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The Hedgehog (Hh) signaling pathway plays many important roles throughout embryonic development, including the regulation of tissue patterning, cell differentiation, proliferation, and apoptosis. The loss of SHH signaling in human development has been shown to cause holoprosencephaly. Conversely, inappropriately activated Shh signaling in adults has been implicated in many cancers. Furthermore, Shh has been found to be a key regulator of neural stem cells in the mammalian brain. To further study the roles of Hh, I have developed a transgenic zebrafish line as a tool to monitor tissues that respond to Hh signaling throughout the vertebrate life-cycle. A number of genes have been identified that are transcriptionally up-regulated by Hh signaling. Transcription of these genes is initiated through binding of activated Gli transcription factors to an identified Gli binding site (GBS) in the cis-regulatory region. This Gli binding site is largely conserved across vertebrate species. I have generated transgene constructs in which 12 GBSs have been placed upstream of a minimum promoter that drives GFP, RFP, or Kaede fluorescent proteins. These plasmid constructs are activated in embryonic regions known to be Hh responsive, such as the ventral CNS. Treatment with cyclopamine eliminates this expression, confirming that these transgenes accurately report an active Hh response. These transgenic lines will be extremely powerful tools for research into the mechanisms by which Hh signaling regulates adult cell types such as neural stem cells. These lines will also be important tools that will help understand how misregulation of Hh signaling can lead to cancer.

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Le présent travail de thèse est consacré à la question du désir et à la façon dont elle émerge dans la philosophie de Giordano Bruno (1548-1600). En dépit de sa place relativement marginale dans le corpus très vaste des études bruniennes, et malgré sa présence non immédiatement évidente dans les écrits du Nolain, nous pensons qu’une recherche sur le statut du désir peut ouvrir une perspective pertinente et radicale sur la pensée de ce philosophe de la Renaissance tardive. Loin d’être une question accessoire, le désir se situe au coeur de la philosophie de Bruno et incarne le rythme immanent de sa spéculation. Face au thème capital de la nolana filosofia – la modalité à travers laquelle le fini réalise et exprime l’infini – la question du désir nous ouvre des chemins suggestifs à travers l’imposante oeuvre de l’ex-moine dominicain. Nous avons abordé ce sujet sous plusieurs perspectives, toujours attentifs à exprimer le caractère systématique sus-jacent à la grande ampleur des thématiques que l’on trouve dans les écrits du philosophe. Nous avons préféré procéder de manière diachronique, en privilégiant une approche conceptuelle plutôt qu’un exposé de la philosophie brunienne dans son déroulement chronologique. Nous nous sommes d’abord penchés sur un traité tardif, la Lampas triginta statuarum, où le désir apparaît comme la force qui amène les « ténèbres »indistinctes à exprimer la richesse infinie de formes qu’elles renferment en puissance. Dans les dialogues cosmologiques en italien, le désir, force immanente aux révolutions des planètes (qui assurent la succession des saisons et des civilisations), réalise dans chaque être la vicissitude qui lui permet « d’être tout et de devenir tout ». La comédie italienne le Chandelier montre comment la poursuite d’un désir statique, obsessionnel et contraire à la nature amène inévitablement à la perte des personnages qui l’incarnent. Cette même aspiration “civile” sera présente dans le traité magique Des liens où le philosophe-mage s’appuie sur l’amour, « le lien le plus puissant », pour donner vie à une république qui, à travers ses citoyens, reflète la puissance infinie inhérente à la nature. En dernier lieu,nous verrons comment, dans Des fureurs héroïques, l’élan cognitif qui amène Actéon à « devenir nature » correspond à la manière la plus humaine qui soit de réaliser l’infini. / My PhD dissertation aims at analysing the concept of desire in relation to Giordano Bruno’s philosophy. Despite the relatively marginal place of this issue among secondary bibliography and its not immediately evident presence in Bruno’s works, I think that this kind of research can open apertinent and radical perspective on Bruno’s thought. Far from being a secondary aspect, the desire is at the core of Giordano Bruno’s philosophy and it embodies its immanent rhythm. In relation to the fundamental theme of Bruno’s philosophy – the way in which the finite realises the infinite – the question of desire can disclose to us new perspectives. I have looked at this problem from many perspectives, always attentive to express the systematic character under the great varieties of topicswe can find in the Nolana filosofia. I have proceeded diachronically, privileging a conceptual approach rather than a chronological account of Bruno’s thought. First, I have considered the Lampas triginta statuarum, a late Latin treatise in which the desire appears as the force that leads the tenebræ toexpress the infinity of forms they contain in potentiality. In the cosmological dialogues in Italian, the desire – immanent force that assures planets’ revolutions (and in that way the cycle of seasons andcivilisations) – realises in all the beings the vicissitude that allows it to “be everything and becomeeverything”. The comedy The Candle Bearer shows how the pursuit of a static, obsessional, andunnatural desire causes the loss of the three main characters. We can find the same “civil afflatus” inthe magical treatise De vinculis where the magic-philosopher builds through love (“the most powerfullink”) a republic that, through its citizens, reflects the infinite power of nature. Lastly, we will see how, in The Heroic Frenzies, the cognitive desire that allows the metamorphosis of the hunter Acteon in nature corresponds to the most human way to realise the infinite.

La letteratura di business internazionale fornisce la prova convincente della diffusione globale di pratiche di responsabilità sociale delle imprese (RSI) e l'importante ruolo svolto dalle multinazionali (MNC) nel trasferimento di pratiche di RSI alle loro controllate estere. La tesi esplora la gestione di strategie di RSI da società controllate di MNC, spiegando il meccanismo che permette loro di bilanciare le pressioni istituzionali divergenti. Questo fenomeno è noto come ‘complessità istituzionale’, derivante dai molteplici ed eterogenee forze istituzionali a cui le controllate di multinazionali e le loro sedi sono esposte in relazione all'adozione di pratiche di RSI. Attingendo alla letteratura su RSI e teoria istituzionale, il primo articolo della tesi sviluppa un framework concettuale e un set di proposizioni da testare per studi futuri, attraverso un approccio configurazionale. Il secondo articolo della tesi esamina come le filiali di MNC gestiscono le pressioni, le barriere e i mezzi che affrontano durante la distribuzione delle loro attività di RSI in cinque paesi africani (Angola, Egitto, Ghana, Kenya e Sud Africa), attraverso 33 interviste, permettendoci di catturare alcuni modelli di variazione nella distribuzione di pratiche di RSI all'interno dei paesi in via di sviluppo. Il terzo documento della tesi analizza le pratiche di dialogo realizzate da 418 società quotate all'indice FTSE4Good in Europa, Nord America e Asia. / The international business literature provides compelling evidence for the global diffusions of Corporate Social Responsibility (CSR) practices and the important role played by Multinational Corporations (MNCs) in transfer of CSR practices to their foreign subsidiaries. The thesis explores the management of CSR strategies by MNCs’ subsidiaries, by explaining the mechanism that allows them to balance divergent institutional pressures. This phenomenon is known as ‘institutional complexity’, resulting from the multiple and heterogeneous institutional forces to which MNCs’ subsidiaries and their headquarters are exposed in relation to the adoption of CSR practices. Drawing on CSR literature and institutional theory, the first paper of the thesis develops a conceptual framework and a set of propositions to be tested for future studies, through a configurational approach. The second paper examines how the MNCs’ subsidiaries manage the pressures, the barriers and the enablers they face when deploying their CSR activities in five African countries (Angola, Egypt, Ghana, Kenya and South Africa), through 33 interviews, allowing us to capture some patterns of variations in CSR deployment within developing countries. The third paper analyses the stakeholder dialogue practices realized by 418 companies listed in the FTSE4Good index in Europe, North America, and Asia.

I uppsatsen utreds vad försäkring är samt vad affärsrisker är och hur de försäkras inom ramen för ansvarsförsäkringen. Viktiga frågor är var, och varför, gränsen för affärsriskers försäkringsbarhet dras som den gör, samt huruvida en ny struktur och systematik kan ge upphov till en mer ändamålsenlig gränsdragning. För att kunna förstå och argumentera kring behandlingen av affärsrisker i ansvarsförsäkringen, samt för att kunna omfamna ämnessfären med ett helhetsgrepp, måste först en relation till försäkringens väsen byggas. Kunskapen om vad försäkring är och varför försäkring finns utgör oumbärliga fundament i argumentationen om affärsriskers försäkringsbara vara eller icke vara. De försäkringsrättsliga principerna och den normativa bas som bygger upp rättsområdet synliggör ramen för försäkringsavtalsparternas förhållande och rekvisiten för försäkringsbarheten. Dessa principer och normer utgör sedermera bakgrunden som affärsriskerna ses emot i analysen. Ansvarsförsäkringen täcker den försäkrades skadeståndsansvar. En uppdelning kan göras mellan hur täckning sker av kontraktuella skadestånds- och ersättningsansvar respektive utomobligatoriska skadeståndsansvar. I och med att professions- och rådgivningsansvaret behandlas annorlunda än ansvaret i andra tjänsteverksamheter finns det en principiell vinst i att belysa det separat. Affärsriskerna leder fram till ett eventuellt ansvar och hur de behandlas kan ses i de omfattnings- och undantagsvillkor som återfinns i den vanliga ansvarsförsäkringen och i GLI-försäkringen. I uppsatsen genomgås följande utvidgande och undantagande villkor: undantaget för ren förmögenhetsskada, undantaget för omhändertagen egendom, undantaget för garantier och utfästelser, undantaget för förutsebar skada, undantaget för skada på levererad egendom, tillägget för ren förmögenhetsskada, återkallelsetillägget, tillägget för ingrediens- och komponentskada, åtkomst- och återställandetillägget samt goodwilltillägget. Gränsdragningen för täckning av affärsrisker i ansvarsförsäkringen är spretig och förefaller inte utgå ifrån en bakomliggande systematik. De gemensamma nämnarna analyseras dock, vilket ger en uppfattning av de syften som försäkringsbranschen vill uppnå med avgränsningen mot vissa affärsrisker. Med erfarenheter från vad försäkringens väsen är, hur och varför gränsdragningen görs samt dess, ur ändamålssynpunkt, inte helt tillfredställande resultat, kan en ny struktur och systematik föreslås. Förhoppningsvis leder det till en mer genomtänkt och förståelig hantering av affärsrisker i ansvarsförsäkringsfrågor. / In this thesis, I examine what insurance is, together with what business risk is and how business risks are insured in the context of liability insurance. Important questions are where, and why, the boundaries of the insurability of business risks are set as they are, and also whether a new structure and systematics could give rise to a more suitable delimitation. To be able to understand and argue about how business risks are treated in the context of liability insurance, and also to be able to approach the sphere of the subject holistically, a relation to the essence of insurance must first be built. The knowledge about what insurance is and why it exists is an indispensable foundation for the argumentation around the insurability of business risks. The principles and the normative base that make up the legal area of insurance law reveal the framework of the relationship between the parties of the insurance contract and the requirements of insurability. These principles and norms subsequently form the background against which the business risks are seen in the analysis. The liability insurance covers the liability of the insured. A distinction can be made between how the insurance covers contractual liability and non-contractual liability. Since professional liability, such as the liability of advisors, is treated differently from the liability of other service businesses, there is a principal benefit in elucidating it separately. The business risks lead to a potential liability, and how they are treated can be seen in the regular and global liability insurance policies. In this thesis, the following expanding and excluding policies are covered. Exclusion of pure financial loss, property in trust, promise or guarantee, foreseeable damage and damage to delivered property. Addition of pure financial loss, recall, claims due to ingredients or components, access and restoration costs, and goodwill. The boundary of coverage of business risks in the context of liability insurance is fuzzy and does not appear to be set based upon any underlying systematics. The common denominators are, however, analyzed which gives an idea of the ends that the insurance industry wants to achieve through the delimitation against certain business risks. With knowledge of what constitutes the essence of insurance, of how and why the boundaries are set as they are and of their, from a purpose-oriented point of view, not entirely satisfactory results, a new structure and systematics can be proposed. Hopefully, it leads to a more thought-out and comprehensible treatment of business risks in matters regarding liability insurance.

Jusqu’en 1481, Marseille fait partie d’un Etat indépendant, le comté de Provence et en est la plus grande ville sans en être toutefois la capitale. Or, en 1481, le dernier comte de Provence meurt sans héritier et il lègue l’ensemble de ses territoires au roi de France, Louis XI. Cependant, en Provence, les structures et pratiques politiques sont différentes du royaume de France, et Marseille appartient à un espace politico-culturel méditerranéen où la vie politique des villes est marquée par le modèle de la commune, également présent en Italie du nord et du centre. L’objectif de cette thèse est d’observer le passage d’un espace politico-culturel marqué par l’héritage des comtes de Provence et des cadres politiques de la commune à un espace politico-culturel dominé par le roi de France, où la relation entre le souverain et les villes s’inscrit dans le cadre de la « bonne ville ». Pour mener à bien ce travail, nous avons choisi de nous intéresser au conseil de ville, qui est la pièce maîtresse du pouvoir municipal, et à ses membres, afin d’observer les mutations introduites par ce transfert de souveraineté. Nous avons décidé de voir ces mutations en ce qui concerne la culture et l’identité du groupe dirigeant de la ville afin de s'inscrire dans une histoire culturelle du pouvoir municipal. Toute ville peut se définir comme un système politique où différents pouvoirs coexistent et se réajustent en permanence les uns par rapport aux autres au gré des événements et des changements qui peuvent surgir. La première partie examine les réajustements aux XIVe et XVe siècles à Marseille, qui permettent au pouvoir municipal de devenir dominant à Marseille face aux autres pouvoirs sous le règne de René Ier d’Anjou (1434-1480). La deuxième partie étudie les hommes à le tête du conseil de ville, les fondements de leur pouvoir et leurs modifications autour du rattachement de 1481. Enfin, la dernière partie examine les changements de culture et d’identité du groupe introduits par le transfert de souveraineté et les nouvelles ambitions en Méditerranée du groupe dirigeant, qui jettent les bases d’une véritable thalassocratie qui s’épanouira au XVIIe siècle. / Until 1481, Marseilles is a part of an independant state, the county of Provence and it’s the biggest city, even if it’s not the capital. But, in 1481, the last count of Provence died without a son and he gives in his testament all his goods and territories to the king of France Louis XI. After that, Marseilles, like the rest of the former county is integrated in the French royal domain. But, in Provence the cultural and political structures and practices are different from the kingdom of France, and Marseilles belongs to a politico-cultural space where the political life is influenced by the model of “commune”, we can also see in the north of Italy. My aim in this thesis is to study the mobility between a politico-cultural space influences by the counts of Provence and the political structures and culture of the “commune” to a politico-cultural space dominated by the king of France thanks to a structure called “bonne ville”. I decided to study the council of the city which is the main structure of the municipal power and the leaders who are in this council in order to see the modifications after 1481 about the culture and the identity of this ruling class. I propose with this thesis an essay of cultural history of the municipal power. Each city is a political system, where different powers coexist. Those powers move and fix themselves towards the other ones. In the 1st part, I study how the municipal power becomes the most important one in Marseilles during the reign of René the 1st of Anjou. Then, in the second part, I study the leaders of the council, the foundations of their power and the modifications after 1481. Finally, in the 3rd part, I study the new ambitions of the leaders of Marseilles which lead in the 17th century to build a real thalassocracy in the Mediterranean world. / Fino al 1481, Marsiglia è la città più grande della contea di Provenza, uno stato indipendente, pur senza esserne la capitale. In quell’anno, l'ultimo conte di Provenza muore senza eredi e dona la sua contea al re di Francia, Luigi XI. Le strutture e le pratiche politiche della Provenza sono però molto diverse rispetto a quelle del regno di Francia: Marsiglia fa parte di uno spazio politico-culturale del Mediterraneo, dove la vita politica urbana è segnata da un modello comunale del tutto simile a quello che si riscontra nelle città dell'Italia centro-settentrionale. L’obiettivo di questa tesi è di studiare il passaggio di questo spazio politico-culturale, segnato dall’eredità angioina e da un governo di tipo comunale, a quello dominato dal re di Francia, nel quale la relazione tra il sovrano e le città è costruita attorno al modello della "bonne ville". Per studiare questo tema, si è scelto di concentrarsi sul consiglio della città di Marsiglia, l'istituzione simbolo del potere municipale, e sugli uomini che lo componevano, al fine di apprezzare le mutazioni dovute al cambiamento di sovranità avvenute al suo interno. L’intento è di analizzare i cambiamenti legati alla cultura e all’identità della classe dirigente, nell’ottica di una storia culturale del potere municipale. Tutte le città possono definirsi come un sistema politico all’interno del quale si trovano a coesistere diversi poteri, che si relazionano fra loro in base agli avvenimenti e ai cambiamenti interni ed esterni alla città stessa. La prima parte della tesi si concentra sul processo mediante il quale il potere municipale ha preso il sopravvento a Marsiglia sotto il regno di Renato I (1434-1480). Nella seconda, invece, si analizzano gli uomini che formano il consiglio della città, l’origine del loro potere e le mutazioni che avvengono dopo il 1481. Infine, l’ultima parte ha per oggetto le trasformazioni nell’identità e nella cultura del gruppo dirigente cittadino in seguito al cambiamento di sovranità, evento che getterà le basi della talassocrazia marsigliese del XVII secolo.

I microrganismi selezionati sono impiegati non solo per il processo di trasformazione della materia grezza in prodotto fermentato, ma anche per migliorare la shelf-life, il gusto, l’aroma, la sicurezza e il valore nutrizionale dei prodotti. La globalizzazione del mercato ha portato a considerare non solo i prodotti tipici popolari europei, come per esempio il vino, ma anche i prodotti tipici dei paesi non europei come la cassava. Per quanto riguarda il settore enologico lo scopo della ricerca è quello di migliorare un tipico vino: l'Ortrugo dei Colli Piacentini con ceppi autoctoni di Saccaromyces cerevisiae. Nelle fermentazioni spontanee i lieviti sono associati all'area geografica, alle condizioni climatiche e alla varietà di vitigno. Alcuni ricercatori sostengono che il micro-ambiente è caratterizzato da specifi Saccaromyces cerevisiae che possono influenzare gli aromi dell'uva. Sfortunatamente le fermentazioni spontanee possono causare aromi indesiderati e arresti fermentativi. L'inoculo del mosto con lieviti selezionati è ormai una pratica consolidata per eliminare i rischi delle fermentazioni spontanee, ma questi lieviti non riescono a enfatizzare le caratteristiche della varietà di uva in quanto derivano da ecosistemi differenti. Nasce quindi l'esigenza di utilizzare ceppi starter autoctoni selezionati, isolati dalle microaree dove i vini sono prodotti in quanto tali ceppi sono potenzialmente meglio adattati a svilupparsi in uno specifico microambiente e meglio esaltano la tipologia di un particolare prodotto. Per quanto riguarda la cassava (Manihot esculenta Crantz) microrganismi selezionati possono essere utilizzati per ridurre la concentrazione di glucoside cianogenetico (linamarina e lotaustralina), molecole tossiche. il consumo di cassava e dei suoi prodotti può causare avvelenamento da cianide con sintomi di vomito, nausea, debolezza e occasionalmente la morte. L'introduzione di cianide tramite il consumo di cassava è quasi certamente la causa dell'insorgenza di neuropatie come per esempio il Konzo (irreversibile paralisi alle gambe) che colpisce particolari zone dell'Africa. La World Health Organisation (WHO)ha stabilito il livello di sicurezza di cianide nella farina di cassava a 10 ppm (FAO/WHO, 1991). / Selected microrganisms are important as agents of the main processes of transformation of the raw materials in fermented product but also as responsible of the improvement in the shelf-life, texture, taste, aroma, as well as safety and nutritional value. The market globalization made us to consider not only popular food and/or beverage in Europe but also in non European countries. In this research I consider wine and cassava products. As regards wine the aim is to improve the Ortrugo wine typicalness by Saccaromyces cerevisiae autochtonous strains. In spontaneous fermentations the yeasts vary according to geography location, climatic conditions and/or grape variety. Some researchers believe that each micro-environment is characterised by specific Saccaromyces cerevisiae that may enhance the grape flavours. Unfortunately spontaneous fermentations may cause off-flavours and fermentation stuck. The selected yeast inoculum in must is one of the consolidated practices to eliminate the risks of spontaneous fermentation, but these yeast are not able to emphasise the characters of grape variety because they are from different ecosystems. Autochthonous yeasts e.g. yeasts isolated from a definite micro-environment are adapted to operate in a must whose characteristics are determined by the variety of the grapes and the “terroir” and, therefore, they able to enhance the peculiarities of a wine. As regards the cassava (Manihot esculenta Crantz) selected microorganisms will be used to reduce the cyanogenic glucosides (mainly linamarin and lotaustralin) toxic molecules. Consumption of cassava and its products may cause cyanide poisoning with symptoms of vomiting, nausea, dizziness, stomach pains, weakness, headache and diarrhoea and occasionally death. Cyanide intake from cassava is almost certainly the cause of Konzo (irreversible paralysis of the legs) in eastern, central and southern Africa. The World Health Organisation (WHO) has set the safe level of cyanogens in cassava flour at 10 ppm (FAO/WHO, 1991).