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The ALICE experiment has measured the inclusive J/ψ production in Pb-Pb collisions at sNN−−−√=2.76 TeV down to zero transverse momentum in the rapidity range 2.5<y<4. A suppression of the inclusive J/ψ yield in Pb-Pb is observed with respect to the one measured in pp collisions scaled by the number of binary nucleon-nucleon collisions. The nuclear modification factor, integrated over the 0-80% most central collisions, is 0.545±0.032(stat.)±0.083(syst.) and does not exhibit a significant dependence on the collision centrality. These features appear significantly different from measurements at lower collision energies. Models including J/ψ production from charm quarks in a deconfined partonic phase can describe our data.
Abelev, Betty ; Adam, Jaroslav ; Adamová, Dagmar ; Adare, A. M. ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agocs, A. G. ; Agostinelli, A. ; Aguilar Salazar, S. ; Ahammed, Zubayer ; Ahmad Masoodi, A. ; Ahmad, Nazeer ; Ahn, Sang Un ; Akindinov, Alexander ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Almaráz Aviña, E. ; Alme, Johan ; Alt, Torsten ; Altini, V. ; Altinpinar, Sedat ; Altsybeev, Igor ; Andrei, Cristian ; Andronic, Anton ; Anguelov, Venelin ; Anielski, Jonas ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arbor, N. ; Arcelli, Silvia ; Arend, A. ; Armesto, Néstor ; Arnaldi, Roberta ; Aronsson, Tomas Robert ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Asryan, A. ; Augustinus, Andre ; Averbeck, Ralf Peter ; Awes, T. 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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 ; Marı́n, A. ; Marin Tobon, C. A. ; Markert, Christina ; Martashvili, Irakli ; Martinengo, Paolo ; Martı́nez, M. I. ; Martı́nez Davalos, A. ; Martı́nez Garcı́a, G. ; 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 ; Müller, 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, Sun Kun ; Oh, Saehanseul ; 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 ; Pastirčák, B. ; Patalakha, D. 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The ALICE experiment has measured the inclusive J/psi production in Pb-Pb collisions at sqrt(sNN) = 2.76 TeV down to pt = 0 in the rapidity range 2.5 < y < 4. A suppression of the inclusive J/psi yield in Pb-Pb is observed with respect to the one measured in pp collisions scaled by the number of binary nucleon-nucleon collisions. The nuclear modification factor, integrated over the 0%-80% most central collisions, is 0.545 +/- 0.032 (stat.) +/- 0.084 (syst.) and does not exhibit a significant dependence on the collision centrality. These features appear significantly different from lower energy measurements. Models including J/psi production from charm quarks in a deconfined partonic phase can describe our data.
Abelev, Betty ; Adam, Jaroslav ; Adamová, Dagmar ; Adare, A. M. ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agocs, A. G. ; Agostinelli, A. ; Aguilar Salazar, S. ; Ahammed, Zubayer ; Ahmad Masoodi, A. ; Ahmad, Nazeer ; Ahn, Sang Un ; Akindinov, Alexander ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Almaráz Aviña, E. ; Alme, Johan ; Alt, Torsten ; Altini, V. ; Altinpinar, Sedat ; Altsybeev, Igor ; Andrei, Cristian ; Andronic, Anton ; Anguelov, Venelin ; Anielski, Jonas ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arbor, N. ; Arcelli, Silvia ; Arend, A. ; Armesto, Néstor ; Arnaldi, Roberta ; Aronsson, Tomas Robert ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Awes, T. 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S. ; Lee, S. C. ; Lefèvre, F. ; Lehnert, Jörg ; Leistam, L. ; Lemmon, Roy Crawford ; Lenhardt, M. ; Lenti, Vito ; León Monzón, Ildefonso ; León Vargas, H. ; Leoncino, Marco ; Lévai, Péter ; Lien, Jørgen André ; Lietava, Roman ; Lindal, Svein ; Lindenstruth, Volker ; Lippmann, Christian ; Lisa, Michael A. ; Liu, L. ; Lønne, Per-Ivar ; Loggins, Vera Renee ; Loginov, Vitaly ; Lohn, S. ; Lohner, D. ; Loizides, Constantinos ; Loo, K. K. ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Løvhøiden, G. ; Lu, X.-G. ; Lüttig, Philipp ; Lunardon, Marcello ; Luo, J. ; Luparello, Grazia ; Luquin, L. ; Luzzi, C. ; Ma, R. ; Maevskaya, Alla ; Mager, Magnus ; Mahapatra, Durga Prasad ; Maire, Antonin ; Mal’Kevich, Dmitry ; Malaev, Mikhail ; Maldonado Cervantes, Ivonne Alicia ; Malinina, Liudmila ; Malzacher, Peter ; Mamonov, Alexander ; Manceau, Loic Henri Antoine ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Marı́n, A. ; Marin Tobon, C. A. ; Markert, Christina ; Martashvili, Irakli ; Martinengo, Paolo ; Martı́nez, M. I. ; Martı́nez Davalos, A. ; Martı́nez Garcı́a, G. ; Martynov, Yevgen ; Mas, Alexis Jean-Michel ; Masciocchi, Silvia ; Masera, Massimo ; Masoni, Alberto ; 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 ; Müller, 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, Sergey ; Nikulin, Vladimir ; Nilsen, B. S. ; Nilsson, M. S. ; Noferini, Francesco ; Nomokonov, Petr V. ; Nooren, Gerardus ; Novitzky, Norbert ; Nyanin, Alexander ; Nyatha, A. ; Nygaard, C. ; Nystrand, Joakim Ingemar ; Oeschler, Helmut ; Oh, Saehanseul ; Oh, Sun Kun ; Oleniacz, Janusz ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Ortona, G. ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Pachmayer, Yvonne C. ; Pachr, Miloš ; Padilla, F. ; Pagano, Paola ; Paić, Guy ; Painke, F. ; Pajares Vales, Carlos ; Pal, S. ; Pal, Susanta Kumar ; Palaha, A. ; Palmeri, A. ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Park, WooJin ; Passfeld, Annika ; Patalakha, D. I. ; Paticchio, Vincenzo ; Pavlinov, A. ; Pawlak, Tomasz Jan ; Peitzmann, Thomas ; Pereira da Costa, Hugo Denis Antonio ; Filho, Elienos Pereira de Oliveira ; 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. ; Piuz, F. ; Piyarathna, Danthasinghe B. ; Płoskoń, Mateusz ; Pluta, Jan Marian ; Pocheptsov, T. ; Pochybova, Sona ; Podesta Lerma, Pedro Luis Manuel ; Poghosyan, Martin G. ; Polichtchouk, Boris ; Pop, Amalia ; Porteboeuf-Houssais, Sarah Julie ; Pospı́šil, 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. ; Räihä, T. S. ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Ramı́rez 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, Jean-Pierre ; Reygers, Klaus ; Riccati, L. ; Ricci, Renato Angelo ; Richert, Tuva Ora Herenui ; Richter, Matthias ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Rodrigues Fernandes Rabacal, B. ; Rodrı́guez Cahuantzi, Mario ; Rodriguez Manso, Alis ; Røed, Ketil ; Rohr, David ; Röhrich, Dieter ; Romita, Rosa ; Ronchetti, Federico ; Rosnet, Philippe ; Rossegger, S. ; Rossi, Andrea ; Roukoutakis, Filimon ; Roy, Christelle Sophie ; Roy, Pradip Kumar ; 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, Masato ; Sano, S. ; 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, P. A. ; Scott, Rebecca Michelle ; 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 ; Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Skjerdal, K. ; Smakal, R. ; Smirnov, Nikolai ; Snellings, Raimond ; Søgaard, C. ; Soltz, Ron ; Son, H. ; Song, J. ; Song, M. ; Soos, C. ; Soramel, Francesca ; Sputowska, Iwona Anna ; Spyropoulou-Stassinaki, Martha ; Srivastava, Brijesh Kumar ; Stachel, Johanna ; Stan, Ionel ; Stefanek, Grzegorz ; Stefanini, G. ; 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 ; Toledo, Alejandro Szanto de ; Szarka, Imrich ; Szczepankiewicz, Adam ; 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. ; Tosello, F. ; Trzaska, Wladyslaw Henryk ; Tsuji, Tomoya ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ulery, Jason Glyndwr ; Ullaland, Kjetil ; Ulrich, Jiri ; Uras, Antonio ; Urbán, J. ; Urciuoli, G. M. ; Usai, Gianluca ; Vajzer, Michal ; Vala, Martin ; Valencia Palomo, Lizardo ; Vallero, Sara ; Kolk, Naomi van der ; Leeuwen, Marco van ; Vyvre, Pierre vande ; 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 ; Vinogradov, Leonid ; Vinogradov, Yury I. ; Virgili, Tiziano ; Viyogi, Yogendra P. ; Vodopyanov, Alexander ; Voloshin, Kirill ; Voloshin, Sergei ; Volpe, Giacomo ; von Haller, B. ; Vranić, Danilo ; Øvrebekk, G. ; Vrláková, Janka ; Vulpescu, Bogdan ; Vyushin, Alexey ; Wagner, Boris ; Wagner, V. ; Wan, R. ; Wang, D. ; Wang, M. ; Wang, Y. ; Wang, Y. ; Watanabe, K. ; Wessels, Johannes P. ; Westerhoff, Uwe ; Wiechula, Jens ; Wikne, Jon ; Wilde, Martin ; Wilk, A. ; Wilk, Grzegorz Andrzej ; Williams, M. Crispin S. ; Windelband, Bernd ; Xaplanteris Karampatsos, L. ; 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, J. ; Zhu, X. ; Zichichi, Antonino ; Zimmermann, Alice ; Zinovjev, Gennady M. ; Zoccarato, Y. ; Zynovyev, M.
The first measurement of neutron emission in electromagnetic dissociation of 208Pb nuclei at the LHC is presented. The measurement is performed using the neutron Zero Degree Calorimeters of the ALICE experiment, which detect neutral particles close to beam rapidity. 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.) +13.2−11.2 (syst.) b and σmutual EMD=5.7±0.1 (stat.) ±0.4 (syst.) b, respectively. The experimental results are compared to the predictions from a relativistic electromagnetic dissociation model.
Tony, Hans-Peter ; Burmester, Gerd-Rüdiger ; Schulze-Koops, Hendrik ; Grunke, Mathias ; Henes, Jörg Christoph ; Kötter, Ina ; Haas, Judith ; Unger, Leonore ; Lovric, Svjetlana ; Haubitz, Marion ; Fischer-Betz, Rebecca ; Chehab, Gamal ; Rubbert-Roth, Andrea ; Specker, Christof ; Weinerth, Jutta ; Holle, Julia Ulrike ; Müller-Ladner, Ulf ; König, Ramona ; Fiehn, Christoph ; Burgwinkel, Philip ; Budde, Klemens ; Sörensen, Helmut ; Meurer, Michael ; Aringer, Martin ; Kieseier, Bernd ; Erfurt-Berge, Cornelia ; Sticherling, Michael ; Veelken, Roland ; Ziemann, Ulf ; Strutz, Frank ; Wussow, Praxis von ; Meier, Florian Matthias Peter ; Hunzelmann, Nico ; Schmidt, Nico ; Bergner, Raoul ; Schwarting, Andreas ; Eming, Rüdiger ; Hertl, Michael ; Stadler, Rudolf ; Schwarz-Eywill, Michael ; Wassenberg, Siegfried ; Fleck, Martin ; Metzler, Claudia ; Zettl, Uwe Klaus ; Westphal, Jens ; Heitmann, Stefan ; Herzog, Anna Laura ; Wiendl, Heinz ; Jakob, Waltraud ; Schmidt, Enno ; Freivogel, Klaus ; Dörner, Thomas
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
Randall, Joshua C. ; Winkler, Thomas W. ; Kutalik, Zoltán ; I. Berndt, Sonja ; Jackson, Anne U. ; Monda, Keri L. ; Kilpeläinen, Tuomas O. ; Esko, Tõnu ; Mägi, Reedik ; Li, Shengxu ; Workalemahu, Tsegaselassie ; Feitosa, Mary F. ; Croteau-Chonka, Damien C. ; Day, Felix R. ; Fall, Tove ; Ferreira, Teresa ; Gustafsson, Stefan ; Locke, Adam E. ; Mathieson, Iain ; Scherag, André ; Vedantam, Sailaja ; Wood, Andrew R. ; Liang, Liming ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Dermitzakis, Emmanouil T. ; Dimas, Antigone S. ; Karpe, Fredrik ; Min, Josine L. ; Nicholson, George ; Clegg, Deborah J. ; Person, Thomas ; Krohn, Jon P. ; Bauer, Sabrina ; Buechler, Christa ; Eisinger, Kristina ; Bonnefond, Amélie ; Froguel, Philippe ; Hottenga, Jouke-Jan ; Prokopenko, Inga ; Waite, Lindsay L. ; Harris, Tamara B. ; Smith, Albert Vernon ; Shuldiner, Alan R. ; McArdle, Wendy L. ; Caulfield, Mark J. ; Munroe, Patricia B. ; Grönberg, Henrik ; Chen, Yii-Der Ida ; Li, Guo ; Beckmann, Jacques S. ; Johnson, Toby ; Thorsteinsdottir, Unnur ; Teder-Laving, Maris ; Khaw, Kay-Tee ; Wareham, Nicholas J. ; Zhao, Jing Hua ; Amin, Najaf ; Oostra, Ben A. ; Kraja, Aldi T. ; Province, Michael A. ; Cupples, L. Adrienne ; Heard-Costa, Nancy L. ; Kaprio, Jaakko ; Ripatti, Samuli ; Surakka, Ida ; Collins, Francis S. ; Saramies, Jouko ; Tuomilehto, Jaakko ; Jula, Antti ; Salomaa, Veikko ; Erdmann, Jeanette ; Hengstenberg, Christian ; Loley, Christina ; Schunkert, Heribert ; Lamina, Claudia ; Wichmann, Heinz Erich ; Albrecht, Eva ; Gieger, Christian ; Hicks, Andrew A. ; Johansson, Åsa ; Pramstaller, Peter P. ; Kathiresan, Sekar ; Speliotes, Elizabeth K. ; Penninx, Brenda W. J. H. ; Hartikainen, Anna-Liisa ; Jarvelin, Marjo-Riitta ; Gyllensten, Ulf ; Boomsma, Dorret I. ; Campbell, Harry ; Wilson, James F. ; Chanock, Stephen J. ; Farrall, Martin ; Goel, Anuj ; Medina-Gomez, Carolina ; Rivadeneira, Fernando ; Estrada, Karol ; Uitterlinden, André G. ; Hofman, Albert ; Zillikens, M. Carola ; Heijer, Martin den ; Kiemeney, Lambertus Adrianus ; Maschio, Andrea ; Hall, Per ; Tyrer, Jonathan ; Teumer, Alexander ; Völzke, Henry ; Kovacs, Peter ; Tönjes, Anke ; Mangino, Massimo ; Spector, Tim D. ; Hayward, Caroline ; Rudan, Igor ; Hall, Alistair S. ; Samani, Nilesh J. ; Attwood, Antony Paul ; Sambrook, Jennifer G. ; Hung, Joseph ; Palmer, Lyle J. ; Lokki, Marja-Liisa ; Sinisalo, Juha ; Boucher, Gabrielle ; Huikuri, Heikki ; Lorentzon, Mattias ; Ohlsson, Claes ; Eklund, Niina ; Eriksson, Johan G. ; Barlassina, Cristina ; Rivolta, Carlo ; Nolte, Ilja M. ; Snieder, Harold ; Klauw, Melanie M. van der ; Vliet-Ostaptchouk, Jana V. van ; Gejman, Pablo V. ; Shi, Jianxin ; Jacobs, Kevin B. ; Wang, Zhaoming ; Bakker, Stephan J. L. ; Mateo Leach, Irene ; Navis, Gerjan ; Harst, Pim van der ; Martin, Nicholas Gordon ; Medland, Sarah E. ; Montgomery, Grant W. ; Yang, Jian ; Chasman, Daniel I. ; Ridker, Paul M. ; Rose, Lynda M. ; Lehtimäki, Terho ; Raitakari, Olli ; Absher, Devin ; Iribarren, Carlos ; Basart, Hanneke ; Hovingh, Kees G. ; Hyppönen, Elina ; Power, Chris ; Power, Chris ; Anderson, Denise ; Beilby, John P. ; Hui, Jennie ; Jolley, Jennifer ; Sager, Hendrik ; Bornstein, Stefan R. ; Schwarz, Peter E. H. ; Kristiansson, Kati ; Perola, Markus ; Lindström, Jaana ; Swift, Amy J. ; Uusitupa, Matti ; Atalay, Mustafa ; Lakka, Timo A. ; Rauramaa, Rainer ; Bolton, Jennifer L. ; Fowkes, Gerry ; Fraser, Ross M. ; Price, Jackie F. ; Fischer, Krista ; KrjutÅ¡kov, Kaarel ; Metspalu, Andres ; Mihailov, Evelin ; Langenberg, Claudia ; Luan, Jian'an ; Ong, Ken K. ; Chines, Peter S. ; Keinanen-Kiukaanniemi, Sirkka M. ; Saaristo, Timo E. ; Edkins, Sarah ; Franks, Paul W. ; Hallmans, Göran ; Shungin, Dmitry ; Morris, Andrew David ; Palmer, Colin N. A. ; Erbel, Raimund ; Moebus, Susanne ; Nöthen, Markus Maria ; Pechlivanis, Sonali ; Hveem, Kristian ; Narisu, Narisu ; Hamsten, Anders ; Humphries, Steve E. ; Strawbridge, Rona J. ; Tremoli, Elena ; Grallert, Harald ; Thorand, Barbara ; Illig, Thomas ; Koenig, Wolfgang ; Müller-Nurasyid, Martina ; Peters, Annette ; Böhm, Bernhard O. ; Kleber, Marcus E. ; März, Winfried ; Winkelmann, Bernhard R. ; Kuusisto, Johanna ; Laakso, Markku ; Arveiler, Dominique ; Cesana, Giancarlo ; Kuulasmaa, Kari ; Virtamo, Jarmo ; Yarnell, John W. G. ; Kuh, Diana ; Wong, Andrew ; Lind, Lars ; Faire, Ulf de ; Gigante, Bruna ; Magnusson, Patrik K. E. ; Pedersen, Nancy L. ; Dedoussis, George ; Dimitriou, Maria ; Kolovou, Genovefa ; Kanoni, Stavroula ; Stirrups, Kathleen ; Bonnycastle, Lori L. ; Njølstad, Inger ; Wilsgaard, Tom ; Ganna, Andrea ; Rehnberg, Emil ; Hingorani, Aroon ; Kivimaki, Mika ; Kumari, Meena ; Assimes, Themistocles L. ; Barroso, Inês ; Boehnke, Michael ; Borecki, Ingrid B. ; Deloukas, Panos ; Fox, Caroline S. ; Frayling, Timothy ; Groop, Leif C. ; Haritunians, Talin ; Hunter, David ; Ingelsson, Erik ; Kaplan, Robert ; Mohlke, Karen L. ; North, Kari E. ; Lindgren, Cecilia M. ; Qi, Lu ; Loos, Ruth J. F. ; Heid, Iris M. ; Hirschhorn, Joel N. ; McCarthy, Mark I. ; Abecasis, Gonçalo R. ; Stefansson, Kari ; Strachan, David P. ; Schlessinger, David ; O'Connell, Jeffrey R. ; Duijn, Cornelia M. van
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Turoňová, Beata ; Sikora, Mateusz ; Schürmann, Christoph ; Hagen, Wim ; Welsch, Sonja ; Blanc, Florian E. C. ; Bülow, Sören von ; Gecht, Michael ; Bagola, Katrin ; Hörner, Cindy ; Zandbergen, Ger van ; Mosalaganti, Shyamal Narayan ; Schwarz, Andre ; Covino, Roberto ; Mühlebach, Michael D. ; Hummer, Gerhard ; Krijnse-Locker, Jacomine ; Beck, Martin
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 Ångstrom, and is publicly available at EMPIAR-10453.
Turoňová, Beata ; Sikora, Mateusz ; Schürmann, Christoph ; Hagen, Wim ; Welsch, Sonja ; Blanc, Florian E. C. ; Bülow, Sören von ; Gecht, Michael ; Bagola, Katrin ; Hörner, Cindy ; Zandbergen, Ger van ; Landry, Jonathan ; Trevisan Doimo de Azevedo, Nayara ; Mosalaganti, Shyamal Narayan ; Schwarz, Andre ; Covino, Roberto ; Mühlebach, Michael D. ; Hummer, Gerhard ; Krijnse-Locker, Jacomine ; Beck, Martin
The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo–electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines.
Information structure
(2007)
Bulli, Lorenzo ; Apolonia, Luis ; Kutzner, Juliane ; Pollpeter, Darja ; Goujon, Caroline ; Herold, Nikolas ; Schwarz, Sarah-Marie ; Giernat, Yannick ; Keppler, Oliver Till ; Malim, Michael H. ; Schaller, Torsten
Type I interferons (IFNs), including IFN-α, upregulate an array of IFN-stimulated genes (ISGs) and potently suppress Human immunodeficiency virus type 1 (HIV-1) infectivity in CD4(+) T cells, monocyte-derived macrophages, and dendritic cells. Recently, we and others identified ISG myxovirus resistance 2 (MX2) as an inhibitor of HIV-1 nuclear entry. However, additional antiviral blocks exist upstream of nuclear import, but the ISGs that suppress infection, e.g., prior to (or during) reverse transcription, remain to be defined. We show here that the HIV-1 CA mutations N74D and A105T, both of which allow escape from inhibition by MX2 and the truncated version of cleavage and polyadenylation specific factor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A, all increase sensitivity to IFN-α-mediated inhibition. Using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology, we demonstrate that the IFN-α hypersensitivity of these mutants in THP-1 cells is independent of MX2 or CPSF6. As expected, CypA depletion had no additional effect on the behavior of the P90A mutant but modestly increased the IFN-α sensitivity of wild-type virus. Interestingly, the infectivity of wild-type or P90A virus could be rescued from the MX2-independent IFN-α-induced blocks in THP-1 cells by treatment with cyclosporine (Cs) or its nonimmunosuppressive analogue SDZ-NIM811, indicating that Cs-sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-α-induced blocks. We propose that cellular interactions with incoming HIV-1 capsids help shield the virus from recognition by antiviral effector mechanisms. Thus, the CA protein is a fulcrum for the dynamic interplay between cell-encoded functions that inhibit or promote HIV-1 infection.
Galarraga‐Vinueza, Maria Elisa ; Dohle, Eva ; Ramanauskaite, Ausra ; Maawi, Sarah al- ; Obreja, Karina Anne-Marie ; Magini, Ricardo ; Sader, Robert Alexander ; Ghanaati, Shahram Michael ; Schwarz, Frank
Background and Objective: Macrophages’ cytokine expression and polarization play a substantial role in the host's “destructive” inflammatory response to periodontal and peri‐implant pathogens. This study aimed to evaluate cell viability, anti‐inflammatory activity, and macrophage polarization properties of different cranberry concentrates.
Methods: THP‐1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB‐G cell line), osteosarcoma‐derived osteoblasts (SAOS‐2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti‐inflammatory analysis, induced macrophages exposed to cranberry concentrates (A‐type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)‐8, IL‐1 ß, IL‐6, and IL‐10 expression of LPS‐stimulated macrophages, and macrophage polarization markers were evaluated through determination of live‐cell protease activity, enzyme‐linked immunosorbent assay, and immunofluorescence staining semi‐quantification.
Results: Cranberry concentrates (A‐type PACs) did not reduce HGF, SAOS‐2, and macrophage viability after 24 hours of exposure. Pro‐inflammatory cytokine expression (ie IL‐8 and IL‐6) was downregulated in LPS‐stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti‐inflammatory IL‐10 expression was significantly upregulated in LPS‐stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS‐stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS‐stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours.
Conclusion: Cranberry‐derived proanthocyanidins may have the potential to act as an anti‐inflammatory component in the therapy of periodontal and peri‐implant diseases.
The title compound, C25H22O5, was obtained by a dehydrogenative carbonylation reaction. It crystallizes with one half-molecule in the asymmetric unit. The molecules have crystallographic C2 symmetry and the two atoms of the carbonyl group are located on the rotation axis. The methoxy groups are coplanar with the benzene ring to which they are attached [C-C-O-C = 1.0 (6)°]. The two furan rings are inclined at 17.3 (3)° with respect to each other and the dihedral angle between the furan ring and the benzene ring is 75.83 (12)°. The crystal structure is stabilized by C-H...O hydrogen bonds. Key indicators: single-crystal X-ray study; T = 183 K; mean ( σ(C–C) = 0.006 Å; R factor = 0.081; wR factor = 0.195; data-to-parameter ratio = 13.4.
Sanchez, Cecilia P. ; Patra, Pintu ; Scott Chang, Shih-Ying ; Karathanasis, Christos ; Hanebutte, Lukas ; Kilian, Nicole ; Cyrklaff, Marek ; Heilemann, Mike ; Schwarz, Ulrich S. ; Kudryashev, Mikhail ; Lanzer, Michael
The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation. Here, we show by super-resolution microscopy that KAHRP initially associates with various skeletal components, including ankyrin bridges, but eventually colocalizes with remnant actin junctions. We further present a 35 Å map of the spiral scaffold underlying knobs and show that a KAHRP-targeting nanoprobe binds close to the spiral scaffold. Single-molecule localization microscopy detected ~60 KAHRP molecules/knob. We propose a dynamic model of KAHRP organization and a function of KAHRP in attaching other factors to the spiral scaffold.
Werner, Inge ; Aldrich, Annette ; Becker, Benjamin ; Becker, Dennis ; Brinkmann, Markus ; Burkhardt, Michael ; Caspers, Norbert ; Campiche, Sophie ; Chèvre, Nathalie ; Düring, Rolf‑Alexander ; Escher, Beate I. ; Fischer, Fabian ; Giebner, Sabrina ; Heye, Katharina ; Hollert, Henner ; Junghans, Marion ; Kienle, Cornelia ; Knauer, Katja ; Korkaric, Muris ; Märkl, Veronika ; Muncke, Jane ; Oehlmann, Jörg ; Reifferscheid, Georg ; Rensch, Daniel ; Schäffer, Andreas ; Schiwy, Sabrina ; Schwarz, Simon ; Segner, Helmut ; Simon, Eszter ; Triebskorn, Rita ; Vermeirssen, Etiënne L. M. ; Wintgens, Thomas ; Zennegg, Markus
This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1.
Sanchez, Cecilia P. ; Patra, Pintu ; Scott Chang, Shih-Ying ; Karathanasis, Christos ; Hanebutte, Lukas ; Kilian, Nicole ; Cyrklaff, Marek ; Heilemann, Mike ; Schwarz, Ulrich S. ; Kudryashev, Mikhail ; Lanzer, Michael
The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation. Here, we show by super-resolution microscopy that KAHRP initially associates with various skeletal components, including ankyrin bridges, but eventually colocalizes with remnant actin junctions. We further present a 35 Å map of the spiral scaffold underlying knobs and show that a KAHRP-targeting nanoprobe binds close to the spiral scaffold. Single-molecule localization microscopy detected ~60 KAHRP molecules/knob. We propose a dynamic model of KAHRP organization and a function of KAHRP in attaching other factors to the spiral scaffold.
Efficacy of platelet-rich fibrin in promoting the healing of extraction sockets: a systematic review
(2021)
Maawi, Sarah al- ; Becker, Kathrin ; Schwarz, Frank ; Sader, Robert Alexander ; Ghanaati, Shahram Michael
Purpose: To address the focused question: in patients with freshly extracted teeth, what is the efficacy of platelet-rich fibrin (PRF) in the prevention of pain and the regeneration of soft tissue and bone compared to the respective control without PRF treatment?
Methods: After an electronic data search in PubMed database, the Web of Knowledge of Thomson Reuters and hand search in the relevant journals, a total of 20 randomized and/or controlled studies were included.
Results: 66.6% of the studies showed that PRF significantly reduced the postoperative pain, especially in the first 1–3 days after tooth extraction. Soft tissue healing was significantly improved in the group of PRF compared to the spontaneous wound healing after 1 week (75% of the evaluated studies). Dimensional bone loss was significantly lower in the PRF group compared to the spontaneous wound healing after 8–15 weeks but not after 6 months. Socket fill was in 85% of the studies significantly higher in the PRF group compared to the spontaneous wound healing.
Conclusions: Based on the analyzed studies, PRF is most effective in the early healing period of 2–3 months after tooth extraction. A longer healing period may not provide any benefits. The currently available data do not allow any statement regarding the long-term implant success in sockets treated with PRF or its combination with biomaterials. Due to the heterogeneity of the evaluated data no meta-analysis was performed.
Sanchez, Cecilia P. ; Karathanasis, Christos ; Sanchez, Rodrigo ; Cyrklaff, Marek ; Jäger, Julia ; Buchholz, Bernd ; Schwarz, Ulrich S. ; Heilemann, Mike ; Lanzer, Michael
PfEMP1 (erythrocyte membrane protein 1) adhesins play a pivotal role in the pathophysiology of falciparum malaria, by mediating sequestration of Plasmodium falciparum-infected erythrocytes in the microvasculature. PfEMP1 variants are expressed by var genes and are presented on membrane elevations, termed knobs. However, the organization of PfEMP1 on knobs is largely unclear. Here, we use super-resolution microscopy and genetically altered parasites expressing a modified var2csa gene in which the coding sequence of the photoactivatable mEOS2 was inserted to determine the number and distribution of PfEMP1 on single knobs. The data were verified by quantitative fluorescence-activated cell sorting analysis and immuno-electron microscopy together with stereology methods. We show that knobs contain 3.3 ± 1.7 and 4.3 ± 2.5 PfEMP1 molecules, predominantly placed on the knob tip, in parasitized erythrocytes containing wild type and sickle haemoglobin, respectively. The ramifications of our findings for cytoadhesion and immune evasion are discussed.
Thomaidis, Thomas ; Maderer, Annett ; Formentini, Andrea ; Bauer, Susanne ; Trautmann, Mario ; Schwarz, Michael ; Neumann, Wiebke ; Kittner, Jens Martin ; Schad, Arno ; Link, Karl-Heinrich ; Rey, Johannes Wilhelm ; Weinmann, Arndt ; Hoffman, Arthur ; Galle, Peter Robert ; Kornmann, Marko ; Möhler, Markus
Background: Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients.
Methods: The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators. Survival analyses were calculated for all patients receiving adjuvant chemotherapy in relation to expression of all makers above.
Results: Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination.
Conclusions: The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/− irinotecan in stage II/III colorectal cancer.
Rabe, Eberhard ; Földi, Ethel ; Gerlach, Horst ; Jünger, Michael ; Lulay, Gerd Rudolf ; Miller, Anya ; Protz, Kerstin ; Reich-Schupke, Stefanie ; Schwarz, Thomas ; Stücker, Markus ; Valesky, Eva Maria ; Pannier, Felizitas
The present guidelines comprise relevant aspects of the use of compression therapy with medical compression stockings (MCS), phlebological compression bandages (PCB), and medical adaptive compression systems (MAC) based on an extensive literature search based on the state of scientific knowledge as of December 2018.
These guidelines were prepared by experts within the framework of an electronic consensus process and a consensus conference which took place in Bielefeld, Germany, on September 27, 2018, on the initiative of the German Society of Phlebology (DGP) and the Professional Association of Phlebologists (BVP). The guidelines were adopted by the boards and advisory councils of the DGP and the BVP, and of the participating professional associations, after preparation by the group of experts and extensive debate, on December 31, 2018.
These guidelines do not cover compression therapy with medical thrombosis prophylaxis stockings (MTPS) or with intermittent pneumatic compression (IPC), which are treated in other guidelines (AWMF 003-001, S3; AWMF 037-001, S1).
The recommendations of the AWMF guidelines “Diagnostics and Treatment of Lymphedema” (registration number 058-001) and “Lipedema” (registration number 037-012) shall also be taken into account where appropriate: https://www.awmf.org/uploads/tx_szleitlinien/058-001l_S2k_Diagnostik_und_Therapie_der_Lymphoedeme_2017-05.pdf, https://www.awmf.org/uploads/tx_szleitlinien/037-012l_S1_Lipoedem_2016-01.pdf.
Barucca, Gianni ; Davì, F. ; Lancioni, G. ; Mengucci, P. ; Montalto, L. ; Natali, P. P. ; Paone, N. ; Rinaldi, D. ; Scalise, L. ; Erni, W. ; Krusche, B. ; Steinacher, M. ; Walford, N. ; Cao, N. ; Liu, Z. ; Liu, C. ; Liu, B. ; Shen, X. ; Sun, S. ; Tao, J. ; Xiong, X. A. ; Zhao, G. ; Zhao, J. ; Albrecht, Malte ; Alkakhi, W. ; Bökelmann, S. ; Coen, S. ; Feldbauer, Florian ; Fink, M. ; Frech, J. ; Freudenreich, V. ; Fritsch, Miriam ; Grochowski, J. ; Hagdorn, R. ; Heinsius, Fritz-Herbert ; Held, T. ; Holtmann, Tobias ; Keshk, Iman ; Koch, H. ; Kopf, Bertram ; Kuhlmann, M. ; Kümmel, M. ; Küßner, M. ; Li, J. ; Linzen, L. ; Maldaner, Stephan ; Oppotsch, J. ; Pankonin, S. ; Pelizäus, Marc ; Pflüger, S. ; Pitka, A. ; Reher, J. ; Reicherz, G. ; Schnier, Claudius ; Steinke, M. ; Triffterer, T. ; Wenzel, C. ; Wiedner, Ulrich ; Denizli, H. ; Er, N. ; Keskin, U. ; Olgun, A. T. ; Yerlikaya, S. ; Yilmaz, A. ; Beck, R. ; Hammann, C. ; Hartmann, J. ; Ketzer, Bernhard ; Müllers, J. ; Rossbach, M. ; Salisbury, B. ; Schmidt, Christian Joachim ; Thoma, U. ; Urban, M. ; Bianconi, A. ; Bragadireanu, Mario ; Pantea, D. ; Domagala, M. ; Filo, G. ; Lisowski, E. ; Lisowski, F. ; Michałek, M. ; Poznański, P. ; Płażek, J. ; Korcyl, K. ; Kozela, A. ; Lebiedowicz, P. ; Pysz, K. ; Schäfer, W. ; Szczurek, A. ; Firlej, M. ; Fiutowski, T. ; Idzik, M. ; Moron, J. ; Swientek, K. ; Terlecki, P. ; Korcyl, G. ; Lalik, R. ; Malige, A. ; Moskal, P. ; Nowakowski, K. ; Przygoda, W. ; Rathod, N. ; Rudy, Z. ; Salabura, P. ; Smyrski, J. ; Augustin, I. ; Böhm, R. ; Lehmann, I. ; Schmitt, L. ; Varentsov, V. ; Al-Turany, Mohammad ; Belias, A. ; Deppe, H. ; Dzhygadlo, R. ; Flemming, H. ; Gerhardt, A. ; Götzen, Klaus ; Heinz, Andreas ; Jiang, P. ; Karabowicz, R. ; Koch, S. ; Kurilla, U. ; Lehmann, D. ; Lühning, J. ; Lynen, U. ; Orth, H. ; Peters, Klaus ; Saito, T. ; Schepers, G. ; Schmidt, C. J. ; Schwarz, C. ; Schwiening, J. ; Täschner, Alexander ; Traxler, M. ; Voss, B. ; Wieczorek, P. ; Abazov, V. ; Alexeev, G. ; Arefiev, V. A. ; Astakhov, V. ; Barabanov, M. Yu. ; Batyunya, B. V. ; Dodokhov, V. Kh. ; Efremov, A. ; Fechtchenko, A. ; Galoyan, A. ; Golovanov, G. ; Koshurnikov, E. K. ; Lobanov, Y. Yu. ; Olshevskiy, A. G. ; Piskun, A. A. ; Samartsev, A. ; Shimanski, S. ; Skachkov, N. B. ; Skachkova, A. N. ; Strokovsky, E. A. ; Tokmenin, V. ; Uzhinsky, V. ; Verkheev, A. ; Vodopianov, A. ; Zhuravlev, N. I. ; Branford, D. ; Watts, D. ; Böhm, M. ; Eyrich, W. ; Lehmann, A. ; Miehling, D. ; Pfaffinger, M. ; Quin, N. ; Robison, L. ; Seth, K. ; Xiao, T. ; Bettoni, Diego ; Ali, A. ; Hamdi, A. ; Himmelreich, Mathilde ; Krebs, M. ; Nakhoul, S. ; Nerling, Frank ; Belousov, A. ; Kisel, Ivan ; Kozlov, Grigory ; Pugach, M. ; Zyzak, Maksym ; Bianchi, Nicola ; Gianotti, Paola ; Lucherini, V. ; Bracco, G. ; Bettner, Y. ; Bodenschatz, S. ; Brinkmann, K. T. ; Brück, L. ; Diehl, S. ; Dormenev, V. ; Düren, M. ; Erlen, T. ; Föhl, K. ; Hahn, C. ; Hayrapetyan, A. ; Hofmann, J. ; Kegel, S. ; Kesselkaul, M. ; Köseoglu, I. ; Kripko, A. ; Kühn, Wolfgang ; Lange, Jens Sören ; Metag, V. ; Moritz, M. ; Nanova, M. ; Novotny, R. ; Orsich, P. ; Pereira-de-Lira, J. ; Peter, M. ; Sachs, M. ; Schmidt, M. ; Schubert, R. ; Stenzel, H. ; Straube, M. ; Strickert, M. ; Thöring, U. ; Wasem, T. ; Wohlfahrt, B. ; Zaunick, H. G. ; Tomasi-Gustafsson, E. ; Glazier, D. ; Ireland, D. ; Seitz, B. ; Deepak, P. N. ; Kulkarni, A. ; Kappert, R. ; Kavatsyuk, Myroslav O. ; Loehner, H. ; Messchendorp, Johannes Gerhardus ; Rodin, Viktor ; Schakel, P. ; Vejdani, S. ; Dutta, K. ; Kalita, K. ; Huang, G. ; Liu, D. ; Peng, H. ; Qi, H. ; Sun, Y. ; Zhou, X. ; Kunze, M. ; Azizi, K. ; Tavukoglu, Z. ; Derichs, A. ; Dosdall, R. ; Esmail, W. ; Gillitzer, A. ; Goldenbaum, F. ; Grunwald, D. ; Jokhovets, L. ; Kannika, J. ; Kulessa, P. ; Orfanitski, S. ; Pérez Andrade, G. ; Prasuhn, D. ; Prencipe, E. ; Pütz, J. ; Ritman, J. ; Rosenthal, E. ; Schadmand, S. ; Schmitz, R. ; Scholl, A. ; Sefzick, T. ; Serdyuk, V. ; Stockmanns, T. ; Veretennikov, D. ; Wintz, P. ; Wüstner, P. ; Xu, H. ; Zhou, Y. ; Cao, X. ; Hu, Q. ; Li, Z. ; Li, H. ; Liang, Y. ; Ma, X. ; Rigato, V. ; Isaksson, L. ; Achenbach, P. ; Corell, O. ; Denig, Achim ; Distler, M. ; Hoek, M. ; Lauth, W. ; Leithoff, H. H. ; Liu, Z. ; Merkel, H. ; Müller, U. ; Pochodzalla, J. ; Schlimme, S. ; Sfienti, C. ; Thiel, M. ; Zambrana, M. ; Ahmed, Samer ; Bleser, S. ; Bölting, M. ; Capozza, L. ; Dbeyssi, A. ; Ehret, A. ; Klasen, R. ; Kliemt, Ralf ; Maas, F. ; Motzko, C. ; Noll, O. ; Piñeiro, D. Rodríguez ; Schupp, F. ; Steinen, M. ; Wolff, S. ; Zimmermann, I. ; Fedorov, A. ; Kazlou, D. ; Korzhik, M. ; Missevitch, O. ; Balanutsa, P. ; Chernetsky, V. ; Demekhin, A. ; Dolgolenko, A. ; Fedorets, P. ; Gerasimov, A. ; Golubev, A. ; Goryachev, V. ; Kantsyrev, Alexey V. ; Kirin, D. Y. ; Kristi, N. ; Ladygina, E. ; Luschevskaya, E. ; Matveev, V. A. ; Panjushkin, V. ; Stavinskiy, A. V. ; Balashoff, A. ; Boukharov, A. ; Malyshev, O. ; Basant, K. N. ; Kumawat, H. ; Roy, B. ; Saxena, Alok ; Yogesh, S. ; Bonaventura, D. ; Brand, P. ; Fritzsch, C. ; Grieser, S. ; Hargens, C. ; Hergemöller, A. K. ; Hetz, B. ; Hüsken, Nils ; Kellers, J. ; Khoukaz, Alfons ; Mannweiler, C. ; Vestrick, S. ; Bumrungkoh, D. ; Herold, Christoph ; Khosonthongkee, K. ; Kobdaj, Chinorat ; Limphirat, A. ; Manasatitpong, K. ; Nasawad, T. ; Pongampai, S. ; Simantathammakul, T. ; Srisawad, P. ; Wongprachanukul, N. ; Yan, Y. ; Yu, C. ; Zhang, X. ; Zhu, W. ; Blinov, A. E. ; Kononov, S. ; Kravchenko, E. A. ; Antokhin, E. ; Barnyakov, A. Yu. ; Beloborodov, K. ; Blinov, V. E. ; Kuyanov, I. A. ; Pivovarov, S. ; Pyata, E. ; Tikhonov, Y. ; Hunter, G. ; Lattery, M. ; Pace, H. ; Boca, Gianluigi ; Duda, D. ; Finger, M. ; Finger, M. ; Kveton, A. ; Pesek, M. ; Peskova, M. ; Prochazka, I. ; Slunecka, M. ; Volf, M. ; Gallus, P. ; Jary, V. ; Korchak, O. ; Marcisovsky, M. ; Neue, G. ; Novy, J. ; Tomasek, L. ; Tomasek, M. ; Virius, M. ; Vrba, V. ; Abramov, V. ; Bukreeva, S. ; Chernichenko, S. ; Derevschikov, A. ; Ferapontov, V. ; Goncharenko, Y. ; Levin, A. ; Maslova, E. ; Melnik, Y. ; Meščanin, Aleksei P. ; Minaev, N. ; Mochalov, V. ; Moiseev, V. ; Morozov, D. ; Nogach, L. ; Poslavskiy, S. ; Ryazantsev, A. ; Ryzhikov, S. ; Semenov, P. ; Shein, I. ; Uzunian, A. ; Vasiliev, Andrey ; Yakutin, A. ; Roy, U. ; Yabsley, B. ; Belostotski, S. ; Fedotov, G. ; Gavrilov, G. ; Izotov, A. ; Manaenkov, S. ; Miklukho, O. ; Zhdanov, A. ; Atac, A. ; Bäck, T. ; Cederwall, B. ; Makonyi, K. ; Preston, M. ; Tegner, P. E. ; Wölbing, D. ; Gandhi, K. ; Rai, A. K. ; Godre, S. ; Crede, V. ; Dobbs, S. ; Eugenio, P. ; Lersch, D. ; Calvo, D. ; De Remigis, P. ; Filippi, A. ; Mazza, G. ; Rivetti, Angelo ; Wheadon, R. ; Bussa, M. P. ; Spataro, Stefano ; Iazzi, F. ; Lavagno, A. ; Martin, A. ; Akram, A. ; Calen, H. ; Ikegami Andersson, Walter ; Johansson, Tord ; Kupsc, Andrzej ; Marciniewski, P. ; Papenbrock, Michael ; Regina, J. ; Rieger, J. ; Schönning, K. ; Wolke, M. ; Pothodi Chackara, V. ; Chlopik, A. ; Kesik, G. ; Melnychuk, D. ; Tarasiuk, J. ; Wojciechowski, M. ; Wronka, S. ; Zwieglinski, B. ; Amsler, C. ; Bühler, Paul ; Marton, J. ; Nalti, W. ; Steinschaden, D. ; Widmann, Eberhard ; Zimmermann, S. ; Zmeskal, Johann
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Harter, Patrick Nikolaus ; Blank, Anna-Eva ; Weide, Benjamin ; Beschorner, Rudi ; Bernatz, Simon ; Baumgarten, Peter ; Braczynski, Anne Kristin ; Hattingen, Elke ; Ronellenfitsch, Michael Wilfried ; Schwarz, Herbert ; Mittelbronn, Michel Guy André
Aim: The cytokine receptor tumor necrosis factor receptor superfamily member 9 (TNFRSF9) is mainly considered to be a co-stimulatory activation marker in hematopoietic cells. Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies. However, preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects. In a previous study, it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system (CNS) tumors, but was largely absent from tumor or inflammatory cells. The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis, a highly immunogenic tumor with a prominent tropism to the CNS.
Methods: Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex, age, survival, tumor size, number of tumor spots, and BRAF V600E expression status.
Results: Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells. In addition, TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates. No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen. Of note, several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels, an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells.
Conclusion: The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool, and therefore further careful (re-) assessment of potential TNFRSF9 functions in cell types other than hematopoietic cells is needed. Furthermore, the hypothesis of hypoxia-driven TNFRSF9 expression in brain metastasis melanoma cells requires further functional testing.