VictorJuiz/thesis huggingface dataset:
Optimising the performance of genetically engineered Aedes aegypti

The mosquito Aedes aegypti is the primary worldwide vector of dengue fever, of which there are an estimated 390 million infections annually. Traditional vector control methods have been unsuccessful in preventing Ae. aegypti from posing a serious threat to human health worldwide, and as a result increasing emphasis is being placed on new control technologies. One of these is RIDL® (Release of Insects carrying a Dominant Lethal), a modified form of the sterile insect technique. Released RIDL males of strain OX513A are genetically engineered to possess a repressible lethal construct. Upon mating with a wild female, the construct is inherited by the offspring, causing their death.
The RIDL strategy depends on the mass production and release of vigorous male insects, capable of competing with wild males to mate with wild females. Chapter 2 investigates how rearing conditions can influence the size, asymmetry, quantity, and timing of OX513A mosquitoes produced. Chapter 3 describes the design and testing of devices for the release of these adult males, and their implementation during the world’s first release of transgenic mosquitoes. Chapter 4 discusses how the modification of male size and nutritional status may affect subsequent performance, and how these changes to male vigour will be assessed in subsequent chapters. Chapter 5 measures changes in competitiveness by examining longevity. Larger males lived longer, and longevity was increased by increasing the duration of the initial sugar feed. Chapter 6 examines the potential improvements in male performance by measuring the flight capacity of OX513A males, using a purpose-built mosquito flight mill. Male size or nutritional status was not found to affect flight capacity, although light intensity was unexpectedly found to modulate the flight speed of the males. Finally, Chapter 7 examines potential improvements in the mating performance of male OX513A Ae. aegypti. When OX513A males and wild-type males were placed in direct competition for virgin females, smaller OX513A males were found to have a significant mating advantage over larger wild-type males. The results of all three of these performance measures are discussed with relevance to field releases.
The results presented in this thesis improve current knowledge of how the performance of male mosquitoes can be effectively measured and improved. This is a vital part of ensuring the success of male-release vector control strategies such as RIDL.

Keywords: Aedes aegypti
dengue
transgenic
RIDL
mosquito
Advisor: Speight, M
John Russell, the fourth Duke of Bedford, and politics, 1745-1751

This dissertation on the fourth duke of Bedford examines the political activities of a member of the House of Lords. It documents the activities of the members of the Pelham Administration, using Bedford's correspondence to provide an outline for the narrative. The aim is to provide a greater understanding of Bedford's political career, and also to illustrate the influence this individual had in determining ministerial policy.
A discussion of Bedford's social connections leads into an overview of the events culminating in his inclusion in the Administration in 1745. Initially First Lord of the Admiralty, Bedford was promoted in 1748 to the office of Secretary of State for the Southern Department. In both offices, his concern was the promotion and protection of trade. He advocated the 'Country' Whig view that the protection of British merchants and their overseas markets by the navy was in the country‘s best interest. Bedford recognized the importance of securing and expanding American markets, and implemented measures, such as the proposed 'reduction' of Canada, to promote this aim. Bedford also lead the negotiations for the commercial treaty with Spain, signed at Madrid in 1750, that gave special trade status to Britain.
Bedford sought to increase his political influence in various constituencies during the 1747 General Election. The local influence he wielded, however, did not enable him to carry through private turnpike legislation in Parliament. His legislation was defeated on 13 February 1750, at third reading, in an unusually high vote (154-208). Newcastle, whose relationship with Bedford had grown increasingly acrimonious, played a role in the defeat of this bill. The deterioration in this relationship contributed to Bedford's resignation from office on 14 June 1751.

Keywords: century
Russell
politics
John
18th
eighteenth
Bedford
Advisor: Langford, P
A stepwise approach to understanding and effectively mitigating human-wildlife interactions

The study of conflicts in conservation (also known as human-wildlife conflicts) is a growing field of research in areas where people and wildlife interact, because of the negative impacts each can have on the other. Addressing conflicts is certainly challenging because of the complexities of considering diverse interests from numerous stakeholders and the specific ecological and socio-economic characteristics of a given study system. No matter how complex the system under study is, the aim is in all cases to find effective and sustainable mitigation strategies for local people, as well as for wildlife conservation and local authorities. In this thesis, I look at two of the preliminary steps required to address conservation conflicts and develop efficient long-lasting management solutions: the gathering of ecological data and the assessment of mitigation strategies in the field. To do this, I use two case studies: crop-foraging by African elephants (Loxodonta africana) in northern Botswana, and selective hunting of the red deer (Cervus elaphus) population on the Isle of Rum in Scotland. In Chapter 2, I built a baseline for the level of conflict in the Okavango Delta Panhandle (Botswana) using temporal trends of crop-foraging by elephants as an index of the level of conflict, and subsequently looked at how this relates to trends in agricultural land allocated in the study area, as well as with trends in human and elephant population size. In Chapter 3, I mapped the distribution of the local population of elephants and assessed its interaction with landscape features and sites where crop-foraging events had been recorded. In both chapters (2 & 3) I found that -in general- the number of elephants was not a determinant of the level of conflict in the study area, but that the spatiotemporal distribution of the species as well as the spatial and temporal scales considered were. In the second half of my thesis, I assessed the effects of two common conflict mitigation methods: the use of deterrents (Chapter 4) and lethal control (Chapter 5). I first evaluated the effectiveness of chilli-briquettes in deterring elephants and secondly, I used a modelling approach to predict the demographic effects of increasing levels of selective hunting in a male red deer population. I found that both mitigation methods showed unexpected results, which would not have been detected had I not tested for them. This thesis highlights the advantages of applying methods that are based on informed decisions in areas of conflict, as well as the value of sharing results in conservation management. My findings contribute towards a better understanding of the negative impacts of human-wildlife interactions, which often lead to conservation conflicts, as well as contributing protocols and methodologies that can be adapted and applied elsewhere.

Keywords: People's livelihood
Red deer
Conflicts in conservation
wildlife management
Elephants
Advisor: Coulson, T
Songhurst, A
Stronza, A
McCulloch, G
Malo, A
PWWP2A - a novel H3K36me3 reading component of the NuRD complex

Epigenetic regulation of gene expression is critical for lineage determination during development and the stable transmission of cellular identity through cell growth and division. Chromatin modifiers are a varied group of enzymes that regulate patterns of gene expression through the modification of DNA and histones. Epigenetic modifications alter the physical structure of chromatin or recruit effectors to promote or inhibit transcription. In this study, I examined the role of pre-existing histone modifications on the activity of Polycomb and Trithorax chromatin modifying enzymes. Additionally, identification of a novel H3K36me3-reader PWWP2A may constitute a new histone crosstalk pathway between H3K36me3 and histone deacetylation.
Polycomb and Trithorax proteins are two important families of transcriptional regulators that promote gene repression and activation respectively. In this study, I find that histone crosstalk between Polycomb complexes PRC1 and PRC2 promote one another’s activity while inhibiting Trithorax function. Recombinant nucleosomes carrying the PRC2 modification H3K27me3 stimulates the activity of CBX-PRC1, and nucleosomes with the PRC1 modification H2AK119u1 stimulates the activity of JARID2-PRC2. H2AK119u1 negatively regulates Trithorax activity and inhibits both the H3K4 methyltransferases MLL1/4 and the H3K36 methyltransferase NSD2. Histone crosstalk appears to be an important mechanism in the regulation of the recruitment and activity of chromatin modifiers.
I identified a novel H3K36me3 binding protein PWWP2A in an unbiased screen for readers of H3K27me3 and H3K36me3. Biochemical characterisation of PWWP2A in HeLa cells and mouse embryonic stem cells (mESCs) showed that PWWP2A interacts with NuRD subunits MTA1-3, HDAC1/2, and RBBP4/7. Genome-wide mapping of PWWP2A targets in mESCs shows that it is enriched over the gene bodies of highly transcribed genes sharing many gene targets with HDAC1. PWWP2A localisation correlates highly with H3K36me3, and its localisation at gene bodies is dependent on the putative H3K36me3-binding PWWP domain. In budding yeast, H3K36me3-mediated recruitment of the yeast HDAC complex Rpd3S is important for maintaining transcriptional integrity over coding regions. PWWP2A-NuRD may represents an analogous pathway of transcriptional regulation in mammalian organisms.

Advisor: Brockdorff, N
Essays on epistemic structure

This thesis is made up of five chapters: one integrative chapter, and four discrete essays. Each of the four essays is concerned with some aspect of epistemic structure. The first essay, Risk, Doubt and Transmission, explores structural analogies between testimonial transmission and closure principles. The second, Testimonial Pessimism, traces the connections between moral and aesthetic testimony’s putative shortcomings and the philosophy of language. The third essay, Epistemic Ambivalence, argues that the ideology of higher-order defeat is paradox prone, and as such, ought to be rejected. The fourth essay, Tragedy and Rationality, makes vivid some costs associated with endorsing an anti-akratic constraint on rationality.

Advisor: Fricker, E
Hawthorne, J
The north-eastern Aegean 1050-600 BC

This thesis aims to construct a historical narrative for the region of the north-eastern Aegean (NEA) during the Early Iron Age (1050-700 BCE) and the early Archaic period (7th century BCE) based primarily on archaeological evidence. Its goals are to investigate the most distinctive material culture elements for the studied period; to explore themes of continuity and connectivity between regions; to trace large- and smaller-scale population movements; to discuss how early communities perceived themselves and each other; and to investigate the social structure and organisation of these communities.
Evidence from settlement sites, funerary contexts, and sanctuaries are presented in the first three chapters in that order. Following that, the final chapter presents the primary, overarching conclusions of the thesis, in four sub-chapters.
Firstly, it is argued that the NEA was characterised by relative cultural continuity from the Late Bronze Age to well within the Archaic period: when new elements were introduced, they were, generally, integrated into earlier paradigms.
Secondly, evidence is provided for an increase in connectivity and maritime traffic peaks during the late 8th century BCE; shortly afterwards, new population groups from the central and southern Aegean arrived in the NEA, and seem to have cohabited relatively peacefully with earlier populations.
Thirdly, it is posited that there is little evidence for overarching NEA regional identities before the 6th century BCE: communities appear to have developed local identities, through association with specific sites and through references to the communal past in cult practice and funerary contexts.
Finally, it is argued that social elites were markedly active in NEA communities of studied period: there is considerable evidence for socially exclusive groups, primarily in funerary and ritual contexts.
The thesis concludes with a short chapter containing the author's closing remarks.

Keywords: Aegean Sea Coast (Turkey)
Archaic Period
Early Iron Age
Aegean Islands
Macedonia
Thrace
Advisor: Lemos, I
The algebra of entanglement and the geometry of composition

String diagrams turn algebraic equations into topological moves that have recurring shapes, involving the sliding of one diagram past another. We individuate, at the root of this fact, the dual nature of polygraphs as presentations of higher algebraic theories, and as combinatorial descriptions of "directed spaces". Operations of polygraphs modelled on operations of topological spaces are used as the foundation of a compositional universal algebra, where sliding moves arise from tensor products of polygraphs. We reconstruct several higher algebraic theories in this framework.
In this regard, the standard formalism of polygraphs has some technical problems. We propose a notion of regular polygraph, barring cell boundaries that are not homeomorphic to a disk of the appropriate dimension. We define a category of non-degenerate shapes, and show how to calculate their tensor products. Then, we introduce a notion of weak unit to recover weakly degenerate boundaries in low dimensions, and prove that the existence of weak units is equivalent to a representability property.
We then turn to applications of diagrammatic algebra to quantum theory. We re-evaluate the category of Hilbert spaces from the perspective of categorical universal algebra, which leads to a bicategorical refinement. Then, we focus on the axiomatics of fragments of quantum theory, and present the ZW calculus, the first complete diagrammatic axiomatisation of the theory of qubits.
The ZW calculus has several advantages over ZX calculi, including a computationally meaningful normal form, and a fragment whose diagrams can be read as setups of fermionic oscillators. Moreover, its generators reflect an operational classification of entangled states of 3 qubits. We conclude with generalisations of the ZW calculus to higher-dimensional systems, including the definition of a universal set of generators in each dimension.

Keywords: PROPs
categorical universal algebra
polygraphs
zw calculus
string diagrams
higher categories
zx calculus
categorical quantum mechanics
Advisor: Coecke, B
Econometric methods for implementing decision functions

This thesis develops econometric methods for implementing data-based decisions. Decisions are viewed as functions of parameters which are estimated from the data. Standard methods focus on providing precise estimates of parameters ignoring intention to use them in decisions. My thesis focuses on designing methods to minimize the expected error in decision functions. The first chapter develops model averaging estimators in multiple regressions that minimize the mean squared error (MSE) of a chosen decision function. Our motivating example is implementing a portfolio choice rule that depends on variables included in assets' returns specification. We characterize the asymptotic MSE of decisions functions based on different models and then describe model-selection and averaging estimators that enable improvements in the MSE. The performance of our method is demonstrated with extensive simulations and empirical applications to futures data. The second chapter describes the risk improvements for a model averaging using two models. This type of averaging is known as shrinkage. Since the risk improvement is over the function of parameters, this shrinkage is referred to as focused shrinkage. The estimator is a weighted average between unrestricted and restricted models. The latter is a minimum distance estimator and requires selecting a projection matrix. The risk improvement of our shrinkage estimator over maximum-likelihood for arbitrary projection matrices is derived. I then show in an application to portfolio choice, that for a specific choice of projection matrix, this improvement can be substantial. The third chapter considers an application of the focused shrinkage estimator to the Global Minimum Variance (GMV) portfolio. Implementing the GMV portfolio requires estimating a covariance matrix and the literature has offered several estimators. Focused shrinkage is particularly suitable here because it can be used to directly minimize the MSE of the GMV portfolio. We illustrate the benefits of our estimator by conducting extensive simulations and empirical applications.

Advisor: Sheppard, K
Estimating and comparing the cost-effectiveness of primary prevention policies affecting diet and physical activity in England

Health and public health services in England are under increasing financial pressure. At the same time, nearly 40% of the total disease burden is potentially amenable to known causes with two of the leading behavioural risk factors being unhealthy diets and physical inactivity. To better inform decision makers and improve health in England, this thesis aims to develop a cost-effectiveness model that can directly compare diet and physical activity interventions.
Published public health economic models were reviewed and the strengths and weaknesses of the modelling structures were explored. A pre-existing multistate life table model, PRIMEtime, was developed into PRIMEtime Cost Effectiveness (PRIMEtime CE). Disease specific NHS England costs were derived from NHS England Programme Budgeting Data and unrelated disease costs from NHS cost curves. Social care costs were quantified using a Department of Health tool for estimating wider societal costs. Disease specific utility decrements were adopted from a catalogue of EuroQoL five dimensions questionnaire scores. The cost effectiveness of reformulating food to have less salt and of expanding access to leisure centres in England were modelled from an NHS and social care perspective over a 10 year time horizon, including government and industry costs.
Salt reformulation was dominant with an estimated cost per quality adjusted life year (QALY) of -£17,000 (95% uncertainty interval, -£40,000 to £39,000), compared with £727,000 (£514,000 to £1,064,000) for increasing access to leisure centres. Sensitivity analyses and cross validation testing of outcomes demonstrated how cost per QALY estimates were sensitive to the choice of model scope, parameters, and structure.
PRIMEtime CE is a tool for decision makers to compare interventions affecting diet and physical activity, enabling them to make better informed choices about how to spend finite resources. Future work will focus on making the model freely available and expanding its risk factors to enable comparisons of other public health interventions.

Keywords: Public health
Health economics
Cost effectiveness
Health policy
Modelling
Multistate life table
Physical activity
Diet
Advisor: Scarborough, P
Wolstenholme, J
The effects of cerebral ischaemia on pericytes and neurovascular function

Acute ischaemic stroke is a major cause of morbidity and mortality in the developed world, yet the treatment options available are limited to therapies that restore vessel patency. Recanalisation of the occluded artery does not necessarily result in reperfusion of the downstream microvasculature, however, and the pathomechanisms involved in this are incompletely understood. One putative mediator of this is the capillary pericyte, a vascular mural cell type that may constrict under ischaemic conditions. The overarching aim of this thesis was to characterise vascular function following cerebral ischaemia, using in vivo, ex vivo and in vitro approaches. First, I demonstrated that ischaemia reduced both ipsilateral and contralateral cerebral blood flow responses to hypercapnia, and diminished reactivity of isolated pressurised arteries. I then developed a novel assay to characterise human pericyte contractility in vitro, and demonstrated that they are responsive to vasoactive substances even in the absence of αSMA expression. In this assay, chemical ischaemia caused pericyte contraction and subsequent death, consistent with in vivo reports describing their role in the no-reflow phenomenon. Finally, I explored whether the voltage-gated Ca2+ channel antagonist nimodipine could improve reperfusion in cerebral ischaemia, and found that rats treated with nimodipine exhibited improved post-ischaemic cerebral blood flow and ameliorated neurological impairment. However, I did not find a direct effect of nimodipine on pericyte contractility during chemical ischaemia in vitro, indicating that nimodipine may be targeting other cell types in the vasculature. Together, these data highlight the importance of vascular function following stroke and shed light on putative vasculoprotective approaches, which have translational potential to improve reperfusion in patients receiving recanalisation therapy.

Advisor: Buchan, A
Anthony, D
An archaeobotanical investigation into the Chalcolithic economy and social organisation of central Anatolia

Limited knowledge about the 3000-year period between the Neolithic and the Bronze Age in central Anatolia, Turkey, prevents any understanding of change or continuity in crop production, consumption and crop husbandry techniques. This research aims to address this bias through the examination of archaeobotanical remains from the four central Anatolian Chalcolithic sites of Çatalhöyük West, Çamlıbel Tarlası, Canhasan I and Kuruçay and the consequent investigation of their crop economies. This work draws on multiple methods and techniques to understand the plant-related activities that occurred at the sites.
The four chosen sites bookend the Chalcolithic period (c. 6000-3000 cal BC) and provide the opportunity for exploring the interrelationship between crop choice, crop husbandry, settlement size, surrounding environment and social organisation. Differences in crop species such as hulled barley, glume wheats and pulses, particularly lentil and bitter vetch occur at all four sites with species choice community specific.
Multiple methods are used to disentangle the depositional processes, such as dung burning, that formed the assemblages, providing an indication of the origin of the archaeobotanical material and allowing inferences about the nature of weed seeds found. Crop processing activities are evident at all sites, with the dehusking of glume wheat contributing significantly to the archaeobotanical assemblage. The analysis of stable carbon and nitrogen isotopes of crops coupled with the functional ecology of arable weeds, indicate that crop husbandry techniques/regimes were site specific and were influenced by site size/population as well as environmental conditions. The identification of the crops grown and the methods used to cultivate and process them have implications for understanding the social context of such activities, and the broader socio-economic background of a period preceding the great changes in social structure seen in the Bronze Age.

Keywords: Kuruçay
Crop processing
Canhasan I
Çamlıbel Tarlası
Çatalhöyük West
Agricultural production
Weed Flora
isotopes
Crop husbandry
Consumption
Advisor: Bogaard, A
Charles, M