Studio di un nuovo processo per la sintesi di acido adipico.

Obiettivo del mio lavoro di tesi è stato quello di verificare la fattibilità di un nuovo processo per la produzione di acido adipico da cicloesene con due stadi di reazione. Il primo stadio di reazione prevede l’ossidazione del cicloesene con soluzione acquosa di acqua ossigenata a formare l’epossido, che idrata a 1,2-cicloesandiolo, mentre nel secondo stadio il glicole viene ossidato con ossigeno ad acido adipico. Il lavoro è stato focalizzato sullo studio del meccanismo di reazione per l’ossidazione del 1,2-cicloesandiolo ad acido adipico, utilizzando catalizzatori a base di Ru(OH)3/Al2O3, Ru(OH)3-Bi(OH)3/Al2O3, Cu/C e Cu/TiO2. Le prove condotte hanno dimostrato che i catalizzatori usati sono attivi nell’ossidazione di 1,2-cicloesandiolo, ma sono caratterizzati da scarsa selettività ad acido adipico. Dall’analisi dei risultati ottenuti si desume che la reazione richiede condizioni fortemente basiche per potere avvenire. In queste condizioni però si vengono a formare degli intermedi che reagiscono rapidamente con l’acqua e con l’ossigeno, dando luogo alla formazione di una serie di prodotti primari e secondari.

Valutazione del danno da stress ossidativo come indicatore di effetto biologico dell'esposizione professionale a xenobiotici

Oxidative DNA damages determine the activation of cell repair processes. These processes originate repair products, including the most studied one, 8-hydroxy-2’-deoxyguanosine (8-OH-dG). Several analytical techniques have been applied to measure urinary 8-OH-dG, but a discrepancy in basal urinary 8-OH-dG levels has been noted when comparing chromatographic techniques with immunoenzymatic assays (ELISA). Our laboratory has developed a fully validated, liquid chromatography-tandem mass spectrometry method presenting high sensitivity and specificity, which has participated in an inter-laboratory validation of assays for the measurement of urinary 8-OH-dG (ESCULA project). Mass Spectrometric techniques showed more accuracy and specificity than immunoenzymatic methods. Human spot urine samples were analyzed in order to investigate the possibility to correct urinary lesion measurements for creatinine and to evaluate the intra- and inter-day variability of 8-OH-dG excretion in urine. Our results confirm the opportunity to delve into these issues. Finally, we measured urinary 8-OH-dG in workers exposed to antineoplastic drugs and in a group of unexposed subjects to evaluate the relationship between occupational exposure and oxidative damage related to the internal dose. We found higher levels of 8-OH-dG in exposed nurses, but, as compared to the non-exposed subjects, the difference was not statistically significant, probably do to the very low level of exposure. The scientific literature is rapidly developing on the topic of DNA damage and related repair capacity. Nevertheless, further studies are needed to achieve a better understanding of the sources of DNA lesions in urine and their significance, both in clinical and occupational medicine.

Il ruolo delle idee e del loro cambiamento nei processi di policy making universitario nel mondo anglosassone dagli anni ottanta ad oggi. I casi di Inghilterra e Nuova Zelanda in prospettiva comparata

THE TITLE OF MY THESIS IS THE ROLE OF THE IDEAS AND THEIR CHANGE IN HIGHER EDUCATION POLICY-MAKING PROCESSES FROM THE EIGHTIES TO PRESENT-DAY: THE CASES OF ENGLAND AND NEW ZEALAND IN COMPARATIVE PERSPECTIVE UNDER A THEORETICAL POINT OF VIEW, THE AIM OF MY WORK IS TO CARRY OUT A RESEARCH MODELLED ON THE CONSTRUCTIVIST THEORY. IT FOCUSES ON THE ANALYSIS OF THE IMPACT OF IDEAS ON THE PROCESSES OF POLICY MAKING BY MEANS OF EPISTEMIC COMMUNITIES, THINK TANKS AND VARIOUS SOCIOECONOMIC CONTEXTS THAT MAY HAVE PLAYED A KEY ROLE IN THE CONSTRUCTION OF THE DIFFERENT PATHS. FROM MY POINT OF VIEW IDEAS CONSTITUTE A PRIORITY RESEARCH FIELD WHICH IS WORTH ANALYSING SINCE THEIR ROLE IN POLICY MAKING PROCESSES HAS BEEN TRADITIONALLY RATHER UNEXPLORED. IN THIS CONTEXT AND WITH THE AIM OF DEVELOPING A RESEARCH STRAND BASED ON THE ROLE OF IDEAS, I INTEND TO CARRY ON MY STUDY UNDER THE PERSPECTIVE OF CHANGE. DEPENDING ON THE DATA AND INFORMATION THAT I COLLECTED I EVALUATED THE WEIGHT OF EACH OF THESE VARIABLES AND MAYBE OTHERS SUCH AS THE INSTITUTIONS AND THE INDIVIDUAL INTERESTS, WHICH MAY HAVE INFLUENCED THE FORMATION OF THE POLICY MAKING PROCESSES. UNDER THIS LIGHT, I PLANNED TO ADOPT THE QUALITATIVE METHODOLOGY OF RESEARCH WHICH I BELIEVE TO BE VERY EFFECTIVE AGAINST THE MORE DIFFICULT AND POSSIBLY REDUCTIVE APPLICATION OF QUANTITIVE DATA SETS. I RECKON THEREFORE THAT THE MOST APPROPRIATE TOOLS FOR INFORMATION PROCESSING INCLUDE CONTENT ANALYSIS, AND IN-DEPTH INTERVIEWS TO PERSONALITIES OF THE POLITICAL PANORAMA (ÉLITE OR NOT) WHO HAVE PARTICIPATED IN THE PROCESS OF HIGHER EDUCATION REFORM FROM THE EIGHTIES TO PRESENT-DAY. THE TWO CASES TAKEN INTO CONSIDERATION SURELY SET AN EXAMPLE OF RADICAL REFORM PROCESSES WHICH HAVE OCCURRED IN QUITE DIFFERENT CONTEXTS DETERMINED BY THE SOCIOECONOMIC CHARACTERISTICS AND THE TRAITS OF THE ÉLITE. IN NEW ZEALAND THE DESCRIBED PROCESS HAS TAKEN PLACE WITH A STEADY PACE AND A GOOD GRADE OF CONSEQUANTIALITY, IN LINE WTH THE REFORMS IN OTHER STATE DIVISIONS DRIVEN BY THE IDEAS OF THE NEW PUBLIC MANAGEMENT. CONTRARILY IN ENGLAND THE REFORMATIVE ACTION OF MARGARET THATCHER HAS ACQUIRED A VERY RADICAL CONNOTATION AS IT HAS BROUGHT INTO THE AMBIT OF HIGHER EDUCATION POLICY CONCEPTS LIKE EFFICIENCY, EXCELLENCE, RATIONALIZATION THAT WOULD CONTRAST WITH THE GENERALISTIC AND MASS-ORIENTED IDEAS THAT WERE FASHIONABLE DURING THE SEVENTIES. THE MISSION I INTEND TO ACCOMPLISH THORUGHOUT MY RESEARCH IS TO INVESTIGATE AND ANALYSE INTO MORE DEPTH THE DIFFERENCES THAT SEEM TO EMERGE FROM TWO CONTEXTS WHICH MOST OF THE LITERATURE REGARDS AS A SINGLE MODEL: THE ANGLO-SAXON MODEL. UNDER THIS LIGHT, THE DENSE ANALYSIS OF POLICY PROCESSES ALLOWED TO BRING OUT BOTH THE CONTROVERSIAL AND CONTRASTING ASPECTS OF THE TWO REALITIES COMPARED, AND THE ROLE AND WEIGHT OF VARIABLES SUCH AS IDEAS (MAIN VARIABLE), INSTITUTIONAL SETTINGS AND INDIVIDUAL INTERESTS ACTING IN EACH CONTEXT. THE CASES I MEAN TO ATTEND PRESENT PECULIAR ASPECTS WORTH DEVELOPING AN IN-DEPTH ANALYSIS, AN OUTLINE OF WHICH WILL BE PROVIDED IN THIS ABSTRACT. ENGLAND THE CONSERVATIVE GOVERNMENT, SINCE 1981, INTRODUCED RADICAL CHANGES IN THE SECTOR OF HIGHER EDUCATION: FIRST CUTTING DOWN ON STATE FUNDINGS AND THEN WITH THE CREATION OF AN INSTITUTION FOR THE PLANNING AND LEADERSHIP OF THE POLYTECHNICS (NON-UNIVERSITY SECTOR). AFTERWARDS THE SCHOOL REFORM BY MARGARET THATCHER IN 1988 RAISED TO A GREAT STIR ALL OVER EUROPE DUE TO BOTH ITS CONSIDERABLE INNOVATIVE IMPRINT AND THE STRONG ATTACK AGAINST THE PEDAGOGY OF THE ‘ACTIVE’ SCHOOLING AND PROGRESSIVE EDUCATION, UNTIL THEN RECOGNIZED AS A MERIT OF THE BRITISH PUBLIC SCHOOL. IN THE AMBIT OF UNIVERSITY EDUCATION THIS REFORM, TOGETHER WITH SIMILAR MEASURES BROUGHT IN DURING 1992, PUT INTO PRACTICE THE CONSERVATIVE PRINCIPLES THROUGH A SERIES OF ACTIONS THAT INCLUDED: THE SUPPRESSION OF THE IRREMOVABILITY PRINCIPLE FOR UNIVERSITY TEACHERS; THE INTRODUCTION OF STUDENT LOANS FOR LOW-INCOME STUDENTS AND THE CANCELLATION OF THE CLEAR DISTINCTION BETWEEN UNIVERSITIES AND POLYTECHNICS. THE POLICIES OF THE LABOUR MAJORITY OF MR BLAIR DID NOT QUITE DIVERGE FROM THE CONSERVATIVES’ POSITION. IN 2003 BLAIR’S CABINET RISKED TO BECOME A MINORITY RIGHT ON THE OCCASION OF AN IMPORTANT UNIVERSITY REFORM PROPOSAL. THIS PROPOSAL WOULD FORESEE THE AUTONOMY FOR THE UNIVERSITIES TO RAISE UP TO 3.000 POUNDS THE ENROLMENT FEES FOR STUDENTS (WHILE FORMERLY THE CEILING WAS 1.125 POUNDS). BLAIR HAD TO FACE INTERNAL OPPOSITION WITHIN HIS OWN PARTY IN RELATION TO A MEASURE THAT, ACCORDING TO THE 150 MPS PROMOTERS OF AN ADVERSE MOTION, HAD NOT BEEN INCLUDED IN THE ELECTORAL PROGRAMME AND WOULD RISK CREATING INCOME-BASED DISCRIMINATION AMONG STUDENTS. AS A MATTER OF FACT THE BILL FOCUSED ON THE INTRODUCTION OF VERY LOW-INTEREST STUDENT LOANS TO BE SETTLED ONLY WHEN THE STUDENT WOULD HAVE FOUND A REMUNERATED OCCUPATION (A SYSTEM ALREADY PROVIDED FOR BY THE AUSTRALIAN LEGISLATION). NEW ZEALAND CONTRARILY TO MANY OTHER COUNTRIES, NEW ZEALAND HAS ADOPTED A VERY WIDE VISION OF THE TERTIARY EDUCATION. IT INCLUDES IN FACT THE FULL EDUCATIONAL PROGRAMME THAT IS INTERNATIONALLY RECOGNIZED AS THE POST-SECONDARY EDUCATION. SHOULD WE SPOTLIGHT A PECULIARITY OF THE NEW ZEALAND TERTIARY EDUCATION POLICY THEN IT WOULD BE ‘CHANGE’. LOOKING AT THE REFORM HISTORY RELATED TO THE TERTIARY EDUCATION SYSTEM, WE CAN CLEARLY IDENTIFY FOUR ‘SUB-PERIODS’ FROM THE EIGHTIES TO PRESENT-DAY: 1. BEFORE THE 80S’: AN ELITARIAN SYSTEM CHARACTERIZED BY LOW PARTICIPATION RATES. 2. BETWEEN MID AND LATE 80S’: A TREND TOWARDS THE ENLARGEMENT OF PARTICIPATION ASSOCIATED TO A GREATER COMPETITION. 3. 1990-1999: A FUTHER STEP TOWARDS A COMPETITIVE MODEL BASED ON THE MARKET-ORIENTED SYSTEM. 4. FROM 2000 TO TODAY: A CONTINUOUS EVOLUTION TOWARDS A MORE COMPETITIVE MODEL BASED ON THE MARKET-ORIENTED SYSTEM TOGETHER WITH A GROWING ATTENTION TO STATE CONTROL FOR SOCIAL AND ECONOMIC DEVELOPMENT OF THE NATION. AT PRESENT THE GOVERNMENT OF NEW ZEALAND OPERATES TO STRENGHTHEN THIS PROCESS, PRIMARILY IN RELATION TO THE ROLE OF TERTIARY EDUCATION AS A STEADY FACTOR OF NATIONAL WALFARE, WHERE PROFESSIONAL DEVELOPMENT CONTRIBUTES ACTIVELY TO THE GROWTH OF THE NATIONAL ECONOMIC SYSTEM5. THE CASES OF ENGLAND AND NEW ZEALAND ARE THE FOCUS OF AN IN-DEPTH INVESTIGATION THAT STARTS FROM AN ANALYSIS OF THE POLICIES OF EACH NATION AND DEVELOP INTO A COMPARATIVE STUDY. AT THIS POINT I ATTEMPT TO DRAW SOME PRELIMINARY IMPRESSIONS ON THE FACTS ESSENTIALLY DECRIBED ABOVE. THE UNIVERSITY POLICIES IN ENGLAND AND NEW ZEALAND HAVE BOTH UNDERGONE A SIGNIFICANT REFORMATORY PROCESS SINCE THE EARLY EIGHTIES; IN BOTH CONTEXTS THE IMPORTANCE OF IDEAS THAT CONSTITUTED THE BASE OF POLITICS UNTIL 1980 WAS QUITE RELEVANT. GENERALLY SPEAKING, IN BOTH CASES THE PRE-REFORM POLICIES WERE INSPIRED BY EGALITARIANISM AND EXPANSION OF THE STUDENT POPULATION WHILE THOSE BROUGHT IN BY THE REFORM WOULD PURSUE EFFICIENCY, QUALITY AND COMPETITIVENESS. UNDOUBTEDLY, IN LINE WITH THIS GENERAL TENDENCY THAT REFLECTS THE HYPOTHESIS PROPOSED, THE TWO UNIVERSITY SYSTEMS PRESENT SEVERAL DIFFERENCES. THE UNIVERSITY SYSTEM IN NEW ZEALAND PROCEEDED STEADILY TOWARDS THE IMPLEMENTATION OF A MANAGERIAL CONCEPTION OF TERTIARY EDUCATION, ESPECIALLY FROM 1996 ONWARDS, IN ACCORDANCE WITH THE REFORMATORY PROCESS OF THE WHOLE PUBLIC SECTOR. IN THE UNITED KINGDOM, AS IN THE REST OF EUROPE, THE NEW APPROACH TO UNIVERSITY POLICY-MAKING HAD TO CONFRONT A DEEP-ROOTED TRADITION OF PROGRESSIVE EDUCATION AND THE IDEA OF EDUCATION EXPANSION THAT IN FACT DOMINATED UNTIL THE EIGHTIES. FROM THIS VIEW POINT THE GOVERNING ACTION OF MARGARET THATCHER GAVE RISE TO A RADICAL CHANGE THAT REVOLUTIONIZED THE OBJECTIVES AND KEY VALUES OF THE WHOLE EDUCATIONAL SYSTEM, IN PARTICULAR IN THE HIGHER EDUCATION SECTOR. IDEAS AS EFFICIENCY, EXCELLENCE AND CONTROL OF THE PERFORMANCE BECAME DECISIVE. THE LABOUR CABINETS OF BLAIR DEVELOPED IN THE WAKE OF CONSERVATIVE REFORMS. THIS APPEARS TO BE A FOCAL POINT OF THIS STUDY THAT OBSERVES HOW ALSO IN NEW ZEALAND THE REFORMING PROCESS OCCURRED TRANSVERSELY DURING PROGRESSIVE AND CONSERVATIVE ADMINISTRATIONS. THE PRELIMINARY IMPRESSION IS THEREFORE THAT IDEAS DEEPLY MARK THE REFORMATIVE PROCESSES: THE AIM OF MY RESEARCH IS TO VERIFY TO WHICH EXTENT THIS STATEMENT IS TRUE. IN ORDER TO BUILD A COMPREHENSIVE ANALYLIS, FURTHER SIGNIFICANT FACTORS WILL HAVE TO BE INVESTIGATED: THE WAY IDEAS ARE PERCEIVED AND IMPLEMENTED BY THE DIFFERENT POLITICAL ELITES; HOW THE VARIOUS SOCIOECONOMIC CONTEXTS INFLUENCE THE REFORMATIVE PROCESS; HOW THE INSTITUTIONAL STRUCTURES CONDITION THE POLICY-MAKING PROCESSES; WHETHER INDIVIDUAL INTERESTS PLAY A ROLE AND, IF YES, TO WHICH EXTENT.

Studio di fenomeni d'instabilità gravitativa sui fondali marini, con particolare riferimento all'isola di Stromboli

In the last decade the interest for submarine instability grew up, driven by the increasing exploitation of natural resources (primary hydrocarbons), the emplacement of bottom-lying structures (cables and pipelines) and by the development of coastal areas, whose infrastructures increasingly protrude to the sea. The great interest for this topic promoted a number of international projects such as: STEAM (Sediment Transport on European Atlantic Margins, 93-96), ENAM II (European North Atlantic Margin, 96-99), GITEC (Genesis and Impact of Tsunamis on the European Coast 92-95), STRATAFORM (STRATA FORmation on Margins, 95-01), Seabed Slope Process in Deep Water Continental Margin (Northwest Gulf of Mexico, 96-04), COSTA (Continental slope Stability, 00-05), EUROMARGINS (Slope Stability on Europe’s Passive Continental Margin), SPACOMA (04-07), EUROSTRATAFORM (European Margin Strata Formation), NGI's internal project SIP-8 (Offshore Geohazards), IGCP-511: Submarine Mass Movements and Their Consequences (05-09) and projects indirectly related to instability processes, such as TRANSFER (Tsunami Risk ANd Strategies For the European region, 06-09) or NEAREST (integrated observations from NEAR shore sourcES of Tsunamis: towards an early warning system, 06-09). In Italy, apart from a national project realized within the activities of the National Group of Volcanology during the framework 2000-2003 “Conoscenza delle parti sommerse dei vulcani italiani e valutazione del potenziale rischio vulcanico”, the study of submarine mass-movement has been underestimated until the occurrence of the landslide-tsunami events that affected Stromboli on December 30, 2002. This event made the Italian Institutions and the scientific community more aware of the hazard related to submarine landslides, mainly in light of the growing anthropization of coastal sectors, that increases the vulnerability of these areas to the consequences of such processes. In this regard, two important national projects have been recently funded in order to study coastal instabilities (PRIN 24, 06-08) and to map the main submarine hazard features on continental shelves and upper slopes around the most part of Italian coast (MaGIC Project). The study realized in this Thesis is addressed to the understanding of these processes, with particular reference to Stromboli submerged flanks. These latter represent a natural laboratory in this regard, as several kind of instability phenomena are present on the submerged flanks, affecting about 90% of the entire submerged areal and often (strongly) influencing the morphological evolution of subaerial slopes, as witnessed by the event occurred on 30 December 2002. Furthermore, each phenomenon is characterized by different pre-failure, failure and post-failure mechanisms, ranging from rock-falls, to turbidity currents up to catastrophic sector collapses. The Thesis is divided into three introductive chapters, regarding a brief review of submarine instability phenomena and related hazard (cap. 1), a “bird’s-eye” view on methodologies and available dataset (cap. 2) and a short introduction on the evolution and the morpho-structural setting of the Stromboli edifice (cap. 3). This latter seems to play a major role in the development of largescale sector collapses at Stromboli, as they occurred perpendicular to the orientation of the main volcanic rift axis (oriented in NE-SW direction). The characterization of these events and their relationships with successive erosive-depositional processes represents the main focus of cap.4 (Offshore evidence of large-scale lateral collapses on the eastern flank of Stromboli, Italy, due to structurally-controlled, bilateral flank instability) and cap. 5 (Lateral collapses and active sedimentary processes on the North-western flank of Stromboli Volcano), represented by articles accepted for publication on international papers (Marine Geology). Moreover, these studies highlight the hazard related to these catastrophic events; several calamities (with more than 40000 casualties only in the last two century) have been, in fact, the direct or indirect result of landslides affecting volcanic flanks, as observed at Oshima-Oshima (1741) and Unzen Volcano (1792) in Japan (Satake&Kato, 2001; Brantley&Scott, 1993), Krakatau (1883) in Indonesia (Self&Rampino, 1981), Ritter Island (1888), Sissano in Papua New Guinea (Ward& Day, 2003; Johnson, 1987; Tappin et al., 2001) and Mt St. Augustine (1883) in Alaska (Beget& Kienle, 1992). Flank landslide are also recognized as the most important and efficient mass-wasting process on volcanoes, contributing to the development of the edifices by widening their base and to the growth of a volcaniclastic apron at the foot of a volcano; a number of small and medium-scale erosive processes are also responsible for the carving of Stromboli submarine flanks and the transport of debris towards the deeper areas. The characterization of features associated to these processes is the main focus of cap. 6; it is also important to highlight that some small-scale events are able to create damage to coastal areas, as also witnessed by recent events of Gioia Tauro 1978, Nizza, 1979 and Stromboli 2002. The hazard potential related to these phenomena is, in fact, very high, as they commonly occur at higher frequency with respect to large-scale collapses, therefore being more significant in terms of human timescales. In the last chapter (cap. 7), a brief review and discussion of instability processes identified on Stromboli submerged flanks is presented; they are also compared with respect to analogous processes recognized in other submerged areas in order to shed lights on the main factors involved in their development. Finally, some applications of multibeam data to assess the hazard related to these phenomena are also discussed.

Carl Gustav Jung a Eranos. Il contributo junghiano al Circolo di Eranos: ideazione, contributi e iniziative dal 1933 al 1952

The dissertation aims to explore the several forms in which the activity of the Swiss psychologist, Carl Gustav Jung (1875-1961) developed on the project and the realisation of the Eranos Conferences, founded in 1933 by Olga Fröbe-Kapteyn (1881-1962). The dissertation, in particular, focuses on the first twenty-year period (1933-1952) that determined the fundamental aspects and shaped the peculiar configuration of the Eranos Conferences as a “research laboratory” on the universal characteristics of the religious phenomenon. The dissertation contains the following chapters: 1) Aspects of C.G. Jung’s intellectual contribution to the religious hermeneutics proposed in the Eranos Conferences; 2) C.G. Jung’s conferences at Eranos: a historical examination; 3) C.G. Jung and the Eranos Archive for Research in Symbolism; 4) C.G. Jung and the hidden history of Eranos; 5) C.G. Jung’s commentary on Opicinus de Canistris’s Codex Palatinus Latinus 1993: fragments of a lost and rediscovered Eranos seminar.

Analisi della risposta dinamica di opere di protezione dalla caduta massi nella provincia autonoma di Bolzano

Nel contesto della progettazione di interventi di difesa da frane di crollo, la tesi è rivolta allo studio del comportamento di opere di protezione dalla caduta massi, con particolare riguardo alle barriere paramassi, strutture metalliche progettate per arrestare blocchi in caduta lungo un versante. Specificamente, il comportamento altamente non lineare di queste strutture è stato osservato mediante modellazione numerica agli elementi finiti con codice di calcolo STRAUS 7 v.2.3.3. La formulazione dei modelli è stata sviluppata a partire dai dati contenuti nel Catasto delle opere di protezione (VISO), recentemente messo a punto dalla Provincia Autonoma di Bolzano, nel contesto di una più ampia procedura di analisi della pericolosità di versante in presenza di opere di protezione, finalizzata ad una appropriata gestione del rischio indotto da frane di crollo. Sono stati messi a punto una serie di modelli agli elementi finiti di alcune tra le tipologie più ricorrenti di barriere paramassi a limitata deformabilità. Questi modelli, sottoposti ad una serie di analisi dinamiche e non-lineari, intese a simulare l’impatto di blocchi aventi massa e velocità nota, hanno permesso di osservare la risposta complessiva di queste strutture in regime dinamico identificando i meccanismi di rottura a partire dall’osservazione della formazione di cerniere plastiche, monitorando contestualmente grandezze rilevanti quali gli spostamenti e le forze mobilitate in fondazione. Questi dati, opportunamente interpretati, possono fornire i parametri necessari all’implementazione di più ampie procedure di analisi del rischio indotto da movimenti frane di crollo.

Studio della trasduzione del Segnale Nucleare Inositide-Dipendente: identificazione di eEF1A2 come nuovo Fosfosubstrato di PKC βI

Introduction Phospholipase Cb1 (PLC-β1) is a key player in the regulation of nuclear inositol lipid signaling and of a wide range of cellular functions, such as proliferation and differentiation (1,2,3). PLCb1 signaling depends on the cleavage of phosphatidylinositol 4,5-bisphosphate and the formation of the second messengers diacylglycerol and Inositol tris-phosphate which activate canonical protein kinase C (cPKC) isoforms. Here we describe a proteomic approach to find out a potential effector of nuclear PLC-b1 dependent signaling during insulin stimulated myogenic differentiation. Methods Nuclear lysates obtained from insulin induced C2C12 myoblasts were immunoprecipitated with anti-phospho-substrate cPKC antibody. Proteins, stained with Comassie blue, were excised, digested and subsequently analysed in LC-MS/MS. For peptide sequence searching, the mass spectra were processed and analyzed using the Mascot MS/MS ion search program with the NCBI database. Western blotting, GST-pull down and co-immunoprecipitation were performed to study the interaction between eEF1A2 and cPKCs. Site direct mutagenesis was performed to confirm the phosphorylated motif recognized by the antibody. Immunofluorescence analysis, GFP-tagged eEF1A2 vector and subcellular fractionation were performed to study nuclear localization and relative distribution of eEF1A2. Results We have previously shown that PLC-β1 is greatly increased at the nuclear level during insulin-induced myoblasts differentiation and that this nuclear localization is essential for induction of differentiation. Thus, nuclear proteins of insulin stimulated C2C12 myoblasts, were immunoprecipitated with an anti-phospho-substrate cPKC antibody. After Electrophoretic gel separation of proteins immunoprecipitated, several molecules were identified by LC-MS/MS. Among these most relevant and unexpected was eukaryotic elongation factor 1 alpha 2 (eEF1A2). We found that eEF1A2 is phosphorylated by PKCb1 and that these two molecules coimmunolocalized at the nucleolar level. eEF1A2 could be phosphorylated in many sites among which both threonine and serine residues. By site direct mutagenesis we demonstrated that it is the serine residue of the motif recognized by the antibody that is specifically phosphorylated by PKCb1. The silencing of PLCb1 gives rise to a reduction of expression and phosphorylation levels of eEF1A2 indicating this molecule as a target of nuclear PLCb1 regulatory network during myoblasts differentiation.

Contributo di un software di quantificazione del segnale contrastografico(SonoLiver®) nella diagnosi ecografica di Epatocarcinoma su Cirrosi.

Introduzione La diagnosi di HCC con le tecniche di immagine ed in particolare con CEUS su fegato cirrotico secondo le ultime linee guida prevede un comportamento contrastografico di ipervascolarizzazione nella fase arteriosa e wash-out nella fase tardiva. CEUS è ormai una metodica accettata per la diagnosi ma il wash out nella fase tardiva presenta notevoli difficoltà nel determinare il comportamento contrastografico in quanto valutato soggettivamente su display, infatti il giudizio di tale fase dipende molto dall’operatore e non è rarissimo che nascono discordanza tra operatori anche per piccole differenze. Recentemente è stato proposto un nuovo software(SonoLiver, Bracco, Italy) in grado di quantificare la perfusione delle lesione durante CEUS. Pertanto lo scopo di questo studio pilota è quello di valutare l’impatto di SonoLiver nel rilevare caratteristiche contrastografiche tipiche dell’HCC e valutare la riproducibilità tra due operatori. Pazienti e metodi: Sono stati presi in considerazione 20 noduli (di dimensioni tra 12-95 mm) con diagnosi di HCC in 20 pazienti con cirrosi . La CEUS è stata valutata dapprima ad occhio nudo su display e successivamente con le curve ottenute con DVP da parte di due operatori diversi in cieco, dopo un periodo di formazione adeguata. Sono state quindi analizzate le performance di ciascuna metodica sia in termini di variabilità tra i due operatori che la variabilità tra CEUS ad occhio nudo e CEUS con SonoLiver dello stesso operatore. Risultati:Operatore 1 ha rilevato ipervascolarizzazione in fase arteriosa in 17 su 20 pazienti con valutazione ad occhio nudo su schermo e su 19/20 con le curve ottenute con DVP (+10% sensibilità) mentre operatore 2 ha rilevato ipervascolarizzazione in fase arteriosa19/20 pazienti sia con valutazione ad occhio nudo che con le curve DVP. Nella fase tardiva il wash-out è stato rilevato in 7/20 ad occhio nudo e 10/20 pazienti con le curve DVP (sensibilità aumenta da 35% a 50%) mentre operatore 2 ha rilevato rispettivamente 8/20 e 11/20 (sensibilità aumenta da 40% a 55%). La riproducibilità tra i due operatori rimane invariata con la valutazione di Sonoliver sia nella fase arteriosa che nella fase tardiva. Conclusione:La quantificazione perfusionale con SonoLiver sembra essere uno strumento promettente nella diagnosi di HCC su fegato cirrotico, aumentando aspetti tipici contrastografici.

Evidenze micropaleontologiche e sedimentologiche di cicli deposizionali e climatici circa millenari nei Depositi Tardoquaternari della Piana dell'Arno e del Delta del Po

A multidisciplinary study was carried out on the Late Quaternary-Holocene subsurface deposits of two Mediterranean coastal areas: Arno coastal plain (Northern Tyrrhenian Sea) and Modern Po Delta (Northern Adriatic Sea). Detailed facies analyses, including sedimentological and micropalaeontological (benthic foraminifers and ostracods) investigations, were performed on nine continuously-cored boreholes of variable depth (ca. from 30 meters to100 meters). Six cores were located in the Arno coastal plain and three cores in the Modern Po Delta. To provide an accurate chronological framework, twenty-four organic-rich samples were collected along the fossil successions for radiocarbon dating (AMS 14C). In order to reconstruct the depositional and palaeoenvironmental evolution of the study areas, core data were combined with selected well logs, provided by local companies, along several stratigraphic sections. These sections revealed the presence of a transgressive-regressive (T-R) sequence, composing of continental, coastal and shallow-marine deposits dated to the Late Pleistocene-Holocene period, beneath the Arno coastal plain and the Modern Po Delta. Above the alluvial deposits attributed to the last glacial period, the post-glacial transgressive succession (TST) consists of back-barrier, transgressive barrier and inner shelf deposits. Peak of transgression (MFS) took place around the Late-Middle Holocene transition and was identified by subtle micropalaeontological indicators within undifferentiated fine-grained deposits. Upward a thick prograding succession (HST) records the turnaround to regressive conditions that led to a rapid delta progradation in both study areas. Particularly, the outbuilding of modern-age Po Delta coincides with mud-belt formation during the late HST (ca. 600 cal yr BP), as evidenced by a fossil microfauna similar to the foraminiferal assemblage observed in the present Northern Adriatic mud-belt. A complex interaction between allocyclic and autocyclic factors controlled facies evolution during the highstand period. The presence of local parameters and the absence of a predominant factor prevent from discerning or quantifying consequences of the complex relationships between climate and deltaic evolution. On the contrary transgressive sedimentation seems to be mainly controlled by two allocyclic key factors, sea-level rise and climate variability, that minimized the effects of local parameters on coastal palaeoenvironments. TST depositional architecture recorded in both study areas reflects a well-known millennial-scale variability of sea-level rising trend and climate during the Late glacial-Holocene period. Repeated phases of backswamp development and infilling by crevasse processes (parasequences) were recorded in the subsurface of Modern Po Delta during the early stages of transgression (ca. 11,000-9,500 cal yr BP). In the Arno coastal plain the presence of a deep-incised valley system, probably formed at OSI 3/2 transition, led to the development of a thick (ca. 35-40 m) transgressive succession composed of coastal plain, bay-head delta and estuarine deposits dated to the Last glacial-Early Holocene period. Within the transgressive valley fill sequence, high-resolution facies analyses allowed the identification and lateral tracing of three parasequences of millennial duration. The parasequences, ca. 8-12 meters thick, are bounded by flooding surfaces and show a typical internal shallowing-upward trend evidenced by subtle micropalaeontological investigations. The vertical stacking pattern of parasequences shows a close affinity with the step-like sea-level rising trend occurred between 14,000-8,000 cal years BP. Episodes of rapid sea-level rise and subsequent stillstand phases were paralleled by changes in climatic conditions, as suggested by pollen analyses performed on a core drilled in the proximal section of the Arno palaeovalley (pollen analyses performed by Dr. Marianna Ricci Lucchi). Rapid shifts to warmer climate conditions accompanied episodes of rapid sea-level rise, in contrast stillstand phases occurred during temporary colder climate conditions. For the first time the palaeoclimatic signature of high frequency depositional cycles is clearly documented. Moreover, two of the three "regressive" pulsations, recorded at the top of parasequences by episodes of partial estuary infilling in the proximal and central portions of Arno palaeovalley, may be correlated with the most important cold events of the post-glacial period: Younger Dryas and 8,200 cal yr BP event. The stratigraphic and palaeoclimatic data of Arno coastal plain and Po Delta were compared with those reported for the most important deltaic and coastal systems in the worldwide literature. The depositional architecture of transgressive successions reflects the strong influence of millennial-scale eustatic and climatic variability on worldwide coastal sedimentation during the Late glacial-Holocene period (ca. 14,000-7,000 cal yr BP). The most complete and accurate record of high-frequency eustatic and climatic events are usually found within the transgressive succession of very high accommodation settings, such as incised-valley systems where exceptionally thick packages of Late glacial-Early Holocene deposits are preserved.

Determinazione di amminotioli mediante elettroforesi capillare

The aminothiols are critical cellular components that play numerous and important roles in metabolism as key extracellular reducing agents, critical substrates for proteins synthesis and detoxificants of free radicals and peroxides. Because altered thiols levels in body fluids are linked to specific pathological conditions, their measurement is thus considered very important. One method to determine these compounds is the capillary electrophoresis, a technique that involves the separation of charged molecules on the basis of their movement under the influence of an applied electric field. The instrument used in this work is equipped with an amperometric detector recording the current of the thiols oxidized at the end of the capillary at a BDD electrode. The aim of this work is to find a valid method for the separations of the aminothiols analyzed, in terms of capillary coating and experimental conditions. In order to find an alternative and less expensive electrode than BDD and to increase sensitivity for the detection of the thiols, a modified electrode consisting in a carbon paste electrode containing Cobalt-phthalocyanine has been studied. In this electrode Cobalt-phthalocyanine works as electrocatalyst to enhance the oxidation reaction, meanwhile the graphite acts as conductive mean. This kind of electrode shows great sensibility and low detection limits for the thiols that have a free thiolic group, but it is not sensible to disulfides. The analysis of human plasma point out that the best method found for the capillary electrophoresis is not useful for the detection of aminothiols in a healthy person, because the very low concentrations in which they are present.

Sintesi di catalizzatori supportati Au/Cu e studio della loro reattività per l'ossidazione selettiva del 5-idrossimetilfurfurale

Al giorno d’oggi i combustibili fossili come carbone, olio e gas naturale forniscono più del 75% dell’energia mondiale. Tuttavia, la crescente richiesta di queste fonti di energia non rinnovabili, si manifesta in un momento in cui le riserve naturali si stanno esaurendo; è stato infatti stimato che le riserve petrolifere di tutto il mondo possano essere sufficienti per fornire energia e produrre prodotti chimici per i prossimi quarant’anni. Per questo motivo la conversione delle biomasse per produrre energia e prodotti chimici sta diventando una valida alternativa per diversificare le fonti energetiche e ridurre il surriscaldamento globale. Le biomasse, infatti, oltre ad essere una fonte rinnovabile, generano minori emissioni di gas serra rispetto ai combustibili fossili, perché la CO2 rilasciata nei processi di utilizzo viene bilanciata da quella consumata nel processo di crescita delle biomasse stesse. Lo sfruttamento delle biomasse per la produzione di building blocks per la chimica suscita particolare interesse, poiché le molecole ottenute sono già parzialmente funzionalizzate; ciò significa che la sintesi di prodotti chimici specifici richiede un minor numero di stadi rispetto ai building blocks petroliferi, con conseguente diminuzione di prodotti di scarto e sottoprodotti. Un esempio di queste potenziali “molecole piattaforma” è il 5-idrossimetilfurfurale (HMF), un importante composto derivato dalla disidratazione di zuccheri, intermedio chiave per la sintesi di un’ampia varietà di prodotti chimici e combustibili alternativi, tra cui l’acido 2,5- furandicarbossilico (FDCA), che è stato identificato tra i dodici composti chimici più importanti degli ultimi anni. Per esempio, il FDCA è un possibile sostituto dell’acido tereftalico, usato per produrre il polietilentereftalato (PET). Recentemente alcuni autori hanno riportato interessanti risultati sull’ossidazione dell’HMF a FDCA utilizzando catalizzatori a base di Au supportato. Questi catalizzatori mostrano però significativi problemi di disattivazione. Lo scopo di questo lavoro di tesi è stato quindi lo sviluppo di catalizzatori attivi e stabili nella reazione di ossidazione dell’HMF a FDCA. Il lavoro portato avanti ha avuto come obbiettivi principali: l’ottimizzazione della sintesi di nanoparticelle di oro e oro/rame a diverso rapporto molare, mediante un processo di sintesi, in acqua, a basso impatto ambientale. Tale metodo di sintesi si basa sull’azione riducente del sistema glucosio-NaOH ed è stato messo a punto in lavori di tesi precedenti. Le nanoparticelle sintetizzate sono state utilizzate, quali fase attiva, per la preparazione di catalizzatori supportati su TiO2 e CeO2 lo studio dell’attività catalitica e riusabilità dei catalizzatori preparati nell’ossidazione in fase liquida del HMF a FDCA.

Modellazione multibody di veicoli ferroviari: sviluppo ed implementazione di modelli innovativi per l'analisi del contatto ruota - rotaia

The wheel - rail contact analysis plays a fundamental role in the multibody modeling of railway vehicles. A good contact model must provide an accurate description of the global contact phenomena (contact forces and torques, number and position of the contact points) and of the local contact phenomena (position and shape of the contact patch, stresses and displacements). The model has also to assure high numerical efficiency (in order to be implemented directly online within multibody models) and a good compatibility with commercial multibody software (Simpack Rail, Adams Rail). The wheel - rail contact problem has been discussed by several authors and many models can be found in the literature. The contact models can be subdivided into two different categories: the global models and the local (or differential) models. Currently, as regards the global models, the main approaches to the problem are the so - called rigid contact formulation and the semi – elastic contact description. The rigid approach considers the wheel and the rail as rigid bodies. The contact is imposed by means of constraint equations and the contact points are detected during the dynamic simulation by solving the nonlinear algebraic differential equations associated to the constrained multibody system. Indentation between the bodies is not permitted and the normal contact forces are calculated through the Lagrange multipliers. Finally the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces respectively. Also the semi - elastic approach considers the wheel and the rail as rigid bodies. However in this case no kinematic constraints are imposed and the indentation between the bodies is permitted. The contact points are detected by means of approximated procedures (based on look - up tables and simplifying hypotheses on the problem geometry). The normal contact forces are calculated as a function of the indentation while, as in the rigid approach, the Hertz’s and the Kalker’s theories allow to evaluate the shape of the contact patch and the tangential forces. Both the described multibody approaches are computationally very efficient but their generality and accuracy turn out to be often insufficient because the physical hypotheses behind these theories are too restrictive and, in many circumstances, unverified. In order to obtain a complete description of the contact phenomena, local (or differential) contact models are needed. In other words wheel and rail have to be considered elastic bodies governed by the Navier’s equations and the contact has to be described by suitable analytical contact conditions. The contact between elastic bodies has been widely studied in literature both in the general case and in the rolling case. Many procedures based on variational inequalities, FEM techniques and convex optimization have been developed. This kind of approach assures high generality and accuracy but still needs very large computational costs and memory consumption. Due to the high computational load and memory consumption, referring to the current state of the art, the integration between multibody and differential modeling is almost absent in literature especially in the railway field. However this integration is very important because only the differential modeling allows an accurate analysis of the contact problem (in terms of contact forces and torques, position and shape of the contact patch, stresses and displacements) while the multibody modeling is the standard in the study of the railway dynamics. In this thesis some innovative wheel – rail contact models developed during the Ph. D. activity will be described. Concerning the global models, two new models belonging to the semi – elastic approach will be presented; the models satisfy the following specifics: 1) the models have to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the models have to consider generic railway tracks and generic wheel and rail profiles 3) the models have to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the models have to evaluate the number and the position of the contact points and, for each point, the contact forces and torques 4) the models have to be implementable directly online within the multibody models without look - up tables 5) the models have to assure computation times comparable with those of commercial multibody software (Simpack Rail, Adams Rail) and compatible with RT and HIL applications 6) the models have to be compatible with commercial multibody software (Simpack Rail, Adams Rail). The most innovative aspect of the new global contact models regards the detection of the contact points. In particular both the models aim to reduce the algebraic problem dimension by means of suitable analytical techniques. This kind of reduction allows to obtain an high numerical efficiency that makes possible the online implementation of the new procedure and the achievement of performance comparable with those of commercial multibody software. At the same time the analytical approach assures high accuracy and generality. Concerning the local (or differential) contact models, one new model satisfying the following specifics will be presented: 1) the model has to be 3D and to consider all the six relative degrees of freedom between wheel and rail 2) the model has to consider generic railway tracks and generic wheel and rail profiles 3) the model has to assure a general and accurate handling of the multiple contact without simplifying hypotheses on the problem geometry; in particular the model has to able to calculate both the global contact variables (contact forces and torques) and the local contact variables (position and shape of the contact patch, stresses and displacements) 4) the model has to be implementable directly online within the multibody models 5) the model has to assure high numerical efficiency and a reduced memory consumption in order to achieve a good integration between multibody and differential modeling (the base for the local contact models) 6) the model has to be compatible with commercial multibody software (Simpack Rail, Adams Rail). In this case the most innovative aspects of the new local contact model regard the contact modeling (by means of suitable analytical conditions) and the implementation of the numerical algorithms needed to solve the discrete problem arising from the discretization of the original continuum problem. Moreover, during the development of the local model, the achievement of a good compromise between accuracy and efficiency turned out to be very important to obtain a good integration between multibody and differential modeling. At this point the contact models has been inserted within a 3D multibody model of a railway vehicle to obtain a complete model of the wagon. The railway vehicle chosen as benchmark is the Manchester Wagon the physical and geometrical characteristics of which are easily available in the literature. The model of the whole railway vehicle (multibody model and contact model) has been implemented in the Matlab/Simulink environment. The multibody model has been implemented in SimMechanics, a Matlab toolbox specifically designed for multibody dynamics, while, as regards the contact models, the CS – functions have been used; this particular Matlab architecture allows to efficiently connect the Matlab/Simulink and the C/C++ environment. The 3D multibody model of the same vehicle (this time equipped with a standard contact model based on the semi - elastic approach) has been then implemented also in Simpack Rail, a commercial multibody software for railway vehicles widely tested and validated. Finally numerical simulations of the vehicle dynamics have been carried out on many different railway tracks with the aim of evaluating the performances of the whole model. The comparison between the results obtained by the Matlab/ Simulink model and those obtained by the Simpack Rail model has allowed an accurate and reliable validation of the new contact models. In conclusion to this brief introduction to my Ph. D. thesis, we would like to thank Trenitalia and the Regione Toscana for the support provided during all the Ph. D. activity. Moreover we would also like to thank the INTEC GmbH, the society the develops the software Simpack Rail, with which we are currently working together to develop innovative toolboxes specifically designed for the wheel rail contact analysis.

Cluster carbonilici di platino contenenti fosfine

Nel corso di questa Tesi sono state studiate le reazioni di cluster carbonil anionici di Platino con fosfine. In particolare, sono state investigate nel dettaglio le reazioni dei cluster [Pt3n(CO)6n]2– (n = 3,4) e [Pt19(CO)22]n– (n = 3,4) con PPh3. Sono state poi preliminarmente studiate anche le reazioni di [Pt24(CO)30]2– e [Pt38(CO)44]2– con PPh3. Questo ha portato alla sintesi e alla completa caratterizzazione mediante diffrazione di raggi X su cristallo singolo delle specie [NBu4]2[Pt9(CO)16(PPh3)2] e [NBu4]x[Pt22(CO)22(PPh3)6]2•yCH3CN, contenenti gli anioni [Pt9(CO)16(PPh3)2]2– e [Pt22(CO)22(PPh3)6]2–. È stato inoltre preparato un nuovo composto tentativamente formulato come [Pt19(CO)20(PPh3)2]4–, sulla base dei dati IR, 31P NMR e ESI-MS. Questi rappresentano i primi esempi di cluster carbonilici anionici di Platino contenenti fosfine. Nel caso delle reazioni di [Pt24(CO)30]2– e [Pt38(CO)44]2– con PPh3 i prodotti sono stati caratterizzati al momento solo mediante spettroscopia IR, e quindi è molto difficile ipotizzare una loro struttura. I composti [Pt9(CO)16(PPh3)2]2– e [Pt19(CO)20(PPh3)2]4– sono stati investigati mediante spettroscopia 31P NMR in soluzione a temperatura variabile. Il primo mostra un unico segnale 31P NMR, in accordo con la struttura allo stato solido, mentre [Pt19(CO)20(PPh3)2]4– è risultato essere flussionale. È stato poi studiato nel dettaglio il comportamento fotochimico dei cluster [Pt3n(CO)6n]2– (n = 3-6) in funzione della concentrazione, confermando la loro natura di “Double emitting quantum dots”. Infine è stato preparato e caratterizzato strutturalmente il sale [DAMS]2[Pt9(CO)18]•dmf, contenente il catione [DAMS]+.

Villa Rasponi a Savignano. Progetto di tutela e valorizzazione di un bene culturale complesso tra architettura storica e paesaggi di Pietro Porcinai.

Oggetto della tesi di laurea è il recupero di Villa Rasponi a Savignano sul Rubicone, un bene storico complesso composto da elementi di varia natura: architettonici e vegetali, di differente pregio, dalla residenza settecentesca agli annessi agricoli di servizio, al parco. Le funzioni d’uso attuali rarefatte e strettamente comuni a quelle originarie, non sono più proponibili per poter garantire la sopravvivenza e la conservazione del complesso. Questo da un punto di vista puramente economico, per l’impegno in termini finanziari che un sito di tali dimensioni richiede, a livello gestionale e circostanziale. Come intervenire su un manufatto di questa natura, tutelandolo, riqualificandolo dal punto di vista architettonico e paesaggistico e, nello stesso tempo, reinserendolo in maniera attiva in un contesto urbano e territoriale dal quale negli anni si è progressivamente distaccato e isolato, chiudendosi nell’accezione di residenza privata? Il progetto, lavorando a vari livelli e confrontandosi con differenti campi disciplinari, dal restauro di un parco storico “firmato” da Pietro Porcinai, all’inserimento di nuovi elementi architettonici, all’analisi di fattibilità finanziaria, si pone principalmente due obiettivi: 1) da un lato intervenire materialmente sul manufatto restaurando gli edifici, anche attraverso la definizione di funzioni che ne permettano la sopravvivenza, e manutenendo il parco storico. In questo senso l’aspetto su cui si insiste maggiormente è il rispetto e la valorizzazione del complesso villa–parco–giardino-annessi come unicum, che assume pregio nella sua totalità e integrità; 2) dall’altro, tenuto conto delle dimensioni, dell’importanza storica, architettonica, culturale e paesaggistica del sito, il progetto intende estendere la sua valenza anche a un intorno in primo luogo locale e poi più ampio, diventando punto di riferimento e polo attrattivo, così come lo era stato nel passato, all’epoca nella quale in esso viveva la principessa Luisa Murat. Non ci si limita dunque a considerare il caso isolato, ma si tiene conto del fatto che la Villa Rasponi sorge all’interno di un contesto, quello della Romagna, di straordinaria ricchezza e molteplicità di espressioni artistiche, architettoniche, naturalistiche che costituiscono un patrimonio di valore, in gran parte scarsamente conosciuto e per nulla. Da qui l’idea di utilizzare una porzione di paesaggio come vetrina e contenitore di informazioni su tutta l’eredità culturale romagnola, legata ad un nuovo modo di intendere il luogo, come contesto che incarna la rete di significati all’interno dei quali le azioni degli uomini diventano fatti culturali. Il complesso della Villa Rasponi, per le sue connotazioni storiche, paesaggistiche, fisiche e posizionali, diventa la concretizzazione di tale idea. Dunque, una porzione di paesaggio che si fa strumento fisico e concettuale, di comunicazione, per trasmettere, valorizzare e promuovere il patrimonio naturale, architettonico e culturale di tutto il territorio in cui è inserito, diventandone icona e sintesi.