Chondroplasia, the development of cartilage-like characteristics in tendinous tissue, is a form of degeneration found in tendons including those of the rotator cuff. The molecular mechanism of its development is currently unknown. An examination of the features of the torn rotator cuff and the cartilage literature led to the identification of several potential drivers of chondroplasia including cell shape change/actin cytoskeleton and hypoxia. Lovastatin caused actin cytoskeleton disruption and promoted cartilage matrix deposition in the ATDC5 model. It was the most effective member of a panel of cytoskeletal inhibitors, increasing expression of the chondrocytic markers Sox5 and Sox9 and decreasing expression of COL1A1 and COL3A1 in primary human tenocytes. Its effects were dose dependent, reversible by mevalonate addition and long term treatment induced de novo expression of collagen II. Short term hypoxia upregulated VEGF-A and chondrocytic marker gene DEC1 expression but not other chondrocyte markers. Combination treatment with hypoxia did not enhance the effects of lovastatin. These data suggest that modulation of pathways that regulate the actin cytoskeleton and cell shape may alter tenocyte phenotype.

Desmosomes are intercellular junctions that anchor intermediate filaments to the sites of intercellular contacts. They are critical for maintaining the integrity of tissues that experience constant mechanical and structural stresses, like the skin and heart. Perturbation of desmosomal adhesion can lead to devastating epidermal and myocardial diseases. However, little is known about the regulators of desmosomes and the role of desmosomes in cell signalling events. Recent work has suggested that iASPP, an inhibitor of the p53 family of proteins, localises at the intercalated discs where desmosomes reside. However, its role at the desmosomes has remained elusive. Thus, in this thesis, it was investigated whether iASPP is a dual function protein that links desmosome adhesion to gene expression and if desmosome-related diseases develop in the absence of iASPP. iASPP was found to be a novel regulator of desmosomes, co-localising with them by physically interacting with the desmosomal components desmoplakin and K5 intermediate filaments. Loss of iASPP resulted in increased phosphorylation and solubilisation of desmoplakin, leading to the formation of K5 aggregates. This culminated in disrupted intercellular adhesion and enhanced cellular migration. Consistent with the role of iASPP in the maintenance of desmosomal adhesion integrity, focal palmoplantar keratoderma was observed in iASPP-deficient mice — a disorder often associated with desmosome dysfunction. This was accompanied by disrupted intracellular signalling, as exemplified by the disrupted expression of differentiation markers; an increase in the thickness of cell layers expressing differentiation marker K1 was noted, and K5 and K6 cells were ectopically expressed throughout the diseased palmoplantar epidermis. Impaired intercellular adhesion and migration had consequences for wound healing, as iASPP-deficient mice exhibited delayed wound closure. Furthermore, defects in eyelid closure in iASPP-deficient mice were found to be due to increased apoptosis. The localisation of apoptotic cells at the leading edge of the eyelid epidermis implied that apoptosis might have occurred due to a loss of cell-matrix or cell-cell contact, i.e. anoikis. Taken together, these results suggest that iASPP is involved in pathological (palmoplantar keratoderma), physiological (wound healing) and developmental processes (embryonic eyelid closure) through its regulation of desmosomes and their dynamics. Therefore, iASPP represents a new candidate gene in cutaneous disorders and could be implicated in a variety of epidermal and myocardial diseases.

Nearly all discussions of Hemingway and his work touch on the theme of masculinity, a recurrent theme in all of his works. Examinations of Hemingway and his relationship to masculinity have almost unanimously treated the author as a misogynist and a champion of violent masculinity. However, since the posthumous publication of The Garden of Eden in 1986, there has been much discussion of Hemingway’s uncharacteristic use of androgynous characters in the novel. Critics have taken this as a clue that Hemingway possessed a complex attitude regarding gender fluidity, but have failed to examine the constructions of gender and identity in his earlier fiction. By examining two of his earliest works, In Our Time (1925) and The Sun Also Rises (1926), I argue that Hemingway’s complex ideas about gender performance have been hidden just beneath the surface all along.

In recent years, there has been an undeniable shift in how we think about nonhuman animals. A growing philosophical literature on animal rights has encouraged a deep consideration of the moral status of animals, while scientific research has simultaneously confirmed the fact that many animals have complex cognitive, emotional, and social capacities that strongly mirror our own. Although there is still disagreement about what all this implies in terms of our responsibilities to animals, the idea that animals can experience physical or emotional pain or pleasure is the starting point and not the conclusion of the present inquiry. Many species of animals are sentient beings who possess a viewpoint from which they experience and act in the world around them - and hence may be said to be agential. My dissertation explores what it means for us to extend, conceptually and morally, agency to animals. I address this "extension of agency" predominantly from an aesthetic perspective, although in doing so I in no way intend to limit the range of related philosophical concerns. On the contrary; to extend agency to animals, I argue, calls for a revised understanding of our habitual spectatorial stances--how we look at animals. To grasp these stances, I investigate how animals have been looked at in literary works of art. Does the literature show our spectatorship to extend agency to animals or do we objectify them so as to deny their capacities as agents altogether? My dissertation focuses on excerpts from three significant works of literature--works by Nathanael West, Ernest Hemingway, and Leo Tolstoy--each of which stages a specifically athletic engagement involving animals, in this way bringing focus to the issue of our spectatorship. Each excerpt serves as philosophically illuminating material and as an exemplary case regarding humanity's willingness or refusal to extend agency to animals. I am particularly interested in the role of animals in human-engineered sports, and in how extending agency to animals in sports changes or ought to change the way we watch sports that involve animals. Within the philosophy of sport, the accepted approach has been to liken animals to sporting equipment or tools, and thus to make no substantive distinction between animal and non-animal sports. This, I argue, reflects a refusal to extend agency to animals, which has led also to an oversimplification and mischaracterization of sports involving animals in the first place. Nathanael West's The Day of the Locust takes up cockfighting, Hemingway's The Sun Also Rises centers around bullfighting, and Tolstoy's Anna Karenina includes a memorable, emotionally stirring, steeplechase episode. In addition to investigating what I refer to as the "extension of agency" to animals in these literary works, I revise some of the basic assumptions that have recently guided the burgeoning subfield of the philosophy of sports. I argue that we must acknowledge that there exists a fundamental difference between the modes of spectatorship that accompany sports that only involve humans, and those that involve animals. For to extend agency is to extend the moral domain to that or those who are "other" than ourselves. Once animals are introduced into a sport, they imbue the sport with all the aesthetic complexities that come with looking at an animal outside of sport: the unique exotic beauty of the animal body and its fitness to function, but also its vitality, wild autonomy, expressiveness, and reciprocity of gaze. This means that our interactions with animals, even in the case of organized sport or performance, are not purely aesthetic in a formal artistic sense; they are also expressive and communicative. The concept of the formal aesthetic that many employ when talking about art - the formal qualities that we attribute to the arts - is not sufficient to accommodate sports that involve animals and a spectatorship of animals. Animals are expressive, and this expressiveness is fundamental to correctly understanding our spectatorship of them. Animals are far more than our equipment. The aesthetic of animal sports must, I conclude, accordingly incorporate expressiveness and empathy, such that we see animals in fellowship with us as participants in sports. Extending agency to animals is the core concept of a morally inflected aesthetic of inter-subjectivity.

A graphical model is simply a representation of the results of an analysis of relationships between sets of variables. It can include the study of the dependence of one variable, or a set of variables on another variable or sets of variables, and can be extended to include variables which could be considered as intermediate to the others. This leads to the concept of representing these chains of relationships by means of a graph; where variables are represented by vertices, and relationships between the variables are represented by edges. These edges can be either directed or undirected, depending upon the type of relationship being represented. The thesis investigates a number of outstanding problems in the area of statistical modelling, with particular emphasis on representing the results in terms of a graph. The thesis will study models for multivariate discrete data and in the case of binary responses, some theoretical results are given on the relationship between two common models. In the more general setting of multivariate discrete responses, a general class of models is studied and an approximation to the maximum likelihood estimates in these models is proposed. This thesis also addresses the problem of measurement errors. An investigation into the effect that measurement error has on sample size calculations is given with respect to a general measurement error specification in both linear and binary regression models. Finally, the thesis presents, in terms of a graphical model, a re-analysis of a set of childhood growth data, collected in South Wales during the 1970s. Within this analysis, a new technique is proposed that allows the calculation of derived variables under the assumption that the joint relationships between the variables are constant at each of the time points.

Zugl.: Frankfurt, Main, Univ., Diss. / Literaturverz. S. 255 - 271

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This thesis is about the lives and civic engagements of Afghans in Germany and the UK. It shows how Afghans living in these two countries relate to Afghanistan, and to what extent they engage in transnational action aimed at promoting change there. In particular, it explores the emergence of diasporic communities and how members exercise agency as development actors in Afghanistan. The research rests on a qualitative case study conducted among Afghan populations in Germany and the UK. Semi-structured interviews and participant observation were primary methods of data collection. Relational sociology is used to capture emerging social identities, patterns of social organisation and forms of social engagement. A first notable finding is that Afghan populations abroad are fractured and cannot be seen as a united diaspora. People tend to coalesce in narrowly defined subgroups rather than under a shared national identity. Second, Afghanistan remains a crucial reference point, notwithstanding fragmented social organisation. Home country attachments tend to be tied to a desire for change and development in the country. Third, despite these shared concerns, transnational engagements are typically carried out by small groups and directed towards confined social spheres. Although people may take action in the name of an imagined Afghan community or an imaginary Afghanistan, this imagined community does not provide a basis for social mobilisation. Thus Afghans do not act as a cohesive diaspora. Fourth, transnational engagements are often a response to the specificities of the social environments in which people are embedded, notably their host countries. The findings show that a relational approach can specify how different dimensions of people’s social identities drive social action and are shaped in interaction with various elements of their social context. Such an actor-centred perspective helps to improve our understanding of how members of diasporas come to engage with their countries of origin.

In this paper, I analyze and compare the novel The Sun Is Also a Star by Nicola Yoon with the filmscript by Tracy Oliver for the 2019 movie adaptation. First, I demonstrate how the narrative in The Sun Is Also a Star deals with the literary ideas of fate and destiny and how scholars have defined the concepts. Secondly, I argue that the filmscript is a literary text that can be equated to the novel in a literary analysis of their narrative features. I claim that the narrative features of the novel and the filmscript embody fate and destiny in different ways because of the differences in their narrative situations and thought representations. I argue that the narrative situation of the novel, with its authorial narrator and narrative levels, embodies a relationship between fate and destiny as different perspectives are put into focus in the narration. However, the filmscript embodies these concepts as distinct because the narrative situation of the heterodiegetic narrator does not represent the same connectedness. I then maintain this argument as the filmscript in its thought representation and replacement of it with images and speech representation continues to portray the concepts as separate. In contrast, the thought representation of the novel embodies the relationship between the concepts because the thoughts represent connectedness and cause and effect. In my concluding remarks, I look at possible areas of future research.