Inflammation in cancer cachexia: To resolve or not to resolve (is that the question?)

Background & aims: Cachexia is associated with poor prognosis and shortened survival in cancer patients. Growing evidence points out to the importance of chronic systemic inflammation in the aetiology of this syndrome. In the recent past, chronic inflammation was considered to result from overexpression and release of pro-inflammatory factors. However, this conception is now the focus of debate, since the importance of a crescent number of pro-resolving agents in the dissolution of inflammation is now recognised - leading to the hypothesis that chronic inflammation occurs rather due to failure in the resolution process. We intend to put forward the possibility that this may also be occurring in cancer cachexia. Methods: Recent reviews on inflammation and cachexia, and on the factors involved in the resolution of inflammation are discussed. Results: The available information suggests that indeed, inflammation resolution failure may be present in cachexia and therefore we speculate on possible mechanisms. Conclusions: We emphasise the importance of studying resolution-related mechanisms in cancer cachexia and propose the opening of a new venue for cachexia treatment. (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Percorsi di gender performance: fotografia tra arte e moda dagli anni Novanta ad oggi

My project explores and compares different forms of gender performance in contemporary art and visual culture according to a perspective centered on photography. Thanks to its attesting power this medium can work as a ready-made. In fact during the 20th century it played a key role in the cultural emancipation of the body which (using a Michel Foucault’s expression) has now become «the zero point of the world». Through performance the body proves to be a living material of expression and communication while photography ensures the recording of any ephemeral event that happens in time and space. My questioning approach considers the gender constructed imagery from the 1990s to the present in order to investigate how photography’s strong aura of realism promotes and allows fantasies of transformation. The contemporary fascination with gender (especially for art and fashion) represents a crucial issue in the global context of postmodernity and is manifested in a variety of visual media, from photography to video and film. Moreover the internet along with its digital transmission of images has deeply affected our world (from culture to everyday life) leading to a postmodern preference for performativity over the more traditional and linear forms of narrativity. As a consequence individual borders get redefined by the skin itself which (dissected through instant vision) turns into a ductile material of mutation and hybridation in the service of identity. My critical assumptions are taken from the most relevant changes occurred in philosophy during the last two decades as a result of the contributions by Jacques Lacan, Michel Foucault, Jacques Derrida, Gilles Deleuze who developed a cross-disciplinary and comparative approach to interpret the crisis of modernity. They have profoundly influenced feminist studies so that the category of gender has been reassessed in contrast with sex (as a biological connotation) and in relation to history, culture, society. The ideal starting point of my research is the year 1990. I chose it as the approximate historical moment when the intersection of race, class and gender were placed at the forefront of international artistic production concerned with identity, diversity and globalization. Such issues had been explored throughout the 1970s but it was only from the mid-1980s onward that they began to be articulated more consistently. Published in 1990, the book "Gender trouble: feminism and the subversion of identity" by Judith Butler marked an important breakthrough by linking gender to performance as well as investigating the intricate connections between theory and practice, embodiment and representation. It inspired subsequent research in a variety of disciplines, art history included. In the same year Teresa de Lauretis launched the definition of queer theory to challenge the academic perspective in gay and lesbian studies. In the meantime the rise of Third Wave Feminism in the US introduced a racially and sexually inclusive vision over the global situation in order to reflect on subjectivity, new technologies and popular culture in connection with gender representation. These conceptual tools have enabled prolific readings of contemporary cultural production whether fine arts or mass media. After discussing the appropriate framework of my project and taking into account the postmodern globalization of the visual, I have turned to photography to map gender representation both in art and in fashion. Therefore I have been creating an archive of images around specific topics. I decided to include fashion photography because in the 1990s this genre moved away from the paradigm of an idealized and classical beauty toward a new vernacular allied with lifestyles, art practices, pop and youth culture; as one might expect the dominant narrative modes in fashion photography are now mainly influenced by cinema and snapshot. These strategies originate story lines and interrupted narratives using models’ performance to convey a particular imagery where identity issues emerge as an essential part of fashion spectacle. Focusing on the intersections of gender identities with socially and culturally produced identities, my approach intends to underline how the fashion world has turned to current trends in art photography and in some case turned to the artists themselves. The growing fluidity of the categories that distinguish art from fashion photography represents a particularly fruitful moment of visual exchange. Varying over time the dialogue between these two fields has always been vital; nowadays it can be studied as a result of this close relationship between contemporary art world and consumer culture. Due to the saturation of postmodern imagery the feedback between art and fashion has become much more immediate and then increasingly significant for anyone who wants to investigate the construction of gender identity through performance. In addition to that a lot of magazines founded in the 1990s bridged the worlds of art and fashion because some of their designers and even editors were art-school graduates encouraging innovation. The inclusion of art within such magazines aimed at validating them as a form of art in themselves supporting a dynamic intersection for music, fashion, design and youth culture: an intersection that also contributed to create and spread different gender stereotypes. This general interest in fashion produced many exhibitions of and about fashion itself at major international venues such as the Victoria and Albert Museum in London, the Metropolitan Museum of Art and the Solomon R. Guggenheim Museum in New York. Since then this celebrated success of fashion has been regarded as a typical element of postmodern culture. Owing to that I have also based my analysis on some important exhibitions dealing with gender performance like "Féminin-Masculin" at the Centre Pompidou of Paris (1995), "Rrose is a Rrose is a Rrose. Gender performance in photography" at the Solomon R. Guggenheim Museum of New York (1997), "Global Feminisms" at the Brooklyn Museum (2007), "Female Trouble" at the Pinakothek der Moderne in München together with the workshops dedicated to "Performance: gender and identity" in June 2005 at the Tate Modern of London. Since 2003 in Italy we have had Gender Bender - an international festival held annually in Bologna - to explore the gender imagery stemming from contemporary culture. In few days this festival offers a series of events ranging from visual arts, performance, cinema, literature to conferences and music. Being aware that any method of research is neither race nor gender neutral I have traced these critical paths to question gender identity in a multicultural perspective taking account of the political implications too. In fact, if visibility may be equated with exposure, we can also read these images as points of intersection of visibility with social power. Since gender assignations rely so heavily on the visual, the postmodern dismantling of gender certainty through performance has wide-ranging effects that need to be analyzed. In some sense this practice can even contest the dominance of visual within postmodernism. My visual map in contemporary art and fashion photography includes artists like Nan Goldin, Cindy Sherman, Hellen van Meene, Rineke Dijkstra, Ed Templeton, Ryan McGinley, Anne Daems, Miwa Yanagi, Tracey Moffat, Catherine Opie, Tomoko Sawada, Vanessa Beecroft, Yasumasa Morimura, Collier Schorr among others.

Who can (not) be Greek? Citizenship, Identity and Belonging among youth of sub-Saharan African background in Athens

‘Who can be Greek?’ This was the question posed to the Greek society for the first time before the implementation of the Act 3838 in March 2010 which gave the right to access the Greek citizenship -under specific preconditions- to all children of legal migrants born or schooled in Greece. This change of the Nationality Code in order to include all those children was coincided by the economic crisis resulting into the rise of xenophobia, racism and extreme-right rhetoric. The outcome was the cancellation of the Act 3838 by the State Council in February 2013. Under this particular framework, the notions of identity and belonging formed among the youth of African background in Athens are explored. The ways those youngsters perceive not only themselves but also their peers, their countries of origin and the country they live in, are crucial elements of their self-identification. Researches have shown that the integration of the second generation is highly connected to their legal and social status. However, integration is a rather complex process, influenced and shaped by many variables and multiple factors. It is not linear; therefore, its outcomes are difficult to be predicted. Yet, I argue that citizenship acquisition facilitates the process as it transforms those children from ‘aliens’ to ‘citizens’. How these youngsters are perceived by the majority society and the State is one of the core questions of the research, focusing on the imposed dual ‘otherness’ they are subject to. On the one hand, they have to deal with the ‘otherness’ originating from the migrant status inherited to them by their parents, and on the other with the ‘otherness’ deriving from their different phenotypic characteristics. Race matters and becomes a means of discrimination against youth of African background who are perceived as inassimilable and ‘forever others’.

Design and development of the new composite-material mainplane of the Dallara T12 race car

Abstract (US) Composite material components design and production techniques are discussed in the present graduation paper. In particular, this paper covers the design process and the production process of a carbon-fiber composite material component for a high performance car, more specifically, the Dallara T12 race car. This graduation paper is split in two. After a brief introduction on existing composite materials (their origins and applications), the first part of the present paper covers the main theoretical concepts behind the design of composite material components: particular focus will be given to carbon-fiber composites. The second part of the present paper covers the whole design and production process that the candidate carried out to create the new front mainplane of the Dallara T12 race car. This graduation paper is the result of a six-months-long internship that the candidate conducted as Design Office Trainee inside Dallara Automobili S.p.A. Abstract (ITA) La presente tesi di laurea discute le metodologie progettuali e produttive legate alla realizzazione di un componente in materiale composito. Nello specifico, viene discussa la progettazione e la produzione di un componente in fibra di carbonio destinato ad una vettura da competizione. La vettura in esame è la Dallara T12. Il lavoro è diviso in due parti. Nella prima parte, dopo una breve introduzione sull’origine e le tipologie di materiali compositi esistenti, vengono trattati i concetti teorici fondamentali su cui si basa la progettazione di generici componenti in materiale composito, con particolare riguardo ai materiali in fibra di carbonio. Nella seconda parte viene discusso tutto il processo produttivo che il candidato ha portato a termine per realizzare il nuovo alettone anteriore della Dallara T12. La presente tesi di laurea è il risultato del lavoro di progettazione che il candidato ha svolto presso l’Ufficio Tecnico di Dallara Automobili S.p.A. nel corso di un tirocinio formativo di sei mesi.

Charakterisierung und funktionelle Analyse verschiedener Isoformen von Clusterin (Apolipoprotein J)

Clusterin (CLU), auch bekannt unter dem Namen Apolipoprotein J (ApoJ), wird von Zellen als hetreodimeres Glykoprotein exprimiert und in den extrazellulären Raum sezerniert. Es wird daher auch als sezerniertes CLU (sCLU) bezeichnet. Neben sCLU sind auch nicht-sezernierte Isoformen von CLU bekannt, die in der vorliegenden Arbeit erforscht wurden. Ziel dabei war es, die Expression, die Biogenese, sowie die Funktion dieser Proteine zu ergründen. Nicht-sezernierte CLU-Formen werden ausschließlich von Zellen exprimiert, die zuvor einer Stresssituation ausgesetzt wurden. Dies konnte insbesondere durch Kultur verschiedener Zelllinien bei erhöhter Temperatur oder durch Behandlung mit dem Proteasominhibitor MG 132 demonstriert werden, worauf neben sCLU auch 50 kDa bzw. 45 kDa große, nicht-sezernierte CLU-Proteine in geringen Mengen exprimiert wurden. Bezüglich der Biogenese dieser Proteine wurden mehrere Hypothesen bzw. Mechanismen diskutiert und in dieser Arbeit untersucht: alternative Translationsstartpunkte auf verschiedenen mRNAs, alternatives Splicing einzelner mRNAs sowie Retrotranslokation oder Mistranslokation von sCLU-Vorläuferproteinen. Um die Hypothesen eruieren zu können, musste zuerst eine Expressionsanalyse der bekannten CLU-mRNAs durchgeführt werden. Über 5’-RACE, semi-quantitative und quantitative PCRs wurde die Expression von vier CLU-mRNAs sowie deren Induktion auf Zellstress hin festgestellt. Variante 1 (BP211675) ist die dominante CLU-mRNA und macht über 99,5 % an CLU-mRNA in unbehandelten sowie in gestressten Zellen aus. Des Weiteren sind geringste Mengen der mRNA-Varianten 2 und 3 (NR_038335.1 und NR_045494.1) detektiert worden, deren Sequenzen sich lediglich in ihrem alternativen Exon 1 von Variante 1 unterscheiden. Schließlich konnte die Expression von Variante 1 [Δex2] festgestellt werden, welcher durch alternatives Splicing, i.e. Exon-skipping, das Exon 2 mit der ER-Signalsequenz-codierenden Region (SSCR) fehlt. HEK 293-Zellen, die transient mit je einer der rekombinanten CLU-mRNAs in Form rekombinanter cDNA transfiziert wurden, exprimierten neben großen Mengen sCLU auch geringe Mengen an den nicht-sezernierten CLU-Isoformen. Die anschließend durchgeführten in vitro Mutagenesen belegen, dass alle Isoformen ausgehend von distinkten Translationsstartpunkten aus synthetisiert werden. CLU1-449 (50 kDa) wird als prä-Proprotein von sCLU ausgehend von einem Startcodon auf Exon 2 unmittelbar vor der SSCR translatiert. Unter Zellstress-Bedingungen kann es zu einer Mistranslokation während der co-translationalen Translokation kommen, sodass Teile von CLU1-449 im Cytosol akkumulieren. CLU21-449 (50 kDa) wird ausgehend von einem CUG-Startcodon downstream der SSCR über interne Translationsinitiation gebildet. Analoges gilt für CLU34-449 (45 kDa), welches von einem AUG-Startcodon auf Exon 3 translatiert wird. CLU34-449 ist außerdem die einzige CLU-Form die von Variante 1 [Δex2] codiert wird. Somit konnten drei der in der Literatur postulierten Mechanismen zur Ent-stehung nicht-sezernierter CLU-Isoformen in gestressten Zellen verifiziert werden. Die Mistranslokation von sCLU-Vorläuferproteinen, welche entscheidend zum Auftreten der nicht-sezernierten CLU-Formen beiträgt, die Alternative Translationsinitiation an distinkten Startcodons sowie das alternative Splicing von CLU-mRNA-Variante 1. Weiterführende Experimente bestätigten, dass alle nicht-sezernierten CLU-Isoformen im Cytosol der Zellen lokalisiert sind und keine Glykosylierungen tragen. Somit konnte ein weiterer, in der Literatur kontrovers diskutierter Punkt bezüglich dieser Proteine geklärt werden. Abschließend wurde die physiologische Funktion der einzelnen CLU-Isoformen analysiert. Dabei zeigte sich, dass ausschließlich sCLU eine Chaperonaktivität zukommt, die es ermöglicht, durch Hitze denaturierte Zielproteine in Lösung zu halten. Diese Funktion konnte nicht für die cytosolischen Iso¬formen bestätigt werden. Weiterhin konnte keine Auswirkung einzelner CLU-Formen auf die intrinsische Apoptose oder auf den NF κB-vermittelten Signaltransduktionsweg festgestellt werden, obgleich entsprechende Einflüsse von anderen Arbeitsgruppen postuliert wurden. Die hier gemachten Beobachtungen werfen daher die Frage auf, ob den nicht-sezernierten, cytosolischen CLU-Isoformen überhaupt eine physiologische Funktion zukommt und stellen aktuelle Hypothesen bezüglich der Rolle von CLU bei pathophysiologischen Prozessen infrage.

The Space Race di Alex Latimer. Traduzione del romanzo di un autore sudafricano.

In the following thesis I present the book The Space Race from South African author Alex Latimer and my translation of some chapters, from English into Italian. Alex Latimer is an illustrator and author based in Cape Town, known mostly for his picture books for children, although his works also appear in magazines and advertisements. The Space Race is his first novel, but it immediately had a good reception amongst readers and critics. The author, his work and his novel The Space Race will be presented in depth in Chapter 1 of the thesis. Then, an overview on the South African fictional production will follow in Chapter 2, focusing mainly on the contemporary trends and trying to understand if and how The Space Race fits. Before presenting my translation and my reflections on the translating process itself, I will outline in Chapter 3 my general approach to the text and its translation, as well as explain the reasons why I chose those specific parts of the book. The original texts and their translations are presented in Chapter 4, preceded by a short introduction to better understand the position of the chapter in the plot and the elements of interests contained in it. A commentary on the translating process will follow in Chapter 5, about problems or just remarks on aspects of interest; also, further elements of complication in the text are described and my solutions presented. The thesis ends with a conclusion on the work done.

The performativity of nonviolent protest in South Asia (1918 - 1948)

This study seeks to address a gap in the study of nonviolent action. The gap relates to the question of how nonviolence is performed, as opposed to the meaning or impact of nonviolent politics. The dissertation approaches the history of nonviolent protest in South Asia through the lens of performance studies. Such a shift allows for concepts such as performativity and theatricality to be tested in terms of their applicability and relevance to contemporary political and philosophical questions. It also allows for a different perspective on the historiography of nonviolent protest. Using concepts, modes of analysis and tropes of thinking from the emerging field of performance studies, the dissertation analyses two different cases of nonviolent protest, asking how politics is performatively constituted. The first two sections of this study set out the parameters of the key terms of the dissertation: nonviolence and performativity, by tracing their genealogies and legacies as terms. These histories are then located as an intersection in the founding of the nonviolent. The case studies at the analytical core of the dissertation are: fasting as a method in Gandhi's political arsenal, and the army of nonviolent soldiers in the North-West Frontier Province, known as the Khudai Khidmatgar. The study begins with an overview of current theorisations of nonviolence. The approach to the subject is through an investigation of commonly held misconceptions about nonviolent action, such as its supposed passivity, the absence of violence, its ineffectiveness and its spiritual basis. This section addresses the lacunae within existing theories of nonviolence and points to possible fertile spaces for further exploration. Section 3 offers an overview of the different shades of the concept of performativity, asking how it is used in various contexts and how these different nuances can be viewed in relation to each other. The dissertation explores how a theory of performativity may be correlated to the theorisation of nonviolence. The correlations are established in four boundary areas: action/inaction, violence/absence of violence, the actor/opponent and the body/spirit. These boundary areas allow for a theorising of nonviolent action as a performative process. The first case study is Gandhi's use of the fast as a method of nonviolent protest. Using a close reading of his own writings, speeches and letters, as well as a reading of responses to his fast in British newspapers and within India, the dissertation asks what made fasting into Gandhi's most favoured mode of protest and political action. The study reconstructs his unique praxis of the fast from a performative perspective, demonstrating how display and ostentation are vital to the political economy of the fast. It also unveils the cultural context and historical reservoir of body practices, which Gandhi drew from and adapted into 'weapons' of political action. The relationship of Gandhian nonviolence to the body forms a crucial part of the analysis. The second case study is the nonviolent army of the Pashtuns, Khudai Khidmatgar (KK), literally Servants of God. This anti-imperialist movement in the North-West Frontier Province of what is today the border between Pakistan and Afghanistan existed between 1929 and 1948. The movement adopted the organisational form of an army. It conducted protest activities against colonial rule, as well as social reform activities for the Pashtuns. This group was connected to the Congress party of Gandhi, but the dissertation argues that their conceptualisation and praxis of nonviolence emerged from a very different tradition and worldview. Following a brief introduction to the socio-political background of this Pashtun movement, the dissertation explores the activities that this nonviolent army engaged in, looking at their unique understanding of the militancy of an unarmed force, and their mode of combat and confrontation. Of particular interest to the analysis is the way the KK re-combined and mixed what appear to be contradictory ideologies and acts. In doing so, they reframed cultural and historical stereotypes of the Pashtuns as a martial race, juxtaposing the institutional form of the army with a nonviolent praxis based on Islamic principles and social reform. The example of the Khudai Khidmatgar is used to explore the idea that nonviolence is not the opposite of violent conflict, but in fact a dialectical engagement and response to violence. Section 5, in conclusion, returns to the boundary areas of nonviolence: action, violence, the opponent and the body, and re-visits these areas on a comparative note, bringing together elements from Gandhi's fasts and the practices of the KK. The similarities and differences in the two examples are assessed and contextualised in relation to the guiding question of this study, namely the question of the performativity of nonviolent action.

Tradurre la saggistica: proposta di traduzione di un estratto di "The invisible history of the human race"

The aim of this dissertation is to propose the translation of four chapters from "The invisible history of the human race", an essay by the Australian author and journalist Christine Kenneally. This essay offers a non-systematic overview upon genealogy in connection to the idea of personal identity; above all, the author wants to persuade the reader that genealogy could be the perfect linking point between history and science, family lines and DNA. The translated chapters particularly concentrate on the reasons of the current underestimation of genealogy, which, according to Kenneally, lies in the Nazi’s distorted use of ancestry and in the exploitation of the idea of biological diversity in order to discriminate people. The dissertation is composed of four chapters. The first chapter consists in a concise analysis of the characteristics of the textual genre and in a theoretical introduction and approach to the translation of essays, where the main generic and essay-specific translation strategies are outlined. The second chapter presents a detailed illustration of the topics treated in the essay and particularly in the translated pages. The third chapter contains the translation and the fourth presents a systematic comment to the translation and to the choices made during the translation of the text.

Different disparities of gender and race among the thrombotic thrombocytopenic purpura and hemolytic-uremic syndromes

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) represent multiple disorders with diverse etiologies. We compared the gender and race of 335 patients enrolled in the Oklahoma TTP-HUS Registry across 21 years for their first episode of TTP or HUS to appropriate control groups. The relative frequency of women and white race among patients with TTP-HUS-associated with a bloody diarrhea prodrome and the relative frequency of women with quinine-associated TTP-HUS were significantly greater than their control populations. The relative frequency of women and black race among patients with idiopathic TTP and TTP-associated with severe ADAMTS13 deficiency was significantly greater than their control populations. The relative frequency of black race among patients who had systemic lupus erythematosus (SLE) preceding TTP was significantly greater than among a population of patients with SLE, and the relative frequency of black race among patients with other autoimmune disorders preceding TTP was significantly greater than their control population. No significant gender or race disparities were present among patients with hematopoietic stem cell transplantation-associated thrombotic microangiopathy, TTP associated with pregnancy, or TTP associated with drugs other than quinine. The validity of these observations is supported by the enrollment of all consecutive patients across 21 years from a defined geographic region, without selection or referral bias. These observations of different gender and race disparities among the TTP-HUS syndromes suggest the presence of different risk factors and may serve as starting points for novel investigations of pathogenesis.

Inactivation of the hypermethylated in cancer 1 tumour suppressor--not just a question of promoter hypermethylation?

The chromosomal region 17p13.3 is frequently deleted or epigenetically silenced in a variety of human cancers. It includes the hypermethylated in cancer 1 (HIC1) gene placed telomerically to the p53 tumour suppressor gene. HIC1 encodes a transcriptional repressor, and its targets identified to date are genes involved in proliferation, tumour growth and angiogenesis. In addition, HIC1 functionally cooperates with p53 to suppress cancer development. Frequent allelic loss at position 17p13.1 in human cancers often points to mutations of the tumour suppressor p53. However, in a variety of cancer types, allelic loss of the short arm of chromosome 17 may hit regions distal to p53 and, interestingly, without leading to p53 mutations. Furthermore, the neighbouring region 17p13.3 often shows loss of heterozygosity or DNA hypermethylation in various types of solid tumours and leukaemias. In line with this concept, Wales et al. described a new potential tumour suppressor in this region and named it hypermethylated in cancer 1 (HIC1). Further, it was shown that in the majority of cases hypermethylation of this chromosomal region leads to epigenetic inactivation of HIC1. A role for HIC1 in tumour development is further supported by a mouse model, since various spontaneous, age- and gender-specific malignant tumours occur in heterozygous Hic1+/- knockout mice. Furthermore, exogenously delivered HIC1 leads to a significant decrease in clonogenic survival in cancer cell lines. This review highlights the role of HIC1 inactivation in solid tumours and particularly in leukaemia development.

Vertical bias in neglect: A question of time?

Neglect is defined as the failure to attend and to orient to the contralesional side of space. A horizontal bias towards the right visual field is a classical finding in patients who suffered from a right-hemispheric stroke. The vertical dimension of spatial attention orienting has only sparsely been investigated so far. The aim of this study was to investigate the specificity of this vertical bias by means of a search task, which taps a more pronounced top-down attentional component. Eye movements and behavioural search performance were measured in thirteen patients with left-sided neglect after right hemispheric stroke and in thirteen age-matched controls. Concerning behavioural performance, patients found significantly less targets than healthy controls in both the upper and lower left quadrant. However, when targets were located in the lower left quadrant, patients needed more visual fixations (and therefore longer search time) to find them, suggesting a time-dependent vertical bias.