VictorJuiz/thesis huggingface dataset:
Structural studies of Norrin dependent Wnt/beta-catenin signaling

Norrin is a secreted cystine-knot growth factor that plays critical roles in vascular development in the brain, retina, and cochlea, as well as the uterus. Although Norrin is unrelated to the lipid-modified morphogens Wnts, Norrin activates the canonical Wnt/β-catenin pathway by binding to receptor Frizzled4 cysteine-rich domain (Fz4-CRD) and co-receptors of low density lipoprotein receptor related protein 5/6 ectodomain (Lrp5/6-ECD) in conjunction with Tetraspanin-12 (Tspan-12). Like Wnts, Norrin has limited extracellular diffusion properties as a result of associating with heparan sulfate proteoglycans (HSPGs). Mutations lead to inherited disordered retinal vascularization diseases such as Norrie disease, familial exudative vitreoretinopathy and coats' disease. However, the molecular mechanism of how Norrin initiates signalling by engagement with Fz4, Lrp5/6, and HSPGs has remained unresolved.
Here, novel strategies for protein production of recombinant human Norrin and Fz4-CRD as well as the complex are developed. The crystal structures of Norrin and its complex with Fz4-CRD, plus complex bound with the heparin mimic sucrose octasulphate, and unliganded structures of Fz4-CRD are presented. These structural data together with biophysical and cellular assays not only reveal the Fz4 and Lrp5/6 binding sites on distinct patches of the Norrin surface, but also indicate the HSPGs binding site on Norrin and Fz4-CRD as well as providing a framework to explain numerous disease-related mutations. Structural comparison with Xenopus Wnt8 in complex with mouse Fz8-CRD provides molecular insights for our understanding of ligand-receptor binding specificity and promiscuity, which has important implications for developing therapeutic strategies against Norrin dependent retinal disorders, and cancers caused by abnormal Wnt signaling.

Keywords: proteoglycan binding
blood brain barrier
cystine-knot growth factor
Wnt signalling
Norrie disease
Familial exudative vitreoretinopathy
Crystal structure
retinal genetic disease
vascularization
angiogenesis
Advisor: Jones, E
Being white

This thesis is concerned with the ways in which whiteness and authenticity are manifested within contemporary visual culture in South Africa. The project begins as an artistic inquiry grounded in autobiography, which becomes an elaborate self-portrait narrated from the distance of the third person. My practice aims to address the trajectories that I am unable to articulate through my theoretical analysis. Through a process of solvent release printing, I explore the dualities of my own identity as African and white in an attempt to counteract the view that one negates the other. Part I attempts to provide an archive-able record of this practice.
Part II shows that a long history of dichotomous art-historical practice has resulted in differentiated artistic pressures for black and white South African artists. I discuss the development of platforms that have contributed to the shifting of such classificatory trends without dissolving them completely, namely the first and second Johannesburg Biennales, Africus (1995) and Trade Routes (1997). In doing so, I trace how these events have troubled such stereotypes. Whiteness is identified as the overriding factor which allows the dominant discourse of Western- and Euro-centric ideals to remain prioritised. Brett Murray and Minnette Vári are discussed as examples of white South African artists who problematise whiteness by addressing racial fluidity, belonging, authenticity and identity.
The theme of autobiography is reintroduced in the conclusion, where I argue that my own practice could be seen to mirror the strategies that each artist has employed to subvert their whiteness, and to build a case for accessing a multiple identity that is African in its ability to be diverse. I conclude that it is ultimately the artists’ performative use of their own bodies which allows them to discuss issues of representation without falling into the ideological position of the coloniser.

Advisor: Malcolm, B
Maria, C
The Englische Komoedianten in German-speaking states, 1592-1620

From the beginning of the Reformation until the outbreak of the Thirty Years' War, there was brisk and far-reaching cultural interaction between England and German-speaking states. Towards the end of this period, the Englische Komoedianten (EK) - itinerant troupes of English actors and musicians - began a century of touring German courts and cities, with remarkable though neglected success. This thesis is a study of the first, truly English, phase of those tours, 1592-1620, arguing that the EK deserve recognition for their achievement as mediators between English and German cultures in their own right, not because of the remote possibility that they may have been the first to take Shakespeare to Germany.
The thesis concentrates on a collection of EK plays, Engelische Comedien vnd Tragedien (1620), which contains a representative selection of their comedies, tragedies and "Singspiele", the genre associated with their clown, Pickelhering, the figure with whom they were most closely associated in the popular mind.
There are five main sections: 1) A survey of scholarly attitudes to the EK; 2) A study of Anglo-German cultural relations in the sixteenth century; 3) The EK on tour, and their dealings with courts, cities and the church; 4) A study of four versions of perhaps the most popular of all fictions in Germany in the sixteenth century, Fortunatus, and his magic gifts, from its origins in the Augsburg Volksbuch (1509), through Hans Sachs (l553), Thomas Dekker (1599), to the EK themselves (1620): this is the one work which crosses from Germany to England and then back again during the century, changing and developing at each step; and 5) a detailed analysis of the 1620 collection of plays, according to questions of recognisability, socio-political immediacy, generic impurity and minimal staging. A brief investigation of English influences on Andreas Gryphius concludes the work.
Teachers' unions, education reform, and the irresistible force paradox: a comparative analysis of Finland, Switzerland, and the United States

In education policy, the irresistible force paradox—what happens when an irresistible force meets an immovable object?—resonates with many characterisations of the dynamics of education reform and the role of teachers’ unions in reform processes. According to many theories of teachers’ unions in the United States, the paradox is resolved in favour of the immovable object: strong teachers’ unions are alleged to block necessary reforms, hampering school effectiveness and efficiency. This research tests these claims about teachers’ unions, and their impact on reform outcomes—particularly, performance-related pay. Despite teachers’ unions’ supposed opposition to performance-related pay (PRP), there are a number of cases—both within and beyond U.S. borders—where PRP has been implemented. By exploring some of these ‘exceptional’ cases, this research outlines the conditions under which reform is likely to occur, and a more specific explanation of reform ‘failure’. It finds that, though education reform is often portrayed as a power struggle between reform proponents and opponents, there are multiple pathways through which reform may occur. Overpowering unions might be one route, but reform can also be secured through cooperation and compromise. These insights have significant implications for theories of teachers’ unions’ strength, preferences, and policy impact. The findings demonstrate that the insufficiency of existing theoretical accounts. Neither union preferences nor power are simple, monolithic, or predictable, and teachers’ unions do not and cannot block reform at all times and in all places. Beyond theory, these findings carry weighty implications for practitioners regarding the role of unions in public policy decision-making.

Keywords: education politics
teachers unions
education reform
Advisor: Seeleib-Kaiser, M
Two problems in dynamic ethics

Time raises a host of difficult ethical questions. This doctoral project focuses on two:
1. How are "static" comparative principles (e.g. equality, desert) to be understood over time? (The Problem of Fairness & Time)
2. How might separation (in time) between agents, objects, and threats affect claims to the relevant resources? (The New Problem of Temporal Distance)
My work begins with a simple observation: our prima facie intuitions about the value of simple distributions change depending on whether such cases are presented as static (occurring at one time) or dynamic (extended over time). Further examination of more complicated distributions leads to the proposal of a new theory, Weighted Progressive Egalitarianism. This theory has two features: only past-regarding complaints matter (a scope restriction), and a comparative complaint between persons located at a great temporal distance matters less than a complaint between contemporaries (a weighting restriction).
This theory provides one plausible answer to the first question, the Problem of Fairness & Time. The evaluation of this theory relies on and reveals some non-standard answers to the second question, the New Problem of Temporal Distance. I conclude by arguing that the theory’s application to a few puzzles in population axiology merits further investigation.

Keywords: ethics
egalitarianism
equality
population axiology
desert
temporal distance
intergenerational justice
distributive justice
comparative desert
inequality
intergenerational
time
Advisor: Broome, J
Britain's contribution to détente: the Conference on Security and Cooperation in Europe, 1972-1975

This thesis examines Britain’s role in the Conference on Security and Cooperation in Europe (CSCE). Based on multi-archival research and interviews with key diplomats, it presents the first in-depth study of Britain’s involvement in the negotiations leading up to the Helsinki Final Act of 1 August 1975. It draws on Marc Trachtenberg’s notion of the ‘constructed peace’, and Alexander Wendt’s concept of ‘cultures of anarchy’ to elucidate how the rapprochement process at once stabilised and transformed the East-West conflict. This forms the theoretical framework of the thesis.
The thesis revises the interpretation of détente as a status quo project driven by the imperatives of ‘Realpolitik’. Rather, different conceptions of stability and change challenged each other during the Helsinki talks. British diplomacy and the Final Act to which it contributed in fact linked the consolidation of the status quo to an ultimately transformative agenda that was infused with liberal ideas such as human rights. Realpolitik blended with Moralpolitik.
To develop this argument, the thesis’ narrative first assesses Britain’s role in the early days of détente politics in the 1950s and 1960s. It then traces Britain’s role in the three main phases of the Helsinki process: the transition from bilateral to multilateral détente (1970-1972); preliminary talks (1972-1973); official negotiations (1973-1975). The British were defensive détente sceptics at the beginning of this process, but became ambitious and positive contributors over the course of the talks.
The thesis thus argues that London played a significant part in the CSCE. British foreign policymakers were initially architects of the Cold War, but then early and active proponents of détente until the mid-1960s, when their continental partners adopted a more proactive approach. London was to return to the forefront of détente diplomacy when the CSCE process got under way. Its involvement in the CSCE also marked an important step in Britain’s own transformation into a European middle power. The multilateralisation of détente coincided with Britain’s integration into the European Community, providing a propitious environment in which London’s negotiators acted with determination and skill, thus reasserting their country’s influence despite its continuing relative decline.

Keywords: diplomacy
negotiations
constructed peace
Conference on Security and Cooperation (CSCE)
Cold War
detente
UK foreign policy
Advisor: Deighton, A
Politics, propaganda and public opinion in the reigns of Henry III and Edward I

This thesis traces the way in which the growing political consciousness of the English nation in the thirteenth century led the king to pay more attention to public opinion, and considers the arguments he used to justify his policies, and in particular his military undertakings, before a wider public audience.
The development of such political propaganda began during Henry Ill's reign. Yet he felt little need to explain his policies until this increasingly unrealistic position was exposed during 1258-65, when the barons made strenuous and successful attempts to exploit public opinion. Edward I probably learnt much from his father's experience, and during his reign took considerable care to explain how his wars were in the interests of the realm. The traditional means of communication and the arguments put across both underwent considerable development as a result.
Much of the material for this study is in print. The king's arguments can be established from the writs entered on the chancery rolls, supplemented by the accounts of the chroniclers, while the outline of the barons' arguments in 1258-65 can be established from the same sources. Bishops' registers and the memoranda rolls provide further information towards the end of the century.
Throughout an attempt has been made to show how the king's claims and arguments were viewed, which is not particularly easy. The main sources for public opinion, the chronicles, supplemented by political songs, reflect mainly the views of literate churchmen, and the opinions of the laity can be ascertained only indirectly. Yet the picture which emerges is of an increasingly politically conscious nation following the main political events with interest, and able to judge the merits of the king's arguments for itself.
Mating behaviour and female mate choice in the Harvest mouse (Micromys minutus)

The harvest mouse (Micromys minutus) is Britain’s smallest rodent, and one of its least‐studied mammals. Mounting concerns over the status of its British populations highlights the paucity of information about this species, not least about different aspects of its behaviour. I study the mating behaviour of the harvest mouse, focusing on female mate choice, and specifically on the effect familiarity with the male has on the female’s mating preference.
In order to isolate the role of familiarity on female mate choice, I conducted a controlled choice experiment, in which the female had a choice between two tethered males ‐ one familiar and one unfamiliar to her. The results support the prediction that female harvest mice prefer familiar males over unfamiliar ones when they are in oestrus. Results also reveal that females spend more time in proximity to unfamiliar males when they are not in oestrus, and that the difference in the body weight of the males affects the strength of their response.
A more naturalistic experiment was also set up, in which a female and two males ‐ again one familiar and one unfamiliar – were allowed to interact unhindered. This setup allowed the recording of full mating cycles, including copulations. These experiments provide descriptive information about both inter‐ and intra‐sexual interactions surrounding mating. Dominance relations between the two males were very clear cut and the female mated with the dominant male, and only with him. Familiarity did not seem to affect the female’s mating preference.
In summary this study shows that female harvest mice prefer familiar males over unfamiliar ones and that male familiarity and dominance interact to influence female mate choice. The study also provides background information about the harvest mouse’s mating behaviour and intra‐male interactions with potential significance for the understanding of other aspects of the natural history of this poorly studied species.

Keywords: mating behaviour
female mate choice
micromys minutus
behavioural ecology
harvest mouse
familiarity
Advisor: Macdonald, D
Imaging neuroinflammatory processes with USPIO-MRI

This thesis examines the utility of USPIO-MRI to provide a tool of tracking macrophage recruitment to sites of neuroinflammation within the CNS. Recruited macrophages and microglia resident in CNS tissue play a key role in the pathophysiology of a number of neuroinflammatory diseases such as neuropathic pain and multiple sclerosis. Under activated conditions, microglia and macrophages will phagocytose invading cells and CNS debris. It has been shown that ultrasmall superparamagnetic particles of iron oxide (USPIO), such as Sinerem, injected systemically, are engulfed by macrophages, which in turn migrate to sites of tissue injury. USPIOs can be visualised as a distinct reduction in signal intensity on T2* weighted MR images. However, there are still some issues regarding the distinction between iron-laden recruited macrophages and the entry of free iron across a permeable blood brain barrier (BBB) in disease cases. Hence, it was shown that intravenously injected Sinerem is cleared from the peripheral circulation within 24 hours, indentifying this as a time point as suitable for MCP-1 injection. Data showed that free USPIO can be visualised in the brain and that there is a linear relationship between Sinerem concentration and T2* signal intensity changes.
MCP-1 induces macrophage recruitment to the site of microinjection and causes BBB breakdown at between 3 and 4 hours. In particular it was shown that T2* signal intensity changes are seen, in the presence of an intact BBB, as a result of Sinerem laden macrophages. This finding was verified by the co-localisation of ED-1 positive cells and Prussian blue positive regions. It was demonstrated that there is a strong correlation between T2* signal changes and the number of macrophages. This demonstrates that USPIO-MRI can be used to characterise macrophage infiltration in neuroinflammation in the presence of an intact BBB.

Keywords: Microglia
Macrophages
Magnetic Resonance Imaging
Blood Brain Barrier
MRI Contrast Agents
Advisor: Sibson, N
Tracey, I
Ultrasound parametric imaging and image analysis for breast cancer characterisation and treatment monitoring

Breast cancer research based on medical ultrasound has traditionally focused on providing early diagnosis and breast cancer classification/characterisation. However, with the advances in cancer therapy treatments and innovations in cancer drug developments, developing methods for treatment monitoring is becoming ever more important. In particular fibrotic change in breast cancer is a common after-effect that accompanies successful breast cancer chemotherapy treatment where breast tumour cells are eradicated and replaced by fibrous tissue. As a result, the ability to monitor fibrotic changes can be used to indicate the effectiveness of chemotherapy treatments. Ultrasound spectral parametric imaging is a method that looks at the information embedded in the frequency/spectral domain of ultrasound RF signals and can be used to characterise tissue ultrasound backscattering properties. In this thesis ultrasound spectral parametric imaging is first applied to characterise breast fibrosis and its efficacy for monitoring breast cancer neoadjuvant chemotherapy treatment is subsequently investigated in a pilot study. The pilot study suggests that an increase in ultrasound spectral intercept is able to indicate fibrotic changes before and after treatments. These encouraging results suggest further work is considered to determine the suitability for monitoring intermediate changes. As histopathology images are considered as the gold standard in breast cancer pathology, ultrasound parametric images need to be studied and compared against histopathology so information provided in ultrasound parametric images can be better understood. A new registration method is shown to improve the alignment of ultrasound parametric images and histopathology images that facilitates the comparison between the images. The registration method is based on the coherent point drift (CPD) algorithm and the thin plate spline (TPS) method. All of the results show that ultrasound spectral parametric imaging is a promising tool for providing further understanding of breast cancer changes during therapy, which in turn will lead to improved breast cancer treatment monitoring and planning.

Keywords: PARAMETRIC IMAGING
ULTRASOUND IMAGING
IMAGE REGISTRATION
BREAST CANCER
CANCER TREATMENT MONITORING
Advisor: Noble, J
Struggling to belong: nativism, identities, and urban social relations in Kano and Amsterdam

The research problem of this thesis is to explore the effects of top-down, bureaucratic definitions of belonging and social identity on urban social relations. More specifically, the thesis analyses the ways in which the nativist categorisations of indigeneity in Kano and autochtonie in Amsterdam can help to understand the tensions between ethnic groups in these two cities. Methodologically, the study is designed as a least-similar, comparative exploration and uses mixed qualitative and quantitative methods in its case studies of Kano and Amsterdam. Theoretically, this study uses identity cleavages and identification as the mediators between policy categories and social relations. It combines social-psychological, historical, and institutional theories to link bureaucratic nativism to ethnic identities and, finally, to conflictual (or ‘destructive’) interethnic relations. The resulting theoretical argument of the thesis is that nativist policy categorisations are likely conducive to antagonism, avoidance, and conflict between groups defined as ‘natives’ and ‘settlers’.
The central finding of the thesis is that both in Kano and in Amsterdam, indigeneity and autochtonie have entrenched a primordial and competitive (or ‘exclusionary’) notion of ethnic identities and have thus been conducive to interethnic antagonism, avoidance, and conflict. Introduced at a time of rapid immigration, social change, and persistent horizontal inequalities, the two top-down policy categories came to redefine urban belonging in Kano and Amsterdam. As a result, previously apolitical ethnic boundaries between ‘natives’ and ‘settlers’ became politicised, connected to exclusionary definitions of religion and class, and ranked on the basis of their claim to a primordial ‘native’ status - that is, their status as historical ‘first-comers’ in their place of residence. The categorisation and group positioning effects of nativism have, therefore, intensified the urban struggle to belong in Kano and Amsterdam. At the same time, however, the thesis underlines that ethnic conflict in Kano and Amsterdam is limited, partly because nativist forms of belonging are continuously challenged by, for example, inclusive multiculturalism in Kano and urban citizenship in Amsterdam.

Keywords: categorisation
ethnicity
identity
nativism
Netherlands
Nigeria
Kano
Amsterdam
integration
conflict
minorities
urban governance
Advisor: Mustapha, A
Lloyd, C