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420 results on '"Pacini, L."'

151. CALET on the International Space Station: a precise measurement of the iron spectrum

Author

Checchia, C., Stolzi, F., Akaike, Y., Adriani, O., Asano, K., Asaoka, Y., Berti, E., Bigongiari, G., Binns, W. R., Bongi, M., Brogi, P., Bruno, A., Buckley, J. H., Cannady, N., Castellini, G., Cherry, M. L., Collazuol, G., Ebisawa, K., Ficklin, A. W., Fuke, H., Gonzi, S., Guzik, T. G., Hams, T., Hibino, K., Ichimura, M., Ioka, K., Ishizaki, W., Israel, M. H., Kasahara, K., Kataoka, J., Kataoka, R., Katayose, Y., Kato, C., Kawanaka, N., Kawakubo, Y., Kobayashi, K., Kohri, K., Krawczynski, H. S., Krizmanic, J. F., Maestro, P., Marrocchesi, P. S., Messineo, A. M., Mitchell, J. W., Miyake, S., Moiseev, A. A., Mori, M., Mori, N., Motz, H. M., Munakata, K., Nakahira, S., Nishimura, J., Nolfo, G. A., Okuno, S., Ormes, J. F., Nataly Ospina, Ozawa, S., Pacini, L., Papini, P., Rauch, B. F., Ricciarini, S. B., Sakai, K., Sakamoto, T., Sasaki, M., Shimizu, Y., Shiomi, A., Spillantini, P., Sugita, S., Sulaj, A., Takita, M., Tamura, T., Terasawa, T., Torii, S., Tsunesada, Y., Uchihori, Y., Vannuccini, E., Wefel, J. P., Yamaoka, K., Yanagita, S., Yoshida, A., Yoshida, K., and Zober, W. V.

152. The High Energy Particle Detector (HEPD-02) for the second China Seismo-Electromagnetic Satellite (CSES-02)

Author

Santis, C., Ricciarini, S. B., Bartocci, S., Battiston, R., Benotto, F., Beolé, S., Burger, W. J., Campana, D., Castellini, G., Cipollone, P., Coli, S., Conti, L., Contin, A., Cristoforetti, M., Cilladi, L., Donato, C., Follega, F. M., Gebbia, G., Iuppa, R., Lolli, M., Marcelli, N., Martucci, M., Masciantonio, G., Mergé, M., Mese, M., Neubuser, C., Nozzoli, F., Oliva, A., Osteria, G., Pacini, L., Palma, F., Palmonari, F., Parmentier, A., Perfetto, F., Picozza, P., Piersanti, M., Pozzato, M., Ricci, E., Ricci, M., Zouleikha Sahnoun, Scotti, V., Sotgiu, A., Sparvoli, R., Vitale, V., Zoffoli, S., and Zuccon, P.

154. Proton fluxes inside the South Atlantic Anomaly measured by the High-Energy Particle Detector (HEPD) on board the CSES-01 satellite during the 2018-2021 period

Author

Martucci, M., Bartocci, S., Battiston, R., Benotto, F., Beolè, S., Burger, W. J., Campana, D., Castellini, G., Cipollone, P., Coli, S., Conti, L., Contin, A., Cristoforetti, M., Cilladi, L., Donato, C., Santis, C., Follega, F. M., Gebbia, G., Iuppa, R., Lolli, M., Marcelli, N., Masciantonio, G., Mergé, M., Mese, M., Neubuser, C., Nozzoli, F., Oliva, A., Osteria, G., Pacini, L., Palma, F., Palmonari, F., Parmentier, A., Perfetto, F., Picozza, P., Piersanti, M., Pozzato, M., Ricci, E., Ricci, M., Ricciarini, S. B., Zouleikha Sahnoun, Scotti, V., Sotgiu, A., Sparvoli, R., Vitale, V., Zoffoli, S., and Zuccon, P.

161. Scientific Goals and In-orbit Performance of the High-energy Particle Detector on Board the CSES

Author

Roberto Battiston, P. Picozza, D. Campana, V. Vitale, Maria Ionica, Valentina Scotti, Marco Casolino, L. Patrizii, R. Sparvoli, Matteo Martucci, Ignazio Lazzizzera, L. Marcelli, M. Merge, S. Bartocci, M. Pozzato, M. Lolli, S. B. Ricciarini, I. Rashevskaya, Alessandro Sotgiu, F. Palma, Ester Ricci, Mirko Piersanti, F. Perfetto, Andrea Contin, Francesco Maria Follega, Bruno Spataro, G. Masciantonio, C. De Donato, S. Zoffoli, F. Palmonari, P. Cipollone, G. Castellini, L. Basara, C. Guandalini, Maria Antonietta Ricci, Livio Conti, G. Ambrosi, Beatrice Panico, C. Manea, A. Parmentier, L. Carfora, M. Puel, P. Zuccon, L. Pacini, G. Laurenti, W.J. Burger, C. De Santis, R. Iuppa, G. Osteria, Picozza, P., Battiston, R., Ambrosi, G., Bartocci, S., Basara, L., Burger, W. J., Campana, D., Carfora, L., Casolino, M., Castellini, G., Cipollone, P., Conti, L., Contin, A., De Donato, C., De Santis, C., Follega, F. M., Guandalini, C., Ionica, M., Iuppa, R., Laurenti, G., Lazzizzera, I., Lolli, M., Manea, C., Marcelli, L., Martucci, M., Masciantonio, G., Mergé, M., Osteria, G., Pacini, L., Palma, F., Palmonari, F., Panico, B., Parmentier, A., Patrizii, L., Perfetto, F., Piersanti, M., Pozzato, M., Puel, M., Rashevskaya, I., Ricci, E., Ricci, M., Ricciarini, S., Scotti, V., Sotgiu, A., Sparvoli, R., Spataro, B., Vitale, V., Zuccon, P., Zoffoli, S., Picozza P., Battiston R., Ambrosi G., Bartocci S., Basara L., Burger W.J., Campana D., Carfora L., Casolino M., Castellini G., Cipollone P., Conti L., Contin A., De Donato C., De Santis C., Follega F.M., Guandalini C., Ionica M., Iuppa R., Laurenti G., Lazzizzera I., Lolli M., Manea C., Marcelli L., Martucci M., Masciantonio G., Merge M., Osteria G., Pacini L., Palma F., Palmonari F., Panico B., Parmentier A., Patrizii L., Perfetto F., Piersanti M., Pozzato M., Puel M., Rashevskaya I., Ricci E., Ricci M., Ricciarini S., Scotti V., Sotgiu A., Sparvoli R., Spataro B., Vitale V., Zuccon P., and Zoffoli S.

Subjects
Astroparticle physics, Physics, High energy particle, solar-terrestrial relation, business.industry, Settore FIS/04, Detector, astroparticle physic, Earth, telescopes, Astronomy and Astrophysics, solar-terrestrial relations, Physics::Geophysics, On board, astroparticle physics, Space and Planetary Science, Physics::Space Physics, Astrophysics::Earth and Planetary Astrophysics, Aerospace engineering, Orbit (control theory), business
Abstract

The China Seismo-Electromagnetic Satellite (CSES) aims to monitor electromagnetic, particle, and plasma perturbations in the iono-magnetosphere and inner Van Allen radiation belts originated by electromagnetic sources external and internal to the geomagnetic cavity, cosmic rays, and solar events. In particular, the objective of the space mission is to investigate lithosphere-atmosphere-ionosphere coupling mechanisms (including the effects of lightning, earthquakes, volcanoes, and artificial electromagnetic emissions) that induce perturbations of the top side of the ionosphere and lower boundary of the radiation belts. To this purpose, the mission has been conceived to take advantage of a multi-instrument payload comprising nine detectors for the measurement of electromagnetic field components, plasma parameters, and energetic particles, as well as X-ray flux. The Italian team participating in the CSES mission has built one of these devices, the High-Energy Particle Detector (HEPD), for high-precision observations of electrons, protons, and light nuclei. During its trip along the orbit, and thanks to the large set of detectors operated on board, CSES completely monitors the Earth, acting as an excellent instrument for space weather. The satellite was launched on 2018 February 2, with an expected life span of 5 yr. This article describes the CSES mission with a particular focus on the HEPD apparatus and its in-flight performance.

Published
2019
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162. Calocube - A highly segmented calorimeter for a space based experiment

Author

S. Bottai, N. Daddi, S. B. Ricciarini, P. Spillantini, P. Papini, E. Vannuccini, Maria Miritello, A. Gregorio, G.F. Rappazzo, Marina Trimarchi, Alessia Tricomi, L. Pacini, G. Pauletta, O. Starodubtsev, R. D' Alessandro, G. Carotenuto, Anna Vedda, A. Tiberio, O. Adriani, M. Chiari, P. W. Cattaneo, A. Basti, A. Rappoldi, V. Bonvicini, N. Zampa, M. Bongi, Paolo Brogi, Antoniangelo Agnesi, Sebastiano Albergo, G. Castellini, S. Detti, L. Santi, Lucrezia Auditore, Lorenzo Bonechi, P. S. Marrocchesi, Mauro Fasoli, A. Sulaj, N. Finetti, Paolo Maestro, Antonio Trifiro, Federico Pirzio, J. E. Suh, B. Zerbo, S. Bonechi, G. Zampa, D. Cauz, Gabriele Bigongiari, Eugenio Berti, Piergiulio Lenzi, Nicola Mori, Maria Giuseppina Bisogni, Marco Grassi, Marco Incagli, Riccardo Paoletti and Giovanni Signorelli, D'Alessandro, R., Adriani, O., Agnesi, A., Albergo, S., Auditore, L., Basti, A., Berti, E., Bigongiari, G., Bonechi, L., Bonechi, S., Bongi, M., Bonvicini, V., Bottai, S., Brogi, P., Carotenuto, G., Castellini, G., Cattaneo, P. W., Cauz, D., Chiari, M., Daddi, N., Detti, S., Fasoli, M., Finetti, N., Gregorio, Anna, Lenzi, P., Maestro, P., Marrocchesi, P. S., Miritello, M., Mori, N., Pacini, L., Papini, P., Pauletta, G., Pirzio, F., Rappazzo, G. F., Rappoldi, A., Ricciarini, S., Santi, L. G., Spillantini, P., Starodubtsev, O., Suh, J. E., Sulaj, A., Tiberio, A., Tricomi, A., Trifiro, A., Trimarchi, M., Vannuccini, E., Vedda, A., Zampa, Gianluigi, Zampa, Nicola, Zerbo, B., D'Alessandro, R, Adriani, O, Agnesi, A, Albergo, S, Auditore, L, Basti, A, Berti, E, Bigongiari, G, Bonechi, L, Bonechi, S, Bongi, M, Bonvicini, V, Bottai, S, Brogi, P, Carotenuto, G, Castellini, G, Cattaneo, P, Cauz, D, Chiari, M, Daddi, N, Detti, S, Fasoli, M, Finetti, N, Gregorio, A, Lenzi, P, Maestro, P, Marrocchesi, P, Miritello, M, Mori, N, Pacini, L, Papini, P, Pauletta, G, Pirzio, F, Rappazzo, G, Rappoldi, A, Ricciarini, S, Santi, L, Spillantini, P, Starodubtsev, O, Suh, J, Sulaj, A, Tiberio, A, Tricomi, A, Trifiro, A, Trimarchi, M, Vannuccini, E, Vedda, A, Zampa, G, Zampa, N, and Zerbo, B

Subjects
Physics, Calorimeter, Nuclear and High Energy Physics, Astroparticle, Crystals, Instrumentation, Calorimeter (particle physics), 010308 nuclear & particles physics, Detector, Cosmic ray, Space (mathematics), 01 natural sciences, Particle identification, Nuclear physics, Acceleration, 0103 physical sciences, Crystal, 010306 general physics, Energy (signal processing)
Abstract

Future research in High Energy Cosmic Ray Physics concerns fundamental questions on their origin, acceleration mechanism, and composition. Unambiguous measurements of the energy spectra and of the composition of cosmic rays at the “knee” region could provide some of the answers to the above questions. Only ground based observations, which rely on sophisticated models describing high energy interactions in the earth׳s atmosphere, have been possible so far due to the extremely low particle rates at these energies. A calorimeter based space experiment can provide not only flux measurements but also energy spectra and particle identification, especially when coupled to a dE/dx measuring detector, and thus overcome some of the limitations plaguing ground based experiments. For this to be possible very large acceptances are needed if enough statistic is to be collected in a reasonable time. This contrasts with the lightness and compactness requirements for space based experiments. A novel idea in calorimetry is discussed here which addresses these issues while limiting the mass and volume of the detector. In fact a small prototype is currently being built and tested with ions. In this paper the results obtained will be presented in light of the simulations performed.

Published
2016

163. Synthetic short-chain peptide analogues of H1 relaxin lack affinity for the RXFP1 receptor and relaxin-like bioactivity. Clues to a better understanding of relaxin agonist design

Author

Annunziata D'Ercole, Silvia Nistri, Lorenzo Pacini, Alfonso Carotenuto, Federica Santoro, Anna Maria Papini, Ross A. D. Bathgate, Daniele Bani, Paolo Rovero, D'Ercole, A., Nistri, S., Pacini, L., Carotenuto, A., Santoro, F., Papini, A. M., Bathgate, R. A. D., Bani, D., and Rovero, P.

Subjects
Pharmacology, RXFP1, ERK1/2, cAMP, relaxin analogue, Pharmacology (medical), relaxin, RXFP1 agonists
Abstract

The peptide hormone relaxin (RLX), also available as clinical-grade recombinant protein (serelaxin), holds great promise as a cardiovascular and anti-fibrotic agent but is limited by the pharmacokinetic issues common to all peptide drugs. In this study, by a computational modelling chemistry approach, we have synthesized and tested a set of low molecular weight peptides based on the putative receptor-binding domain of the B chain of human H1 RLX isoform, with the objective to obtain RLX analogues with improved pharmacokinetic features. Some of them were stabilized to induce the appropriate 3-D conformation by intra-chain tri-azolic staples, which should theoretically enhance their resistance to digestive enzymes making them suited for oral administration. Despite these favourable premises, none of these H1 peptides, either linear or stapled, revealed a sufficient affinity to the specific RLX receptor RXFP1. Moreover, none of them was endowed with any RLX-like biological effects in RXFP1-expressing THP-1 human monocytic cells and mouse NIH-3T3-derived myofibroblasts in in vitro culture, in terms of significantly relevant cAMP elevation and ERK1/2 phosphorylation, which represent two major signal transduction events downstream RXFP1 activation. This was at variance with authentic serelaxin, which induced a clear-cut, significant activation of both these classical RLX signaling pathways. Albeit negative, the results of this study offer additional information about the structural requirements that new peptide therapeutics shall possess to effectively behave as RXFP1 agonists and RLX analogues.

Published
2022
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164. A SARS–CoV-2 Spike Receptor Binding Motif Peptide Induces Anti-Spike Antibodies in Mice andIs Recognized by COVID-19 Patients

Author

Federico Pratesi, Fosca Errante, Lorenzo Pacini, Irina Charlot Peña-Moreno, Sebastian Quiceno, Alfonso Carotenuto, Saidou Balam, Drissa Konaté, Mahamadou M. Diakité, Myriam Arévalo-Herrera, Andrey V. Kajava, Paolo Rovero, Giampietro Corradin, Paola Migliorini, Anna M. Papini, Sócrates Herrera, Pratesi, F., Errante, F., Pacini, L., Pena-Moreno, I. C., Quiceno, S., Carotenuto, A., Balam, S., Konate, D., Diakite, M. M., Arevalo-Herrera, M., Kajava, A. V., Rovero, P., Corradin, G., Migliorini, P., Papini, A. M., and Herrera, S.

Subjects
SARS-CoV-2, Animal, Immunology, COVID-19, Antibodies, Viral, neutralizing Ab, Mice, Spike Glycoprotein, Coronavirus, Peptide, Animals, Humans, immunized animal, receptor binding motif, Immunology and Allergy, Peptides, spike (S) protein, Spike Glycoprotein, Coronaviru, Human
Abstract

The currently devastating pandemic of severe acute respiratory syndrome known as coronavirus disease 2019 or COVID-19 is caused by the coronavirus SARS-CoV-2. Both the virus and the disease have been extensively studied worldwide. A trimeric spike (S) protein expressed on the virus outer bilayer leaflet has been identified as a ligand that allows the virus to penetrate human host cells and cause infection. Its receptor-binding domain (RBD) interacts with the angiotensin-converting enzyme 2 (ACE2), the host-cell viral receptor, and is, therefore, the subject of intense research for the development of virus control means, particularly vaccines. In this work, we search for smaller fragments of the S protein able to elicit virus-neutralizing antibodies, suitable for production by peptide synthesis technology. Based on the analysis of available data, we selected a 72 aa long receptor binding motif (RBM436-507) of RBD. We used ELISA to study the antibody response to each of the three antigens (S protein, its RBD domain and the RBM436-507 synthetic peptide) in humans exposed to the infection and in immunized mice. The seroreactivity analysis showed that anti-RBM antibodies are produced in COVID-19 patients and immunized mice and may exert neutralizing function, although with a frequency lower than anti-S and -RBD. These results provide a basis for further studies towards the development of vaccines or treatments focused on specific regions of the S virus protein, which can benefit from the absence of folding problems, conformational constraints and other advantages of the peptide synthesis production.

Published
2022
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165. Design of an Antimatter Large Acceptance Detector In Orbit (ALADInO)

Author

Oscar Adriani, Corrado Altomare, Giovanni Ambrosi, Philipp Azzarello, Felicia Carla Tiziana Barbato, Roberto Battiston, Bertrand Baudouy, Benedikt Bergmann, Eugenio Berti, Bruna Bertucci, Mirko Boezio, Valter Bonvicini, Sergio Bottai, Petr Burian, Mario Buscemi, Franck Cadoux, Valerio Calvelli, Donatella Campana, Jorge Casaus, Andrea Contin, Raffaello D’Alessandro, Magnus Dam, Ivan De Mitri, Francesco de Palma, Laurent Derome, Valeria Di Felice, Adriano Di Giovanni, Federico Donnini, Matteo Duranti, Emanuele Fiandrini, Francesco Maria Follega, Valerio Formato, Fabio Gargano, Francesca Giovacchini, Maura Graziani, Maria Ionica, Roberto Iuppa, Francesco Loparco, Jesús Marín, Samuele Mariotto, Giovanni Marsella, Gustavo Martínez, Manel Martínez, Matteo Martucci, Nicolò Masi, Mario Nicola Mazziotta, Matteo Mergé, Nicola Mori, Riccardo Munini, Riccardo Musenich, Lorenzo Mussolin, Francesco Nozzoli, Alberto Oliva, Giuseppe Osteria, Lorenzo Pacini, Mercedes Paniccia, Paolo Papini, Mark Pearce, Chiara Perrina, Piergiorgio Picozza, Cecilia Pizzolotto, Stanislav Pospíšil, Michele Pozzato, Lucio Quadrani, Ester Ricci, Javier Rico, Lucio Rossi, Enrico Junior Schioppa, Davide Serini, Petr Smolyanskiy, Alessandro Sotgiu, Roberta Sparvoli, Antonio Surdo, Nicola Tomassetti, Valerio Vagelli, Miguel Ángel Velasco, Xin Wu, Paolo Zuccon, Adriani O., Altomare C., Ambrosi G., Azzarello P., Barbato F.C.T., Battiston R., Baudouy B., Bergmann B., Berti E., Bertucci B., Boezio M., Bonvicini V., Bottai S., Burian P., Buscemi M., Cadoux F., Calvelli V., Campana D., Casaus J., Contin A., D'alessandro R., Dam M., De Mitri I., de Palma F., Derome L., Di Felice V., Di Giovanni A., Donnini F., Duranti M., Fiandrini E., Follega F.M., Formato V., Gargano F., Giovacchini F., Graziani M., Ionica M., Iuppa R., Loparco F., Marin J., Mariotto S., Marsella G., Martinez G., Martinez M., Martucci M., Masi N., Mazziotta M.N., Merge M., Mori N., Munini R., Musenich R., Mussolin L., Nozzoli F., Oliva A., Osteria G., Pacini L., Paniccia M., Papini P., Pearce M., Perrina C., Picozza P., Pizzolotto C., Pospisil S., Pozzato M., Quadrani L., Ricci E., Rico J., Rossi L., Schioppa E.J., Serini D., Smolyanskiy P., Sotgiu A., Sparvoli R., Surdo A., Tomassetti N., Vagelli V., Velasco M.A., Wu X., Zuccon P., Département des Accélérateurs, de Cryogénie et de Magnétisme (ex SACM) (DACM), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), and Université Grenoble Alpes (UGA)

Subjects
antimatter, cosmic rays, dark matter, particle detectors, space instrumentation, Astrophysics::High Energy Astrophysical Phenomena, Settore FIS/01 - Fisica Sperimentale, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Instrumentation
Abstract

International audience; A new generation magnetic spectrometer in space will open the opportunity to investigate the frontiers in direct high-energy cosmic ray measurements and to precisely measure the amount of the rare antimatter component in cosmic rays beyond the reach of current missions. We propose the concept for an Antimatter Large Acceptance Detector In Orbit (ALADInO), designed to take over the legacy of direct measurements of cosmic rays in space performed by PAMELA and AMS-02. ALADInO features technological solutions conceived to overcome the current limitations of magnetic spectrometers in space with a layout that provides an acceptance larger than 10 m sr. A superconducting magnet coupled to precision tracking and time-of-flight systems can provide the required matter–antimatter separation capabilities and rigidity measurement resolution with a Maximum Detectable Rigidity better than 20 TV. The inner 3D-imaging deep calorimeter, designed to maximize the isotropic acceptance of particles, allows for the measurement of cosmic rays up to PeV energies with accurate energy resolution to precisely measure features in the cosmic ray spectra. The operations of ALADInO in the Sun–Earth L2 Lagrangian point for at least 5 years would enable unique revolutionary observations with groundbreaking discovery potentials in the field of astroparticle physics by precision measurements of electrons, positrons, and antiprotons up to 10 TeV and of nuclear cosmic rays up to PeV energies, and by the possible unambiguous detection and measurement of low-energy antideuteron and antihelium components in cosmic rays.

Published
2022
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166. The CaloCube calorimeter for high-energy cosmic-ray measurements in space: Performance of a large-scale prototype

Author

Anna Vedda, P. Spillantini, A. Rappoldi, N. Zampa, J. E. Suh, M. Olmi, A. Sulaj, G. Zampa, Raffaello D'Alessandro, V. Bonvicini, A. Sciuto, Lucrezia Auditore, S. B. Ricciarini, Alessia Tricomi, Gabriele Bigongiari, M. Bongi, S. Bottai, Eugenio Berti, P. Papini, E. Vannuccini, P. S. Marrocchesi, F. Stolzi, Mauro Fasoli, A. Basti, S. Detti, G. Orzan, C. Poggiali, Paolo Brogi, C. Checchia, Sebastiano Albergo, Paolo Maestro, Antonio Trifiro, M. Antonelli, G. Castellini, C. Pizzolotto, Antonio Italiano, O. Adriani, Federico Pirzio, P. W. Cattaneo, Lorenzo Bonechi, O. Starodubtsev, M. Trimarchi, Nicola Mori, A. Tiberio, L. Pacini, Antonio Agnesi, M. G. Pellegriti, N. Finetti, Adriani, O, Agnesi, A, Albergo, S, Antonelli, M, Auditore, L, Basti, A, Berti, E, Bigongiari, G, Bonechi, L, Bongi, M, Bonvicini, V, Bottai, S, Brogi, P, Castellini, G, Cattaneo, P, Checchia, C, D'Alessandro, R, Detti, S, Fasoli, M, Finetti, N, Italiano, A, Maestro, P, Marrocchesi, P, Mori, N, Orzan, G, Olmi, M, Pacini, L, Papini, P, Pellegriti, M, Pirzio, F, Pizzolotto, C, Poggiali, C, Rappoldi, A, Ricciarini, S, Sciuto, A, Spillantini, P, Starodubtsev, O, Stolzi, F, Suh, J, Sulaj, A, Tiberio, A, Tricomi, A, Trifiro, A, Trimarchi, M, Vedda, A, Vannuccini, E, Zampa, G, and Zampa, N

Subjects
Calorimeters, Large detector systems for particle and astroparticle physics, Space instrumentation, Physics - Instrumentation and Detectors, Scale (ratio), Physics::Instrumentation and Detectors, FOS: Physical sciences, Cosmic ray, High Energy Physics - Experiment, High Energy Physics - Experiment (hep-ex), Aerospace engineering, Absorption (electromagnetic radiation), Instrumentation, Instrumentation and Methods for Astrophysics (astro-ph.IM), Mathematical Physics, Physics, Calorimeter, Large Hadron Collider, business.industry, Isotropy, Instrumentation and Detectors (physics.ins-det), Large detector systems for particle and astroparticle physic, Granularity, business, Astrophysics - Instrumentation and Methods for Astrophysics, Energy (signal processing)
Abstract

The direct observation of high-energy cosmic rays, up to the PeV energy region, will increasingly rely on highly performing calorimeters, and the physics performance will be primarily determined by their geometrical acceptance and energy resolution. Thus, it is extremely important to optimize their geometrical design, granularity and absorption depth, with respect to the totalmass of the apparatus, which is amongst the most important constraints for a space mission. CaloCube is an homogeneous calorimeter whose basic geometry is cubic and isotropic, obtained by filling the cubic volume with small cubic scintillating crystals. In this way it is possible to detect particles arriving from every direction in space, thus maximizing the acceptance. This design summarizes a three-year R&D activity, aiming to both optimize and study the full-scale performance of the calorimeter, in the perspective of a cosmic-ray space mission, and investigate a viable technical design by means of the construction of several sizable prototypes. A large scale prototype, made of a mesh of 5x5x18 CsI(Tl) crystals, has been constructed and tested on high-energy particle beams at CERN SPS accelerator. In this paper we describe the CaloCube design and present the results relative to the response of the large scale prototype to electrons., 24 pages, 19 figures

Published
2021

167. Abruzzo: ceppo epidemico di legno nero

Author

D’Ascenzo, D., Mori, N., Posenato, G., Pacini, F., Crivelli, L., Di Loreto, D., Scotillo, M. A., Contaldo, N., Bertaccini, A., and D’Ascenzo D., N. Mori, G. Posenato, F. Pacini, L. Crivelli, D. Di Loreto, M.A. Scotillo, N. Contaldo, A. Bertaccini

Subjects
Giallumi della vite, vite, giallumi, legno nero, Scaphoideus titanus, Giallumi della vite, Hyalesthes obsoletus, indagini genetiche, Hyalesthes obsoletus, indagini genetiche
Abstract

I fitoplasmi della vite associati alla presenza di giallumi in Italia so- no stati studiati dal 2017 nell’am- bito del progetto europeo H2020 TROPICSAFE (Malattie associate alla presenza di procarioti e trasmesse da insetti in colture arboree in aree tro- picali e subtropicali). Le malattie studiate sono giallume letale della palma da cocco; giallu- me della vite e «huanglongbing» degli agrumi («citrus greening»), tutte gravi malattie infettive che solo di recente sono state riconosciute e studiate. Il progetto è finalizzato ad una loro ge- stione efficace, efficiente e sostenibile per ottenere la quale è necessario col- mare importanti lacune scientifiche. Il progetto cui partecipano dodici na- zioni (Italia, Spagna, Slovenia, Dani- marca, Regno Unito, Ghana, Sudafrica, Cile, Cuba, Messico, Giamaica e Francia - Guadalupa) è coordinato dalla profes- soressa Assunta Bertaccini dell’Alma Mater Studiorum - Università di Bolo- gna. Alcuni dei risultati delle ricerche sui giallumi della vite in collaborazio- ne con Istituzioni, colleghi e studenti sono riassunti nelle brevi note che se- guono e forniscono un aggiornamen- to sulla situazione della malattia in alcune delle aree viticole italiane più importanti.

Published
2021

168. Exploring Allosteric Pathways of a V-Type Enzyme with Dynamical Perturbation Networks

Author

Ivan Rivalta, Laurent Vuillon, Lorenza Pacini, Aria Gheeraert, Victor S. Batista, Claire Lesieur, Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Ampère, Département Bioingénierie (BioIng), Ampère (AMPERE), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Rhône-Alpin des systèmes complexes (IXXI), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Mathématiques (LAMA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Chemistry [New Haven], Yale University [New Haven], Dipartimento di Chimica Industriale 'Toso Montanari', Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Gheeraert A., Pacini L., Batista V.S., Vuillon L., Lesieur C., Rivalta I., École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Ampère, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Joseph Fourier - Grenoble 1 (UJF)-École normale supérieure - Lyon (ENS Lyon), Laboratoire d'Analyse et de Mathématiques Appliquées (LAMA), Université Paris-Est Marne-la-Vallée (UPEM)-Fédération de Recherche Bézout-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Università di Bologna [Bologna] (UNIBO), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École Centrale de Lyon (ECL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Jean Moulin - Lyon 3 (UJML), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Allosteric regulation, Drug design, Molecular Dynamics Simulation, 010402 general chemistry, 01 natural sciences, Protein Structure, Secondary, Article, Molecular dynamics, Protein structure, Allosteric Regulation, 0103 physical sciences, Materials Chemistry, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, Physics, [PHYS]Physics [physics], 010304 chemical physics, biology, Allostery, Molecular Dynamics, Network Analysis, Allosteric Enzyme, Graph theory, Protein engineering, 0104 chemical sciences, Surfaces, Coatings and Films, Enzymes, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Allosteric enzyme, biology.protein, Biological system, Network analysis
Abstract

International audience; Elucidation of the allosteric pathways in proteins is a computational challenge that strongly benefits from combination of atomistic molecular dynamics (MD) simulations and coarse-grained analysis of the complex dynamical network of chemical interactions based on graph theory. Here, we introduce and assess the performances of the dynamical perturbation network analysis of allosteric pathways in a prototypical V-type allosteric enzyme. Dynamical atomic contacts obtained from MD simulations are used to weight the allosteric protein graph, which involves an extended network of contacts perturbed by the effector binding in the allosteric site. The outcome showed good agreement with previously reported theoretical and experimental extended studies and it provided recognition of new potential allosteric spots that can be exploited in future mutagenesis experiments. Overall, the dynamical perturbation network analysis proved to be a powerful computational tool, complementary to other network-based approaches that can assist the full exploitation of allosteric phenomena for advances in protein engineering and rational drug design.

Published
2019
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169. A new approach to calorimetry in space-based experiments for high-energy cosmic rays

Author

M. Duranti, S. B. Ricciarini, Piergiulio Lenzi, Miriam Olmi, E. Vannuccini, Anna Vedda, Noemi Finetti, Maria Grazia Pellegriti, V. Bonvicini, Gabriele Bigongiari, Massimo Bongi, Eugenio Berti, Jung Eun Suh, Sebastiano Albergo, Alessio Tiberio, A. Sciuto, F. Stolzi, S. Bonechi, Lucrezia Auditore, Marina Trimarchi, Maria Ionica, Paolo Papini, S. Detti, Gianluigi Silvestre, P. W. Cattaneo, Paolo Maestro, S. Bottai, N. Zampa, Antonio Trifiro, G. Orzan, Giovanni Ambrosi, Gigi Cappello, P. S. Marrocchesi, O. Adriani, A. Rappoldi, L. Pacini, Valerio Formato, A. Sulaj, Antonio Italiano, Lorenzo Bonechi, Mauro Fasoli, Paolo Brogi, Nicola Mori, Gianluigi Zampa, Raffaello D'Alessandro, Alessia Tricomi, A. Basti, O. Starodubtsev, Bigongiari, G, Adriani, O, Albergo, S, Ambrosi, G, Auditore, L, Basti, A, Berti, E, Bonechi, L, Bonechi, S, Bongi, M, Bonvicini, V, Bottai, S, Brogi, P, Cappello, G, Cattaneo, P, D'Alessandro, R, Detti, S, Duranti, M, Fasoli, M, Finetti, N, Formato, V, Ionica, M, Italiano, A, Lenzi, P, Maestro, P, Marrocchesi, P, Mori, N, Orzan, G, Olmi, M, Pacini, L, Papini, P, Pellegriti, M, Rappoldi, A, Ricciarini, S, Sciuto, A, Silvestre, G, Starodubtsev, O, Stolzi, F, Suh, J, Sulaj, A, Tiberio, A, Tricomi, A, Trifiro, A, Trimarchi, M, Vannuccini, E, Vedda, A, Zampa, G, and Zampa, N

Subjects
lcsh:QC793-793.5, Physics::Instrumentation and Detectors, Hadron, Monte Carlo method, General Physics and Astronomy, Cosmic ray, Calorimetry, Electron, 01 natural sciences, Spectral line, Physics and Astronomy (all), Astroparticle, 0103 physical sciences, 7-ray astronomy, Astroparticles, Cosmic rays, Ultra-high-energy cosmic ray, 010306 general physics, ++++γ<%2Fmml%3Ami>+<%2Fmml%3Amrow>+<%2Fmml%3Asemantics>+<%2Fmml%3Amath>+<%2Finline-formula><%2Fnamed-content>-ray+astronomy%22"> γ -ray astronomy, Gamma-ray astronomy, Physics, 010308 nuclear & particles physics, lcsh:Elementary particle physics, Detector, Computational physics, γ -ray astronomy
Abstract

Precise measurements of the energy spectra and of the composition of cosmic rays in the PeV region could improve our knowledge regarding their origin, acceleration mechanism, propagation, and composition. At the present time, spectral measurements in this region are mainly derived from data collected by ground-based detectors, because of the very low particle rates at these energies. Unfortunately, these results are affected by the high uncertainties typical of indirect measurements, which depend on the complicated modeling of the interaction of the primary particle with the atmosphere. A space experiment dedicated to measurements in this energy region has to achieve a balance between the requirements of lightness and compactness, with that of a large acceptance to cope with the low particle rates. CaloCube is a four-year-old R&amp, D project, approved and financed by the Istituto Nazionale di Fisica Nucleare (INFN) in 2014, aiming to optimize the design of a space-borne calorimeter. The large acceptance needed is obtained by maximizing the number of entrance windows, while thanks to its homogeneity and high segmentation this new detector achieves an excellent energy resolution and an enhanced separation power between hadrons and electrons. In order to optimize detector performances with respect to the total mass of the apparatus, comparative studies on different scintillating materials, different sizes of crystals, and different spacings among them have been performed making use of MonteCarlo simulations. In parallel to simulations studies, several prototypes instrumented with CsI(Tl) (Caesium Iodide, Tallium doped) cubic crystals have been constructed and tested with particle beams. Moreover, the last development of CaloCube, the Tracker-In-Calorimeter (TIC) project, financed by the INFN in 2018, is focused on the feasibility of including several silicon layers at different depths in the calorimeter in order to reconstruct the particle direction. In fact, an important requirement for &gamma, ray astronomy is to have a good angular resolution in order to allow precise identification of astrophysical sources in space. In respect to the traditional approach of using a tracker with passive material in front of the calorimeter, the TIC solution can save a significant amount of mass budget in a space satellite experiment, which can then be exploited to improve the acceptance and the resolution of the calorimeter. In this paper, the status of the project and perspectives for future developments are presented.

Published
2019
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170. CaloCube: A new concept calorimeter for the detection of high energy cosmic rays in space

Author

E Berti, O Adriani, S Albergo, G Ambrosi, L Auditore, A Basti, G Bigongiari, L Bonechi, S Bonechi, M Bongi, V Bonvicini, S Bottai, P Brogi, G Cappello, P W Cattaneo, R D Alessandro, S Detti, M Duranti, M Fasoli, N Finetti, V Formato, M Ionica, A Italiano, P Lenzi, P Maestro, P S Marrocchesi, N Mori, G Orzan, M Olmi, L Pacini, P Papini, A Rappoldi, S Ricciarini, A Sciuto, G Silvestre, O Starodubtsev, F Stolzi, J E Suh, A Sulaj, A Tiberio, A Tricomi, A Trifirò, M Trimarchi, E Vannuccini, A Vedda, G Zampa, N Zampa, Berti, E, Adriani, O, Albergo, S, Ambrosi, G, Auditore, L, Basti, A, Bigongiari, G, Bonechi, L, Bonechi, S, Bongi, M, Bonvicini, V, Bottai, S, Brogi, P, Cappello, G, Cattaneo, P, Alessandro, R, Detti, S, Duranti, M, Fasoli, M, Finetti, N, Formato, V, Ionica, M, Italiano, A, Lenzi, P, Maestro, P, Marrocchesi, P, Mori, N, Orzan, G, Olmi, M, Pacini, L, Papini, P, Rappoldi, A, Ricciarini, S, Sciuto, A, Silvestre, G, Starodubtsev, O, Stolzi, F, Suh, J, Sulaj, A, Tiberio, A, Tricomi, A, Trifir, A, Trimarchi, M, Vannuccini, E, Vedda, A, Zampa, G, and Zampa, N

Subjects
Energy resolutions, History, Calorimeters, CsI, Physics::Instrumentation and Detectors, calorimeter, energy resolution, High Energy Physics::Experiment, High energy physics, Cosmic rays, Computer Science Applications, Education, crystal
Abstract

Given the good performances in terms of geometrical acceptance and energy resolution, calorimeters are the best suited detectors to measure high energy cosmic rays directly in space. However, in order to exploit this potential, the design of calorimeters must be carefully optimized to take into account all limitations related to space missions, due mainly to the mass of the experimental apparatus. CaloCube is a three years R&D project, approved and financed by INFN in 2014, aiming to optimize the design of a space-borne calorimeter by the use of a cubic, homogeneous and isotropic geometry. In order to maximize detector performances with respect to the total mass of the apparatus, comparative studies on different scintillating materials, different sizes of crystals and different spacings among them have been performed making use of Monte Carlo simulations. In parallel to this activity, several prototypes instrumented with CsI:Tl cubic crystals have been constructed and tested with particle beams (muons, electrons, protons and ions). Both simulations and prototypes showed that the CaloCube design leads to a good particle energy resolution (< 2% for electromagnetic showers, < 40% for hadronic showers) and a good effective geometric factor (> 3:5 m2 sr for electromagnetic showers, > 2:5 m2 sr for hadronic showers). Thanks to these performances, in 5 years of operation it would be possible to measure the ux of electrons+positrons up to some tens of TeV and the uxes of protons and nuclei up to some units of PeV/nucleon, hence extending these measurements by at least one order of magnitude in energy compared to the experiments currently operating in space.

Published
2019

171. The HEPD particle detector of the CSES satellite mission for investigating seismo-associated perturbations of the Van Allen belts

Author

F. Perfetto, Bruno Spataro, P. Cipollone, S. B. Ricciarini, L. Pacini, Roberta Sparvoli, Piergiorgio Picozza, Cinzia De Donato, Roberto Battiston, F. Palma, Vincenzo Vitale, S. Bartocci, M. Pozzato, Beatrice Panico, Giovanni Ambrosi, G. Laurenti, I. Lazzizzera, Valentina Scotti, L. Carfora, L. Patrizii, G. Masciantonio, G. Castellini, Cristina Guandalini, L. Marcelli, M. Ricci, Francesco Maria Follega, Ester Ricci, Andrea Contin, Irina Rashevskaya, Matteo Puel, F. Palmonari, Alessando Sotgiu, Roberto Iuppa, Livio Conti, Cristian De Santis, M. Merge, C. Manea, Laurent Basara, William J. Burger, G. Osteria, Maria Ionica, M. Lolli, Ambrosi, Giovanni, Bartocci, Simona, Basara, Laurent, Battiston, Roberto, Burger, William J., Carfora, Luca, Castellini, Guido, Cipollone, Piero, Conti, Livio, Contin, Andrea, De Donato, Cinzia, De Santis, Cristian, Follega, Francesco M., Guandalini, Cristina, Ionica, Maria, Iuppa, Roberto, Laurenti, Giuliano, Lazzizzera, Ignazio, Lolli, Mauro, Manea, Christian, Marcelli, Laura, Masciantonio, Giuseppe, Mergé, Matteo, Osteria, Giuseppe, Pacini, Lorenzo, Palma, Francesco, Palmonari, Federico, Panico, Beatrice, Patrizii, Laura, Perfetto, Francesco, Picozza, Piergiorgio, Pozzato, Michele, Puel, Matteo, Rashevskaya, Irina, Ricci, Ester, Ricci, Marco, Ricciarini, Sergio Bruno, Scotti, Valentina, Sotgiu, Alessando, Sparvoli, Roberta, Spataro, Bruno, Vitale, Vincenzo, Ambrosi, G., Bartocci, S., Basara, L., Battiston, R., Burger, W. J., Carfora, L., Castellini, G., Cipollone, P., Conti, L., Contin, A., De Donato, C., De Santis, C., Follega, F. M., Guandalini, C., Ionica, M., Iuppa, R., Laurenti, G., Lazzizzera, I., Lolli, M., Manea, C., Marcelli, L., Masciantonio, G., Mergé, M., Osteria, G., Pacini, L., Palma, F., Palmonari, F., Panico, B., Patrizii, L., Perfetto, F., Picozza, P., Pozzato, M., Puel, M., Rashevskaya, I., Ricci, E., Ricci, M., Ricciarini, S. B., Scotti, V., Sotgiu, A., Sparvoli, R., Spataro, B., and Vitale, V.

Subjects
High energy particle, 010504 meteorology & atmospheric sciences, seismic-precursor, space weather, Magnetosphere, Cosmic ray, ionosphere, Space weather, 010502 geochemistry & geophysics, 01 natural sciences, Particle detector, Physics::Geophysics, symbols.namesake, Engineering (all), cosmic rays, General Materials Science, Van Allen belts, cosmic ray, 0105 earth and related environmental sciences, particle detector, Settore FIS/01, Physics, Van Allen belt, General Engineering, Astronomy, Charged particle, Van Allen radiation belt, earthquake, Physics::Space Physics, symbols, magnetosphere, seismic-precursors, Satellite, Materials Science (all)
Abstract

CSES (China Seismo-Electromagnetic Satellite) is a mission developed by CNSA (Chinese National Space Administration) and ASI (Italian Space Agency), to investigate the near-Earth electromagnetic, plasma and particle environment, for studying the seismo-associated disturbances in the ionosphere-magnetosphere transition zone. The anthropogenic and electromagnetic noise, as well as the natural non-seismic electromagnetic emissions is mainly due to tropospheric activity. In particular, the mission aims to confirming the existence of possible temporal correlations between the occurrence of earthquakes for medium and strong magnitude and the observation in space of electromagnetic perturbations, plasma variations and precipitation of bursts with high-energy charged particles from the inner Van Allen belt. In this framework, the high energy particle detector (HEPD) of the CSES mission has been developed by the Italian LIMADOU Collaboration. HEPD is an advanced detector based on a tower of scintillators and a silicon tracker that provides good energy and angular resolution and a wide angular acceptance, for electrons of 3-100 MeV, protons of 30-200 MeV and light nuclei up to the oxygen. CSES satellite has been launched on February 2nd, 2018 from the Jiuquan Satellite Launch Center (China). © 2018, Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.

Published
2018
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172. Absence of the Fragile X Mental Retardation Protein results in defects of RNA editing of neuronal mRNAs in mouse

Author

Caroline Lacoux, Jessica Mingardi, Daniela Bonini, Luca La Via, Claudia Bagni, Maria Zingariello, Alice Filippini, Laura Pacini, Daniela Bosisio, Laura Sancillo, Francesca Zalfa, Alessandro Barbon, Valentina Salvi, Filippini, A, Bonini, D, Lacoux, C, Pacini, L, Zingariello, M, Sancillo, L, Bosisio, D, Salvi, V, Mingardi, J, LA VIA, L, Zalfa, F, Bagni, C, Barbon, A, University of Brescia, Department of Biomedicine and Prevention, Università degli Studi di Roma Tor Vergata [Roma], Università Campus Bio-Medico di Roma, Partenaires INRAE, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Flanders Institute for Biotechnology, Lausanne University Hospital, MIUR (PRIN) [2012A9T2S9_004], Fondazione Cariplo, Associazione Italiana Sindrome X Fragile, Telethon [GGP15257], Lejeune Foundation, and La Via, L

Subjects
Male, 0301 basic medicine, RNA editing, Adenosine Deaminase, [SDV]Life Sciences [q-bio], Messenger, Adenosine Deaminase/genetics, Adenosine Deaminase/metabolism, Animals, Cell Nucleus/metabolism, Cell Nucleus/ultrastructure, Cerebral Cortex/metabolism, Cerebral Cortex/pathology, Disease Models, Animal, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/genetics, Fragile X Syndrome/metabolism, Fragile X Syndrome/pathology, Gene Deletion, Hippocampus/metabolism, Hippocampus/pathology, Humans, Mice, Mice, Knockout, Neurons/metabolism, Neurons/pathology, Phenotype, Primary Cell Culture, Protein Binding, RNA Editing, RNA, Messenger/genetics, RNA, Messenger/metabolism, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism, ADAR2, FMRP, Fragile X syndrome, RNA-binding protein, Proximity ligation assay, Hippocampus, Fragile X Mental Retardation Protein, Zebrafish, Cerebral Cortex, Neurons, Settore BIO/13, RNA-Binding Proteins, medicine.anatomical_structure, Cell Nucleus, Fragile X Syndrome, RNA, Messenger, Research Paper, congenital, hereditary, and neonatal diseases and abnormalities, Knockout, Biology, 03 medical and health sciences, medicine, RNA editing, FMRP, Molecular Biology, Animal, RNA, Cell Biology, biology.organism_classification, FMR1, Molecular biology, nervous system diseases, Cell nucleus, 030104 developmental biology, Disease Models, ADAR
Abstract

The fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to the absence of FMRP, a protein regulating RNA metabolism. Recently, an unexpected function of FMRP in modulating the activity of Adenosine Deaminase Acting on RNA (ADAR) enzymes has been reported both in Drosophila and Zebrafish. ADARs are RNA-binding proteins that increase transcriptional complexity through a post-transcriptional mechanism called RNA editing. To evaluate the ADAR2-FMRP interaction in mammals we analyzed several RNA editing re-coding sites in the fmr1 knockout (KO) mice. Ex vivo and in vitro analysis revealed that absence of FMRP leads to an increase in the editing levels of brain specific mRNAs, indicating that FMRP might act as an inhibitor of editing activity. Proximity Ligation Assay (PLA) in mouse primary cortical neurons and in non-neuronal cells revealed that ADAR2 and FMRP co-localize in the nucleus. The ADAR2-FMRP co-localization was further observed by double-immunogold Electron Microscopy (EM) in the hippocampus. Moreover, ADAR2-FMRP interaction appeared to be RNA independent. Because changes in the editing pattern are associated with neuropsychiatric and neurodevelopmental disorders, we propose that the increased editing observed in the fmr1-KO mice might contribute to the FXS molecular phenotypes.

Published
2017
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173. CaloCube: A new-concept calorimeter for the detection of high-energy cosmic rays in space

Author

Anna Vedda, E. Vannuccini, P. Papini, G. Castellini, O. Adriani, Raffaello D'Alessandro, Lorenzo Bonechi, A. Basti, P. W. Cattaneo, A. Sulaj, O. Starodubtsev, Gianluigi Zampa, G. Orzan, P. Spillantini, A. Tricomi, Maria Miritello, Antoniangelo Agnesi, L. Auditore, S. Albergo, J. E. Suh, M. Olmi, Emilio Berti, Mauro Fasoli, Nicola Mori, B. Zerbo, M. Bongi, S. Bonechi, Paolo Maestro, M. Trimarchi, S. B. Ricciarini, P. Lenzi, Gabriele Bigongiari, P. S. Marrocchesi, Paolo Brogi, Federico Pirzio, N. Finetti, A. Rappoldi, N. Zampa, G. Carotenuto, A. Tiberio, S. Detti, V. Bonvicini, S. Bottai, A. Trifiro, F. Stolzi, L. Pacini, M. G. Pellegriti, Vannuccini, E, Adriani, O, Agnesi, A, Albergo, S, Auditore, L, Basti, A, Berti, E, Bigongiari, G, Bonechi, L, Bonechi, S, Bongi, M, Bonvicini, V, Bottai, S, Brogi, P, Carotenuto, G, Castellini, G, Cattaneo, P, D'Alessandro, R, Detti, S, Fasoli, M, Finetti, N, Lenzi, P, Maestro, P, Marrocchesi, P, Miritello, M, Mori, N, Orzan, G, Olmi, M, Pacini, L, Papini, P, Pellegriti, M, Pirzio, F, Rappoldi, A, Ricciarini, S, Spillantini, P, Starodubtsev, O, Stolzi, F, Suh, J, Sulaj, A, Tiberio, A, Tricomi, A, Trifiro, A, Trimarchi, M, Vedda, A, Zampa, G, Zampa, N, and Zerbo, B

Subjects
Scintillating crystal, Nuclear and High Energy Physics, Physics::Instrumentation and Detectors, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), Cosmic ray, Space (mathematics), 01 natural sciences, Scintillating crystals, 0103 physical sciences, Ultra-high-energy cosmic ray, Absorption (electromagnetic radiation), 010303 astronomy & astrophysics, Cosmic rays, Instrumentation, Nuclear and High Energy Physic, Physics, Calorimeter, Basis (linear algebra), 010308 nuclear & particles physics, Isotropy, Computational physics, FIS/01 - FISICA SPERIMENTALE, Granularity
Abstract

The direct observation of high-energy cosmic rays, up to the PeV region, will increasingly rely on highly performing calorimeters, and the physics performance will be primarily determined by their geometrical acceptance and energy resolution. Thus, it is extremely important to optimize their geometrical design, granularity, and absorption depth, with respect to the total mass of the apparatus, which is among the most important constraints for a space mission. Calocube is a homogeneous calorimeter whose basic geometry is cubic and isotropic, so as to detect particles arriving from every direction in space, thus maximizing the acceptance; granularity is obtained by filling the cubic volume with small cubic scintillating crystals. This design forms the basis of a three-year R & D activity which has been approved and financed by INFN. A comparative study of different scintillating materials has been performed. Optimal values for the size of the crystals and spacing among them have been studied. Different geometries, besides the cubic one, and the possibility to implement dual-readout techniques have been investigated. A prototype, instrumented with CsI(Tl) cubic crystals, has been constructed and tested with particle beams. An overview of the obtained results will be presented and the perspectives for future space experiments will be discussed.

Published
2017

174. CaloCube: a novel calorimeter for high-energy cosmic rays in space

Author

N. Finetti, F. Stolzi, Gigi Cappello, P. W. Cattaneo, Lucrezia Auditore, S. Bottai, M. G. Pellegriti, A. Basti, A. Rappoldi, L. Pacini, A Vedda, J. E. Suh, S. Albergo, P. S. Marrocchesi, M. Olmi, P. Spillantini, M Fasoli, Maria Miritello, N. Zampa, Gabriele Bigongiari, S. Bonechi, Eugenio Berti, G. Zampa, Raffaello D'Alessandro, Paolo Brogi, P. Lenzi, Antonio Trifiro, G. Carotenuto, Bonvicini, S. Detti, A. Tiberio, Lorenzo Bonechi, Alessia Tricomi, A Agnesi, A. Sulaj, G. Castellini, S. B. Ricciarini, P. Papini, E. Vannuccini, O. Starodubtsev, M. Bongi, O. Adriani, A Italiano, F Pirzio, M. Trimarchi, Nicola Mori, G. Orzan, Paolo Maestro, Rappoldi, A, Morselli, A, Cattaneo, P, Adriani, O, Agnesi, A, Albergo, S, Auditore, L, Basti, A, Berti, E, Bigongiari, G, Bonechi, L, Bonechi, S, Bongi, M, Bonvicini, V, Bottai, S, Brogi, P, Cappello, G, Carotenuto, G, Castellini, G, D'Alessandro, R, Detti, S, Fasoli, M, Finetti, N, Italiano, A, Lenzi, P, Maestro, P, Marrocchesi, P, Miritello, M, Mori, N, Olmi, M, Orzan, G, Pacini, L, Papini, P, Pellegriti, M, Pirzio, F, Ricciarini, S, Spillantini, P, Starodubtsev, O, Stolzi, F, Suh, J, Sulaj, A, Tiberio, A, Tricomi, A, Trifirò, A, Trimarchi, M, Vannuccini, E, Vedda, A, Zampa, G, and Zampa, N

Subjects
Physics, Calorimeter (particle physics), 010308 nuclear & particles physics, Physics::Instrumentation and Detectors, QC1-999, Astrophysics, Space (mathematics), 7. Clean energy, 01 natural sciences, Nuclear physics, Physics and Astronomy (all), 0103 physical sciences, Ultra-high-energy cosmic ray, Detectors and Experimental Techniques, 010306 general physics
Abstract

CaloCube is an R&D project borne to develop a novel calorimeter design, optimized for high-energy cosmic ray measurements in space. A small prototype made of CsI(Tl) elements has been built and tested on particle beams. A final version, made of 5×5×18 crystals and with dual readout (two photodiodes for each crystal), to cover the full required dynamic range, is under construction and will be tested at CERN SPS in Summer 2016. The dual readout compensation technique were developed and the feasibility to extract ÄŒ erenkov signals from CsI crystals verified.

Published
2017

175. CaloCube: an innovative homogeneous calorimeter for the next-generation space experiments

Author

L. Pacini, N. Finetti, N. Daddi, Raffaello D'Alessandro, F. Stolzi, Anna Vedda, Antonio Agnesi, J. E. Suh, A. Sulaj, M. Olmi, Paolo Maestro, Sebastiano Albergo, Gigi Cappello, A. Basti, S. Bonechi, P. W. Cattaneo, O. Adriani, Emanuele Berti, G. Orzan, P. Lenzi, M. G. Pellegriti, Lucrezia Auditore, P. Spillantini, Maria Miritello, G. Zampa, S. Detti, M. Chiari, Lorenzo Bonechi, M. Bongi, Antonio Trifiro, P. S. Marrocchesi, Gabriele Bigongiari, Alessia Tricomi, Paolo Brogi, S. B. Ricciarini, Federico Pirzio, P. Papini, E. Vannuccini, G. Castellini, O. Starodubtsev, G. Carotenuto, M. Trimarchi, V. Bonvicini, A. Tiberio, Nicola Mori, N. Zampa, S. Bottai, A. Rappoldi, Mauro Fasoli, Pacini, L, Adriani, O, Agnesi, A, Albergo, S, Auditore, L, Basti, A, Berti, E, Bigongiari, G, Bonechi, L, Bonechi, S, Bongi, M, Bonvicini, V, Bottai, S, Brogi, P, Cappello, G, Carotenuto, G, Castellini, G, Cattaneo, P, Chiari, M, Daddi, N, Dalessandro, R, Detti, S, Fasoli, M, Finetti, N, Lenzi, P, Maestro, P, Marrocchesi, P, Miritello, M, Mori, N, Orzan, G, Olmi, M, Papini, P, Pellegriti, M, Pirzio, F, Rappoldi, A, Ricciarini, S, Spillantini, P, Starodubtsev, O, Stolzi, F, Suh, J, Sulaj, A, Tiberio, A, Tricomi, A, Trifiro, A, Trimarchi, M, Vannuccini, E, Vedda, A, Zampa, G, and Zampa, N

Subjects
Physics, History, business.industry, Physics::Instrumentation and Detectors, Isotropy, Monte Carlo method, Detector, Space launch, Computer Science Applications, Education, Calorimeter, Physics and Astronomy (all), Quality (physics), FIS/01 - FISICA SPERIMENTALE, Particle, Aerospace engineering, Detectors and Experimental Techniques, business, Energy (signal processing)
Abstract

The direct measurement of the cosmic-ray spectrum, up to the knee region, is one of the instrumental challenges for next generation space experiments. The main issue for these measurements is a steeply falling spectrum with increasing energy, so the physics performance of the space calorimeters are primarily determined by their geometrical acceptance and energy resolution. CaloCube is a three-year R&D; project, approved and financed by INFN in 2014, aiming to optimize the design of a space-born calorimeter. The peculiarity of the design of CaloCube is its capability of detecting particles coming from any direction, and not only those on its upper surface. To ensure that the quality of the measurement does not depend on the arrival direction of the particles, the calorimeter will be designed as homogeneous and isotropic as possible. In addition, to achieve a high discrimination power for hadrons and nuclei with respect to electrons, the sensitive elements of the calorimeter need to have a fine 3-D sampling capability. In order to optimize the detector performances with respect to the total mass of the apparatus, which is the most important constraint for a space launch, a comparative study of different scintillating materials has been performed using detailed Monte Carlo simulation based on the FLUKA package. In parallel to simulation studies, a prototype consisting in 14 layers of 3 x 3 CsI(Tl) crystals per layer has been assembled and tested with particle beams. An overview of the obtained results during the first two years of the project will be presented and the future of the detector will be discussed too.

Published
2017

177. Status and performance of the High Energy Particle Detector (HEPD) on-board the CSES-01 satellite

Author

C. De Donato, Ignazio Lazzizzera, C. Guandalini, F. De Persio, M. Puel, Matteo Martucci, Maria Antonietta Ricci, L. Basara, B Di Ruzza, Francesco Maria Follega, Paolo Zuccon, L. Carfora, F. Palma, Ester Ricci, V. Vitale, S. Bartoccia, C. De Santis, P. Picozza, I. Rashevskaya, Alessandro Sotgiu, Valentina Scotti, W. J. Burger, G. Laurenti, G. Osteria, G. Masciantonio, G. Ambrosi, F. Perfetto, R. Iuppa, G. Castellini, Bruno Spataro, L. Marcelli, P. Cipollone, L. Pacini, Beatrice Panico, A. Parmentier, Andrea Contin, Maria Ionica, M. Merge, M. Lolli, L. Patrizii, R. Sparvoli, S. B. Ricciarini, Mirko Piersanti, F. Palmonari, D. Campana, Marco Casolino, Livio Conti, C. Manea, M. Pozzato, Simona Zoffoli, Roberto Battiston, Sotgiu, A., Ambrosi, G., Battiston, R., Bartocci, S., Basara, L., Burger, W. J., Campana, D., Carfora, L., Casolino, M., Castellini, G., Cipollone, P., Conti, L., Contin, A., de Donato, C., de Persio, F., de Santis, C., Di Ruzza, B., Follega, F. M., Guandalini, C., Ionica, M., Iuppa, R., Laurenti, G., Lazzizzera, I., Lolli, M., Manea, C., Marcelli, L., Martucci, M., Masciantonio, G., Merge, M., Osteria, G., Pacini, L., Palma, F., Palmonari, F., Panico, B., Parmentier, A., Patrizii, L., Perfetto, F., Picozza, P., Piersanti, M., Pozzato, M., Puel, M., Rashevskaya, I., Ricci, E., Ricci, M., Ricciarini, S., Scotti, V., Sparvoli, R., Spataro, B., Vitale, V., Zuccon, P., and Zoffoli, S.

Subjects
Plastic scintillator, Physics, Settore FIS/01, Range (particle radiation), High energy particle, Calorimeter (particle physics), Charged particles, Electric and magnetic fields, Satellites, Detector, In-flight performance, Particle detectors, Charged particle, Particle identification, Cosmology, High-energy particles, Computational physics, Charged particles, Cosmic rays, Cosmology, Particle detectors, Charged particle flux, Electric and magnetic fields, High energy particle detectors, High-energy particles, In-flight performance, Operational conditions, Particle identifications, Plastic scintillator, Satellites, Charged particle flux, Particle identifications, High energy particle detectors, Satellite, Operational conditions, Cosmic rays, Space environment
Abstract

CSES-01 (China Seismo-Electromagnetic Satellite) is a space mission dedicated to the study of the ionospheric environment, searching for disturbances that can be correlated to seismic activity. For this reason, the satellite is equipped with several instruments to monitor various physical parameters including the Earth's electric and magnetic field, ionospheric plasma principal parameters (i.e. density, temperature, and ions composition) and high energy particle flux fluctuations. The High Energy Particle Detector (HEPD), built by the Italian CSES-Limadou collaboration, is designed to detect mostly electrons in the energy range between 3 MeV and 100 MeV and protons in the energy range between 30 MeV and 300 MeV. The detector is composed of a tracking system, a segmented layer of plastic scintillator (used for the trigger), a range calorimeter and a veto system. After CSES-01 launch (February 2, 2018), the apparatus underwent the commissioning phase where its configuration was adjusted in order to guarantee optimal operational conditions in the space environment. Now the satellite is in stable data-taking mode. In this work a description of the HEPD detector will be reported, focusing on the results of the electron and proton test beam calibrations. In addition, a particular relevance will be given to the presentation of the HEPD in-flight performance, such as its good capability in particle identification. The high statistic collected by HEPD, thanks to its large acceptance window, makes it perfectly suitable for the investigation of fluctuations in the charged particle fluxes.

178. Space-weather capabilities and preliminary results of the high energy particle detector (HEPD) on board the CSES-01 satellite

Author

L. Patrizii, R. Sparvoli, F. De Persio, Roberto Battiston, Andrea Contin, M. Pozzato, V. Vitale, Valentina Scotti, S. Bartocci, F. Perfetto, L. Pacini, Bruno Spataro, L. Marcelli, Ignazio Lazzizzera, D. Campana, F. Palmonari, P. Cipollone, M. Puel, G. Masciantonio, L. Basara, S. B. Ricciarini, Livio Conti, W. J. Burger, Marco Casolino, Mirko Piersanti, Paolo Zuccon, G. Castellini, C. De Santis, B Di Ruzza, Francesco Maria Follega, P. Picozza, F. Palma, C. Manea, Beatrice Panico, G. Laurenti, A. Parmentier, Maria Ionica, Simona Zoffoli, Ester Ricci, M. Merge, R. Iuppa, I. Rashevskaya, M. Lolli, Alessandro Sotgiu, L. Carfora, Maria Antonietta Ricci, G. Osteria, G. Ambrosi, C. De Donato, C. Guandalini, Matteo Martucci, Martucci, M., Ambrosi, G., Battiston, R., Bartocci, S., Basara, L., Burger, W. J., Campana, D., Carfora, L., Casolino, M., Castellini, G., Cipollone, P., Conti, L., Contin, A., de Donato, C., de Persio, F., de Santis, C., Di Ruzza, B., Follega, F. M., Guandalini, C., Ionica, M., Iuppa, R., Laurenti, G., Lazzizzera, I., Lolli, M., Manea, C., Marcelli, L., Masciantonio, G., Merge, M., Osteria, G., Pacini, L., Palma, F., Palmonari, F., Panico, B., Parmentier, A., Patrizii, L., Perfetto, F., Picozza, P., Piersanti, M., Pozzato, M., Puel, M., Rashevskaya, I., Ricci, E., Ricci, M., Ricciarini, S., Scotti, V., Sotgiu, A., Sparvoli, R., Spataro, B., Vitale, V., Zuccon, P., and Zoffoli, S.

Subjects
Settore FIS/01, High energy particle, Detector, Space administration, Orbits, Particle detectors, Data analysis techniques, Italian Space Agency, Space weather, Galactic cosmic rays, Population statistics, Cosmology, On board, Cosmic rays, Cosmology, Ionosphere, Magnetosphere, Particle detectors, Population statistics, Data analysis techniques, Detection and discriminations, Different time scale, Galactic cosmic rays, High energy particle detectors, Italian Space Agency, Near-Earth environments, Space administration, Orbits, Detection and discriminations, Magnetosphere, Environmental science, High energy particle detectors, Satellite, Ionosphere, Near-Earth environments, Cosmic rays, Different time scale, Remote sensing
Abstract

CSES-01 (China Seismo-Electromagnetic Satellite) is a mission developed by CNSA (Chinese National Space Administration) and ASI (Italian Space Agency) to investigate the near-Earth electromagnetic, plasma and particle environment, focusing on the disturbances of the ionosphere-magnetosphere transition region. In this framework, the Italian High Energy Particle Detector (HEPD) on board CSES-01, is an advanced detector based on a tower of scintillators and a silicon tracker that provide good energy resolution as well as a wide angular acceptance for electrons of 3-100 MeV, protons of 30-200 MeV and light nuclei (up to Oxygen). The very good capabilities in both detection and discrimination of particles make the detector well suited for space-weather purposes; indeed HEPD is able to continuously monitor the magnetospheric environment with high precision and stability in time. Turbulent conditions in the near-Earth environment translate into modification of particles and magnetic/electric measurements at different time-scales. In this work, the data-analysis techniques and some preliminary results concerning the study of different proton populations encountered along CSES-01 orbit (galactic cosmic rays, re-entrant albedo etc.) are presented.

179. The hepd apparatus for the cses mission

Author

Beatrice Panico, Maria Teresa Ricci, Matteo Sposito, C. De Donato, Livio Conti, S. Bartocci, Roberto Iuppa, Ester Ricci, Maria Ionica, Francesco Maria Follega, Andrea Contin, W. J. Burger, M. Merge, V. Vitale, G. Laurenti, C. Manea, G. Ambrosi, Valentina Scotti, M. Lolli, C. Guadalini, G. Masciantonio, M. Pozzato, L. Patrizii, R. Sparvoli, L. Pacini, G. Castellini, Roberto Battiston, P. Picozza, C. De Santis, F. Palma, I. Rashevskaya, Alessandro Sotgiu, F. Perfetto, Bruno Spataro, P. Cipollone, Ignazio Lazzizzera, F. Palmonari, L. Marcelli, G. Osteria, S. B. Ricciarini, Panico, B., Osteria, G., Perfetto, F., Scotti, V., Cipollone, P., De Donato, C., De Santis, C., Marcelli, L., Masciantonio, G., Mergè, M., Palma, F., Picozza, P., Sotgiu, A., Sparvoli, R., Contin, A., Guadalini, C., Laurenti, G., Lolli, M., Palmonari, F., Patrizii, L., Pozzato, M., Ricci, M., Spataro, B., Burger, W. J., Battiston, R., Follega, F. M., Iuppa, R., Lazzizzera, I., Manea, C., Rashevskaya, I., Ricci, E., Vitale, V., Ambrosi, G., Ionica, M., Sposito, M., Bartocci, S., Conti, L., Castellini, G., Pacini, L., Ricciarini, S. B., and Merge, M.

Subjects
History, High energy particle, Proton, Nuclear Theory, Cyclotron, Cosmic ray, Electron, Particle detector, Education, Physics::Geophysics, law.invention, Nuclear physics, Atmosphere, symbols.namesake, law, Aerospace engineering, Nuclear Experiment, Trapped particle, Low-energy components, Physics, Settore FIS/01, business.industry, Radiation belts, Computer Science Applications, Magnetic field, Van Allen radiation belt, Physics::Space Physics, symbols, Physics::Accelerator Physics, Environmental science, Satellite, business, Beam (structure)
Abstract

The High-Energy Particle Detector (HEPD) is one of the payloads of the CSES space mission. The HEPD is built by the Italian Limadou collaboration and has different goals. It will study the temporal stability of the inner Van Allen radiation belts, the precipitation of trapped particles in the atmosphere and the low energy component of the cosmic rays (5-100 MeV for electrons and 15 - 300 MeV for protons). It has been tested at the Beam Test Facility of the INFN National Laboratory of Frascati, for electrons, and at the Proton Cyclotron of Trento, for protons. Here is presented a study of the performance of the apparatus to separate electrons and protons and identify nuclei up to iron.

180. Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome.

Author

Cencelli G, Pedini G, Ricci C, Rosina E, Cecchetti G, Gentile A, Aiello G, Pacini L, Garrone B, Ombrato R, Coletta I, Prati F, Milanese C, and Bagni C

Abstract

The finely tuned regulation of mitochondria activity is essential for proper brain development. Fragile X Syndrome (FXS), the leading cause of inherited intellectual disability, is a neurodevelopmental disorder in which mitochondrial dysfunction has been increasingly implicated. This study investigates the role of Glycogen Synthase Kinase 3β (GSK3β) in FXS. Several studies have reported GSK3β deregulation in FXS, and its role in mitochondrial function is known. However, the link between disrupted GSK3β activity and mitochondrial dysfunction in FXS remains unexplored. Utilizing Fmr1 knockout (KO) mice and human cell lines from FXS individuals, we uncovered a developmental window where dysregulated GSK3β activity disrupts mitochondrial function. Notably, a partial inhibition of GSK3β activity in FXS fibroblasts from young individuals rescues the observed mitochondrial defects, suggesting that targeting GSK3β in the early stages may offer therapeutic benefits for this condition., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Inc.)

Published
2024
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181. Optimization of peptide synthesis time and sustainability using novel eco-friendly binary solvent systems with induction heating on an automated peptide synthesizer.

Author

Pacini L, Muthyala M, Aguiar L, Zitterbart R, Rovero P, and Papini AM

Subjects
Amyloid beta-Peptides chemistry, Green Chemistry Technology, Dimethylformamide chemistry, Dimethyl Sulfoxide chemistry, Peptide Fragments chemistry, Peptide Fragments chemical synthesis, SARS-CoV-2, Heating, Automation, Hot Temperature, Solvents chemistry, Peptides chemistry, Peptides chemical synthesis, Solid-Phase Synthesis Techniques methods
Abstract

On December 12th, 2023, the European Commission took regulatory action to amend Annex XVII of REACH, imposing restrictions on the use of N,N-dimethylformamide (DMF) within the EU market owing to its high toxicity. Historically, DMF has been widely considered the gold standard for solid-phase peptide synthesis (SPPS). Being urgent to propose alternative solvents, we tested the suitability of non-hazardous neat and mixed solvents. Notably, binary solvent mixtures containing dimethyl sulfoxide as one of the solvent partners demonstrated high efficacy in solubilizing reagents while maintaining the desired swelling characteristics of common resins. A series of binary solvent mixtures were tested in automated SPPS, both at room temperature and high temperature, employing the PurePep® Chorus synthesizer, which enabled controlled induction heating between 25 and 90°C with oscillation mixing. The performances were assessed in challenging peptide sequences, i.e., ACP (65-74), and in longer and aggregating sequences like SARS-CoV-2 RBM (436-507) and β-amyloid (1-42). Furthermore, as part of the proposed sustainable approach to minimize the utilization of hazardous solvents, we coupled the novel PurePep EasyClean catch-and-release purification technology. This work, addressing regulatory compliance, emphasizes the crucial role of green chemistry in advancing safer and more environmentally friendly practices in SPPS., (© 2024 European Peptide Society and John Wiley & Sons Ltd.)

Published
2024
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182. A Promising Compound for Green Multiresponsive Materials Based on Acyl Carrier Protein.

Author

Acar M, Tatini D, Fidi A, Pacini L, Quagliata M, Nuti F, Papini AM, and Lo Nostro P

Subjects
Hydrogen-Ion Concentration, Temperature, Gels chemistry, Glycerol chemistry, Water chemistry, Acyl Carrier Protein chemistry
Abstract

A gel that exhibits intrinsically multiple-responsive behavior was prepared from an oligopeptide and studied. ACP(65-74) is an active decapeptide fragment of acyl carrier protein. We investigated 3% w/v ACP(65-74)-NH 2 self-healing physical gels in water, glycerol carbonate (GC), and their mixtures. The morphology was investigated by optical, birefringence, and confocal laser scanning microscopy, circular dichroism, Fourier transform infrared, and fluorescence spectroscopy experiments. We found that all samples possess pH responsiveness with fully reversible sol-to-gel transitions. The rheological properties depend on the temperature and solvent composition. The temperature dependence of the gels in water shows a peculiar behavior that is similar to that of thermoresponsive polymer solutions. The results reveal the presence of several β-sheet structures and amyloid aggregates, offering valuable insights into the fibrillation mechanism of amyloids in different solvent media.

Published
2024
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183. The Role of the Unbinding Cycle on the Coordination Abilities of the Bi-Cyclopeptides toward Cu(II) Ions.

Author

Lisowska A, Świątek P, Dębicki F, Lewińska A, Marciniak A, Pacini L, Papini AM, and Brasuń J

Subjects
Coordination Complexes chemistry, Ligands, Ions chemistry, Potentiometry, Copper chemistry, Peptides, Cyclic chemistry
Abstract

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties, putting them on a new path in medicine. Their conformational rigidity improves proteolytic stability and leads to rapid penetration into tissues via any possible route of administration. Moreover, elimination of renal metabolism is of great importance, for example, for people with a history of liver diseases. In addition, each ring can function independently, making bicyclic peptides extremely versatile molecules for further optimization. In this paper, we compared the potentiometric and spectroscopic properties studied by UV-vis, MCD, and EPR of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH) (BCL). In particular, we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL1 (Ac-PKKHPc(CFWKTC)PKKH-NH 2 ) that contains the unbinding cycle and N- and C-terminal linear parts with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position, i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH 2 ) and in the C-terminal position, i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH 2 ), respectively; and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH 2 ). Potentiometric results have shown that the bicyclic structure promotes the involvement of the side chain imidazole donors in Cu(II) binding. On the other hand, the results obtained for the mono-cyclic analogues lead to the conclusion that the coordination of the histidine moiety as an anchoring group is promoted by its location in the peptide sequence further from the nonbinding cycle, strongly influencing the involvement of the amide donors in Cu(II) coordination.

Published
2024
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184. A new approach to estimate soil organic carbon content targets in European croplands topsoils.

Author

Pacini L, Arbelet P, Chen S, Bacq-Labreuil A, Calvaruso C, Schneider F, Arrouays D, Saby NPA, Cécillon L, and Barré P

Abstract

Adopting land management practices that increase the stock of soil organic carbon (SOC) in croplands is widely promoted as a win-win strategy to enhance soil health and mitigate climate change. In this context, the definition of reference SOC content and stock values is needed to provide reliable targets to farmers, policymakers, and stakeholders. In this study, we used the LUCAS dataset to compare different methods for evaluating reference SOC content and stock values in European croplands topsoils (0-20 cm depth). Methods gave generally similar estimates although being built on very different assumptions. In the absence of an objective criterion to establish which approach is the most suitable to determine SOC reference values, we propose an ensemble modelling approach that consists in extracting the estimates using different relevant methods and retaining the median value among them. Interestingly, this approach led us to select values from the three different approaches with similar frequencies. Using estimated bulk density values, we obtained a first rough estimate of 3.5 Gt C of SOC storage potential in the cropland topsoils that we interpret as a long-term aspirational target that would be reachable only under extreme changes in agricultural practices. The use of additional methods in the ensemble modelling approach and more valid statistical spatial estimates may further refine our approach designed for the estimation of SOC reference values for croplands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2023
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185. Direct Measurement of the Spectral Structure of Cosmic-Ray Electrons+Positrons in the TeV Region with CALET on the International Space Station.

Author

Adriani O, Akaike Y, Asano K, Asaoka Y, Berti E, Bigongiari G, Binns WR, Bongi M, Brogi P, Bruno A, Buckley JH, Cannady N, Castellini G, Checchia C, Cherry ML, Collazuol G, de Nolfo GA, Ebisawa K, Ficklin AW, Fuke H, Gonzi S, Guzik TG, Hams T, Hibino K, Ichimura M, Ioka K, Ishizaki W, Israel MH, Kasahara K, Kataoka J, Kataoka R, Katayose Y, Kato C, Kawanaka N, Kawakubo Y, Kobayashi K, Kohri K, Krawczynski HS, Krizmanic JF, Maestro P, Marrocchesi PS, Messineo AM, Mitchell JW, Miyake S, Moiseev AA, Mori M, Mori N, Motz HM, Munakata K, Nakahira S, Nishimura J, Okuno S, Ormes JF, Ozawa S, Pacini L, Papini P, Rauch BF, Ricciarini SB, Sakai K, Sakamoto T, Sasaki M, Shimizu Y, Shiomi A, Spillantini P, Stolzi F, Sugita S, Sulaj A, Takita M, Tamura T, Terasawa T, Torii S, Tsunesada Y, Uchihori Y, Vannuccini E, Wefel JP, Yamaoka K, Yanagita S, Yoshida A, Yoshida K, and Zober WV

Abstract

Detailed measurements of the spectral structure of cosmic-ray electrons and positrons from 10.6 GeV to 7.5 TeV are presented from over 7 years of observations with the CALorimetric Electron Telescope (CALET) on the International Space Station. The instrument, consisting of a charge detector, an imaging calorimeter, and a total absorption calorimeter with a total depth of 30 radiation lengths at normal incidence and a fine shower imaging capability, is optimized to measure the all-electron spectrum well into the TeV region. Because of the excellent energy resolution (a few percent above 10 GeV) and the outstanding e/p separation (10^{5}), CALET provides optimal performance for a detailed search of structures in the energy spectrum. The analysis uses data up to the end of 2022, and the statistics of observed electron candidates has increased more than 3 times since the last publication in 2018. By adopting an updated boosted decision tree analysis, a sufficient proton rejection power up to 7.5 TeV is achieved, with a residual proton contamination less than 10%. The observed energy spectrum becomes gradually harder in the lower energy region from around 30 GeV, consistently with AMS-02, but from 300 to 600 GeV it is considerably softer than the spectra measured by DAMPE and Fermi-LAT. At high energies, the spectrum presents a sharp break around 1 TeV, with a spectral index change from -3.15 to -3.91, and a broken power law fitting the data in the energy range from 30 GeV to 4.8 TeV better than a single power law with 6.9 sigma significance, which is compatible with the DAMPE results. The break is consistent with the expected effects of radiation loss during the propagation from distant sources (except the highest energy bin). We have fitted the spectrum with a model consistent with the positron flux measured by AMS-02 below 1 TeV and interpreted the electron+positron spectrum with possible contributions from pulsars and nearby sources. Above 4.8 TeV, a possible contribution from known nearby supernova remnants, including Vela, is addressed by an event-by-event analysis providing a higher proton-rejection power than a purely statistical analysis.

Published
2023
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186. Erratum: Charge-Sign Dependent Cosmic-Ray Modulation Observed with the Calorimetric Electron Telescope on the International Space Station [Phys. Rev. Lett. 130, 211001 (2023)].

Author

Adriani O, Akaike Y, Asano K, Asaoka Y, Berti E, Bigongiari G, Binns WR, Bongi M, Brogi P, Bruno A, Buckley JH, Cannady N, Castellini G, Checchia C, Cherry ML, Collazuol G, de Nolfo GA, Ebisawa K, Ficklin AW, Fuke H, Gonzi S, Guzik TG, Hams T, Hibino K, Ichimura M, Ioka K, Ishizaki W, Israel MH, Kasahara K, Kataoka J, Kataoka R, Katayose Y, Kato C, Kawanaka N, Kawakubo Y, Kobayashi K, Kohri K, Krawczynski HS, Krizmanic JF, Maestro P, Marrocchesi PS, Messineo AM, Mitchell JW, Miyake S, Moiseev AA, Mori M, Mori N, Motz HM, Munakata K, Nakahira S, Nishimura J, Okuno S, Ormes JF, Ozawa S, Pacini L, Papini P, Rauch BF, Ricciarini SB, Sakai K, Sakamoto T, Sasaki M, Shimizu Y, Shiomi A, Spillantini P, Stolzi F, Sugita S, Sulaj A, Takita M, Tamura T, Terasawa T, Torii S, Tsunesada Y, Uchihori Y, Vannuccini E, Wefel JP, Yamaoka K, Yanagita S, Yoshida A, Yoshida K, and Zober WV

Abstract

This corrects the article DOI: 10.1103/PhysRevLett.130.211001.

Published
2023
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187. SARS-CoV-2 inhibitory activity of a short peptide derived from internal fusion peptide of S2 subunit of spike glycoprotein.

Author

Stincarelli MA, Quagliata M, Di Santo A, Pacini L, Fernandez FR, Arvia R, Rinaldi S, Papini AM, Rovero P, and Giannecchini S

Subjects
Humans, SARS-CoV-2 metabolism, Peptides pharmacology, Peptides metabolism, Glycoproteins, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus chemistry, COVID-19
Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a great concern in human population. To fight coronavirus emergence, we have dissected the conserved amino acid region of the internal fusion peptide in the S2 subunit of Spike glycoprotein of SARS-CoV-2 to design new inhibitory peptides. Among the 11 overlapping peptides (9-23-mer), PN19, a 19-mer peptide, exhibited a powerful inhibitory activity against different SARS-CoV-2 clinical isolate variants in absence of cytotoxicity. The PN19 inhibitory activity was found to be dependent on conservation of the central Phe and C-terminal Tyr residues in the peptide sequence. Circular dichroism spectra of the active peptide exhibited an alpha-helix propensity, confirmed by secondary structure prediction analysis. The PN19 inhibitory activity, exerted in the first step of virus infection, was reduced after peptide adsorption treatment with virus-cell substrate during fusion interaction. Additionally, PN19 inhibitory activity was reduced by adding S2 membrane-proximal region derived peptides. PN19 showed binding ability to the S2 membrane proximal region derived peptides, confirmed by molecular modelling, playing a role in the mechanism of action. Collectively, these results confirm that the internal fusion peptide region is a good candidate on which develop peptidomimetic anti SARS-CoV-2 antivirals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2023
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188. FMRP expression in primary breast tumor cells correlates with recurrence and specific site of metastasis.

Author

Caredda E, Pedini G, D'Amico F, Scioli MG, Pacini L, Orsaria P, Vanni G, Buonomo OC, Orlandi A, Bagni C, and Palombi L

Subjects
Animals, Humans, Female, Fragile X Mental Retardation Protein genetics, Fragile X Mental Retardation Protein metabolism, Case-Control Studies, Retrospective Studies, Proteins metabolism, Breast Neoplasms genetics, Mammary Neoplasms, Animal, Fragile X Syndrome genetics
Abstract

Breast cancer is the most common cancer among women worldwide. Molecular and clinical evidence indicated that Fragile X Messenger Ribonucleoprotein 1 (FMRP) plays a role in different types of cancer, including breast cancer. FMRP is an RNA binding protein that regulates the metabolism of a large group of mRNAs coding for proteins involved in both neural processes and in epithelial-mesenchymal transition, a pivotal mechanism that in cancer is associated to tumor progression, aggressiveness and chemoresistance. Here, we carried out a retrospective case-control study of 127 patients, to study the expression of FMRP and its correlation with metastasis formation in breast cancer. Consistent with previous findings, we found that FMRP levels are high in tumor tissue. Two categories have been analyzed, tumor with no metastases (referred as control tumors, 84 patients) and tumor with distant metastatic repetition, (referred as cases, 43 patients), with a follow-up of 7 years (mean). We found that FMRP levels were lower in both the nuclei and the cytoplasm in the cases compared to control tumors. Next, within the category cases (tumor with metastases) we evaluated FMRP expression in the specific sites of metastasis revealing a nuclear staining of FMRP. In addition, FMRP expression in both the nuclear and cytoplasmic compartment was significantly lower in patients who developed brain and bone metastases and higher in hepatic and pulmonary sites. While further studies are required to explore the underlying molecular mechanisms of FMRP expression and direct or inverse correlation with the secondary metastatic site, our findings suggest that FMRP levels might be considered a prognostic factor for site-specific metastasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Caredda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
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189. Charge-Sign Dependent Cosmic-Ray Modulation Observed with the Calorimetric Electron Telescope on the International Space Station.

Author

Adriani O, Akaike Y, Asano K, Asaoka Y, Berti E, Bigongiari G, Binns WR, Bongi M, Brogi P, Bruno A, Buckley JH, Cannady N, Castellini G, Checchia C, Cherry ML, Collazuol G, de Nolfo GA, Ebisawa K, Ficklin AW, Fuke H, Gonzi S, Guzik TG, Hams T, Hibino K, Ichimura M, Ioka K, Ishizaki W, Israel MH, Kasahara K, Kataoka J, Kataoka R, Katayose Y, Kato C, Kawanaka N, Kawakubo Y, Kobayashi K, Kohri K, Krawczynski HS, Krizmanic JF, Maestro P, Marrocchesi PS, Messineo AM, Mitchell JW, Miyake S, Moiseev AA, Mori M, Mori N, Motz HM, Munakata K, Nakahira S, Nishimura J, Okuno S, Ormes JF, Ozawa S, Pacini L, Papini P, Rauch BF, Ricciarini SB, Sakai K, Sakamoto T, Sasaki M, Shimizu Y, Shiomi A, Spillantini P, Stolzi F, Sugita S, Sulaj A, Takita M, Tamura T, Terasawa T, Torii S, Tsunesada Y, Uchihori Y, Vannuccini E, Wefel JP, Yamaoka K, Yanagita S, Yoshida A, Yoshida K, and Zober WV

Subjects
Protons, Electrons, Space Flight, Telescopes, Cosmic Radiation
Abstract

We present the observation of a charge-sign dependent solar modulation of galactic cosmic rays (GCRs) with the Calorimetric Electron Telescope onboard the International Space Station over 6 yr, corresponding to the positive polarity of the solar magnetic field. The observed variation of proton count rate is consistent with the neutron monitor count rate, validating our methods for determining the proton count rate. It is observed by the Calorimetric Electron Telescope that both GCR electron and proton count rates at the same average rigidity vary in anticorrelation with the tilt angle of the heliospheric current sheet, while the amplitude of the variation is significantly larger in the electron count rate than in the proton count rate. We show that this observed charge-sign dependence is reproduced by a numerical "drift model" of the GCR transport in the heliosphere. This is a clear signature of the drift effect on the long-term solar modulation observed with a single detector.

Published
2023
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190. Direct Measurement of the Cosmic-Ray Helium Spectrum from 40 GeV to 250 TeV with the Calorimetric Electron Telescope on the International Space Station.

Author

Adriani O, Akaike Y, Asano K, Asaoka Y, Berti E, Bigongiari G, Binns WR, Bongi M, Brogi P, Bruno A, Buckley JH, Cannady N, Castellini G, Checchia C, Cherry ML, Collazuol G, de Nolfo GA, Ebisawa K, Ficklin AW, Fuke H, Gonzi S, Guzik TG, Hams T, Hibino K, Ichimura M, Ioka K, Ishizaki W, Israel MH, Kasahara K, Kataoka J, Kataoka R, Katayose Y, Kato C, Kawanaka N, Kawakubo Y, Kobayashi K, Kohri K, Krawczynski HS, Krizmanic JF, Maestro P, Marrocchesi PS, Messineo AM, Mitchell JW, Miyake S, Moiseev AA, Mori M, Mori N, Motz HM, Munakata K, Nakahira S, Nishimura J, Okuno S, Ormes JF, Ozawa S, Pacini L, Papini P, Rauch BF, Ricciarini SB, Sakai K, Sakamoto T, Sasaki M, Shimizu Y, Shiomi A, Spillantini P, Stolzi F, Sugita S, Sulaj A, Takita M, Tamura T, Terasawa T, Torii S, Tsunesada Y, Uchihori Y, Vannuccini E, Wefel JP, Yamaoka K, Yanagita S, Yoshida A, Yoshida K, and Zober WV

Abstract

We present the results of a direct measurement of the cosmic-ray helium spectrum with the CALET instrument in operation on the International Space Station since 2015. The observation period covered by this analysis spans from October 13, 2015, to April 30, 2022 (2392 days). The very wide dynamic range of CALET allowed for the collection of helium data over a large energy interval, from ∼40  GeV to ∼250  TeV, for the first time with a single instrument in low Earth orbit. The measured spectrum shows evidence of a deviation of the flux from a single power law by more than 8σ with a progressive spectral hardening from a few hundred GeV to a few tens of TeV. This result is consistent with the data reported by space instruments including PAMELA, AMS-02, and DAMPE and balloon instruments including CREAM. At higher energy we report the onset of a softening of the helium spectrum around 30 TeV (total kinetic energy). Though affected by large uncertainties in the highest energy bins, the observation of a flux reduction turns out to be consistent with the most recent results of DAMPE. A double broken power law is found to fit simultaneously both spectral features: the hardening (at lower energy) and the softening (at higher energy). A measurement of the proton to helium flux ratio in the energy range from 60  GeV/n to about 60  TeV/n is also presented, using the CALET proton flux recently updated with higher statistics.

Published
2023
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191. Age-Dependent Dysregulation of APP in Neuronal and Skin Cells from Fragile X Individuals.

Author

Cencelli G, Pacini L, De Luca A, Messia I, Gentile A, Kang Y, Nobile V, Tabolacci E, Jin P, Farace MG, and Bagni C

Subjects
Humans, Amyloid beta-Protein Precursor metabolism, Neurons metabolism, Fragile X Syndrome genetics, Neural Stem Cells metabolism
Abstract

Fragile X syndrome (FXS) is the most common form of monogenic intellectual disability and autism, caused by the absence of the functional fragile X messenger ribonucleoprotein 1 (FMRP). FXS features include increased and dysregulated protein synthesis, observed in both murine and human cells. Altered processing of the amyloid precursor protein (APP), consisting of an excess of soluble APPα (sAPPα), may contribute to this molecular phenotype in mice and human fibroblasts. Here we show an age-dependent dysregulation of APP processing in fibroblasts from FXS individuals, human neural precursor cells derived from induced pluripotent stem cells (iPSCs), and forebrain organoids. Moreover, FXS fibroblasts treated with a cell-permeable peptide that decreases the generation of sAPPα show restored levels of protein synthesis. Our findings suggest the possibility of using cell-based permeable peptides as a future therapeutic approach for FXS during a defined developmental window.

Published
2023
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192. Biomaterial Inks from Peptide-Functionalized Silk Fibers for 3D Printing of Futuristic Wound-Healing and Sensing Materials.

Author

Ceccarini MR, Palazzi V, Salvati R, Chiesa I, De Maria C, Bonafoni S, Mezzanotte P, Codini M, Pacini L, Errante F, Rovero P, Morabito A, Beccari T, Roselli L, and Valentini L

Subjects
Humans, Silk chemistry, Ink, Biocompatible Materials chemistry, Wound Healing, Peptides, Printing, Three-Dimensional, Fibroins chemistry, Smart Materials
Abstract

This study illustrates the sensing and wound healing properties of silk fibroin in combination with peptide patterns, with an emphasis on the printability of multilayered grids, and envisions possible applications of these next-generation silk-based materials. Functionalized silk fibers covalently linked to an arginine-glycine-aspartic acid (RGD) peptide create a platform for preparing a biomaterial ink for 3D printing of grid-like piezoresistors with wound-healing and sensing properties. The culture medium obtained from 3D-printed silk fibroin enriched with RGD peptide improves cell adhesion, accelerating skin repair. Specifically, RGD peptide-modified silk fibroin demonstrated biocompatibility, enhanced cell adhesion, and higher wound closure rates at lower concentration than the neat peptide. It was also shown that the printing of peptide-modified silk fibroin produces a piezoresistive transducer that is the active component of a sensor based on a Schottky diode harmonic transponder encoding information about pressure. We discovered that such biomaterial ink printed in a multilayered grid can be used as a humidity sensor. Furthermore, humidity activates a transition between low and high conductivity states in this medium that is retained unless a negative voltage is applied, paving the way for utilization in non-volatile organic memory devices. Globally, these results pave the way for promising applications, such as monitoring parameters such as human wound care and being integrated in bio-implantable processors.

Published
2023
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193. Porcine Relaxin but Not Serelaxin Shows Residual Bioactivity after In Vitro Simulated Intestinal Digestion-Clues for the Development of New Relaxin Peptide Agonists Suitable for Oral Delivery.

Author

Pacini L, D'Ercole A, Papini AM, Bani D, Nistri S, and Rovero P

Subjects
Humans, Animals, Swine, Signal Transduction, Vasodilator Agents, Digestion, Recombinant Proteins pharmacology, Relaxin pharmacology, Relaxin metabolism, Cardiovascular Agents
Abstract

Despite human recombinant H2 relaxin or serelaxin holding promise as a cardiovascular drug, its actual efficacy in chronic treatment of heart failure patients was hampered by the need to be administered by multiple daily IV injections for a long time, with obvious drawbacks in terms of patients' compliance. This in vitro study aimed at exploring the molecular background for a possible administration of the peptide hormone relaxin by the oral route. Serelaxin and purified porcine relaxin (pRLX) were subjected to simulated intestinal fluid (SIF) enzymatic digestion in vitro to mimic the behavior of gastroprotective formulations. The digestion time course was studied by HPLC, and the relative bio-potency of the intact molecules and their proteolytic fragments was assessed by second messenger (cAMP) response in RXFP1 relaxin receptor-bearing THP-1 human monocytic cells. Both intact proteins (100 ng/mL) induced a significant cAMP rise in THP-1 cells. Conversely, SIF-treated serelaxin showed a brisk (30 s) bioactivity decay, dropping down to the levels of the unstimulated controls at 120 s, whereas SIF-treated pRLX retained significant bioactivity for up to 120 s. After that, it progressively declined to the levels of the unstimulated controls. HPLC analysis indicates that this bioactivity could be ascribed to a minor component of the pRLX sample more resistant to proteolysis. When identified and better characterized, this peptide could be exploited for the development of synthetic relaxin agonists suitable for oral formulations., Competing Interests: The authors declare no conflict of interest.

Published
2022
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194. Cosmic-Ray Boron Flux Measured from 8.4  GeV/n to 3.8  TeV/n with the Calorimetric Electron Telescope on the International Space Station.

Author

Adriani O, Akaike Y, Asano K, Asaoka Y, Berti E, Bigongiari G, Binns WR, Bongi M, Brogi P, Bruno A, Buckley JH, Cannady N, Castellini G, Checchia C, Cherry ML, Collazuol G, de Nolfo GA, Ebisawa K, Ficklin AW, Fuke H, Gonzi S, Guzik TG, Hams T, Hibino K, Ichimura M, Ioka K, Ishizaki W, Israel MH, Kasahara K, Kataoka J, Kataoka R, Katayose Y, Kato C, Kawanaka N, Kawakubo Y, Kobayashi K, Kohri K, Krawczynski HS, Krizmanic JF, Maestro P, Marrocchesi PS, Messineo AM, Mitchell JW, Miyake S, Moiseev AA, Mori M, Mori N, Motz HM, Munakata K, Nakahira S, Nishimura J, Okuno S, Ormes JF, Ozawa S, Pacini L, Papini P, Rauch BF, Ricciarini SB, Sakai K, Sakamoto T, Sasaki M, Shimizu Y, Shiomi A, Spillantini P, Stolzi F, Sugita S, Sulaj A, Takita M, Tamura T, Terasawa T, Torii S, Tsunesada Y, Uchihori Y, Vannuccini E, Wefel JP, Yamaoka K, Yanagita S, Yoshida A, Yoshida K, and Zober WV

Abstract

We present the measurement of the energy dependence of the boron flux in cosmic rays and its ratio to the carbon flux in an energy interval from 8.4  GeV/n to 3.8  TeV/n based on the data collected by the Calorimetric Electron Telescope (CALET) during ∼6.4  yr of operation on the International Space Station. An update of the energy spectrum of carbon is also presented with an increase in statistics over our previous measurement. The observed boron flux shows a spectral hardening at the same transition energy E&#95;{0}∼200  GeV/n of the C spectrum, though B and C fluxes have different energy dependences. The spectral index of the B spectrum is found to be γ=-3.047±0.024 in the interval 25

Published
2022
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195. GCAT: A network model of mutational influences between amino acid positions in PSD95 pdz3 .

Author

Pacini L and Lesieur C

Abstract

Proteins exist for more than 3 billion years: proof of a sustainable design. They have mechanisms coping with internal perturbations (e.g., amino acid mutations), which tie genetic backgrounds to diseases or drug therapy failure. One difficulty to grasp these mechanisms is the asymmetry of amino acid mutational impact: a mutation at position i in the sequence, which impact a position j does not imply that the mutation at position j impacts the position i . Thus, to distinguish the influence of the mutation of i on j from the influence of the mutation of j on i , position mutational influences must be represented with directions. Using the X ray structure of the third PDZ domain of PDS-95 (Protein Data Bank 1BE9) and in silico mutations, we build a directed network called GCAT that models position mutational influences. In the GCAT, a position is a node with edges that leave the node (out-edges) for the influences of the mutation of the position on other positions and edges that enter the position (in-edges) for the influences of the mutation of other positions on the position. 1BE9 positions split into four influence categories called G, C, A and T going from positions influencing on average less other positions and influenced on average by less other positions (category C) to positions influencing on average more others positions and influenced on average by more other positions (category T). The four categories depict position neighborhoods in the protein structure with different tolerance to mutations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pacini and Lesieur.)

Published
2022
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196. Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma.

Author

Rosa P, De Falco E, Pacini L, Piazza A, Ciracì P, Ricciardi L, Fiorentino F, Trungu S, Miscusi M, Raco A, and Calogero A

Abstract

The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of utmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EVs) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors, including glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next-Generation Sequencing (UMI system) in circulating EVs of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare the corresponding matched tissue samples and potential variants with pathogenic significance of the DNA contained in peripheral-blood-derived EVs. The NGS analysis has revealed that patients with grade IV glioblastoma exhibited lesser DNA content in EVs than controls and that, both in EVs and matched cancer tissues, the NF1 gene was consistently mutated in all patients, with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of circulating EVs in glioblastoma as an eligible tool for personalized medicine.

Published
2022
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197. Bicyclopeptides: a new class of ligands for Cu(II) ions.

Author

Marciniak A, Pacini L, Papini AM, and Brasuń J

Subjects
Ions, Ligands, Peptides chemistry, Copper chemistry, Histidine chemistry
Abstract

There is growing interest in bicyclic peptides among scientists. This group of compounds has more advantageous properties than monocyclic ligands and their application in medicine and biological sciences is possible. It is known that sometimes the presence of metal ions is crucial for the activity of peptides in biological systems, like in the case of oxytocin or vasopressin. Therefore, in this study, we performed a series of experiments with the new bicyclic peptide c(PKKHP-c(CFWKTC)-PKKH) ( BCL ) that was designed and synthesized by a fully automated induction-assisted solid phase synthesizer. We analyzed the coordination abilities of BCL relative to copper(II) ions. The new bicyclic peptide contains two histidine moieties, separated by proline residues, with two distinct sites for metal ion coordination. The obtained results showed that in all analyzed systems both mono- and dinuclear complexes are formed.

Published
2022
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198. Observation of Spectral Structures in the Flux of Cosmic-Ray Protons from 50 GeV to 60 TeV with the Calorimetric Electron Telescope on the International Space Station.

Author

Adriani O, Akaike Y, Asano K, Asaoka Y, Berti E, Bigongiari G, Binns WR, Bongi M, Brogi P, Bruno A, Buckley JH, Cannady N, Castellini G, Checchia C, Cherry ML, Collazuol G, Ebisawa K, Ficklin AW, Fuke H, Gonzi S, Guzik TG, Hams T, Hibino K, Ichimura M, Ioka K, Ishizaki W, Israel MH, Kasahara K, Kataoka J, Kataoka R, Katayose Y, Kato C, Kawanaka N, Kawakubo Y, Kobayashi K, Kohri K, Krawczynski HS, Krizmanic JF, Maestro P, Marrocchesi PS, Messineo AM, Mitchell JW, Miyake S, Moiseev AA, Mori M, Mori N, Motz HM, Munakata K, Nakahira S, Nishimura J, de Nolfo GA, Okuno S, Ormes JF, Ozawa S, Pacini L, Papini P, Rauch BF, Ricciarini SB, Sakai K, Sakamoto T, Sasaki M, Shimizu Y, Shiomi A, Spillantini P, Stolzi F, Sugita S, Sulaj A, Takita M, Tamura T, Terasawa T, Torii S, Tsunesada Y, Uchihori Y, Vannuccini E, Wefel JP, Yamaoka K, Yanagita S, Yoshida A, Yoshida K, and Zober WV

Abstract

A precise measurement of the cosmic-ray proton spectrum with the Calorimetric Electron Telescope (CALET) is presented in the energy interval from 50 GeV to 60 TeV, and the observation of a softening of the spectrum above 10 TeV is reported. The analysis is based on the data collected during ∼6.2  years of smooth operations aboard the International Space Station and covers a broader energy range with respect to the previous proton flux measurement by CALET, with an increase of the available statistics by a factor of ∼2.2. Above a few hundred GeV we confirm our previous observation of a progressive spectral hardening with a higher significance (more than 20 sigma). In the multi-TeV region we observe a second spectral feature with a softening around 10 TeV and a spectral index change from -2.6 to -2.9 consistently, within the errors, with the shape of the spectrum reported by DAMPE. We apply a simultaneous fit of the proton differential spectrum which well reproduces the gradual change of the spectral index encompassing the lower energy power-law regime and the two spectral features observed at higher energies.

Published
2022
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200. FMRP modulates the Wnt signalling pathway in glioblastoma.

Author

Pedini G, Buccarelli M, Bianchi F, Pacini L, Cencelli G, D'Alessandris QG, Martini M, Giannetti S, Sasso F, Melocchi V, Farace MG, Achsel T, Larocca LM, Ricci-Vitiani L, Pallini R, and Bagni C

Subjects
Animals, Cell Line, Tumor, Humans, Mice, Neoplastic Stem Cells metabolism, Ribonucleoproteins, Wnt Signaling Pathway genetics, beta Catenin metabolism, Brain Neoplasms pathology, Fragile X Mental Retardation Protein metabolism, Glioblastoma pathology
Abstract

Converging evidence indicates that the Fragile X Messenger Ribonucleoprotein (FMRP), which absent or mutated in Fragile X Syndrome (FXS), plays a role in many types of cancers. However, while FMRP roles in brain development and function have been extensively studied, its involvement in the biology of brain tumors remains largely unexplored. Here we show, in human glioblastoma (GBM) biopsies, that increased expression of FMRP directly correlates with a worse patient outcome. In contrast, reductions in FMRP correlate with a diminished tumor growth and proliferation of human GBM stem-like cells (GSCs) in vitro in a cell culture model and in vivo in mouse brain GSC xenografts. Consistently, increased FMRP levels promote GSC proliferation. To characterize the mechanism(s) by which FMRP regulates GSC proliferation, we performed GSC transcriptome analyses in GSCs expressing high levels of FMRP, and in these GSCs after knockdown of FMRP. We show that the WNT signalling is the most significantly enriched among the published FMRP target genes and genes involved in ASD. Consistently, we find that reductions in FMRP downregulate both the canonical WNT/β-Catenin and the non-canonical WNT-ERK1/2 signalling pathways, reducing the stability of several key transcription factors (i.e. β-Catenin, CREB and ETS1) previously implicated in the modulation of malignant features of glioma cells. Our findings support a key role for FMRP in GBM cancer progression, acting via regulation of WNT signalling., (© 2022. The Author(s).)

Published
2022
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