VictorJuiz/thesis huggingface dataset:
A theory of early classical Ḥanafism
Keywords: The Hidāyah
Islamic legal epistemology
al-Marghīnānī
Hanafi law

Fiqh, literally 'deep understanding', is the science of religious law in Islam. What does it mean for an Islamic jurist to 'do fiqh'? And how does an engagement with fiqh guide a jurist to produce statements of law for particular social contexts? These are perennial questions in the field of Islamic legal studies. The current thesis offers an answer to these questions from the viewpoint of jurists from the early classical Ḥanafī tradition of Central Asia. The thesis starts with an examination of Central-Asian Ḥanafī works of legal theory to extract the underlying epistemological foundations of this legal tradition. The remainder of the thesis presents a series of investigations into a leading work of legal commentary – the Hidāyah of Burhān al-Dīn 'Alī ibn Abī Bakr al-Marghīnānī (d. 593/1197) – to assess how these epistemological foundations inform the work. These investigations range from a study of the processes by which the legal cases commented on in the work were seen to be authoritative, to a study of the use of rational arguments, dialectical sequences and juristic disagreement in exploring and expositing cases of the law. The thesis also studies points of theory employed in the commentary that reveal how social context was seen to impact on the production of law. The study concludes by suggesting a general theory of Ḥanafī jurisprudence, explaining what it means to 'do fiqh' – presented as a particular form of engagement with the legal cases transmitted from the teaching circle of Abū Ḥanīfah (d. 150/767), the school's eponym – and how this fiqh engagement with Ḥanafī precedent informed the production of legal statements tailored to specific contexts – by the application of a particular filter of legal mechanisms, each of which reflects an understanding of the overarching principle of 'necessity' (ḍarūrah). The study presents a uniquely Ḥanafī legal epistemology which is underpinned by particular notions of authority, rationality and tradition.
Inference on Markov random fields: methods and applications
Keywords: Variational Inference
Computational Bayesian Statistics
Expectation Propagation
Bayesian Machine Learning
Sampling Methods
Bouncy Particle Sampler
Markov Random Fields

This thesis considers the problem of performing inference on undirected graphical models with continuous state spaces. These models represent conditional independence structures that can appear in the context of Bayesian Machine Learning. In the thesis, we focus on computational methods and applications. The aim of the thesis is to demonstrate that the factorisation structure corresponding to the conditional independence structure present in high-dimensional models can be exploited to decrease the computational complexity of inference algorithms. First, we consider the smoothing problem on Hidden Markov Models (HMMs) and discuss novel algorithms that have sub-quadratic computational complexity in the number of particles used. We show they perform on par with existing state-of-the-art algorithms with a quadratic complexity. Further, a novel class of rejection free samplers for graphical models known as the Local Bouncy Particle Sampler (LBPS) is explored and applied on a very large instance of the Probabilistic Matrix Factorisation (PMF) problem. We show the method performs slightly better than Hamiltonian Monte Carlo methods (HMC). It is also the first such practical application of the method to a statistical model with hundreds of thousands of dimensions. In a second part of the thesis, we consider approximate Bayesian inference methods and in particular the Expectation Propagation (EP) algorithm. We show it can be applied as the backbone of a novel distributed Bayesian inference mechanism. Further, we discuss novel variants of the EP algorithms and show that a specific type of update mechanism, analogous to the mirror descent algorithm outperforms all existing variants and is robust to Monte Carlo noise. Lastly, we show that EP can be used to help the Particle Belief Propagation (PBP) algorithm in order to form cheap and adaptive proposals and significantly outperform classical PBP.
Genomic approaches to virus discovery and molecular epidemiology
Keywords: Genetics
Avian influenza virus
Evolution
Metagenomics
Viruses
Genomics
Birds
Epidemiology
Metaviromics
Ecology
Virology
Phylodynamics

Viral sequence data has great potential for answering questions about the epidemiological dynamics and evolution of viruses. Classical approaches have sought amino acid changes that alter pathogenesis or transmissibility by influencing a virus's ability to enter or replicate within cells. However, this approach rarely recognises the fundamental impact of heterogeneous host contact structures and existing immunological responses on viral transmission. This thesis draws heavily on ecological and immunological concepts to explore the epidemiological dynamics, diversity and evolution of viruses using molecular sequence data.
A number of different research approaches and study systems are used in this thesis. I begin by describing a novel polyomavirus in a European badger, and apply phylogenetic techniques to analyze the evolutionary history of the Polyomaviridae. I subsequently describe a large metaviromic study in a population of wild mute swans, for which host demographic data are available. I describe nine new viral species and test whether age and season are associated with differences in abundance and prevalence of different viral taxonomic groups. The study highlights the potential of metaviromics for investigating viral epidemiological dynamics in natural populations.
Influenza A viruses of avian origin (AIV) threaten human and animal health. Using phylogeographic methods, I reconstruct the spatial spread of an H5N8 virus at a regional scale, and investigate how bird density and migration shaped this dispersal. Despite the importance of acquisition of humoral immunity to different strains throughout the lifespan of wild birds for epidemiological dynamics, this topic is poorly understood. I assess the accumulation of immune responses to AIV with age in mute swans. I consider how ecological factors, including age-structured immunity, might have affected the epidemiology of an H5N8 outbreak in the population.
For God, Country, and Empire? New Zealand and Irish boys in elite secondary education, 1914-1918
Keywords: New Zealand
History of Childhood and Youth
British Empire
History of Education
First World War
Ireland

This thesis compares adolescent engagement with the First World War in Ireland and New Zealand between 1914 and 1918. Twenty-five elite boys’ secondary schools are used as case studies, including Catholic and Protestant institutions. This approach not only captures a common adolescent cohort, but also brings transnational connections to the fore; Catholics comprised approximately 14 percent of New Zealand’s population, at least nine-tenths of whom were of Irish descent. In addition to differentiating student behaviour from adult-articulated expectations, boys’ responses to the war are juxtaposed against those of their teachers. Using school periodicals, newspapers, and memoirs, this thesis partially recovers the neglected history of adolescent wartime experiences in two under-researched regions of the British Empire. It also elucidates the ways in which hostilities disrupted age-specific concerns and practices in elite school settings.
Age was critical in shaping how male non-combatants were impacted by, and reacted to, the conflict. This argument is substantiated by in-depth analyses of several related themes, including ‘war enthusiasm’, death, dissent, and cultural ‘re-mobilization’. While the First World War was near-uniformly identified as a crucial event, staff responses were mediated by longstanding orientations and responsibilities. Teachers prioritised institutional concerns such as state funding and school status throughout. Irish and New Zealand adolescents also engaged with hostilities on their own terms; ‘boy culture’ and age-related interests provided a constant baseline against which external interventions into daily life were evaluated. These cross-national similarities were modulated by immediate contexts. Coercive measures implemented by the state did not always receive popular support, contributing to new political trajectories and visions of the future within particular communities. National parameters also had the final say as to when students could legally enlist. This intersection of age and place ultimately proved pivotal in determining civilian reactions to major global developments during the 1910s.
Electronic communication in heterometallated porphyrin oligomers
Keywords: Electronic communication
Template
self-assembly
Nano
Porphyrin
heterometallated

This thesis presents the synthesis and characterisation of a range of heterometallated porphyrin oligomers and other novel 3D π-conjugated porphyrin nanostructures. Subsequently, their physical organic properties were evaluated which revealed some fascinating electronic properties.
Chapter 1 summarises some of the work done in the Anderson group on porphyrin nanostructures and reviews the literature regarding heterometallated porphyrin oligomers. In addition it introduces the main concepts and techniques used in the remainder of the thesis.
In Chapter 2 the stabilities of a family of four linear porphyrin pentamer complexes are determined by UV-vis-NIR titrations and analysed using chemical double-mutant cycles which reveal that the binding energy of the copper centre to an axial pyridine ligand is –6.2 kJ mol–1. Subsequently, the Zn-Zn-Cu-Zn-Zn pentamer is used in the synthesis of a heterometallated 10-porphyrin nanoring.
Chapter 3 will describe the investigation of quantum interference phenomena in a bis-copper six-porphyrin nanoring by using EPR spectroscopy. We show that the exchange coupling between two spin centres is increased by a factor 4.5 in the ring structure with two parallel coupling pathways as compared to an otherwise identical system with just one coupling path.
In Chapter 4 the syntheses of three isomers of the bis-copper 6-porphyrin nanoring are described. DFT calculations have indicated potential destructive interference phenomena in one of the isomers which would allow for the formation of a molecular system with behaviour resembling that of a hypothetical molecular interferometer.
Chapter 5 reports on the template-directed synthesis of a π-conjugated 14-porphyrin nanoball. This bicyclic structure consists of two intersecting nanorings of 6 and 10 porphyrin units. Fluorescence up-conversion spectroscopy experiments demonstrate that electronic excitation delocalises over the whole 3D π-system within 0.3 ps if the nanoball is bound to its templates or within 5 ps if the nanoball is empty.
In Chapter 6 the synthesis and characterisation of a D4h symmetric analogue of the porphyrin nanoball is described. The structure consists of ten porphyrin units arranged as two perpendicular 6-porphyrin nanorings intersecting at two porphyrins. In the synthesis, a combination of magnesium and zinc porphyrins are used which allows for the introduction of a selective demetallation method crucial for accessing this novel structure.
Understanding pneumothorax: epidemiology, physiology and predicting outcome
Keywords: Predicting outcomes
Epidemiology
Spontaneous
Pneumothorax

Contrary to traditional teaching, patients with Primary Spontaneous Pneumothorax (PSP) do not have normal lungs. Emphysema-like change (ELC) and inflammation are common. However, the natural history of ELC and its significance in terms of future disease is not known. Current management of pneumothorax is generic and not personalised.
This thesis updates the UK epidemiology of pneumothorax, describes the use of two novel methods to examine the lungs, a method of predicting early treatment failure, the association of CT findings and recurrence, and a systematic review of chemical pleurodesis to reduce recurrence.
Analysis of fifty years’ data on ~150,000 admissions demonstrated that the incidence of pneumothorax is increasing, and established a method to identify primary from secondary pneumothoraces and their relative risk of recurrence.
Reduced ventilation of hyperpolarised Xenon on enhanced-Magnetic Resonance Imaging (MRI) was seen in those PSP patients with greater low attenuation areas on Computed Tomography (CT) and with reduced pulmonary function. A model of lung inhomogeneity found that metrics of lung ventilation distinguished pneumothorax patients from healthy volunteers and Chronic Obstructive Pulmonary Disease (COPD) patients. This may represent subtle or mild disease, not identified on standard testing, which may be exacerbated by smoking.
CT scanning found that mild emphysema and cystic airspaces were common in PSP patients. Ex- or current smokers had more (and larger) cysts. Emphysema was more common in smokers and patients with a history of previous pneumothorax: who were at higher risk of recurrence. However, variation in number and size of cysts were seen in both those patients with and without recurrence. As such, no single algorithm to predict recurrence was identified.
Airflow measurement early in the patient pathway has the potential to identify those likely to fail treatment, potentially allowing early triage to surgery. The addition of talc or minocycline as an adjunct to surgery provides the lowest recurrence rates, but physician-led talc poudrage may be similarly effective. Those in whom surgery is not suitable, chemical pleurodesis could be offered via chest drain.
Data presented in this thesis thus provides insights into the underlying abnormalities in PSP and lays the groundwork for strategies to fundamentally alter the management paradigm.
An autophagy-related single nucleotide polymorphism in artemisinin-resistant Plasmodium falciparum
Keywords: Artemisinin-resistance
Plasmodium falciparum
Autophagy-related protein 18

Artemisinin-resistant Plasmodium falciparum parasites have been reported in the Greater Mekong Subregion since 2007. Artemisinin combination therapy (ACT) is the mainstay of antimalarial treatment and is responsible for decreases in malaria-related morbidity and mortality over the past fifteen years. The slowed parasite clearance rates following ACT indicates resistance to artemisinin derivatives. This resistance places increasing selective pressure for variants or traits that confer resistance to the partner drug used in combination and has led to the rapid failure of several partner drugs. While a single nucleotide polymorphism (SNP) in kelch13 has been shown to mediate some resistance phenotypes, the complete mechanism of artemisinin resistance is poorly understood. The known mechanisms of resistance hint at a connection to autophagy, an intracellular pathway that cells use to degrade waste molecules or organelles in response to stress and starvation, which is poorly characterized in Plasmodium. In this doctoral thesis project, I investigated the role of an autophagy-like mechanism in P. falciparum in the mechanism of artemisinin resistance. I found a SNP in autophagy-related gene 18 (atg18) that was associated with clinical delayed parasite clearance half-life following ACT. This gene encodes PfAtg18, a protein that I characterized as being similar to mammalian/yeast homologues in terms of structure, binding abilities, and ability to form puncta in response to stress. In order to investigate the contribution of the mutation in this protein, I edited the atg18 gene using CRISPR/Cas9 and screened the mutant and parent parasites against a drug library of over 6000 unique compounds. I discovered that while the SNP did not change the mutant parasite’s susceptibility to any of the antimalarial compounds using a 72-hour drug pulse, it did alter the susceptibility to 227 other compounds. Further, I found that the SNP offers parasites a fitness advantage by allowing them to grow better in nutrient-limited settings. Finally, I determined that neither this atg18 SNP nor several polymorphisms in kelch13 modulate a dormancy phenotype that appears to be involved in the artemisinin-resistance mechanism.
Self-referential rhetoric: the evolution of the Elizabethan 'wit'
Keywords: Francis Bacon
John Lyly
Thomas Nashe
Euphuism
Robert Greene
Philip Sidney
Gabriel Harvey
Roger Ascham

The thesis traces the evolving attitudes towards rhetoric in the highly-rhetorised English-language prose of the late sixteenth century by focusing on a term that was itself subject to significant change: ‘wit’. To wit’s pre-existing denotations of intellectual acumen, capacity for reason and good judgement was added a novel meaning, related to the capacity for producing lively speech. As a term encompassing widely divergent meanings, many Elizabethan and early Stuart works explored ‘wit’ as a central theme or treated the term as significant to explorations of the human mind, its capacity for rhetoric, and the social and moral dimensions of this relationship.
The research centres on how ‘wit’ is seen and how it corresponds to rhetorical wittiness as produced in practice, and questions the implications of this for understanding the social and moral dimensions of the authorial wit. By focusing on the early vernacular manuals of rhetoric by author such as Thomas Wilson and Roger Ascham, on Lyly’s and Greene’s euphuist prose, and on Thomas Lodge’s and Sir Philip Sidney’s prose defences of poetry, the first half of the thesis explores the term’s conceptual ambiguity. Potentially both reformative and deceptive, this ambiguity becomes a useful tool for the author looking to construct a profitable persona as a Wit, or a brilliant-yet-unruly master of rhetoric. The second half of the research notes how ‘wit’ tends to outlive its usefulness as a multivalent term in later writings when these seek to move away from the social commodification of an author’s rhetoric. Examining Sidney’s theological and political aims in The New Arcadia, Thomas Nashe’s carnivalesque questioning of the idea of profit, and Francis Bacon’s systematic interpretation of Nature, the research suggests that rhetoric and ‘wit’ maintain both their significance and their ambiguity into the seventeenth century. A meta-rhetorical signpost, ‘wit’ comes to reflect through its use and disuse both the issues at hand and the inherent self-reflexivity of any attempt to deal directly with rhetoric.
Gaussian process tools for modelling stellar signals and studying exoplanets
Keywords: Bayesian inference
Stellar activity
Gaussian processes
Exoplanetary science
Exoplanets

The discovery of exoplanets represents one of the greatest scientific revolutions in history, and exoplanetary science has rapidly become uniquely positioned to address profound questions about the origins of life, and about humanity's place (and future) in the cosmos. Since the discovery of the first exoplanet over two decades ago, the radial velocity (RV) method has been one of the most productive techniques for discovering new planets. It has also become indispensable for characterising exoplanets detected via other techniques, notably transit photometry. Unfortunately, signals intrinsic to stars themselves - especially magnetic activity signals - can induce RV variations that can drown out or even mimic planetary signals. Modelling and thus mitigating these signals is notoriously difficult, which represents a major obstacle to using next-generation instruments to detect lower mass planets, planets with longer periods, and planets around more magnetically-active stars. Enter Gaussian processes (GPs), which have a number of features that make them very well suited to the joint modelling of stochastic activity processes and dynamical (e.g. planetary) signals. In this thesis, I leverage GPs to enable the study of smaller planets around a wider variety of stars than has previously been possible. In particular, I develop a principled and sophisticated Bayesian framework, based on GPs, for modelling RV time series jointly with ancillary activity-sensitive proxies, thus allowing activity signals to be constrained and disentangled from genuine planetary signals. I show that my framework succeeds even in cases where existing techniques would fail to detect planets, e.g. the case of a weak planetary signal with period identical to its host star's rotation period. In a first application of the framework, I demonstrate that Alpha Centauri Bb - until 2016, thought to be the closest exoplanet to Earth, and also the lowest minimum-mass exoplanet around a Sun-like star - was, in fact, an astrophysical false positive. Next, I use the framework to re-characterise the well-studied Kepler-10 system, thereby resolving a mystery surrounding the mass of planet Kepler-10c. I also use the framework to help discover or characterise various exoplanets. Finally, the activity modelling framework aside, I also present in outline form a few promising applications of GPs in the context of modelling stellar signals and studying exoplanets, viz. GPs for (i) enhanced characterisation of stellar rotation; (ii) generating realistic synthetic observations, and modelling in a systematic way the effects of an observing window function; and (iii) ultra-precise extraction of RV shifts directly from observed spectra, without requiring template cross-correlation.
Total synthesis of (–)-6,7-dideoxysqualestatin H5 by carbonyl ylide cycloaddition and cross–electrophile coupling
Keywords: catalysis
cross-coupling
total synthesis of (–)-6,7- Dideoxysqualestatin H5
cross-electrophile coupling

The work presented in this thesis focuses on the total synthesis of (–)-6,7- Dideoxysqualestatin H5. Particular emphasis was the development of a cross– coupling strategy for direct delivery of the side chain towards the end of the synthesis.
Various methods investigated to perform the key Csp3–Csp2 coupling initially led to the Fu variant of the Negishi coupling at elevated temperatures and subsequent cross– electrophile coupling at rt. Key features of the asymmetric synthesis of (–)-6,7- dideoxysqualestatin H5, include: (1) highly diastereoselective n-alkylation of a tartrate acetonide enolate and subsequent oxidation-hydrolysis to provide an asymmetric entry to a β-hydroxy-α-ketoester motif; (2) facilitation of Rh(II)-catalysed cyclic carbonyl ylide formation-cycloaddition by cogeneration of keto and diazo functionality through ozonolysis of an unsaturated hydrazone; and (3) stereoretentive Ni-catalysed Csp3–Csp2 cross–electrophile coupling between tricarboxylate core and unsaturated side-chain to complete the natural product.
Following completion of the natural product, further work was carried out on the ozonolysis of unsaturated tosylhydrazones as a direct approach to diazocarbonyls. The scope and limitations of reacting unsaturated tosylhydrazones with O3 followed by Et3N for the generation of 1,4- and 1,5-diazocarbonyl systems were explored. Tosylhydrazones, from tosylhydrazide condensation with readily available δ- and ε- unsaturated α-ketoesters, led in the former case to a 2-pyrazoline whereas the latter cases led to α-diazo-ε-ketoesters, although a terminal alkene produced a tetrahydropyridazinol. Tosylhydrazones from cyclic enones also allowed access to 1,4- and 1,5-diazocarbonyl systems using the ozonolysis–Et3N strategy.