Search

Your search keyword '"Bertolin M"' showing total 97 results
Start Over Author "Bertolin M"
97 results on '"Bertolin M"'

1. Positron driven muon source for a muon collider

Author

Alesini, D., Antonelli, M., Biagini, M. E., Boscolo, M., Blanco-García, O. R., Ciarma, A., Cimino, R., Iafrati, M., Giribono, A., Guiducci, S., Pellegrino, L., Rotondo, M., Vaccarezza, C., Variola, A., Allegrucci, A., Anulli, F., Bauce, M., Collamati, F., Cavoto, G., Cesarini, G., Iacoangeli, F., Voti, R. Li, Bacci, A., Drebot, I., Raimondi, P., Liuzzo, S., Chaikovska, I., Chehab, R., Amapane, N., Bartosik, N., Biino, C., Cappati, A., Cotto, G., Pastrone, N., Pelliccioni, M., Planell, O. Sans, Casarza, M., Vallazza, E., Ballerini, G., Brizzolari, C., Mascagna, V., Prest, M., Bertolin, M. Soldani A., Curatolo, C., Gonella, F., Lorenzon, A., Lucchesi, D., Morandin, M., Pazzini, J., Rossin, R., Sestini, L., Ventura, S., Zanetti, M., Carra, F., Sievers, P., Keller, L., Peroni, L., and Scapin, M.

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

The design of a future multi-TeV muon collider needs new ideas to overcome the technological challenges related to muon production, cooling, accumulation and acceleration. In this paper a layout of a positron driven muon source known as the Low EMittance Muon Accelerator (LEMMA) concept is presented. The positron beam, stored in a ring with high energy acceptance and low emittance, is extracted and driven to a multi-target system, to produce muon pairs at threshold. This solution alleviates the issues related to the power deposited and the integrated Peak Energy Density Deposition (PEDD) on the targets. Muons produced in the multi-target system will then be accumulated before acceleration and injection in the collider. A multi-target line lattice has been designed to cope with the focusing of both the positron and muon beams. Studies on the number, material and thickness of the targets have been carried out. A general layout of the overall scheme and a description is presented, as well as plans for future R&D., Comment: 18 pages, 32 figures

Published
2019

5. Identification of the regulatory circuit governing corneal epithelial fate determination and disease

Author

Smits, J.G.A., Cunha, D.L., Amini, M., Bertolin, M., Laberthonnière, C.A.J., Qu, J., Owen, N., Latta, L., Seitz, B., Roux, L.N., Stachon, T., Ferrari, S., Moosajee, M., Aberdam, D., Szentmary, N., Heeringen, S.J. van, Zhou, H., Smits, J.G.A., Cunha, D.L., Amini, M., Bertolin, M., Laberthonnière, C.A.J., Qu, J., Owen, N., Latta, L., Seitz, B., Roux, L.N., Stachon, T., Ferrari, S., Moosajee, M., Aberdam, D., Szentmary, N., Heeringen, S.J. van, and Zhou, H.

Abstract

Contains fulltext : 298476.pdf (Publisher’s version ) (Open Access)

Published
2023

10. Comparative analysis of environmental noise levels in two paediatric intensive care units

Author

Bosch-Alcaraz A, Fernández-Lorenzo R, Saz-Roy MA, Domínguez-Delso MC, Santaolalla-Bertolin M, Ferrer-Orona M, and Alcolea-Monge S

Subjects
Ruido, Unidad de cuidados intensivos, Pediatría, Intensive care unit, Paediatrics, Noise
Abstract

AIMS: 1) To determine noise levels in two paediatric intensive care units (PICU) of a tertiary hospital and 2) to analyse whether these values comply with the current standards. METHOD: Observational, descriptive and cross-sectional study carried out in two PICU with different infrastructure: bays separated by curtains and individual bedrooms. A PCE-999 sound level meter was used to determine noise levels, which were registered in decibels (dB). At the same time, an ad hoc data recording document was designed in which we differentiated between each unit (open concept or closed), time of recording. RESULTS: A total of 330 tests, 72 from open PICUs and 258 from closed PICUs were collected. The noise in the open PICU was 56.74 ± 3.61 decibels versus 50.36 ± 4.71 in the closed PICU, obtaining the highest levels during the morning. DISCUSSION: As it occurs in other studies, noise levels exceed the allowed limits. At the same time, the main sources of noise in the PICU came from alarms, medical equipment, such as monitors or respirators, and conversations between health professional. CONCLUSIONS: This investigation has shown high levels of environmental noise in the two PICUs analysed. The data obtained indicate that the architectural concept of individual bedrooms may have an impact in decreasing this environmental input.

Published
2019

11. Foraging patterns of the Antarctic Shag Phalacrocorax bransfieldensis at Harmony Point, Antarctica

Author

Casaux, Ricardo Jorge and Bertolin M.

Subjects
Ciencias Biológicas, purl.org/becyt/ford/1 [https], SOUTH SHETLAND ISLANDS, FEEDING EFFORT, Ecología, CORMORANTS, purl.org/becyt/ford/1.6 [https], CIENCIAS NATURALES Y EXACTAS, ECOSYSTEM MONITORING
Abstract

During the 1995 and1996 summer seasons the foraging patterns of the Antarctic Shag Phalacrocorax bransfieldensis werestudied by direct observation at Harmony Point, Nelson Island, South ShetlandIslands. During pre-laying and incubation, individuals of both sexes usuallyforaged once a day, females early in the morning and males when their partnersreturned to their nests. Due to increasing energy requirements at the nest, rearingindividuals incremented the daily time invested in foraging activitiesdisplaying more, but shorter, foraging trips. The reduction in the duration ofthe foraging trips through the breeding season suggests that Antarctic shags budgettheir activities in order to buffer variable food abundance or energyrequirements at the nests. The possibility of using the foraging parametersconsidered in this study in ecosystem monitoring programmes is discussed. Fil: Casaux, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; Argentina Fil: Bertolin M.. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; Argentina

Published
2018

19. FORAGING PATTERNS OF THE ANTARCTIC SHAG PHALACROCORAX BRANSFIELDENSIS AT HARMONY POINT, ANTARCTICA.

Author

CASAUX, R. and BERTOLIN, M. L.

Subjects
*NEOTROPIC cormorant, *BIRD breeding, *BIRD populations, *SURVIVAL behavior (Animals), *BIRD behavior
Abstract

During the 1995 and 1996 summer seasons, the foraging patterns of the Antarctic Shag Phalacrocorax bransfieldensis were studied hy direct observation at Harmony Point, Nelson Island, South Shetland Islands. During pre-laying and incubation, individuals of both sexes usually foraged once a day--females early in the morning and males when their partners returned to their nests. Due to increasing energy requirements at the nest, rearing individuals increased the daily lime invested in foraging activities, displaying more--but shorter--foraging trips. The reduction in the duration of the foraging trips through the breeding season suggests that Antarctic shags budget their activities to buffer variable food abundance or energy requirements at their nests. Here, we discuss the possibility of using the foraging parameters measured in this study in ecosystem monitoring programs. [ABSTRACT FROM AUTHOR]

Published
2018

23. The OPERA experiment in the CERN to Gran Sasso neutrino beam

Author

Acquafredda, R., A, Adam, 1 T., Agafonova, b. N., Alvarez Sanchez, c. P., Ambrosio, d. M., Anokhina, a. A., Aoki, e. S., Ariga, f. A., Ariga, g. T., Arrabito, h. L., Aufranc, i. C., Autiero, i. D., Badertscher, i. A., Bagulya, j. A., Baussan, k. E., Bergnoli, b. A., L, Bersani Greggio, 2 F., Bertolin, m. A., Besnier, l. M., N, Biar ´e, 3 D., Bick, n. D., Blin, o. S., Borer, p. K., Boucrot, g. J., Boutigny, p. D., Boyarkin, 4 V., Bozza, c. C., Brugi `ere, q. T., Brugnera, i. R., R, Brunetti, l. G., S, Buontempo, t. S., Campagne, a. J. E., Carlus, p. B., Carrara, i. E., R, L, Cazes, 5 A., Chaussard, u. L., Chernyavsky, i. M., Chiarella, k. V., Chon Sen, u. N., Chukanov, b. A., Ciesielski, a. R., Consiglio, l. L., Cozzi, t. M., D’Amato, s. G., Dal Corso, q. F., D’Ambrosio, l. N., Damet, v. J., de La Taille, 6 C., De Lellis, p. G., W, A, D´eclais, 7 Y., Descombes, i. T., I, De Serio, 8 M., Di Capua, x. F., Di Ferdinando, a. D., Di Giovanni, t. A., Di Marco, y. N., Di Troia, y. C., Dick, u. N., Dmitrievski, b. S., Dominjon, z. A., Dracos, i. M., Duchesneau, b. D., Dulach, n. B., Dusini, u. S., Ebert, l. J., Efthymiopoulos, o. I., Egorov, d. O., Elsener, aa K., Enikeev, d. R., Ereditato, c. A., Esposito, g. L. S., Fanin, v. C., Favier, l. J., Felici, n. G., Ferber, u. T., Fini, o. R., Fournier, x. L., Franceschi, n. A., Frekers, u. D., Fukuda, ab T., Fukushima, h. C., Galkin, ac V. I., Galkin, e. V. A., Gallet, ad R., Gardien, n. S., Garfagnini, i. A., Gaudiot, l. G., Giacomelli, b. G., Giorgini, t. M., Girerd, t. C., Goellnitz, i. C., Goeltzenlichter, o. T., Goldberg, b. J., Golubkov, ae D., Gornushkin, aa Y., Grapton, z. J. N., Grella, b. G., Grianti, q. F., Gschwendtner, m. E., Guerin, d. C., Guler, i. M., Gustavino, a. f. C., Guyonnet, v. J. L., Hagner, b. C., Hamane, o. T., Hara, 9 T., Hauger, f. M., Hess, g. M., Hierholzer, g. M., Hoshino, ag K., Ieva, h. M., Incurvati, x. M., Jakovcic, u. K., Janicsko Csathy, ah J., Janutta, g. B., Jollet, o. C., Juget, b. F., Kazuyama, g. M., Kim, h. S. H., Khovansky, 10 N., Kimura, z. M., Klicek, ac B., Knuesel, ah J., Kodama, g. K., Kolev, a. j. D., Komatsu, M., Kose, h. U., a. f., Krasnoperov, 11 A., Kreslo, z. I., Krumstein, g. Z., Kutsenov, z. V. V., Kuznetsov, c. V. A., Laktineh, c. I., Lavy, i. M., Lazzaro, 12 C., j. T. D., Le, Le Flour, b. T., Lenkeit, n. J., Lewis, o. J., Lieunard, d. S., Ljubicic, n. A., Longhin, ah A., Lutter, r. G., Malgin, g. A., Manai, c. K., Mandrioli, i. G., Marotta, t. A., Marteau, a. J., Martin Chassard, i. G., Matveev, p. V., Mauri, c. N., Meddahi, t. M., Meisel, d. F., Meregaglia, g. A., Meschini, b. A., Messina, v. M., Migliozzi, g. P., Monacelli, a. P., Monteiro, y. I., Moreau, n. F., Morishima, 13 K., Moser, h. U., Muciaccia, g. M. T., Mugnier, x. P., Naganawa, n. N., Nakamura, h. M., Nakano, h. T., Napolitano, h. T., Nikitina, u. V., Niwa, e. K., Nonoyama, h. Y., Nozdrin, h. A., Ogawa, z. S., Olchevski, ac A., Orlandi, z. D., Orlova, v. G., Osedlo, k. V., Ossetski, e. D., Paniccia, ad M., Paoloni, u. A., Park, u. B. D., Park, h. I. G., Pastore, ai A., Patrizii, x. L., Pellegrino, t. L., Pennacchio, u. E., Pessard, i. H., Pilipenko, n. V., Pistillo, ab C., Polukhina, g. N., Pozzato, k. M., Pretzl, t. K., Publichenko, g. P., Pupilli, e. F., Raux, y. L., Repellin, p. J. P., Rescigno, p. R., Rizhikov, q. D., Roganova, ad T., Romano, e. G., Rosa, q. G., Rostovtseva, am I., Rubbia, aa A., Russo, j. A., W, Ryasny, a. V., Ryazhskaya, c. O., Sadovski, c. A., Sanelli, z. C., Sato, u. O., Sato, h. Y., Saveliev, an V., Sazhina, ad G., Schembri, e. A., Schmidt Parzefall, am W., Schroeder, o. H., Sch¨utz, ag H. U., Schuler, g. J., Scotto Lavina, b. L., Serrano, a. J., Shibuya, d. H., Simone, ac S., Sioli, x. M., Sirignano, Chiara, Sirri, q. G., Song, t. J. S., Spinetti, ai M., Stanco, u. L., Starkov, r. N., Stipcevic, k. M., Strauss, ah T., Strolin, j. P., Sugonyaev, a. V., Takahashi, 14 S., Talochkin, h. V., Tenti, c. M., Tereschenko, t. V., Terranova, z. F., U, Tezuka, 15 I., Tioukov, an V., Tolun, a. P., Tsarev, a. f. V., Tsenov, k. R., Tufanli, ak S., Ugolino, a. f. U., Ushida, a. N., Van Beek, a. j. G., Verguilov, ao V., Viant, ak T., Vilain, j. P., Vladimirov, ao M., Votano, k. L., Vuilleumier, u. J. L., Waelchli, g. T., Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Département Recherches Subatomiques (DRS-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'Accélérateur Linéaire (LAL), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), OPERA, Acquafredda, R, Adam, T, Agafonova, N, Sanchez, P, Ambrosio, M, Anokhina, A, Aoki, S, Ariga, A, Ariga, T, Arrabito, L, Aufranc, C, Autiero, D, Badertscher, A, Bagulya, A, Baussan, E, Bergnoli, A, Greggio, F, Bertolin, A, Besnier, M, Biaré, D, Bick, D, Blin, S, Borer, K, Boucrot, J, Boutigny, D, Boyarkin, V, Bozza, C, Brugière, T, Brugnera, R, Brunetti, G, Buontempo, S, Campagne, J, Carlus, B, Carrara, E, Cazes, A, Chaussard, L, Chernyavsky, M, Chiarella, V, Chon Sen, N, Chukanov, A, Ciesielski, R, Consiglio, L, Cozzi, M, D'Amato, G, Corso, F, D'Ambrosio, N, Damet, J, Taille, C, Lellis, G, Déclais, Y, Descombes, T, Serio, M, Capua, F, Ferdinando, D, Giovanni, A, Marco, N, Troia, C, Dick, N, Dmitrievski, S, Dominjon, A, Dracos, M, Duchesneau, D, Dulach, B, Dusini, S, Ebert, J, Efthymiopoulos, I, Egorov, O, Elsener, K, Enikeev, R, Ereditato, A, Esposito, L, Fanin, C, Favier, J, Felici, G, Ferber, T, Fini, R, Fournier, L, Franceschi, A, Frekers, D, Fukuda, T, Fukushima, C, Galkin, V, Gallet, R, Gardien, S, Garfagnini, A, Gaudiot, G, Giacomelli, G, Giorgini, M, Girerd, C, Goellnitz, C, Goeltzenlichter, T, Goldberg, J, Golubkov, D, Gornushkin, Y, Grapton, J, Grella, G, Grianti, F, Gschwendtner, E, Guerin, C, Guler, M, Gustavino, C, Guyonnet, J, Hagner, C, Hamane, T, Hara, T, Hauger, M, Hess, M, Hierholzer, M, Hoshino, K, Ieva, M, Incurvati, M, Jakovcic, K, Csathy, J, Janutta, B, Jollet, C, Juget, F, Kazuyama, M, Kim, S, Khovansky, N, Kimura, M, Klicek, B, Knuesel, J, Kodama, K, Kolev, D, Komatsu, M, Kose, U, Krasnoperov, A, Kreslo, I, Krumstein, Z, Kutsenov, V, Kuznetsov, V, Laktineh, I, Lavy, M, Lazzaro, C, Le, T, Flour, T, Lenkeit, J, Lewis, J, Lieunard, S, Ljubicic, A, Longhin, A, Lutter, G, Malgin, A, Manai, K, Mandrioli, G, Marotta, A, Marteau, J, Martin Chassard, G, Matveev, V, Mauri, N, Meddahi, M, Meisel, F, Meregaglia, A, Meschini, A, Messina, M, Migliozzi, P, Monacelli, P, Monteiro, I, Moreau, F, Morishima, K, Moser, U, Muciaccia, M, Mugnier, P, Naganawa, N, Nakamura, M, Nakano, T, Napolitano, T, Nikitina, V, Niwa, K, Nonoyama, Y, Nozdrin, A, Ogawa, S, Olchevski, A, Orlandi, D, Orlova, G, Osedlo, V, Ossetski, D, Paniccia, M, Paoloni, A, Park, B, Park, I, Pastore, A, Patrizii, L, Pellegrino, L, Pennacchio, E, Pessard, H, Pilipenko, V, Pistillo, C, Polukhina, N, Pozzato, M, Pretzl, K, Publichenko, P, Pupilli, F, Raux, L, Repellin, J, Rescigno, R, Rizhikov, D, Roganova, T, Romano, G, Rosa, G, Rostovtseva, I, Rubbia, A, Russo, A, Ryasny, V, Ryazhskaya, O, Sadovski, A, Sanelli, C, Sato, O, Sato, Y, Saveliev, V, Sazhina, G, Schembri, A, Parzefall, W, Schroeder, H, Schütz, H, Schuler, J, Lavina, L, Serrano, J, Shibuya, H, Simone, S, Sioli, M, Sirignano, C, Sirri, G, Song, J, Spinetti, M, Stanco, L, Starkov, N, Stipcevic, M, Strauss, T, Strolin, P, Sugonyaev, V, Takahashi, S, Talochkin, V, Tenti, M, Tereschenko, V, Terranova, F, Tezuka, I, Tioukov, V, Tolun, P, Tsarev, V, Tsenov, R, Tufanli, S, Ugolino, U, Ushida, N, Beek, G, Verguilov, V, Viant, T, Vilain, P, Vladimirov, M, Votano, L, Vuilleumier, J, Waelchli, T, Weber, M, Wilquet, G, Wonsak, B, Wurtz, J, Yakushev, V, Yoon, C, Zaitsev, Y, Zghiche, A, Zimmermann, R, Sanchez, P. Alvarez, Greggio, F. Bersani, Campagne, J. E, Corso, F. Dal, Taille, C. de La, Lellis, G. De, Serio, M. De, DI CAPUA, Francesco, Ferdinando, D. Di, Giovanni, A. Di, Marco, N. Di, Troia, C. Di, Esposito, L. S, Galkin, V. I, Galkin, V. A, Grapton, J. N, Guyonnet, J. L, Csathy, J. Janicsko, Kim, S. H, Kutsenov, V. V, Kuznetsov, V. A, Le, T. D, Flour, T. Le, Muciaccia, M. T, Park, B. D, Park, I. G, Repellin, J. P, Parzefall, W. Schmidt, Schütz, H. U, Lavina, L. Scotto, Song, J. S, Beek, G. Van, Vuilleumier, J. L, Yoon, C. S, Zimmermann, R., R. ACQUAFREDDA, T. ADAM, N. AGAFONOVA, P. ALVAREZ SANCHEZ, M. AMBROSIO, A. ANOKHINA, S. AOKI, A. ARIGA, T. ARIGA, L. ARRABITO, C. AUFRANC, D. AUTIERO, A. BADERTSCHER, A. BAGULYA, E. BAUSSAN, A. BERGNOLI, F. BERSANI GREGGIO, A. BERTOLIN, M. BESNIER, D. BIARÉ, D. BICK, S. BLIN, K. BORER, J. BOUCROT, D. BOUTIGNY, V. BOYARKIN, C. BOZZA, T. BRUGIÈRE, R. BRUGNERA, G. BRUNETTI, S. BUONTEMPO, J.E. CAMPAGNE, B. CARLUS, E. CARRARA, A. CAZES, L. CHAUSSARD, M. CHERNYAVSKY, V. CHIARELLA, N. CHON-SEN, A. CHUKANOV, R. CIESIELSKI, L. CONSIGLIO, M. COZZI, G. D’AMATO, F. DAL CORSO, N. D’AMBROSIO, J. DAMET, C. DE LA TAILLE, G. DE LELLIS, Y. D´ECLAIS, T. DESCOMBES, M. DE SERIO, F. DI CAPUA, D. DI FERDINANDO, A. DI GIOVANNI, N. DI MARCO, C. DI TROIA, N. DICK, S. DMITRIEVSKI, A. DOMINJON, M. DRACOS, D. DUCHESNEAU, B. DULACH, S. DUSINI, J. EBERT, I. EFTHYMIOPOULOS, O. EGOROV, K. ELSENER, R. ENIKEEV, A. EREDITATO, L. S. ESPOSITO, C. FANIN, J. FAVIER, G. FELICI, T. FERBER, R. FINI, L. FOURNIER, A. FRANCESCHI, D. FREKERS, T. FUKUDA, C. FUKUSHIMA, V.I. GALKIN, V.A. GALKIN, R. GALLET, S. GARDIEN, A. GARFAGNINI, G. GAUDIOT, G. GIACOMELLI, M. GIORGINI, C. GIRERD, C. GOELLNITZ, T. GOELTZENLICHTER, J. GOLDBERG, D. GOLUBKOV, Y. GORNUSHKIN, J.-N. GRAPTON, G. GRELLA, F. GRIANTI, E. GSCHWENDTNER, C. GUERIN, M. GULER, C. GUSTAVINO, J.-L. GUYONNET, C. HAGNER, T. HAMANE, T. HARA, M. HAUGER, M. HESS, M. HIERHOLZER, K. HOSHINO, M. IEVA, M. INCURVATI, K. JAKOVCIC, J. JANICSKO CSATHY, B. JANUTTA, C. JOLLET, F. JUGET, M. KAZUYAMA, S.H. KIM, N. KHOVANSKY, M. KIMURA, B. KLICEK, J. KNUESEL, K. KODAMA, D. KOLEV, M. KOMATSU, U. KOSE, A. KRASNOPEROV, I. KRESLO, Z. KRUMSTEIN, V.V. KUTSENOV, V.A. KUZNETSOV, I. LAKTINEH, M. LAVY, C. LAZZARO, T.D. LE, T. LE FLOUR, J. LENKEIT, J. LEWIS, S. LIEUNARD, A. LJUBICIC, A. LONGHIN, G. LUTTER, A. MALGIN, K. MANAI, G. MANDRIOLI, A. MAROTTA, J. MARTEAU, G. MARTIN-CHASSARD, V. MATVEEV, N. MAURI, M. MEDDAHI, F. MEISEL, A. MEREGAGLIA, A. MESCHINI, M. MESSINA, P. MIGLIOZZI, P. MONACELLI, I. MONTEIRO, F. MOREAU, K. MORISHIMA, U. MOSER, M.T. MUCIACCIA, P. MUGNIER, N. NAGANAWA, M. NAKAMURA, T. NAKANO, T. NAPOLITANO, V. NIKITINA, K. NIWA, Y. NONOYAMA, A. NOZDRIN, S. OGAWA, A. OLCHEVSKI, D. ORLANDI, G. ORLOVA, V. OSEDLO, D. OSSETSKI, M. PANICCIA, A. PAOLONI, B. D PARK, I.G. PARK, A. PASTORE, L. PATRIZII, L. PELLEGRINO, E. PENNACCHIO, H. PESSARD, V. PILIPENKO, C. PISTILLO, N. POLUKHINA, M. POZZATO, K. PRETZL, P. PUBLICHENKO, F. PUPILLI, L. RAUX, J.P. REPELLIN, R. RESCIGNO, D. RIZHIKOV, T. ROGANOVA, G. ROMANO, G. ROSA, I. ROSTOVTSEVA, A. RUBBIA, J A. RUSSO, V. RYASNY, O. RYAZHSKAYA, A. SADOVSKI, C. SANELLI, O. SATO, Y. SATO, V. SAVELIEV, G. SAZHINA, A. SCHEMBRI, W. SCHMIDT PARZEFALL, H. SCHROEDER, H.U. SCH¨UTZ, J. SCHULER, L. SCOTTO LAVINA, J. SERRANO, H. SHIBUYA, S. SIMONE, M. SIOLI, C. SIRIGNANO, G. SIRRI, J.S. SONG, M. SPINETTI, L. STANCO, N. STARKOV, M. STIPCEVIC, T. STRAUSS, P. STROLIN, V. SUGONYAEV, S. TAKAHASHI, V. TALOCHKIN, M. TENTI, V. TERESCHENKO, F. TERRANOVA, I. TEZUKA, V. TIOUKOV, P. TOLUN, V. TSAREV, R. TSENOV, S. TUFANLI, U. UGOLINO, N. USHIDA, G. VAN BEEK, V. VERGUILOV, T. VIANT, P. VILAIN, M. VLADIMIROV, L. VOTANO, J.L. VUILLEUMIER, T. WAELCHLI, M. WEBER, G. WILQUET, B. WONSAK, J. WURTZ, V. YAKUSHEV, C.S. YOON, Y. ZAITSEV, A. ZGHICHEN, R. ZIMMERMANN, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Annecy de Physique des Particules (LAPP/Laboratoire d'Annecy-le-Vieux de Physique des Particules), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Particle physics, [PHYS.ASTR.HE]Physics [physics]/Astrophysics [astro-ph]/High Energy Astrophysical Phenomena [astro-ph.HE], NEUTRINO OSCILLATIONS, FUNDAMENTAL PHYSICS, Physics::Instrumentation and Detectors, 7. Clean energy, 01 natural sciences, Nuclear physics, neutrino, Particle tracking detectors, 0103 physical sciences, Nuclear emulsion, Detectors and Experimental Techniques, 010306 general physics, Neutrino oscillation, Instrumentation, Mathematical Physics, ICARUS, Physics, Large Hadron Collider, Spectrometers, Large detector systems for particle and astroparticle physics, 010308 nuclear & particles physics, Hybrid detector, [SDU.ASTR.HE]Sciences of the Universe [physics]/Astrophysics [astro-ph]/High Energy Astrophysical Phenomena [astro-ph.HE], Detector, Hybrid detectors, NEUTRINO DETECTORS, Particle tracking detector, FIS/01 - FISICA SPERIMENTALE, Large detector systems for particle and astroparticle physic, Physique des particules élémentaires, PARTICLE PHYSICS, High Energy Physics::Experiment, hybrid detectors, particle tracking detectors, large detector systems for particle and astroparticle physics, spectrometers, Supermodule, Neutrino, Lepton
Abstract

The OPERA neutrino oscillation experiment has been designed to prove the appearance of ντ in a nearly pure νμ beam (CNGS) produced at CERN and detected in the underground Hall C of the Gran Sasso Laboratory, 730 km away from the source. In OPERA, τ leptons resulting from the interaction of ντ are produced in target units called bricks made of nuclear emulsion films interleaved with lead plates. The OPERA target contains 150000 of such bricks, for a total mass of 1.25 kton, arranged into walls interleaved with plastic scintillator strips. The detector is split into two identical supermodules, each supermodule containing a target section followed by a magnetic spectrometer for momentum and charge measurement of penetrating particles. Real time information from the scintillators and the spectrometers provide the identification of the bricks where the neutrino interactions occurred. The candidate bricks are extracted from the walls and, after X-ray marking and an exposure to cosmic rays for alignment, their emulsion films are developed and sent to the emulsion scanning laboratories to perform the accurate scan of the event. In this paper, we review the design and construction of the detector and of its related infrastructures, and report on some technical performances of the various components. The construction of the detector started in 2003 and it was completed in Summer 2008. The experiment is presently in the data taking phase. The whole sequence of operations has proven to be successful, from triggering to brick selection, development, scanning and event analysis. © 2009 IOP Publishing Ltd and SISSA., 0, P04018, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2009

24. Valutazione dell´endothelin axis (ET-1, ETAR, ETBR) come markers prognostici per il carcinoma invasivo della vulva mediante tecnica immunoistochimica su microarray tissutale

Author

Bertolin, M. (Matteo) and Universitäts- und Landesbibliothek Münster

Subjects
Vulvakarzinom, Prognosefaktoren, Endothelinachse, Endothelin-1, ETAR, ETBR, Medicine and health, ddc:610
Abstract

Background: Vulvar carcinoma is a rare gynecologic malignancy (incidence rate 3-5% of all female genital tract neoplasias) and mainly affects elderly women. Squamous cell carcinoma represent the vast majority of vulvar carcinomas (90-95%). TNM staging, deep of stromal invasion and presence of lymph node metastasis are the most important prognostic factors. Surgery is the standard treatment for primary vulvar carcinoma, followed by post operative radiotherapy when is neccesary. After primary treatment a high rate of patients develop recurrences, and a routine follow-up is necessary. Purpose: The ET-axis (Endothelin-1 and its receptors ETAR and ETBR) is overexpressed in various human tumors. We analyzed the ET-axis expression in vulva cancer, and its prognostic value. Methods: Samples were obtained from local excision and radical vulvectomy patients. ET-axis expression was investigated immunohistochemistry on tissue microarrays of 68 vulva cancer patients. Results: Elevated ET-1 expression of tumour cells is correlated high significantly to early stages pT1-T2 (P=0,004), and presence of metastasis (P=0,04). High staining levels ETBR within tumour tissue was related significantly to tumour progression (P=0,01), relapse-free survival (P=0,019), delayed metastasis (P=0,09 as a trend) and lymph node involvement (P=0,059 as a trend). A significant reduced overall survival could be shown concerning the low stages (pT1-2) (log rank P=0,036) and the patients without radiotherapy (log rank P=0,0539) as well as for the pM1 stage (log rank P= 0,0019). A significant reduced disease free survival could be shown concerning the low stages (pT1-T2) (long rank P=0,0206) with high ETBR expression. A correlation of both receptors was related significantly with tumour progression (P=0,022) and with local recurrence (P=0,005). Conclusions: These results suggest that, in addition to known histological risk factors and TNM classification criteria, measurement of ET-R expression with a simple immunohistochemical analysis might further help in predicting the prognosis of patients with vulva squamous cell carcinoma.

Published
2006

28. Circulating tumor cells detection and evaluation of their apoptotic status in patients with localized breast cancer before and after surgery.

Author

Bertolin, M., primary, Pigozzo, J., additional, Koussis, H., additional, Ghiotto, C., additional, Valente, S., additional, Michieletto, S., additional, Magro, C., additional, Rossi, E., additional, Zamarchi, R., additional, Bozza, F., additional, Jirillo, A., additional, Chiarion-Sileni, V., additional, and Amadori, A., additional

Published
2011
Full Text
View/download PDF

32. The diet of post-breeding Antarctic shags Phalacrocorax bransfieldensis at the Danco Coast, Antarctic Peninsula.

Author

Casaux, R., Baroni, A., Ramón, A., Bertolin, M., and Di Prinzio, C.Y.

Subjects
FISH breeding, OCTOPODA, GASTROPODA, NOTOTHENIA, MARINE animals
Abstract

The diet of post-breeding Antarctic shags Phalacrocorax bransfieldensis was investigated at four colonies at the Danco Coast, Antarctic Peninsula, by the analysis of 399 pellets (regurgitated casts) collected during February and March 1998 and 2000. Overall, demersal-benthic fish were the most frequent and important prey at all the colonies sampled, followed by octopods and gastropods. Amongst the fish, Notothenia coriiceps and Gobionotothen gibberifrons were the main prey in all of the sampling sites in both seasons. The composition of the diet of post-breeding shags differed from that observed in the previous breeding season. Post-breeders preyed on the same fish species consumed by breeders, although in different proportions and on larger specimens. The information provided here differs from that reported for post-breeding individuals belonging to other shag species and also for post-breeding Antarctic shags. Our results, as well as the differences with previous studies, are discussed in relation to differences in prey availability among localities and to the use of alternative foraging grounds at the end of the breeding period. [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

34. Structure Elucidation of Secalosides A and B by NMR Spectroscopy

Author

Jaun, B., Martinoni, B., Marazza, F., and Bertolin, M.

Abstract

The constitution of secalosides A and B was elucidated through NMR spectroscopy using fast 2D-NMR experiments with pulsed-field gradients for coherence selection. Secalosides A and B are epimers at center C-3‘ of aglycon I and have the constitution shown as 1. The presence of a saccharose unit was confirmed independently by mild basic hydrolysis and enzymatic quantification. The relative configuration of the stereogenic centers of aglycon II could be deduced from ROESY data. Assignments of the two epimers to the R- and S- configurations at C-3‘ in aglycon I, as well as the absolute configuration of aglycon II remain to be determined.

Published
1997

36. Study of the azimuthal asymmetry of jets in neutral current deep inelastic scattering at HERA

Author

Chekanov, S, ZEUS Collaboration, Missing, Krakauer, D, Magill, S, Musgrave, B, Repond, J, Yoshida, R, Mattingly, M C K, Antonioli, P, Bari, G, Basile, M, Bellagamba, L, Boscherini, D, Bruni, A, Bruni, G, Romeo, G C, Cifarelli, L, Cindolo, F, Contin, A, Corradi, M, De Pasquale, S, Giusti, P, Iacobucci, G, Margotti, A, Nania, R, Palmonari, F, Pesci, A, Sartorelli, G, Zichichi, A, Aghuzumtsyan, G, Bartsch, D, Brock, I, Goers, S, Hartmann, H, Hilger, E, Irrgang, P, Jakob, H P, Kappes, A, Katz, U F, Kind, O, Paul, E, Rautenberg, J, Renner, R, Schnurbusch, H, Stifutkin, A, Tandler, J, Voss, K C, Wang, M, Weber, A, Bailey, D S, Brook, N H, Cole, J E, Foster, B, Heath, G P, Heath, H F, Robins, S, Rodrigues, E, Scott, J, Tapper, R J, Wing, M, Capua, M, Mastroberardino, A, Susinno, G, Kim, J Y, Kim, Y K, Lee, J H, Lim, I T, Pac, M Y, Bauerdick, L A T, Behrens, U, Bloch, I, Borras, K, Chiochia, V, Dannheim, D, Derrick, M, Drews, G, Fourletova, J, Fox-Murphy, A, Fricke, U, Geiser, A, Goebel, R, Gottlicher, P, Gutsche, O, Haas, T, Hain, W, Hartner, G F, Hillert, S, Kotz, U, Kowalski, H, Kramberger, G, Labes, H, Lelas, D, Lohr, B, Mankel, R, Melzer-Pellmann, I A, Moritz, M, Notz, D, Petrucci, M C, Polini, A, Raval, A, Schneekloth, U, Selonke, F, Wessoleck, H, Wichmann, R, Wolf, G, Youngman, C, Zeuner, W, Viani, A L D, Meyer, A, Schlenstedt, S, Barbagli, G, Gallo, E, Genta, C, Pelfer, P G, Bamberger, A, Benen, A, Coppola, N, Bell, M, Bussey, P J, Doyle, A T, Glasman, C, Hanlon, S, Lee, S W, Lupi, A, McCance, G J, Saxon, D H, Skillicorn, I O, Gialas, I, Bodmann, B, Carli, T, Holm, U, Klimek, K, Krumnack, N, Lohrmann, E, Milite, M, Salehi, H, Stonjek, S, Wick, K, Ziegler, A, Collins-Tooth, C, Foudas, C, Goncalo, R, Long, K R, Metlica, F, Tapper, A D, Cloth, P, Filges, D, Kuze, M, Nagano, K, Tokushuku, K, Yamada, S, Yamazaki, Y, Barakbaev, A N, Boos, E G, Pokrovskiy, N S, Zhautykov, B O, Lim, H, Son, D, Barreiro, F, Gonzalez, O, Labarga, L, Del Peso, J, Redondo, I, Tassi, E, Terron, J, Vazquez, M, Bertolin, M B, Corriveau, F, Ochs, A, Padhi, S, Stairs, D G, St-Laurent, M, Tsurugai, T, Antonov, A, Danilov, P, Dolgoshein, B A, Gladkov, D, Sosnovtsev, V S, Suchkov, S, Dementiev, R K, Ermolov, P F, Golubkov, Y A, Katkov, I I, Khein, L A, Korzhavina, I A, Kuzmin, V A, Levchenko, B B, Lukina, O Y, Proskuryakov, A S, Shcheglova, L M, Vlasov, N N, Zotkin, S A, Bokel, C, Engelen, J, Grijpink, S, Koffeman, E, Kooijman, P, Maddox, E, Pellegrino, A, Schagen, S, Tiecke, H, Tuning, N, Velthuis, J J, Wigger's, L, De Wolf, E, Brummer, N, Bylsma, B, Durkin, L S, Ling, T Y, Boogert, S, Cooper-Sarkar, A M, Devenish, R C E, Ferrando, J, Grzelak, G, Matsushita, T, Rigby, M, Ruske, O, Sutton, M R, Walczak, R, Brugnera, R, Carlin, R, Dal Corso, F, Dusini, S, Garfagnini, A, Limentani, S, Longhin, A, Parenti, A, Posocco, M, Stanco, L, Turcato, M, Heaphy, E A, Oh, B Y, Saull, P R B, Whitmore, J J, Iga, Y, D'Agostini, G, Marini, G, Nigro, A, Cormack, C, Hart, J C, McCubbin, N A, Heusch, C, Park, I H, Pavel, N, Abramowicz, H, Gabareen, A, Kananov, S, Kreisel, A, Levy, A, Abe, T, Fusayasu, T, Kagawa, S, Kohno, T, Tawara, T, Yamashita, T, Hamatsu, R, Hirose, T, Inuzuka, M, Kitamura, S, Matsuzawa, K, Nishimura, T, Arneodo, M, Ferrero, M I, Monaco, V, Ruspa, M, Sacchi, R, Solano, A, Galea, R, Koop, T, Levman, G M, Martin, J F, Mirea, A, Sabetfakhri, A, Butterworth, J M, Gwenlan, C, Hall-Wilton, R, Jones, T W, Lightwood, M S, Loizides, J H, West, B J, Ciborowski, J, Ciesielski, R, Nowak, R J, Pawlak, J M, Smalska, B, Sztuk, J, Tymieniecka, T, Ukleja, A, Ukleja, J, Zarnecki, A F, Adamus, M, Plucinski, P, Eisenberg, Y, Gladilin, L K, Hochman, D, Karshon, U, Kcira, D, Lammers, S, Li, L, Reeder, D D, Savin, A A, Smith, W H, Deshpande, A, Dhawan, S, Hughes, V W, Straub, P B, Bhadra, S, Catterall, C D, Fourletov, S, Menary, S, Soares, M, Standage, J, Chekanov, S, ZEUS Collaboration, Missing, Krakauer, D, Magill, S, Musgrave, B, Repond, J, Yoshida, R, Mattingly, M C K, Antonioli, P, Bari, G, Basile, M, Bellagamba, L, Boscherini, D, Bruni, A, Bruni, G, Romeo, G C, Cifarelli, L, Cindolo, F, Contin, A, Corradi, M, De Pasquale, S, Giusti, P, Iacobucci, G, Margotti, A, Nania, R, Palmonari, F, Pesci, A, Sartorelli, G, Zichichi, A, Aghuzumtsyan, G, Bartsch, D, Brock, I, Goers, S, Hartmann, H, Hilger, E, Irrgang, P, Jakob, H P, Kappes, A, Katz, U F, Kind, O, Paul, E, Rautenberg, J, Renner, R, Schnurbusch, H, Stifutkin, A, Tandler, J, Voss, K C, Wang, M, Weber, A, Bailey, D S, Brook, N H, Cole, J E, Foster, B, Heath, G P, Heath, H F, Robins, S, Rodrigues, E, Scott, J, Tapper, R J, Wing, M, Capua, M, Mastroberardino, A, Susinno, G, Kim, J Y, Kim, Y K, Lee, J H, Lim, I T, Pac, M Y, Bauerdick, L A T, Behrens, U, Bloch, I, Borras, K, Chiochia, V, Dannheim, D, Derrick, M, Drews, G, Fourletova, J, Fox-Murphy, A, Fricke, U, Geiser, A, Goebel, R, Gottlicher, P, Gutsche, O, Haas, T, Hain, W, Hartner, G F, Hillert, S, Kotz, U, Kowalski, H, Kramberger, G, Labes, H, Lelas, D, Lohr, B, Mankel, R, Melzer-Pellmann, I A, Moritz, M, Notz, D, Petrucci, M C, Polini, A, Raval, A, Schneekloth, U, Selonke, F, Wessoleck, H, Wichmann, R, Wolf, G, Youngman, C, Zeuner, W, Viani, A L D, Meyer, A, Schlenstedt, S, Barbagli, G, Gallo, E, Genta, C, Pelfer, P G, Bamberger, A, Benen, A, Coppola, N, Bell, M, Bussey, P J, Doyle, A T, Glasman, C, Hanlon, S, Lee, S W, Lupi, A, McCance, G J, Saxon, D H, Skillicorn, I O, Gialas, I, Bodmann, B, Carli, T, Holm, U, Klimek, K, Krumnack, N, Lohrmann, E, Milite, M, Salehi, H, Stonjek, S, Wick, K, Ziegler, A, Collins-Tooth, C, Foudas, C, Goncalo, R, Long, K R, Metlica, F, Tapper, A D, Cloth, P, Filges, D, Kuze, M, Nagano, K, Tokushuku, K, Yamada, S, Yamazaki, Y, Barakbaev, A N, Boos, E G, Pokrovskiy, N S, Zhautykov, B O, Lim, H, Son, D, Barreiro, F, Gonzalez, O, Labarga, L, Del Peso, J, Redondo, I, Tassi, E, Terron, J, Vazquez, M, Bertolin, M B, Corriveau, F, Ochs, A, Padhi, S, Stairs, D G, St-Laurent, M, Tsurugai, T, Antonov, A, Danilov, P, Dolgoshein, B A, Gladkov, D, Sosnovtsev, V S, Suchkov, S, Dementiev, R K, Ermolov, P F, Golubkov, Y A, Katkov, I I, Khein, L A, Korzhavina, I A, Kuzmin, V A, Levchenko, B B, Lukina, O Y, Proskuryakov, A S, Shcheglova, L M, Vlasov, N N, Zotkin, S A, Bokel, C, Engelen, J, Grijpink, S, Koffeman, E, Kooijman, P, Maddox, E, Pellegrino, A, Schagen, S, Tiecke, H, Tuning, N, Velthuis, J J, Wigger's, L, De Wolf, E, Brummer, N, Bylsma, B, Durkin, L S, Ling, T Y, Boogert, S, Cooper-Sarkar, A M, Devenish, R C E, Ferrando, J, Grzelak, G, Matsushita, T, Rigby, M, Ruske, O, Sutton, M R, Walczak, R, Brugnera, R, Carlin, R, Dal Corso, F, Dusini, S, Garfagnini, A, Limentani, S, Longhin, A, Parenti, A, Posocco, M, Stanco, L, Turcato, M, Heaphy, E A, Oh, B Y, Saull, P R B, Whitmore, J J, Iga, Y, D'Agostini, G, Marini, G, Nigro, A, Cormack, C, Hart, J C, McCubbin, N A, Heusch, C, Park, I H, Pavel, N, Abramowicz, H, Gabareen, A, Kananov, S, Kreisel, A, Levy, A, Abe, T, Fusayasu, T, Kagawa, S, Kohno, T, Tawara, T, Yamashita, T, Hamatsu, R, Hirose, T, Inuzuka, M, Kitamura, S, Matsuzawa, K, Nishimura, T, Arneodo, M, Ferrero, M I, Monaco, V, Ruspa, M, Sacchi, R, Solano, A, Galea, R, Koop, T, Levman, G M, Martin, J F, Mirea, A, Sabetfakhri, A, Butterworth, J M, Gwenlan, C, Hall-Wilton, R, Jones, T W, Lightwood, M S, Loizides, J H, West, B J, Ciborowski, J, Ciesielski, R, Nowak, R J, Pawlak, J M, Smalska, B, Sztuk, J, Tymieniecka, T, Ukleja, A, Ukleja, J, Zarnecki, A F, Adamus, M, Plucinski, P, Eisenberg, Y, Gladilin, L K, Hochman, D, Karshon, U, Kcira, D, Lammers, S, Li, L, Reeder, D D, Savin, A A, Smith, W H, Deshpande, A, Dhawan, S, Hughes, V W, Straub, P B, Bhadra, S, Catterall, C D, Fourletov, S, Menary, S, Soares, M, and Standage, J

Abstract

The azimuthal distribution of jets produced in the Breit frame in high-Q(2) deep inelastic e(+)p scattering has been studied with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb( -1). The measured azimuthal distribution shows a structure that is well described by next-to-leading-order QCD predictions over the Q(2) range considered, Q(2)> 125 GeV2. (C) 2002 Elsevier Science B.V. All rights reserved.

37. Study of the azimuthal asymmetry of jets in neutral current deep inelastic scattering at HERA

Author

Chekanov, S, ZEUS Collaboration, Missing, Krakauer, D, Magill, S, Musgrave, B, Repond, J, Yoshida, R, Mattingly, M C K, Antonioli, P, Bari, G, Basile, M, Bellagamba, L, Boscherini, D, Bruni, A, Bruni, G, Romeo, G C, Cifarelli, L, Cindolo, F, Contin, A, Corradi, M, De Pasquale, S, Giusti, P, Iacobucci, G, Margotti, A, Nania, R, Palmonari, F, Pesci, A, Sartorelli, G, Zichichi, A, Aghuzumtsyan, G, Bartsch, D, Brock, I, Goers, S, Hartmann, H, Hilger, E, Irrgang, P, Jakob, H P, Kappes, A, Katz, U F, Kind, O, Paul, E, Rautenberg, J, Renner, R, Schnurbusch, H, Stifutkin, A, Tandler, J, Voss, K C, Wang, M, Weber, A, Bailey, D S, Brook, N H, Cole, J E, Foster, B, Heath, G P, Heath, H F, Robins, S, Rodrigues, E, Scott, J, Tapper, R J, Wing, M, Capua, M, Mastroberardino, A, Susinno, G, Kim, J Y, Kim, Y K, Lee, J H, Lim, I T, Pac, M Y, Bauerdick, L A T, Behrens, U, Bloch, I, Borras, K, Chiochia, V, Dannheim, D, Derrick, M, Drews, G, Fourletova, J, Fox-Murphy, A, Fricke, U, Geiser, A, Goebel, R, Gottlicher, P, Gutsche, O, Haas, T, Hain, W, Hartner, G F, Hillert, S, Kotz, U, Kowalski, H, Kramberger, G, Labes, H, Lelas, D, Lohr, B, Mankel, R, Melzer-Pellmann, I A, Moritz, M, Notz, D, Petrucci, M C, Polini, A, Raval, A, Schneekloth, U, Selonke, F, Wessoleck, H, Wichmann, R, Wolf, G, Youngman, C, Zeuner, W, Viani, A L D, Meyer, A, Schlenstedt, S, Barbagli, G, Gallo, E, Genta, C, Pelfer, P G, Bamberger, A, Benen, A, Coppola, N, Bell, M, Bussey, P J, Doyle, A T, Glasman, C, Hanlon, S, Lee, S W, Lupi, A, McCance, G J, Saxon, D H, Skillicorn, I O, Gialas, I, Bodmann, B, Carli, T, Holm, U, Klimek, K, Krumnack, N, Lohrmann, E, Milite, M, Salehi, H, Stonjek, S, Wick, K, Ziegler, A, Collins-Tooth, C, Foudas, C, Goncalo, R, Long, K R, Metlica, F, Tapper, A D, Cloth, P, Filges, D, Kuze, M, Nagano, K, Tokushuku, K, Yamada, S, Yamazaki, Y, Barakbaev, A N, Boos, E G, Pokrovskiy, N S, Zhautykov, B O, Lim, H, Son, D, Barreiro, F, Gonzalez, O, Labarga, L, Del Peso, J, Redondo, I, Tassi, E, Terron, J, Vazquez, M, Bertolin, M B, Corriveau, F, Ochs, A, Padhi, S, Stairs, D G, St-Laurent, M, Tsurugai, T, Antonov, A, Danilov, P, Dolgoshein, B A, Gladkov, D, Sosnovtsev, V S, Suchkov, S, Dementiev, R K, Ermolov, P F, Golubkov, Y A, Katkov, I I, Khein, L A, Korzhavina, I A, Kuzmin, V A, Levchenko, B B, Lukina, O Y, Proskuryakov, A S, Shcheglova, L M, Vlasov, N N, Zotkin, S A, Bokel, C, Engelen, J, Grijpink, S, Koffeman, E, Kooijman, P, Maddox, E, Pellegrino, A, Schagen, S, Tiecke, H, Tuning, N, Velthuis, J J, Wigger's, L, De Wolf, E, Brummer, N, Bylsma, B, Durkin, L S, Ling, T Y, Boogert, S, Cooper-Sarkar, A M, Devenish, R C E, Ferrando, J, Grzelak, G, Matsushita, T, Rigby, M, Ruske, O, Sutton, M R, Walczak, R, Brugnera, R, Carlin, R, Dal Corso, F, Dusini, S, Garfagnini, A, Limentani, S, Longhin, A, Parenti, A, Posocco, M, Stanco, L, Turcato, M, Heaphy, E A, Oh, B Y, Saull, P R B, Whitmore, J J, Iga, Y, D'Agostini, G, Marini, G, Nigro, A, Cormack, C, Hart, J C, McCubbin, N A, Heusch, C, Park, I H, Pavel, N, Abramowicz, H, Gabareen, A, Kananov, S, Kreisel, A, Levy, A, Abe, T, Fusayasu, T, Kagawa, S, Kohno, T, Tawara, T, Yamashita, T, Hamatsu, R, Hirose, T, Inuzuka, M, Kitamura, S, Matsuzawa, K, Nishimura, T, Arneodo, M, Ferrero, M I, Monaco, V, Ruspa, M, Sacchi, R, Solano, A, Galea, R, Koop, T, Levman, G M, Martin, J F, Mirea, A, Sabetfakhri, A, Butterworth, J M, Gwenlan, C, Hall-Wilton, R, Jones, T W, Lightwood, M S, Loizides, J H, West, B J, Ciborowski, J, Ciesielski, R, Nowak, R J, Pawlak, J M, Smalska, B, Sztuk, J, Tymieniecka, T, Ukleja, A, Ukleja, J, Zarnecki, A F, Adamus, M, Plucinski, P, Eisenberg, Y, Gladilin, L K, Hochman, D, Karshon, U, Kcira, D, Lammers, S, Li, L, Reeder, D D, Savin, A A, Smith, W H, Deshpande, A, Dhawan, S, Hughes, V W, Straub, P B, Bhadra, S, Catterall, C D, Fourletov, S, Menary, S, Soares, M, Standage, J, Chekanov, S, ZEUS Collaboration, Missing, Krakauer, D, Magill, S, Musgrave, B, Repond, J, Yoshida, R, Mattingly, M C K, Antonioli, P, Bari, G, Basile, M, Bellagamba, L, Boscherini, D, Bruni, A, Bruni, G, Romeo, G C, Cifarelli, L, Cindolo, F, Contin, A, Corradi, M, De Pasquale, S, Giusti, P, Iacobucci, G, Margotti, A, Nania, R, Palmonari, F, Pesci, A, Sartorelli, G, Zichichi, A, Aghuzumtsyan, G, Bartsch, D, Brock, I, Goers, S, Hartmann, H, Hilger, E, Irrgang, P, Jakob, H P, Kappes, A, Katz, U F, Kind, O, Paul, E, Rautenberg, J, Renner, R, Schnurbusch, H, Stifutkin, A, Tandler, J, Voss, K C, Wang, M, Weber, A, Bailey, D S, Brook, N H, Cole, J E, Foster, B, Heath, G P, Heath, H F, Robins, S, Rodrigues, E, Scott, J, Tapper, R J, Wing, M, Capua, M, Mastroberardino, A, Susinno, G, Kim, J Y, Kim, Y K, Lee, J H, Lim, I T, Pac, M Y, Bauerdick, L A T, Behrens, U, Bloch, I, Borras, K, Chiochia, V, Dannheim, D, Derrick, M, Drews, G, Fourletova, J, Fox-Murphy, A, Fricke, U, Geiser, A, Goebel, R, Gottlicher, P, Gutsche, O, Haas, T, Hain, W, Hartner, G F, Hillert, S, Kotz, U, Kowalski, H, Kramberger, G, Labes, H, Lelas, D, Lohr, B, Mankel, R, Melzer-Pellmann, I A, Moritz, M, Notz, D, Petrucci, M C, Polini, A, Raval, A, Schneekloth, U, Selonke, F, Wessoleck, H, Wichmann, R, Wolf, G, Youngman, C, Zeuner, W, Viani, A L D, Meyer, A, Schlenstedt, S, Barbagli, G, Gallo, E, Genta, C, Pelfer, P G, Bamberger, A, Benen, A, Coppola, N, Bell, M, Bussey, P J, Doyle, A T, Glasman, C, Hanlon, S, Lee, S W, Lupi, A, McCance, G J, Saxon, D H, Skillicorn, I O, Gialas, I, Bodmann, B, Carli, T, Holm, U, Klimek, K, Krumnack, N, Lohrmann, E, Milite, M, Salehi, H, Stonjek, S, Wick, K, Ziegler, A, Collins-Tooth, C, Foudas, C, Goncalo, R, Long, K R, Metlica, F, Tapper, A D, Cloth, P, Filges, D, Kuze, M, Nagano, K, Tokushuku, K, Yamada, S, Yamazaki, Y, Barakbaev, A N, Boos, E G, Pokrovskiy, N S, Zhautykov, B O, Lim, H, Son, D, Barreiro, F, Gonzalez, O, Labarga, L, Del Peso, J, Redondo, I, Tassi, E, Terron, J, Vazquez, M, Bertolin, M B, Corriveau, F, Ochs, A, Padhi, S, Stairs, D G, St-Laurent, M, Tsurugai, T, Antonov, A, Danilov, P, Dolgoshein, B A, Gladkov, D, Sosnovtsev, V S, Suchkov, S, Dementiev, R K, Ermolov, P F, Golubkov, Y A, Katkov, I I, Khein, L A, Korzhavina, I A, Kuzmin, V A, Levchenko, B B, Lukina, O Y, Proskuryakov, A S, Shcheglova, L M, Vlasov, N N, Zotkin, S A, Bokel, C, Engelen, J, Grijpink, S, Koffeman, E, Kooijman, P, Maddox, E, Pellegrino, A, Schagen, S, Tiecke, H, Tuning, N, Velthuis, J J, Wigger's, L, De Wolf, E, Brummer, N, Bylsma, B, Durkin, L S, Ling, T Y, Boogert, S, Cooper-Sarkar, A M, Devenish, R C E, Ferrando, J, Grzelak, G, Matsushita, T, Rigby, M, Ruske, O, Sutton, M R, Walczak, R, Brugnera, R, Carlin, R, Dal Corso, F, Dusini, S, Garfagnini, A, Limentani, S, Longhin, A, Parenti, A, Posocco, M, Stanco, L, Turcato, M, Heaphy, E A, Oh, B Y, Saull, P R B, Whitmore, J J, Iga, Y, D'Agostini, G, Marini, G, Nigro, A, Cormack, C, Hart, J C, McCubbin, N A, Heusch, C, Park, I H, Pavel, N, Abramowicz, H, Gabareen, A, Kananov, S, Kreisel, A, Levy, A, Abe, T, Fusayasu, T, Kagawa, S, Kohno, T, Tawara, T, Yamashita, T, Hamatsu, R, Hirose, T, Inuzuka, M, Kitamura, S, Matsuzawa, K, Nishimura, T, Arneodo, M, Ferrero, M I, Monaco, V, Ruspa, M, Sacchi, R, Solano, A, Galea, R, Koop, T, Levman, G M, Martin, J F, Mirea, A, Sabetfakhri, A, Butterworth, J M, Gwenlan, C, Hall-Wilton, R, Jones, T W, Lightwood, M S, Loizides, J H, West, B J, Ciborowski, J, Ciesielski, R, Nowak, R J, Pawlak, J M, Smalska, B, Sztuk, J, Tymieniecka, T, Ukleja, A, Ukleja, J, Zarnecki, A F, Adamus, M, Plucinski, P, Eisenberg, Y, Gladilin, L K, Hochman, D, Karshon, U, Kcira, D, Lammers, S, Li, L, Reeder, D D, Savin, A A, Smith, W H, Deshpande, A, Dhawan, S, Hughes, V W, Straub, P B, Bhadra, S, Catterall, C D, Fourletov, S, Menary, S, Soares, M, and Standage, J

Abstract

The azimuthal distribution of jets produced in the Breit frame in high-Q(2) deep inelastic e(+)p scattering has been studied with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb( -1). The measured azimuthal distribution shows a structure that is well described by next-to-leading-order QCD predictions over the Q(2) range considered, Q(2)> 125 GeV2. (C) 2002 Elsevier Science B.V. All rights reserved.

38. Mitochondria Transplantation Promotes Corneal Epithelial Wound Healing.

Author

Raz D, Ben-Yaakov K, Levi M, Bertolin M, Ferrari S, Ponzin D, Busin M, Leiba H, Marcovich AL, Eisenberg-Lerner A, and Rotfogel Z

Subjects
Animals, Mice, Humans, Burns, Chemical surgery, Burns, Chemical physiopathology, Mice, Inbred C57BL, Corneal Injuries, Cells, Cultured, Eye Burns chemically induced, Epithelium, Corneal, Wound Healing physiology, Mitochondria, Cell Proliferation physiology, Disease Models, Animal
Abstract

Purpose: The integrity of the corneal epithelium is essential in maintaining normal corneal function. Conditions disrupting the corneal epithelial layer range from chemical burns to dry eye disease and may result in impairment of both corneal transparency and sensation. Identifying factors that regulate corneal wound healing is key for the development of new treatment strategies. Here, we investigated a direct role of mitochondria in corneal wound healing via mitochondria transplantation., Methods: Human corneal epithelial cells (hCECs) were isolated from human corneas and incubated with mitochondria which were isolated from human ARPE-19 cells. We determined the effect of mitochondria transplantation on wound healing and proliferation of hCECs. In vivo, we used a mouse model of corneal chemical injury. Mitochondria were isolated from mouse livers and topically applied to the ocular surface following injury. We evaluated the time of wound repair, corneal re-epithelization, and stromal abnormalities., Results: Mitochondria transplantation induced the proliferation and wound healing of primary hCECs. Further, mitochondria transplantation promoted wound healing in vivo. Specifically, mice receiving mitochondria recovered twice as fast as control mice following corneal injury, presenting both enhanced and improved repair. Corneas treated with mitochondria demonstrated the re-epithelization of the wound area to a multi-layer appearance, compared to thinning and complete loss of the epithelium in control mice. Mitochondria transplantation also prevented the thickening and disorganization of the corneal stromal lamella, restoring normal corneal dehydration., Conclusions: Mitochondria promote corneal re-epithelization and wound healing. Augmentation of mitochondria levels via mitochondria transplantation may serve as an effective treatment for inducing the rapid repair of corneal epithelial defects.

Published
2024
Full Text
View/download PDF

39. Identification of the regulatory circuit governing corneal epithelial fate determination and disease.

Author

Smits JGA, Cunha DL, Amini M, Bertolin M, Laberthonnière C, Qu J, Owen N, Latta L, Seitz B, Roux LN, Stachon T, Ferrari S, Moosajee M, Aberdam D, Szentmary N, van Heeringen SJ, and Zhou H

Subjects
Humans, Cornea metabolism, Transcription Factors genetics, Transcription Factors metabolism, Cell Differentiation genetics, Limbus Corneae metabolism, Epithelium, Corneal metabolism, Corneal Opacity metabolism
Abstract

The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells (LSCs), while the nontransparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human LSCs from the cornea and keratinocytes from the epidermis and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors (TFs) that define specific cell fates and established their regulatory hierarchy. Single-cell RNA-seq (scRNA-seq) analyses of the cornea and the epidermis confirmed these shared and cell type-specific TFs. Notably, the shared and LSC-specific TFs can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the LSC fate and its association with corneal opacity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Smits 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
Full Text
View/download PDF

40. Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Promote Corneal Wound Repair by Regulating Inflammation and Angiogenesis.

Author

Saccu G, Menchise V, Gai C, Bertolin M, Ferrari S, Giordano C, Manco M, Dastrù W, Tolosano E, Bussolati B, Calautti E, Camussi G, Altruda F, and Fagoonee S

Subjects
Animals, Humans, Mice, Bone Marrow, Inflammation metabolism, Extracellular Vesicles metabolism, Mesenchymal Stem Cells metabolism, Corneal Injuries therapy, Corneal Injuries metabolism
Abstract

Severe corneal damage leads to complete vision loss, thereby affecting life quality and impinging heavily on the healthcare system. Current clinical approaches to manage corneal wounds suffer from severe drawbacks, thus requiring the development of alternative strategies. Of late, mesenchymal stromal/stem cell (MSC)-derived extracellular vesicles (EVs) have become a promising tool in the ophthalmic field. In the present study, we topically delivered bone-marrow-derived MSC-EVs (BMSC-EVs), embedded in methylcellulose, in a murine model of alkali-burn-induced corneal damage in order to evaluate their role in corneal repair through histological and molecular analyses, with the support of magnetic resonance imaging. Our data show that BMSC-EVs, used for the first time in this specific formulation on the damaged cornea, modulate cell death, inflammation and angiogenetic programs in the injured tissue, thus leading to a faster recovery of corneal damage. These results were confirmed on cadaveric donor-derived human corneal epithelial cells in vitro. Thus, BMSC-EVs modulate corneal repair dynamics and are promising as a new cell-free approach for intervening on burn wounds, especially in the avascularized region of the eye.

Published
2022
Full Text
View/download PDF

41. Cryopreservation of human amniotic membrane for ocular surface reconstruction: a comparison between protocols.

Author

Lamon M, Bertolin M, Trojan D, Spagnol L, Donisi PM, Camposampiero D, Ponzin D, and Ferrari S

Subjects
Humans, Amnion, Dextrans, Cryopreservation methods, Cryoprotective Agents pharmacology, Dimethyl Sulfoxide
Abstract

Purpose: To compare the effects on adhesive and structural properties of newer preservation conditions to those obtained with an established, standardized protocol (dimethyl sulfoxide at -180 °C). In attempt to simplify and enhance the safety of the procedure, we tested dextran-based freezing medium and a dry condition (no medium) at temperatures of -80 °C., Methods: Five patches of human amniotic membrane were obtained from three different donors. For each donor, five preservation condition were tested: dimethyl sulfoxide at -180 °C, dimethyl sulfoxide at -80 °C, dextran-based medium at -180 °C, dextran-based medium at -80 °C and dry freezing at -80 °C (no medium). At the end of four months storage period, adhesive properties and structure were analyzed., Results: None of the newer preservation protocols showed differences in adhesive and structural properties of the tissues. The stromal layer always kept its adhesiveness, while both structure and basement membrane were not altered by any the preservation protocol., Conclusions: Switching from liquid nitrogen cryopreservation to -80 °C would reduce manipulation, simplify the procedure, making it also cheaper. The use of dextran-based freezing medium or no medium at all (dry condition) would avoid the potential toxicity of the dimethyl sulfoxide-based freezing media., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Published
2022
Full Text
View/download PDF

42. Autologous simple conjunctival epithelial transplantation for primary pterygium.

Author

Pedrotti E, Bertolin M, Fasolo A, Bonacci E, Bosello F, Ponzin D, and Marchini G

Subjects
Humans, Recurrence, Conjunctiva transplantation, Transplantation, Autologous, Follow-Up Studies, Pterygium surgery, Pterygium diagnosis
Abstract

Purpose: To evaluate the feasibility of a new method of conjunctival transplantation to achieve recovery of the normal conjunctival epithelium over the bare sclera after pterygium excision and prevent its recurrence., Methods: After excision of the primary pterygium, we performed simple conjunctival epithelial transplantation (SCET) in which we glued an amniotic membrane patch pre-loaded with tiny autologous conjunctival tissue fragments over the scleral defect. Slit-lamp evaluation was performed at 2 and 7-10 days, and then at 1, 3, 6, and 12 months after surgery, together with confocal microscopy at 3, 6, and 12 months., Results: Surgical excision and SCET for nasal primary pterygium were performed in 6 eyes (6 patients). No graft detachment occurred. An inflammatory granuloma was excised without sequelae in one patient 2 months after surgery. No signs of recurrence or sight-threatening complications were recorded at 12 months, and in vivo confocal microscopy showed progressive expansion of the conjunctival cell population and formation of a clear corneal-conjunctival transition., Conclusions: SCET takes advantage of the ability of the amniotic membrane and conjunctival cells to renew. Outcomes after SCET are comparable to conventional conjunctival flap surgery and can be achieved in less surgical time and with less donor tissue to be removed., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Published
2022
Full Text
View/download PDF

43. 22 Renewal of conjunctival epithelium over amniotic membrane to perform autologous simple conjunctival epithelial transplantation (SCET): in vitro validation and results of clinical application for primary pterygium.

Author

Bertolin M, Pedrotti E, Bonacci E, Bosello F, Barbaro V, Breda C, Ponzin D, Marchini G, and Fasolo A

Subjects
Humans, Amnion transplantation, Conjunctiva surgery, Epithelium, Pterygium surgery
Abstract

Background: Transplantation of ex vivo cultured conjunctival cell layers, generated on amniotic membrane or other scaffolds, provides a viable option in treating heterogeneous ocular surface conditions. By comparison, cell therapy is costly, labour-intensive and subject to good manufacturing practice requirements and regulatory approval; no conjunctival cell-based therapy is currently available. Several techniques are available after primary pterygium excision to recover the ocular surface anatomy by restoring healthy conjunctival epithelium and preventing recurrence and complications. However, application of conjunctival free autograft or transpositional flap to cover the bared scleral area is limited when the conjunctiva are to be spared for future glaucoma filtering surgery, in patients with large or double-headed pterygia, in recurrent pterygia, or when the harvesting of donor conjunctival is precluded by scarring., Aim: To develop a simple technique to obtain expansion of the conjunctival epithelium when applied in vivo in diseased eyes., Methods: We evaluated in vitro the best way of gluing conjunctival fragments over the AM, the efficiency of the fragments to generate conjunctival cell outgrowths, the molecular marker expression, and the feasibility of shipping preloaded AM.We performed simple conjunctival epithelial transplantation (SCET) in which we glued an amniotic membrane patch pre-loaded with autologous conjunctival tissue fragments over the scleral defect after pterygium excision and evaluated the recovery of the normal conjunctival epithelium and the disease recurrence up to 12 months after surgery., Results: 65-80% of fragments generated outgrowth 48-72h after gluing, without differences between type of AM preparation and fragment size. Within 6-13 days, a full epithelium covered the surface of the amniotic membrane. Specific marker expression (Muc1, K19, K13, p63, ZO-1) was detected. The shipping test showed after 24h the 31% of the fragments glued over the AM epithelial side, compared to more than 90% of fragments stayed attached in the remaining conditions (stromal side, stromal without spongy layer, epithelial side without epithelium).Surgical excision and SCET for nasal primary pterygium were performed in 6 eyes/patients. No graft detachment and recurrence occurred within 12 months. In vivo confocal microscopy showed progressive expansion of the conjunctival cell population and formation of a clear cornea-conjunctiva transition., Conclusions: We established the most suitable conditions for a novel strategy based on in vivo expansion of conjunctival cells from conjunctival fragments glued over the AM. The application of SCET seems to be effective and replicable for the renewal of conjunctiva in patients requiring ocular surface reconstruction., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
Full Text
View/download PDF

44. 23 Cryopreservation of human amniotic membrane (HAM) for ocular surface reconstruction: a comparison beetween protocols.

Author

Bertolin M, Gassa SD, Trojan D, Spagnol L, Donisi PM, Camposampiero D, Ponzin D, and Ferrari S

Subjects
Humans, Dextrans, Cornea, Cryopreservation, Amnion transplantation, Dimethyl Sulfoxide
Abstract

Purpose: In the past decades, the human amniotic membrane has been largely applied for several surgical and non-surgical procedures. It has been farther demonstrated that both hAM and cornea share similar patterns of expression of structural components of the basement membrane (like laminin 5 and collagen IV) making hAM an useful tissue for ocular surface reconstruction. Since 1996 in fact, amniotic membrane transplantation has been applied to a large number of ocular surface diseases including Stevens-Johnson syndrome, pterygium, corneal ulceration, ocular surface reconstruction after chemical/thermal burns and in the reconstruction after excision of ocular surface neoplasia. During the previous decades, hAM has achieved a pivotal role in regenerative medicine too.The possibility to preserve human amniotic membrane, without affecting membrane's features, has become pivotal, allowing virological and microbiological analyses to be carried out before grafting. The purpose of the present study is to investigate an easier and cheaper protocol for human amniotic membrane preservation without affecting its properties and structure, ensuring the safety profile of the tissue. We compared the effects on adhesive and structural properties of newer preservation conditions to those obtained with an established, standardized protocol (dimethyl sulfoxide at -160°C). In attempt to simplify and enhance the safety of the procedure, we tested dextran-based freezing medium and a dry condition (no medium) at temperatures of -80°C., Methods: Five patches of human amniotic membrane were obtained from three different donors. For each donor, five preservation condition were tested: dimethyl sulfoxide at -160°C, dimethyl sulfoxide at -80°C, dextran-based medium at -160°C, dextran-based medium at -80°C and dry freezing at -80°C (no medium). At the end of four months storage period, adhesive properties and structure were analyzed., Results: None of the newer preservation protocols showed differences in adhesive and structural properties of the tissues. The stromal layer always kept its adhesiveness, while both structure and basement membrane were not altered by any the preservation protocol., Conclusions: Switching from liquid nitrogen cryopreservation to -80°C would reduce manipulation, simplify the procedure, making it also cheaper. The use of dextran-based freezing medium or no medium at all (dry condition) would avoid the potential toxicity of the dimethyl sulfoxide-based freezing media., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
Full Text
View/download PDF

45. Analysis and pharmacological modulation of senescence in human epithelial stem cells.

Author

Barbaro V, Orvieto A, Alvisi G, Bertolin M, Bonelli F, Liehr T, Harutyunyan T, Kankel S, Joksic G, Ferrari S, Daniele E, Ponzin D, Bettio D, Salviati L, and Di Iorio E

Subjects
Humans, Platelet Aggregation Inhibitors, Stem Cells, Cleft Lip diagnosis, Cleft Palate diagnosis, Ectodermal Dysplasia diagnosis, Ectodermal Dysplasia genetics
Abstract

Human epithelial stem cells (ESCs) are characterized by long-term regenerative properties, much dependent on the tissue of origin and varying during their lifespan. We analysed such variables in cultures of ESCs isolated from the skin, conjunctiva, limbus and oral mucosa of healthy donors and patients affected by ectrodactyly-ectodermal dysplasia-clefting syndrome, a rare genetic disorder caused by mutations in the p63 gene. We cultured cells until exhaustion in the presence or in the absence of DAPT (γ-secretase inhibitor; N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine T-butyl ester). All cells were able to differentiate in vitro but exhibited variable self-renewal potential. In particular, cells carrying p63 mutations stopped prematurely, compared with controls. Importantly, administration of DAPT significantly extended the replicative properties of all stem cells under examination. RNA sequencing analysis revealed that distinct sets of genes were up- or down-regulated during their lifetime, thus allowing to identify druggable gene networks and off-the-shelf compounds potentially dealing with epithelial stem cell senescence. These data will expand our knowledge on the genetic bases of senescence and potentially pave the way to the pharmacological modulation of ageing in epithelial stem cells., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Published
2022
Full Text
View/download PDF

46. In vitro establishment, validation and characterisation of conjunctival epithelium outgrowth using tissue fragments and amniotic membrane.

Author

Bertolin M, Barbaro V, Breda C, Ferrari S, Marchini G, Pedrotti E, Ferrari B, Diego P, and Fasolo A

Subjects
Epithelial Cells, Epithelium, Humans, Amnion transplantation, Conjunctiva
Abstract

Background/aims: To set up the in vitro conditions for renewal of the conjunctival epithelium using healthy fragments of conjunctival tissue glued over an amniotic membrane., Methods: We evaluated the capability of conjunctival tissue fragments to generate conjunctival cell outgrowth after seeding them onto amniotic membrane and culture plates; we then assessed conjunctival molecular marker expression by immunofluorescence. We also evaluated the efficiency of glueing the fragments over the amniotic membrane to determine the best setting and the feasibility of shipping preloaded amniotic membranes., Results: Epithelial outgrowth was detected in 65%-80% of conjunctival fragments starting 48-72 hours after glueing, without major differences between type of membrane preparation and fragment size. Within 6-13 days, a full epithelium covered the surface of the amniotic membrane. Specific marker expression (conjunctival epithelium, Muc1, K19, K13; stemness, p63; tight junctions, ZO-1) was detected. Results of the shipping test showed that only 31% of the fragments were still glued over the epithelial side of the membrane within 24 hours compared to more than 90% of fragments stayed attached in the remaining conditions., Conclusion: The in vitro regeneration of conjunctival epithelium following outgrowth from conjunctival tissue fragments glued over an amniotic membrane may offer a viable strategy to renew the epithelium in vivo once applied over the ocular surface at the recipient site., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
Full Text
View/download PDF

47. Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses.

Author

Valdivia E, Bertolin M, Breda C, Carvalho Oliveira M, Salz AK, Hofmann N, Börgel M, Blasczyk R, Ferrari S, and Figueiredo C

Subjects
Cells, Cultured, HLA Antigens genetics, Humans, Limbus Corneae cytology, Transplantation, Homologous, HLA Antigens immunology, Hematopoietic Stem Cell Transplantation, Limbus Corneae immunology, Stem Cells immunology
Abstract

Limbal stem cell (LSC) transplantation is the only efficient treatment for patients affected by LSC deficiency (LSCD). Allogeneic LSC transplantation is one of the most successful alternative for patients with bilateral LSCD. Nevertheless, the high variability of the human leukocyte antigens (HLA) remains a relevant obstacle to long-term allogeneic graft survival. This study characterized the immunologic properties of LSCs and proposed a genetic engineering strategy to reduce the immunogenicity of LSCs and of their derivatives. Hence, LSC HLA expression was silenced using lentiviral vectors encoding for short hairpin (sh) RNAs targeting β2-microglobulin (β2M) or class II major histocompatibility complex transactivator (CIITA) to silence HLA class I and II respectively. Beside the constitutive expression of HLA class I, LSCs showed the capability to upregulate HLA class II expression under inflammatory conditions. Furthermore, LSCs demonstrated the capability to induce T-cell mediated immune responses. LSCs phenotypical and functional characteristics are not disturbed after genetic modification. However, HLA silenced LSC showed to prevent T cell activation, proliferation and cytotoxicity in comparison to fully HLA-expressing LSCs. Additionally; HLA-silenced LSCs were protected against antibody-mediated cellular-dependent cytotoxicity. Our data is a proof-of-concept of the feasibility to generate low immunogenic human LSCs without affecting their typical features. The use of low immunogenic LSCs may support for long-term survival of LSCs and their derivatives after allogeneic transplantation., 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 © 2021 Valdivia, Bertolin, Breda, Carvalho Oliveira, Salz, Hofmann, Börgel, Blasczyk, Ferrari and Figueiredo.)

Published
2021
Full Text
View/download PDF

48. Culture of corneal endothelial cells obtained by descemetorhexis of corneas with Fuchs endothelial corneal dystrophy.

Author

Bertolin M, Lamon M, Franco E, Barbaro V, Ferrari S, Bovone C, Yu AC, Parekh M, Ponzin D, and Busin M

Subjects
Aged, Biomarkers metabolism, Cell Count, Cell Culture Techniques, Cell Separation, Endothelium, Corneal metabolism, Female, Humans, Male, Middle Aged, Descemet Membrane surgery, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal cytology, Fuchs' Endothelial Dystrophy surgery
Abstract

Currently, endothelial keratoplasty is the gold standard for the surgical treatment of Fuchs endothelial corneal dystrophy (FECD). Despite the remarkable success in terms of surgical outcomes, a shortage of corneal donor tissue poses a limitation to performing endothelial keratoplasty in many parts of the world. Cell therapy is a potential alternative strategy to keratoplasty and is currently under investigation. Considering that corneas with FECD may contain relatively healthy endothelial cells, samples obtained by descemetorhexis of eyes undergoing EK for FECD can be used for ex vivo expansion of endothelial cells as an autologous cell culture. In this study, we established corneal endothelial cell cultures derived from 40 patients that underwent endothelial keratoplasty for advanced FECD. Several parameters were evaluated including patient characteristics such as age, gender, and endothelial cell density as well as various processing and cell culture protocols based on different combinations of shipping temperatures, stabilization periods and treatment methods for corneal endothelial cell dissociation. FECD cultures were classified into three groups as: (i) no cells, (ii) cell cultures with endothelial-like morphology or (iii) cell cultures with fibroblast-like features. Our data seem to suggest that some factors can influence FECD cell culture characteristics including young age, high paracentral endothelial cell density, low shipping temperature and short stabilization period prior to cell isolation. Treatment with type 1 collagenase for cell isolation can delay endothelial-to-mesenchymal transition, but does not increase proliferative capacity. Although heterologous corneal endothelial cultures from healthy donors have shown encouraging outcomes, the feasibility of autologous cell therapy as a potential treatment for FECD remains challenging. Low initial cell concentration as well as endothelial to mesenchymal transition are the main obstacles to the application of FECD cultures in the clinical setting., (Copyright © 2021. Published by Elsevier Ltd.)

Published
2021
Full Text
View/download PDF

49. A new standardized immunofluorescence method for potency quantification (SMPQ) of human conjunctival cell cultures.

Author

Bertolin M, Breda C, Ferrari S, Lamon M, Ponzin D, Ferrari B, and Barbaro V

Subjects
Cell- and Tissue-Based Therapy, Epithelial Cells, Fluorescent Antibody Technique, Humans, Limbus Corneae, Stem Cells, Cell Culture Techniques, Conjunctiva
Abstract

The aim of this study is to set up a standardized and reproducible method to determine the potency (= stem cell content) of human conjunctival cell cultures by means of immunofluorescence-based analyses. This will help the development of new Advanced Therapy Medicinal Products (ATMPs) to use in future cell therapy clinical studies when fewer cells are available to perform the quality controls. To achieve this purpose, a reference standard was investigated and the expression levels of ΔNp63α (considered as a marker of conjunctival stem cells) was correlated to cell size. The limbal hTERT cells were used as reference standard to define the expression value of ΔNp63α. The mean intensity value of limbal hTERT cells ranging between 15 and 20 µm in diameter was used to distinguish between ΔNp63α bright and not bright cells. As ΔNp63α bright expression was mainly seen in the smaller cell size group (10-15 µm), we defined as conjunctival stem cells (= potency) those cells which were bright and with sizes between 10 and 15 µm. Assays on cells from clonal analyses were used to validate the method, as they do allow to observe a decrease in potency (Holoclones > Meroclones > Paraclones). The stem cell content of conjunctival grafts was found to be 11.3% ± 5.0 compared to 21.9% ± 0.6, 9.0% ± 8.1 and 0% from Holoclones, Meroclones and Paraclones, respectively. This new method, here named as Standardized Method for Potency Quantification, will allow to detect the potency in conjunctival cell cultures, thus obtaining a quality control assay responding to the GMP standards required for ATMP release.

Published
2021
Full Text
View/download PDF

50. Increased Cell Survival of Human Primary Conjunctival Stem Cells in Dimethyl Sulfoxide-Based Cryopreservation Media.

Author

van Velthoven AJH, Bertolin M, Barbaro V, Sthijns MMJPE, Nuijts RMMA, LaPointe VLS, Dickman MM, and Ferrari S

Subjects
Cryopreservation, Cryoprotective Agents, Dimethyl Sulfoxide, Humans, Cell Survival, Stem Cells
Abstract

Glycerol and dimethyl sulfoxide (DMSO) are widely used cryoprotectants for freezing human cell cultures. During the manufacturing process of ocular stem cell-based autographs, ex vivo cultivated ocular cells are cryopreserved for quality control purposes in accordance with regulatory requirements. The efficiency of the cryopreservation methods is limited by their effect on cell survival and quality. We compared two cryopreservation reagents, glycerol and DMSO, for their influence on the survival and quality of human primary conjunctival cultures. We found increased cell viability after cryopreservation in DMSO compared to cryopreservation in glycerol. The clonogenic and proliferative capacity was unaffected by the cryopreservation reagents, as shown by the colony forming efficiency and cumulative cell doubling. Importantly, the percentage of p63α- and keratin 19 (K19)-positive cells following cryopreservation in DMSO or glycerol was comparable. Taken together, our results demonstrate that cryopreservation in DMSO improves cell survival compared to cryopreservation in glycerol, with no subsequent effect on cell proliferative-, clonogenic-, or differentiation capacity. Therefore, we advise the use of a 10% DMSO-based cryopreservation medium for the cryopreservation of human primary conjunctival cells, as it will improve the number of cells available for the manufacturing of conjunctival stem cell-based autografts for clinical use.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results