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4. Interpretable and Reliable Rule Classification Based on Conformal Prediction

Author

Abdelqader, H., Smirnov, E., Pont, M., Geijselaers, M., Koprinska, I, Mignone, P, Guidotti, R, Jaroszewicz, S, Froning, H, Gullo, F, Ferreira, PM, Roqueiro, D, Ceddia, G, Nowaczyk, S, Gama, J, Ribeiro, R, Gavalda, R, Masciari, E, Ras, Z, Ritacco, E, Naretto, F, Theissler, A, Biecek, P, Verbeke, W, Schiele, G, Pernkopf, F, Blott, M, Bordino, I, Danesi, IL, Ponti, G, Severini, L, Appice, A, Andresini, G, Medeiros, I, Graca, G, Cooper, L, Ghazaleh, N, Richiardi, J, Saldana, D, Sechidis, K, Canakoglu, A, Pido, S, Pinoli, P, Bifet, A, Pashami, S, RS: FSE DACS, and Dept. of Advanced Computing Sciences

Subjects
Interpretable machine learning, Decision rules, Reliable machine learning, Conformal prediction
Abstract

This paper deals with the challenging problem of simultaneously integrating interpretablility and reliability into prediction models in machine learning. It proposes to combine the interpretable models of decision rules with the reliable models based on conformal prediction. The result is a new technique of conformal decision rules. Given a test instance, the technique is capable of providing a point prediction, an explanation, and a confidence value for that prediction plus a prediction set. The experiments show when and how conformal decision rules can be used for interpretable and reliable machine learning.

Published
2023
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7. Are SHAP Values Biased Towards High-Entropy Features?

Author

Koprinska, null, Mignone, P, Guidotti, R, Jaroszewicz, S, Froning, H, Gullo, F, Ferreira, PM, Roqueiro, D, Ceddia, G, Nowaczyk, S, Gama, J, Ribeiro, R, Gavalda, R, Masciari, E, Ras, Z, Ritacco, E, Naretto, F, Theissler, A, Biecek, P, Verbeke, W, Schiele, G, Pernkopf, F, Blott, M, Bordino, null, Danesi, IL, Ponti, G, Severini, L, Appice, A, Andresini, G, Medeiros, null, Graca, G, Cooper, L, Ghazaleh, N, Richiardi, J, Saldana, D, Sechidis, K, Canakoglu, A, Pido, S, Pinoli, P, Bifet, A, Pashami, S, Baudeu, Raphael, Wright, Marvin N., Loecher, Markus, Koprinska, null, Mignone, P, Guidotti, R, Jaroszewicz, S, Froning, H, Gullo, F, Ferreira, PM, Roqueiro, D, Ceddia, G, Nowaczyk, S, Gama, J, Ribeiro, R, Gavalda, R, Masciari, E, Ras, Z, Ritacco, E, Naretto, F, Theissler, A, Biecek, P, Verbeke, W, Schiele, G, Pernkopf, F, Blott, M, Bordino, null, Danesi, IL, Ponti, G, Severini, L, Appice, A, Andresini, G, Medeiros, null, Graca, G, Cooper, L, Ghazaleh, N, Richiardi, J, Saldana, D, Sechidis, K, Canakoglu, A, Pido, S, Pinoli, P, Bifet, A, Pashami, S, Baudeu, Raphael, Wright, Marvin N., and Loecher, Markus

Abstract

n this paper, we examine the bias towards high-entropy features exhibited by SHAP values on tree-based structures such as classification and regression trees, random forests or gradient boosted trees. Previous work has shown that many feature importance measures for tree-based models assign higher values to high-entropy features, i.e. with high cardinality or balanced categories, and that this bias also applies to SHAP values. However, it is unclear if this bias is a major problem in practice or merely a statistical artifact with little impact on real data analyses. In this paper, we show that the severity of the bias strongly depends on the signal to noise ratio (SNR) in the dataset and on adequate hyperparameter tuning. In high-SNR settings, the bias is still present but is unlikely to affect feature rankings and thus can be safely ignored in many real data applications. On the other hand, in low-SNR settings, a feature without ground-truth effect but with high entropy could be ranked higher than a feature with ground-truth effect but low entropy. Here, we show that careful hyperparameter tuning can remove the bias., In this paper, we examine the bias towards high-entropy features exhibited by SHAP values on tree-based structures such as classification and regression trees, random forests or gradient boosted trees. Previous work has shown that many feature importance measures for tree-based models assign higher values to high-entropy features, i.e. with high cardinality or balanced categories, and that this bias also applies to SHAP values. However, it is unclear if this bias is a major problem in practice or merely a statistical artifact with little impact on real data analyses. In this paper, we show that the severity of the bias strongly depends on the signal to noise ratio (SNR) in the dataset and on adequate hyperparameter tuning. In high-SNR settings, the bias is still present but is unlikely to affect feature rankings and thus can be safely ignored in many real data applications. On the other hand, in low-SNR settings, a feature without ground-truth effect but with high entropy could be ranked higher than a feature with ground-truth effect but low entropy. Here, we show that careful hyperparameter tuning can remove the bias.

Published
2023

13. SMA-miRs (MiR-181a- 5p, -324-5p, and -451a) are overexpressed in spinal muscular atrophy skeletal muscle and serum samples

Author

Abiusi, E., Infante, P., Cagnoli, C., Severini, L. L., Pane, M., Coratti, G., Pera, M. C., D'amico, A., Diano, F., Novelli, A., Spartano, S., Fiori, S., Baranello, G., Moroni, I., Mora, M., Pasanisi, M. B., Pocino, K., Le Pera, L., D'Amico, D., Travaglini, L., Ria, F., Bruno, C., Locatelli, D., Bertini, E. S., Morandi, L. O., Mercuri, E., Di Marcotullio, L., Tiziano, F. D., Abiusi E. (ORCID:0000-0001-9028-012X), Pane M. (ORCID:0000-0002-4851-6124), Coratti G. (ORCID:0000-0001-6666-5628), Pera M. C. (ORCID:0000-0001-6777-1721), D'amico A., Diano F., Novelli A., Spartano S., Fiori S., Baranello G., Pocino K. (ORCID:0000-0003-2456-5308), Ria F. (ORCID:0000-0002-8444-0307), Bertini E. S., Mercuri E. (ORCID:0000-0002-9851-5365), Tiziano F. D. (ORCID:0000-0002-5545-6158), Abiusi, E., Infante, P., Cagnoli, C., Severini, L. L., Pane, M., Coratti, G., Pera, M. C., D'amico, A., Diano, F., Novelli, A., Spartano, S., Fiori, S., Baranello, G., Moroni, I., Mora, M., Pasanisi, M. B., Pocino, K., Le Pera, L., D'Amico, D., Travaglini, L., Ria, F., Bruno, C., Locatelli, D., Bertini, E. S., Morandi, L. O., Mercuri, E., Di Marcotullio, L., Tiziano, F. D., Abiusi E. (ORCID:0000-0001-9028-012X), Pane M. (ORCID:0000-0002-4851-6124), Coratti G. (ORCID:0000-0001-6666-5628), Pera M. C. (ORCID:0000-0001-6777-1721), D'amico A., Diano F., Novelli A., Spartano S., Fiori S., Baranello G., Pocino K. (ORCID:0000-0003-2456-5308), Ria F. (ORCID:0000-0002-8444-0307), Bertini E. S., Mercuri E. (ORCID:0000-0002-9851-5365), and Tiziano F. D. (ORCID:0000-0002-5545-6158)

Abstract

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the degeneration of the second motor neuron. The phenotype ranges from very severe to very mild forms. All patients have the homozygous loss of the SMN1 gene and a variable number of SMN2 (generally 2–4 copies), inversely related to the severity. The amazing results of the available treatments have made compelling the need of prognostic biomarkers to predict the progression trajectories of patients. Besides the SMN2 products, few other biomarkers have been evaluated so far, including some miRs. Methods: We performed whole miRNome analysis of muscle samples of patients and controls (14 biopsies and 9 cultures). The levels of muscle differentially expressed miRs were evaluated in serum samples (51 patients and 37 controls) and integrated with SMN2 copies, SMN2 full-length transcript levels in blood and age (SMA-score). Results: Over 100 miRs were differentially expressed in SMA muscle; 3 of them (hsa-miR-181a-5p, -324-5p, -451a; SMA-miRs) were significantly upregulated in the serum of patients. The severity predicted by the SMA-score was related to that of the clinical classification at a correlation coefficient of 0.87 (p<10-5). Conclusions: MiRNome analyses suggest the primary involvement of skeletal muscle in SMA pathogenesis. The SMA-miRs are likely actively released in the blood flow; their function and target cells require to be elucidated. The accuracy of the SMA-score needs to be verified in replicative studies: If confirmed, its use could be crucial for the routine prognostic assessment, also in presymptomatic patients.

Published
2021

14. SMA-miRs (MiR-181a- 5p, -324-5p, and -451a) are overexpressed in spinal muscular atrophy skeletal muscle and serum samples

Author

Abiusi, Emanuela, Infante, P., Cagnoli, C., Severini, L. L., Pane, Marika, Coratti, Giorgia, Pera, Maria Carmela, D'Amico, Adele, Diano, Federica, Novelli, Agnese, Spartano, Serena, Fiori, Simona, Baranello, Giovanni, Moroni, I., Mora, M., Pasanisi, M. B., Pocino, Krizia, Le Pera, L., D'Amico, D., Travaglini, L., Ria, Francesco, Bruno, C., Locatelli, D., Bertini, Enrico Silvio, Morandi, L. O., Mercuri, Eugenio Maria, Di Marcotullio, L., Tiziano, Francesco Danilo, Abiusi E. (ORCID:0000-0001-9028-012X), Pane M. (ORCID:0000-0002-4851-6124), Coratti G. (ORCID:0000-0001-6666-5628), Pera M. C. (ORCID:0000-0001-6777-1721), D'amico A., Diano F., Novelli A., Spartano S., Fiori S., Baranello G., Pocino K. (ORCID:0000-0003-2456-5308), Ria F. (ORCID:0000-0002-8444-0307), Bertini E. S., Mercuri E. (ORCID:0000-0002-9851-5365), Tiziano F. D. (ORCID:0000-0002-5545-6158), Abiusi, Emanuela, Infante, P., Cagnoli, C., Severini, L. L., Pane, Marika, Coratti, Giorgia, Pera, Maria Carmela, D'Amico, Adele, Diano, Federica, Novelli, Agnese, Spartano, Serena, Fiori, Simona, Baranello, Giovanni, Moroni, I., Mora, M., Pasanisi, M. B., Pocino, Krizia, Le Pera, L., D'Amico, D., Travaglini, L., Ria, Francesco, Bruno, C., Locatelli, D., Bertini, Enrico Silvio, Morandi, L. O., Mercuri, Eugenio Maria, Di Marcotullio, L., Tiziano, Francesco Danilo, Abiusi E. (ORCID:0000-0001-9028-012X), Pane M. (ORCID:0000-0002-4851-6124), Coratti G. (ORCID:0000-0001-6666-5628), Pera M. C. (ORCID:0000-0001-6777-1721), D'amico A., Diano F., Novelli A., Spartano S., Fiori S., Baranello G., Pocino K. (ORCID:0000-0003-2456-5308), Ria F. (ORCID:0000-0002-8444-0307), Bertini E. S., Mercuri E. (ORCID:0000-0002-9851-5365), and Tiziano F. D. (ORCID:0000-0002-5545-6158)

Abstract

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the degeneration of the second motor neuron. The phenotype ranges from very severe to very mild forms. All patients have the homozygous loss of the SMN1 gene and a variable number of SMN2 (generally 2–4 copies), inversely related to the severity. The amazing results of the available treatments have made compelling the need of prognostic biomarkers to predict the progression trajectories of patients. Besides the SMN2 products, few other biomarkers have been evaluated so far, including some miRs. Methods: We performed whole miRNome analysis of muscle samples of patients and controls (14 biopsies and 9 cultures). The levels of muscle differentially expressed miRs were evaluated in serum samples (51 patients and 37 controls) and integrated with SMN2 copies, SMN2 full-length transcript levels in blood and age (SMA-score). Results: Over 100 miRs were differentially expressed in SMA muscle; 3 of them (hsa-miR-181a-5p, -324-5p, -451a; SMA-miRs) were significantly upregulated in the serum of patients. The severity predicted by the SMA-score was related to that of the clinical classification at a correlation coefficient of 0.87 (p<10-5). Conclusions: MiRNome analyses suggest the primary involvement of skeletal muscle in SMA pathogenesis. The SMA-miRs are likely actively released in the blood flow; their function and target cells require to be elucidated. The accuracy of the SMA-score needs to be verified in replicative studies: If confirmed, its use could be crucial for the routine prognostic assessment, also in presymptomatic patients.

Published
2021

15. Eye- and mouth-opening movements replacing head and hand responses in a microswitch program for an adolescent with deteriorating motor condition

Author

Lancioni, G.E., Singh, N.N., O'Reilly, M.F., Sigafoos, J., Oliva, D., Severini, L., and Groeneweg, J.

Subjects
Motor ability -- Evaluation, Motor ability -- Technology application, Movement disorders -- Evaluation, Human mechanics -- Evaluation, Human mechanics -- Technology application, Technology application, Health, Psychology and mental health
Abstract

This study assessed the possibility of replacing head and hand responses (no-longer feasible) with minimal movements within the microswitch-based program of an adolescent with deteriorating motor condition and multiple disabilities. The new movements, i.e., eye- and mouth-opening, were introduced individually and then combined through the simultaneous availability of the related microswitches. Data showed the participant acquired the new movements (responses) successfully and retained them at a 2-mo. postintervention check. Mood improvements, i.e., increases in indices of happiness, also occurred through the program. The conclusion was that a person with deteriorating motor conditions may be able to revitalize a microswitchbased occupational program and retain a constructive engagement if new, feasible responses are identified.

Published
2007

16. Enabling persons with multiple disabilities to choose among environmental stimuli and request stimulus repetitions through microswitch and computer technology

Author

Lancioni, G.E., O'Reilly, M.F., Singh, N.N., Sigafoos, J., Oliva, D., and Severini, L.

Subjects
Chronically ill -- Research, Chronically ill -- Psychological aspects, Stimuli (Psychology) -- Research, Stimulus compounding -- Research, Health, Psychology and mental health
Abstract

This study assessed microswitch and computer technology to enable two participants with multiple disabilities, 32 and 19 years of age, to choose among environmental stimuli and request their repetition whenever they so desired. Within each session, 18 stimuli (12 preferred and 6 nonpreferred) were available. For each stimulus, a computer system provided a sample of 3 sec. duration. During the intervention, participants' vocal responding in relation to a stimulus sample activated a microswitch and a computer system turned on that stimulus for 15-30 sec. When participants did not vocally respond, the computer system paused briefly and then presented the next scheduled stimulus sample. When participants vocally responded at the end of a stimulus presentation, the stimulus was repeated. Intervention data showed that the participants learned to choose preferred stimuli and bypass nonpreferred ones as well as to request repetitions of the preferred stimuli. This performance was maintained at a 1-mo. postintervention check and transferred to sets of stimuli not used in the intervention. The implications of these results were discussed.

Published
2006

17. Assessing a microswitch-based stimulation procedure for eye-blinking responses in a young woman with profound multiple disabilities

Author

Lancioni, G.E., Singh, N.N., O'Reilly, M.F., Oliva, D., and Severini, L.

Subjects
Disabled women -- Research, Eye -- Movements, Eye -- Research, Health, Psychology and mental health
Abstract

We applied a new microswitch-based stimulation procedure for eye-blinking responses with a young woman with profound multiple disabilities, and compared effects of this procedure on the eye-blinking responses and smiling with the effects of a caregiver based stimulation condition. Analysis showed that the microswitch-based stimulation procedure, with stimulation occurring contingent on eye-blinking responses, increased the frequencies of these responses significantly above the levels recorded in baseline and caregiver-based stimulation conditions. No changes in smiling frequencies occurred. Implications of the findings in terms of alertness, learning, and quality of life are discussed.

Published
2005

19. This title is unavailable for guests, please login to see more information.

Author

Bufalieri, F., Infante, P., Bernardi, F., Caimano, M., Romania, P., Moretti, M., Lospinoso Severini, L., Talbot, J., Melaiu, O., Tanori, M., Di Magno, L., Bellavia, D., Capalbo, C., Puget, S., De Smaele, E., Canettieri, G., Guardavaccaro, D., Busino, L., Peschiaroli, A., Pazzaglia, S., Giannini, G., Melino, G., Locatelli, Franco, Gulino, A., Ayrault, O., Fruci, D., Di Marcotullio, L., Locatelli F. (ORCID:0000-0002-7976-3654), Bufalieri, F., Infante, P., Bernardi, F., Caimano, M., Romania, P., Moretti, M., Lospinoso Severini, L., Talbot, J., Melaiu, O., Tanori, M., Di Magno, L., Bellavia, D., Capalbo, C., Puget, S., De Smaele, E., Canettieri, G., Guardavaccaro, D., Busino, L., Peschiaroli, A., Pazzaglia, S., Giannini, G., Melino, G., Locatelli, Franco, Gulino, A., Ayrault, O., Fruci, D., Di Marcotullio, L., and Locatelli F. (ORCID:0000-0002-7976-3654)

Published
2019

20. Chemical, computational and functional insights into the chemical stability of the Hedgehog pathway inhibitor GANT61

Author

Calcaterra, A., Iovine, V., Botta, B., Quaglio, D., D'Acquarica, I., Ciogli, A., Iazzetti, Antonia, Alfonsi, R., Lospinoso Severini, L., Infante, P., Di Marcotullio, L., Mori, M., Ghirga, F., Iazzetti A. (ORCID:0000-0002-7792-774X), Calcaterra, A., Iovine, V., Botta, B., Quaglio, D., D'Acquarica, I., Ciogli, A., Iazzetti, Antonia, Alfonsi, R., Lospinoso Severini, L., Infante, P., Di Marcotullio, L., Mori, M., Ghirga, F., and Iazzetti A. (ORCID:0000-0002-7792-774X)

Abstract

This work aims at elucidating the mechanism and kinetics of hydrolysis of GANT61, the first and most-widely used inhibitor of the Hedgehog (Hh) signalling pathway that targets Glioma-associated oncogene homologue (Gli) proteins, and at confirming the chemical nature of its bioactive form. GANT61 is poorly stable under physiological conditions and rapidly hydrolyses into an aldehyde species (GANT61-A), which is devoid of the biological activity against Hh signalling, and a diamine derivative (GANT61-D), which has shown inhibition of Gli-mediated transcription. Here, we combined chemical synthesis, NMR spectroscopy, analytical studies, molecular modelling and functional cell assays to characterise the GANT61 hydrolysis pathway. Our results show that GANT61-D is the bioactive form of GANT61 in NIH3T3 Shh-Light II cells and SuFu−/− mouse embryonic fibroblasts, and clarify the structural requirements for GANT61-D binding to Gli1. This study paves the way to the design of GANT61 derivatives with improved potency and chemical stability.

Published
2018

22. Favourable outcome in a dog after snake bite (Bothrops sp.) in Corrientes, Argentina

Author

Cardozo, R. O., Tarrago, N. M., Severini, L., Peralta, Luis O., and Teibler, Gladys Pamela

Subjects
Treatment, Canino, Envenenamiento bothrópico, Symptoms, Dog, Lesions, Tratamiento, Bothropic poisoning, Síntomas, Lesiones
Abstract

Fil: Cardozo, R. O. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina. Fil: Tarrago, N. M. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina. Fil: Severini, L. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina. Fil: Peralta, Luis O. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina. Fil: Teibler, Gladys Pamela. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; Argentina. Se describen los síntomas y lesiones registradas en un perro mordido por una serpiente del genero Bothrops (“yarará”), en una zona rural cercana a la ciudad de Corrientes, Argentina. El veneno de esta víbora posee proteasas y fosfolipasas que inducen daño local (hemorragia, edema, necrosis), así como hemorragia sistémica por acción de hemorraginas y metaloproteinasas (lesión de paredes capilares), agravada por la incoagulabilidad generada por enzimas semejantes a la trombina, que consumen el fibrinógeno sanguíneo. El canino reveló hemorragia a través de dos orificios contiguos en una mejilla, la cual estaba dolorida, caliente y edematosa. No se registraron signos de hemorragia sistémica. Se administró suero antiofídico bivalente anti-Bothrops y dexametasona, acompañados de fluidoterapia para proteger a los riñones. El tiempo de coagulación activado se mantuvoprolongado hasta las 6 h, normalizándose a las 8 h de iniciado el tratamiento. Se postula que la precocidad de la intervención y el buen estado físico del animal fueron cruciales para su completa recuperación. Symptoms and lesions observed in a dog bitten by a venomous snake (Bothrops sp., “yarará”) in a rural area of Corrientes, Argentina, are described. The venom of this viper contains proteases and phospholipases that induce local damage (hemorrhage, edema, necrosis) as well as systemic hemorrhage due to hemorrhagines and metalloproteinases (damage of capillary walls), worsened due to the incoagulability generated by thrombinlike enzymes that consume fibrinogen. Bleeding from two adjacent holes in a cheek which was aching, hot and edematous were the local symptoms. No systemic hemorrhage signs were observed. Bothropic bivalent antivenom and dexametasone, together with fluids were administered. The activated clotting time remained prolonged for 6 h, being normalized 8 h after the administration of the antivenom. It can be concluded that the early administration of the antivenom together with the fact that the patient was a healthy dog, were crucial for the favorable outcome.

Published
2016

23. Correspondence

Author

Gardner, Geo. H. and Severini, L.

Published
1867

24. A microswitch-based program to enable students with multiple disabilities to choose among environmental stimuli

Author

Giulio Lancioni, O Reilly, M. F., Singh, N. N., Sigafoos, J., Didden, R., Oliva, D., and Severini, L.

Subjects
Learning and Plasticity
Abstract

Item does not contain fulltext Students with multiple disabilities, such as severe to profound mental retardation combined with motor and visual impairment, are usually unable to engage in constructive activity or play a positive role in their daily context. Microswitches are technical tools that may help them improve their status by allowing them to control environmental events with small and simple responses suitable to their condition. Recently, a pilot study was conducted to assess such a program with a boy who had multiple disabilities, including total blindness and minimal motor behavior. The results were encouraging, in that the boy became quite active and chose stimuli he was expected to prefer and bypassed those he was not, thus exhibiting purposeful choice behavior. The present study reported in this paper served as a replication and extension of the pilot study, with two new students who had multiple disabilities. These students relied on a vocalization response to activate the microswitch as opposed to the eyebrow movements used in the pilot study. A computer system was used to handle sets of expected preferred and nonpreferred stimuli: it presented brief samples of the stimuli and eventually turned them on for longer periods of time if students selected them. The results of this study found encouraging evidence for the possibility of using specifically developed microswitch programs to enable individuals with minimal residual vision, limited motor behavior, and circumscribed intellectual ability to choose among environmental stimuli. Further research may help determine the generalizability of these results and assess ways of integrating different microswitch programs into the daily educational schedule of such individuals. 7 p.

Published
2006

25. Dynamic response of masonry arch with geometrical irregularities subjected to a pulse-type ground motion.

Author

Severini, L., Cavalagli, N., DeJong, M., and Gusella, V.

Abstract

Ancient masonry structures often rely on the masonry arch as a load bearing element. The understanding of its response under seismic actions is a first fundamental step towards the comprehension of the behaviour of more complex structures. It is well known that the stability of masonry arches is primarily related to the geometry. The safety assessment under seismic actions is usually carried out by considering known deterministic geometrical parameters, such as thickness, rise and span, and the voussoirs are assumed with equal dimensions. However, many factors, like defects or irregularities in the shape of the voussoirs and imprecise construction, produce variations of the geometry with respect to the nominal one and, as a consequence, may effect the ability of the arch to resist seismic actions. In this paper, the effect of geometrical irregularities on the dynamic response of circular masonry arches is considered. Irregular geometries are obtained through a random generation of the key geometrical parameters, and the effect of these irregularities is quantified by analysing the dynamic response to ground motion. The masonry arch is modelled as a four-link mechanism, i.e. a system made of three rigid blocks hinged at their ends. The position of the hinges at the instant of activation of the motion is determined through limit analysis. Lagrange's equations of motion have been written for the generated irregular geometries and solved through numerical integration. The results are summarised by a fragility surface that quantify the extent to which geometrical uncertainties can alter the dynamic response of the masonry arch and increase its seismic vulnerability. [ABSTRACT FROM AUTHOR]

Published
2018
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26. Effects of Microswitch-Based Programs on Indices of Happiness of Students With Multiple Disabilities: A New Research Evaluation

Author

Lancioni, G.E., Singh, N.N., O'Reilly, M.F., Sigafoos, J., Didden, H.C.M., Oliva, D., Severini, L., Smaldone, A., Tota, A., Lancioni, G.E., Singh, N.N., O'Reilly, M.F., Sigafoos, J., Didden, H.C.M., Oliva, D., Severini, L., Smaldone, A., and Tota, A.

Abstract

Item does not contain fulltext, The effects of microswitch-based programs on indices of happiness were evaluated with 9 students who had profound multiple disabilities. Each student received an ABAB sequence in which A represented baseline phases and B, intervention phases. During the latter phases, microswitches were used to enable the students to control preferred environmental stimulation with simple/feasible responses, such as hand-pushing and foot-lifting. Results show that all students increased microswitch responding during the intervention phases. Seven of them also had significant increases in indices of happiness, whereas the other 2 did not. In an attempt to shed some light on the reasons underlying the different outcomes, we examined procedural and methodological aspects of the study.

Published
2007

27. Fostering adaptive responses and head control in students with multiple disabilities through a microswitch-based program: Follow-up assessment and program revision

Author

Lancioni, G.E., Singh, N.N., O'Reilly, M.F., Sigafoos, J., Didden, H.C.M., Oliva, D., Severini, L., Lancioni, G.E., Singh, N.N., O'Reilly, M.F., Sigafoos, J., Didden, H.C.M., Oliva, D., and Severini, L.

Abstract

Item does not contain fulltext, A program was recently developed to promote adaptive responses and upright head position in students with multiple disabilities through the use of microswitch clusters (i.e., combinations of two microswitches). The five students exposed to the program showed a significant increase in adaptive responses performed with head upright. The first purpose of this study was to carry out a long-term follow-up assessment of the five students’ frequencies of adaptive responses and percentages of those responses combined with head upright. Recordings were also made of the length of time the head position was kept during each stimulation period following a successful response event and through the sessions. The second purpose of this study was to arrange a program revision for the students with less favorable data on head upright. The revision consisted of making the stimulation following successful response events synchronous with head upright with a maximum duration of 9 s per event. The results of the follow-up assessment showed that two of the students kept the upright head position for nearly the entire stimulation periods that followed successful response events as well as much of the session time. The other three students kept such position for small or intermediate portions of the stimulation periods and of the session time. For these three students, the revised program was applied with substantial benefits. Implications of the findings were discussed.

Published
2007

28. A microswitch-based program to enable students with multiple disabilities to choose among environmental stimuli

Author

Lancioni, G.E., O'Reilly, M.F., Singh, N.N., Sigafoos, J., Didden, H.C.M., Oliva, D., Severini, L., Lancioni, G.E., O'Reilly, M.F., Singh, N.N., Sigafoos, J., Didden, H.C.M., Oliva, D., and Severini, L.

Abstract

Item does not contain fulltext, Students with multiple disabilities, such as severe to profound mental retardation combined with motor and visual impairment, are usually unable to engage in constructive activity or play a positive role in their daily context. Microswitches are technical tools that may help them improve their status by allowing them to control environmental events with small and simple responses suitable to their condition. Recently, a pilot study was conducted to assess such a program with a boy who had multiple disabilities, including total blindness and minimal motor behavior. The results were encouraging, in that the boy became quite active and chose stimuli he was expected to prefer and bypassed those he was not, thus exhibiting purposeful choice behavior. The present study reported in this paper served as a replication and extension of the pilot study, with two new students who had multiple disabilities. These students relied on a vocalization response to activate the microswitch as opposed to the eyebrow movements used in the pilot study. A computer system was used to handle sets of expected preferred and nonpreferred stimuli: it presented brief samples of the stimuli and eventually turned them on for longer periods of time if students selected them. The results of this study found encouraging evidence for the possibility of using specifically developed microswitch programs to enable individuals with minimal residual vision, limited motor behavior, and circumscribed intellectual ability to choose among environmental stimuli. Further research may help determine the generalizability of these results and assess ways of integrating different microswitch programs into the daily educational schedule of such individuals.

Published
2006

31. Microswitch technology to promote adaptive responses and reduce mouthing in two children with multiple disabilities.

Author

Lancioni GE, Singh NN, O'Reilly MF, Sigafoos J, Oliva D, Severini L, Smaldone A, and Tamma M

Abstract

This study assessed the viability of using microswitch clusters (combinations of microswitches) plus contingent stimulation to promote adaptive responding and to reduce aberrant behavior in two children with multiple disabilities. The results revealed that both children increased their adaptive responses, learned to perform these responses free from aberrant behavior, and maintained this level of performance three months later. [ABSTRACT FROM AUTHOR]

Published
2007
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32. EYE- AND MOUTH-OPENING MOVEMENTS REPLACING HEAD AND HAND RESPONSES IN A MICROS WITCH PROGRAM FOR AN ADOLESCENT WITH DETERTORATING MOTOR CONDITION.

Author

Lancioni, G. E., Singh, N. N., O'Reilly, M. F., Sigafoos, J., Oliva, D., Severini, L., and Groeneweg, J.

Subjects
MOTOR ability, CONDITIONED response, MOOD (Psychology), HAND, HEAD, DISABILITIES
Abstract

This study assessed the possibility of replacing head and hand responses (no longer feasible) with minimal movements within the microswitch-based program of an adolescent with deteriorating motor condition and multiple disabilities. The new movements, i.e., eye- and mouth-opening, were introduced individually and then combined through the simultaneous availability of the related microswitches. Data showed the participant acquired the new movements (responses) successfully and retained them at a 2-mo. postintervention check. Mood improvements, i.e., increases in indices of happiness, also occurred through the program. The conclusion was that a person with deteriorating motor conditions may be able to revitalize a microswitch-based occupational program and retain a constructive engagement if new, feasible responses are identified. [ABSTRACT FROM AUTHOR]

Published
2007
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33. ENABLING PERSONS WITH MULTIPLE DISABILITIES TO CHOOSE AMONG ENVIRONMENTAL STIMULI AND REQUEST STIMULUS REPETITIONS THROUGH MICROS WITCH AND COMPUTER TECHNOLOGY.

Author

Lancioni, G. E., O'Reilly, M. F., Singh, N. N., Sigafoos, J., Oliva, D., and Severini, L.

Subjects
LEARNING disabilities, LEARNING disabilities research, COMPUTER systems, STIMULUS satiation, SENSORY perception, CONDITIONED response, PSYCHOLOGY of learning, VERBAL behavior, VERBAL behavior testing, VERBAL ability, INTERACTION analysis in education, PSYCHOLOGY
Abstract

This study assessed microswitch and computer technology to enable two participants with multiple disabilities, 32 and 19 years of age, to choose among environmental stimuli and request their repetition whenever they so desired. Within each session, 18 stimuli (12 preferred and 6 nonpreferred) were available. For each stimulus, a computer system provided a sample of 3 sec. duration. During the intervention, participants' vocal responding in relation to a stimulus sample activated a mi- croswitch and a computer system turned on that stimulus for 15-30 sec. When participants did not vocally respond, the computer system paused briefly and then presented the next scheduled stimulus sample. When participants vocally responded at the end of a stimulus presentation, the stimulus was repeated. Intervention data showed that the participants learned to choose preferred stimuli and bypass nonpreferred ones as well as to request repetitions of the preferred stimuli. This performance was maintained at a 1-mo. postintervention check and transferred to sets of stimuli not used in the intervention. The implications of these results were discussed. [ABSTRACT FROM AUTHOR]

Published
2006
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35. Micro-switch programmes for students with multiple disabilities and minimal motor behaviour: Assessing response acquisition and choice

Author

Lancioni, G. E., O'Reilly, M. F., Singh, N. N., Oliva, D., Baccani, S., Severini, L., and Groeneweg, J.

Abstract

This study assessed (a) whether three girls with multiple disabilities and minimal motor behaviour could acquire pairs of responses taught through micro-switch-based programmes and (b) how the girls would eventually choose between those responses. In relation to the choice issue, a response-choice analysis was conducted to find out whether possible differences in performance rates for the two responses were due to the stimuli linked to them and/or to potential response preferences. Results indicated that all three girls succeeded in the acquisition of the two responses programmed for them and showed clear response choices. The choices seemed to be largely motivated by the stimuli linked to the responses. Implications of these findings were discussed, including the need to assess their generality and extend the scope of the work in this area.

Published
2006
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38. Effects of Microswitch-Based Programs on Indices of Happiness of Students With Multiple Disabilities: A New Research Evaluation

Author

Lancioni, GE, Lamartire, ML, Singh, NN, O'Reilly, M, Sigafoos, J, Didden, R, Olivia, D, Severini, L, Smaldone, A, Tota, A, Lancioni, GE, Lamartire, ML, Singh, NN, O'Reilly, M, Sigafoos, J, Didden, R, Olivia, D, Severini, L, Smaldone, A, and Tota, A

Abstract

The effects of microswitch-based programs on indices of happiness were evaluated with 9 students who had profound multiple disabilities. Each student received an ABAB sequence in which A represented baseline phases and B, intervention phases. During the latter phases, microswitches were used to enable the students to control preferred environmental stimulation with simple/feasible responses, such as hand-pushing and foot-lifting. Results show that all students increased microswitch responding during the intervention phases. Seven of them also had significant increases in indices of happiness, whereas the other 2 did not. In an attempt to shed some light on the reasons underlying the different outcomes, we examined procedural and methodological aspects of the study.

39. Effects of Microswitch-Based Programs on Indices of Happiness of Students With Multiple Disabilities: A New Research Evaluation

Author

Lancioni, GE, Lamartire, ML, Singh, NN, O'Reilly, M, Sigafoos, J, Didden, R, Olivia, D, Severini, L, Smaldone, A, Tota, A, Lancioni, GE, Lamartire, ML, Singh, NN, O'Reilly, M, Sigafoos, J, Didden, R, Olivia, D, Severini, L, Smaldone, A, and Tota, A

Abstract

The effects of microswitch-based programs on indices of happiness were evaluated with 9 students who had profound multiple disabilities. Each student received an ABAB sequence in which A represented baseline phases and B, intervention phases. During the latter phases, microswitches were used to enable the students to control preferred environmental stimulation with simple/feasible responses, such as hand-pushing and foot-lifting. Results show that all students increased microswitch responding during the intervention phases. Seven of them also had significant increases in indices of happiness, whereas the other 2 did not. In an attempt to shed some light on the reasons underlying the different outcomes, we examined procedural and methodological aspects of the study.

40. Framework to Evaluate Deep Learning Algorithms for Edge Inference and Training

Author

Tiberius-George Sorescu, Chandrakanth R. Kancharla, Jeroen Boydens, Hans Hallez, Mathias Verbeke, Koprinska, I, Mignone, P, Guidotti, R, Jaroszewicz, S, Froning, H, Gullo, F, Ferreira, PM, Roqueiro, D, Ceddia, G, Nowaczyk, S, Gama, J, Ribeiro, R, Gavalda, R, Masciari, E, Ras, Z, Ritacco, E, Naretto, F, Theissler, A, Biecek, P, Verbeke, W, Schiele, G, Pernkopf, F, Blott, M, Bordino, I, Danesi, IL, Ponti, G, Severini, L, Appice, A, Andresini, G, Medeiros, I, Graca, G, Cooper, L, Ghazaleh, N, Richiardi, J, Saldana, D, Sechidis, K, Canakoglu, A, Pido, S, Pinoli, P, Bifet, A, and Pashami, S

Abstract

Edge computing is a paradigm in which data is intelligently processed close to its source. Along with advancements in deep learning, there is a growing interest in using deep neural networks at the edge for predictive analytics. Given the realistic constraints in computational resources of edge devices, this combination is challenging. In order to bridge the gap between deep learning models and efficient edge analytics, a container-based framework is presented that evaluates user-specified deep learning models for efficiency on the edge. The proposed framework is validated on a rotating machinery fault diagnosis use case. Conclusions on efficient state-of-the-art models for rotating machine fault diagnosis were drawn and appropriately reported. ispartof: pages:569-581 ispartof: Communications in Computer and Information Science vol:1752 pages:569-581 ispartof: Joint European Conference on Machine Learning and Knowledge Discovery in Databases location:Grenoble, France date:19 Sep - 23 Sep 2022 status: Published online

Published
2023

41. Toward a Reversible Consolidation of Paper Materials Using Cellulose Nanocrystals

Author

Laura Micheli, Alessandra Operamolla, Claudia Mazzuca, Valter Castelvetro, Andrea Martinelli, Mattia Titubante, L. Capodieci, Francesca Di Benedetto, Leonardo Severini, Operamolla, A., Mazzuca, C., Capodieci, L., Di Benedetto, F., Severini, L., Titubante, M., Martinelli, A., Castelvetro, V., and Micheli, L.

Subjects
Materials science, Nanotechnology, Settore CHIM/06, Nanocellulose, chemistry.chemical_compound, Settore CHIM/01, Settore CHIM/02, amperometric sensors, Ultimate tensile strength, General Materials Science, paper conservation, Cellulose, Fourier transform infrared spectroscopy, Settore CHIM/12 - Chimica dell'Ambiente e dei Beni Culturali, cellulose nanocrystals, cellulose nanocrystals, FT-IR spectroscopy, nanotechnology, amperometric sensors, microscopy, cultural heritage, paper restoration, paper conservation, cultural heritage, FT-IR spectroscopy, microscopy, nanotechnology, paper restoration, Consolidation (soil), chemistry, Compatibility (mechanics), Surface modification, Degradation (geology)
Abstract

An innovative consolidation strategy for degraded paper is presented based on the reversible application of cellulose nanocrystals as sustainable fillers to reinforce mechanical properties and resistance to further degradation. The compatibility and efficacy of the proposed consolidation treatment are assessed first on pure cellulose paper, used as a model, by reliable techniques such as field emission scanning electron microscopy, atomic force microscopy, tensile tests, X-ray powder diffraction, and Fourier transform infrared spectroscopy, evidencing the influence of the surface functionalization of nanocellulose on the consolidation and protection effects. Then, the consolidation technique is applied to real aged paper samples from Breviarium romanum ad usum Fratrum Minorum S.P. (1738), demonstrating the promising potential of the suggested approach. Amperometric measurements, carried out with a smart electrochemical tool developed in our laboratory, demonstrate the reversibility of the proposed treatment by removal of the nanocrystalline cellulose from the paper surface with a suitable cleaning hydrogel. This completely new feature of the consolidation treatment proposed here satisfies a pivotal requisite in cultural heritage conservation because the methodological requirement for the ″reversibility″ of any conservation measure is a fundamental goal for restorers. A paper artifact, in fact, is subject to a number of natural and man-made hazards, inducing continuous degradation. With time, monitoring and consolidation actions need to be often performed to ensure conservation, and this tends to modify the status quo and compromise the artifact integrity. Removable treatments can potentially avoid erosion of the artifact integrity.

Published
2021
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42. ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of beta TrCP

Author

Alberto Gulino, Stéphanie Puget, Carlo Capalbo, Daniele Guardavaccaro, Olivier Ayrault, Doriana Fruci, Giuseppe Giannini, Paola Infante, Luca Busino, Mirella Tanori, Laura Di Magno, Diana Bellavia, Ludovica Lospinoso Severini, Miriam Caimano, Flavia Bernardi, Ombretta Melaiu, Enrico De Smaele, Franco Locatelli, Gerry Melino, Lucia Di Marcotullio, Gianluca Canettieri, Julie Talbot, Angelo Peschiaroli, Francesca Bufalieri, Simonetta Pazzaglia, Marta Moretti, Paolo Romania, Bufalieri, F., Infante, P., Bernardi, F., Caimano, M., Romania, P., Moretti, M., Lospinoso Severini, L., Talbot, J., Melaiu, O., Tanori, M., Di Magno, L., Bellavia, D., Capalbo, C., Puget, S., De Smaele, E., Canettieri, G., Guardavaccaro, D., Busino, L., Peschiaroli, A., Pazzaglia, S., Giannini, G., Melino, G., Locatelli, F., Gulino, A., Ayrault, O., Fruci, D., Di Marcotullio, L., Bufalieri, Francesca [0000-0002-9571-318X], Capalbo, Carlo [0000-0001-8445-6782], De Smaele, Enrico [0000-0003-4524-4423], Busino, Luca [0000-0001-6758-9276], Melino, Gerry [0000-0001-9428-5972], Fruci, Doriana [0000-0003-3388-7296], and Apollo - University of Cambridge Repository

Subjects
animal structures, ERAP1, Hedgehog, tumorigenesis, Carcinogenesis, Molecular biology, Science, Regulator, General Physics and Astronomy, medicine.disease_cause, medulloblastoma, Aminopeptidases, USP47, General Biochemistry, Genetics and Molecular Biology, Article, Minor Histocompatibility Antigens, Mice, Ubiquitin, ubiquitin, medicine, ERAP, Animals, Hedgehog Proteins, E3 ligasi, lcsh:Science, Transcription factor, Tissue homeostasis, Cancer, Multidisciplinary, biology, Protein Stability, Settore BIO/11, ubiquitin, medulloblastoma, ERAP, General Chemistry, beta-Transducin Repeat-Containing Proteins, Ubiquitin ligase, Cell biology, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Proteolysis, biology.protein, NIH 3T3 Cells, lcsh:Q, Ubiquitin-Specific Proteases, Signal transduction, Signal Transduction
Abstract

The Hedgehog (Hh) pathway is essential for embryonic development and tissue homeostasis. Aberrant Hh signaling may occur in a wide range of human cancers, such as medulloblastoma, the most common brain malignancy in childhood. Here, we identify endoplasmic reticulum aminopeptidase 1 (ERAP1), a key regulator of innate and adaptive antitumor immune responses, as a previously unknown player in the Hh signaling pathway. We demonstrate that ERAP1 binds the deubiquitylase enzyme USP47, displaces the USP47-associated βTrCP, the substrate-receptor subunit of the SCFβTrCP ubiquitin ligase, and promotes βTrCP degradation. These events result in the modulation of Gli transcription factors, the final effectors of the Hh pathway, and the enhancement of Hh activity. Remarkably, genetic or pharmacological inhibition of ERAP1 suppresses Hh-dependent tumor growth in vitro and in vivo. Our findings unveil an unexpected role for ERAP1 in cancer and indicate ERAP1 as a promising therapeutic target for Hh-driven tumors., ERAP1 is an endoplasmic reticulum aminopeptidase that trims MHC Class-I peptides for antigen presentation. Here, the authors show that ERAP1 enhances Hedgehog signalling by sequestering USP47 from βTrCP and promoting tumorigenesis through βTrCP degradation and increased Gli protein stability.

Published
2019
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43. Dynamic response of masonry arch with geometrical irregularities subjected to a pulse-type ground motion

Author

L. Severini, N. Cavalagli, M. DeJong, V. Gusella, Severini, L [0000-0002-7677-9386], and Apollo - University of Cambridge Repository

Subjects
Applied Mathematics, Mechanical Engineering, Dynamic analysis, Geometrical irregularities, Limit analysis, Masonry arch, Aerospace Engineering, Ocean Engineering, 020101 civil engineering, 02 engineering and technology, 0201 civil engineering, 020303 mechanical engineering & transports, 0203 mechanical engineering, Control and Systems Engineering, Geometrical irregularities, Dynamic analysis, Limit analysis, 4005 Civil Engineering, Electrical and Electronic Engineering, Masonry arch, 40 Engineering
Abstract

Ancient masonry structures often rely on the masonryarch as a load bearing element. The understanding ofits response under seismic actions is a first fundamental steptoward the comprehension of the behaviour of more complexstructures. It is well known that the stability of masonryarches is primarily related to the geometry. The safety assessmentunder seismic actions is usually carried out by consideringknown deterministic geometrical parameters, suchas thickness, rise and span, and the voussoirs are assumedwith equal dimensions. However, many factors, like defectsor irregularities in the shape of the voussoirs and impreciseconstruction, produce variations of the geometry withrespect to the nominal one and, as a consequence, may effectthe ability of the arch to resist seismic actions. In thispaper, the effect of geometric irregularities on the dynamicresponse of circular masonry arches is considered. Irregulargeometries are obtained through a random generation ofthe key geometric parameters, and the effect of these irregularitiesis quantified by analysing the dynamic response toground motion. The masonry arch is modelled as a four-linkmechanism, i.e., a system made of three rigid blocks hingedat their ends. The position of the hinges at the instant of activationof the motion is determined through limit analysis.Lagrange’s equations of motion have been written for thegenerated irregular geometries and solved through numericalintegration. The results are summarised by a fragilitysurface that quantify the extent to which geometrical uncertaintiescan alter the dynamic response of the masonry archand increase its seismic vulnerability.

Published
2018
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44. Combination of Tevatron searches for the standard model Higgs boson in the W+W- decay mode

Author

Maxim Perfilov, B. Carls, V. Sorin, P. Lukens, Kevin Lannon, P. Verdier, Guenakh Mitselmakher, Guillelmo Gomez-Ceballos, Marcelo Vogel, V. A. Kuzmin, U. K. Yang, Chris Hays, W. T. Fedorko, Y. A. Yatsunenko, M. Mussini, Y. C. Yang, J. Keung, G. C. Blazey, D. Torretta, A. F. Barfuss, L. Bellantoni, Viatcheslav Stolin, Frank Würthwein, M. Shochet, C. Plager, F. Canelli, V. A. Bezzubov, A. Hocker, P. D. Grannis, Jun Guo, Q. Z. Li, Mark Kruse, Alison Lister, J. P. Fernandez, J. P. Negret, J. Nett, Stefano Giagu, Paul Tipton, G. L. Strycker, C. Mesropian, R. Yamada, D. N. Brown, P. Squillacioti, Kazuhiko Hara, J. Osta, Carlos Avila, L. E. Kirsch, Ricardo Eusebi, J. Galyardt, Alexei Safonov, R. Luna-Garcia, Raimund Ströhmer, V. Simak, D. Krop, Sabine Lammers, Jonas Rademacker, D. Amidei, J. M. Heuser, J. Sekaric, Michael A. Strauss, Jean-Francois Grivaz, K. Devaughan, A. T. Goshaw, P. Padley, Michael Hildreth, P. Skubic, A. Semenov, D. Clark, J. Boudreau, Wendy Taylor, M. Pangilinan, Jason Nielsen, G. Introzzi, B. Casal, Mitchell Wayne, N. Miladinovic, Y. Tu, H. Schellman, J. M. Kohli, K. Potamianos, Z. Gunay-Unalan, Darren Price, A. Sanchez-Hernandez, M. Wiok, Sergo Jindariani, Fedor Prokoshin, P. Jonsson, Thomas Hebbeker, Katsufumi Sato, A. J. Slaughter, Stefan Grünendahl, S. Cihangir, V. Zutshi, Yasuyoshi Nagai, Francesco Crescioli, S. Uzunyan, S. W. Lee, P. Ttito-Guzmán, T. Okusawa, B. Gómez, R. Madrak, Chong-Yu Xu, J. Naganoma, B. Tuchming, P. Wagner, V. Bunichev, Shinhong Kim, J. Budagov, Fabrice Couderc, K. Makhoul, Manfred Paulini, B. Tiller, Dmitri Tsybychev, R. L. McCarthy, Thomas LeCompte, Manuela Campanelli, I. Lazzizzera, Eva Halkiadakis, M. Gold, Tetsuo Arisawa, C. Neu, Amnon Harel, W. M. Lee, K. Kondo, Mary Beth Adams, D. Whiteson, I. Shreyber, K. Yamamoto, Malte Renz, Andrew Askew, R. L. Lander, G. De Lorenzo, A. Savoy-Navarro, Allan G Clark, Roger Moore, D. O. Litvintsev, S. Söldner-Rembold, A. Anastassov, G. Giurgiu, L. Sartori, Sooran Kim, O. Poukhov, A. Jonckheere, H. E. Fisk, P. Lebrun, M. N. Mondragon, I. Hall, A. Lobodenko, Wolfgang Wagner, Liang Li, J. C. Yun, J. Lueck, Stephen Wimpenny, S. Carrillo, J. Backusmayes, Martin Grunewald, Nicola D'Ascenzo, J. A. Appel, P. H. Beauchemin, M. Heck, D. Beecher, Peter McIntyre, G. Pauletta, M. Martínez, J. Patrick, E. Strauss, Guennadi Borissov, M. Jones, C. Pagliarone, D. Menezes, Intae Yu, Oliver Stelzer-Chilton, Th Muller, D. W. Jang, R. Van Kooten, B. Y. Han, I. Heredia-De La Cruz, Michael L. Norman, Yongsun Kim, Lev Dudko, Milos Lokajicek, D. Karmanov, M. M. Deninno, Markus Wobisch, R. Magaña-Villalba, S. W. Cho, G. Obrant, B. Whitehouse, S. Y. Jun, Julia Thom, W. C. Fisher, Adrian Buzatu, V. Boisvert, Daria Zieminska, Suneel Dutt, J. E. Kim, Aran Garcia-Bellido, M. D. Corcoran, S. Cabrera, D. E. Pellett, M. Binkley, R. D. Schamberger, M. Corbo, Y. C. Chen, F. Guo, A. J. Martin, C. Vellidis, Darien Wood, Y. Shon, D. K. Cho, T. R. Wyatt, E. Brubaker, Shabnam Jabeen, S. De Cecco, A. Dubey, G. Grenier, Hwi Dong Yoo, Zdenek Hubacek, L. Santi, A. Alton, Meng Wang, Neeti Parashar, L. Pondrom, E. Wicklund, Christoph Paus, C. P. Buszello, S. Hou, A. Das, M. Sosebee, A. Manousakis-Katsikakis, Emily Nurse, M. Merkin, L. Han, Giorgio Chiarelli, A. Rahaman, J. Huston, J. D. Lewis, Yuehong Xie, T. Scanlon, S. Kermiche, W. H. Chung, M. Rominsky, L. Brigliadori, V. M. Abazov, D. Buchholz, I. Ripp-Baudot, R. McNulty, M. Hare, M. Tecchio, A. Gessler, Helio Nogima, I. Razumov, S. Blessing, M. Zielinski, V. Rusu, A. Elagin, Vyacheslav Krutelyov, G. S. Muanza, Jay Dittmann, W. Ashmanskas, D. Hirschbuehl, H. C. Fang, Frederic Deliot, Michele Gallinaro, G. Savage, Peter Wittich, A. Napier, A. Meyer, Scott Snyder, J. Hays, S. Tokar, Suman Bala Beri, C.S. Johnson, G. Sajot, V. Hynek, Robert Hirosky, Alberto Annovi, P. Murat, Y. Hu, D. J. Cox, A. Di Canto, V. Khotilovich, Y. Seiya, O. Atramentov, Elizaveta Shabalina, M. Lancaster, G. Alkhazov, Y. Zheng, Jian Tang, L. Oakes, A. Gresele, Y. N. Kharzheev, A. Varganov, Sudhir Malik, E. G. Zverev, M. Vidal, Ia Iashvili, G. Manca, P. Roy, Raymond Brock, Robin Erbacher, M. Datta, R. Beuselinck, C. Cuenca Almenar, Javier Cuevas, Jean-Arcady Meyer, J. Mülmenstädt, D. V. Bandurin, S. Greder, Y. W. Liu, Iain Alexander Bertram, Virgil E Barnes, M. Padilla, L. Bagby, M. S. Rangel, Jahred Adelman, Jane Nachtman, Graham Wilson, Sergio F Novaes, S. Hossain, B. Jayatilaka, Kyung-Suk Cho, R. E. Hughes, P. Rich, T. Rodriguez, D. Gillberg, H. Wolfe, B. Sanghi, Suyong Choi, J. Parsons, G. Velev, J. M. Hauptman, Cecilia Elena Gerber, V. M. Podstavkov, G. Chlachidze, Michael Rijssenbeek, S. Zelitch, Jeannine Wagner-Kuhr, M. A. Strang, Brajesh C Choudhary, D. Lucchesi, Bernd Stelzer, S. Tkaczyk, F. Vázquez, P. Svoisky, C. Zeitnitz, J. Yamaoka, Arnulf Quadt, Petar Maksimovic, A. Juste, E. De La Cruz-Burelo, A. Attal, E. Pueschel, T. Wright, S. Grinstein, Todd Adams, K. M. Chan, A. S. Ito, A. Melnitchouk, T. Aaltonen, J. Antos, Thorsten Chwalek, Elemer Nagy, C. J. Lin, W. M. Van Leeuwen, M. Fortner, Sarah Catherine Eno, Horst Severini, Tiehui Liu, Rodolfo Carosi, A. Barbaro-Galtieri, R. G. Feild, J. S. Suh, K. Osterberg, D. Mietlicki, S. Richter, Michal Kreps, T. Nunnemann, B. Baldin, Corrinne Mills, G. P. Yeh, C. S. Moon, M. J. Kim, S. J. Park, A. Menzione, M. E. Convery, E. Palencia, J. C. Cully, Aron Soha, M. Cordelli, G. Busetto, Brian L Winer, G. Ginther, G. Bauer, G. Golovanov, M. J. Morello, F. D. Snider, J. Y. Han, N. Giokaris, Junjie Zhu, S. Wolbers, V. V. Tokmenin, L. S. Vertogradov, R. J. Miller, J. Martínez-Ortega, M. Weinberger, Bjoern Penning, G. Facini, M. Kurata, Andrea Castro, G. D. Alexeev, Flera Rizatdinova, M. Milnik, U. Husemann, B. Álvarez González, V. N. Evdokimov, A. Bridgeman, K. Sliwa, S. Klimenko, Evelyn Thomson, C. Deluca, Fabrizio Scuri, D. Wicke, Dennis Stephen Mackin, Andrew Brandt, Kirti Ranjan, Jianming Qian, J. L. Gimmell, V. V. Lipaev, J. Lellouch, H. A. Neal, Ivan-Kresimir Furic, Y. D. Oh, D. Bauer, M. C. Cousinou, V. A. Giakoumopoulou, Carsten Hensel, A. Mukherjee, C. Belanger-Champagne, B. S. Acharya, Nicola Turini, J. Pursley, H. Nilsen, R. G. Wagner, B. Spurlock, G. Piacentino, M. Buehler, A. T. Laasanen, Zeno Dixon Greenwood, Y. Arnoud, Richard B. Lipton, D. W. Gerdes, Pedro G Mercadante, Ph Gris, T. Kuhr, P. Houben, M. H. Kirby, H. Miyake, F. Happacher, Kristian Harder, Dario Bisello, G. Gutierrez, M. D'Errico, Joe Kroll, B. C.K. Casey, X. Wu, T. A. Schwarz, A. Bhatti, P. A. Kasper, Hugh Williams, M. P. Sanders, Ignacio Redondo, Hyun-Chul Kim, Yurii Maravin, Vladimir Gavrilov, A. Aurisano, Teresa Rodrigo, D. Boline, K. Chung, Peter Love, Pushpalatha C Bhat, W. Geng, N. Ranjan, R. Jesik, S. Carron, L. Demortier, S. Dube, S. H. Oh, M. A. Schmidt, Mark Richard James Williams, R. Bernhard, W. E. Cooper, P. N. Dong, D. Khatidze, Giovanni Bellettini, M. Rossi, J. Slaunwhite, D. Cutts, J. T. 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Kwang, M. Hurwitz, S. R. Hahn, M. Vesterinen, N. Osman, A. Deisher, T. R. Junk, Patrick Slattery, A. Chandra, J. Yoh, D. A. Stoyanova, C. L. McGivern, Gervasio Gomez, Michael Begel, Andrey Korytov, Eduardo De Moraes Gregores, Luiz Mundim, R. Takashima, T. H. Burnett, Amitabh Lath, Anna Sfyrla, Paola Giannetti, B. A. Barnett, Giorgio Apollinari, J. A. Benitez, Teruki Kamon, P. Mazzanti, Craig Blocker, Ulrich Heintz, D. Cauz, Kaori Maeshima, P. K. Mal, H. S. Lee, Frank Filthaut, Paolo Mastrandrea, M. Diesburg, P. Wilson, J. E. Garcia, A. Tanasijczuk, T. Davies, C. S. Hill, Sandra Leone, S. Uvarov, B. Quinn, W. K. Sakumoto, C. Schwanenberger, Alice Bean, C. Grosso-Pilcher, I. Oksuzian, N. Goldschmidt, Volker Buescher, Peter Bussey, T. Gadfort, Maria Elena Pol, Kai Yi, C. M. Ginsburg, R. Roser, Ivan Vila, P. F. Shepard, B. Rutherford, Alexander Ivanov, N. Van Remortel, S. C. Hsu, Reisaburo Tanaka, Guido Volpi, Nikos Varelas, O. González, Bing Zhou, Luis Mendoza, R. K. Shivpuri, S. Donati, Kenichi Hatakeyama, M. Franklin, D. R. Claes, Gavin Davies, Philippe Calfayan, Itsuo Nakano, Harald Fox, S. M. Lietti, Y. Scheglov, J. C. Freeman, Kaushik De, A. Ruiz, Giuseppe Latino, Alan Garfinkel, Jan Stark, Fabrizio Margaroli, S. Errede, Maiko Takahashi, Henry Lubatti, J. Cammin, I. A. Vasilyev, Vipin Bhatnagar, A. Cerri, R. Partridge, Markus Frank, P. M. Tuts, D. MacQueen, H. Gerberich, Kenneth Bloom, V. L. Malyshev, Mark Neubauer, R. Orava, G. Lungu, R. D. Field, D. J. Kong, W. C. Yang, Department of Physics, Helsinki Institute of Physics, CDF Collaboration, D0 Collaboration, Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Joseph Fourier - Grenoble 1 (UJF)-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), 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), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), CDF, D0, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-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), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Universidad de Cantabria, T. 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Stefan Institute, Augustana College, SLAC, ICREA/IFAE, Centro de Investigacion en Computacion-IPN, Universidad Autonoma de Sinaloa, Universiẗt Bern, University of Massachusetts Amherst, Universiteit Antwerpen, University of Bristol, University of California Santa Cruz, Chinese Academy of Sciences, Clark, Allan Geoffrey, Garcia Navarro, Jose Enrique, Lister, Alison, and Wu, Xin

Subjects
Particle physics, Astrophysics::High Energy Astrophysical Phenomena, Tevatron, FOS: Physical sciences, General Physics and Astronomy, Elementary particle, ddc:500.2, PARTON DISTRIBUTIONS, HADRON COLLIDERS, QCD, NNLO, 7. Clean energy, 01 natural sciences, 114 Physical sciences, High Energy Physics - Experiment, Standard Model, Nuclear physics, High Energy Physics - Experiment (hep-ex), Particle decay, 0103 physical sciences, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Grand Unified Theory, Fermilab, TEVATRON, Nuclear Experiment, 010306 general physics, Boson, Physics, HIGGS BOSON, 010308 nuclear & particles physics, High Energy Physics::Phenomenology, 3. Good health, Higgs boson, CDF, Physics::Accelerator Physics, High Energy Physics::Experiment, +W%2B+W-+|+W%3A+pair+production+|+W%3A+leptonic+decay+|+dilepton%3A+final+state+|+jet%3A+multiplicity+|+cross+section%3A+upper+limit+|+mass+dependence+|+Higgs+particle%3A+mass+|+background+|+DZERO+|+CDF+|+Batavia+TEVATRON+Coll+|+anti-p+p+-->+Higgs+particle+anything+|+anti-p+p+-->+Higgs+particle+anything+intermediate+boson+anything+|+anti-p+p+-->+Higgs+particle+anything+quark+antiquark+anything+|+1960+GeV-cms%22">Anti-p p: interaction | Higgs particle: search for | gluon gluon: fusion | intermediate boson: fusion | quark antiquark: annihilation | Higgs particle: decay | Higgs particle --> W+ W- | W: pair production | W: leptonic decay | dilepton: final state | jet: multiplicity | cross section: upper limit | mass dependence | Higgs particle: mass | background | DZERO | CDF | Batavia TEVATRON Coll | anti-p p --> Higgs particle anything | anti-p p --> Higgs particle anything intermediate boson anything | anti-p p --> Higgs particle anything quark antiquark anything | 1960 GeV-cms
Abstract

11 páginas, 4 figuras, 1 tabla.-- CDF Collaboration: et al., We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L., We thank the Fermilab staff and the technical staffs of the participating institutions for their vital contributions. This work was supported by DOE and NSF (USA), CONICET and UBACyT (Argentina), CNPq, FAPERJ, FAPESP and FUNDUNESP (Brazil), CRC Program, CFI, NSERC and WestGrid Project (Canada), CAS and CNSF (China), Colciencias (Colombia), MSMT and GACR (Czech Republic), Academy of Finland (Finland), CEA and CNRS/IN2P3 (France), BMBF and DFG (Germany), Ministry of Education, Culture, Sports, Science and Technology (Japan), World Class University Program, National Research Foundation (Korea), KRF and KOSEF (Korea), DAE and DST (India), SFI (Ireland),INFN (Italy), CONACyT (Mexico), NSC(Republic of China), FASI, Rosatom and RFBR (Russia), Slovak R&D Agency (Slovakia), Ministerio de Ciencia e Innovación, and Programa Consolider-Ingenio 2010 (Spain), The Swedish Research Council (Sweden), Swiss National Science Foundation (Switzerland), FOM (The Netherlands), STFC and the Royal Society (UK), and the A.P. Sloan Foundation (USA).

Published
2010
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45. Unveiling the self-assembly process of gellan-chitosan complexes through a combination of atomistic simulations and experiments.

Author

Severini L, Tavagnacco L, Sennato S, Celi E, Chiessi E, Mazzuca C, and Zaccarelli E

Subjects
Static Electricity, Polyelectrolytes chemistry, Chitosan chemistry, Polysaccharides, Bacterial chemistry, Molecular Dynamics Simulation
Abstract

Polyelectrolyte complexes (PECs), formed via the self-assembly of oppositely charged polysaccharides, are highly valued for their biocompatibility, biodegradability, and hydrophilicity, offering significant potential for biotechnological applications. However, the complex nature and lack of insight at a molecular level into polyelectrolytes conformation and aggregation often hinders the possibility of achieving an optimal control of PEC systems, limiting their practical applications. To address this problem, an in-depth investigation of PECs microscopic structural organization is required. In this work, for the first time, a hybrid approach that combines experimental techniques with atomistic molecular dynamics simulations is used to elucidate, at a molecular level, the mechanisms underlying the aggregation and structural organization of complexes formed by gellan and chitosan, i.e. PECs commonly used in food technology. This combined analysis reveals a two-step complexation process: gellan initially self-assembles into a double-helix structure, subsequently surrounded and stabilized by chitosan via electrostatic interactions. Furthermore, these results show that complexation preserves the individual conformation and intrinsic functionality of both polyelectrolytes, thereby ensuring the efficacy of the PECs in biotechnological applications., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2025
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46. Gellan-based hydrogels and microgels: A rheological perspective.

Author

Franco S, Severini L, Buratti E, Tavagnacco L, Sennato S, Micheli L, Missori M, Ruzicka B, Mazzuca C, Zaccarelli E, and Angelini R

Abstract

Gellan gum-based systems have gained significant attention due to their versatility for multiple applications. In particular, they have shown a great potentiality in the field of cultural heritage, as efficient paper artwork cleaning agents in restoration processes. This efficacy is enhanced when gellan gum is assembled to form stable microgels, by controlling the gelation process under shear. Moreover, the use of methacrylated gellan gum provides additional functionality to the systems, that are also able to remove hydrophobic residues during the cleaning process. However, in order to optimize the manufacturing process, it is fundamental to obtain a thorough understanding of the rheological behaviour of the employed gellan gels in the optimal working conditions for paper cleaning. The present work aims to thoroughly characterize the rheological properties of low-acyl gellan gum, also during hydrogel and microgel formation, assessing the role of temperature (25-80 °C), gellan concentration (0.5-5 % for hydrogels and 0.1-0.5 % for microgels), methacrylation, presence of different cations (Na + , Ca 2+ ) and salt concentration (0.25-5.0 mM for hydrogels and 100 mM for microgels), on the behaviour of viscosity and viscoelastic moduli. We find the notable result that gellan hydrogels and microgels exhibit a double yielding behaviour in the conditions where they are mostly efficient for art restoration. Furthermore, we identify the optimal rheological conditions of these gels for efficient artwork restoration, opening the possibility to extend their applications to different substrates and in other fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2025
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47. Shaping the Future: Proposed Bills to Regulate New and Emerging Tobacco and Nicotine Products in Latin America and the Caribbean Amidst Public Health Concerns and Industry Interests.

Author

Severini L, de Figueiredo BA, Severini G, Tran B, Sebrié EM, and Crosbie E

Subjects
Latin America, Caribbean Region, Humans, Electronic Nicotine Delivery Systems economics, Electronic Nicotine Delivery Systems statistics & numerical data, Nicotine, Government Regulation, Tobacco Products legislation & jurisprudence, Tobacco Products economics, Public Health legislation & jurisprudence, Tobacco Industry legislation & jurisprudence
Abstract

Introduction: To examine legislative efforts to regulate new and emerging tobacco and nicotine products (NETNPs) in Latin America and the Caribbean (LAC) between 2017 and 2022., Aims and Methods: Analysis of online national legislation databases to track NETNP bills using standard snowball search methods., Results: Bills were identified in 15 out of the 33 LAC countries, accounting for a total of 91 bills targeting NETNPs. Mexico had the highest number (n = 38) of bills, followed by Brazil (n = 16), Argentina (n = 10), Colombia (n = 8), and Chile (n = 5). The remaining countries introduced two or fewer NETNP bills. Among the identified 91 bills, the majority (n = 60) addressed both electronic cigarettes and heated tobacco products (HTPs), almost one-third of bills (n = 29) applied only to electronic cigarettes, and only two focused solely on HTPs. Six of the fifteen countries with identified bills, enacted one NETNP law including Barbados, Bolivia, Costa Rica, Guyana, Mexico, and Panama. Since 2019, there has been a steady increase in the amount of NETNP bills introduced in LAC. In 2017 and 2018, 10 NETNP bills were introduced each year followed by 23 NETNP bills introduced in each 2019 and 2020, 19 in 2021, and 16 by August 2022., Conclusions: The substantial increase in the number of NETNP bills introduced since 2019 indicates the growing importance of regulating NETNPs in LAC. As NETNPs continue to evolve and grow it is important to continue monitoring and evaluating tobacco and nicotine regulatory initiatives while also staying ahead of the evolving market of NETNPs., Implications: Previous studies have analyzed the regulatory environment of NETNPs but it is less known about legislative and regulatory efforts and attempts. This is the first known study to analyze legislative bills to regulate NETNPs in Latin America and the Caribbean (LAC). The substantial increase in the number of NETNP bills introduced in LAC since 2019 indicates the growing importance of regulating NETNPs in LAC. As NETNPs continue to evolve and grow it is important to continue monitoring and evaluating tobacco and nicotine regulatory initiatives while also staying ahead of the evolving market of NETNPs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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48. Tobacco industry strategies to influence the regulation of new and emerging tobacco and nicotine products in Latin America and the Caribbean.

Author

Crosbie E, Tran B, Albuquerque de Figueiredo B, Severini L, Severini G, and Sebrié EM

Abstract

Objective: To document tobacco industry strategies to influence regulation of new and emerging tobacco and nicotine products (NETNPs) in Latin America and the Caribbean., Methods: We analyzed industry websites, advocacy reports, news media and government documents related to NETNPs, focusing on electronic cigarettes and heated tobacco products. We also conducted a survey of leading health advocates. We applied the policy dystopia model to analyze industry action and argument-based strategies on NETNP regulations., Results: Industry actors engaged in four instrumental strategies to influence NETNP regulation - coalition management, information management, direct involvement in and access to the policy process, and litigation. Their actions included: lobbying key policy-makers, academics and vaping associations; providing grants to media groups to disseminate favorable NETNP information; participating in public consultations; presenting at public hearings; inserting industry-inspired language into draft NETNP legislation; and filing lawsuits to challenge NETNP bans. The industry disseminated its so-called harm reduction argument through large/influential countries (e.g., Argentina, Brazil, and Mexico). Industry discursive strategies claimed NETNPs were less harmful, provided safer alternatives, and should be regulated as so-called harm reduction products or have fewer restrictions on their sale and use than those currently in place., Conclusion: Our analysis provides a better understanding of industry strategies to undermine tobacco and nicotine control. To help counter industry efforts, health advocates should proactively strengthen government capacities and alert policy-makers to industry attempts to create new regulatory categories (so-called reduced-risk products), provide misleading information of government authorizations of NETNPs, and co-opt so-called harm-reduction messages that serve the industry's agenda., Competing Interests: Conflicts of interest. None declared.

Published
2024
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49. SALL4 is a CRL3 REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma.

Author

Lospinoso Severini L, Loricchio E, Navacci S, Basili I, Alfonsi R, Bernardi F, Moretti M, Conenna M, Cucinotta A, Coni S, Petroni M, De Smaele E, Giannini G, Maroder M, Canettieri G, Mastronuzzi A, Guardavaccaro D, Ayrault O, Infante P, Bufalieri F, and Di Marcotullio L

Subjects
Animals, Humans, Mice, Cell Cycle Proteins, Hedgehog Proteins metabolism, Proteomics, Transcription Factors genetics, Transferases, Zinc Finger Protein GLI1 genetics, Brain Neoplasms, Cerebellar Neoplasms genetics, Cerebellar Neoplasms pathology, Medulloblastoma genetics
Abstract

The Sonic Hedgehog (SHH) pathway is crucial regulator of embryonic development and stemness. Its alteration leads to medulloblastoma (MB), the most common malignant pediatric brain tumor. The SHH-MB subgroup is the best genetically characterized, however the molecular mechanisms responsible for its pathogenesis are not fully understood and therapeutic benefits are still limited. Here, we show that the pro-oncogenic stemness regulator Spalt-like transcriptional factor 4 (SALL4) is re-expressed in mouse SHH-MB models, and its high levels correlate with worse overall survival in SHH-MB patients. Proteomic analysis revealed that SALL4 interacts with REN/KCTD11 (here REN), a substrate receptor subunit of the Cullin3-RING ubiquitin ligase complex (CRL3 REN ) and a tumor suppressor lost in ~30% of human SHH-MBs. We demonstrate that CRL3 REN induces polyubiquitylation and degradation of wild type SALL4, but not of a SALL4 mutant lacking zinc finger cluster 1 domain (ΔZFC1). Interestingly, SALL4 binds GLI1 and cooperates with HDAC1 to potentiate GLI1 deacetylation and transcriptional activity. Notably, inhibition of SALL4 suppresses SHH-MB growth both in murine and patient-derived xenograft models. Our findings identify SALL4 as a CRL3 REN substrate and a promising therapeutic target in SHH-dependent cancers., (© 2023. The Author(s).)

Published
2024
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50. Investigation into the Influence of the Process Parameters on the Stability of a Poly(Vinyl)-Alcohol-Based Coating System.

Author

Canale VC, Paleari L, Bragaglia M, Petrella G, Severini L, Nanni F, Mazzuca C, and Palleschi A

Abstract

Most tablets put on the market are coated with polymers soluble in water. The Opadry II 85 series from Colorcon Inc., is a family of PVA-based products marketed since the 1990s. Despite numerous publications on the properties of PVA, to date, limited work has been undertaken to determine the physico-chemical parameters (i.e., UV light, high temperature, and relative humidity) that could affect the performance of PVA-based coatings. To this end, we performed artificial ageing processes on samples made of Opadry Orange II or of some selected components of this coating and analysed them by means of a multidisciplinary approach, using, for example, FTIR, NMR, rheology, and DMTA measurements. In this way, we analysed the influence of the critical components of the Opadry Orange II formula, such as titanium dioxide and aluminium hydroxide, on the coating characteristics under ageing conditions.

Published
2024
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