Influence of the chemokine CXCL12 on the progression and the signaling in colorectal cancer

Das Chemokin CXCL12 (auch bekannt als SDF-1) ist ein kleines Protein (8-14) KDa, das in sechs Isoformen exprimiert wird (SDF-1α, SDF-1β, SDF-1γ, SDF- 1δ, SDF-1ε und SDF-1θ) von einem einzigen Gen, dass die Leukozyten-Wanderung regelt und variabel in einer Reihe von normalen und Krebsgeweben exprimiert wird.rnCXCL12 spielt verschiedene Rollen in der Tumorpathogenese. Es wurde nachgewiesen, dass CXCL12 das Tumorwachstum und die Malignität fördert, die Tumorangiogenese stärkt, sich an der Metastasierung beteiligt und zu immunsuppressiven Netzwerken innerhalb des Tumormikromilieus beiträgt. Daher liegt es nahe, dass der CXCL12/CXCR4-Signalweg ein wichtiges Ziel ist für die Entwicklung von neuartigen Krebstherapien.rnUm Licht auf die Rolle der Chemokin CXCL12 Splicevarianten in der Entwicklung von Krebs zu werfen und die mögliche physiologische Relevanz und ihre möglichen funktionellen Unterschiede bei Darmkrebs zu verstehen, haben wir alle CXCL12 Splicevarianten (alpha, beta, gamma, delta, epsilon und theta) in die kolorektalen Zelllinie SW480 und die Melanomzellinie D05 transfiziert und exprimiert.rnrnDiese Arbeit wurde erstellt, um die folgenden Ziele zu erreichen. Untersuchung der Rolle von CXCL12 Splicevarianten bei der Vermittlung von Tumorprogression, Adhäsion, Migration, Invasion und Metastasierung von Darmkrebs. Untersuchung, ob die CXCL12 Variantenwege ein wichtiges Ziel für die Entwicklung von Krebstherapien darstellen.rn• Um eine in vivo Mausmodell zu entwickeln, um die Rolle der CXCL12 Varianten im Rahmen des Tumorwachstums zu verstehen.rnrnUnsere Ergebnisse zeigen, dass:Der CXCL12 G801A Polymorphismus ist ein Low-Penetranz Risikofaktor für die Entwicklung von Darmkrebs. Der CXCL12-Gen-Polymorphismus rs1801157 ist mit dem T-Status (Tumor-node-Metastasen) assoziiert. Es gab keine Beziehung zwischen CXCL12-Gen-Polymorphismus rs1801157 und Fernmetastisen oder LN metastasen. Alle sechs CXCL12 Splicevarianten werden im Darmkrebs und in gesunder Kolon mucosa exprimiert. Die höchste Expression wird bei SDF-1alpha, dann SDF-1 beta gefunden. Alle sechs CXCL12 Varianten zeigen erhöhte Tumorzellproliferation in vitro. SDF-1beta, gefolgt von SDF-1alpha zeigte die größte Aktivität im Proliferationsassay.rn• Alle sechs CXCL12 Varianten induzieren die Tumorzelladhäsion.SDF-1beta dann SDF-1alpha zeigte die größte Aktivität im Rahmen des Adhäsionsassay. Alle sechs CXCL12 Varianten erhöhten die Zellmigration und Invasion von Tumorzellen in vitro. SDF-1theta und SDF-1epsilon 1theta zeigten die größte Aktivität, während die schwächste Aktivität mit SDF-1alpha und SDF-1beta beobachtet wurde. Alle sechs CXCL12 Varianten aktivieren Akt und (MAPK) Mitogen- acktivatedierte Protein kinase Wege und damit die Regulierung viele essentieller Prozesse in Tumorzellen, wie Proliferation, Migration, Invasion und Adhäsion. Es ist interessant festzustellen, dass AMD3100 die CXCL12 Splicevarianten inhibriert, die AKT-MEK-1/2-Phosphorylierung induzieren.rnDer Inhibitor AMD3100 unterdrückt stark die CXCL12 Varianten -delta, -epsilon und theta-und unterdrückt schwach CXCL12-gamma. während es keine signifikante Wirkung auf CXCL12-alpha und beta hatte. Es hat möglicherweise Auswirkungen auf mehrere große Signalwage in Bezug auf Proliferation, Migration und Invasions.rn• Es ist wichtig anzumerken, dass die Hemmung von CXCL12-Varianten durch AMD3100 einen der möglichen Ansaätze in der Krebstherapie darstellen kann.Wir schlagen vor, dass weitere Studien erwogen werden, die wir brauchen, um die biologische Aktivität dieser neuen CXCL12 Varianten bei verschiedenen Arten von Krebs klar zu verstehen.

Mythos und Mathematik : Hermann Brochs Roman "Die Schuldlosen" und seine Essays

„Natürlich habe ich mich [...] unausgesetzt mit Mathematik beschäftigt, umso mehr als ich sie für meine erkenntnistheoretisch-philosophischen Studien brauchte, denn ohne Mathematik lässt sich kaum mehr philosophieren.“, schreibt Hermann Broch 1948, ein Schriftsteller, der ca. zehn Jahre zuvor von sich selbst sogar behauptete, das Mathematische sei eine seiner stärksten Begabungen.rnDiesem Hinweis, die Bedeutung der Mathematik für das Brochsche Werk näher zu untersuchen, wurde bis jetzt in der Forschung kaum Folge geleistet. Besonders in Bezug auf sein Spätwerk Die Schuldlosen fehlen solche Betrachtungen ganz, sie scheinen jedoch unentbehrlich für die Entschlüsselung dieses Romans zu sein, der oft zu Unrecht als Nebenarbeit abgewertet wurde, weil ihm „mit gängigen literaturwissenschaftlichen Kategorien […] nicht beizukommen ist“ (Koopmann, 1994). rnDa dieser Aspekt insbesondere mit Blick auf Die Schuldlosen ein Forschungsdesiderat darstellt, war das Ziel der vorliegenden Arbeit, Brochs mathematische Studien genauer nachzuvollziehen und vor diesem Hintergrund eine Neuperspektivierung der Schuldlosen zu leisten. Damit wird eine Grundlage geschaffen, die einen adäquaten Zugang zur Struktur dieses Romans eröffnet.rnDie vorliegende Arbeit ist in zwei Teile gegliedert. Nach einer Untersuchung von Brochs theoretischen Betrachtungen anhand ausgewählter Essays folgt die Interpretation der Schuldlosen aus diesem mathematischen Blickwinkel. Es wird deutlich, dass Brochs Poetik eng mit seinen mathematischen Anschauungen verquickt ist, und somit nachgewiesen, dass sich die spezielle Bauform des Romans wie auch seine besondere Form des Erzählens tatsächlich aus dem mathematischen Denken des Autors ableiten lassen. Broch nutzt insbesondere die mathematische Annäherung an das Unendliche für seine Versuche einer literarischen Erfassung der komplexen Wirklichkeit seiner Zeit. Dabei spielen nicht nur Elemente der fraktalen Geometrie eine zentrale Rolle, sondern auch Brochs eigener Hinweis, es handele sich „um eine Art Novellenroman“ (KW 13/1, 243). Denn tatsächlich ergibt sich aus den poetologischen Forderungen Brochs und ihren Umsetzungen im Roman die Gattung des Novellenromans, wie gezeigt wird. Dabei ist von besonderer Bedeutung, dass Broch dem Mythos eine ähnliche Rolle in der Literatur zuspricht wie der Mathematik in den Wissenschaften allgemein.rnMit seinem Roman Die Schuldlosen hat Hermann Broch Neuland betreten, indem er versuchte, durch seine mathematische Poetik die komplexe Wirklichkeit seiner Epoche abzubilden. Denn „die Ganzheit der Welt ist nicht erfaßbar, indem man deren Atome einzelweise einfängt, sondern nur, indem man deren Grundzüge und deren wesentliche – ja, man möchte sagen, deren mathematische Struktur aufzeigt“ (Broch).

The Trauma Towers: Dimensions of Trauma in 9/11 Literature

The topic of this dissertation is the aspects of trauma and reaction to the traumatic experience that can be found in 9/11 literature. The research engages in a comparative analysis of five books that can be categorised as 9/11 literature, which means that the events of 9/11 are central in the novels and are a recurrent theme. The books have been written by authors of different nationalities: "Extremely Loud & Incredibily Close" by J. S. Foer, "Falling Man" by D. DeLillo, "Windows on the World" by F. Beigbeder, "Saturday" by I. McEwan and "The Reluctant Fundamentalist" by M. Hamid. The characters have either experienced the attacks personally or their lives have been largely influenced by the event. In either case, the protagonist has been traumatised by the tragedy. Therefore, in this study two different fields are fused together – the field of comparative literature and that of trauma studies.

La traduzione del romanzo per ragazzi Apache - Girl Warrior di Tanya Landman: Un incontro tra storia, genere e culture.

This dissertation deals with the translation into Italian of selected passages from the Young Adult historical novel Apache – Girl Warrior by English author Tanya Landman. The book was chosen after contacting Italian publisher Settenove, dedicated to preventing gender-based violence through children's books and essays. The novel, set in the second half of the Nineteenth Century, tells the story of Siki, a fourteen years old Native American girl who decides to become a warrior in order to avenge her family, killed by the Mexicans. The story also deals with the contact and conflict between Native Americans and white settlers during the so-called Apache Wars. Chapter I deals with Apache's genre; it consists in an overview of the historical novel form and its diffusion, both in Italy and in the English-speaking world. Typical features and themes are also dealt with in this chapter. Chapter II is dedicated to Apache's author. Landman's other works and her mission as a writer are taken into account, as well as the inspirations that led her to writing the novel and the process of research on American history it involved. This chapter also includes a comparison between Tanya Landman's and Louise Erdrich's works. In chapter III, Apache is compared to two well-known novels for children and young adults, The little house on the prairie and Caddie Woodlawn; the aim of this is to demonstrate how widespread misrepresentations about Native Americans are in mainstream literature. Chapter IV analyzes the novel and serves as an introduction to its translation, focusing on its plot, themes, characters and language, while chapter V presents the passages I've chosen to translate; their translation can be found later in the same chapter. In chapter VI, I comment on the choices made during the translation process; translation problems are divided into culture-specific, stylistic, semantic and linguistic.

`Faudrait-il le dire à vous, âEtranger?': enjeux intertextuels dans Vingt Ans de Nguyên Duc Giang

By reworking the thread of colonial initiation commonly found in French novels about Indochina, Nguyên Duc Giang's francophone novel Vingt ans (1940) draws upon novelistic and colonial intertexts to reflect upon the novel's role both in educating metropolitan readers and as a possible foundation for Franco-Vietnamese relations. Francophone and francophile, the young Vietnamese represented by this novel's Vietnamese narrator seem to exist outside of the colonial context; at the same time, a 'foreign' reader, presumably French, haunts the story through a dialogical, and unstable, relationship with the narrator. The latter provides the reader with familiar landmarks and immediately reshuffles them, thus transgressing the relationship that links him to the reader. In this way, the narrator reveals his ambiguity towards the reader and his/her culture, calling French hegemony into question.

The Nightmare of Actual Identity": Franco-Algerian Literature after Liberation"

In this thesis I examine the issues of postcolonial Algerian identity expressed in literature, and the difficulty of defining an Algerian identity independent of French influence. I analyze and contextualize three novels (Le Polygone etoile by Kateb Yacine,L'Amour, la fantasia by Assia Djebar, and Le Village de l'allemand ou le journal des freres Schiller) representative of their respective periods. I explore the evolution of expressions of identity through post-liberation Algeria. The years immediately following decolonization are marked by the effort to return to aprecolonial blank slate, an effort that Yacine cautions against. The 1980s and 1990s are most concerned with re-inserting Algeria into the Western historical discourse, and the most recent literature moves beyond decolonization to discuss the current Islamistchallenge and immigration. Among the pertinent issues are language, oral vs. written traditions, the often blatant absence of Algerians and women from the accounts in the French colonial archives, and, of course, the Self/Other binary. I have found that theserepresentative authors and texts use asynchronic time, fragmented narrative, re-written history, and expressions of violence in an attempt to cope with the colonial period and decolonization. I show that these authors provide a commentary on those who have triedto erase their French side, but with little success. Ultimately, though in different ways, each author writes that Algerians much accept their French past and move beyond it,rather than fighting their collective history.

The Assertion of Identity: Storytelling and Testimony in the Works of Edwidge Danticat

Haitian-American author Edwidge Danticat evokes the Haitian tradition of storytelling in many of her novels and short story collections. A tradition formulated by vodou religion and the amalgamation of African cultures, storytelling acts to entertain, educate and enlighten the people of Haiti. Additionally, her novels are often written in the context of traumatic events in Haitian history. While Danticat's works have been studied with focus on their depiction of storytelling and of trauma, little has been done on the restorative power that storytelling provides. In this thesis, I seek to examine the potential for Danticat's characters and works to create narratives that build community, present testimony, and aid traumatized individuals in recovery.

Fantasy Making the Invisible Visible: Liminality in Neil Gaiman's Neverwhere and American Gods

The purpose of this thesis was to examine the ways in which the fantasy genre is ideally positioned for discussing social issues, such as invisibility and liminality. Elements associated with invisibility, such as poverty, homelessness, and alienation, were explored within two novels by Neil Gaiman: Neverwhere and American Gods. Gaiman's application of these elements within the fantasy genre were juxtaposed with samples from other genres, including Plato's 'Parable of the Cave' and Jennifer Toth's The Mole People. Another aim was to contrast Gaiman's use of the 'beast in the sewer' metaphor with previous renditions of the myth, demonstrating how fantasy, paradoxically, offers a unique and privileged view of reality.

Psychological Real Estate: Fractured Female Identity in the Victorian Novel

"Psychological Real Estate: Fractured Female Identity in the Victorian Novel" examines the use of domestic space in three Victorian novels, Charlotte Bronte's Jane Eyre (1847), Mary Elizabeth Braddon's Lady Audley's Secret (1862), and George Eliot's Middlemarch (1871-2). Because Victorian gender identity was conceived of in spatial terms, this thesis explores how the three female authors use complicated domestic environments to engage the problem of conventional Victorian femininity. In the Victorian mindset, a woman's place is confined to the home, or private sphere; however, even the private sphere is intruded upon by public spaces. Expected to conform to the Victorian formulation of femininity in public spaces within the home, women had only their private spaces to cultivate the unique, individualistic aspects of their selves. This thesis explores the ways in which the female protagonists negotiate these gender encoded spaces to argue that because Victorian women had to maintain separate and often disparate identities within domestic space, their identities became problematically fractured. Additionally, in each of these texts, the authors use the failure or loss of the estate, the structure which rigidly upholds the gendered binaries, to expose the harm such fracturing identity formulation caused for Victorian society as a whole. This thesis concludes by examining the final residences of the female characters and arguing that the authors use these final private spaces to assert more feminist re-envisionings of their society's construction of femininity.

Harry Potter and the Theory of Things

This thesis investigates the boundaries between body and object in J.K. Rowling’s Harry Potter series, seven children’s literature novels published between 1997 and 2007. Lord Voldemort, Rowling’s villain, creates Horcruxes—objects that contain fragments of his soul—in order to ensure his immortality. As vessels for human soul, these objects rupture the boundaries between body and object and become “things.” Using contemporary thing theorists including John Plotz and materialists Jean Baudrillard and Walter Benjamin, I look at Voldemort’s Horcruxes as transgressive, liminal, unclassifiable entities in the first chapter. If objects can occupy the juncture between body and object, then bodies can as well. Dementors and Inferi, dark creatures that Rowling introduces throughout the series, live devoid of soul. Voldemort, too, becomes a thing as he splits his soul and creates Horcruxes. These soulless bodies are uncanny entities, provoking fear, revulsion, nausea, and the loss of language. In the second chapter, I use Sigmund Freud’s theorization of the uncanny as well as literary critic Kelly Hurley to investigate how Dementors, Inferi, and Voldemort exist as body-turned-object things at the juncture between life and death. As Voldemort increasingly invests his immaterial soul into material objects, he physically and spiritually degenerates, transforming from the young, handsome Tom Marvolo Riddle into the snake-like villain that murdered Harry’s parents and countless others. During his quest to find and destroy Voldemort’s Horcruxes, Harry encounters a different type of object, the Deathly Hallows. Although similarly accessing boundaries between body/object, life/death, and materiality/immateriality, the three Deathly Hallows do not transgress these boundaries. Through the Deathly Hallows, Rowling provides an alternative to thingification: objects that enable boundaries to fluctuate, but not breakdown. In the third chapter, I return to thing theorists, Baudrillard, and Benjamin to study how the Deathly Hallows resist thingification by not transgressing the boundaries between body and object.

Sexing the Male: Manifestations of Masculinity in Jane Eyre, Wuthering Heights, and Villette

Abstract: This project considers Emily and Charlotte Brontë's constructions of masculinity in Jane Eyre, Wuthering Heights, and Villette. There is a vast proliferation of scholarship focusing on gender in the Victorian Era, but as much of this criticism focuses on women, the analysis of heterosexual masculinity in these novels provides a unique perspective on the complexities involved in gender constructions during this period. Masculine identity was in a transitory state in the early nineteenth century, as Romantic values were replaced by Victorian conceptions of masculinity, largely influencing the expectations of men. This paper argues that based on an understanding of femininity and masculinity as defined in relation to each other, the Brontë heroes look to the female characters as a source of stability to define themselves against, constructing a stagnant feminine role to frame an understanding of how masculinity was changing. The female characters resist this categorization, however, never allowing the men to fully classify them into stable feminine roles, which leads both shifting gender roles to intertwine and collapse in the novels, undermining any conceptualization of a stable or universal understanding of gender. The paper considers the role of masculinity based in class, relationships with women, and the understanding of sexual passion, to argue that the Brontës' portrayal of men emulates the anxieties surrounding the shift from Romantic to Victorian values of manliness, ultimately rejecting any stable definition of the nineteenth-century man.

Radical Verses: Aku Päiviö's Literary Influence on the Finnish Working-Class

Aku Päiviö was one of the most influential voices of the Finnish labor movement in North America—a poet who also wrote plays and novels, and an editor who worked for a variety of newspapers across the United States and Canada. During the height of the Finnish socialist movement from around 1904-1916, Päiviö published a number of poems that identified with the actions and ideologies of the working-class. He also edited for newspapers such as Kansan Lehti and Raivaaja, further extending his literary reach. Despite his prodigious publications and influence, however, little of Päiviö’s writing has been translated into English. This paper celebrates Päiviö’s legacy with some English translations of his poems, specifically those commemorating the 1913-14 Michigan Copper Strike, and illuminates how various thematic and structural relationships in these poems relate to the ideologies and movements of the time.

Schul-, Praxis- und habituelles Herrschaftswissen. Bildung ländlicher Eliten mit Blick auf die korporative Selbstverwaltung in der frühmodernen Schweiz (18. und 19. Jahrhundert)

Knowledge taught at schools, everyday skills and practical know-how. The relevancy of formation for local elites and the corporative self-government of Early Modern Switzerland Daniel Schläppi, Bern There were different kinds of rural elites in Early Modern Switzerland. The diverse parts of the country developed in very dissimilar ways politically and economically. Some regions were dominated by traditional types of agriculture. Some territories were ruled by major cities. In some of the rural Cantons like Uri, Schwyz, Unterwalden, Glarus and Zug a political elite took control over generations and practiced a cultural lifestyle comparable to the famous aristocracies in cities like Bern, Basel, Freiburg, Luzern, Solothurn and Zurich. Intense proto-industrialization formed a completely different sort of elite with strong affinities to industry and trade in other regions. Meanwhile the habitants of the valley close-by stayed farmers like their ancestors (like in Appenzell). In the most conservative parts of the country mercenary business played an important role till the very end of the Ancien Regime and even furthermore. In summery the variety of historical circumstances caused heterogeneous elites all over. Such socio-political diversity provoked a variety of educational backgrounds. I an academic understanding of the term we know only little about literacy in local rural elites. But there is strong evidence that a lively culture of reading and story-telling existed. This means that even simple countrymen seem to have been in possession of some books. The organisation and capacity of the school system is subject of controversial discussions among up to date researchers. The state of research makes us suppose that the people designed to political careers learned their essential skills not only in school but also in everyday life or on the job. Based on the fact that every community and countless public corporations managed their affairs by their own it’s evident that the local elite’s key-players had a large repertoire of techniques and skills like writing, calculating, strategic thinking or knowledge of oral tradition, old usage or important rituals. Unfortunately the historical actors left not that many sources that would tell us precisely how knowledge and know-how were transferred in former times. Hardly any private account books or common correspondence have been conserved. But a huge bunch of sources that originate from corporative self-administration shows us that most local elites were well-educated and had the necessary skills anyway. Above all other sources like for instance the «Topographische Beschreibungen» (topographic descriptions) that were initiated by the «Ökonomische Gesellschaft» of Berne since the sixties of the 18th century provide an insight into pre-modern classrooms. More important information on the historical formation-reality can be gained by the autobiography of the famous poor peasant Ulrich Bräker (1735‒1798) or some of the novels by Albert Bitzius (1797‒1854, better known as Jeremias Gotthelf). The pedagogic writings by Johann Heinrich Pestalozzi (1746‒1827) and the influences by his mentors Johann Rudolf Tschiffeli (1716‒1780) or Philipp Emanuel von Fellenberg (1771‒1884) are quite illustrative as well.

"Fact versus Fiction – How paratextual information shapes our reading processes"

Our life is full of stories: some of them depict real-life events and were reported, e.g. in the daily news or in autobiographies, whereas other stories, as often presented to us in movies and novels, are fictional. However, we have only little insights in the neurocognitive processes underlying the reading of factual as compared to fictional contents. We investigated the neurocognitive effects of reading short narratives, labeled to be either factual or fictional. Reading in a factual mode engaged an activation pattern suggesting an action-based reconstruction of the events depicted in a story. This process seems to be past-oriented and leads to shorter reaction times at the behavioral level. In contrast, the brain activation patterns corresponding to reading fiction seem to reflect a constructive simulation of what might have happened. This is in line with studies on imagination of possible past or future events.