30 results on '"Soncini C"'
Search Results
2. The 'Personal Health Budget' intervention model in early psychosis: Preliminary findings from the Parma experience
- Author
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Pelizza, L., Leuci, E., Landi, G., Quattrone, E., Azzali, S., Pelosi, A., Ceroni, P., Soncini, C., Daolio, M. C., Dall'Aglio, R., Paulillo, G., Pellegrini, C., Raballo, A., and Pellegrini, P.
- Subjects
First episode psychosis ,Early intervention in psychosis ,Mental health services ,Early psychosis ,Personal health budget ,Rehabilitation - Published
- 2020
3. PROPERTIES OF A STRAIN OF ARABIS MOSAIC VIRUS ISOLATED FROM GRAPEVINE IN ITALY
- Author
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BELLI, G., VEGETTI, G., CINQUANTA, S., SONCINI, C., PRATI, S., and TOLENTINO, D.
- Published
- 1984
4. INFEZIONI MISTE DI MDMV (Maize Dwarf Mosaic Virus) E BYDV (Barley Yellow Dwarf Virus) IN PIANTE DI MAIS IN LOMBARDIA
- Author
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BELLI, G., CINQUANTA, S., and SONCINI, C.
- Published
- 1980
5. PURIFICATION AND SEROLOGICAL IDENTIFICATION OF AN ISOLATE OF BARLEY YELLOW DWARF VIRUS CAUSING RICE GIALLUME
- Author
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BELLI, G., CINQUANTA, S., PRATI, S., and SONCINI, C.
- Published
- 1986
6. IDENTIFICAZIONE E PRIME CARATTERISTICHE DI UN CEPPO DI SLRV (STRAWBERRY LATENT RINGSPOT VIRUS) ISOLATO DA COLTIVAZIONI DI LAMPONE IN LOMBARDIA
- Author
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VEGETTI, G., BELLI, G., CINQUANTA, S., and SONCINI, C.
- Published
- 1979
7. The SUPERB silicon vertex tracker RID C-9883-2009
- Author
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Forti, Francesco, Avanzini, Carlo, Batignani, Giovanni, Bettarini, Stefano, Bosi, F, Calderini, Giovanni, Ceccanti, M, Cenci, R, Cervelli, Alberto, Crescioli, Francesco, Dell'Orso, Mauro, Giannetti, P, Giorgi, Marcello, Lusiani, A, Gregucci, S, Mammini, P, Marchiori, Giovanni, Massa, M, Morsani, F, Neri, Nicola, Paoloni, Eugenio, Piendibene, Marco, Profeti, A, Rizzo, Giuliana, Sartori, L, Walsh, J, Yurtsev, E, Manghisoni, M, Re, V, Traversi, G, Bruschi, M, Di Sipio, R, Giacobbe, B, Gabrielli, A, Giorgi, F, Pellegrini, G, Sbarra, C, Semprini, N, Spighi, R, Valentinetti, S, Villa, M, Zoccoli, A, Citterio, M, Liberali, V, Palombo, F, Andreoli, C, Gaioni, L, Pozzati, E, Ratti, L, Speziali, V, Gamba, D, Giraudo, G, Mereu, P, Betta, Gfd, Soncini, C, Fontana, G, Bomben, M, Bosisio, L, Cristaudo, P, Giacomini, G, Jugovaz, D, Lanceri, L, Rashevskaya, I, Vitale, L, and Venier, G.
- Published
- 2011
8. 'Disturbo da Uso di Alcool'
- Author
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Guazzelli, M., Guerrini, I., Mauri, Mauro, Pezzica, P., Banti, S., Marino, C., Muratorio, A., Bonuccelli, Ubaldo, Nuti, A., Scotti, G., Livian, S., Naccarato, R., Riolo, R., Salvagnini, M., Bevilacqua, Generoso, Naccarato, A. G., Torre, E., Gallimberti, L., Spella, R. M., and Soncini, C. A.
- Published
- 1999
9. AURORA-A T288E COMPLEXED WITH PHA-828300
- Author
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Bindi, S., primary, Fancelli, D., additional, Alli, C., additional, Berta, D., additional, Bertrand, J.A., additional, Cameron, A.D., additional, Cappella, P., additional, Carpinelli, P., additional, Cervi, G., additional, Croci, W., additional, D'Anello, M., additional, Forte, B., additional, LauraGiorgini, M., additional, Marsiglio, A., additional, Moll, J., additional, Pesenti, E., additional, Pittala, V., additional, Pulici, M., additional, Riccardi-Sirtori, F., additional, Roletto, F., additional, Soncini, C., additional, Storici, P., additional, Varasi, M., additional, Volpi, D., additional, Zugnoni, P., additional, and Vianello, P., additional
- Published
- 2010
- Full Text
- View/download PDF
10. Crystal structure of the T315I Abl mutant in complex with the inhibitor PHA-739358
- Author
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Modugno, M., primary, Casale, E., additional, Soncini, C., additional, Rosettani, P., additional, Colombo, R., additional, Lupi, R., additional, Rusconi, L., additional, Fancelli, D., additional, Carpinelli, P., additional, Cameron, A.D., additional, Isacchi, A., additional, and Moll, J., additional
- Published
- 2007
- Full Text
- View/download PDF
11. High-Level Expression in Escherichia coli and Purification of Yeast Transcription Factor IIIA
- Author
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Ottonello, S., primary, Ballabeni, A., additional, Soncini, C., additional, and Dieci, G., additional
- Published
- 1994
- Full Text
- View/download PDF
12. Potent and Selective Aurora Inhibitors Identified by the Expansion of a Novel Scaffold for Protein Kinase Inhibition
- Author
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Fancelli, D., Berta, D., Bindi, S., Cameron, A., Cappella, P., Carpinelli, P., Catana, C., Forte, B., Giordano, P., Giorgini, M. L., Mantegani, S., Marsiglio, A., Meroni, M., Moll, J., Pittala, V., Roletto, F., Severino, D., Soncini, C., Storici, P., Tonani, R., Varasi, M., Vulpetti, A., and Vianello, P.
- Abstract
Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC
50 of 0.027 μM in the enzymatic assay for Aur-A inhibition and IC50 s between 0.05 μM and 0.5 μM for the inhibition of proliferation of different tumor cell lines.- Published
- 2005
13. Catecholic Flavonoids Acting as Telomerase Inhibitors
- Author
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Menichincheri, M., Ballinari, D., Bargiotti, A., Bonomini, L., Ceccarelli, W., D'Alessio, R., Fretta, A., Moll, J., Polucci, P., Soncini, C., Tibolla, M., Trosset, J.-Y., and Vanotti, E.
- Abstract
In recent years telomerase has been identified as a new promising target in oncology and consequently new telomerase inhibitors have been intensely explored as anticancer agents. Focused screening of several polyhydroxylated flavonoids has allowed us to identify 7,8,3,4-tetrahydroxyflavone
1 as a new telomerase inhibitor with an interesting in vitro activity in a Flash-Plate assay (IC50 = 0.2 μM) that has been confirmed in the classical TRAP assay. Starting from this compound, we developed a medicinal chemistry program to optimize our lead, and in particular to replace one of the two catechols with potential bioisosteres. From this study, new structural analogues characterized by submicromolar potencies have been obtained. Their synthesis and biological activity are described.- Published
- 2004
14. Gamma-hydroxybutyric acid in the treatment of alcohol and heroin dependence
- Author
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Gallimberti, L., Spella, M. R., Soncini, C. A., and Gessa, G. L.
- Published
- 2000
- Full Text
- View/download PDF
15. High-Level Expression in Escherichia coliand Purification of Yeast Transcription Factor IIIA
- Author
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Ottonello, S., Ballabeni, A., Soncini, C., and Dieci, G.
- Abstract
Saccharomyces cerevisiaetranscription factor IIIA, a sequence-specific DNA binding protein that is required for transcription of 5S rRNA genes by RNA polymerase III, has been expressed in Escherichia coliin a full length, native form. High level expression was achieved through the combined use of a T7 RNA polymerase expression system and of a multicopy plasmid carrying an E.coligene, argU, which codes for a minor Arg(AGA/AGG) tRNA species. Recombinant yeast transcription factor IIIA was purified to 95% homogeneity, at a final yield of 8 mg/liter of bacterial culture, by three chromatographic steps, and it was shown to be at least 55% active by quantitative in vitrotranscription assays.
- Published
- 1994
- Full Text
- View/download PDF
16. The accumulation of a cold-regulated chloroplastic protein is light-dependent
- Author
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Cristina Crosatti, A. M. Stanca, Soncini C, and Luigi Cattivelli
- Subjects
Messenger RNA ,Chloroplasts ,Light ,Molecular Sequence Data ,food and beverages ,Hordeum ,Plant Science ,Biology ,biology.organism_classification ,Cell biology ,Chloroplast ,Cold Temperature ,Chloroplast stroma ,Botany ,Genetics ,Cold acclimation ,Protein biosynthesis ,Hordeum vulgare ,Amino Acid Sequence ,Gene ,Heat-Shock Proteins ,Plant Proteins - Abstract
The protein encoded by cDNA clone pt59 and induced in barley (Hordeum vulgare L.) by cold was overexpressed in coli to produce the matching antibody, which in vivo recognized a cold-induced protein of 14 kDa (COR 14) that was found in the chloroplast stroma. The accumulation of COR14 occurred only at low temperatures after even a brief exposure of the plants to light. Plants grown and fully hardened in the dark accumulated a reduced amount of pt59-corresponding mRNA and only traces of COR14. Light exposure for as short as 5 min was enough to normalize the expression of pt59-corresponding mRNA and increase the accumulation of COR14. These findings indicate that one or more light-dependent factors are involved in transcription of the gene and accumulation of the protein. The COR14 protein was stored in amounts only slightly greater in the resistant barley cultivar Onice than in the susceptible cultivar Gitane, although the former had a higher induction-temperature threshold for COR14 than the latter. This fact is an evolutionary advantage, enabling the resistant varieties in the field to prepare for the cold well ahead of the susceptible ones.
17. The superB silicon vertex tracker
- Author
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Marco Bruschi, Massimo Manghisoni, S. Bettarini, E. Pozzati, P. Cristaudo, Giuseppe Pellegrini, Alberto Lusiani, C. Andreoli, Giovanni Soncini, G. Venier, R. Cenci, V. Speziali, R. Spighi, Paola Giannetti, Fabio Morsani, Alessandro Gabrielli, R. Di Sipio, Mauro Villa, M. Dell'Orso, G. Fontana, G. Rizzo, F. Palombo, F. M. Giorgi, Carla Sbarra, D. Jugovaz, G. Calderini, G.-F. Dalla Betta, S. Gregucci, Eugenio Paoloni, G. Batignani, N. Semprini, Valentino Liberali, A. Profeti, Lodovico Ratti, Irina Rashevskaya, D. Gamba, Valerio Re, L. Lanceri, P. Mereu, Gianluca Traversi, F. Forti, M. Piendibene, M. Bomben, M. Massa, Mario Giorgi, B. Giacobbe, M. Citterio, G. Marchiori, G. Giacomini, J. J. Walsh, L. Vitale, Alberto Cervelli, Francesco Crescioli, C. Avanzini, Luigi Gaioni, Sara Valentinetti, G. Giraudo, Filippo Bosi, Nicola Neri, Luciano Bosisio, Antonio Zoccoli, Eugene Yurtsev, M. Ceccanti, P. Mammini, L. Sartori, G. Rizzo, C. Avanzini, G. Batignani, S. Bettarini, F. Bosi, G. Calderini, M. Ceccanti, R. Cenci, A. Cervelli, F. Crescioli, M. Dell'Orso, F. Forti, P. Giannetti, M.A. Giorgi, A. Lusiani, S. Gregucci, P. Mammini, G. Marchiori, M. Massa, F. Morsani, N. Neri, E. Paoloni, M. Piendibene, A. Profeti, L. Sartori, J. Walsh, E. Yurtsev, M. Manghisoni, V. Re, G. Traversi, M. Bruschi, R. Di Sipio, B. Giacobbe, A. Gabrielli, F. Giorgi, G. Pellegrini, C. Sbarra, N. Semprini, R. Spighi, S. Valentinetti, M. Villa, A. Zoccoli, M. Citterio, V. Liberali, F. Palombo, C. Andreoli, L. Gaioni, E. Pozzati, L. Ratti, V. Speziali, D. Gamba, G. Giraudo, P. Mereu, G.F. Dalla Betta, G. Soncini, G. Fontana, M. Bomben, L. Bosisio, P. Cristaudo, G. Giacomini, D. Jugovaz, L. Lanceri, I. Rashevskaya, L. Vitale, G. Venier, Forti, F, Avanzini, C, Batignani, G, Bettarini, S, Bosi, F, Calderini, G, Ceccanti, M, Cenci, R, Cervelli, A, Crescioli, F, Dell'Orso, M, Giannetti, P, Giorgi, Ma, Lusiani, Alberto, Gregucci, S, Mammini, P, Marchiori, G, Massa, M, Morsani, F, Neri, N, Paoloni, E, Piendibene, M, Profeti, A, Rizzo, G, Sartori, L, Walsh, J, Yurtsev, E, Manghisoni, M, Re, V, Traversi, G, Bruschi, M, Di Sipio, R, Giacobbe, B, Gabrielli, A, Giorgi, F, Pellegrini, G, Sbarra, C, Semprini, N, Spighi, R, Valentinetti, S, Villa, M, Zoccoli, A, Citterio, M, Liberali, V, Palombo, F, Andreoli, C, Gaioni, L, Pozzati, E, Ratti, L, Speziali, V, Gamba, D, Giraudo, G, Mereu, P, Betta, Gfd, Soncini, C, Fontana, G, Bomben, M, Bosisio, L, Cristaudo, P, Giacomini, G, Jugovaz, D, Lanceri, L, Rashevskaya, I, Vitale, L, Venier, G., Bomben, Marco, Bosisio, Luciano, Giacomini, Gabriele, Lanceri, Livio, I., Rachevskaia, Vitale, Lorenzo, SLIM5 Collaboration, et a. l., F., Forti, C., Avanzini, G., Batignani, S., Bettarini, F., Bosi, G., Calderini, M., Ceccanti, R., Cenci, A., Cervelli, F., Crescioli, M., Dell’Orso, P., Giannetti, M. A., Giorgi, A., Lusiani, S., Gregucci, P., Mammini, G., Marchiori, M., Massa, F., Morsani, N., Neri, E., Paoloni, M., Piendibene, A., Profeti, G., Rizzo, L., Sartori, J., Walsh, E., Yurtsev, M., Manghisoni, V., Re, G., Traversi, M., Bruschi, R., Di Sipio, B., Giacobbe, A., Gabrielli, F., Giorgi, G., Pellegrini, C., Sbarra, N., Semprini, R., Spighi, S., Valentinetti, M., Villa, A., Zoccoli, M., Citterio, V., Liberali, F., Palombo, C., Andreoli, L., Gaioni, E., Pozzati, L., Ratti, V., Speziali, D., Gamba, G., Giraudo, P., Mereu, G. F., Dalla Betta, G., Soncini, G., Fontana, P., Cristaudo, D., Jugovaz, Rashevskaya, Irina, and G., Venier
- Subjects
Nuclear and High Energy Physics ,Vertex (computer graphics) ,Silicon ,chemistry.chemical_element ,HYBRID PIXELS ,Settore ING-INF/01 - Elettronica ,law.invention ,Combinatorics ,B factory ,Silicon tracking detectors ,MAPS ,Microstrip detectors ,Optics ,law ,SILICON TRACKING ,Collider ,Instrumentation ,Silicon tracking detector ,Physics ,Luminosity (scattering theory) ,Interaction point ,business.industry ,Detector ,Vertex detectors ,Hybrid Pixels ,CMOS MAPS pixel sensors ,Charged particle tracking ,VERTEX DETECTORS ,CMOS MAPS PIXEL SENSORS ,CHARGED PARTICLE TRACKING ,B-factory ,chemistry ,SuperB silicon vertex tracker ,business ,Beam (structure) - Abstract
The SUPERB asymmetric e(+)e(-) collider, to be built near the INFN National Frascati Laboratory in Italy, has been designed to deliver a luminosity greater than 10(36) cm(-2) s(-1) with moderate beam currents, allowing precision measurements in the flavour sector sensitive to New Physics. The conceptual design of the Silicon Vertex Tracker for the SUPERB Detector is presented, based on double-sided silicon strip detectors for the outer layers, with the addition of an innermost Layer 0 close to the interaction point, with low material budget and capable of sustaining a background rate of several MHz/cm(2). (C) 2010 Elsevier B.V. All rights reserved.
- Published
- 2010
18. Intermixing of Unoccupied States of Metal Phthalocyanine Chains Assembled on Au(110).
- Author
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Kumar A, Betti MG, Mariani C, Kumar M, Gargiani P, Soncini C, and Pedio M
- Abstract
A detailed inverse photoemission study unveils the unoccupied electronic structure induced by the adsorption of CuPc and CoPc phthalocyanines on Au(110) reconstructed channels. The different behavior in the two systems is related to the different intermixing of orbitals with the underlying gold states. Broadening of the density of states at the Fermi level is detected after CoPc adsorption, absent in the case CuPc. A detailed comparison with the element-selective X-ray absorption spectroscopy enlightens and complements the IPES results and confirms a surface-driven intermixing of the CoPc orbitals involved in the interaction, with the out-of-plane Co 3d
z 2 orbital strongly hybridized with the gold electronic states. Moreover, the contribution of the 3d empty states to the IPES data is reported for FePc, CoPc, and CuPc thin films.- Published
- 2024
- Full Text
- View/download PDF
19. High-Resolution Photoemission Study of Neutron-Induced Defects in Amorphous Hydrogenated Silicon Devices.
- Author
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Peverini F, Bizzarri M, Boscardin M, Calcagnile L, Caprai M, Caricato AP, Cirrone GAP, Crivellari M, Cuttone G, Dunand S, Fanò L, Gianfelici B, Hammad O, Ionica M, Kanxheri K, Large M, Maruccio G, Menichelli M, Monteduro AG, Moscatelli F, Morozzi A, Pallotta S, Papi A, Passeri D, Petasecca M, Petringa G, Pis I, Quarta G, Rizzato S, Rossi A, Rossi G, Scorzoni A, Soncini C, Servoli L, Tacchi S, Talamonti C, Verzellesi G, Wyrsch N, Zema N, and Pedio M
- Abstract
In this paper, by means of high-resolution photoemission, soft X-ray absorption and atomic force microscopy, we investigate, for the first time, the mechanisms of damaging, induced by neutron source, and recovering (after annealing) of p-i-n detector devices based on hydrogenated amorphous silicon (a-Si:H). This investigation will be performed by mean of high-resolution photoemission, soft X-Ray absorption and atomic force microscopy. Due to dangling bonds, the amorphous silicon is a highly defective material. However, by hydrogenation it is possible to reduce the density of the defect by several orders of magnitude, using hydrogenation and this will allow its usage in radiation detector devices. The investigation of the damage induced by exposure to high energy irradiation and its microscopic origin is fundamental since the amount of defects determine the electronic properties of the a-Si:H. The comparison of the spectroscopic results on bare and irradiated samples shows an increased degree of disorder and a strong reduction of the Si-H bonds after irradiation. After annealing we observe a partial recovering of the Si-H bonds, reducing the disorder in the Si (possibly due to the lowering of the radiation-induced dangling bonds). Moreover, effects in the uppermost coating are also observed by spectroscopies.
- Published
- 2022
- Full Text
- View/download PDF
20. Personal health budget in patients with first episode psychosis: A new rehabilitation model based on a community care system in Italy.
- Author
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Leuci E, Pelizza L, Landi G, Quattrone E, Maestri D, Azzali S, Pelosi A, Ceroni P, Soncini C, Daolio MC, Paulillo G, Raballo A, and Pellegrini P
- Subjects
- Adult, Analysis of Variance, Brief Psychiatric Rating Scale, Humans, Italy, Community Mental Health Services, Psychotic Disorders psychology
- Abstract
Aim: Recently, there has been increasing interest in providing Personal Health Budgets (PHBs) to patients with severe mental illness. However, information on implementing PHB initiatives is still limited. Aim of this observational study was to evaluate the applicability of a PHB intervention model in a sample of Italian adults with first-episode psychosis (FEP) across a 2-year follow-up period., Methods: Participants (n = 104; 18-50 years) were recruited within the 'Parma-Early Psychosis' program and completed the brief psychiatric rating scale (BPRS), the health of nation outcome scale (HoNOS) and the global assessment of functioning (GAF). Mixed-design analysis of variance (ANOVA) and Kaplan-Maier survival analysis (as drop-out measure) were performed., Results: A significant effect of time on all BPRS, HoNOS and GAF scores along the follow-up was observed in both the FEP subgroups (i.e., with [n = 49] and without [n = 55] PHB intervention). Mixed-design ANOVA results showed a significant 'time x group' interaction effects on BPRS 'Disorganization', HoNOS 'Psychiatric Symptoms' and GAF scores in FEP participants with PHB. Kaplan-Meyer survival analysis showed a longer survival mean for FEP patients with PHB., Conclusions: Our results support the applicability of a PHB model within an 'Early Intervention in Psychosis' program in public community mental health services., (© 2021 John Wiley & Sons Australia, Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
21. Personal Health Budget as a new rehabilitation model for severe mental illness within a caring community: An Italian evaluation study of beneficial effects.
- Author
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Pelizza L, Leuci E, Landi G, Maestri D, Paulillo G, Ceroni P, Soncini C, Daolio MC, Quattrone E, and Pellegrini P
- Subjects
- Adult, Humans, Italy, Mental Health, Community Mental Health Services, Mental Disorders therapy
- Abstract
Objective: Personal Health Budget has been provided to consumers with severe mental illness within a policy shift toward a person-tailored mental healthcare treatment based on individual unmet needs. Evidence of beneficial effects of Personal Health Budget is still scarce. The aim of this study was to provide preliminary data on clinical and social benefits of adding Personal Health Budget to a standard pharmacotherapy in patients with severe mental illness across a 24-month follow-up period., Methods: Participants ( n = 137) were individuals with severe mental illness, aged 18-50 years, recruited in one of the adult mental health services of the Parma Department of Mental Health. They completed the Global Assessment of Functioning scale, the Health of the Nation Outcome Scale and the Brief Psychiatric Rating Scale. This age range was chosen to limit Personal Health Budget interventions to adults with a non-prolonged illness duration. Friedman's test for repeated measure was used to assess the longitudinal stability of functioning and clinical parameters. A linear regression analysis was also performed., Results: A significant decrease in all Global Assessment of Functioning scale, Health of the Nation Outcome Scale and Brief Psychiatric Rating Scale scores along the 24 months of follow-up was observed. Regression analysis results specifically showed a relevant association between a Personal Health Budget multiaxial intervention and the longitudinal reduction in Brief Psychiatric Rating Scale 'Negative Symptoms' and Health of the Nation Outcome Scale 'Social Problems' subscores., Conclusion: Our findings support the useful implementation of a Health of the Nation Outcome Scale approach for severe mental illness patients within the Italian mental health service network.
- Published
- 2021
- Full Text
- View/download PDF
22. Electronic properties of carbon nanotubes as detected by photoemission and inverse photoemission.
- Author
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Soncini C, Bondino F, Magnano E, Bhardwaj S, Kumar M, Cepek C, and Pedio M
- Abstract
The relation between morphology and energy level alignment in carbon nanotubes (CNT) is a crucial information for the optimization of applications in nanoelectronics, optics, mechanics and (bio)chemistry. Here we present a study of the relation between the electronic properties and the morphology of single wall CNT (SWCNT), aligned multi wall CNT (MWCNT) and unaligned MWCNT. The CNT were synthesized via catalytic chemical vapor deposition in ultra-high vacuum conditions. Combined ultraviolet photoemission and inverse photoemission (IPES) spectra reveal a high sensitivity to the nanotube morphology. In the case of unaligned SWCNT the distinctive unoccupied Van Hove singularities (vHs) features are observed in the high resolution IPES spectra. Those features are assigned to semiconducting and metallic SWCNT states, according to calculated vHs DOS. The two MWCNT samples are similar in the diameter of the tube (about 15 nm) and present similar filled and empty electronic states, although the measured features in the aligned MWCNT are more defined. Noteworthy, interlayer states are also revealed. Their intensities are directly related to the MWCNT alignment. Focussing and geometrical effects associated to the MWCNT alignment are discussed to account the spectral differences.
- Published
- 2021
- Full Text
- View/download PDF
23. Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity.
- Author
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Bindi S, Fancelli D, Alli C, Berta D, Bertrand JA, Cameron AD, Cappella P, Carpinelli P, Cervi G, Croci V, D'Anello M, Forte B, Giorgini ML, Marsiglio A, Moll J, Pesenti E, Pittalà V, Pulici M, Riccardi-Sirtori F, Roletto F, Soncini C, Storici P, Varasi M, Volpi D, Zugnoni P, and Vianello P
- Subjects
- Animals, Antineoplastic Agents chemistry, Aurora Kinases, Cell Cycle drug effects, Cell Proliferation drug effects, Computational Biology, Crystallography, X-Ray, Drug Screening Assays, Antitumor, Enzyme Inhibitors chemistry, HL-60 Cells, Humans, Male, Mice, Mice, SCID, Models, Molecular, Molecular Dynamics Simulation, Molecular Structure, Neoplasms, Experimental drug therapy, Pyrazoles chemical synthesis, Pyrazoles chemistry, Stereoisomerism, Structure-Activity Relationship, Thiophenes chemical synthesis, Thiophenes chemistry, Transplantation, Heterologous, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrazoles pharmacology, Thiophenes pharmacology
- Abstract
A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
24. PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer.
- Author
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Carpinelli P, Ceruti R, Giorgini ML, Cappella P, Gianellini L, Croci V, Degrassi A, Texido G, Rocchetti M, Vianello P, Rusconi L, Storici P, Zugnoni P, Arrigoni C, Soncini C, Alli C, Patton V, Marsiglio A, Ballinari D, Pesenti E, Fancelli D, and Moll J
- Subjects
- Animals, Aurora Kinase B, Aurora Kinases, Benzamides pharmacokinetics, Benzamides therapeutic use, Cell Line, Tumor, Cell Proliferation drug effects, Female, Humans, Immunohistochemistry, Male, Mice, Mice, Nude, Neoplasms enzymology, Phosphorylation, Pyrazoles pharmacokinetics, Pyrazoles therapeutic use, Rats, Rats, Sprague-Dawley, Benzamides pharmacology, Neoplasms drug therapy, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrazoles pharmacology
- Abstract
PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity against Aurora kinases and cross-reactivities with some receptor tyrosine kinases relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and shows a dominant Aurora B kinase inhibition-related cellular phenotype and mechanism of action in cells in vitro and in vivo. p53 status-dependent endoreduplication is observed upon treatment of cells with PHA-739358, and phosphorylation of histone H3 in Ser(10) is inhibited. The compound has significant antitumor activity in different xenografts and spontaneous and transgenic animal tumor models and shows a favorable pharmacokinetic and safety profile. In vivo target modulation is observed as assessed by the inhibition of the phosphorylation of histone H3, which has been validated preclinically as a candidate biomarker for the clinical phase. Pharmacokinetics/pharmacodynamics modeling was used to define drug potency and to support the prediction of active clinical doses and schedules. We conclude that PHA-739358, which is currently tested in clinical trials, has great therapeutic potential in anticancer therapy in a wide range of cancers.
- Published
- 2007
- Full Text
- View/download PDF
25. Crystal structure of the T315I Abl mutant in complex with the aurora kinases inhibitor PHA-739358.
- Author
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Modugno M, Casale E, Soncini C, Rosettani P, Colombo R, Lupi R, Rusconi L, Fancelli D, Carpinelli P, Cameron AD, Isacchi A, and Moll J
- Subjects
- Aurora Kinases, Crystallography, X-Ray, Drug Resistance, Neoplasm genetics, Humans, Imatinib Mesylate, Models, Molecular, Mutant Proteins chemistry, Mutant Proteins metabolism, Piperazines pharmacology, Protein Binding, Proto-Oncogene Proteins c-abl metabolism, Pyrimidines pharmacology, Benzamides chemistry, Benzamides metabolism, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors metabolism, Protein Serine-Threonine Kinases antagonists & inhibitors, Proto-Oncogene Proteins c-abl chemistry, Proto-Oncogene Proteins c-abl genetics, Pyrazoles chemistry, Pyrazoles metabolism
- Abstract
Mutations in the kinase domain of Bcr-Abl are the most common cause of resistance to therapy with imatinib in patients with chronic myelogenous leukemia (CML). Second-generation Bcr-Abl inhibitors are able to overcome most imatinib-resistant mutants, with the exception of the frequent T315I substitution, which is emerging as a major cause of resistance to these drugs in CML patients. Structural studies could be used to support the drug design process for the development of inhibitors able to target the T315I substitution, but until now no crystal structure of the T315I Abl mutant has been solved. We show here the first crystal structure of the kinase domain of Abl T315I in complex with PHA-739358, an Aurora kinase inhibitor currently in clinical development for solid and hematologic malignancies. This compound inhibits in vitro the kinase activity of wild-type Abl and of several mutants, including T315I. The cocrystal structure of T315I Abl kinase domain provides the structural basis for this activity: the inhibitor associates with an active conformation of the kinase domain in the ATP-binding pocket and lacks the steric hindrance imposed by the substitution of threonine by isoleucine.
- Published
- 2007
- Full Text
- View/download PDF
26. 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile.
- Author
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Fancelli D, Moll J, Varasi M, Bravo R, Artico R, Berta D, Bindi S, Cameron A, Candiani I, Cappella P, Carpinelli P, Croci W, Forte B, Giorgini ML, Klapwijk J, Marsiglio A, Pesenti E, Rocchetti M, Roletto F, Severino D, Soncini C, Storici P, Tonani R, Zugnoni P, and Vianello P
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Aurora Kinases, Cell Line, Tumor, Drug Screening Assays, Antitumor, Male, Mice, Models, Molecular, Pyrazoles pharmacokinetics, Pyrazoles pharmacology, Pyrroles pharmacokinetics, Pyrroles pharmacology, Solubility, Structure-Activity Relationship, Antineoplastic Agents chemical synthesis, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrazoles chemical synthesis, Pyrroles chemical synthesis
- Abstract
The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.
- Published
- 2006
- Full Text
- View/download PDF
27. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity.
- Author
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Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, and Moll J
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents therapeutic use, Aurora Kinase B, Aurora Kinases, Biomarkers, Tumor antagonists & inhibitors, Biomarkers, Tumor metabolism, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Enzyme Inhibitors chemistry, Enzyme Inhibitors therapeutic use, HL-60 Cells, HeLa Cells, Humans, Inhibitory Concentration 50, Mice, Mice, Transgenic, Molecular Structure, Phenotype, Phosphorylation drug effects, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Pyrazoles therapeutic use, Pyrroles therapeutic use, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins genetics, Recombinant Proteins metabolism, Reverse Transcriptase Polymerase Chain Reaction methods, Antineoplastic Agents pharmacology, Enzyme Inhibitors pharmacology, Mammary Neoplasms, Experimental drug therapy, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrazoles pharmacology, Pyrroles pharmacology
- Abstract
Purpose: Aurora kinases play critical roles during mitosis in chromosome segregation and cell division. The aim of this study was to determine the preclinical profile of a novel, highly selective Aurora kinase inhibitor, PHA-680632, as a candidate for anticancer therapy., Experimental Design: The activity of PHA-680632 was assayed in a biochemical ATP competitive kinase assay. A wide panel of cell lines was evaluated for antiproliferative activity. Cell cycle analysis. Immunohistochemistry, Western blotting, and Array Scan were used to follow mechanism of action and biomarker modulation. Specific knockdown of the targets by small interfering RNA was followed to validate the observed phenotypes. Efficacy was determined in different xenograft models and in a transgenic animal model of breast cancer., Results: PHA-680632 is active on a wide range of cancer cell lines and shows significant tumor growth inhibition in different animal tumor models at well-tolerated doses. The mechanism of action of PHA-680632 is in agreement with inhibition of Aurora kinases. Histone H3 phosphorylation in Ser10 is mediated by Aurora B kinase, and our kinetic studies on its inhibition by PHA-680632 in vitro and in vivo show that phosphorylation of histone H3 is a good biomarker to follow activity of PHA-680632., Conclusions: PHA-680632 is the first representative of a new class of Aurora inhibitors with a high potential for further development as an anticancer therapeutic. On treatment, different cell lines respond differentially, suggesting the absence of critical cell cycle checkpoints that could be the basis for a favorable therapeutic window.
- Published
- 2006
- Full Text
- View/download PDF
28. Removal of C-terminal SRC kinase from the immune synapse by a new binding protein.
- Author
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Rahmouni S, Vang T, Alonso A, Williams S, van Stipdonk M, Soncini C, Moutschen M, Schoenberger SP, and Mustelin T
- Subjects
- Adaptor Proteins, Signal Transducing, CD3 Complex immunology, CD3 Complex metabolism, CSK Tyrosine-Protein Kinase, Carrier Proteins analysis, Carrier Proteins genetics, DNA Helicases, Humans, Jurkat Cells, Ligands, Lymphocyte Activation immunology, Lymphocyte Activation physiology, Membrane Microdomains metabolism, Membrane Microdomains physiology, Membrane Proteins metabolism, Phosphoproteins metabolism, Phosphorylation, Phosphotransferases analysis, Phosphotransferases metabolism, Poly-ADP-Ribose Binding Proteins, Protein-Tyrosine Kinases, Proto-Oncogene Proteins analysis, Proto-Oncogene Proteins metabolism, RNA Helicases, RNA Recognition Motif Proteins, RNA, Small Interfering genetics, Receptors, Antigen, T-Cell physiology, Signal Transduction genetics, Signal Transduction physiology, T-Lymphocytes chemistry, T-Lymphocytes immunology, Tyrosine metabolism, src Homology Domains physiology, src-Family Kinases, Carrier Proteins metabolism, Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism, Phosphotransferases physiology, Proto-Oncogene Proteins physiology, Receptors, Antigen, T-Cell immunology, Signal Transduction immunology, T-Lymphocytes enzymology
- Abstract
The Csk tyrosine kinase negatively regulates the Src family kinases Lck and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk becomes associated with an approximately 72-kDa tyrosine-phosphorylated protein, which we identify here as G3BP, a phosphoprotein reported to bind the SH3 domain of Ras GTPase-activating protein. G3BP reduced the ability of Csk to phosphorylate Lck at Y505 by decreasing the amount of Csk in lipid rafts. As a consequence, G3BP augmented T-cell activation as measured by interleukin-2 gene activation. Conversely, elimination of endogenous G3BP by RNA interference increased Lck Y505 phosphorylation and reduced TCR signaling. In antigen-specific T cells, endogenous G3BP moved into a intracellular location adjacent to the immune synapse, but deeper inside the cell, upon antigen recognition. Csk colocalization with G3BP occurred in this "parasynaptic" location. We conclude that G3BP is a new player in T-cell-antigen receptor signaling and acts to reduce the amount of Csk in the immune synapse.
- Published
- 2005
- Full Text
- View/download PDF
29. Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease.
- Author
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Soncini C, Berdo I, and Draetta G
- Subjects
- Amino Acid Sequence, Base Sequence, Carrier Proteins genetics, DNA Helicases, DNA, Complementary, Endopeptidases classification, Endopeptidases genetics, Humans, Molecular Sequence Data, Molecular Weight, Poly-ADP-Ribose Binding Proteins, RNA Helicases, RNA Recognition Motif Proteins, Ubiquitin Thiolesterase, Carrier Proteins metabolism, Endopeptidases metabolism, Ubiquitins metabolism
- Abstract
Degradation of cellular proteins through ubiquitination is a fundamental strategy for regulating biological pathways. De-ubiquitination, i.e. the removal of ubiquitin from proteins and peptides to which ubiquitin is attached, is catalyzed by processing proteases known as de-ubiquitinating enzymes. We are studying the biology of a family of de-ubiquitinating enzymes, the mammalian ubiquitin-specific proteases (USPs), some of which appear to play a role in growth control. Given the fact that the modes of regulation of USPs and of their substrate specificity are poorly understood, we decided to attempt the identification of USP interacting proteins. Using the yeast two-hybrid system (2HS), we have isolated a cDNA clone whose product specifically interacts with USP10 but not with other USP baits tested. The isolated clone encodes a protein known to interact with the Ras-GTPase activating protein (G3BP). This interaction was further confirmed by performing a 2HS with G3BP, which led to the isolation of USP10 encoding cDNAs. We validated the interaction between the two proteins by performing in vitro binding assays and immunoprecipitations in human cells. G3BP does not appear to be a substrate of USP10; it rather inhibits the ability of USP10 to disassemble ubiquitin chains. The USP10/G3BP complex appears to co-immunoprecipitate with ubiquitinated species that could be substrates of USP10.
- Published
- 2001
- Full Text
- View/download PDF
30. The accumulation of a cold-regulated chloroplastic protein is light-dependent.
- Author
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Crosatti C, Soncini C, Stanca AM, and Cattivelli L
- Subjects
- Amino Acid Sequence, Chloroplasts radiation effects, Hordeum radiation effects, Molecular Sequence Data, Chloroplasts metabolism, Cold Temperature, Heat-Shock Proteins metabolism, Hordeum metabolism, Light, Plant Proteins metabolism
- Abstract
The protein encoded by cDNA clone pt59 and induced in barley (Hordeum vulgare L.) by cold was over-expressed in coli to produce the matching antibody, which in vivo recognized a cold-induced protein of 14 kDa (COR14) that was found in the chloroplast stroma. The accumulation of COR14 occurred only at low temperatures after even a brief exposure of the plants to light. Plants grown and fully hardened in the dark accumulated a reduced amount of pt59-corresponding mRNA and only traces of COR14. Light exposure for as short as 5 min was enough to normalize the expression of pt59-corresponding mRNA and increase the accumulation of COR14. These findings indicate that one or more light-dependent factors are involved in transcription of the gene and accumulation of the protein. The COR14 protein was stored in amounts only slightly greater in the resistant barley cultivar. Onice than in the susceptible cultivar Gitane, although the former had a higher induction-temperature threshold for COR14 than the latter. This fact is an evolutionary advantage, enabling the resistant varieties in the field to prepare the cold well ahead of the susceptible ones.
- Published
- 1995
- Full Text
- View/download PDF
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