<p>Radiotherapy is one of the most common therapeutic methods for treatment of many types of cancer. Despite many decades of development and experience there is much to improve, both in efficacy of treatment and to decrease the incidences of adverse healthy tissue reactions. Around 20 % of the radiotherapy patients show a broad range in the severity of normal tissue reactions to radiotherapy, and dose limits are governed by severe reactions in the most radiosensitive patients (< 5 %). Identification of patients with low, moderate or high clinical radiosensitivity before commencing of radiotherapy would allow individual adaptation of the maximum dose with an overall increase in the cure rate. Characterization of factors that may modify the biological effects of ionizing radiation has been a subject of intense research efforts. Still, there is no assay currently available that can reliably predict the clinical radiosensitivity. The aim of this work has been to investigate the role of oxidative stress in individual radiosensitivity and evaluate novel markers of radiation response, which could be adapted for clinical use.</p><p>8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a general marker of oxidative stress, is one of the major products of interaction of ionizing radiation with DNA and the nucleotide pool of the cell. As 8-oxo-dG is highly mutagenic due to incorrect base pairing with deoxyadenosine, various repair mechanisms recognize and remove 8-oxo-dG. The repaired lesions are released from cells to the extracellular milieu (serum, urine and cell culture medium) where they can be detected as markers for free radical reactions with the nucleic acids.</p><p>Significant variations in background levels as well as in radiation induced levels of 8-oxo-dG in urine have been demonstrated in breast cancer patients (paper 1). Two major patterns were observed: high background and no therapy-related increase vs. low background and significant increase during radiotherapy for the radiosensitive and non radiosensitive patients respectively.</p><p>Studies in paper 2 indicated major contribution of the nucleotide pool to the extracellular 8-oxo-dG levels. The results also implicated induction of prolonged endogenous oxidative stress in the irradiated cells. RNA “knock-down” experiments on the nucleotide pool sanitization enzyme hMTH1 in paper 3 lend further experimental evidence to this assumption.</p><p>The applicability of 8-oxo-dG as a diagnostic marker of oxidative stress was demonstrated in paper 4. Studies on dialysis patients revealed a good correlation between inflammatory responses (known to be associated with persistent oxidative stress) and extracellular 8-oxo-dG.</p><p>In summary, our results confirm that extracellular 8-oxo-dG is a sensitive <i>in vivo</i> biomarker of oxidative stress, primarily formed by oxidative damage of dGTP in the nucleotide pool with a potential to become a clinical tool for prediction of individual responses to radiotherapy.</p>

Radiotherapy is one of the most common therapeutic methods for treatment of many types of cancer. Despite many decades of development and experience there is much to improve, both in efficacy of treatment and to decrease the incidences of adverse healthy tissue reactions. Around 20 % of the radiotherapy patients show a broad range in the severity of normal tissue reactions to radiotherapy, and dose limits are governed by severe reactions in the most radiosensitive patients (&lt; 5 %). Identification of patients with low, moderate or high clinical radiosensitivity before commencing of radiotherapy would allow individual adaptation of the maximum dose with an overall increase in the cure rate. Characterization of factors that may modify the biological effects of ionizing radiation has been a subject of intense research efforts. Still, there is no assay currently available that can reliably predict the clinical radiosensitivity. The aim of this work has been to investigate the role of oxidative stress in individual radiosensitivity and evaluate novel markers of radiation response, which could be adapted for clinical use. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a general marker of oxidative stress, is one of the major products of interaction of ionizing radiation with DNA and the nucleotide pool of the cell. As 8-oxo-dG is highly mutagenic due to incorrect base pairing with deoxyadenosine, various repair mechanisms recognize and remove 8-oxo-dG. The repaired lesions are released from cells to the extracellular milieu (serum, urine and cell culture medium) where they can be detected as markers for free radical reactions with the nucleic acids. Significant variations in background levels as well as in radiation induced levels of 8-oxo-dG in urine have been demonstrated in breast cancer patients (paper 1). Two major patterns were observed: high background and no therapy-related increase vs. low background and significant increase during radiotherapy for the radiosensitive and non radiosensitive patients respectively. Studies in paper 2 indicated major contribution of the nucleotide pool to the extracellular 8-oxo-dG levels. The results also implicated induction of prolonged endogenous oxidative stress in the irradiated cells. RNA “knock-down” experiments on the nucleotide pool sanitization enzyme hMTH1 in paper 3 lend further experimental evidence to this assumption. The applicability of 8-oxo-dG as a diagnostic marker of oxidative stress was demonstrated in paper 4. Studies on dialysis patients revealed a good correlation between inflammatory responses (known to be associated with persistent oxidative stress) and extracellular 8-oxo-dG. In summary, our results confirm that extracellular 8-oxo-dG is a sensitive in vivo biomarker of oxidative stress, primarily formed by oxidative damage of dGTP in the nucleotide pool with a potential to become a clinical tool for prediction of individual responses to radiotherapy.

The thesis explores how far enclosure was pivotal in shaping the female Franciscan spirituality in thirteenth-century Umbria as cloistered and contemplative. It focuses on how enclosure influenced the development of representations of female urban sainthood, with particular reference to three Umbrian saints; Clare of Assisi, Clare of Montefalco and Angela of Foligno. The issue of enclosure came to the fore because of the success of the Franciscan movement in promoting the apostolic life, which emphasised the itinerant life, evangelisation and participation within the urban community. However, women who aspired to follow these values were instead directed towards introspective, contemplative seclusion. The claustration of Clare of Assisi exemplified this type of response. Using a combination of a wide range of sources, the nature of enclosure and the processes by which claustration was consistently articulated and promoted are reconstructed. My research reveals that the creation of the cloistered ideal was a negotiated process. The first, chapter, Challenging the stabilitas loci, examines the significance of hagiographic sources, in the form of vitae and canonisation proceedings, in revealing the nature of enclosure for religious women, and, by utilising a wide number of saintly examples, shows how often enclosure was in reality broken by women. The following two chapters concentrate on the construction of male textual authority and the importance they placed on the seclusion for religious women. Chapter 2, The regularisation of chastity: between doctrine practice, examines the theological arguments that were put forward in the development of monastic rules for women and how they reflected a trend that assumed that professed religious women ought to remain within the cloister. In doing so, the regularisation of the cloister emphasised the preservation of the chastity of nuns, through their affiliation to established orders, their supervision and material provision.

This thesis examines representations of Roman female suicide in a variety of genres and periods from the history and poetry of the Augustan age (especially Livy, Ovid, Horace, Propertius and Vergil), through the drama and history of the early Principate (particularly Seneca and Tacitus), to some of the Church fathers (Tertullian, Jerome and Augustine) and martyr acts of Late Antiquity. The thesis explores how the highly ambiguous and provocative act of female suicide was developed, adapted and reformulated in historical, poetic, dramatic and political narratives. The writers of antiquity continually appropriated this controversial motif in order to comment on and evoke debates about issues relating to the moral, social and political concerns of their day: the ethics of a voluntary death, attitudes towards female sexuality, the uses and abuses of power, and traditionally expected female behaviour. In different literary contexts, and in different periods of Roman history, writers and thinkers engaged in this same intellectual exercise by utilising the suicidal female figure in their works.

The thesis sets out to examine the little studied phenomenon of translating and rewriting children’s literature during Fascism. Under Mussolini’s rule, books for children had to perform the important task of forging the ‘new Italians’. For this reason, the presence of foreign literature on the Italian book market became increasingly problematic, as the regime attempted to achieve cultural and economic autarchy. This research aims to show how, rather than merely reflecting dominant ideologies, the translation of books for children was a site for negotiation, allowing different, and sometimes conflicting narratives and discourses to be identified and fruitfully examined. By adopting an interdisciplinary theoretical framework, where theories from Translation Studies, Children’s Literature, and studies on Fascism, are integrated, translations and rewritings of books for children are employed as hermeneutic tools to explore the multifaceted nature of the regime’s ideology and cultural production, beyond the official façade of unity and consistency. Central questions concerning the construction and defense of Fascist identity are addressed through a selection of case studies, showing different strategies and functions of translating and rewriting for children. The Fascist rewritings of Collodi’s Pinocchio are analysed in relation to Fascism’s relationship with tradition, focusing on the ways in which the past was ‘rewritten’ at different phases of the dictatorship. The challenges of translating a book that had been openly condemned by Fascist institutions are examined by looking at the two translations of Alice in Wonderland which appeared during the 1930s. The complex reception and the controversial success of American comics is investigated, where the different strategies of translation and re-creation reveal complex dynamics of interactions between imported and native products. Finally, the process of rewriting an apparently timeless and universal tradition is observed in the book series ‘La Scala d’Oro’, which was highly regarded by official culture, despite publishing mostly foreign titles.

This thesis asks how stereotypical images of a foreign country are reinforced or contested through translation in the context of the contemporary consumer book market. Taking Italy and the British publishing market as its focus, it sets out to examine the translation process for one popular genre of Italian fiction and two Italian bestsellers published in Britain after 2000. Gomorra by Roberto Saviano (2006) and Cento colpi di spazzola prima di andare a dormire by Melissa P. (2003) and the so-called ‘new Italian crime fiction’, are three recent Italian publishing phenomena that have been selected for translation into English. Once translated and distributed in the British market, they attracted significant commercial and critical attention in the literary field. How important was the association with stereotypical images of Italy in determining the success of these texts in Britain, a market that is famously resistant to translation? How was the idea of Italy re-negotiated and re-imagined throughout the translation process? In order to provide an answer to the above questions, both the translation and the paratranslation of the Italian texts are investigated. The translation of new Italian crime fiction is examined with a focus on the Italian and the British history of the genre and on its paratranslation. The fascinating implications of the new branding of the author Roberto Saviano, which emerged in the British literary field when Gomorra was translated into English, are explored in the context of both translation and paratranslation. Finally, in analysing the translation of Cento colpi I have focused on the work of the translator, Lawrence Venuti, and particularly on the implicationsthat his ideology of translation has on the idea of Italy and on that of “cultural difference” as they emerge from the target text. This thesis adopts an interdisciplinary theoretical framework, in which theoretical understandings from Translation Studies, Italian Studies, studies of the contemporary book market and media culture are integrated. It uses translation as a method to look into the workings of the contemporary book market and, more generally, to shed light on contemporary representations of Italy that circulate in the large mass mediated textual space through the mirror of translation.

This study is about discourses of bilingualism in Bolzano-Bozen, Italy, and what they reveal about language, identity, hegemony and the production of social space. The theoretical and methodological framework I use is Nexus Analysis and Geosemiotics: approaches developed by Scollon and Wong Scollon (2004 and 2003, respectively). These approaches have revealed how and why place names, their public placement, Fascist-era monuments and bilingual education maintained a constant presence, under broader discourses on bilingualism, during the research period. Nexus Analysis focuses on social action and Geosemiotics pays meticulous attention to fundamental aspects of signs, including where they are in the material world, and how social actors interact with them. This has led to an investigation of the historical past, and how this is represented, understood and indexed in the present by those who align (or not) to ideologies of language and nation. In the complex multilingual context of this study, this approach has revealed how such ideologies are mobilized to contest ownership of geographic place and to make social space. I have traced discourses across disparate discursive genres, to reveal the complex interrelationships between language and other social semiotic data in discourses on bilingualism in Bolzano-Bozen through time, and across space.

This dissertation studies the diplomatic and political communication between Florence, the Byzantine and the Ottoman empires in the fifteenth century (1439-1481). The first chapter is introductory to the thesis and reconstructs the contacts between Florence and Byzantium. The second chapter and the third chapter examine the privileges granted by John VIII to Florence; the chapters present the contents and contextualise the privileges within the humanist environment. The fourth chapter studies the Florentine-Byzantine contacts after the Council (1439-1453), focusing on why Florence abandoned Byzantium. The fifth chapter analyses the beginning of Florentine-Ottoman relations and reconstructs the commercial privileges given by the sultan to Florence. The sixth and seventh chapters investigate Florence’s diplomacy during the Ottoman-Venetian war (1463-1479) and Otranto (1480-1481) until Mehmet II’s death. The thesis is accompanied by three appendices including a number of unpublished documents, a prosopography of the Florentines involved in the Levant, and selected Byzantine charters used for the analysis in chapter two. I aim to demonstrate that the relations between the eastern and the western part of the Mediterranean in the fifteenth century were determined by political and economic considerations rather than faith. These considerations guided Florence’s diplomacy to achieve commercial superiority in Constantinople.

Since the first definition of “italiano neostandard” appeared in the Eighties, more and more often “neostandard” forms, while already present in common speech, feature today in the written media, and even find their space in contemporary grammaticography. Through a corpus-based analysis, this dissertation aims at assessing the vitality of the neostandard as it appears in the written columns of three daily papers during a selected period of time in 2007. In particular, two phenomena are explored: the usage of the clitics ci, ne and lo in function of case marker (marca complementare); and the tendency to reduce the use of the subjunctive in epistemic modality. This contribution proposes the integration of different approaches into one interpretation of mechanism of cliticization as a continuum which goes from facultative usages of case markers to obligatory ones. In the second case the phenomenon of reduction of usage of epistemic subjunctive is described here as a reorganization (ristrutturazione). According to this study, within the category of epistemic subjunctive it is necessary to distinguish particular contexts after which the subjunctive preserves its status from the ones in which tends to be substituted by the indicative or the conditional.

This thesis explores the increasing representation of sexual dissidence on contemporary Italian mainstream television from 1990 to 2012. It argues that TV programming and regulations have been historically influenced by notions of an ideal family audience assumed to be traditionally nuclear, patriarchal, heterosexual and normative. The visual representation of sexuality in the media has been the subject of considerable international debate which has problematised the historical invisibilisation and misrepresentation of sexual dissidents, particularly in film and with an almost exclusive methodological emphasis on Anglophone texts. Less attention has been given to more integrated and empirical approaches to the representation, circulation and reception of dissident sexualities on TV. This study combines historical examinations of sexual portrayals on Italian television with two online ethnographies targeting non-heterosexual and heterosexually-identified respondents, discursively analysing whether and how these samples of viewers have engaged with this increasing TV visibility. The majority of participants seem interested in these portrayals and disagree with restrictive decision-making by networks. Nonetheless, a considerable portion of respondents appears to be problematically influenced not so much by the content of programmes as by perceptions of the views of others. The thesis demonstrates that audience research is an under-explored, yet very productive, field of enquiry in Sexuality Studies. Further research in this direction could have implications for network recommendations, transnational policy-making and new theoretical approaches.