VictorJuiz/thesis huggingface dataset:
Public men on public stages: the performance of state authority in popular drama, 1590-1610
Keywords: performance
law and literature
magistrates
state formation
authority
practice as research
early modern drama
popular drama

This thesis explores the representation of the early modern English state in a selection of drama performed in London’s public theatres between 1590 and 1610. It examines nine plays that enact recognisable legal process and relationships between magistrate and community, to investigate how the public theatres manifested the state. The state has been of great interest to historians over the last twenty years, with social historians often relying upon the term ‘performance’ to articulate the way that magistrates needed to enact their legitimacy to those they attempted to govern. My thesis develops this historiography by conceptualising the exercise of magisterial authority as a performance that brought the state into being. While magistrates needed to perform legitimacy, they performed the state every time they successfully carried out their duties: they constituted a version of the state where the magistrate did have legitimate authority in the minds of witnesses.
As such, I examine the plays in performance, partly by using practice-as-research workshops which stage the plays according to early modern production conventions. While these plays have largely been ignored as representations of the state, in performance they vividly manifest their own states, often presenting the state’s failings as the source of tragedy. These plays articulate concerns and debates about the state’s functioning and structure, often without expressing these ideas verbally: embodied action manifested the state for audience interpretation, the drama’s manipulation of genre and emotional response shaping praise and criticism of the state enacted onstage. This has profound historiographical ramifications. While ordinary Londoners might not use the terms in which jurists and monarchs debated the state, they could recognise the state processes enacted in the public theatres: the state was perfectly apprehensible by those audiences, and drama was a key participant in debate over the structure and functioning of the state.
Sextus propertius, praeceptor amoris: teaching love, loving poetry
Keywords: propertius
Latin
didactic poetry
Augustan poetry

Propertius has been known to teach for as long as he has been read. Modern scholarship, however, has tended to privilege discussion of other aspects of his poetry, or to view him as an incidental contributor to a didactic trend among Roman love elegists that culminates in Ovid’s Ars Amatoria and Remedia Amoris. This thesis, therefore, turns the spotlight squarely onto Propertius, and provides a reading of his collection that centres around his role as a praeceptor.
My approach is four-pronged, and derives from the themes and rhetoric common to the works of poets generally agreed to form part of the Greco-Roman didactic tradition. In the first chapter, I consider how Propertius develops his authority as a poet and teacher, and mediates it by establishing common ground with his addressee(s) through the use of the first-person plural in poems 1.1 and 1.7-9. In the second, I read Propertius’ teaching of Gallus in poems 1.5, 1.10, 1.13, and 1.20 as a single cycle to see how the addressee’s progress becomes a commentary on the instructive capabilities of the poet’s work. In the third, I examine the way in which Propertius plays with the theme of sight in the didactic narratives of poems 2.1, 2.12, 2.13, 2.14, 2.25, and 2.34 to indicate that he teaches from, and about, a world of our collective imagination. In the fourth, my attention turns to the poet’s articulation of his (and his work’s) trustworthiness in poems 3.1-6, 3.23-5, 4.1a/b, 4.2, and 4.5 as he reveals that his collection is shifting away from its prior focus on love.
In so doing, I seek neither to argue for Propertius to be viewed as one of the didactic poets nor to gauge the validity of his instruction. My concern, rather, is to show that Propertius makes teaching a fundamental characteristic of his collection by using it as a narrative device that shows his control over, and the changeability of, the elegiac world written up in his Cynthia.
Correlative and functional analysis of genomic instability and immune response in colorectal and endometrial cancer
Keywords: T-cell
clinical outcome
immune response
colorectal cancer

Cancer is a common disease, which results in considerable amounts of morbidity and mortality worldwide. It is now recognised that the tumour immune response is essential in determining cancer biology. However, anti-tumour immunity varies considerably between cancers, and even within the same cancer type. In part, it is determined by the tumour mutational landscape. But much remains to be understood about how the interaction with the cancer genome shapes the tumour immune microenvironment, and influences clinical outcomes.
In this research, I demonstrated that tumour CD8+cell infiltrate is significantly associated with reduced recurrence risk and improved overall survival in stage II/III colorectal cancer (CRC). Importantly, this relationship was independent of key confounding factors, including genomic instabilities that have been shown to influence both anti-tumour immunity and clinical outcomes. Furthermore, this relationship was not consistent across all stage II/III CRCs, but rather varied according to tumour and nodal status. Mismatch repair deficiency (MMRd) is a form of genomic instability that contributes to the development of both CRC and endometrial cancer (EC). I showed that MMRd is associated with improved outcomes in CRC, but not EC. This might be a reflection of differences in the immune landscape between MMRd CRC and EC: MMRd CRCs had much greater levels of infiltrate T lymphocytes. Furthermore, MMRd ECs showed an enrichment for loss of function JAK1 mutations, which was associated with abrogated IFNγ signalling activation. Finally, this research demonstrated a murine model to allow functional investigation of MMR loss and its impact on the tumour microenvironment. Conditional, inducible Mlh1 loss resulted in a specific phenotype, with the development of intestinal polyps. In contrast to human disease, these polyps showed CD8+ T cell exclusion, which may be a secondary to Beta-2 Microglobulin loss.
In summary, this work constitutes a correlative and functional study of the associated between the immune response and clinical outcome, and how the this is influenced by tumour genomic instability.
Stroke risk evaluation in a contemporary population of 0.5 million Chinese adults
Keywords: machine learning
risk prediction
cardiovascular disease
China
stroke

Stroke is a leading cause of death and disability globally, with China bearing the largest stroke burden in the world. Global strokes can be halved through primary prevention strategies including the use of risk prediction models to identify individuals with high risk of stroke. However, the models advocated for in current international guidelines have been derived mainly in high-income countries, and their clinical utility in a contemporary Chinese population is uncertain. Moreover, these models generally do not account for the heterogeneity between ischaemic stroke (IS) and haemorrhagic stroke (HS) pathological types as well as further aetiological subtypes of IS. The investigations in this thesis describe the assessment of existing risk prediction methods and development of novel models for evaluating primary stroke risk in the China Kadoorie Biobank – a prospective cohort study of 0.5 million Chinese adults recruited from 10 areas in China in 2004-2008. First, we evaluated the 2017 Framingham Stroke Risk Profile in CKB, and used a similar Cox modelling approach to develop novel models for 9-year risk prediction of total stroke that yielded a 6%-8% increase in area under the receiver operating characteristic curve (AUC) and >90% reduction in the calibration χ^2 test statistic. Risk prediction models for IS and HS were developed with similar results. Second, machine learning approaches including logistic regression, support vector machines, random survival forests, gradient boosted trees (GBT), and multilayer perceptrons were compared for 9-year risk prediction of total stroke. We also developed an ensemble approach combining Cox and GBT predictions, which identified individuals at high-risk of stroke with higher accuracy, specificity, and precision than any single-model approach. Third, we explored the utility of single versus sequential measurements of risk factors for prediction of stroke, and did not find any substantial improvements from sequential risk factor measurements. Fourth, we developed models to assess differential risk of IS and HS and estimated reductions in events and fatalities using optimised statin therapy policies informed by such models. Finally, we characterised the heterogeneity of IS aetiological subtypes and developed models to classify 24% of CKB’s primary IS events that were previously characterised as having undetermined aetiology by the existing Causative Classification System (CCS) for Ischemic Stroke. The contributions of this thesis advance the understanding and prevention of stroke in China.
New approaches to pre-erythrocytic malaria vaccination
Keywords: malaria, vaccine

Malaria is an infectious parasitic disease and a global threat responsible for an estimated 200 million cases and half a million deaths every year. Although progress has been made in recent years with a number of vaccines advancing into later stages of clinical trials, a vaccine with both high efficacy and durability still remains a target to achieve. This thesis presents the results of pre-clinical studies performed with the aim to obtain an improved version of the existing R21 vaccine capable of enhancing immunogenicity, protective efficacy and durability. With this aim, a set of novel R21 variants were designed exploring all immunogenic regions of the Plasmodium falciparum circumsporozoite protein in a VLP vaccine platform. Along with creating new variants, an alternative strategy of using pre-formed immune complexes consisting of R21 complexed with monoclonal antibody 2A10 to the central NANP repeats has been explored. With this strategy already in use for animal vaccines, promising published results obtained with Zika virus, and still unexplored for parasitic infections, I considered to apply this approach to malaria and have obtained promising results. Glycans linked to parasitic surface proteins remain relatively less explored in comparison to proteins and are capable of eliciting immune response that might hold protective potential. With this aim, the last results chapter of this thesis describes results obtained from using sporozoite surface specific glycan alpha- galactose as a vaccine candidate.
The morality of promises and contracts
Keywords: Promises
Normative powers
Contracts

This thesis explores the morality of promises, and the relationship between promises and contracts. It offers an account of the grounds of promissory and contractual powers, duties, and rights, and of the relationship between these powers, duties, and rights and the law. The first part is devoted to exploring aspects of the morality of promising (Chapters 1 and 2). The second part (Chapters 3-5), draws on the conclusions reached in previous chapters and defends a thesis about the relationship between the morality of promising and the law of contracts.
Convincing in the Tokyo start-up village: possibilities of malleable structure
Keywords: Organisational Anthropology
Start-ups
Japan
Uncertainty
Founders
Future
Tokyo

This thesis focuses on the ‘village’ (mura), an assemblage of actors in Tokyo’s start-up scene characterised by first-time founders in their 20s or early 30s and their supporters. I analyse how efforts to retain key stakeholders lead to conflicts between founders, employees, and VCs (venture capitalists) throughout different start-up stages (seed, early, and growth stages). For this analysis, I have engaged in 12 months of multi-sited fieldwork and conducted 39 further semi-structured interviews in para-ethnographic fashion. Anthropological explorations of start-ups are rare, and this is one of the first long-term fieldwork-based studies in a Japanese context.
Following this inquiry, I find that start-up actors across field sites invoke similar discourse that criticises regulation and bureaucracy in the light of Japan’s lost decades of post-bubble low growth. Instead they appreciate the notion of ‘making one’s own opportunities’, which relates to the start-up’s emergent and thus ‘malleable structure’. Absent in such ideals are the tensions such structure can entail, which stem from the conflict inherent in relying on a founder’s performative vision and the manifold ways in which people’s perceptions refute such vision as futures becomes ‘present’. These tensions become manifest once teams fall apart and founders resign.
The reliance on one embodied ‘vision’ relates to the uncertainties and fears the future brings into people’s lives. The introduction of audit techniques can destabilise such ‘visions’, as they provide visible evaluation mechanisms. This leads to ‘temporal’ gaps between those who expect ‘change’ due to what such mechanisms indicate, and others who wish to persevere by following the ‘vision’. Overcoming such gaps seems difficult due to internal role arrangements that stress the importance of execution rather than discussion or deliberation. This partly relates to the structural arrangements of the start-up model, functional models of the company, and the emic notion of company-as-family.
Unsteady loading on floating horizontal axis tidal turbine
Keywords: tidal turbine
pitch motion
floating turbine
surge motion
fully coupled model
heave motion
added mass and damping

Floating tidal turbines (FTT) are gaining popularity in the field of tidal energy these past few years due to some advantages they had when compared to the bottom fixed devices. However, the floating motion of an FTT, due to waves and tidal current, leads to unsteady loadings on the rotor. This motivates the present study to pursue this topic to further understand and characterize the hydrodynamic of an FTT. To conduct a study on a device scale, a floating tidal turbine undergoing single degrees of freedom (DoF) is preferable to isolate the effect of each motion on the device performance. Blade resolved computational fluid dynamic (CFD) simulations of floating tidal turbines undergoing surge, heave, and pendulum (pitch) motions were carried out over a range of motion’s amplitude and frequency and also using multiple rotor rotational speeds. The present study seeks to determine the effect of each motion on the floating turbine’s performance. The rotor goes into stall at higher motion amplitude and frequency for the surge and pendulum motions. The mean power decrease while the mean thrust increase as the motion amplitude and frequency is increased, due to the loss in the lift at the maximum apparent velocity which increases the angle of attack on the blade, causing the flow to separate, thus stalling the rotor. This can be minimized when operating the rotor at a higher rotational speed, i.e., using speed control to reduce the stalling effect. A floating tidal turbine undergoing the heave motion can be viewed as a dynamic yawing motion case; there is evidence of the advancing and retreating phases and wake skewness formation at every heave motion cycle. The added mass and damping forces are calculated based on the blade resolved CFD results, which can be used as standardized hydrodynamic coefficients to be included in a simplified model, such as an actuator disc, for a fully coupled model simulation. Modifications to include the added mass and damping forces into an existing fully coupled model are presented in this thesis. The result shows good improvement from the original model when verified against the blade resolved simulations. The model is then tested under various wave frequencies, including the combined wave-current conditions. The present model increases the mean thrust on the rotor while decreasing the loading amplitude compared to the original model.
Developing gene therapy for inherited retinal degenerations
Keywords: AAV
photoreceptor
outer segments
cadherin
gene therapy
retina
cone-rod dystrophy
macula dystrophy
CDHR1
retinal degeneration

The aim of this thesis was to evaluate the efficacy and safety of retinal gene therapy in a pre-clinical model of CDHR1-associated retinal degeneration – a hitherto untreatable, blinding disorder.
Deep phenotyping of the Cdhr1-/- murine model demonstrated severe early deficits in cone and rod photoreceptor function followed by progressive photoreceptor cell death – recapitulating CDHR1 cone-rod dystrophy. Two AAV8 vectors expressing the full-length human CDHR1 coding sequence were designed, manufactured, validated and titrated in vivo.
Sub-retinal injection of AAV8.GRK1.CDHR1.pA (1.5 x 108 vg) in Cdhr1-/- mice at 3-4 weeks of age resulted in functional rescue of cone and rod photoreceptors with improved response amplitudes and decreased implicit times to 12-months post-injection; a slowing of photoreceptor cell death with regeneration of full-length photoreceptor outer segments confirmed on ultrastructural analysis to 21-months post-injection; and a behavioural rescue effect on photopic and scotopic optomotor testing, sustained to 21-months post-injection. AAV8.GRK1.CDHR1.pA at 1.5 x 108 vg appeared safe in C57BL/6J mice by the same outcome measures to 22-months post-injection.
Genetic prevalence estimates presented herein suggest more than 200,000 affected individuals worldwide. We characterised 146 individuals with biallelic variants in CDHR1, describing the retinal phenotype, natural history, genotype-phenotype associations, with 25 novel pathological sequence variants.
This is the first therapy shown to improve retinal structure and function in a pre-clinical model of CDHR1-associated retinal degeneration. A patent to protect the vectors described herein has been filed on behalf of the University of Oxford, with commercial agreements obtained in preparation for an onward phase 1 clinical trial.
Sir Arthur Hesilrige and the development of civil war in England
Keywords: Civil War
Hesilrige
Great Britain
Sir Arthur Hesilrige
War
Parliamentarians

The thesis provides a detailed account of Hesilrige's involvement in the local politics of Leicestershire, tactical struggles at Westminster and the conflicts between Parliament's generals. In the process it casts light on the nature of the politics of the 1630s and early 1640s and indicates the reasons for Hesilrige's successes and failures in later years.
It demonstrates the convergence of national and local grievances in government during the 1630s and suggests that central pressure on local government had similar effects elsewhere. It argues that the combined force of these grievances together with opposition to Laudian aggression produced a strong reaction which in Leicestershire led to Hesilrige's election to the parliaments of 1640. It traces the steps by which the opposition leaders were forced, in the absence of a settlement, to adopt increasingly confrontational tactics during 1641, and the part played by Hesilrige in this process. The drift to war in 1642 was accelerated by the struggle for control of the Leicestershire militia which brought together national and local conflicts.
Hesilrige became an enthusiastic soldier and leading partisan of Sir William Waller's political army in the competition between military lobbies which intensified political divisions and bitterness at Westminster during 1643 and 1644. At the same time he remained interested in securing influence and power in his county and became involved in fresh conflicts there during 1644. Political battles at Westminster, the rivalry of the generals, and struggles in Leicestershire came to a head in late 1644 and early 1645 and propelled Hesilrige into a position of leadership amongst his allies in the Commons and of dominance in his own county. The question raised by his immersion in short-term tactical struggles during the early 1640s was whether he could make constructive use of power.
Judging interpretations
Keywords: judging interpretations
legitimacy of governments
illegitimacy
philosophy
meaning
judicial discretion

Interpretation is fashionable, and not just in jurisprudence. Yet for all the attention interpretation has received in the past few decades, we have a poor understanding of what it is and what counts as doing it well. This thesis begins with the question, ‘What is interpretation?’ I argue that the reigning orthodoxy which holds that interpretation seeks meaning is misguided. A more illuminating account of interpretation is developed on which interpretation seeks understandings. After explaining what interpretation is and how it works, I explore the norms which govern it. As part of this exploration, I expose a number of mistakes in Stanley Fish’s account of the nature of interpretive constraints. Ib then develop an alternative account of what it means to say that objects (including texts) constrain their own interpretation, and I show that they often do so. I outline a view of interpretation I call almost pragmatism according to which the appropriate standards for judging an interpretation vary with the purpose for making the interpretation. I also argue that legal theorists have misunderstood and misapplied Ludwig Wittgenstein’s remarks on rules and interpretation in a variety of ways. I conclude that there is nothing useful we can learn about law from Wittgenstein’s remarks on rules.
The second part of this thesis uses the improved understanding of interpretation developed in the first part to shed light on problems which have long perplexed students of jurisprudence. I begin by considering what standards should be used to assess judicial interpretation. I argue that the appropriate standards to use will properly vary among different legal systems, and thus general jurisprudence can contribute little to the debate. Two general suggestions for norms which might govern legal interpretation—fidelity to legislative intent and Ronald Dworkin’s best light requirement—are taken up in the final chapters. In preparation for the final chapters, I summarize Joseph Raz’s account of authority, which forms the basis of many of the arguments to be considered. I suggest that Raz’s account of legitimacy is inadequate for understanding the legitimacy of political authorities. I then turn to arguments Raz offers suggesting that, in a limited sense, judicial interpretations ought to be judged according to their fidelity to legislative intent. I contend that Raz is wrong in thinking that we must interpret in accord with the intention of law-makers in order to make sense of their authority. The final chapter examines Dworkin’s best light requirement. I present an understanding of its content and scope consistent with what we learned about interpretation in the opening chapters and consider important objections to it. I conclude that Dworkin’s interpretive method is not inconsistent with law’s authority, as Raz and others have maintained.