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204 results on '"A. Kreuzeder"'

1. 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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2. Physical activity levels are positively related to progression-free survival and reduced adverse events in advanced ER+ breast cancer

Author

Zimmer, Philipp, Esser, Tobias, Lueftner, Diana, Schuetz, Florian, Baumann, Freerk T., Rody, Achim, Schneeweiss, Andreas, Hartkopf, Andreas D., Decker, Thomas, Uleer, Christoph, Stoetzer, Oliver J., Foerster, Frank, Schmidt, Marcus, Mundhenke, Christoph, Steindorf, Karen, Tesch, Hans, Jackisch, Christian, Fischer, Thomas, Hanson, Sven, Kreuzeder, Julia, Guderian, Gernot, Fasching, Peter A., and Bloch, Wilhelm

Published
2024
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5. Efficacy, safety, and prognosis prediction in patients treated with ribociclib in combination with letrozole: Final results of phase 3b RIBECCA study in hormone receptor positive, human epidermal growth factor receptor-2 negative, locally advanced or metastatic breast cancer

Author

Fasching, Peter A., Decker, Thomas, Hartkopf, Andreas, Nusch, Arnd, Heinrich, Bernhard J., Kurbacher, Christian, Fuchs, Roswitha, Tesch, Hans, Krabisch, Petra, Huober, Jens, Kuemmel, Sherko, Brucker, Sara, Janni, Wolfgang, Schneeweiss, Andreas, Schuler, Martin, Fehm, Tanja, Lüftner, Diana, Quiering, Claudia, Voges, Claudia, Kreuzeder, Julia, and Reinisch, Mattea

Published
2024
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7. Observation of magnetic islands in tokamak plasmas during the suppression of edge-localized modes

Author

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

Abstract

In tokamaks, a leading platform for fusion energy, periodic filamentary plasma eruptions known as edge-localized modes occur in plasmas with high-energy confinement and steep pressure profiles at the plasma edge. These edge-localized modes could damage the tokamak wall but can be suppressed using small three-dimensional magnetic perturbations. Here we demonstrate that these magnetic perturbations can change the magnetic topology just inside the steep gradient region of the plasma edge. We identify signatures of a magnetic island, and their observation is linked to the suppression of edge-localized modes. We compare high-resolution measurements of perturbed magnetic surfaces with predictions from ideal magnetohydrodynamic theory where the magnetic topology is preserved. Although ideal magnetohydrodynamics adequately describes the measurements in plasmas exhibiting edge-localized modes, it proves insufficient for plasmas where these modes are suppressed. Nonlinear resistive magnetohydrodynamic modelling supports this observation. Our study experimentally confirms the predicted role of magnetic islands in inhibiting the occurrence of edge-localized modes. This will be beneficial for physics-based predictions in future fusion devices to control these modes.The suppression of edge-localized modes in tokamak plasmas is crucial to prevent them from damaging the walls of the chamber. Now experiments confirm the role that magnetic islands play in suppressing these detrimental modes.

Published
2024

8. Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble

Author

Moritz Mühlhofer, Carsten Peters, Thomas Kriehuber, Marina Kreuzeder, Pamina Kazman, Natalia Rodina, Bernd Reif, Martin Haslbeck, Sevil Weinkauf, and Johannes Buchner

Subjects
Science
Abstract

Small heat shock proteins (sHsps) form large spherical assemblies and their regulation is not well understood. Here, the authors provide insights into the mechanism of Hsp26 activation by characterising phospho-mimetic mutants of yeast Hsp26. They present cryo-EM structures of the wild-type Hsp26 40mer and its phospho-mimetic mutants that reveal the location of the thermosensor in the oligomer, and the authors also show that the thermosensor domain is targeted by phosphorylation, which relieves the intrinsic inhibition of chaperone activity.

Published
2021
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9. Physical activity levels are positively related to progression-free survival and reduced adverse events in advanced ER+ breast cancer.

Author

Zimmer, Philipp, Esser, Tobias, Lueftner, Diana, Schuetz, Florian, Baumann, Freerk T., Rody, Achim, Schneeweiss, Andreas, Hartkopf, Andreas D., Decker, Thomas, Uleer, Christoph, Stoetzer, Oliver J., Foerster, Frank, Schmidt, Marcus, Mundhenke, Christoph, Steindorf, Karen, Tesch, Hans, Jackisch, Christian, Fischer, Thomas, Hanson, Sven, and Kreuzeder, Julia

Subjects
METASTATIC breast cancer, PHYSICAL activity, CANCER patients, HORMONE receptor positive breast cancer, FATIGUE (Physiology), HORMONE receptors
Abstract

Background : Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case–control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. Methods: In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3 months during treatment. Participants were then classified into "active" and "insufficiently active" to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3 months until study termination. Results: Compared to "insufficiently active" patients, "active" individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p =.0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be "active" at baseline revealed significantly fewer AEs compared to "insufficiently" active patients. In detail, both severe and non-severe AEs occurred less frequently in the "active" patients group. In line with that, QoL and fatigue were better in physical "active" patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. Conclusions: Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients' QoL and fatigue. Trial registration: EUPAS9462. Registered 30th October 2012 "retrospectively registered." [ABSTRACT FROM AUTHOR]

Published
2024
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10. Fabrication and thermo-mechanical behavior of ultra-fine porous copper

Author

Kreuzeder, Marius, Abad, Manuel-David, Primorac, Mladen-Mateo, Hosemann, Peter, Maier, Verena, and Kiener, Daniel

Subjects
Engineering, Macromolecular and Materials Chemistry, Materials Engineering, Chemical Sciences, Materials, Chemical sciences
Abstract

Porous materials with ligament sizes in the submicrometer to nanometer regime have a high potential for future applications such as catalysts, actuators, or radiation tolerant materials, which require properties like high strength-to-weight ratio, high surface-to-volume ratio, or large interface density as for radiation tolerance. The objective of this work was to manufacture ultra-fine porous copper, to determine the thermo-mechanical properties, and to elucidate the deformation behavior at room as well as elevated temperatures via nanoindentation. The experimental approach for manufacturing the foam structures used high pressure torsion, subsequent heat treatments, and selective dissolution. Nanoindentation at different temperatures was successfully conducted on the ultra-fine porous copper, showing a room temperature hardness of 220 MPa. During high temperature experiments, oxidation of the copper occurred due to the high surface area. A model, taking into account the mechanical properties of the copper oxides formed during the test, to describe the measured mechanical properties in dependence on the proceeding oxidation was developed. The strain rate sensitivity of the copper foam at room temperature was ∼0.03 and strongly correlated with the strain rate sensitivity of ultra-fine grained bulk copper. Although oxidation occurred near the surface, the rate-controlling process was still the deformation of the underlying copper. An increase in the strain rate sensitivity was observed, comparably to that of ultra-fine-grained copper, which can be linked to thermally activated processes at grain boundaries. Important insights into the effects of oxidation on the deformation behavior were obtained by assessing the activation volume. Oxidation of the ultra-fine porous copper foam, thereby hindering dislocations to exit to the surface, resulted in a pronounced reduction of the apparent activation volume from ~800 to ~50 b3, as also typical for ultra-fine grained materials.

Published
2015

11. Efficacy and safety of everolimus plus exemestane in patients with hormone receptor‐positive, HER‐2‐negative advanced breast cancer: Results from the open‐label, multicentre, non‐interventional BRAWO study

Author

Lüftner, Diana, primary, Schuetz, Florian, additional, Schneeweiss, Andreas, additional, Hartkopf, Andreas, additional, Bloch, Wilhelm, additional, Decker, Thomas, additional, Uleer, Christoph, additional, Stötzer, Oliver, additional, Foerster, Frank, additional, Schmidt, Marcus, additional, Mundhenke, Christoph, additional, Tesch, Hans, additional, Jackisch, Christian, additional, Fischer, Thomas, additional, Kreuzeder, Julia, additional, Guderian, Gernot, additional, and Fasching, Peter A., additional

Published
2024
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12. The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial

Author

Hadji, Peyman, Stoetzer, Oliver, Decker, Thomas, Kurbacher, Christian M., Marmé, Frederik, Schneeweiss, Andreas, Mundhenke, Christoph, Distelrath, Andrea, Fasching, Peter A., Lux, Michael P., Lüftner, Diana, Janni, Wolfgang, Muth, Mathias, Kreuzeder, Julia, Quiering, Claudia, Grischke, Eva-Marie, and Tesch, Hans

Published
2019
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15. Investigating focal spot position drift in a mobile imaging system equipped with a monobloc‐based x‐ray generator.

Author

Messner, Ivan Michael, Keuschnigg, Peter, Stöllinger, Bernhard, Kraihamer, Mathias, Coste‐Marin, Julia, Huber, Philipp, Kellner, Daniel, Kreuzeder, Elisa Maria, Steininger, Philipp, and Deutschmann, Heinz

Subjects
IMAGING systems, CONE beam computed tomography, INTRAOPERATIVE radiotherapy, X-rays
Abstract

Background: Misalignment or double‐contouring artifacts can appear in high‐resolution 3D cone beam computed tomography (CBCT) images, potentially indicating geometric accuracy issues in the projection data. Such artifacts may go unnoticed in low‐resolution images and could be associated with changes in the focal spot (FS) position. Purpose: High‐resolution 3D‐CBCT imaging by a mobile imaging device with a large gantry clearance offers more versatility for clinical workflows in image‐guided brachytherapy (IGBT), intraoperative radiation therapy (IORT), and spinal, as well as maxillofacial surgery. However, misalignment or double‐contouring artifacts hinder workflow advancements in these domains. This paper introduces intrinsic calibration and geometrical correction methods as extensions to a well‐established technique for addressing geometrical deviations resulting from factors such as gravity or mechanical inconsistencies. These extensions cover shifts and drifts of the FS depending on FS size selection, temperature, tube current, and tube potential. The proposed methods effectively mitigate artifacts in high‐resolution CBCT images stemming from geometrical inaccuracies in projection data, without requiring additional equipment like a pinhole device. Methods: Geometrical offsets and drifts of the x‐ray tube FS were characterized on a mobile multi‐purpose imaging system, the ImagingRing‐m. A pinhole‐like experiment was simulated by adjusting the movable collimation unit to a small rectangular aperture within the FS size range. The influence of filament selection, that is, FS size, temperature, the relatively low tube currents, as well as tube potential settings have been studied on two different monobloc types sharing the same x‐ray tube insert. The Catphan 504 and an Alderson head phantom were used to assess resulting image artifacts. Results: Switching the FS size to one different from what was used for geometrical (gravitation, mechanical variations) calibration induced the most notable position changes of the x‐ray FS, resulting in double‐contouring artifacts and blurring of high‐resolution 3D‐CBCT images. Incorporating these shifts into a geometrical correction method effectively minimized these artifacts. Thermal drifts exhibited the second largest geometrical changes, comparable to FS size shifts across the thermal operating conditions of the x‐ray system. The proposed thermal drift compensation markedly reduced thermal drift effects. Tube current and potential had little impact within the range of available tube currents, eliminating the need for compensation in current applications. Conclusions: Augmenting the geometrical calibration pipeline with proposed FS drift compensations yielded significant enhancements in image quality for high‐resolution reconstructions. While compensation for thermal effects posed challenges, it proved achievable. The roles of tube current and potential were found to be negligible. [ABSTRACT FROM AUTHOR]

Published
2024
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16. The Endocrine Treatment Landscape for Patients with HR+ HER2− Early-stage Breast Cancer in Germany Before the Introduction of CDK4/6 Inhibitor Therapy – A Real-World Analysis

Author

Nabieva, Naiba, additional, Altmann, Falk, additional, Apel, Klaus, additional, Baerens, Dirk-Toralf, additional, Beha, Michaela, additional, Belau, Antje, additional, Busch, Steffi, additional, Guth, Dagmar, additional, Heinrich, Georg, additional, Kreiss-Sender, Janine, additional, Markmann, Susanne, additional, Olbermann, Andreas, additional, Oskay-Özcelik, Gülten, additional, Schuback, Beatrix, additional, Steinfeld-Birg, Dieter, additional, Quiering, Claudia, additional, Kiss, Ferenc, additional, Kreuzeder, Julia, additional, Nuti, Paolo, additional, and Schilling, Jörg, additional

Published
2023
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18. Endokrine Therapielandschaft bei Patient*innen mit HR+ HER2− frühem Mammakarzinom in Deutschland vor Einführung der CDK4/6-Inhibitor-Behandlung – eine Real-World-Analyse.

Author

Nabieva, Naiba, Altmann, Falk, Apel, Klaus, Baerens, Dirk-Toralf, Beha, Michaela, Belau, Antje, Busch, Steffi, Guth, Dagmar, Heinrich, Georg, Kreiss-Sender, Janine, Markmann, Susanne, Olbermann, Andreas, Oskay-Özcelik, Gülten, Schuback, Beatrix, Steinfeld-Birg, Dieter, Quiering, Claudia, Kiss, Ferenc, Kreuzeder, Julia, Nuti, Paolo, and Schilling, Jörg

Published
2024
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19. Systemische Therapie von prämenopausalen Patientinnen mit hormonrezeptorpositivem, HER2-negativem Brustkrebs in den Frühstadien – Kontroversen und Standards in der Krankenversorgung.

Author

Müller, Volkmar, Fasching, Peter A., Nabieva, Naiba, Fehm, Tanja N., Thill, Marc, Schmidt, Marcus, Kühn, Thorsten, Banys-Paluchowski, Maggie, Belleville, Erik, Juhasz-Böss, Ingolf, Untch, Michael, Kolberg, Hans-Christian, Harbeck, Nadia, Aktas, Bahriye, Stickeler, Elmar, Kreuzeder, Julia, Hartkopf, Andreas D., Janni, Wolfgang, and Ditsch, Nina

Published
2024
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20. Systemic Therapy of Premenopausal Patients with Early Stage Hormone Receptor-Positive, HER2-Negative Breast Cancer – Controversies and Standards in Healthcare

Author

Müller, Volkmar, additional, Fasching, Peter A., additional, Nabieva, Naiba, additional, Fehm, Tanja N., additional, Thill, Marc, additional, Schmidt, Marcus, additional, Kühn, Thorsten, additional, Banys-Paluchowski, Maggie, additional, Belleville, Erik, additional, Juhasz-Böss, Ingolf, additional, Untch, Michael, additional, Kolberg, Hans-Christian, additional, Harbeck, Nadia, additional, Aktas, Bahriye, additional, Stickeler, Elmar, additional, Kreuzeder, Julia, additional, Hartkopf, Andreas D., additional, Janni, Wolfgang, additional, and Ditsch, Nina, additional

Published
2023
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22. Systemic Therapy of Premenopausal Patients with Early Stage Hormone Receptor-Positive, HER2-Negative Breast Cancer – Controversies and Standards in Healthcare

Author

Volkmar Müller, Peter A. Fasching, Naiba Nabieva, Tanja N. Fehm, Marc Thill, Marcus Schmidt, Thorsten Kühn, Maggie Banys-Paluchowski, Erik Belleville, Ingolf Juhasz-Böss, Michael Untch, Hans-Christian Kolberg, Nadia Harbeck, Bahriye Aktas, Elmar Stickeler, Julia Kreuzeder, Andreas D. Hartkopf, Wolfgang Janni, and Nina Ditsch

Subjects
Maternity and Midwifery, Obstetrics and Gynecology
Abstract

In patients with existing ovarian function, there are some special aspects to adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive, HER2-negative (HR pos./HER2 neg.) breast cancer. Treatment options include tamoxifen with or without a GnRH analog, and aromatase inhibitors with a GnRH analog. Furthermore, ovarian function is affected by previous chemotherapy. Both aromatase inhibitors (+GnRH analogs) and GnRH analogs in combination with tamoxifen are supposed to be indicated for patients at increased risk of recurrence.However, national and international guidelines and therapy recommendations do not provide a clear definition of intermediate or high risk; as a result, therapy decisions are often made for each patient on an individual basis. This is also reflected in the considerable variability at national and international levels, e.g., with regard to the use of aromatase inhibitors + GnRH analogs.This review summarizes the data on completed studies (e.g., SOFT, TEXT, EBCTCG meta-analyses) and the current multigene testing studies (TailorX, RxPonder, ADAPT), discusses the rationale for current studies (e.g., CLEAR-B), and looks ahead to future questions.

Published
2023
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28. First Steps

Author

Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, Kreuzeder, Ulrich, Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, and Kreuzeder, Ulrich

Published
1997
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31. Object-Oriented Programming

Author

Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, Kreuzeder, Ulrich, Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, and Kreuzeder, Ulrich

Published
1997
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33. Introduction to Oberon-2

Author

Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, Kreuzeder, Ulrich, Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, and Kreuzeder, Ulrich

Published
1997
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34. Introduction

Author

Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, Kreuzeder, Ulrich, Mühlbacher, Jörg R., Leisch, Bernhard, Kirk, Brian, and Kreuzeder, Ulrich

Published
1997
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36. Abstract P4-01-05: Machine learning to predict treatment response and tolerability in HR+, HER2– advanced breast cancer: German study AI4ANNA

Author

Peter A. Fasching, Achim Wöckel, Hans Tesch, Bernhard Volz, Uwe Pritzsche, Marc Bachmann, Asmir Vodencarevic, Julia Kreuzeder, and Diana Lüftner

Subjects
Cancer Research, Oncology
Abstract

Background: Predicting the probability of tumor progression and tolerability with sufficient accuracy remains a significant challenge in advanced breast cancer. The objective of AI4ANNA study was to assess the predictive potential of machine learning (ML) methods with respect to tumor control and safety outcomes using German study data (RIBECCA, RIBANNA) and to identify the most relevant baseline factors for prediction. Methods: Anonymized study data from two studies of ribociclib and endocrine therapy in patients with advanced HR+, HER2– breast cancer were used for predictive analysis. RIBECCA (N=487) was a multicenter, open-label, single-arm, phase 3b trial, and RIBANNA (N=1904) is an ongoing non-interventional study evaluating the real-world efficacy and safety of first-line ribociclib in combination with aromatase inhibitor/fulvestrant, endocrine monotherapy or chemotherapy. Study baseline features were used to develop prediction models for a variety of tumor control (including progression-free survival (PFS), overall response rate (ORR) at week 24, death) and safety outcomes (including general number of adverse events (AEs) as well as selected AEs belonging to blood system, cardiac, hepatobiliary, and gastrointestinal disorders). LASSO (Least Absolute Shrinkage and Selection Operator) and XGBoost (eXtreme Gradient Boosting) ML algorithms were employed to train prediction models. LASSO was selected as a representative of fully interpretable, linear models and XGBoost as a representative of highly flexible, nonlinear models. Predictive performance of these two algorithms was compared and predictive value of single baseline features was assessed using feature permutation importance method. Results were validated internally within the training study (10 times repeated 5-fold stratified cross-validation) as well as externally, ie, implementation and training of the prediction models on one study and validation on the other and vice versa. Results: Moderate predictive signal (at baseline) could be identified for the following two outcomes: ORR (area under the curve [AUC] mean 0.628 [RIBANNA] and 0.626 [RIBECCA]) and PFS (AUC mean 0.626 [RIBANNA], 0.604 [RIBECCA]). Model performance could be validated with very similar AUCs by cross-study evaluation. Patients could be assigned to one of three risk groups. The most important features for ORR prediction included the presence of locally advanced cancer and metastases presenting as bone only disease and for PFS the presence of liver metastases, histological grade and prior (neo)adjuvant treatment. For three safety endpoints, a predictive signal (AUC >0.6) was identified only in one study but not in the other (AEs “QT prolongation”, “leukopenia grade 3/4” and serious AE “vomiting”). However, insufficient predictive signals were found for all other outcomes. Conclusion: Prediction models for tumor control and safety outcomes were trained on a broad number of clinical baseline features. Moderate predictive signals could be identified for ORR and PFS. Even though the predictive performance (AUC) seems to be limited, patients could be assigned to one of three differently behaving risk groups at the baseline. The key predictive features for PFS included clinically known prognostic factors like liver metastasis, histological grade and prior (neo)adjuvant treatment. Citation Format: Peter A. Fasching, Achim Wöckel, Hans Tesch, Bernhard Volz, Uwe Pritzsche, Marc Bachmann, Asmir Vodencarevic, Julia Kreuzeder, Diana Lüftner. Machine learning to predict treatment response and tolerability in HR+, HER2– advanced breast cancer: German study AI4ANNA [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-05.

Published
2023
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37. Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble

Author

Mühlhofer, Moritz, Peters, Carsten, Kriehuber, Thomas, Kreuzeder, Marina, Kazman, Pamina, Rodina, Natalia, Reif, Bernd, Haslbeck, Martin, Weinkauf, Sevil, and Buchner, Johannes

Subjects
Models, Molecular, Binding Sites, Saccharomyces cerevisiae Proteins, Protein Conformation, Science, Circular Dichroism, Cryoelectron Microscopy, Temperature, macromolecular substances, Saccharomyces cerevisiae, Article, Tandem Mass Spectrometry, Chaperones, Mutation, Fluorescence Resonance Energy Transfer, Phosphorylation, Protein Multimerization, Heat-Shock Proteins, Heat-Shock Response, Protein Binding
Abstract

Hsp26 is a small heat shock protein (sHsp) from S. cerevisiae. Its chaperone activity is activated by oligomer dissociation at heat shock temperatures. Hsp26 contains 9 phosphorylation sites in different structural elements. Our analysis of phospho-mimetic mutations shows that phosphorylation activates Hsp26 at permissive temperatures. The cryo-EM structure of the Hsp26 40mer revealed contacts between the conserved core domain of Hsp26 and the so-called thermosensor domain in the N-terminal part of the protein, which are targeted by phosphorylation. Furthermore, several phosphorylation sites in the C-terminal extension, which link subunits within the oligomer, are sensitive to the introduction of negative charges. In all cases, the intrinsic inhibition of chaperone activity is relieved and the N-terminal domain becomes accessible for substrate protein binding. The weakening of domain interactions within and between subunits by phosphorylation to activate the chaperone activity in response to proteotoxic stresses independent of heat stress could be a general regulation principle of sHsps., Small heat shock proteins (sHsps) form large spherical assemblies and their regulation is not well understood. Here, the authors provide insights into the mechanism of Hsp26 activation by characterising phospho-mimetic mutants of yeast Hsp26. They present cryo-EM structures of the wild-type Hsp26 40mer and its phospho-mimetic mutants that reveal the location of the thermosensor in the oligomer, and the authors also show that the thermosensor domain is targeted by phosphorylation, which relieves the intrinsic inhibition of chaperone activity.

Published
2021

39. Pseudo-atomic model for Hsp26 residues 63 to 214. Please be advised that the target map is not of sufficient resolution to unambiguously position backbone or side chain atoms. This model represents a likely fit.

Author

Muehlhofer, M., primary, Peters, C., additional, Kriehuber, T., additional, Kreuzeder, M., additional, Kazman, P., additional, Rodina, N., additional, Reif, B., additional, Haslbeck, M., additional, Weinkauf, S., additional, and Buchner, J., additional

Published
2021
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40. Efficacy and safety of ribociclib (RIB) in combination with letrozole (LET) in patients with estrogen receptor–positive advanced breast cancer (ABC) : Secondary and exploratory results of phase 3b RIBECCA study

Author

Decker, T., Fasching, P.A., Nusch, A., Hartkopf, A., Heinrich, B.J., Kurbacher, C.M., Fuchs, R., Tesch, H., Krabisch, P., Huober, J., Kümmel, S., Brucker, S.Y., Janni, W., Schneeweiss, A., Schuler, Martin, Fehm, T.N., Lüftner, D., C. Quiering, Kreuzeder, J., and Reinisch, M.

Subjects
Medizin
Published
2021

42. Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor‐positive, human epidermal growth factor receptor 2‐negative locally advanced or metastatic breast cancer: Results of the single‐arm, phase IIIB 4EVER trial

Author

Claudia Quiering, Frederik Marmé, Christian M. Kurbacher, Florin-Andrei Taran, Christoph Mundhenke, J Kreuzeder, Thomas Decker, Wolfgang Janni, Oliver J. Stoetzer, Hans Tesch, Andrea Distelrath, Michael P. Lux, Diana Lüftner, Andreas Schneeweiss, Mathias Muth, Peter A. Fasching, and Peyman Hadji

Subjects
Oncology, Adult, Cancer Research, medicine.medical_specialty, medicine.drug_class, Receptor, ErbB-2, medicine.medical_treatment, Breast Neoplasms, Kaplan-Meier Estimate, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Exemestane, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, medicine, Clinical endpoint, Humans, Neoplasm Metastasis, Adverse effect, Cancer Therapy and Prevention, Aged, advanced breast cancer, Aged, 80 and over, Chemotherapy, Aromatase inhibitor, Everolimus, business.industry, estrogen receptor‐positive, Cancer, Middle Aged, medicine.disease, everolimus, Metastatic breast cancer, Androstadienes, Postmenopause, chemistry, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, business, Receptors, Progesterone, exemestane, HER2‐negative, medicine.drug
Abstract

In BOLERO‐2, adding everolimus to exemestane resulted in a twofold increase in median progression‐free survival (PFS) vs exemestane in postmenopausal women with hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2−) advanced breast cancer (aBC) after progression on a non‐steroidal aromatase inhibitor (NSAI). Here, we report on the open‐label, single‐arm, phase IIIB 4EVER trial (NCT01626222). This trial evaluated the clinical effectiveness of everolimus plus exemestane in postmenopausal women with HR+, HER2− aBC who had progressed on or after an NSAI, but with no restrictions on the time of progression after NSAI, prior chemotherapy for advanced disease or previous exemestane. The primary endpoint was overall response rate (ORR; i.e. the percentage of patients with a best overall response of complete or partial response per RECIST 1.1) within the first 24 weeks of treatment. Secondary endpoints included PFS, overall survival, safety and health‐related quality of life. Between June 2012 and November 2013, 299 patients were enrolled at 82 German centers: 281 patients were evaluable for efficacy and 299 for safety. The ORR was 8.9% (95% confidence interval [CI]: 5.8–12.9%). Median PFS was 5.6 months (95% CI: 5.4–6.0 months). The most frequent grade 3/4 adverse events were stomatitis (8.4%), general physical health deterioration (6.7%), dyspnea (4.7%) and anemia (4.3%). The ORR in 4EVER was lower than in BOLERO‐2, likely due to inclusion of patients with more advanced disease and extensive pretreatment. These data confirm the clinical benefits and known safety profile of everolimus plus exemestane in postmenopausal women with HR+, HER2− aBC., What's new? Current treatment guidelines for HR+, HER2– advanced breast cancer support continued endocrine therapy after progression on first‐line treatment, including the use of everolimus and exemestane combined. Here, the authors report on the phase IIIB 4EVER trial, which evaluated the efficacy, safety and quality of life effects of everolimus plus exemestane in postmenopausal women with pretreated, HR+, HER2– advanced breast cancer. The patient population was broader than that evaluated in previous major trials, and thus more reflective of real‐world practice. Overall, the results confirm the clinical benefits and known safety profile of everolimus plus exemestane in this patient population.

Published
2018

43. 247P Efficacy and safety of ribociclib (RIB) in combination with letrozole (LET) in patients with estrogen receptor–positive advanced breast cancer (ABC): Secondary and exploratory results of phase 3b RIBECCA study

Author

Andreas Schneeweiss, Wolfgang Janni, Tanja Fehm, Claudia Quiering, J Kreuzeder, Hans Tesch, Sara Y. Brucker, Mattea Reinisch, S Kümmel, Christian M. Kurbacher, Andreas D. Hartkopf, Thomas Decker, Arnd Nusch, Bernhard Heinrich, Diana Lüftner, Petra Krabisch, R. Fuchs, J Huober, Martin Schuler, and Peter A. Fasching

Subjects
Oncology, medicine.medical_specialty, business.industry, Letrozole, Advanced breast, Cancer, Estrogen receptor, Ribociclib, Hematology, medicine.disease, Internal medicine, Medicine, In patient, business, medicine.drug
Published
2021
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47. Analyse kleiner Hitzeschockproteine und deren Interaktion mit Sustratproteinen

Author

Kreuzeder, Marina Angelika, Buchner, Johannes (Prof. Dr.), and Sattler, Michael (Prof. Dr.)

Subjects
ddc:540, ddc:660, Chemie, Chemische Verfahrenstechnik
Abstract

In the present thesis, structural analysis of Hsp26 from S. cerevisiae was performed with a focus on the mode of dimerization. Furthermore, phosphomimetic Hsp26 mutants were analyzed revealing phosphorylation as a potential regulatory mechanism for Hsp26. In addition, the substrate spectra of the human proteins HspB1 to HspB7 and of the Hsp16 protein core family from C. elegans were investigated by co-imunoprecipitation and mass spectrometric approaches. In der vorliegenden Arbeit wurde Hsp26 aus S. cerevisiae strukturell, vor allem hinsichtlich der Art der Dimerisierung, untersucht. Des Weiteren wurden phophomimetische Hsp26 Mutanten analysiert und die mögliche Regulation von Hsp26 durch Phosphorylierung aufgezeigt. Außerdem wurden die Substratspektren der humanen Proteine HspB1 bis HspB7 und der Hsp16 Kernfamilie aus C. elegans mithilfe von Co-Immunopräzipitation und massenspektrometrischen Analysen bestimmt.

Published
2019

49. The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial

Author

Oliver Stoetzer, Christoph Mundhenke, Eva-Marie Grischke, Peyman Hadji, Wolfgang Janni, Hans Tesch, Frederik Marmé, Christian M. Kurbacher, Thomas Decker, Andreas Schneeweiss, Diana Lüftner, Mathias Muth, J Kreuzeder, Peter A. Fasching, Andrea Distelrath, Michael P. Lux, and Claudia Quiering

Subjects
0301 basic medicine, Oncology, lcsh:Diseases of the musculoskeletal system, Parathyroid hormone, Bone remodeling, NSAI, non-steroidal aromatase inhibitor, chemistry.chemical_compound, Breast cancer, PR, partial response, 0302 clinical medicine, Exemestane, PTH, parathyroid hormone, HER2-negative, human epidermal growth factor receptor 2-negative, Mammalian target of rapamycin, OR, overall response, biology, 25-OH-vitamin D, 25-hydroxyvitamin D, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, CTX, C-terminal cross-linking telopeptide of type 1 collagen, Metastatic breast cancer, PFS, progression-free survival, ORR24w, overall response rate within the first 24 weeks of treatment, 030220 oncology & carcinogenesis, CR, complete response, Osteocalcin, SRE, skeletal-related event, Research Article, ORR, overall response rate, medicine.drug, medicine.medical_specialty, mTOR, mammalian target of rapamycin, HR +, hormone receptor-positive, lcsh:RC254-282, Bone health, P1NP, procollagen type 1 N-terminal peptide, 03 medical and health sciences, N-terminal telopeptide, Internal medicine, Hormone receptor-positive, medicine, Everolimus, Bone marker, Art, antiresorptive therapy, business.industry, medicine.disease, HR, hazard ratio, CI, confidence interval, 030104 developmental biology, chemistry, biology.protein, BSAP, bone-specific alkaline phosphatase, lcsh:RC925-935, SD, standard deviation, business
Abstract

Background: Breast cancer and its treatments are associated with a detrimental effect on bone health. Here we report the results of an exploratory analysis assessing changes in levels of biomarkers of bone metabolism in patients enrolled in the phase IIIb 4EVER study. Methods: The 4EVER trial investigated everolimus in combination with exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. In this prespecified exploratory analysis, changes in biomarkers of bone turnover were assessed in patients from baseline to weeks 4, 12, and 24. The serum bone markers assessed were procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25-OH-vitamin D). On-treatment changes in bone markers over time were described per subgroup of interest and efficacy outcomes. Results: Bone marker data were available for 241 of 299 enrolled patients. At the final assessment, P1NP, osteocalcin, PTH, 25-OH-vitamin D (all P

Published
2018

50. Abstract P5-19-12: Subgroup analysis on efficacy in the routine treatment - Results of the 2nd interim analysis of BRAWO, the non-interventional trial 'Breast Cancer Treatment with Everolimus and Exemestane for HR+ Women'

Author

Hans Tesch, Nadia Harbeck, J Kreuzeder, Sherko Kuemmel, Christoph Mundhenke, Christian Jackisch, Andreas Schneeweiss, Mathias Muth, Christian M. Kurbacher, Oliver Tomé, Christoph Uleer, Eva-Maria Grischke, Bettina Mueller, Florian Schütz, Diana Lüftner, Peter A. Fasching, Wilhelm Bloch, Thomas Decker, Pauline Wimberger, and F Förster

Subjects
Gerontology, Cancer Research, medicine.medical_specialty, Everolimus, business.industry, Cancer, Subgroup analysis, Interim analysis, medicine.disease, chemistry.chemical_compound, Breast cancer, Oncology, Exemestane, chemistry, Quality of life, Internal medicine, medicine, Medical history, business, medicine.drug
Abstract

Introduction BRAWO is a German non-interventional study of 3000 patients (pts) with advanced or metastatic, hormone-receptor-positive, HER2-negative breast cancer treated with everolimus (EVE) and exemestane (EXE). We report results of the 2nd preplanned interim analysis (IA) with a data cut-off on 8th July 2014. Methods BRAWO collects data on the routine clinical treatment with EVE and EXE at about 400 sites. Main objectives are to extend the knowledge on a) the efficacy in the clinical routine and the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis, and c) the sequence of therapy in the clinical routine. The 2nd IA was defined to take place 12 months after the inclusion of the 500. patient into the documentation. Results Efficacy data will be reported for the first 500 documented pts. Apart from data on the total study population we will present the PFS results for subgroups including pts with or without prior EXE therapy, with or without prior chemotherapy for the advanced setting, with or without visceral metastasis and with regard to the line of treatment in the advanced setting and the extent of physical activity. The respective summary of adverse events for these patients will be presented as well as results on treatment compliance and dosing. Baseline characteristics and medical history as well as insights into treatment sequences before EVE and EXE will further be shown for all enrolled patients with valid baseline documentation (approx. 1200). Conclusion This subgroup analysis will provide insights into the treatment efficacy in the clinical routine and will add to a more comprehensive understanding of the treatment with EVE/EXE. Citation Format: Christian Jackisch, Eva-Maria Grischke, Andreas Schneeweiss, Thomas Decker, Christoph Uleer, Frank Förster, Oliver Tomé, Pauline Wimberger, Christian M Kurbacher, Bettina Mueller, Nadia Harbeck, Christoph Mundhenke, Sherko Kuemmel, Mathias Muth, Julia Kreuzeder, Wilhelm Bloch, Hans Tesch, Diana Lüftner, Florian Schütz, Peter A Fasching. Subgroup analysis on efficacy in the routine treatment - Results of the 2nd interim analysis of BRAWO, the non-interventional trial "Breast Cancer Treatment with Everolimus and Exemestane for HR+ Women" [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-12.

Published
2015
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