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2. A MHz-repetition-rate hard X-ray free-electron laser driven by a superconducting linear accelerator

Author

Decking, W., Abeghyan, S., Abramian, P., Abramsky, A., Aguirre, A., Albrecht, C., Alou, P., Altarelli, M., Altmann, P., Amyan, K., Anashin, V., Apostolov, E., Appel, K., Auguste, D., Ayvazyan, V., Baark, S., Babies, F., Baboi, N., Bak, P., Balandin, V., Baldinger, R., Baranasic, B., Barbanotti, S., Belikov, O., Belokurov, V., Belova, L., Belyakov, V., Berry, S., Bertucci, M., Beutner, B., Block, A., Blöcher, M., Böckmann, T., Bohm, C., Böhnert, M., Bondar, V., Bondarchuk, E., Bonezzi, M., Borowiec, P., Bösch, C., Bösenberg, U., Bosotti, A., Böspflug, R., Bousonville, M., Boyd, E., Bozhko, Y., Brand, A., Branlard, J., Briechle, S., Brinker, F., Brinker, S., Brinkmann, R., Brockhauser, S., Brovko, O., Brück, H., Brüdgam, A., Butkowski, L., Büttner, T., Calero, J., Castro-Carballo, E., Cattalanotto, G., Charrier, J., Chen, J., Cherepenko, A., Cheskidov, V., Chiodini, M., Chong, A., Choroba, S., Chorowski, M., Churanov, D., Cichalewski, W., Clausen, M., Clement, W., Cloué, C., Cobos, J. A., Coppola, N., Cunis, S., Czuba, K., Czwalinna, M., D’Almagne, B., Dammann, J., Danared, H., de Zubiaurre Wagner, A., Delfs, A., Delfs, T., Dietrich, F., Dietrich, T., Dohlus, M., Dommach, M., Donat, A., Dong, X., Doynikov, N., Dressel, M., Duda, M., Duda, P., Eckoldt, H., Ehsan, W., Eidam, J., Eints, F., Engling, C., Englisch, U., Ermakov, A., Escherich, K., Eschke, J., Saldin, E., Faesing, M., Fallou, A., Felber, M., Fenner, M., Fernandes, B., Fernández, J. M., Feuker, S., Filippakopoulos, K., Floettmann, K., Fogel, V., Fontaine, M., Francés, A., Martin, I. Freijo, Freund, W., Freyermuth, T., Friedland, M., Fröhlich, L., Fusetti, M., Fydrych, J., Gallas, A., García, O., Garcia-Tabares, L., Geloni, G., Gerasimova, N., Gerth, C., Geßler, P., Gharibyan, V., Gloor, M., Głowinkowski, J., Goessel, A., Gołębiewski, Z., Golubeva, N., Grabowski, W., Graeff, W., Grebentsov, A., Grecki, M., Grevsmuehl, T., Gross, M., Grosse-Wortmann, U., Grünert, J., Grunewald, S., Grzegory, P., Feng, G., Guler, H., Gusev, G., Gutierrez, J. L., Hagge, L., Hamberg, M., Hanneken, R., Harms, E., Hartl, I., Hauberg, A., Hauf, S., Hauschildt, J., Hauser, J., Havlicek, J., Hedqvist, A., Heidbrook, N., Hellberg, F., Henning, D., Hensler, O., Hermann, T., Hidvégi, A., Hierholzer, M., Hintz, H., Hoffmann, F., Hoffmann, Markus, Hoffmann, Matthias, Holler, Y., Hüning, M., Ignatenko, A., Ilchen, M., Iluk, A., Iversen, J., Iversen, J., Izquierdo, M., Jachmann, L., Jardon, N., Jastrow, U., Jensch, K., Jensen, J., Jeżabek, M., Jidda, M., Jin, H., Johansson, N., Jonas, R., Kaabi, W., Kaefer, D., Kammering, R., Kapitza, H., Karabekyan, S., Karstensen, S., Kasprzak, K., Katalev, V., Keese, D., Keil, B., Kholopov, M., Killenberger, M., Kitaev, B., Klimchenko, Y., Klos, R., Knebel, L., Koch, A., Koepke, M., Köhler, S., Köhler, W., Kohlstrunk, N., Konopkova, Z., Konstantinov, A., Kook, W., Koprek, W., Körfer, M., Korth, O., Kosarev, A., Kosiński, K., Kostin, D., Kot, Y., Kotarba, A., Kozak, T., Kozak, V., Kramert, R., Krasilnikov, M., Krasnov, A., Krause, B., Kravchuk, L., Krebs, O., Kretschmer, R., Kreutzkamp, J., Kröplin, O., Krzysik, K., Kube, G., Kuehn, H., Kujala, N., Kulikov, V., Kuzminych, V., La Civita, D., Lacroix, M., Lamb, T., Lancetov, A., Larsson, M., Le Pinvidic, D., Lederer, S., Lensch, T., Lenz, D., Leuschner, A., Levenhagen, F., Li, Y., Liebing, J., Lilje, L., Limberg, T., Lipka, D., List, B., Liu, J., Liu, S., Lorbeer, B., Lorkiewicz, J., Lu, H. H., Ludwig, F., Machau, K., Maciocha, W., Madec, C., Magueur, C., Maiano, C., Maksimova, I., Malcher, K., Maltezopoulos, T., Mamoshkina, E., Manschwetus, B., Marcellini, F., Marinkovic, G., Martinez, T., Martirosyan, H., Maschmann, W., Maslov, M., Matheisen, A., Mavric, U., Meißner, J., Meissner, K., Messerschmidt, M., Meyners, N., Michalski, G., Michelato, P., Mildner, N., Moe, M., Moglia, F., Mohr, C., Mohr, S., Möller, W., Mommerz, M., Monaco, L., Montiel, C., Moretti, M., Morozov, I., Morozov, P., Mross, D., Mueller, J., Müller, C., Müller, J., Müller, K., Munilla, J., Münnich, A., Muratov, V., Napoly, O., Näser, B., Nefedov, N., Neumann, Reinhard, Neumann, Rudolf, Ngada, N., Noelle, D., Obier, F., Okunev, I., Oliver, J. A., Omet, M., Oppelt, A., Ottmar, A., Oublaid, M., Pagani, C., Paparella, R., Paramonov, V., Peitzmann, C., Penning, J., Perus, A., Peters, F., Petersen, B., Petrov, A., Petrov, I., Pfeiffer, S., Pflüger, J., Philipp, S., Pienaud, Y., Pierini, P., Pivovarov, S., Planas, M., Pławski, E., Pohl, M., Polinski, J., Popov, V., Prat, S., Prenting, J., Priebe, G., Pryschelski, H., Przygoda, K., Pyata, E., Racky, B., Rathjen, A., Ratuschni, W., Regnaud-Campderros, S., Rehlich, K., Reschke, D., Robson, C., Roever, J., Roggli, M., Rothenburg, J., Rusiński, E., Rybaniec, R., Sahling, H., Salmani, M., Samoylova, L., Sanzone, D., Saretzki, F., Sawlanski, O., Schaffran, J., Schlarb, H., Schlösser, M., Schlott, V., Schmidt, C., Schmidt-Foehre, F., Schmitz, M., Schmökel, M., Schnautz, T., Schneidmiller, E., Scholz, M., Schöneburg, B., Schultze, J., Schulz, C., Schwarz, A., Sekutowicz, J., Sellmann, D., Semenov, E., Serkez, S., Sertore, D., Shehzad, N., Shemarykin, P., Shi, L., Sienkiewicz, M., Sikora, D., Sikorski, M., Silenzi, A., Simon, C., Singer, W., Singer, X., Sinn, H., Sinram, K., Skvorodnev, N., Smirnow, P., Sommer, T., Sorokin, A., Stadler, M., Steckel, M., Steffen, B., Steinhau-Kühl, N., Stephan, F., Stodulski, M., Stolper, M., Sulimov, A., Susen, R., Świerblewski, J., Sydlo, C., Syresin, E., Sytchev, V., Szuba, J., Tesch, N., Thie, J., Thiebault, A., Tiedtke, K., Tischhauser, D., Tolkiehn, J., Tomin, S., Tonisch, F., Toral, F., Torbin, I., Trapp, A., Treyer, D., Trowitzsch, G., Trublet, T., Tschentscher, T., Ullrich, F., Vannoni, M., Varela, P., Varghese, G., Vashchenko, G., Vasic, M., Vazquez-Velez, C., Verguet, A., Vilcins-Czvitkovits, S., Villanueva, R., Visentin, B., Viti, M., Vogel, E., Volobuev, E., Wagner, R., Walker, N., Wamsat, T., Weddig, H., Weichert, G., Weise, H., Wenndorf, R., Werner, M., Wichmann, R., Wiebers, C., Wiencek, M., Wilksen, T., Will, I., Winkelmann, L., Winkowski, M., Wittenburg, K., Witzig, A., Wlk, P., Wohlenberg, T., Wojciechowski, M., Wolff-Fabris, F., Wrochna, G., Wrona, K., Yakopov, M., Yang, B., Yang, F., Yurkov, M., Zagorodnov, I., Zalden, P., Zavadtsev, A., Zavadtsev, D., Zhirnov, A., Zhukov, A., Ziemann, V., Zolotov, A., Zolotukhina, N., Zummack, F., and Zybin, D.

Published
2020
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13. Author Correction: A MHz-repetition-rate hard X-ray free-electron laser driven by a superconducting linear accelerator

Author

Decking, W., Abeghyan, S., Abramian, P., Abramsky, A., Aguirre, A., Albrecht, C., Alou, P., Altarelli, M., Altmann, P., Amyan, K., Anashin, V., Apostolov, E., Appel, K., Auguste, D., Ayvazyan, V., Baark, S., Babies, F., Baboi, N., Bak, P., Balandin, V., Baldinger, R., Baranasic, B., Barbanotti, S., Belikov, O., Belokurov, V., Belova, L., Belyakov, V., Berry, S., Bertucci, M., Beutner, B., Block, A., Blöcher, M., Böckmann, T., Bohm, C., Böhnert, M., Bondar, V., Bondarchuk, E., Bonezzi, M., Borowiec, P., Bösch, C., Bösenberg, U., Bosotti, A., Böspflug, R., Bousonville, M., Boyd, E., Bozhko, Y., Brand, A., Branlard, J., Briechle, S., Brinker, F., Brinker, S., Brinkmann, R., Brockhauser, S., Brovko, O., Brück, H., Brüdgam, A., Butkowski, L., Büttner, T., Calero, J., Castro-Carballo, E., Cattalanotto, G., Charrier, J., Chen, J., Cherepenko, A., Cheskidov, V., Chiodini, M., Chong, A., Choroba, S., Chorowski, M., Churanov, D., Cichalewski, W., Clausen, M., Clement, W., Cloué, C., Cobos, J. A., Coppola, N., Cunis, S., Czuba, K., Czwalinna, M., D’Almagne, B., Dammann, J., Danared, H., de Zubiaurre Wagner, A., Delfs, A., Delfs, T., Dietrich, F., Dietrich, T., Dohlus, M., Dommach, M., Donat, A., Dong, X., Doynikov, N., Dressel, M., Duda, M., Duda, P., Eckoldt, H., Ehsan, W., Eidam, J., Eints, F., Engling, C., Englisch, U., Ermakov, A., Escherich, K., Eschke, J., Saldin, E., Faesing, M., Fallou, A., Felber, M., Fenner, M., Fernandes, B., Fernández, J. M., Feuker, S., Filippakopoulos, K., Floettmann, K., Fogel, V., Fontaine, M., Francés, A., Martin, I. Freijo, Freund, W., Freyermuth, T., Friedland, M., Fröhlich, L., Fusetti, M., Fydrych, J., Gallas, A., García, O., Garcia-Tabares, L., Geloni, G., Gerasimova, N., Gerth, C., Geßler, P., Gharibyan, V., Gloor, M., Głowinkowski, J., Goessel, A., Gołębiewski, Z., Golubeva, N., Grabowski, W., Graeff, W., Grebentsov, A., Grecki, M., Grevsmuehl, T., Gross, M., Grosse-Wortmann, U., Grünert, J., Grunewald, S., Grzegory, P., Feng, G., Guler, H., Gusev, G., Gutierrez, J. L., Hagge, L., Hamberg, M., Hanneken, R., Harms, E., Hartl, I., Hauberg, A., Hauf, S., Hauschildt, J., Hauser, J., Havlicek, J., Hedqvist, A., Heidbrook, N., Hellberg, F., Henning, D., Hensler, O., Hermann, T., Hidvégi, A., Hierholzer, M., Hintz, H., Hoffmann, F., Hoffmann, Markus, Hoffmann, Matthias, Holler, Y., Hüning, M., Ignatenko, A., Ilchen, M., Iluk, A., Iversen, J., Iversen, J., Izquierdo, M., Jachmann, L., Jardon, N., Jastrow, U., Jensch, K., Jensen, J., Jeżabek, M., Jidda, M., Jin, H., Johansson, N., Jonas, R., Kaabi, W., Kaefer, D., Kammering, R., Kapitza, H., Karabekyan, S., Karstensen, S., Kasprzak, K., Katalev, V., Keese, D., Keil, B., Kholopov, M., Killenberger, M., Kitaev, B., Klimchenko, Y., Klos, R., Knebel, L., Koch, A., Koepke, M., Köhler, S., Köhler, W., Kohlstrunk, N., Konopkova, Z., Konstantinov, A., Kook, W., Koprek, W., Körfer, M., Korth, O., Kosarev, A., Kosiński, K., Kostin, D., Kot, Y., Kotarba, A., Kozak, T., Kozak, V., Kramert, R., Krasilnikov, M., Krasnov, A., Krause, B., Kravchuk, L., Krebs, O., Kretschmer, R., Kreutzkamp, J., Kröplin, O., Krzysik, K., Kube, G., Kuehn, H., Kujala, N., Kulikov, V., Kuzminych, V., La Civita, D., Lacroix, M., Lamb, T., Lancetov, A., Larsson, M., Le Pinvidic, D., Lederer, S., Lensch, T., Lenz, D., Leuschner, A., Levenhagen, F., Li, Y., Liebing, J., Lilje, L., Limberg, T., Lipka, D., List, B., Liu, J., Liu, S., Lorbeer, B., Lorkiewicz, J., Lu, H. H., Ludwig, F., Machau, K., Maciocha, W., Madec, C., Magueur, C., Maiano, C., Maksimova, I., Malcher, K., Maltezopoulos, T., Mamoshkina, E., Manschwetus, B., Marcellini, F., Marinkovic, G., Martinez, T., Martirosyan, H., Maschmann, W., Maslov, M., Matheisen, A., Mavric, U., Meißner, J., Meissner, K., Messerschmidt, M., Meyners, N., Michalski, G., Michelato, P., Mildner, N., Moe, M., Moglia, F., Mohr, C., Mohr, S., Möller, W., Mommerz, M., Monaco, L., Montiel, C., Moretti, M., Morozov, I., Morozov, P., Mross, D., Mueller, J., Müller, C., Müller, J., Müller, K., Munilla, J., Münnich, A., Muratov, V., Napoly, O., Näser, B., Nefedov, N., Neumann, Reinhard, Neumann, Rudolf, Ngada, N., Noelle, D., Obier, F., Okunev, I., Oliver, J. A., Omet, M., Oppelt, A., Ottmar, A., Oublaid, M., Pagani, C., Paparella, R., Paramonov, V., Peitzmann, C., Penning, J., Perus, A., Peters, F., Petersen, B., Petrov, A., Petrov, I., Pfeiffer, S., Pflüger, J., Philipp, S., Pienaud, Y., Pierini, P., Pivovarov, S., Planas, M., Pławski, E., Pohl, M., Polinski, J., Popov, V., Prat, S., Prenting, J., Priebe, G., Pryschelski, H., Przygoda, K., Pyata, E., Racky, B., Rathjen, A., Ratuschni, W., Regnaud-Campderros, S., Rehlich, K., Reschke, D., Robson, C., Roever, J., Roggli, M., Rothenburg, J., Rusiński, E., Rybaniec, R., Sahling, H., Salmani, M., Samoylova, L., Sanzone, D., Saretzki, F., Sawlanski, O., Schaffran, J., Schlarb, H., Schlösser, M., Schlott, V., Schmidt, C., Schmidt-Foehre, F., Schmitz, M., Schmökel, M., Schnautz, T., Schneidmiller, E., Scholz, M., Schöneburg, B., Schultze, J., Schulz, C., Schwarz, A., Sekutowicz, J., Sellmann, D., Semenov, E., Serkez, S., Sertore, D., Shehzad, N., Shemarykin, P., Shi, L., Sienkiewicz, M., Sikora, D., Sikorski, M., Silenzi, A., Simon, C., Singer, W., Singer, X., Sinn, H., Sinram, K., Skvorodnev, N., Smirnow, P., Sommer, T., Sorokin, A., Stadler, M., Steckel, M., Steffen, B., Steinhau-Kühl, N., Stephan, F., Stodulski, M., Stolper, M., Sulimov, A., Susen, R., Świerblewski, J., Sydlo, C., Syresin, E., Sytchev, V., Szuba, J., Tesch, N., Thie, J., Thiebault, A., Tiedtke, K., Tischhauser, D., Tolkiehn, J., Tomin, S., Tonisch, F., Toral, F., Torbin, I., Trapp, A., Treyer, D., Trowitzsch, G., Trublet, T., Tschentscher, T., Ullrich, F., Vannoni, M., Varela, P., Varghese, G., Vashchenko, G., Vasic, M., Vazquez-Velez, C., Verguet, A., Vilcins-Czvitkovits, S., Villanueva, R., Visentin, B., Viti, M., Vogel, E., Volobuev, E., Wagner, R., Walker, N., Wamsat, T., Weddig, H., Weichert, G., Weise, H., Wenndorf, R., Werner, M., Wichmann, R., Wiebers, C., Wiencek, M., Wilksen, T., Will, I., Winkelmann, L., Winkowski, M., Wittenburg, K., Witzig, A., Wlk, P., Wohlenberg, T., Wojciechowski, M., Wolff-Fabris, F., Wrochna, G., Wrona, K., Yakopov, M., Yang, B., Yang, F., Yurkov, M., Zagorodnov, I., Zalden, P., Zavadtsev, A., Zavadtsev, D., Zhirnov, A., Zhukov, A., Ziemann, V., Zolotov, A., Zolotukhina, N., Zummack, F., and Zybin, D.

Published
2020
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14. Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer

Author

Beyer, J., Albers, P., Altena, R., Aparicio, J., Bokemeyer, C., Busch, J., Cathomas, R., Cavallin-Stahl, E., Clarke, N.W., Claßen, J., Cohn-Cedermark, G., Dahl, A.A., Daugaard, G., De Giorgi, U., De Santis, M., De Wit, M., De Wit, R., Dieckmann, K.P., Fenner, M., Fizazi, K., Flechon, A., Fossa, S.D., Germá Lluch, J.R., Gietema, J.A., Gillessen, S., Giwercman, A., Hartmann, J.T., Heidenreich, A., Hentrich, M., Honecker, F., Horwich, A., Huddart, R.A., Kliesch, S., Kollmannsberger, C., Krege, S., Laguna, M.P., Looijenga, L.H.J., Lorch, A., Lotz, J.P., Mayer, F., Necchi, A., Nicolai, N., Nuver, J., Oechsle, K., Oldenburg, J., Oosterhuis, J.W., Powles, T., Rajpert-De Meyts, E., Rick, O., Rosti, G., Salvioni, R., Schrader, M., Schweyer, S., Sedlmayer, F., Sohaib, A., Souchon, R., Tandstad, T., Winter, C., and Wittekind, C.

Published
2013
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20. Seedlings

Author

Fenner, M.

Published
1987

24. Plenary Sessions Proffered Communications

Author

Maguire, P., Davis, L. J., Ross, D. M., Weis, J., Bartelink, H., Fenner, M., Menzel, T., Ackermann, M., Kirchner, H., Inbar, M., Gardner, R., Bliss, J., Horwich, A., Piazza, M., Brown, P., Goodwin, P., Pritchard, K., Hobbs, J., Schulz, H., Smith, P. M., and Brennan, C.

Published
1993

37. Kelvin probe force microscopy studies of the charge effects upon adsorption of carbon nanotubes and C60 fullerenes on hydrogen-terminated diamond.

Author

Kölsch, S., Fritz, F., Fenner, M. A., Kurch, S., Wöhrl, N., Mayne, A. J., Dujardin, G., and Meyer, C.

Subjects
DIAMONDS, SURFACE conductivity, ELECTRONS, CARBON nanotubes, HYDROGEN
Abstract

Hydrogen-terminated diamond is known for its unusually high surface conductivity that is ascribed to its negative electron affinity. In the presence of acceptor molecules, electrons are expected to transfer from the surface to the acceptor, resulting in p-type surface conductivity. Here, we present Kelvin probe force microscopy (KPFM) measurements on carbon nanotubes and C60 adsorbed onto a hydrogen-terminated diamond(001) surface. A clear reduction in the Kelvin signal is observed at the position of the carbon nanotubes and C60 molecules as compared with the bare, air-exposed surface. This result can be explained by the high positive electron affinity of carbon nanotubes and C60, resulting in electron transfer from the surface to the adsorbates. When an oxygen-terminated diamond(001) is used instead, no reduction in the Kelvin signal is obtained. While the presence of a charged adsorbate or a difference in work function could induce a change in the KPFM signal, a charge transfer effect of the hydrogen-terminated diamond surface, by the adsorption of the carbon nanotubes and the C60 fullerenes, is consistent with previous theoretical studies. [ABSTRACT FROM AUTHOR]

Published
2018
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45. Scholarly infrastructures for research software

Author

Di Cosmo R., Gonzalez Lopez J.B., Abramatic J-F., Graf K., Colom M., Manghi P., Harrison M., Barborini Y., Tenhunen V., Wagner M, Dalitz W., Maassen J., Martinez-Ortiz C., Ronchieri E., Yates S., Schubotz M., Candela L., Fenner M., and Jeangirard E.

Subjects
Archiving Research Software, Referencing Research Software, Crediting Research Software, Research Software, Describing Research Software, Infrastructures for Research Software
Abstract

The TF on Scholarly Infrastructures of Research Software, as part of the Architecture WG of the European Open Science Cloud (EOSC) Executive Board, has established a set of recommendations to allow EOSC to include software, next to other research outputs like publications and data, in the realm of its research artifacts. This work is built upon a survey and documentation of a representative panel of current operational infrastructures across Europe, comparing their scopes and approaches. This report summarizes the state of the art, identifies best practices, as well as open problems, and paves the way for federating the different approaches in view of supporting the software pillar of EOSC.

Published
2020

46. DINI Certificate for Open Access Repositories and Publication Services 2019

Author

Müller, U., Scholze, F., Arning, U., Beucke, D., Blumtritt, U., Braun, K., Deppe, A., Deinzer, G., Fenner, M., Klotz-Berendes, B., Isabella Meinecke, Pampel, H., Schirrwagen, J., Bove, K., Severiens, T., Summann, F., Steinke, T., Tullney, M., Vierkant, P., Voigt, M., Walger, N., Weiland, J., Weimar, A., and Wolf, S.

Subjects
Open Access, 020 Bibliotheks- und Informationswissenschaften, publication services, DINI Certificate, electronic publishing, ddc:020, journal, ddc:004, 004 Datenverarbeitung, Informatik, repositories
Abstract

Publishing is an important pillar for the advancement of scientific knowledge and of science as a whole. Among its characteristics are a) the organization of effective communication between researchers (between authors and all potential recipients, i.e. securing an adequate dissemination), b) a high degree of trustworthiness (e.g. with regard to priority, copyrights, authenticity, and quality of content) that is communicated to the users of publications (i.e. researchers), and c) sustainability and verifiability (persistent citations, long-term availability, traceability of the steps on the way to publication). The present catalog of criteria translates these general expectations of scientific publishing into concrete minimum requirements of Open Access publication services. As platforms for the publication and presentation of scientific and scholarly works these represent important hubs in the scientific communication process. As Open Access services they facilitate the dissemination and democratization of knowledge.

Published
2020

48. Effect of Selective IK,ACh Inhibition by XAF-1407 in an Equine Model of Tachypacing-induced Persistent Atrial Fibrillation (AF)

Author

Fenner, M F, Carstensen, H, Nissen, S D, Hesselkilde, E Z, Lunddahl, C, Jensen, Maja Adler Hess, Loft-Andersen, A V, Sattler, S M, Platonov, P G, El-Haou, S, Jackson, C, Tang, R, Kirby, R, Ford, J W, Schotten, U, Milnes, J T, Sørensen, U S, Jespersen, T, Buhl, R, Fenner, M F, Carstensen, H, Nissen, S D, Hesselkilde, E Z, Lunddahl, C, Jensen, Maja Adler Hess, Loft-Andersen, A V, Sattler, S M, Platonov, P G, El-Haou, S, Jackson, C, Tang, R, Kirby, R, Ford, J W, Schotten, U, Milnes, J T, Sørensen, U S, Jespersen, T, and Buhl, R

Abstract

BACKGROUND AND PURPOSE: Inhibition of the G-protein gated acetylcholine-activated inward rectifier potassium (K+ ) current, IK,ACh , may be an effective atrial selective treatment strategy for atrial fibrillation. Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in an in vivo equine, atrial-tachypacing-induced model of persistent AF in the following.EXPERIMENTAL APPROACH: The in vitro ion channel pharmacological profile of XAF-1407, was investigated using cell lines stably expressing Kir 3.1/3.4, Kir 3.4/3.4, Kir 2.1, Kir 6.2/SUR2A, hERG, Kv 1.5, Kv 4.3 and Nav 1.5. A tachypacing induced model of persistent AF in the horse, a large animal model suited to pre-clinical investigations of longer duration AF, was employed to study the in vivo electrophysiological and anti-arrhythmic profile of XAF-1407. Eleven horses were implanted with implantable cardioverter defibrillators (ICD) enabling atrial-tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated at different time points over a period of one month. Cardioversion success, drug induced changes of atrial tissue refractoriness and ventricular electrophysiology were assessed at baseline (day 0) and at day 3, 5, 11, 17 and 29 after AF induction.KEY RESULTS: XAF-1407 potently and selectively inhibited Kir 3.1/3.4 hetero- and Kir 3.4 homotetramers, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period (aERP) as well as decreased atrial fibrillatory rate (AFR) significantly by approximately 20% and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened AV-nodal refractoriness, without effect on the QRS dura

Published
2020

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