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5,057 results on '"A. Paccagnella"'

1. Simulation tools, first results and experimental status of the MURAVES experiment

Author

Giammanco, Andrea, Hong, Yanwen, Moussawi, Marwa Al, Ambrosino, Fabio, Anastasio, Antonio, Basnet, Samip, Bonechi, Lorenzo, Bongi, Massimo, Borselli, Diletta, Bross, Alan, Caputo, Antonio, Ciaranfi, Roberto, Cimmino, Luigi, Ciulli, Vitaliano, D'Alessandro, Raffaello, D'Errico, Mariaelena, Frosin, Catalin, Giudicepietro, Flora, Gonzi, Sandro, Macedonio, Giovanni, Masone, Vincenzo, Orazi, Massimo, Paccagnella, Andrea, Peluso, Rosario, Pla-Dalmau, Anna, Samalan, Amrutha, Saracino, Giulio, Scarpato, Giovanni, Strolin, Paolo, Tytgat, Michael, Vertechi, Enrico, and Viliani, Lorenzo

Subjects
High Energy Physics - Experiment, Physics - Instrumentation and Detectors
Abstract

The MUon RAdiography of VESuvius (MURAVES) project aims at the study of Mt. Vesuvius, an active and hazardous volcano near Naples, Italy, with the use of muons freely and abundantly produced by cosmic rays. In particular, the MURAVES experiment intends to perform muographic imaging of the internal structure of the summit of Mt. Vesuvius. The challenging measurement of the rock density distribution in its summit by muography, in conjunction with data from other geophysical techniques, can help model possible eruption dynamics. The MURAVES apparatus consists of an array of three independent and identical muon trackers, with a total sensitive area of 3 square meters. In each tracker, a sequence of 4 XY tracking planes made of plastic scintillators is complemented by a 60 cm thick lead wall inserted between the two downstream planes to improve rejection of background from low energy muons. The apparatus is currently acquiring data. This paper presents preliminary results from the analysis of the first data samples acquired with trackers pointing towards Mt. Vesuvius, including the first relative measurement of the density projection of two flanks of the volcano at three different altitudes; we also present the workflow of the simulation chain of the MURAVES experiment and its ongoing developments.

Published
2023
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2. Multicenter development of a PET-based risk assessment tool for product-specific outcome prediction in large B-cell lymphoma patients undergoing CAR T-cell therapy

Author

Voltin, Conrad-Amadeus, Paccagnella, Andrea, Winkelmann, Michael, Heger, Jan-Michel, Casadei, Beatrice, Beckmann, Laura, Herrmann, Ken, Dekorsy, Franziska J., Kutsch, Nadine, Borchmann, Peter, Fanti, Stefano, Kunz, Wolfgang G., Subklewe, Marion, Kobe, Carsten, Zinzani, Pier Luigi, Stelljes, Matthias, Roth, Katrin S., Drzezga, Alexander, Noppeney, Richard, Rahbar, Kambiz, Reinhardt, H. Christian, von Tresckow, Bastian, Seifert, Robert, Albring, Jörn C., Blumenberg, Viktoria, Farolfi, Andrea, Flossdorf, Sarah, Gödel, Philipp, and Hanoun, Christine

Published
2024
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3. Technical Design Report for the LUXE Experiment

Author

Abramowicz, H., Soto, M. Almanza, Altarelli, M., Aßmann, R., Athanassiadis, A., Avoni, G., Behnke, T., Benettoni, M., Benhammou, Y., Bhatt, J., Blackburn, T., Blanch, C., Bonaldo, S., Boogert, S., Borysov, O., Borysova, M., Boudry, V., Breton, D., Brinkmann, R., Bruschi, M., Burkart, F., Büßer, K., Cavanagh, N., Corso, F. Dal, Decking, W., Deniaud, M., Diner, O., Dosselli, U., Elad, M., Epshteyn, L., Esperante, D., Ferber, T., Firlej, M., Fiutowski, T., Fleck, K., Fuster-Martinez, N., Gadow, K., Gaede, F., Gallas, A., Cabrera, H. Garcia, Gerstmayr, E., Ghenescu, V., Giorato, M., Golubeva, N., Grojean, C., Grutta, P., Grzelak, G., Hallford, J., Hartman, L., Heinemann, B., Heinzl, T., Helary, L., Hendriks, L., Hoffmann, M., Horn, D., Huang, S., Huang, X., Idzik, M., Irles, A., Jacobs, R., King, B., Klute, M., Kropf, A., Kroupp, E., Lahno, H., Manghi, F. Lasagni, Lawhorn, J., Levanon, A., Levi, A., Levinson, L., Levy, A., Levy, I., Liberman, A., Liss, B., List, B., List, J., Lohmann, W., Maalmi, J., Madlener, T., Malka, V., Marsault, T., Mattiazzo, S., Meloni, F., Miron, D., Morandin, M., Moroń, J., Nanni, J., Neagu, A. T., Negodin, E., Paccagnella, A., Pantano, D., Pietruch, D., Pomerantz, I., Pöschl, R., Potlog, P. M., Prasad, R., Quishpe, R., Ranken, E., Ringwald, A., Roich, A., Salgado, F., Santra, A., Sarri, G., Sävert, A., Sbrizzi, A., Schmitt, S., Schulthess, I., Schuwalow, S., Seipt, D., Simi, G., Soreq, Y., Spataro, D., Streeter, M., Swientek, K., Hod, N. Tal, Teter, T., Thiebault, A., Thoden, D., Trevisani, N., Urmanov, R., Vasiukov, S., Walker, S., Warren, M., Wing, M., Yap, Y. C., Zadok, N., Zanetti, M., Żarnecki, A. F., Zbińkowski, P., Zembaczyński, K., Zepf, M., Zerwas, D., Ziegler, W., and Zuffa, M.

Subjects
High Energy Physics - Experiment, Physics - Instrumentation and Detectors
Abstract

This Technical Design Report presents a detailed description of all aspects of the LUXE (Laser Und XFEL Experiment), an experiment that will combine the high-quality and high-energy electron beam of the European XFEL with a high-intensity laser, to explore the uncharted terrain of strong-field quantum electrodynamics characterised by both high energy and high intensity, reaching the Schwinger field and beyond. The further implications for the search of physics beyond the Standard Model are also discussed.

Published
2023

4. Characterizing hail-prone environments using convection-permitting reanalysis and overshooting top detections over south-central Europe

Author

A. Giordani, M. Kunz, K. M. Bedka, H. J. Punge, T. Paccagnella, V. Pavan, I. M. L. Cerenzia, and S. Di Sabatino

Subjects
Environmental technology. Sanitary engineering, TD1-1066, Geography. Anthropology. Recreation, Environmental sciences, GE1-350, Geology, QE1-996.5
Abstract

The challenges associated with reliably observing and simulating hazardous hailstorms call for new approaches that combine information from different available sources, such as remote sensing instruments, observations, or numerical modelling, to improve understanding of where and when severe hail most often occurs. In this work, a proxy for hail frequency is developed by combining overshooting cloud top (OT) detections from the Meteosat Second Generation (MSG) weather satellite with convection-permitting High rEsolution ReAnalysis over Italy (SPHERA) reanalysis predictors describing hail-favourable environmental conditions. Atmospheric properties associated with ground-based reports from the European Severe Weather Database (ESWD) are considered to define specific criteria for data filtering. Five convection-related parameters from reanalysis data quantifying key ingredients for hailstorm occurrence enter the filter: most unstable convective available potential energy (CAPE), K index, surface lifted index, deep-layer shear, and freezing-level height. A hail frequency estimate over the extended summer season (April–October) in south-central Europe is presented for a test period of 5 years (2016–2020). OT-derived hail frequency peaks at around 15:00 UTC in June–July over the pre-Alpine regions and the northern Adriatic Sea. The hail proxy statistically matches with ∼63 % of confirmed ESWD reports, which is roughly 23 % more than the previous estimate over Europe coupling deterministic satellite detections with coarser global reanalysis ambient conditions. The separation of hail events according to their severity highlights the enhanced appropriateness of the method for large-hail-producing hailstorms (with hailstone diameters ≥ 3 cm). Further, signatures for missed small-hail occurrences are identified, which are characterized by lower instability and organization and warmer cloud top temperatures.

Published
2024
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5. Fast neutron irradiation tests of flash memories used in space environment at the ISIS spallation neutron source

Author

C. Andreani, R. Senesi, A. Paccagnella, M. Bagatin, S. Gerardin, C. Cazzaniga, C. D. Frost, P. Picozza, G. Gorini, R. Mancini, and M. Sarno

Subjects
Physics, QC1-999
Abstract

This paper presents a neutron accelerated study of soft errors in advanced electronic devices used in space missions, i.e. Flash memories performed at the ChipIr and VESUVIO beam lines at the ISIS spallation neutron source. The two neutron beam lines are set up to mimic the space environment spectra and allow neutron irradiation tests on Flash memories in the neutron energy range above 10 MeV and up to 800 MeV. The ISIS neutron energy spectrum is similar to the one occurring in the atmospheric as well as in space and planetary environments, with intensity enhancements varying in the range 108- 10 9 and 106- 10 7 respectively. Such conditions are suitable for the characterization of the atmospheric, space and planetary neutron radiation environments, and are directly applicable for accelerated tests of electronic components as demonstrated here in benchmark measurements performed on flash memories.

Published
2018
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7. Adaptive Voronoi Binning in Muon Radiography for Detecting Subsurface Cavities

Author

Paccagnella, A., Ciulli, V., D’Alessandro, R., Bonechi, L., Borselli, D., Frosin, C., Gonzi, S., Beni, T., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Foresti, Gian Luca, editor, Fusiello, Andrea, editor, and Hancock, Edwin, editor

Published
2024
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8. Possible effects on avionics induced by terrestrial gamma-ray flashes

Author

M. Tavani, A. Argan, A. Paccagnella, A. Pesoli, F. Palma, S. Gerardin, M. Bagatin, A. Trois, P. Picozza, P. Benvenuti, E. Flamini, M. Marisaldi, C. Pittori, and P. Giommi

Subjects
Environmental technology. Sanitary engineering, TD1-1066, Geography. Anthropology. Recreation, Environmental sciences, GE1-350, Geology, QE1-996.5
Abstract

Terrestrial gamma-ray flashes (TGFs) are impulsive (intrinsically sub-millisecond) events associated with lightning in powerful thunderstorms. TGFs turn out to be very powerful natural accelerators known to accelerate particles and generate radiation up to hundreds of MeV energies. The number ratio of TGFs over normal lightning has been measured in tropical regions to be near 10−4. We address in this Article the issue of the possible susceptibility of typical aircraft electronics exposed to TGF particle, gamma ray and neutron irradiation. We consider possible scenarios regarding the intensity, the duration, and geometry of TGFs influencing nearby aircraft, and study their effects on electronic equipment. We calculate, for different assumptions, the total dose and the dose-rate, and estimate single-event-effects. We find that in addition to the electromagnetic component (electrons/positrons, gamma rays) also secondary neutrons produced by gamma-ray photo production in the aircraft structure substantially contribute to single-event effects in critical semiconductors components. Depending on the physical characteristics and geometry, TGFs may deliver a large flux of neutrons within a few milliseconds in an aircraft. This flux is calculated to be orders of magnitude larger than the natural cosmic-ray background, and may constitute a serious hazard to aircraft electronic equipment. We present a series of numerical simulations supporting our conclusions. Our results suggest the necessity of dedicated measurement campaigns addressing the radiative and particle environment of aircraft near or within thunderstorms.

Published
2013
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14. Orange fruit peels from PDO varieties of Ribera (Sicily, Italy): An insight into the chemistry and bioactivity of volatile and non-volatile secondary metabolites extracted using a microwave-assisted method

Author

Gregorio Peron, Giulia Bernabé, Sara Marcheluzzo, Gokhan Zengin, Kouadio Ibrahime Sinan, Jan Hošek, Jakub Treml, Ignis Kaja, Michela Paccagnella, Paola Brun, Ignazio Castagliuolo, Mirella Zancato, and Stefano Dall'Acqua

Subjects
Orange fruit peels, Volatile metabolites, Secondary metabolites, Antioxidants, Antimicrobials, Nutrition. Foods and food supply, TX341-641
Abstract

Peels of Washington Navel (WAS), Navelina (NAV), and Vaniglia Apireno (VAN) orange fruits from Ribera (Sicily, Italy) represent abundant by-products of the Italian agro-food sector. In this work, volatile (VE) and non-volatile (NVE) extracts were obtained from fresh peels using a microwave-assisted protocol, and were characterized for their content in secondary metabolites and bioactivity. VEs exerted antibacterial activity against different pathogens, and were toxic on Caco2 cells. Their main component was limonene (>85 %). NVEs inhibited tyrosinase, amylase, and glucosidase in vitro, and exerted significant antioxidant effects on THP-1 XBlue cells. They showed also anti-inflammatory properties, by decreasing NF-κB activity in LPS-stimulated cells. Putative molecular effectors were highlighted by multivariate correlation analysis. Overall, NVEs may represent novel sustainable nutraceutical ingredients with anti-inflammatory and metabolic properties, and can be obtained by using eco-sustainable approaches. Our results will encourage the reuse of by-products of the orange processing chain and will contribute to increase its circularity in the future.

Published
2024
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16. Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy

Author

Porcari, Aldostefano, Fontana, Marianna, Canepa, Marco, Biagini, Elena, Cappelli, Francesco, Gagliardi, Christian, Longhi, Simone, Pagura, Linda, Tini, Giacomo, Dore, Franca, Bonfiglioli, Rachele, Bauckneht, Matteo, Miceli, Alberto, Girardi, Francesca, Martini, Anna Lisa, Barbati, Giulia, Costanzo, Egidio Natalino, Caponetti, Angelo Giuseppe, Paccagnella, Andrea, Sguazzotti, Maurizio, La Malfa, Giovanni, Zampieri, Mattia, Sciagrà, Roberto, Perfetto, Federico, Rowczenio, Dorota, Gilbertson, Janet, Hutt, David F., Hawkins, Philip N., Rapezzi, Claudio, Merlo, Marco, Sinagra, Gianfranco, and Gillmore, Julian D.

Published
2024
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17. From Tumor Macroenvironment to Tumor Microenvironment: The Prognostic Role of the Immune System in Oral and Lung Squamous Cell Carcinoma

Author

Rosa Alessia Battista, Giacomo Maria Pini, Alex Finco, Filippo Corso, Andrea Galli, Gianluigi Arrigoni, Claudio Doglioni, Marcella Callea, Matteo Paccagnella, Luca Porcu, Federica Filipello, Marco Mazzola, Giorgia Foggetti, Vanesa Gregorc, Leone Giordano, Mario Bussi, Aurora Mirabile, and Giulia Veronesi

Subjects
immune system, oral squamous cell carcinoma, lung squamous cell carcinoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. Results: Associations were found between systemic inflammation markers—NLR, MLR, and PLR—and tumor microenvironment factors, such as TILs and CD8+ cell prevalence—elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. Discussion: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response’s role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. Conclusions: Future integration into cancer classification could improve risk stratification and treatment guidance.

Published
2024
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18. RD53 pixel chips for the ATLAS and CMS Phase-2 upgrades at HL-LHC

Author

Loddo, F., Andreazza, A., Arteche, F., Barbero, M.B., Barillon, P., Beccherle, R., Bilei, G.M., Bjalas, W., Bonaldo, S., Bortoletto, D., Calderini, G., Caratelli, A., Christian, D.C., Christiansen, J., Conti, E., Crescioli, F., Daas, M., De Robertis, G., Demaria, N., Deptuch, G.C., Dieter, Y., Dimitrievska, A., Ding, L., Esposito, S., Exarchou, D., Fahim, F., Fioriti, A., Fougeron, D., Gaioni, L., Garcia-Sciveres, M., Gerardin, S., Gnani, D., Grippo, M., Gromov, V., Hamer, M., Havranek, M., Heim, T., Hemperek, T., Hinterkeuser, F., Hoff, J., Huiberts, S., Janssen, J., Jara Casas, L.M., Jirsa, J., John, J.J., Kampkotter, J., Karagounis, M., Khwaira, Y., Kluit, R., Krieger, A., Krueger, H., Lalic, J., Lauritzen, M., Licciulli, F., Lipton, R., Liu, T., Lopez Morillo, E., Lounis, A., Luongo, F., Magazzu, G., Marcisovsky, M., Marconi, S., Marquez Lasso, F., Marzocca, C., Mattiazzo, S., Menouni, M., Minuti, M., Mironova, M., Miryala, S., Monteil, E., Moustakas, K., Muõz Chavero, F., Neue, G., Orfanelli, S., Paccagnella, A., Pacher, L., Palla, F., Palomo Pinto, F.R., Papadopoulou, A., Paterno, A., Petri, A., Placidi, P., Pohl, D., Pradas, A., Prydderch, M.L., Pulli, A., Ratti, L., Re, V., Rehman, A., Rymaszewski, P., Solal, M.C., Standke, M., Stiller, A., Strebler, T., Stugu, B., Thomas, S., Traversi, G., Vogrig, D., Vogt, M., Wang, T., Yang, H., Zdenko, J., and Zimmerman, T.

Published
2024
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20. Network approach in liquidomics landscape

Author

Santini, Daniele, Botticelli, Andrea, Galvano, Antonio, Iuliani, Michele, Incorvaia, Lorena, Gristina, Valerio, Taffon, Chiara, Foderaro, Simone, Paccagnella, Elisa, Simonetti, Sonia, Fazio, Federico, Scagnoli, Simone, Pomati, Giulia, Pantano, Francesco, Perrone, Giuseppe, De Falco, Elena, Russo, Antonio, and Spinelli, Gian Paolo

Published
2023
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21. Fermi Large Area Telescope Performance After 10 Years Of Operation

Author

The Fermi LAT Collaboration, Ajello, M., Atwood, W. B., Axelsson, M., Bagagli, R., Bagni, M., Baldini, L., Bastieri, D., Bellardi, F., Bellazzini, R., Bissaldi, E., Bloom, E. D., Bonino, R., Bregeon, J., Brez, A., Bruel, P., Buehler, R., Buson, S., Cameron, R. A., Caraveo, P. A., Cavazzuti, E., Ceccanti, M., Chen, S., Cheung, C. C., Ciprini, S., Cognard, I., Cohen-Tanugi, J., Cutini, S., D'Ammando, F., Luque, P. de la Torre, de Palma, F., Digel, S. W., Dirirsa, F., Di Lalla, N., Di Venere, L., Domínguez, A., Fabiani, D., Ferrara, E. C., Fiori, A., Foglia, G., Fukazawa, Y., Fusco, P., Gargano, F., Gasparrini, D., Giroletti, M., Glanzman, T., Green, D., Griffin, S., Grondin, M. -H., Grove, J. E., Guillemot, L., Guiriec, S., Gustafsson, M., Hays, E., Horan, D., Jóhannesson, G., Johnson, T. J., Kamae, T., Kerr, M., Kuss, M., Larsson, S., Latronico, L., Lemoine-Goumard, M., Li, J., Liodakis, I., Longo, F., Loparco, F., Lovellette, M. N., Lubrano, P., Maldera, S., Manfreda, A., Martí-Devesa, G., Mazziotta, M. N., Menon, N., Mereu, I., Meyer, M., Michelson, P. F., Minuti, M., Mitthumsiri, W., Mizuno, T., Mongelli, M., Monzani, M. E., Moskalenko, I. V., Negro, M., Nuss, E., Ojha, R., Orienti, M., Orlando, E., Paccagnella, A., Paliya, V. S., Paneque, D., Pei, Z., Perkins, J. S., Pesce-Rollins, M., Pinchera, M., Piron, F., Poon, H., Porter, T. A., Primavera, R., Principe, G., Racusin, J. L., Rainò, S., Rando, R., Rani, B., Rapposelli, E., Razzano, M., Razzaque, S., Reimer, A., Reimer, O., Russell, J. J., Saggini, N., Parkinson, P. M. Saz, Scolieri, N., Serini, D., Sgrò, C., Siskind, E. J., Smith, D. A., Spandre, G., Spinelli, P., Suson, D. J., Tajima, H., Thayer, J. G., Thompson, D. J., Tibaldo, L., Torres, D. F., Tosti, G., Valverde, J., Vigiani, L., and Zaharijas, G.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The Large Area Telescope (LAT), the primary instrument for the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from 30 MeV to more than 300 GeV. We describe the performance of the instrument at the 10-year milestone. LAT performance remains well within the specifications defined during the planning phase, validating the design choices and supporting the compelling case to extend the duration of the Fermi mission. The details provided here will be useful when designing the next generation of high-energy gamma-ray observatories., Comment: 60 pages, 28 figures. Published in ApJS

Published
2021
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22. Muon detection in electron-positron annihilation for muon collider studies

Author

Amapane, N., Antonelli, M., Anulli, F., Ballerini, G., Bandiera, L., Bartosik, N., Bauce, M., Bertolin, A., Biino, C., Garcia, O. R. Blanco, Boscolo, M., Brizzolari, C., Cappati, A., Casaburo, F., Casarsa, M., Cavoto, G., Cesarini, G., Collamati, F., Cotto, G., Curatolo, C., Di Nardo, R., Gonella, F., Hoh, S., Iafrati, M., Iacoangeli, F., Kiani, B., Voti, R. Li, Lucchesi, D., Mascagna, V., Paccagnella, A., Pastrone, N., Pazzini, J., Pelliccioni, M., Ponzio, B., Prest, M., Ricci, M., Rosati, S., Rossin, R., Rotondo, M., Planell, O. Sans, Sestini, L., Soldani, M., Triossi, A., Vallazza, E., Ventura, S., and Zanetti, M.

Subjects
Physics - Instrumentation and Detectors
Abstract

The investigation of the energy frontier in physics requires novel concepts for future colliders. The idea of a muon collider is very appealing since it would allow to study particle collisions at up to tens of TeV energy, while offering a cleaner experimental environment with respect to hadronic colliders. One key element in the muon collider design is the low-emittance muon production. Recently,the Low EMittance Muon Accelerator (LEMMA) collaboration has explored the muon pair production close to its kinematic threshold by annihilating 45 GeV positrons with electrons in a low Z material target. In this configuration, muons are emerging from the target with a naturally low-emittance. In this paper we describe the performance of a system, to study this production mechanism, that consists in several segmented absorbers with alternating active layers composed of fast Cherenkov detectors together with a muon identification technique based on this detector. Passive layers were made of tungsten. We collected data corresponding to muon and electron beams produced at the H2 line in the North Area of the European Organization for Nuclear Research (CERN) in September 2018.

Published
2021
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27. An Electrochemical Biosensor for the Detection of Bacteriophage of Lactococcus Lactis

Author

Bonaldo, Stefano, Cretaio, Erica, Pasqualotto, Elisabetta, Scaramuzza, Matteo, Franchin, Lara, Poggi, Sara, Paccagnella, Alessandro, Angrisani, Leopoldo, Series Editor, Arteaga, Marco, Series Editor, Panigrahi, Bijaya Ketan, Series Editor, Chakraborty, Samarjit, Series Editor, Chen, Jiming, Series Editor, Chen, Shanben, Series Editor, Chen, Tan Kay, Series Editor, Dillmann, Rüdiger, Series Editor, Duan, Haibin, Series Editor, Ferrari, Gianluigi, Series Editor, Ferre, Manuel, Series Editor, Hirche, Sandra, Series Editor, Jabbari, Faryar, Series Editor, Jia, Limin, Series Editor, Kacprzyk, Janusz, Series Editor, Khamis, Alaa, Series Editor, Kroeger, Torsten, Series Editor, Li, Yong, Series Editor, Liang, Qilian, Series Editor, Martín, Ferran, Series Editor, Ming, Tan Cher, Series Editor, Minker, Wolfgang, Series Editor, Misra, Pradeep, Series Editor, Möller, Sebastian, Series Editor, Mukhopadhyay, Subhas, Series Editor, Ning, Cun-Zheng, Series Editor, Nishida, Toyoaki, Series Editor, Oneto, Luca, Series Editor, Pascucci, Federica, Series Editor, Qin, Yong, Series Editor, Seng, Gan Woon, Series Editor, Speidel, Joachim, Series Editor, Veiga, Germano, Series Editor, Wu, Haitao, Series Editor, Zamboni, Walter, Series Editor, Zhang, Junjie James, Series Editor, Cocorullo, Giuseppe, editor, Crupi, Felice, editor, and Limiti, Ernesto, editor

Published
2023
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28. Network approach in liquidomics landscape

Author

Daniele Santini, Andrea Botticelli, Antonio Galvano, Michele Iuliani, Lorena Incorvaia, Valerio Gristina, Chiara Taffon, Simone Foderaro, Elisa Paccagnella, Sonia Simonetti, Federico Fazio, Simone Scagnoli, Giulia Pomati, Francesco Pantano, Giuseppe Perrone, Elena De Falco, Antonio Russo, and Gian Paolo Spinelli

Subjects
Liquid biopsy, CTC, ctDNA, MRD, Targeted therapy, Liquidomics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Tissue-based biopsy is the present main tool to explore the molecular landscape of cancer, but it also has many limits to be frequently executed, being too invasive with the risk of side effects. These limits and the ability of cancer to constantly evolve its genomic profile, have recently led to the need of a less invasive and more accurate alternative, such as liquid biopsy. By searching Circulating Tumor Cells and residues of their nucleic acids or other tumor products in body fluids, especially in blood, but also in urine, stools and saliva, liquid biopsy is becoming the future of clinical oncology. Despite the current lack of a standardization for its workflows, that makes it hard to be reproduced, liquid biopsy has already obtained promising results for cancer screening, diagnosis, prognosis, and risk of recurrence. Through a more accessible molecular profiling of tumors, it could become easier to identify biomarkers predictive of response to treatment, such as EGFR mutations in non-small cell lung cancer and KRAS mutations in colorectal cancer, or Microsatellite Instability and Mismatch Repair as predictive markers of pembrolizumab response. By monitoring circulating tumor DNA in longitudinal repeated sampling of blood we could also predict Minimal Residual Disease and the risk of recurrence in already radically resected patients. In this review we will discuss about the current knowledge of limitations and strengths of the different forms of liquid biopsies for its inclusion in normal cancer management, with a brief nod to their newest biomarkers and its future implications.

Published
2023
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29. CAR t-cell therapy in BOlogNa–NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON–NEUTRAL): proposed protocol and results from an Italian study

Author

Pensato, Umberto, Amore, Giulia, Muccioli, Lorenzo, Sammali, Susanna, Rondelli, Francesca, Rinaldi, Rita, D’Angelo, Roberto, Nicodemo, Marianna, Mondini, Susanna, Sambati, Luisa, Asioli, Gian Maria, Rossi, Simone, Santoro, Rossella, Cretella, Lucia, Ferrari, Susy, Spinardi, Luca, Faccioli, Luca, Fanti, Stefano, Paccagnella, Andrea, Pierucci, Elisabetta, Casadei, Beatrice, Pellegrini, Cinzia, Zinzani, Pier Luigi, Bonafè, Massimiliano, Cortelli, Pietro, Bonifazi, Francesca, and Guarino, Maria

Published
2023
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30. Lord of the Ring(s): Side Channel Attacks on the CPU On-Chip Ring Interconnect Are Practical

Author

Paccagnella, Riccardo, Luo, Licheng, and Fletcher, Christopher W.

Subjects
Computer Science - Cryptography and Security, Computer Science - Hardware Architecture
Abstract

We introduce the first microarchitectural side channel attacks that leverage contention on the CPU ring interconnect. There are two challenges that make it uniquely difficult to exploit this channel. First, little is known about the ring interconnect's functioning and architecture. Second, information that can be learned by an attacker through ring contention is noisy by nature and has coarse spatial granularity. To address the first challenge, we perform a thorough reverse engineering of the sophisticated protocols that handle communication on the ring interconnect. With this knowledge, we build a cross-core covert channel over the ring interconnect with a capacity of over 4 Mbps from a single thread, the largest to date for a cross-core channel not relying on shared memory. To address the second challenge, we leverage the fine-grained temporal patterns of ring contention to infer a victim program's secrets. We demonstrate our attack by extracting key bits from vulnerable EdDSA and RSA implementations, as well as inferring the precise timing of keystrokes typed by a victim user., Comment: This is the extended version of a paper that appears in USENIX Security 2021

Published
2021

32. Effects of a Personalized Diet on Nutritional Status and Renal Function Outcome in Nephrectomized Patients with Renal Cancer

Author

Francesco Trevisani, Fabiana Laurenti, Francesco Fiorio, Matteo Paccagnella, Matteo Floris, Umberto Capitanio, Michele Ghidini, Ornella Garrone, Andrea Abbona, Andrea Salonia, Francesco Montorsi, and Arianna Bettiga

Subjects
nutrition, kidney cancer, onco-nephrology, CKD, diet, Nutrition. Foods and food supply, TX341-641
Abstract

Nutritional therapy (NT) based on a controlled protein intake represents a cornerstone in managing chronic kidney disease (CKD). However, if a CKD patient is at the same time affected by cancer, oncologists and nutritionists tend to suggest a dietary regimen based on high protein intake to avoid catabolism and malnutrition. International guidelines are not clear when we consider onco-nephrological patients and, as a consequence, no clinical shared strategy is currently applied in clinical practice. In particular, no precise nutritional management is established in nephrectomized patients for renal cell carcinoma (RCC), a specific oncological cohort of patients whose sudden kidney removal forces the remnant one to start a compensatory mechanism of adaptive hyperfiltration. Our study aimed to investigate the efficacy of a low–normal-protein high-calorie (LNPHC) diet based on a Mediterranean model in a consecutive cohort of nephrectomized RCC patients using an integrated nephrologist and nutritionist approach. A consecutive cohort of 40 nephrectomized RCC adult (age > 18) patients who were screened for malnutrition (malnutrition screening tool, MST < 2) were enrolled in a tertiary institution between 2020 and 2022 after signing a specific informed consent form. Each patient underwent an initial nephrological and nutritional evaluation and was subsequently subjected to a conventional CKD LNPHC diet integrated with aproteic foods (0.8 g/Kg/die: calories: 30–35 kcal per kg body weight/die) for a period of 6 months (±2 months). The diet was structured after considering eGFR (CKD-EPI 2021 creatinine formula), comorbidities, and nutritional status. MST, body mass index (BMI), phase angle (PA), fat mass percentage (FM%), fat-free mass index (FFMI), body cell mass index (BCMI), extracellular/intracellular water ratio (ECW/ICW), extracellular matrix/body cell mass ratio (ECM/BCM), waist/hip circumference ratio (WHC), lab test exams, and clinical variables were examined at baseline and after the study period. Our results clearly highlighted that the LNPHC diet was able to significantly improve several nutritional parameters, avoiding malnutrition and catabolism. In particular, the LNPHC diet preserved the BCM index (delta on median, ΔM + 0.3 kg/m2) and reduced the ECM/BCM ratio (ΔM − 0.03 *), with a significant reduction in the ECW/ICW ratio (ΔM − 0.02 *), all while increasing TBW (ΔM + 2.3% *). The LNPHC diet was able to preserve FFM while simultaneously depleting FM and, moreover, it led to a significant reduction in urea (ΔM − 11 mg/dL **). In conclusion, the LNPHC diet represents a new important therapeutic strategy that should be considered when treating onco-nephrological patients with solitary kidney due to renal cancer.

Published
2024
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33. Speculative Interference Attacks: Breaking Invisible Speculation Schemes

Author

Behnia, Mohammad, Sahu, Prateek, Paccagnella, Riccardo, Yu, Jiyong, Zhao, Zirui, Zou, Xiang, Unterluggauer, Thomas, Torrellas, Josep, Rozas, Carlos, Morrison, Adam, Mckeen, Frank, Liu, Fangfei, Gabor, Ron, Fletcher, Christopher W., Basak, Abhishek, and Alameldeen, Alaa

Subjects
Computer Science - Hardware Architecture, Computer Science - Cryptography and Security
Abstract

Recent security vulnerabilities that target speculative execution (e.g., Spectre) present a significant challenge for processor design. The highly publicized vulnerability uses speculative execution to learn victim secrets by changing cache state. As a result, recent computer architecture research has focused on invisible speculation mechanisms that attempt to block changes in cache state due to speculative execution. Prior work has shown significant success in preventing Spectre and other vulnerabilities at modest performance costs. In this paper, we introduce speculative interference attacks, which show that prior invisible speculation mechanisms do not fully block these speculation-based attacks. We make two key observations. First, misspeculated younger instructions can change the timing of older, bound-to-retire instructions, including memory operations. Second, changing the timing of a memory operation can change the order of that memory operation relative to other memory operations, resulting in persistent changes to the cache state. Using these observations, we demonstrate (among other attack variants) that secret information accessed by mis-speculated instructions can change the order of bound-to-retire loads. Load timing changes can therefore leave secret-dependent changes in the cache, even in the presence of invisible speculation mechanisms. We show that this problem is not easy to fix: Speculative interference converts timing changes to persistent cache-state changes, and timing is typically ignored by many cache-based defenses. We develop a framework to understand the attack and demonstrate concrete proof-of-concept attacks against invisible speculation mechanisms. We provide security definitions sufficient to block speculative interference attacks; describe a simple defense mechanism with a high performance cost; and discuss how future research can improve its performance., Comment: Updated CR Version

Published
2020

34. The effect of toroidicity on relaxed states at low aspect ratio

Author

Paccagnella, R., Masamune, S., Predebon, I., and Sanpei, A.

Subjects
Physics - Plasma Physics
Abstract

The experimentally measured single helical states in the low aspect ratio (R/a=2) RELAX device have been compared with the predictions of a cylindrical relaxation theory and a substantial deviation in terms of some macroscopic characteristics has been found, in particular for cases corresponding to a large reversal of the edge toroidal field. In this paper we consider the effect of the toroidal geometry by employing the VMEC and the RelaxFit equilibrium codes. We show that the inclusion of toroidicity produces significant corrections to the cylindrical states, especially for the deep reversed cases.

Published
2020

35. Nuclear physics midterm plan at Legnaro National Laboratories (LNL)

Author

Ballan, M., Bottoni, S., Caamaño, M., Caciolli, A., Campostrini, M., Cicerchia, M., Crespi, F. C. L., Cristallo, S., Dell’Aquila, D., Depalo, R., Fioretto, E., Galtarossa, F., Gasques, L. R., Gottardo, A., Gramegna, F., Gulminelli, F., Kurtukian-Nieto, T., La Cognata, M., Lenzi, S. M., Marchi, T., Mazurek, K., Mengoni, D., Mou, L., Nania, R., Pupillo, G., Valiente-Dobón, J. J., Zanon, I., Acosta, L., Alvarez, M. A. G., Andrighetto, A., Arazi, A., Arzenton, A., Assié, M., Bagatin, M., Barbaro, F., Barbieri, C., Barlini, S., Basiricò, L., Battistoni, G., Beaumel, D., Bentley, M. A., Benzoni, G., Bertoldo, S., Bertulani, C., Bonasera, A., Camaiani, A., Canton, L., Capirossi, V., Carante, M. P., Carraro, C., Carturan, S. M., Casini, G., Cavanna, F., Centofante, L., Chávez, E. R., Chbihi, A., Ciemała, M., Cisternino, S., Colombi, A., Colucci, M., Compagnucci, A., Corradetti, S., Corradi, L., D’Agata, G., de Angelis, G., De Dominicis, L., De Salvador, D., DeFilippo, E., Del Fabbro, M., Di Nitto, A., Ditalia Tchernij, S., Donzella, A., Duguet, T., Esposito, J., Favela, F., Fernández-García, J. P., Flavigny, F., Fontana, A., Fornal, B., Forneris, J., Fraboni, B., Frankland, J., Gamba, E., Geraci, E., Gerardin, S., Giuliani, S. A., Gnoffo, B., Groppi, F., Gruyer, D., Haddad, F., Isaak, J., Kmiecik, M., Koning, A., Lamia, L., Le Neindre, N., Leoni, S., Lépine-Szily, A., Lilli, G., Lombardo, I., Loriggiola, M., Loriggiola, L., Lunardon, M., Maggioni, G., Maj, A., Manenti, S., Manzolaro, M., Marcucci, L. E., Marín-Lámbarri, D. J., Mariotti, E., Martin Hernandez, G., Massimi, C., Mastinu, P., Mazzocco, M., Mazzolari, A., Mijatović, T., Mishenina, T., Mizuyama, K., Monetti, A., Montagnoli, G., Morselli, L., Moschini, L., Musacchio Gonzalez, E., Nannini, A., Niu, Y. F., Ota, S., Paccagnella, A., Palmerini, S., Pellegri, L., Perego, A., Piantelli, S., Piatti, D., Picollo, F., Pignatari, M., Pinna, F., Pirrone, S., Pizzone, R. G., Polettini, M., Politi, G., Popescu, L., Prete, G., Quaranta, A., Raabe, R., Ramos, J. P., Raniero, W., Rapisarda, G. G., Recchia, F., Rigato, V., Roca Maza, X., Rocchini, M., Rodriguez, T., Roncolato, C., Rudolph, D., Russotto, P., Sánchez-Benítez, Á. M., Savran, D., Scarpa, D., Scheck, M., Sekizawa, K., Sergi, M. L., Sgarbossa, F., Silvestrin, L., Singh Khwairakpam, O., Skowronski, J., Somà, V., Spartà, R., Spieker, M., Stefanini, A. M., Steiger, H., Stevanato, L., Stock, M. R., Vardaci, E., Verney, D., Vescovi, D., Vittone, E., Werner, V., Wheldon, C., Wieland, O., Wimmer, K., Wyss, J., Zago, L., and Zenoni, A.

Published
2023
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36. Question order and panel conditioning analysing self-reported data

Author

Omar Paccagnella and Mariangela Guidolin

Subjects
Anchoring vignettes, Differential Item Functioning, panel conditioning, online banking, priming, question order, Social sciences (General), H1-99
Abstract

Self-ratings might not be directly comparable in socio-economic groups because of the presence of Differential Item Functioning (DIF) across individuals: survey respondents might interpret, understand or use the response categories for the same question in different ways, due to different perceptions, attitude and so on. The instrument of the anchoring vignettes has been introduced in the literature to provide DIF-free individual assessments. To take the DIF problem into account, in this paper we apply the anchoring vignette approach to investigate the extent of longitudinal priming effects for measuring the customer satisfaction of some online banking services in Italy, when the self-evaluation question is asked after (instead of before) the vignette questions. To this aim, a sample composed by a panel and a cross-sectional component of respondents is used: the former experienced the anchoring vignettes in the previous wave of the survey, the latter did not. We show that only in the longitudinal component priming effects due to the question order are not observed. Moreover, the knowledge of the anchoring vignette tool through participation in previous waves (that may lead to a better understanding of the meaning of the questions providing self-evaluations) leads to some changes in the response styles and in the perceived level of satisfaction with respect to the answers of the respondents who experienced the anchoring vignettes for the first time. The introduction of the anchoring vignettes induces some priming effects, that occur in different ways both in the perceived level of satisfaction and in the individual response style. These question order effects move in two opposite directions that, in some cases, might lead to some forms of compensation.

Published
2023
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42. Family role in paediatric safety incidents: a retrospective study protocol

Author

Andrew Carson-Stevens, Davide Paccagnella, Philippa Rees, Stuart Hellard, Isobel Joy McFadzean, Kathleen Walsh, Elena Jones, Jillian Beggs, Emily Ball, Thomas Purchase, Francesca Gabriel, Sioned Gwyn, and Philippa Robb

Subjects
Medicine
Abstract

Introduction Healthcare-associated harm is an international public health issue. Children are particularly vulnerable to this with 15%–35% of hospitalised children experiencing harm during medical care. While many factors increase the risk of adverse events, such as children’s dependency on others to recognise illness, children have a unique protective factor in the form of their family, who are often well placed to detect and prevent unsafe care. However, families can also play a key role in the aetiology of unsafe care.We aim to explore the role of families, guardians and parents in paediatric safety incidents, and how this may have changed during the pandemic, to learn how to deliver safer care and codevelop harm prevention strategies across healthcare settings.Methods and analysis This will be a retrospective study inclusive of an exploratory data analysis and thematic analysis of incident report data from the Learning from Patient Safety Events service (formerly National Reporting and Learning System), using the established PatIent SAfety classification system. Reports will be identified by using specific search terms, such as *parent* and *mother*, to capture narratives with explicit mention of parental involvement, inclusive of family members with parental and informal caregiver responsibilities.Paediatricians and general practitioners will characterise the reports and inter-rater reliability will be assessed. Exploratory descriptive analysis will allow the identification of types of incidents involving parents, contributing factors, harm outcomes and the specific role of the parents including inadvertent contribution to or mitigation of harm.Ethics and dissemination This study was approved by Cardiff University Research Ethics Committee (SMREC 22/32). Findings will be submitted to a peer-reviewed journal, presented at international conferences and presented at stakeholder workshops.

Published
2023
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43. Study of muon pair production from positron annihilation at threshold energy

Author

Amapane, N., Antonelli, M., Anulli, F., Ballerini, G., Bandiera, L., Bartosik, N., Bauce, M., Bertolin, A., Biino, C., Blanco-Garcia, O. R., Boscolo, M., Brizzolari, C., Cappati, A., Casarsa, M., Cavoto, G., Collamati, F., Cotto, G., Curatolo, C., Di Nardo, R., Gonella, F., Hoh, S., Iafrati, M., Iacoangeli, F., Kiani, B., Lucchesi, D., Mascagna, V., Paccagnella, A., Pastrone, N., Pazzini, J., Pelliccioni, M., Ponzio, B., Prest, M., Ricci, M., Rossin, R., Rotondo, M., Planell, O. Sans, Sestini, L., Soldani, M., Triossi, A., Vallazza, E., Ventura, S., and Zanetti, M.

Subjects
High Energy Physics - Experiment, Physics - Instrumentation and Detectors
Abstract

The muon collider represents one of the most promising solutions for a future machine exploring the high energy frontier, but several challenges due to the 2.2 $\mu$sec muon lifetime at rest have to be carefully considered. The LEMMA project is investigating the possibility of producing low emittance muon/antimuon pairs from the e$^+$e$^-$ annihilation process at threshold energy, resulting in small transverse emittance beams without any additional beam cooling. However most of the measurements available are performed at higher $\sqrt{s}$ values. It is therefore necessary to measure muons production in positron annihilation at threshold energy and compare the experimental results with the predictions in this specific energy regime. Apart from being a topic of physical interest by itself, these near to threshold measurements can have a sizeable impact on the estimation of the ultimate luminosity achievable in a muon collider with the LEMMA injection scheme., Comment: 13 pages, 8 figures

Published
2019
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44. Multiple imputation and selection of ordinal level 2 predictors in multilevel models. An analysis of the relationship between student ratings and teacher beliefs and practices

Author

Grilli, Leonardo, Marino, Maria Francesca, Paccagnella, Omar, and Rampichini, Carla

Subjects
Statistics - Applications
Abstract

The paper is motivated by the analysis of the relationship between ratings and teacher practices and beliefs, which are measured via a set of binary and ordinal items collected by a specific survey with nearly half missing respondents. The analysis, which is based on a two-level random effect model, must face two about the items measuring teacher practices and beliefs: (i) these items level 2 predictors severely affected by missingness; (ii) there is redundancy in the number of items and the number of categories of their measurement scale. tackle the first issue by considering a multiple imputation strategy based on information at both level 1 and level 2. For the second issue, we consider regularization techniques for ordinal predictors, also accounting for the multilevel data structure. The proposed solution combines existing methods in an original way to solve specific problem at hand, but it is generally applicable to settings requiring to select predictors affected by missing values. The results obtained with the final model out that some teacher practices and beliefs are significantly related to ratings about teacher ability to motivate students., Comment: Presented at the 12th International Multilevel Conference is held April 9-10, 2019 , Utrecht

Published
2019

45. Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Author

Chouli, Mohamed, Hamadouche, Nacera, Ladj, Mohamed Samir, Agrimbau Vázquez, Jorge, Carmona, Rodrigo, Collia, Adrian Gustavo, Ellis, Alejandro, Natta, Diego, Pérez, Laura, Rubiños, Mayra, Veliz, Natalia, Yori, Silvana, Britton, Philip N., Burgner, David P., Carey, Emma, Crawford, Nigel W., Giuliano, Hayley, McMinn, Alissa, Wong, Shirley, Wood, Nicholas, Holter, Wolfgang, Krainz, Matthias, Ulreich, Raphael, Zurl, Christoph, Dehoorne, Joke, Haerynck, Filomeen, Hoste, Levi, Schelstraete, Petra, Vandekerckhove, Kristof, Willems, Jef, Almeida Farias, Camila Giuliana, Almeida, Flávia Jacqueline, Alves Leal, Izabel, Araujo da Silva, André Ricardo, Araujo e Silva, Anna Esther, Barreiro, Sabrina T.A., Bomfim Prado da Silva, Daniella Gregória, Cervi, Maria Celia, dos Santos Naja Cardoso, Mirian Viviane, Henriques Teixeira, Cristiane, Jarovsky, Daniel, Martins Araujo, Julienne, Naaman Berezin, Eitan, Palazzi Sáfadi, Marco Aurélio, Paternina-de la Ossa, Rolando Andres, Souza Vieira, Cristina, Dimitrova, Anna, Ganeva, Margarita, Stefanov, Stefan, Telcharova-Mihaylovska, Albena, Biggs, Catherine M., Lopez, Alison, Scuccimarri, Rosie, Tan, Ryan, Wasserman, Sam, Withington, Davinia, Ampuero, Camila, Aravena, Javiera, Bustos B, Raul, Casanova, Daniel, Cruces, Pablo, Diaz, Franco, García-Salum, Tamara, Godoy, Loreto, Medina, Rafael A., Valenzuela Galaz, Gonzalo, Camacho-Moreno, Germán, Avila-Aguero, María L., Brenes-Chacón, Helena, Camacho-Badilla, Kattia, Ivankovich-Escoto, Gabriela, Naranjo-Zuniga, Gabriela, Soriano-Fallas, Alejandra, Ulloa-Gutierrez, Rolando, Yock-Corrales, Adriana, Amer, Maysa Abbas, Abdelmeguid, Yasmine, Ahmed, Yomna H.H.Z., Badib, Adham, Badreldin, Karim, Elkhashab, Yara, Heshmat, Hassan, Hussein, Amna, Mohamed Hussein, Amna Hussein, Ibrahim, Sandra, Shoman, Walaa, Yakout, Radwa M, Heinonen, Santtu, Angoulvant, François, Belot, Alexandre, Ouldali, Naïm, Beske, Florian, Heep, Axel, Masjosthusmann, Katja, Reiter, Karl, van den Heuvel, Ingeborg, von Both, Ulrich, Agrafiotou, Aikaterini, Antachopoulos, Charalampos, Charisi, Konstantina, Eleftheriou, Irini, Farmaki, Evangelia, Fotis, Lampros, Kafetzis, Dimitrios, Koletsi, Patra, Kourtesi, Katerina, Lampidi, Stavroula, Liakopoulou, Theodota, Maritsi, Despoina, Michailidou, Elisa, Milioudi, Maria, Mparmpounaki, Ioanna, Papadimitriou, Eleni, Papaevangelou, Vassiliki, Roilides, Emmanuel, Tsiatsiou, Olga, Tsolas, Georgios, Tsolia, Maria, Vantsi, Petrina, Banegas Pineda, Linda Yajeira, Borjas Aguilar, Karla Leversia, Cantillano Quintero, Edwin Mauricio, Ip, Patrick, Kwan, Mike Yat Wah, Kwok, Janette, Lau, Yu Lung, To, Kelvin, Wong, Joshua Sung Chih, David, Mate, Farkas, David, Kalcakosz, Szofia, Szekeres, Klaudia, Zsigmond, Borbala, Aslam, Nadeem, Luder, Anthony, Andreozzi, Laura, Bianco, Francesco, Bucciarelli, Valentina, Buonsenso, Danilo, Cimaz, Rolando, De Luca, Maia, Dellepiane, Rosa Maria, Fabi, Marianna, Filice, Emanuele, Lanari, Marcello, Lo Vecchio, Andrea, Mastrolia, Maria Vincenza, Mauro, Angela, Mazza, Angelo, Papa, Mario Virgilio, Romani, Lorenza, Scarano, Sara Maria, Simonini, Gabriele, Tipo, Vincenzo, Verdoni, Lucio, Macharia, Anne-Marie, Musiime, Grace, Reel, Bhupi, Wangai, Frederick, Pace, David, Torpiano, Paul, Anaya-Enriquez, Nancy, Carreon-Guerrero, Juan Manuel, Chacon-Cruz, Enrique, Cheung López, Mariana, Faugier Fuentes, Enrique, Fonseca Flores, Marisol, García-Domínguez, Miguel, Giron Vargas, Ana Luisa, Lopez-Delgado, Ivan, Lopez Hernández, Liliana, Menchaca Aguayo, Hector F., Montaño-Duron, Jesus Gilberto, Pérez-Gaxiola, Giordano, Ramos Tiñini, Pamela, Tostado-Morales, Edgardo, Valadez, Julio, Inchley, Christopher, Klevberg, Sjur, Knudsen, Per Kristian, Måseide, Per Helge, Carrera, Jose Manuel, Castaño, Elizabeth, Daza Timana, Carlos Alberto, De Leon, Tirza, Estripeaut, Dora, Levy, Jacqueline, Norero, Ximena, Record, Javier, Rojas-Bonilla, Magda, Wong, Mayra, Iramain, Ricardo, Hernandez, Roger, Huamán, Gian, Munaico, Manuel, Peralta, Carlos, Seminario, Diego, Zapata Yarlequé, Elmer Hans, Gadzinska, Justyna, Ludwikowska, Kamila, Mandziuk, Joanna, Okarska-Napierała, Magdalena, Alacheva, Zalina A., Alexeeva, Ekaterina, Ananin, Petr V., Antsupova, Margarita, Bakradze, Maya D., Berbenyuk, Anna, Bobkova, Polina, Borzakova, Svetlana, Chashchina, Irina L., El-Taravi, Yasmin, Fisenko, Andrey P., Gautier, Marina S., Glazyrina, Anastasia, Gorlenko, Cyrill, Grosheva, Mariia, Kiselev, Herman, Kondrikova, Elena, Korobyants, Evgeniya, Korsunskiy, Anatoliy A., Kovygina, Karina, Krasnaya, Ekaterina, Kurbanova, Seda, Kurdup, Maria K., Mamutova, Anna V., Mazankova, Lyudmila, Mitushin, Ilya L., Munblit, Daniel, Nargizyan, Anzhelika, Orlova, Yanina O., Osmanov, Ismail M., Polyakova, Anastasia S., Pushkareva, Anna, Romanova, Olga, Samitova, Elmira, Shvedova, Anastasia, Sologub, Anna, Iakovleva, Ekaterina, Tepaev, Rustem F., Tkacheva, Anna A., Yegiyan, Margarita, Yusupova, Valeriya, Zholobova, Elena, Grasa, Carlos Daniel, Epalza, Cristina, Lopez Segura, Nuria, Martinon-Torres, Federico, Melendo, Susana, Mendez-Echevarria, Ana, Mesa Guzmán, Juan Miguel, Palacios Argueta, Jorge Roberto, Rivero-Calle, Irene, Rivière, Jacques, Rodríguez-González, Moisés, Rojo, Pablo, Sanchez Manubens, Judith, Soler-Palacin, Pere, Soriano-Arandes, Antoni, Tagarro, Alfredo, Villaverde, Serena, Altman, Maria, Brodin, Petter, Horne, AnnaCarin, Palmblad, Karin, Brotschi, Barbara, Meyer Sauteur, Patrick, Pachlopnik Schmid, Jana, Prader, Seraina, Relly, Christa, Schlapbach, Luregn J., Seiler, Michelle, Strasser, Sophie, Trück, Johannes, Weber, Kathrin, Wütz, Daniela, Hamdan, Alaa, Melhem, Ibrahim, Moussa, Ahmed, Dunk, Joke, Ketharanathan, Naomi, Vermont, Clementien, Akyüz Özkan, Esra, Cetin, Benhur Sirvan, Erdeniz, Emine Hafize, Şahin, Irfan Oğuz, Borisova, Galina, Boyarchuk, Oksana, Boychenko, Lidiya, Boyko, Yaryna, Diudenko, Nadiia, Dyvonyak, Olha, Kasiyan, Olexandr, Katerynych, Kostiantyn, Kostyuchenko, Larysa, Mamenko, Marina, Melnyk, Kateryna, Miagka, Nelia, Nazarenko, Liliya, Nezgoda, Iryna, Rykova, Stanislava, Svyst, Olga, Teslenko, Maria, Trykosh, Mykola, Vasilenko, Nataliya, Volokha, Alla, Adams, Charlotte, Akomolafe, Toju, Al-Abadi, Eslam, Alders, Nele, Alifieraki, Styliani, Ansumanu, Hareef, Aston, Emily, Avram, Paula, Bamford, Alasdair, Banks, Millie, Basu Roy, Robin, Beattie, Thomas, Boleti, Olga, Bracken, Abbey, Broad, Jonathan, Cai, James, Carrol, Enitan D., Carter, Michael, Chandran, Anchit, Charlesworth, James, Chawla, Jaya, Cooper, Hannah, Cooray, Samantha, Davies, Patrick, Davis, Francesca, Drysdale, Simon B., Dzora, Ella, Emonts, Marieke, Evans, Ceri, Fidler, Katy, Foster, Caroline, Gong, Chen, Gongrun, Berin, Gonzalez, Carmen, Gorgun, Berin, Grandjean, Louis, Grant, Karlie, Guo, Jonathan, Hacohen, Yael, Hall, Jack, Hamid, Hytham K.S., Hassell, Jane, Hesketh, Christine, Hewlett, Jessica, Hnieno, Ahmad, Holt-Davis, Hannah, Hossain, Aleena, Hu, Shiying, Hudson, Lee D., Jheeta, Sharon, Johnson, Mae, Johnson, Sarah, Jyothish, Deepthi, Kampmann, Beate, Kavirayani, Akhila, Kelly, Deborah, Kirubakaran, Arangan, Kucera, Filip, Langer, Daniel, Lawson, George, Lees, Emily A, Lenihan, Rebecca, Lillie, Jon, Longbottom, Katherine, Lyall, Hermione, Mackdermott, Niamh, Maltby, Sarah, Mclelland, Thomas, McMahon, Anne-Marie, Miller, Danielle, Miranda, Mariana, Mirza, Luwaiza, Morrison, Zoe, Moshal, Karyn, Muller, Jennifer, Musuka, Phoebe, Myttaraki, Evangelia, Nadel, Simon, Nair, Sreedevi, Nuttall, Luke, Oremakinde, Oyinkansola, Osaghae, Daniella, Osman, Fatima, Ostrzewska, Anna, Paccagnella, Davide, Panthula, Mrinalini, Papachatzi, Eleni, Papadopoulou, Charalampia, Patel, Fahim, Patel, Harsita, Payne, Helen, Penner, Justin, Polandi, Shervin, Prendergast, Andrew J., Ramnarayan, Padmanabhan, Ranasinghe, Lasith, Ravichandran, Muthukumaran, Rhys-Evans, Sophie, Riordan, Andrew, Rodrigues, Charlene M.C., Roe, Lauren, Romaine, Sam, Schobi, Nina, Seddon, James, Shingadia, Delane, Sikdar, Oishi, Srivastava, Anand, Struik, Siske, Sun, Thomas, Tan, Rachel Wei, Taylor, Alice, Taylor, Amanda, Taylor, Andrew, Tran, Steven, Tsagkaris, Stavros, Tudor-Williams, Gareth, van den Berg, Sarah, van der Velden, Fabian, Ventilacion, Lyn, Wellman, Paul A., Withers Green, Joseph, Yanney, Michael P., Yeung, Shunmay, Badheka, Aditya, Badran, Sarah, Bailey, Dwight M., Burch, Anna Kathryn, Burns, Jane C., Cichon, Catherine, Cirks, Blake, Dallman, Michael D., Delany, Dennis R., Fairchok, Mary, Friedman, Samantha, Geracht, Jennifer, Langs-Barlow, Allison, Mann, Kelly, Padhye, Amruta, Quade, Alexis, Ramirez, Kacy Alyne, Rockett, John, Sayed, Imran Ali, Santos, Roberto P., Shahin, Amr A., Tremoulet, Adriana, Umaru, Samuel, Widener, Rebecca, Mujuru, Hilda Angela, Kandawasvika, Gwendoline, Channon-Wells, Samuel, Vito, Ortensia, McArdle, Andrew J, Seaby, Eleanor G, Shah, Priyen, Pazukhina, Ekaterina, Wilson, Clare, Broderick, Claire, D'Souza, Giselle, Keren, Ilana, Nijman, Ruud G, Carter, Michael J, De, Tisham, Hoggart, Clive, Whittaker, Elizabeth, Herberg, Jethro A, Kaforou, Myrsini, Cunnington, Aubrey J, Blyuss, Oleg, and Levin, Michael

Published
2023
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49. Origin of the 3-methylglutaryl moiety in caprazamycin biosynthesis

Author

Daniel Bär, Benjamin Konetschny, Andreas Kulik, Houchao Xu, Davide Paccagnella, Patrick Beller, Nadine Ziemert, Jeroen S. Dickschat, and Bertolt Gust

Subjects
Streptomyces coelicolor, Caprazamycin, Leucine/isovalerate utilization pathway, 3-methylglutaryl-CoA, Primary metabolism, Microbiology, QR1-502
Abstract

Abstract Background Caprazamycins are liponucleoside antibiotics showing bioactivity against Gram-positive bacteria including clinically relevant Mycobacterium tuberculosis by targeting the bacterial MraY-translocase. Their chemical structure contains a unique 3-methylglutaryl moiety which they only share with the closely related liposidomycins. Although the biosynthesis of caprazamycin is understood to some extent, the origin of 3-methylglutaryl-CoA for caprazamycin biosynthesis remains elusive. Results In this work, we demonstrate two pathways of the heterologous producer Streptomyces coelicolor M1154 capable of supplying 3-methylglutaryl-CoA: One is encoded by the caprazamycin gene cluster itself including the 3-hydroxy-3-methylglutaryl-CoA synthase Cpz5. The second pathway is part of primary metabolism of the host cell and encodes for the leucine/isovalerate utilization pathway (Liu-pathway). We could identify the liu cluster in S. coelicolor M1154 and gene deletions showed that the intermediate 3-methylglutaconyl-CoA is used for 3-methylglutaryl-CoA biosynthesis. This is the first report of this intermediate being hijacked for secondary metabolite biosynthesis. Furthermore, Cpz20 and Cpz25 from the caprazamycin gene cluster were found to be part of a common route after both individual pathways are merged together. Conclusions The unique 3-methylglutaryl moiety in caprazamycin originates both from the caprazamycin gene cluster and the leucine/isovalerate utilization pathway of the heterologous host. Our study enhanced the knowledge on the caprazamycin biosynthesis and points out the importance of primary metabolism of the host cell for biosynthesis of natural products.

Published
2022
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