15 results on '"Kessler, Tobias"'
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2. A H3K27M-targeted vaccine in adults with diffuse midline glioma
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Grassl, Niklas, Poschke, Isabel, Lindner, Katharina, Bunse, Lukas, Mildenberger, Iris, Boschert, Tamara, Jähne, Kristine, Green, Edward W., Hülsmeyer, Ingrid, Jünger, Simone, Kessler, Tobias, Suwala, Abigail K., Eisele, Philipp, Breckwoldt, Michael O., Vajkoczy, Peter, Grauer, Oliver M., Herrlinger, Ulrich, Tonn, Joerg-Christian, Denk, Monika, Sahm, Felix, Bendszus, Martin, von Deimling, Andreas, Winkler, Frank, Wick, Wolfgang, Platten, Michael, and Sahm, Katharina
- Abstract
Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M+tumors in major histocompatibility complex-humanized mice. Here we describe a first-in-human treatment with H3K27M-vac of eight adult patients with progressive H3K27M+diffuse midline glioma on a compassionate use basis. Five patients received H3K27M-vac combined with anti-PD-1 treatment based on physician’s discretion. Repeat vaccinations with H3K27M-vac were safe and induced CD4+T cell-dominated, mutation-specific immune responses in five of eight patients across multiple human leukocyte antigen types. Median progression-free survival after vaccination was 6.2 months and median overall survival was 12.8 months. One patient with a strong mutation-specific T cell response after H3K27M-vac showed pseudoprogression followed by sustained complete remission for >31 months. Our data demonstrate safety and immunogenicity of H3K27M-vac in patients with progressive H3K27M+diffuse midline glioma.
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- 2023
- Full Text
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3. Mixed-Integer Motion Planning on German Roads Within the Apollo Driving Stack
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Kessler, Tobias, Esterle, Klemens, and Knoll, Alois
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Traffic situations with interacting participants pose difficulties for today’s autonomous vehicles to interpret situations and eventually achieve their own mission goal. Interactive planning approaches are promising solutions for solving such situations. However, most approaches are only assessed in simulation, as researchers lack the resources to operate an autonomous vehicle. Likewise, open-source stacks for autonomous driving, such as Apollo, provide competitive and resource-efficient state-of-the-art planning algorithms. However, promising planning concepts from research are usually not included within a reasonable time, possibly due to resource restrictions or technical limitations. Without evaluating these novel algorithms in reality, the benefits and shortcomings of proposed approaches cannot be thoroughly assessed. This work aims to contribute methodology and implementation to integrate a novel mixed-integer optimization-based planning algorithm in Apollo’s planning component and assess its performance and real-time capability in theory and practice. It discusses the necessary modifications of Apollo for deployment on a different vehicle and presents three real-world driving experiments on a public road alongside a detailed experience report. The driving experiments show a smooth trajectory tracking performance operating robustly under varying perception data quality and the real-time capability of the closed-loop system.
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- 2023
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4. Autonomous rhythmic activity in glioma networks drives brain tumour growth
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Hausmann, David, Hoffmann, Dirk C., Venkataramani, Varun, Jung, Erik, Horschitz, Sandra, Tetzlaff, Svenja K., Jabali, Ammar, Hai, Ling, Kessler, Tobias, Azoŕin, Daniel D., Weil, Sophie, Kourtesakis, Alexandros, Sievers, Philipp, Habel, Antje, Breckwoldt, Michael O., Karreman, Matthia A., Ratliff, Miriam, Messmer, Julia M., Yang, Yvonne, Reyhan, Ekin, Wendler, Susann, Löb, Cathrin, Mayer, Chanté, Figarella, Katherine, Osswald, Matthias, Solecki, Gergely, Sahm, Felix, Garaschuk, Olga, Kuner, Thomas, Koch, Philipp, Schlesner, Matthias, Wick, Wolfgang, and Winkler, Frank
- Abstract
Diffuse gliomas, particularly glioblastomas, are incurable brain tumours1. They are characterized by networks of interconnected brain tumour cells that communicate via Ca2+transients2–6. However, the networks’ architecture and communication strategy and how these influence tumour biology remain unknown. Here we describe how glioblastoma cell networks include a small, plastic population of highly active glioblastoma cells that display rhythmic Ca2+oscillations and are particularly connected to others. Their autonomous periodic Ca2+transients preceded Ca2+transients of other network-connected cells, activating the frequency-dependent MAPK and NF-κB pathways. Mathematical network analysis revealed that glioblastoma network topology follows scale-free and small-world properties, with periodic tumour cells frequently located in network hubs. This network design enabled resistance against random damage but was vulnerable to losing its key hubs. Targeting of autonomous rhythmic activity by selective physical ablation of periodic tumour cells or by genetic or pharmacological interference with the potassium channel KCa3.1 (also known as IK1, SK4 or KCNN4) strongly compromised global network communication. This led to a marked reduction of tumour cell viability within the entire network, reduced tumour growth in mice and extended animal survival. The dependency of glioblastoma networks on periodic Ca2+activity generates a vulnerability7that can be exploited for the development of novel therapies, such as with KCa3.1-inhibiting drugs.
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- 2022
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5. Deep-learning-based synthesis of post-contrast T1-weighted MRI for tumour response assessment in neuro-oncology: a multicentre, retrospective cohort study
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Jayachandran Preetha, Chandrakanth, Meredig, Hagen, Brugnara, Gianluca, Mahmutoglu, Mustafa A, Foltyn, Martha, Isensee, Fabian, Kessler, Tobias, Pflüger, Irada, Schell, Marianne, Neuberger, Ulf, Petersen, Jens, Wick, Antje, Heiland, Sabine, Debus, Jürgen, Platten, Michael, Idbaih, Ahmed, Brandes, Alba A, Winkler, Frank, van den Bent, Martin J, Nabors, Burt, Stupp, Roger, Maier-Hein, Klaus H, Gorlia, Thierry, Tonn, Jörg-Christian, Weller, Michael, Wick, Wolfgang, Bendszus, Martin, and Vollmuth, Philipp
- Abstract
Gadolinium-based contrast agents (GBCAs) are widely used to enhance tissue contrast during MRI scans and play a crucial role in the management of patients with cancer. However, studies have shown gadolinium deposition in the brain after repeated GBCA administration with yet unknown clinical significance. We aimed to assess the feasibility and diagnostic value of synthetic post-contrast T1-weighted MRI generated from pre-contrast MRI sequences through deep convolutional neural networks (dCNN) for tumour response assessment in neuro-oncology.
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- 2021
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6. Rut: Theologische Fortbildung zu Migration und Flucht.
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Keßler, Tobias
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- FRANKFURT am Main (Germany)
- Abstract
Bei »Rut« handelt es sich um ein theologisches, über Drittmittel finanziertes Fortbildungsprojekt zu den Themen Migration und Flucht, das von Herbst 2016 bis zum Frühjahr 2021 durchgeführt wurde. Das Angebot richtete sich an haupt- und ehrenamtliche kirchliche MitarbeiterInnen, die auf verschiedenen Ebenen mit Migrierten und Geflüchteten arbeiten. Grundlage und Ausgangspunkt des Projekts war die Dissertation des Projektkoordinators Tobias Keßler, einem langjährigen wissenschaftlichen Mitarbeiter des Instituts für Weltkirche und Mission an der Philosophisch-Theologischen Hochschule Sankt Georgen in Frankfurt am Main. Der Beitrag versteht sich als Dokumentation des Projekts und seiner Umsetzung. [ABSTRACT FROM AUTHOR]
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- 2021
7. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data
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Thomalla, Götz, Boutitie, Florent, Ma, Henry, Koga, Masatoshi, Ringleb, Peter, Schwamm, Lee H, Wu, Ona, Bendszus, Martin, Bladin, Christopher F, Campbell, Bruce C V, Cheng, Bastian, Churilov, Leonid, Ebinger, Martin, Endres, Matthias, Fiebach, Jochen B, Fukuda-Doi, Mayumi, Inoue, Manabu, Kleinig, Timothy J, Latour, Lawrence L, Lemmens, Robin, Levi, Christopher R, Leys, Didier, Miwa, Kaori, Molina, Carlos A, Muir, Keith W, Nighoghossian, Norbert, Parsons, Mark W, Pedraza, Salvador, Schellinger, Peter D, Schwab, Stefan, Simonsen, Claus Z, Song, Shlee S, Thijs, Vincent, Toni, Danilo, Hsu, Chung Y, Wahlgren, Nils, Yamamoto, Haruko, Yassi, Nawaf, Yoshimura, Sohei, Warach, Steven, Hacke, Werner, Toyoda, Kazunori, Donnan, Geoffrey A, Davis, Stephen M, Gerloff, Christian, Acosta, Boris Raul, Aegidius, Karen, Albiker, Christian, Alegiani, Anna, Almendrote, Miriam, Alonso, Angelika, Althaus, Katharina, Amarenco, Pierre, Amiri, Hemasse, Anders, Bettina, Aniculaesei, Adriana, Appleton, Jason, Arenillas, Juan, Back, Christina, Bähr, Christian, Bardutzky, Jürgen, Baronnet-Chauvet, Flore, Bathe-Peters, Rouven, Bayer-Karpinska, Anna, Becerra, Juan L., Beck, Christoph, Belchí Guillamon, Olga, Benoit, Amandine, Berhoune, Nadia, Bindila, Daniela, Birchenall, Julia, Blanc-Lasserre, Karine, Blanco Gonzales, Miguel, Bobinger, Tobias, Bodechtel, Ulf, Bodiguel, Eric, Bojaryn, Urszula, Bonnet, Louise, Bouamra, Benjamin, Bourgeois, Paul, Boutitie, Florent, Breuer, Lorenz, Breynaert, Ludovic, Broughton, David, Brouns, Raf, Brugirard, Sébastian, Bruneel, Bart, Buggle, Florian, Cakmak, Serkan, Calleja, Ana, Calvet, David, Carrera, David, Chen, Hsin-Chieh, Cheng, Bastian, Cheripelli, Bharath, Cho, Tae-Hee, Choe, Chi-un, Choy, Lillian, Christensen, Hanne, Ciatipis, Mareva, Cloud, Geoffrey, Cogez, Julien, Cortijo, Elisa, Crozier, Sophie, Damgaard, Dorte, Dani, Krishna, De Coene, Beatrijs, De Hollander, Isabel, De Keyser, Jacques, De Klippel, Nina, De Maeseneire, Charlotte, De Smedt, Ann, del Mar Castellanos Rodrigo, Maria, Deltour, Sandrine, Demeestere, Jelle, Derex, Laurent, Desfontaines, Philippe, Dittrich, Ralf, Dixit, Anand, Dobbels, Laurens, Domigo, Valérie, Dorado, Laura, Druart, Charlotte, Dupont, Kristina Hougaard, Dusart, Anne, Dziewas, Rainer, Ebinger, Martin, Ebner, Matthias, Edjali-Goujon, Myriam, Eisele, Philipp, El Tawil, Salwa, Elhfnawy, Ahmed, Endres, Matthias, Etexberria, Ana, Evans, Nicholas, Fandler, Simon, Fazekas, Franz, Felix, Sandra, Fiebach, Jochen B., Fiehler, Jens, Filipov, Alexandra, Filipski, Katharina, Fleischmann, Robert, Foerch, Christian, Ford, Ian, Gaenslen, Alexandra, Galinovic, Ivana, Gancedo, Elena Meseguer, Ganeshan, Ramanan, García Esperón, Carlos, Garrido, Alicia, Gattringer, Thomas, Geraghty, Olivia, Geran, Rohat, Gerloff, Christian, Gerner, Stefan, Godon-Hardy, Sylvie, Göhler, Jos, Golsari, Amir, Gomis, Meritxell, Gorriz, David, Gramse, Verena, Grau, Laia, Griebe, Martin, Guerrero, Cristina, Guerzoglu, Damla, Guettier, Sophie, Guiraud, Vincent, Gumbinger, Christoph, Gunreben, Ignaz, Haertig, Florian, Hametner, Christian, Hanseeuw, Bernard, Hansen, Andreas, Hansen, Jakob, Harbo, Thomas, Harloff, Andreas, Harmel, Peter, Häusler, Karl Georg, Heinen, Florian, Held, Valentin, Hellwig, Simon, Hemelsoet, Dimitri, Hennerici, Michael, Herm, Juliane, Hermans, Sylvia, Hernández, María, Hervas Vicente, Jose, Hjort, Niels, Hobeanu, Cristina, Hobohm, Carsten, Höfner, Elmar, Hohenbichler, Katharina, Hommel, Marc, Hoppe, Julia, Hornberger, Eva, Hoyer, Carolin, Huang, Xuya, Ipsen, Nils, Isern, Irina, Ispierto, Lourdes, Iversen, Helle, Jeppesen, Lise, Jimenez, Marta, Jungehülsing, Jan, Jüttler, Eric, Kalladka, Dheeraj, Kallmünzer, Bernd, Kar, Arindam, Kellert, Lars, Kemmling, André, Kessler, Tobias, Khan, Usman, Klein, Matthias, Kleinschnitz, Christoph, Klockziem, Matti, Knops, Michael, Koehler, Luzie, Koehrmann, Martin, Kohlfürst, Heinz, Kollmar, Rainer, Kraft, Peter, Krause, Thomas, Kristensen, Bo, Kröber, Jan M., Kurka, Natalia, Ladoux, Alexandre, Laloux, Patrice, Lamy, Catherine, Landrault, Emmanuelle, Lauer, Arne, Lebely, Claire, Leempoel, Jonathan, Lees, Kennedy, Leger, Anne, Legrand, Laurence, Lemmens, Robin, Li, Lin, Löbbe, Anna-Mareike, London, Frederic, Lopez-cancio, Elena, Lorenz, Matthias, Louw, Stephen, Lovelock, Caroline, Lozano Sánchez, Manuel, Lucente, Giuseppe, Lückl, Janos, Luna, Alain, Macha, Kosmas, Machet, Alexandre, Mackenrodt, Daniel, Madzar, Dominik, Majoie, Charles, Männer, Anika, Maqueda, Vicky, Marstrand, Jacob, Martinez, Alicia, Marzina, Annika, Mechthouff, Laura, Meden, Per, Meersman, Guy, Meier, Julia, Mellerio, Charles, Menn, Oliver, Meyer, Nadja, Michalski, Dominik, Michels, Peter, Michelsen, Lene, Millán Torne, Monica, Minnerup, Jens, Modrau, Boris, Moeller, Sebastian, Møller, Anette, Morel, Nathalie, Moreton, Fiona, Morin, Ludovic, Moulin, Thierry, Moynihan, Barry, Mueller, Anne K., Muir, Keith W., Mulero, Patricia, Mundiyanapurath, Sibu, Mutzenbach, Johannes, Nagel, Simon, Naggara, Oliver, Nallasivan, Arumugam, Navalpotro, Irene, Nave, Alexander H., Nederkoorn, Paul, Neeb, Lars, Neugebauer, Hermann, Neumann-Haefelin, Tobias, Nighoghossian, Norbert, Oberndorfer, Stefan, Opherk, Christian, Oppel, Lorenz, Oppenheim, Catherine, Orthgieß, Johannes, Ostergaard, Leif, Paindeville, Perrine, Palomeras, Ernest, Panitz, Verena, Patel, Bhavni, Peeters, Andre, Peeters, Dirk, Pellisé, Anna, Pelz, Johann, Pereira, Anthony, Pérez de la Ossa, Natalia, Perry, Richard, Petraza, Salvador, Peysson, Stéphane, Pfeilschifter, Waltraud, Pichler, Alexander, Pierskalla, Alexandra, Pledl, Hans-Werner, Poli, Sven, Pomrehn, Katrin, Poulsen, Marika, Prats, Luis, Presas, Silvia, Prohaska, Elisabeth, Puetz, Volker, Puig, Josep, Puig Alcántara, Josep, Purrucker, Jan, Quenardelle, Veronique, Ramachandran, Sankaranarayanan, Raphaelle, Soulliard, Raposo, Nicolas, Reiff, Tilman, Remmers, Michel, Renou, Pauline, Ribitsch, Martin, Richter, Hardy, Ringleb, Peter, Ritter, Martin, Ritzenthaler, Thomas, Rodier, Gilles, Rodriguez-Regent, Christine, Rodríguez-Yáñez, Manuel, Roennefarth, Maria, Roffe, Christine, Rosenbaum, Sverre, Rosso, Charlotte, Röther, Joachim, Rozanski, Michal, Ruiz de Morales, Noelia, Russo, Francesca, Rutgers, Matthieu, Sagnier, Sharmilla, Samson, Yves, Sánchez, Josep, Sauer, Tamara, Schäfer, Jan H., Schieber, Simon, Schill, Josef, Schlak, Dennis, Schlemm, Ludwig, Schmidt, Sein, Schonewille, Wouter, Schröder, Julian, Schulz, Andreas, Schurig, Johannes, Schwarting, Sönke, Schwarz, Alexander, Schwarzbach, Christopher, Seidel, Matthias, Seiler, Alexander, Sembill, Jochen, Serena Leal, Joaquin, Shetty, Ashit, Sibon, Igor, Simonsen, Claus Z., Singer, Oliver, Sivagnanaratham, Aravinth, Smets, Ide, Smith, Craig, Soors, Peter, Sprigg, Nikola, Spruegel, Maximilian, Stark, David, Steinert, Susanne, Stösser, Sebastian, Stuermlinger, Markus, Swinnen, Bart, Tamazyan, Ruben, Tembl, Jose, Terceno Izaga, Mikel, Thijs, Vincent, Thomalla, Götz, Touze, Emmanuel, Truelsen, Thomas, Turc, Guillaume, Turine, Gaetane, Tütüncü, Serdar, Tyrell, Pippa, Ustrell, Xavier, Vadot, Wilfried, Vallet, Anne-Evelyne, Vallet, Pauline, van den Berg, Lucie, van den Berg, Sophie, van Eendenburg, Cecile, Van Hooff, Robbert-Jan, van Sloten, Isabelle, Vanacker, Peter, Vancaester, Evelien, Vanderdonckt, Patrick, Vandermeeren, Yves, Vanhee, Frederik, Veltkamp, Roland, Vestergaard, Karsten, Viguier, Alain, Vilas, Dolores, Villringer, Kersten, Voget, Dieke, von Schrader, Jörg, von Weitzel, Paul, Warburton, Elisabeth, Weber, Claudia, Weber, Jörg, Wegscheider, Karl, Wegscheider, Mirko, Weimar, Christian, Weinstich, Karin, Weise, Christopher, Weise, Gesa, Willems, Chris, Winder, Klemens, Wittayer, Matthias, Wolf, Marc, Wolf, Martin, Wolff, Valerie, Wollboldt, Christian, Wollenweber, Frank, Wouters, Anke, Yalo, Bertrand, Yger, Marion, Younan, Nadia, Yperzeele, Laetita, Zegarac, Vesna, Zeiner, Pia, Ziemann, Ulf, Zonneveld, Thomas, Zuber, Mathieu, Akutsu, Tsugio, Aoki, Junya, Aoki, Junya, Arakawa, Shuji, Doijiri, Ryosuke, Egashira, Yusuke, Enomoto, Yukiko, Fukuda-Doi, Mayumi, Furui, Eisuke, Furuta, Konosuke, Gotoh, Seiji, Hamasaki, Toshimitsu, Hasegawa, Yasuhiro, Hirano, Teryuki, Homma, Kazunari, Ichijyo, Masahiko, Ide, Toshihiro, Igarashi, Shuichi, Iguchi, Yasuyuki, Ihara, Masafumi, Ikenouchi, Hajime, Inoue, Manabu, Inoue, Tsuyoshi, Itabashi, Ryo, Ito, Yasuhiro, Iwama, Toru, Kamiyama, Kenji, Kamiyoshi, Shoko, Kanai, Haruka, Kanematsu, Yasuhisa, Kanzawa, Takao, Kimura, Kazumi, Kitayama, Jiro, Kitazono, Takanari, Koga, Masatoshi, Kondo, Rei, Kudo, Kohsuke, Kusumi, Masayoshi, Kuwahara, Ken, Matsumoto, Shoji, Matsuoka, Hideki, Mihara, Ban, Minematsu, Kazuo, Miura, Ken, Miwa, Kaori, Morita, Naomi, Mouri, Wataru, Murata, Kayo, Nagakane, Yoshinari, Nakase, Taizen, Ohara, Hiromi, Ohara, Nobuyuki, Ohnishi, Hideyuki, Ohta, Hajime, Ohtaki, Masafumi, Ohtani, Ryo, Ohtsuki, Toshiho, Ohyama, Hideo, Okada, Takashi, Okada, Yasushi, Osaki, Masato, Sakai, Nobuyuki, Sanbongi, Yoshiki, Sasaki, Naoshi, Sasaki, Makoto, Sato, Shoichiro, Seki, Kenta, Shimizu, Wataru, Shiokawa, Yoshiaki, Sozu, Takashi, Suzuki, Junichiro, Suzuki, Rieko, Takagi, Yasushi, Takizawa, Shunya, Tanahashi, Norio, Tanaka, Eijiro, Tanaka, Ryota, Tateishi, Yohei, Terada, Tomoaki, Terasaki, Tadashi, Todo, Kenichi, Tokunaga, Azusa, Toyoda, Kazunori, Tsujino, Akira, Ueda, Toshihiro, Uesaka, Yoshikazu, Uotani, Mihoko, Urabe, Takao, Watanabe, Masao, Yagita, Yoshiki, Yakushiji, Yusuke, Yamamoto, Haruko, Yasui, Keizo, Yonehara, Toshiro, Yoshimura, Sohei, Yoshimura, Shinichi, Aarnio, K., Alemseged, F., Anderson, C., Ang, T., Archer, M.L., Attia, J., Bailey, P., Balabanski, A., Barber, A., Barber, P.A., Bernhardt, J., Bivard, A., Blacker, D., Bladin, C.F., Brodtmann, A., Cadilhac, D., Campbell, B.C.V., Carey, L., Celestino, S., Chan, L., Chang, W.H., ChangI, A., Chen, C.H., Chen, C.-I., Chen, H.F., Chen, T.C., Chen, W.H., Chen, Y.Y., Cheng, C.A., Cheong, E., Chiou, Y.W., Choi, P.M., Chu, H.J., Chuang, C.S., Chung, T.C., Churilov, L., Clissold, B., Connelly, A., Coote, S., Coulton, B., Cowley, E., Cranefield, J., Curtze, S., D'Este, C., Davis, S.M., Day, S., Desmond, P.M., Dewey, H.M., Ding, C., Donnan, G.A., Drew, R., Eirola, S., Field, D., Frost, T., Garcia-Esperon, C., George, K., Gerraty, R., Grimley, R., Guo, Y.C., Hankey, G., Harvey, J., Ho, S.C., Hogan, K., Howells, D., Hsiao, P.M., Hsu, C.H., Hsu, C.T., Hsu, C.-S., Hsu, J.P., Hsu, Y.D., Hsu, Y.T., Hu, C.J., Huang, C.C., Huang, H.Y., Huang, M.Y., Huang, S.C., Huang, W.S., Jackson, D., Jeng, J.S., Jiang, S.K., Kaauwai, L., Kasari, O., King, J., Kleinig, T.J., Koivu, M., Kolbe, J., Krause, M., Kuan, C.W., Kung, W.L., Kyndt, C., Lau, C.L., Lee, A., Lee, C.Y., Lee, J.T., Lee, Y., Lee, Y.C., Levi, C., Levi, C.R., Lien, L.M., Lim, J.C., Lin, C.C., Lin, C.H., Lin, C.M., Lin, D., Liu, C.H., Liu, J., Lo, Y.C., Loh, P.S., Low, E., Lu, C.H., Lu, C.J., Lu, M.K., Ly, J., Ma, H., Macaulay, L., Macdonnell, R., Mackey, E., Macleod, M., Mahadevan, J., Maxwell, V., McCoy, R., McDonald, A., McModie, S., Meretoja, A., Mishra, S., Mitchell, P.J., Miteff, F., Moore, A., Muller, C., Ng, F., Ng, F.C., Ng, J-L., O'Brian, W., O'Collins, V., Oxley, T.J., Parsons, M.W., Patel, S., Peng, G.S., Pesavento, L., Phan, T., Rodrigues, E., Ross, Z., Sabet, A., Sallaberger, M., Salvaris, P., Shah, D., Sharma, G., Sibolt, G., Simpson, M., Singhal, S., Snow, B., Spratt, N., Stark, R., Sturm, J., Sun, M.C., Sun, Y., Sung, P.S., Sung, Y.F., Suzuki, M., Tan, M., Tang, S.C., Tatlisumak, T., Thijs, V., Tiainen, M., Tsai, C.H., Tsai, C.K., Tsai, C.L., Tsai, H.T., Tsai, L.K., Tseng, C.H., Tseng, L.T., Tsoleridis, J., Tu, H., Tu, H.T-H., Vallat, W., Virta, J., Wang, W.C., Wang, Y.T., Waters, M., Weir, L., Wijeratne, T., Williams, C., Wilson, W., Wong, A.A., Wong, K., Wu, T.Y., Wu, Y.H., Yan, B., Yang, F.C., Yang, Y.W., Yassi, N., Yeh, H.L., Yeh, J.H., Yeh, S.J., Yen, C.H., Young, D., Ysai, C.L., Zhang, W.W., Zhao, H., Zhao, L., Althaus-Knaurer, Katharina, Bendszus, Martin, Berrouschot, Jörg, Bluhmki, Erich, Bovi, Paolo, Chatellier, Gilles, Cove, Lynda, Davis, Stephen, Dixit, A., Donnan, Geoffrey, Dziewas, Rainer, Ehrenkrona, Christina, Eschenfelder, Christoph, Fatar, Marc, Francisco Arenillas, Juan, Gruber, Franz, Hacke, Werner, Kala, Lalit, Kapeller, Peter, Kaste, Markku, Kessler, Christof, Köhrmann, Martin, Laage, Rico, Lees, Kennedy R., Leys, Didier, Luna Rodriguez, Alain, Mas, Jean-Louis, Mikulik, Robert, Molina, Carlos, Muddegowda, Girish, Muir, Keith, Niederkorn, Kurt, Nuñez, Xavier, Oppenheim, Catherine, Poli, Sven, Ringleb, Peter, Schellinger, Peter, Schwab, Stefan, Serena, Joaquin, Sobesky, Jan, Steiner, Thorsten, Svenson, Ann-Sofie, Toni, Danilo, Veltkamp, Roland, von Kummer, Rüdiger, Wahlgren, Nils, Wardlaw, Joanna, Betensky, Rebecca A., Boulouis, Gregoire, Carandang, Raphael A., Copen, William A., Cougo, Pedro, Cutting, Shawna, Drake, Kendra, Ford, Andria L., Hallenbeck, John, Harris, Gordon J., Hoesch, Robert, Hsia, Amie, Kase, Carlos, Latour, Lawrence, Lauer, Arne, Lev, Michael H., Muzikansky, Alona, Nagaraja, Nandakumar, Schwamm, Lee H., Searls, Eric, Song, Shlee S., Starkman, Sidney, Warach, Steven, Wu, Ona, Yoo, Albert J., and Zand, Ramin
- Abstract
Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.
- Published
- 2020
- Full Text
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8. Noninvasive Characterization of Tumor Angiogenesis and Oxygenation in Bevacizumab-treated Recurrent Glioblastoma by Using Dynamic Susceptibility MRI: Secondary Analysis of the European Organization for Research and Treatment of Cancer 26101 Trial
- Author
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Kickingereder, Philipp, Brugnara, Gianluca, Hansen, Mikkel Bo, Nowosielski, Martha, Pflüger, Irada, Schell, Marianne, Isensee, Fabian, Foltyn, Martha, Neuberger, Ulf, Kessler, Tobias, Sahm, Felix, Wick, Antje, Heiland, Sabine, Weller, Michael, Platten, Michael, Deimling, Andreas von, Maier-Hein, Klaus H., Østergaard, Leif, Bent, Martin J. van den, Gorlia, Thierry, Wick, Wolfgang, and Bendszus, Martin
- Abstract
This secondary analysis of European Organization for Research and Treatment of Cancer 26101 highlights the biological activity and effectiveness of bevacizumab for extending progression-free survival for patients with glioblastoma, however, identifying patients with overall survival benefit remains challenging.
- Published
- 2020
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9. Glutamatergic synaptic input to glioma cells drives brain tumour progression
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Venkataramani, Varun, Tanev, Dimitar Ivanov, Strahle, Christopher, Studier-Fischer, Alexander, Fankhauser, Laura, Kessler, Tobias, Körber, Christoph, Kardorff, Markus, Ratliff, Miriam, Xie, Ruifan, Horstmann, Heinz, Messer, Mirko, Paik, Sang Peter, Knabbe, Johannes, Sahm, Felix, Kurz, Felix T., Acikgöz, Azer Aylin, Herrmannsdörfer, Frank, Agarwal, Amit, Bergles, Dwight E., Chalmers, Anthony, Miletic, Hrvoje, Turcan, Sevin, Mawrin, Christian, Hänggi, Daniel, Liu, Hai-Kun, Wick, Wolfgang, Winkler, Frank, and Kuner, Thomas
- Abstract
A network of communicating tumour cells that is connected by tumour microtubes mediates the progression of incurable gliomas. Moreover, neuronal activity can foster malignant behaviour of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here we report a direct communication channel between neurons and glioma cells in different disease models and human tumours: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumour microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype. Neuronal activity including epileptic conditions generates synchronised calcium transients in tumour-microtube-connected glioma networks. Glioma-cell-specific genetic perturbation of AMPA receptors reduces calcium-related invasiveness of tumour-microtube-positive tumour cells and glioma growth. Invasion and growth are also reduced by anaesthesia and the AMPA receptor antagonist perampanel, respectively. These findings reveal a biologically relevant direct synaptic communication between neurons and glioma cells with potential clinical implications.
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- 2019
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10. Global optimization of distillation columns using surrogate models
- Author
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Keßler, Tobias, Kunde, Christian, Mertens, Nick, Michaels, Dennis, and Kienle, Achim
- Abstract
Surrogate-based optimization of distillation columns using an iterative Kriging approach is investigated. Focus is on deterministic global optimization to avoid suboptimal local minima. The determination of optimal setups and operating conditions for ideal and non-ideal distillation columns, leading to mixed-integer nonlinear programming problems, serve as case studies. It is found that the optimization using the adapted Kriging approach yields similar results compared to the direct global optimization of the original problem in the ideal case, while it leads to a huge improvement compared to a multistart local optimization approach in the non-ideal case.
- Published
- 2019
- Full Text
- View/download PDF
11. Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate
- Author
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Bunse, Lukas, Pusch, Stefan, Bunse, Theresa, Sahm, Felix, Sanghvi, Khwab, Friedrich, Mirco, Alansary, Dalia, Sonner, Jana K., Green, Edward, Deumelandt, Katrin, Kilian, Michael, Neftel, Cyril, Uhlig, Stefanie, Kessler, Tobias, von Landenberg, Anna, Berghoff, Anna S., Marsh, Kelly, Steadman, Mya, Zhu, Dongwei, Nicolay, Brandon, Wiestler, Benedikt, Breckwoldt, Michael O., Al-Ali, Ruslan, Karcher-Bausch, Simone, Bozza, Matthias, Oezen, Iris, Kramer, Magdalena, Meyer, Jochen, Habel, Antje, Eisel, Jessica, Poschet, Gernot, Weller, Michael, Preusser, Matthias, Nadji-Ohl, Minou, Thon, Niklas, Burger, Michael C., Harter, Patrick N., Ratliff, Miriam, Harbottle, Richard, Benner, Axel, Schrimpf, Daniel, Okun, Jürgen, Herold-Mende, Christel, Turcan, Sevin, Kaulfuss, Stefan, Hess‐Stumpp, Holger, Bieback, Karen, Cahill, Daniel P., Plate, Karl H., Hänggi, Daniel, Dorsch, Marion, Suvà, Mario L., Niemeyer, Barbara A., von Deimling, Andreas, Wick, Wolfgang, and Platten, Michael
- Abstract
The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. Here, we identify an additional activity of R-2-HG: tumor cell–derived R-2-HG is taken up by T cells where it induces a perturbation of nuclear factor of activated T cells transcriptional activity and polyamine biosynthesis, resulting in suppression of T cell activity. IDH1-mutant gliomas display reduced T cell abundance and altered calcium signaling. Antitumor immunity to experimental syngeneic IDH1-mutant tumors induced by IDH1-specific vaccine or checkpoint inhibition is improved by inhibition of the neomorphic enzymatic function of mutant IDH1. These data attribute a novel, non-tumor cell-autonomous role to an oncometabolite in shaping the tumor immune microenvironment.
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- 2018
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12. Debugging Autonomous Driving Systems Using Serialized Software Components
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Minnerup, Pascal, Lenz, David, Kessler, Tobias, and Knoll, Alois
- Abstract
In the development of software-intensive systems in a vehicle, like an autonomous driving system, defects are often only recognized during trials on the physical vehicle. In contrast to a simulation environment, a physically executed maneuver does not offer the possibility to pause and debug critical code sections or to reproduce and repeat faulty trials. Furthermore, development space and capacities are limited inside the car. Therefore, it is best practice to analyze faults observed during a physical execution offline and to reproduce faulty trials in a simulation environment. The repetition in a simulation environment is a time consuming effort but necessary for pushing the software component towards a state in which it showed the faulty behavior. This paper shows an approach for executing the faulty state again in a simulation environment by serializing the exact state of the software system and summarizes practical experience gained by this approach.
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- 2016
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13. Behandlung distaler artikulärer Oberschenkelfrakturen
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Winkler, Hartmut, Haber, Thomas, and Kessler, Tobias
- Abstract
Die Behandlung distaler Femurfrakturen ist wegen der Nähe zum Kniegelenk eine therapeutische Herausforderung. Hohe Komplikationsraten durch Infektionen und knöcherne Fehlheilungen wurden berichtet. Die Ursachen Liegen in der Biomechanik der problematischen lateralen Plattenfixation, der Störung der Vaskularisation durch ausgedehnte knöcherne Exposition und der häufig osteoporotischen Knochenqualität mit unzureichender Verankerungsmöglichkeiten der Implantate im distalen Femur. Die retrograde Marknagelung mit dem distalen Femurnagel (DFN) ist ein Verfahren, welches aufgrund der minimalinvasiven Technik möglicherweise in der Lage ist, einen Teil der Probleme zu lösen. Im Folgenden soll über die bisherigen Erfahrungen mit der retrograden Nagelung bei 20 Patienten mit 21 Frakturen berichtet werden. The treatment of distal femur fractures is challenging because the knee is so near. A high incidence of such complications as infection and deficient bony healing has been reported. Problematic biomechanical aspects of lateral plate fixation, disturbance of the vascularisation as the result of extensive bony exposure, and the frequently osteoporotic bone quality, which makes adequate fixation of implants in the distal femur impossible, are some reasons for the high complication rate. Retrograge medullary nailing is a procedure that might offer a solution to some of the problems as the technique is minimally invasive. We report our experience of treating 21 fractures with retrograde nailing.
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- 2002
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14. Toll-Like Receptor 3 Is a Mediator of the Innate Immune Response to Cytomegalovirus in Immature Dendritic Cells.
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Einsele, Hermann, Bonin, Michael, Gebhardt, Florian, Kessler, Tobias, Riegler, Susanne, Haddad, Ziad, Hebart, Holger, and Loeffler, Juergen
- Abstract
Dendritic cells (DCs), contribute to the initiation of immune responses to viral infection. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and initiate antimicrobial immune responses. TLR3 in DCs recognizes viral double-stranded RNA and triggers downstream signals to activate the NF?B and the interferon ß promoter. Double-stranded RNA may also be produced by double-stranded DNA viruses, such as HCMV, through bidirectional transcription from the genome during infection. Here we investigated whether TLR3 mediates the interaction between monocyte-derived immature DCs (iDCs) and HCMV after either active viral replication or viral penetration. We observed that HCMV strains differ in their interactions with iDCs. Strains that show no tropism for DCs, such as AD169, only penetrate iDCs, whereas the DC-tropic strains, e.g. TB40-E, actively replicate in iDCs. This difference provides an opportunity to study different forms of virus-DC interaction. Genome-wide expression array analysis showed that although 23 genes encoding cytokines, chemokines, and transcription factors are upregulated in iDCs after incubation with either strain, subsets of genes are induced specifically by DC-tropic or DC-nontropic strains. Only interaction with the DC-tropic HCMV strain TB40E, which replicates and produces mature virions, led to up-regulation of the TLR3 gene as well as genes downstream of TLR3 in the TLR3-signaling pathway, including class I interferon genes, NF?B, TRAF family member-associated NFKB activator (TANK), TANK-binding kinase 1 (TBK1), CXCL10, and CXCL11. The DC-nontropic HCMV strain AD169, which penetrates iDCs without replicating, did not upregulate genes of the TLR3 pathways. For selected genes, array data were confirmed by quantitative real-time PCR assay and ELISA to detect the gene products. To further confirm that the DC-tropic HCMV strain TB40E interacts with iDCs via TLR3, we transfected DCs with TLR3-specific siRNA prior to infection. TLR3 gene expression was potently silenced, while levels of the hALAS housekeeping gene mRNA remained normal. After these transfected DCs were infected with TB40E, HCMV-induced TLR3 gene expression was still markedly downregulated (−219 x), as were the downstream genes of the TLR3-signaling pathway (IFNa, −2.8 x; IFNß, −12.8 x; NF?B, −7.7 x; CCL5, −14.4 x; CXCL10, −16.5 x; CXCL11, −10.9 x). In contrast, TLR3 siRNA alone did not significantly modulate the expression of NF?B, CCL5, CXCL10, and class I interferons. Our results are consistent with those of McWirther et al., who reported that mice with a deficiency of TBK1 which is downstream of TLR3 show marked defects in IFNa and IFNß gene expression after viral infection or after engagement of TLR3 by double-stranded RNA. Thus, a key mediator of HCMV-DC interaction, which activates both a MyD88-dependent pathway that leads to early NF?B activation and a MyD88-independent pathway that leads to a class I interferon response (IFNa and IFNß) via interferon regulatory factor 3 (IRF3). This activation of the TLR3 signalling pathway was not observed when the DC-nontropic HCMV strain AD169 penetrated DCs without replicating. The identification of pathways that enhance innate antiviral immune responses may provide new avenues of therapeutic intervention for viral infections.
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- 2004
- Full Text
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15. New glioblastoma heterogeneity atlas - a shared resource.
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Wick W and Kessler T
- Subjects
- Humans, Atlases as Topic, Brain Neoplasms pathology, Glioblastoma pathology
- Published
- 2018
- Full Text
- View/download PDF
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