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4. Evaluation of the interest to combine a CD4 Th1-inducer cancer vaccine derived from telomerase and atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: a randomized non-comparative phase II study (TERTIO – PRODIGE 82)

Author

Vienot, Angélique, Jacquin, Marion, Rebucci-Peixoto, Magali, Pureur, Dimitri, Ghiringhelli, François, Assenat, Eric, Hammel, Pascal, Rosmorduc, Olivier, Stouvenot, Morgane, Allaire, Manon, Bouattour, Mohamed, Regnault, Hélène, Fratte, Serge, Raymond, Eric, Soularue, Emilie, Husson-Wetzel, Stéphanie, Di Martino, Vincent, Muller, Allison, Clairet, Anne-Laure, Fagnoni-Legat, Christine, Adotevi, Olivier, Meurisse, Aurélia, Vernerey, Dewi, and Borg, Christophe

Published
2023
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5. Differential acclimation kinetics of the two forms of type IV chromatic acclimaters occurring in marine Synechococcus cyanobacteria

Author

Louison Dufour, Laurence Garczarek, Bastian Gouriou, Julia Clairet, Morgane Ratin, and Frédéric Partensky

Subjects
marine picocyanobacteria, Synechococcus, chromatic acclimation, spectral niche, phycobilisome, comparative physiology, Microbiology, QR1-502
Abstract

Synechococcus, the second most abundant marine phytoplanktonic organism, displays the widest variety of pigment content of all marine oxyphototrophs, explaining its ability to colonize all spectral niches occurring in the upper lit layer of oceans. Seven Synechococcus pigment types (PTs) have been described so far based on the phycobiliprotein composition and chromophorylation of their light-harvesting complexes, called phycobilisomes. The most elaborate and abundant PT (3d) in the open ocean consists of cells capable of type IV chromatic acclimation (CA4), i.e., to reversibly modify the ratio of the blue light-absorbing phycourobilin (PUB) to the green light-absorbing phycoerythrobilin (PEB) in phycobilisome rods to match the ambient light color. Two genetically distinct types of chromatic acclimaters, so-called PTs 3dA and 3dB, occur at similar global abundance in the ocean, but the precise physiological differences between these two types and the reasons for their complementary niche partitioning in the field remain obscure. Here, photoacclimation experiments in different mixes of blue and green light of representatives of these two PTs demonstrated that they differ by the ratio of blue-to-green light required to trigger the CA4 process. Furthermore, shift experiments between 100% blue and 100% green light, and vice-versa, revealed significant discrepancies between the acclimation pace of the two types of chromatic acclimaters. This study provides novel insights into the finely tuned adaptation mechanisms used by Synechococcus cells to colonize the whole underwater light field.

Published
2024
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6. Evaluation of the interest to combine a CD4 Th1-inducer cancer vaccine derived from telomerase and atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: a randomized non-comparative phase II study (TERTIO – PRODIGE 82)

Author

Angélique Vienot, Marion Jacquin, Magali Rebucci-Peixoto, Dimitri Pureur, François Ghiringhelli, Eric Assenat, Pascal Hammel, Olivier Rosmorduc, Morgane Stouvenot, Manon Allaire, Mohamed Bouattour, Hélène Regnault, Serge Fratte, Eric Raymond, Emilie Soularue, Stéphanie Husson-Wetzel, Vincent Di Martino, Allison Muller, Anne-Laure Clairet, Christine Fagnoni-Legat, Olivier Adotevi, Aurélia Meurisse, Dewi Vernerey, and Christophe Borg

Subjects
Hepatocellular carcinoma, Immunotherapy, Vaccination, Telomerase, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non–small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV+ cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study. Methods Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously. Discussion Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. Trial registration NCT05528952.

Published
2023
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9. WEST full tungsten operation with an ITER grade divertor

Author

J. Bucalossi, A. Ekedahl, and the WEST Team, J. Achard, K. Afonin, O. Agullo, T. Alarcon, L. Allegretti, F. Almuhisen, H. Ancher, G. Antar, Y. Anquetin, S. Antusch, V. Anzallo, C. Arnas, J.F. Artaud, M.H. Aumeunier, S.G. Baek, X.Y. Bai, M. Balden, C. Balorin, T. Barbui, A. Barbuti, J. Barlerin, J. Barra, V. Basiuk, T. Batal, O. Baulaigue, A. Bec, M. Becoulet, E. Benoit, E. Bernard, J.M. Bernard, M. Bernert, N. Bertelli, E. Bertrand, P. Beyer, J. Bielecki, P. Bienvenu, R. Bisson, B. Bliewert, G. Bodner, S. Bose, C. Bottereau, C. Bouchand, Y. Boumendjel, F. Bouquey, C. Bourdelle, J. Bourg, S. Brezinsek, F. Brochard, C. Brun, V. Bruno, H. Bufferand, A. Bureau, S. Burles, Y. Camenen, B. Cantone, E. Caprin, M. Carole, S. Carpentier-Chouchana, G. Caulier, F. Causa, N. Cazanave, N. Chanet, O. Chellai, Y. Chen, M. Chernyshova, P. Chmielewski, W. Choe, A. Chomiczewska, G. Ciraolo, F. Clairet, J. Coenen, L. Colas, G. Colledani, J. Colnel, P. Coquillat, E. Corbel, Y. Corre, X. Courtois, T. Czarski, A. Da Ros, R. Daniel, J. Daumas, M. De Combarieu, P. De Vries, C. Dechelle, F. Deguara, R. Dejarnac, J.M. Delaplanche, L.F. Delgado-Aparicio, E. Delmas, L. Delpech, C. Desgranges, P. Devynck, J. Denis, S. Di Genova, R. Diab, A. Diallo, M. Diez, G. Dif-Pradalier, M. Dimitrova, R. Ding, T. Dittmar, L. Doceul, M. Domenes, D. Donovan, D. Douai, L. Dubus, N. Dumas, R. Dumont, F. Durand, A. Durif, F. Durodié, D. Elbeze, S. Ertmer, A. Escarguel, F. Escourbiac, B. Esposito, K. Ezato, F. Faisse, J.L. Farjon, N. Faure, N. Fedorczak, P. Fejoz, F. Felici, C. Fenzi-Bonizec, F. Ferlay, L. Ferrand, L. Fevre, M. Firdaouss, L. Fleury, D. Flouquet, T. Fonghetti, A. Gallo, X. Garbet, J. Garcia, J.L. Gardarein, L. Gargiulo, P. Garibaldi, S. Garitta, J. Gaspar, E. Gauthier, S. Gazzotti, F. Gely, J. Gerardin, G. Gervasini, E. Geulin, M. Geynet, P. Ghendrih, I. Giacalone, C. Gil, S. Ginoux, S. Girard, E. Giroux, G. Giruzzi, M. Goniche, V. Gorse, T. Gray, E. Grelier, C. Grisolia, A. Grosjean, A. Grosman, O. Grover, D. Guibert, D. Guilhem, C. Guillemaut, B. Guillermin, R. Guirlet, J.P. Gunn, Y. Gunsu, T. Gyergyek, S. Hacquin, A. Hakola, J. Harris, J.C. Hatchressian, W. Helou, P. Hennequin, C. Hernandez, L. Hijazi, J. Hillairet, T. Hirai, G.T. Hoang, C. Honoré, M. Houry, A. Huart, G. Huijsmans, P. Huynh, M. Iafrati, F. Imbeaux, N. Imbert, I. Ivanova-Stanik, P. Ivanova, R. Jalageas, A. Jamann, C. Jammes, A. Jardin, L. Jaubert, G. Jiolat, E. Joffrin, C. Johnson, A. Jonas, A. Kirschner, C.C. Klepper, M. Komm, M. Koubiti, S. Kosslow, J. Kovacic, M. Kozeiha, K. Krieger, K. Krol, I. Kudashev, B. Lacroix, L. Laguardia, V. Lamaison, V. Lapleigne, H. Laqua, C. Lau, Y. Lausenaz, R. Lé, M. Le Bohec, N. Lefevre, N. Lemoine, E. Lerche, Y. Lesourd, L. Letellier, M. Lewerentz, Y. Li, A. Liang, P. Linczuk, C. Linsmeier, M. Lipa, X. Litaudon, X. Liu, J. Llorens, T. Loarer, A. Loarte, T. Loewenhoff, G. Lombard, J. Lore, P. Lorenzetto, B. Lu, A. Lumsdaine, R. Lunsford, T. Lunt, G. Luo, P. Magaud, P. Maget, J.F. Mahieu, P. Maini, P. Malard, K. Malinowski, P. Manas, L. Manenc, V. Maquet, Y. Marandet, C. Martin, E.J. Martin, P. Martino, M. Mayer, D. Mazon, S. Mazzi, P. Messina, L. Meunier, D. Midou, G. Miglionico, Y. Mineo, M. Missirlian, R. Mitteau, B. Mitu, D. Moiraf, P. Mollard, G. Momparler, V. Moncada, T. Mondiere, C. Monti, J. Morales, M. Moreau, Ph. Moreau, Y. Moudden, G. Moureau, D. Mouyon, M. Muraglia, T. Nakano, E. Nardon, A. Neff, F. Nespoli, J. Nichols, L. Nicolas, S. Nicollet, R. Nouailletas, M. Ono, V. Ostuni, O. Paillat, C. Parish, H. Park, H. Parrat, J.Y. Pascal, B. Pegourie, F.P. Pellissier, Y. Peneliau, M. Peret, E. Pignoly, G. Pintsuk, R. Pitts, C. Pocheau, A. Podolnik, C. Portafaix, M. Poulos, P. Prochet, A. Puig Sitjes, R. Ragona, M. Rasinski, S. Ratynskaia, G. Raup, X. Regal-Mezin, C. Reux, J. Rice, M. Richou, F. Rigollet, N. Rivals, H. Roche, S. Rodrigues, J. Romazanov, G. Ronchi, C. Ruset, R. Sabot, A. Saille, R. Sakamoto, B. Salamon, F. Samaille, A. Santagiustina, B. Santraine, Y. Sarazin, O. Sauter, Y. Savoie-Peysson, L. Schiesko, M. Scholz, J.L. Schwob, E. Serre, H. Shin, S. Shiraiwa, Ja. Signoret, O. Skalli-Fettachi, P. Sogorb, Y. Song, A. Spring, P. Spuig, S. Sridhar, B. Stratton, C. Talatizi, P. Tamain, R. Tatali, Q. Tichit, A. Torre, L. Toulouse, W. Treutterer, E. Tsitrone, E.A. Unterberg, G. Urbanczyk, G. Van Rooij, N. Varadarajan, S. Vartanian, E. Velly, J.M. Verger, L. Vermare, D. Vezinet, N. Vignal, B. Vincent, S. Vives, D. Volpe, G. Wallace, E. Wang, L. Wang, Y. Wang, Y.S. Wang, T. Wauters, D. Weldon, B. Wirth, M. Wirtz, A. Wojenski, M. Xu, Q.X. Yang, H. Yang, B. Zago, R. Zagorski, B. Zhang, X.J. Zhang, X.L. Zou, and the EUROfusion Tokamak Exploitation Team

Subjects
nuclear fusion, magnetic confinement, tokamak, divertor, WEST, ITER, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

The mission of WEST (tungsten-W Environment in Steady-state Tokamak) is to explore long pulse operation in a full tungsten (W) environment for preparing next-step fusion devices (ITER and DEMO) with a focus on testing the ITER actively cooled W divertor in tokamak conditions. Following the successful completion of phase 1 (2016-2021), phase 2 started in December 2022 with the lower divertor made entirely of actively cooled ITER-grade tungsten mono-blocks. A boronization prior the first plasma attempt allowed for a smooth startup with the new divertor. Despite the reduced operating window due to tungsten, rapid progress has been made in long pulse operation, resulting in discharges with a pulse length of 100 s and an injected energy of around 300 MJ per discharge. Plasma startup studies were carried out with equatorial boron nitride limiters to compare them with tungsten limiters, while Ion Cyclotron Resonance Heating assisted startup was attempted. High fluence operation in attached regime, which was the main thrust of the first campaigns, already showed the progressive build up of deposits and appearance of dust, impacting the plasma operation as the plasma fluence increased. In total, the cumulated injected energy during the first campaigns reached 43 GJ and the cumulated plasma time exceeded 5 h. Demonstration of controlled X-Point Radiator regime is also reported, opening a promising route for investigating plasma exhaust and plasma-wall interaction issues in more detached regime. This paper summarises the lessons learned from the manufacturing and the first operation of the ITER-grade divertor, describing the progress achieved in optimising operation in a full W environment with a focus on long pulse operation and plasma wall interaction.

Published
2024
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10. Overview of ASDEX upgrade results in view of ITER and DEMO

Author

H. Zohm, E. Alessi, C. Angioni, N. Arden, V. Artigues, M. Astrain, O. Asunta, M. Balden, V. Bandaru, A. Banon Navarro, M. Bauer, A. Bergmann, M. Bergmann, J. Bernardo, M. Bernert, A. Biancalani, R. Bielajew, R. Bilato, G. Birkenmeier, T. Blanken, V. Bobkov, A. Bock, L. Bock, T. Body, T. Bolzonella, N. Bonanomi, A. Bortolon, B. Böswirth, C. Bottereau, A. Bottino, H. van den Brand, M. Brenzke, S. Brezinsek, D. Brida, F. Brochard, J. Buchanan, A. Buhler, A. Burckhart, Y. Camenen, B. Cannas, P. Cano Megías, D. Carlton, M. Carr, P. Carvalho, C. Castaldo, A. Castillo Castillo, A. Cathey, M. Cavedon, C. Cazzaniga, C. Challis, A. Chankin, A. Chomiczewska, C. Cianfarani, F. Clairet, S. Coda, R. Coelho, J.W. Coenen, L. Colas, G. Conway, S. Costea, D. Coster, T. Cote, A.J. Creely, G. Croci, D.J. Cruz Zabala, G. Cseh, I. Cziegler, O. D’Arcangelo, A. Dal Molin, P. David, C. Day, M. de Baar, P. de Marné, R. Delogu, P. Denner, A. Di Siena, M. Dibon, J.J. Dominguez-Palacios Durán, D. Dunai, M. Dreval, M. Dunne, B.P. Duval, R. Dux, T. Eich, S. Elgeti, A. Encheva, B. Esposito, E. Fable, M. Faitsch, D. Fajardo Jimenez, U. Fantz, M. Farnik, H. Faugel, F. Felici, O. Ficker, A. Figueredo, R. Fischer, O. Ford, L. Frassinetti, M. Fröschle, G. Fuchert, J.C. Fuchs, H. Fünfgelder, S. Futatani, K. Galazka, J. Galdon-Quiroga, D. Gallart Escolà, A. Gallo, Y. Gao, S. Garavaglia, M. Garcia Muñoz, B. Geiger, L. Giannone, S. Gibson, L. Gil, E. Giovannozzi, I. Girka, O. Girka, T. Gleiter, S. Glöggler, M. Gobbin, J.C. Gonzalez, J. Gonzalez Martin, T. Goodman, G. Gorini, T. Görler, D. Gradic, G. Granucci, A. Gräter, G. Grenfell, H. Greuner, M. Griener, M. Groth, O. Grover, A. Gude, L. Guimarais, S. Günter, D. Hachmeister, A.H. Hakola, C. Ham, T. Happel, N. den Harder, G. Harrer, J. Harrison, V. Hauer, T. Hayward-Schneider, B. Heinemann, P. Heinrich, T. Hellsten, S. Henderson, P. Hennequin, M. Herschel, S. Heuraux, A. Herrmann, E. Heyn, F. Hitzler, J. Hobirk, K. Höfler, S. Hörmann, J.H. Holm, M. Hölzl, C. Hopf, L. Horvath, T. Höschen, A. Houben, A. Hubbard, A. Huber, K. Hunger, V. Igochine, M. Iliasova, J. Illerhaus, K. Insulander Björk, C. Ionita-Schrittwieser, I. Ivanova-Stanik, S. Jachmich, W. Jacob, N. Jaksic, A. Jansen van Vuuren, F. Jaulmes, F. Jenko, T. Jensen, E. Joffrin, A. Kallenbach, J. Kalis, A. Kappatou, J. Karhunen, C.-P. Käsemann, S. Kasilov, Y. Kazakov, A. Kendl, W. Kernbichler, E. Khilkevitch, M. Kircher, A. Kirk, S. Kjer Hansen, V. Klevarova, F. Klossek, G. Kocsis, M. Koleva, M. Komm, M. Kong, A. Krämer-Flecken, M. Krause, I. Krebs, A. Kreuzeder, K. Krieger, O. Kudlacek, D. Kulla, T. Kurki-Suonio, B. Kurzan, B. Labit, K. Lackner, F. Laggner, A. Lahtinen, P. Lainer, P.T. Lang, P. Lauber, M. Lehnen, L. Leppin, E. Lerche, N. Leuthold, L. Li, J. Likonen, O. Linder, H. Lindl, B. Lipschultz, Y. Liu, Z. Lu, T. Luda Di Cortemiglia, N.C. Luhmann, T. Lunt, A. Lyssoivan, T. Maceina, J. Madsen, A. Magnanimo, H. Maier, J. Mailloux, R. Maingi, O. Maj, E. Maljaars, V. Maquet, A. Mancini, A. Manhard, P. Mantica, M. Mantsinen, P. Manz, M. Maraschek, C. Marchetto, M. Markl, L. Marrelli, P. Martin, F. Matos, M. Mayer, P.J. McCarthy, R. McDermott, G. Meng, R. Merkel, A. Merle, H. Meyer, M. Michelini, D. Milanesio, V. Mitterauer, P. Molina Cabrera, M. Muraca, F. Nabais, V. Naulin, R. Nazikian, R.D. Nem, R. Neu, A.H. Nielsen, S.K. Nielsen, T. Nishizawa, M. Nocente, I. Novikau, S. Nowak, R. Ochoukov, J. Olsen, P. Oyola, O. Pan, G. Papp, A. Pau, G. Pautasso, C. Paz-Soldan, M. Peglau, E. Peluso, P. Petersson, C. Piron, U. Plank, B. Plaum, B. Plöckl, V. Plyusnin, G. Pokol, E. Poli, A. Popa, L. Porte, J. Puchmayr, T. Pütterich, L. Radovanovic, M. Ramisch, J. Rasmussen, G. Ratta, S. Ratynskaia, G. Raupp, A. Redl, D. Réfy, M. Reich, F. Reimold, D. Reiser, M. Reisner, D. Reiter, B. Rettino, T. Ribeiro, D. Ricci, R. Riedl, J. Riesch, J.F. Rivero Rodriguez, G. Rocchi, P. Rodriguez-Fernandez, V. Rohde, G. Ronchi, M. Rott, M. Rubel, D.A. Ryan, F. Ryter, S. Saarelma, M. Salewski, A. Salmi, O. Samoylov, L. Sanchis Sanchez, J. Santos, O. Sauter, G. Schall, A. Schlüter, J. Scholte, K. Schmid, O. Schmitz, P.A. Schneider, R. Schrittwieser, M. Schubert, C. Schuster, N. Schwarz, T. Schwarz-Selinger, J. Schweinzer, F. Sciortino, O. Seibold-Benjak, A. Shabbir, A. Shalpegin, S. Sharapov, U. Sheikh, A. Shevelev, G. Sias, M. Siccinio, B. Sieglin, A. Sigalov, A. Silva, C. Silva, D. Silvagni, J. Simpson, S. Sipilä, A. Snicker, E. Solano, C. Sommariva, C. Sozzi, M. Spacek, G. Spizzo, M. Spolaore, A. Stegmeir, M. Stejner, D. Stieglitz, J. Stober, U. Stroth, E. Strumberger, G. Suarez Lopez, W. Suttrop, T. Szepesi, B. Tál, T. Tala, W. Tang, G. Tardini, M. Tardocchi, D. Terranova, M. Teschke, E. Thorén, W. Tierens, D. Told, W. Treutterer, G. Trevisan, M. Tripský, P. Ulbl, G. Urbanczyk, M. Usoltseva, M. Valisa, M. Valovic, S. van Mulders, M. van Zeeland, F. Vannini, B. Vanovac, P. Varela, S. Varoutis, T. Verdier, G. Verdoolaege, N. Vianello, J. Vicente, T. Vierle, E. Viezzer, I. Voitsekhovitch, U. von Toussaint, D. Wagner, X. Wang, M. Weiland, D. Wendler, A.E. White, M. Willensdorfer, B. Wiringer, M. Wischmeier, R. Wolf, E. Wolfrum, Q. Yang, C. Yoo, Q. Yu, R. Zagórski, I. Zammuto, T. Zehetbauer, W. Zhang, W. Zholobenko, A. Zibrov, M. Zilker, C.F.B. Zimmermann, A. Zito, S. Zoletnik, the EUROfusion Tokamak Exploitation Team, and the ASDEX Upgrade Team

Subjects
tokamak, MHD stability, transport modelling, radiative exhaust, disruption physics, ELM free scenarios, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Experiments on ASDEX Upgrade (AUG) in 2021 and 2022 have addressed a number of critical issues for ITER and EU DEMO. A major objective of the AUG programme is to shed light on the underlying physics of confinement, stability, and plasma exhaust in order to allow reliable extrapolation of results obtained on present day machines to these reactor-grade devices. Concerning pedestal physics, the mitigation of edge localised modes (ELMs) using resonant magnetic perturbations (RMPs) was found to be consistent with a reduction of the linear peeling-ballooning stability threshold due to the helical deformation of the plasma. Conversely, ELM suppression by RMPs is ascribed to an increased pedestal transport that keeps the plasma away from this boundary. Candidates for this increased transport are locally enhanced turbulence and a locked magnetic island in the pedestal. The enhanced D-alpha (EDA) and quasi-continuous exhaust (QCE) regimes have been established as promising ELM-free scenarios. Here, the pressure gradient at the foot of the H-mode pedestal is reduced by a quasi-coherent mode, consistent with violation of the high-n ballooning mode stability limit there. This is suggestive that the EDA and QCE regimes have a common underlying physics origin. In the area of transport physics, full radius models for both L- and H-modes have been developed. These models predict energy confinement in AUG better than the commonly used global scaling laws, representing a large step towards the goal of predictive capability. A new momentum transport analysis framework has been developed that provides access to the intrinsic torque in the plasma core. In the field of exhaust, the X-Point Radiator (XPR), a cold and dense plasma region on closed flux surfaces close to the X-point, was described by an analytical model that provides an understanding of its formation as well as its stability, i.e., the conditions under which it transitions into a deleterious MARFE with the potential to result in a disruptive termination. With the XPR close to the divertor target, a new detached divertor concept, the compact radiative divertor, was developed. Here, the exhaust power is radiated before reaching the target, allowing close proximity of the X-point to the target. No limitations by the shallow field line angle due to the large flux expansion were observed, and sufficient compression of neutral density was demonstrated. With respect to the pumping of non-recycling impurities, the divertor enrichment was found to mainly depend on the ionisation energy of the impurity under consideration. In the area of MHD physics, analysis of the hot plasma core motion in sawtooth crashes showed good agreement with nonlinear 2-fluid simulations. This indicates that the fast reconnection observed in these events is adequately described including the pressure gradient and the electron inertia in the parallel Ohm’s law. Concerning disruption physics, a shattered pellet injection system was installed in collaboration with the ITER International Organisation. Thanks to the ability to vary the shard size distribution independently of the injection velocity, as well as its impurity admixture, it was possible to tailor the current quench rate, which is an important requirement for future large devices such as ITER. Progress was also made modelling the force reduction of VDEs induced by massive gas injection on AUG. The H-mode density limit was characterised in terms of safe operational space with a newly developed active feedback control method that allowed the stability boundary to be probed several times within a single discharge without inducing a disruptive termination. Regarding integrated operation scenarios, the role of density peaking in the confinement of the ITER baseline scenario (high plasma current) was clarified. The usual energy confinement scaling ITER98( p,y ) does not capture this effect, but the more recent H20 scaling does, highlighting again the importance of developing adequate physics based models. Advanced tokamak scenarios, aiming at large non-inductive current fraction due to non-standard profiles of the safety factor in combination with high normalised plasma pressure were studied with a focus on their access conditions. A method to guide the approach of the targeted safety factor profiles was developed, and the conditions for achieving good confinement were clarified. Based on this, two types of advanced scenarios (‘hybrid’ and ‘elevated’ q -profile) were established on AUG and characterised concerning their plasma performance.

Published
2024
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11. Overview of the EUROfusion Tokamak Exploitation programme in support of ITER and DEMO

Author

E. Joffrin, M. Wischmeier, M. Baruzzo, A. Hakola, A. Kappatou, D. Keeling, B. Labit, E. Tsitrone, N. Vianello, the ASDEX Upgrade Team, JET Contributors, the MAST-U Team, the TCV Team, the WEST Team, the EUROfusion Tokamak Exploitation Team:, D. Abate, J. Adamek, M. Agostini, C. Albert, F.C.P. Albert Devasagayam, S. Aleiferis, E. Alessi, J. Alhage, S. Allan, J. Allcock, M. Alonzo, G. Anastasiou, E. Andersson Sunden, C. Angioni, Y. Anquetin, L. Appel, G.M. Apruzzese, M. Ariola, C. Arnas, J.F. Artaud, W. Arter, O. Asztalos, L. Aucone, M.H. Aumeunier, F. Auriemma, J. Ayllon, E. Aymerich, A. Baciero, F. Bagnato, L. Bähner, F. Bairaktaris, P. Balázs, L. Balbinot, I. Balboa, M. Balden, A. Balestri, M. Baquero Ruiz, T. Barberis, C. Barcellona, O. Bardsley, S. Benkadda, T. Bensadon, E. Bernard, M. Bernert, H. Betar, R. Bianchetti Morales, J. Bielecki, R. Bilato, P. Bilkova, W. Bin, G. Birkenmeier, R. Bisson, P. Blanchard, A. Bleasdale, V. Bobkov, A. Boboc, A. Bock, K. Bogar, P. Bohm, T. Bolzonella, F. Bombarda, N. Bonanomi, L. Boncagni, D. Bonfiglio, R. Bonifetto, M. Bonotto, D. Borodin, I. Borodkina, T.O.S.J. Bosman, C. Bourdelle, C. Bowman, S. Brezinsek, D. Brida, F. Brochard, R. Brunet, D. Brunetti, V. Bruno, R. Buchholz, J. Buermans, H. Bufferand, P. Buratti, A. Burckhart, J. Cai, R. Calado, J. Caloud, S. Cancelli, F. Cani, B. Cannas, M. Cappelli, S. Carcangiu, A. Cardinali, S. Carli, D. Carnevale, M. Carole, M. Carpita, D. Carralero, F. Caruggi, I.S. Carvalho, I. Casiraghi, A. Casolari, F.J. Casson, C. Castaldo, A. Cathey, F. Causa, J. Cavalier, M. Cavedon, J. Cazabonne, M. Cecconello, L. Ceelen, A. Celora, J. Cerovsky, C.D. Challis, R. Chandra, A. Chankin, B. Chapman, H. Chen, M. Chernyshova, A.G. Chiariello, P. Chmielewski, A. Chomiczewska, C. Cianfarani, G. Ciraolo, J. Citrin, F. Clairet, S. Coda, R. Coelho, J.W. Coenen, I.H. Coffey, C. Colandrea, L. Colas, S. Conroy, C. Contre, N.J. Conway, L. Cordaro, Y. Corre, D. Costa, S. Costea, D. Coster, X. Courtois, C. Cowley, T. Craciunescu, G. Croci, A.M. Croitoru, K. Crombe, D.J. Cruz Zabala, G. Cseh, T. Czarski, A. Da Ros, A. Dal Molin, M. Dalla Rosa, Y. Damizia, O. D’Arcangelo, P. David, M. De Angeli, E. De la Cal, E. De La Luna, G. De Tommasi, J. Decker, R. Dejarnac, D. Del Sarto, G. Derks, C. Desgranges, P. Devynck, S. Di Genova, L.E. di Grazia, A. Di Siena, M. Dicorato, M. Diez, M. Dimitrova, T. Dittmar, L. Dittrich, J.J. Domínguez Palacios Durán, P. Donnel, D. Douai, S. Dowson, S. Doyle, M. Dreval, P. Drews, L. Dubus, R. Dumont, D. Dunai, M. Dunne, A. Durif, F. Durodie, G. Durr Legoupil Nicoud, B. Duval, R. Dux, T. Eich, A. Ekedahl, S. Elmore, G. Ericsson, J. Eriksson, B. Eriksson, F. Eriksson, S. Ertmer, A. Escarguel, B. Esposito, T. Estrada, E. Fable, M. Faitsch, N. Fakhrayi Mofrad, A. Fanni, T. Farley, M. Farník, N. Fedorczak, F. Felici, X. Feng, J. Ferreira, D. Ferreira, N. Ferron, O. Fevrier, O. Ficker, A.R. Field, A. Figueiredo, N. Fil, D. Fiorucci, M. Firdaouss, R. Fischer, M. Fitzgerald, M. Flebbe, M. Fontana, J. Fontdecaba Climent, A. Frank, E. Fransson, L. Frassinetti, D. Frigione, S. Futatani, R. Futtersack, S. Gabriellini, D. Gadariya, D. Galassi, K. Galazka, J. Galdon, S. Galeani, D. Gallart, A. Gallo, C. Galperti, M. Gambrioli, S. Garavaglia, J. Garcia, M. Garcia Munoz, J. Gardarein, L. Garzotti, J. Gaspar, R. Gatto, P. Gaudio, M. Gelfusa, J. Gerardin, S.N. Gerasimov, R. Gerru Miguelanez, G. Gervasini, Z. Ghani, F.M. Ghezzi, G. Ghillardi, L. Giannone, S. Gibson, L. Gil, A. Gillgren, E. Giovannozzi, C. Giroud, G. Giruzzi, T. Gleiter, M. Gobbin, V. Goloborodko, A. González Ganzábal, T. Goodman, V. Gopakumar, G. Gorini, T. Görler, S. Gorno, G. Granucci, D. Greenhouse, G. Grenfell, M. Griener, W. Gromelski, M. Groth, O. Grover, M. Gruca, A. Gude, C. Guillemaut, R. Guirlet, J. Gunn, T. Gyergyek, L. Hagg, J. Hall, C.J. Ham, M. Hamed, T. Happel, G. Harrer, J. Harrison, D. Harting, N.C. Hawkes, P. Heinrich, S. Henderson, P. Hennequin, R. Henriques, S. Heuraux, J. Hidalgo Salaverri, J. Hillairet, J.C. Hillesheim, A. Hjalmarsson, A. Ho, J. Hobirk, E. Hodille, M. Hölzl, M. Hoppe, J. Horacek, N. Horsten, L. Horvath, M. Houry, K. Hromasova, J. Huang, Z. Huang, A. Huber, E. Huett, P. Huynh, A. Iantchenko, M. Imrisek, P. Innocente, C. Ionita Schrittwieser, H. Isliker, P. Ivanova, I. Ivanova Stanik, M. Jablczynska, S. Jachmich, A.S. Jacobsen, P. Jacquet, A. Jansen van Vuuren, A. Jardin, H. Järleblad, A. Järvinen, F. Jaulmes, T. Jensen, I. Jepu, S. Jessica, T. Johnson, A. Juven, J. Kalis, J. Karhunen, R. Karimov, A.N. Karpushov, S. Kasilov, Y. Kazakov, P.V. Kazantzidis, W. Kernbichler, HT. Kim, D.B. King, V.G. Kiptily, A. Kirjasuo, K.K. Kirov, A. Kirschner, A. Kit, T. Kiviniemi, F. Kjær, E. Klinkby, A. Knieps, U. Knoche, M. Kochan, F. Köchl, G. Kocsis, J.T.W. Koenders, L. Kogan, Y. Kolesnichenko, Y. Kominis, M. Komm, M. Kong, B. Kool, S.B. Korsholm, D. Kos, M. Koubiti, J. Kovacic, Y. Kovtun, E. Kowalska Strzeciwilk, K. Koziol, M. Kozulia, A. Krämer Flecken, A. Kreter, K. Krieger, U. Kruezi, O. Krutkin, O. Kudlacek, U. Kumar, H. Kumpulainen, M.H. Kushoro, R. Kwiatkowski, M. La Matina, M. Lacquaniti, L. Laguardia, P. Lainer, P. Lang, M. Larsen, E. Laszynska, K.D. Lawson, A. Lazaros, E. Lazzaro, M.Y.K. Lee, S. Leerink, M. Lehnen, M. Lennholm, E. Lerche, Y. Liang, A. Lier, J. Likonen, O. Linder, B. Lipschultz, A. Listopad, X. Litaudon, E. Litherland Smith, D. Liuzza, T. Loarer, P.J. Lomas, J. Lombardo, N. Lonigro, R. Lorenzini, C. Lowry, T. Luda di Cortemiglia, A. Ludvig Osipov, T. Lunt, V. Lutsenko, E. Macusova, R. Mäenpää, P. Maget, C.F. Maggi, J. Mailloux, S. Makarov, K. Malinowski, P. Manas, A. Mancini, D. Mancini, P. Mantica, M. Mantsinen, J. Manyer, M. Maraschek, G. Marceca, G. Marcer, C. Marchetto, S. Marchioni, A. Mariani, M. Marin, M. Markl, T. Markovic, D. Marocco, S. Marsden, L. Martellucci, P. Martin, C. Martin, F. Martinelli, L. Martinelli, J.R. Martin Solis, R. Martone, M. Maslov, R. Masocco, M. Mattei, G.F. Matthews, D. Matveev, E. Matveeva, M.L. Mayoral, D. Mazon, S. Mazzi, C. Mazzotta, G. McArdle, R. McDermott, K. McKay, A.G. Meigs, C. Meineri, A. Mele, V. Menkovski, S. Menmuir, A. Merle, H. Meyer, K. Mikszuta Michalik, D. Milanesio, F. Militello, A. Milocco, I.G. Miron, J. Mitchell, R. Mitteau, V. Mitterauer, J. Mlynar, V. Moiseenko, P. Molna, F. Mombelli, C. Monti, A. Montisci, J. Morales, P. Moreau, J.M. Moret, A. Moro, D. Moulton, P. Mulholland, M. Muraglia, A. Murari, A. Muraro, P. Muscente, D. Mykytchuk, F. Nabais, Y. Nakeva, F. Napoli, E. Nardon, M.F. Nave, R.D. Nem, A. Nielsen, S.K. Nielsen, M. Nocente, R. Nouailletas, S. Nowak, H. Nyström, R. Ochoukov, N. Offeddu, S. Olasz, C. Olde, F. Oliva, D. Oliveira, H.J.C. Oliver, P. Ollus, J. Ongena, F.P. Orsitto, N. Osborne, R. Otin, P. Oyola Dominguez, D.I. Palade, S. Palomba, O. Pan, N. Panadero, E. Panontin, A. Papadopoulos, P. Papagiannis, G. Papp, V.V. Parail, C. Pardanaud, J. Parisi, A. Parrott, K. Paschalidis, M. Passoni, F. Pastore, A. Patel, B. Patel, A. Pau, G. Pautasso, R. Pavlichenko, E. Pawelec, B. Pegourie, G. Pelka, E. Peluso, A. Perek, E. Perelli Cippo, C. Perez Von Thun, P. Petersson, G. Petravich, Y. Peysson, V. Piergotti, L. Pigatto, C. Piron, L. Piron, A. Pironti, F. Pisano, U. Plank, B. Ploeckl, V. Plyusnin, A. Podolnik, Y. Poels, G. Pokol, J. Poley, G. Por, M. Poradzinski, F. Porcelli, L. Porte, C. Possieri, A. Poulsen, I. Predebon, G. Pucella, M. Pueschel, P. Puglia, O. Putignano, T. Pütterich, V. Quadri, A. Quercia, M. Rabinski, L. Radovanovic, R. Ragona, H. Raj, M. Rasinski, J. Rasmussen, G. Ratta, S. Ratynskaia, R. Rayaprolu, M. Rebai, A. Redl, D. Rees, D. Refy, M. Reich, H. Reimerdes, B.C.G. Reman, O. Renders, C. Reux, D. Ricci, M. Richou, S. Rienacker, D. Rigamonti, F. Rigollet, F.G. Rimini, D. Ripamonti, N. Rispoli, N. Rivals, J.F. Rivero Rodriguez, C. Roach, G. Rocchi, S. Rode, P. Rodrigues, J. Romazanov, C.F. Romero Madrid, J. Rosato, R. Rossi, G. Rubino, J. Rueda Rueda, J. Ruiz Ruiz, P. Ryan, D. Ryan, S. Saarelma, R. Sabot, M. Salewski, A. Salmi, L. Sanchis, A. Sand, J. Santos, K. Särkimäki, M. Sassano, O. Sauter, G. Schettini, S. Schmuck, P. Schneider, N. Schoonheere, R. Schramm, R. Schrittwieser, C. Schuster, N. Schwarz, F. Sciortino, M. Scotto D’Abusco, S. Scully, A. Selce, L. Senni, M. Senstius, G. Sergienko, S.E. Sharapov, R. Sharma, A. Shaw, U. Sheikh, G. Sias, B. Sieglin, S.A. Silburn, C. Silva, A. Silva, D. Silvagni, B. Simmendefeldt Schmidt, L. Simons, J. Simpson, L. Singh, S. Sipilä, Y. Siusko, S. Smith, A. Snicker, E.R. Solano, V. Solokha, M. Sos, C. Sozzi, F. Spineanu, G. Spizzo, M. Spolaore, L. Spolladore, C. Srinivasan, A. Stagni, Z. Stancar, G. Stankunas, J. Stober, P. Strand, C.I. Stuart, F. Subba, G.Y. Sun, H.J. Sun, W. Suttrop, J. Svoboda, T. Szepesi, G. Szepesi, B. Tal, T. Tala, P. Tamain, G. Tardini, M. Tardocchi, D. Taylor, G. Telesca, A. Tenaglia, A. Terra, D. Terranova, D. Testa, C. Theiler, E. Tholerus, B. Thomas, E. Thoren, A. Thornton, A. Thrysoe, Q. TICHIT, W. Tierens, A. Titarenko, P. Tolias, E. Tomasina, M. Tomes, E. Tonello, A. Tookey, M. Toscano Jiménez, C. Tsironis, C. Tsui, A. Tykhyy, M. Ugoletti, M. Usoltseva, D.F. Valcarcel, A. Valentini, M. Valisa, M. Vallar, M. Valovic, SI. Valvis, M. van Berkel, D. Van Eester, S. Van Mulders, M. van Rossem, R. Vann, B. Vanovac, J. Varela Rodriguez, J. Varje, S. Vartanian, M. Vecsei, L. Velarde Gallardo, M. Veranda, T. Verdier, G. Verdoolaege, K. Verhaegh, L. Vermare, G. Verona Rinati, J. Vicente, E. Viezzer, L. Vignitchouk, F. Villone, B. Vincent, P. Vincenzi, M.O. Vlad, G. Vogel, I. Voitsekhovitch, I. Voldiner, P. Vondracek, N.M.T. VU, T. Vuoriheimo, C. Wade, E. Wang, T. Wauters, M. Weiland, H. Weisen, N. Wendler, D. Weston, A. Widdowson, S. Wiesen, M. Wiesenberger, T. Wijkamp, M. Willensdorfer, T. Wilson, A. Wojenski, C. Wuethrich, I. Wyss, L. Xiang, S. Xu, D. Yadykin, Y. Yakovenko, H. Yang, V. Yanovskiy, R. Yi, B. Zaar, G. Zadvitskiy, L. Zakharov, P. Zanca, D. Zarzoso, Y. Zayachuk, J. Zebrowski, M. Zerbini, P. Zestanakis, C. F. B. Zimmermann, M. Zlobinski, A. Zohar, V.K. Zotta, X. Zou, M. Zuin, M. Zurita, and I. Zychor

Subjects
JET, ASDEX Upgrade, MAST-U, TCV, WEST, Tokamak Exploitation Task Force, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Within the 9th European Framework programme, since 2021 EUROfusion is operating five tokamaks under the auspices of a single Task Force called ‘Tokamak Exploitation’. The goal is to benefit from the complementary capabilities of each machine in a coordinated way and help in developing a scientific output scalable to future largre machines. The programme of this Task Force ensures that ASDEX Upgrade, MAST-U, TCV, WEST and JET (since 2022) work together to achieve the objectives of Missions 1 and 2 of the EUROfusion Roadmap: i) demonstrate plasma scenarios that increase the success margin of ITER and satisfy the requirements of DEMO and, ii) demonstrate an integrated approach that can handle the large power leaving ITER and DEMO plasmas. The Tokamak Exploitation task force has therefore organized experiments on these two missions with the goal to strengthen the physics and operational basis for the ITER baseline scenario and for exploiting the recent plasma exhaust enhancements in all four devices (PEX: Plasma EXhaust) for exploring the solution for handling heat and particle exhaust in ITER and develop the conceptual solutions for DEMO. The ITER Baseline scenario has been developed in a similar way in ASDEX Upgrade, TCV and JET. Key risks for ITER such as disruptions and run-aways have been also investigated in TCV, ASDEX Upgrade and JET. Experiments have explored successfully different divertor configurations (standard, super-X, snowflakes) in MAST-U and TCV and studied tungsten melting in WEST and ASDEX Upgrade. The input from the smaller devices to JET has also been proven successful to set-up novel control schemes on disruption avoidance and detachment.

Published
2024
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13. A new 3MW ECRH system at 105 GHz for WEST

Author

Delpech, Lena, Alberti, Stefano, Avramidis, Konstantinos, Ayreault, Aline, Batal, Tristan, Bernard, Jean-Michel, Bouquey, Francis, Chelis, Ioannis, Clairet, Frederic, Corbel, Elodie, Doceul, Louis, Durand, Frederic, Dumont, Remi, Fonghetti, Theo, Gantenbein, Gerd, Garibaldi, Pascal, Giruzzi, Gerardo, Goodman, Tim, Hogge, Jean-Philippe, Illy, Stefan, Jelonnek, John, Jin, Jianbo, Laqua, Heinrich, Legrand, Francois, Lievin, Christophe, Magaud, Philippe, Maget, Patrick, Manas, Pierre, Marsen, Stefan, Regal-Mezin, Xavier, Mollard, Patrick, Mouyon, David, Nicolas, Laurent, Ouerfelli, Adam, Pagonakis, Ioannis, Robinet, Benjamin, Ruess, Tobias, Santraine, Benjamin, Thumm, Manfred, and Ioannidis, Zisis

Published
2023
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14. Transport barrier onset and edge turbulence shortfall in fusion plasmas

Author

Guilhem Dif-Pradalier, Philippe Ghendrih, Yanick Sarazin, Elisabetta Caschera, Frédéric Clairet, Yann Camenen, Peter Donnel, Xavier Garbet, Virginie Grandgirard, Yann Munschy, Laure Vermare, and Fabien Widmer

Subjects
Astrophysics, QB460-466, Physics, QC1-999
Abstract

A central problem in magnetized fusion plasmas is to understand whether the plasma edge sustains a turbulent state and transitions to improved confinement. The authors simulate the detailed organization of turbulence from the primitive flux-driven kinetic equations including plasma-solid interaction and identify basic mechanisms which allow to cure the oft-reported shortfall of turbulence power in the plasma edge and to describe spontaneous onset of a transport barrier.

Published
2022
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15. Collective fabrication of guided longitudinal SAW resonator without Bragg grating mirror

Author

Thomas Baron, Stefania Oliveri, Thomas Richard, Valerie Soumann, Djaffar Belharet, Laurent Robert, Marina Raschetti, Roland Salut, Emilie Courjon, Thierry Laroche, Florent Bernard, Alexandre Clairet, and Sylvain Ballandras

Subjects
5G mobile communication, acoustic devices, etching, microfabrication, nanofabrication, piezoelectric devices, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

Abstract This Research article document discussed about a new structure composed of a sub‐micron‐thick layer of a single‐crystal piezoelectric material on a substrate. Longitudinal waves are used for experimental demonstration with 4’’ collective processes. Electrical experimental–computation validate the concept with Q × f products near 1012.

Published
2023
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19. High Q-Factor Low Band SAW Filter Based on High Performance POI Substrate

Author

Seah, Xavier, primary, Ballandras, Sylvain, additional, Courjon, Emilie, additional, Bernard, Florent, additional, Clairet, Alexandre, additional, Makdissy, Tony, additional, Laroche, Thierry, additional, Aspar, Gabrielle, additional, Michoulier, Eric, additional, Ndiaye, Saly, additional, Raveski, Alexandre, additional, Chappaz, Cedrick, additional, Hilt, Thierry, additional, Alami-Idrissi, Aziz, additional, Achatz, Philipp, additional, Rolland, Laure, additional, Didier, Christophe, additional, Allibert, Frederic, additional, Drouin, Alexis, additional, and Huyet, Isabelle, additional

Published
2024
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23. Nucleosome patterns in four plant pathogenic fungi with contrasted genome structures

Author

Clairet, Colin, Lapalu, Nicolas, Simon, Adeline, Soyer, Jessica L., Viaud, Muriel, Zehraoui, Enric, Dalmais, Berengère, Fudal, Isabelle, and Ponts, Nadia

Subjects
Archaeology, CC1-960, Science
Abstract

Fungal pathogens represent a serious threat towards agriculture, health, and environment. Control of fungal diseases on crops necessitates a global understanding of fungal pathogenicity determinants and their expression during infection. Genomes of phytopathogenic fungi are often compartmentalized: the core genome contains housekeeping genes whereas the fast-evolving genome mainly contains transposable elements and species-specific genes. In this study, we analysed nucleosome landscapes of four phytopathogenic fungi with contrasted genome organizations to describe and compare nucleosome repartition patterns in relation with genome structure and gene expression level. We combined MNase-seq and RNA-seq analyses to concomitantly map nucleosome-rich and transcriptionally active regions during fungal growth in axenic culture; we developed the MNase-seq Tool Suite (MSTS) to analyse and visualise data obtained from MNase-seq experiments in combination with other genomic data and notably RNA-seq expression data. We observed different characteristics of nucleosome profiles between species, as well as between genomic regions within the same species. We further linked nucleosome repartition and gene expression. Our findings support that nucleosome positioning and occupancies are subjected to evolution, in relation with underlying genome sequence modifications. Understanding genomic organization and its role in expression regulation is the next gear to understand complex cellular mechanisms and their evolution.

Published
2023
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33. A Phase II Study Evaluating the Interest to Combine UCPVax, a Telomerase CD4 TH1-Inducer Cancer Vaccine, and Atezolizumab for the Treatment of HPV Positive Cancers: VolATIL Study

Author

Magali Rebucci-Peixoto, Angélique Vienot, Olivier Adotevi, Marion Jacquin, Francois Ghiringhelli, Christelle de la Fouchardière, Benoit You, Tristan Maurina, Elsa Kalbacher, Fernando Bazan, Guillaume Meynard, Anne-Laure Clairet, Christine Fagnoni-Legat, Laurie Spehner, Adeline Bouard, Dewi Vernerey, Aurélia Meurisse, Stefano Kim, Christophe Borg, and Laura Mansi

Subjects
HPV-related cancer, anal carcinoma, head and neck, cervix, atezolizumab, immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundThere is a strong rational of using anti–programmed cell death protein-1 and its ligand (anti–PD-1/L1) antibodies in human papillomavirus (HPV)–induced cancers. However, anti–PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti–PD-1/L1 is therefore of interest. Combining anti–PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non–small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV+ cancers.MethodsPatients with HPV+ cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously.DiscussionAnti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific TH1 CD4 T cells sustain the quality and homing of an antigen-specific CD8+ T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based TH1 inducing vaccine (UCPVax) and an anti–PD-L1 (atezolizumab) immunotherapy in HPV+ cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials.Clinical Trial Registrationhttps://www.clinicaltrials.gov/, identifier NCT03946358.

Published
2022
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36. Estudos em Dermatologia

Author

MARRONE, VITTORIA GIULIA DA SILVA, primary, OLIVEIRA, ANNA VITORIA GONÇALVES SOARES DE, additional, Luz, Denise de Souza, additional, FREITAS, ELUANY NOGUEIRA DE, additional, ARAÚJO, IOHANNA MELO DE, additional, NOGUEIRA, MARIA ISABEL TELES, additional, Silva, Karolayne Carvalho, additional, Lima, Aparecida das Dores Silva de, additional, Godone, Roberta Luciana do Nascimento, additional, Craveiro, Caroline Linhares Ferreira, additional, Souza, Giovana Maria Leite de, additional, França, Isis Marinho, additional, Silva, Suellen Gleyce França da, additional, Moura, Victória Freitas de Souza, additional, Galvão, Fábio Freitas de Sousa Passos, additional, Pinheiro, Evandra Marielly Leite Nogueira, additional, Nascimento, Josenil Bezerra, additional, Sobrinho, Weberton Dorásio, additional, Cristino, Filipe Martins, additional, Carvalho, Lanna do Carmo, additional, Mereb, William Miranda, additional, Langer, Layany Hewelyn Hamann, additional, VILAÇA, JHEMILY LOPES LIMA, additional, Zaibak, Carla Azevedo, additional, Fonseca, Fabiana Rodrigues, additional, Borges, Polliane, additional, Nascimento, Luana, additional, Caldas, Isabella Ferreira, additional, Mendes, Monielly Tawiny Monteiro Moura, additional, Peixoto, Paula Mendes, additional, Domingues, Ana Clara Oliveira, additional, MARQUES, CAMYLLA MACHADO, additional, Alves, Allana Victória Pereira, additional, Carvalho, Ana Nicole Fernandes de, additional, Brayner, Analine Domingos Rezende, additional, Figueiredo, Camila Oliveira de, additional, Magalhães, Danilo Amorim, additional, Cruz, Elizabeth Fechine, additional, Rocha, Fernanda Sampaio Feitosa, additional, Siqueira, Gabriel Teles de Souza, additional, Macedo, Júlia Tenório Lossio de, additional, Lima, Laura de Souza, additional, Nunes, Luana Lócio, additional, Teixeira, Maria Alice Oliveira Magalhães, additional, Matias, Maria Inês de Araújo Sousa, additional, Montenegro, Marina Ataide, additional, Santos, Taynara Souza, additional, Tavares, Bianca Rodrigues, additional, Ribeiro, Samuel Melo, additional, Ribeiro, Bruno Melo, additional, RIBEIRO, MARIANE MELO, additional, Mendes, Marcos Antônio Ribeiro, additional, Frattari, Ana Laura Vaz de Mello, additional, Ferreira, Beatriz Duarte, additional, Silva, Ana Beatriz Gangana de Castro, additional, Esteves, Ana Clara Amaral, additional, Moraes, Ana Laura Cruzeiro de, additional, Braga, Ana Lídia Barbosa, additional, Ramalho, Fernando Lonardelli Saraiva, additional, Costa, Laura Vidal Gomes Teixeira da, additional, Fortunati, Lorenza Alves de Carvalho, additional, Castro, Marcelo Fernandes Quintão Dias de, additional, Silva, Luan Nilton da, additional, Melo, Maria Carolina Alves Monteiro de, additional, Mahon, Juliana Florêncio, additional, Oliveira, Milena Aguiar Alencar de, additional, Morais, Rafael X B de, additional, Albuquerque, Ana Carolina Magalhães Vasconcelos de, additional, Pacas, Clarissa Machado, additional, Tavares, João F C J, additional, Xavier, Jônatas da Costa, additional, Machado, Maria Carolina Teixeira, additional, Laranjeira, Maria Luiza Florêncio, additional, Souza, Gessienne Clívia Alves e, additional, Barretto, Lucília Willa Andrade, additional, Albuquerque, Natalia Parahyba, additional, Medeiros, Angela Cristina Rapela, additional, Vilefort, Laís Assunção, additional, Lopes, Amanda Brandão, additional, Carvalho, Ana Cláudia de, additional, Oliveira, Beatriz Abreu Silva de, additional, Heringer, Victor Cabral Costa Ribeiro, additional, Silva, Isabella Juliana Nascimento da, additional, Lima, Roberto Cláudio de Oliveira, additional, Hollunder, Renata Gouvea, additional, Morais, Lucas Costa de, additional, Castro, Gabriela Basilio de, additional, Laredo, Isabella Greco Queiroz, additional, Pereira, Maria Thereza Diniz, additional, Rocha, Karinne Nancy Sena, additional, Batista, Eduardo Expedito Valeriano, additional, Magalhaes, Geovanna de Oliveira, additional, Resende, Bernardo Tavares, additional, Sousa, Leticia Resende, additional, Cabral, Maria Eduarda Galhardo, additional, Rodrigues, Yan Sze, additional, Sebe, Ana Luiza Oliveira, additional, Oliveira, Letícia Barbosa, additional, Marinho, Iara Helena de Meireles, additional, Porto, Eduarda Arduim Maia, additional, Gomes, Ana Luísa Gondim Diniz, additional, Acioli, Rebeca Vital Matias, additional, Mestre, Amanda Montenegro, additional, Oliveira, Paloma Fernandes D, additional, Sarmento, Manuella Fagundes Damaceno, additional, Barbosa, Adriano de Amorim, additional, Santos, Eric Malveira dos, additional, Bezerra, Igo Marcel Medeiros, additional, Vieira, Matheus Alves, additional, Souza, Iago Felipe Camilo, additional, Zanata, Indira Coan, additional, Freire, Samya Sayonara Rocha Santos, additional, Pereira, Carolina Pinheiro, additional, Almeida, Sulyanne Saraiva de, additional, Marra, Verônica Senna, additional, Dadalto, Grasiele, additional, OLIVEIRA, AMANDA VASCONCELOS DE, additional, COSTA, HELENA FONTENELLE DE CARVALHO, additional, Madureira, Mariana Landim, additional, Magalhães, Thaíza Pereira, additional, Freitas, Stephannie, additional, DIAS, FERNANDA DAS GRAÇAS, additional, Viana, Taynne da Silva, additional, Santiago, Matheus de Souza, additional, Dayrell, Natália Ribeiro, additional, COSTA, JULIANA SILVEIRA MARTINS DA, additional, Muniz, Laura Rafaella Ferrari Munoz, additional, Tonaco, Vanessa De Carvalho, additional, ALVARENGA, ALICE MARTINS, additional, Mazzoni, Sofia Moreira, additional, FRAZÃO, VICTOR CABREIRA, additional, Bauer, Nathália Vescia, additional, Guntzel, Camila, additional, Pacheco, Geovana, additional, Pereira, Marina Caroline Hoffmann, additional, Souza, Guilherme Briczinski de, additional, Sarmento, Letícia Azevedo, additional, Monte, Kahena Monteiro Almeida, additional, Mellara, Gabriel Guimarães, additional, Gomes, Melissa Vieira, additional, Santana, José Vinícius Lima, additional, Souza, José Luis Francisco Gomes, additional, Melo, Vitória Farias de, additional, Araujo, Ângelo Marcel Santana Duarte, additional, Dantas, Lucas Gomes, additional, Barros, Pablo da Cruz, additional, Pimenta, Camila de Melo, additional, Sotta, João Marcos Constantino, additional, Cazotto, Eliena Perini, additional, Loureiro, Eduardo Sales, additional, Alves, Arthur Palauro, additional, Arão, Ana Elisa Choucair Hosken, additional, COSTA, BRUNA DIULY SANTOS, additional, Barbosa, Christina Santos, additional, BATISTA, TAINÁ RESENDE, additional, Chaves, Ana Elisa Carvalho Santos, additional, Paiva, Larissa Afonso, additional, Barbosa, Filipe da Silva, additional, Avelar, Luiza Magalhães, additional, SOUSA, KARLA SILVIA DE, additional, Melo, Marina Viana, additional, Lacerda, Ana Luiza Queiroz da Silva, additional, Castro, Sophia Mourão Gontijo de, additional, Gatti, Julie Caldeira, additional, Trotta, Gabriella Moté, additional, Almeida, Anna Gabriela Figueiredo de, additional, Freitas, Anna Rebecka Rodrigues Silva de, additional, Queiroz, Roberta Gracielle Amorim de, additional, Silva, Carlos Roberto Gomes da, additional, Maior, Lavínia Paola Vega Souto, additional, Queiroz, Maria Beatriz Pires Nóbrega de, additional, Soares, Gabriel Lucena de Carvalho, additional, Wanderley, Bianca Gonçalves, additional, Loureiro, Gabriela Bezerra, additional, Falcão, Mariana Vieira, additional, Loureiro, Lautônio Neto Bezerra, additional, Silva, Pedro Igor Gontijo, additional, Barbosa, Luiza Morais, additional, Moura, Rafaela Lopes Freitas, additional, Cunha, Raquel Camilo da, additional, Castro, Renata Costa Café de, additional, Vilela, Sofia Fagundes, additional, Kalil, Luiza Laborne Sousa Pinto, additional, Miranda, Carolina Queiroga de, additional, Jerônimo, Dayanne Nunes, additional, Silva, Fernando Ítalo Lessa Neto, additional, Moreira, Lamark Melo Silva, additional, Vaz, Louise Mendonça, additional, Cunha, Maria Clara de Sousa Lima, additional, Soares, Maria Luíza Cerqueira Wanderley de Lima, additional, Pedrosa, Mariana Oliveira, additional, Tenório, Natália dos Anjos, additional, Andrade, Pedro Nogueira de, additional, Lima, Zuíla Caroline Olegário, additional, Vilefort, Lais Assunção, additional, Sousa, Gustavo Túlio Silveira, additional, carneiro, Isabela de andrade, additional, Silva, Aline Dias da, additional, Borges, Nayara Souza, additional, Leste, Rebecca Guerra Murta, additional, Pereira, Sarah Dias, additional, Matoso, Fernanda Bicalho, additional, Nascimento, Karollinne Paiva do, additional, Martins, Caio Henrique Andrade, additional, Coser, Natália Bobylow, additional, Castro, Raphael Silva, additional, Missio, Aloysio Gabriel, additional, Mohr, Pedro Henrique, additional, Batista, Lucas Teixeira, additional, Cótica, Lara figueira Aguiar, additional, Barbosa, Vitor Cunha de Almeida, additional, Boechat, Alexandre Strapasson, additional, Teixeira, Rafaela de Avellar Guedes, additional, Mendonça, Livia Figueiredo de, additional, Sá, Caio Augusto Lucas de, additional, Moreira, Marcus Vinícius Santos, additional, Campos, Amanda Ferreira de Souza, additional, Hollunder, Guilherme Gouveia, additional, Vieira, Laís Maria Peixoto, additional, Yamada, Vinicius Orsine, additional, Miareli, Felipe, additional, Obeid, Victória Feio, additional, BANDEIRA, LORENA DE SOUZA, additional, rocha, Sophia de medeiros borém tibo, additional, Cascaes, Letícia Romão, additional, ARAÚJO, PATRÍCIA MORAIS DE, additional, Pacheco, Luiz Phelipe Gontijo, additional, ARAUJO, ANA CAROLINA LOPES, additional, PARAGUAY, LUIZ FILLIPE GODINHO, additional, Ribeiro, Michelle Alves, additional, Evangelista, Junia Murta Pedras Lopes, additional, Salles, Ana Bárbara Dumont, additional, Paiva, Maralina Peixoto, additional, Mendes, Rafael Lucas Cecílio, additional, Sampaio, Maria Carolina Ferraz Cajado, additional, Fernandes, Brunna Karolyna Rocha, additional, Guedes, Gabriella Thalya, additional, Guimarães, Marinna Barbosa, additional, Ferreira, Joyce Fernanda Rocha, additional, Batista, Lorena Rodrigues, additional, Abrantes, Karolyne Mariano, additional, lima, Maria Eduarda Araújo Tomaz de, additional, Rodrigues, Gabriela Neto, additional, Gomes, Karen Teixeira, additional, Ferraz, Biatriz de Quadros, additional, Antonini, Francielle, additional, Mea, Vivian Pena Della, additional, FOGAÇA, LIVIA CAPUANO, additional, Nicolino, Clarice Romero, additional, Rabelo, Carolina Saiol, additional, Leon, Cristiano do A de, additional, Fogaça, Lívia Capuano, additional, Leon, Cristiano Amaral de, additional, Pires, Ana Cecília Gadelha, additional, FAUSTINO, Brenda Barbosa, additional, Ferreira, Daniel Antônio Rodrigues de Assis, additional, Oliveira, George Estrela de, additional, Hinojosa, Joanna Lidia Fernandes, additional, Araújo, Maria Eduarda de Oliveira, additional, Sarmento, Marina Crispim, additional, Cunha, Sílvia Viana Bezerra da, additional, Silva, Thalita de Sá Lira Braga e, additional, Clairet, Laurent Martial, additional, Diniz, Edisângela Mirella de Sousa Passos, additional, Ferreira, Maria Eduarda Sales, additional, Dias, Jamila Cury-Rad Santos Bezerra, additional, Rocha, Antônio Vitor da, additional, Araújo, Maria Karolinne de Sousa, additional, Brigido, Bryan Victor Serafim, additional, Queiroz, Anna Luíza Rocha, additional, Sasaki, Beatriz Yumi Fukue, additional, Figueiredo, Ingrid Caroline, additional, Piovezan, Isabela Botelho, additional, Diniz, Leandra Prates, additional, Evangelista, Pedro Mazzini Leone, additional, Barros, Talisson Taglialegna de, additional, Daoud, Victor Michel, additional, Rodrigues, Luiz Oswaldo Carneiro, additional, Vieira, Cintya Martins, additional, Lopes, Bruna Rocha, additional, Carlos, Elisandra Barbara Pontes, additional, Marques, Nathália Couri Vieira, additional, MAIA, LAIS RODRIGUES, additional, PAULA, ANA CLARA ABREU LIMA DE, additional, Reis, Tatiana Vasconcelos, additional, Carvalho, Bruna da Silva Pereira, additional, Oliveira, Iran Roger Alkimin de, additional, Valle, Annair Freitas do, additional, Andrade, Maria Cristina Vieira de, additional, Gamonal, Shirley Braga Lima, additional, Bonetti, Simone Caruso, additional, Gamonal, Aloísio Carlos Couri, additional, Carvalho, Maria Teresa Feital de, additional, Silva, Serginara Cristina Flexa Pereira da, additional, Santos, Bruno Souza dos, additional, Costa, Francisca Jullyanna Silva da, additional, Vilaça, Jhemily Lopes Lima, additional, Marques, Camylla Machado, additional, Yonemoto, Ana Cláudia Ferreira, additional, Choptian, Mario Ciro, additional, Silva, Isabella Juliana Nascimento, additional, Lima, Camila Araujo Novais, additional, Lima, Camila Araújo Novais, additional, Oliveira, Paloma Fernandes de, additional, Oliveira, Halley Ferraro, additional, Lima, Milena Sonely Mendonça Bezerra, additional, Gomes, Waléria Ronina Feitosa, additional, Pessoa, Maria Clara Ribeiro, additional, Galvão, Evandra Marielly Leite Nogueira Freitas, additional, and SEVERO DINIZ, EDISANGELA MIRELLA, additional

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2021
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37. ANÁLISE COMPARATIVA DOS RESULTADOS EM LONGO PRAZO DA ANASTOMOSE ESOFAGOGÁSTRICA CERVICAL PELA SUTURA MANUAL E MECÂNICA EM PACIENTES SUBMETIDOS À MUCOSECTOMIA ESOFÁGICA POR MEGAESÔFAGO AVANÇADO

Author

Aquino, José Luis Braga de, primary, Leandro-Merhi, Vania Aparecida, additional, Mendonça, José Alexandre, additional, Mendes, Elisa Donalisio Teixeira, additional, Clairet, Conceição de Maria Aquino Vieira, additional, and Reis, Leonardo Oliveira, additional

Published
2021
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38. Separatrix parameters and core performances across the WEST L-mode database

Author

C. Bourdelle, J. Morales, J.F. Artaud, O. Grover, T. Radenac, J. Bucalossi, Y. Camenen, G. Ciraolo, F. Clairet, R. Dumont, N. Fedorczak, J. Gaspar, C. Gil, M. Goniche, C. Guillemaut, J. Gunn, P. Maget, P. Manas, V. Ostuni, B. Pégourié, Y. Peysson, P. Tamain, L. Vermare, D. Vézinet, and the WEST Team

Subjects
plasma, tokamak, database, confinement, separatrix, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

WEST database analysis shows a correlation of the recycled neutral source around the separatrix with core performances. This observation questions the causality chain between particle source and turbulent transport up to the core in L-mode, high recycling plasmas, an unavoidable phase of all scenarios. The best core performances correlate with the lowest values of the density at the separatrix, ${n_{{\text{sep}}}}$ , similarly to ASDEX Upgrade (AUG) tokamak and Joint European Torus (JET) tokamak in H-mode (Verdoolaege et al 2021 Nucl. Fusion 61 076006). Reflectometry in the midplane provides ${n_{{\text{sep}}}}$ , while the temperature at the separatrix, ${T_{{\text{sep}}}}$ is inferred by the ‘two-point model’ using Langmuir probe data on divertor targets. Lower separatrix resistivity does not correlate with better core performances, unlike H-mode observations (Eich et al 2020 Nucl. Fusion 60 056016). As expected in the presence of an efficient neutral source due to recycling fluxes, ${n_{{\text{sep}}}}$ correlates with the D recycled particle flux at the divertor measured by visible spectroscopy. Coherently, at a given controlled central line integrated density $\bar n$ , lower ${n_{{\text{sep}}}}$ correlates with a larger density gradient around the separatrix as well as a larger global density peaking, $\bar n/\langle n\rangle $ , measured by interferometry. The latter correlates as well with lower collisionality in the core, similarly to JET and AUG H-modes (Angioni et al 2007 Nucl. Fusion 47 1326). The correlations reported allow phrasing the subsequent causality question: what is the interplay chain between low neutral recycling at the divertor plates, low density at the separatrix, high density peaking at the separatrix, high global density peaking, higher central temperature and better core energy confinement quality? Understanding the causality chain is essential to prepare ITER operation and design DEMO scenarios where the ratio of the divertor leg to the ionization length will be larger and where the pumped flux with respect to the plasma volume will be lower than presently operating tokamaks.

Published
2023
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47. Manual da Cirurgia Moderna

Author

Moura, Victória F S, primary, Rêgo, Júlia Leandro, additional, Moreira, Ellen de O S, additional, Silva, Idell Bruno G, additional, Correia, Maria Clara S, additional, Pessoa, Maria Clara R, additional, Januário, Ana Luiza A P, additional, Clairet, Laurent M, additional, Bomfim, Luana M de C, additional, Silva, Manuelli A da, additional, Dantas, Herbet Matheus Neves, additional, Pisacane, Luisa, additional, Galvão, Fábio Freitas de Sousa Passos, additional, Moura, Edvaldo Pereira de, additional, Campos, João Victor Reis, additional, Cavalcanti, Marilia de Macedo, additional, Guimarães, Larissa Gusmão, additional, Silva, Adriano Bezerra da, additional, Nogueira, Tatiane de Oliveira, additional, and Coelho, Vinícius Leal, additional

Published
2021
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