VictorJuiz/thesis huggingface dataset:
The role of tryptophan and the mTOR pathway in T cell fate determination

The adaptive immune response forms an essential part of the cancer immuno-editing process, whereby nascent malignant cells are detected and destroyed prior to forming tumours. The process is tightly controlled to minimise collateral damage to healthy tissue. One of the mechanisms evolved for this purpose and frequently co-opted by malignant cells is the creation of a microenvironment scarce in essential amino-acids through the use of catabolic enzymes such as Indoleamine 2,3-dioxygenase (IDO) , responsible for the rate-limiting step in tryptophan catabolism. The evolutionary conserved GCN2 and mTORC1 pathways respond to amino-acid starvation by triggering emergency homeostatic response programmes that aim to conserve nutrients by shutting down biosynthetic pathways, slowing cell cycle progression and facilitating autophagy. This research project focuses on elucidating the interaction between IDO activity and these pathways and its implications for the immune-editing process.
The role of the mTOR kinase as a regulator of T cell fate following exposure to cognate antigen has recently become apparent. Experiments described herein confirm that in murine and human models of T cell activation exposure to tryptophan starvation results in significant mTORC1 inhibition and a modified phenotype with reduced Tbet expression, altered cytokine secretion profile, greatly impaired proliferative capability and expanded CD4+ FoxP3+ CD25high subpopulations. Additional results confirmed that the action of IDO is sufficient to deplete tryptophan from the microenvironment to levels sufficient to depress the mTORC1 axis and trigger GCN2 activity even in tumour cell lines. Lower extracellular tryptophan levels were necessary to perturb these pathways In IDO expressing cell lines, suggesting that compensatory mechanisms allow continued proliferation of malignant cells in the face of conditions that severely impede an anti-cancer immune response. In conclusion, manipulation of the mTORC1 axis via IDO-induced tryptophan depletion is an important tumour immune-escape mechanism that can be a target for cancer immunotherapies.

Keywords: immune escape
tumour immunology
T cell biology
Advisor: Cerundolo, V
Computer modelling of mixed age, polyspecific broadleaf woodland in the United Kingdom

Commensurate with the increase in the planting rate of broadleaf species is the need to investigate forest management that uses mixtures of species and ages. Reliable data for woodland of this type is exceedingly rare and the need to advise managers is immediate. Management and investment decisions can be examined with models of forest growth and economics.
PART 1 Forest growth models.
Many models have been reviewed and the most appropriate selected for further development. This thesis concentrates on the improvement of distance independent individual tree models. This is a modelling approach that is compatible with current knowledge and ideas in ecology.
Several general improvements have been made. New growth equations have been produced and then calibrated to diameter increment data. Estimates for height prediction have been derived from analysis of a large survey of trees. Competition has been represented by a new multiplier, with a consequent improvement in the predicted diameter frequency distributions. The prediction of biomass for a given quality of site was modified such that control is mediated by measures of density dependence and biomass increment, via mortality.
Finally, the results from improved versions of the model were tested against the known change in diameter frequency distribution for Meathop Wood in Cumbria. The result showed a promising similarity, and the minor disparities appear to be linked to the modelling of regeneration.
PART 2 A forest economics model.
A new model to assess the relative profitability of a wide variety of management options has been devised. The model is easy to operate and allows comparison for many differing financial circumstances. It has been used for investigating the importance of major financial variables in the selection of forestry investments. Research into changing fiscal incentives, 'natural' management, and ideal planting densities for oak have also been completed by use of the model.

Advisor: Harrison, A
Savill, P
Harrison, T
Indigenous resistance to German rule in the Pacific colonies of Samoa, Ponape and New Guinea, 1884 to 1914

This study of resistance in the Pacific Islands is an attempt to achieve both a wider and deeper understanding of colonization as it impinged on the Pacific peoples and as it was perceived by their German rulers. The thesis is by no means another imperial history. The major focus is on the Pacific Islander himself, the processes of change in local socirty under the impact of European expansion and a western cash economy, and on the way the colonial relationship functioned at the level of the individual island administration. It emphasizes the power and ability of the Pacific Islanders to make their own adjustments - of interest and ideology - to the new culture and its demands and does so through the comparison of three cultural regions within the one historical dimension, a method which Pacific historians have barely exploited at all. It represents the first intensive history of German Ponape in particular, using original documentation, while it opens up totally unexplored areas of that 'forgotten imperialism' which was such a critical phase in the modern histories of the new states of Samoa and New Guinea.
The thesis is divided into two parts. Part One consists of three 'case studies' of colonial contact and interaction. In each case the pre-German period has been examined for a broader historical background. The modes of adaptation achieved in this earlier period largely determined the pattern of Pacific Island response under German rule.
For more than two decades before 1900, Europeans and Samoans had been engaged in a constantly fluctuating struggle for the right to control the group's economic and political destiny. The Samoan district factions often encouraged this conflict in an effort to have their various candidates recognized as the paramount chief of the Samoan Islands, but they were also capable of offering solid opposition when Europeans interfered in their political affairs above certain limits. The history of Samoan response to German rule after 1899 details the struggle between the older chiefly elites and the Governor, tfilhelm Solf. The chiefs, under the orator Lauaki, campaigned shrewdly to have their traditional political authority and prerogatives institutionalized as part of the German system of colonial rule. Though Golf, whose objectives were diametrically opposed to the traditional political dynamics of the group, was at first forced to compromise with the chiefs, he thwarted their campaign in the end by exploiting inherent weaknesses in the political structure and relying on his growing paternal authority with the mass of the people.
[Please see pdf. for full abstract.]
Mechanically interlocked and redox switchable molecules at surfaces

This thesis explores the surface assembly of mechanically interlocked molecular architectures at gold surfaces for potential applications in molecular switches, anion sensing and stimuli (redox and optical) responsive molecular films.
Chapter One introduces the field of mechanically interlocked molecules focusing on rotaxane and catenane surface assemblies in the form of single molecule thick self-assembled monolayers. A review of the surface-attached characteristics of mechanically interlocked molecules is given before exploring specific anion template directed strategies for their construction. The potential to incorporate both redox-active and optically-active functional groups within these mechanically interlocked molecules is also discussed.
Chapter Two provides the experimental details and procedures employed in this thesis to characterise the molecular systems under investigation.
Chapter Three introduces several surface characterisation techniques such as; ellipsometry, contact angle, X-ray reflectivity and X-ray photoelectron spectroscopy, with a particular focus of applying these tools to probe the surface co-conformation of switchable and interlocked molecules at surfaces. Electroanalytical techniques such as cyclic voltammetry, chronoamperometry and electrical impedance spectroscopy are also introduced.
Chapter Four details the surface assembly of a series of ferrocene containing anion templated catenane self-assembled monolayers on gold. Detailed electrochemical and angle resolved X- ray photoelectron spectroscopy characterisation elucidates the co-conformation upon surface attachment.
Chapter Five details the anion templated surface assembly of a redox-active rotaxane self- assembled monolayer on gold. Subsequent electroanalysis and X-ray photoelectron spectroscopy characterisation confirms the structural integrity of the film and a possible co- conformation at the surface is discussed.
Chapter Six describes efforts towards constructing optically responsive hybrid d-f lanthanide containing mechanically interlocked molecules. Initial work focuses on switching characteristics of a redox switchable antennae and its ability to modulate the luminescence of a series of lanthanide complexes in solution. Subsequent surface attachment of the lanthanide complexes in the form of emissive self-assembled monolayers is also investigated.

Keywords: rotaxane
optically-active functional groups
redox-active
catenane
mechanically interlocked molecules
self assembled monolayer
Advisor: Davis, J
Structural characterization of liver fibrosis in magnetic resonance images

The overall clinical motivation of this thesis is to differentiate between the different stages of liver disease stratifying into: no disease, mild disease, and severe fibrosis using Magnetic Resonance Imaging (MRI). As a related aim, we seek to differentiate as much as possible pericellular and nonpericellular fibrosis. This latter is clinically important, but currently no method exists that is able to perform this. Quickly, we realised that these aims push low level image analysis beyond their current bounds and so a great deal of the thesis is dedicated to extending such techniques before they can be applied.
To work on the most fundamental low level image analysis concepts and algorithms we choose one of the most recent developments, namely continuous intrinsic dimensionality (ciD), which allows the continuous classification of homogeneous patches from 1D structures to intrinsically 2D structures. We show that the current formalism has several fundamental limitations and we propose a number of developments to improve on these.
We re-evaluated feature energy statistics that were originally proposed in ciD, and additionally we examined the confidence one may have in stateof- the-art methods to estimate the orientation of features. We show that new statistical methods are required for feature energy, and that orientation predictability is more important than correctness of the estimation. This evaluation led us to the monogenic signal local orientation.
Analysis of feature or texture energy is also a main contribution of this thesis. Within this framework we propose the Riesz-weighted phase congruency model. This is able to detect internal texture structures but it is not capable of delineating boundaries. Nevertheless, it proves an appropriate basis for texture quantification.
Finally, we show that in contrast to using the standard established Kovesi approach, the developed texture measure leads to good results on the suboptimal T1w MRI liver image staging images. We show that we are able to differentiate automatically between the separate disease scores and between pericellular and non-pericellular fibrosis.

Keywords: local phase
texture
MRI
liver disease
Advisor: Professor Sir Michael Brady
Professor Alison Noble
Dr. Catherine Kelly
Developing paediatric quality indicators for UK general practice

The overall aim of this thesis is to define a candidate set of quality indicators that are evidence-based, feasible to implement, and have the potential to improve the quality of care provided for children in UK general practice.
The indicators were developed using a three-stage process. First, the areas and aspects of care of highest priority for quality indicator development were identified. This was achieved by seeking the views of primary care clinicians and by undertaking a formal analysis of unplanned hospital admissions for ambulatory care sensitive conditions. Then, the evidence-base to underpin indicator development was identified through an overview of Cochrane systematic reviews of interventions relevant to the primary care of children. A search of SIGN and NICE national guidelines was also conducted to inform the evidence-base. Lastly, an expert panel determined the formulation and selection of indicators by applying the RAND appropriateness methodology.
This process created a final set of 26 quality indicators in six priority areas: early recognition of potentially serious illness (n=7); child protection and safeguarding (n=4); mental health (n=4); health promotion (n=1); routinely managed conditions (n=6); and general practice management (n=4). The main strength of these indicators is that they reflect a strong professional consensus on their validity and feasibility. The main weakness is that the indicators are underpinned by evidence mainly derived from expert opinion rather than formal research; the requirement for professional consensus means that they do not challenge existing models of care delivery.

Keywords: general practice
paediatrics
quality indicator
primary health care
consensus study
Advisor: Harnden, A
Mant, D
Measurement of the inclusive W+/- cross section at (sq.root)s = 7 TeV with the ATLAS detector

A measurement of the W+ and W− cross section in the electron channel is presented. The measurement is performed using data collected with the ATLAS experiment in 2011, amounting to an integrated luminosity of 4.58 fb−1. The centre of mass energy is √—s = 7 TeV. The measurement is performed differentially in the electron pseudorapidity. The W charge asymmetry is also presented. The results are compared to theoretical predictions calculated at next-to-next-to-leading order in perturbative QCD using various Parton Distribution Functions.

Keywords: ATLAS
LHC
W boson
Advisor: Tseng, J
Voltammetry of electrochemically heterogeneous surfaces

In this thesis, mathematical modelling is used to theoretically investigate the electrochemical behaviour of surfaces which can be broadly classified as being ‘electrochemically heterogeneous’. Simulated voltammetry is used in the exploration of a number of specific systems as listed below.
The cyclic voltammetry of electrodes composed of two different electroactive materials that differ in terms of their electrochemical rate constants towards any given redox couple. The effect of the distribution of the two materials was investigated and the occurrence of split peak cyclic voltammetry where two peaks are observed in the forward sweep, was studied. The technique was specifically applied to the modelling of highly-ordered pyrolytic graphite (HOPG).
The steady-state voltammetry of a conducting spherical particle resting on an insulating supporting surface. An algebraic expression that completely describes the voltammetric waveform in the limit of irreversible kinetics was developed.
The cyclic voltammetry of the EC′ (catalytic) mechanism at a regularly distributed array of hemispherical particles on an insulating supporting surface. Particular attention was paid to the ‘split-wave’ phenomenon, where two peaks are observed in the forward scan of a cyclic voltammogram and the conditions under which these peaks are resolvable were elucidated.
The linear sweep voltammetry of micro- and nano-particle modified electrodes and other electrodes of partially covered and non-planar geometry. It was demonstrated that the apparent electrochemical rate constant of the reaction and thus the peak position of the voltammetry is dependent only on the relative electroactive surface area of the particles on the surface and not upon their shape or distribution. This has wide reaching implications as it can be used to explain some instances of a purported nano-catalytic effect without appeal to altered properties at the nanoscale.
The linear sweep voltammetry of the interior of a partially electroactive cylindrical pore. Four limiting cases were observed and fully characterised.
The linear sweep voltammetry of porous surfaces. It was established that if the pores are less than a certain threshold depth, then a porous surface will also display an apparent catalytic effect that is dependent on the relative electroactive surface area (including the area in the interior of the pores).

Keywords: voltammetry
numerical modelling
heterogeneous surfaces
electrochemistry
Advisor: Compton, RG
Firm behaviour in international markets

This thesis consists of three essays on firm behaviour in international markets. Abstracts can be found at the beginning of their respective chapters. The first chapter, titled "Trading Tasks and Quality", presents a tractable trade model that combines vertical product differentiation at the firm-level with international fragmentation of production to explain some recently unearthed stylised facts about exporters in developing countries. In line with the recent empirical evidence, it suggests that there is a close link between exports and imports at the firm-level, and it is quality that establishes the link between the two. The second and third chapters revisit the debate on globalisation and wage inequality. The second chapter, titled "The Trade and Wages Debate Revisited: A new explanation for an old mystery", develops a general equilibrium model where trade liberalisation between two identical countries increases wage inequality in favour of white-collar workers. It shows that country characteristics, such as the relative endowment of white-collar workers and the degree of competition, matter for the equilibrium level of wage inequality after trade liberalisation. The endowment of white-collar labour also affects the level of openness; an increase in the worldwide supply of white-collar labour expands the range of traded goods and increases the volume of trade in already-traded goods. Furthermore, it improves global welfare. The third chapter, titled "Cross-border Mergers and Wage Inequality", focuses on another aspect of globalisation and its effect on wage inequality. It suggests a two-way relationship between cross-border mergers and wage inequality: on the one hand, wage inequality in favour of white-collar workers increases the protability of cross-border mergers; on the other hand, at any level of openness, wage inequality is lower in the presence of cross-border mergers than in their absence. Therefore, participation of a country in global business raises wage inequality, but its level is lower under trade and investment integration compared to trade integration only.

Keywords: international trade and investment
globalisation
Advisor: Neary, P
Javorcik, B
Reading Egils saga Skallagrímssonar

This thesis is concerned with how a set of different texts, all titled with various English or Icelandic versions of Egils saga, exists, can be interrelated, and may be read.
The first level of interpretation, before reading of the text even begins to occur, is a response to the book as a physical object whose ordering encourages and excludes certain interpretations. The first two chapters analyze the six English translations of Egils saga: W.C. Green (1893), E.R. Eddison (1930), Gwyn Jones (1960), Christine Fell and John Lucas (1975), Hermann Palsson and Paul Edwards (1976), Bernard Scudder (1997): together with the Icelandic editions used as their source texts, in terms of paratext, as developed by Gerard Genette.
The third chapter consists of translation analyses. These use some of the methods of traditional translation criticism, together with more liberal methods of analysis associated with 'Translation Studies', as established by Susan Bassnett, among others. I conclude that the reader of translations who intends to move between 'target language' (language of translation) and 'source language' (language for translation), or who is in the process of getting the freedom to make transitions between these languages, is a special case, and that there is a literature which exists for them. By this I mean that, while it can be liberating to read literary translations as works 'in their own right', there are areas in some literary translations where it is best, or possible, to manipulate several languages and culture levels. There are also literary translations where the play between source language and target language, texts and paratexts, is necessary to their existence. Although I retain the 'source' and 'target' terminology of Translation Studies, I begin the chapter by questioning the direction of the vector: "target" texts are in some senses the 'source' texts for the 'source' texts subsequently encountered by readers between languages.
The final chapter studies processes of transformation in Egils saga, following the Islenzk fornrit text. It shows how the saga itself is concerned with the meaning and powers of language and processes of transmission: it translates itself, not in a modern self-reflexive sense, but with its own, historically particular aesthetic.

Advisor: O'Donoghue, H
Matched Asymptotic Expansions for Valuing Spread Options

Spread Options are crucial in the energy, currency and fixed income, and com- modity markets. The problem with spread options is that there are no closed- form formulae to price or hedge them. In this paper, we use matched asymptotic expansions in order to price spread options. We use both one-factor and two- factor models. In the one-factor models we assume the spread follows one of the following processes: Geometric Brownian Motion, Ornstein-Uhlenbeck and Arithmetic Brownian Motion. In the two-factor models, we assume the assets follow one of these processes.
Asymmetric electrocyclic reactions

Pericyclic reactions are a class of transformations that comprise sigmatropic rearrangements, group transfer reactions, cycloadditions and electrocyclic reactions. Since Woodward and Hoffmann rationalized the mechanism and stereochemistry of pericyclic reactions they have become powerful synthetic tools. Whilst sigmatropic rearrangements and cycloadditions are cornerstones of contemporary synthetic methodology, many electrocyclic reactions are not fully exploited currently; there are no general methods for the asymmetric catalysis of electrocyclic reactions and as a consequence, opportunities for exerting stereocontrol in these manifolds are limited. We aim to establish general methods for the asymmetric catalysis of 6π electrocyclic reactions. Our initial studies are focused on a pentadienyl anion moiety due to the greater ease of cyclization observed with such systems in comparison to the corresponding neutral hexatriene systems.

Keywords: Catalysis
Electrocyclization
Asymmetric
Advisor: Smith, M