VictorJuiz/thesis huggingface dataset:
Doctrine, progress and history: British religious debate 1845-1914

Religion and history became closely related in new ways in the Victorian imagination. This thesis asks why this was so, by focusing on arguments within British Protestant culture over progress and development in the history of Christianity. In an intellectual movement approximately beginning with the 1845 publication of John Henry Newman's 'Essay on the Development of Christian Doctrine', and powerfully spreading and developing until the earlier years of the twentieth century, British intellectuals came to treat the history of religion – both as a past and present process, and as a didactic genre - as a vital element of broader attempts to stabilise or reconstruct religious belief and social order.
Religious revivalists, determined to use church history as a raw material for the inculcation of exclusive confessional identities and dogmatic theology, were highly successful in pressing it on the attention of early Victorian audiences. But they proved unable to control its meaning. Historians rose to prominence who instead interpreted the history of Christianity as a guide to how religious culture, which many treated as indistinguishable from society as a whole, might eventually supersede denominational and dogmatic divisions. Humanity’s spiritual development in time, which numerous British critics assessed with the aid of German Idealist thought, also became an attractive apologetic resource as the epistemological basis of Christian belief came under unprecedented public challenge. A major part of that danger was perceived to come from rival, avowedly secularising interpretations of human social progress. Such accounts – the ancestors of twentieth-century secularisation theory – were vigorously opposed by historians who understood modernity as involving not the decline, but the purification of Christianity. By exploring the ways in which Victorian critics – clerical and lay, religious and secular – approached religious history as a resource for solving the problems of their own age, this thesis offers a new way of understanding the importance of history, claims to knowledge, and the nature and ends of 'liberalism' in the long nineteenth century.

Advisor: Garnett, J
Application of genomic technologies for molecular diagnosis of genetic diseases

Methods for sequencing deoxyribonucleic acid (DNA) have improved rapidly in the past decade. Recent methods, termed "next-generation sequencing" (NGS), have made sequencing large quantities of DNA economically viable in molecular diagnostics of genetic diseases. This thesis describes some of the first investigations to use NGS for such a purpose.
Several different NGS platforms, each of which differs substantially in terms of sample preparation, chemistry, and sequencing methodology, were tested, in addition to several sequence capture and enrichment technologies that allow sequencing to be targeted, and these combinations were compared to Sanger sequencing. They were each found to have different strengths and weaknesses, which affect their accuracy, reliability, time taken to results, financial cost, and ease of use, but all showed high accuracy and dramatically increased throughput over Sanger sequencing.
NGS was used to identify pathogenic mutations in two groups of patients who had either inherited retinal dystrophies (IRD), or severe early onset epilepsies. NGS was able to identify pathogenic variants, demonstrating the ability of the technology to provide medically useful information for genetically heterogeneous conditions. NGS combined with a novel data analysis pipeline was able to make a secure molecular diagnosis in 25% of a cohort of IRD patients who previously did not have a genetic diagnosis.
The greatest challenge presented by NGS was found to be filtering the vast amounts of data produced to identify potential pathogenic variants. In silico pathogenicity prediction programs were used, but none were 100% accurate. Other methods were also employed to provide further evidence of pathogenicity. These included family based DNA testing for cosegregation of variants with phenotype, and transcript based analysis. In some patients, despite extensive genetic testing, a secure molecular diagnosis could not be made using DNA sequencing technologies, illustrating that challenges still remain in the field of genetic diagnostics.

Keywords: Macular degeneration
IRD
Molecular diagnostics
NGS
ABCA4
Stargardt
Ohtahara syndrome
Next-generation sequencing
Inherited retinal degeneration
Advisor: Neméth, A
Halford, S
Downes, S
Climate change v Eurozone crisis: social and economic views of risk in inter-expert risk communication

This DPhil thesis discusses how two divergent risk conceptions, a 'social view' and an 'economic view' of risk, are constructed through inter-expert risk communication. Different and sometimes contradictory concepts of risk are mobilised in regulatory practice, but the origins of these divergent risk conceptions are not extensively studied. This thesis seeks to unpack this divergence.
Empirically, I analyse risk communication among experts in the European Union (EU) during the creation of two risk regulation standards. The two case studies, one related to the development of the two-degree target of EU climate policies (the climate case) and the other about the negotiation of the excessive deficit criteria of the Maastricht Treaty (the euro case), can shed light on the relations between risk conceptions and inter-expert risk communication. I argue that through risk communication, an initial 'view' of risk can be entrenched and developed into a paradigmatic 'risk conception'. My analysis uses historical and sociological institutionalism, by focusing on path dependence of risk communication and social construction risk conceptions among EU experts.
Through the two case studies, I identify four analytical dimensions of inter-expert risk communication: networks (the institutional setting and relationships between different experts), cultures (the mentalities of experts in relation to discussing risks), dynamics (the actual processes of transmitting and receiving risk messages) and strategies (the rationales supporting the decisions of risk regulation standards). My thematic analysis reveals four key distinct 'features' of social/economic views of risk: expertise (the types of knowledge mobilised), normality (characterising risk as either 'special' or 'routine'), probability (considering risk as either uncertain or calculable) and impact (seeing risk as either negative or positive). I argue that these four features can help explain the construction of risk conceptions, and more broadly, provide an analytical framework for studying how views of risk evolve and interact over time.

Keywords: Risk Regulation
Risk Communication
Climate Change
Economic and Monetary Union
Advisor: Lange, B
Restructuring of education, youth, and citizenship:  an ethnographic study of private higher education in contemporary Singapore

In spite of widespread critiques about the neoliberalisation of higher education and its production of citizenship in relation to the market, transformation of students into profit-maximising individuals, and the vitalisation of a self-enterprising subjectivity, many of these claims remain under-examined with respect to cultural production. The objective of this research is to explore the neoliberal production of middle-class citizenship through the lens of educated non-elite local youth in Singapore. By combining geographical, sociological and anthropological insights about education and youth, I develop a theoretically informed ethnographic case study to examine how this segment of young people reproduce themselves as middle-class citizens. The research is based on eleven months of fieldwork at a local private institute of higher education, where I hanged around, talked to, and observed Singaporean young people between ages 18 and 25 studying for their first degree.
The ethnographic materials are written up into four substantive papers, demonstrating the ways in which educated non-elite Singaporean youth in private higher education engage with state disseminated ideas around neoliberal accumulation and human capital formation. I argue that these students draw on class-based sensibilities and feelings to produce vibrant forms of normativities, subjectivities, and politics that pose a challenge to dominant assumptions of a "hollowed out" citizenship under neoliberalism. The research makes two overall interventions in geographic and social scientific writings about neoliberal restructuring of higher education and its implications for youth citizenship. First, it cautions against a straightforward claim that neoliberal technologies of control have extended market values into citizenship subjectivity and, with it, the erosion of progressive political projects. Second, it provides a much-needed analysis of middle-class citizenship formation among young people caught at the losing end of a diversifying educational landscape.

Keywords: Youth citizenship
Singapore
Neoliberal education
Educational class
Advisor: Jeffrey, C
Waters, J
The burden of Plasmodium vivax malaria

Plasmodium vivax is the most geographically widespread of the human malarias and is capable of causing severe debilitating disease. The parasite’s unique biology poses challenges to control of the disease and the understanding of its epidemiology. It is less researched and well understood than the more deadly P. falciparum. In this thesis, spatial relapse patterns and models of endemicity and clinical disease were applied to generate robust estimates of the P. vivax burden to address a key knowledge gap in malaria epidemiology.
First, a review of the distribution of the parasite, its vectors and populations at risk found nearly one third of the global population living at risk, and more potential vectors than P. falciparum. In spite of low observed endemicity, the public health impact of P. vivax is likely to have been seriously underestimated in the past.
To accurately define the burden of P. vivax it was necessary to improve understanding of one of the parasite’s most unique and challenging aspects, its ability to relapse. A meta-analysis of individual records of relapse showed that relapse periodicity varied systematically by geographic region and could be categorized by nine global regions. The nine regions were applied to a model to quantify the relationship between prevalence of infection and incidence of clinical disease. As relapse would have an influence on both measures, separate relationships were drawn for each relapse zone.
The prevalence-incidence model was used to translate maps of predicted endemicity into measures of clinical burden. The evidence-base of P. vivax prevalence was poor in some regions and therefore a burden estimate based on surveillance reports was also derived. Reported cases must be adjusted for parameters such as under-reporting and treatment-seeking behaviours. A model used to fill gaps in treatment-seeking data available from national household surveys was developed to allow burden to be estimated using both cartographic modelling and surveillance reporting methods. To improve fidelity, the results of the two approaches were combined to enumerate P. vivax burden globally.
The results and conclusions of these studies are discussed with recommendations for how these findings influence our understanding of P. vivax epidemiology and implications for future control and elimination efforts.

Advisor: Hay, S
Gething, P
Farlow, A
Indexing, reporting and identification of time-to-event survival analyses in the dental literature

Objective: This research explored how time-to-event dental articles were indexed and reported, and sought solutions to help improve the reporting and identification of these articles, so that they could be more easily found and used to inform practice and research.
Methods: Articles reporting time-to-event dental outcomes in humans were identified from the 50 dental journals with the highest impact factor for 2008. These were handsearched, identifying ‘case’ articles (n=95), active controls (likely false positives, n=91), and passive controls (other true negatives, n=6796). The medical subject headings (MESH) that had been assigned to the articles in MEDLINE, and words used in titles and abstracts describing time-to-events were compared between the ‘cases’ and controls. Time-to-event words and figures within articles were also sought, and reporting quality was assessed. Search strategies to identify time-toevent articles were developed, using indexing terms and free-text words. An independent cohort of articles was used to validate the search strategies, consisting of 148 time-to-event articles handsearched from 6514 articles in the 50 dental journals with the highest impact factor for 2012. The findings of the research were used to draft guidance to improve reporting, which was circulated amongst 78 stakeholder experts for comment, and modified.
Results: MeSH indexing of time-to-event analyses was inconsistent and inaccurate, author descriptions in abstracts and titles varied, and the quality of time-to-event reporting and graphics in the body of those articles was poor. The burden faced by someone wishing to find and use these articles was considered high. Sensitive, precise and optimized electronic search strategies were developed and validated with sensitivities up to 92% and precisions up to 93%. The draft guidance attracted comment from 46 experts across 15 countries, with approximately 90% of the 130 comments accepted into the revised version. The importance of good quality reporting was endorsed, and there was high interest in commending the guidance to authors, reviewers, and training dental specialists.
Conclusions: This research programme explored how time-to-event dental articles were reported, and used those findings to suggest solutions that would help to improve the identification and use of these data, reducing research waste.

Advisor: Clarke, M
Rapid, electrostatic self-assembly of nanoparticles with kelvin probe characterisation

The pick-and-place of components to build up complex working machines, such as the robotic arms on automotive assembly lines, has been integral to the enormous success and complexity of modern heavy industry. Modern nanomanufacturing stands in stark contrast to this strategy, reliant instead on the two-dimensional patterning of radiation-sensitive resists to build high-density machines of relative simplicity. The driving goal of our research has thus been to develop a new method of manipulation that would allow the pick-and-place of nanoscale components to mirror that of the assembly lines. A manipulator that could reliably perform this process would open the door to a new age of complex nanomachines.
After analysing the current state-of-the-art in nano-object manipulation, we decided to utilise a combination of voltage-driven electric fields with chemically functional monolayers to achieve this goal. The mechanism was intended to be highly compatible with a Scanning Probe Microscope-style tip that could act as the manipulator tool on such an assembly line. This led to the design of several devices that were intended to capture single nanoparticles from a colloidal suspension, which had a negative surface charge in solution. We used numerical simulations using the Guoy-Chapman model of ionic solutions to determine what electrical and geometrical parameters would create the best devices single particle selectivity. We then describe the fabrication of devices using nanolithography techniques including electron-beam lithography, thin-film deposition and etching. Scanning electron microscopy of these devices after voltage-driven assembly showed that the mechanism had very limited success with few incidences of nanoparticle funnelling. This led through several different troubleshooting analyses of the mechanism that identified a myriad of issues affecting these devices. Ultimately we successfully created a radical new approach that incorporated hydrophobic monolayers with polar surfaces. This method exploited the hydrophobic interaction to overcome the hydrostatic barrier and resulted in repeatable single-particle assembly onto devices in sub 5-minute timeframes.
Another aspect identified in this work was that the electronic state of nano-objects and monolayers on device surfaces is very important, but is difficult to pinpoint even when data sheets are available. We developed an emerging method of open-loop Dual-Harmonic Kelvin Probe Microscopy to identify these materials by their electronic surface potentials, successfully performing measurements in electrolytes where nanomanipulation would take place. This line of research led to novel considerations of how the size of the nanoparticles fundamentally distorts KPM measurements. We identify this as an important and often ignored effect that must be considered when using probes to differentiate between different materials at the nanoscale.

Keywords: nanofabrication
nanoparticles
self-assembly
electrophoresis
Advisor: Bhaskaran, H
Exploiting the use of induced pluripotent stem cell derived immune cells for immunotherapy

Immunotherapy traditionally made use of biological agents such as cytokines and monoclonal antibodies. Such first generation therapies lack antigen specificity and fail to induce immunological memory, suggesting that cell therapies may provide the next generation of treatments that are more discerning in their mode of action. Nevertheless, difficulties in obtaining sufficient immunologically-relevant cell types from patients has limited their success. Given that induced pluripotent stem cells (iPSC) may be generated from patients, we have investigated the feasibility of deriving two cell types whose availability is restricted in vivo: regulatory T cells (Tregs) and CD141+ cross-presenting dendritic cells (DCs).
We describe the optimization of protocols for differentiation and purification of CD141+ DCs, focussing on their utility as a therapeutic vaccine for HIV-1. We investigate their phenotype, chemotactic capacity, phagocytic ability and propensity to harbour infectious virus. We also assess their immunostimulatory capacity and ability to cross-present exogenous antigen to MHC class I-restricted T cells.
Our findings led us to speculate that iPSC-derived DCs (iPDCs) possess fetal phenotype, which is characterised by excessive secretion of IL-10 and failure to secrete IL-12, under all but the most stringent conditions. We hypothesised that constitutive secretion of IL-10 may be responsible for maintaining the fetal phenotype, a hypothesis we tested by developing an appropriate mouse model. iPSCs were derived from WT and IL-10-/- mice and were shown to differentiate into iPDCs which recapitulate the fetal phenotype observed among human cells. However, loss of the endogenous Il-10 gene failed to restore full immunogenicity and IL-12 secretion.
Finally, we developed protocols for differentiation of FoxP3+ Tregs from iPSCs, a feat that has not previously been achieved. These findings pave the way for the differentiation of Tregs from iPSCs reprogrammed from antigen-specific pathogenic T cells, thereby creating a source of Tregs with matched specificity for therapeutic intervention.

Keywords: Immunotherapy
induced pluripotent stem cells
Dendritic cells
HIV
Advisor: Fairchild, P
Electron spin resonance of molecular magnets for quantum information processing

Quantum information processors have been shown theoretically to outperform their classical counterparts at certain tasks. They comprise two level systems, which can exist in an arbitrary superposition of states: qubits. A strong candidate qubit is the molecular nanomagnet (MNM). In this thesis, electron spin resonance is used to explore the potential of Cr7M based MNMs as elements of a quantum information processor.
We explore the possibility and effect of replacing H atoms with D or a halogen atom in a S &equals; 1/2 Cr7Ni ring. Decoherence mechanisms in the resulting compounds are found to be dominated by structural effects. We conclude that halogenation does not seem to be a productive strategy for extension of coherence times in Cr7Ni based compounds.
We examine an asymmetric dimer, in which a Cr7Ni ring is linked to a highly coherent nitrogen atom within a carbon cage. Measurement of phase memory time across a range of temperatures for the N spin, provides insight into the ring's spin dynamics. At high temperature, fluctuations on the ring are so rapid that the N spin appears magnetically disconnected; as they slow, we see a sharp rise in the decoherence rate of the N spin. At the lowest temperatures, a recovery of the decoherence rate reflects the onset of the ring’s coherent ground state.
A group of symmetric Cr7Ni-Cr7Ni dimers is investigated. Through use of double electron-electron resonance, the strength of the ring-ring dipolar interaction, governing the two qubit gate time, is estimated for each. It is found that many exhibit the hierarchy of timescales required for implementation of a two qubit gate: a short single qubit manipulation time, intermediate two-qubit gate time and long phase coherence time. A possible scheme for the future implementation of a CNOT gate is presented.
The final study explores rings of spin, S > 1/2. We present the first ever coherent measurements on a dilute oriented ensemble of the S &equals; 3/2 rings, Cr7Zn, performing nutations at various powers. In addition, we investigate the anisotropic Mn2+ (s &equals; 5/2, I &equals; 5/2) defect in ZnO. We develop the 'echo kill' method for identification of a three level subsystem whose transition frequencies both fall within the cavity bandwidth. Such a subsystem is then used to perform indirectly detected nutations between the upper two levels over a range of applied powers. Finally, a method for initialisation of the subsystem into a pseudopure state is presented and shown to enhance nutation amplitude.

Advisor: Ardavan, A
Effect of oocyte glycoproteins on ovarian follicle development and function

The precise mechanisms that regulate the ovulation rate of species are not entirely understood. The C1galt1 Mutant mouse, in which oocytes lack core 1-derived O-glycans, is characterised by (i) increased fertility, evident from ~40-50% larger litters as a result of increased number of growing follicles and (ii) modified cumulus expansion. Work carried out in this thesis investigated both of these phenotypes and led to the understanding of possible mechanisms involved in increased fertility.
Through detailed analysis of the cumulus complex both prior- and post-ovulation in Control mice, novel characteristics regarding the physiology of cumulus expansion have been found. In addition, the analysis of C1galt1 Mutants has revealed that a functional cumulus-oocyte-complex requires the essential components to be present above a minimum threshold level, and thus some variation in ECM composition does not adversely affect oocyte development, ovulation or fertilisation. These data have important implications for IVF and the use of cumulus expansion as a criterion for oocyte assessment.
C1galt1 Mutants have (i) altered follicle growth characteristics, (ii) reduction in apoptosis levels and (iii) reduction in AMH levels, all of which could be directly or indirectly contributing to the increased fertility phenotype. These data reveal new and important roles for the oocyte in follicle development and female fertility, providing perspectives for future work in female reproduction.

Advisor: Williams, S