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MicroRNA e il recettore adenosinico A3 come biomarcatori del mesotelioma maligno della pleura
Background: Malignant pleural mesothelioma (MPM) is an aggressive asbestosrelated cancer that develops via mesothelial cell transformation. At present there are no effective therapies for MPM. Great efforts have been made in finding specific markers/mechanisms for MPM onset, including studies into microRNAs and adenosine receptors (ARs). Recent studies have shown the differential expression of mature microRNAs in several human cancers, suggesting their potential role as oncogenes or tumor suppressor genes, and the involvement of ARs in the regulation of cell death and proliferation. Methods: In this study, we investigated miRNAs profile and the expression of A3ARs in MPM. MiRNAs profile was investigated in 5 HMCs (human normal pleural mesothelial short term cell cultures) and 5 MPMs, with microarray approach. These results were confirmed by Real Time quantitative RT-PCR and western blotting. ARs were analyzed by using RT-PCR, western blotting and saturation binding assays. HMC were treated with crocidolite asbestos which is the principal risk factor of MM. The role of A3ARs on these cellular models, evaluating cAMP production, Akt phosphorylation and NF-kB activation was investigated. The dual effect of A3AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis and cytotoxicity assays. Results: A comparative analysis of miRNA expression in MPM and HMCs was carried out. Microarray profiling showed different miRNA expression between MPM and HMCs. Specifically, 13 miRNAs (17-5p, 18a, 19b, 20a, 20b, 25, 92, 106a, 106b), members of the oncomiRNA miR 17-92 and its paralogs were markedly dysregulated. Besides, in our investigation, additional miRNAs, such as miR-7, miR-182, miR-214 and miR-497 were found to be dysregulated in MPM. A3AR was up-regulated by 2.5 fold (P<0.01) in MMP when compared with HMP. Stimulation of A3ARs decreases proliferation and exerts cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and TNF-�, but not in HMC with an involvement of the de-regulation of Akt/NF-kB cell survival pathway. Conclusion: These data are in agreement with results which have previously been reported on dysregulated miRNAs for other solid human tumors. Moreover, in our investigation, additional miRNAs were found to be dysregulated in MPM. Interestingly, gene products which regulate the cell cycle are targets and predicted targets for these miRNAs. Our data suggest that specific miRNAs and A3ARs could be key players in MPM development/progression. In addition, some of these miRNAs may represent MPM markers and potential targets for new therapeutic approaches. Besides, our data suggest that A3AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full blown MPM.Background: Malignant pleural mesothelioma (MPM) is an aggressive asbestosrelated cancer that develops via mesothelial cell transformation. At present there are no effective therapies for MPM. Great efforts have been made in finding specific markers/mechanisms for MPM onset, including studies into microRNAs and adenosine receptors (ARs). Recent studies have shown the differential expression of mature microRNAs in several human cancers, suggesting their potential role as oncogenes or tumor suppressor genes, and the involvement of ARs in the regulation of cell death and proliferation. Methods: In this study, we investigated miRNAs profile and the expression of A3ARs in MPM. MiRNAs profile was investigated in 5 HMCs (human normal pleural mesothelial short term cell cultures) and 5 MPMs, with microarray approach. These results were confirmed by Real Time quantitative RT-PCR and western blotting. ARs were analyzed by using RT-PCR, western blotting and saturation binding assays. HMC were treated with crocidolite asbestos which is the principal risk factor of MM. The role of A3ARs on these cellular models, evaluating cAMP production, Akt phosphorylation and NF-kB activation was investigated. The dual effect of A3AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis and cytotoxicity assays. Results: A comparative analysis of miRNA expression in MPM and HMCs was carried out. Microarray profiling showed different miRNA expression between MPM and HMCs. Specifically, 13 miRNAs (17-5p, 18a, 19b, 20a, 20b, 25, 92, 106a, 106b), members of the oncomiRNA miR 17-92 and its paralogs were markedly dysregulated. Besides, in our investigation, additional miRNAs, such as miR-7, miR-182, miR-214 and miR-497 were found to be dysregulated in MPM. A3AR was up-regulated by 2.5 fold (P<0.01) in MMP when compared with HMP. Stimulation of A3ARs decreases proliferation and exerts cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and TNF-�, but not in HMC with an involvement of the de-regulation of Akt/NF-kB cell survival pathway. Conclusion: These data are in agreement with results which have previously been reported on dysregulated miRNAs for other solid human tumors. Moreover, in our investigation, additional miRNAs were found to be dysregulated in MPM. Interestingly, gene products which regulate the cell cycle are targets and predicted targets for these miRNAs. Our data suggest that specific miRNAs and A3ARs could be key players in MPM development/progression. In addition, some of these miRNAs may represent MPM markers and potential targets for new therapeutic approaches. Besides, our data suggest that A3AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full blown MPM
Non-invasive spectroscopic study of 19th century artists’ materials
In recent years, several studies have been conducted on 19th century works of art mainly from a cognitive or conservation point of view. Paintings of that period were usually made with new, as opposed to non traditional, pigments, a result of the fast development of chemical manufacturing processes. As a consequence, it can be particularly difficult to retrieve information needed to plan effective interventions for the proper conservation of these objects due to the lack of knowledge of the original materials used. The goal of this thesis is to provide information on 19th century painting materials, mainly pigments and dyes, through the spectroscopic study of works of art, by analysing laboratory mock-ups expressly prepared, and by analysing original pigments (in this specific case watercolours). The investigation of works of art and precious objects often present problems due to necessity of non destructive examination techniques. However, noninvasive analysis usually provides less information than that achievable by sampling. In order to improve the results obtainable with noninvasive investigations, a multidisciplinary approach based on the data\u27s complementarities must be developed. In this thesis, point by point spectroscopic information using Fibre Optics Reflectance Spectroscopy (FORS) was integrated with High Hyperspectral Image Spectroscopy (HHIS) and, in a few selected cases, X-ray Fluorescence (XRF) spectroscopy, to better frame the case studies.In recent years, several studies have been conducted on 19th century works of art mainly from a cognitive or conservation point of view. Paintings of that period were usually made with new, as opposed to non traditional, pigments, a result of the fast development of chemical manufacturing processes. As a consequence, it can be particularly difficult to retrieve information needed to plan effective interventions for the proper conservation of these objects due to the lack of knowledge of the original materials used. The goal of this thesis is to provide information on 19th century painting materials, mainly pigments and dyes, through the spectroscopic study of works of art, by analysing laboratory mock-ups expressly prepared, and by analysing original pigments (in this specific case watercolours). The investigation of works of art and precious objects often present problems due to necessity of non destructive examination techniques. However, noninvasive analysis usually provides less information than that achievable by sampling. In order to improve the results obtainable with noninvasive investigations, a multidisciplinary approach based on the data\u27s complementarities must be developed. In this thesis, point by point spectroscopic information using Fibre Optics Reflectance Spectroscopy (FORS) was integrated with High Hyperspectral Image Spectroscopy (HHIS) and, in a few selected cases, X-ray Fluorescence (XRF) spectroscopy, to better frame the case studies
Modified U1snRNAs as innovative therapeutic strategy for inherited coagulation factor deficiencies
The theoretical framework in which this study is framed concerns the internationalization of production dynamics of firms abroad. The international literature in this field argues that there is not a conventional definition nor a universally tested theory that can explain all forms of foreign-owned production (see, among others, Dunning, 1988b and 1993a, Ietto-Gillies, 2005 and 2007). In this complex context, a large amount of Italian literature has been published around the theoretical framework of internationalization of production of Italian companies abroad (Tattara, Corò and Volpe, 2006, Mariotti and Mutinelli, 2005, et.al.). Nevertheless, a limited number of quantitative studies are available about the topic of Italian firms “migration” in Romania - as a particular expression of productive internationalization of our companies in this Country (Majocchi, 2002, Unimpresa Romania, 2005 and Antenna Veneto Romania, 2005). Thus, in order to investigate it by an industrial policy perspective a multilevel modelling approach has been applied. In particular, a two level model has been used to determine the effects of Romanian regions (romanian judets) in which Italian manufacturing firms internationalized the production in 2009 on their industrial performance. Based on a business register-based survey a business register of the Italian business community in Romania has been created. The data on Italian manufacturing firms located in Romania in 2009 have been selected from this register. The dataset used for the analysis includes 796 cases of firms internationalized in Romania. Therefore, a two level model has been carried out in order to determine the effects of intra-industry characteristics of these firms (i.e. Firm size and Firm Industrial specialization) on their industrial performance in 2009 both at individual and area level. The model results have shown that: as the firms dimension increase they have to be extremely sensible in the choice of the romanian region in which they want to (de)localize the production. Furthermore, the choice of the romanian region of productive delocalization has to be chosen by firms according to their sectors of activity.The theoretical framework in which this study is framed concerns the internationalization of production dynamics of firms abroad. The international literature in this field argues that there is not a conventional definition nor a universally tested theory that can explain all forms of foreign-owned production (see, among others, Dunning, 1988b and 1993a, Ietto-Gillies, 2005 and 2007). In this complex context, a large amount of Italian literature has been published around the theoretical framework of internationalization of production of Italian companies abroad (Tattara, Corò and Volpe, 2006, Mariotti and Mutinelli, 2005, et.al.). Nevertheless, a limited number of quantitative studies are available about the topic of Italian firms “migration” in Romania - as a particular expression of productive internationalization of our companies in this Country (Majocchi, 2002, Unimpresa Romania, 2005 and Antenna Veneto Romania, 2005). Thus, in order to investigate it by an industrial policy perspective a multilevel modelling approach has been applied. In particular, a two level model has been used to determine the effects of Romanian regions (romanian judets) in which Italian manufacturing firms internationalized the production in 2009 on their industrial performance. Based on a business register-based survey a business register of the Italian business community in Romania has been created. The data on Italian manufacturing firms located in Romania in 2009 have been selected from this register. The dataset used for the analysis includes 796 cases of firms internationalized in Romania. Therefore, a two level model has been carried out in order to determine the effects of intra-industry characteristics of these firms (i.e. Firm size and Firm Industrial specialization) on their industrial performance in 2009 both at individual and area level. The model results have shown that: as the firms dimension increase they have to be extremely sensible in the choice of the romanian region in which they want to (de)localize the production. Furthermore, the choice of the romanian region of productive delocalization has to be chosen by firms according to their sectors of activity
...in ventos vita recessit": la Didone di Giovan Battista Giraldi Cinzio fra invenzione drammaturgica e progetto per la scena
On the basis of an innate predisposition to tragic reading, already well established by ancient and modern critics, we tried to identify in Virgil\u27s episode dedicated to Dido that dimension of accomplished pièce, so to speak, extrapolated from the context of narrative epic, through the reconstruction of the mantuan poet\u27s theatrical imaginary. From the evidence of a direct experience and a probable knowledge of contemporary performing arts practice, we have attempted the origins of virgilian "directing skills" that helped develop the myth sub species ragoediae, in terms of drama, vision and representation. Reflection on the generative nucleus of the legend\u27s tragic declination has been used as a path through which summarize the different forms of dramatization of the episode from the late antiquity and medieval experiences, to the exploit in the Renaissance that sees the synchronous and geographically transversal combination of different tragedies entitled to the queen of Carthage. Among the various possible outcomes in the theater of the XVI century we chose the tragic experience of Giovan Battista Giraldi Cinthio for his dramatic and scenic features and his ability to grasp the inherent theatricality of the virgilian narrative episode. Approaching to a deep investigation into Dido tragedy, it was established to propose a new edition, an interpretative one, using the only cinquecentina (posthumous) edited in 1583. Missing the manuscript and having no other prints but a recent diplomatic transcription made by the spanish scholar Irene Romera Pintor (Madrid, Editorial Complutense, 2008) – it has not been possible to proceed to the critical edition. The accurate reconstruction of the text is the essential link between the successive enlargements with which we attempted to outline the trends of giraldian culture, to see its applications in his theories of drama, on his theatrical project , and directly on the play. Starting from a contextual biography of the “uomo di teatro” with the purpose of evading the traditional and conventional literary measure and bring it instead to the socio-cultural complexity, to the conditions that have promoted, influenced and hindered his work, we attempted to probe the extended and expert performing practice of the ferrarese playwright, as well as his theoretical proposals, highlightened precisely through the connection with the dramatic production and with the "directing" practice. Giraldi\u27s Dido is not to be considered a mere deployment of compositional techniques, or even an erudite example set within a period of academic and theoretical debate about the nature of the tragic genre, but the result of many interests of its author. The critical line we chose aims to stress the dialectic between theory and representation practice, between tradition and innovation, between fidelity to the models and watchful eye on the contemporary world, taking into account the personality of Giraldi Cinthio and his material needs addressed to the scene. For this purpose we decided to use the scenic and dramaturgical analysis through which probe the interrelationship between text and theater practice. This method has therefore been carried out on a tripartite path: the reconstruction of detailed references to the virgilian source and to the literary tradition that has allowed us to understand the philological work with which the ancient myth has been written and bowed to the contemporary demands; the recognition of moral,ideological civil instances, that show how giraldian Dido is a snippet of the history of civilization of the Sixteenth century Ferrara; and finally the reconstuction of the game of similarities and transgressions between theoretical works and elements of the spectacular text by which we can let emerge some of the real substance of the textual structure\u27s scenic potential.On the basis of an innate predisposition to tragic reading, already well established by ancient and modern critics, we tried to identify in Virgil\u27s episode dedicated to Dido that dimension of accomplished pièce, so to speak, extrapolated from the context of narrative epic, through the reconstruction of the mantuan poet\u27s theatrical imaginary. From the evidence of a direct experience and a probable knowledge of contemporary performing arts practice, we have attempted the origins of virgilian "directing skills" that helped develop the myth sub species ragoediae, in terms of drama, vision and representation. Reflection on the generative nucleus of the legend\u27s tragic declination has been used as a path through which summarize the different forms of dramatization of the episode from the late antiquity and medieval experiences, to the exploit in the Renaissance that sees the synchronous and geographically transversal combination of different tragedies entitled to the queen of Carthage. Among the various possible outcomes in the theater of the XVI century we chose the tragic experience of Giovan Battista Giraldi Cinthio for his dramatic and scenic features and his ability to grasp the inherent theatricality of the virgilian narrative episode. Approaching to a deep investigation into Dido tragedy, it was established to propose a new edition, an interpretative one, using the only cinquecentina (posthumous) edited in 1583. Missing the manuscript and having no other prints but a recent diplomatic transcription made by the spanish scholar Irene Romera Pintor (Madrid, Editorial Complutense, 2008) – it has not been possible to proceed to the critical edition. The accurate reconstruction of the text is the essential link between the successive enlargements with which we attempted to outline the trends of giraldian culture, to see its applications in his theories of drama, on his theatrical project , and directly on the play. Starting from a contextual biography of the “uomo di teatro” with the purpose of evading the traditional and conventional literary measure and bring it instead to the socio-cultural complexity, to the conditions that have promoted, influenced and hindered his work, we attempted to probe the extended and expert performing practice of the ferrarese playwright, as well as his theoretical proposals, highlightened precisely through the connection with the dramatic production and with the "directing" practice. Giraldi\u27s Dido is not to be considered a mere deployment of compositional techniques, or even an erudite example set within a period of academic and theoretical debate about the nature of the tragic genre, but the result of many interests of its author. The critical line we chose aims to stress the dialectic between theory and representation practice, between tradition and innovation, between fidelity to the models and watchful eye on the contemporary world, taking into account the personality of Giraldi Cinthio and his material needs addressed to the scene. For this purpose we decided to use the scenic and dramaturgical analysis through which probe the interrelationship between text and theater practice. This method has therefore been carried out on a tripartite path: the reconstruction of detailed references to the virgilian source and to the literary tradition that has allowed us to understand the philological work with which the ancient myth has been written and bowed to the contemporary demands; the recognition of moral,ideological civil instances, that show how giraldian Dido is a snippet of the history of civilization of the Sixteenth century Ferrara; and finally the reconstuction of the game of similarities and transgressions between theoretical works and elements of the spectacular text by which we can let emerge some of the real substance of the textual structure\u27s scenic potential
‘Ululant more luporum’. Frank Perceptions of Other Christians’ Liturgies in Churches of the Holy Land
In this essay I will discuss how Frank pilgrims perceived Christian rites different from their own in the Fourteenth and Fifteenth centuries. Yet, it cannot escape us that the topic of relations between different creeds is much more complex than it seems, and is likewise highly relevant and strongly confrontational to this day, since still today many cultural stereotypes (often unknowingly) affect the interpretation of what is observed. To illustrate that point, I will borrow an example that may appear unrealistic but is instead a really occurred event: years ago, the US consul in Jerusalem received a call for help. An American woman, […] a devout Christian, called from a Palestinian village where her American church had sent her to help a parish. The poor woman was on the edge of a nervous breakdown. ‘I came to the Holy Land to help Christians!’ she shouted to the consul. As the diplomat didn’t seem to understand her distress, she continued more forcefully: ‘My church told me that I was going to work with Christians, and now instead I’m in a city of Arabs![1]’
[1] Lorieux (2001, I).In questo saggio discuterò di come i pellegrini franchi percepissero i riti cristiani diversi dai loro nei secoli XIV e XV. Tuttavia, non può sfuggirci che il tema dei rapporti tra fedi diverse è molto più complesso di quanto sembri, ed è ugualmente di grande attualità e fortemente conflittuale ancora oggi, poiché ancora oggi molti stereotipi culturali (spesso inconsapevolmente) influenzano l\u27interpretazione di ciò che si osserva. Per illustrare questo punto, prenderò in prestito un esempio che può sembrare irrealistico ma che è invece un evento realmente accaduto: anni fa, il console statunitense a Gerusalemme ricevette una richiesta di aiuto. Una donna americana, una devota cristiana, chiamava da un villaggio palestinese dove la sua chiesa americana l\u27aveva mandata per aiutare una parrocchia. La povera donna era sull\u27orlo di un esaurimento nervoso: “Sono venuta in Terra Santa per aiutare i cristiani!", gridò al console. Poiché il diplomatico non sembrava capire la sua angoscia, continuò con più forza: “La mia chiesa mi ha detto che avrei lavorato con i cristiani, e invece mi trovo in una città di arabi!”.[1]
[1] Lorieux (2001, I)
J.-C. Maire Vigueur, Attrazioni fatali. Una storia di donne e potere in una corte rinascimentale, Bologna, il Mulino, 2022, pp. 320
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Studio dei reperti dalla ricognizione della villa romana Bocca delle Menate (Comacchio-FE): i contenitori da trasporto e i laterizi bollati
More than 60 years after the discovery of the Roman villa of Bocca delle Menate in Comacchio (FE) (I-II century AD), the University of Ferrara has undertaken an archaeological survey on the site. Despite the Villa was buried after the discovery, from the ground are still emerging several findings. The aim of the archeological project was to verify the site preservation conditions on behalf of the VALUE-enVironmental and cuLtUral hEritage development project for the enhancement of the local archaeological sites. Implementing the previous studies of the archeological materials found in the 50s emergency excavations, the contribution analyzes the two most represented ceramic assemblages collected during the survey: transport containers and building materials. Despite the extremely fragmented state, the analyzed findings have returned numerous confirmations and new data. The focus of the presentation is on the production centers of amphorae and building materials to outline the territorial network, trade flows and local productive sources. The Adriatic productive centers are the most documented despite few containers from the Tyrrhenian side and from the provinces of the Mediterranean region are recorded. Brick stamps of minor private workshops within the well-known Pansiana and Solonas provide a new documentation of the villa’s local short and medium-range network, especially with the Regio VIII Aemilia and the Regio X Venetia et Histria.A più di 60 anni dalla scoperta della villa romana di Bocca delle Menate a Comacchio (FE) (I-II secolo d.C.), l\u27Università di Ferrara ha intrapreso un\u27indagine archeologica sul sito. Nonostante la villa sia stata interrata dopo la scoperta, dal terreno sono ancora emersi diversi reperti. L\u27obiettivo del progetto archeologico è stato quello di verificare le condizioni di conservazione del sito per conto del progetto di sviluppo VALUE-ambientale e cuLtUral hEritage per la valorizzazione dei siti archeologici locali. Implementando i precedenti studi sui materiali archeologici rinvenuti negli scavi di emergenza degli anni \u2750 del Novecento, il contributo analizza i due assemblaggi ceramici più rappresentati raccolti durante l\u27indagine: i contenitori da trasporto e i materiali da costruzione. Nonostante lo stato estremamente frammentario, i reperti analizzati hanno restituito numerose conferme e nuovi dati. La presentazione si concentra sui centri di produzione di anfore e materiali da costruzione per delineare la rete territoriale, i flussi commerciali e le fonti produttive locali. I centri produttivi adriatici sono i più documentati, nonostante si registrino pochi contenitori dal versante tirrenico e dalle province della regione mediterranea. I bolli laterizi di officine private minori all\u27interno delle note Pansiana e Solonas forniscono una nuova documentazione della rete locale a breve e medio raggio della villa, soprattutto con la Regio VIII Aemilia e la Regio X Venetia et Histria
Introduzione al concetto di probabilità nella scuola secondaria superiore
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We present an approach to the probability concept, based on a sequence of problems, with the aim to promote probabilistic thinking and not deterministic reasoning that are fundamental to an understanding of probability.
Si presenta un approccio al concetto di probabilità, basato su di una sequenza di problemi che hanno lo scopo di promuovere il pensiero probabilistico ed il ragionamento non deterministico, fondamentali per la comprensione della probabilità
Processi di generalizzazione nell’insegnamento-apprendimento dell’algebra
This paper deals with the question of generalization in the teaching and learning of mathematics. In particular, a few theoretical works on generalisation processes in the field of algebra are introduced, after which some studies concerning the students’ behaviour and the role of the teacher in dealing with the exploration of figural sequences are analysed and theorized. The need for an adequate teachers’ education in the teaching of this kind of task is stressed.In questo lavoro è affrontato il tema della generalizzazione nell’insegnamento e apprendimento della matematica. In particolare, si introducono dapprima alcuni studi teorici sui processi di generalizzazione in campo algebrico. Sono quindi considerati alcuni studi in cui sono analizzati e teorizzati i comportamenti degli studenti nella esplorazione di successioni figurali, richiamando brevemente il ruolo dell’insegnante e sottolineando la necessità di una sua adeguata preparazione.