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1. MuCol Milestone Report No. 5: Preliminary Parameters

Author

Accettura, Carlotta, Adrian, Simon, Agarwal, Rohit, Ahdida, Claudia, Aimé, Chiara, Aksoy, Avni, Alberghi, Gian Luigi, Alden, Siobhan, Alfonso, Luca, Amapane, Nicola, Amorim, David, Andreetto, Paolo, Anulli, Fabio, Appleby, Rob, Apresyan, Artur, Asadi, Pouya, Mahmoud, Mohammed Attia, Auchmann, Bernhard, Back, John, Badea, Anthony, Bae, Kyu Jung, Bahng, E. J., Balconi, Lorenzo, Balli, Fabrice, Bandiera, Laura, Barbagallo, Carmelo, Barlow, Roger, Bartoli, Camilla, Bartosik, Nazar, Barzi, Emanuela, Batsch, Fabian, Bauce, Matteo, Begel, Michael, Berg, J. Scott, Bersani, Andrea, Bertarelli, Alessandro, Bertinelli, Francesco, Bertolin, Alessandro, Bhat, Pushpalatha, Bianchi, Clarissa, Bianco, Michele, Bishop, William, Black, Kevin, Boattini, Fulvio, Bogacz, Alex, Bonesini, Maurizio, Bordini, Bernardo, de Sousa, Patricia Borges, Bottaro, Salvatore, Bottura, Luca, Boyd, Steven, Breschi, Marco, Broggi, Francesco, Brunoldi, Matteo, Buffat, Xavier, Buonincontri, Laura, Burrows, Philip Nicholas, Burt, Graeme Campbell, Buttazzo, Dario, Caiffi, Barbara, Calatroni, Sergio, Calviani, Marco, Calzaferri, Simone, Calzolari, Daniele, Cantone, Claudio, Capdevilla, Rodolfo, Carli, Christian, Carrelli, Carlo, Casaburo, Fausto, Casarsa, Massimo, Castelli, Luca, Catanesi, Maria Gabriella, Cavallucci, Lorenzo, Cavoto, Gianluca, Celiberto, Francesco Giovanni, Celona, Luigi, Cemmi, Alessia, Ceravolo, Sergio, Cerri, Alessandro, Cerutti, Francesco, Cesarini, Gianmario, Cesarotti, Cari, Chancé, Antoine, Charitonidis, Nikolaos, Chiesa, Mauro, Chiggiato, Paolo, Ciccarella, Vittoria Ludovica, Puviani, Pietro Cioli, Colaleo, Anna, Colao, Francesco, Collamati, Francesco, Costa, Marco, Craig, Nathaniel, Curtin, David, Damerau, Heiko, Da Molin, Giacomo, D'Angelo, Laura, Dasu, Sridhara, de Blas, Jorge, De Curtis, Stefania, De Gersem, Herbert, Delahaye, Jean-Pierre, Del Moro, Tommaso, Denisov, Dmitri, Denizli, Haluk, Dermisek, Radovan, Valdor, Paula Desiré, Desponds, Charlotte, Di Luzio, Luca, Di Meco, Elisa, Diociaiuti, Eleonora, Di Petrillo, Karri Folan, Di Sarcina, Ilaria, Dorigo, Tommaso, Dreimanis, Karlis, Pree, Tristan du, Yildiz, Hatice Duran, Edgecock, Thomas, Fabbri, Siara, Fabbrichesi, Marco, Farinon, Stefania, Ferrand, Guillaume, Somoza, Jose Antonio Ferreira, Fieg, Max, Filthaut, Frank, Fox, Patrick, Franceschini, Roberto, Ximenes, Rui Franqueira, Gallinaro, Michele, Garcia-Sciveres, Maurice, Garcia-Tabares, Luis, Gargiulo, Ruben, Garion, Cedric, Garzelli, Maria Vittoria, Gast, Marco, Generoso, Lisa, Gerber, Cecilia E., Giambastiani, Luca, Gianelle, Alessio, Gianfelice-Wendt, Eliana, Gibson, Stephen, Gilardoni, Simone, Giove, Dario Augusto, Giovinco, Valentina, Giraldin, Carlo, Glioti, Alfredo, Gorzawski, Arkadiusz, Greco, Mario, Grojean, Christophe, Grudiev, Alexej, Gschwendtner, Edda, Gueli, Emanuele, Guilhaudin, Nicolas, Han, Chengcheng, Han, Tao, Hauptman, John Michael, Herndon, Matthew, Hillier, Adrian D, Hillman, Micah, Holmes, Tova Ray, Homiller, Samuel, Jana, Sudip, Jindariani, Sergo, Johannesson, Sofia, Johnson, Benjamin, Jones, Owain Rhodri, Jurj, Paul-Bogdan, Kahn, Yonatan, Kamath, Rohan, Kario, Anna, Karpov, Ivan, Kelliher, David, Kilian, Wolfgang, Kitano, Ryuichiro, Kling, Felix, Kolehmainen, Antti, Kong, K. C., Kosse, Jaap, Krintiras, Georgios, Krizka, Karol, Kumar, Nilanjana, Kvikne, Erik, Kyle, Robert, Laface, Emanuele, Lane, Kenneth, Latina, Andrea, Lechner, Anton, Lee, Junghyun, Lee, Lawrence, Lee, Seh Wook, Lefevre, Thibaut, Leonardi, Emanuele, Lerner, Giuseppe, Li, Peiran, Li, Qiang, Li, Tong, Li, Wei, Lindroos, Mats, Lipton, Ronald, Liu, Da, Liu, Miaoyuan, Liu, Zhen, Voti, Roberto Li, Lombardi, Alessandra, Lomte, Shivani, Long, Kenneth, Longo, Luigi, Lorenzo, José, Losito, Roberto, Low, Ian, Lu, Xianguo, Lucchesi, Donatella, Luo, Tianhuan, Lupato, Anna, Ma, Yang, Machida, Shinji, Madlener, Thomas, Magaletti, Lorenzo, Maggi, Marcello, Durand, Helene Mainaud, Maltoni, Fabio, Manczak, Jerzy Mikolaj, Mandurrino, Marco, Marchand, Claude, Mariani, Francesco, Marin, Stefano, Mariotto, Samuele, Martin-Haugh, Stewart, Masullo, Maria Rosaria, Mauro, Giorgio Sebastiano, Mazzolari, Andrea, Mękała, Krzysztof, Mele, Barbara, Meloni, Federico, Meng, Xiangwei, Mentink, Matthias, Métral, Elias, Miceli, Rebecca, Milas, Natalia, Mohammadi, Abdollah, Moll, Dominik, Montella, Alessandro, Morandin, Mauro, Morrone, Marco, Mulder, Tim, Musenich, Riccardo, Nardecchia, Marco, Nardi, Federico, Nenna, Felice, Neuffer, David, Newbold, David, Novelli, Daniel, Olvegård, Maja, Onel, Yasar, Orestano, Domizia, Osborne, John, Otten, Simon, Torres, Yohan Mauricio Oviedo, Paesani, Daniele, Griso, Simone Pagan, Pagani, Davide, Pal, Kincso, Palmer, Mark, Pampaloni, Alessandra, Panci, Paolo, Pani, Priscilla, Papaphilippou, Yannis, Paparella, Rocco, Paradisi, Paride, Passeri, Antonio, Pasternak, Jaroslaw, Pastrone, Nadia, Pellecchia, Antonello, Piccinini, Fulvio, Piekarz, Henryk, Pieloni, Tatiana, Plouin, Juliette, Portone, Alfredo, Potamianos, Karolos, Potdevin, Joséphine, Prestemon, Soren, Puig, Teresa, Qiang, Ji, Quettier, Lionel, Rabemananjara, Tanjona Radonirina, Radicioni, Emilio, Radogna, Raffaella, Rago, Ilaria Carmela, Ratkus, Andris, Resseguie, Elodie, Reuter, Juergen, Ribani, Pier Luigi, Riccardi, Cristina, Ricciardi, Stefania, Robens, Tania, Robert, Youri, Rogers, Chris, Rojo, Juan, Romagnoni, Marco, Ronald, Kevin, Rosser, Benjamin, Rossi, Carlo, Rossi, Lucio, Rozanov, Leo, Ruhdorfer, Maximilian, Ruiz, Richard, Saini, Saurabh, Sala, Filippo, Salierno, Claudia, Salmi, Tiina, Salvini, Paola, Salvioni, Ennio, Sammut, Nicholas, Santini, Carlo, Saputi, Alessandro, Sarra, Ivano, Scarantino, Giuseppe, Schneider-Muntau, Hans, Schulte, Daniel, Scifo, Jessica, Sen, Tanaji, Senatore, Carmine, Senol, Abdulkadir, Sertore, Daniele, Sestini, Lorenzo, Rêgo, Ricardo César Silva, Simone, Federica Maria, Skoufaris, Kyriacos, Sorbello, Gino, Sorbi, Massimo, Sorti, Stefano, Soubirou, Lisa, Spataro, David, Queiroz, Farinaldo S., Stamerra, Anna, Stapnes, Steinar, Stark, Giordon, Statera, Marco, Stechauner, Bernd Michael, Su, Shufang, Su, Wei, Sun, Xiaohu, Sytov, Alexei, Tang, Jian, Tang, Jingyu, Taylor, Rebecca, Kate, Herman Ten, Testoni, Pietro, Thiele, Leonard Sebastian, Garcia, Rogelio Tomas, Topp-Mugglestone, Max, Torims, Toms, Torre, Riccardo, Tortora, Luca, Tortora, Ludovico, Trifinopoulos, Sokratis, Udongwo, Sosoho-Abasi, Vai, Ilaria, Valente, Riccardo Umberto, van Rienen, Ursula, Van Weelderen, Rob, Vanwelde, Marion, Velev, Gueorgui, Venditti, Rosamaria, Vendrasco, Adam, Verna, Adriano, Vernassa, Gianluca, Verweij, Arjan, Verwilligen, Piet, Villamizar, Yoxara, Vittorio, Ludovico, Vitulo, Paolo, Vojskovic, Isabella, Wang, Dayong, Wang, Lian-Tao, Wang, Xing, Wendt, Manfred, Widorski, Markus, Wozniak, Mariusz, Wu, Yongcheng, Wulzer, Andrea, Xie, Keping, Yang, Yifeng, Yap, Yee Chinn, Yonehara, Katsuya, Yoo, Hwi Dong, You, Zhengyun, Zanetti, Marco, Zaza, Angela, Zhang, Liang, Zhu, Ruihu, Zlobin, Alexander, Zuliani, Davide, and Zurita, José Francisco

Subjects
Physics - Accelerator Physics
Abstract

This document is comprised of a collection of updated preliminary parameters for the key parts of the muon collider. The updated preliminary parameters follow on from the October 2023 Tentative Parameters Report. Particular attention has been given to regions of the facility that are believed to hold greater technical uncertainty in their design and that have a strong impact on the cost and power consumption of the facility. The data is collected from a collaborative spreadsheet and transferred to overleaf.

Published
2024
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2. Young Citizens' Views and Engagement in a Changing Europe: IEA International Civic and Citizenship Education Study 2022 European Report

Author

International Association for the Evaluation of Educational Achievement (IEA) (Netherlands), Australian Council for Educational Research (ACER), Valeria Damiani, Bruno Losito, Gabriella Agrusti, and Wolfram Schulz

Abstract

The IEA's International Civic and Citizenship Education Study (ICCS) investigates the ways in which young people around the world are prepared to undertake their roles as citizens. This report presents the European results from the third cycle of the study (ICCS 2022). Eighteen countries and two benchmarking participants (the German states of North Rhine-Westphalia and Schleswig-Holstein) administered the European student questionnaire to target grade students in this study cycle. ICCS 2022 studied contexts for and learning outcomes of civic and citizenship education in a wide range of national contexts at the beginning of the third decade of the 21st Century. The general purpose of the European student questionnaire is to explore specific European-related civic and citizenship issues derived from the overarching ICCS 2022 assessment framework, supplementing the data obtained from the international survey with a specific European perspective. The ICCS 2022 European student questionnaire included 12 questions aimed at examining students' interest and their opinions regarding European-related civic and citizenship issues such as students' sense of European identity; students' opportunities for learning about Europe provided by schools; and students' attitudes toward free movement of European citizens within Europe, toward the European Union, and toward cooperation among European countries. It also encompasses questions on students' perceptions of discrimination in their country, of the future of Europe, and of their life in the future, as well as on students' sustainable behaviors and those related to political and ethical consumerism. Over the past 50 years, the IEA has conducted comparative research studies in a range of domains focusing on educational policies, practices, and outcomes in many countries around the world. Prior to ICCS 2022, the IEA had conducted four international comparative studies of civic and citizenship education, with a first survey implemented in 1971, a second in 1999, a third in 2009 and a fourth in 2016. ICCS 2022 data will allow education systems to evaluate the strengths of educational policies, both internationally and in the European regional context, and to measure progress in achieving critical social objectives of their educational policy. [This report was jointly prepared by Libera Università Maria Santissima Assunta (LUMSA Università -- Rome, Italy).]

Published
2024

3. Report on the Advanced Linear Collider Study Group (ALEGRO) Workshop 2024

Author

Vieira, J., Cros, B., Muggli, P., Andriyash, I. A., Apsimon, O., Backhouse, M., Benedetti, C., Bulanov, S. S., Caldwell, A., Chen, Min, Cilento, V., Corde, S., D'Arcy, R., Diederichs, S., Ericson, E., Esarey, E., Farmer, J., Fedeli, L., Formenti, A., Foster, B., Garten, M., Geddes, C. G. R., Grismayer, T., Hogan, M. J., Hooker, S., Huebl, A., Jalas, S., Kirchen, M., Lehe, R., Leemans, W., Li, Boyuan, Lindström, C. A., Losito, R., Mitchell, C. E., Mori, W. B., Piot, P., Terzani, D., Thévenet, M., Turner, M., Vay, J. -L., Völker, D., Zhang, Jie, and Zhang, W.

Subjects
Physics - Accelerator Physics
Abstract

The workshop focused on the application of ANAs to particle physics keeping in mind the ultimate goal of a collider at the energy frontier (10\,TeV, e$^+$/e$^-$, e$^-$/e$^-$, or $\gamma\gamma$). The development of ANAs is conducted at universities and national laboratories worldwide. The community is thematically broad and diverse, in particular since lasers suitable for ANA research (multi-hundred-terawatt peak power, a few tens of femtosecond-long pulses) and acceleration of electrons to hundreds of mega electron volts to multi giga electron volts became commercially available. The community spans several continents (Europe, America, Asia), including more than 62 laboratories in more than 20 countries. It is among the missions of the ICFA-ANA panel to feature the amazing progress made with ANAs, to provide international coordination and to foster international collaborations towards a future HEP collider. The scope of this edition of the workshop was to discuss the recent progress and necessary steps towards realizing a linear collider for particle physics based on novel-accelerator technologies (laser or beam driven in plasma or structures). Updates on the relevant aspects of the European Strategy for Particle Physics (ESPP) Roadmap Process as well as of the P5 (in the US) were presented, and ample time was dedicated to discussions. The major outcome of the workshop is the decision for ALEGRO to coordinate efforts in Europe, in the US, and in Asia towards a pre-CDR for an ANA-based, 10\,TeV CM collider. This goal of this coordination is to lead to a funding proposal to be submitted to both EU and EU/US funding agencies. This document presents a summary of the workshop, as seen by the co-chairs, as well as short 'one-pagers' written by the presenters at the workshop., Comment: 72 pages

Published
2024

4. Interim report for the International Muon Collider Collaboration (IMCC)

Author

Accettura, C., Adrian, S., Agarwal, R., Ahdida, C., Aimé, C., Aksoy, A., Alberghi, G. L., Alden, S., Amapane, N., Amorim, D., Andreetto, P., Anulli, F., Appleby, R., Apresyan, A., Asadi, P., Mahmoud, M. Attia, Auchmann, B., Back, J., Badea, A., Bae, K. J., Bahng, E. J., Balconi, L., Balli, F., Bandiera, L., Barbagallo, C., Barlow, R., Bartoli, C., Bartosik, N., Barzi, E., Batsch, F., Bauce, M., Begel, M., Berg, J. S., Bersani, A., Bertarelli, A., Bertinelli, F., Bertolin, A., Bhat, P., Bianchi, C., Bianco, M., Bishop, W., Black, K., Boattini, F., Bogacz, A., Bonesini, M., Bordini, B., de Sousa, P. Borges, Bottaro, S., Bottura, L., Boyd, S., Breschi, M., Broggi, F., Brunoldi, M., Buffat, X., Buonincontri, L., Burrows, P. N., Burt, G. C., Buttazzo, D., Caiffi, B., Calatroni, S., Calviani, M., Calzaferri, S., Calzolari, D., Cantone, C., Capdevilla, R., Carli, C., Carrelli, C., Casaburo, F., Casarsa, M., Castelli, L., Catanesi, M. G., Cavallucci, L., Cavoto, G., Celiberto, F. G., Celona, L., Cemmi, A., Ceravolo, S., Cerri, A., Cerutti, F., Cesarini, G., Cesarotti, C., Chancé, A., Charitonidis, N., Chiesa, M., Chiggiato, P., Ciccarella, V. L., Puviani, P. Cioli, Colaleo, A., Colao, F., Collamati, F., Costa, M., Craig, N., Curtin, D., D'Angelo, L., Da Molin, G., Damerau, H., Dasu, S., de Blas, J., De Curtis, S., De Gersem, H., Del Moro, T., Delahaye, J. -P., Denisov, D., Denizli, H., Dermisek, R., Valdor, P. Desiré, Desponds, C., Di Luzio, L., Di Meco, E., Di Petrillo, K. F., Di Sarcina, I., Diociaiuti, E., Dorigo, T., Dreimanis, K., Pree, T. du, Edgecock, T., Fabbri, S., Fabbrichesi, M., Farinon, S., Ferrand, G., Somoza, J. A. Ferreira, Fieg, M., Filthaut, F., Fox, P., Franceschini, R., Ximenes, R. Franqueira, Gallinaro, M., Garcia-Sciveres, M., Garcia-Tabares, L., Gargiulo, R., Garion, C., Garzelli, M. V., Gast, M., Gerber, C. E., Giambastiani, L., Gianelle, A., Gianfelice-Wendt, E., Gibson, S., Gilardoni, S., Giove, D. A., Giovinco, V., Giraldin, C., Glioti, A., Gorzawski, A., Greco, M., Grojean, C., Grudiev, A., Gschwendtner, E., Gueli, E., Guilhaudin, N., Han, C., Han, T., Hauptman, J. M., Herndon, M., Hillier, A. D., Hillman, M., Holmes, T. R., Homiller, S., Jana, S., Jindariani, S., Johannesson, S., Johnson, B., Jones, O. R., Jurj, P. -B., Kahn, Y., Kamath, R., Kario, A., Karpov, I., Kelliher, D., Kilian, W., Kitano, R., Kling, F., Kolehmainen, A., Kong, K. C., Kosse, J., Krintiras, G., Krizka, K., Kumar, N., Kvikne, E., Kyle, R., Laface, E., Lane, K., Latina, A., Lechner, A., Lee, J., Lee, L., Lee, S. W., Lefevre, T., Leonardi, E., Lerner, G., Li, P., Li, Q., Li, T., Li, W., Voti, R. Li, Lindroos, M., Lipton, R., Liu, D., Liu, M., Liu, Z., Lombardi, A., Lomte, S., Long, K., Longo, L., Lorenzo, J., Losito, R., Low, I., Lu, X., Lucchesi, D., Luo, T., Lupato, A., Métral, E., Mękała, K., Ma, Y., Mańczak, J. M., Machida, S., Madlener, T., Magaletti, L., Maggi, M., Durand, H. Mainaud, Maltoni, F., Mandurrino, M., Marchand, C., Mariani, F., Marin, S., Mariotto, S., Martin-Haugh, S., Masullo, M. R., Mauro, G. S., Mazzolari, A., Mele, B., Meloni, F., Meng, X., Mentink, M., Miceli, R., Milas, N., Mohammadi, A., Moll, D., Montella, A., Morandin, M., Morrone, M., Mulder, T., Musenich, R., Nardecchia, M., Nardi, F., Neuffer, D., Newbold, D., Novelli, D., Olvegård, M., Onel, Y., Orestano, D., Osborne, J., Otten, S., Torres, Y. M. Oviedo, Paesani, D., Griso, S. Pagan, Pagani, D., Pal, K., Palmer, M., Pampaloni, A., Panci, P., Pani, P., Papaphilippou, Y., Paparella, R., Paradisi, P., Passeri, A., Pastrone, N., Pellecchia, A., Piccinini, F., Piekarz, H., Pieloni, T., Plouin, J., Portone, A., Potamianos, K., Potdevin, J., Prestemon, S., Puig, T., Qiang, J., Quettier, L., Rabemananjara, T. R., Radicioni, E., Radogna, R., Rago, I. C., Ratkus, A., Resseguie, E., Reuter, J., Ribani, P. L., Riccardi, C., Ricciardi, S., Robens, T., Robert, Y., Roger, C., Rojo, J., Romagnoni, M., Ronald, K., Rosser, B., Rossi, C., Rossi, L., Rozanov, L., Ruhdorfer, M., Ruiz, R., Queiroz, F. S., Saini, S., Sala, F., Salierno, C., Salmi, T., Salvini, P., Salvioni, E., Sammut, N., Santini, C., Saputi, A., Sarra, I., Scarantino, G., Schneider-Muntau, H., Schulte, D., Scifo, J., Sen, T., Senatore, C., Senol, A., Sertore, D., Sestini, L., Rêgo, R. C. Silva, Simone, F. M., Skoufaris, K., Sorbello, G., Sorbi, M., Sorti, S., Soubirou, L., Spataro, D., Stamerra, A., Stapnes, S., Stark, G., Statera, M., Stechauner, B. M., Su, S., Su, W., Sun, X., Sytov, A., Tang, J., Taylor, R., Kate, H. Ten, Testoni, P., Thiele, L. S., Garcia, R. Tomas, Mugglestone, M. Topp, Torims, T., Torre, R., Tortora, L. T., Trifinopoulos, S., Udongwo, S. -A., Vai, I., Valente, R. U., van Rienen, U., van Weelderen, R., Vanwelde, M., Velev, G., Venditti, R., Vendrasco, A., Verna, A., Verweij, A., Verwilligen, P., Villamzar, Y., Vittorio, L., Vitulo, P., Vojskovic, I., Wang, D., Wang, L. -T., Wang, X., Wendt, M., Widorski, M., Wozniak, M., Wu, Y., Wulzer, A., Xie, K., Yang, Y., Yap, Y. C., Yonehara, K., Yoo, H. D., You, Z., Zanetti, M., Zaza, A., Zhang, L., Zhu, R., Zlobin, A., Zuliani, D., and Zurita, J. F.

Subjects
Physics - Accelerator Physics, High Energy Physics - Experiment
Abstract

The International Muon Collider Collaboration (IMCC) [1] was established in 2020 following the recommendations of the European Strategy for Particle Physics (ESPP) and the implementation of the European Strategy for Particle Physics-Accelerator R&D Roadmap by the Laboratory Directors Group [2], hereinafter referred to as the the European LDG roadmap. The Muon Collider Study (MuC) covers the accelerator complex, detectors and physics for a future muon collider. In 2023, European Commission support was obtained for a design study of a muon collider (MuCol) [3]. This project started on 1st March 2023, with work-packages aligned with the overall muon collider studies. In preparation of and during the 2021-22 U.S. Snowmass process, the muon collider project parameters, technical studies and physics performance studies were performed and presented in great detail. Recently, the P5 panel [4] in the U.S. recommended a muon collider R&D, proposed to join the IMCC and envisages that the U.S. should prepare to host a muon collider, calling this their "muon shot". In the past, the U.S. Muon Accelerator Programme (MAP) [5] has been instrumental in studies of concepts and technologies for a muon collider., Comment: This document summarises the International Muon Collider Collaboration (IMCC) progress and status of the Muon Collider R&D programme

Published
2024

6. Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study

Author

Giacobbe, Daniele Roberto, Labate, Laura, Russo Artimagnella, Chiara, Marelli, Cristina, Signori, Alessio, Di Pilato, Vincenzo, Aldieri, Chiara, Bandera, Alessandra, Briano, Federica, Cacopardo, Bruno, Calabresi, Alessandra, Capra Marzani, Federico, Carretta, Anna, Cattelan, Annamaria, Ceccarelli, Luca, Cenderello, Giovanni, Corcione, Silvia, Cortegiani, Andrea, Cultrera, Rosario, De Rosa, Francesco Giuseppe, Del Bono, Valerio, Del Puente, Filippo, Fanelli, Chiara, Fava, Fiorenza, Francisci, Daniela, Geremia, Nicholas, Graziani, Lucia, Lombardi, Andrea, Losito, Angela Raffaella, Maida, Ivana, Marino, Andrea, Mazzitelli, Maria, Merli, Marco, Monardo, Roberta, Mularoni, Alessandra, Oltolini, Chiara, Pallotto, Carlo, Pontali, Emanuele, Raffaelli, Francesca, Rinaldi, Matteo, Ripa, Marco, Santantonio, Teresa Antonia, Serino, Francesco Saverio, Spinicci, Michele, Torti, Carlo, Trecarichi, Enrico Maria, Tumbarello, Mario, Mikulska, Malgorzata, Giacomini, Mauro, Marchese, Anna, Vena, Antonio, and Bassetti, Matteo

Published
2024
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13. General Overview

Author

Damiani, Valeria, Losito, Bruno, Agrusti, Gabriella, Schulz, Wolfram, Damiani, Valeria, Losito, Bruno, Agrusti, Gabriella, and Schulz, Wolfram

Published
2025
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14. Explaining Variation in Civic Learning Outcomes

Author

Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, and Friedman, Tim

Published
2025
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15. Conclusion

Author

Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, and Friedman, Tim

Published
2025
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16. Civic Knowledge

Author

Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, and Friedman, Tim

Published
2025
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17. Attitudes Toward Important Issues in Society

Author

Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, and Friedman, Tim

Published
2025
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18. Aspects of Students’ Civic Engagement

Author

Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Ainley, John, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Damiani, Valeria, and Friedman, Tim

Published
2025
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22. Education for Citizenship in Times of Global Challenge: IEA International Civic and Citizenship Education Study 2022 International Report (Revised Edition)

Author

International Association for the Evaluation of Educational Achievement (IEA) (Netherlands), Australian Council for Educational Research (ACER), Wolfram Schulz, John Ainley, Julian Fraillon, Bruno Losito, Gabriella Agrusti, Valeria Damiani, and Tim Friedman

Abstract

The IEA's International Civic and Citizenship Education Study (ICCS) investigates the ways in which young people around the world are prepared to undertake their roles as citizens. This report presents the international results from the third cycle of the study (ICCS 2022). Based on data from 24 countries or benchmarking participants from Europe, Latin America, and Asia, ICCS 2022 studies contexts for and learning outcomes of civic and citizenship education in a wide range of national contexts at the beginning of the third decade of the 21st Century. It responds to both enduring and emerging challenges of educating young people in a world where contexts of democracy and civic participation continue to change. The study addresses issues related to young people's engagement through digital technologies, migration and diversity, perceptions of the political system, global citizenship, and education for sustainable development. Further, it contains data that reflect civic-related aspects of recent developments such as students' perceptions of restrictions in response to national emergencies and their trust in scientists. Over the past 50 years, the IEA has conducted comparative research studies in a range of domains focusing on educational policies, practices, and outcomes in many countries around the world. Prior to ICCS 2022, the IEA had conducted four international comparative studies of civic and citizenship education, with a first survey implemented in 1971, a second in 1999, a third in 2009 and a fourth in 2016. ICCS 2022 data will allow education systems to evaluate the strengths of educational policies, from a comparative perspective, and to measure progress in achieving critical social objectives of their educational policy agendas. [This report was also prepared by Libera Università Maria Santissima Assunta (LUMSA Università).]

Published
2023

25. Young people’s civic engagement in Italy: evidence on grade 8 students from the international civic and citizenship education study (ICCS) 2016

Author

Valeria Damiani, Elisa Caponera, Bruno Losito, Laura Palmerio, and Gabriella Agrusti

Subjects
Civic and citizenship education, ICCS 2016, Italy, Self-efficacy, Education (General), L7-991
Abstract

Abstract Civic engagement represents a key aspect of a democratic society and is itself a multidimensional construct. Research has shown that the promotion of civic engagement is an important component of civic and citizenship education intended in a broad sense, pertaining to formal, non-formal and informal learning situations. Within a national scenario characterised by increasing levels of general institutional disaffection and a lack of electoral and political involvement, the recent reform in the area of civic and citizenship education (Law 92/2019) has led to lively debates on the status of its implementation in Italian schools and recent research at the national level has highlighted the lack of activities to promote students’ engagement. This study further investigates the ICCS 2016 findings on civic engagement of Italian students with two objectives: to identify possible groups of Italian eighth-grade students on the basis of their level of civic engagement and to examine the associations among these groups and some key factors reflecting school contexts and students’ attitudes and behaviours. To reach these goals, the data analyses encompassed a latent profile analysis and a logistic regression model. The latent profile analysis allowed the identification of three groups of Italian students: disengaged, moderately engaged and engaged students. The results of the regression model showed that engaged students were characterised by a higher level of citizenship self-efficacy. These findings confirm those of previous research on the key role of internal self-efficacy in promoting students’ civic engagement.

Published
2024
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27. Towards a Muon Collider

Author

Accettura, Carlotta, Adams, Dean, Agarwal, Rohit, Ahdida, Claudia, Aimè, Chiara, Amapane, Nicola, Amorim, David, Andreetto, Paolo, Anulli, Fabio, Appleby, Robert, Apresyan, Artur, Apyan, Aram, Arsenyev, Sergey, Asadi, Pouya, Mahmoud, Mohammed Attia, Azatov, Aleksandr, Back, John, Balconi, Lorenzo, Bandiera, Laura, Barlow, Roger, Bartosik, Nazar, Barzi, Emanuela, Batsch, Fabian, Bauce, Matteo, Berg, J. Scott, Bersani, Andrea, Bertarelli, Alessandro, Bertolin, Alessandro, Boattini, Fulvio, Bogacz, Alex, Bonesini, Maurizio, Bordini, Bernardo, Bottaro, Salvatore, Bottura, Luca, Braghieri, Alessandro, Breschi, Marco, Bruhwiler, Natalie, Buffat, Xavier, Buonincontri, Laura, Burrows, Philip, Burt, Graeme, Buttazzo, Dario, Caiffi, Barbara, Calviani, Marco, Calzaferri, Simone, Calzolari, Daniele, Capdevilla, Rodolfo, Carli, Christian, Casaburo, Fausto, Casarsa, Massimo, Castelli, Luca, Catanesi, Maria Gabriella, Cavoto, Gianluca, Celiberto, Francesco Giovanni, Celona, Luigi, Cerri, Alessandro, Cesarini, Gianmario, Cesarotti, Cari, Chachamis, Grigorios, Chance, Antoine, Chen, Siyu, Chien, Yang-Ting, Chiesa, Mauro, Colaleo, Anna, Collamati, Francesco, Collazuol, Gianmaria, Costa, Marco, Craig, Nathaniel, Curatolo, Camilla, Curtin, David, Da Molin, Giacomo, Dam, Magnus, Damerau, Heiko, Dasu, Sridhara, de Blas, Jorge, De Curtis, Stefania, De Matteis, Ernesto, De Rosa, Stefania, Delahaye, Jean-Pierre, Denisov, Dmitri, Denizli, Haluk, Densham, Christopher, Dermisek, Radovan, Di Luzio, Luca, Di Meco, Elisa, Di Micco, Biagio, Dienes, Keith, Diociaiuti, Eleonora, Dorigo, Tommaso, Dudarev, Alexey, Edgecock, Robert, Errico, Filippo, Fabbrichesi, Marco, Farinon, Stefania, Ferrari, Anna, Somoza, Jose Antonio Ferreira, Filthaut, Frank, Fiorina, Davide, Fol, Elena, Forslund, Matthew, Franceschini, Roberto, Ximenes, Rui Franqueira, Gabrielli, Emidio, Gallinaro, Michele, Garosi, Francesco, Giambastiani, Luca, Gianelle, Alessio, Gilardoni, Simone, Giove, Dario Augusto, Giraldin, Carlo, Glioti, Alfredo, Greco, Mario, Greljo, Admir, Groeber, Ramona, Grojean, Christophe, Grudiev, Alexej, Gu, Jiayin, Han, Chengcheng, Han, Tao, Hauptman, John, Henning, Brian, Hermanek, Keith, Herndon, Matthew, Holmes, Tova Ray, Homiller, Samuel, Huang, Guoyuan, Jana, Sudip, Jindariani, Sergo, Kahn, Yonatan, Karpov, Ivan, Kelliher, David, Kilian, Wolfgang, Kolehmainen, Antti, Kong, Kyoungchul, Koppenburg, Patrick, Kreher, Nils, Krintiras, Georgios, Krizka, Karol, Krnjaic, Gordan, Kumar, Nilanjana, Lechner, Anton, Lee, Lawrence, Li, Qiang, Voti, Roberto Li, Lipton, Ronald, Liu, Zhen, Lomte, Shivani, Long, Kenneth, Gomez, Jose Lorenzo, Losito, Roberto, Low, Ian, Lu, Qianshu, Lucchesi, Donatella, Ma, Lianliang, Ma, Yang, Machida, Shinji, Maltoni, Fabio, Mandurrino, Marco, Mansoulie, Bruno, Mantani, Luca, Marchand, Claude, Mariotto, Samuele, Martin-Haugh, Stewart, Marzocca, David, Mastrapasqua, Paola, Mauro, Giorgio, Mazzolari, Andrea, McGinnis, Navin, Meade, Patrick, Mele, Barbara, Meloni, Federico, Mentink, Matthias, Merlassino, Claudia, Metral, Elias, Miceli, Rebecca, Milas, Natalia, Mokhov, Nikolai, Montella, Alessandro, Mulder, Tim, Musenich, Riccardo, Nardecchia, Marco, Nardi, Federico, Neufeld, Niko, Neuffer, David, Onel, Yasar, Orestano, Domizia, Paesani, Daniele, Griso, Simone Pagan, Palmer, Mark, Panci, Paolo, Panico, Giuliano, Paparella, Rocco, Paradisi, Paride, Passeri, Antonio, Pastrone, Nadia, Pellecchia, Antonello, Piccinini, Fulvio, Portone, Alfredo, Potamianos, Karolos, Prioli, Marco, Quettier, Lionel, Radicioni, Emilio, Radogna, Raffaella, Rattazzi, Riccardo, Redigolo, Diego, Reina, Laura, Resseguie, Elodie, Reuter, Jürgen, Ribani, Pier Luigi, Riccardi, Cristina, Ricci, Lorenzo, Ricciardi, Stefania, Ristori, Luciano, Robens, Tania Natalie, Rodejohann, Werner, Rogers, Chris, Romagnoni, Marco, Ronald, Kevin, Rossi, Lucio, Ruiz, Richard, Queiroz, Farinaldo S., Sala, Filippo, Sala, Paola, Salko, Jakub, Salvini, Paola, Salvioni, Ennio, Santiago, Jose, Sarra, Ivano, Esteban, Francisco Javier Saura, Schieck, Jochen, Schulte, Daniel, Selvaggi, Michele, Senatore, Carmine, Senol, Abdulkadir, Sertore, Daniele, Sestini, Lorenzo, Sharma, Varun, Shiltsev, Vladimir, Shu, Jing, Simone, Federica Maria, Simoniello, Rosa, Skoufaris, Kyriacos, Sorbi, Massimo, Sorti, Stefano, Stamerra, Anna, Stapnes, Steinar, Stark, Giordon Holtsberg, Statera, Marco, Stechauner, Bernd, Stolarski, Daniel, Stratakis, Diktys, Su, Shufang, Su, Wei, Sumensari, Olcyr, Sun, Xiaohu, Sundrum, Raman, Swiatlowski, Maximilian J, Sytov, Alexei, Kuchma, Benjamin T., Tait, Tim M. P., Tang, Jian, Tang, Jingyu, Tesi, Andrea, Testoni, Pietro, Thomas, Brooks, Thompson, Emily Anne, Torre, Riccardo, Tortora, Ludovico, Tortora, Luca, Trifinopoulos, Sokratis, Vai, Ilaria, Valente, Riccardo, Valente, Riccardo Umberto, Valente, Marco, Valenti, Alessandro, Valle, Nicolò, van Rienen, Ursula, Venditti, Rosamaria, Verweij, Arjan, Verwilligen, Piet, Vittorio, Ludovico, Vitulo, Paolo, Wang, Liantao, Weber, Hannsjorg, Wozniak, Mariusz, Wu, Richard, Wu, Yongcheng, Wulzer, Andrea, Xie, Keping, Yamamoto, Akira, Yang, Yifeng, Yonehara, Katsuya, Zaza, Angela, Zhao, Xiaoran, Zlobin, Alexander, Zuliani, Davide, and Zurita, Jose

Subjects
Physics - Accelerator Physics, High Energy Physics - Experiment, High Energy Physics - Phenomenology
Abstract

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10~TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work., Comment: 118 pages, 103 figures

Published
2023

28. Genetic testing, another important tool in presurgical evaluation of focal epilepsies in childhood

Author

Rocio Garcia‐Uzquiano, Giulia Barcia, Emma Losito, Nicole Chemaly, Anna Kaminska, Isabelle Desguerre, Thomas Blauwblomme, Nathalie Boddaert, and Rima Nabbout

Subjects
drug‐resistant epilepsy, epilepsy gene panel, epilepsy surgery, focal epilepsy, MRI negative, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Epilepsy surgery may be a curative therapy for patients with drug‐resistant epilepsies when focal lesions or foci are identified. Genetic testing is not yet routinely included in many presurgical evaluation programs although recent evidence support that finding a germline genetic mutation could help to better delineate the patient candidacy to surgery and provide valuable information on the expected surgery outcome. In this study, we report nine patients presenting drug‐resistant focal epilepsy enrolled in presurgical evaluation. We show how the identification of genetic pathogenic variant in epilepsy known genes led to the interruption of the presurgical work‐up and ruled out surgery in 7 of them. We observed that the co‐existence of some recurrent clinical characteristics as early seizures' onset, frequent precipitating factors including fever, and developmental delay or intellectual disability may be useful markers for germline genetic pathogenic variants. In this group, genetic assessment should be mandatory during presurgical work up, mainly in patients with negative magnetic resonance imaging (MRI) or doubtful structural lesions. The integration of next generation targeted sequencing into the presurgical evaluation can improve the selection of candidates for resective surgery and fosters a personalized medicine approach with a better outcome. Plaine Language Abstract Genetic testing is not yet systematically included in the pre‐surgical assessment of patients with drug‐resistant focal epilepsies. In this study, through the description of nine patients, we underline how the integration of genomics into the presurgical work up can help in evaluating the patient candidacy to surgery and provide valuable information on expected surgery outcome.

Published
2024
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29. Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study

Author

Daniele Roberto Giacobbe, Laura Labate, Chiara Russo Artimagnella, Cristina Marelli, Alessio Signori, Vincenzo Di Pilato, Chiara Aldieri, Alessandra Bandera, Federica Briano, Bruno Cacopardo, Alessandra Calabresi, Federico Capra Marzani, Anna Carretta, Annamaria Cattelan, Luca Ceccarelli, Giovanni Cenderello, Silvia Corcione, Andrea Cortegiani, Rosario Cultrera, Francesco Giuseppe De Rosa, Valerio Del Bono, Filippo Del Puente, Chiara Fanelli, Fiorenza Fava, Daniela Francisci, Nicholas Geremia, Lucia Graziani, Andrea Lombardi, Angela Raffaella Losito, Ivana Maida, Andrea Marino, Maria Mazzitelli, Marco Merli, Roberta Monardo, Alessandra Mularoni, Chiara Oltolini, Carlo Pallotto, Emanuele Pontali, Francesca Raffaelli, Matteo Rinaldi, Marco Ripa, Teresa Antonia Santantonio, Francesco Saverio Serino, Michele Spinicci, Carlo Torti, Enrico Maria Trecarichi, Mario Tumbarello, Malgorzata Mikulska, Mauro Giacomini, Anna Marchese, Antonio Vena, Matteo Bassetti, and CEFI-SITA investigators

Subjects
Cefiderocol, Antimicrobial resistance, Clinical practice, Carbapenem resistance, Carbapenemases, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Published
2024
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30. IEA International Civic and Citizenship Education Study 2022: Assessment Framework

Author

International Association for the Evaluation of Educational Achievement (IEA) (Netherlands), Australian Council for Educational Research (ACER), Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, and Friedman, Tim

Abstract

The purpose of the International Civic and Citizenship Education Study (ICCS) is to investigate the changing ways in which young people are prepared to undertake their roles as citizens across a wide range of countries. This assessment framework provides a conceptual underpinning for the international instrumentation for ICCS 2022. It needs to identify and define those aspects of cognitive and affective-behavioral content that should be considered important learning outcomes of civic and citizenship education, as well as contextual factors that are setting the context for students' civic learning. The ICCS 2022 assessment framework consists of four parts: (1) the civic knowledge framework (describing aspects to be addressed when measuring students' civic knowledge and understanding); (2) the civic attitudes and engagement framework (describing the affective-behavioral constructs to be measured); (3) the contextual framework (outlining the relevant context factors measured through student, teacher, school, and national contexts questionnaires necessary to understand cognitive and affective-behavioral learning outcomes); and (4) the assessment design (describing the coverage of framework domains, the different item types, the assessment design, features of computer-enhanced measurement used in the international option of a computer-based delivery, and the expected cognitive, affective-behavioral and contextual indices). The framework also includes appendices with information about staff and institutions involved in ICCS 2022, key terms related to the civic knowledge framework, information on the described levels of civic knowledge, and examples of ICCS 2022 test items. [This framework was created in collaboration with Laboratorio di Pedagogia Sperimentale (LPS) at the Roma Tre University, Rome and LUMSA University of Rome.]

Published
2022

31. Lipidomics reveals the reshaping of the mitochondrial phospholipid profile in cells lacking OPA1 and mitofusins

Author

Andrea Castellaneta, Ilario Losito, Vito Porcelli, Serena Barile, Alessandra Maresca, Valentina Del Dotto, Valentina Losacco, Ludovica Sofia Guadalupi, Cosima Damiana Calvano, David C. Chan, Valerio Carelli, Luigi Palmieri, and Tommaso R.I. Cataldi

Subjects
glycerophospholipids, lipidomics, mitochondria, phospholipids, phospholipids/biosynthesis, OPA1, Biochemistry, QD415-436
Abstract

Depletion or mutations of key proteins for mitochondrial fusion, like optic atrophy 1 (OPA1) and mitofusins 1 and 2 (Mfn 1 and 2), are known to significantly impact the mitochondrial ultrastructure, suggesting alterations of their membranes’ lipid profiles. In order to make an insight into this issue, we used hydrophilic interaction liquid chromatography coupled with electrospray ionization–high resolution MS to investigate the mitochondrial phospholipid (PL) profile of mouse embryonic fibroblasts knocked out for OPA1 and Mfn1/2 genes. One hundred sixty-seven different sum compositions were recognized for the four major PL classes of mitochondria, namely phosphatidylcholines (PCs, 63), phosphatidylethanolamines (55), phosphatidylinositols (21), and cardiolipins (28). A slight decrease in the cardiolipin/PC ratio was found for Mfn1/2-knockout mitochondria. Principal component analysis and hierarchical cluster analysis were subsequently used to further process hydrophilic interaction liquid chromatography–ESI-MS data. A progressive decrease in the incidence of alk(en)yl/acyl species in PC and phosphatidylethanolamine classes and a general increase in the incidence of unsaturated acyl chains across all the investigated PL classes was inferred in OPA1 and Mfn1/2 knockouts compared to WT mouse embryonic fibroblasts. These findings suggest a reshaping of the PL profile consistent with the changes observed in the mitochondrial ultrastructure when fusion proteins are absent. Based on the existing knowledge on the metabolism of mitochondrial phospholipids, we propose that fusion proteins, especially Mfns, might influence the PL transfer between the mitochondria and the endoplasmic reticulum, likely in the context of mitochondria-associated membranes.

Published
2024
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32. A Work Proposal for a Collaborative Study of Magnet Technology for a Future Muon Collider

Author

Bottura, L., Aguglia, D., Auchmann, B., Arndt, T., Beard, J., Bersani, A., Boattini, F., Breschi, M., Caiffi, B., Chaud, X., Dam, M., Debray, F., De Gersem, H., De Matteis, E., Dudarev, A., Farinon, S., Kario, A., Losito, R., Mariotto, S., Mentink, M., Musenich, R., Ogitsu, T., Prioli, M., Quettier, L., Rossi, L., Schulte, D., Senatore, C., Sorbi, M., Statera, M., Kate, H. Ten, Valente, R. U., Yamamoto, A., and Yang, Y.

Subjects
Physics - Accelerator Physics
Abstract

In this paper we elaborate on the nature and challenges for the magnet systems of a muon collider as presently considered within the scope of the International Muon Collider Collaboration (IMCC). We outline the structure of the work proposed over the coming period of five years to study and demonstrate relevant magnet technology. The proposal, which is part of the overall work planned to establish feasibility of a muon collider, is in direct response to the recent recommendations received from the Laboratories Directors Group (LDG). The plan is to profit from joint activities, within the scope of the IMCC and beyond, implemented through direct and EU-funded contributions., Comment: contribution to Snowmass 2021

Published
2022

33. Future Circular Hadron Collider FCC-hh: Overview and Status

Author

Benedikt, M., Chance, A., Dalena, B., Denisov, D., Giovannozzi, M., Gutleber, J., Losito, R., Mangano, M., Raubenheimer, T., Riegler, W., Shiltsev, V., Schulte, D., Tommasini, D., and Zimmermann, F.

Subjects
Physics - Accelerator Physics
Abstract

The Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. Its goal is to push the field to the next energy frontier beyond LHC, increasing by an order of magnitude the mass of particles that could be directly produced, and decreasing by an order of magnitude the subatomic distances to be studied. The FCC study covers two accelerators, namely, an energy-frontier hadron collider (FCC-hh) and a highest luminosity, high-energy lepton collider (FCC-ee). Both rings are hosted in the same 100 km tunnel infrastructure, replicating the CERN strategy for LEP and LHC, i.e. developing a lepton and a hadron ring sharing the same tunnel. This paper is devoted to the FCC-hh and summarizes the key features of the FCC-hh accelerator design, performance reach, and underlying technologies. The material presented in this paper builds on the conceptual design report published in 2019, and extends it, including also the progress made and the results achieved since then., Comment: Contribution to Snowmass 2021

Published
2022

34. Future Circular Lepton Collider FCC-ee: Overview and Status

Author

Agapov, I., Benedikt, M., Blondel, A., Boscolo, M., Brunner, O., Llatas, M. Chamizo, Charles, T., Denisov, D., Fischer, W., Gianfelice-Wendt, E., Gutleber, J., Janot, P., Koratzinos, M., Losito, R., Nagaitsev, S., Oide, K., Raubenheimer, T., Rimmer, R., Seeman, J., Shatilov, D., Shiltsev, V., Sullivan, M., Wienands, U., and Zimmermann, F.

Subjects
Physics - Accelerator Physics, High Energy Physics - Experiment
Abstract

The worldwide High Energy Physics community widely agrees that the next collider should be a Higgs factory. Acknowledging this priority, in 2021 CERN has launched the international Future Circular Collider (FCC) Feasibility Study (FS). The FCC Integrated Project foresees, in a first stage, a high-luminosity high-energy electron-positron collider, serving as Higgs, top and electroweak factory, and, in a second stage, an energy frontier hadron collider, with a centre-of-mass energy of at least 100 TeV. In this paper, we address a few key elements of the FCC-ee accelerator design, its performance reach, and underlying technologies, as requested by the Snowmass process. The Conceptual Design Report for the FCC, published in 2019, serves as our primary reference. We also summarize a few recent changes and improvements., Comment: Contribution to Snowmass 2021

Published
2022

35. Erratum: Towards a muon collider

Author

Carlotta Accettura, Dean Adams, Rohit Agarwal, Claudia Ahdida, Chiara Aimè, Nicola Amapane, David Amorim, Paolo Andreetto, Fabio Anulli, Robert Appleby, Artur Apresyan, Aram Apyan, Sergey Arsenyev, Pouya Asadi, Mohammed Attia Mahmoud, Aleksandr Azatov, John Back, Lorenzo Balconi, Laura Bandiera, Roger Barlow, Nazar Bartosik, Emanuela Barzi, Fabian Batsch, Matteo Bauce, J. Scott Berg, Andrea Bersani, Alessandro Bertarelli, Alessandro Bertolin, Kevin Black, Fulvio Boattini, Alex Bogacz, Maurizio Bonesini, Bernardo Bordini, Salvatore Bottaro, Luca Bottura, Alessandro Braghieri, Marco Breschi, Natalie Bruhwiler, Xavier Buffat, Laura Buonincontri, Philip N. Burrows, Graeme Burt, Dario Buttazzo, Barbara Caiffi, Marco Calviani, Simone Calzaferri, Daniele Calzolari, Rodolfo Capdevilla, Christian Carli, Fausto Casaburo, Massimo Casarsa, Luca Castelli, Maria Gabriella Catanesi, Lorenzo Cavallucci, Gianluca Cavoto, Francesco Giovanni Celiberto, Luigi Celona, Alessandro Cerri, Gianmario Cesarini, Cari Cesarotti, Grigorios Chachamis, Antoine Chance, Siyu Chen, Yang-Ting Chien, Mauro Chiesa, Anna Colaleo, Francesco Collamati, Gianmaria Collazuol, Marco Costa, Nathaniel Craig, Camilla Curatolo, David Curtin, Giacomo Da Molin, Magnus Dam, Heiko Damerau, Sridhara Dasu, Jorge de Blas, Stefania De Curtis, Ernesto De Matteis, Stefania De Rosa, Jean-Pierre Delahaye, Dmitri Denisov, Haluk Denizli, Christopher Densham, Radovan Dermisek, Luca Di Luzio, Elisa Di Meco, Biagio Di Micco, Keith Dienes, Eleonora Diociaiuti, Tommaso Dorigo, Alexey Dudarev, Robert Edgecock, Filippo Errico, Marco Fabbrichesi, Stefania Farinon, Anna Ferrari, Jose Antonio Ferreira Somoza, Frank Filthaut, Davide Fiorina, Elena Fol, Matthew Forslund, Roberto Franceschini, Rui Franqueira Ximenes, Emidio Gabrielli, Michele Gallinaro, Francesco Garosi, Luca Giambastiani, Alessio Gianelle, Simone Gilardoni, Dario Augusto Giove, Carlo Giraldin, Alfredo Glioti, Mario Greco, Admir Greljo, Ramona Groeber, Christophe Grojean, Alexej Grudiev, Jiayin Gu, Chengcheng Han, Tao Han, John Hauptman, Brian Henning, Keith Hermanek, Matthew Herndon, Tova Ray Holmes, Samuel Homiller, Guoyuan Huang, Sudip Jana, Sergo Jindariani, Paul Bogdan Jurj, Yonatan Kahn, Ivan Karpov, David Kelliher, Wolfgang Kilian, Antti Kolehmainen, Kyoungchul Kong, Patrick Koppenburg, Nils Kreher, Georgios Krintiras, Karol Krizka, Gordan Krnjaic, Benjamin T. Kuchma, Nilanjana Kumar, Anton Lechner, Lawrence Lee, Qiang Li, Roberto Li Voti, Ronald Lipton, Zhen Liu, Shivani Lomte, Kenneth Long, Jose Lorenzo Gomez, Roberto Losito, Ian Low, Qianshu Lu, Donatella Lucchesi, Lianliang Ma, Yang Ma, Shinji Machida, Fabio Maltoni, Marco Mandurrino, Bruno Mansoulie, Luca Mantani, Claude Marchand, Samuele Mariotto, Stewart Martin-Haugh, David Marzocca, Paola Mastrapasqua, Giorgio Mauro, Andrea Mazzolari, Navin McGinnis, Patrick Meade, Barbara Mele, Federico Meloni, Matthias Mentink, Claudia Merlassino, Elias Metral, Rebecca Miceli, Natalia Milas, Nikolai Mokhov, Alessandro Montella, Tim Mulder, Riccardo Musenich, Marco Nardecchia, Federico Nardi, Niko Neufeld, David Neuffer, Daniel Novelli, Yasar Onel, Domizia Orestano, Daniele Paesani, Simone Pagan Griso, Mark Palmer, Paolo Panci, Giuliano Panico, Rocco Paparella, Paride Paradisi, Antonio Passeri, Nadia Pastrone, Antonello Pellecchia, Fulvio Piccinini, Alfredo Portone, Karolos Potamianos, Marco Prioli, Lionel Quettier, Emilio Radicioni, Raffaella Radogna, Riccardo Rattazzi, Diego Redigolo, Laura Reina, Elodie Resseguie, Jürgen Reuter, Pier Luigi Ribani, Cristina Riccardi, Lorenzo Ricci, Stefania Ricciardi, Luciano Ristori, Tania Natalie Robens, Werner Rodejohann, Chris Rogers, Marco Romagnoni, Kevin Ronald, Lucio Rossi, Richard Ruiz, Farinaldo S. Queiroz, Filippo Sala, Jakub Salko, Paola Salvini, Ennio Salvioni, Jose Santiago, Ivano Sarra, Francisco Javier Saura Esteban, Jochen Schieck, Daniel Schulte, Michele Selvaggi, Carmine Senatore, Abdulkadir Senol, Daniele Sertore, Lorenzo Sestini, Varun Sharma, Vladimir Shiltsev, Jing Shu, Federica Maria Simone, Rosa Simoniello, Kyriacos Skoufaris, Massimo Sorbi, Stefano Sorti, Anna Stamerra, Steinar Stapnes, Giordon Holtsberg Stark, Marco Statera, Bernd Stechauner, Daniel Stolarski, Diktys Stratakis, Shufang Su, Wei Su, Olcyr Sumensari, Xiaohu Sun, Raman Sundrum, Maximilian J. Swiatlowski, Alexei Sytov, Tim M. P. Tait, Jingyu Tang, Jian Tang, Andrea Tesi, Pietro Testoni, Brooks Thomas, Emily Anne Thompson, Riccardo Torre, Ludovico Tortora, Luca Tortora, Sokratis Trifinopoulos, Ilaria Vai, Marco Valente, Riccardo Umberto Valente, Alessandro Valenti, Nicolò Valle, Ursula van Rienen, Rosamaria Venditti, Arjan Verweij, Piet Verwilligen, Ludovico Vittorio, Paolo Vitulo, Liantao Wang, Hannsjorg Weber, Mariusz Wozniak, Richard Wu, Yongcheng Wu, Andrea Wulzer, Keping Xie, Akira Yamamoto, Yifeng Yang, Katsuya Yonehara, Sangsik Yoon, Angela Zaza, Xiaoran Zhao, Alexander Zlobin, Davide Zuliani, and Jose Zurita

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Published
2024
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36. Correction: Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

Author

Caterina Vianello, Veronica Cocetta, Daniela Catanzaro, Gerald W Dorn, Angelo De Milito, Flavio Rizzolio, Vincenzo Canzonieri, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli, Vincenzo Quagliariello, Annabella Di Mauro, Simona Losito, Nicola Maurea, Cono Scaffa, Gabriele Sales, Luca Scorrano, Marta Giacomello, and Monica Montopoli

Subjects
Cytology, QH573-671
Published
2024
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37. Multiple scattering of channeled and non-channeled positively charged particles in bent monocrystalline silicon

Author

Scandale, W., Arduini, G., Cerutti, F., Esposito, L. S., Garattini, M., Gilardoni, S., Losito, R., Masi, A., Mirarchi, D., Montesano, S., Redaelli, S., Rossi, R., Smirnov, G., Burmistrov, L., Dubos, S., Puill, V., Stocchi, A., Bandiera, L., Guidi, V., Mazzolari, A., Romagnoni, M., Murtas, F., Addesa, F., Cavoto, G., Iacoangeli, F., Galluccio, F., Afonin, A. G., Chesnokov, Yu. A., Durum, A. A., Maisheev, V. A., Sandomirskiy, Yu. E., Yanovich, A. A., Kovalenko, A. D., Taratin, A. M., Denisov, A. S., Gavrikov, Yu. A., Ivanov, Yu. M., Malyarenko, L. G., Borg, J., James, T., Hall, G., and Pesaresi, M.

Subjects
Physics - Accelerator Physics
Abstract

We present the results of an experimental study of multiple scattering of positively charged high energy particles in bent samples of monocrystalline silicon. This work confirms the recently discovered effect of a strong reduction in the rms multiple scattering angle of particles channeled in the silicon (111) plane. The effect is observed in the plane orthogonal to the bending plane. We show in detail the influence of angular constraints on the magnitude of the effect. Comparison of the multiple scattering process at different energies indicates a violation of the law of inverse proportionality of the rms angle of channeled particles with energy. By increasing the statistics, we have improved the results of multiple scattering measurements for particles moving, but not channeled, in silicon crystals., Comment: arXiv admin note: text overlap with arXiv:1910.00250 minor fixes

Published
2022

38. European Strategy for Particle Physics -- Accelerator R&D Roadmap

Author

Adolphsen, C., Angal-Kalinin, D., Arndt, T., Arnold, M., Assmann, R., Auchmann, B., Aulenbacher, K., Ballarino, A., Baudouy, B., Baudrenghien, P., Benedikt, M., Bentvelsen, S., Blondel, A., Bogacz, A., Bossi, F., Bottura, L., Bousson, S., Brüning, O., Brinkmann, R., Bruker, M., Brunner, O., Burrows, P. N., Burt, G., Calatroni, S., Cassou, K., Castilla, A., Catalan-Lasheras, N., Cenni, E., Chancé, A., Colino, N., Corde, S., Corner, L., Cros, B., Cross, A., Delahaye, J. P., Devanz, G., Etienvre, A. -I., Evtushenko, P., Faus-Golfe, A., Fazilleau, P., Ferrario, M., Gallo, A., García-Tabarés, L., Geddes, C., Gerigk, F., Gianotti, F., Gilardoni, S., Grudiev, A., Gschwendtner, E., Hoffstaetter, G., Hogan, M., Hooker, S., Hutton, A., Ischebeck, R., Jakobs, K., Janot, P., Jensen, E., Kühn, J., Kaabi, W., Kayran, D., Klein, M., Knobloch, J., Koratzinos, M., Kuske, B., Lamont, M., Latina, A., Lebrun, P., Leemans, W., Li, D., Long, K., Longuevergne, D., Losito, R., Lu, W., Lucchesi, D., Lundh, O., Métral, E., Marhauser, F., Michizono, S., Militsyn, B., Mnich, J., Montesinos, E., Mounet, N., Muggli, P., Musumeci, P., Nagaitsev, S., Nakada, T., Neumann, A., Newbold, D., Nghiem, P., Noe, M., Oide, K., Osterhoff, J., Palmer, M., Pastrone, N., Pietralla, N., Prestemon, S., Previtali, E., Proslier, T., Quettier, L., Raubenheimer, T., Rimmer, B., Rivkin, L., Rochepault, E., Rogers, C., Rosaz, G., Roser, T., Rossi, L., Ruber, R., Schulte, D., Seidel, M., Senatore, C., Shepherd, B., Shi, J., Shipman, N., Specka, A., Stapnes, S., Stocchi, A., Stratakis, D., Syratchev, I., Tanaka, O., Tantawi, S., Tennant, C., Tsesmelis, E., Vaccarezza, C., Valente, A. -M., Védrine, P., Vieira, J., Vinokurov, N., Weise, H., Wenskat, M., Williams, P., Wing, M., Yamamoto, A., Yamamoto, Y., Yokoya, K., and Zimmermann, F.

Subjects
Physics - Accelerator Physics, High Energy Physics - Experiment
Abstract

The 2020 update of the European Strategy for Particle Physics emphasised the importance of an intensified and well-coordinated programme of accelerator R&D, supporting the design and delivery of future particle accelerators in a timely, affordable and sustainable way. This report sets out a roadmap for European accelerator R&D for the next five to ten years, covering five topical areas identified in the Strategy update. The R&D objectives include: improvement of the performance and cost-performance of magnet and radio-frequency acceleration systems; investigations of the potential of laser / plasma acceleration and energy-recovery linac techniques; and development of new concepts for muon beams and muon colliders. The goal of the roadmap is to document the collective view of the field on the next steps for the R&D programme, and to provide the evidence base to support subsequent decisions on prioritisation, resourcing and implementation., Comment: 270 pages, 58 figures. Editor: N. Mounet. LDG chair: D. Newbold. Panel chairs: P. V\'edrine (HFM), S. Bousson (RF), R. Assmann (plasma), D. Schulte (muon), M. Klein (ERL). Panel editors: B. Baudouy (HFM), L. Bottura (HFM), S. Bousson (RF), G. Burt (RF), R. Assmann (plasma), E. Gschwendtner (plasma), R. Ischebeck (plasma), C. Rogers (muon), D. Schulte (muon), M. Klein (ERL)

Published
2022
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39. Integrating Epoxidation, High-Resolution Mass Spectrometry and Ultraviolet Spectroscopy to Unravel the Complex Profile of Boswellic Acids and Related Compounds in the Boswellia serrata Gum Resin Extract

Author

Andrea Castellaneta, Ilario Losito, Stefania Cometa, Francesco Busto, Elvira De Giglio, and Tommaso R. I. Cataldi

Subjects
boswellic acids, Boswellia serrata, epoxidation reaction, meta-chloroperoxybenzoic acid, UV spectroscopy, high-resolution tandem mass spectrometry, Organic chemistry, QD241-441
Abstract

The chemical characterization of natural products is often a complex task that demands powerful analytical techniques. Liquid chromatography with high-resolution tandem mass spectrometry (HRMS/MS) is often employed, yet it can face hard challenges when isomeric species are present, and reference standards are lacking. In such cases, the confidence level in compound identification can be significantly improved by the collection of orthogonal information on target analytes. In this work, 23 key compounds in Boswellia serrata extract (BSE), 12 of which correspond to boswellic acids (BAs) and 11 to triterpenoidic acid isomers, were identified by combining RPLC followed by serial UV and ESI(-)-FTMS and FTMS/MS detections with the evaluation of the reactivity towards C=C bond epoxidation with meta-chloroperoxybenzoic acid (m-CPBA), proposed as a fast chemical tool to gather information about C=C bond steric hindrance, a key structural feature of BAs and related compounds. The interpretation of UV spectra acquired after chromatographic separation corroborated the identification of the substitution patterns of enonic and dienic residues in ketoboswellic and dehydroboswellic acids. Moreover, MS/MS based on higher-energy collision-induced dissociation (HCD) unveiled new fragmentation pathways, providing important structural details on target analytes. The integrated approach developed during this study might pave the way for a deeper understanding of the BSE bioactive properties. Moreover, it can be considered an example of a more general strategy for the analysis of complex mixtures of natural compounds including also isomeric species.

Published
2024
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41. Assessment Design

Author

Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, and Friedman, Tim

Published
2023
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42. Civic Knowledge Framework

Author

Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, and Friedman, Tim

Published
2023
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43. Overview

Author

Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, and Friedman, Tim

Published
2023
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44. Civic Attitudes and Engagement Framework

Author

Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, and Friedman, Tim

Published
2023
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45. Contextual Framework

Author

Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, Friedman, Tim, Schulz, Wolfram, Fraillon, Julian, Losito, Bruno, Agrusti, Gabriella, Ainley, John, Damiani, Valeria, and Friedman, Tim

Published
2023
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47. Correction: Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

Author

Vianello, Caterina, Cocetta, Veronica, Catanzaro, Daniela, Dorn, II, Gerald W, De Milito, Angelo, Rizzolio, Flavio, Canzonieri, Vincenzo, Cecchin, Erika, Roncato, Rossana, Toffoli, Giuseppe, Quagliariello, Vincenzo, Di Mauro, Annabella, Losito, Simona, Maurea, Nicola, Scaffa, Cono, Sales, Gabriele, Scorrano, Luca, Giacomello, Marta, and Montopoli, Monica

Published
2024
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48. Erratum: Towards a muon collider

Author

Accettura, Carlotta, Adams, Dean, Agarwal, Rohit, Ahdida, Claudia, Aimè, Chiara, Amapane, Nicola, Amorim, David, Andreetto, Paolo, Anulli, Fabio, Appleby, Robert, Apresyan, Artur, Apyan, Aram, Arsenyev, Sergey, Asadi, Pouya, Mahmoud, Mohammed Attia, Azatov, Aleksandr, Back, John, Balconi, Lorenzo, Bandiera, Laura, Barlow, Roger, Bartosik, Nazar, Barzi, Emanuela, Batsch, Fabian, Bauce, Matteo, Berg, J. Scott, Bersani, Andrea, Bertarelli, Alessandro, Bertolin, Alessandro, Black, Kevin, Boattini, Fulvio, Bogacz, Alex, Bonesini, Maurizio, Bordini, Bernardo, Bottaro, Salvatore, Bottura, Luca, Braghieri, Alessandro, Breschi, Marco, Bruhwiler, Natalie, Buffat, Xavier, Buonincontri, Laura, Burrows, Philip N., Burt, Graeme, Buttazzo, Dario, Caiffi, Barbara, Calviani, Marco, Calzaferri, Simone, Calzolari, Daniele, Capdevilla, Rodolfo, Carli, Christian, Casaburo, Fausto, Casarsa, Massimo, Castelli, Luca, Catanesi, Maria Gabriella, Cavallucci, Lorenzo, Cavoto, Gianluca, Celiberto, Francesco Giovanni, Celona, Luigi, Cerri, Alessandro, Cesarini, Gianmario, Cesarotti, Cari, Chachamis, Grigorios, Chance, Antoine, Chen, Siyu, Chien, Yang-Ting, Chiesa, Mauro, Colaleo, Anna, Collamati, Francesco, Collazuol, Gianmaria, Costa, Marco, Craig, Nathaniel, Curatolo, Camilla, Curtin, David, Da Molin, Giacomo, Dam, Magnus, Damerau, Heiko, Dasu, Sridhara, de Blas, Jorge, De Curtis, Stefania, De Matteis, Ernesto, De Rosa, Stefania, Delahaye, Jean-Pierre, Denisov, Dmitri, Denizli, Haluk, Densham, Christopher, Dermisek, Radovan, Di Luzio, Luca, Di Meco, Elisa, Di Micco, Biagio, Dienes, Keith, Diociaiuti, Eleonora, Dorigo, Tommaso, Dudarev, Alexey, Edgecock, Robert, Errico, Filippo, Fabbrichesi, Marco, Farinon, Stefania, Ferrari, Anna, Somoza, Jose Antonio Ferreira, Filthaut, Frank, Fiorina, Davide, Fol, Elena, Forslund, Matthew, Franceschini, Roberto, Ximenes, Rui Franqueira, Gabrielli, Emidio, Gallinaro, Michele, Garosi, Francesco, Giambastiani, Luca, Gianelle, Alessio, Gilardoni, Simone, Giove, Dario Augusto, Giraldin, Carlo, Glioti, Alfredo, Greco, Mario, Greljo, Admir, Groeber, Ramona, Grojean, Christophe, Grudiev, Alexej, Gu, Jiayin, Han, Chengcheng, Han, Tao, Hauptman, John, Henning, Brian, Hermanek, Keith, Herndon, Matthew, Holmes, Tova Ray, Homiller, Samuel, Huang, Guoyuan, Jana, Sudip, Jindariani, Sergo, Jurj, Paul Bogdan, Kahn, Yonatan, Karpov, Ivan, Kelliher, David, Kilian, Wolfgang, Kolehmainen, Antti, Kong, Kyoungchul, Koppenburg, Patrick, Kreher, Nils, Krintiras, Georgios, Krizka, Karol, Krnjaic, Gordan, Kuchma, Benjamin T., Kumar, Nilanjana, Lechner, Anton, Lee, Lawrence, Li, Qiang, Voti, Roberto Li, Lipton, Ronald, Liu, Zhen, Lomte, Shivani, Long, Kenneth, Gomez, Jose Lorenzo, Losito, Roberto, Low, Ian, Lu, Qianshu, Lucchesi, Donatella, Ma, Lianliang, Ma, Yang, Machida, Shinji, Maltoni, Fabio, Mandurrino, Marco, Mansoulie, Bruno, Mantani, Luca, Marchand, Claude, Mariotto, Samuele, Martin-Haugh, Stewart, Marzocca, David, Mastrapasqua, Paola, Mauro, Giorgio, Mazzolari, Andrea, McGinnis, Navin, Meade, Patrick, Mele, Barbara, Meloni, Federico, Mentink, Matthias, Merlassino, Claudia, Metral, Elias, Miceli, Rebecca, Milas, Natalia, Mokhov, Nikolai, Montella, Alessandro, Mulder, Tim, Musenich, Riccardo, Nardecchia, Marco, Nardi, Federico, Neufeld, Niko, Neuffer, David, Novelli, Daniel, Onel, Yasar, Orestano, Domizia, Paesani, Daniele, Griso, Simone Pagan, Palmer, Mark, Panci, Paolo, Panico, Giuliano, Paparella, Rocco, Paradisi, Paride, Passeri, Antonio, Pastrone, Nadia, Pellecchia, Antonello, Piccinini, Fulvio, Portone, Alfredo, Potamianos, Karolos, Prioli, Marco, Quettier, Lionel, Radicioni, Emilio, Radogna, Raffaella, Rattazzi, Riccardo, Redigolo, Diego, Reina, Laura, Resseguie, Elodie, Reuter, Jürgen, Ribani, Pier Luigi, Riccardi, Cristina, Ricci, Lorenzo, Ricciardi, Stefania, Ristori, Luciano, Robens, Tania Natalie, Rodejohann, Werner, Rogers, Chris, Romagnoni, Marco, Ronald, Kevin, Rossi, Lucio, Ruiz, Richard, Queiroz, Farinaldo S., Sala, Filippo, Salko, Jakub, Salvini, Paola, Salvioni, Ennio, Santiago, Jose, Sarra, Ivano, Esteban, Francisco Javier Saura, Schieck, Jochen, Schulte, Daniel, Selvaggi, Michele, Senatore, Carmine, Senol, Abdulkadir, Sertore, Daniele, Sestini, Lorenzo, Sharma, Varun, Shiltsev, Vladimir, Shu, Jing, Simone, Federica Maria, Simoniello, Rosa, Skoufaris, Kyriacos, Sorbi, Massimo, Sorti, Stefano, Stamerra, Anna, Stapnes, Steinar, Stark, Giordon Holtsberg, Statera, Marco, Stechauner, Bernd, Stolarski, Daniel, Stratakis, Diktys, Su, Shufang, Su, Wei, Sumensari, Olcyr, Sun, Xiaohu, Sundrum, Raman, Swiatlowski, Maximilian J., Sytov, Alexei, Tait, Tim M. P., Tang, Jingyu, Tang, Jian, Tesi, Andrea, Testoni, Pietro, Thomas, Brooks, Thompson, Emily Anne, Torre, Riccardo, Tortora, Ludovico, Tortora, Luca, Trifinopoulos, Sokratis, Vai, Ilaria, Valente, Marco, Valente, Riccardo Umberto, Valenti, Alessandro, Valle, Nicolò, Rienen, Ursula van, Venditti, Rosamaria, Verweij, Arjan, Verwilligen, Piet, Vittorio, Ludovico, Vitulo, Paolo, Wang, Liantao, Weber, Hannsjorg, Wozniak, Mariusz, Wu, Richard, Wu, Yongcheng, Wulzer, Andrea, Xie, Keping, Yamamoto, Akira, Yang, Yifeng, Yonehara, Katsuya, Yoon, Sangsik, Zaza, Angela, Zhao, Xiaoran, Zlobin, Alexander, Zuliani, Davide, and Zurita, Jose

Published
2024
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50. Functional characterization of CRISPR-Cas interactions with DNA

Author

Losito, Marialucrezia

Abstract

The recent Nobel-prize-winning CRISPR technology has revolutionised the gene-editing field with its ability to precisely modify any target DNA sequence and its relevance in a wide range of applications, from functional characterisation of gene variants in biological sciences to mutation of plant genomes in agriculture. New prospectives for CRISPR-therapeutic applications are also rapidly advancing, particularly for the modification of disease-causing genes and ex-vivo editing of immune cells for cancer treatment. However, off-target editing exists as collateral damage and it represents a significant hurdle to realise CRISPR's full potential. To date, the scientific community lacks extensive knowledge regarding the impact of the eukaryotic cellular context on Cas nucleases activity, and how this affects Cas efficiency and specificity on human DNA. In this thesis, I use a combination of cellular and single-molecule assays to investigate this specific topic. First, I developed a strategy to demonstrate that Cas9 specificity is diminished by a local distortion of the DNA 3D structure in human cells. Next, by using the CRISPR system as a tool for gene expression regulation, I investigated the correlation between target transcription in cells and Cas9 editing efficiency. Together this first part of my work suggests that in vivo processes, which occur in eukaryotic cells and destabilise the DNA structure, have the potential to induce off-targets. However, this effect is highly dependent on the target itself and its genomic context. Finally, I extended my study to two other CRISPR-Cas systems: Cas12a and a new engineered Cas (AZ-Cas9). By applying single-molecule technologies, I contributed to the characterization of these nucleases, and obtained new information about the mechanisms underlining the DNA target search, the binding and cleavage kinetics and the off-target discrimination. These findings fill important knowledge gaps for future applications of these variants, and will be useful for the rational design of new high-fidelity nucleases.

Published
2022

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