VictorJuiz/thesis huggingface dataset:
Combined decision making with multiple agents
Keywords: Variational Inference
Multi-classifier Systems
Classification
Bayesian
Variational Bayes
Ensemble Methods
Variational
Classifier combination
Classifiers
Citizen Science
Crowdsourcing
Bayes

In a wide range of applications, decisions must be made by combining information from multiple agents with varying levels of trust and expertise. For example, citizen science involves large numbers of human volunteers with differing skills, while disaster management requires aggregating information from multiple people and devices to make timely decisions. This thesis introduces efficient and scalable Bayesian inference for decision combination, allowing us to fuse the responses of multiple agents in large, real-world problems and account for the agents’ unreliability in a principled manner.
As the behaviour of individual agents can change significantly, for example if agents move in a physical space or learn to perform an analysis task, this work proposes a novel combination method that accounts for these time variations in a fully Bayesian manner using a dynamic generalised linear model. This approach can also be used to augment agents’ responses with continuous feature data, thus permitting decision-making when agents’ responses are in limited supply.
Working with information inferred using the proposed Bayesian techniques, an information-theoretic approach is developed for choosing optimal pairs of tasks and agents. This approach is demonstrated by an algorithm that maintains a trustworthy pool of workers and enables efficient learning by selecting informative tasks.
The novel methods developed here are compared theoretically and empirically to a range of existing decision combination methods, using both simulated and real data. The results show that the methodology proposed in this thesis improves accuracy and computational efficiency over alternative approaches, and allows for insights to be determined into the behavioural groupings of agents.
The role of nitric oxide as a hypoxic cell radiosensitizer
Keywords: tumour hypoxia
DNA damage
radosensitizer
nitric oxide

Many tumours contain regions of hypoxia which are difficult to treat by conventional radiotherapy. There is much interest in the ability of nitric oxide (•NO) to radiosensitize hypoxic mammalian cells as a possible adjunct to radiotherapy but mechanisms for its action are unclear. It has been proposed that •NO may radiosensitize cells by ‘fixing’ radiation-induced DNA free radicals, and elevated radiation response by •NO in cells has been partly attributed to increased formation of DNA double strand breaks.
In the work carried out for this thesis it is shown that reaction of •NO with radiation-induced nucleobase radicals produces some novel products. New pathways for the reactions of radiation-induced hydroxyl radicals with purine radicals are proposed. In addition, the effects of •NO on the yields of radiation-induced single strand breaks in anoxic plasmid DNA, and on anoxic mammalian cell radiosensitivity are investigated. Kinetics of formation and repair of radiation-induced double strand breaks indicate different effects of •NO on radiation-induced clustered and non-clustered DNA damage involving replication-induced DNA breaks.
As •NO is an inhibitor of ribonucleotide reductase, some of the radiosensitizing properties of •NO may be due to reduction in the availability of 2-deoxyribonucleotides. Through studying reactions of •NO with tyrosine radicals, essential components of ribonucleotide reductase, this work has enhanced understanding into how •NO may inhibit the enzyme, which may offer new insights into the development of •NO-releasing anti-cancer agents.
The potential for delivery of •NO to hypoxic tissue for radiotherapy has also been investigated in this work, through the development of bioreductively-activated pro-drugs. These novel agents are stable until reduced by one-electron reductants, when a •NO-releasing pro-drug is rapidly evolved, only in those regions which are sufficiently hypoxic.
By increasing our understanding into the mechanisms involved in the ability of •NO to radiosensitize hypoxic cells, especially the reactivity of •NO with DNA radicals, knowledge has been gained into the identification, development and repair of radiation-induced DNA damage in cells, including clustered damage, in the presence of •NO. These studies contribute to further development of novel anti-cancer therapies based upon the release of •NO in hypoxic cells.
The eighteenth-century luxury debate: the case of Voltaire
Keywords: Voltaire
Luxury debate
Eighteenth-Century

Voltaire's role in the luxury debate, the controversy about civilisation, capitalism, and progress which accompanied the birth of modern consumer society in the eighteenth century, is generally limited to his Mondain and its Défense, and reduced to a hedonist apology for luxury. The thesis sets out to re-examine and refute this.
It analyses Voltaire's discovery of commercial societies in Holland and England, and, focussing on the latter, it finds that the apology for commerce became a centralising theme in the Lettres philosophiques, explaining its purpose and coherence.
The thesis then turns to Voltaire's apology for luxury in the 1730s, analysing how du Châtelet and Voltaire, having recourse to classic Epicureanism and deist voluntarism, transformed Mandeville's Fable of the Bees into a justification of commercial societies. Close readings of the Mondain and its companion pieces provide further proof that Voltaire's position on luxury was more nuanced than previously assumed.
The Siècle de Louis XIV and the Essai sur les moeurs demonstrate the importance of luxury in Voltaire's view of civilisation, which in turn serves to explain the shift in Voltaire's appreciation of Montesquieu.
The thesis opposes the claim that in later life Voltaire adopted a Rousseauian view of luxury. Examining Voltaire's later poetry on luxury in light of the analyses offered in the previous chapters, it concludes that his position remained consistent and showed no Rousseauian influence.
Concluding with Voltaire's last defence of luxury, his entries 'Luxe' in the Dictionnaire philosophique and the Questions sur l'Encyclopédie, the thesis explains, with the help of the Fragments sur l'Inde, why and how his attitude to luxury seemed ambiguous in the latter work.
The thesis thus proves that Voltaire's contribution to the debate was not only sustained, independent, and carefully nuanced, but that the debate itself played a crucial rule in Voltaire's thought and writing.
Landscapes of welfare: concepts and cultures of British women's philanthropy 1918-1939
Keywords: women
interwar Britain
citizenship
philanthropy

This thesis offers a new conceptual framework for the study of women’s philanthropy between the end of the First World War and the beginning of the Second World War. Contesting the dominant historiographical narrative which essentialises the association of women with philanthropy, it argues that interwar female philanthropy operated through an inherently creative and flexible methodology. By interrogating gender as a category of analysis alongside other definitional variables of generation, religion, informal and formal modes of influence, and professionalisation, it reveals female philanthropy as an intellectual, as much as a practical endeavour, through which women philanthropists sought to achieve and encourage self-development and societal improvement. Moving beyond a social history framework that concentrates on philanthropic activity in terms of its relationship to social policy, six thematic chapters argue for the critical significance of concepts of language, performance and space in the meanings and presentations of interwar female philanthropy. A central remit of the thesis is to relate the social and cultural processes that underpinned women’s philanthropy between the wars to the subjective experiences of the individual women who engaged them.
The thesis examines the personal archives, published oeuvres and publicity materials (alongside presentations of philanthropy in public discourse) of four philanthropic women who achieved celebrity in the interwar period: Evangeline Booth, Lettice Fisher, Emily Kinnaird and Muriel Paget. It interrogates the contemporary meanings attached to female philanthropy in a period of transformations in mass transport, mass communication and mass democracy, and in women’s position within society. An analysis of this process sheds new light on the historiography of work, civil society and citizenship. Problematising the centrality placed on the national as a sphere of citizenship (embodied in the state), the thesis reveals the critical interconnections between the local and global domains in female philanthropists’ visions. It also illuminates the hitherto underexplored connections between philanthropy, celebrity, the mass media and mass culture. Far from outmoded, female philanthropy lay at the heart of interwar cultural transformations. Female philanthropists contributed dynamically to debates about civil agency and sought to remap the contours of a good society.
A Bayesian cost-benefit approach to sample size determination and evaluation in clinical trials
Keywords: evalution
bridging studies
sample sizes
clinical trials
Bayesian
cost-benefit

Current practice for sample size computations in clinical trials is largely based on frequentist or classical methods. These methods have the drawback of requiring a point estimate of the variance of treatment effect and are based on arbitrary settings of type I and II errors. They also do not directly address the question of achieving the best balance between the costs of the trial and the possible benefits by using a new medical treatment, and fail to consider the important fact that the number of users depends on evidence for improvement compared with the current treatment.
A novel Bayesian approach, Behavioral Bayes (or BeBay for short) (Gittins and Pezeshk, 2000a,b, 2002a,b; Pezeshk, 2003), assumes that the number of patients switching to the new treatment depends on the strength of the evidence which is provided by clinical trials, and takes a value between zero and the number of potential patients in the country. The better a new treatment, the more patients switch to it and the more the resulting benefit. The model defines the optimal sample size to be the sample size that maximises the expected net benefit resulting from a clinical trial. Gittins and Pezeshk use a simple form of benefit function for paired comparisons between two medical treatments and assume that the variance of the efficacy is known.
The research in this thesis generalises these original conditions by introducing a logistic benefit function to take account of differences in efficacy and safety between two drugs. The model is also extended to the more general cases of unpaired comparisons and unknown variance. The expected net benefit defined by Gittins and Pezeshk is based on the efficacy of the new drug only. It does not consider the incidence of adverse reactions and their effect on patients’ preferences. Here we include the costs of treating adverse reactions and calculate the total benefit in terms of how much the new drug can reduce societal expenditure.
We describe how our model may be used for the design of phase III clinical trials, cluster randomised clinical trials and bridging studies. This is done in some detail and using illustrative examples based on published studies. For phase III trials we allow the possibility of unequal treatment group sizes, which often occur in practice. Bridging studies are those carried out to extend the range of applicability of an established drug, for example to new ethnic groups. Throughout the objective of our procedures is to optimise the costbenefit in terms of national health-care. BeBay is the leading methodology for determining sample sizes on this basis. It explicitly takes account of the roles of three decision makers, namely patients and doctors, pharmaceutical companies and the health authority.
Advances in fine-grained visual categorization
Keywords: computer vision
artificial intelligence
image classification
fine graind visual categorization

The objective of this work is to improve performance in fine-grained visual categorization (FGVC). In particular, we are interested in the large-scale classification between hundreds of different flower, bird, dog species. FGVC is challenging due to high intra-class variances caused by deformation, view angle, illumination and occlusion, and low inter-class variance since some categories only differ in detail that only experts notice. Applications include field guides, automatic image annotation, one-click shopping app and 3D reconstruction.
At the start, we discuss the importance of foreground segmentation in FGVC, where we focus on the unsupervised segmentation of image training sets into fore- ground and background in order to improve image classification performance. To this end, we introduce a new scalable, alternation-based algorithm for co-segmentation, Bi-CoS, which is simpler than many of its predecessors, and yet has superior performance on standard benchmark image datasets. Next, we extend BiCos to a new model, Tri- CoS, that adds a class-discriminitiveness term directly into the segmentation objective. The new term aims at removing image regions that, although appearing as foreground, do not contribute to the discrimination between classes.
We also propose a model that combines parts alignment and foreground segmentation into a unified convex framework. The model is called Symbiotic in that part discovery/localization is helped by segmentation and, conversely, the segmentation is helped by the detection (e.g. part layout). The joined system improves over what can be achieved with an analogous system that runs segmentation and part-localization independently.
Finally, we built a new flower dataset consisting of 26,798 high quality images collected by ourselves and 187,559 images gathered from existing datasets. The construction of this dataset follows a strict biological taxonomy. We also evaluate the impact of using the Amazon Mechanical Turk (AMT) service for filtering fine-grained data.
Interconnections, exchanges and influences relating to medicine, warfare and rulership between Egypt and the Aegean during the Middle and Late Bronze Age
Keywords: Egyptian-Aegean relations; intercultural contacts; medicine in antiquity; kingship; warfare in antiquity

This thesis studies interactions between Egypt and the Aegean during the Middle to Late Bronze Ages, focusing on reciprocal influences in the spheres of healing, warfare, and legitimation of power.
Chapter 1 provides an introduction, starting with an overview of previous research. The next two sections discuss a couple of issues of general significance, namely chronology and the Egyptian terminology for Aegean peoples and locations. The last two sections deal with issues of methodology and explain the aims of this work.
Chapter 2 is devoted to healing practices. Like the two chapters that follow, it begins with a cross-cultural comparison between the Egyptian and Aegean milieus. The basis for the discussion is provided by references to Crete in a couple of Egyptian medical texts. Other potential indications of an exchange of medical lore include containers that might have been used for medical preparations, amulets with healing properties, and possible similarities in practices and medical terminology.
Chapter 3 treats warfare, considering it in its broadest sense as a cultural phenomenon, besides looking for evidence suggesting military interaction or cooperation between Egypt and the Aegean. The material under scrutiny ranges from the decoration of weapons to the exchange of raw materials destined for the production of military equipment. Ideology and iconography also contribute to the discussion.
Chapter 4 explores the possibility of Egyptian influence in the development of the Aegean ideologies of power and the exploitation of foreign contacts as a source of legitimation. The main body of the chapter deals with the role of exotica in the pursuit of prestige. Some potential examples of the adoption of foreign customs and ideas are also discussed.
Chapter 5 summarises the conclusions of the previous chapters concisely and discusses how they may fit within the broader context of the study of Egyptian–Aegean relations. Finally, some possible lines of research for the future are suggested.
Analysis of incomplete and complete contacts in sliding and partial slip
Keywords: asymptotic analysis
complete contacts
incomplete contacts
fretting fatigue

Fretting fatigue is a type of contact fatigue which causes premature failure in a number of engineering assemblies subjected to vibration or other forms of cyclic loading. It is concerned with the nucleation of cracks due to oscillatory micro slip between contacting bodies. Therefore, a detailed knowledge of the interface conditions and the means of quantifying crack nucleation are very important, and will be the ultimate goal of this thesis. The analysis of an incomplete contact (Herzian contact) is considered first followed by various complete contacts. Fretting fatigue tests employing a Hertzian contact are analysed accurately by introducing several modifications needed to the classical formulation. With the total state of stress in a strip established, the crack tip stress intensity factor for a crack growing inward from the trailing edge of the contact is determined by the distributed dislocation technique. The results are then correlated with local solutions for the contact stress field which enable an estimate of the crack nucleation life, and hence a characteristic material property quantifying initiation, to be found. The interfacial contact pressure distribution beneath a complete sliding contact between elastically similar components, in the presence of friction, has been studied in detail, with particular reference to contacts whose edge angles are 60 degree, 90 degree and 120 degree. The possible types of behaviour at the edge of contacts, namely power order singularity, power order bounded and square root bounded, are discussed. A full understanding of the behaviour requires a detailed study of a characteristic equation, and this shows the kinds of pressure distribution to be anticipated, which can vary very markedly. The transition from power order behaviour to local separation and bounded behaviour is examined, and an appropriate asymptotic form developed. The problem of trapezium shaped punches pressed into a frictional, elastically similar half-plane, and subject to sequential normal and shear loading, under partial slip, is studied. Detailed considerations have again been given to the specific cases of 60 degree, 90 degree and 120 degree punches, and maps have been developed showing the initial mix of stick, slip and separation regions, together with the steady state response when the shearing force is cycled. Conditions for full stick are established.
Confocal single-molecule fluorescence as a tool for investigating biomolecular dynamics in vitro and in vivo
Keywords: DNA structure
single molecule fluorescence in vivo
DNA polymerase
FRET
Single molecule fluorescence
confocal fluorescence

Confocal single-molecule fluorescence is a powerful tool for monitoring conformational dynamics, and has provided new insight into the enzymatic activities of complex biological molecules such as DNA and RNA polymerases. Though useful, such studies are typically qualitative in nature, and performed almost exclusively in highly purified, in vitro settings. In this work, I focus on improving the methodology of confocal single-molecule fluorescence in two broad ways: (i) by enabling the quantitative identification of molecular dynamics in proteins and nucleic acids in vitro, and (ii) developing the tools needed to perform these analyses in vivo.
Toward the first goal, and together with several colleagues, I have developed three novel methods for the quantitative identification of dynamics in biomolecules: (i) Burst Variance Analysis (BVA), which unambiguously identifies dynamics in single-molecule FRET experiments; (ii) Dynamic Probability Density Analysis (PDA), which hypothesis-tests specific kinetic models against smFRET data and extracts rate information; and (iii) a novel molecular counting method useful for studying single-molecule thermodynamics. We validated these methods against Monte Carlo simulations and experimental DNA controls, and demonstrated their practical application in vitro by analyzing the “fingers-closing” conformational change in E.coli DNA Polymerase I; these studies identified unexpected conformational flexibility which may be important to the fidelity of DNA synthesis.
To enable similar studies in the context of a living cell, we generated a nuclease-resistant DNA analogue of the Green Fluorescent Protein, or “Green Fluorescent DNA,” and developed an electroporation method to efficiently transfer it into the cytoplasm of E.coli. We demonstrate in vivo confocal detection of smFRET from this construct, which is both bright and photostable in the cellular milieu. In combination with PDA, BVA and our novel molecular counting method, this Green Fluorescent DNA should enable the characterization of DNA and protein-DNA dynamics in living cells, at the single-molecule level. I conclude by discussing the ways in which these methods may be useful in investigating the dynamics of processes such as transcription, translation and recombination, both in vitro and in vivo.
Duchenne muscular dystrophy: RNA-based therapeutics and microRNA biology
Keywords: DMD
microRNA
epigenetics

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder caused by absence of functional dystrophin protein. This thesis describes investigations into the role of small non-coding RNAs in both DMD pathology, and as potential therapeutic molecules.
MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression and are implicated in wide-ranging cellular processes and pathological conditions. This study has compared differential miRNA expression in proximal and distal limb muscles, diaphragm, heart and serum in the mdx dystrophic mouse model relative to wild-type controls. Global transcriptome analysis revealed muscle-specific patterns of differential miRNA expression as well as commonalities between tissues, including previously identified dystromirs. miR-1, miR-133a and miR-206 were found to be highly abundant in mdx serum, suggesting that these miRNAs are promising disease biomarkers. Indeed, the relative serum levels of these miRNAs were normalised in response to peptide-PMO mediated dystrophin restoration therapy. This study has revealed further complexity in the miRNA transcriptome of the mdx mouse, an understanding of which will be valuable for the development of novel DMD therapeutics and for monitoring their efficacy.
Myostatin is a secreted growth factor that negatively regulates muscle mass and is therefore a potential pharmacological target for the treatment of muscle wasting disorders such as DMD. This study describes a novel myostatin inhibition approach in which small interfering RNAs (siRNAs) complementary to a promoter-associated transcript induce transcriptional gene silencing (TGS) in cultured myotubes. Silencing was sensitive to treatment with the histone deacetylase inhibitor Trichostatin A, and the silent state chromatin mark H3K9me2 was enriched at the myostatin promoter following siRNA transfection, suggesting epigenetic remodelling underlies the silencing effect. These observations suggest that long-term epigenetic silencing may be feasible for myostatin and that TGS is a promising novel therapeutic strategy for the treatment of muscle wasting disorders.
The work in this thesis therefore demonstrates the potential of small RNAs as therapeutic agents and as disease biomarkers in the context of DMD.