VictorJuiz/thesis huggingface dataset:
Divine assemblies in early Greek and Mesopotamian narrative poetry
Keywords: Epic Poetry
Greek Gods
Comparative Mythology
Ancient Near Eastern Gods
Divine Assemblies
Comparative Literature

This thesis charts divine assembly scenes in ancient Mesopotamian narrative poetry and the early Greek hexameter corpus, and aims to contribute to a cross-cultural comparison in terms of literary systems. The recurrent scene of the divine gathering is shown to underpin the construction of small- and large-scale compositions in both the Sumero-Akkadian and early Greek traditions. Parts 1 and 2 treat each corpus in turn, reflecting a methodological concern to assess the comparanda within their own context first. Part 1 (Chapters 1-4) examines Sumerian narrative poems, and the Akkadian narratives Atra-ḫasīs, Anzû, Enūma eliš, Erra and Išum and the Epic of Gilgameš. Part 2 (Chapters 5-8) considers Homer's Iliad, the Odyssey, the Homeric Hymns and Hesiod's Theogony. The comparative approaches in Part 3 are developed in two chapters (9-10). Chapter 9 offers a detailed comparison of this typical scene's poetic morphology and compositional purpose. Relevant techniques and effects, a function of the aural reception of literature, are shown to overlap to a considerable degree. Although the Greeks are unlikely to have taken over the feature from the Near East, it is suggested that the Greek divine assembly is not to be detached form a Near Eastern context. Because the shared elements are profoundly embedded in the Greek orally-derived poetic tradition, it is possible to envisage a long-term process of oral contact and communication fostered by common structures. Chapter 10 turns to a comparison of the literary pantheon: a focus on the organisation of divine prerogatives and the chief god figures illuminates culture-specific differences which can be related to historical socio-political conditions. Thus, this thesis seeks to enhance our understanding of the representation of the gods in Mesopotamian poetry and early Greek epic, and develops a systemic approach to questions of transmission and cultural appreciation.
The shifting sands of evidence: a socio-legal enquiry into the development of medical guidelines
Keywords: medical guidelines
regulation
evidence-based medicine
socio-legal studies

Medical guidelines on the same medical condition differ between England and the Netherlands. These guidelines are referred to as evidence-based because they are supposedly based on a systematic searching for and appraisal of medical studies to drive recommendations for appropriate care for specific clinical circumstances. This comparative study interrogates what causes these differences and similarities between guidelines and tries to uncover the mechanisms behind the development of medical practice guidelines. Four case studies, on lower back pain and on type 2 diabetes in both countries, are used to provide a detailed empirical account of the development of medical guidelines. Interviews with guideline developers are combined with a detailed analysis of available guideline documents. The overarching finding of this thesis is that medical evidence plays a more limited and nuanced role in guideline construction than might be expected and that guidelines are manifestations of professional (self-) regulation. Importantly, the research also finds that institutions shape guidelines in a multitude of ways. This study has endeavoured to add to a more nuanced understanding of evidence within the literature: conceptualising evidence as part of a process of a social and institutional construction. This construction is used within a collaborative and communicative process aimed at creating 'objective facts'. Contrary to existing scholarship, this thesis argues that evidence merely informs the understanding of members of guideline groups while a range of economic, cultural, institutional, and political factors, that together form cognitive frames, provide the driving force behind the development of guidelines. Institutional factors have shown to be essential elements in guideline development, influencing all aspects of development through institutional cultures of practice. This study concludes that calling guidelines evidence-based is an important rhetorical instrument, which helps to conceal and legitimize some of the normative choices that are inherent in guideline making.
Analysis and management of temperature fields in F1 cars
Keywords: Linear superposition
Thermal analysis
Heat transfer
Combustion engines

This thesis investigates the broad subject of thermal management problems currently encountered in Formula One race car design.
A computationally economical tool, based on linear superposition, for predicting the temperature field arising from a set of thermal and inlet velocity boundary conditions was developed. Using a set of base analyses, the research showed that it is possible to superpose and scale these results in order to predict the temperature field for differing sets of boundary conditions. This method was shown to have a significant speed advantage over typical computational simulations. An experimental facility was designed and built to provide validation for aspects of the linear superposition approach.
A method of measuring the cylinder wall heat flux has been developed using thin film gauge technology. The resulting sensor was designed to fit the mounting of existing instrumentation in order to avoid requiring large scale modifications to existing test facilities. The design makes use of modern rapid prototyping techniques in order to meet this mounting requirement and to provide a novel solution to routing the signal from the thin film gauge.
In addition, the research investigated a method for predicting the cylinder wall temperature in real-time. The cylinder wall is subject to heat fluxes from in-cylinder gases during the engine cycle on the inner face and the effect of the coolant jacket on the outer face. Two separate methods were used to process these thermal boundary conditions respectively, before being superposed in order to form the whole solution. The computation time of the method is characterised in order to demonstrate its feasibility for real-time operation.
The sustainability assessment of energy policy in Nigeria: scenario planning and integrated modelling
Keywords: energy policy
integrated modelling
Nigeria
austainability assessment
scenario planning

This thesis presents a novel policy assessment tool that serves as a decision support framework for analysis of energy policy problems involving multilevel, multidimensional and multi-stakeholder complexity. This new approach, The Energy Policy Assessment Technique (E-PAT), integrates System Dynamics Simulation and Multi-Criteria Evaluation models into a unified assessment framework. The E-PAT doubles as a systems-thinking model and a multi-criteria evaluation archetype. The E-PAT is designed for assessing policy issues, particularly those relating to energy planning in a national context. It is a suitable tool for evaluation and selection of optimal policies from competing and conflicting alternatives. To test its robustness and practical application, a case study on energy policy evaluation in Nigeria is carried out with this tool. A model of the Nigerian energy economy was constructed, and three proposed government policies for Sustainable Energy Development were evaluated relative to a Business-As-Usual case. The evaluation process identified ‘best’ policy options according to stakeholder viewpoints. The original contribution of this research is the creation of an integrated, transparent and comprehensive assessment tool, and the development of measurable Energy Sustainability Indicators (ESI), to aid policymakers in diverse policy analysis. The new tool is intended to support assessment of energy policies in relation to impacts on the economy, society and environment.
The invention of an investment incentive for pharmaceutical invention
Keywords: drug regulation
R&amp;D
investment
prizes
investment protection
patents
international trade law
TRIPS
data exclusivity
public funding
pharmaceuticals
WTO
drugs
compulsory licensing

Pharmaceutical drugs are often hailed as the poster child for the proposition that patents foster accelerated rates of innovation. This sentiment stems, in large part, from the significantly high research and development (R&D;) costs endemic to the pharmaceutical sector. I argue that if the role of the patent regime is one of fostering higher amounts of investment in the R&D; process, it is better served by a direct investment protection regime, where the protection does not depend upon whether or not the underlying idea behind the drug is “new” and “inventive”, the two central tenets of patent law. Rather, any drug that successfully makes it past the regulatory filter ought to be entitled to protection, since its discovery and development entail significant investment and risk.
Owing to the inadequacy of the current patent regime in appropriately protecting intensive pharmaceutical R&D; investments from free-riders, I propose a comprehensive investment protection regime that protects all the investment costs incurred during the drug discovery and development process. Though similar to existing data protection regimes in some respects, it differs in others. Firstly, it enables a recovery of all R&D; costs, and not only costs associated with clinical trials. Secondly, unlike patents and data exclusivity which offer uniform periods of protection, it rewards investments in a proportionate manner, wherein drug originators are entitled to protection against free-riders only until such time as they recoup their specific investments and earn a rate of return on investment that is dependent on the health value of the drug.
Given that a pure market exclusivity based investment protection regime is likely to foster excessive pricing and subject the market to the dictates of a single firm, I advocate a compensatory liability model based on a novel cost sharing methodology, where follow-on entrants are free to manufacture the drug, but must pay a reasonable amount of compensation to the originator.
Human cleavage factor I (CFIm) and its role in alternative polyadenylation of pre-mRNA
Keywords: cleavage factor
mRNA
alternative polyadenylation

For many human protein-coding genes, alternative cleavage and polyadenylation (APA) of pre-mRNA generates distinct 3' untranslated regions (3'UTRs) with differing regulatory potential. Widespread 3'UTR shortening via APA occurs in proliferative cell states, including cancer, where it can lead to oncogene overexpression. There has therefore been significant interest in identifying factors which influence poly(A) site choice in different physiological states. The multi-subunit human cleavage factor I complex (CFIm), a core component of the mammalian pre-mRNA cleavage machinery, has been identified as a potential master regulator of APA, as its depletion leads to widespread 3'UTR shortening. However, mechanistic understanding of how CFIm influences poly(A) site selection, and how its activity is regulated, is lacking. In this work, gene editing was used to generate cell lines with substantial, permanent depletion of the 25 kDa or 68 kDa subunits of CFIm (CFIm25 and CFIm68), which exhibited the expected 3'UTR shortening for representative transcripts. Reversal of this 3'UTR shortening by CFIm25 or CFIm68 re-expression provided the basis for a complementation assay, which allowed various aspects of CFIm25 and CFIm68 function to be investigated in vivo. The capacity of CFIm25 to recognise UGUA RNA sequences was shown to make an important contribution to poly(A) site selection transcriptome-wide, and a novel function for the C-terminal arginine/serine-rich (RS domain) of CFIm68 in poly(A) site selection was identified. The potential contribution of CFIm post-translational modification (PTM) to APA regulation was also explored. Novel acetylation sites on CFIm25 and CFIm68 were identified, as well as extensive serine phosphorylation in the CFIm68 RS domain. Complementation analysis revealed that phosphomimetic mutations in this RS domain inhibited distal poly(A) site selection, suggesting a potential role for CFIm68 phosphorylation in APA regulation. Taken together, the findings presented here provide insights into several important determinants of CFIm function, and the complementation assay developed provides a useful tool for future investigations.
Enantioselective synthesis of chiral building blocks with non-stabilized nucleophiles
Keywords: Electrochemistry
Suzuki–Miyaura coupling
Boronic Acid
Siloxane
Enantioselective catalysis
Hiyama coupling
Organocatalysis

This thesis describes the combination of non-stabilized nucleophiles and prochiral/racemic electrophiles in transition metal catalyzed asymmetric transformations. These enantioselective reactions have tremendous potential for the formation of chiral building blocks and new structural motifs that can be found in a variety of natural products and their derivatives.
The first part of the thesis focuses on the synthetic approach towards anti-cancer active diterpenoid structures. The two key steps involve a Cu-catalyzed asymmetric conjugate addition of alkylzirconocenes to enones and an intramolecular oxidative cyclisation. Particular investigations into the cyclisation are made with organocatalysis, transition metal catalysis and electrochemistry for the formation of these tricyclic scaffolds.
In the second part this work builds on the Rh-catalyzed asymmetric Suzuki–Miyaura coupling of benzeneboronic acids and cyclic allyl chlorides, which has been developed in our group. Here, the main point is to use more challenging coupling partners, such as heteroaromatic boronic acids, which are coupled to racemic cyclic allyl halides. The utility of this method is demonstrated by performing further transformations and an asymmetric synthesis of the natural product (+)- isoanabasine.
The last chapter describes the development of a new asymmetric Hiyama coupling of arylsiloxanes with racemic cyclic allyl chloride. Attempts are made to generate substrates that are not accessible via the asymmetric Suzuki–Miyaura reaction. After extensive optimisation a variety of arylsiloxanes is generated and tested with the best conditions to prove its utility in comparison to the asymmetric Suzuki–Miyaura coupling.
Structural insights into innate immunity against African trypanosomes
Keywords: Human African Trypanosomiasis
Strucutral biology
Sleeping sickness

The haptoglobin-haemoglobin receptor (HpHbR) is expressed by the African try- panosome, T. brucei, whilst in the bloodstream of the mammalian host. This allows ac- quisition of haem, but also results in uptake of trypanolytic factor 1, a mediator of in- nate immunity against non-human African trypanosomes. Here, the structure of HpHbR in complex with its ligand, haptoglobin-haemoglobin (HpHb), is presented, revealing an elongated binding site along the membrane-distal half of the receptor. A &Tilde;50° kink allows the simultaneous binding of two receptors to one dimeric HpHb, increasing the efficiency of ligand uptake whilst also increasing binding site exposure within the densely packed cell surface. The possibility of targeting this receptor with antibody-drug conjugates is ex- plored. The characterisation of the unexpected interaction between T. congolense HpHbR and its previously unknown ligand, haemoglobin, is also presented. This receptor is iden- tified as an epimastigote-specific protein expressed whilst the trypanosome occupies the mouthparts of the tsetse fly vector. An evolutionary pathway of the receptor is proposed, describing how the receptor has changed to adapt to a role as a bloodstream form-specific protein in T. brucei. Apolipoprotein L1 (ApoL1) is the pore-forming component of the trypanolytic factors. An expression and purification protocol for ApoL1 is presented here, and the functionality of the protein established. Initial attempts to characterise the pores and structure of ApoL1 are described.
'The defence of contraries'
Keywords: sixteenth
disciplines
paradox
life
Renaissance
17th
seventeenth
Europe
16th
contraries
century
intellectuals

The aim of this thesis is to examine the meanings and functions of paradox in the late Renaissance. My understanding of Renaissance paradox, in contrast to that of most critics and historians, rests entirely on contemporary definitions of the term, rather than on its present-day meaning. Paradoxes as they are envisaged in this study begin to appear in the wake of the humanist rediscovery and dissemination of Cicero's Paradoxa Stoicorum. In this work, paradoxes are characterized as 'admirabilia contraque opinionem omnium', a definition that draws attention to two important traits of paradox, repeatedly invoked in the Renaissance: its association with wonder, and its opposition to common opinion. This thesis examines the history of classical paradox as it was revived, expanded beyond the narrow confines of Stoic ethics, and adapted to new purposes so successfully that it became a recognisable genre of polemical writing, with hundreds of works in Latin and the vernacular being described as paradoxes. Previous studies of Renaissance paradox have centred almost exclusively on its literary and vernacular manifestations, and on the paradoxical encomium in particular. My own work charts the rise to prominence and the ensuing transformations of paradox in a range of disciplines: rhetoric and ethics, theology, law, medicine, and natural philosophy. I compare the different associations that paradoxes acquire in all these areas, and the argumentative strategies that they deploy. My analysis of specific examples of paradox is informed by the methods of both literary analysis and intellectual history. Paradoxes, I argue, offered their authors the possibility of departing from established norms and of voicing novel views in a period of intellectual unrest. In their challenge to received and common opinion, they paved the way for more radical ideas in the following century, and they have much to tell us about dissident ways of thinking in the late Renaissance.
Supply services of English armed forces, 1509-50
Keywords: supply
forces
English
armed
services

This thesis attempts to trace the effect of the increased size and complexity of armies and navies in the early VIth Century on the English supply services, and also to analyse selected campaigns as a test of governmental efficiency.
The provision of ships, guns, gunpowder, and hand-weapons is first discussed, in relation to national self—sufficiency. Ship timber was occasionally imported, but England could, if necessary, have done without foreign supplies; the timber problem was not a pressing one at this period. Naval stores (pitch, cordage etc.) on the other hand, were almost always imported, and the Baltic had thus already acquired something of its later strategic importance. Equally important were the Netherlands. In 1509 all but the smallest artillery was obtained there. This was remedied by the beginning of large-scale bronze and cast-iron gun-manufacture in England; but England still depended on the Netherlands in 1550 for saltpetre (for gunpowder) and copper (for bronze).
Werner Sombart's contention that military requirements stimulated the growth of large-scale industry is discussed; shipbuilding and cannon-founding support his argument, provided that the small-scale of industry in general at this period is borne in mind.
[Continued in thesis ...]
Insights into the design of an improved PfRH5 malaria immunogen using vaccine-induced monoclonal antibodies
Keywords: Synergy
Malaria
Vaccine
Monoclonal antibody

The causative agent of the most deadly form of malaria, P. falciparum, was identified over 130 years ago, yet this disease still causes 430,000 deaths each year. Although naturally-acquired immunity exists, it requires a heavy and sustained exposure to the parasite, with most succumbing as young children, before this immunity has fully developed. Effective treatments exist but with small-molecule drug resistance on the rise and little in the way of affordable alternatives, the need for an efficacious malaria vaccine is as great as ever. A successful malaria vaccine is likely to necessitate targeting each stage of the parasite's lifecycle. Immunity directed to the blood-stage, the stage which causes all the symptoms of malaria, is unique in that it would allow for a concomitant development of naturally-acquired immunity along with a reduction in morbidity and mortality. To date, antibody-mediated immunity to the blood stage requires intractably high levels of antibody and this problem is compounded by a paucity of viable candidates with which to effectively target different strains. Other fields of vaccinology, over the past decade, have been employing various structure-based strategies to increase the specific activity of the immune response thus lowering the antibody levels required for protection. However, very few detailed investigations of this kind have been conducted on a P. falciparum vaccine candidate, and certainly none as promising as PfRH5. In a world's first, fully-human antibodies raised in response to PfRH5 vaccination were isolated and extensively characterised, both functionally and structurally with the intention of elucidating the important features necessary to inform the design of an improved PfRH5-based vaccine. Synergistic and antagonistic effects of antibody combinations were noted and highlight new complexities of the immune response to PfRH5, opening the door to unanticipated potential for rational vaccine design.