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1. Systematic profiling of conditional degron tag technologies for target validation studies

Author

Bondeson, DP, Mullin-Bernstein, Z, Oliver, S, Skipper, TA, Atack, TC, Bick, N, Ching, M, Guirguis, AA, Kwon, J, Langan, C, Millson, D, Paolella, BR, Tran, K, Wie, SJ, Vazquez, F, Tothova, Z, Golub, TR, Sellers, WR, Ianari, A, Bondeson, DP, Mullin-Bernstein, Z, Oliver, S, Skipper, TA, Atack, TC, Bick, N, Ching, M, Guirguis, AA, Kwon, J, Langan, C, Millson, D, Paolella, BR, Tran, K, Wie, SJ, Vazquez, F, Tothova, Z, Golub, TR, Sellers, WR, and Ianari, A

Abstract

Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs: AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh. We demonstrate the utility of this system against 16 unique protein targets. We find that expression and degradation are highly dependent on the specific CDT, the construct design, and the target. None of the CDTs leads to efficient expression and/or degradation across all targets; however, our systematic approach enables the identification of at least one optimal CDT fusion for each target. To enable the adoption of CDT strategies more broadly, we have made these reagents, and a detailed protocol, available as a community resource.

Published
2022

2. Akzidentelle Übertragung topisch angewandter Sexualhormone auf Kinder und Haustiere

Author

Bick, N., Neubert, A., Kammler, H.-J., and Kayser, C.

Abstract

Schon seit Ende der 1960er-Jahre gibt es Publikationen über potenzielle Risiken durch akzidentelle Übertragungen topisch angewandter Hormonpräparate auf weitere im Haushalt lebende Personen, insbesondere auf Kinder. Die dadurch ausgelösten Symptome können schwerwiegend, teilweise irreversibel und die diagnostische Aufarbeitung langwierig sein. In neueren veterinärmedizinischen Fachbüchern wird die exogene Östrogenexposition von Hunden aufgrund der topischen Hormonersatztherapie der Besitzerin bereits als Differenzialdiagnose bei Symptomen aufgeführt, die auf Hyperöstrogenismus schließen lassen. Der folgende Artikel gibt einen Überblick über die aktuelle wissenschaftliche Evidenz aus der Literatur und Spontanberichterfassung und fokussiert dabei auf östrogen- sowie testosteronhaltige topische Hormonpräparate. Ziel ist es, Patienten sowie Angehörige der Heilberufe für das Risiko einer Übertragung von topisch angewandtem Östrogen und Testosteron auf Kinder und Haustiere zu sensibilisieren, um die damit verbundenen Risiken weiter zu reduzieren.

Published
2022

3. Cyproteronacetat: Meningeomrisiko führt zu weiteren Anwendungseinschränkungen

Author

Bick, N. and Sachs, B.

Abstract

Bei Cyproteronacetat (CPA) handelt es sich um ein Gestagen mit antiandrogener Partialwirkung, das als Monosubstanz oder in Kombination mit anderen Wirkstoffen zur Therapie unterschiedlicher sexualhormonempfindlicher Erkrankungen eingesetzt wird. Das Risiko der Entwicklung von Meningeomen unter langfristiger Anwendung hoher CPA-Dosen ist schon seit vielen Jahren bekannt. In einer aktuellen Studie aus Frankreich wurde dieses Risiko nun weiter untersucht und charakterisiert. Die Ergebnisse der Studie triggerten ein Risikobewertungsverfahren, das mit Empfehlungen für risikoadaptierte Maßnahmen für die unterschiedlichen CPA-haltigen Arzneimittel abgeschlossen wurde, die jetzt von den einzelnen EU-Mitgliedstaaten umgesetzt werden. Dieser Beitrag stellt die Hintergründe des Verfahrens und die beschlossenen Maßnahmen ausführlicher dar.

Published
2020

5. Depressionen und Suizidalität unter Anwendung hormonaler Kontrazeptiva

Author

Sachs, B., Bücker, B., and Bick, N.

Abstract

Hormonale Kontrazeptiva zählen zu den zuverlässigsten Methoden der reversiblen Empfängnisverhütung.1 Sie enthalten, anders als nicht hormonale Kontrazeptiva wie z.B. die Kupferspirale, hormonartige Wirkstoffe, die die kontrazeptive Wirkung – meist durch Unterdrückung der Ovulation – vermitteln.1–3 Schon vor 50 Jahren wurde publiziert, dass hormonale Kontrazeptiva Stimmungsveränderungen verursachen können.4–6 In den Fachund Gebrauchsinformationen werden neben Stimmungsveränderungen auch Depressionen als Nebenwirkungen aufgeführt. Schwere Depressionen wiederum erhöhen das Risiko für Suizidalität. Der folgende Artikel führt in diese Thematik ein und berichtet über die Ergebnisse einer großen aktuellen Studie, die das Suizidrisiko unter Anwendung hormonaler Kontrazeptiva untersuchte. Abschließend werden die regulatorischen Maßnahmen vorgestellt, die aufgrund der neuen Erkenntnisse angeordnet wurden.

Published
2019

7. Depressionen und sexuelle Funktionsstörungen unter Anwendung von Finasterid zur Behandlung der androgenetischen Alopezie

Author

Bick, N., Sachs, B., and Fischer-Barth, W.

Abstract

Der Wirkstoff Finasterid ist in Deutschland in einer Formulierung von 1 mg pro Tablette zur Behandlung von frühen Stadien der androgenetischen Alopezie bei Männern und in einer Formulierung von 5 mg pro Tablette zur Behandlung der benignen Prostatahyperplasie zugelassen. Im Rahmen der Anwendung nach der Zulassung gab es Berichte über Depressionen und sexuelle Funktionsstörungen, die teilweise auch nach Absetzen von Finasterid persistierten. Ziel des Artikels ist es, diese Thematik zusammenfassend darzustellen und Ärzte sowie Patienten über diese Nebenwirkungen zu informieren, damit ihr mögliches Auftreten im Rahmen der individuellen Nutzen-Risiko-Abwägung vor Beginn einer Therapie mit Finasterid berücksichtigt werden kann.

Published
2018

8. Biotininterferenzen: Ein mögliches Problem bei klinischen Laboruntersuchungen

Author

Katić, J. and Bick, N.

Abstract

Das Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) hat auf europäischer Ebene ein Signalverfahren initiiert, um das Risiko der Biotininterferenz mit klinischen Laboruntersuchungen zu evaluieren. Hintergrund war eine erhöhte Anzahl an Fallberichten, in denen bei Patienten, die Biotin eingenommen hatten, verfälschte Ergebnisse von Laboruntersuchungen beschrieben wurden. Betroffene Laboruntersuchungen beziehen sich auf Assays, die auf einem Streptavidin-Biotin-Testprinzip beruhen. Unerkannte, durch Biotin verursachte Störungen von Laboruntersuchungen (z.B. bei der Schilddrüsenhormonbestimmung oder der Messung kardialer Marker) können ein Risiko für verzögerte Diagnosestellungen, falsche Diagnosen und unnötige Behandlungen darstellen. Ziel dieses Artikels ist es, den Zusammenhang der Anwendung von Biotin und möglichen Interferenzen mit Immunoassays aufzuzeigen, eine Übersicht über potenziell betroffene Biomarker zu geben sowie mögliche Handlungsempfehlungen zu beschreiben.

Published
2018

9. 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
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10. What's doing in Melbourne.

Author

Bick, N.

Subjects
*TRAVEL
Abstract

Refers to a page 10 article on Melbourne, Australia, which is preparing to celebrate the approaching fall. Events, culture, excursions, crafts, restaurants, hotels.

Published
1990

11. Virtually isolated: social identity threat predicts social approach motivation via sense of belonging in computer-supported collaborative learning.

Author

Bick N, Froehlich L, Voltmer JB, Raimann J, Reich-Stiebert N, Seidel N, Burchart M, Martiny SE, Nikitin J, Stürmer S, and Martin A

Abstract

Collaboration improves multiple academic and social outcomes. Accordingly, computer-supported collaborative learning (CSCL) can be beneficial in distance education contexts to overcome the issues specific to online learning (e.g., underperformance, low identification with university). Distance universities often attract a substantial number of non-traditional students (e.g., students with disability, students with migration background). Despite their representation, non-traditional students face negative stereotypes and associated social consequences, including social identity threat, diminished sense of belonging, and less motivation for social interactions. In the context of online learning, where there is little individuating information, social categories like socio-demographic group memberships become salient, activating stereotypes. Consequently, socio-demographic group memberships can have detrimental consequences for the integration of non-traditional students. The purpose of the present study was to (a) determine the extent of social identity threat for students in higher distance education, (b) explore the social consequences of this threat in the same context, (c) validate these findings through longitudinal analyses embedded in a CSCL task, and (d) use learning analytics to test behavioral outcomes. In a longitudinal study with three measurement occasions over 8 weeks ( N  = 1,210), we conducted path analyses for cross-sectional associations and Random Intercept Cross-Lagged Panel Models for longitudinal predictions. The results showed that non-traditional students mostly reported higher social identity threat than traditional students. While the expected longitudinal within-person effects could not be demonstrated, we found stable between-person effects: students who reported higher levels of social identity threat also reported lower sense of belonging and lower social approach motivation. Exploratory analyses of actual online collaboration during CSCL offer potential avenues for future research. We conclude that social identity threat and its social consequences play an important role in higher distance education and should therefore be considered for successful CSCL., Competing Interests: MB was employed by Research Institute for Telecommunications and Cooperation e.V. This research institute is a legally independent organization at the FernUniversität that is connected to the FernUniversität regarding staff, place, and organizationally but is no part of the university. The remaining 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 © 2024 Bick, Froehlich, Voltmer, Raimann, Reich-Stiebert, Seidel, Burchart, Martiny, Nikitin, Stürmer and Martin.)

Published
2024
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12. Social identity threat is related to ethnic minority adolescents' social approach motivation towards classmates via reduced sense of belonging.

Author

Froehlich L, Bick N, Nikitin J, and Martiny SE

Abstract

The integration of ethnic minority youth can only be successful if they are motivated to establish and maintain social relationships in important institutions such as school. At the same time, worries about negative stereotypes about one's ethnic group can undermine ethnic minority students' motivation to approach others. In the present study, we tested whether social identity threat predicts ethnic minority adolescents' social approach motivation via reduced sense of belonging. We also examined whether multiple social identities (i.e., high endorsement of ethnic and national idenitiy) buffer against the negative effects of social identity threat. In a sample of 426 ethnic minority students from 36 9 th -grade classes in Germany, social identity threat was indirectly related to social approach motivation via reduced sense of belonging to the school and class. The interplay of students' ethnic and national identity moderated the relationship of social identity threat and sense of belonging. The relationship was particularly negative for students who endorsed either ethnic or national identity. However, it was less negative for students with integrated multiple social identities and non-significant for students who identified neither with the ethnic nor the national group. Results generalized for social approach motivation towards ethnic majority and minority classmates. These patterns were only found for social approach motivation in face-to-face contact situations, but not in online situations. We discuss these findings in light of the literature on social identity threat and multiple social identities. Practical implications include measures to foster students' sense of belonging and to reduce social identity threat., (© The Author(s) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Published
2023
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13. Systematic profiling of conditional degron tag technologies for target validation studies.

Author

Bondeson DP, Mullin-Bernstein Z, Oliver S, Skipper TA, Atack TC, Bick N, Ching M, Guirguis AA, Kwon J, Langan C, Millson D, Paolella BR, Tran K, Wie SJ, Vazquez F, Tothova Z, Golub TR, Sellers WR, and Ianari A

Subjects
Kinetics, Proteolysis
Abstract

Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs: AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh. We demonstrate the utility of this system against 16 unique protein targets. We find that expression and degradation are highly dependent on the specific CDT, the construct design, and the target. None of the CDTs leads to efficient expression and/or degradation across all targets; however, our systematic approach enables the identification of at least one optimal CDT fusion for each target. To enable the adoption of CDT strategies more broadly, we have made these reagents, and a detailed protocol, available as a community resource., (© 2022. The Author(s).)

Published
2022
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14. Prevalence of Somatic Mutations in Aldosterone-Producing Adenomas in Japanese Patients.

Author

Nanba K, Yamazaki Y, Bick N, Onodera K, Tezuka Y, Omata K, Ono Y, Blinder AR, Tomlins SA, Rainey WE, Satoh F, and Sasano H

Subjects
Adrenal Cortex Neoplasms pathology, Adrenocortical Adenoma pathology, Aged, Female, High-Throughput Nucleotide Sequencing, Humans, Japan, Male, Middle Aged, Adrenal Cortex Neoplasms genetics, Adrenocortical Adenoma genetics, Calcium Channels, L-Type genetics, Cytochrome P-450 CYP11B2 genetics, G Protein-Coupled Inwardly-Rectifying Potassium Channels genetics, Mutation, Sodium-Potassium-Exchanging ATPase genetics
Abstract

Context: Results of previous studies demonstrated clear racial differences in the prevalence of somatic mutations among patients with aldosterone-producing adenoma (APA). For instance, those in East Asian countries have a high prevalence of somatic mutations in KCNJ5, whereas somatic mutations in other aldosterone-driving genes are rare., Objectives: To determine somatic mutation prevalence in Japanese APA patients using an aldosterone synthase (CYP11B2) immunohistochemistry (IHC)-guided sequencing approach., Method: Patients with a unilateral form of primary aldosteronism who underwent adrenalectomy at the Tohoku University Hospital were studied. Based on CYP11B2 immunolocalization of resected adrenals, genomic DNA was isolated from the relevant positive area of 10% formalin-fixed, paraffin-embedded tissue of the APAs. Somatic mutations in aldosterone-driving genes were studied in APAs by direct Sanger sequencing and targeted next-generation sequencing., Results: CYP11B2 IHC-guided sequencing determined APA-related somatic mutations in 102 out of 106 APAs (96%). Somatic KCNJ5 mutation was the most frequent genetic alteration (73%) in this cohort of Japanese patients. Somatic mutations in other aldosterone-driving genes were also identified: CACNA1D (14%), ATP1A1 (5%), ATP2B3 (4%), and CACNA1H (1%), including 2 previously unreported mutations. KCNJ5 mutations were more often detected in APAs from female patients compared with those from male patients [95% (36/38) vs 60% (41/68); P < 0.0001]., Conclusion: IHC-guided sequencing defined somatic mutations in over 95% of Japanese APAs. While the dominance of KCNJ5 mutations in this particular cohort was confirmed, a significantly higher KCNJ5 prevalence was detected in female patients. This study provides a better understanding of genetic spectrum of Japanese APA patients., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2020
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15. Invasive squamous cell carcinomas and precursor lesions on UV-exposed epithelia demonstrate concordant genomic complexity in driver genes.

Author

Lazo de la Vega L, Bick N, Hu K, Rahrig SE, Silva CD, Matayoshi S, Picciarelli P, Wang X, Sugar A, Soong HK, Mian SI, Robinson DR, Chinnaiyan AM, Demirci H, Daniels AB, Worden F, Eberhart CG, Tomlins SA, Rao RC, and Harms PW

Subjects
Aged, Carcinoma in Situ genetics, Carcinoma, Squamous Cell genetics, Conjunctival Neoplasms genetics, Eye Neoplasms genetics, Female, High-Throughput Nucleotide Sequencing, Humans, Keratosis, Actinic genetics, Keratosis, Actinic pathology, Male, Middle Aged, Skin Neoplasms genetics, Carcinoma in Situ pathology, Carcinoma, Squamous Cell pathology, Conjunctival Neoplasms pathology, Eye Neoplasms pathology, Mutation, Skin pathology, Skin Neoplasms pathology
Abstract

Although squamous cell carcinomas (SCC) are the most frequent human solid tumor at many anatomic sites, the driving molecular alterations underlying their progression from precursor lesions are poorly understood, especially in the context of photodamage. Therefore, we used high-depth, targeted next-generation sequencing (NGS) of RNA and DNA from routine tissue samples to characterize the progression of both well- (cutaneous) and poorly (ocular) studied SCCs. We assessed 56 formalin-fixed paraffin-embedded (FFPE) cutaneous lesions (n = 8 actinic keratosis, n = 30 carcinoma in situ [CIS], n = 18 invasive) and 43 FFPE ocular surface lesions (n = 2 conjunctival/corneal intraepithelial neoplasia, n = 20 CIS, n = 21 invasive), from institutions in the US and Brazil. An additional seven cases of advanced cutaneous SCC were profiled by hybrid capture-based NGS of >1500 genes. The cutaneous and ocular squamous neoplasms displayed a predominance of UV-signature mutations. Precursor lesions had highly similar somatic genomic landscapes to SCCs, including chromosomal gains of 3q involving SOX2, and highly recurrent mutations and/or loss of heterozygosity events affecting tumor suppressors TP53 and CDKN2A. Additionally, we identify a novel molecular subclass of CIS with RB1 mutations. Among TP53 wild-type tumors, human papillomavirus transcript was detected in one matched pair of cutaneous CIS and SCC. Amplicon-based whole-transcriptome sequencing of select 20 cutaneous lesions demonstrated significant upregulation of pro-invasion genes in cutaneous SCCs relative to precursors, including MMP1, MMP3, MMP9, LAMC2, LGALS1, and TNFRSF12A. Together, ocular and cutaneous squamous neoplasms demonstrate similar alterations, supporting a common model for neoplasia in UV-exposed epithelia. Treatment modalities useful for cutaneous SCC may also be effective in ocular SCC given the genetic similarity between these tumor types. Importantly, in both systems, precursor lesions possess the full complement of major genetic changes seen in SCC, supporting non-genetic drivers of invasiveness.

Published
2020
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