Oral cavity cancers (OSCC) are among the most malignances worldwide. OSCC tipically affects men in their IV or V dedade of life, and the most relevant risk factors are tobacco and alcohol consumption. OSCCs generally exhibit poor prognosis, and late stage identification correlates with higher mortality rates. Basic prognostic factors, are tumor size and presence of lymph node and/or distance metastases (T classification, N, M). However, tumors with the same TNM grade and similar morphology may have completely different evolution, because of their intrinsic biological characteristics. For these reasons, the identification of new molecular markers with a predictive value, could represent useful tools in OSCC prevention, prognosis and treatment. In the first part of my PhD project I evaluated the loss of heterozygosity as a possible cause of deregulation of well-known tumor suppressors genes. Obtained data put on light the importance of this rearrangement and genes PDCD4, CTNB1, CASP4 and HSP23, in the onset and progression of OSCC. Subsequently, the analysis of the expression profile of miRNAs, led to the identification of some miRNAs that seems to be involved in cancer development and metastatic progression. In both cases, we need further investigations to understand whether these molecules may be used ideal markers in OSCC diagnosis and treatment.

Cross Reacting Material 197(CRM197) is a Diphteria toxin non toxic mutant that had shown anti-tumor activity in mice and humans. CRM197 is utilized as a specific inhibitor of heparin-binding epidermal growth factor (HB-EGF), that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. We evaluated the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible effects on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment, or changes in cell cycle distribution, in EGFR localization or activation, they show a change in gene expression profile analyzed by microarray. This is the first study where the CRM197 treatment on HT-29 show the alteration of a specific and selected number of genes.

Lo studio è stato condotto seguendo una duplice prospettiva, che trae spunto da alcune assimilazioni operate dalla giurisprudenza italiana. Da un lato, si è cercato di capire come debbano essere interpretate norme create per la valutazione di realtà storicamente ben identificate, quali l’art. 416 bis c.p., nel momento in cui si applicano a realtà nuove, come le mafie straniere. Dall’altro lato, si è cercato di indagare i fondamenti dell’equiparazione dell’impresa che delinque al paradigma dell’associazione per delinquere, punita dall’art. 416 c.p., allorchè imprese formalmente lecite si trovano a operare per fini esclusivamente illeciti, facendo della organizzazione imprenditoriale una vera e propria organizzazione criminale. Gli obiettivi posti dalla ricerca si possono sintetizzare, dunque, nella verifica dell’adattabilità di tradizionali fattispecie criminose al nuovo contesto criminologico e nell’individuazione del confine tra l’azione occasionalmente illecita di una impresa lecita e la connotazione di una impresa come illecita tout court. / The study has two different perspectives, connected to different interpretation of various type of offences of the Italian penal code. From one side, the research deals with the application of article 416 bis c. p., which punishes the “mafia association”, to the foreign organized groups that work in the Italian country. From another side, the research deals with the application of article 416 c. p., which punishes the criminal organization, to the enterprises which committee economic crimes. Finally, the main objective is to verify the compatibility of traditional criminal offences to new expressions of crime.

Il lavoro è suddiviso in due sezioni, che si compongono rispettivamente di tre e due capitoli. La prima sezione è dedicata all'esame dei principi fondamentali e della "parte generale" della disciplina della responsabilità amministrativa degli enti: il primo capitolo si concentra sull'evoluzione storica del principio Societas delinquere non potest nell'ordinamento giuridico italiano, prodromica all'analisi della natura della responsabilità amministrativa dipendente da reato degli enti. svolta nel secondo capitolo. Nel terzo capitolo della prima sezione si affronta la disciplina di "parte generale" del decreto 231, evidenziando, in particolare. i principi fondamentali che caratterizzano questo paradigma di illecito. La seconda sezione affronta invece due degli aspetti maggiormente problematici della "parte speciale" del decreto, ovvero la responsabilità degli enti per i delitti di omicidio e lesioni colpose (ai quali è dedicato il primo capitolo) e quella derivante dalla commissione di reati associativi (ai quali è dedicato il secondo capitolo). / The paper is divided into two sections, which are composed respectively of three and two chapters. The first section is devoted to the consideration of the fundamental principles and the "general part" of the corporate liability: the first chapter focuses on the historical evolution of the principle Societas delinquere non potest, prodromal for the analysis concerning the nature of corporate crime liability, carried out in the second chapter. In the third chapter of the first section deals with the discipline of "general part" of Decree 231, highlighting in particular. the fundamental principles that characterize this paradigm responsibility. The second section addresses instead of two of the most problematic aspects of the "special part" of the decree, or the liability of legal entities for the crimes of homicide and unintentional injuries (to whom is dedicated the first chapter) and that caused by the commission of crimes of association (the which is dedicated to the second chapter).

The research aims at developing a framework for semantic-based digital survey of architectural heritage. Rooted in knowledge-based modeling which extracts mathematical constraints of geometry from architectural treatises, as-built information of architecture obtained from image-based modeling is integrated with the ideal model in BIM platform. The knowledge-based modeling transforms the geometry and parametric relation of architectural components from 2D printings to 3D digital models, and create large amount variations based on shape grammar in real time thanks to parametric modeling. It also provides prior knowledge for semantically segmenting unorganized survey data. The emergence of SfM (Structure from Motion) provides access to reconstruct large complex architectural scenes with high flexibility, low cost and full automation, but low reliability of metric accuracy. We solve this problem by combing photogrammetric approaches which consists of camera configuration, image enhancement, and bundle adjustment, etc. Experiments show the accuracy of image-based modeling following our workflow is comparable to that from range-based modeling. We also demonstrate positive results of our optimized approach in digital reconstruction of portico where low-texture-vault and dramatical transition of illumination bring huge difficulties in the workflow without optimization. Once the as-built model is obtained, it is integrated with the ideal model in BIM platform which allows multiple data enrichment. In spite of its promising prospect in AEC industry, BIM is developed with limited consideration of reverse-engineering from survey data. Besides representing the architectural heritage in parallel ways (ideal model and as-built model) and comparing their difference, we concern how to create as-built model in BIM software which is still an open area to be addressed. The research is supposed to be fundamental for research of architectural history, documentation and conservation of architectural heritage, and renovation of existing buildings.

Oggetto della ricerca è la rilevanza nell’ambito del diritto penale del principio di precauzione. Quest’ultimo deve la sua diffusione e popolarità al fatto di presentarsi come criterio guida al problema del rischio e dell’incertezza. L’esigenza di adottare scelte normative in condizioni di incertezza scientifica è infatti oggi ineludibile. Si cercherà in primo luogo di circoscrivere l’oggetto dell’indagine analizzando il rilievo che il principio di precauzione ha a livello legislativo e giurisprudenziale. Quindi si analizzeranno le problematiche che il ricorso allo stesso suscita con riferimento alla struttura classica del reato e legate al contesto di incertezza nel quale viene invocato. Tali problematiche si riferiscono alla possibilità o meno di dare rilevanza al modello del reato di pericolo, alla ricostruzione del nesso causale e all’influenza che il principio di precauzione può determinare nell’accertamento dell’elemento soggettivo delle colpa. Si concluderà l’analisi analizzando le diverse posizioni assunte dalla dottrina italiana circa l’opportunità o meno dell’intervento penale in contesti di incertezza scientifica, individuando, in caso di risposta affermativa, le modalità di intervento. / The precautionary principle states that if an action or policy has a suspected risk of causing harm to the public or to the environment, in the absence of scientific consensus that the action or policy is harmful, the burden of proof that it is not harmful falls on those taking the action. This principle allows policy makers to make discretionary decisions in situations where there is the possibility of harm from taking a particular course or making a certain decision when extensive scientific knowledge on the matter is lacking. The principle implies that there is a social responsibility to protect the public from exposure to harm, when scientific investigation has found a plausible risk. In some legal systems, as in the law of the European Union, the application of the precautionary principle has been made a statutory requirement. Transposed in a criminal law context precautionary principle meets him with the characteristics of this branch of law. Criminal law is in fact a retrospective law and the classic type of crime (behaviour and event) clashes with a criminal policy time to avoid harmful events. The first stage of the research will be the analysis of actual characteristics of criminal law with particular regards to the meaning of that principle, according to the law and to the case law. The second proposal of the present project is to investigate whether the criminal intervention is feasible in case of scientific uncertainty, according to the different points of view of the Italian doctrine and I will try to identify a method of intervention, if it is possible.

Il presente lavoro si prefigge di indagare come la produzione normativa comunitaria abbia influenzato il diritto penale nazionale fino a delineare i tratti di un diritto penale di matrice europea. Ai fini dell’individuazione dei rapporti intercorrenti tra i due sistemi, è stata prescelta come chiave di lettura trasversale la materia ambientale: accanto al meccanismo di influenza riflessa, è da ravvisare come proprio in tale ambito si sia sviluppata l’evoluzione di un possibile diritto penale europeo e, dunque, di una esplicita influenza dell’ordinamento sovrannazionale nelle scelte di criminalizzazione nazionali. The present work aims at investigating how the Community legislation has influenced the national criminal law to the point of delineating the features of a criminal law of European origin. In order to identify the relationship between the two systems, the environmental has been chosen as the cross-reading key: in addition to the mechanism of reflected influence, it is precisely in this area that a European criminal law has been developed and, therefore, an explicit influence of the supranational legal order in the domestic choices of criminalization has been implemented. / In Chapter I, after having briefly analyzed the concept of environment, the steps of the gradual recognition of a still limited punitive power of the European Union are retraced. More specifically we explore: firstly the various forms of influence that the supranational legislation exerts on the Italian criminal justice system, with particular regard to the so called “triadic conflicts”; secondly the ruling of the Court of Justice, 13 September 2005, Case C-176/03, where it is stated the Community legislative competence in criminal matters, including the possibility of an express request for criminal protection by means of directives; subsequently, the Directive 2008/99/EC of 19 November 2008 on the protection of the environment through criminal law, which, by requiring Member States to introduce into their national criminal systems some criminal offenses so to enforce more effectively the environmental protection, can been seen as the synthesis between the expansionist pressures from the European Commission and the conservative ones from the Council, as well as also a place of mediation among the different models of indictment in force in the various national systems, providing a minimum common denominator of protection of supranational source;then, the changes introduced by the Legislative Decree of 7 July 2011 n. 121, that transposes the Directive in question, and, lastly, the characteristics of the environmental crime and some issues related to the technique of indictment adopted.

The aim of this thesis was to investigate the regenerative potential of alternative sources of stem cells, derived from human dental pulp (hDPSCs) and amniotic fluid (hAFSCs) and, specifically, to evaluate their capability to be committed towards osteogenic and myogenic lineages, for the eventual applicability of these stem cells to translational strategies in regenerative medicine of bone and skeletal muscle tissues. The in vitro bone production by stem cells may represent a radical breakthrough in the treatment of pathologies and traumas characterized by critical bone mass defects, with no medical or surgical solution. Human DPSCs and AFSCs were seeded and pre-differentiated on different scaffolds to test their capability to subsequently reach the osteogenic differentiation in vivo, in order to recover critical size bone defects. Fibroin scaffold resulted to be the best scaffold promoting mature bone formation and defect correction when combined to both hDPSCs and hAFSCs. This study also described a culture condition that might allow human DPSCs to be used for human cell therapy in compliance with good manufacturing practices (GMPs): the use of human serum (HS) promoted the expansion and the osteogenic differentiation of hDPSCs in vitro and, furthermore, allowed pre-differentiated hDPSCs to regenerate critical size bone defects in vivo. This thesis also showed that hDPSCs and hAFSCs can be differentiated towards the myogenic lineage in vitro, either when co-cultured with murine myoblasts and when differentiated alone after DNA demethylation treatment. Interestingly, when injected into dystrophic muscles of SCID/mdx mice - animal model of Duchenne Muscular Dystrophy (DMD) - hDPSCs and hAFSCs pre-differentiated after demethylating treatment were able to regenerate the skeletal muscle tissue and, particularly, to restore dystrophin expression. These observations suggest that human DPSCs and AFSCs might be eventually applied to translational strategies, in order to enhance the repair of injured skeletal muscles in DMD patients.

Il campo d’interesse della ricerca è stato l’attuale processo di ricentralizzazione del Social Housing nelle periferie urbane in una parte del contesto internazionale, che sembra stia portando le città a ricrearsi e ripensarsi grazie alla presa di coscienza delle differenze esistenti, rispetto al passato, nei nuovi processi di trasformazione nei quali la città è intesa sia come spazio costruito ma anche sociale. In virtù di quest’ultimi due aspetti complementari della città, oggi, il ruolo della periferia contemporanea sembra essere diversamente interpretato, così come gli interventi di riqualificazione di tipo assistenziale - migliorativo tenderebbero a trasformarne i suoi caratteri alla ricerca del “modello di città”. L’interesse alla tematica è inoltre scaturito dalla constatazione che alla base della crisi dei modelli d’intervento pubblico starebbero sia l’insostenibilità economica ma soprattutto l’errata lettura dei bisogni delle famiglie nella loro specificità e diversità e che in tal senso l’eventuale partecipazione della cittadinanza costituirebbe effettivamente una proposta valida, anche per risolvere la crescente domanda abitativa che si pone a livello mondiale. L’obiettivo della ricerca è stato quello d’analizzare, nel contesto internazionale del Social Housing, le caratteristiche di partecipazione e sussidiarietà che connotano particolarmente gli interventi di riqualificazione destinati a famiglie economicamente carenti, nello specifico analizzando i metodi e gli strumenti atti alla comunicazione partecipativa del progetto in aree urbane periferiche italiane e brasiliane. Nella prima e seconda fase della ricerca è stato svolto, rispettivamente, un lavoro di analisi bibliografica sul tema dell’emergenza casa e sulle nuove politiche abitative di sviluppo urbano ed uno specifico sulla tematica della riqualificazione partecipata del Social Housing in aree della periferia urbana, infine nella terza fase sono stati analizzati i casi di studio prescelti dando rilievo all’analisi delle caratteristiche e requisiti prestazionali delle tecniche partecipative di rappresentazione - comunicazione, più idonee ad influenzare positivamente il suddetto processo. / The research covers the current process of re-centralization of Social Housing in the suburbs in a part of the international context, which seems to be leading the cities to rethink and reshape themselves thanks to the awareness of the existing differences, as compared to the past, in the new processes of transformation in which the city is considered both as made up buildings and as a social space. As a conseguence of these two complementary aspects of the city, today, the role of contemporary suburbs seems to be interpreted differently, likewise the welfare rehabilitation tend to transform their characters in search of the "model city". Moreover the interest in this topic is the result of the realization that at the basis of the crisis of public models of intervention lies economic unsustainability and above all the misunderstanding of the needs of families in their specificity and diversity. In this sense the participation of citizens would actually be a valid proposal, even to solve the growing housing demand that is arising in the world. The aim of the research is to analyze, on the international level of Social Housing, the characteristics of participation and subsidiarity that characterize the redevelopment works aimed at less well-off families, in particular by analyzing the methods and means suitable to participatory communication in the project in Italian and Brazilian suburb areas. The first and second steps of the research were, respectively, a work of literature review on home emergency and new housing policies of urban development and a specific on the issue of participatory rehabilitation of Social Housing in suburb areas. Then the third step analyzes case studies selected by highlighting the analysis of the characteristics and performance requirements of participatory techniques of representation - communication, best suited to positively influence this process.

München, Techn. Univ., Diss., 2001. / Computerdatei im Fernzugriff.