12 research outputs found

    * (Mostra collettiva). * Mostra sul tema “I Teatri a Lecce nell’Italia Unita”, a cura del gruppo Cultura_Ordine Architetti PP.PP. e CC. della Provincia di Lecce, nov. 2011. * Mostra documentaria sul tema “I Teatri a Lecce nell’Italia Unita” allestita presso il teatro “Paisiello” (Lecce, via Giuseppe Palmieri) dal 5 al 26 novembre 2011 (vernissage: 4 novembre 2011), a cura del gruppo Attività culturali, comunicazione e informazione dell’Ordine: Fabiana Cicirillo-consigliere delegato; Barbara Bruno, Luigi Calcagnile, Walter Carrozzo, Francesco D’Ercole, Ugo Gelli, Patrizia Marzo, Marcello Messa, Katy Tundo, Nicole Valenza, Raffaela Zizzari, Antonio Zunno. * Catalogo (“Teatri a Lecce nell’Italia Unita”).

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    * Mostra documentaria sul tema “I Teatri a Lecce nell’Italia Unita” allestita presso il teatro “Paisiello” (Lecce, via Giuseppe Palmieri) dal 5 al 26 novembre 2011 (vernissage: 4 novembre 2011), a cura del gruppo Attività culturali, comunicazione e informazione dell’Ordine: Fabiana Cicirillo-consigliere delegato; Barbara Bruno, Luigi Calcagnile, Walter Carrozzo, Francesco D’Ercole, Ugo Gelli, Patrizia Marzo, Marcello Messa, Katy Tundo, Nicole Valenza, Raffaela Zizzari, Antonio Zunno. * Catalogo (“Teatri a Lecce nell’Italia Unita”)

    Culture Takeaway

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    This keynote is mainly based on Wallace's research for Volume X of La Cultura Italiana published by UTET in 2010. The volume is in Italian and, by translating it, it can now be shared with colleagues, students and friends. The relationship that each citizen has with his/her own country and culture is mediated by personal experiences and matured during a lifetime. It is a delicate task to identify what motivates the consciousness of “insiders” of a culture whilst, at the same time, stimulating the interest of outsiders. To be able to observe the prodigious artistic production of one’s own country from the point of view of another culture and another genetic material offers fresh cues. Curiosity, prodded by geographical and physical distance, helps to identify in a schematic way those characteristics that define a country’s visual culture in a decisively distinctive way

    The role of tax assessment in the fight against criminal phenomena

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    Lo scritto si occupa del possibile ruolo che l’attività di accertamento effettuata dall’Amministrazione finanziaria può assumere nella lotta ai fenomeni criminali. Ricostruendo i principali strumenti di accertamento sia in ambito nazionale che internazionale, l’Autore si interroga sui possibili punti di contatto e sulle sinergie interistituzionali che possono instaurarsi fra l’Amministrazione finanziaria e l’Autorità penale.The paper addresses the potential role that the assessment activity carried out by the Tax Administration can play in the fight against criminal phenomena. By reconstructing the main assessment tools at both national and international levels, the Author examines the possible contacts and the inter-institutional synergies that may be established between the Tax Administration and the Criminal Justice Authority

    “Bimbo semplice che fui / dal cuore in mano e dalla fronte alta”: sui modi di dire nella poesia di Guido Gozzano

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    In this paper, we will focus on a few poems by Guido Gozzano, which are taken from the only poetic collections published by the author during his lifetime: La via del rifugio (1907) and I colloqui (1911). Several collocations will be examined, i.e. some sequences of words linked together by more or less solid, more or less fixed connections. Of these, moreover, we will attempt to outline very briefly the history, the evolution in the field of Italian literature from its origins up to contemporary times, because it is precisely from the diachronic study of such material that it will be possible to derive information on the function it plays in Gozzani's poetry. On the other hand, as Uberto Motta stated: «studying the “sources” of a text, reconstructing its references and the comparisons generated from the words and images of which it is composed, [...] allows us to relocate it within the system [...] into which it was conceived». As we will try to demonstrate, idiomatic expressions, because of their fixedness, participate in that operation which allows the poet of I Colloqui to «satisfy the radical need [...] to possess something that is now past, immobile». Therefore, the presence of this phenomena of crystallisation of language (literary and daily), of a word which can no longer mutate, which becomes a certain and secure anchorage, takes on absolute importance. A word which, thanks to its own immobility, is perceived by Gozzano as a stable landing place, and ends up constituting the one and only reassuring «way of refuge»

    Electrostatic Map of Proteasome α-Rings Encodes the Design of Allosteric Porphyrin-Based Inhibitors Able to Affect 20S Conformation by Cooperative Binding

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    The importance of allosteric proteasome inhibition in the treatment of cancer is becoming increasingly evident. Motivated by this urgent therapeutic need, we have recently identified cationic porphyrins as a highly versatile class of molecules able to regulate proteasome activity by interfering with gating mechanisms. In the present study, the mapping of electrostatic contacts bridging the regulatory particles with the α-rings of the human 20S proteasome led us to the identification of (meso-tetrakis(4-N-methylphenyl pyridyl)-porphyrin (pTMPyPP4) as a novel non-competitive inhibitor of human 20S proteasome. pTMPyPP4 inhibition mechanism implies a positive cooperative binding to proteasome, which disappears when a permanently open proteasome mutant (α-3ΔN) is used, supporting the hypothesis that the events associated with allosteric proteasome inhibition by pTMPyPP4 interfere with 20S gating and affect its "open-closed" equilibrium. Therefore, we propose that the spatial distribution of the negatively charged residues responsible for the interaction with regulatory particles at the α-ring surface of human 20S may be exploited as a blueprint for the design of allosteric proteasome regulators. © 2017 The Author(s)

    “Teatri a Lecce nell’Italia Unita”

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    Catalogo della Mostra documentaria sul tema i “Teatri a Lecce nell’Italia Unita” allestita presso il teatro “Paisiello” (Lecce, via Giuseppe Palmieri) dal 5 al 26 novembre 2011 (vernissage: 4 novembre 2011)

    Utopia versus metafora?

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    Il saggio è incentrato sull'utopia della decrescita come superamento di quel modello di sviluppo che, per secoli, ha dominato il pensiero occidentale: la metafora della crescita. Da diversi anni, infatti, ci si chiede se la mitica crescita abbia effettivamente assicurato quel diffuso benessere di cui si è tanto parlato. Un orientamento riflessivo, che l’autrice analizza individuando due principali prospettive: una più moderata, che continua a usare la metafora della crescita riconfigurandone, però, senso e significato, attraverso aggettivazioni quali intelligente, inclusiva, sostenibile; un’altra più radicale, che ha intenzionalmente abbandonato l’idea della crescita optando per l’utopia della decrescita. Questa utopia porterà alla scomparsa della metafora dello sviluppo come crescita? Di fatto, l’utopia della decrescita sta modificando lo stile di vita di molte persone, contribuendo a dare forma a un possibile scenario futuro in un contesto di crisi diffusa. E proprio nell'attuale contesto di crisi, sottolinea l’autrice, l’utopia è riemersa, come esperienza e progetto, nel suo senso autentico: l’utopia-eutopia di Tommaso Moro.The essay focuses on decrease as a utopia which is surpassing the metaphor of growth, the model of development that has dominated the western thought so far. In fact, we have been wondering for years about the mythical growth as an actual producer of that widespread wellbeing which was proclaimed. A reflective orientation has been gaining ground, and on this orientation the author concentrates her attention identifying two main perspectives: a more moderate one, which continues to use the metaphor of growth, but reconfiguring its sense and meaning through adjectives such as intelligent, inclusive, sustainable; and a more radical one, which has intentionally abandoned the idea of growth and opted for the utopia of decrease. Will this utopia lead to the disappearance of the metaphor of development in terms of growth? Actually, the utopia of decrease is changing many people’s lifestyle, contributing to the creation of a possible future scenario in a context of widespread crisis. In this context of crisis, underlines the author, utopia has reappeared as experience and project, recovering its authentic meaning: Thomas More’s Utopia-Eutopia. Keywords: Utopia, Decrease, Metaphor, Growth, Post-growth, Crisis

    Targeted delivery of advanced functionality by nanomaterials : focus on nucleic acids delivery by novel block copolymers

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    Abstract: Smart drug delivery systems are versatile examples of successful nanomedicine with potential in diagnostics and medical therapy. The thesis presents selected approaches in current drug delivery systems in the (pre-)clinical trials, and deals with potential side effects, including complement activation and hypersensitivity reactions as well as the design requirements of the delivery systems. Furthermore, it presents approaches of cationic block copolymers, which are capable to condense negatively charged nucleic acid molecules such as plasmid deoxyribonucleic acid (pDNA) and small interfering ribonucleic acid (siRNA) with the aim of efficient cell gene delivery and specific gene suppression, respectively. The first part addresses the transfection efficiency of circular versus linearized plasmid DNA using a green fluorescent protein expressing vector with Lipofectamine 2000 and linear 25 kDA polyethylenimine (PEI). These results show a considerably improved transfection efficiency with the circular compared to the linearized DNA for the two transfection reagents. The electron microscopy images with Lipofectamine or PEI demonstrate that the circular DNA gives rise to random coil appearance of compact, spherical shape, while linearized DNA appear as worm-like strands. Particle size and shape are important in the cell biology of endocytosis and phagocytosis. The findings indicate that the shape of the transfection particle is vital for successful gene transfer. To develop a delivery system for gene therapy, two cationic diblock copolymers consisting of primary and tertiary amines were synthesized and analyzed with respect to DNA condensation properties, morphology of the condensed plasmid DNA and transfection efficiency using two cell lines. This study revealed proof-of-concept showing an order of magnitude lower transfection efficiency of primary amine diblock copolymers compared to PEI after 48 h with increasing plasmid DNA concentration. Furthermore, primary amines compared to tertiary ones show much stronger binding to DNA and improved transfection efficiency. Transmission electron and atomic force microscopy data revealed morphologies of primary and tertiary amines regarding the condensation of the plasmid DNA, in agreement with the transfection efficiency. In a second part the design and characterization of pentablock-based polyplexes based on the combination of cationic pentablock copolymers with folic acid functionalized copolymers for targeted specific siRNA delivery is described. The achieved 31 % knockdown efficiency shows its potential regarding cancer gene therapy. The pentablock architecture allows the formation of highly stable micelleplexes of (21 ± 3) nm in 10 mM PBS buffer solution with a neutral surface charge, excellent siRNA condensation properties, outstanding colloidal stability in 10 % serum over 24 h and biocompatibility deduced from the absence of considerable cytotoxicity even after 48 h incubation. Furthermore, selective delivery of the siRNA could be proven by the introduction of a ligand-linked block copolymer, resulting in 31 % compared to 8 % gene suppression for targeted a non-targeted micelleplexes. This pentablock-based delivery system might yield impact to future delivery systems as well as being a potential platform to be applied in vivo for cancer gene therapy. ---------- Zusammenfassung Innerhalb des Bereichs der Nanomedizin weisen intelligente Wirkstoffabgabesysteme ein großes Potenzial auf, sowohl hinsichtlich der Diagnostik wie auch der medizinischen Therapie. Die vorliegende Arbeit stellt im Rahmen einer Literaturrecherche ausgewählte Wirkstoffabgabesysteme vor, welche sich in (vor-) klinischen Studien befinden, den Nebenwirkungen welche durch diese entstehen können, im speziellen der Komplementaktivierung und Überempfindlichkeitsreaktionen, sowie deren Konstruktionsanforderungen. Des weiteren werden in einem experimentellen Teil kationische Block-Kopolymere präsentiert, welche in der Lage sind, negativ geladene Nukleinsäuremoleküle zu binden - wie etwa Plasmid Desoxyribonukleinsäure (pDNA) und kleine interferierende Ribonukleinsäuren (siRNA) - mit dem Ziel der Transfektion von fremder DNA in die Wirtszellen und damit der spezifischen Unterdrückung der Genexpression. Der erste Teil der experimentellen Arbeit untersucht die Transfektionseffizienz von zirkulärer gegenüber linearisierter Plasmid-DNA mittels eines Vektors, welcher ein grün fluoreszierendes Protein exprimiert. Transfiziert wurde einerseits mit Lipofectamine 2000 und andererseits mit linearem 25 kDa Polyethylenimin (PEI), zwei etablierten Transfektionsreagenzien. Die Ergebnisse zeigen eine wesentlich verbesserte Transfektionseffizienz der zirkulären, verglichen mit der linearisierten DNA für beide Transfektionsreagenzien. Die elektronenmikroskopischen Bilder von Lipofectamine sowie PEI komplexiert mit DNA zeigen, dass die zirkuläre DNA zufällige, kompakte Kugelformen bildet, während die linearisierte DNA wurmartige Stränge aufweist. Partikelgröße und -form spielen in der Zellbiologie eine wichtige Rolle bei der Endozytose und Phagozytose. Die Ergebnisse legen die Vermutung nahe dass die Form der zu transfizierenden DNA-Transfektions-Komplexen eine wichtige Rolle einnimmt für einen erfolgreichen Gentransfer. Für die Entwicklung eines intelligenten Wirkstoffabgabe-Systems für die Gentherapie wurden zwei kationische Diblock-Kopolymere, die aus primären und tertiären Aminen bestehen synthetisiert und im Hinblick auf deren DNA-Kondensationseigenschaften, Morphologie der kondensierten Plasmid-DNA sowie Transfektionseffizienz unter Verwendung von zwei Zelllinien analysiert. Die Studie bestätigt trotz einer um den Faktor 10 schwächeren Transfektionseffizienz der primären Amin-DiblockKopolymeren im Vergleich zu PEI nach 48 h mit zunehmender pDNA Konzentration eine Bestätigung des Konzepts. Außerdem weisen die primären Amin-Block- Kopolymere im Vergleich zu den tertiären eine viel stärkere Komplexbildung der DNA auf - wie transmissions-elektronen- und rasterkraft-mikroskopische Daten ergaben - als auch eine verbesserte Transfektionseffizienz. Diese physikalischmorphologischem Erkenntnisse über die Kondensation der primären und tertiären Amine mit Plasmid-DNA konnten mittels der biologischen Transfektionseffizienzdaten validiert werden. Der zweite Teil der experimentellen Arbeit befasst sich mit dem Design sowie der Charakterisierung von pentablock-basierten Polyplexen für einen gezielten siRNA Transport. Diese Polyplexe beruhen auf einer Kombination von kationischen Pentablock-Kopolymeren mit folsäure-funktionalisierten Kopolymeren. Die erreichten 31% Gen-Suppression in einem Krebszellkulturmodell, zeigen das Potenzial des Wirkstoffabgabesystems in Bezug auf eine Krebstherapie auf. Die Architektur ermöglicht die Bildung von sehr stabilen Mizellen mit einer Grösse von (21 ± 3) nm in 10 mM PBS Pufferlösung, eine neutrale Oberflächenladung, ausgezeichneten siRNAKondensationseigenschaften, hervorragender kolloidaler Stabilität in Zellkulturmedium supplementiert mit 10 % Serum über 24 h, sowie guter Biokompatibilität aufgrund fehlender erheblicher Zytotoxizität auch nach 48 h Inkubation in einem Zellkulturmodell. Ferner konnte durch die Einführung eines liganden-gebundenen Block-Kopolymers der selektive Transport der siRNA nachgewiesen werden, was zu einer Gen Suppression von 31% gegenüber 8% nicht funktionalisierter Polyplexen führte. Das in dieser Arbeit eingeführte und charakterisierte pentablock-basierte Wirkstoffabgabesystem könnte Auswirkungen auf das Design zukünftiger Wirkstoffabgabesystem haben als auch als eine potentielle Plattform für in vivo-Krebsgentherapien angewendet werden

    Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

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    Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin. © 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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