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1. La construction de l’altérité par la « définition naturelle »

Author

Puccini, Paola

Subjects
Definitional linguistic activity. Intercultural communication. Missionary discourse. Quebec literature, English literature, PR1-9680, French literature - Italian literature - Spanish literature - Portuguese literature, PQ1-3999, Colonies and colonization. Emigration and immigration. International migration, JV1-9480
Abstract

Through his works, Celestino Testore gave an important reflection on the construction of otherness by the “natural definition”. The missionary discourse ends up confirming or invalidating, through the play of representation, the identity of the young protagonists. In order to understand the linguistic and cultural issues of missionary discourse in a given intercultural context, this article is centred on a corpus of 23 missionary narratives for youth. These texts – published in Quebec and edited by l’Apostolat de la Presse – present a classical ethnological approach for which the identification of the Other results in a closed network of meanings that use comparisons based on an ethno-centred perspective. However, in this kind of discourse we can also observe some unexpected signs of interculturality.

Published
2022
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2. La traduction comme paradigme de la communication interculturelle

Author

Puccini, Paola

Subjects
Intercultural communication. Mediation. Migrant Writer. Quebec literature. Translation, English literature, PR1-9680, French literature - Italian literature - Spanish literature - Portuguese literature, PQ1-3999, Colonies and colonization. Emigration and immigration. International migration, JV1-9480
Abstract

Marco Micone is among the most important French-speaking writers in Quebec. Through his works, he gave an important reflection on literature as a means of mediation and expression of intercultural communication. He also translated some classics of Italian literature. In our work, we intend to investigate how much the translation of Carlo Goldoni’s La Locandiera can become a paradigm through which to investigate the characteristics of intercultural communication. His Locandiera can be defined as a migrant translation, in the sense that, through it, its author expresses the complex approach to diversity and inclusion.

Published
2021
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4. Discovery, Multiparametric Optimization, and Solid-State Driven Identification of CHF-6550, a Novel Soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases

Author

Carzaniga, Laura, primary, Linney, Ian D., additional, Rizzi, Andrea, additional, Schmidt, Wolfgang, additional, Knight, Christopher K., additional, Mileo, Valentina, additional, Amadei, Francesco, additional, Pastore, Fiorella, additional, Miglietta, Daniela, additional, Cesari, Nicola, additional, Riccardi, Benedetta, additional, Mazzucato, Roberta, additional, Ghidini, Eleonora, additional, Blackaby, Wesley P., additional, Patacchini, Riccardo, additional, Battipaglia, Loredana, additional, Villetti, Gino, additional, Puccini, Paola, additional, Catinella, Silvia, additional, Civelli, Maurizio, additional, and Rancati, Fabio, additional

Published
2024
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5. Electron FLASH radiotherapy in vivo studies. A systematic review

Author

Giannini, Noemi, primary, Gadducci, Giovanni, additional, Fuentes, Taiusha, additional, Gonnelli, Alessandra, additional, Di Martino, Fabio, additional, Puccini, Paola, additional, Naso, Monica, additional, Pasqualetti, Francesco, additional, Capaccioli, Simone, additional, and Paiar, Fabiola, additional

Published
2024
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6. A bioconvergence study on platinum-free concurrent chemoradiotherapy for the treatment of HPV-negative head and neck carcinoma

Author

Gonnelli, Alessandra, primary, Sarogni, Patrizia, additional, Giannini, Noemi, additional, Linsalata, Stefania, additional, Di Martino, Fabio, additional, Zamborlin, Agata, additional, Frusca, Valentina, additional, Ermini, Maria Laura, additional, Puccini, Paola, additional, Voliani, Valerio, additional, and Paiar, Fabiola, additional

Published
2024
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7. Discovery, Multiparametric Optimization, and Solid-State Driven Identification of CHF-6550, a Novel Soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases.

Author

Carzaniga, Laura, Linney, Ian D., Rizzi, Andrea, Schmidt, Wolfgang, Knight, Christopher K., Mileo, Valentina, Amadei, Francesco, Pastore, Fiorella, Miglietta, Daniela, Cesari, Nicola, Riccardi, Benedetta, Mazzucato, Roberta, Ghidini, Eleonora, Blackaby, Wesley P., Patacchini, Riccardo, Battipaglia, Loredana, Villetti, Gino, Puccini, Paola, Catinella, Silvia, and Civelli, Maurizio

Published
2024
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8. Discovery, Multiparametric Optimization, and Solid-State Driven Identification of CHF-6550, a Novel Soft Dual Pharmacology Muscarinic Antagonist and β2Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases

Author

Carzaniga, Laura, Linney, Ian D., Rizzi, Andrea, Schmidt, Wolfgang, Knight, Christopher K., Mileo, Valentina, Amadei, Francesco, Pastore, Fiorella, Miglietta, Daniela, Cesari, Nicola, Riccardi, Benedetta, Mazzucato, Roberta, Ghidini, Eleonora, Blackaby, Wesley P., Patacchini, Riccardo, Battipaglia, Loredana, Villetti, Gino, Puccini, Paola, Catinella, Silvia, Civelli, Maurizio, and Rancati, Fabio

Abstract

Clinical guidelines for COPD and asthma recommend inhaled β-adrenergic agonists, muscarinic antagonists, and, for frequent exacerbators, inhaled corticosteroids, with the challenge of combining them into a single device. The MABA (muscarinic antagonist and β2agonist) concept has the potential to simplify this complexity while increasing the efficacy of both pharmacologies. In this article, we report the outcome of our solid-state driven back-up program that led to the discovery of the MABA compound CHF-6550. A soft drug approach was applied, aiming at high plasma protein binding and high hepatic clearance, concurrently with an early stage assessment of crystallinity through a dedicated experimental workflow. A new chemotype was identified, the diphenyl hydroxyacetic esters, able to generate crystalline material. Among this class, CHF-6550demonstrated in vivoefficacy, suitability for dry powder inhaler development, favorable pharmacokinetics, and safety in preclinical settings and was selected as a back-up candidate, fulfilling the desired pharmacological and solid-state profile.

Published
2024
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9. Optimization of M3 Antagonist–PDE4 Inhibitor (MAPI) Dual Pharmacology Molecules for the Treatment of COPD

Author

Rizzi, Andrea, primary, Amari, Gabriele, additional, Pivetti, Fausto, additional, Delcanale, Maurizio, additional, Amadei, Francesco, additional, Pappani, Alice, additional, Fornasari, Luca, additional, Villetti, Gino, additional, Marchini, Gessica, additional, Pisano, Anna Rita, additional, Pitozzi, Vanessa, additional, Pittelli, Maria Gloria, additional, Trevisani, Marcello, additional, Salvadori, Michela, additional, Cenacchi, Valentina, additional, Fioni, Alessandro, additional, Puccini, Paola, additional, Civelli, Maurizio, additional, Patacchini, Riccardo, additional, Baker-Glenn, Charles, additional, Van de Poël, Hervé, additional, Blackaby, Wesley, additional, Nash, Kevin, additional, and Armani, Elisabetta, additional

Published
2023
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11. Discovery of a Potent, Selective, and Orally Bioavailable Tool Compound for Probing the Role of Lysophosphatidic Acid Type 2 Receptor Antagonists in Fibrotic Disorders

Author

Armani, Elisabetta, primary, Rizzi, Andrea, additional, Iotti, Nicolò, additional, Saccani, Francesca, additional, Di Lascia, Maria Rosaria, additional, Tigli, Laura, additional, Pappani, Alice, additional, Marchini, Gessica, additional, Murgo, Annalisa, additional, Capelli, Anna Maria, additional, Delcanale, Maurizio, additional, Puccini, Paola, additional, Villetti, Gino, additional, Civelli, Maurizio, additional, Beato, Claudia, additional, Giuliani, Marta, additional, Mundi, Claudia, additional, Murarolli, Francesca, additional, Pagano, Mafalda, additional, Raveglia, Luca F., additional, Remelli, Rosaria, additional, and Amari, Gabriele, additional

Published
2023
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13. Optimization of M3 Antagonist–PDE4 Inhibitor (MAPI) Dual Pharmacology Molecules for the Treatment of COPD.

Author

Rizzi, Andrea, Amari, Gabriele, Pivetti, Fausto, Delcanale, Maurizio, Amadei, Francesco, Pappani, Alice, Fornasari, Luca, Villetti, Gino, Marchini, Gessica, Pisano, Anna Rita, Pitozzi, Vanessa, Pittelli, Maria Gloria, Trevisani, Marcello, Salvadori, Michela, Cenacchi, Valentina, Fioni, Alessandro, Puccini, Paola, Civelli, Maurizio, Patacchini, Riccardo, and Baker-Glenn, Charles

Published
2023
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14. Lymph-vascular Space Involvement and/or p53 Overexpression Correlated With the Clinical Outcome of Early-stage Endometrial Cancer Patients Treated With Adjuvant Vaginal Brachytherapy

Author

LALISCIA, CONCETTA, primary, GADDUCCI, ANGIOLO, additional, COCCIA, NATALINA, additional, MATTIONI, ROBERTO, additional, FUENTES, TAIUSHA, additional, CARETTO, MARTA, additional, PISTOLESI, SABINA, additional, PUCCINI, PAOLA, additional, PERRONE, FRANCO, additional, MORGANTI, RICCARDO, additional, and PAIAR, FABIOLA, additional

Published
2022
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16. Discovery of Clinical Candidate CHF-6366: A Novel Super-soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases

Author

Carzaniga, Laura, primary, Linney, Ian D., additional, Rizzi, Andrea, additional, Delcanale, Maurizio, additional, Schmidt, Wolfgang, additional, Knight, Christopher K., additional, Pastore, Fiorella, additional, Miglietta, Daniela, additional, Carnini, Chiara, additional, Cesari, Nicola, additional, Riccardi, Benedetta, additional, Mileo, Valentina, additional, Venturi, Luca, additional, Moretti, Elisa, additional, Blackaby, Wesley P., additional, Patacchini, Riccardo, additional, Accetta, Alessandro, additional, Biagetti, Matteo, additional, Bassani, Franco, additional, Tondelli, Marina, additional, Murgo, Annalisa, additional, Battipaglia, Loredana, additional, Villetti, Gino, additional, Puccini, Paola, additional, Catinella, Silvia, additional, Civelli, Maurizio, additional, and Rancati, Fabio, additional

Published
2022
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17. Design, Synthesis, and Biological Characterization of Inhaled p38α/β MAPK Inhibitors for the Treatment of Lung Inflammatory Diseases

Author

Armani, Elisabetta, primary, Capaldi, Carmelida, additional, Bagnacani, Valentina, additional, Saccani, Francesca, additional, Aquino, Giancarlo, additional, Puccini, Paola, additional, Facchinetti, Fabrizio, additional, Martucci, Cataldo, additional, Moretto, Nadia, additional, Villetti, Gino, additional, Patacchini, Riccardo, additional, Civelli, Maurizio, additional, Hurley, Chris, additional, Jennings, Andrew, additional, Alcaraz, Lilian, additional, Bloomfield, Dawn, additional, Briggs, Michael, additional, Daly, Stephen, additional, Panchal, Terry, additional, Russell, Vince, additional, Wicks, Sharon, additional, Finch, Harry, additional, Fitzgerald, Mary, additional, Fox, Craig, additional, and Delcanale, Maurizio, additional

Published
2022
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18. ADME properties of CHF6366, a novel bi-functional M3 muscarinic receptor antagonist and ß2 adrenoceptor agonist (MABA) radiolabelled at both functional moieties.

Author

Ghiglieri, Alberto, Messina, Monica, Cenacchi, Valentina, Piutti, Claudia, Cinato, Flavio, Brogin, Giandomenico, and Puccini, Paola

Subjects
MUSCARINIC receptors, BIOAVAILABILITY, MUSCARINIC antagonists, CHRONIC obstructive pulmonary disease, ORAL drug administration, MOIETIES (Chemistry), LIVER microsomes
Abstract

CHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD) was [14C]-radiolabelled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterise its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration. A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution throughout the body and a complete metabolic transformation of the parent drug without relevant gender difference. CHF6366 was observed fully hydrolysed to alcohol (CHF6387) and carboxylic acid (CHF6361) in plasma and urine after IV and IT administration, and mainly unchanged in faeces only after oral administration. An important number of metabolites containing aminobutanolic moiety was excreted via urine, whereas carbamate-containing derivatives were excreted mainly by bile. The major metabolic routes of the alcoholic moiety (CHF6387) included isomerisation (Ma7), conjugation with glucuronic acid and dehydrogenation, while the carboxylic acid moiety (CHF6361) was mainly metabolised through oxidation, glucuronide conjugation and, in both pathways, combinations of those metabolic reactions. No major differences arose also from in vitro metabolism profiles investigated using liver microsomes and hepatocytes of different species. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Diversit�� e inclusione: per una fissit�� distratta

Author

Puccini, Paola and Zironi, Alessandro

Subjects
education, respiratory system, human activities, health care economics and organizations
Abstract

DIVE-IN ��� An International Journal on Diversity and Inclusion, No. 1 (2021): Diversity and Inclusion. Overcoming Fragmentation

Published
2021
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23. Introduzione. Letteratura e pubblicità: verso nuovi orizzonti di senso

Author

PUCCINI PAOLA, Anna Paola Soncini Fratta, Paola Puccini, Andrea Battistini, Rossella Elisei, Alberto Sebastiani, Alessandro Canale, Guglielmo Pescatore, Marta Rocchi, Anton Peter Margoni, Elisabetta Zurovac, Giovanni Boccia Artieri, Eleonora Marzi, Eleonora Marzi, and PUCCINI PAOLA

Subjects
PUBBLICITA-ANALISI DEL DISCORSO-LINGUISTICA-ANALISI DELL'IMPLICITO
Abstract

La pubblicità e la letteratura lette insieme costruiscono la nostra realtà espressiva e intellettuale. Le modalità della loro interazione sono varie e complesse, cambiano nel tempo e con i supporti comunicativi. E’ dunque importante produrre una riflessione su questo tema che prenda in considerazione i vari aspetti contemporanei.

Published
2020

24. Functionalized pyrazoles and pyrazolo[3,4- d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity

Author

Biagini, Pierfrancesco, Biancalani, Claudio, Graziano, Alessia, Cesari, Nicoletta, Giovannoni, Maria Paola, Cilibrizzi, Agostino, Piaz, Vittorio Dal, Vergelli, Claudia, Crocetti, Letizia, Delcanale, Maurizio, Armani, Elisabetta, Rizzi, Andrea, Puccini, Paola, Gallo, Paola Maria, Spinabelli, Daniele, and Caruso, Paola

Published
2010
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26. Discovery of M3 Antagonist-PDE4 Inhibitor Dual Pharmacology Molecules for the Treatment of Chronic Obstructive Pulmonary Disease

Author

Armani, Elisabetta, primary, Rizzi, Andrea, additional, Capaldi, Carmelida, additional, De Fanti, Renato, additional, Delcanale, Maurizio, additional, Villetti, Gino, additional, Marchini, Gessica, additional, Pisano, Anna Rita, additional, Pitozzi, Vanessa, additional, Pittelli, Maria Gloria, additional, Trevisani, Marcello, additional, Salvadori, Michela, additional, Cenacchi, Valentina, additional, Puccini, Paola, additional, Amadei, Francesco, additional, Pappani, Alice, additional, Civelli, Maurizio, additional, Patacchini, Riccardo, additional, Baker-Glenn, Charles A.G., additional, Van de Poël, Hervé, additional, Blackaby, Wesley P., additional, Nash, Kevin, additional, and Amari, Gabriele, additional

Published
2021
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27. Discovery of Clinical Candidate CHF-6366: A Novel Super-soft Dual Pharmacology Muscarinic Antagonist and β2Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases

Author

Carzaniga, Laura, Linney, Ian D., Rizzi, Andrea, Delcanale, Maurizio, Schmidt, Wolfgang, Knight, Christopher K., Pastore, Fiorella, Miglietta, Daniela, Carnini, Chiara, Cesari, Nicola, Riccardi, Benedetta, Mileo, Valentina, Venturi, Luca, Moretti, Elisa, Blackaby, Wesley P., Patacchini, Riccardo, Accetta, Alessandro, Biagetti, Matteo, Bassani, Franco, Tondelli, Marina, Murgo, Annalisa, Battipaglia, Loredana, Villetti, Gino, Puccini, Paola, Catinella, Silvia, Civelli, Maurizio, and Rancati, Fabio

Abstract

The development of molecules embedding two distinct pharmacophores acting as muscarinic antagonists and β2agonists (MABAs) promises to be an excellent opportunity to reduce formulation issues and boost efficacy through cross-talk and allosteric interactions. Herein, we report the results of our drug discovery campaign aimed at improving the therapeutic index of a previous MABA series by exploiting the super soft-drug concept. The incorporation of a metabolic liability, stable at the site of administration but undergoing rapid systemic metabolism, to generate poorly active and quickly eliminated fragments was pursued. Our SAR studies yielded MABA 29, which demonstrated a balanced in vivo profile up to 24 h, high instability in plasma and the liver, as well as sustained exposure in the lung. In vitro safety and non-GLP toxicity studies supported the nomination of 29(CHF-6366) as a clinical candidate, attesting to the successful development of a novel super-soft MABA compound.

Published
2022
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28. « La grâce de montrer son âme dans le vêtement » Scrivere di tessuti, abiti, accessori. Studi in onore di Liana Nissim

Author

Allovio, Stefano, Amatulli, Margareth, Auraix-Jonchière, Pascale, Balestra, Gianfranca, Benelli, Graziano, Bhêly-Quenum, Olympe, Bini, Valerio, Bosco, Gabriella, Botta, Giorgio, Brancaglion, Cristina, Cerullo, Maria, Colombini Mantovani, Adriana, Conenna, Mirella, Corona, René, Di Bernardini, Gian Luigi, Dotoli, Giovanni, Dubois, Jacques, Elefante, Chiara, Emina, Antonella, Franchi, Franca, Galazzi, Enrica, Genetti, Stefano, Giansante, Gabriella, Giaufret, Anna, Gnocchi, Maria Chiara, Mathieu, Paul, Mauri, Daniela, Melzi d’Eril Kaucisvili, Francesca, Miconi, Jada, Molinari, Chiara, Monneyron, Frédéric, Mootoosamy, Vidoolah, Morinière, Claude Benoit, Pedrazzini, Maria Cristina, Pessini, Alba, Placella Sommella, Paola, Preumont, Yannick, Puccini, Paola, Quaglia, Elena, Raccanello, Manuela, Raffi, Maria Emanuela, Raschi, Nataša, Riva, Silvia, Rossi, Micaela, Salerni, Paola, Scotto, Fabio, Soncini Fratta, Anna, Sparvoli, Eleonora, Sperti, Valeria, Tallarico, Giovanni, Urbani, Bernard, Vago, Davide, Vecchiato, Sara, Vinti, Claudio, Zecchi, Lina, Zoppellari, Anna, Modenesi, Marco, Collini, Maria Benedetta, and Paraboschi, Francesca

Subjects
ARC000000, AM, French, LIT000000, français, Literature (General), francesistica, DS, Art, Québec
Abstract

Eminente francesista, Liana Nissim ha dedicato la sua intensa attività di ricerca al XIX secolo, in particolare a Gustave Flaubert e Stéphane Mallarmé. I suoi studi si sono concentrati anche sulle letterature francofone dell’Africa Nera e del Québec, che ha contribuito a introdurre in Italia e a diffondere su scala internazionale. Questo trittico di volumi «La grâce de montrer son âme dans le vêtement». Scrivere di tessuti, abiti e accessori illustra e approfondisce in molteplici direzioni una tematica a lei cara e ampiamente presente nei suoi lavori. Tramite la ricchezza delle metodologie e delle prospettive critiche, la comunità scientifica che ha condiviso con lei la passione per la ricerca e la dedizione alla vita universitaria vuole renderle un omaggio riconoscente.

Published
2020

29. Da una lingua all’altra. I costumi e gli accessori di scena nel teatro di Marco Micone

Author

Puccini, Paola

Subjects
ARC000000, AM, French, LIT000000, français, Literature (General), francesistica, DS, Art, Québec
Abstract

Teatro migrante, l’opera drammaturgica di Marco Micone ha messo in scena costumi ed accessori che si caricano di una valenza che rinvia alla cultura d’origine offerta allo sguardo dello spettatore quebecchese. Essi appaiono come segni di un’identità che incontra un’alterità alla ricerca di un’accoglienza. L’opera prima, Gens du silence, declinata nelle sue tre versioni del 1982, del 1991 e del 1996, mostra, infatti, come l’uso dei costumi di scena risponda ad una esigenza di rappresentazione ...

Published
2020

31. A Hybrid In Silico/In Vitro Target Fishing Study to Mine Novel Targets of Urolithin A and B: A Step Towards a Better Comprehension of Their Estrogenicity

Author

Dellafiora, Luca, primary, Milioli, Marco, additional, Falco, Angela, additional, Interlandi, Margherita, additional, Mohamed, Abdelrahman, additional, Frotscher, Martin, additional, Riccardi, Benedetta, additional, Puccini, Paola, additional, Rio, Daniele Del, additional, Galaverna, Gianni, additional, and Dall'Asta, Chiara, additional

Published
2020
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39. Il testo letterario nell’apprendimento linguistico: Esperienze a confronto

Author

Ivancic, Barbara, Puccini, Paola, Rodrigo Mora, Maria José, and Turci, Monica

Subjects
L-LIN/02 Didattica delle lingue moderne, Quaderni del CeSLiC. Atti di Convegni
Abstract

Nel maggio del 2016 il Centro di Studi Linguistico-Culturali, Ricerca – Prassi – Formazione (CeSLiC) del Dipartimento di Lingue, Letterature e Culture Moderne dell’Università di Bologna ha promosso una Giornata di studi sul tema “Il testo letterario nell’apprendimento linguistico: Esperienze a confronto”. Scopo dell’iniziativa era quello di avviare una riflessione interdisciplinare sul ruolo del testo letterario nello sviluppo delle competenze linguistico-culturali, nella convinzione che, come scrive Hasan (1989 [1985]: 91), “nell’arte verbale il ruolo della lingua è centrale. […] la lingua non è come l’abbigliamento per il corpo, ma è il corpo stesso”. La Giornata ha visto la partecipazione di relatrici e relatori provenienti da scuola e università, i quali hanno illustrato diverse proposte e modelli di analisi e uso del testo letterario, partendo dalle proprie esperienze di insegnamento e ricerca. Ne è nato uno scambio intenso e fecondo, da cui sono emersi stimoli e idee utili tanto dal punto di vista didattico quanto da quello della riflessione scientifica. Il presente volume raccoglie nove interventi presentati e discussi in quell’occasione.

Published
2018
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43. La prise en compte du Sujet. Une approche anthropologique de l’autotraduction

Author

PUCCINI, PAOLA, A. Ferraro, R . Grutman, and Puccini, Paola

Subjects
Autotraduction Petspective théorique interdisciplinarité
Abstract

De nombreuses études ont à ce jour démontré que l’autotraduction est bien loin d’être une pratique isolée et sporadique . Depuis l’Antiquité jusqu’à nos jours, les auteurs se sont autotraduits de différentes langues, sur plusieurs continents, avec des motivations fort variées. L’étude de l’autotraduction intéresse maintes disciplines: la linguistique, la traductologie, la philologie, la sociolinguistique, la théorie littéraire et d’autres encore. Parmi ces disciplines l’apport des sciences sociales, en particulier de l’anthropologie culturelle, nous paraît intéressant surtout quand on se penche sur le phénomène autotraductif dans la modernité et la surmodernité. La pratique autotraductive montre des dynamiques interculturelles, au niveau individuel et collectif, qui en font un phénomène de l’époque contemporaine.

Published
2016

44. Discovery of M3Antagonist-PDE4 Inhibitor Dual Pharmacology Molecules for the Treatment of Chronic Obstructive Pulmonary Disease

Author

Armani, Elisabetta, Rizzi, Andrea, Capaldi, Carmelida, De Fanti, Renato, Delcanale, Maurizio, Villetti, Gino, Marchini, Gessica, Pisano, Anna Rita, Pitozzi, Vanessa, Pittelli, Maria Gloria, Trevisani, Marcello, Salvadori, Michela, Cenacchi, Valentina, Puccini, Paola, Amadei, Francesco, Pappani, Alice, Civelli, Maurizio, Patacchini, Riccardo, Baker-Glenn, Charles A.G., Van de Poël, Hervé, Blackaby, Wesley P., Nash, Kevin, and Amari, Gabriele

Abstract

In this paper, we report the discovery of dual M3antagonist-PDE4 inhibitor (MAPI) compounds for the inhaled treatment of pulmonary diseases. The identification of dual compounds was enabled by the intuition that the fusion of a PDE4 scaffold derived from our CHF-6001series with a muscarinic scaffold through a common linking ring could generate compounds active versus both the transmembrane M3receptor and the intracellular PDE4 enzyme. Two chemical series characterized by two different muscarinic scaffolds were investigated. SAR optimization was aimed at obtaining M3nanomolar affinity coupled with nanomolar PDE4 inhibition, which translated into anti-bronchospastic efficacy ex vivo(inhibition of rat trachea contraction) and into anti-inflammatory efficacy in vitro(inhibition of TNFα release). Among the best compounds, compound 92aachieved the goal of demonstrating in vivoefficacy and duration of action in both the bronchoconstriction and inflammation assays in rat after intratracheal administration.

Published
2021
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45. L’autotraduction comme malheureuse nécessité : le cas de La Maculée/sTain de Madeleine Blais-Dahlem

Author

PUCCINI, PAOLA and Puccini, Paola

Subjects
Autotraduction Canada franacophone
Abstract

Cette étude analyse l’édition de La Maculée/sTain publiée en 2012, qui contient la pièce de Madeleine Blais-Dahlem dans sa double version, l’original en français et l’autotraduction en anglais, avec des paratextes distincts. Le but est d’examiner d’abord les éléments qui indiquent un déplacement ou un mouvement de la version française à la version anglaise ; ensuite les éléments qui dessinent un mouvement contraire, de la version anglaise à la française ; enfin l’analyse approfondit l’aspect d’un nouvel espace créé par le croisement de ces deux mouvements opposés. Mots-clés : Autotraduction, Blais-Dahlem, Maculée, sTain, bilingue.

Published
2015

46. Avant-propos. Pour une cartographie de l’autotraduction

Author

PUCCINI, PAOLA, Paola Puccini, and Puccini, Paola

Subjects
Europe, Maghreb, Autotraduction littéraire, Francophonie, Canada Francophone
Abstract

L’autotraduction est un phénomène global qui connaît une diffusion importante ; ses contours ne cessent d’être explorés par les cartographes de l’autotraduction qui, surtout depuis une vingtaine d’années, s’appliquent à en dresser les cartes. Le phénomène a une ampleur historique, géographique, littéraire et socioculturelle très significative. Les approches, découlant de différentes disciplines tracent une sorte de carte d’identité, avec ses lignes fondamentales. Ce numéro, présente des questions théoriques et définitoires, des études de cas et des réflexions métalinguistiques de la part des écrivains autotraducteurs ; l’objectif est de participer à une mise au point de la carte identitaire de ce voyage dans l’altérité qu’est l’autotraduction, aventure qui ne cesse de passionner.

Published
2015

47. Discovery and Optimization of Thiazolidinyl and Pyrrolidinyl Derivatives as Inhaled PDE4 Inhibitors for Respiratory Diseases

Author

Carzaniga, Laura, Amari, Gabriele, Rizzi, Andrea, Capaldi, Carmelida, De Fanti, Renato, Ghidini, Eleonora, Villetti, Gino, Carnini, Chiara, Moretto, Nadia, Facchinetti, Fabrizio, Caruso, Paola, Marchini, Gessica, Battipaglia, Loredana, Patacchini, Riccardo, Cenacchi, Valentina, Volta, Roberta, Amadei, Francesco, Pappani, Alice, Capacchi, Silvia, Bagnacani, Valentina, Delcanale, Maurizio, Puccini, Paola, Catinella, Silvia, Civelli, Maurizio, and Armani, Elisabetta

Abstract

Phosphodiesterase 4 (PDE4) is a key cAMP-metabolizing enzyme involved in the pathogenesis of inflammatory disease, and its pharmacological inhibition has been shown to exert therapeutic efficacy in chronic obstructive pulmonary disease (COPD). Herein, we describe a drug discovery program aiming at the identification of novel classes of potent PDE4 inhibitors suitable for pulmonary administration. Starting from a previous series of benzoic acid esters, we explored the chemical space in the solvent-exposed region of the enzyme catalytic binding pocket. Extensive structural modifications led to the discovery of a number of heterocycloalkyl esters as potent in vitroPDE4 inhibitors. (S*,S**)-18eand (S*,S**)-22e, in particular, exhibited optimal in vitroADME and pharmacokinetics properties and dose-dependently counteracted acute lung eosinophilia in an experimental animal model. The optimal biological profile as well as the excellent solid-state properties suggest that both compounds have the potential to be effective topical agents for treating respiratory inflammatory diseases.

Published
2024
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48. Functional analysis of OCTN2 and ATB0,+ in normal human airway epithelial cells.

Author

Rotoli, Bianca Maria, Visigalli, Rossana, Barilli, Amelia, Ferrari, Francesca, Bianchi, Massimiliano G., Di Lascia, Maria, Riccardi, Benedetta, Puccini, Paola, and Dall'Asta, Valeria

Subjects
EPITHELIAL cells, FUNCTIONAL analysis, ESSENTIAL fatty acids, DRUG delivery systems, MOUNTAIN biking
Abstract

In human, OCTN2 (SLC22A5) and ATB0,+ (SLC6A14) transporters mediate the uptake of L-carnitine, essential for the transport of fatty acids into mitochondria and the subsequent degradation by β-oxidation. Aim of the present study was to characterize L-carnitine transport in EpiAirway™, a 3D organotypic in vitro model of primary human tracheal-bronchial epithelial cells that form a fully differentiated, pseudostratified columnar epithelium at air-liquid interface (ALI) condition. In parallel, Calu-3 monolayers grown at ALI for different times (8d or 21d of culture) were used as comparison. OCTN2 transporter was equally expressed in both models and functional at the basolateral side. ATB0,+ was, instead, highly expressed and active on the apical membrane of EpiAirway™ and only in early-cultures of Calu-3 (8d but not 21d ALI). In both cell models, L-carnitine uptake on the apical side was significantly inhibited by the bronchodilators glycopyrrolate and tiotropium, that hence can be considered substrates of ATB0,+; ipratropium was instead effective on the basolateral side, indicating its interaction with OCTN2. Inflammatory stimuli, such as LPS or TNFα, caused an induction of SLC6A14/ATB0,+ expression in Calu-3 cells, along with a 2-fold increase of L-carnitine uptake only at the apical side; on the contrary SLC22A5/OCTN2 was not affected. As both OCTN2 and ATB0,+, beyond transporting L-carnitine, have a significant potential as delivery systems for drugs, the identification of these transporters in EpiAirway™ can open new fields of investigation in the study of drug inhalation and pulmonary delivery. [ABSTRACT FROM AUTHOR]

Published
2020
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