VictorJuiz/thesis huggingface dataset:
A molecular analysis of the T-cell receptor

The recognition of MHC-peptide ligands by the T cell receptor (TCR) is central to the induction of the adaptive immune response. This thesis describes the development of a bioassay for TCR recognition which was then used to undertake a molecular analysis of the TCR/MHC-peptide interaction.
1. A TCR-CD3ϛ chimeric receptor was stably expressed in the cell line RBL-2H3 to give the transfectant RBL-008. RBL-008 was shown to exhibit MHC-restricted peptide-specific responses to both cellular and multimerised recombinant HLA-A2-pol peptide targets (Chapter 3).
2. By competitively inhibiting the response of RBL-008 to HLAA2 pol complexes with monovalent soluble recombinant MHCpeptide complexes it was confirmed that the TCR makes significant contact with both the MHC and peptide parts of its ligand. Furthermore it was found that only a few peptides in a random mixture can prevent contact between the TCR and HLA-A2. This has implications for positive selection since it supports evidence suggesting that some TCRs can be selected on a wide range of unrelated peptides (Chapter 4).
2. The bioassay was used to examine the flexibility of TCRpeptide interactions using a panel of variant peptides designed on the basis of the previously published HLA-A2-pol peptide structure (Chapter 5). Several variant peptides were recognised by the TCR and interestingly one of these altered peptide ligands was actually recognised better than the index peptide, raising the prospect of designing 'improved epitopes'.
3. By mutating the β chain of TCR-CD3ϛ chimeric receptor it was shown that allelic variation in the TCR genes can have a significant effect on antigen recognition and may therefore be disease susceptibility candidates genes (Chapter 6).
4. The structural relationship between the V and C domains of the TCR was examined and found to be of considerable functional significance since disruption of this relationship resulted in loss of expression of the TCR-CD3ϛ receptor.
Equality and global justice

This dissertation aims to defend an egalitarian conception of global distributive justice. Many hold that the scope of egalitarian justice should be defined by membership of a single political community but my dissertation will challenge this view. I begin by considering three distinctive arguments against the ideal of global equality. They maintain that egalitarian obligations of justice apply only to those people who are subject to the same sovereign authority which coerces them to abide by its rules; or to those who contribute to the preservation of each other’s autonomy through collectively sustaining a state; or to those who belong to the same nation. The first three chapters deal with these arguments respectively. Central to these arguments is the assumption that the domestic and the global contexts are different in some morally relevant way so egalitarian principles of justice apply to the former but not the latter. After rebutting these anti-egalitarian arguments I turn to the more constructive task of developing a form of global egalitarianism that is grounded in the value of equality as a normative ideal of how human relations should be conducted. I argue in Chapter 4 that relational equality—that is, standing in relations of equality to one another (rather than relations characterized by domination or exploitation)—is a demand of justice in the global context. This ideal of relational equality has distributive implications. In Chapter 5 I try to spell out these implications by defending a set of principles of global distributive justice that would follow from our commitment to global relational equality. In the sixth and final chapter, I discuss what responsibilities we have in relation to global injustice, how to distribute the burdens associated with these responsibilities, and whether they are excessively demanding on complying agents.

Keywords: distributive justice
global justice
equality
Advisor: Caney, S
Multidimensional In Vivo NMR

A proton nuclear magnetic resonance spectrum of the brain in vivo contains peaks from every proton-containing molecule in the brain. Sensitivity limitations mean that only those molecules present at concentrations of at least a few millimolar are detectable in a reasonable period of time; this still leaves many important molecules such as amino acids and other small metabolites. Most of their resonance frequencies fall in the region between 1.0 and 4.5 p.p.m.. A typical linewidth in vivo is about 0.05 p.p.m., so the number of distinct peaks observable is restricted. The use of two-dimensional NMR techniques such as COSY can spread peaks out into a second dimension enabling otherwise overlapping peaks to be resolved. This thesis describes the development, testing and application of two such 2D NMR pulse sequences, dubbed ISIS-COSY and ISIS-JRES. They are based on an existing magnetisation localisation sequence and excite detected magnetisation in a manner analogous to the high-resolution sequences COSY and 2D J-resolved spectroscopy. A method for quantifying the metabolites visible in an ISIS-COSY spectrum from their cross-peak intensities is described, and results presented from both control rat brains and those of animals treated with vigabatrin, an inhibitor of GABA-transaminase that has the effect of increasing brain γ-amino butyric acid (GABA) levels. Further applications mentioned are in the study of neutrophil-infiltrated rat brain and adaptation of the ISIS-COSY technique for human use.

Keywords: Vigabatrin
In Vivo
ISIS
COSY
brain
NMR
JRES
Nuclear Magnetic Resonance
GABA
Advisor: Blamire, A
Dixon, R
Spectral analysis of breast ultrasound data with application to mass sizing and characterization

Ultrasound is a commonly used imaging modality in diagnosis and pre-operative assessment of breast masses. However, radiologists often find it very difficult to correctly size masses using conventional ultrasound images. Consequently, there exists a strong need for more accurate sizing tools to avoid either the removal of an over-estimated amount of tissue or a second surgical procedure to remove margins involved by tumour not removed in the primary operation.
In this thesis, we propose a new method of processing the backscattered ultrasound signals from breast tissue (based on the Fourier spectral analysis) to better estimate the degree of echogenicity and generate parametric images where the visibility of breast mass boundaries is improved (SPV parametric image). Moreover, an algorithm is proposed to recover some anatomical structures (particularly, Cooper’s ligaments) which are shadowed during the image acquisition process (LWSPV parametric image). The information from both algorithms is combined to generate a final SPV+LWSPV parametric image.
A 20-case pilot study was conducted on clinical data, which showed that the SPV+LWSPV parametric image added useful information to the B-mode image for clinical assessment in 85% of the cases (increase in diagnostic confidence in at least one boundary). Moreover, in 35% of the cases, the SPV+LWSPV parametric image provided a better definition of the entire boundary. Note that the radiologist knew the final diagnosis from histopathology.
In addition, the SPV+LWSPV method has the advantage that it uses the I/Q data from a standard ultrasound equipment without the need for additional hardware.
On the basis of these facts, we believe there to be a case for further investigation of the SPV+LWSPV imaging as a useful clinical tool in the pre-operative assessment of breast mass boundaries.

Keywords: ultrasound medical imaging
breast cancer
spectral analysis
ultrasonic tissue characterization
Advisor: Noble, A
Class, race and nation

The 1930s and 1940s in Durban have been relatively under-researched, and yet these two decades constituted a crucial phase in the city's growth. This thesis concentrates on the political experiences of Africans during the period.
The beer hall riots of 1929 and the 'African-Indian' riots of 1949 serve as significant points at which to start and end the thesis. These two flashpoints were very different in nature, and their differences signalled the changes that took place in Durban between the late 1920s and the late 1940s. Yet the riots can also be linked: they both reflected extreme frustration amongst Africans at their exclusion from the resources of the city. The two riots illuminate key issues in African politics, in municipal and state policy, and in the changing structures of Durban society.
These comparative findings are based on a detailed study of the period between the two riots. A wide variety of African political experiences in Durban is examined. These fall into four broad categories of political ideology and practice: populism, nationalism, ethnicity and 'workerism'. The narrative begins with the radical anti-municipal populism of 1929-30 and then attempts to explain the politically 'quiet' 1930s. The Second World War brought significant changes, giving rise to a range of important new ideologies and political strategies. The most important developments were in worker organisation and nationalist politics. The struggle for the city was heightened even further in the post-war period. Wide-ranging expressions of urban populism and racial ethnicity set the scene for the 1949 riots.
Due to the nature of the evidence collected, much of the thesis concentrates on the roles played by the (largely middle class) political leadership. The analysis portrays African politics as a complex process of 'negotiation', and the historical narrative is informed by theoretical perspectives which integrate 'class' and 'race'.
Analytical and topological aspects of signatures

In both physical and social sciences, we usually use controlled differential equation to model various continuous evolving system; describing how a response y relates to another process x called control. For regular controls x, the unique existence of the response y is guaranteed while it would never be the case for non-smooth controls via the classical approach. Besides, uniform closeness of controls may not imply closeness of their corresponding responses. Theory of rough paths provides a solution to both concerns. Since the creation of rough path theory, it enjoys a fruitful development and finds wide applications in stochastic analysis. In particular, rough path theory provides an effective method to study irregularity of curves and its geometric consequences in relation to integration of differential forms. In the chapter 2, we demonstrate the power of rough path theory in classical complex analysis by showing the rough path nature of the boundaries of a class of Holder's domains; as an immediate application, we extend the classical Gauss-Green's theorem.
Until recently, there has been only limited research on applications of theory of rough paths to high dimensional geometry. It is clear to us that many geometric objects, in some senses appearing as solids, are actually comprised of filaments. In the chapter 3, two basic results in the theory of rough paths which will motivate later development of my thesis has been included. In the chapters 4 and 5, we identify a sensible way to do geometric calculus via those filaments (more precisely, space-filling rough paths) in dimension 3.
In a recent joint work of Hambly and Lyons, they have shown that every rectifiable path can be completely characterized, up to tree-like deformation, by an algebraic object called the signature, tensor of all iterated integrals, of the path. It is clear that all tree-like deformation of the path would not change its topological features. For instance, the number of times a planar loop of finite length winds around a point (not lying on the path) is unaltered if one deforms the path in tree-like ways. Therefore, it should be plausible to extract this topological information out from the signature of the loop since the signature is a complete algebraic invariant. In the chapter 6, we express the winding number of a nice loop (respectively linking number of a pair of nice loops) as a linear functional of the signature of the loop (respectively signatures of the pair of loops).

Advisor: Lyons, T
Studies of disorder in fastionics and of a nuclear quadrupole interaction in ordered markets

This thesis consists of two completely separate parts. In Part I, we look at disorder in fastionic conductors, and in Part II we examine the pseudoquadrupole effect in ordered magnets.
Part I looks at two aspects of the disordered state in fastionics, where the disorder is due to ions moving off their regular sites to positions close to other regular sites, a feature especially characteristic of the fluorites.
The first aspect is how Coulomb interactions could be responsible for the co-operative behaviour of defects which causes the transition to fastionic behaviour. We look at this with a model of charged defects on a lattice, applying techniques involving classical diagrammatic perturbation theory to find the free energy of our model system. Using elementary thermodynamics, we show how this model can predict co-operative behaviour.
The second aspect is the nature of the disorder above the fastionic transition. We look at disorder in lead fluoride using a molecular dynamics simulation with an interionic potential that we obtained. We use the simulation to examine the distribution of anions in both real space and k space. Simulations have been made on the other fluorites CaF2 and SrCl2 and it is possible that the high dielectric constant of lead fluoride might lead to qualitatively different behaviour. Our results show that this is not the case and we find defect concentrations similar to those obtained from CaF2 and SrCl2. Our Is space analysis however gives defect concentrations an order of magnitude larger, in approximate agreement with experiment.
In Part II we set up a theory for the pseudoquadrupole effect in cubic ferromagnets and show that it is related to the difference in longitudinal and transverse magnetic susceptibilities. Model calculations are performed for a Heisenberg ferromagnet using molecular field theory near the critical temperature tc, and spin wave theory at low temperatures; and the itinerant model at absolute zero and tc.
We find that the pseudoquadrupole effect in iron and nickel and at impurities in these metals appears to be very much less than measured quadrupole effects. We also look at the effect in GdAl2 and show that it can not explain a temperature dependent quadrupole interaction seen experimentally We therefore conclude that the observed quadrupole effects are due to real electric field gradients.

Advisor: Gehring, G
Gillan, M
Stem and progenitor cells in wound healing

As more patients with large body surface area burns are surviving and requiring reconstructive surgery, there is a necessity for advances in the provision of bioengineered alternatives to autologous skin cover. The aims of this Thesis are to identify feasible source tissues of Endothelial Colony Forming Cells and Mesenchymal Stem/Stromal Cells for microvascular network formation in vitro with three-dimensional dermal substitute scaffolds. The working hypothesis is that pre-vascularised dermal scaffolds will result in better quality scarring when used with split thickness skin grafts.
Human umbilical cord blood, peripheral blood and adipose tissue were collected and processed with ethical approval and informed consent. Samples were cultured to form endothelial outgrowth colonies and confluent Mesenchymal Stem/Stromal Cells, which were characterised using flow cytometry and expanded in vitro. Mesenchymal Stem/Stromal Cell multipotency was confirmed with tri-lineage mesenchymal differentiation. Primary cells were tested in a two-dimensional tubule formation co-culture assay and differences assessed using a proangiogenic antibody array. Tubule formation was tested in four different acellular dermal substitute scaffolds; Integra® Dermal Regeneration Template, Matriderm®, Neuskin-F® and De-cellularised Human Cadaveric Dermis.
Umbilical cord blood was the most reliable source of Endothelial Colony Forming Cells, the yield of which could be predicted from placental weight. Microvasculature dissected free from adipose tissue was a reliable source of Mesenchymal Stem/Stromal Cells which supported significantly more tubule formation than Mesenchymal Stem/Stromal Cells from whole adipose tissue. Microvasculature Mesenchymal Stem/Stromal Cells secreted significantly higher levels of the proangiogenic hormone leptin, and addition of exogenous leptin to the tubule formation assay resulted in significantly increased tubule formation. Microvasculature was cultured in all four of the scaffolds tested, but depth of penetration was limited to 100µm. The artificial oxygen carrier perfluorocarbon was shown to increase two-dimensional tubule formation and may be useful in further three-dimensional scaffolds studies to improve microvascular penetration.

Keywords: STEM CELLS
UMBILICAL CORD BLOOD
ADIPOSE TISSUE
BURNS.
PROGENITOR CELLS
WOUND HEALING
Advisor: Watt, S
Martin-Rendon, E
The regulation of stem cell engraftment

The engraftment of haemopoietic stem/progenitor cells (HSPCs) from umbilical cord blood (UCB) into adult recipients, although advantageous in terms of sourcing units, the decreased need to match donor and recipient and reduced risk of graft versus host disease (GvHD), is delayed compared to grafts using HSPCs from mobilised peripheral blood (MPB) or bone marrow (BM). One reason for this is the limited number of HSPCs (CD34+/CD133+ cells) in a unit of UCB compared to MPB or BM. The CXCR4-CXCL12 axis is widely recognised as a key player in the bone marrow homing, retention, and engraftment of HSPCs. The aim of this thesis was to investigate whether the engraftment of HSPCs from UCB into the bone marrow could be improved. Firstly, a novel in vitro 3D time-lapse chemotaxis assay to assess the homing capacity of human UCB CD133+ HSPCs, towards the chemokine CXCL12 was developed. One advantage of this assay was that it distinguished cell chemotaxis from chemokinesis and allowed these parameters to be quantified. Human UCB CD133+ HSPC chemotaxis towards CXCL12 was inhibited by the CXCR4 antagonist, AMD3100. Importantly, the presence of CXCL12 or AMD3100 had no affect on cell chemokinesis. To complement the in vitro chemotaxis assay, a short term in vivo homing assay in NSG mice was successfully established. The effect of siRNA silencing of the CXCR4 co-receptor, CD164, which is also expressed on CD133+ HSPCs, on cell migratory and homing ability was investigated. CD164 knock-down using siRNA in human UCB CD133+ HSPCs did not demonstrate an effect on homing to NSG bone marrow in vivo or chemotaxis to CXCL12 in vitro. However, homing to NSG mouse spleen was significantly reduced in cells silenced for CD164. Following this, an 8 day HSPC expansion system using nanofibre scaffolds (Nanex) and differing cytokines was investigated. These serum and feeder free conditions yielded a significant expansion of cells that retained CD133+CD34+ expression and their in vitro chemotactic ability to CXCL12. Time constraints did not permit the engrafting ability of these cells to be analysed in an in vivo HSC reconstitution assay that was initiated. However these studies will provide the basis to support future related research in this laboratory.

Keywords: CD164
Stem Cell Engraftment
Bone marrow transplantation
umbilical cord blood
Migration
Chemotaxis
Endolyn
Haemopoietic Stem/progenitor Cells
haemopoietic cell expansion
Advisor: Watt, S
New methods for the construction of C-18F bonds

The main electrophilic source used in radiolabelling is [18F]F2, which is highly reactive, toxic and requires specialist equipment for safe handling. The Gouverneur group has initiated a research programme focused on the preparation of new stable and easy-to-handle N-18F reagents. In the development of [18F]radiolabelling reactions it would be extremely valuable to develop a library of selective N-18F reagents possessing reactivity tailored to the desired chemical transformation. The aim of this thesis is to further assess the scope of electrophilic N- 18F reagents in new transformations for the construction of C-18F bonds.

Keywords: PET
Radiochemistry
18F-DOPA
Organic synthesis
Fluorine-18
Advisor: Gouverneur, V
Social mobility and educational attainment among Romanian Rroma

Academic researches suggests that Rroma face challenges of overcoming poverty, improving access to education, increasing employability and improving health. This thesis describes a qualitative investigation into the role of education to ensuring upward mobility for Rroma.
Using a purposive sample, the research analysed the ethnic make-up of Rroma individuals and found that contrary to uninformed perceptions, Rroma community is immensely diverse and can be described through two generic types: a Traditional Gypsies type and a Modern Rroma type. The Traditional Gypsies type would generally describe the Gypsies who at individual or collective level still preserve in their day to day life a collection of Gypsy ethnic practices. By contrast, the Modern Rroma type would refer to those Rroma who having began recently or generations back a process of ethnic transition and/or assimilation into the wider Romanian community now share only a few traditional ethnic practices.
Next, the research classified occupations encountered, analysed whether intra-generational and inter-generational social mobility occurs and found that Rroma community experiences a dynamic pattern of multi-directional and multi-speed social mobility as well as a distinct process of ethnic transition. Ethnic transition describes the process through which respondents shed ethnic practices and move away from distinct Gypsy ethnic identities towards "symbolic" identities.
Thirdly, the research analysed the impact of education on social trajectories and found that contrary to uninformed prejudice, a majority of Rroma tend to hold education in high esteem and that they do benefit socially from it. Far from questioning its relevance or fearing it, formal education is accepted and aspired to by Traditional Gypsies who understand its potential impact upon their living standard. Modem Rroma too, value education though their ideal attainment levels tend to be higher than those of Traditional Gypsies. The gap between abstract preferences and real school participation is maintained less by discrimination alone but by a rational choice evaluation through a cost (including discrimination) benefit analysis.
Formal education is essential for Rroma's social mobility though Traditional Gypsies necessitate lesser levels than Modern Rroma who, to compete in the Gadje world, require the same amount of education for comparative occupation levels as other members of the wider community.

Advisor: Heath, A