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C. ; Aysto, J. ; Azmi, Mohd Danish ; Bach, Matthias ; Badalà, Angela ; Baek, Yong Wook ; Bailhache, Raphaëlle ; Bala, Remu ; Baldini Ferroli, Rinaldo ; Baldisseri, Alberto ; Baldit, A. ; Baltasar Dos Santos Pedrosa, Fernando ; Ban, J. ; Baral, Rama Chandra ; Barbera, Roberto ; Barile, Francesco ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Barret, Valerie ; Bartke, Jerzy ; Basile, Maurizio ; Bastid, Nicole ; Basu, Sumit ; Bathen, Bastian ; Batigne, Guillaume ; Batyunya, Boris ; Baumann, C. ; Bearden, Ian Gardner ; Beck, Hans ; Belikov, Iouri ; Bellini, Francesca ; Bellwied, Rene ; Belmont-Moreno, Ernesto ; Bencédi, Gyula ; Beolè, Stefania ; Berceanu, Ionela ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berényi, Dániel ; Berzano, Dario ; Betev, Latchezar ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bhom, Jihyun ; Bianchi, Nicola ; Bianchi, Livio ; Bianchin, Chiara ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bilandzic, Ante ; Bjelogrlic, Sandro ; Blanco, Fernando ; Blanco, Fernando ; Blau, Dmitry S. ; Blume, Christoph ; Boccioli, M. ; Bock, N. ; Bogdanov, Alexey A. ; Boggild, H. ; Bogolyubsky, M. ; Boldizsar, László ; Bombara, Marek ; Book, Julian ; Borel, Hervé ; Borissov, Alexander ; Bose, S. ; Bossú, Francesco ; Botje, Michiel ; Bottger, Stefan ; Boyer, B. ; Braidot, E. ; Braun-Munzinger, Peter ; Bregant, Marco ; Breitner, Timo ; Browning, Tyler Allen ; Broz, Michal ; Brun, René ; Bruna, Elena ; Bruno, Giuseppe Eugenio ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bugaiev, K. ; Busch, Oliver ; Buthelezi, Edith Zinhle ; Caballero Orduna, D. ; Caffarri, Davide ; Cai, Xiao ; Caines, Helen Louise ; Calvo Villar, Ernesto ; Camerini, Paolo ; Canoa Roman, Veronica ; Cara Romeo, G. ; Carena, Wisla ; Carena, Francesco ; Carlin Filho, N. ; Carminati, F. ; Carrillo Montoya, C. A. ; Casanova Diaz, A. ; Castillo Castellanos, Javier Ernesto ; Castillo Hernández, Juan Francisco ; Casula, E. A.R. ; Catanescu, V. ; Cavicchioli, Costanza ; Ceballos Sanchez, Cesar ; Čepila, Jan ; Cerello, Piergiorgio ; Chang, B. ; Chapeland, Sylvain ; Charvet, Jean-Luc Fernand ; Chattopadhyay, S. ; Chattopadhyay, S. ; Chawla, I. ; Cherney, Michael Gerard ; Cheshkov, Cvetan Valeriev ; Cheynis, Brigitte ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Chochula, Peter ; Chojnacki, Marek ; Choudhury, Subikash ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Chung, Suh-Urk ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Cleymans, Jean Willy Andre ; Coccetti, F. ; Colamaria, Fabio Filippo ; Colella, Domenico ; Conesa Balbastre, Gustavo ; Conesa Del Valle, Zaida ; Constantin, P. ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Cormier, Thomas Michael ; Corrales Morales, Yasser ; Cortese, Pietro ; Cortes Maldonado, Ismael ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Cotallo, M. E. ; Crescio, E. ; Crochet, Philippe ; Cruz Alaniz, E. ; Cuautle Flores, Eleazar ; Cunqueiro Mendez, Leticia ; Dainese, Andrea ; Dalsgaard, Hans Hjersing ; Danu, Andrea ; Das, K. ; Das, Indranil ; Das, Debasish ; Dash, Ajay Kumar ; Dash, Sadhana ; De, Sudipan ; De Barros, G. O.V. ; De Caro, Annalisa ; De Cataldo, Giacinto ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; Delagrange, H. ; Del Castillo Sanchez, E. ; Deloff, Andrzej ; Demanov, V. ; De Marco, Nora ; Denes, Ervin Sandor ; De Pasquale, Salvatore ; Deppman, A. ; Erasmo, G. D. ; De Rooij, R. ; Diaz Corchero, Miguel Angel ; Di Bari, Domenico ; Dietel, Thomas ; Di Giglio, C. ; Di Liberto, S. ; Di Mauro, Antonio ; Di Nezza, Pasquale ; Divià, Roberto ; Djuvsland, Øystein ; Dobrin, Alexandru Florin ; Dobrowolski, Tadeusz Antoni ; Dominguez, I. ; Donigus, Benjamin ; Dordic, Olja ; Driga, O. ; Dubey, Anand Kumar ; Ducroux, Laurent ; Dupieux, Pascal ; Dutta Majumdar, A. K. ; Dutta Majumdar, M. R. ; Elia, Domenico ; Emschermann, D. ; Engel, Heiko ; Erdal, H. A. ; Espagnon, Bruno ; Estienne, Magali Danielle ; Esumi, ShinIchi ; Evans, David ; Eyyubova, Gyulnara ; Fabris, Daniela ; Faivre, Julien ; Falchieri, D. ; Fantoni, Alessandra ; Fasel, Markus ; Fearick, R. ; Fedunov, A. ; Fehlker, D. ; Feldkamp, Linus ; Felea, Daniel ; Fenton-Olsen, B. ; Feofilov, Grigori A. ; Fernández Téllez, Arturo ; Ferretti, Alessandro ; Ferretti, R. ; Figiel, Jan ; Figueredo, M. A.S. ; Filchagin, Sergey ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Fiore, Enrichetta Maria ; Floris, Michele ; Foertsch, Siegfried Valentin ; Foka, Panagiota ; Fokin, Sergey ; Fragiacomo, Enrico ; Fragkiadakis, M. ; Frankenfeld, Ulrich ; Fuchs, Ulrich ; Furget, Christophe ; Fusco Girard, Mario ; Gaardhoje, J. J. ; Gagliardi, Martino ; Gago, A. ; Gallio, Mauro ; Gangadharan, Dhevan Raja ; Ganoti, Paraskevi ; Garabatos, Chilo ; Garcia-Solis, Edmundo Javier ; Garishvili, I. ; Gerhard, J. ; Germain, Marie ; Geuna, C. ; Gheata, Mihaela ; Gheata, Andrei George ; Ghidini, B. ; Ghosh, Premomoy ; Gianotti, Paola ; Girard, M. R. ; Giubellino, Paolo ; Gładysz-Dziaduś, Ewa ; Glässel, Peter ; Gomez, R. ; Gonzalez Ferreiro, Elena ; González Trueba, Laura Helena ; González Zamora, Pedro ; Gorbunov, Sergey ; Goswami, A. ; Gotovac, Sven ; Grabski, Varlen ; Graczykowski, Łukasz Kamil ; Grajcarek, R. ; Grelli, Alessandro ; Grigoraș, Costin ; Grigoras, Alina Gabriela ; Grigoriev, Vladislav A. ; Grigoryan, Smbat ; Grigoryan, Ara ; Grinyov, Boris V. ; Grion, Nevio ; Gros, P. ; Große-Oetringhaus, Jan Fiete ; Grossiord, Grossiord Jean-Yves ; Grosso, Raffaele ; Guber, Fedor ; Guernane, Rachid ; Guerra Gutierrez, C. ; Guerzoni, Barbara ; Guilbaud, Maxime Rene Joseph ; Gulbrandsen, Kristjan Herlache ; Gunji, Taku ; Gupta, Ramni ; Gupta, Anik ; Gutbrod, H. ; Haaland, Øystein Senneset ; Hadjidakis, Cynthia Marie ; Haiduc, Maria ; Hamagaki, Hideki ; Hamar, Gergö ; Han, B. H. ; Hanratty, Luke David ; Hansen, Alexander ; Harmanova, Z. ; Harris, John W. ; Hartig, M. ; Hasegan, D. ; Hatzifotiadou, Despina ; Hayrapetyan, A. ; Heckel, Stefan Thomas ; Heide, Markus ; Helstrup, Håvard ; Herghelegiu, Andrei Ionut ; Herrera Corral, Gerardo Antonio ; Herrmann, Norbert ; Hetland, Kristin Fanebust ; Hicks, B. ; Hille, P. T. ; Hippolyte, Boris ; Horaguchi, T. ; Hori, Y. ; Hristov, Peter ; Hřivnačova, I. ; Huang, M. ; Humanic, Thomas J. ; Hwang, Dae Sung ; Ichou, R. ; Ilkaev, Radiy ; Ilkiv, Iryna ; Inaba, Motoi ; Incani, E. ; Innocenti, P. G. ; Innocenti, G. M. ; Ippolitov, Mikhail ; Irfan, M. ; Ivan, C. ; Ivanov, V. ; Ivanov, A. ; Ivanov, Marian ; Ivanytskyi, O. ; Jacholkowski, Adam Wlodzimierz ; Jacobs, Peter Martin ; Jancurova, L. ; Jang, Haeng Jin ; Jangal, S. ; Janik, R. ; Janik, Malgorzata Anna ; Jayarathna, P. H.S.Y. ; Jena, Satyajit ; Jha, D. M. ; Jiménez Bustamante, Raúl Tonatiuh ; Jirden, L. ; Jones, Peter Graham ; Jung, H. ; Jusko, Anton ; Kaidalov, A. B. ; Kakoyan, V. ; Kalcher, S. ; Kaliňak, Peter ; Kalisky, M. ; Kalliokoski, T. ; Kalweit, Alexander Philipp ; Kanaki, K. ; Kang, Ju Hwan ; Kaplin, Vladimir ; Karasu Uysal, Ayben ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karpechev, Evgeny ; Kazantsev, Andrey ; Kebschull, Udo ; Keidel, Ralf ; Khan, M. M. ; Khan, Shuaib Ahmad ; Khanzadeev, Alexei ; Kharlov, Yury ; Kileng, Bjarte ; Kim, J. S. ; Kim, D. W. ; Kim, S. H. ; Kim, J. H. ; Kim, M. ; Kim, D. 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M. ; Maevskaya, Alla ; Mager, Magnus ; Mahapatra, Durga Prasad ; Maire, Antonin ; Malaev, Mikhail ; Maldonado Cervantes, Ivonne Alicia ; Malinina, Liudmila ; Mal’Kevich, Dmitry ; Malzacher, Peter ; Mamonov, Alexander ; Manceau, Loic Henri Antoine ; Mangotra, L. ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Marin, Ana ; Marin Tobon, C. A. ; Markert, Christina ; Martashvili, Irakli ; Martinengo, Paolo ; Martínez Hernández, Mario Iván ; Martinez Davalos, A. ; Martínez Garcia, Ginés ; Martynov, Yevgen ; Mas, Alexis Jean-Michel ; Masciocchi, Silvia ; Masera, Massimo ; Masoni, Alberto ; Massacrier, Laure Marie ; Mastromarco, Mario ; Mastroserio, Annalisa ; Matthews, Z. L. ; Matyja, Adam Tomasz ; Mayani, D. ; Mayer, Christoph ; Mazer, Joel Anthony ; Mazzoni, Alessandra Maria ; Meddi, Franco ; Menchaca-Rocha, Arturo Alejandro ; Mercado Pérez, Jorge ; Meres, Michal ; Miake, Yasuo ; Milano, Leonardo ; Milošević, Jovan ; Mischke, André ; Mishra, Aditya Nath ; Miśkowiec, Dariusz Czesław ; Mitu, C. ; Mlynarz, J. ; Mohanty, A. K. ; Mohanty, Bedangadas ; Molnar, Levente ; Montaño Zetina, Luis Manuel ; Monteno, M. ; Montes Prado, Esther ; Moon, T. ; Morando, Maurizio ; Godoy, Denise Aparecida Moreira de ; Moretto, Sandra ; Morsch, Andreas ; Muccifora, Valeria ; Mudnic, Eugen ; Muhuri, Sanjib ; Mukherjee, Maitreyee ; Muller, H. ; Munhoz, Marcelo Gameiro ; Musa, Luciano ; Musso, A. ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Nattrass, Christine ; Naumov, N. P. ; Navin, S. ; Nayak, Tapan Kumar ; Nazarenko, Sergey ; Nazarov, G. ; Nedosekin, Alexander ; Nicassio, Maria ; Nielsen, Borge Svane ; Niida, Takafumi ; Nikolaev, Sergey ; Nikolic, V. ; Nikulin, Vladimir ; Nikulin, Sergey ; Nilsen, B. S. ; Nilsson, M. S. ; Noferini, Francesco ; Nomokonov, Petr V. ; Nooren, Gerardus ; Novitzky, Norbert ; Nyanin, Alexander ; Nyatha, A. ; Nygaard, C. ; Nystrand, Joakim Ingemar ; Ochirov, A. ; Oeschler, Helmut ; Oh, Saehanseul ; Oh, Sun Kun ; Oleniacz, Janusz ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Ortona, G. ; Oskarsson, Anders Nils Erik ; Ostrowski, P. ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Ozawa, K. ; Pachmayer, Yvonne C. ; Pachr, Miloš ; Padilla, F. ; Pagano, Paola ; Paić, Guy ; Painke, F. ; Pajares Vales, Carlos ; Pal, Susanta Kumar ; Pal, S. ; Palaha, A. ; Palmeri, A. ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Park, WooJin ; Passfeld, Annika ; Pastirčak, B. ; Patalakha, D. I. ; Paticchio, Vincenzo ; Pavlinov, A. ; Pawlak, Tomasz Jan ; Peitzmann, Thomas ; Pereira da Costa, Hugo Denis Antonio ; De Oliveira Filho, E. Pereira ; Peresunko, Dmitry Yurevich ; Pérez Lara, Carlos Eugenio ; Pérez Lezama, Edgar ; Perini, D. ; Perrino, D. ; Peryt, Wiktor Stanislaw ; Pesci, A. ; Peskov, Vladimir ; Pestov, Yury N. ; Petráček, Vojtech ; Petran, M. ; Petris, M. ; Petrov, P. ; Petrovici, Mihai A. ; Petta, Catia ; Piano, Stefano ; Piccotti, A. ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pitz, N. ; Piyarathna, Danthasinghe B. ; Płoskoń, Mateusz ; Pluta, Jan Marian ; Pocheptsov, T. ; Pochybova, Sona ; Podesta Lerma, P. L.M. ; Poghosyan, Martin G. ; Polak, K. ; Polichtchouk, Boris ; Pop, Amalia ; Porteboeuf-Houssais, Sarah Julie ; Pospišil, V. ; Potukuchi, B. ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puchagin, S. ; Puddu, Giovanna ; Pujol Teixido, J. ; Pulvirenti, A. ; Punin, Valery ; Putiš, M. ; Putschke, Jörn H. ; Quercigh, E. ; Qvigstad, Henrik ; Rachevski, Alexandre ; Rademakers, A. ; Radomski, S. ; Raiha, T. S. ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Ramirez Reyes, A. ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rascanu, Bogdan Theodor ; Rathee, Deepika ; Read, Kenneth Francis ; Real, Jean-Sébastien ; Redlich, Krzysztof ; Reichelt, Patrick ; Reicher, Martijn ; Renfordt, Rainer Arno Ernst ; Reolon, Anna Rita ; Reshetin, Andrey ; Rettig, Felix Vincenz ; Revol, J. P. ; Reygers, Klaus ; Riccati, L. ; Ricci, Renato Angelo ; Richert, Tuva Ora Herenui ; Richter, Matthias ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Rabacal, B. Rodrigues Fernandes ; Cahuantzi, M. Rodriguez ; Manso, A. Rodriguez ; Røed, Ketil ; Rohr, David ; Röhrich, Dieter ; Romita, Rosa ; Ronchetti, Federico ; Rosnet, Philippe ; Rossegger, S. ; Rossi, Andrea ; Roukoutakis, Filimon ; Roy, Pradip Kumar ; Roy, Christelle Sophie ; Rubio Montero, Antonio Juan ; Rui, Rinaldo ; Ryabinkin, Evgeny ; Rybicki, Andrzej ; Sadovskiy, Sergey ; Šafařík, Karel ; Sahoo, Raghunath ; Sahu, Pradip Kumar ; Saini, Jogender ; Sakaguchi, H. ; Sakai, Shingo ; Sakata, D. ; Salgado, Carlos A. ; Salzwedel, Jai ; Sambyal, Sanjeev Singh ; Samsonov, Vladimir ; Sanchez Castro, Xitzel ; Šándor, Ladislav ; Sandoval, Andres ; Sano, S. ; Sano, Masato ; Santo, R. ; Santoro, R. ; Sarkamo, J. ; Scapparone, Eugenio ; Scarlassara, Fernando ; Scharenberg, Rolf Paul ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schreiner, S. ; Schuchmann, Simone ; Schukraft, Jürgen ; Schutz, Yves Roland ; Schwarz, Kilian ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Scott, Rebecca Michelle ; Scott, P. A. ; Segato, G. ; Selyuzhenkov, Ilya ; Senyukov, Serhiy ; Seo, Jeewon ; Serci, S. ; Serradilla, Eulogio ; Sevcenco, Adrian ; Sgura, I. ; Shabetai, Alexandre ; Shabratova, G. ; Shahoyan, Ruben ; Sharma, Natasha ; Sharma, S. ; Shigaki, Kenta ; Shimomura, Maya ; Shtejer, Katherin ; Sibiriak, Yury ; Siciliano, M. ; Sicking, E. ; Siddhanta, Sabyasachi ; Siemiarczuk, Teodor ; Silvermyr, David Olle Rickard ; Silvestre, Catherine Micaela ; Simonetti, Giuseppe ; Singaraju, Rama Narayana ; Singh, R. ; Singha, Subhash ; Sinha, Bikash ; Sarkar-Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Skjerdal, K. ; Smakal, R. ; Smirnov, Nikolai ; Snellings, Raimond ; Sogaard, C. ; Soltz, Ron ; Son, H. ; Song, M. ; Song, J. ; Soos, C. ; Soramel, Francesca ; Sputowska, Iwona Anna ; Spyropoulou-Stassinaki, Martha ; Srivastava, Brijesh Kumar ; Stachel, Johanna ; Stan, Ionel ; Stan, Ionel ; Stefanek, Grzegorz ; Steinbeck, T. ; Steinpreis, M. ; Stenlund, Evert Anders ; Steyn, Gideon Francois ; Stiller, Johannes Hendrik ; Stocco, Diego ; Stolpovskiy, M. ; Strabykin, K. ; Strmen, Peter ; Suaide, Alexandre Alarcon do Passo ; Subieta Vasquez, Martin Alfonso ; Sugitate, Toru ; Suire, Christophe Pierre ; Sukhorukov, M. ; Sultanov, Rishat ; Šumbera, Michal ; Šuša, Tatjana ; De Toledo, A. Szanto ; Szarka, Imrich ; Szostak, A. ; Tagridis, C. ; Takahashi, Jun ; Tapia Takaki, Jesus Daniel ; Tauro, Arturo ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terrevoli, Cristina ; Thäder, Jochen ; Thomas, Deepa ; Tieulent, Raphael Noel ; Timmins, Anthony Robert ; Tlusty, David ; Toia, Alberica ; Torii, H. ; Toscano, L. ; Truesdale, David Christopher ; Trzaska, Wladyslaw Henryk ; Tsuji, Tomoya ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ulery, Jason Glyndwr ; Ullaland, Kjetil ; Ulrich, Jiri ; Uras, Antonio ; Urban, J. ; Urciuoli, G. M. ; Usai, Gianluca ; Vajzer, Michal ; Vala, Martin ; Valencia Palomo, Lizardo ; Vallero, Sara ; Kolk, Naomi van der ; Vyvre, Pierre vande ; Leeuwen, Marco van ; Vannucci, L. ; Vargas Treviño, Maria Aurora Diozcora ; Varma, Raghava ; Vasileiou, Maria ; Vasiliev, Andrey ; Vechernin, Vladimir ; Veldhoen, Misha ; Venaruzzo, Massimo ; Vercellin, Ermanno ; Vergara, S. ; Vernet, Renaud ; Verweij, Marta ; Vicković, Linda ; Viesti, Giuseppe ; Vikhlyantsev, O. ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Vinogradov, Alexander A. ; Vinogradov, Leonid ; Vinogradov, Yury I. ; Virgili, Tiziano ; Viyogi, Yogendra P. ; Vodopyanov, Alexander ; Voloshin, Sergei ; Voloshin, Kirill ; Volpe, Giacomo ; Haller, Barthélémy von ; Vranić, Danilo ; Ovrebekk, G. ; Vrlakova, Janka ; Vulpescu, Bogdan ; Vyushin, Alexey ; Wagner, Boris ; Wagner, V. ; Wan, R. ; Wang, Y. ; Wang, D. ; Wang, Y. ; Wang, M. ; Watanabe, K. ; Wessels, Johannes P. ; Westerhoff, Uwe ; Wiechula, Jens ; Wikne, Jon ; Wilde, Martin ; Wilk, Grzegorz Andrzej ; Wilk, A. ; Williams, M. C.S. ; Windelband, Bernd ; Karampatsos, L. Xaplanteris ; Yaldo, Chris G. ; Yang, H. ; Yang, S. ; Yasnopolskiy, S. ; Yi, J. ; Yin, Zhongbao ; Yoo, In-Kwon ; Yoon, J. ; Yu, W. ; Yuan, X. ; Yushmanov, Igor E. ; Zach, C. ; Zampolli, Chiara ; Zaporozhets, Sergey ; Zarochentsev, Andrey ; Závada, Petr ; Zaviyalov, Nikolaj ; Zbroszczyk, Hanna Paulina ; Zelnicek, P. ; Zgura, Ion-Sorin ; Zhalov, Mikhail ; Zhang, H. ; Zhang, X. ; Zhou, D. ; Zhou, F. ; Zhou, Y. ; Zhu, X. ; Zhu, J. ; Zhu, J. ; Zichichi, Antonino ; Zimmermann, Alice ; Zinovjev, Gennady M. ; Zoccarato, Y. ; Zynovyev, M.
The ALICE Zero Degree Calorimeter system (ZDC) is composed of two identical sets of calorimeters, placed at opposite sides with respect to the interaction point, 114 meters away from it, complemented by two small forward electromagnetic calorimeters (ZEM). Each set of detectors consists of a neutron (ZN) and a proton (ZP) ZDC. They are placed at zero degrees with respect to the LHC axis and allow to detect particles emitted close to beam direction, in particular neutrons and protons emerging from hadronic heavy-ion collisions (spectator nucleons) and those emitted from electromagnetic processes. For neutrons emitted by these two processes, the ZN calorimeters have nearly 100% acceptance.
During the √sNN = 2.76 TeV Pb-Pb data-taking, the ALICE Collaboration studied forward neutron emission with a dedicated trigger, requiring a minimum energy deposition in at least one of the two ZN. By exploiting also the information of the two ZEM calorimeters it has been possible to separate the contributions of electromagnetic and hadronic processes and to study single neutron vs. multiple neutron emission.
The measured cross sections of single and mutual electromagnetic dissociation of Pb nuclei at √sNN = 2.76 TeV, with neutron emission, are σsingle EMD = 187:4 ± 0.2 (stat.)−11.2+13.2 (syst.) b and σmutual EMD = 5.7 ± 0.1 (stat.) ±0.4 (syst.) b, respectively [1]. This is the first measurement of electromagnetic dissociation of 208Pb nuclei at the LHC energies, allowing a test of electromagnetic dissociation theory in a new energy regime. The experimental results are compared to the predictions from a relativistic electromagnetic dissociation model.
Androic, Ilija ; Krämer, Andrea ; Yan, Ruilan ; Rödel, Franz ; Gätje, Regine ; Kaufmann, Manfred ; Strebhardt, Klaus ; Yuan, Juping
Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.
Faltus, Timo ; Yuan, Juping ; Zimmer, Brigitte ; Krämer, Andrea ; Loibl, Sibylle ; Kaufmann, Manfred ; Strebhardt, Klaus
In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi). We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA) targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SKBR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neuoverexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as anti proliferative agents that display activity against neoplastic cells at very low doses.
Raab, Monika ; Kappel, Sven ; Krämer, Andrea ; Sanhaji, Mourad ; Matthess, Yves ; Kurunci-Csacsko, Elisabeth ; Calzada-Wack, Julia ; Rathkolb, Birgit ; Rozman, Jan ; Adler, Thure ; Busch, Dirk H. ; Esposito, Irene ; Fuchs, Helmut ; Gailus-Durner, Valérie ; Klingenspor, Martin ; Wolf, Eckhard ; Sänger, Nicole ; Prinz, Florian ; Hrabé de Angelis, Martin ; Seibler, Jost ; Yuan, Juping ; Bergmann, Martin ; Knecht, Rainald ; Kreft, Bertolt ; Strebhardt, Klaus
High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions.
Beyer, Mandy ; Romanski, Annette ; Al-Hassan, M. Mustafa ; Pons, Miriam ; Büchler, Iris ; Vogel, Anja ; Pautz, Andrea ; Sellmer, Andreas ; Schneider, Günter ; Bug, Gesine ; Krämer, Oliver Holger
Therapy of acute myeloid leukemia (AML) is unsatisfactory. Histone deacetylase inhibitors (HDACi) are active against leukemic cells in vitro and in vivo. Clinical data suggest further testing of such epigenetic drugs and to identify mechanisms and markers for their efficacy. Primary and permanent AML cells were screened for viability, replication stress/DNA damage, and regrowth capacities after single exposures to the clinically used pan-HDACi panobinostat (LBH589), the class I HDACi entinostat/romidepsin (MS-275/FK228), the HDAC3 inhibitor RGFP966, the HDAC6 inhibitor marbostat-100, the non-steroidal anti-inflammatory drug (NSAID) indomethacin, and the replication stress inducer hydroxyurea (HU). Immunoblotting was used to test if HDACi modulate the leukemia-associated transcription factors β-catenin, Wilms tumor (WT1), and myelocytomatosis oncogene (MYC). RNAi was used to delineate how these factors interact. We show that LBH589, MS-275, FK228, RGFP966, and HU induce apoptosis, replication stress/DNA damage, and apoptotic fragmentation of β-catenin. Indomethacin destabilizes β-catenin and potentiates anti-proliferative effects of HDACi. HDACi attenuate WT1 and MYC caspase-dependently and -independently. Genetic experiments reveal a cross-regulation between MYC and WT1 and a regulation of β-catenin by WT1. In conclusion, reduced levels of β-catenin, MYC, and WT1 are molecular markers for the efficacy of HDACi. HDAC3 inhibition induces apoptosis and disrupts tumor-associated protein expression.
Noack, Sabrina ; Raab, Monika ; Matthess, Yves ; Sanhaji, Mourad ; Krämer, Andrea ; Győrffy, Balázs ; Kaderali, Lars ; Balat, Ahmed el- ; Becker, Sven ; Strebhardt, Klaus
The taxanes are effective microtubule-stabilizing chemotherapy drugs that inhibit mitosis, induce apoptosis, and produce regression in a fraction of cancers that arise at many sites including the ovary. Novel therapeutic targets that augment taxane effects are needed to improve clinical chemotherapy response in CCNE1-amplified high grade serous ovarian cancer (HGSOC) cells. In this study, we conducted an siRNA-based kinome screen to identify modulators of mitotic progression in CCNE1-amplified HGSOC cells that may influence clinical paclitaxel response. PLK1 is overexpressed in many types of cancer, which correlates with poor prognosis. Here, we identified a novel synthetic lethal interaction of the clinical PLK1 inhibitor BI6727 and the microtubule-targeting drug paclitaxel in HGSOC cell lines with CCNE1-amplification and elucidated the underlying molecular mechanisms of this synergism. BI6727 synergistically induces apoptosis together with paclitaxel in different cell lines including a patient-derived primary ovarian cancer culture. Moreover, the inhibition of PLK1 reduced the paclitaxel-induced neurotoxicity in a neurite outgrowth assay. Mechanistically, the combinatorial treatment with BI6727/paclitaxel triggers mitotic arrest, which initiates mitochondrial apoptosis by inactivation of anti-apoptotic BCL-2 family proteins, followed by significant loss of the mitochondrial membrane potential and activation of caspase-dependent effector pathways. This conclusion is supported by data showing that BI6727/paclitaxel-co-treatment stabilizes FBW7, a component of SCF-type ubiquitin ligases that bind and regulate key modulators of cell division and growth including MCL-1 and Cyclin E. This identification of a novel synthetic lethality of PLK1 inhibitors and a microtubule-stabilizing drug has important implications for developing PLK1 inhibitor-based combination treatments in CCNE1-amplified HGSOC cells.
Stein, Stefan ; Ott, Marion Gabriele ; Schultze-Straßer, Stephan ; Jauch, Anna ; Burwinkel, Barbara ; Kinner, Andrea ; Schmidt, Manfred ; Krämer, Alwin ; Schwäble, Joachim ; Glimm, Hanno ; Köhl, Ulrike ; Preiss, Carolin ; Ball, Claudia ; Martin, Hans ; Göhring, Gudrun ; Schwarzwaelder, Kerstin ; Hofmann, Wolf-Karsten ; Karakaya, Kadin ; Tchatchou, Sandrine ; Yang, Rongxi ; Reinecke, Petra ; Kühlcke, Klaus ; Schlegelberger, Brigitte ; Thrasher, Adrian J. ; Hoelzer, Dieter ; Seger, Reinhard ; Kalle, Christof von ; Grez, Manuel
Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1). One subject died from overwhelming sepsis 27 months after gene therapy, whereas a second subject underwent an allogeneic HSC transplantation. Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia.