VictorJuiz/thesis huggingface dataset:
The agrarian foundations of early twentieth-century Japanese anarchism: Ishikawa Sanshirō’s revolutionary practices of everyday life, 1903-1945

This dissertation examines the link between anarchism and agrarian thought in modern Japan through the investigation of the life and ideas of radical intellectual Ishikawa Sanshirō (1876-1956). I track its emergence from the time of Ishikawa's involvement in the socialist movement in the early 1900s to its development during his exile years in Europe between 1913 and 1920 and then after his return home through to the end of the Pacific War. I show how concern for the traditions and condition of farming communities informed a certain strand of non-violent anarchism premised on environmental awareness and cooperative principles fostered through the practices of everyday life.
By rescuing from near historiographical oblivion a major dissenting figure of modern Japan, this study gives prominence to a distinctive anarchist intellectual contribution. I examine both the theoretical premises and related socio-political applications, highlighting Ishikawa's role for over five decades as a creative force of social change and a bulwark against authoritarianism. Thus, this work puts forward a more nuanced understanding of the movement of popular agrarianism that marked the interwar period, often pigeon-holed by historians as an adjunct of radical nationalism. I also probe the ecological critique embedded in Ishikawa's vision of the man-nature interaction, which remained vital over the decades and has direct relevance to presentday concerns.
The tracing of Ishikawa's connections, both transnational and within Japan, provides the main methodological axis of this study. It appraises dissenting politics through the lens of actual praxis rather than categorization of ideological differences. Likewise, transnational connections are given agency as a mutually creative process rather than as a unidirectional transmission of ideas and values from West to East.

Advisor: Konishi, S
Kato's perturbation theorem and honesty theory

We study an additive perturbation theorem for substochastic semigroups which is known as Kato's Theorem. There are two previously-known generalisations of Kato's Theorem, namely for abstract state spaces and for KB-spaces. We prove a version of Kato's Theorem for a class of spaces which encompasses both, namely ordered Banach spaces with generating cone and monotone norm. We also study a property of the perturbed semigroup in Kato's Theorem known as honesty of the semigroup. We add a few results to the fairly extensive existing theory of honesty for Kato's Theorem for abstract state spaces. In light of our new generalisation of Kato's Theorem to ordered Banach spaces with monotone norm, we investigate generalising the theory of honesty to these spaces as well. The results for the general case are less complete as many of the results for the case of abstract state spaces depend on the additive norm structure of the space.
We also consider some new applications of honesty theory in abstract state spaces. We begin by applying honesty theory to the study of the heat equation on graphs. We prove that honesty of the heat semigroup coincides with a concept known as stochastic completeness of the graph which has been studied independently of honesty. We then look at the application of honesty theory to quantum dynamical semigroups. We show that honesty is the natural generalisation of the concept of conservativity of quantum dynamical semigroups. Conservative quantum dynamical semigroups are known to have certain "nice" properties. We show that similar properties hold for honest semigroups using honesty theory results. Finally, we consider a form of boundary perturbations in the context of transport semigroups. There exists an analogous theory of honesty for this set-up. We formulate a general result from which honesty results of both Kato's Theorem and transport semigroups can be derived.

Keywords: Kato's Perturbation Theorem
honesty theory
semigroups of operators
Advisor: Batty, C
High-fidelity quantum logic in Ca+

Trapped atomic ions are one of the most promising systems for building a quantum computer -- all of the fundamental operations needed to build a quantum computer have been demonstrated in such systems. The challenge now is to understand and reduce the operation errors to below the 'fault-tolerant threshold' (the level below which quantum error correction works), and to scale up the current few-qubit experiments to many qubits. This thesis describes experimental work concentrated primarily on the first of these challenges. We demonstrate high-fidelity single-qubit and two-qubit (entangling) gates with errors at or below the fault-tolerant threshold. We also implement an entangling gate between two different species of ions, a tool which may be useful for certain scalable architectures.
We study the speed/fidelity trade-off for a two-qubit phase gate implemented in 43Ca&plus; hyperfine trapped-ion qubits. We develop an error model which describes the fundamental and technical imperfections / limitations that contribute to the measured gate error. We characterize and minimise various error sources contributing to the measured fidelity, allowing us to account for errors due to the single-qubit operations and state readout (each at the 0.1% level), and to identify the leading sources of error in the two-qubit entangling operation. We achieve gate fidelities ranging between 97.1(2)% (for a gate time tg = 3.8 μs) and 99.9(1)% (for tg = 100 μs), representing respectively the fastest and lowest-error two-qubit gates reported between trapped-ion qubits by nearly an order of magnitude in each case. We also characterise single-qubit gates with average errors below 10-4 per operation, over an order of magnitude better than previously achieved with laser-driven operations.
Additionally, we present work on a mixed-species entangling gate. We entangle of a single 40Ca&plus; ion and a single 43Ca&plus; ion with a fidelity of 99.8(5)%, and perform full tomography of the resulting entangled state. We describe how this mixed-species gate mechanism could be used to entangle 43Ca&plus; and 88Sr&plus;, a promising combination of ions for future experiments.

Advisor: Lucas, D
Discovery and investigation of novel radiosensitising genes

Radiotherapy is second only to surgery in the curative management of patients with cancer, and yet the molecular mechanisms that determine the sensitivity of tumours to radiation remain largely unclear. A high-throughput radiosensitivity screening method based on clonogenicity was developed and a siRNA library against kinase targets was screened. The gold standard colony formation endpoint was chosen for determining reproductive cell death after radiation treatment, since effects on proliferation often do not reflect survival.
Thiamine pyrophosphokinase-1 (TPK1), a key component of Vitamin B1/thiamine metabolism, was identified as a target for radiosensitisation. TPK1 knockdown caused significant radiosensitisation in cancer but not normal tissue cell lines. Other means of blocking this pathway such as knockdown of thiamine transporter-1 (THTR1) or treatment with the thiamine analogue pyrithiamine hydrobromide (PyrH) caused significant tumour specific radiosensitisation. There was persistent DNA damage in cells irradiated after TPK1 and THTR1 knockdown or PyrH treatment. Thus this screen allowed the identification of thiamine metabolism as a novel radiosensitisation target that affects DNA repair. Short-term modulation of thiamine metabolism could be a clinically exploitable strategy to achieve tumour specific radiosensitisation.
Three additional genes, signal recognition particle-72 kDa (SRP72), glycogen synthase 3-beta (GSK3β) and MAP/Microtubule Affinity-Regulating Kinase 2 (MARK2) were also investigated. Knockdown of these genes radiosensitised both tumour and normal tissue cell lines and expression of two of them, GSK3β and SRP72 were found to be associated with poor recurrence-free survival in early breast cancer patients.

Advisor: McKenna, W
Higgins, G
Emotion unbound: asyndeton and emotionality in ancient Greek  and early modern English prose romance

— asyndeton, n., from the Greek ἀσύνδετον (ἀ without + συν together + δεῖν to bind)

This thesis seeks to demonstrate that the mode of figurative speech known as asyndeton, and the related asyndetic matrix, offers a unique insight into the way emotionality is depicted in early modern English prose romances. It charts the translation of asyndeton from ancient Greek prose romances, where the figure is used at moments of heightened emotional conflict. It examines the complex process through which this translation and the figure’s adaptation into asyndetic matrices in English continues to express and evoke subjective emotional concepts, by breaking down asyndeton's propensity for 'vehemence', 'earnestness', 'special vigour', 'agitation' and even 'frenzy' into a three-step process: dissolution, amplification and union.
In so doing, the thesis examines the asyndetic natures of Achilles Tatios's Leukippe and Kleitophon and Heliodoros's Ethiopian History, John Lyly's two volumes about Euphues, Sir Philip Sidney’s Old and New Arcadias and Robert Greene’s two volumes of Mamillia. By suggesting that the development of linguistic tropes stems from emotional tropes rather than vice versa, the thesis argues that social, emotional or psychological patterns may be potently transcribed in figures of speech, rather than that figures of speech served to fashion emotionality.

Advisor: Moore, H
Structural and functional characterisation of human carboxylesterases

Carboxylesterases are glycosylated general detoxification enzymes belonging to the serine esterase superfamily and play a critical role in the hydrolysis of numerous ester- and amide- containing molecules, including active metabolites, drugs and prodrugs. Three functionally active carboxyleterases have been identified in man (CES1-3), which all show differential tissue expression and critically overlapping, yet specific substrate selectivities. Elucidating the basis of their exact substrate preference would help facilitate the design of clinical prodrugs which are activated by carboxylesterases. Because of their widespread applications, carboxylesterases have attracted much attention in recent years, with CES1 being the most extensively studied human carboxylesterase to date.
The work presented here addresses the structure-function relationship of the three human carboxylesterases using a combination of X-ray crystallography, kinetic analysis and biophysical techniques. Recombinant proteins were successfully produced using a mammalian expression system in high yield (5.0 – 84.0 mg/ L cell culture). Analytic ultracentrifugation and size-exclusion chromatography coupled to multi-angle laser light scattering were used to investigate the proteins in solution. These results showed CES1 exists primarily in a trimeric arrangement, whilst CES2 and CES3 are monomeric. Interestingly, atypical mechanisms of substrate inhibition, positive cooperativity and biphasic kinetics were observed for both CES1 and CES2.
Three structures of CES1 were solved: wild type, an aglycosylated form and a catalytically inactive form, to 1.48, 1.86 and 2.01 Å respectively. The novel structure of CES2 was solved to 2.04 Å, which revealed that the enzyme forms a strand exchange dimer in contrast to the trimeric CES1.
To summarise, this thesis documents a platform that has been generated for the production, characterisation and crystallization of human carboxylesterases. This will aid future structural work for protein ligand binding studies.

Advisor: Owens, R
Walsh, M
Viral genetics of HIV-2 infection

HIV-2 is a contemporary human retrovirus with the majority of infections localised to West Africa. Both HIV-1 and HIV-2 are able to cause AIDS; however, in contrast to HIV-1 infection, a common outcome following HIV-2 infection (&Tilde; 37% of patients in this study cohort) is long-term non-progression (LTNP), where patients remain aviraemic and asymptomatic in the absence of treatment, often for decades. HIV-1 and HIV-2 both arose following zoonotic transmission of SIVs from non-human primates at around the beginning of the 20th century and when patients develop AIDS caused by HIV-2 infection, it is clinically indistinguishable from AIDS following HIV-1 infection.
Whilst the estimated number of HIV-2 infections remains small in the context of the global HIV pandemic (HIV-2 &Tilde; 2 million, HIV-1 group M &Tilde;75 million), the differences in pathogenicity between these two viruses has been a source of great interest, particularly the features of LTNPs that allow control of viral replication in the absence of anti-retroviral treatment.
The studies described in this thesis were carried out using samples collected from a well-characterised longitudinal community cohort in Caió, Guinea-Bissau. Chapter 3 of this thesis presents an investigation into the variation and evolution present in the HIV-2 specific accessory gene vpx. The data showed significantly increased signals of positive selection pressure in vpx in viraemic when compared to non-viraemic patients and also allowed the identification of novel variations at high frequencies (up to 22%) in this cohort that were previously un-described. Chapters 4 and 5 present a novel application of shotgun RNA sequencing (RNA- Seq) to HIV ex vitro and ex vivo samples. Chapter 4 demonstrates the divergence seen in a cultured viral isolate at the level of the whole genome, in the absence of many of the biases typically involved in sequencing of RNA viruses. Chapter 5 further extends this method to show the applicability of using RNA-Seq on primary patient HIV samples for the first time. Analysis of diversity estimates over the whole genome in the context of a low bias sequencing method show a high level of diversity in HIV-2 pol and low diversity in vpx.
The aim of this work was to combine traditional and novel sequencing methods to facilitate assessment of the variation and evolution acting on vpx and to generate an accurate picture of the genetic diversity over the whole genome of HIV-2.

Advisor: Rowland-Jones, S
McVean, G
Harnessing the immune system to reject cancers through genetic modifications of tumour cells

The immune system, which defends the body against a wide array of threats, is gaining a growing role in the fight against cancer. For an immunotherapy to be successful, it needs to overcome intrinsically weak tumour-specific immune responses. There are two broad approaches to achieving this goal: targeting the various arms of the immune system or targeting the cancer and its microenvironment. The experiments discussed in this thesis adopt the second approach. Tumours were transduced with a combination of costimulatory molecules: CD48, CD54, CD70 & CD86, the chemokine CX3CL1 and the cytokines: IFNγ, GM-CSF and IL-12. Transduction of costimulatory molecules enhances priming in-vitro and cause tumour rejection and delayed tumour growth in-vivo. This effect is demonstrated with single costimulatory molecules but is more pronounced when multiple costimulatory molecules are transduced. Addition of the cytokines and chemokine enhanced tumour rejection, and also resulted in partial rejection of contralateral parental tumours. Attempts to enhance anti-tumour memory by fusing IL-2 and IL-15 to their respective receptors are also discussed. Work in a human/mouse chimeric PD-1 mouse model shows that transduction of multiple costimulatory molecules is able to overcome intrinsic anti-PD-1 resistance. Radiation is known to result in upregulation of several costimulatory molecules within tumours or their infiltrating dendritic cells. The experiments presented here suggest that radiation therapy may be useful in overcoming anti-PD-1 therapy resistance. In human trials, approximately three quarters of cancers fail to respond to anti-PD-1 therapies. Understanding and potentially overcoming anti-PD-1 therapy resistance is therefore of great interest.

Advisor: Muschel, R
Cerundolo, V
Combined experimental and computational investigation into inter-subject variability in cardiac electrophysiology

The underlying causes of variability in the electrical activity of hearts from individuals of the same species are not well understood. Understanding this variability is important to enable prediction of the response of individual hearts to diseases and therapies. Current experimental and computational methods for investigating the behaviour of the heart do not incorporate biological variation between individuals. In experimental studies, experimental results are averaged together to control errors and determine the average behaviour of the studied organism. In computational studies, averaged experimental data is usually used to develop models, and these models therefore represent a 'typical' organism, with all information on variability within the species having been lost.
In this thesis we develop a methodology for modelling variability between individuals of the same species in cardiac cellular electrophysiology, motivated by the inability of traditional computational modelling approaches to capture experimental variability. A first study is conducted using traditional modelling approaches to investigate potentially pro-arrhythmic abnormalities in rabbit Purkinje fibres. A comparison with experimental recordings highlights their wide variability and the inability of existing computer modelling approaches to capture it. This leads to the development of a novel methodology that integrates the variability observed in experimental data with computational modelling and simulation, by building experimentally-calibrated populations of computational models, that collectively span the variability seen in experimental data.
We apply this methodology to construct a population of rabbit Purkinje cell models. We show that our population of models can quantitatively predict the range of responses, not just the average response, to application of the potassium channel blocking drug dofetilide. This demonstrates an important potential application of our methodology, for predicting pro-arrhythmic drug effects in safety pharmacology. We then analyse a data set of experimental recordings from human ventricular tissue preparations, and use this data to develop a population of human ventricular cell models. We apply this population to study how variability between individuals alters the susceptibility of cardiac cells to developing drug-induced repolarisation abnormalities. These abnormalities can increase the chance of fatal arrhythmias, but the mechanisms that determine individual susceptibility are not well-understood.

Keywords: Cardiac electrophysiology
Systems biology
Repolarisation abnormalities
Population of models
Inter-subject variability
Computational biology
Inter-individual variability
Cardiac modelling
Mathematical modelling
Computational modelling
Advisor: Lopez, B
Orovio, A
Cold War at the centre: liberalism and the politics of Euratlantic strategy, 1945-1990

Patterns of domestic political contestation in international affairs often see the centre aligned against both the left and the right of the ideological spectrum. This is observable in a range of issues, from democracy promotion, intervention, international law, European integration, free trade, globalization and the creation of international regimes. Why centre-periphery ideological competition occurs is an interesting puzzle, given the challenge it offers to the idea that partisanship is an inherently left-right phenomenon. Yet the role of the political centre in foreign policy has not been subjected to systematic analysis.
This thesis studies the nature and effects of the foreign policy position of the political centre. It argues that the centre is distinguished from left and right by its embrace of distinct elements of liberal ideology. The liberal view of international politics differs in thee important respects from its socialist and conservative competitors: It is particular, rather than pluralist, when it comes to questions of sovereignty and international legitimacy; it views interdependence, rather than independence, as a natural and desirable condition of the international; and it views deterrence, rather than diplomacy, as the best means of achieving security.
To test the validity of this thesis I discuss the role of ideology in explaining variation in relations between four Euratlantic states (Britain, France, West Germany and Canada) and the United States during the Cold War. This is a hard case given the intensity of global threat at the time. The thesis tests the claim that the strength of Euratlantic-American relations is a function of the relative influence of the political centre at the time. To do this it outlines a mixed-methods research design that combines in-depth case studies with a quantitative analysis of Euratlantic-US relations. The results from both elements confirm the validity of the theoretical proposition.

Advisor: Snidal, D
Number in Meryam Mir

This thesis examines the role of number in the syntax and semantics of Meryam Mir. It aims to provide evidence to support the claim that verbal number is a grammatical category in the language and can provide a more complete account of various syntactic phenomena than that of Piper (1989/2013) based solely on argument number. It also considers the number feature set within the syntax of the language and provides evidence to challenge Arka's (2012) assumption that the same feature set is used for argument and verbal number. This has wider implications for understanding the syntax of other languages with grammaticalised verbal number.
The thesis is divided into six chapters:
Chapter 1 introduces Meryam Mir, and gives a brief overview of the grammar of the language. It includes a literature review and notes on the creation of the text corpus used for this thesis, including orthographic and glossing conventions. It also sets out methodological challenges and constraints and defines the number theoretical concepts that will be used throughout the analysis.
Chapter 2 provides a systematic review of number marking in the grammar of Meryam Mir, which motivates a focus on number in the language and presents the data which are used in the subsequent analyses and accounts.
Chapter 3 proposes an account of argument number in Meryam Mir, considering the availability of categories through constructive number and relating these to Corbett's (2000) number hierarchy.
Chapter 4 proposes an account of verbal number in Meryam Mir. It examines in more detail those patterns that are not explained by argument number, and reanalyses them assuming verbal number categories developed in the light of Wood's (2007) semantic typology of pluractionality and Moens and Steedman's (1988) work on verbal plurality and aspect.
Chapter 5 proposes an account of the number feature system, drawing on work within the Lexical Functional Grammar framework (Bresnan, 2001) and in particular extending Arka's (2012) work on Marori to account for the oppositions seen in Meryam Mir.
Chapter 6 draws together these three accounts, identifies outstanding issues, and pro- poses questions that can be tested through targeted data collection with native speakers.

Advisor: Dalrymple, M