 expression, while T-ALL cells did not display increased global DNA methylation. Targeted SAMHD1 degradation using virus-like particles containing Vpx sensitised B-ALL cells to AraG, while ectopic SAMHD1 expression in SAMHD1-null T-ALL cells induced AraG resistance. SAMHD1 had a larger impact on cytarabine activity than on nelarabine/ AraG activity in acute myeloid leukaemia (AML) cells, but more strongly affected nelarabine/ AraG activity in ALL cells. This indicates a critical role of the cancer entity. In conclusion, lineage-specific differences in SAMHD1 promoter methylation and, in turn, SAMHD1 expression levels determine ALL cell response to nelarabine. SAMHD1 is a potential biomarker for the identification of ALL patients likely to benefit from nelarabine therapy and a therapeutic target to overcome nelarabine resistance.
Cuntz, Hermann ; Bird, Alexander D ; Beining, Marcel ; Schneider, Marius ; Mediavilla Santos, Laura ; Hoffmann, Felix Z. ; Deller, Thomas ; Jedlička, Peter
Reducing neuronal size results in less cell membrane and therefore lower input conductance. Smaller neurons are thus more excitable as seen in their voltage responses to current injections in the soma. However, the impact of a neuron’s size and shape on its voltage responses to synaptic activation in dendrites is much less understood. Here we use analytical cable theory to predict voltage responses to distributed synaptic inputs and show that these are entirely independent of dendritic length. For a given synaptic density, a neuron’s response depends only on the average dendritic diameter and its intrinsic conductivity. These results remain true for the entire range of possible dendritic morphologies irrespective of any particular arborisation complexity. Also, spiking models result in morphology invariant numbers of action potentials that encode the percentage of active synapses. Interestingly, in contrast to spike rate, spike times do depend on dendrite morphology. In summary, a neuron’s excitability in response to synaptic inputs is not affected by total dendrite length. It rather provides a homeostatic input-output relation that specialised synapse distributions, local non-linearities in the dendrites and synaptic plasticity can modulate. Our work reveals a new fundamental principle of dendritic constancy that has consequences for the overall computation in neural circuits.
Podoliak, Elizaveta ; Lamm, Gerrit H. U. ; Alekseev, Alexey ; Marin, Egor ; Schellbach, Anna V. ; Fedotov, Daniil A. ; Stetsenko, Artem ; Maliar, Nina ; Bourenkov, Gleb ; Balandin, Taras ; Baeken, Christian ; Astashkin, Roman ; Schneider, Thomas R. ; Bateman, Alex ; Wachtveitl, Josef ; Schapiro, Igor ; Busskamp, Volker ; Guskov, Albert ; Gordeliy, Valentin ; Kovalev, Kirill
Light-driven sodium pumps (NaRs) are unique ion-transporting microbial rhodopsins. The major group of NaRs is characterized by an NDQ motif and has two aspartic acid residues in the central region essential for sodium transport. Here we identified a new subgroup of the NDQ rhodopsins bearing an additional glutamic acid residue in the close vicinity to the retinal Schiff base. We thoroughly characterized a member of this subgroup, namely the protein ErNaR from Erythrobacter sp. HL-111 and showed that the additional glutamic acid results in almost complete loss of pH sensitivity for sodium-pumping activity, which is in contrast to previously studied NaRs. ErNaR is capable of transporting sodium efficiently even at acidic pH levels. X-ray crystallography and single particle cryo-electron microscopy reveal that the additional glutamic acid residue mediates the connection between the other two Schiff base counterions and strongly interacts with the aspartic acid of the characteristic NDQ motif. Hence, it reduces its pKa. Our findings shed light on a new subgroup of NaRs and might serve as a basis for their rational optimization for optogenetics.
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