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Recent evidence demonstrates that Crocus sativus L. (saffron) counteracts oxidative stress, mitochondrial dysfunction and neuroinflammation, closely linked to initiation and progression of major brain pathologies. Interestingly, saffron constituents such as crocin, crocetin and safranal can exert antioxidant or toxic effects depending on their endogenous concentration. According to the hormesis principles, at low dose they act as antioxidants in a wide range of brain diseases by upregulating Nrf2 signaling pathway and the expression of vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system. Importantly, neuronal dysregulation of Nrf2 pathway can be a prominent cause of selective susceptibility, under neuroinflammatory conditions, due to the high vulnerability of brain cells to oxidative stress. Here we discuss natural inducers from saffron targeting Nrf2/vitagene pathway for development of new therapeutical strategies to suppress oxidative stress and neuroinflammation and consequently cognitive dysfunction. In this review we also focus on the hormetic effect of saffron active constituents, summarizing their neuroprotective and anti-neuroinflammatory properties, as well as pharmacological perspectives in brain disorders.

During the first test divertor campaign of the stellarator experiment Wendelstein 7-X (Pedersen et al 2022 Nucl. Fusion 62 042022), OP1.2b, 13 neutral gas pressure gauges collected data in different locations in the plasma vessel, enabling a detailed analysis of the neutral gas pressures, the compression ratios and the particle exhaust rates via the turbomolecular pumps in the different magnetic field configurations. In Wendelstein 7-X, the edge magnetic islands are intersected by the divertor target plates and used to create a plasma-wall interface. As the number and position of the magnetic islands varies in different magnetic field configurations, the position of the strike line on the target plates and thus the neutral gas pressure in the subdivertor differs between the configurations. Neutral gas pressures on the order of few 10−4 mbar were measured in the subdivertor region. The highest neutral gas pressure of 1.75 × 10 − 3 mbar was obtained in the so-called high iota configuration featuring four edge magnetic islands per cross section. The neutral particle flux through the pumping gaps into the subdivertor volume was provided by EMC3-EIRENE simulations and allowed to analyze the relation between the particle flux entering the subdivertor and the pressure distribution in the subdivertor. Finite element simulations in ANSYS provide a detailed picture of the pressure distribution in the subdivertor volume and agree with the neutral gas pressure measurements in the subdivertor in the standard configuration featuring an island chain of 5 edge magnetic islands. Surprisingly high neutral gas pressures that were not predicted by the simulation were measured in the subdivertor region away from the main strike line for discharges in the most used magnetic configuration, the standard configuration. While the pressure ratio between the two sections of the subdivertor volume, the low and high iota section is 0.06 in high iota configuration, a ratio of 2–5 was obtained in the other configurations, indicating significant particle loads and exhaust rates on the high iota section of the subdivertor in magnetic configurations with the main strike line on the low iota divertor targets.

We present recent highlights from the most recent operation phases of Wendelstein 7-X, the most advanced stellarator in the world. Stable detachment with good particle exhaust, low impurity content, and energy confinement times exceeding 100 ms, have been maintained for tens of seconds. Pellet fueling allows for plasma phases with reduced ion-temperature-gradient turbulence, and during such phases, the overall confinement is so good (energy confinement times often exceeding 200 ms) that the attained density and temperature profiles would not have been possible in less optimized devices, since they would have had neoclassical transport losses exceeding the heating applied in W7-X. This provides proof that the reduction of neoclassical transport through magnetic field optimization is successful. W7-X plasmas generally show good impurity screening and high plasma purity, but there is evidence of longer impurity confinement times during turbulence-suppressed phases. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 and 2019-2020 under Grant Agreement No. 633053. Peer Reviewed Article signat per 497 autors/es: Thomas Sunn Pedersen1,2,∗ , I. Abramovic3, P. Agostinetti4, M. Agredano Torres1, S. Äkäslompolo1, J. Alcuson Belloso1, P. Aleynikov1, K. Aleynikova1, M. Alhashimi1, A. Ali1, N. Allen5, A. Alonso6, G. Anda7, T. Andreeva1, C. Angioni8, A. Arkhipov8, A. Arnold1, W. Asad8, E. Ascasibar6, M.-H. Aumeunier9, K. Avramidis10, E. Aymerich11, S.-G. Baek3, J. Bähner1, A. Baillod12, M. Balden1, M. Balden8, J. Baldzuhn1, S. Ballinger3, M. Banduch1, S. Bannmann1, A. Banon Navarro8, A. Bañon Navarro ´ 1, T. Barbui13, C. Beidler1, C. Belafdil9, A. Bencze7, A. Benndorf1, M. Beurskens1, C. Biedermann1, O. Biletskyi14, B. Blackwell15, M. Blatzheim1, T. Bluhm1, D. Böckenhoff1, G. Bongiovi16, M. Borchardt1, D. Borodin17, J. Boscary8, H. Bosch1,18, T. Bosmann19, B. Böswirth8, L. Böttger1, A. Bottino8, S. Bozhenkov1, R. Brakel1, C. Brandt1, T. Bräuer1, H. Braune1, S. Brezinsek17, K. Brunner1, S. Buller1, R. Burhenn1, R. Bussiahn1, B. Buttenschön1, A. Buzás7, V. Bykov1, I. Calvo6, K. Camacho Mata1, I. Caminal20, B. Cannas11, A. Cappa6, A. Carls1, F. Carovani1, M. Carr21, D. Carralero6, B. Carvalho22, J. Casas20, D. Castano-Bardawil17, F. Castejon6, N. Chaudhary1, I. Chelis23, A. Chomiczewska24, J.W. Coenen13,17, M. Cole1, F. Cordella25, Y. Corre9, K. Crombe26, G. Cseh7, B. Csillag7, H. Damm1, C. Day10, M. de Baar27, E. De la Cal6, S. Degenkolbe1, A. Demby13, S. Denk3, C. Dhard1, A. Di Siena8,28, A. Dinklage12, T. Dittmar17, M. Dreval14, M. Drevlak1, P. Drewelow1, P. Drews17, D. Dunai7, E. Edlund3, F. Effenberg29, G. Ehrke1, M. Endler1, D.A. Ennis5, F.J. Escoto6, T. Estrada6, E. Fable8, N. Fahrenkamp1, A. Fanni11, J. Faustin1, J. Fellinger1, Y. Feng1, W. Figacz4, E. Flom13, O. Ford1, T. Fornal24, H. Frerichs13, S. Freundt1, G. Fuchert1, M. Fukuyama30, F. Füllenbach1, G. Gantenbein10, Y. Gao1, K. Garcia13, J.M. García Regaña6, I. García-Cortés6, J. Gaspar31, D.A. Gates29, J. Geiger1, B. Geiger13, L. Giudicotti32, A. González6, A. Goriaev26,33, D. Gradic1, M. Grahl1, J.P. Graves12, J. Green13, E. Grelier9, H. Greuner8, S. Groß1, H. Grote1, M. Groth34, M. Gruca24, O. Grulke1,35, M. Grün1, J. Guerrero Arnaiz1, S. Günter8, V. Haak1, M. Haas1, P. Hacker1, A. Hakola36, A. Hallenbert1, K. Hammond29, X. Han17,37, S.K. Hansen3, J.H. Harris38, H. Hartfuß1, D. Hartmann1, D. Hathiramani1, R. Hatzky8, J. Hawke39, S. Hegedus7, B. Hein8, B. Heinemann8, P. Helander12, S. Henneberg1, U. Hergenhahn8,40, C. Hidalgo6, F. Hindenlang8, M. Hirsch1, U. Höfel1, K.P. Hollfeld17, A. Holtz1, D. Hopf8, D. Höschen17, M. Houry9, J. Howard19, X. Huang41, M. Hubeny17, S. Hudson29, K. Ida9, Y. Igitkhanov10, V. Igochine8, S. Illy10, C. Ionita-Schrittwieser42, M. Isobe39, M. Jabłczynska ´ 24, S. Jablonski24, B. Jagielski1, M. Jakubowski1, A. Jansen van Vuuren1, J. Jelonnek10, F. Jenko8, F. Jenko8, T. Jensen35, H. Jenzsch1, P. Junghanns8, J. Kaczmarczyk24, J. Kallmeyer1, U. Kamionka1, M. Kandler8, S. Kasilov43, Y. Kazakov26, D. Kennedy1, A. Kharwandikar1, M. Khokhlov1, C. Kiefer8, C. Killer1, A. Kirschner17, R. Kleiber1, T. Klinger12, S. Klose1, J. Knauer1, A. Knieps17, F. Köchl44, G. Kocsis7, Ya.I. Kolesnichenko45, A. Könies1, R. König1, J. Kontula34, P. Kornejew1, J. Koschinsky, M.M. Kozulia14, A. Krämer-Flecken17, R. Krampitz1, M. Krause1, N. Krawczyk24, T. Kremeyer1, L. Krier10, D.M. Kriete5, M. Krychowiak1, I. Ksiazek46, M. Kubkowska24, M. Kuczynski1, G. Kühner1, A. Kumar15, T. Kurki-Suonio34, S. Kwak1, M. Landreman47, P.T. Lang8, A. Langenberg1, H.P. Laqua12, H. Laqua1, R. Laube1, S. Lazerson1, M. Lewerentz1, C. Li17, Y. Liang17, Ch. Linsmeier17, J. Lion1, A. Litnovsky17,48, S. Liu37, J. Lobsien1, J. Loizu12, J. Lore38, A. Lorenz1, U. Losada6, F. Louche26, R. Lunsford29, V. Lutsenko45, M. Machielsen12, F. Mackel8, J. Maisano-Brown3, O. Maj8, D. Makowski49, G. Manduchi50, E. Maragkoudakis6, O. Marchuk17, S. Marsen1, E. Martines4, J. Martinez-Fernandez6, M. Marushchenko1, S. Masuzaki41, D. Maurer5, M. Mayer8, K.J. McCarthy6, O. Mccormack4, P. McNeely1, H. Meister8, B. Mendelevitch8, S. Mendes1, A. Merlo1, A. Messian26, A. Mielczarek49, O. Mishchenko1, B. Missal1, R. Mitteau9, V.E. Moiseenko14, A. Mollen1, V. Moncada9, T. Mönnich1, T. Morisaki41, D. Moseev1, G. Motojima41, S. Mulas6, M. Mulsow1, M. Nagel1, D. Naujoks1, V. Naulin35, T. Neelis19, H. Neilson29, R. Neu8, O. Neubauer17, U. Neuner1, D. Nicolai17, S.K. Nielsen35, H. Niemann1, T. Nishiza1, T. Nishizawa1, T. Nishizawa8, C. Nührenberg1, R. Ochoukov8, J. Oelmann17, G. Offermanns17 K. Ogawa41, S. Okamura41, J. Ölmanns17, J. Ongena26, J. Oosterbeek1, M. Otte1, N. Pablant29, N. Panadero Alvarez6, N. Panadero Alvarez6, A. Pandey1, E. Pasch1, R. Pavlichenko14, A. Pavone1, E. Pawelec46, G. Pechstein1, G. Pelka24, V. Perseo1, B. Peterson41, D. Pilopp1, S. Pingel1, F. Pisano11, B. Plöckl8, G. Plunk1, P. Pölöskei1, B. Pompe2, A. Popov51, M. Porkolab3, J. Proll19, M.J. Pueschel19,27, M.-E. Puiatti52, A. Puig Sitjes1, F. Purps1, K. Rahbarnia1, M. Rasinski ´ 17, J. Rasmussen35, A. Reiman29, F. Reimold1, M. Reisner8, D. Reiter17, M. Richou9, R. Riedl8, J. Riemann1, K. Riße1, G. Roberg-Clark1, V. Rohde8, J. Romazanov17, D. Rondeshagen1, P. Rong1, L. Rudischhauser1, T. Rummel1, K. Rummel1, A. Runov1, N. Rust1, L. Ryc24, P. Salembier20, M. Salewski35, E. Sanchez6, S. Satake41, G. Satheeswaran17, J. Schacht1, E. Scharff1, F. Schauer8, J. Schilling1, G. Schlisio1, K. Schmid8, J. Schmitt5, O. Schmitz13, W. Schneider1, M. Schneider1, P. Schneider8, R. Schrittwieser42, T. Schröder1, M. Schröder1, R. Schroeder1, B. Schweer26, D. Schwörer1, E. Scott1, E. Scott8, B. Shanahan1, G. Sias11, P. Sichta29, M. Singer1, P. Sinha29, S. Sipliä34, C. Slaby1, M. Sleczka53, H. Smith1, J. Smoniewski54, E. Sonnendrücker8, M. Spolaore4, A. Spring1, R. Stadler8, D. Stanczak24, T. Stange1, I. Stepanov26, L. Stephey13, J. Stober8, U. Stroth8,55, E. Strumberger8, C. Suzuki41, Y. Suzuki41, J. Svensson1, T. Szabolics7, T. Szepesi7, M. Szücs7, F.L. Tabares6, N. Tamura41, A. Tancetti35, C. Tantos10, J. Terry3, H. Thienpondt6, H. Thomsen1, M. Thumm10, J.M. Travere9, P. Traverso5, J. Tretter8, E. Trier8, H. Trimino Mora1, T. Tsujimura41, Y. Turkin1, A. Tykhyi45, B. Unterberg17, P. van Eeten1, B.Ph. van Milligen6, M. van Schoor26, L. Vano1, S. Varoutis10, M. Vecsei7, L. Vela56, J.L. Velasco6, M. Vervier17, N. Vianello50, H. Viebke1, R. Vilbrandt1, G. Vogel8, N. Vogt1, C. Volkhausen1, A. von Stechow1, F. Wagner1, E. Wang17, H. Wang57, F. Warmer1, T. Wauters26, L. Wegener1, T. Wegner1, G. Weir1, U. Wenzel1, A. White3, F. Wilde1, F. Wilms1, T. Windisch1, M. Winkler1, A. Winter1, V. Winters1, R. Wolf118, A.M. Wright29, G.A. Wurden39, P. Xanthopoulos1, S. Xu17, H. Yamada58, H. Yamaguchi41, M. Yokoyama41, M. Yoshinuma41, Q. Yu8, M. Zamanov14, M. Zanini1, M. Zarnstorff29, D. Zhang1, S. Zhou17, J. Zhu1, C. Zhu29, M. Zilker8, A. Zocco1, H. Zohm8, S. Zoletnik7 and L. Zsuga7 // 1 Max Planck Institute for Plasma Physics, Garching and Greifswald, Germany: 2 University of Greifswald, Greifswald, Germany; 3 Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, United States of America; 4 Consorzio RFX, Corso Stati Uniti, 4-35127 Padova, Italy; 5 Auburn University, Auburn, AL 36849, United States of America; 6 CIEMAT, Avenida Complutense, 40, 28040 Madrid, Spain; 7 Center for Energy Research, Konkoly-Thegeut 29-33, 1121 Budapest, Hungary; 8 Max-Planck-Institute for Plasma Physics, Boltzmannstraße 2, 85748 Garching bei München, Germany; 9 CEA Cadarache, 13115 Saint-Paul-lez-Durance, France; 10 Karlsruhe Institute of Technology, Kaiserstr. 12, 76131 Karlsruhe, Germany; 11 University of Cagliari, Via Universita, 40, 09124 Cagliari, Italy; 12 École Polytechnique Fédérale de Lausanne, Swiss Plasma Center, CH-1015 Lausanne, Switzerland; 13 University of Wisconsin–Madison, Engineering Drive, Madison, WI 53706, United States of America; 14 Institute of Plasma Physics, National Science Center ‘Kharkiv Institute of Physics and Technology’, Kharkiv, Ukraine; 15 The Australian National University, Acton ACT 2601, Canberra, Australia; 16 Department of Engineering, University of Palermo, Viale delle Scienze, Edificio 6, Palermo, 90128, Italy; 17 Forschungszentrum Jülich GmbH, Institut für Energie-und Klimaforschung—Plasmaphysik, 52425 Jülich, Germany; 18 Technical University of Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany; 19 Eindhoven University of Technology, 5600 MB Eindhoven, Netherlands; 20 Universitat Politècnica de Catalunya. BarcelonaTech, C. Jordi Girona, 31, 08034 Barcelona, Spain; 21 Culham Center for Fusion Energy, Abingdon OX14 3EB, United Kingdom; 22 Instituto de Plasmas e Fusao Nuclear, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; 23 Department of Physics, National and Kapodistrian University of Athens, 15784 Athens, Greece; 24 Institute of Plasma Physics and Laser Microfusion, 23 Hery Str., 01-497 Warsaw, Poland; 25 ENEA—Centro Ricerche Frascati, Via Enrico Fermi, 45, 00044 Frascati RM, Italy; 26 Laboratory for Plasma Physics, LPP-ERM/KMS, TEC Partner, B-1000 Brussels, Belgium; 27 Dutch Institute for Fundamental Energy Research, PO Box 6336, 5600 HH Eindhoven, Netherlands; 28 University of Texas, Austin, TX, United States of America; 29 Princeton Plasma Physics Laboratory, Princeton, NJ 08543, United States of America; 30 Kyushu University, 744 Motooka Nishi-ku, Fukuoka 819-0395, Japan; 31 Aix-Marseille University, Jardin du Pharo, 58 Boulevard Charles Livon, 13007, Marseille, France; 32 Department of Physics and Astronomy, Padova University, Via Marzolo 8, 35131 Padova, Italy; 33 Department of Applied Physics, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Ghent, Belgium; 34 Aalto University, 02150 Espoo, Finland; 35 Department of Physics, Technical University of Denmark, Anker Engelunds Vej, 2800 Kgs Lyngby, Denmark; 36 VTT Technical Research Center of Finland Ltd., PO Box 1000, FI-02044 VTT, Finland; 37 Institute of Plasma Physics, Chinese Academy of Sciences, 230031 Hefei, Anhui, China; 38 Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37830, United States of America; 39 Los Alamos National Laboratory, NM 87545, United States of America; 40 Fritz-Haber-Institut der Max-Planck-Gesellschaft, 14195 Berlin, Germany; 41 National Institute for Fusion Science, National Institutes of Natural Sciences, 322-6 Oroshi-cho, Toki, Gifu Prefecture 509-5292, Japan; 42 Institute for Ion Physics and Applied Physics, University of Innsbruck, Innsbruck, Austria; 43 Graz University of Technology, Rechbauerstraße 12, 8010 GRAZ, Austria; 44 Austrian Academy of Science, Doktor-Ignaz-Seipel-Platz 2, 1010 Wien, Austria; 45 Institute for Nuclear Research, prospekt Nauky 47, Kyiv 03028, Ukraine; 46 University of Opole, plac Kopernika 11a, 45-001 Opole, Poland; 47 University of Maryland, Paint Branch Drive, College Park, MA 20742, United States of America; 48 National Research Nuclear University MEPhI, 115409 Moscow, Russian Federation; 49 Department of Microelectronics and Computer Science, Lodz University of Technology, Wolczanska 221/223, 90-924 Lodz, Poland; 50 Consiglio Nazionale delle Ricerche, Piazzale Aldo Moro, 7, 00185 Roma, Italy; 51 Ioffe Physical-Technical Institute of the Russian Academy of Sciences, 26 Politekhnicheskaya, St Petersburg 194021, Russian Federation; 52 Istituto di Fisica del Plasma Piero Caldirola, Via Roberto Cozzi, 53, 20125 Milano, Italy; 53 University of Szczecin, 70-453, aleja Papieza Jana Pawła II 22A, Szczecin, Poland; 54 Lawrence University, 711 E Boldt Way, Appleton, WI 54911, United States of America; 55 Physik-Department E28, Technische Universität München, 85747 Garching, Germany; 56 Universidad Carlos III de Madrid, Av. de la Universidad, 30 Madrid, Spain; 57 Yale University, New Haven, CT 06520, United States of America; 58 University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chhiab 277-0882, Japan Objectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminant Objectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminant::7.a - Per a 2030, augmentar la cooperació internacional per tal de facilitar l’accés a la investigació i a les tecnolo­gies energètiques no contaminants, incloses les fonts d’energia renovables, l’eficiència energètica i les tecnologies de combustibles fòssils avançades i menys contaminants, i promoure la inversió en infraestructures energètiques i tecnologies d’energia no contaminant

Chronic activation of the mineralocorticoid receptor (MR) through the agonist aldosterone leads to pathological processes like inflammation, fibrosis, and increased blood pressure. Therefore, MR antagonists (MRA) belong to guideline-based therapy for hypertension and heart failure with reduced ejection fraction. The nonsteroidal, selective MRA finerenone (FIN) induces distinct pharmacological actions when compared to steroidal MRAs including less adverse effects and improved efficacy (e.g. anti-fibrosis). In this study, we investigated the effects of FIN in a deoxycorticosterone acetate (DOCA)-salt model which induces an increase of blood pressure and end organ damage including hypertrophy, fibrosis, and inflammatory cell infiltration in heart and kidney. Male C57BL6/J mice were either uni-nephrectomized in addition to DOCA-pellet application (2.4mg/d) and 0.9% NaCl in the drinking water (DOCA/UNX) or received a sham operation. One week prior to the surgery, oral treatment with FIN (10mg/kg/d) or vehicle (VEH) started and lasted throughout the experiment. Five weeks after the procedure, final examinations including blood pressure (BP) measurement, urine analysis, speckle-tracking echocardiography (STE), and FACS analysis of the heart and kidney were performed. BP was significantly reduced by FIN treatment. FACS analysis revealed a notable immune response due to DOCA/ UNX exposure. Especially infiltrating renal RORγt γδ T-Cells were upregulated, which was significantly ameliorated by the FIN-treatment. This was accompanied by an improvement of kidney function shown by a reduction of the urinary albumin/creatinine ratio in FIN-treated mice. In the heart, FIN reduced DOCA/ UNX-induced cardiac hypertrophy, cardiac fibrosis and led to an improvement of the global longitudinal strain (GLS) in the STE-analysis. Cardiac actions of FIN were not associated with a regulation of cardiac RORγt γδ T-Cells. The present study shows cardiac and renal protective effects of FIN in a DOCA/UNX model. The cardiorenal protection was accompanied by a reduction of renal RORγt γδ T-Cells. Anti-inflammatory actions of FIN may provide a potential mechanism of its clinical efficacy recently observed in clinical trials. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer AG

The investigation of fuel retention in fusion experiments is important in view of plasma density control as well as tritium inventory for future fusion reactors. We present a first gas balance of the stellarator Wendelstein 7-X with its inertially cooled graphite divertor. The gas balance is used to estimate the wall inventory and it is found that the wall plays an important and dynamic role, absorbing or releasing particles depending on the plasma conditions. Several different scenarios are presented and the effect of fueling and heating on the wall inventory is assessed. We find that the record duration plasma experiment of 100 s required previous shorter plasmas to be successfully conducted.

Wendelstein 7-X (W7-X), the largest advanced stellarator, is built to demonstrate high power, high performance quasi-continuous operation. Therefore, in the recent campaign, experiments were performed to prepare for long pulse operation, addressing three critical issues: the development of stable detachment, control of the heat and particle exhaust, and the impact of leading edges on plasma performance. The heat and particle exhaust in W7-X is realized with the help of an island divertor, which utilizes large magnetic islands at the plasma boundary. This concept shows very efficient heat flux spreading and favourable scaling with input power. Experiments performed to overload leading edges showed that the island divertor yields good impurity screening. A highlight of the recent campaign was a robust detachment scenario, which allowed reducing power loads even by a factor of ten. At the same time, neutral pressures at the pumping gap entrance yielded the particle removal rate close to the values required for stable density control in steady-state operation.

The fundamental behavior of the W7-X island divertor under detached conditions, which has been theoretically predicted with the EMC3-Eirene code, is re-examined here under the experimental conditions achieved so far and compared with the first experimental results. Both simulations and experiments cover a range of divertor configurations and plasma parameters, and show the following common trends: (1) with rising impurity radiation, the target heat load decreases ‘uniformly’ over the entire target surface in the sense that both the peak and average heat loads can drop by an order of magnitude. Impurity radiation (mainly from intrinsic carbon) occurs primarily at the plasma edge and the resulting negative impact on the stored energy is less than 10%. (2) When the total radiation exceeds a critical level, the target particle flux (the recycling flux Γrecy) begins to fall and can drop by a factor of 3–5 at high radiation levels without an obvious indication of significant volume recombination. (3) While Γrecy decreases, the divertor neutral pressure continues to build up and reaches a maximum, at which point Γrecy has declined significantly. (4) During detachment, the electron temperature at the last closed flux surface falls in a way that is not quantitatively understandable from parallel classical heat conduction processes. This paper presents a physical explanation of the numerical/experimental results described above. Furthermore, using the EMC3-Eirene code as a diagnostic tool, we are able, apparently for the first time, to provide a full quantitative analysis of each transport channel in the island divertor, aiming to clarify how the island divertor plasma self-regulates to maintain particle, energy, and momentum balance under detached conditions.

The optimized superconducting stellarator device Wendelstein 7-X (with major radius , minor radius , and plasma volume) restarted operation after the assembly of a graphite heat shield and 10 inertially cooled island divertor modules. This paper reports on the results from the first high-performance plasma operation. Glow discharge conditioning and ECRH conditioning discharges in helium turned out to be important for density and edge radiation control. Plasma densities of with central electron temperatures were routinely achieved with hydrogen gas fueling, frequently terminated by a radiative collapse. In a first stage, plasma densities up to were reached with hydrogen pellet injection and helium gas fueling. Here, the ions are indirectly heated, and at a central density of a temperature of with was transiently accomplished, which corresponds to with a peak diamagnetic energy of and volume-averaged normalized plasma pressure . The routine access to high plasma densities was opened with boronization of the first wall. After boronization, the oxygen impurity content was reduced by a factor of 10, the carbon impurity content by a factor of 5. The reduced (edge) plasma radiation level gives routinely access to higher densities without radiation collapse, e.g. well above line integrated density and central temperatures at moderate ECRH power. Both X2 and O2 mode ECRH schemes were successfully applied. Core turbulence was measured with a phase contrast imaging diagnostic and suppression of turbulence during pellet injection was observed.

Observations on confinement in the first experimental campaign on the optimized Stellarator Wendelstein 7-X are summarized. In this phase W7-X was equipped with five inboard limiters only and thus the discharge length restricted to avoid local overheating. Stationary plasmas are limited to low densities

There is a current lack of effective mucosal vaccines against major gastroenteric pathogens and particularly against Helicobacter pylori, which causes a chronic infection that can lead to peptic ulcers and gastric cancer in a subpopulation of infected individuals. Mucosal CD4+ T‐cell responses have been shown to be essential for vaccine‐induced protection against H. pylori infection. The current study addresses the influence of the adjuvant and site of mucosal immunization on early CD4+ T‐cell priming to H. pylori antigens. The vaccine formulation consisted of H. pylori lysate antigens and mucosal adjuvants, cholera toxin (CT) or a detoxified double‐mutant heat‐labile enterotoxin from Escherichia coli (dmLT), which were administered by either the sublingual or intragastric route. We report that in vitro, adjuvants CT and dmLT induce up‐regulation of pro‐inflammatory gene expression in purified dendritic cells and enhance the H. pylori‐specific CD4+ T‐cell response including interleukin‐17A (IL‐17A), interferon‐γ (IFN‐γ) and tumour necrosis factor‐α (TNF‐α) secretion. In vivo, sublingual immunization led to an increased frequency of IL‐17A+, IFN‐γ + and TNF‐α + secreting CD4+ T cells in the cervical lymph nodes compared with in the mesenteric lymph nodes after intragastric immunization. Subsequently, IL‐17A+ cells were visualized in the stomach of sublingually immunized and challenged mice. In summary, our results suggest that addition of an adjuvant to the vaccine clearly activated dendritic cells, which in turn, enhanced CD4+ T‐cell cytokines IL‐17A, IFN‐γ and TNF‐α responses, particularly in the cervical lymph nodes after sublingual vaccination.

The control of rotational transform in Wendelstein 7-X (W7-X) is key to both the island divertor operation and safety of plasma facing components. The island divenor concept in W7-X relies on an edge flux surface with rotational transform of t = 1 resonating with an intrinsic n/m = 5/5 resonance to form a five lobed island chain. This island chain intersects with divertor plates to give rise to the island divertor. Changes in the relative position of the rational surface and the divertor plates can result in changes in divenor performance, thus the control of the rotational transform is essential to operation of the W7-X device. During the first divertor campaign electromagnetic loads resulted in elastic deformations of the shaped modular stellarator coils. Such deformations made these coils more planar, reducing the vacuum rotational transform, subsequently shifting the t = 1 resonance outward. Unintended plasma wall interactions provided the first clear evidence of this effect during plasma operation. Flux surface measurements were utilized to estimate the correct level of current in the planar coils for correction of t, and found to be around similar to-100 A. Scans the planar coil current for iota correction were performed during plasma operation. These measurements suggest planar coil currents between -250 and similar to 0 A would place the strike lines at the designed distance from the pumping gaps. Divertor Langmuir and upstream probe measurements confirm these estimates along with measurements of divertor neutral gas pressure.

International audience; The Wendelstein 7-X (W7-X) optimized stellarator fusion experiment,which went into operation in 2015, has been operating since 2017 with anun-cooled modular graphite divertor. This allowed first divertor physicsstudies to be performed at pulse energies up to 80 MJ, as opposed to 4MJ in the first operation phase, where five inboard limiters wereinstalled instead of a divertor. This, and a number of other upgrades tothe device capabilities, allowed extension into regimes of higher plasmadensity, heating power, and performance overall, e.g. setting a newstellarator world record triple product. The paper focuses on the firstphysics studies of how the island divertor works. The plasma heat loadsarrive to a very high degree on the divertor plates, with only minorheat loads seen on other components, in particular baffle structuresbuilt in to aid neutral compression. The strike line shapes andlocations change significantly from one magnetic configuration toanother, in very much the same way that codes had predicted they would.Strike-line widths are as large as 10 cm, and the wetted areas alsolarge, up to about 1.5 m2, which bodes well for futureoperation phases. Peak local heat loads onto the divertor were ingeneral benign and project below the 10 MW m?2 limit of thefuture water-cooled divertor when operated with 10 MW of heating power,with the exception of low-density attached operation in the high-iotaconfiguration. The most notable result was the complete (in all 10divertor units) heat-flux detachment obtained at high-density operationin hydrogen.

BACKGROUND An analysis of 2 kidney transplants from the same donor at the same center enables us to analyze the influence of risk factors on the outcome of the grafts in different recipients. METHODS We retrospectively analyzed 88 kidneys from 44 donors that were implanted in 88 recipients at our institution between 2007-2016. We defined unsatisfactory outcome as glomerular filtration rate

We report here on a potentially significant improvement in the design of neutral pressure gauges of the so-called ASDEX-type which were first used in the Axially Symmetric Divertor EXperiment (ASDEX). Such gauges are considered state-of-the-art and are in wide use in fusion experiments, but they nonetheless suffer from a relatively high failure rate when operated at high magnetic field strengths for long times. This is therefore a significant concern for long-pulse, high-field experiments such as Wendelstein 7-X (W7-X) and ITER. The new design is much more robust. The improvement is to use a LaB

Wendelstein 7-X (W7‐X) is the world’s largest superconducting nuclear fusion experiment of the optimized stellarator type. In the first Operation Phase (OP1.1) helium and hydrogen plasmas were studied in limiter configuration. The heating energy was limited to 4 MJ and the main purpose of that campaign was the integral commissioning of the machine and diagnostics, which was achieved very successfully. Already from the beginning a comprehensive set of diagnostics was available to study the plasma. On the path towards high-power, high-performance plasmas, W7‐X will be stepwise upgraded from an inertially cooled (OP1.2, limited to 80 MJ) to an actively cooled island divertor (OP2, 10 MW steady-state plasma operation). The machine is prepared for OP1.2 with 10 inertially cooled divertor units, and the experimental campaign has started recently. The paper describes a subset of diagnostics which will be available for OP1.2 to study the plasma edge, divertor and scrape-off layer physics including those already available for OP1.1, plus modifications, upgrades and new systems. The focus of this summary will be on technical and engineering aspects, like feasibility and assembly but also on reliability, thermal loads and shielding against magnetic fields.

This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under grant agreement No 633053.

Fusion reactors and long pulse fusion experiments heavily depend on a continuous fuel cycle, which requires detailed monitoring of exhaust gases. We have used a diagnostic residual gas analyzer (DRGA) built as a prototype for ITER and integrated it on the most advanced stellarator fusion experiment, Wendelstein 7-X (W7-X). The DRGA was equipped with a sampling tube and assessed for gas time of flight sample response, effects of magnetic field on gas detection and practical aspects of use in a state of the art fusion environment. The setup was successfully commissioned and operated and was used to observe the gas composition of W7-X exhaust gases. The measured time of flight gas response was found to be in the order of a second for a 7 m sample tube. High values of magnetic field were found to affect the partial pressure readings of the DRGA and suggest that additional shielding is necessary in future experimental campaigns.

Electron cyclotron resonance heating (ECRH) is the main heating mechanism in the Wendelstein 7-X stellarator (W7-X). W7-X is equipped with five absolutely calibrated sniffer probes that are installed in each of the five modules of the device. The sniffer probes monitor energy flux of unabsorbed ECRH radiation in the device and interlocks are fed with the sniffer probe signals. The stray radiation level in the device changes significantly during the start-up phase: Plasma is a strong microwave absorber and during its formation the stray radiation level in sniffer probes reduces by more than 95%. In this paper, we discuss the influence of neutral gas pressure and gyrotron power on plasma breakdown processes.

Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4. This structure is presumably triggered by an inadvertent plasma-wall interaction in module 4 resulting in a high impurity influx that terminates some discharges by radiation cooling. The main plasma parameters achieved in OP1.1 exceeded predicted values in discharges of a length reaching 6 s. Although OP1.1 is characterized by short pulses, many of the diagnostics are already designed for quasi-steady state operation of 30 min discharges heated at 10 MW of ECRH. An overview of diagnostic performance for OP1.1 is given, including some highlights from the physics campaigns.

Das Shiga-Toxin-assoziierte hamolytisch-uramische Syndrom (HUS) ist eine Form der thrombotischen Mikroangiopathie mit hamolytischer Anamie, Thrombozytopenie und akuter Nierenschadigung. Im Mai 2011 kam es in Norddeutschland zu einem Ausbruch mit enterohamorrhagischen Escherichia coli (EHEC; O104:H4). Ende Juli waren fast 4000 Patienten an einer EHEC-Infektion erkrankt. Dem Robert Koch-Institut wurden 855 Patienten mit der Diagnose eines HUS gemeldet, 35 (4,1%) starben. Das EHEC-assoziierte HUS ist eine meist sporadisch auftretende Erkrankung. Kontrollierte Therapiestudien liegen nicht vor. Erste Analysen lassen vermuten, dass der bei einem Grosteil der Patienten eingesetzte Plasmaaustausch eher schadigend als therapeutisch erfolgreich war. Die Rolle des monoklonalen Antikorpers Eculizumab, eines Inhibitors des Komplementsystems, wird in einer noch unveroffentlichten Multicenterstudie gepruft. Vielversprechend konnte der Einsatz einiger Antibiotika zu bewerten sein. Dies wurde einen Paradigmenwechsel in Bezug auf bisherige Therapiestrategien bedeuten. Weitere laufende und geplante Analysen der Epidemie sollten abgewartet werden, bevor eine endgultige Empfehlung zu den verschiedenen Therapieverfahren erfolgt.

Hintergrund Das Cholesterinembolie-Syndrom ist eine unterschatzte Komplikation nach Katheterinterventionen an arteriellen Gefasen. 8–10 Wochen nach dem Eingriff zeigen die Patienten akutes Nierenversagen, Zyanose der Fuse und weitere dermatologische Befunde, Diarrhoen und anderes.

Wendelstein 7-X (W7-X) relies on wall conditioning to control the density and the impurity content of the plasma. Wall conditioning in the first operation campaign of W7-X consisted of baking at 150 °C during 1 week prior to operation, glow discharge conditioning (GDC) in helium (He) and electron cyclotron resonance heating (ECRH) discharges. Additionally, the usage of He-GDC was limited to avoid sputtering and migration of metallic plasma facing components. This presented a unique opportunity for studying the applicability of ECRH discharges for initial wall conditioning on a stellarator, albeit in the carbon limiter configuration. A single envelope curve is observed in the normalised outgassing data that takes into account all ECRH discharges. This illustrates that the majority of discharges operates at the limits of a radiative collapse. Hydrogen recycling dominated the fuelling of ECRH discharges throughout while CO outgassing was found strongest at the start of the campaign. A reduction of recycling was observed throughout the campaign. Temporarily depleting the walls from H and impurities was possible by He-GDC. It was shown that the recycling coefficient in -ECRH plasmas could be reduced and the pulse duration significantly extended by He-'recovery' ECRH plasmas. Good wall conditions were defined by normalised outgassing values below mbar kJ−1. In absence of -GDC, more than 311 cumulated discharge seconds of ECRH discharges are needed for obtaining lasting low outgassing levels. A release model with two trapping reservoirs could reproduce the normalised outgassing trend, including ECRH and GDC plasma wall interactions.

Scanning proximity probes are uniquely powerful tools for analysis, manipulation, and bottom-up synthesis. A massively parallel cantilever-probe platform is demonstrated. 128 self-sensing and self-actuated proximal probes are discussed. Readout based on piezoresistive sensors and bending control based on bimorph dc/ac actuations are described in detail.

Direct measurements of the helium (He) fractional neutral pressure in the neutral gas around fusion devices is challenging because of the small mass difference between the abundant D2 molecules and the He ash which will be produced by deuterium-tritium fusion. To study He exhaust, an in situ Penning gauge system is being developed at UW-Madison that is optimized for good pressure and high spectroscopic sensitivity. Three different anode geometries have been studied regarding their vacuum electrostatic fields, light output, and ion current. The light output of the two new anode configurations are at least one order of magnitude above the currently available designs, hence improving the spectroscopic sensitivity at similar total neutral pressure resolution.

In fusion devices the hydrogen Balmer lines are used to measure the neutral flux from the walls into the plasma using the atomic physics factor S/XB. This is a standard diagnostic which can be applied in ionizing plasma using , or without knowledge of the electron density. We will extend this method to a recombining plasma in front of a surface. can be used in an analogous way to measure the plasma flow to this surface which can be e.g. a divertor target. The other Balmer lines are not suitable because the corresponding atomic physics factor R/YB depends on density due to three-body recombination. An application of this diagnostic method is provided.

Hydrogen plasmas out of ionization equilibrium are either ionizing or recombining depending on the electron temperature Te. Within the transition region between these two opposite states a minimum of the Hα emission is often experimentally observed. Simple cases were previously analyzed which could be interpreted assuming only a temperature variation, i.e the electron density was constant in the transition region. Here we discuss two examples in which both the density and the temperature vary at the transition. In the linear plasma generator PSI-II a hydrogen plasma is cooled down by puffing additional gas. We find a minimum at Tmin ≈ 1.1 eV. A second example is the effect of an ELM(edge localized mode) pulse propagating through a recombining divertor plasma in the tokamak ASDEX Upgrade. The Hα response shows a double peak which can be interpreted as a local minimum assuming a simultaneous rise of density and temperature during an ELM. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Wendelstein 7-X (W7-X) is a large optimized stellarator (B=2.5T, V=30m3) aiming at demonstrating the reactor relevance of the optimized stellarators. In 2015 W7-X will begin its first operation phase (OP1.1) with five inertially cooled inboard limiters made of graphite. Assuming the heat loads can be spread out evenly between the limiters, 1 second discharges at 2 MW of ECRH heating power could be run in OP1.1. The expected plasma parameters will be sufficient to demonstrate the readiness of the installed diagnostics and even to run a first physics program. The diagnostics available for this first operation phase, including some special limiter diagnostics, and their capabilities are being presented. A shorter version of this contribution is due to be published in PoS at: 1st EPS conference on Plasma Diagnostics

At high plasma density we find two types of radiation belts at the edge of the Wendelstein-7AS stellarator. The first one is observed in the inboard scrape-off layer (SOL) when the edge plasma is detached. It seems to be specific to the stellarator. The second one is found on closed flux surfaces and resembles the Marfe phenomenon known from tokamaks. They are experimentally characterized and modeling calculations are presented.

This paper presents a detailed analysis of the transport behaviour of the detached plasmas in W7-AS based on an extended numerical study using the EMC3-EIRENE code, aimed at understanding the underlying physics responsible for the geometry-dependent detachment stability observed in W7-AS island divertor experiments. Here, a stable detachment can only be established when the control coils are switched on to generate sufficiently large islands with relatively short connection lengths. Special attention will be paid to a discussion of the carbon radiation, location and dynamics of the radiation layer, the neutral screening efficiency specific to the island divertor geometry and its impact on the detachment stability. Based on the three-dimensional simulation results, a linear stability model is presented in order to obtain some insight into the mechanisms driving the instability. The radiation behaviour and the location and evolution of the radiation zone in the island divertor will be discussed with respect to those of tokamak-MARFEs.

In the high-density H-mode of the Stellarator Wendelstein 7-AS, the plasma detaches from the island divertor targets when the line-averaged density exceeds a critical value. This quasi-stationary detachment is found to be partial and shows edge-localized, poloidally asymmetric radiation. The spectroscopic characteristics of the deeply detached plasma are reported, including evidence for volume recombination. The detached plasma radiates up to 90% of the absorbed power with larger contributions from the locations close to magnetic X-points outside the divertor region. The spectral analysis of the Balmer series indicate very high densities and low temperatures at the detached regions. The results of the spectral analysis underline the importance of three-dimensional modelling. An initial comparison is made with the latest results from EMC3-EIRENE modelling.

In the Wendelstein 7-AS stellarator (Renner et al 1989 Plasma Phys. Control. Fusion 31 1579), under particularly high plasma densities, a non-stationary radiation zone is observed to be formed on the inboard side of the torus. It causes a degradation of the diamagnetic energy of up to 50%. The configurational aspects of the magnetic field influence the development of the radiation zone as follows. The critical density is related to the connection length of the magnetic field, i.e. the observed degradation sets in at lower densities for magnetic configurations with large connection lengths. From camera observations, in conjunction with forward calculations, it is found that the radiation zone is located on closed field lines and forms a toroidal belt. Based on complementary observations, it is concluded that the radiation zone is caused by a radiative condensation instability (or multi-faceted asymmetric radiation from the edge). Fluctuations of the radiation zone were recorded using a fast framing camera with a time resolution of 25 µs. Temporal variations as well as spatial movements were observed. The fluctuations were found on various lines-of-sight around the torus with correlation and phase shifts compatible with a toroidal propagation.

The research on divertors for stellarators is at the beginning. Extensive studies are being prepared on large helical device (LHD) and W7-X. W7-AS is now being operated with an open island divertor (ID) which serves as a test bed for the W7-X diverter. The divertor enables access to a new NBI-heated, high-density operating regime with improved confinement properties. This regime-the high-density H-mode (HDH)-displays no evident mode activity, is extant above a threshold density and characterized by flat density profiles. high-energy- and low-impurity-confinement times and edge-localized radiation. Impurity accumulation, normally associated with ELM-free H-modes, is avoided. Quasi-steady-state discharges with n e up to 4 x 10 20 m -3 , edge radiation levels up to 90% and plasma partial detachment at the divertor targets can be simultaneously realized. The accessibility to other improved confinement modes in W7-AS (conventional H-mode anti OC-mode) is not restricted by the divertor. The results provide a promising basis for future experiments, in particular on W7-X, and recommend the ID as a serious candidate for solving the plasma exhaust problem in stellarators.

In the W7-AS stellerator with island divertor very high densities can be achieved in the high-density H-mode. As a consequence, the plasma in the divertor detaches as previously shown by the reduction of the particle flux at some strike point positions and an upward movement of the ionisation front. Our spectroscopic measurements prove the simultaneous formation of a high-density (8×1020 m−3), low temperature (0.2 eV) region at the detachment transition in the divertor on top. This plasma is strongly recombining, as a result a strong up/down pressure asymmetry develops. Since flux amplification at the strike points was not found in the island divertor, we suppose that a nonlinear thermal condensation instability leads to the observed high-density region.

The new island divertor in W7-AS enables quasi steady-state operation with NBI at very high density including scenarios with stable detachment from the targets. Experiments with reversed B-field indicate that the interaction zones on the targets are affected in first order by E×B drifts. Stable detachment is restricted to magnetic field configurations with sufficiently large separation between x-points and targets and not too small field line pitch inside the islands. It is always partial in the sense that it does not extend over the full target area. This inhomogeneity is ascribed to an in/out asymmetry of the electron temperature at the upstream separatrix position.

A promisingnew operational reg ime on the Wendelstein stellarator W7-AS has been discovered, fulfillingthe conditions of optimal core behavior in combination with edge parameters suitable for successful divertor scenarios. This regime, the high density H-mode (HDH), displays no systematically evident mode activity, and is edge localized mode (ELM)-free. It is extant above a power-dependent threshold density and characterized by flat density profiles, high energy- and low impurity-confinement times and edge-localized radiation. Impurity accumulation, normally as

Extensive parameter studies have been carried out with the EMC3-EIRENE code. Major code predictions, namely the absence of high recycling prior to detachment, additional momentum losses associated with the specific island divertor geometry and the jump of the radiation at detachment transition have been verified by the W7-AS divertor experiments. Measurements and simulations are compared for high density, high power W7-AS divertor discharges and the physics related to rollover and detachment is discussed in detail. Local comparisons with the W7-AS experiment have been started with a new code version accounting for the real open-island geometry. Specifically, the observed asymmetric power unloading of the target plates at detachment transition could now be reproduced and explained. Agreement with the experiment was also found for the unexpected spatial structure of particle deposition by including classical E×B drifts into the code.

The island divertor concept, which is regarded as being the natural concept for low shear advanced stellarators like W7-AS and W7-X, has for the first time been put to a realistic test in the present experimental campaign of W7-AS. A large number of diagnostics, specifically geared towards the diagnosis of island divertor plasmas, have been installed in the course of the last two years. This report will introduce some of the newly installed active and passive spectroscopy based divertor diagnostics.