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1. Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics

Author

Ludivine Brandt, Paolo Angelino, Raquel Martinez, Sara Cristinelli, and Angela Ciuffi

Subjects
HIV-1, HIV susceptibility, immune activation, sex differences, age differences, Cytology, QH573-671
Abstract

Cellular composition and the responsiveness of the immune system evolve upon aging and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit a decreased viral replication ex vivo compared to men’s. We, thus, hypothesized that these findings could be recapitulated in vitro and infected primary CD4+ T cells with HIV-based vectors pseudotyped with VSV-G or HIV envelopes. We used cells isolated from twenty donors to interrogate the effect of sex and age on permissiveness over a six-day activation kinetics. Our data identified an increased permissiveness to HIV between 24 and 72 h post-stimulation. Sex- and age-based analyses at these time points showed an increased susceptibility to HIV of the cells isolated from males and from donors over 50 years of age, respectively. A parallel assessment of surface markers’ expression revealed higher frequencies of activation marker CD69 and of immune checkpoint inhibitors (PD-1 and CTLA-4) in the cells from highly permissive donors. Furthermore, positive correlations were identified between the expression kinetics of CD69, PD-1 and CTLA-4 and HIV expression kinetics. The cell population heterogeneity was assessed using a single-cell RNA-Seq analysis and no cell subtype enrichment was identified according to sex. Finally, transcriptomic analyses further highlighted the role of activation in those differences with enriched activation and cell cycle gene sets in male and older female cells. Altogether, this study brought further evidence about the individual features affecting HIV replication at the cellular level and should be considered in latency reactivation studies for an HIV cure.

Published
2023
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2. Mutant CTNNB1 and histological heterogeneity define metabolic subtypes of hepatoblastoma

Author

Stefania Crippa, Pierre‐Benoit Ancey, Jessica Vazquez, Paolo Angelino, Anne‐Laure Rougemont, Catherine Guettier, Vincent Zoete, Mauro Delorenzi, Olivier Michielin, and Etienne Meylan

Subjects
glucose transporter, glycolysis, mutant β‐catenin, pediatric liver cancer, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Hepatoblastoma is the most common malignant pediatric liver cancer. Histological evaluation of tumor biopsies is used to distinguish among the different subtypes of hepatoblastoma, with fetal and embryonal representing the two main epithelial components. With frequent CTNNB1 mutations, hepatoblastoma is a Wnt/β‐catenin‐driven malignancy. Considering that Wnt activation has been associated with tumor metabolic reprogramming, we characterized the metabolic profile of cells from hepatoblastoma and compared it to cells from hepatocellular carcinoma. First, we demonstrated that glucose transporter GLUT3 is a direct TCF4/β‐catenin target gene. RNA sequencing enabled to identify molecular and metabolic features specific to hepatoblastoma and revealed that several glycolytic enzymes are overexpressed in embryonal‐like compared to fetal‐like tumor cells. This led us to implement successfully three biomarkers to distinguish embryonal from fetal components by immunohistochemistry from a large panel of human hepatoblastoma samples. Functional analyses demonstrated that embryonal‐like hepatoblastoma cells are highly glycolytic and sensitive to hexokinase‐1 silencing. Altogether, our findings reveal a new, metabolic classification of human hepatoblastoma, with potential future implications for patients’ diagnosis and treatment.

Published
2017
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3. The Transcription Factor Tcf1 Contributes to Normal NK Cell Development and Function by Limiting the Expression of Granzymes

Author

Beena Jeevan-Raj, Jasmine Gehrig, Mélanie Charmoy, Vijaykumar Chennupati, Camille Grandclément, Paolo Angelino, Mauro Delorenzi, and Werner Held

Subjects
NK cells, T cell factor 1, Tcf1, granzyme B, self-destruction, Biology (General), QH301-705.5
Abstract

The transcription factor Tcf1 is essential for the development of natural killer (NK) cells. However, its precise role has not been clarified. Our combined analysis of Tcf1-deficient and transgenic mice indicated that Tcf1 guides NK cells through three stages of development. Tcf1 expression directed bone marrow progenitors toward the NK cell lineage and ensured the survival of NK-committed cells, and its downregulation was needed for terminal maturation. Impaired survival of NK-committed cells was due to excessive expression of granzyme B (GzmB) and other granzyme family members, which induced NK cell self-destruction during maturation and following activation with cytokines or target cells. Mechanistically, Tcf1 binding reduced the activity of a Gzmb-associated regulatory element, and this accounted for the reduced Gzmb expression in Tcf1-expressing NK cells. These data identify an unexpected requirement to limit the expression of cytotoxic effector molecules for the normal expansion and function of NK cells.

Published
2017
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4. C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3 -Mutant Leukemia

Author

Marie Sabatier, Rudy Birsen, Laura Lauture, Sarah Mouche, Paolo Angelino, Jonas Dehairs, Lea Goupille, Ismael Boussaid, Mael Heiblig, Emeline Boet, Ambrine Sahal, Estelle Saland, Juliana C. Santos, Marc Armengol, Miranda Fernandez-Serrano, Thomas Farge, Guillaume Cognet, Federico Simonetta, Corentin Pignon, Antoine Graffeuil, Celine Mazzotti, Herve Avet-Loiseau, Oceane Delos, Justine Bertrand-Michel, Amelie Chedru, Vilma Dembitz, Paolo Gallipoli, Natasha S. Anstee, Sun Loo, Andrew H. Wei, Martin Carroll, Armelle Goubard, Remy Castellano, Yves Collette, Francois Vergez, Veronique Mansat-De Mas, Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Christian Recher, Nathalie Bourges-Abella, Fanny Granat, Olivier Kosmider, Pierre Sujobert, Benoit Colsch, Carine Joffre, Lucille Stuani, Johannes V. Swinnen, Herve Guillou, Gael Roue, Nawad Hakim, Anne S. Dejean, Petros Tsantoulis, Clement Larrue, Didier Bouscary, Jerome Tamburini, Jean-Emmanuel Sarry, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Faculté de médecine [Genève], Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Leuven Cancer Institute [Leuven, Belgium] (LKI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Josep Carreras Leukaemia Research Institute (IJC), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Queen Mary University of London (QMUL), The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Peter MacCallum Cancer Center, Perelman School of Medicine, University of Pennsylvania, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Leuven Cancer Institute (LKI), Leuven, Belgium, ToxAlim (ToxAlim), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Genève = University of Geneva (UNIGE), and 2018/Ligue Nationale de Lutte contre le Cancer C57799/A27964/Cancer Research UK (CRUK) Institut National Du Cancer (INCa)

Subjects
Oncology, [SDV]Life Sciences [q-bio]
Abstract

Although transcription factor CCAAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role in cell and metabolic homeostasis is largely unknown in cancer. Here, multiomics analyses uncovered a coordinated activation of C/EBPα and Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism in vivo and in patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, C/EBPα regulated the fatty acid synthase (FASN)–stearoyl-CoA desaturase (SCD) axis to promote fatty acid (FA) biosynthesis and desaturation. We further demonstrated that FLT3 or C/EBPα inactivation decreased monounsaturated FA incorporation to membrane phospholipids through SCD downregulation. Consequently, SCD inhibition enhanced susceptibility to lipid redox stress that was exploited by combining FLT3 and glutathione peroxidase 4 inhibition to trigger lipid oxidative stress, enhancing ferroptotic death of FLT3-mutant AML cells. Altogether, our study reveals a C/EBPα function in lipid homeostasis and adaptation to redox stress, and a previously unreported vulnerability of FLT3-mutant AML to ferroptosis with promising therapeutic application. Significance: FLT3 mutations are found in 30% of AML cases and are actionable by tyrosine kinase inhibitors. Here, we discovered that C/EBPα regulates FA biosynthesis and protection from lipid redox stress downstream mutant-FLT3 signaling, which confers a vulnerability to ferroptosis upon FLT3 inhibition with therapeutic potential in AML. This article is highlighted in the In This Issue feature, p. 1501

Published
2023

5. Orb5: A global electromagnetic gyrokinetic code using the PIC approach in toroidal geometry

Author

Noé Ohana, Paolo Angelino, Ben F. McMillan, P. Donnel, Sébastien Jolliet, Claudio Gheller, Zhixin Lu, Aaron Lewis Scheinberg, Julien Dominski, Roman Hatzky, Laurent Villard, Alessandro Biancalani, Andreas Jocksch, Alberto Bottino, J. P. Martin Collar, I. Novikau, T. Hayward-Schneider, T. Vernay, Alexey Mishchenko, Natalia Tronko, Stephan Brunner, Eric Sonnendrücker, and Emmanuel Lanti

Subjects
Tokamak, TK, General Physics and Astronomy, FOS: Physical sciences, Control variates, System of linear equations, 01 natural sciences, 010305 fluids & plasmas, law.invention, Momentum, Filter (large eddy simulation), law, 0103 physical sciences, Code (cryptography), Gyrokinetic, 010306 general physics, Adiabatic process, Orb (optics), Physics, PIC, Physics - Plasma Physics, Computational physics, Turbulence, Plasma Physics (physics.plasm-ph), Hardware and Architecture
Abstract

This paper presents the current state of the global gyrokinetic code ORB5 as an update of the previous reference [Jolliet et al., Comp. Phys. Commun. 177 409 (2007)]. The ORB5 code solves the electromagnetic Vlasov-Maxwell system of equations using a PIC scheme and also includes collisions and strong flows. The code assumes multiple gyrokinetic ion species at all wavelengths for the polarization density and drift-kinetic electrons. Variants of the physical model can be selected for electrons such as assuming an adiabatic response or a ``hybrid'' model in which passing electrons are assumed adiabatic and trapped electrons are drift-kinetic. A Fourier filter as well as various control variates and noise reduction techniques enable simulations with good signal-to-noise ratios at a limited numerical cost. They are completed with different momentum and zonal flow-conserving heat sources allowing for temperature-gradient and flux-driven simulations. The code, which runs on both CPUs and GPUs, is well benchmarked against other similar codes and analytical predictions, and shows good scalability up to thousands of nodes.

Published
2020

6. The Consensus Molecular Subtypes of Colorectal Cancer

Author

David Barras, Sarah Gerster, Sabine Tejpar, Krisztian Homicsko, Xingwu Wang, Rodrigo Dienstmann, Hena R. Ramay, Lodewyk F. A. Wessels, Mauro Delorenzi, Felipe De Sousa E Melo, Gift Nyamundanda, Louis Vermeulen, Iris Simon, Douglas Hanahan, Charlotte Soneson, Edoardo Missiaglia, Bradley M. Broom, Justin Guinney, Joe W. Gray, Aurélien de Reyniès, Anguraj Sadanandam, Brian M. Bot, Paul Roepman, Jeffrey S. Morris, René Bernards, Evelyn Fessler, Andreas Schlicker, Ted Laderas, Scott Kopetz, Dipen M. Maru, Pierre Laurent-Puig, Beatriz Perez-Villamil, Josep Tabernero, Stephen H. Friend, Valérie Boige, Ganiraju C. Manyam, Ramon Salazar, Laetitia Marisa, Jan Paul Medema, Paolo Angelino, Center of Experimental and Molecular Medicine, CCA -Cancer Center Amsterdam, Radiotherapy, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Universitat de Barcelona

Subjects
Classificació de tumors, Oncologia, Angiogenesis, Colorectal cancer, Genes, myc, Disease, Bioinformatics, Transforming Growth Factor beta, Medicine, Non-U.S. Gov't, Wnt Signaling Pathway, biology, Neovascularization, Pathologic, Research Support, Non-U.S. Gov't, Wnt signaling pathway, General Medicine, Prognosis, Phenotype, 3. Good health, Gene Expression Regulation, Neoplastic, Oncology, Microsatellite Instability, Colorectal Neoplasms, Proto-Oncogene Proteins B-raf, Consensus, DNA Copy Number Variations, Research Support, General Biochemistry, Genetics and Molecular Biology, Article, N.I.H, Proto-Oncogene Proteins p21(ras), Research Support, N.I.H., Extramural, Càncer colorectal, Proto-Oncogene Proteins, Journal Article, Humans, business.industry, Information Dissemination, Tumors classification, Gene Expression Profiling, Carcinoma, Extramural, Microsatellite instability, Transforming growth factor beta, DNA Methylation, medicine.disease, Gene expression profiling, Mutation, biology.protein, Cancer research, ras Proteins, CpG Islands, business
Abstract

Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use -- https://www.nature.com/authors/policies/license.html#terms Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC - with clear biological interpretability - and the basis for future clinical stratification and subtype-based targeted interventions.

Published
2015

7. Rapid Fourier space solution of linear partial integro-differential equations in toroidal magnetic confinement geometries

Author

Sébastien Jolliet, Laurent Villard, Trach-Minh Tran, Alberto Bottino, Ben F. McMillan, and Paolo Angelino

Subjects
Laplace's equation, Screened Poisson equation, Partial differential equation, Elliptic partial differential equation, Method of characteristics, Hardware and Architecture, Differential equation, Mathematical analysis, First-order partial differential equation, General Physics and Astronomy, Spectral method, Mathematics
Abstract

Fluctuating quantities in magnetic confinement geometries often inherit a strong anisotropy along the field lines. One technique for describing these structures is the use of a certain set of Fourier components on the tori of nested flux surfaces. We describe an implementation of this approach for solving partial differential equations, like Poisson's equation, where a different set of Fourier components may be chosen on each surface according to the changing safety factor profile. Allowing the resolved components to change to follow the anisotropy significantly reduces the total number of degrees of freedom in the description. This can permit large gains in computational performance. We describe, in particular, how this approach can be applied to rapidly solve the gyrokinetic Poisson equation in a particle code, ORB5 (Jolliet et al., (2007) [5]), with a regular (non-field-aligned) mesh. (C) 2009 Published by Elsevier B.V.

Published
2010

8. Investigation of steady-state tokamak issues by long pulse experiments on Tore Supra

Author

Nicolas Crouseilles, R. Guirlet, J. Hourtoule, W. Xiao, J. L. Gardarein, Frédéric Schwander, E. Delchambre, A. Martinez, F. Bouquey, D. Boilson, M. Richou, L. Allegretti, V. Lamaison, T. Loarer, B. Lacroix, A. Vatry, W. Zwingmann, D. Ciazynski, J. Decker, P. Hertout, A. Bécoulet, R. Abgrall, M. Chatelier, B. Guillerminet, J. Lasalle, Yannick Marandet, M. Lipa, S. Nicollet, C. Reux, F. Benoit, E. Delmas, P. Reynaud, J. Y. Journeaux, F. Jullien, H. Bottollier-Curtet, Y. Buranvand, M. Schneider, D. Moreau, Karl Vulliez, M. Tena, P. Pastor, C. Le Niliot, S. Balme, G. Falchetto, V. Martin, L. Svensson, S. H. Hong, C. Laviron, M. Houry, J. M. Theis, S. Madeleine, T. Hutter, T. Salmon, L. Manenc, C. Bouchand, M. Davi, S. Rosanvallon, N. Dolgetta, Pascale Roubin, Eric Nardon, L.-G. Eriksson, B. Pégourié, D. Douai, O. Chaibi, Patrick Mollard, Didier Mazon, J. P. Gunn, Marie Farge, M. Prou, M. Thonnat, L. Begrambekov, J. Garcia, Philippe Ghendrih, L. Colas, Jacques Blum, J. Clary, P. Spuig, C. Gil, M. Kocan, Ph. Lotte, Paolo Angelino, B. Saoutic, M. Ottaviani, P. Devynck, X. Courtois, L. Doceul, Gilles Berger-By, Patrick Tamain, Marc Missirlian, K. Schneider, Yanick Sarazin, Lena Delpech, J.M. Ané, Pascale Hennequin, A. Durocher, Patrick Maget, P. Huynh, David Henry, P. Decool, Marc Goniche, F. Clairet, Julien Hillairet, A. Geraud, J. Signoret, Stéphane Heuraux, P. Bayetti, T. Gerbaud, X. L. Zou, Y. Peysson, H. Parrat, L. Million, Jérôme Bucalossi, S. Hacquin, Clarisse Bourdelle, F. Samaille, Bernard Bertrand, E. Sonnendruker, G. Chevet, A. Simonin, Ph. Cara, J. L. Maréchal, J. Johner, M. S. Benkadda, J. C. Hatchressian, R. Magne, J. Schlosser, A. Grosman, F. Brémond, R. Masset, Estelle Gauthier, S. Song, G. Giruzzi, M. Nannini, Caroline Hernandez, H.P.L. de Esch, P. Garibaldi, R. J. Dumont, Stanislas Pamela, M. Geynet, C. Nguyen, L. Zani, A. Casati, Cyrille Honoré, G. Gros, Fabrice Rigollet, A. Argouarch, Yann Corre, A. Marcor, H. Dougnac, E. Tsitrone, C. Grisolia, D. Pacella, Guillaume Latu, Céline Martin, T. Aniel, G. Darmet, R. Daviot, J.P. Martins, J. L. Farjon, P. Magaud, A. Ekedahl, Francesca Turco, D. Elbeze, P. Beyer, S. Carpentier, Roger Reichle, F. Faisse, X. Litaudon, R. Guigon, F.G. Rimini, F. Linez, L. Gargiulo, C. Fenzi-Bonizec, G. Marbach, Alexandre Torre, P. Monier-Garbet, N. Ravenel, Laure Vermare, J.-M. Travere, Xavier Garbet, R. Mitteau, H. Roche, C. Desgranges, V. Moncada, F. Villecroze, Jean-François Luciani, G. Ciraolo, F. Kazarian, J. Roth, C. Brosset, F. Saint-Laurent, H. Nehme, T. Parisot, Nicolas Fedorczak, F. Escourbiac, D. Guilhem, J. L. Duchateau, P. Moreau, O. Meyer, D. Yu, A. L. Pecquet, V. Petrzilka, E. Trier, Roland Sabot, G. T. A. Huysmans, G. T. Hoang, E. Joffrin, L. Meunier, P. Chantant, C. Portafaix, D. Voyer, J. C. Vallet, S. Salasca, J. L. Segui, A. Santagiustina, J.F. Artaud, G. Dunand, M. Lennholm, Frederic Imbeaux, V. Grandgirard, A. Escarguel, F. Leroux, Y. Lausenaz, P. Chappuis, V. Basiuk, F. Lott, Hinrich Lütjens, Sylvain Brémond, D. Villegas, Marina Becoulet, Institut de Recherche sur la Fusion par confinement Magnétique (IRFM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Physique Théorique [Palaiseau] (CPHT), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Association EURATOM-CEA (CEA/DSM/DRFC), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Nuclear and High Energy Physics, fusion, Tokamak, MHD, Nuclear engineering, Cyclotron, Ultra-high vacuum, Electron, Tore Supra, 01 natural sciences, 7. Clean energy, 010305 fluids & plasmas, law.invention, Nuclear physics, law, [PHYS.PHYS.PHYS-PLASM-PH]Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph], 0103 physical sciences, 52.35, 010306 general physics, ComputingMilieux_MISCELLANEOUS, Physics, Magnetic confinement fusion, plasma heating, Plasma, Condensed Matter Physics, Magnetohydrodynamics
Abstract

The main results of the Tore Supra experimental programme in the years 2007–2008 are reported. They document significant progress achieved in the domain of steady-state tokamak research, as well as in more general issues relevant for ITER and for fusion physics research. Three areas are covered: ITER relevant technology developments and tests in a real machine environment, tokamak operational issues for high power and long pulses, and fusion plasma physics. Results presented in this paper include test and validation of a new, load-resilient concept of ion cycotron resonance heating antenna and of an inspection robot operated under ultra-high vacuum and high temperature conditions; an extensive experimental campaign (5 h of plasma) aiming at deuterium inventory and carbon migration studies; real-time control of sawteeth by electron cyclotron current drive in the presence of fast ion tails; ECRH-assisted plasma start-up studies; dimensionless scalings of transport and turbulence; transport experiments using active perturbation methods; resistive and fast-particle driven MHD studies. The potential role of Tore Supra in the worldwide fusion programme before the start of ITER operation is also discussed.

Published
2009

9. Quasisteady and steady states in global gyrokinetic particle-in-cell simulations

Author

T. Vernay, Alberto Bottino, Sébastien Jolliet, Laurent Villard, Paolo Angelino, and Ben F. McMillan

Subjects
Physics, Tokamak, law, Turbulence, Plasma turbulence, Evolution equation, Particle-in-cell, Plasma, Statistical physics, Dissipation, Condensed Matter Physics, Entropy (arrow of time), law.invention
Abstract

Collisionless delta-f gyrokinetic particle-in-cell simulations suffer from the entropy paradox, in which the entropy grows linearly in time while low-order moments are saturated. As a consequence, these simulations do not reach a steady state and are unsuited to make quantitative predictions. A solution to this issue is the introduction of artificial dissipation. The notion of steady state in gyrokinetic simulations is studied by deriving an evolution equation for the fluctuation entropy and applying it to the global collisionless particle-in-cell code ORB5 [S. Jolliet et al., Comput. Phys. Commun. 177, 409 (2007)]. It is shown that a recently implemented noise-control algorithm [B. F. McMillan et al., Phys. Plasmas 15, 052308 (2008)] based on a W-stat provides the necessary dissipation to reach a steady state. The two interesting situations of decaying and driven turbulence are considered. In addition, it is shown that a separate heating algorithm, not based on a W-stat, does not lead to a statistical steady state.

Published
2009

10. The role of plasma elongation on the linear damping of zonal flows

Author

Ph. Ghendrih, T. M. Tran, Ben F. McMillan, Guilhem Dif-Pradalier, Virginie Grandgirard, Alberto Bottino, Yanick Sarazin, Laurent Villard, S. Jolliet, Paolo Angelino, and Xavier Garbet

Subjects
Physics, Geodesic, Turbulence, Wave turbulence, Magnetic confinement fusion, Mechanics, Condensed Matter Physics, Physics::Fluid Dynamics, Classical mechanics, Flow (mathematics), Physics::Plasma Physics, Energy cascade, Microturbulence, Magnetohydrodynamics
Abstract

Drift wave turbulence is known to self-organize to form axisymmetric macroscopic flows. The basic mechanism for macroscopic flow generation is called inverse energy cascade. Essentially, it is an energy transfer from the short wavelengths to the long wavelengths in the turbulent spectrum due to nonlinear interactions. A class of macroscopic flows, the poloidally symmetric zonal flows, is widely recognized as a key constituent in nearly all cases and regimes of microturbulence, also because of the realization that zonal flows are a critical agent of self-regulation for turbulent transport. In tokamaks and other toroidal magnetic confinement systems, axisymmetric flows exist in two branches, a zero frequency branch and a finite frequency branch, named Geodesic Acoustic Modes (GAMs). The finite frequency is due to the geodesic curvature of the magnetic field. There is a growing body of evidence that suggests strong GAM activity in most devices. Theoretical investigation of the GAMs is still an open field of ...

Published
2008

11. Long global gyrokinetic simulations: Source terms and particle noise control

Author

Paolo Angelino, Laurent Villard, Ben F. McMillan, Trach-Minh Tran, Sébastien Jolliet, and Alberto Bottino

Subjects
Physics, Turbulence, Operator (physics), turbulence, Dissipation, Condensed Matter Physics, gyrokinetic, Physics::Fluid Dynamics, Noise, Gyrokinetics, Convergence (routing), Noise control, Particle, Statistical physics, plasma
Abstract

In global gyrokinetic simulations it takes a long time for the turbulence to reach a quasisteady state, and quantitative predictions about the quasisteady state turbulence have been difficult to obtain computationally. In particular, global particle-in-cell gyrokinetic simulations have been inefficient for long simulations due to the accumulation of noise. It is demonstrated that a simple Krook operator can effectively control noise; it also introduces an unphysical dissipation, which damps the zonal flows and can significantly affect simulation results even when the relaxation time is very long. However, it is possible to project out the effects of the Krook operator on the zonal flows. This permits noise accumulation to be controlled while preserving the physics of interest; simulations are then run to determine the level of quasisteady state transport and the variation across the ensemble of turbulent dynamics. Convergence is demonstrated both in the number of computational particles and the unphysical relaxation time. © 2008 American Institute of Physics.

Published
2008

12. Beyond scale separation in gyrokinetic turbulence

Author

Ph. Ghendrih, Paolo Angelino, Pierre Bertrand, Stephan Brunner, T. M. Tran, X. Lapillonne, E. Gravier, Guilhem Dif-Pradalier, Guillaume Latu, Virginie Grandgirard, G. Darmet, Nicolas Crouseilles, Yanick Sarazin, Laurent Villard, Maura Brunetti, E. Violard, M. Boulet, Jean-Michel Dischler, Nicolas Besse, Xavier Garbet, Pierre Morel, Eric Sonnendrücker, Association EURATOM-CEA (CEA/DSM/DRFC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département de Recherche sur la Fusion Contrôlée (DRFC), Institut de Recherche sur la Fusion par confinement Magnétique (IRFM), University of California [San Diego] (UC San Diego), University of California (UC), Laboratoire de physique des milieux ionisés et applications (LPMIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Élie Cartan de Nancy (IECN), Institut National de Recherche en Informatique et en Automatique (Inria)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Scientific computation and visualization (CALVI), Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des Sciences de l'Image, de l'Informatique et de la Télédétection (LSIIT), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences de l'Image, de l'Informatique et de la Télédétection (LSIIT), Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Physique des Plasmas (CRPP), Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratoire de Détection et de Géophysique (CEA) (LDG), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CALVI, University of California, and Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Lorraine (INPL)-Université Nancy 2-Université Henri Poincaré - Nancy 1 (UHP)-Institut National de Recherche en Informatique et en Automatique (Inria)

Subjects
Physics, Nuclear and High Energy Physics, Toroid, Scale (ratio), K-epsilon turbulence model, Turbulence, Flux, Initialization, K-omega turbulence model, Condensed Matter Physics, Kinetic energy, 01 natural sciences, 010305 fluids & plasmas, Physics::Fluid Dynamics, Physics::Plasma Physics, 0103 physical sciences, Statistical physics, 010306 general physics, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract

International audience; This paper presents the results obtained with a set of gyrokinetic codes based on a semi-Lagrangian scheme. Several physics issues are addressed, namely, the comparison between fluid and kinetic descriptions, the intermittent behaviour of flux driven turbulence and the role of large scale flows in toroidal ITG turbulence. The question of the initialization of full-F simulations is also discussed.

Published
2007

13. Effects of plasma current on nonlinear interactions of ITG turbulence, zonal flows and geodesic acustic modes

Author

Roman Hatzky, Alberto Bottino, Paolo Angelino, Sébastien Jolliet, Laurent Villard, Trach-Minh Tran, and Olivier Sauter

Subjects
Physics, Tokamak, Turbulence, Magnetic confinement fusion, Mechanics, Zonal flow (plasma), Plasma, Condensed Matter Physics, law.invention, Temperature gradient, Classical mechanics, Amplitude, Nuclear Energy and Engineering, Physics::Plasma Physics, law, Physics::Space Physics, Magnetohydrodynamics
Abstract

The mutual interactions of ion temperature gradient (ITG) driven modes, zonal flows and geodesic acoustic modes (GAM) in tokamak plasmas are investigated using a global nonlinear gyrokinetic formulation with totally unconstrained evolution of temperature gradient and profile. A series of numerical simulations with the same initial temperature and density profile specifications is performed using a sequence of ideal MHD equilibria differing only in the value of the total plasma current, in particular with identical magnetic shear profiles and shapes of magnetic surfaces. On top of a bursty or quasi-steady state behaviour the zonal flows oscillate at the GAM frequency. The amplitude of these oscillations increases with the value of the safety factor q, resulting in a less effective suppression of ITG turbulence by zonal flows at a lower plasma current. The turbulence-driven volume-averaged radial heat transport is found to scale inversely with the total plasma current.

Published
2006

14. On the definition of a kinetic equilibrium in global gyrokinetic simulations

Author

Olivier Sauter, Paolo Angelino, Alberto Bottino, Trach-Minh Tran, Sébastien Jolliet, Laurent Villard, and Roman Hatzky

Subjects
Physics, Toroid, Turbulence, Rotational symmetry, Plasma, Mechanics, Condensed Matter Physics, Physics::Fluid Dynamics, Nonlinear system, Distribution function, Physics::Plasma Physics, Gyrokinetics, Physics::Space Physics, Electron temperature, Statistical physics
Abstract

Nonlinear electrostatic global gyrokinetic simulations of collisionless ion temperature gradient (ITG) turbulence and ExB zonal flows in axisymmetric toroidal plasmas are examined for different choices of the initial distribution function. Using a local Maxwellian leads to the generation of axisymmetric ExB flows that can be so strong as to prevent ITG mode growth. A method using a canonical Maxwellian is shown to avoid this spurious generation of ExB flows. In addition, a revised delta f scheme is introduced and compared to the standard delta f method. (c) 2006 American Institute of Physics.

Published
2006

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