VictorJuiz/thesis huggingface dataset:
Structural studies of DNP-binding immunoglobulins

The importance of tryptophan in the combining sites of anti-DNP antibodies is evaluated from a series of model studies. The thermodynamic parameters characterizing the formation of a DNP/tryptophan complex are determined. The contribution of this interaction to the affinity and specificity of anti-DNP antibodies is discussed.
The accuracy of antibody combining site structures generated by model-building is examined, using available crystallographic data. The average error of alpha-carbon atom positions is estimated to be 1-2 Å.
The binding of nitrophenyl compounds to the VL dimer of the DNP-binding mouse myeloma protein 315 is investigated by 1H n.m.r. It is concluded that any corformational changes are small, and that the physical basis for the DNP-binding specificity of the VL dimer is the conservation of structural features which are important in determining the specificity of the intact protein 315. A model of the combining site of the VL dimer is described. The proposed site is a large cavity bounded by the aromatic side-chains of the Trp-93L and Tyr-34L residues. The structure is able to explain the large upfield chemical shift changes of the ligand resonances observed on binding. The kinetic parameters and structural extent of the pH-dependent conformational change of the VL dimer are investigated by fluorescence and 1H n.m.r. The transition does not obey a reversible one-step mechanism, and is limited in extent.
The involvement of two tyrosine residues in the hypervariable regions of protein 315 is investigated by specific nitration. Nitration of Tyr-34L has no effect on the affinity of protein 315 or of the VL dimer for several ligands. It is concluded that no hydrogen bond is formed between the phenolic group of Tyr-34L and the 2-nitro group of the ligand. From measurements of the perturbation of the visible absorption spectrum of protein 315 nitrated at Tyr-33H, it is concluded that this residue is in proximity to the side-chains, but not the nitrophenyl rings, of bound ligands.
Several aspects of the interaction of a homogeneous mouse anti-DNP antibody, protein A3, with nitrophenyl and similar ligands are described. The findings are discussed in relation to the heterogeneity and cross-reactivity of antisera.

Advisor: Dwek, R
Analysis and synthesis of inductive families

Based on a natural unification of logic and computation, Martin-Löf’s intuitionistic type theory can be regarded simultaneously as a computationally meaningful higher-order logic system and an expressively typed functional programming language, in which proofs and programs are treated as the same entities. Two modes of programming can then be distinguished: in externalism, we construct a program separately from its correctness proof with respect to a given specification, whereas in internalism, we encode the specification in a sophisticated type such that any program inhabiting the type also encodes a correctness proof, and we can use type information as a guidance on program construction. Internalism is particularly effective in the presence of inductive families, whose design can have a strong influence on program structure. Techniques and mechanisms for facilitating internalist programming are still lacking, however.
This dissertation proposes that internalist programming can be facilitated by exploiting an interconnection between internalism and externalism, expressed as isomorphisms between inductive families into which data structure invariants are encoded and their simpler variants paired with predicates expressing those invariants. The interconnection has two directions: one analysing inductive families into simpler variants and predicates, and the other synthesising inductive families from simpler variants and specific predicates. They respectively give rise to two applications, one achieving a modular structure of internalist libraries, and the other bridging internalist programming with relational specifications and program derivation. The datatype-generic mechanisms supporting the applications are based on McBride’s ornaments. Theoretically, the key ornamental constructs — parallel composition of ornaments and relational algebraic ornamentation — are further characterised in terms of lightweight category theory. Most of the results are completely formalised in the Agda programming language.

Keywords: inductive families
datatype ornamentation
dependent types
Advisor: Gibbons, J
Discrete quantum walks and quantum image processing

In this thesis we have focused on two topics: Discrete Quantum Walks and Quantum Image Processing. Our work is a contribution within the field of quantum computation from the perspective of a computer scientist. With the purpose of finding new techniques to develop quantum algorithms, there has been an increasing interest in studying Quantum Walks, the quantum counterparts of classical random walks. Our work in quantum walks begins with a critical and comprehensive assessment of those elements of classical random walks and discrete quantum walks on undirected graphs relevant to algorithm development. We propose a model of discrete quantum walks on an infinite line using pairs of quantum coins under different degrees of entanglement, as well as quantum walkers in different initial state configurations, including superpositions of corresponding basis states. We have found that the probability distributions of such quantum walks have particular forms which are different from the probability distributions of classical random walks. Also, our numerical results show that the symmetry properties of quantum walks with entangled coins have a non-trivial relationship with corresponding initial states and evolution operators. In addition, we have studied the properties of the entanglement generated between walkers, in a family of discrete Hadamard quantum walks on an infinite line with one coin and two walkers. We have found that there is indeed a relation between the amount of entanglement available in each step of the quantum walk and the symmetry of the initial coin state. However, as we show with our numerical simulations, such a relation is not straightforward and, in fact, it can be counterintuitive. Quantum Image Processing is a blend of two fields: quantum computation and image processing. Our aim has been to promote cross-fertilisation and to explore how ideas from quantum computation could be used to develop image processing algorithms. Firstly, we propose methods for storing and retrieving images using non-entangled and entangled qubits. Secondly, we study a case in which 4 different values are randomly stored in a single qubit, and show that quantum mechanical properties can, in certain cases, allow better reproduction of original stored values compared with classical methods. Finally, we briefly note that entanglement may be used as a computational resource to perform hardware-based pattern recognition of geometrical shapes that would otherwise require classical hardware and software.

Keywords: image processing
quantum algorithms
quantum walks
quantum computation
Advisor: Burnett, K
Bose, S
Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria

Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes (IEs) is a common property of field isolates associated with severe disease (Pain, Ferguson et al. 2001). Platelet receptors CD36 (Pain, Ferguson et al. 2001), P-Selectin (Wassmer, Taylor et al. 2008) and gC1qR (Biswas, Hafiz et al. 2007) mediate clumping. To characterize the molecular specificities of the clumping phenotype, I cloned clumping parasite line IT/C10 by limiting dilution. I characterized var gene expression in the IT/C10 clones using generic primers for the DBL tag region (Bull, Berriman et al. 2005). Clumping assays were conducted in the presence of specific reagents to delineate host factors hypothesized to contribute to development of the clumping phenotype. Finally, I conducted a clinical study with isolates from children with malaria in Kilifi, Kenya.
This study shows that in parasite line IT/C10, platelet-mediated clumping is associated with Itvar30 suggesting a prominent role for the PfEMP-1 encoded by this var gene in development of platelet-mediated clumping. For IT/C10 parasites, platelet activation appears to be involved in platelet-mediated clumping. Platelet P-Selectin appears to mediate clumping using lectin-dependent interactions. To further elucidate the mechanisms that mediate clumping by host platelets, I have used a panel of platelet antagonists to delineate specific platelet activation pathways. Our results show that platelet activation plays an important role in platelet-mediated clumping. Finally, in this study, platelet-mediated clumping was associated with parasitaemia, but not with disease severity.

Keywords: malaria
platelet-mediated clumping
Plasmodium falciparum
var gene
PfEMP1
Advisor: Roberts, D
Bull, P
Monte Carlo Based Numerical Pricing of Multiple Strike-Reset Options

In the last few years the complexity of some contracts offered by many financial markets has increased a lot. A common but complex financial contract is the Shout option, which grants the allowance to the holder to alter certain features of this contract, according to some specific rules. An example of a Shout option, and the one analysed in this thesis, is the Strike Reset option, which grands the option holder the right to reset the strike of the option a predetermined number of times before maturity. The pricing and hedging of these contacts is much more complex than the simple European options, and for most of them there does not exist a closed form formulae. As a result the valuation of these options is mainly done using multiple layer binomial trees, using Finite Difference methods or using Monte-Carlo techniques. [6] and [5] analyse the Strike Reset Put option on a single underlying asset and consider optimal reset policies using a PDE approach. Moreover [19] uses Finite Difference methods to price Strike Reset Put options with more complex restrictions in the reset features. In this thesis we use Least Squares Regression method, which was introduced by Longstaff and Schwartz, to price the Strike Reset Put option. Moreover we use Pathwise Sensitivities Approach and Likelihood Ratio Method to obtain the Greeks of this Strike Reset option within the Monte Carlo framework. Note that this thesis is an extension of a previous thesis, [20], submitted by Yudaken, where in this thesis we handle the increased complexity due to the multiple strike resets that the holder of the option has. Note that we present all theoretical and numerical results for the specic case of Strike Reset Put option. These results can be very easily extended to similar Strike Reset options, for example the Strike Reset Call option and the Strike Reset Asian Call and Put options. This thesis is structured as follows. In chapter 1, we present a description of the Strike Reset option. Then we extend the Least Squares approach to price the Strike Reset Put option. Moreover we present theoretical results for estimating the sensitivities of this option using Likelihood Ratio Method and Pathwise Sensitivities Approach. In chapter 2, we present numerical results for modelling the Strike Reset Put option. This thesis ends by a conclusion and a suggestion for possible extensions.
Development of molecular targeted imaging methods for detection of lung metastasis and angiogenesis

The focus of this thesis is the development of two molecularly targeted imaging methods, in both cases based on contrast agents encompassing micron-sized microparticles of iron oxide (MPIO). MPIO are obligate intravascular agents and as presented in this thesis the half-life in the blood circulation is < 1min.
In the first approach described in the thesis, the overall goal was to detect metastasis in mouse lungs, very early in metastatic development, by targeting vascular cell adhesion molecule 1 (VCAM-1) using conjugates of an anti-VCAM-1 antibody and 1 μm MPIO (VCAM-MPIO). In Chapter 3, I demonstrate specific retention of VCAM-MPIO in the vasculature of a lung metastasis model, and also the very short blood half-life of the contrast agent; both of which suggest the potential for in vivo detection. In Chapter 4, I show that whilst the bound VCAM-MPIO do not sufficiently dephase the signal obtained with the bright lung MRI approaches used (hyperpolarized 3He/129Xe or 19F MRI), it is possible to sensitively detect the presence of lung metastases in vivo using radiolabelled VCAM-MPIO (89Zr-DFO-VCAM-MPIO) in combination with PET imaging.
The overall goal of the second approach described, was to detect and characterize tumour angiogenesis by targeting αvβ3-expressing endothelium in vivo, using a conjugate of cyclic penta-peptides c(RGDyK) and 2.8 μm MPIO [c(RGDyK)-MPIO]. To this end, I demonstrate in Chapter 5 that c(RGDyK)-MPIO specifically binds to αvβ3-expressing endothelium in subcutaneous tumours and yields quantifiable contrast effects on T2&ast;-weighted MRI. Furthermore, I have implemented in this approach gadolinium DCE imaging, providing dynamic vascular information.
To date there is no reported detection method for pulmonary metastasis at the micrometastastic stage, as presented in this thesis. Translation of this method into clinic could allow for earlier therapeutic intervention and, thus, more effective treatment. The angiogenesis characterization imaging method presented here may provide a sensitive approach for the characterization of heterogeneity in tumour angiogenesis/vascularity and monitoring of anti-angiogenic therapies.

Keywords: Micrometastasis
Angiogenesis
MPIO
Lungs
RGD
PET
Advisor: Sibson, N
Muschel, R
The nineteenth-century British Jesuits, with special reference to their relations with the vicars apostolic and the bishops

This thesis sets out to examine the relations between the Society of Jesus, the Roman Catholic religious order known as the Jesuits, and the Vicars Apostolic and Bishops during the nineteenth-century. Suppressed in 1773 by the Pope, the Jesuits were restored at the beginning of the nineteenth-century and became the largest group among the Regular clergy in the United Kingdom. They possessed a reputation which provoked strong reactions both within and beyond the Roman Catholic community. The thesis concentrates on the relations during the protracted restoration of the Jesuits, which occurred during the struggle for full Roman Catholic emancipation, and on the various disputes (mainly concerned with the Bishops' jurisdiction and the exempt status of Regulars) which arose between the restoration of the Hierarchy in 1850 and 1881, in which year Rome provided a new constitution, Romanes Pontifices. which governed the relations between Bishops and the Regular clergy. Discussion is concentrated on the Jesuits' relations with Henry Manning in Westminster and Herbert Vaughan in Salford, in whose diocese the Jesuits attempted to open a college in Manchester; attention is also given to John Henry Newman, who, whilst not a diocesan Bishop, was a figure of related significance in this context. The interrelationship between the respective attitudes of these men to the Jesuits, and Jesuit views of them, forms the central focus of the thesis. It illuminates the central problem of the Jesuits' identity and activity in the nineteenth century, and reveals the continuity of nineteenth-century disputes with earlier conflicts on the English mission.
Huguenot general assemblies in France, 1579-1622

A large measure of the durability of the Huguenot movement was derived from then- general political assemblies. The assembly held at Montauban in 1579 was the first attended by a deputy north of the Loire; after the final and twenty-second general assembly at La Rochelle in 1622, only localised gatherings were held. This thesis argues that the assemblies were primarily a corps: their principal purpose was both to oversee the implementation of the edicts of pacification and to mobilize resources if peace broke down. Essentially based on the available manuscript sources, many of them unexplored, this thesis approaches the general assemblies as an institution. The first two chapters highlight the process of convocation of the general assemblies and the manner in which political representation (both within the assemblies and to the monarchy) took place. The third chapter principally explores the relationship between the general assemblies and the chambers created for Huguenots in the parlements from 1576. The assemblies supported these chambers as a means of obtaining implementation of the edicts of pacification. In the fourth chapter, the apparently conflicting attitudes of the general assemblies to property and civil rights are addressed. For instance, while the assemblies regulated the taking of lay and ecclesiastical property, revenue from these sources was often reinvested to support ministers, schools and charitable purposes. The fifth and sixth chapters examine the provisions for war made by the general assemblies and their attempts to ensure the adequate financing of Huguenot troops. The assemblies always stated that they acted in self-defence; a primary concern was the need to ensure the protection of local civilian populations. The monarchy allowed the assemblies to organise levies for the repayment of debts owed to mercenary troops and provided for the maintenance of Huguenot garrison troops from royal revenue. This thesis concludes that while the general assemblies worked as a corps, they never received letters of corporation from the monarchy; they remained ad hoc, susceptible to events and to the manipulation of public opinion through wellaimed pamphlet literature.

Advisor: Brockliss, L
A genome wide screen for loci involved in specific language impairment

Approximately 4% of English-speaking children are affected by Specific Language Impairment (SLI); a disorder in the development of language skills despite adequate opportunity and normal intelligence. Several studies have indicated the importance of genetic factors in SLI; a positive family history confers an increased risk of development, and monozygotic concordance consistently exceeds that of dizygotic twins. However, like many behavioural traits, SLI is assumed to be genetically complex with several loci contributing to the overall risk. This thesis aims to clarify the genetic mechanisms underlying Specific Language Impairment by the exploitation of recent advances in technological, genetic and statistical techniques. This goal is achieved, for the main part, through the completion of the first-ever, systematic genome- wide screen for loci involved in the disorder. A collection of 98 families was drawn from both epidemiological and clinical populations, all with probands who display severe deficits in language skills. Genome-wide linkage analyses were completed for three language-related measures and identified two regions which may harbour susceptibility gene variants for SLI, one on chromosome 16 and a second on chromosome 19. Both of these loci yielded maximum LOD scores of 3.55 and exceeded the threshold for suggestive linkage under all types of analysis performed. Fine mapping of the chromosome 19 locus with a high-density map of microsatellite markers provided further support for the role of this region in SLI but failed to narrow the area of linkage.
The second section of the thesis therefore explores alternative genetic strategies that may facilitate the localisation of susceptibility variants from the genomic regions identified. Mutation screening and association analyses were performed for two candidate genes within a subset of 48 families affected by SLI. The first ⎼ numblike (NBL), or numb-related (NUMB-R) (MIM 604018) ⎼ was selected from the region of linkage on chromosome 19q and the second ⎼ Forkhead-bOX domain P2 (FOXP2) (MIM 605317) ⎼ has recently been shown to be mutated in a family with a severe speech and language disorder.
Finally, I describe the mapping of a translocation breakpoint within a child affected by a severe language impairment and orofacial dyspraxia. This breakpoint lies on chromosome 2q and coincides with a putative region of linkage in both language impairment and autism. In the long-term it is hoped that techniques similar to those described here will allow the identification of the gene variants which underlie SLI allowing to the development of better diagnosis and treatment for those children with language impairments.
The global diffusion of national human rights institutions and their political impact in Latin America

In this thesis, two questions are analysed: (1) why have National Human Rights Institutions (NHRIs) become so widely disseminated among contemporary states? And, (2) what explains the variable institutionalisation of NHRIs once activated? The thesis first traces the diffusion of NHRIs across political regimes in general, with particular attention to unstable democratic regimes. It argues that NHRI creation can be attributed to three principal diffusion mechanisms: coercion, acculturation, and persuasion. These three explanatory models, however, lack precision. Linking each mechanism to recent processes of diffusion in Latin America, the analysis identifies how the diffusion of an Iberian variant to the generic NHRI category - the Defensorfa del Pueblo - corresponds to three intermediate categories: compulsion, material inducement and framing of ideas. The initial political circumstance of Defensoria creation in Latin America, in turn, has significant implications for their institutionalisation.
A domestic level of analysis is necessary to explain the institutionalisation of Defensorias operating in the democratic regimes of Latin America. The standard explanation correlates performance with structural form. While this thesis recognises the development of formal design principles is important in explaining institutionalisation, it adds a major qualification. It shows that the informal dimension of Defensorias' relations with organised state and social actors and rules of access across accountability arenas is often decisive. A typological framework is generated to assess the impact of these two dimensions on Defensorias when formal rules are enforced in a variable manner and tend to lack stability over time. This comparative analysis highlights the accountability gap which these institutions attempt, importantly, to address. By explaining how Defensorias actually work, including when and why they matter, this thesis goes beyond narrow institutionalism as suggested by the political accountability literature.

Advisor: Whitehead, L