VictorJuiz/thesis huggingface dataset:
Analysis of b cell responses to blood-stage malaria antigens in humans following immunization with candidate vaccines and controlled human malaria infection

The apicomplexan parasite Plasmodium falciparum is the causative agent of the most severe and deadly form of human malaria. The production of an efficacious malaria vaccine is seen as one of the key steps towards the eradication of the disease, however to date only one candidate has progressed to application for licensure. Candidate malaria vaccines target the different stages of the P. falciparum lifecycle through induction of a functional immune response. Vaccines targeting the blood-stage parasite require induction of high titre neutralising antibodies. To achieve this, vaccine regimens have been designed specifically to maximise antibody induction and maintenance in humans. The ultimate test of any candidate vaccine is clinical efficacy and controlled human malaria infection (CHMI) is a powerful tool for measuring this. This model can also be used to study how vaccine induced antigen-specific components of the immune system respond to native antigen exposure in the context of parasitic infection
In this Thesis I describe the induction and maintenance of B cell responses, including memory B cells (mBC) and antibody secreting cells (ASC) to the candidate blood-stage malaria antigens MSP1 and AMA1 following vaccination with a variety of regimens and CHMI. These B cell populations along with peripheral blood T follicular helper (Tfh) cells correlate strongly with antibody induction. Within these populations I have identified a number of phenotypically distinct subsets which contribute to a functional response to vaccine and/or parasite antigen. From single cell sorting of ASC at day seven post-boost I have managed to produce the first fully human monoclonal antibodies (hmAbs) specific for AMA1, one of which shows significant growth inhibitory activity (GIA).
Despite promise the vaccine candidates MSP1 and AMA1 have been disappointing in terms of human efficacy. In this Thesis I have attempted to provide explanations on a cellular level as to why there is such disparity between pre-clinical and human data and ultimately why these candidates may have failed to provide efficacy. Such work will provide a strong basis for analysing future clinical trials of alternative candidate blood-stage vaccines and allow accurate characterisation of immune correlates and clinical efficacy when it is achieved.

Keywords: vaccines
malaria
B cell
Advisor: Draper, S
Modelling residual stresses and deformation in metal at different scales

This thesis is devoted to the numerical and experimental investigation of residual stress and deformation in polycrystalline metallic alloys at different scales. The emphasis in the current study is placed on establishing the connection between the simulation of deformation by the Finite Element (FE) method and experimental characterisation by synchrotron X-Ray Diffraction (XRD). Of particular importance is the interpretation of modelling results and their validation by careful comparison with experimental data. The concept of eigenstrain was used extensively throughout the report to study the residual elastic strain distributions and their sources. A pseudo-thermal strain FE procedure was used systematically to simulate the residual stress states in samples and engineering components of different shape and dimensionality. The case of 1-D strain variation was considered using the example of a plastically bent bar. The direct and inverse problems of eigenstrain analysis were solved, and validated experimentally by the use of XRD and EDM slitting methods. A novel 2-D discrete inverse eigenstrain algorithm was proposed and implemented to reconstruct the residual stress distribution in a worn rail head. The link between the residual stress and deformation history was studied via thermo-mechanical modelling of the Linear Friction Welding (LFW) process. To advance the understanding of polycrystalline deformation behaviour across the scales, a crystal plasticity model was employed to simulate the elastic-plastic deformation behaviour of Ti-6Al-4V alloy. A post-processor was developed to extract the average elastic strains for orientation-specific grain groups and to compare them with XRD data. A “peak constructor” post-processor was developed that utilised the knowledge of both the elastic strain and dislocation density. In a further development step, a strain gradient crystal plasticity formulation was adopted to account for the local dislocation evolution. Intra-granular deformation analysis was carried out and micro-beam Laue experimental diffraction technique was used for validation. Thus, local lattice arrangement was studied at the microscopic, intragranular scale. Special attention was paid to the phenomenon of Laue spot “streaking”, indicative of the local lattice misorientation caused by dislocation activity during deformation. The results presented in this thesis contributed to the fundamental understanding of the residual stress and deformation in polycrystalline metallic alloys and lead to more than 20 publications in peer-reviewed journals and conference proceedings, which are listed in the Appendix.

Keywords: finite element analysis
x-ray diffraction
neutron diffraction
Advisor: Korsunsky, A
Gender mainstreaming in development organisations: policy, practice and institutional change

‘Gender and Development’ (GAD) is currently seen as the dominant theoretical model within international development for promoting social justice and equality for women. As a consequence, many development organisations are undertaking gender mainstreaming. The most interesting fact about the vast number of analyses about gender mainstreaming is the consistency with which they tell of GAD influenced policies failing to implement GAD approaches in practice. This should raise suspicion rather than simple condemnation. It is time to ask: ‘How are, often very progressive, gender policies and strategies consistently silenced across the range of organisational contexts?’ This thesis focuses upon the contemporary process of gender mainstreaming in development organisations – a term that specifically refers to a ‘process of organisational change’ that aims to explicitly develop the ‘use of GAD approaches within all projects and programmes’ of development institutions in order to achieve ‘a vision of development that creates gender equitable social change’ in society. Moreover, it takes an approach that specifically details the ‘organisational process’ element of change inferred in the term. As such, this thesis uses the literature of organisational culture as a lens to make previously unnoticed and submerged sites of conflict and acts of resistance visible, allowing an understanding to be gained of how gender mainstreaming has so consistently faced a policy-practice impasse. It develops this analysis using an in-depth case study of Oxfam GB and demonstrates that the process of gender mainstreaming in the organisation has resulted in the removal of ‘responsibility for’ implementing GAD approaches among staff in the organisation. It goes on to highlight that the unwillingness of development organisations and practitioners to recognise gender mainstreaming as an explicitly feminist and political process of change directly couched at the level of the organisation and not just at the level of the actual development project (or society more widely) has resulted in the ‘process of organisational change’ becoming rationalised and technical rather than personal and politically charged. In reaching this understanding of gender mainstreaming, the thesis develops an awareness of organisational change processes and highlights that ‘norms’ and ‘values’ in organisations are often confused. This confusion has led to an ineffective process of change in institutions as well as a poor conceptualisation and practice of gender mainstreaming in international development.

Keywords: development organisations
feminism
gender and development
mainstreaming
gender
Advisor: Cathie, L
Digital signal processing methods for large-N, low-frequency radio telescopes

Current attempts to make precision measurements of the HI power spectrum at high redshifts have led to the construction of several low-frequency, large-N, interferometric arrays. The computational demands of digital correlators required by these arrays present a significant challenge. These demands stem from the treatment of radio telescopes as collections of two-element interferometers, which results in the need to multiply O(N2) pairs of antenna signals in an N-element array. Given the unparalleled flexibility offered by modern digital processing systems, it is apt to consider whether a different way of treating the signals from antennas in an array might be fruitful in current and future radio telescopes. Such methods potentially avoid the unfavourable N2 scaling of computation rate with array size.
In this thesis I examine the prospect of using direct-imaging methods to map the sky without first generating correlation matrices. These methods potentially provide great computational savings by creating images using efficient, FFT-based algorithms. This thesis details the design and deployment of such a system for the Basic Element of SKA Training II (BEST-2) array in Medicina, Italy. Here the 32-antenna BEST-2 array is used as a test bed for comparison of FX correlation and direct-imaging systems, and to provide a frontend for a real-time transient event detection pipeline.
Even in the case of traditional O(N2) correlation methods, signal processing algorithms can be significantly optimized to deliver large performance gains. In this thesis I present a new mechanism for optimizing the cross-correlation operation on Field Programmable Gate Array (FPGA) hardware. This implementation is shown to achieve a 75% reduction in multiplier usage, and has a variety of benefits over existing optimization strategies.
Finally, this thesis turns its focus towards The Square Kilometre Array (SKA). When constructed, the SKA will be the world's largest radio telescope and will comprise a variety of arrays targeting different observing frequencies and science goals. The low-frequency component of the SKA (SKA-low) will feature ~250,000 individual antennas, sub-divided into a number of stations. This thesis explores the impact of the station size on the computational requirements of SKA-low, investigating the optimal array configuration and signal processing realizations.

Keywords: FPGA
beamforming
radio astronomy
interferometry
X-Engine
correlator
BEST-2
direct imaging
SKA
Square Kilometre Array
Advisor: Jones, M
Zarb Adami, K
Courtship and courtliness

In its current sense, courting means 'wooing'; but its original meaning was 'residing at court'. The amorous sense of the word developed from a purely social sense in most major European languages around the turn of the sixteenth century, a time when, according to some historians, Western states were gradually moving toward the genesis of absolutism and the establishment of courts as symbols and agents of centralised monarchical power. This study examines the shift in meaning of the words courtship and to court, seeking the origins of courtship in court society, with particular reference to the court and literature of the Elizabethan period.
Chapter 1 charts the traditional association between courts and love, first in the historiography of 'courtly love', and then in historical and sociological accounts of court society. Recent studies have questioned the quasi- Marxist notion that the amorous practices of the court and the 'bourgeois' ideals of harmonious, fruitful marriage were antithetical, and this thesis examines whether the development of 'romantic love' has a courtly as well as a bourgeois provenance. Chapter 2 conducts a lexical study of the semantic change of the verb to court in French, Italian, and English, with an extended synchronic analysis of the word in Elizabethan literature. Chapter 3 goes on to diversify the functional classification required by semantic analysis and considers the implications of courtship as a social, literary and rhetorical act in the works of Lyly and Sidney. It considers the 'humanist' dilemma of a language that was aimed primarily at seduction, and suggests that, in the largely discursive mode of the courtly questione d'amore, courtship could be condoned as a verbalisation of love, and a postponement of the satisfaction of desire. Chapter 4 then moves away from the distinction between humanist and courtly concerns, to examine the practice of courtship at the court of Elizabeth I. It focuses on allegorical representations of Desire in courtly pageants, and suggests that the ambiguities inherent in the 'legitimised' Desire of Elizabethan shows exemplify the situation of poets and courtiers who found themselves at the court of a female sovereign. In chapter 5 discussions of the equivocation inveterate to courtly texts leads to a study of The Faerie Queene, and specifically to Spenser's presentation of courtship and courtly society in the imperialist themes of Book II and their apparent subversion in Book VI. The study concludes with a brief appraisal of Spenser's Amoretti as a model for the kind of courtship that has been under review.
Debates about witchcraft in England, 1650-1736

This thesis shows the evolution of educated belief in witchcraft in England from 1650, at the end of the last decade of largescale prosecution, to 1735/6, when the Jacobean witchcraft legislation was repealed. It looks at this belief as a body of ideas more or less susceptible to serious use, rather than as the property of a social group, something measurable in statistical terms.
There are three overlapping areas:
1. The early chapters show how witchcraft theory had an ideological import in the years 1650-1670. For Sir Robert Filmer, witchcraft prosecution was tainted by its association with puritan politics and theology. Hobbes viewed the metaphysical underpinnings of the theory with disdain, but felt it necessary to preserve witchcraft as crime within his system. For Meric Casaubon, witchcraft theory was an ideal embodiment of the restoration of traditional belief, and a boundary condition of a religiously defined community. The third chapter shows how witchcraft belief could colour mutual perceptions of Anglo- Scottish relations.
2. Having been a useful symbol of a broadly-based, religious, but non-factional society for the Harleyite Daniel Defoe in the crisis of 1710-11, witchcraft was coopted into the party struggle during the notorious Wenham case. Subsequently, witchcraft theory was a dangerous subject for a regime which, as Walpole's did, sought to disentangle the religious and secular threads which the witchcraft issue bound together.
3. Witchcraft, factionalized, became for Defoe a satirical symbol of party rule. Elsewhere it emerged, verbally and visually, whenever ferment about Church-State relations bubbled once more to the surface. These issues are examined in chapters on the last great witchcraft debate, images of witchcraft, and on repeal of English, Scottish, and Irish witchcraft legislation. The central conclusions are chronological and causal. Witchcraft theory continued to count well into the eighteenth century; and its demise had very specific political and ideological occasions.
The Beveridge curve and institutional arrangements

The main objective of our analysis is to investigate the causes of shifts of the Beveridge curve in Great Britain, the Netherlands and Sweden.
In chapter 2., we will outline the model which is the basis for our analysis. The cornerstone of our theoretical framework regarding the long-run relationship between unemployment and vacancies otherwise known as the Beveridge curve is the matching process. We will describe how certain features such as structural mismatch, the relative attractiveness of benefit provisions and changes in search intensity and search effectiveness of the unemployed, could theoretically affect the Beveridge curve.
In order to analyse a possible shift of the Beveridge curve, time series analysis will be used. In chapter 3., we describe the patterns of the relevant data series. Also, we describe the significance of the long-term unemployment problem in Great Britain and the Netherlands.
In the following chapter we describe the characteristics of the disability arrangements in the three relevant countries. We do this in order to explain how the disability arrangements have affected the unemployment patterns in one of our sample countries. The focal point is the existence of a hidden unemployment component in the disability stock.
In order to estimate the Beveridge curve for each country, we will use the instrumental variables technique. In chapter 5., after first having tested for the suitability of our econometric practice regarding the data series in the context of the theory of cointegration, we will present and discuss several model specifications regarding the Beveridge curve. We will also test for the sensitivy of our main results to variations in data and estimation method. Also, we present models of the British and Dutch long-term unemployment patterns.
In chapter 6., we will discuss the most relevant results and compare the British, Dutch and Swedish labour market experiences. Conclusions are presented in the final chapter.
Mental files

It is often supposed that we can make progress understanding singular thought about objects by claiming that thinkers use ‘mental files’. However, the proposal is rarely subject to sustained critical evaluation. This thesis aims to clarify and critique the claim that thinkers use mental files.
In my introductory first chapter, I motivate my subsequent discussion by introducing the claim that thinkers deploy modes of presentation in their thought about objects, and lay out some of my assumptions and terminology. In the second chapter, I introduce mental files, responding to the somewhat fragmented files literature by setting out a core account of files, and outlining different ways of implementing the claim that thinkers use mental files. I highlight pressing questions about the synchronic and diachronic individuation conditions for files.
In chapters three and four, I explore whether ‘de jure coreference’ can be used to give synchronic individuation conditions on mental files. I explore existing characterisations of de jure coreference before presenting my own, but conclude that de jure coreference does not give a useful account of the synchronic individuation conditions on files. In chapter five, I consider the proposal that thinkers must sometimes trade on the coreference of their mental representations, and argue that we can give synchronic individuation conditions on files in terms of trading on coreference. In chapter six, I bring together the account of files developed so far, compare it to the most developed theory of mental files published to date, and defend my account from the objection that it is circular. In chapter seven, I explore routes for giving diachronic individuation conditions on mental files. In my concluding chapter, I distinguish the core account of files from the idea that the file metaphor should be taken seriously. I suggest that my investigation of the consequences of the core account has shown that the file metaphor is unhelpful, and I outline reasons to exercise caution when using ‘files’ terminology.

Keywords: philosohy of mind
de jure coreference
mental files
singular thought
philosophy of language
Advisor: Hawthorne, J
Investigating the role of iASPP and ASPP2 in human carcinoma

The apoptotic function of p53 is specifically regulated by iASPP and ASPP2 and their additional modulation of p63, a key regulator of squamous epithelial homeostasis, has been demonstrated in mice. In this study the role of iASPP and ASPP2 in human carcinomas was explored with a particular focus on the development of squamous cell carcinomas.
The predominant expression of cytoplasmic ASPP2 is seen in the superficial, terminally differentiated cell layers of normal squamous epithelia and its loss is documented in areas of dysplasia and in squamous cell carcinomas. In addition the absence of nuclear ASPP2 in association with human papillomavirus infection suggests it could be a novel viral target.
Furthermore in a novel mouse model of lung tumourigenesis, the somatic deletion of ASPP2 is shown to promote the over expression of markers associated with specific lung progenitor cells and to be associated with the development of non small cell lung carcinomas.
Conversely nuclear iASPP expression is seen in p63 expressing, replication competent, basal and parabasal squamous epithelial cells and is increased in areas of dysplasia and in squamous cell carcinomas. Moreover the combination of nuclear iASPP, p63 and loss of ASPP2 expression is seen to be associated with cell survival and characterises the invasive edges of lingual squamous cell carcinomas.
The novel interaction of iASPP with ERα is also demonstrated together with the negative impact of nuclear iASPP on ER positive breast cancer survival, potentially identifying iASPP as a novel player in estrogen signalling and an important factor in breast tumourigenesis.
Together the data presented here provide significant corroborative evidence implicating ASPP2 and iASPP in tumourigenesis. Specifically ASPP2 is shown to promote cellular differentiation and inhibit the expansion of proliferative populations whereas nuclear iASPP promotes the survival of potentially neoplastic clones. It is likely that the balance of these proteins is a key factor in determining individual cell fate decisions.

Keywords: carcinoma
ASPP
Advisor: Lu, X
Trajectories of Peircean philosophical theology :

The writings of the American pragmatist thinker Charles S. Peirce (1839-1914) provide resources for what this thesis calls the “nested continua model” of theological interpretation. A diagrammatic demonstration of iconic relational logic akin to Peirce’s Existential Graphs, the nested continua model is imagined as a series of concentric circles graphed upon a two-dimensional plane. When faced with some problem of interpretation, one may draw discrete markings that signify that problem’s logical distinctions, then represent in the form of circles successive contexts by which these distinctions may be examined in relation to one another, arranged ordinally at relative degrees of specificity and vagueness, aesthetic intensity and concrete reasonableness. Drawing from Peter Ochs’s Scriptural Reasoning model of interfaith dialogue and Robert C. Neville’s axiology of thinking—each of which makes creative use of Peirce’s logic—this project aims to achieve an analytical unity between these two thinkers’ projects, which can then be addressed to further theological ends. The model hinges between diagrammatic and ameliorative functions, honing its logic to disclose contexts in which its theological or metaphysical claims might, if needed, be revised. Such metaphysical claims include love as that which unites feeling with intelligibility, hell as imprisonment within an opaque circle of interpretation whose distorted reflections render violence upon oneself and others, and the divine as both the center of aesthetic creativity and outermost horizon from which our many layers of interpretive criteria emerge. These are claims made from a particular identity in a particular cultural context, but the logical rules upon which they are based are accessible to all, and the hope of the model is to help people overcome problems of interpretation and orient themselves toward eternity without ignoring the world around them.

Keywords: Charles Sanders Peirce
Robert C. Neville
Scriptural Reasoning
Peter Ochs
Nested Continua
Advisor: Rasmussen, J