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3. Liquid Biopsy-Guided Interventional Oncology: A Proof of Concept with a Special Focus on Radiotherapy and Radiology

Author

Malara, N., Kovacs, Gyorgy, Bussu, Francesco, Ferrazzo, T., Garo, V., Raso, C., Cornacchione, Patrizia, Iezzi, Roberto, Tagliaferri, Luca, Kovacs G., Bussu F. (ORCID:0000-0001-6261-2772), Cornacchione P., Iezzi R. (ORCID:0000-0002-2791-481X), Tagliaferri L. (ORCID:0000-0003-2308-0982), Malara, N., Kovacs, Gyorgy, Bussu, Francesco, Ferrazzo, T., Garo, V., Raso, C., Cornacchione, Patrizia, Iezzi, Roberto, Tagliaferri, Luca, Kovacs G., Bussu F. (ORCID:0000-0001-6261-2772), Cornacchione P., Iezzi R. (ORCID:0000-0002-2791-481X), and Tagliaferri L. (ORCID:0000-0003-2308-0982)

Abstract

Although the role of liquid biopsy (LB) to measure minimal residual disease (MRD) in the treatment of epithelial cancer is well known, the biology of the change in the availability of circulating biomarkers arising throughout treatments such as radiotherapy and interventional radio-oncology is less explained. Deep knowledge of how therapeutic effects can influence the biology of the release mechanism at the base of the biomarkers available in the bloodstream is needed for selecting the appropriate treatment-induced tumor circulating biomarker. Combining existing progress in the LB and interventional oncology (IO) fields, a proof of concept is provided, discussing the advantages of the traditional risk assessment of relapsing lesions, limitations, and the timing of detection of the circulating biomarker. The current review aims to help both interventional radiologists and interventional radiation oncologists evaluate the possibility of drawing a tailor-made board of blood-based surveillance markers to reveal subclinical diseases and avoid overtreatment.

Published
2022

7. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D

Author

Kennedy, S. A., Jarboui, M. -A, Srihari, S., Raso, C., Bryan, K., Dernayka, L., Charitou, T., Bernal-Llinares, M., Herrera-Montavez, C., Krstic, A., Matallanas, D., Kotlyar, M., Jurisica, I., Curak, J., Wong, V., Stagljar, I., LeBihan, T., Imrie, L., Pillai, P., Lynn, M. A., Fasterius, Erik, Al-Khalili Szigyarto, Cristina, Breen, J., Kiel, C., Serrano, L., Rauch, N., Rukhlenko, O., Kholodenko, B. N., Iglesias-Martinez, L. F., Ryan, C. J., Pilkington, R., Cammareri, P., Sansom, O., Shave, S., Auer, M., Horn, N., Klose, F., Ueffing, M., Boldt, K., Lynn, D. J., Kolch, W., Kennedy, S. A., Jarboui, M. -A, Srihari, S., Raso, C., Bryan, K., Dernayka, L., Charitou, T., Bernal-Llinares, M., Herrera-Montavez, C., Krstic, A., Matallanas, D., Kotlyar, M., Jurisica, I., Curak, J., Wong, V., Stagljar, I., LeBihan, T., Imrie, L., Pillai, P., Lynn, M. A., Fasterius, Erik, Al-Khalili Szigyarto, Cristina, Breen, J., Kiel, C., Serrano, L., Rauch, N., Rukhlenko, O., Kholodenko, B. N., Iglesias-Martinez, L. F., Ryan, C. J., Pilkington, R., Cammareri, P., Sansom, O., Shave, S., Auer, M., Horn, N., Klose, F., Ueffing, M., Boldt, K., Lynn, D. J., and Kolch, W.

Abstract

Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes., QC 20200304

Published
2020
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8. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D.

Author

Kennedy, SA, Jarboui, M-A, Srihari, S, Raso, C, Bryan, K, Dernayka, L, Charitou, T, Bernal-Llinares, M, Herrera-Montavez, C, Krstic, A, Matallanas, D, Kotlyar, M, Jurisica, I, Curak, J, Wong, V, Stagljar, I, LeBihan, T, Imrie, L, Pillai, P, Lynn, MA, Fasterius, E, Al-Khalili Szigyarto, C, Breen, J, Kiel, C, Serrano, L, Rauch, N, Rukhlenko, O, Kholodenko, BN, Iglesias-Martinez, LF, Ryan, CJ, Pilkington, R, Cammareri, P, Sansom, O, Shave, S, Auer, M, Horn, N, Klose, F, Ueffing, M, Boldt, K, Lynn, DJ, Kolch, W, Kennedy, SA, Jarboui, M-A, Srihari, S, Raso, C, Bryan, K, Dernayka, L, Charitou, T, Bernal-Llinares, M, Herrera-Montavez, C, Krstic, A, Matallanas, D, Kotlyar, M, Jurisica, I, Curak, J, Wong, V, Stagljar, I, LeBihan, T, Imrie, L, Pillai, P, Lynn, MA, Fasterius, E, Al-Khalili Szigyarto, C, Breen, J, Kiel, C, Serrano, L, Rauch, N, Rukhlenko, O, Kholodenko, BN, Iglesias-Martinez, LF, Ryan, CJ, Pilkington, R, Cammareri, P, Sansom, O, Shave, S, Auer, M, Horn, N, Klose, F, Ueffing, M, Boldt, K, Lynn, DJ, and Kolch, W

Abstract

Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.

Published
2020

9. RASSF1A uncouples Wnt from Hippo signalling and promotes YAP mediated differentiation via p73

Author

Papaspyropoulos, A, Bradley, L, Thapa, A, Leung, C, Toskas, K, Koennig, D, Pefani, D, Raso, C, Grou, C, Hamilton, G, Vlahov, N, Grawenda, A, Haider, S, Chauhan, J, Buti, L, Kanapin, A, Lu, X, Buffa, F, Dianov, G, von Kriegsheim, A, Matallanas, D, Samsonova, A, Zernicka-Goetz, M, and O'Neill, E

Subjects
Male, endocrine system, Science, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Article, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Hippo Signaling Pathway, lcsh:Science, Embryonic Stem Cells, beta Catenin, Adaptor Proteins, Signal Transducing, Tumor Suppressor Proteins, Gene Expression Regulation, Developmental, TEA Domain Transcription Factors, Cell Differentiation, Tumor Protein p73, YAP-Signaling Proteins, Phosphoproteins, DNA-Binding Proteins, Mice, Inbred C57BL, Wnt Proteins, Mice, Inbred CBA, lcsh:Q, Female, Octamer Transcription Factor-3, Signal Transduction, Transcription Factors
Abstract

Transition from pluripotency to differentiation is a pivotal yet poorly understood developmental step. Here, we show that the tumour suppressor RASSF1A is a key player driving the early specification of cell fate. RASSF1A acts as a natural barrier to stem cell self-renewal and iPS cell generation, by switching YAP from an integral component in the β-catenin-TCF pluripotency network to a key factor that promotes differentiation. We demonstrate that epigenetic regulation of the Rassf1A promoter maintains stemness by allowing a quaternary association of YAP–TEAD and β-catenin–TCF3 complexes on the Oct4 distal enhancer. However, during differentiation, promoter demethylation allows GATA1-mediated RASSF1A expression which prevents YAP from contributing to the TEAD/β-catenin–TCF3 complex. Simultaneously, we find that RASSF1A promotes a YAP–p73 transcriptional programme that enables differentiation. Together, our findings demonstrate that RASSF1A mediates transcription factor selection of YAP in stem cells, thereby acting as a functional “switch” between pluripotency and initiation of differentiation., In development, the switch from pluripotency to differentiation is important but it is often unclear how it is regulated. Here, the authors show that the tumour suppressor RASSF1A mediates this switch by promoting YAP-p73 transcription, which in turn enables differentiation.

Published
2018

12. Study of the fragmentation of b quarks into B mesons at the Z peak

Author

Heister A, Schael S, Barate R, De Bonis I, Decamp D, Goy C, Lees JP, Merle E, Minard MN, Pietrzyk B, Bravo S, Casado MP, Chmeissani M, Crespo JM, Fernandez E, Fernandez Bosman M, Garrido L, Grauges E, Martinez M, Merino G, Miquel R, Mir LM, Pacheco A, Ruiz H, Colaleo A, Creanza D, de Palma M, Iaselli G, Maggi G, Maggi M, Nuzzo S, Ranieri A, Raso C, Ruggieri E, Selvaggi G, Silvestris L, Tempesta P, Tricomi A, Zito G, Huang X, Lin J, Ouyang Q, Wang T, Xie Y, Xu R, Xue S, Zhang J, Zhang L, Zhao W, Abbaneo D, Azzurri P, Boix G, Buchmuller O, Cattaneo M, Cerutti F, Clerbaux B, Dissertori G, Drevermann H, Forty RW, Frank M, Greening TC, Hansen JB, Harvey J, Janot P, Jost B, Kado M, Mato P, Moutoussi A, Ranjard F, Schlatter D, Schneider O, Spagnolo P, Tejessy W, Teubert F, Tournefier E, Ward J, Ajaltouni Z, Badaud F, Falvard A, Gay P, Henrard P, Jousset J, Michel B, Monteil S, Montret JC, Pallin D, Perret P, Podlyski F, Hansen PD, Hansen JR, Hansen PH, Nilsson BS, Waananen A, Kyriakis A, Markou C, Simopoulou E, Vayaki A, Zachariadou K, Blondel A, Bonneaud G, Brient JC, Rouge A, Rumpf M, Swynghedauw M, Verderi M, Videau H, Ciulli V, Focardi E, Parrini G, Antonelli A, Antonelli M, Bencivenni G, Bologna G, Bossi F, Campana P, Capon G, Chiarella V, Laurelli P, Mannocchi G, Murtas F, Murtas GP, Passalacqua L, Pepe Altarelli M, Halley AW, Lynch JG, Negus P, O'Shea V, Raine C, Thompson AS, Wasserbaech S, Cavanaugh R, Dhamotharan S, Geweniger C, Hanke P, Hansper G, Hepp V, Kluge EE, Putzer A, Sommer J, Tittel K, Werner S, Wunsch M, Beuselinck R, Binnie DM, Cameron W, Dornan PJ, Girone M, Marinelli N, Sedgbeer JK, Thompson JC, Ghete VM, Girtler P, Kneringer E, Kuhn D, Rudolph G, Bouhova Thacker E, Bowdery CK, Finch AJ, Foster F, Hughes G, Jones RWL, Pearson MR, Robertson NA, Giehl I, Jakobs K, Kleinknecht K, Quast G, Renk B, Rohne E, Sander HG, Wachsmuth H, Zeitnitz C, Bonissent A, Carr J, Coyle P, Leroy O, Payre P, Rousseau D, Talby M, Aleppo M, Ragusa F, David A, Dietl H, Ganis G, Huttmann K, Lutjens G, Mannert C, Manner W, Moser HG, Settles R, Stenzel H, Wiedenmann W, Wolf G, Boucrot J, Callot O, Davier M, Duflot L, Grivaz JF, Heusse P, Jacholkowska A, Lefrancois J, Veillet JJ, Videau I, Yuan C, Bagliesi G, Boccali T, Calderini G, Foa L, Giammanco A, Giassi A, Messineo A, Palla F, Sanguinetti G, Sciaba A, Sguazzoni G, Tenchini R, Venturi A, Verdini PG, Blair GA, Cowan G, Green MG, Medcalf T, Misiejuk A, Strong JA, Teixeira Dias P, von Wimmersperg Toeller JH, Clifft RW, Edgecock TR, Norton PR, Tomalin IR, Bloch Devaux B, Colas P, Emery S, Kozanecki W, Lancon E, Lemaire MC, Locci E, Perez P, Rander J, Renardy JF, Roussarie A, Schuller JP, Schwindling J, Trabelsi A, Vallage B, Konstantinidis N, Litke AM, Taylor G, Booth CN, Cartwright S, Combley F, Lehto M, Thompson LF, Affholderbach K, Bohrer A, Brandt S, Grupen C, Ngac A, Prange G, Sieler U, Giannini G, Rothberg J, Armstrong SR, Cranmer K, Elmer P, Ferguson DPS, Gao Y, Gonzalez S, Hayes OJ, Hu H, Jin S, Kile J, McNamara PA, Nielsen J, Orejudos W, Pan YB, Saadi Y, Scott IJ, Walsh J, Wu SL, Wu X, Zobernig G, RI ANTONELLI ANTONELLA/C 6238 2011 Jones Roger/H 5578 2011 Passalacqua Luca/F 5127 2011 Murtas Fabrizio/B 5729 2012 O'Shea Val/G 1279 2010, ROLANDI, LUIGI, LIGABUE, FRANCO, 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 Physique Corpusculaire - Clermont-Ferrand (LPC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Leprince-Ringuet (LLR), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-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), ALEPH, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), 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), Heister, A, Schael, S, Barate, R, De Bonis, I, Decamp, D, Goy, C, Lees, Jp, Merle, E, Minard, Mn, Pietrzyk, B, Bravo, S, Casado, Mp, Chmeissani, M, Crespo, Jm, Fernandez, E, Fernandez Bosman, M, Garrido, L, Grauges, E, Martinez, M, Merino, G, Miquel, R, Mir, Lm, Pacheco, A, Ruiz, H, Colaleo, A, Creanza, D, de Palma, M, Iaselli, G, Maggi, G, Maggi, M, Nuzzo, S, Ranieri, A, Raso, C, Ruggieri, E, Selvaggi, G, Silvestris, L, Tempesta, P, Tricomi, A, Zito, G, Huang, X, Lin, J, Ouyang, Q, Wang, T, Xie, Y, Xu, R, Xue, S, Zhang, J, Zhang, L, Zhao, W, Abbaneo, D, Azzurri, P, Boix, G, Buchmuller, O, Cattaneo, M, Cerutti, F, Clerbaux, B, Dissertori, G, Drevermann, H, Forty, Rw, Frank, M, Greening, Tc, Hansen, Jb, Harvey, J, Janot, P, Jost, B, Kado, M, Mato, P, Moutoussi, A, Ranjard, F, Rolandi, Luigi, Schlatter, D, Schneider, O, Spagnolo, P, Tejessy, W, Teubert, F, Tournefier, E, Ward, J, Ajaltouni, Z, Badaud, F, Falvard, A, Gay, P, Henrard, P, Jousset, J, Michel, B, Monteil, S, Montret, Jc, Pallin, D, Perret, P, Podlyski, F, Hansen, Pd, Hansen, Jr, Hansen, Ph, Nilsson, B, Waananen, A, Kyriakis, A, Markou, C, Simopoulou, E, Vayaki, A, Zachariadou, K, Blondel, A, Bonneaud, G, Brient, Jc, Rouge, A, Rumpf, M, Swynghedauw, M, Verderi, M, Videau, H, Ciulli, V, Focardi, E, Parrini, G, Antonelli, A, Antonelli, M, Bencivenni, G, Bologna, G, Bossi, F, Campana, P, Capon, G, Chiarella, V, Laurelli, P, Mannocchi, G, Murtas, F, Murtas, Gp, Passalacqua, L, Pepe Altarelli, M, Halley, Aw, Lynch, Jg, Negus, P, O'Shea, V, Raine, C, Thompson, A, Wasserbaech, S, Cavanaugh, R, Dhamotharan, S, Geweniger, C, Hanke, P, Hansper, G, Hepp, V, Kluge, Ee, Putzer, A, Sommer, J, Tittel, K, Werner, S, Wunsch, M, Beuselinck, R, Binnie, Dm, Cameron, W, Dornan, Pj, Girone, M, Marinelli, N, Sedgbeer, Jk, Thompson, Jc, Ghete, Vm, Girtler, P, Kneringer, E, Kuhn, D, Rudolph, G, Bouhova Thacker, E, Bowdery, Ck, Finch, Aj, Foster, F, Hughes, G, Jones, Rwl, Pearson, Mr, Robertson, Na, Giehl, I, Jakobs, K, Kleinknecht, K, Quast, G, Renk, B, Rohne, E, Sander, Hg, Wachsmuth, H, Zeitnitz, C, Bonissent, A, Carr, J, Coyle, P, Leroy, O, Payre, P, Rousseau, D, Talby, M, Aleppo, M, Ragusa, F, David, A, Dietl, H, Ganis, G, Huttmann, K, Lutjens, G, Mannert, C, Manner, W, Moser, Hg, Settles, R, Stenzel, H, Wiedenmann, W, Wolf, G, Boucrot, J, Callot, O, Davier, M, Duflot, L, Grivaz, Jf, Heusse, P, Jacholkowska, A, Lefrancois, J, Veillet, Jj, Videau, I, Yuan, C, Bagliesi, G, Boccali, T, Calderini, G, Foa, L, Giammanco, A, Giassi, A, Ligabue, Franco, Messineo, A, Palla, F, Sanguinetti, G, Sciaba, A, Sguazzoni, G, Tenchini, R, Venturi, A, Verdini, Pg, Blair, Ga, Cowan, G, Green, Mg, Medcalf, T, Misiejuk, A, Strong, Ja, Teixeira Dias, P, von Wimmersperg Toeller, Jh, Clifft, Rw, Edgecock, Tr, Norton, Pr, Tomalin, Ir, Bloch Devaux, B, Colas, P, Emery, S, Kozanecki, W, Lancon, E, Lemaire, Mc, Locci, E, Perez, P, Rander, J, Renardy, Jf, Roussarie, A, Schuller, Jp, Schwindling, J, Trabelsi, A, Vallage, B, Konstantinidis, N, Litke, Am, Taylor, G, Booth, Cn, Cartwright, S, Combley, F, Lehto, M, Thompson, Lf, Affholderbach, K, Bohrer, A, Brandt, S, Grupen, C, Ngac, A, Prange, G, Sieler, U, Giannini, G, Rothberg, J, Armstrong, Sr, Cranmer, K, Elmer, P, Ferguson, Dp, Gao, Y, Gonzalez, S, Hayes, Oj, Hu, H, Jin, S, Kile, J, Mcnamara, Pa, Nielsen, J, Orejudos, W, Pan, Yb, Saadi, Y, Scott, Ij, Walsh, J, Wu, Sl, Wu, X, Zobernig, G, and RI ANTONELLI ANTONELLA/C 6238 2011 Jones Roger/H 5578 2011 Passalacqua Luca/F 5127 2011 Murtas Fabrizio/B 5729 2012 O'Shea Val/G 1279, 2010

Subjects
Quark, Nuclear and High Energy Physics, Particle physics, Meson, Electron–positron annihilation, Nuclear Theory, Hadron, FOS: Physical sciences, 7. Clean energy, 01 natural sciences, High Energy Physics - Experiment, Nuclear physics, High Energy Physics - Experiment (hep-ex), 0103 physical sciences, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], B meson, Nuclear Experiment, 010306 general physics, ALEPH experiment, Physics, Missing energy, 010308 nuclear & particles physics, High Energy Physics::Phenomenology, High Energy Physics::Experiment, Particle Physics - Experiment, Lepton
Abstract

The fragmentation of b quarks into B mesons is studied with four million hadronic Z decays collected by the ALEPH experiment during the years 1991-1995. A semi-exclusive reconstruction of B->l nu D(*) decays is performed, by combining lepton candidates with fully reconstructed D(*) mesons while the neutrino energy is estimated from the missing energy of the event. The mean value of xewd, the energy of the weakly-decaying B meson normalised to the beam energy, is found to be mxewd = 0.716 +- 0.006 (stat) +- 0.006 (syst) using a model-independent method; the corresponding value for the energy of the leading B meson is mxel = 0.736 +- 0.006 (stat) +- 0.006 (syst). The reconstructed spectra are compared with different fragmentation models., 21 pages, 5 figures

Published
2001

14. Massive pulmonary embolism as a rare complication of a stab in the inguinal region in a HIV-positive patient: a case report

Author

Sermoneta, D, Gentili, V, Nucera, P, Raso, C, Iozzino, M, Rabuffi, P, and Mellacina, M

Subjects
Adult, Intensive Care Units, Risk Factors, Humans, Female, HIV Infections, Wounds, Stab, Emergency Service, Hospital, Pulmonary Embolism, Tomography, X-Ray Computed
Abstract

Venous thromboembolism (VTE) is a severe preventable disease; HIV-infection represents a prothrombotic condition, because of specific factors due to the virus itself, the host response and the antiretroviral therapy. Our aim is to raise awareness of thromboembolic risk when dealing with HIV-positive patients presenting to the Emergency Department for treatment of injuries, even though small.We present a case of a 33-year-old woman suffering from HIV-infection who presented to the Emergency Department with two small stab wounds. Laboratory tests and radiologic examinations were normal. About 8 hours after admission the patient developed a syncopal attack: a CT scan performed after hemodynamic stabilization revealed a massive pulmonary embolism (PE); the patient was then transferred to the Intensive Care Unit and treated with systemic thrombolysis.This case confirms that HIV-positive patients carry a higher risk for VTE and PE compared to general population, similarly to patients suffering from cancer: emergency physicians must be aware even in case of minor wounds.

Published
2015

15. Four-fermion production in e+e- collisions at centre-of-mass energies of 130 and 136 GeV

Author

Buskulic, D, Debonis, I, Decamp, D, Ghez, P, Goy, C, Lees, J, Lucotte, A, Minard, M, Nief, J, Odier, P, Pietrzyk, B, Casado, M, Chmeissani, M, Crespo, J, Delfino, M, Efthymiopoulos, I, Fernandez, E, Fernandezbosman, M, Garrido, L, Juste, A, Martinez, M, Orteu, S, Padilla, C, Park, I, Pascual, A, Perlas, J, Riu, I, Sanchez, F, Teubert, F, Colaleo, A, Creanza, D, Depalma, M, Gelao, G, Girone, M, Iaselli, G, Maggi, G, Maggi, M, Marinelli, N, Nuzzo, S, Ranieri, A, Raso, C, Ruggieri, F, Selvaggi, G, Silvestris, L, Tempesta, P, Zito, G, Huang, X, Lin, J, Ouyang, Q, Wang, T, Xie, Y, Xu, R, Xue, S, Zhang, J, Zhang, L, Zhao, W, Alemany, R, Bazarko, A, Cattaneo, M, Comas, P, Coyle, P, Drevermann, H, Forty, R, Frank, M, Hagelberg, R, Harvey, J, Janot, P, Jost, B, Kneringer, E, Knobloch, J, Lehraus, I, Lutters, G, Martin, E, Mato, P, Minten, A, Miquel, R, Mir, L, Moneta, L, Oeste, T, Pacheco, A, Pusztaszeri, J, Ranjard, F, Rensing, P, Rolandi, L, Schlatter, D, Schmelling, M, Schmitt, M, Schneider, O, Tejessy, W, Tomalin, I, Venturi, A, Wachsmuth, H, Wagner, A, Ajaltouni, Z, Barres, A, Boyer, C, Falvard, A, Gray, P, Guicheney, C, Henrard, P, Jousset, J, Michel, B, Monteil, S, Montret, J, Pallin, D, Perret, P, Podlyski, F, Proriol, J, Rosnet, P, Rossignol, J, Fearnley, T, Hansen, J, Hansen, P, Nilsson, B, Rensch, B, Waananen, A, Kyriakis, A, Markou, C, Simopoulou, E, Vayaki, A, Zachariadou, K, Blondel, A, Brient, J, Rouge, A, Rumpf, M, Valassi, A, Videau, H, Focardi, E, Parrini, G, Corden, M, Georgiopoulos, C, Jaffe, D, Antonelli, A, Bencivenni, G, Bologna, G, Bossi, F, Campana, P, Capon, G, Casper, D, Chiarella, V, Felici, G, Laurelli, P, Mannocchi, G, Murtas, F, Murtas, G, Passalacqua, L, Pepealtarelli, M, Curtis, L, Dorris, S, Halley, A, Knowles, I, Lynch, J, Oshea, V, Raine, C, Reeves, P, Scarr, J, Smith, K, Teixeiradias, P, Thompson, A, Thomson, F, Thorn, S, Turnbull, R, Becker, U, Geweniger, C, Graefe, G, Hanke, P, Hansper, G, Hepp, V, Kluge, E, Putzer, A, Schmidt, M, Sommer, J, Stenzel, H, Tittel, K, Werner, S, Wunsch, M, Abbaneo, D, Beuselinck, R, Binnie, D, Cameron, W, Dornan, P, Morawitz, P, Moutoussi, A, Nash, J, Sedgbeer, J, Stacey, A, Williams, M, Dissertori, G, Girtler, P, Kuhn, D, Rudolph, G, Betteridge, A, Bowdery, C, Colrain, P, Crawford, G, Finch, A, Foster, F, Hughes, G, Sloan, T, Whelan, E, Galla, A, Greene, A, Hoffmann, C, Jacobs, K, Kleinknecht, K, Quast, G, Renk, B, Rohne, E, Sander, H, Vangemmeren, P, Zeitnitz, C, Aubert, J, Bencheikh, A, Benchouk, C, Bonissent, A, Bujosa, G, Calvet, D, Carr, J, Diaconu, C, Konstantinidis, N, Payre, P, Rousseau, D, Talby, M, Sadouki, A, Thulasidas, M, Tilquin, A, Trabelsi, K, Aleppo, M, Ragusa, F, Bauer, C, Berlich, R, Blum, W, Buscher, V, Dietl, H, Dydak, F, Ganis, G, Gotzhein, C, Kroha, H, Lutjens, G, Lutz, G, Manner, W, Moser, H, Richter, R, Rosadoschlosser, A, Schael, S, Settles, R, Seywerd, H, Denis, R, Wiedenmann, W, Wolf, G, Boucrot, J, Callot, O, Cordier, A, Davier, M, Duflot, L, Grivaz, J, Heusse, P, Hocker, A, Jacholkowska, A, Jacquet, M, Kim, D, Lediberder, F, Lefrancois, J, Lutz, A, Nikolic, I, Park, H, Schune, M, Simion, S, Veillet, J, Videau, I, Zerwas, D, Azzurri, P, Bagliesi, G, Batignani, G, Bettarini, S, Bozzi, C, Calderini, G, Carpinelli, M, Ciocci, M, Ciulli, V, Dellorso, R, Fantechi, R, Ferrante, I, Giassi, A, Gregorio, A, Ligabue, F, Lusiani, A, Marrocchesi, P, Messineo, A, Palla, F, Rizzo, G, Sanguinetti, G, Sciaba, A, Spagnolo, P, Steinberger, J, Tenchini, R, Tonelli, G, Vannini, C, Verdini, P, Walsh, J, Blair, G, Bryant, L, Cerutti, F, Chambers, J, Gao, Y, Green, M, Medcalf, T, Perrodo, P, Strong, J, Vonwimmerspergtoeller, J, Botterill, D, Clifft, R, Edgecock, T, Haywood, S, Maley, P, Norton, P, Thompson, J, Wright, A, Blochdevaux, B, Colas, P, Emery, S, Kozanecki, W, Lancon, E, Lemaire, M, Locci, E, Marx, B, Perez, P, Rander, J, Renardy, J, Roussarie, A, Schuller, J, Schwindling, J, Trabelsi, A, Vallage, B, Black, S, Dann, J, Johnson, R, Kim, C, Litke, A, Mcneil, M, Taylor, G, Booth, C, Boswell, R, Brew, C, Cartwright, S, Combley, F, Koksal, A, Letho, M, Newton, W, Reeve, J, Thompson, L, Bohrer, A, Brandt, S, Cowan, G, Grupen, C, Saraiva, P, Smolik, L, Stephan, F, Apollonio, M, Bosisio, L, Dellamarina, R, Giannini, G, Gobbo, B, Musolino, G, Putz, J, Rothberg, J, Wasserbaech, S, Williams, R, Armstrong, S, Elmer, P, Feng, Z, Ferguson, D, Gonzalez, S, Grahl, J, Greening, T, Hayes, O, Hu, H, Mcnamara, P, Nachtman, J, Orejudos, W, Pan, Y, Saadi, Y, Scott, I, Walsh, A, Wu, S, Wu, X, Yamartino, J, Zheng, M, Zobernig, G, Buskulic D, DeBonis I, Decamp D, Ghez P, Goy C, Lees JP, Lucotte A, Minard MN, Nief JY, Odier P, Pietrzyk B, Casado MP, Chmeissani M, Crespo JM, Delfino M, Efthymiopoulos I, Fernandez E, FernandezBosman M, Garrido L, Juste A, Martinez M, Orteu S, Padilla C, Park IC, Pascual A, Perlas JA, Riu I, Sanchez F, Teubert F, Colaleo A, Creanza D, dePalma M, Gelao G, Girone M, Iaselli G, Maggi G, Maggi M, Marinelli N, Nuzzo S, Ranieri A, Raso C, Ruggieri F, Selvaggi G, Silvestris L, Tempesta P, Zito G, Huang X, Lin J, Ouyang Q, Wang T, Xie Y, Xu R, Xue S, Zhang J, Zhang L, Zhao W, Alemany R, Bazarko AO, Cattaneo M, Comas P, Coyle P, Drevermann H, Forty RW, Frank M, Hagelberg R, Harvey J, Janot P, Jost B, Kneringer E, Knobloch J, Lehraus I, Lutters G, Martin EB, Mato P, Minten A, Miquel R, Mir LM, Moneta L, Oeste T, Pacheco A, Pusztaszeri JF, Ranjard F, Rensing P, Rolandi L, Schlatter D, Schmelling M, Schmitt M, Schneider O, Tejessy W, Tomalin IR, Venturi A, Wachsmuth H, Wagner A, Ajaltouni Z, Barres A, Boyer C, Falvard A, Gray P, Guicheney C, Henrard P, Jousset J, Michel B, Monteil S, Montret JC, Pallin D, Perret P, Podlyski F, Proriol J, Rosnet P, Rossignol JM, Fearnley T, Hansen JB, Hansen JD, Hansen JR, Hansen PH, Nilsson BS, Rensch B, Waananen A, Kyriakis A, Markou C, Simopoulou E, Vayaki A, Zachariadou K, Blondel A, Brient JC, Rouge A, Rumpf M, Valassi A, Videau H, Focardi E, Parrini G, Corden M, Georgiopoulos C, Jaffe DE, Antonelli A, Bencivenni G, Bologna G, Bossi F, Campana P, Capon G, Casper D, Chiarella V, Felici G, Laurelli P, Mannocchi G, Murtas F, Murtas GP, Passalacqua L, PepeAltarelli M, Curtis L, Dorris SJ, Halley AW, Knowles IG, Lynch JG, OShea V, Raine C, Reeves P, Scarr JM, Smith K, TeixeiraDias P, Thompson AS, Thomson F, Thorn S, Turnbull RM, Becker U, Geweniger C, Graefe G, Hanke P, Hansper G, Hepp V, Kluge EE, Putzer A, Schmidt M, Sommer J, Stenzel H, Tittel K, Werner S, Wunsch M, Abbaneo D, Beuselinck R, Binnie DM, Cameron W, Dornan PJ, Morawitz P, Moutoussi A, Nash J, Sedgbeer JK, Stacey AM, Williams MD, Dissertori G, Girtler P, Kuhn D, Rudolph G, Betteridge AP, Bowdery CK, Colrain P, Crawford G, Finch AJ, Foster F, Hughes G, Sloan T, Whelan EP, Williams MI, Galla A, Greene AM, Hoffmann C, Jacobs K, Kleinknecht K, Quast G, Renk B, Rohne E, Sander HG, vanGemmeren P, Zeitnitz C, Aubert JJ, Bencheikh AM, Benchouk C, Bonissent A, Bujosa G, Calvet D, Carr J, Diaconu C, Konstantinidis N, Payre P, Rousseau D, Talby M, Sadouki A, Thulasidas M, Tilquin A, Trabelsi K, Aleppo M, Ragusa F, Bauer C, Berlich R, Blum W, Buscher V, Dietl H, Dydak F, Ganis G, Gotzhein C, Kroha H, Lutjens G, Lutz G, Manner W, Moser HG, Richter R, RosadoSchlosser A, Schael S, Settles R, Seywerd H, Denis RS, Wiedenmann W, Wolf G, Boucrot J, Callot O, Cordier A, Davier M, Duflot L, Grivaz JF, Heusse P, Hocker A, Jacholkowska A, Jacquet M, Kim DW, LeDiberder F, Lefrancois J, Lutz AM, Nikolic I, Park HJ, Schune MH, Simion S, Veillet JJ, Videau I, Zerwas D, Azzurri P, Bagliesi G, Batignani G, Bettarini S, Bozzi C, Calderini G, CARPINELLI, Massimo, Ciocci MA, Ciulli V, DellOrso R, Fantechi R, Ferrante I, Giassi A, Gregorio A, Ligabue F, Lusiani A, Marrocchesi PS, Messineo A, Palla F, Rizzo G, Sanguinetti G, Sciaba A, Spagnolo P, Steinberger J, Tenchini R, Tonelli G, Vannini C, Verdini PG, Walsh J, Blair GA, Bryant LM, Cerutti F, Chambers JT, Gao Y, Green MG, Medcalf T, Perrodo P, Strong JA, vonWimmerspergToeller JH, Botterill DR, Clifft RW, Edgecock TR, Haywood S, Maley P, Norton PR, Thompson JC, Wright AE, BlochDevaux B, Colas P, Emery S, Kozanecki W, Lancon E, Lemaire MC, Locci E, Marx B, Perez P, Rander J, Renardy JF, Roussarie A, Schuller JP, Schwindling J, Trabelsi A, Vallage B, Black SN, Dann JH, Johnson RP, Kim CAJ, Litke AM, McNeil MA, Taylor G, Booth CN, Boswell R, Brew CAJ, Cartwright S, Combley F, Koksal A, Letho M, Newton WM, Reeve J, Thompson LF, Bohrer A, Brandt S, Cowan G, Grupen C, Saraiva P, Smolik L, Stephan F, Apollonio M, Bosisio L, DellaMarina R, Giannini G, Gobbo B, Musolino G, Putz J, Rothberg J, Wasserbaech S, Williams RW, Armstrong SR, Elmer P, Feng Z, Ferguson DPS, Gao YS, Gonzalez S, Grahl J, Greening TC, Hayes OJ, Hu H, McNamara PA, Nachtman JM, Orejudos W, Pan YB, Saadi Y, Scott IJ, Walsh AM, Wu SL, Wu X, Yamartino JM, Zheng M, Zobernig G., Buskulic, D, Debonis, I, Decamp, D, Ghez, P, Goy, C, Lees, J, Lucotte, A, Minard, M, Nief, J, Odier, P, Pietrzyk, B, Casado, M, Chmeissani, M, Crespo, J, Delfino, M, Efthymiopoulos, I, Fernandez, E, Fernandezbosman, M, Garrido, L, Juste, A, Martinez, M, Orteu, S, Padilla, C, Park, I, Pascual, A, Perlas, J, Riu, I, Sanchez, F, Teubert, F, Colaleo, A, Creanza, D, Depalma, M, Gelao, G, Girone, M, Iaselli, G, Maggi, G, Maggi, M, Marinelli, N, Nuzzo, S, Ranieri, A, Raso, C, Ruggieri, F, Selvaggi, G, Silvestris, L, Tempesta, P, Zito, G, Huang, X, Lin, J, Ouyang, Q, Wang, T, Xie, Y, Xu, R, Xue, S, Zhang, J, Zhang, L, Zhao, W, Alemany, R, Bazarko, A, Cattaneo, M, Comas, P, Coyle, P, Drevermann, H, Forty, R, Frank, M, Hagelberg, R, Harvey, J, Janot, P, Jost, B, Kneringer, E, Knobloch, J, Lehraus, I, Lutters, G, Martin, E, Mato, P, Minten, A, Miquel, R, Mir, L, Moneta, L, Oeste, T, Pacheco, A, Pusztaszeri, J, Ranjard, F, Rensing, P, Rolandi, L, Schlatter, D, Schmelling, M, Schmitt, M, Schneider, O, Tejessy, W, Tomalin, I, Venturi, A, Wachsmuth, H, Wagner, A, Ajaltouni, Z, Barres, A, Boyer, C, Falvard, A, Gray, P, Guicheney, C, Henrard, P, Jousset, J, Michel, B, Monteil, S, Montret, J, Pallin, D, Perret, P, Podlyski, F, Proriol, J, Rosnet, P, Rossignol, J, Fearnley, T, Hansen, J, Hansen, P, Nilsson, B, Rensch, B, Waananen, A, Kyriakis, A, Markou, C, Simopoulou, E, Vayaki, A, Zachariadou, K, Blondel, A, Brient, J, Rouge, A, Rumpf, M, Valassi, A, Videau, H, Focardi, E, Parrini, G, Corden, M, Georgiopoulos, C, Jaffe, D, Antonelli, A, Bencivenni, G, Bologna, G, Bossi, F, Campana, P, Capon, G, Casper, D, Chiarella, V, Felici, G, Laurelli, P, Mannocchi, G, Murtas, F, Murtas, G, Passalacqua, L, Pepealtarelli, M, Curtis, L, Dorris, S, Halley, A, Knowles, I, Lynch, J, Oshea, V, Raine, C, Reeves, P, Scarr, J, Smith, K, Teixeiradias, P, Thompson, A, Thomson, F, Thorn, S, Turnbull, R, Becker, U, Geweniger, C, Graefe, G, Hanke, P, Hansper, G, Hepp, V, Kluge, E, Putzer, A, Schmidt, M, Sommer, J, Stenzel, H, Tittel, K, Werner, S, Wunsch, M, Abbaneo, D, Beuselinck, R, Binnie, D, Cameron, W, Dornan, P, Morawitz, P, Moutoussi, A, Nash, J, Sedgbeer, J, Stacey, A, Williams, M, Dissertori, G, Girtler, P, Kuhn, D, Rudolph, G, Betteridge, A, Bowdery, C, Colrain, P, Crawford, G, Finch, A, Foster, F, Hughes, G, Sloan, T, Whelan, E, Galla, A, Greene, A, Hoffmann, C, Jacobs, K, Kleinknecht, K, Quast, G, Renk, B, Rohne, E, Sander, H, Vangemmeren, P, Zeitnitz, C, Aubert, J, Bencheikh, A, Benchouk, C, Bonissent, A, Bujosa, G, Calvet, D, Carr, J, Diaconu, C, Konstantinidis, N, Payre, P, Rousseau, D, Talby, M, Sadouki, A, Thulasidas, M, Tilquin, A, Trabelsi, K, Aleppo, M, Ragusa, F, Bauer, C, Berlich, R, Blum, W, Buscher, V, Dietl, H, Dydak, F, Ganis, G, Gotzhein, C, Kroha, H, Lutjens, G, Lutz, G, Manner, W, Moser, H, Richter, R, Rosadoschlosser, A, Schael, S, Settles, R, Seywerd, H, Denis, R, Wiedenmann, W, Wolf, G, Boucrot, J, Callot, O, Cordier, A, Davier, M, Duflot, L, Grivaz, J, Heusse, P, Hocker, A, Jacholkowska, A, Jacquet, M, Kim, D, Lediberder, F, Lefrancois, J, Lutz, A, Nikolic, I, Park, H, Schune, M, Simion, S, Veillet, J, Videau, I, Zerwas, D, Azzurri, P, Bagliesi, G, Batignani, G, Bettarini, S, Bozzi, C, Calderini, G, Carpinelli, M, Ciocci, M, Ciulli, V, Dellorso, R, Fantechi, R, Ferrante, I, Giassi, A, Gregorio, A, Ligabue, F, Lusiani, A, Marrocchesi, P, Messineo, A, Palla, F, Rizzo, G, Sanguinetti, G, Sciaba, A, Spagnolo, P, Steinberger, J, Tenchini, R, Tonelli, G, Vannini, C, Verdini, P, Walsh, J, Blair, G, Bryant, L, Cerutti, F, Chambers, J, Gao, Y, Green, M, Medcalf, T, Perrodo, P, Strong, J, Vonwimmerspergtoeller, J, Botterill, D, Clifft, R, Edgecock, T, Haywood, S, Maley, P, Norton, P, Thompson, J, Wright, A, Blochdevaux, B, Colas, P, Emery, S, Kozanecki, W, Lancon, E, Lemaire, M, Locci, E, Marx, B, Perez, P, Rander, J, Renardy, J, Roussarie, A, Schuller, J, Schwindling, J, Trabelsi, A, Vallage, B, Black, S, Dann, J, Johnson, R, Kim, C, Litke, A, Mcneil, M, Taylor, G, Booth, C, Boswell, R, Brew, C, Cartwright, S, Combley, F, Koksal, A, Letho, M, Newton, W, Reeve, J, Thompson, L, Bohrer, A, Brandt, S, Cowan, G, Grupen, C, Saraiva, P, Smolik, L, Stephan, F, Apollonio, M, Bosisio, L, Dellamarina, R, Giannini, G, Gobbo, B, Musolino, G, Putz, J, Rothberg, J, Wasserbaech, S, Williams, R, Armstrong, S, Elmer, P, Feng, Z, Ferguson, D, Gonzalez, S, Grahl, J, Greening, T, Hayes, O, Hu, H, Mcnamara, P, Nachtman, J, Orejudos, W, Pan, Y, Saadi, Y, Scott, I, Walsh, A, Wu, S, Wu, X, Yamartino, J, Zheng, M, Zobernig, G, Buskulic D, DeBonis I, Decamp D, Ghez P, Goy C, Lees JP, Lucotte A, Minard MN, Nief JY, Odier P, Pietrzyk B, Casado MP, Chmeissani M, Crespo JM, Delfino M, Efthymiopoulos I, Fernandez E, FernandezBosman M, Garrido L, Juste A, Martinez M, Orteu S, Padilla C, Park IC, Pascual A, Perlas JA, Riu I, Sanchez F, Teubert F, Colaleo A, Creanza D, dePalma M, Gelao G, Girone M, Iaselli G, Maggi G, Maggi M, Marinelli N, Nuzzo S, Ranieri A, Raso C, Ruggieri F, Selvaggi G, Silvestris L, Tempesta P, Zito G, Huang X, Lin J, Ouyang Q, Wang T, Xie Y, Xu R, Xue S, Zhang J, Zhang L, Zhao W, Alemany R, Bazarko AO, Cattaneo M, Comas P, Coyle P, Drevermann H, Forty RW, Frank M, Hagelberg R, Harvey J, Janot P, Jost B, Kneringer E, Knobloch J, Lehraus I, Lutters G, Martin EB, Mato P, Minten A, Miquel R, Mir LM, Moneta L, Oeste T, Pacheco A, Pusztaszeri JF, Ranjard F, Rensing P, Rolandi L, Schlatter D, Schmelling M, Schmitt M, Schneider O, Tejessy W, Tomalin IR, Venturi A, Wachsmuth H, Wagner A, Ajaltouni Z, Barres A, Boyer C, Falvard A, Gray P, Guicheney C, Henrard P, Jousset J, Michel B, Monteil S, Montret JC, Pallin D, Perret P, Podlyski F, Proriol J, Rosnet P, Rossignol JM, Fearnley T, Hansen JB, Hansen JD, Hansen JR, Hansen PH, Nilsson BS, Rensch B, Waananen A, Kyriakis A, Markou C, Simopoulou E, Vayaki A, Zachariadou K, Blondel A, Brient JC, Rouge A, Rumpf M, Valassi A, Videau H, Focardi E, Parrini G, Corden M, Georgiopoulos C, Jaffe DE, Antonelli A, Bencivenni G, Bologna G, Bossi F, Campana P, Capon G, Casper D, Chiarella V, Felici G, Laurelli P, Mannocchi G, Murtas F, Murtas GP, Passalacqua L, PepeAltarelli M, Curtis L, Dorris SJ, Halley AW, Knowles IG, Lynch JG, OShea V, Raine C, Reeves P, Scarr JM, Smith K, TeixeiraDias P, Thompson AS, Thomson F, Thorn S, Turnbull RM, Becker U, Geweniger C, Graefe G, Hanke P, Hansper G, Hepp V, Kluge EE, Putzer A, Schmidt M, Sommer J, Stenzel H, Tittel K, Werner S, Wunsch M, Abbaneo D, Beuselinck R, Binnie DM, Cameron W, Dornan PJ, Morawitz P, Moutoussi A, Nash J, Sedgbeer JK, Stacey AM, Williams MD, Dissertori G, Girtler P, Kuhn D, Rudolph G, Betteridge AP, Bowdery CK, Colrain P, Crawford G, Finch AJ, Foster F, Hughes G, Sloan T, Whelan EP, Williams MI, Galla A, Greene AM, Hoffmann C, Jacobs K, Kleinknecht K, Quast G, Renk B, Rohne E, Sander HG, vanGemmeren P, Zeitnitz C, Aubert JJ, Bencheikh AM, Benchouk C, Bonissent A, Bujosa G, Calvet D, Carr J, Diaconu C, Konstantinidis N, Payre P, Rousseau D, Talby M, Sadouki A, Thulasidas M, Tilquin A, Trabelsi K, Aleppo M, Ragusa F, Bauer C, Berlich R, Blum W, Buscher V, Dietl H, Dydak F, Ganis G, Gotzhein C, Kroha H, Lutjens G, Lutz G, Manner W, Moser HG, Richter R, RosadoSchlosser A, Schael S, Settles R, Seywerd H, Denis RS, Wiedenmann W, Wolf G, Boucrot J, Callot O, Cordier A, Davier M, Duflot L, Grivaz JF, Heusse P, Hocker A, Jacholkowska A, Jacquet M, Kim DW, LeDiberder F, Lefrancois J, Lutz AM, Nikolic I, Park HJ, Schune MH, Simion S, Veillet JJ, Videau I, Zerwas D, Azzurri P, Bagliesi G, Batignani G, Bettarini S, Bozzi C, Calderini G, CARPINELLI, Massimo, Ciocci MA, Ciulli V, DellOrso R, Fantechi R, Ferrante I, Giassi A, Gregorio A, Ligabue F, Lusiani A, Marrocchesi PS, Messineo A, Palla F, Rizzo G, Sanguinetti G, Sciaba A, Spagnolo P, Steinberger J, Tenchini R, Tonelli G, Vannini C, Verdini PG, Walsh J, Blair GA, Bryant LM, Cerutti F, Chambers JT, Gao Y, Green MG, Medcalf T, Perrodo P, Strong JA, vonWimmerspergToeller JH, Botterill DR, Clifft RW, Edgecock TR, Haywood S, Maley P, Norton PR, Thompson JC, Wright AE, BlochDevaux B, Colas P, Emery S, Kozanecki W, Lancon E, Lemaire MC, Locci E, Marx B, Perez P, Rander J, Renardy JF, Roussarie A, Schuller JP, Schwindling J, Trabelsi A, Vallage B, Black SN, Dann JH, Johnson RP, Kim CAJ, Litke AM, McNeil MA, Taylor G, Booth CN, Boswell R, Brew CAJ, Cartwright S, Combley F, Koksal A, Letho M, Newton WM, Reeve J, Thompson LF, Bohrer A, Brandt S, Cowan G, Grupen C, Saraiva P, Smolik L, Stephan F, Apollonio M, Bosisio L, DellaMarina R, Giannini G, Gobbo B, Musolino G, Putz J, Rothberg J, Wasserbaech S, Williams RW, Armstrong SR, Elmer P, Feng Z, Ferguson DPS, Gao YS, Gonzalez S, Grahl J, Greening TC, Hayes OJ, Hu H, McNamara PA, Nachtman JM, Orejudos W, Pan YB, Saadi Y, Scott IJ, Walsh AM, Wu SL, Wu X, Yamartino JM, Zheng M, and Zobernig G.

Abstract

Four-fermion events have been selected in a data sample of 5.8 pb-1 collected with the ALEPH detector at centre-of-mass energies of 130 and 136 GeV. The final states l+l-qq̄, l+l-l+l -,vv̄qq̄, and vv̄l+l- have been examined. Five events are observed in the data, in agreement with the Standard Model predictions of 6.67 ± 0.38 events from four-fermion processes and 0.14 +0.19 -0.05 from background processes.

Published
1996

19. Singao: A very large telescope for neutrino gamma astronomy and cosmic rays studies

Author

De Palma, M., primary, Iaselli, G., additional, Maggi, C., additional, Natali, S., additional, Nuzzo, S., additional, Ranieri, A., additional, Raso, C., additional, Romano, F., additional, Ruggeri, F., additional, Selvaggi, G., additional, Tempesta, P., additional, Zito, G., additional, Rossi, A., additional, Susinno, G., additional, Grillo, A., additional, Ronga, F., additional, Valente, V., additional, Bernardini, P., additional, Pistilli, P., additional, Watson, A., additional, Reid, R., additional, Lawrence, M., additional, Ambrosio, M., additional, Barbarino, G., additional, Bartoli, B., additional, Silvestrini, V., additional, Buccheri, R., additional, Carollo, M., additional, Catalano, O., additional, Linsley, J., additional, Scarsi, L., additional, Bressi, G., additional, Lanza, A., additional, Cambiaghi, M., additional, Ratti, S., additional, Bonori, M., additional, D'Agostini, G., additional, De Vincenzi, M., additional, Lamanna, E., additional, Lipari, P., additional, Martellotti, G., additional, Massa, F., additional, Mattioli, M., additional, Nigro, A., additional, Petrera, S., additional, Cardarelli, R., additional, Rossi, F., additional, Santonico, R., additional, De Cesare, L., additional, Grella, G., additional, Guida, M., additional, Mancini, F., additional, Marini, G., additional, Romano, G., additional, Vitiello, G., additional, Cappa, C., additional, D'Ettorre Piazzoli, B., additional, Ghia, P., additional, Gomez, G., additional, and Trivero, P., additional

Published
1990
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21. Assessing modifications of the intestinal bacterial flora in patients on long-term oral treatment with bacampicillin or amoxicillin: a random study

Author

Gipponi, M., Sciutto, C., Accornero, L., stefano bonassi, Raso, C., Vignolo, C., and Cafiero, F.

Subjects
Adult, Intestines, Time Factors, Amoxicillin, Humans, Ampicillin, Middle Aged, Aged
Abstract

The authors conducted a randomized trial on 16 patients to evaluate intestinal aerobic microfloral changes after prolonged oral treatment with bacampicillin (b.) (16 g/die) or amoxicillin (a.) (2 g/die). The analysis showed a quantitative reduction of isolates in 6 patients: 2 patients were treated with b. while 4 with a. (Odd ratio, O.R. = 3). Mean values of CFU presented as well a more evident reduction in a.-treated patients. From the qualitative point of view, bacteria modifications occurred in one patient treated with b. and 3 with a, (O.R. = 4.2). Bacterial changes, although not statistically significant, were thus greater in patients treated with a. than b.

Published
1985

24. Gliomatosis cerebri presenting as rapidly progressive dementia and parkinsonism in an elderly woman: a case report

Author

Duron Emmanuelle, Lazareth Anne, Gaubert Jean-Yves, Raso Carole, Hanon Olivier, and Rigaud Anne-Sophie

Subjects
Medicine
Abstract

Abstract Introduction Dementia is one of the most important neurological disorders in the elderly. Dementia of tumoral origin is rare and parkinsonism of neoplastic origin is unusual. We herein report a case of gliomatosis cerebri, a very rare brain tumor seldom affecting the elderly, which presented as rapidly progressive dementia and parkinsonism. Case presentation An 82-year-old woman very rapidly developed progressive dementia and akineto-rigid parkinsonism. Brain CT scan was normal. Cerebral magnetic resonance imaging (MRI) with gadolinium injection highlighted a diffuse tumor-related infiltration involving both lobes, the putamen, the pallidum, the substantia nigra, and the brainstem, corresponding to the specific description and definition of gliomatosis cerebri. Conclusion This atypical presentation of a gliomatosis cerebri, and the infiltration of the substantia nigra by the tumor, merits attention.

Published
2008
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25. Sigma-2 Receptor Expression in Bovine Papillomavirus-Associated Urinary Bladder Tumours

Author

Franco Roperto, Cinzia Raso, S. Staibano, Chiara Urraro, Sante Roperto, Valentina Russo, R. Brun, E. Palma, Nicola Antonio Colabufo, Carmela Inglese, E. Mezza, Paola Maiolino, Roperto, Sante, Colabufo, N. A., Inglese, C., Urraro, Chiara, Brun, R., Mezza, E., Staibano, S., Raso, C., Maiolino, Paola, Russo, Valeria, Palma, E., Roperto, FRANCO PEPPINO, Colabufo, Na, Inglese, C, Urraro, C, Brun, R, Mezza, E, Staibano, Stefania, Raso, C, Russo, V, and Palma, E

Subjects
Pathology, medicine.medical_specialty, biosynthesis, Papillomavirus Infection, Animals, Carcinoma, Nuclear area, Sigma-2 receptor, Cattle Diseases, sigma, Urine, Polymerase Chain Reaction, Pathology and Forensic Medicine, biosynthesis, Urinary Bladder Neoplasm, Bladder Tissue, medicine, Carcinoma, Animals, Immunoprecipitation, Receptors, sigma, analysis, Immunoprecipitation, Oncogene Protein, Viral, Receptor, Bovine papillomavirus, Urinary bladder, General Veterinary, biology, Papillomavirus Infections, Oncogene Proteins, Viral, biology.organism_classification, medicine.disease, Molecular biology, complications/metabolism/therapy/veterinary, Polymerase Chain Reaction, Receptor, metabolism/virology, DNA, medicine.anatomical_structure, Urinary Bladder Neoplasms, DNA, Viral, Cattle, metabolism/veterinary/virology, Cattle, Cattle Disease, metabolism/veterinary/virology
Abstract

Summary The expression of sigma-2 receptors was investigated in nine urothelial tumours of the urinary bladder of cattle. Each tumour was associated with the presence of DNA of bovine papillomavirus type-2 (BPV-2) and expression of the E5 viral oncoprotein. Five tumours were classified as low-grade carcinoma on the basis of morphological criteria and calculation of mean nuclear area (MNA) and mean nuclear perimeter (MNP). Four tumours were classified as high-grade carcinoma. Sigma-2 receptors were overexpressed in both types of carcinoma. In control normal bovine bladder tissue the density of receptors (expressed as the Bmax) was 0.37 pmol/mg of protein. Low-grade carcinomas had a mean Bmax of 1.37 � 0.32 pmol/mg of protein (range 1.03e1.86) and in high-grade carcinomas the mean Bmax was 10.9 � 2.8 pmol/mg of protein (range 8.2e14). The difference in Bmax between low- and high-grade carcinomas was statistically significant (P ¼ 0.0001). 2009 Elsevier Ltd. All rights reserved.

Published
2010

26. Searches for neutral Higgs bosons in e+e− collisions at centre-of-mass energies from 192 to 202 GeV

Author

H. Videau, A. Misiejuk, B. Gobbo, H. Dietl, Alain Bonissent, S. Dhamotharan, S. L. Cartwright, Dirk Zerwas, Pablo Rodriguez Perez, Maria Girone, Boris Tuchming, Duccio Abbaneo, J. F. Renardy, Elizabeth Locci, Jiali Lin, Andrea Venturi, J.M. Pascolo, P. Coyle, L. Duflot, L. Garrido, L. Passalacqua, J.C. Thompson, L. M. Mir, G. Maggi, Andrea Valassi, J H. Von Wimmersperg-Toller, Salvatore Nuzzo, Dominique Pallin, David J. Smith, Gerardo Ganis, M. Aleppo, H. Drevermann, Paolo Spagnolo, D. Fouchez, R. Settles, Werner Wiedenmann, C. Curtil, Alan Litke, M. Kröcker, J. Carr, E. Fernandez, Georg Zobernig, M. G. Green, K. Affholderbach, S. Gonzalez, K. Tittel, Konrad Kleinknecht, Claus Grupen, G. Hughes, A.E. Wright, P. Girtler, G. Merino, H.-A. Nürnberger, W. Zhao, A. Antonelli, Vitaliano Chiarella, André Rosowsky, A. Vayaki, Giacomo Sguazzoni, Jie Zhang, G. Lütjens, G. B. Taylor, P. Tempesta, Pierluigi Campana, John-Bjarne Hansen, I.J. Scott, M. Davier, J. Hess, W. Tejessy, M. Maggi, M. C. Lemaire, Donato Creanza, Aristotelis Kyriakis, Massimo Antonelli, J. Kile, K. Zachariadou, Y. B. Pan, G. Calderini, P. A. McNamara, D. Fayolle, N. A. Robertson, X. Huang, Paolo Laurelli, B. Bloch-Devaux, J. Coles, F. Ruggieri, D. Decamp, Paul Hodgson, Markus Frank, D. Kuhn, John T Harvey, Alessandro Giassi, Giuseppe Iaselli, F. Ranjard, G. Mannocchi, N. De Filippis, E. Rohne, C. Mannert, F. Murtas, Emmerich Kneringer, Oliver Buchmuller, W. Orejudos, Ian R Tomalin, G. Ellis, M. Swynghedauw, P. Teixeira-Dias, G. Leibenguth, Kyle Cranmer, A. Sciabà, G. Prange, A. Jacholkowska, O. Callot, E. Tournefier, V. Lemaitre, F. Combley, Q. Ouyang, Giuseppe Raso, S. Wasserbaech, S. Werner, David Hutchcroft, A. Ealet, S. Brandt, O.J. Hayes, Roberto Tenchini, Ting Wang, S. L. Wu, F. Teubert, V. Hepp, G. Rudolph, P.G. Buck, B. Pietrzyk, H. Przysiezniak, M. Pepe-Altarelli, C. Markou, T. R. Edgecock, Piero Giorgio Verdini, Lorenzo Foà, C. Borean, Simone Gilardoni, J. Nowell, B. Michel, D.P.S. Ferguson, J. B. De Vivie De Regie, H. G. Sander, V. M. Ghete, G.P. Murtas, Anna Colaleo, E. Grauges, F. Machefert, F. Gianotti, G. Bologna, M. Chalmers, Nancy Marinelli, J. J. Walsh, G. Boix, D. Schlatter, Karl Jakobs, E. Merle, Paul Hanke, I. Giehl, T. Ziegler, D. Rousseau, B. Fabbro, B. Jost, Pascal Perret, Alberto Messineo, J.J. Ward, Gy. Wolf, B. Raven, G. Bencivenni, Barbara Clerbaux, Reisaburo Tanaka, Roger Forty, P. Ghez, W. Cameron, F. Hölldorfer, P. Seager, Maria Pilar Casado, Djamel Eddine Boumediene, G. Giannini, C. N. Booth, H. Hu, T.C. Greening, M. Fernandez-Bosman, Maria Smizanska, Evelyn Thomson, A. Minten, J. Putz, Jean-Francois Grivaz, Andrea Giammanco, P. Negus, Paolo Azzurri, Günther Dissertori, C. K. Bowdery, Jean-Claude Montret, Yuehong Xie, Giuseppe Bagliesi, B. Vallage, G. A. Cowan, Chang-Zheng Yuan, Y. S. Gao, Lester D.R. Thompson, J. Jousset, Michael Schmitt, D.P. Clarke, J. Kennedy, N. Konstantinidis, R. White, Ziad Ajaltouni, J. A. Strong, Y. Saadi, E. Simopoulou, Giuseppe Zito, D. M. Binnie, Ettore Focardi, V. Ciulli, S. Dessagne, F. Badaud, John Rander, A. J. Finch, Giovanna Selvaggi, M. De Palma, O. Schneider, J. P. Lees, P. Mato, JunJie Wu, P. J. Dornan, P. H. Hansen, B.S. Nilsson, A. David, S. Xue, J. Nielsen, Fabrizio Palla, Hasko Stenzel, R. Xu, J. J. Veillet, Franco Ligabue, G. Sanguinetti, Francesco Ragusa, Peter Elmer, Lei Zhang, J. Boucrot, B. Renk, Richard Cavanaugh, Patrick Janot, H. G. Moser, Marumi Kado, L. Rolandi, I. Videau, L.T. Jones, G. Parrini, A. Blondel, G. Capon, S. Schael, P. Colas, H. He, M. Martinez, Ramon Miquel, A. Trabelsi, A. S. Thompson, P. R. Norton, J. Lopez, Gavin Davies, J. D. Hansen, P. Payre, Marco Cattaneo, M. Chmeissani, Georgios Daskalakis, Laurent Serin, R. Beuselinck, C. Geweniger, W. Männer, C. Goy, F. Bossi, Val O'Shea, A. Wäänänen, A. Putzer, Olivier Leroy, F. Podlyski, F. Foster, A. Pacheco, A. Böhrer, Eric Lancon, H. Ruiz, R. W.L. Jones, R. Barate, Gunter Quast, Pierre Henrard, A. Ranieri, Tommaso Boccali, John H. L. Hansen, S.R. Armstrong, S. Schmeling, Stephane Monteil, U. Sieler, E. E. Kluge, T. Kachelhoffer, David Paneque, E. Bouhova-Tracker, K. Hüttmann, J. Rothberg, Alessia Tricomi, M.-N. Minard, M. Wunsch, Stephane Jezequel, Fabio Cerutti, J. M. Crespo, R. W. Clifft, Xin Wu, H. Wachsmuth, J.G. Lynch, A. Rougé, F. Martin, C. Loomis, Alain Falvard, J. K. Sedgbeer, P. Maley, M H. Lehto, Christian Zeitnitz, S. Bravo, T. Medcalf, G.A. Blair, Lucia Silvestris, S. Jin, Ph. Heusse, A.-S. Müller, A. W. Halley, A. Moutoussi, J. C. Brient, Andre Tilquin, 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 Physique Corpusculaire - Clermont-Ferrand (LPC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Leprince-Ringuet (LLR), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'Accélérateur Linéaire (LAL), 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), ALEPH, Barate, R, Decamp, D, Ghez, P, Goy, C, Jezequel, S, Lees, Jp, Martin, F, Merle, E, Minard, Mn, Pietrzyk, B, Bravo, S, Casado, Mp, Chmeissani, M, Crespo, Jm, Fernandez, E, Fernandez Bosman, M, Garrido, L, Grauges, E, Lopez, J, Martinez, M, Merino, G, Miquel, R, Mir, Lm, Pacheco, A, Paneque, D, Ruiz, H, Colaleo, A, Creanza, D, De Filippis, N, de Palma, M, Iaselli, G, Maggi, C, Maggi, M, Nuzzo, S, Ranieri, A, Raso, C, Ruggieri, F, Selvaggi, G, Silvestris, L, Tempesta, P, Tricomi, A, Zito, G, Huang, X, Lin, J, Ouyang, J, Wang, T, Xie, Y, Xu, R, Xue, S, Zhang, J, Zhang, L, Zhao, W, Abbaneo, D, Azzurri, P, Boix, G, Buchmuller, O, Cattaneo, M, Cerutti, F, Clerbaux, B, Dissertori, G, Drevermann, H, Forty, Rw, Frank, M, Gianotti, F, Greening, Tc, Hansen, Jb, Harvey, J, Hutchcroft, De, Janot, P, Jost, B, Kado, M, Lemaitre, V, Maley, P, Mato, P, Minten, A, Moutoussi, A, Ranjard, F, Rolandi, Luigi, Schlatter, D, Schmitt, M, Schneider, O, Spagnolo, P, Tejessy, W, Teubert, F, Tournefier, E, Valassi, A, Ward, Jj, Wright, Ae, Ajaltouni, Z, Badaud, F, Dessagne, S, Falvard, A, Fayolle, D, Gay, P, Henrard, P, Jousset, J, Michel, B, Monteil, S, Montret, Jc, Pallin, D, Pascolo, Jm, Perret, P, Podlyski, F, Hansen, Jd, Hansen, Jr, Hansen, Ph, Nilsson, B, Waananen, A, Daskalakis, G, Kyriakis, A, Markou, C, Simopoulou, E, Vayaki, A, Blondel, A, Brient, Jc, Machefert, F, Rouge, A, Swynghedauw, M, Tanaka, R, Videau, H, Focardi, E, Parrini, G, Zachariadou, K, Antonelli, A, Antonelli, M, Bencivenni, G, Bologna, C, Bossi, F, Campana, P, Capon, G, Chiarella, V, Laurelli, P, Mannocchi, G, Murtas, F, Murtas, Gp, Passalacqua, L, Pepe Altarelli, M, Chalmers, M, Halley, Aw, Kennedy, J, Lynch, Jg, Negus, P, O'Shea, V, Raeven, B, Smith, D, Teixeira Dias, P, Thompson, A, Cavanaugh, R, Dhamotharan, S, Geweniger, C, Hanke, P, Hepp, V, Kluge, Ee, Leibenguth, G, Putzer, A, Tittel, K, Werner, S, Wunsch, M, Beuselinck, R, Binnie, Dm, Cameron, W, Davies, G, Dornan, Pj, Girone, M, Marinelli, N, Nowell, J, Przysiezniak, H, Sedgbeer, Jk, Thompson, Jc, Thomson, E, White, R, Ghete, Vm, Girtler, P, Kneringer, E, Kuhn, D, Rudolph, G, Bouhova Tracker, E, Bowdery, Ck, Buck, Pg, Clarke, Dp, Ellis, G, Finch, Aj, Foster, F, Hughes, G, Jones, Rwl, Robertson, Na, Smizanska, M, Giehl, I, Holldorfer, F, Jakobs, K, Kleinknecht, K, Krocker, M, Muller, A, Nurnberger, Ha, Quast, G, Renk, B, Rohne, E, Sander, Hg, Schmeling, S, Wachsmuth, H, Zeitnitz, C, Ziegler, T, Bonissent, A, Carr, J, Coyle, P, Curtil, C, Ealet, A, Fouchez, D, Leroy, O, Kachelhoffer, T, Payre, P, Rousseau, D, Tilquin, A, Aleppo, M, Gilardoni, S, Ragusa, F, David, A, Dietl, H, Ganis, C, Huttmann, K, Lutjens, G, Mannert, C, Manner, W, Moser, Hg, Schael, S, Settles, R, Stenzel, H, Wiedenmann, W, Wolf, G, Boucrot, J, Callot, O, Davier, M, Duflot, L, Grivaz, Jf, Heusse, P, Jacholkowska, A, Serin, L, Veillet, Jj, Videau, I, de Regie, Jbd, Yuan, C, Zerwas, D, Bagliesi, G, Boccali, T, Calderini, G, Ciulli, V, Foa, L, Giammanco, A, Giassi, A, Ligabue, Franco, Messineo, A, Palla, F, Sanguinetti, G, Sciaba, A, Sguazzoni, G, Tenchini, R, Venturi, A, Verdini, Pg, Blair, Ga, Coles, J, Cowan, G, Green, Mg, Jones, Lt, Medcalf, T, Strong, Ja, von Wimmersperg Toeller, Jh, Clifft, Rw, Edgecock, Tr, Norton, Pr, Tomalin, Ir, Bloch Devaux, B, Boumediene, D, Colas, P, Fabbro, B, Lancon, E, Lemaire, Mc, Locci, E, Perez, P, Rander, J, Renardy, Jf, Rosowsky, A, Seager, P, Trabelsi, A, Tuchming, B, Vallage, B, Konstantinidis, N, Loomis, C, Litke, Am, Taylor, G, Booth, Cn, Cartwright, S, Combley, F, Hodgson, Pn, Lehto, M, Thompson, Lf, Affholderbach, K, Bohrer, A, Brandt, S, Grupen, C, Hess, J, Misiejuk, A, Prange, G, Sieler, U, Borean, C, Giannini, C, Gobbo, B, He, H, Putz, J, Rothberg, J, Wasserbaech, S, Armstrong, Sr, Cranmer, K, Elmer, P, Ferguson, Dp, Gao, Y, Gonzalez, S, Hayes, Oj, Hu, H, Jin, S, Kile, J, Mcnamara, Pa, Nielsen, J, Orejudos, W, Pan, Yb, Saadi, Y, Scott, Ij, Walsh, J, Wu, J, Wu, Sl, Wu, X, Zobernig, C., Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), and 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)

Subjects
Condensed Matter::Quantum Gases, Physics, Nuclear and High Energy Physics, Aleph, Particle physics, 010308 nuclear & particles physics, Electron–positron annihilation, High Energy Physics::Phenomenology, FOS: Physical sciences, Technicolor, Context (language use), Supersymmetry, 01 natural sciences, High Energy Physics - Experiment, Standard Model, Nuclear physics, High Energy Physics - Experiment (hep-ex), 0103 physical sciences, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Higgs boson, High Energy Physics::Experiment, 010306 general physics, Particle Physics - Experiment, Boson
Abstract

Searches for neutral Higgs bosons are performed with the 237 pb-1 of data collected in 1999 by the ALEPH detector at LEP, for centre-of-mass energies between 191.6 and 201.6 GeV. These searches apply to Higgs bosons within the context of the Standard Model and its minimal supersymmetric extension (MSSM) as well as to invisibly decaying Higgs bosons. No evidence of a signal is seen. A lower limit on the mass of the Standard Model Higgs boson of 107.7 GeV/c2 at 95% confidence level is set. In the MSSM, lower limits of 91.2 and 91.6 GeV/c2 are derived for the masses of the neutral Higgs bosons h and A, respectively. For a Higgs boson decaying invisibly and produced with the Standard Model cross section, masses below 106.4 GeV/c2 are excluded., Comment: 13 pages, 8 figures

Published
2001

27. Characterization of breast cancer interstitial fluids by TmT labeling, LTQ-Orbitrap Velos mass spectrometry, and pathway analysis

Author

Nuria Vadalà, Cinzia Raso, Xuemei Han, John R. Yates, Giovanni Cuda, Sung Kyu Park, M. Renne, Ubaldo Prati, Natalia Malara, Vincenzo Mollace, Carlo Cosentino, Marco Gaspari, Daniel B. McClatchy, Francesco Amato, Raso, C., Cosentino, C., Gaspari, M., Malara, N., Han, X., Mcclatchy, D., Park, S. K., Renne, M., Vadala, N., Prati, U., Cuda, G., Mollace, V., Amato, F., and Yates, J. R.

Subjects
Stromal cell, Proteome, Breast Neoplasms, Computational biology, Biology, Tandem mass tag, Bioinformatics, Orbitrap, Tandem mass spectrometry, Biochemistry, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, law, Phyllodes Tumor, Tandem Mass Spectrometry, Protein Interaction Mapping, medicine, Humans, Protein Interaction Maps, 030304 developmental biology, Epigenomics, 0303 health sciences, Staining and Labeling, Carcinoma, Ductal, Breast, Cancer, Extracellular Fluid, General Chemistry, medicine.disease, 3. Good health, Molecular Weight, 030220 oncology & carcinogenesis, Female, Protein Interaction Map, Breast Neoplasm, Human
Abstract

Cancer is currently considered as the end point of numerous genomic and epigenomic mutations and as the result of the interaction of transformed cells within the stromal microenvironment. The present work focuses on breast cancer, one of the most common malignancies affecting the female population in industrialized countries. In this study, we perform a proteomic analysis of bioptic samples from human breast cancer, namely, interstitial fluids and primary cells, normal vs disease tissues, using tandem mass tags (TmT) quantitative mass spectrometry combined with the MudPIT technique. To the best of our knowledge, this work, with over 1700 proteins identified, represents the most comprehensive characterization of the breast cancer interstitial fluid proteome to date. Network analysis was used to identify functionally active networks in the breast cancer associated samples. From the list of differentially expressed genes, we have retrieved the associated functional interaction networks. Many different signaling pathways were found activated, strongly linked to invasion, metastasis development, proliferation, and with a significant cross-talking rate. This pilot study presents evidence that the proposed quantitative proteomic approach can be applied to discriminate between normal and tumoral samples and for the discovery of yet unknown carcinogenesis mechanisms and therapeutic strategies.

Published
2012

28. Calpain3 is expressed in a proteolitically active form in papillomavirus-associated urothelial tumors of the urinary bladder in cattle

Author

Franco Roperto, Gianni Cuda, Monica Averna, Marco Gaspari, Roberta De Tullio, Valeria Russo, Sante Roperto, Cinzia Raso, Giuseppe Borzacchiello, Roberto Stifanese, Orlando Paciello, Roperto, Sante, De Tullio, R, Raso, C, Stifanese, R, Russo, Valeria, Gaspari, M, Borzacchiello, Giuseppe, Averna, M, Paciello, Orlando, Cuda, G, and Roperto, FRANCO PEPPINO

Subjects
Urinary system, Science, Biology, medicine.disease_cause, Virology/Emerging Viral Diseases, Infectious Diseases/Viral Infections, medicine, Animals, Neoplasms, Glandular and Epithelial, Urothelium, Bovine papillomavirus 1, Bovine papillomavirus, Multidisciplinary, Bladder cancer, Urinary bladder, Calpain, Reverse Transcriptase Polymerase Chain Reaction, Papillomavirus Infections, medicine.disease, biology.organism_classification, Molecular biology, Pathology/Molecular Pathology, Gene Expression Regulation, Neoplastic, Reverse transcription polymerase chain reaction, medicine.anatomical_structure, Urinary Bladder Neoplasms, E2F3 Transcription Factor, Virology/Animal Models of Infection, Immunohistochemistry, Medicine, Calcium, Cattle, Carcinogenesis, Research Article, Virology/Viruses and Cancer
Abstract

BackgroundCalpain 3 (Capn3), also named p94, is a skeletal muscle tissue-specific protein known to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A). Recent experimental studies have hypothesized a pro-apoptotic role of Capn3 in some melanoma cell lines. So far the link between calpain3 and tumors comes from in vitro studies. The objective of this study was to describe Capn3 activation in naturally occurring urothelial tumors of the urinary bladder in cattle.Methods and findingsHere we describe, for the first time in veterinary and comparative oncology, the activation of Capn3 in twelve urothelial tumor cells of the urinary bladder of cattle. Capn3 protein was initially identified with nanoscale liquid chromatography coupled with tandem mass spectrometry (nano LC-MS/MS) in a co-immunoprecipitation experiment on E2F3, known to be a transcription factor playing a crucial role in bladder carcinogenesis in humans. Capn3 expression was then confirmed by reverse transcription polymerase chain reaction (RT-PCR). Finally, the Ca(2+)-dependent proteolytic activity of Capn3 was assayed following ion exchange chromatography. Morphologically, Capn3 expression was documented by immunohistochemical methods. In fact numerous tumor cells showed an intracytoplasmic immunoreactivity, which was more rarely evident also at nuclear level. In urothelial tumors, bovine papillomavirus type 2 (BPV-2) DNA was amplified by PCR and the expression of E5 protein, the major oncogenic protein of BVP-2, was detected by western blotting, immunohistochemistry, and immunofluorescence. E2F3 overexpression and pRb protein downregulation were shown by western blotting.ConclusionThe role of capn3 protein in urothelial cancer of the urinary bladder remains to be elucidated: further studies would be required to determine the precise function of this protease in tumor development and progression. However, we suggest that activated Capn3 may be involved in molecular pathways leading to the overexpression of E2F3, which in turn could be responsible for urothelial tumor cell proliferation also in cattle, though other mechanisms are likely to exist. If further studies corroborate the important role of Capn3 in urothelial tumors of the urinary bladder, cattle with urinary tumors may prove useful as animal model for bladder carcinogenesis.

Published
2010

29. The eighth fibronectin type III domain of protein tyrosine phosphatase receptor J influences the formation of protein complexes and cell localization

Author

Francesco Trapasso, Alfina Quintiero, Cinzia Raso, Tiziana Palumbo, Ilaria Le Pera, Alfredo Fusco, Giuseppe Viglietto, Dario Palmieri, Carlo M. Croce, Flavia Pichiorri, Tullio Florio, Alessandra Pattarozzi, Rodolfo Iuliano, Iuliano, R., Raso, C., Quintiero, A., Le Pera, I., Picchiorri, F., Palumbo, T., Palmieri, Dario, Pattarozzi, A., Florio, T., Viglietto, G., Trapasso, F., Croce, C. M., and Fusco, Alfredo

Subjects
Protein domain, Phosphatase, Protein tyrosine phosphatase, Fibronectin type III domain, protein tyrosine phosphatase, Biochemistry, Cell Line, Cell membrane, protein complexe, Structure-Activity Relationship, medicine, Humans, Disulfides, Molecular Biology, Cell Proliferation, Sequence Deletion, biology, fibronectin domain, Chemistry, Cell Membrane, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Wild type, cell localization, General Medicine, Oxidants, Fibronectins, Protein Structure, Tertiary, Cell biology, Molecular Weight, Fibronectin, Protein Transport, medicine.anatomical_structure, Cytoplasm, Multiprotein Complexes, biology.protein, Mutant Proteins, disulfide bond, Protein Multimerization
Abstract

Regulation of receptor-type phosphatases can involve the formation of higher-order structures, but the exact role played in this process by protein domains is not well understood. In this study we show the formation of different higher-order structures of the receptor-type phosphatase PTPRJ, detected in HEK293A cells transfected with different PTPRJ expression constructs. In the plasma membrane PTPRJ forms dimers detectable by treatment with the cross-linking reagent BS(3) (bis[sulfosuccinimidyl]suberate). However, other PTPRJ complexes, dependent on the formation of disulfide bonds, are detected by treatment with the oxidant agent H(2)O(2) or by a mutation Asp872Cys, located in the eighth fibronectin type III domain of PTPRJ. A deletion in the eighth fibronectin domain of PTPRJ impairs its dimerization in the plasma membrane and increases the formation of PTPRJ complexes dependent on disulfide bonds that remain trapped in the cytoplasm. The deletion mutant maintains the catalytic activity but is unable to carry out inhibition of proliferation on HeLa cells, achieved by the wild type form, since it does not reach the plasma membrane. Therefore, the intact structure of the eighth fibronectin domain of PTPRJ is critical for its localization in plasma membrane and biological function.

Published
2009

30. Genetic ablation of Ptprj, a mouse cancer susceptibility gene, results in normal growth and development and does not predispose to spontaneous tumorigenesis

Author

Stefan Costinean, Cinzia Raso, Francesco Trapasso, Eugenio Gaudio, Rodolfo Iuliano, Carlo M. Croce, Alfredo Fusco, Rami I. Aqeilan, Nicola Zanesi, Alessandra Drusco, Hansjuerg Alder, Trapasso, F., Drusco, A., Costinean, S., Alder, H., Aqeilan, R. I., Iuliano, R., Gaudio, E., Raso, C., Zanesi, N., Croce, C. M., and Fusco, Alfredo

Subjects
Candidate gene, Colorectal cancer, Blotting, Western, Locus (genetics), Protein tyrosine phosphatase, Biology, medicine.disease_cause, Mice, Genetics, medicine, Animals, Genetic Predisposition to Disease, Receptor, Molecular Biology, Gene, DNA Primers, Mice, Knockout, Cell growth, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Cell Biology, General Medicine, Neoplasms, Experimental, medicine.disease, Cancer research, Protein Tyrosine Phosphatases, Carcinogenesis, Cell Division
Abstract

Ptprj is a ubiquitously expressed murine gene encoding a receptor-type protein tyrosine phosphatase, which has recently been proposed as a candidate gene on the locus Scc1 for colon cancer susceptibility. It has been demonstrated that PTPRJ, the human homologue of Ptprj, is involved in the control of cell growth and adhesion, being furthermore altered in several types of cancer including mammary, thyroid, lung, colon, and pancreatic cancers. To investigate the biological functions of Ptprj, we have generated mice deficient in this receptor protein tyrosine phosphatase. Ptprj-deficient mice are viable, fertile, and show no gross anatomical alterations. Furthermore, neither changes in life span nor spontaneous tumor appearance were observed in Ptprj-null mice. Our results indicate that Ptprj is dispensable for normal growth and development in mice.

Published
2006

31. Four-fermion production in $e^+e^-$ collisions at centre-of-mass energies of 130 and 136 GeV

Author

J. Reeve, I.J. Scott, B. Gobbo, A. Pascual, H. Kroha, H. Seywerd, G. Calderini, R.W. Williams, G. Giannini, W. M. Newton, Jordan Nash, Arnaud Lucotte, M. Maggi, P. Azzurri, Y. Saadi, C. K. Bowdery, S.R. Armstrong, P. Perez, L. Moneta, J.P. Lees, C. Markou, L. Curtis, P.G. Verdini, Guido Tonelli, F. Stephan, M. Cattaneo, G. Zobernig, V. Büscher, R. Miquel, R. Fantechi, G. Mannocchi, M.D. Williams, E. Lancon, M. Wunsch, S. J. Dorris, M. A. McNeil, A. Roussarie, S. Gonzalez, K. Tittel, A. M. Bencheikh, J.P. Schuller, A. Rouge, M. Fernandez-Bosman, D. Rousseau, C. Diaconu, M. Pepe-Altarelli, S. Orteu, L. Passalacqua, Dominique Pallin, P. Mato, G. Lutters, B.S. Nilsson, B. Renk, A. Ranieri, A. Gregorio, A. Sadouki, E.E. Kluge, G. Lütjens, J. Sommer, T. Oest, Z. Y. Feng, C. Bozzi, E. Fernandez, J. J. Aubert, F. Sanchez, Ph. Heusse, F. Foster, L. Rolandi, P. Elmer, G. Bagliesi, I. G. Knowles, R. Richter, T. Sloan, D. M. Binnie, Claus Grupen, D. Casper, A. Pacheco, L. Smolik, O. Schneider, C. Geweniger, A. Böhrer, R. Denis, A. Cordier, I. Lehraus, J. Carr, A. M. Walsh, F. Bossi, A. Putzer, Maria Agnese Ciocci, H. Hu, Alain Falvard, R. Alemany, Hasko Stenzel, P. Coyle, J. H. von Wimmersperg-Toeller, P. Colrain, H.Y. Kim, J. Grahl, S. Schael, A. Sciabà, G. Wolf, M. Zheng, L. Silvestris, J.Y. Nief, G. Zito, M. I. Martínez, H.G. Moser, J. Putz, J. Boucrot, G. Sanguinetti, E. B. Martin, R. Xu, S.N. Black, M. De Palma, J.G. Lynch, L. Zhang, B. Vallage, G. Felici, F. Teubert, G. Quast, I. C. Park, P. Colas, D. E. Jaffe, K. Smith, P. Comas, G. Taylor, G. Iaselli, G. Gelao, G. Bencivenni, J. D. Hansen, J. C. Thompson, S. Emery, M.N. Minard, Philippe Odier, B. Michel, A. Kyriakis, G. Bologna, E. Simopoulou, F. Combley, U. Becker, A. W. Halley, A. Colaleo, R.P. Johnson, Alexander Finch, R. Della Marina, G. Hansper, R. Hagelberg, P. Perrodo, A. Wäänänen, I. Riu, S. Wasserbaech, M. C. Lemaire, F. Ranjard, Jie Zhang, I. Efthymiopoulos, D. Kuhn, M. Schmidt, S. Thorn, P. Reeves, A. Minten, F. Ragusa, S. Werner, P. A. McNamara, J. M. Rossignol, P. Saraiva, A.S. Thompson, A. M. Greene, L. M. Bryant, D. R. Botterill, F. Cerutti, S. Nuzzo, M. Talby, P. Girtler, S. Brandt, Patrick Janot, P.S. Marrocchesi, A. Galla, R.W. Clifft, F. Ligabue, P. Campana, J.T. Chambers, G. Crawford, A. Moutoussi, J. Rander, J. Schwindling, K. Jacobs, A.O. Bazarko, E. Kneringer, E. Focardi, F. Le Diberder, J. F. Pusztaszeri, J. F. Renardy, P. Spagnolo, I.R. Tomalin, B. Marx, A. Valassi, J.M. Yamartino, S. L. Wu, C. N. Booth, C. Bauer, M. Letho, F. Ruggieri, M. Chmeissani, A. Lusiani, W. Zhao, A. M. Lutz, E. Rohne, Peter Hansen, M. Schmelling, C. Georgiopoulos, J. M. Scarr, G. Musolino, Vitaliano Chiarella, R. Beuselinck, M. Delfino, P. Hanke, J. A. Perlas, P. van Gemmeren, B. Pietrzyk, R. Boswell, K. Trabelsi, A. Blondel, H. Drevermann, V. Hepp, M. Rumpf, Joseph Proriol, Y. Xie, Ll. Garrido, G. Capon, Werner Wiedenmann, A. P. Betteridge, B. Rensch, G. Graefe, J.H. Dann, A. Trabelsi, Maria Pilar Casado, S. Bettarini, L. Bosisio, G.A. Blair, W. Cameron, J. M. Crespo, J. Steinberger, Yang Gao, A. Juste, G. Parrini, G. A. Cowan, C. Guicheney, D. Buskulic, A. Jacholkowska, I. De Bonis, Caj Brew, Xin Wu, Gerardo Ganis, A. Hocker, G. Dissertori, R.W. Forty, R. Dell'Orso, A. Bonissent, D. Creanza, A.E. Wright, B. Bloch-Devaux, W. Männer, C. Goy, J.C. Brient, D. Schlatter, P.R. Norton, J.A. Strong, A. Giassi, Ziad Ajaltouni, M. Davier, T. Wang, C. Padilla, Jean-Francois Grivaz, O.J. Hayes, R. Settles, H.J. Park, B. Jost, P. J. Dornan, G. Selvaggi, J.B. Hansen, H. Wachsmuth, F. Dydak, W. Orejudos, Pierre Henrard, J.M. Nachtman, G. Bujosa, F. Murtas, I. Nikolic, M. Aleppo, A. Koksal, M. Corden, S. Xue, D. Decamp, Val O'Shea, V. Ciulli, W. Tejessy, G. Rizzo, F. Palla, E. Locci, M. Apollonio, F. Podlyski, Jean-Claude Montret, J. K. Sedgbeer, T. Medcalf, M. I. Williams, Nikolaos Konstantinidis, P. Rensing, S. Monteil, Y. S. Gao, W. Blum, G. Raso, A. Venturi, A. Antonelli, Christian Zeitnitz, A. Vayaki, D.P.S. Ferguson, J. Lefrançois, C. Benchouk, A. Barres, C. Hoffmann, A. Tilquin, T.C. Greening, J. J. Veillet, D. W. Kim, P. Laurelli, G. Rudolph, R. Berlich, R. M. Turnbull, P. Morawitz, J. Walsh, G. Hughes, A. Messineo, K. Kleinknecht, H. Dietl, I. Videau, R. Tenchini, S. L. Cartwright, Dirk Zerwas, E. P. Whelan, H.G. Sander, Jiali Lin, A. M. Stacey, C. Gotzhein, C. Boyer, G. Maggi, P. Payre, P. Teixeira-Dias, W. Kozanecki, J. Rothberg, J. Jousset, C. Raine, K. Zachariadou, M. H. Schune, P. Maley, I. Ferrante, M. Schmitt, M. Carpinelli, G. Batignani, A. Rosado-Schlosser, Alan Litke, M. Frank, S. Simion, M. Girone, X. Huang, O. Callot, Laurent Duflot, Lester D.R. Thompson, A. Wagner, P. Ghez, C. Vannini, T. Fearnley, Pascal Perret, M. Jacquet, Philippe Rosnet, Ll.M. Mir, J. Harvey, N. Marinelli, F. Thomson, D. Calvet, H. Videau, J.D. Hansen, S. Haywood, Y.B. Pan, Q. Ouyang, T. R. Edgecock, D. Abbaneo, G.P. Murtas, J. Knobloch, M. Thulasidas, G. Lutz, M. G. Green, P. Tempesta, Chadelas, Michèle, 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 Physique Corpusculaire - Clermont-Ferrand (LPC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Leprince-Ringuet (LLR), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'Accélérateur Linéaire (LAL), 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), ALEPH, Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), 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), D., Buskulic, I., De Boni, D., Decamp, P., Ghez, C., Goy, J. P., Lee, A., Lucotte, M. N., Minard, J. Y., Nief, P., Odier, B., Pietrzyk, M. P., Casado, M., Chmeissani, J. M., Crespo, M., Delfino, I., Efthymiopoulo, E., Fernandez, M., Fernandez Bosman, Ll, Garrido, A., Juste, M., Martinez, S., Orteu, C., Padilla, I. C., Park, A., Pascual, J. A., Perla, I., Riu, F., Sanchez, F., Teubert, A., Colaleo, D., Creanza, M., de Palma, G., Gelao, M., Girone, G., Iaselli, G., Maggi, M., Maggi, N., Marinelli, S., Nuzzo, A., Ranieri, G., Raso, F., Ruggieri, G., Selvaggi, L., Silvestri, P., Tempesta, G., Zito, X., Huang, J., Lin, Q., Ouyang, T., Wang, Y., Xie, R., Xu, S., Xue, J., Zhang, L., Zhang, W., Zhao, R., Alemany, A. O., Bazarko, M., Cattaneo, P., Coma, P., Coyle, H., Drevermann, R. W., Forty, M., Frank, R., Hagelberg, J., Harvey, P., Janot, B., Jost, E., Kneringer, J., Knobloch, I., Lehrau, G., Lutter, E. B., Martin, P., Mato, A., Minten, R., Miquel, Mir, L. l. M., L., Moneta, T., Oest, A., Pacheco, J. F., Pusztaszeri, F., Ranjard, P., Rensing, L., Rolandi, D., Schlatter, M., Schmelling, M., Schmitt, O., Schneider, W., Tejessy, I. R., Tomalin, A., Venturi, H., Wachsmuth, A., Wagner, Z., Ajaltouni, A., Barrè, C., Boyer, A., Falvard, P., Gay, C., Guicheney, P., Henrard, J., Jousset, B., Michel, S., Monteil, J. C., Montret, D., Pallin, P., Perret, F., Podlyski, J., Proriol, P., Rosnet, J. M., Rossignol, T., Fearnley, J. B., Hansen, J. D., Hansen, J. R., Hansen, P. H., Hansen, B. S., Nilsson, B., Rensch, A., Wäänänen, A., Kyriaki, C., Markou, E., Simopoulou, A., Vayaki, K., Zachariadou, A., Blondel, J. C., Brient, A., Rougé, M., Rumpf, A., Valassi, H., Videau, E., Focardi, G., Parrini, M., Corden, C., Georgiopoulo, D. E., Jaffe, A., Antonelli, G., Bencivenni, G., Bologna, F., Bossi, P., Campana, G., Capon, D., Casper, V., Chiarella, G., Felici, P., Laurelli, G., Mannocchi, F., Murta, G. P., Murta, L., Passalacqua, M., Pepe Altarelli, L., Curti, S. J., Dorri, A. W., Halley, I. G., Knowle, J. G., Lynch, V., O'Shea, C., Raine, P., Reeve, J. M., Scarr, K., Smith, P., Teixeira Dia, A. S., Thompson, F., Thomson, S., Thorn, R. M., Turnbull, U., Becker, C., Geweniger, G., Graefe, P., Hanke, G., Hansper, V., Hepp, E. E., Kluge, A., Putzer, M., Schmidt, J., Sommer, H., Stenzel, K., Tittel, S., Werner, M., Wunsch, D., Abbaneo, R., Beuselinck, D. M., Binnie, W., Cameron, P. J., Dornan, P., Morawitz, A., Moutoussi, J., Nash, J. K., Sedgbeer, A. M., Stacey, M. D., William, G., Dissertori, P., Girtler, D., Kuhn, G., Rudolph, A. P., Betteridge, C. K., Bowdery, P., Colrain, G., Crawford, A. J., Finch, F., Foster, G., Hughe, T., Sloan, E. P., Whelan, M. I., William, A., Galla, A. M., Greene, C., Hoffmann, K., Jacob, K., Kleinknecht, G., Quast, B., Renk, E., Rohne, H. G., Sander, P., van Gemmeren, C., Zeitnitz, J. J., Aubert, A. M., Bencheikh, C., Benchouk, A., Bonissent, G., Bujosa, D., Calvet, J., Carr, C., Diaconu, N., Konstantinidi, P., Payre, D., Rousseau, M., Talby, A., Sadouki, M., Thulasida, A., Tilquin, K., Trabelsi, M., Aleppo, F., Ragusa, C., Bauer, R., Berlich, W., Blum, V., Büscher, H., Dietl, F., Dydak, G., Gani, C., Gotzhein, H., Kroha, G., Lütjen, G., Lutz, W., Männer, H. G., Moser, R., Richter, A., Rosado Schlosser, S., Schael, R., Settle, H., Seywerd, R., St Deni, W., Wiedenmann, G., Wolf, J., Boucrot, O., Callot, A., Cordier, M., Davier, L., Duflot, J. F., Grivaz, Ph, Heusse, A., Höcker, A., Jacholkowska, M., Jacquet, D. W., Kim, F., Le Diberder, J., Lefrançoi, A. M., Lutz, I., Nikolic, H. J., Park, M. H., Schune, S., Simion, J. J., Veillet, I., Videau, D., Zerwa, P., Azzurri, G., Bagliesi, G., Batignani, S., Bettarini, C., Bozzi, G., Calderini, M., Carpinelli, M. A., Ciocci, V., Ciulli, R., Dell'Orso, R., Fantechi, I., Ferrante, A., Giassi, Gregorio, Anna, F., Ligabue, A., Lusiani, P. S., Marrocchesi, A., Messineo, F., Palla, G., Rizzo, G., Sanguinetti, A., Sciabà, P., Spagnolo, J., Steinberger, R., Tenchini, G., Tonelli, C., Vannini, P. G., Verdini, J., Walsh, G. A., Blair, L. M., Bryant, F., Cerutti, J. T., Chamber, Y., Gao, M. G., Green, T., Medcalf, P., Perrodo, J. A., Strong, J. H., von Wimmersperg Toeller, D. R., Botterill, R. W., Clifft, T. R., Edgecock, S., Haywood, P., Maley, P. R., Norton, J. C., Thompson, A. E., Wright, B., Bloch Devaux, P., Cola, S., Emery, W., Kozanecki, E., Lançon, M. C., Lemaire, E., Locci, B., Marx, P., Perez, J., Rander, J. F., Renardy, A., Roussarie, J. P., Schuller, J., Schwindling, A., Trabelsi, B., Vallage, S. N., Black, J. H., Dann, R. P., Johnson, H. Y., Kim, A. M., Litke, M. A., Mcneil, G., Taylor, C. N., Booth, R., Boswell, C. A. J., Brew, S., Cartwright, F., Combley, A., Koksal, M., Letho, W. M., Newton, J., Reeve, L. F., Thompson, A., Böhrer, S., Brandt, G., Cowan, C., Grupen, P., Saraiva, L., Smolik, F., Stephan, M., Apollonio, Bosisio, Luciano, R., Della Marina, Giannini, Gianrossano, B., Gobbo, G., Musolino, J., Putz, J., Rothberg, S., Wasserbaech, R. W., William, S. R., Armstrong, P., Elmer, Z., Feng, D. P. S., Ferguson, Y. S., Gao, S., González, J., Grahl, T. C., Greening, O. J., Haye, H., Hu, P. A., Mcnamara, J. M., Nachtman, W., Orejudo, Y. B., Pan, Y., Saadi, I. J., Scott, A. M., Walsh, Sau Lan, Wu, X., Wu, J. M., Yamartino, M., Zheng, G., Zobernig, Buskulic, D, Debonis, I, Decamp, D, Ghez, P, Goy, C, Lees, J, Lucotte, A, Minard, M, Nief, J, Odier, P, Pietrzyk, B, Casado, M, Chmeissani, M, Crespo, J, Delfino, M, Efthymiopoulos, I, Fernandez, E, Fernandezbosman, M, Garrido, L, Juste, A, Martinez, M, Orteu, S, Padilla, C, Park, I, Pascual, A, Perlas, J, Riu, I, Sanchez, F, Teubert, F, Colaleo, A, Creanza, D, Depalma, M, Gelao, G, Girone, M, Iaselli, G, Maggi, G, Maggi, M, Marinelli, N, Nuzzo, S, Ranieri, A, Raso, C, Ruggieri, F, Selvaggi, G, Silvestris, L, Tempesta, P, Zito, G, Huang, X, Lin, J, Ouyang, Q, Wang, T, Xie, Y, Xu, R, Xue, S, Zhang, J, Zhang, L, Zhao, W, Alemany, R, Bazarko, A, Cattaneo, M, Comas, P, Coyle, P, Drevermann, H, Forty, R, Frank, M, Hagelberg, R, Harvey, J, Janot, P, Jost, B, Kneringer, E, Knobloch, J, Lehraus, I, Lutters, G, Martin, E, Mato, P, Minten, A, Miquel, R, Mir, L, Moneta, L, Oeste, T, Pacheco, A, Pusztaszeri, J, Ranjard, F, Rensing, P, Rolandi, L, Schlatter, D, Schmelling, M, Schmitt, M, Schneider, O, Tejessy, W, Tomalin, I, Venturi, A, Wachsmuth, H, Wagner, A, Ajaltouni, Z, Barres, A, Boyer, C, Falvard, A, Gray, P, Guicheney, C, Henrard, P, Jousset, J, Michel, B, Monteil, S, Montret, J, Pallin, D, Perret, P, Podlyski, F, Proriol, J, Rosnet, P, Rossignol, J, Fearnley, T, Hansen, J, Hansen, P, Nilsson, B, Rensch, B, Waananen, A, Kyriakis, A, Markou, C, Simopoulou, E, Vayaki, A, Zachariadou, K, Blondel, A, Brient, J, Rouge, A, Rumpf, M, Valassi, A, Videau, H, Focardi, E, Parrini, G, Corden, M, Georgiopoulos, C, Jaffe, D, Antonelli, A, Bencivenni, G, Bologna, G, Bossi, F, Campana, P, Capon, G, Casper, D, Chiarella, V, Felici, G, Laurelli, P, Mannocchi, G, Murtas, F, Murtas, G, Passalacqua, L, Pepealtarelli, M, Curtis, L, Dorris, S, Halley, A, Knowles, I, Lynch, J, Oshea, V, Raine, C, Reeves, P, Scarr, J, Smith, K, Teixeiradias, P, Thompson, A, Thomson, F, Thorn, S, Turnbull, R, Becker, U, Geweniger, C, Graefe, G, Hanke, P, Hansper, G, Hepp, V, Kluge, E, Putzer, A, Schmidt, M, Sommer, J, Stenzel, H, Tittel, K, Werner, S, Wunsch, M, Abbaneo, D, Beuselinck, R, Binnie, D, Cameron, W, Dornan, P, Morawitz, P, Moutoussi, A, Nash, J, Sedgbeer, J, Stacey, A, Williams, M, Dissertori, G, Girtler, P, Kuhn, D, Rudolph, G, Betteridge, A, Bowdery, C, Colrain, P, Crawford, G, Finch, A, Foster, F, Hughes, G, Sloan, T, Whelan, E, Galla, A, Greene, A, Hoffmann, C, Jacobs, K, Kleinknecht, K, Quast, G, Renk, B, Rohne, E, Sander, H, Vangemmeren, P, Zeitnitz, C, Aubert, J, Bencheikh, A, Benchouk, C, Bonissent, A, Bujosa, G, Calvet, D, Carr, J, Diaconu, C, Konstantinidis, N, Payre, P, Rousseau, D, Talby, M, Sadouki, A, Thulasidas, M, Tilquin, A, Trabelsi, K, Aleppo, M, Ragusa, F, Bauer, C, Berlich, R, Blum, W, Buscher, V, Dietl, H, Dydak, F, Ganis, G, Gotzhein, C, Kroha, H, Lutjens, G, Lutz, G, Manner, W, Moser, H, Richter, R, Rosadoschlosser, A, Schael, S, Settles, R, Seywerd, H, Denis, R, Wiedenmann, W, Wolf, G, Boucrot, J, Callot, O, Cordier, A, Davier, M, Duflot, L, Grivaz, J, Heusse, P, Hocker, A, Jacholkowska, A, Jacquet, M, Kim, D, Lediberder, F, Lefrancois, J, Lutz, A, Nikolic, I, Park, H, Schune, M, Simion, S, Veillet, J, Videau, I, Zerwas, D, Azzurri, P, Bagliesi, G, Batignani, G, Bettarini, S, Bozzi, C, Calderini, G, Carpinelli, M, Ciocci, M, Ciulli, V, Dellorso, R, Fantechi, R, Ferrante, I, Giassi, A, Gregorio, A, Ligabue, F, Lusiani, A, Marrocchesi, P, Messineo, A, Palla, F, Rizzo, G, Sanguinetti, G, Sciaba, A, Spagnolo, P, Steinberger, J, Tenchini, R, Tonelli, G, Vannini, C, Verdini, P, Walsh, J, Blair, G, Bryant, L, Cerutti, F, Chambers, J, Gao, Y, Green, M, Medcalf, T, Perrodo, P, Strong, J, Vonwimmerspergtoeller, J, Botterill, D, Clifft, R, Edgecock, T, Haywood, S, Maley, P, Norton, P, Thompson, J, Wright, A, Blochdevaux, B, Colas, P, Emery, S, Kozanecki, W, Lancon, E, Lemaire, M, Locci, E, Marx, B, Perez, P, Rander, J, Renardy, J, Roussarie, A, Schuller, J, Schwindling, J, Trabelsi, A, Vallage, B, Black, S, Dann, J, Johnson, R, Kim, C, Litke, A, Mcneil, M, Taylor, G, Booth, C, Boswell, R, Brew, C, Cartwright, S, Combley, F, Koksal, A, Letho, M, Newton, W, Reeve, J, Thompson, L, Bohrer, A, Brandt, S, Cowan, G, Grupen, C, Saraiva, P, Smolik, L, Stephan, F, Apollonio, M, Bosisio, L, Dellamarina, R, Giannini, G, Gobbo, B, Musolino, G, Putz, J, Rothberg, J, Wasserbaech, S, Williams, R, Armstrong, S, Elmer, P, Feng, Z, Ferguson, D, Gonzalez, S, Grahl, J, Greening, T, Hayes, O, Hu, H, Mcnamara, P, Nachtman, J, Orejudos, W, Pan, Y, Saadi, Y, Scott, I, Walsh, A, Wu, S, Wu, X, Yamartino, J, Zheng, M, Zobernig, G, Lees, Jp, Minard, Mn, Nief, Jy, Casado, Mp, Crespo, Jm, Park, Ic, Perlas, Ja, Bazarko, Ao, Forty, Rw, Martin, Eb, Mir, Lm, Pusztaszeri, Jf, Rolandi, Luigi, Tomalin, Ir, Montret, Jc, Rossignol, Jm, Hansen, Jb, Hansen, Jd, Hansen, Jr, Hansen, Ph, Brient, Jc, Jaffe, De, Murtas, Gp, Dorris, Sj, Halley, Aw, Knowles, Ig, Lynch, Jg, Scarr, Jm, Turnbull, Rm, Kluge, Ee, Binnie, Dm, Dornan, Pj, Sedgbeer, Jk, Stacey, Am, Williams, Md, Betteridge, Ap, Bowdery, Ck, Finch, Aj, Whelan, Ep, Williams, Mi, Greene, Am, Sander, Hg, Aubert, Jj, Bencheikh, Am, Moser, Hg, Grivaz, Jf, Kim, Dw, Lutz, Am, Park, Hj, Schune, Mh, Veillet, Jj, Ciocci, Ma, Ligabue, Franco, Lusiani, Alberto, Verdini, Pg, Blair, Ga, Bryant, Lm, Chambers, Jt, Green, Mg, Strong, Ja, Vonwimmerspergtoeller, Jh, Botterill, Dr, Clifft, Rw, Edgecock, Tr, Norton, Pr, Thompson, Jc, Wright, Ae, Lemaire, Mc, Renardy, Jf, Schuller, Jp, Black, Sn, Dann, Jh, Johnson, Rp, Kim, Caj, Litke, Am, Mcneil, Ma, Booth, Cn, Brew, Caj, Newton, Wm, Thompson, Lf, Williams, Rw, Armstrong, Sr, Ferguson, Dp, Greening, Tc, Hayes, Oj, Mcnamara, Pa, Nachtman, Jm, Pan, Yb, Scott, Ij, Walsh, Am, Wu, Sl, Yamartino, Jm, and Zobernig, G.

Subjects
Physics, Nuclear and High Energy Physics, Aleph, [PHYS.HEXP] Physics [physics]/High Energy Physics - Experiment [hep-ex], 010308 nuclear & particles physics, Fermion, 01 natural sciences, Standard Model, Nuclear physics, ALEPH Experiment, 0103 physical sciences, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Production (computer science), 010306 general physics, Particle Physics - Experiment
Abstract

Four-fermion events have been selected in a data sample of 5.8 pb(-1) collected with the ALEPH detector at centre-of-mass energies of 130 and 136 GeV. The final states l(+)l(-), l(+)l(-)l(+)l(-), , and

Published
1996

32. Histiocytic Sarcoma in a Captive Hybrid Orangutan ( Pongo sp.): Morphological and Immunohistochemical Features.

Author

Galietta V, Fonti N, Cocumelli C, Raso C, Di Cerbo P, Parisi F, Bovi E, Parmigiani R, Pietrella G, Cersini A, Friedrich KG, and Eleni C

Abstract

Histiocytic sarcoma (HS), an infrequent highly aggressive hematopoietic tumor, has been observed in diverse animal species, with isolated occurrences in non-human primates. This study describes the first case of disseminated HS in a 45-year-old female hybrid captive orangutan. The clinical profile mirrored symptoms seen in human HS cases, encompassing anorexia and ascites. Detailed histopathological examination demonstrated characteristic features of this tumor and immunohistochemistry, using markers such as Iba-1 and HLA-DR, confirmed the diagnosis. Significantly, the absence of CD163 and CD204 expression challenges their diagnostic utility in non-human primates. This investigation enhances our understanding of HS diagnosis in non-human primates, underscoring the necessity for standardized markers and diagnostic protocols.

Published
2024
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34. Ectopic Pregnancy and T-Cell Lymphoma in a Eurasian Red Squirrel ( Sciurus vulgaris ): Possible Comorbidity and a Comparative Pathology Perspective.

Author

Raso C, Galietta V, Eleni C, Innocenti M, Fonti N, Palmerini T, Grillo M, Calderini P, and Borgogni E

Abstract

Ectopic pregnancy (EP) is a life-threatening disease that affects humans and other mammals. Tumors causing ruptures of the reproductive tract have been identified as possible predisposing factors in human and veterinary medicine. We here describe a case of concomitant ectopic pregnancy and lymphoma in a Eurasian red squirrel found deceased in Italy and submitted to the public health laboratory Istituto Zooprofilattico Sperimentale del Lazio e della Toscana (IZSLT) for post-mortem examination. A full-term partially mummified ectopic fetus in the abdomen and a large fibrinonecrotic tubal scar adjacent to the right ovary were observed at necropsy. The tubal scar is likely the point of tubal rupture through which the fetus displaced. Histology revealed the presence of neoplastic cells referable to lymphoma infiltrating the ovary, spleen, small intestine, heart and peripancreatic adipose tissue. The lymphoma was further characterized as T-cell-type using immunohistochemistry. We suggest that the lymphoma, by involving the ovary, played a pathogenetic role in the development of a secondary EP by altering the genital tract at the structural and hormonal levels. To the best of our knowledge, this is the first report of concomitant ovarian lymphoma and EP in animals and humans in the literature.

Published
2024
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35. Proteomic Mapping of the Interactome of KRAS Mutants Identifies New Features of RAS Signalling Networks and the Mechanism of Action of Sotorasib.

Author

Nolan A, Raso C, Kolch W, Kriegsheim AV, Wynne K, and Matallanas D

Abstract

RAS proteins are key regulators of cell signalling and control different cell functions including cell proliferation, differentiation, and cell death. Point mutations in the genes of this family are common, particularly in KRAS . These mutations were thought to cause the constitutive activation of KRAS, but recent findings showed that some mutants can cycle between active and inactive states. This observation, together with the development of covalent KRASG12C inhibitors, has led to the arrival of KRAS inhibitors in the clinic. However, most patients develop resistance to these targeted therapies, and we lack effective treatments for other KRAS mutants. To accelerate the development of RAS targeting therapies, we need to fully characterise the molecular mechanisms governing KRAS signalling networks and determine what differentiates the signalling downstream of the KRAS mutants. Here we have used affinity purification mass-spectrometry proteomics to characterise the interactome of KRAS wild-type and three KRAS mutants. Bioinformatic analysis associated with experimental validation allows us to map the signalling network mediated by the different KRAS proteins. Using this approach, we characterised how the interactome of KRAS wild-type and mutants is regulated by the clinically approved KRASG12C inhibitor Sotorasib. In addition, we identified novel crosstalks between KRAS and its effector pathways including the AKT and JAK-STAT signalling modules.

Published
2023
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36. Detection of Endoparasites in Non-Native Raccoons from Central Italy.

Author

Lombardo A, Diano M, Brocherel G, Palmerini L, Giovannini S, Mezher Z, Iurescia M, Cerci T, Caprioli A, Eleni C, Raso C, Mariacher A, Del Lesto I, Cappai N, Mattioli L, De Liberato C, and Fichi G

Abstract

The raccoon ( Procyon lotor ) is a carnivore native to North and Central America, gradually introduced into Asia and Europe, including Italy. It is an important carrier of multiple endoparasites, both Protozoa and Helminths, some of them being zoonotic. The aim of this study was to investigate the endoparasites of the non-native raccoon population of Central Italy. Sixty-two raccoons were collected by local competent authorities (sixty trapped and euthanized, two found dead) and subjected to necroscopic examination. Carcasses underwent a broad parasitological investigation, including coprological techniques (macroscopic examination of the gastrointestinal tract, lungs, trachea, and heart, Flotac ® , Baermann test, and immunofluorescence for Giardia duodenalis and Cryptosporidium spp.), research on respiratory/urinary capillariosis and artificial digestion for Trichinella spp. larvae, and a histopathological examination of the ileum. Ascarid parasites were further identified at the species level using a next-generation sequencing-based amplicon sequencing approach. The results showed the presence of different Protozoa and Nematodes: Baylisascaris procyonis (26/62; 41.9%), Pearsonema sp. (6/62; 9.6%), Capillariidae (6/62; 9.6%), Eimeria sp. (2/62; 3.2%), Cryptosporidium sp. (2/62; 3.2%), and Ancylostomatidae (2/62; 3.2%). B. procyonis is an emerging helminthic zoonotic agent considered a serious concern for public and animal health, given the possibility of its transmission to paratenic hosts, including humans and pets. The demonstrated role of the raccoon as a multi-parasite carrier should be an incentive to continuing the eradication/control of this alien species, and supports the need to implement related disease surveillance programs.

Published
2023
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37. Dietary Preferences of Loggerhead Sea Turtles ( Caretta caretta ) in Two Mediterranean Feeding Grounds: Does Prey Selection Change with Habitat Use throughout Their Life Cycle?

Author

Mariani G, Bellucci F, Cocumelli C, Raso C, Hochscheid S, Roncari C, Nerone E, Recchi S, Di Giacinto F, Olivieri V, Pulsoni S, Matiddi M, Silvestri C, Ferri N, and Renzo LD

Abstract

According to their life stage, the loggerhead sea turtle ( Caretta caretta ) is found in a wide range of habitats, from neritic to more oceanic areas. Their feeding habits are expected to change as they develop, along with habitat use. Juvenile sea turtles are hypothesized to feed on pelagic species in oceanic areas, shifting to more benthic prey during the subadult and adult stages. We analyzed the gastrointestinal content from 150 loggerhead sea turtles stranded and/or bycaught along the Adriatic coast of the Abruzzo and Molise regions ( n = 89) and the Tyrrhenian coast of the Lazio and Campania regions ( n = 61) from 2018 to 2021. Food items were identified to the lowest taxonomic level, and the frequency of occurrence was calculated for each taxon and most recurrent species to assess changes in prey selection during the development. The marine litter was categorized, and the frequency of occurrence was calculated for the ingestion of litter. The most recurrent taxonomic prey group recorded in the Adriatic sample was Arthropoda (94%), followed by Mollusca (63%) and Chordata (34%). In the Tyrrhenian sample, loggerhead sea turtles fed mostly on Mollusca (84%), Arthropoda (38%), and Chordata (26%). Surprisingly, the Adriatic-Tyrrhenian sample groups showed similar feeding behavior between juveniles, subadults, and adults. A similar correlation has been observed concerning the ingestion of litter. Moreover, this study confirms the opportunistic feeding behavior of loggerhead sea turtles and their high adaptability., Competing Interests: The authors declare no conflict of interest.

Published
2023
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38. Liquid Biopsy-Guided Interventional Oncology: A Proof of Concept with a Special Focus on Radiotherapy and Radiology.

Author

Malara N, Kovacs G, Bussu F, Ferrazzo T, Garo V, Raso C, Cornacchione P, Iezzi R, and Tagliaferri L

Abstract

Although the role of liquid biopsy (LB) to measure minimal residual disease (MRD) in the treatment of epithelial cancer is well known, the biology of the change in the availability of circulating biomarkers arising throughout treatments such as radiotherapy and interventional radio-oncology is less explained. Deep knowledge of how therapeutic effects can influence the biology of the release mechanism at the base of the biomarkers available in the bloodstream is needed for selecting the appropriate treatment-induced tumor circulating biomarker. Combining existing progress in the LB and interventional oncology (IO) fields, a proof of concept is provided, discussing the advantages of the traditional risk assessment of relapsing lesions, limitations, and the timing of detection of the circulating biomarker. The current review aims to help both interventional radiologists and interventional radiation oncologists evaluate the possibility of drawing a tailor-made board of blood-based surveillance markers to reveal subclinical diseases and avoid overtreatment.

Published
2022
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39. Systemic Infection by Angiostrongylus vasorum in a Fennec ( Vulpes zerda ) in an Italian Zoological Garden.

Author

Galietta V, Eleni C, Raso C, Cocumelli C, Friedrich KG, Di Cerbo P, Iurescia M, Diaconu EL, Alba P, and De Liberato C

Abstract

This paper reported a case of a metastrongyloid nematode Angiostrongylus vasorum infection in a fennec ( Vulpes zerda ) kept in a zoo in central Italy. The fennec had shown paralysis of the hind limbs, anorexia, weakness and respiratory signs before death. Cardiomegaly and granulomatous pneumonia were the major anatomopathological findings. Inflammatory lesions associated with parasitic larvae were observed in the lungs, brain, liver, heart, spinal cord and kidney of the fennec at histology. A. vasorum diagnosis was confirmed by both morphological and molecular identification of adult worms recovered at necropsy. Fennecs are active predators and maintain their hunting behaviour in captivity. Hence, it is likely that the animal was exposed to infection by preying on parasitised gastropods, intermediate hosts of A. vasorum , entering zoo enclosures from the surrounding environment. This is the first report of A. vasorum systemic infection in a captive fennec ( V. zerda) in a zoo in Italy.

Published
2022
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40. An activity-based bioprobe differentiates a novel small molecule inhibitor from a LOXL2 antibody and provides renewed promise for anti-fibrotic therapeutic strategies.

Author

Findlay A, Turner C, Schilter H, Deodhar M, Zhou W, Perryman L, Foot J, Zahoor A, Yao Y, Hamilton R, Brock M, Raso C, Stolp J, Galati M, Hamprecht D, Charlton B, and Jarolimek W

Subjects
Amino Acid Oxidoreductases analysis, Amino Acid Oxidoreductases therapeutic use, Antifibrotic Agents analysis, Antifibrotic Agents therapeutic use, Biosensing Techniques methods, Fibrosis drug therapy, Fibrosis prevention & control, Humans, Amino Acid Oxidoreductases pharmacology, Antifibrotic Agents pharmacology, Biosensing Techniques instrumentation, Biosensing Techniques standards
Published
2021
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41. Plasmodium matutinum Causing Avian Malaria in Lovebirds ( Agapornis roseicollis ) Hosted in an Italian Zoo.

Author

Cocumelli C, Iurescia M, Diaconu EL, Galietta V, Raso C, Buccella C, Stravino F, Grande F, Fiorucci L, De Liberato C, Caprioli A, and Battisti A

Abstract

Avian malaria is a worldwide distributed, vector-born disease of birds caused by parasites of the order Haemosporida. There is a lack of knowledge about the presence and pathogenetic role of Haemosporida in Psittacidae. Here we report a case of avian malaria infection in lovebirds ( Agapornis roseicollis ), with the genetic characterization of the Plasmodium species involved. The birds were hosted in a zoo located in Italy, where avian malaria cases in African penguins ( Spheniscus demersus ) were already reported. Animals ( n = 11) were submitted for necropsy after sudden death and were subjected to further analyses including histopathology, bacteriology, and PCR for the research of haemosporidians. Clinical history, gross lesions and histopathological observation of schizonts, together with positive PCR results for Plasmodium spp., demonstrated that avian malaria was the cause of death for one animal and the possible cause of death for the other nine. The sequences obtained were compared using BLAST and analyzed for similarity to sequences available at the MalAvi database. Genetic analyses demonstrated a 100% nucleotide identity to Plasmodium matutinum LINN1 for all the obtained sequences. To our knowledge, this is the first report describing avian malaria in lovebirds.

Published
2021
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42. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS G13D .

Author

Kennedy SA, Jarboui MA, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn MA, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko BN, Iglesias-Martinez LF, Ryan CJ, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn DJ, and Kolch W

Subjects
Cell Line, Tumor, Humans, Phosphorylation, Prognosis, Survival Analysis, bcl-Associated Death Protein metabolism, Cell Transformation, Neoplastic pathology, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, ErbB Receptors metabolism, Mutation genetics, Protein Interaction Maps, Proto-Oncogene Proteins p21(ras) genetics
Abstract

Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRAS G13D ) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRAS G13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.

Published
2020
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43. Fhit-Fdxr interaction in the mitochondria: modulation of reactive oxygen species generation and apoptosis in cancer cells.

Author

Druck T, Cheung DG, Park D, Trapasso F, Pichiorri F, Gaspari M, Palumbo T, Aqeilan RI, Gaudio E, Okumura H, Iuliano R, Raso C, Green K, Huebner K, and Croce CM

Subjects
A549 Cells, Acid Anhydride Hydrolases genetics, Atovaquone pharmacology, Cell Survival drug effects, Cell Survival genetics, Chaperonin 10 metabolism, Chaperonin 60 metabolism, Colonic Neoplasms pathology, HCT116 Cells, Humans, Lung Neoplasms pathology, Mitochondrial Proteins metabolism, Neoplasm Proteins genetics, Oxidative Phosphorylation drug effects, Transfection, Acid Anhydride Hydrolases metabolism, Apoptosis genetics, Colonic Neoplasms metabolism, Ferredoxin-NADP Reductase metabolism, Lung Neoplasms metabolism, Mitochondria metabolism, Neoplasm Proteins metabolism, Reactive Oxygen Species metabolism
Abstract

Fhit protein is lost in cancers of most, perhaps all, cancer types; when restored, it can induce apoptosis and suppress tumorigenicity, as shown in vitro and in mouse tumor models in vivo. Following protein cross-linking and proteomics analyses, we characterized a Fhit protein complex involved in triggering Fhit-mediated apoptosis. The complex includes the heat-shock chaperonin pair, HSP60/10, which is likely involved in importing Fhit into the mitochondria, where it interacts with ferredoxin reductase, responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin, in electron transport chain complex III. Overexpression of Fhit protein in Fhit-deficient cancer cells modulates the production of intracellular reactive oxygen species, causing increased ROS, following peroxide treatment, with subsequent increased apoptosis of lung cancer cells under oxidative stress conditions; conversely, Fhit-negative cells escape ROS overproduction and ROS-induced apoptosis, likely carrying oxidative damage. Thus, characterization of Fhit-interacting proteins has identified direct effectors of a Fhit-mediated apoptotic signal pathway that is lost in many cancers. This is of translational interest considering the very recent emphasis in a number of high-profile publications, concerning the role of oxidative phosphorylation in the treatment of human cancers, and especially cancer stem cells that rely upon oxidative phosphorylation for survival. Additionally, we have shown that cells from a Fhit-deficient lung cancer cell line, are sensitive to killing by exposure to atovaquone, thought to act as a selective oxidative phosphorylation inhibitor by targeting the CoQ10 dependence of the mitochondrial complex III, while the Fhit-expressing sister clone is resistant to this treatment.

Published
2019
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44. RASSF1A uncouples Wnt from Hippo signalling and promotes YAP mediated differentiation via p73.

Author

Papaspyropoulos A, Bradley L, Thapa A, Leung CY, Toskas K, Koennig D, Pefani DE, Raso C, Grou C, Hamilton G, Vlahov N, Grawenda A, Haider S, Chauhan J, Buti L, Kanapin A, Lu X, Buffa F, Dianov G, von Kriegsheim A, Matallanas D, Samsonova A, Zernicka-Goetz M, and O'Neill E

Subjects
Adaptor Proteins, Signal Transducing genetics, Animals, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Cycle Proteins, Cell Differentiation, DNA-Binding Proteins metabolism, Embryonic Stem Cells physiology, Female, Gene Expression Regulation, Developmental, Hippo Signaling Pathway, Humans, Male, Mice, Inbred C57BL, Mice, Inbred CBA, Octamer Transcription Factor-3 genetics, Octamer Transcription Factor-3 metabolism, Phosphoproteins genetics, Protein Serine-Threonine Kinases genetics, Signal Transduction, TEA Domain Transcription Factors, Transcription Factors metabolism, Tumor Protein p73 genetics, Tumor Suppressor Proteins genetics, Wnt Proteins metabolism, YAP-Signaling Proteins, beta Catenin metabolism, Adaptor Proteins, Signal Transducing metabolism, Embryonic Stem Cells cytology, Phosphoproteins metabolism, Protein Serine-Threonine Kinases metabolism, Tumor Protein p73 metabolism, Tumor Suppressor Proteins metabolism
Abstract

Transition from pluripotency to differentiation is a pivotal yet poorly understood developmental step. Here, we show that the tumour suppressor RASSF1A is a key player driving the early specification of cell fate. RASSF1A acts as a natural barrier to stem cell self-renewal and iPS cell generation, by switching YAP from an integral component in the β-catenin-TCF pluripotency network to a key factor that promotes differentiation. We demonstrate that epigenetic regulation of the Rassf1A promoter maintains stemness by allowing a quaternary association of YAP-TEAD and β-catenin-TCF3 complexes on the Oct4 distal enhancer. However, during differentiation, promoter demethylation allows GATA1-mediated RASSF1A expression which prevents YAP from contributing to the TEAD/β-catenin-TCF3 complex. Simultaneously, we find that RASSF1A promotes a YAP-p73 transcriptional programme that enables differentiation. Together, our findings demonstrate that RASSF1A mediates transcription factor selection of YAP in stem cells, thereby acting as a functional "switch" between pluripotency and initiation of differentiation.

Published
2018
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46. A novel RNA sequencing data analysis method for cell line authentication.

Author

Fasterius E, Raso C, Kennedy S, Rauch N, Lundin P, Kolch W, Uhlén M, and Al-Khalili Szigyarto C

Subjects
Cell Line, Tumor, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Gene Expression Profiling methods, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease genetics, HCT116 Cells, HT29 Cells, Humans, Proto-Oncogene Proteins p21(ras) genetics, Reproducibility of Results, DNA Mutational Analysis methods, Mutation, Sequence Analysis, RNA methods, Transcriptome genetics
Abstract

We have developed a novel analysis method that can interrogate the authenticity of biological samples used for generation of transcriptome profiles in public data repositories. The method uses RNA sequencing information to reveal mutations in expressed transcripts and subsequently confirms the identity of analysed cells by comparison with publicly available cell-specific mutational profiles. Cell lines constitute key model systems widely used within cancer research, but their identity needs to be confirmed in order to minimise the influence of cell contaminations and genetic drift on the analysis. Using both public and novel data, we demonstrate the use of RNA-sequencing data analysis for cell line authentication by examining the validity of COLO205, DLD1, HCT15, HCT116, HKE3, HT29 and RKO colorectal cancer cell lines. We successfully authenticate the studied cell lines and validate previous reports indicating that DLD1 and HCT15 are synonymous. We also show that the analysed HKE3 cells harbour an unexpected KRAS-G13D mutation and confirm that this cell line is a genuine KRAS dosage mutant, rather than a true isogenic derivative of HCT116 expressing only the wild type KRAS. This authentication method could be used to revisit the numerous cell line based RNA sequencing experiments available in public data repositories, analyse new experiments where whole genome sequencing is not available, as well as facilitate comparisons of data from different experiments, platforms and laboratories., Competing Interests: The authors have declared that no competing interests exist.

Published
2017
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47. The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer.

Author

Tonry CL, Leacy E, Raso C, Finn SP, Armstrong J, and Pennington SR

Abstract

Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i) provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii) address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii) make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making., Competing Interests: Stephen R. Pennington is the founder of Atturos, a UCD spinout company that is developing multiplexed protein biomarkers to improve patient decision making.

Published
2016
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48. HiQuant: Rapid Postquantification Analysis of Large-Scale MS-Generated Proteomics Data.

Author

Bryan K, Jarboui MA, Raso C, Bernal-Llinares M, McCann B, Rauch J, Boldt K, and Lynn DJ

Subjects
Animals, Computational Biology, Data Interpretation, Statistical, Humans, Mass Spectrometry methods, Protein Interaction Mapping, Protein Kinases, Protein Serine-Threonine Kinases, Proteome, Proteomics methods, Software, Workflow
Abstract

Recent advances in mass-spectrometry-based proteomics are now facilitating ambitious large-scale investigations of the spatial and temporal dynamics of the proteome; however, the increasing size and complexity of these data sets is overwhelming current downstream computational methods, specifically those that support the postquantification analysis pipeline. Here we present HiQuant, a novel application that enables the design and execution of a postquantification workflow, including common data-processing steps, such as assay normalization and grouping, and experimental replicate quality control and statistical analysis. HiQuant also enables the interpretation of results generated from large-scale data sets by supporting interactive heatmap analysis and also the direct export to Cytoscape and Gephi, two leading network analysis platforms. HiQuant may be run via a user-friendly graphical interface and also supports complete one-touch automation via a command-line mode. We evaluate HiQuant's performance by analyzing a large-scale, complex interactome mapping data set and demonstrate a 200-fold improvement in the execution time over current methods. We also demonstrate HiQuant's general utility by analyzing proteome-wide quantification data generated from both a large-scale public tyrosine kinase siRNA knock-down study and an in-house investigation into the temporal dynamics of the KSR1 and KSR2 interactomes. Download HiQuant, sample data sets, and supporting documentation at http://hiquant.primesdb.eu .

Published
2016
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49. Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells.

Author

Malara N, Coluccio ML, Limongi T, Asande M, Trunzo V, Cojoc G, Raso C, Candeloro P, Perozziello G, Raimondo R, De Vitis S, Roveda L, Renne M, Prati U, Mollace V, and Di Fabrizio E

Subjects
5-Methylcytosine blood, 5-Methylcytosine metabolism, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Blood Chemical Analysis methods, Cells, Cultured, DNA Methylation, Enzyme-Linked Immunosorbent Assay, Folic Acid pharmacology, Genes, Neoplasm, Humans, Microscopy, Confocal instrumentation, Microscopy, Confocal methods, Neoplasms blood, Neoplasms genetics, Neoplasms mortality, Neoplastic Cells, Circulating pathology, Surface Properties, Survival Analysis, 5-Methylcytosine analysis, Biomarkers, Tumor analysis, Blood Chemical Analysis instrumentation, Folic Acid chemistry, Neoplasms diagnosis, Neoplastic Cells, Circulating metabolism
Abstract

Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2014
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50. In vitro expansion of tumour cells derived from blood and tumour tissue is useful to redefine personalized treatment in non-small cell lung cancer patients.

Author

Malara NM, Givigliano F, Trunzo V, Macrina L, Raso C, Amodio N, Aprigliano S, Minniti AM, Russo V, Roveda L, Coluccio ML, Fini M, Voci P, Prati U, Di Fabrizio E, and Mollace V

Subjects
Aged, Aged, 80 and over, Biopsy, Carcinoma, Non-Small-Cell Lung therapy, Cell Cycle, Humans, Lung Neoplasms therapy, Lymphocytes, Tumor-Infiltrating pathology, Male, Middle Aged, Precision Medicine, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology, Neoplastic Cells, Circulating
Abstract

The clinical development of locally and advanced non-small cell lung cancer (NSCLC) suffers from a lack of biomarkers as a guide in the selection of optimal prognostic prediction. Circulating Tumour Cells (CTCs) are correlated to prognosis and show efficacy in cancer monitoring in patients. However, their enumeration alone might be inadequate; it might also be critical to understand the viability, the apoptotic state and the kinetics of these cells. Here, we report what we believe to be a new and selective approach to visually detect tumour specific CTCs. Firstly, using labelled human lung cancer cells, we detected a specific density interval in which NSCL-CTCs were concentrated. Secondly, to better characterize CTCs in respect to their heterogeneous composition and tumour reference, blood and tumour biopsy were performed on specimens taken from the same patient. The approach consisted in comparing phenotype profile of CTCs, and their progenitor Tumour Stem Cells, (TSCs). Moreover, NSCL-CTCs were cultivated in short-time human cultures to provide response to drug sensitivity. Our bimodal approach allowed to reveal two items. Firstly, that one part of a tumour, proximal to the bronchial structure, displays a predominance of CD133+. Secondly, specific NSCL-CTCs Epithelial Cell Adhesion Molecule (EpCAM)+CD29+ can be used as a negative prognostic factor as well the high expression of CTCs EpCAM+. These data were confirmed by drug-sensitivity tests, in vitro, and by the survival curves, in vivo.

Published
2014

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