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254 results on '"Miro S"'

9. Uncertainties and robustness with regard to the safety of a repository for high-level radioactive waste: introduction of a research initiative

Author

Kurgyis, K., Achtziger-Zupančič, P., Bjorge, M., Boxberg, M.S., Broggi, M., Buchwald, Jörg, Ernst, O.G., Flügge, J., Ganopolski, A., Graf, T., Kortenbruck, P., Kowalski, J., Kreye, P., Kukla, P., Mayr, S., Miro, S., Nagel, T., Nowak, W., Oladyshkin, S., Renz, A., Rienäcker-Burschil, J., Röhlig, K.-J., Sträter, O., Thiedau, J., Wagner, F., Wellmann, F., Wengler, M., Wolf, J., Rühaak, W., Kurgyis, K., Achtziger-Zupančič, P., Bjorge, M., Boxberg, M.S., Broggi, M., Buchwald, Jörg, Ernst, O.G., Flügge, J., Ganopolski, A., Graf, T., Kortenbruck, P., Kowalski, J., Kreye, P., Kukla, P., Mayr, S., Miro, S., Nagel, T., Nowak, W., Oladyshkin, S., Renz, A., Rienäcker-Burschil, J., Röhlig, K.-J., Sträter, O., Thiedau, J., Wagner, F., Wellmann, F., Wengler, M., Wolf, J., and Rühaak, W.

Abstract

The Federal Company for Radioactive Waste Disposal (BGE mbH) is tasked with the selection of a site for a high-level radioactive waste repository in Germany in accordance with the Repository Site Selection Act. In September 2020, 90 areas with favorable geological conditions were identified as part of step 1 in phase 1 of the Site Selection Act. Representative preliminary safety analyses are to be carried out next  to support decisions on the question, which siting regions should undergo surface-based exploration. These safety analyses are supported by numerical simulations building on geoscientific and technical data. The models that are taken into account are associated with various sources of uncertainties. Addressing these uncertainties and the robustness of the decisions pertaining to sites and design choices is a central component of the site selection process. In that context, important research objectives are associated with the question of how uncertainty should be treated through the various data collection, modeling and decision-making processes of the site selection procedure, and how the robustness of the repository system should be improved. BGE, therefore, established an interdisciplinary research cluster to identify open questions and to address the gaps in knowledge in six complementary research projects. In this paper, we introduce the overall purpose and the five thematic groups that constitute this research cluster. We discuss the specific questions addressed as well as the proposed methodologies in the context of the challenges of the site selection process in Germany. Finally, some conclusions are drawn on the potential benefits of a large method-centered research cluster in terms of simulation data management.

Published
2024

19. Increased PD-1 expression in livers associated with PD-1-antibody-induced hepatotoxicity

Author

Miro Saarela, Essi Parviainen, Ana Lleo, Luca di Tommaso, Hanna Raunio, Krista Kankaanranta, Katri Vuopala, Aino Rönkä, Sini Nurmenniemi, Raija Kallio, Arja Jukkola, and Katri S. Selander

Subjects
Checkpoint inhibitors, Adverse event, Lymphocyte infiltration, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Vanishing bile duct syndrome (VBDS) is a serious drug induced liver injury characterized by chronic cholestasis and loss of intrahepatic bile ducts. VBDS has been reported also following checkpoint inhibitor treatment. We compared CD3 + , CD4 + , CD8 + , CD20 + , CD57 + , PD-1 + and PD-L1 + lymphocyte infiltrates in liver biopsies of patients that encountered VBDS (n = 2) or hepatotoxicity (n = 3) after pembrolizumab (n = 4) or nivolumab (n = 1) treatment with samples from normal liver (n = 10), non-alcohol steatohepatitis (NASH, n = 10), primary biliary cholangitis (PBC, n = 10) or pembrolizumab-treated patients without adverse events (n = 2). Notably, none of the cancer patients had primary nor metastatic liver tumors. We also studied direct growth effects of pembrolizumab on primary human intrahepatic biliary epithelial cells (HIBEpiC) in vitro. Liver sections of all checkpoint inhibitor- treated patients exhibited significantly higher CD3 + infiltration than normal livers, and significantly higher PD-L1 + , CD4 + and CD8 + infiltration, than other groups. PD-1 + infiltration was significantly increased in livers of patients with severe hepatic adverse event. CD57 + infiltration was similar in normal livers, NASH- and PBC groups, but highly increased in the checkpoint inhibitor-treated patients. Immune cell infiltrates were similar between NASH and normal livers. PBC samples had significantly higher CD3 + , CD4 + , CD8 + and CD20 + infiltrates than normal livers. HIBEpiC express PD-L1 but pembrolizumab did not affect their viability in vitro. Our findings suggest that VBDS is not due to direct cytotoxicity of checkpoint inhibitors and that the immunological attack against livers induced by these drugs is different from other cholestatic liver conditions. Biological insight: Checkpoint inhibitors upregulate PD-1 and PD-L1, as well as cytotoxic CD57 + cells in the non-cancerous liver tissues and this may be associated with checkpoint inhibitor-induced hepatotoxicity.

Published
2025
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36. Radiation effects in nuclear materials: Role of nuclear and electronic energy losses and their synergy

Author

Thomé, Lionel, Debelle, A., Garrido, F., Mylonas, S., Décamps, B., Bachelet, C., Sattonnay, G., Moll, S., Pellegrino, S., Miro, S., Trocellier, P., Serruys, Y., Velisa, G., Grygiel, C., Monnet, I., Toulemonde, M., Simon, P., Jagielski, J., Jozwik-Biala, I., Nowicki, L., Behar, M., Weber, W.J., Zhang, Y., Backman, M., Nordlund, K., and Djurabekova, F.

Published
2013
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48. Approach of He/dpa Synergistic Effects in Iron-Based Materials Using JANNUS

Author

Trocellier, P., primary, Serruys, Y., additional, Miro, S., additional, Bordas, E., additional, Martin, H., additional, Beck, L., additional, Pellegrino, S., additional, Chaâbane, N., additional, Vaubaillon, S., additional, Meslin, E., additional, Barbu, A., additional, Brimbal, D., additional, Henry, J., additional, Robertson, C., additional, Décamps, B., additional, Fluss, M., additional, Tumey, S., additional, Hsiung, L., additional, Schaüblin, R., additional, and Panigrahi, B. K., additional

Published
2012
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49. Use of MeV Ion Beams to Simulate the Irradiation Effects in Advanced Materials at JANNUS Saclay

Author

Trocellier, P., primary, Serruys, Y., additional, Miro, S., additional, Bordas, E., additional, Martin, H., additional, Beck, L., additional, Pellegrino, S., additional, Chaâbane, N., additional, Vaubaillon, S., additional, Meslin, E., additional, Barbu, A., additional, Brimbal, D., additional, Henry, J., additional, Décamps, B., additional, Fluss, M., additional, Tumey, S., additional, and Hsiung, L., additional

Published
2012
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