VictorJuiz/thesis huggingface dataset:
Cytokine and growth factor regulation of murine macrophage scavenger receptor expression and function

The macrophage (Mφ) foam cell in the atherosclerotic plaque microenvironment is subjected to cytokines and growth factors secreted by smooth muscle cells (SMCs), endothelial cells (ECs), platelets and lesional Mφ themselves. This thesis examines the effects of some of these soluble factors on a murine macrophage membrane molecule, the macrophage scavenger receptor (MSR), considered pivotal in foam cell formation and atherogenesis. Macrophage Colony-stimulating factor (MCSF) enhances MSR expression and functional activity (including MSR-dependent adhesion) in elicited peritoneal Mφ markedly and selectively. The T lymphocyte products, Th1 (interferon-gamma(IFN-γ)) and Th2 (chiefly interleukin-4 (IL-4)) cytokines, have divergent effects with IL-4 upregulating and IFN-γ either maintaining or downregulating MSR status. IL-4 induced MSR microheterogeneity is due to changes in N-linked glycosylation, specifically sialylation and may be physiologically significant. In contrast to interleukin-10 (IL-10), transforming growth factor-beta (TGF-β) inhibits MSR upregulation, also when produced endogenously. TGF-β is as potent an inhibitor of MSR function as M-CSF is a stimulator. A cleaved truncated soluble form of MSR which lacks the cytoplasmic domain is present, by immunochemical assays, in culture supernatants. M-CSF increases soluble MSR release in vitro which is functionally active. Following upregulation of MSR surface expression in transfected CHO cells by prolonged culture, a modest MSR-dependent contribution to adhesion becomes apparent. To determine a possible adhesionpromoting region in the MSR, the binding site of mAb 2F8 was mapped using a series of MSR truncation mutants, and localized to residues 183 to 197 in the proximal cchelical coiled-coil domain. Morphological evidence, obtained by confocal and electron microscopy, supports an adhesion role for the MSR in primary Mφ and transfected CHO cells. MSR expression is prominently directed to the adherent surface and its distribution is restricted to cellular contact areas with the substratum. Organs and atherosclerotic lesions from mice deficient in M-CSF (osteopetrotic) and apolipoprotein E were examined to determine the effects of M-CSF on Mφ phenotype (including MSR expression) and lesion development in vivo. Though severely hypercholesterolemic, doubly deficient mice are protected against atherosclerosis and exhibit fewer Mφ and low MSR expression on remaining M-CSF independent populations. Prominent hepatic lipid accumulation suggests a crucial M-CSF dependent role for Kupffer cells in lipoprotein uptake, transfer to hepatocytes and biliary excretion of cholesterol. Regulation of MSR activity may therefore be important for the recruitment of Mφ into the arterial wall and, at the post-endothelial stage, to anchor Mφ at specific locations, thus favouring foam cell formation.

Advisor: Gordon, S
Transition metal catalysed C-C bond formation via C-H functionalisation

The functionalisation of C-H bonds has been widely studied in organic synthesis. This work presents the results of investigation into two areas of current research, copper-catalysed aromatic C-H functionalisation and rhodium-catalysed hydroacylation. Chapter 1 presents the development of palladium- and copper-catalysed aromatic C-H functionalisation with particular attention paid to regiocontrol. Chapter 2 describes the development of copper-catalysed cross-coupling of perfluorinated arenes and alkenyl halides along with efforts to expand this methodology to a more general reaction. In Chapter 3 the development of chelation-controlled rhodium-catalysed hydroacylation is discussed. Chapter 4 outlines the utilisation of amino acid derived N-methylthiomethyl aldehydes in rhodium-catalysed hydroacylation methodology.

Keywords: C-C bond formation
hydroacylation
C-H functionalisation
rhodium
copper
cross coupling
Advisor: Willis, MC
Powder processing of oxide dispersion strengthened steels for nuclear applications

Ferritic ODS steels show improved high temperature strength and irradiation tolerance compared with conventional ferritic steels, and are one of the key potential materials for fusion blanket structural applications. The processing of ODS steels is critical to their subsequent performance; however knowledge of the optimum processing approaches for these alloys is not complete.
The microstructural evolution of ODS steels containing Y2O3 and other additions during manufacture has been investigated and the processing conditions optimised based on microstructural and mechanical investigations.
Ferritic powders with Y2O3 and other additions were investigated, primarily using analysis on the micro- and nano-scale, with an emphasis on identifying the requirements for homogenization of the Y within the steel matrix. The Y2O3 dispersion and subsequent development of the nano-precipitates during thermal treatment was investigated using in-situ neutron diﬀraction. The nano-precipitates were resolved at approximately 900◦C after 1hr, with coarsening and/or re-precipitation progressively increasing at higher temperatures.
A signiﬁcantly increased number density of nano-precipitates (∼2x1023m−3 to ∼7x1023m−3) was established by hot isostatically pressing an Fe-14Cr-3W-0.2Ti0.25Y2O3 alloy at 950◦C compared with more traditional temperatures at 1150◦C, attributed to the increased coarsening and/or re-precipitation of the nano-precipitates at the higher temperatures.
The inﬂuence of the mechanical alloy (MA)ing conditions on bulk mechanical properties was investigated using four point bend. The highest fracture toughness of ∼55MN/m3/2 and ultimate strength of ∼1450MPa was achieved under conditions that minimised the mechanical alloying time and increased the average ﬁnal size of the powders.
An Fe-14Cr-3W-0.2Ti-0.25Y2O3 (wt%) ODS alloy manufactured under optimised conditions showed a bi-modal grain structure size distribution and had a comparatively high yield strength of >1200MPa at 20◦C and >330MPa at 700◦C. The grain structure and high yield strength were attributed to the random distribution of 25nm radius of gyration (Rg) Y, Ti and O rich nano-precipitates randomly dispersed throughout the alloy. Long term thermal ageing (750hr at 1000◦C) reduced the room temperature yield strength and increased the proportion of larger grains in the bi-modal distribution, but high temperature yield strength was remarkably stable.

Keywords: Powder processing
Steels
Nuclear
Fusion
Oxide dispersion stengthened
Fission
Advisor: Grant, P
Roberts, S
Bagot, P
Dudarev, S
Myocardial microstructure and its role in propagation dynamics

Computational modelling and simulation, in close interaction with experiments, has provided invaluable insight into the biochemical, mechanical and electrophysiological function and dysfunction of the heart. However, limitations in imaging techniques and computing resources have precluded the analysis of tissue architecture near the cellular scale and the effect of this architecture on cardiac function.
It is the wider aim of this thesis to develop a framework to characterise cardiac microstructure and to investigate the role of microstructure in cardiac propagation dynamics and arrhythmogenesis. An initial modelling study elucidates the effect of blood vessels in sustaining arrhythmic episodes, and how the accurate modelling of fibre direction in the vicinity of the vessels mitigates this detrimental mechanism. A mathematical model of fibre orientation in a simple geometry around blood vessels has been developed, based on information obtained from highly detailed histological and MRI datasets. A simulation regime was chosen, guided by the vasculature extracted from whole heart MRI images, to analyse ventricular wavefront propagation for different orientations and positions of blood vessels. Our results demonstrate not only that the presence of the blood vessels encourages curvature in the activation wavefront around the blood vessels, but further that vessels act to restrict and prolong phase singularities. When compared to a more simplistic implementation of fibre orientation, the model is shown to weaken wavefront curvature and reduce phase singularity anchoring. Having established the importance of microstructural detail in computational models, it seems expedient to generate accurate data in this regard. An automated registration toolchain is developed to reconstruct histological slices based on coherent block face volumes, in order to present the first 3-D sub-cellular resolution images of cardiac tissue. Although mesoscopic geometry is faithfully reproduced throughout much of the dataset, low levels of transformational noise obfuscate tissue microstructure. These distortions are all but eradicated by a novel transformational diffusion algorithm, with characteristics that outperform any previous method in the literature in this domain, with respect to robustness, conservation of geometry and extent of information transfer. Progress is made towards extracting microstructural models from the resultant histological volumes, with a view to incorporating this detail into simulations and yielding a deeper understanding of the role of microstructure in arrhythmia.

Keywords: registration
computational biology
medical imaging
Advisor: Martin, B
Blanca, R
Vicente, G
Ideology or pragmatism: the Conservative Party in opposition, 1974-79

In January 1979, Stuart Hall claimed to have identified a new ‘radical Right’ ideology he termed ‘Thatcherism’, which was attempting to ‘command the space’ occupied by the social democracy of the then Labour government and the ‘moderate wing’ of the Conservative Party. In short, the Thatcher Conservative Opposition was detaching itself from ‘traditional’ Conservatism. This thesis examines the validity of the claim at the time it was made, through a detailed scrutiny of the positions taken up between 1974 and 1979 by those identified as being on the ‘radical Right’ of the Party and those designated as ‘moderates’. In particular, it analyses the programme proposed by Sir Keith Joseph, the leading advocate of New Conservatism, within the context of the policy-making processes adopted by the Party in those years and the outcome of those processes. It concentrates on efforts to formulate policies in the key economic and industrial relations fields and examines how what emerged was shaped by the opposing views of those involved and by outside events. It considers how Margaret Thatcher, in order to keep the Party intact, contrived to avoid entering into potentially unsustainable policy commitments and, at the same time, impressed herself sufficiently on the electorate that when the opportunity arose, it was prepared to vote her and her Party into office. It became possible, once the first Thatcher government started its work, to regard much of what it did as ideological and radical. However, so inchoate was the programme developed in opposition that one can only conclude that there was no body of doctrine at the time of the 1979 election which warranted the name of ‘Thatcherism’ and that victory was achieved by acting in accordance with ‘traditional’ Conservatism – by doing what was necessary in the circumstances to attain power.

Keywords: Thatcherism
opposition
Conservative Party
Advisor: Davis, J
Neighbourhood negotiations: network governance in post-Katrina New Orleans

This inquiry into informal networks and policy negotiations is set in the theoretical framework of network governance. It builds theory to explain informal networks by examining neighbourhood associations in post-Katrina New Orleans through a variety of qualitative methodologies including interviews, document analysis, surveying and ethnography.
In New Orleans, neighbourhood associations do not engage in social-service delivery, they prioritise neighbourhood protection and neighbourhood change. They represent their neighbourhoods through a system of intensive volunteering not elections. That system burns out neighbourhood leaders and leaves associations constantly looking for new volunteers. These associations partner with non-profits, work with politicians, and engage in fierce conflict when excluded from policy negotiations. Finally, they set their agenda based upon the physical characteristics of their neighbourhoods, investing in local institutions.
These findings contribute to network governance theory. New Orleans’ democracy of volunteers introduces a new form of democratic anchorage to governance theory. Actors in informal networks have varying priorities. This demonstrates the importance of early involvement by these actors in policy creation and the ways in which policy construction can ignore community. Neighbourhood associations blackmail, bribe and coerce to create their own power, showing how power at the micro-level includes not only resources and decision-making, but also interest.
These findings fit into a broader theme. Negotiations with multiple actors improve policy by incorporating complex priorities and neighbourhood context into the policy system. This wider theme of how to address complexity is the policy equivalent of the wisdom of crowds. Policy-makers can either incorporate complexity such as local context and differing priorities or face the conflict and consequences of ignoring it.

Keywords: neighbourhoods
New Orleans
associations
grassroots
citizen participation
neighborhoods
Advisor: Walker, R
Mechanisms of NKG2D ligand regulation

Background: The NKG2D ligands are a set of cell surface proteins, the expression of which can make cells susceptible to immunity mediated by NKG2D receptor expressing cells, which include NK cells, CD8+ αβ T cells and γδ T cells. The NKG2D ligands are known to be expressed in distinct settings, including viral infection, cancer, T cell activation, and cellular proliferation, settings also tightly associated with Warburg metabolism. The molecular events which determine NKG2D ligand expression status are unknown.
Aims: We aim to enhance understanding of the deterministic molecular events that control NKG2D ligand expression. Specifically, to explore the relationship between Warburg metabolism and NKG2D ligand expression in cell line and physiological models, and second, to identify open chromatin elements at NKG2D ligand loci, and develop computational methods to analyse this data.
Methods: We use a range of molecular biology techniques to delineate the role of glucose metabolism in NKG2D ligand expression in a HEK293T cell model. We develop a physiological CMV-primary fibroblast model of NKG2D ligand induction to validate our key findings. We adapt, optimise and validate a DNaseI-seq protocol, to define open chromatin sites at the NKG2D ligand loci. We develop a data analysis `pipeline', including our own peak-finding software (“PeakHunter"), to identify open chromatin sites in the data.
Key results: Glucose drives NKG2D ligand expression. This effect requires cellular uptake and metabolism of glucose. Purine nucleotides are a key glucose metabolite for this effect, and purine nucleosides are sufficient to induce NKG2D ligand expression in our HEK293T model. We have identified the open chromatin sites at the NKG2D loci in MCF7 breast cancer cells, and optimised and validated this protocol. Finally we have developed “PeakHunter" a multifunctional software tool for mapped DNaseI-seq data analysis.
Conclusions: Glucose and its contribution to purine metabolism play a central role in the induction of NKG2D ligand expression in physiological settings. The influence of glucose leads to significant alterations in cellular NKG2D-dependent immunogenicity. PeakHunter is a useful tool for analysis of mapped DNaseI-seq data.

Keywords: immunology
NKG2D
Warburg
NK cell
innate immunity
glucose
MICA
metabolism
Advisor: O'Callaghan, C
Exchange rate appreciation, competitiveness and export performance

This thesis principally studies the determination of UK export performance between the wars. Several improvements to the measurement of sterling's nominal and real effective exchange rate in the period are implemented, and the path of the exchange rate is related to UK and foreign exchange rate policies. The nature of competitiveness and the demand and supply mechanisms by which it may influence exports are discussed. In the light of this, and the commodity and geographical breakdown of UK exports, we suggest alternative measures of competitiveness which may appropriately be tested in econometric work.
Aggregate UK export volume and price equations for the inter- war period are then estimated. Competitiveness, which is in turn influenced by the exchange rate, and the economic position of primary producing countries, are found to have had significant effects on UK export performance. Similarly specified equations are estimated for UK exports in eight industrial sectors. Distinctive characteristics of sectors may lead to substantial divergences between sectoral and aggregate behaviour. This is confirmed in further work on UK coal exports. Nevertheless, measures of the price of UK exports relative to the price of exports of other industrial countries generally give explanations of UK export performance which are superior to other competitiveness measures.
A substantial statistical appendix containing data on, inter alia, UK and foreign exchange rates, trade volumes and values (with geographcial and commodity breakdown), labour costs and prices, together with the sources and methods used in their construction, is provided both for historical interest and to facilitate replication of results and further research.
Eloquence as profession and art

This thesis is a study of the use of the ars dictaminis (the art of letter-writing) in fourteenth and early fifteenth century England. It has three aims: firstly to examine the extent to which the ars was an integral and important part of professional administration, ecclesiastical and secular; secondly to describe the nature of eloquent epistolary composition and compare this to the traditional requirements of the
ars; and thirdly to investigate in the context of the preceding discussion the relationship between medieval rhetoric, middle English literature and renaissance humanism. The well documented career of Gilbert Stone, an episcopal chancellor, is used to initiate a wider investigation into those of his secretarial contemporaries. There is no evidence in later medieval England of a highly self conscious secretarial profession nor of a cult of eloquence. Letter collections point however to the importance of form and style, and an examination of their contents suggests that the rules of the ars. and particularly of the cursus, were used, adapted and developed, sometimes in quite routine documents, but more especially in 'eloquent' letters of persuasion. The ars, it is argued, was more vibrant, flexible and appropriate to its context than later critics have imagined. The ars, notably through Thomas Hoccleve, exercised an influence on poetic form and style; and even in a case such as that of Chaucer where there was not such a strong direct influence, it is possible that the ars may be seen as part of a complex conditioning literary environment. Finally the professional-literary structure underlying the use of the ars provided a motive and a means for the introduction of humanism into England.
Private vices, public benefits

This thesis examines the relationship between Mandeville's medical and non-medical thought, to assess the relevance of the former for an understanding of the latter. By locating his medical text, A Treatise of the Hypochondriack and Hysterick Passions, within the context of an early modern discourse on the nature and treatment of melancholic and nervous disorders, three distinctive features of his medical thought and practice are identified, namely: his commitment to the physiological principles of iatromechanism; his adherence to the precepts of Hippocratic medical practice; and his use of the talking cure in the treatment of hypochondriacal disorders. Those aspects of his medical thought and practice are then taken up and explored in an analysis of his philosophical and polemical performances in The Fable of the Bees. First, it is argued that The Fable of the Bees contains a systematic and coherent theory of man and society, the key elements of which were dictated by Mandeville's reductive and physiological understanding of man as a sentient and passionate machine. It is further argued that the mechanistic and homeostatic principles which informed his model of human functioning also informed his similarly reductive account of both the evolution and the contemporary functioning of the body politic. To distinguish Mandeville's from other reductive social theories, his adherence to the methodological precepts of Hippocratic medicine and his understanding of the development of its rules of diet and regimen are invoked to explain his distinctive and evolutionary account of the social institutions which made civilization and its flourishing possible. Finally, Mandeville's contrasting polemical and rhetorical performances in Parts I and II of The Fable of the Bees are explained by reference to his understanding of the medical art of diagnosis and curing in general and his use of the talking cure in particular.
Educational homogamy, parenting practices and children’s early development

This thesis investigates the pattern of parental educational homogamy and its implications for parenting practices and children’s early development in contemporary Britain. At the heart of the thesis lies an interest in the mechanisms behind the intergenerational transmission of educational success and, more specifically, the consequences for children of new patterns of parental resemblance in education.
The thesis is composed of three empirical chapters, each of which is concerned with a different outcome: 1) trends in educational attainment and educational assortative mating amongst parental couples; 2) parents’ childrearing values and stimulation-oriented interactions with children; and 3) children’s early cognitive and behavioural skills. The first chapter combines data from four birth cohort studies from 1958, 1970, 1990 and 2000-01 while the second and third chapters rely exclusively on the latter study. The empirical analyses use Log-linear and Diagonal Reference models.
With regard to trends in educational assortative mating, the thesis finds that the strength of homogamy increased between 1958 and 1970 to decrease thereafter and remain stable, at its lowest level, throughout the 1990s. Moreover, amongst recent cohorts of parental couples the percentage of unions where mothers are more educated than their male partners equalled that of unions exhibiting the opposite pattern. The findings concerning the dynamics of parenting in heterogamous couples suggest a pattern of female dominance in the attitudinal domain as fathers align with the views that can be expected on the basis of the mother’s level of education rather than their own; however, no significant adjustments between partners are observed in parenting behaviours.
Lastly, the thesis finds a positive gradient in the association between parental education and children’s early cognitive and socio-emotional development but little or no support for the hypotheses of differential effects for sons and daughters or gender biases in parental preferences for children. That is, no significant interactions are observed between the gender of children and the impact of parents’ absolute and relative levels of education.
Taken together, the findings of the thesis qualify concerns about the increase of educational assortative mating in industrialised societies and its potential consequences for the intergenerational reproduction of inequalities in education.

Keywords: educational assortative mating
educational homogamy
parenting practices
parenting attitudes
child development
Advisor: Gershuny, J