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1. TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels

Author

Hong, SJ, Dobricic, V, Ohlei, O, Bos, I, Vos, SJB, Prokopenko, D, Tijms, BM, Andreasson, U, Blennow, K, Vandenberghe, R, Gabel, S, Scheltens, P, Teunissen, CE, Engelborghs, S, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Lleo, A, Alcolea, D, Popp, J, Clark, C, Peyratout, G, Martinez-Lage, P, Tainta, M, Dobson, RJB, Legido-Quigley, C, Sleegers, K, Van Broeckhoven, C, Tanzi, RE, ten Kate, M, Wittig, M, Franke, A, Lill, CM, Barkhof, F, Lovestone, S, Streffer, J, Zetterberg, H, Visser, PJ, Bertram, L, and Neuroimaging Initiative

Subjects
s disease, wide association study, chitinase&#8208, like protein 1, neurogranin, neurofilament light, 3&#8208, biomarker, genome&#8208, Alzheimer&apos, cerebrospinal fluid
Abstract

Introduction Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Methods We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates. Results We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1. Discussion Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.

Published
2021

2. Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset

Author

Hong, SJ, Prokopenko, D, Dobricic, V, Kilpert, F, Bos, I, Vos, SJB, Tijms, BM, Andreasson, U, Blennow, K, Vandenberghe, R, Cleynen, I, Gabel, S, Schaeverbeke, J, Scheltens, P, Teunissen, CE, Niemantsverdriet, E, Engelborghs, S, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Molinuevo, JL, Rami, L, Kettunen, P, Wallin, A, Lleo, A, Sala, I, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Dobson, RJB, Legido-Quigley, C, Sleegers, K, Van Broeckhoven, C, ten Kate, M, Barkhof, F, Zetterberg, H, Lovestone, S, Streffer, J, Wittig, M, Franke, A, Tanzi, RE, Visser, PJ, Bertram, L, and Alzheimers Dis Neuroimaging Initia

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (A beta) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to A beta 42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-A beta 38 and CSF-A beta 40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-A beta and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.

Published
2020

3. Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset

Author

Hong, SJ, Prokopenko, D, Dobricic, V, Kilpert, F, Bos, I, Vos, SJB, Tijms, BM, Andreasson, U, Blennow, K, Vandenberghe, R, Cleynen, I, Gabel, S, Schaeverbeke, J, Scheltens, P, Teunissen, CE, Niemantsverdriet, E, Engelborghs, S, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Molinuevo, JL, Rami, L, Kettunen, P, Wallin, A, Lleo, A, Sala, I, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Dobson, RJB, Legido-Quigley, C, Sleegers, K, Van Broeckhoven, C, ten Kate, M, Barkhof, F, Zetterberg, H, Lovestone, S, Streffer, J, Wittig, M, Franke, A, Tanzi, RE, Visser, PJ, Bertram, L, and Alzheimers Dis Neuroimaging Initia

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (A beta) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to A beta 42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-A beta 38 and CSF-A beta 40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-A beta and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.

Published
2020

4. Inflammatory biomarkers in Alzheimer's disease plasma

Author

Leckey, C, Nevado-Holgado, AJ, Barkhof, F, Bertram, L, Blin, O, Bos, I, Dobricic, V, Engelborghs, S, Frisoni, G, Frolich, L, Gabel, S, Johannsen, P, Kettunen, P, Koszewska, I, Legido-Quigley, C, Lleo, A, Martinez-Lage, P, Mecocci, P, Meersmans, K, Molinuevo, JL, Peyratout, G, Popp, J, Richardson, J, Sala, I, Scheltens, P, Streffer, J, Soininen, H, Tainta-Cuezva, M, Teunissen, C, Tsolaki, M, Vandenberghe, R, Visser, PJ, Vos, S, Wahlund, LO, Wallin, A, Westwood, S, Zetterberg, H, Bullmore, ET, Bhatti, J, Chamberlain, SJ, Correia, MM, Crofts, AL, Dickinson, A, Foster, AC, Kitzbichler, MG, Knight, C, Lynall, ME, Maurice, C, O'Donnell, C, Pointon, LJ, Hyslop, PS, Turner, L, Vertes, P, Widmer, B, Williams, GB, Morgan, BP, Morgan, AR, O'Hagan, C, Touchard, S, Cavanagh, J, Deith, C, Farmer, S, McClean, J, McColl, A, McPherson, A, Scouller, P, Sutherland, M, Boddeke, HWGM, Richardson, JC, Khan, S, Murphy, P, Parker, CA, Patel, J, Jones, D, Boer, P, Kemp, J, Drevets, WC, Nye, JS, Wittenberg, G, Isaac, J, Bhattacharya, A, Carruthers, N, Kolb, H, Pariante, CM, Turkheimer, F, Barker, GJ, Byrom, H, Cash, D, Cattaneo, A, Gee, A, Hastings, C, Mariani, N, McLaughlin, A, Mondelli, V, Nettis, M, Nikkheslat, N, Randall, K, Sheridan, H, Simmons, C, Singh, N, Van Loo, V, Vicente-Rodriguez, M, Wood, TC, Worrell, C, Zajkowska, Z, Plath, N, Egebjerg, J, Eriksson, H, Gastambide, F, Adams, KH, Jeggo, R, Thomsen, C, Pederson, JT, Campbell, B, Moller, T, Nelson, B, Zorn, S, O'Connor, J, Attenburrow, MJ, Baird, A, Benjamin, J, Clare, S, Cowen, P, Huang, IS, Hurley, S, Jones, H, Lovestone, S, Mada, F, Nevado-Holgado, A, Oladejo, A, Ribe, E, Smith, K, Vyas, A, Hughes, Z, Balice-Gordon, R, Duerr, J, Piro, JR, Sporn, J, Perry, VH, Cleal, M, Fryatt, G, Gomez-Nicola, D, Mancuso, R, Reynolds, R, Harrison, NA, Cercignani, M, Clarke, CL, Hoskins, E, Kohn, C, Murray, R, Wilcock, L, Wlazly, D, NIMA Consortium, and NIMA-Wellcome Trust Consortium

Subjects
Inflammation, Plasma, Complement, Biomarker, Alzheimer's disease
Abstract

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOe4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Published
2019

5. Pharmacological Basis of Immunotherapy in Autoimmune Diseases

Author

Rouveix B and Blin O

Subjects
Pharmacology, Autoimmune disease, Clinical pharmacology, business.industry, medicine.medical_treatment, Chronic inflammatory demyelinating polyneuropathy, Disease, Immunotherapy, medicine.disease, Autoimmune Diseases, law.invention, Clinical trial, Immune system, Adjuvants, Immunologic, law, Rheumatoid arthritis, Immunology, medicine, Animals, Humans, Pharmacology (medical), Neurology (clinical), business
Abstract

The clinical development of immunomodulatory agents for the treatment of autoimmune diseases is an arduous process. This can be explained by the fact that the true pathogenic mechanism of the disease(s) is unknown. Moreover, the properties and pharmacokinetic profile of these immunomodulatory agents are different from other classic therapeutic compounds. The aim of this brief review is to discuss a number of general aspects of the clinical pharmacology of i.v. immune globulin as well as more recent immunotherapeutic approaches such as anti-cytokine therapy, which are currently being applied in the immunotherapy for neurologic and rheumatic autoimmune disorders such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and rheumatoid arthritis. A better understanding of the interaction of the therapeutic compound and the host immune response, the knowledge of its kinetic profile, and the development of surrogate markers of clinical efficacy should help in designing randomized and blinded clinical trials that will ultimately determine the optimal therapeutic regimen.

Published
1993
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6. 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
Full Text
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8. GABAERGIC CONTROL OF VISUAL-PERCEPTION IN HEALTHY-VOLUNTEERS - EFFECTS OF MIDAZOLAM, A BENZODIAZEPINE, ON SPATIOTEMPORAL CONTRAST SENSITIVITY

Author

Blin, O., Daniel Mestre, Paut, O., Vercher, Jl, Audebert, C., Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Vercher, Jean-Louis, and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
BENZODIAZEPINE, GABA, genetic structures, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, MOTION PERCEPTION, MIDAZOLAM, SPATIOTEMPORAL CONTRAST SENSITIVITY
Abstract

International audience; 1 We studied the effects of midazolam (MDZ), a benzodiazepine, on spatio-temporal contrast sensitivity, choice reaction time, and mood visual analogue scales in healthy volunteers. 2 Eight extensively trained, healthy volunteers were included in a placebo-controlled cross-over double-blind trial of MDZ (0.15 mg kg-1). Treatments were injected intramuscularly and evaluations were performed before and 0.5, 1, 2, 3 and 4 h after drug administration. Spatio-temporal contrast sensitivity was measured using a micro-computer with appropriate software. Stimuli were vertical gratings with adjustable contrast, with spatial frequencies of 0.25, 1 and 4 cpd. Four conditions of temporal modulation were used: the grating was either static or drifting laterally with temporal frequencies of 1, 3 and 9 Hz. 3 An analysis of variance was performed on the data. As compared with placebo, MDZ induced an increase in choice reaction time and sedation (as assessed on visual analogue scales). From 0.5-4 h after the injection, MDZ produced an overall decrease in visual sensitivity, as compared with placebo. More specifically, MDZ preferentially affected medium to high spatial frequencies and low temporal frequencies. Several non-exclusive hypotheses may account for the results: 1) an increase in the size of the receptive fields, 2) a preferential effect on the visual parvocellular pathways which mediate the sensitivity to high spatial and low temporal frequencies.

9. [Study methods of drugs in Alzheimer disease]

Author

Dubois B, Stehlé B, Jp, Lehner, Derouesné C, Bourin M, Lamour Y, Blin O, Gonzague Jourdain, and Alperovitch A

Subjects
Clinical Trials as Topic, Cognition, Neuroprotective Agents, Alzheimer Disease, Animals, Drug Evaluation, Humans, Guidelines as Topic, France
Abstract

The availability of new drugs for Alzheimer's disease, with different pharmacological profiles, leads to a redefinition the relevant methodology for developing drugs in this indication, including the inclusion/exclusion criteria, the duration of the studies, and therefore, the relevant guidelines. This was the purpose of the Giens Round-table devoted to the new methodology for drug development in Alzheimer disease.

11. Longitudinal imaging and biochemical assessments

Author

Marizzoni, M., Galluzzi, S., Ferrari, C., Jovicich, J., Nobili, F., Ranjeva, J. -P, Bartres-Faz, D., Fiedler, U., Schoenknech, P., Payoux, P., Beltramello, A., Caulo, M., Soricelli, A., Parnetti, L., Tsolaki, M., Rossini, P. M., Pieter Jelle Visser, Albani, D., Forloni, G., Bordet, R., Richardson, J., Blin, O., Frisoni, G. B., Consortium, Pharmacog, Neurology, and Amsterdam Neuroscience - Neurodegeneration

12. [Pharmacological modulation of the effects induced by ketamine at subanesthetic doses]

Author

Mechri A, Micallef J, Blin O, Mohamed Saoud, Daléry J, and Gaha L

Subjects
Anesthetics, Dissociative, Dose-Response Relationship, Drug, Animals, Humans, Ketamine, Clozapine, Receptors, N-Methyl-D-Aspartate
Abstract

The similarity between ketamine effects and endogenous psychoses has created interest in the capacity of antipsychotic medications to block ketamine effects. In healthy subjects, a sub-anaesthetic single dose of lorazepam, typical neuroleptics, such as haloperidol, and atypical neuroleptics, such as clozapine and olanzapine, failed to block ketamine-induced positive and negative symptoms resembling schizophrenia. However, haloperidol is able to decrease ketamine-induced impairment in executive cognitive functions. Recently, lamotrigine reduced ketamine-induced psychotic symptoms, perceptual alterations, and cognitive impairments. In schizophrenic subjects, single doses of olanzapine do not decrease the effects of ketamine. However, long term treatment with clozapine has been reported to decrease ketamine-induced positive symptoms. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.

14. How to prevent Surgical Site Infections? A new squalamine analogue demonstrates potent anti-staphylococcal properties

Author

Del-Bano, J., Sakr, A., Rolain, J. M., Guilhaumou, R., Marc Leone, Argenson, J. N., Brunel, J. M., Raoult, D., Blin, O., Service de Pharmacologie Clinique [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Membranes et cibles thérapeutiques (MCT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA)-Aix Marseille Université (AMU), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), and Institut de Neurosciences de la Timone, Aix-Marseille Univ, CNRS UMR 7289, Marseille, France (INT)

Subjects
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Meeting Abstract: PM-014

16. Cross-sectional clinical, neuropsychological, neuroimaging, and neurophysiological characterization of mild cognitive impairment patients in WP5 PharmaCog/E-ADNI study

Author

Galluzzi, S., Marizzoni, M., Babiloni, C., Bartres-Faz, D., Blin, O., Bordet, R., Bosch, B., Anna, F., Didic, M., Farotti, L., Forloni, G., Jovicich, J., Marra, C., Marzano, N., Molinuevo, Jl, Nobili, F., Pariente, J., Parnetti, L., Payoux, P., Picco, A., Quaranta, D., Ranjeva, Jp, Roccatagliata, L., Rossini, Pm, Salvadori, N., Schonknecht, P., Soricelli, A., Tsolaki, M., Vecchio Fabrizio, Visser, Pj, Wiltfang, J., and Frisoni, Gb

17. In vitro antibacterial activity of squalamine and squalamine derivatives against mupirocin-resistant bacteria

Author

Sakr, A., Hadjadj, L., Blin, O., Pitel, S., Gallice, S., Rolain, J. M., Didier Raoult, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de neurosciences cognitives de la méditerranée - UMR 6193 (INCM), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), and COMBE, Isabelle

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

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