VictorJuiz/thesis huggingface dataset:
The molecular genetics of haemochromatosis

Haemochromatosis is the most common single gene disorder to afflict North- West European populations. It is probably the most common genetic disorder of iron metabolism worldwide. As many as 1 in 250 people in the UK are affected and although the phenotype causes only a mild increase in gastrointestinal iron absorption a proportion of affected individuals will accumulate sufficient iron over their life-time to cause cirrhosis and hepatocellular carcinoma. Venesection treatment instituted before cirrhosis has established ensures a normal life expectancy, but clinical presentation is often late in life after irreversible organ injury has occurred. Identification of people at risk in the early, asymptomatic stage by measurements of iron status is unreliable.
The genetic defect responsible for haemochromatosis has been sought in the hope that its identification might facilitate early diagnosis and that studies on the gene product would lead to a greater understanding of the mechanisms of mammalian iron absorption. Genetic linkage to HLA-A3 placed the gene responsible for haemchromatosis in, or close to, the major histocompatibilty complex (MHC) on the short arm of chromosome 6 and a positional cloning strategy has been adopted.
This thesis describes work directed to the identification of the haemochromatosis gene by positional cloning. The region telomeric to the MHC was mapped using yeast artificial chromosomes, from which new microsatellites were isolated. These markers were used in linkage disequilibrium analyses and the mapping of a recombination breakpoint that defined a haemochromatosis gene region. This region was physically mapped in fine detail and positional candidates sought by EST database analysis.
Before a systematic search for genes in the region began a strong positional candidate was reported (Feder et al 1996). Analysis of this mutation in patients from the UK confirmed this to be the ancestral haemochromatosis mutation.
Immunodominant CD8+ T cell responses to HIV-1 infection - 'The good and the bad'

Many lines of evidence indicate that CD8+ T cells are important in the control of HIV-1 infection and this has led to much vaccine research focused at eliciting virus specific CTL. However to date, the few large-scale trials of HIV-1 vaccines designed to elicit CD8+ T cells have produced disappointing results. This has highlighted our incomplete knowledge of the factors that determine if such cells are capable of viral control. The aim of this thesis is to further characterise qualitative aspects of HIV-1 specific CTL that are associated with both good and bad anti-viral activity.
HIV-1 specific CTL responses were investigated in three ways. Firstly, by longitudinally analysing an immunodominant HLA-B*08 restricted CD8+ T cell response in a single rapid progression patient. Secondly, HLA-B*40 restricted CTL responses to HIV-1 where characterised within a Chinese slow progressor cohort. Lastly, factors that affect the processing and presentation of certain overlapping HIV-1 specific CD8+ T cell epitopes were examined.
The results of these studies reveal that subtle variations in both host and viral proteins can have a substantial impact on virus specific CTL and in turn may impact on the outcome of disease. The generation of HIV-1 specific CD8+ T cells is a complex process affected by many variables including the viral sequence of epitope flanking regions as well as polymorphisms in the proteins involved in antigen processing and presentation. To add a further layer of complexity, it appears that HIV-1 virus specific CTL can modulate their functionality throughout the course of infection. Such factors should therefore be taken into account during HIV-1 vaccine design.

Keywords: medicine
immunology
HIV-1
Advisor: Rowland-Jones, S
Dong, T
Transmission electron microscope studies of emitters of silicon bipolar transistors

Transmission Electron Microscope (TEM) studies have been carried out of emitter regions in polysilicon contacted emitter bipolar transistors. The preparation of suitable TEM thin foils is described. In addition a technique is developed for the observation and quant jtative interpretation of the break-up of the interfacial oxide layers observed in these samples.
The effect of annealing the samples prior to emitter dopant implantation (pre-annealing) is investigated for phosphorus and arsenic doped samples, implanted into a polysilicon layer 0.4μm thick, with a dose of 1x1016cm2. Two wafer pre-cleans have been used prior to polysilicon deposition to produce a thin oxide (0-8Å) and a thicker oxide (14Å). In the presence of the thinner oxide, the phosphorus doped samples enhance epitaxial regrowth of the polysilicon layer compared with the arsenic doped or undoped samples. In the presence of the thicker oxide, no difference is observed between the samples. A mechanism is proposed to explain this.
The mechanisms controlling the gain of a phosphorus doped device are investigated and a model proposed to explain the observed electrical characteristics. It is concluded that there are two mechanisms responsible for the observed supression of hole current. Firstly tunnelling through the interfacial oxide and secondly some blocking effect of the interface. Carrier transport in the polysilicon is not believed to contribute to this supression.
A dopant sensitive etch has been applied to TEM thin foils containing fully processed emitters in state-of-the-art devices. The shape of the emitter dopant distribution is revealed in such devices for the first time, and a 2-D profile is obtained from the emitter. It is shown that reduction in the emitter depth to 8OOÅ or less does not alter the emitter dopant geometry. The technique is demonstrated to be capable of resolving spatial separations of dopant iso-concentration contours of 100Å or less.

Advisor: Booker, G
Complementarity of searches for dark matter

The striking evidence for the existence of dark matter in the Universe implies that there is new physics to be discovered beyond the Standard Model. To identify the nature of this dark matter is a key task for modern astroparticle physics, and a large number of experiments pursuing a range of different search strategies have been developed to solve it. The topic of this thesis is the complementarity of these different experiments and the issue of how to combine the information from different searches independently of experimental and theoretical uncertainties. The first part focuses on the direct detection of dark matter scattering in nuclear recoil detectors, with a special emphasis on the impact of the assumed velocity distribution of Galactic dark matter particles. By converting experimental data to variables that make the astrophysical unknowns explicit, different experiments can be compared without implicit assumptions concerning the dark matter halo. We extend this framework to include annual modulation signals and apply it to recent experimental hints for dark matter, showing that the tension between these results and constraints from other experiments is independent of astrophysical uncertainties. We explore possible ways of ameliorating this tension by changing our assumptions on the properties of dark matter interactions. In this context, we propose a new approach for inferring the properties of the dark matter particle, which does not require any assumptions about the structure of the dark matter halo. A particularly interesting option is to study dark matter particles that couple differently to protons and neutrons (so-called isospin-violating dark matter). Such isospin-violation arises naturally in models where the vector mediator is the gauge boson of a new U(1) that mixes with the Standard Model gauge bosons. In the second part, we first discuss the case where both the Z' and the dark matter particle have a mass of a few GeV and then turn to the case where the Z' is significantly heavier. While the former case is most strongly constrained by precision measurements from LEP and B-factories, the latter scenario can be probed with great sensitivity at the LHC using monojet and monophoton searches, as well as searches for resonances in dijet, dilepton and diboson final states. Finally, we study models of dark matter where loop contributions are important for a comparison of LHC searches and direct detection experiments. This is the case for dark matter interactions with Yukawa-like couplings to quarks and for interactions that lead to spin-dependent or momentum suppressed scattering cross sections at tree level. We find that including the contribution from heavy-quark loops can significantly alter the conclusions obtained from a tree-level analysis.

Keywords: cosmology of theories beyond the standard model
dark matter phenomenology
astroparticle physics
Advisor: Sarkar, S
Mechanisms of immunoglobulin deactivation by Streptococcus pyogenes

The bacteria Streptococcus pyogenes produces a multitude of proteins which interact with and alter the functions of the host immune system. Two such proteins, Endoglycosidase S (EndoS) and Immunoglobulin G-degrading enzyme from S. pyogenes (IdeS) are able to specifically alter the effector functions of immunoglobulin G (IgG). EndoS is a glycoside hydrolase which removes the conserved N-linked glycan from IgG Fc whereas IdeS is a cysteine protease that cleaves the exible protein hinge of IgG. The activity of both proteins results in the reduced ability of IgG to elicit immune responses through Fc receptor binding and complement activation. Amongst other applications, both EndoS and IdeS are actively being explored as new therapeutics for IgG-mediated autoimmune diseases. Given the therapeutic potential of EndoS and IdeS, experiments were designed to investigate the structural and functional characteristics of these enzymes in an effort to understand their specficity for and activity against IgG.
Here, bioinformatic and biophysical characterisation of EndoS identified subdomains outside of the catalytic domain which contribute to glycoside hydrolase activity. The substrate specificity of EndoS was also explored and showed that EndoS hydrolyses a broad range of glycans from the IgG scaffold. EndoS was also shown to have activity against alternative glycoprotein substrates, however, this non-specific activity was negligible in the context of whole serum. The effect of EndoS-mediated deglycosylation on the structure of the IgG Fc domain was explored using both X-ray crystallography and small-angle X-ray scattering. Small angle X-ray scattering was also used to characterise both EndoS and IdeS in complex with IgG Fc. Solution-state models of each complex were produced providing preliminary data towards how these enzymes interact with IgG. Overall, the results presented here contribute to our understanding of these enzymes which is of importance as they go forward into clinical applications.

Keywords: EndoS
glycobiology
antibodies
Streptococcus pyogenes
biophysics
immunology
structural biology
IdeS
IgG
Advisor: Zitzmann, N
Automotive combustion modelling and control

This thesis seeks to bring together advances in control theory, modelling and controller hardware and apply them to automotive powertrains. Automotive powertrain control is dominated by PID controllers, look-up tables and their derivatives. These controllers have been constantly refined over the last two decades and now perform acceptably well. However, they are now becoming excessively complicated and time consuming to calibrate. At the same time the industry faces ever increasing pressure to improve fuel consumption, reduce emissions and provide driver responsiveness. The challenge is to apply more sophisticated control approaches which address these issues and at the same time are intuitive and straightforward to tune for good performance by calibration engineers.
This research is based on a combustion model which, whilst simplified, facilitates an accurate estimate of the harmful NOx and soot emissions. The combustion model combines a representation of the fuel spray and mixing with charge air to give a time varying distribution of in-cylinder air and fuel mixture which is used to calculate flame temperatures and the subsequent emissions.
A combustion controller was developed, initially in simulation, using the combustion model to minimise emissions during transient manoeuvres. The control approach was implemented on an FPGA exploiting parallel computations that allow the algorithm to run in real-time. The FPGA was integrated into a test vehicle and tested over a number of standard test cycles demonstrating that the combustion controller can be used to reduce NOx emissions by over 10% during the US06 test cycle.
A further use of the combustion model was in the optimisation of fuel injection parameters to minimise fuel consumption, whilst delivering the required torque and respecting constraints on cylinder pressure (to preserve engine integrity) and rate of increase in cylinder pressure (to reduce noise).

Keywords: combustion
diesel
FPGA
control
modelling
automotive
Advisor: Limebeer, D
Images of the self

The aim of this thesis is to explore the images of the self constructed by Florbela Espanca in her poetry, viewing the complexities of her work in the light of her difficult position as a woman writing in the early twentieth century and showing how this work challenges conventional ideas of womanhood.
The first part of the study provides the necessary background to understand the poet's early career. Chapter 1 examines the emergence of women's poetry in Portugal at the turn of the century, showing how it provided a favourable context for her aspirations to become a writer. Chapter 2 focuses on Florbela Espanca's poetic beginnings and her assimilation and reworking of male influences, while drawing attention to the problems facing a woman writer trying to emulate male authors.
The central part of the study is divided into three chapters. They deal in turn with each of her collections, Livro de Mágoas (1919, Livro de Soror Saudade (1923) and her most famous work, Charneca em Flor (1931, posthumous. The chronological order aims to throw into relief the evolution in her poetry. Each chapter provides a detailed analysis of the poet's treatment of her problematic identity as a woman and as a writer, and of love as a means to self-assertion, through which traditional sexual stereotypes can be subverted.
The final part of the thesis looks at the transformations which her image has undergone since her death. It shows how initially Florbela Espanca was viewed as a neglected romantic artist, forever seeking something more. It analyses how it then took a lengthy argument over the erection of her bust in Évora to reinforce the poet's place in the literary canon and to ensure that her stock image became that of a representative woman writer.
Incremental modelling for verified communication architectures

Modern computer systems are advancing from multi-core to many-core designs and System-on-chips (SoC) are becoming increasingly complex while integrating a great variety of components, thus constituting complex distributed systems. Such architectures rely on extremely complex communication protocols to exchange data with required performance. Arguing formally about the correctness of communication is an acknowledged verification challenge.
This thesis presents a generic framework that formalises the idea of incremental modelling and step-wise verification to tackle this challenge: to control the overall complexity, features are added incrementally to a simple initial model and the complexity of each feature is encapsulated into an independent modelling step. Two main strategies reduce the verification effort. First, models are constructed with verification support in mind and the verification process is spread over the modelling process. Second, generic correctness results for framework components allow the verification to be reduced to discharging local assumptions when a component is instantiated. Models in the framework are based on abstract state machines formalised in higher order logic using the Isabelle theorem prover.
Two case studies show the utility and breadth of the approach: the ARM AMBA Advanced High-performance Bus protocol, an arbiter-based master-slave bus protocol, represents the family of SoC protocols; the PCI Express protocol, an off-chip point-to-point protocol, illustrates the application of the framework to sophisticated, performance-related features of current and future on-chip protocols.
The presented methodology provides an alternative to the traditional monolithic and post-hoc verification approach.

Keywords: communication protocols
verification
theorem proving
Advisor: Melham, T
La gloire et le malentendu: Goldoni and the Comédie-Italienne, 1760-93

Eighteenth-century Paris was the cultural capital of Europe and home to a vibrant network of theatres, not all of which are equally present in modern scholarship. The Comédie-Italienne in particular has frequently been downplayed in historical accounts, and there is no existing work outlining its relationship with its authors.
This thesis aims to address this gap through a case study of the Italian author Carlo Goldoni, who began work for the Comédie-Italienne in 1762. His thirty years in Paris hold an ambiguous place in his career: the preface to his autobiography draws attention to France as the site of his authorial glory, but his work for the Comédie-Italienne is dismissed as a failure; a view echoed by many modern critics. This study therefore also sets out to explore this apparent contradiction.
Substantial original work on the Comédie-Italienne archives sheds new light on the administration of this theatre, building up the most comprehensive existing account of its finances, audiences and author relations in the 1760s, and situating it in the contemporary cultural field. Dramatic authors are revealed to be at the heart of tensions between symbolic and financial concerns across eighteenth-century theatrical Paris.
This re-evaluation also provides a new context for understanding Goldoni’s equivocal account of his Parisian career. He desired a glorious image in posterity, yet the Comédie-Italienne’s collaborative production and lack of publication thwarted the reputation-shaping tactics he had developed in Italy. The only weapon that remained was his French Mémoires (1787), in which he consciously constructed his image and the claim of Parisian glory.
Goldoni’s case also raises broader questions about the creation of literary gloire, and the fate of the cosmopolitan artist in a strange land. In modern France, Goldoni is remembered as a famous foreigner, not the Frenchman he believed he had become. The thesis concludes that this failure in posterity stems from his misunderstanding of how to achieve gloire in his French context: to rely on artificially created image alone is not enough, and yet Goldoni had no choice.

Advisor: Viala, A
Study of High Energy Density Matter through Quantum Molecular Dynamics and Time Resolved X-ray Scattering

The warm dense matter regime (WDM), defined by temperatures of a few electron volts and densities comparable with solids, is a complex state of matter where multi-body particle correlations and quantum effects play an important role in determining the overall structure and equation of state. The study of WDM states represents the laboratory analogue of the astrophysical environments found in the cores of planets and in the crusts of old stars, but also has practical applications for controlled thermonuclear fusion.
Time resolved X-ray diffraction is used to study the temporal evolution of a sample from solid state towards WDM, either after irradiation with an intense proton/electron beam, in carbon samples, or direct laser illumination, in thin gold nanofoils. The electron-ion equilibration time is extracted through the use of the two-temperature model and in highly excited carbon shown to be longer than previously thought, this is attributed to strong ion-ion coupling screening the interaction (coupled mode theory).
Calculation of the dynamic ion-ion structure factor is performed using orbital-free density functional theory (OF-DFT) and shown to compare well with Kohn-Sham DFT in both the static and dynamic cases. Experimental verification of these results is vital and measurement of the microscopic dynamics of warm dense aluminium have been successfully demonstrated through inelastic X-ray scattering. Using the self-seeded beam at the linear coherent light source (LCLS) scattering at a small momentum exchange allowed the first direct measurement of ion acoustic waves in WDM. This data provides the basis for a direct experimental test of many dense plasma theories through direct comparison with the ion-ion dynamic structure factor.

Keywords: Warm dense matter
Non-equilibrium plasmas
Molecular Dynamics
Density functional theory
Advisor: Gregori, G
Basil, C
Stéphane Mallarmé: Mode de Création / Création de Mode

This thesis examines the eight issues of Stéphane Mallarmé's 1874 fashion magazine, La Dernière Mode, focussing on ideas of process. On the one hand, it views La Dernière Mode as a vital phase in the evolution of Mallarmé’s aesthetic and, on the other, it sees the discourse of fashion itself as being in a continual state of trial and re-definition.
The thesis begins with a citation from Mallarmé's 1886 article, 'Mimique'; this passage showcases the complex relationship between the interpenetrating themes of Time, Drama and Fiction, which form the three main chapter headings. Taking a thematic and linguistic approach, the thesis will explore literary, theoretical and philosophical mechanisms in La Dernière Mode, assessing ways in which these can be seen to have evolved from ideas established in Mallarmé's early verse and prose writing, and tracing their evolution over the course of the poet's later works. This study will also acknowledge the importance of crisis, both personal and social, and its influence on Mallarmé’s aesthetic, showing La Dernière Mode to be part of a dynamic process by which the parameters of literature are tested and re-defined.
My study aims to contribute to the development of recent scholarship of Mallarmé, which acknowledges and celebrates his engagement with the material world and his interest in the aesthetic value of the practices of everyday life. Challenging views of Mallarmé as the 'ivory-tower poet' and destabilizing distinctions between his poetic and 'alimentary' works, this thesis thus makes a case for seeing La Dernière Mode as a testing ground for fundamental aspects of the poet's aesthetic with significant implications for the direction his æuvre would take in the 1880s and 1890s. The fashion magazine can thus, I contend, be considered as having a dynamic relationship with the poet's unattainable ideal of the 'Livre'.

Advisor: McGuinness, P