VictorJuiz/thesis huggingface dataset:
In vitro assessment of the nutritive value of mixtures of leaves from tropical fodder trees

Previous work in animal nutrition has focused on single feeds and assumed additivity in ration systems. In the tropics, farmers are likely to feed mixtures of feeds, including tree fodders, which may not be simply additive in nutritional terms. This study has increased our understanding of the mechanisms that determine the associative effects on the in vitro fermentation of mixtures of fodder tree leaves. Associative effects are governed by a synchronisation in the fermentation rates of the components of the mixture. This is in turn dependent on the fermentability of their chemical constituents. Effects were demonstrated by changes in the fermentation kinetics of gas production curves.
The chemical components of fodder tree leaves that affect the fermentation, and the time at which the effect occurs, were identified, using two media of different nitrogen contents. The fermentation of mixtures of pure chemical entities in various combinations was then examined. The greatest associative effects were found when the mixture had components of similar fermentability. It is proposed that associative effects are a function of the synchronisation of fermentation of the different components and was shown to occur at the point when the rate was maximal.
With two types of protein (casein and bovine serum albumin (BSA)), utilisation of a protein by rumen microbes was shown to be a function of its fermentability and not of its solubility. This is also influenced by the type of associated carbohydrate. Fodder tree leaves were then combined with different pure chemical entities. Associative effects between fodder tree leaves and carbohydrates were shown to occur and the responses were similar to those obtained with mixtures of pure carbohydrates and proteins. The effect of tannins and phenolic compounds was studied using quebracho tannin as a model, and in five of the tree species. They were shown to affect the fermentability of both carbohydrates and proteins. The effect was greater with carbohydrates of medium to low fermentability. They also reacted with both soluble and insoluble protein. Forages with phenolic compounds showed both positive and negative effects. The effects were possible due to a synchrony or asynchrony in the release of protein.
In mixtures of leaves from different species, associative effects were related to their fermentability. Again, this appeared to be the result of the synchronisation of the release of nutrients. Associative effects with fodder tree leaves were of a composite nature and can be both positive and negative. The implications of these findings in relation to in vivo digestion and animal production are discussed. Due to the diversity of fodder trees, there is the potential to develop feeding systems based on mixtures which make better use of available resources. This will also contribute to improved efficiency in the management and use of natural resources, and take advantage of natural plant diversity in the tropics.
Nonlinear model evaluation: $\iota$ shadowing, probabilistic prediction and weather forecasting

Physical processes are often modelled using nonlinear dynamical systems. If such models are relevant then they should be capable of demonstrating behaviour observed in the physical process. In this thesis a new measure of model optimality is introduced: the distribution of ι
shadowing times defines the durations over which there exists a model trajectory consistent with the observations. By recognising the uncertainty present in every observation, including the initial condition, ι
shadowing distinguishes model sensitivity from model error; a perfect model will always be accepted as optimal. The traditional root mean square measure may confuse sensitivity and error, and rank an imperfect model over a perfect one. In a perfect model scenario a good variational assimilation technique will yield an ι
shadowing trajectory but this is not the case given an imperfect model; the inability of the model to ι
shadow provides information on model error, facilitating the definition of an alternative assimilation technique and enabling model improvement. While the ι
shadowing time of a model defines a limit of predictability, it does not validate the model as a predictor. Ensemble forecasting provides the preferred approach for evaluating the uncertainty in predictions, yet questions remain as to how best to construct ensembles. The formation of ensembles is contrasted in perfect and imperfect model scenarios in systems ranging from the analytically tractable to the Earth's atmosphere, thereby addressing the question of whether the apparent simplicity often observed in very high-dimensional weather models fails `even in or only in' low-dimensional chaotic systems. Simple tests of the consistency between constrained ensembles and their methods of formulation are proposed and illustrated. Specifically, the commonly held belief that initial uncertainties in the state of the atmosphere of realistic amplitude behave linearly for two days is tested in operational numerical weather prediction models and found wanting: nonlinear effects are often important on time scales of 24 hours. Through the kind consideration of the European Centre for Medium-range Weather Forecasting, the modifications suggested by this are tested in an operational model.
Genetic susceptibility to common mycobacterial diseases

Common mycobacterial diseases, including tuberculosis and leprosy, contribute to major mortality and morbidity worldwide. Despite evidence of an important role of host genetic factors in susceptibility to these infections, few compelling genetic associations have been identified with previous candidate gene and linkage approaches.
This thesis investigates the genetic factors of human immunity to these mycobacterial diseases using a high-throughput approach of association testing. To assess genetic susceptibility to tuberculosis, I have conducted a genome-wide association study in the Gambian population as part of the Wellcome Trust Case Control Consortium (WTCCC). The study reveals the region flanking CADM1 as a potential susceptibility locus. Combining this study with a Ghanaian cohort further implicates two genetic loci at chromosome 18q11.2 (P = 9.2x10⁻⁹) and PARD3B (P = 1.4x10⁻⁶). For leprosy, I have performed a gene-centric association study in the New Delhi Indian population. Evidence of significant association was observed in the HLA-DRB1/DQA1 (P = 4.9x10⁻14 and TLR1 (P = 1.7x10⁻⁹) loci. These studies identify important genomic regions that may be involved in immunity to tuberculosis and leprosy. Further analysis revealed a significant immunogenetic overlap between tuberculosis and leprosy. This provides proof-of-principle for the subsequent aggregate analysis for mycobacterial susceptibility, which suggests that the steroid biosynthesis pathway may be important in anti-mycobacterial immunity.
This thesis represents one of the largest studies to identify the genetic factors for human immunity against mycobacteria. These novel findings will further enhance vaccine and pharmaceutical efforts into prevention and treatment of these mycobacterial diseases.

Keywords: mycobacteria
susceptibility
genetics
leprosy
tuberculosis
Advisor: Hill, A
Measuring Excess Demand and its Impact on Inflation.

Excess demand pressures play a fundamental role in macroeconomic policy and analysis. The output gap, as a proxy for excess demand, is widely used but is notoriously difficult to measure due to it being a latent variable. This thesis discusses the most prominent measures of the output gap, analysing their advantages and drawbacks. The use of articially generated data enables explicit evaluation of the performance of univariate 'gap' measures, exposing the degree of disparity between measures. Analysis of the production function approach suggests modelling output in a dynamic setting in order to overcome the problems of systematic and substantial measurement errors in stock variables. The empirical application of the paper assesses the importance of excess demand in explaining inflation. Inflation is modelled in a dynamic single equation framework in which a general to specic modelling strategy is used, encompassing all relevant theories. The output gap, based on a composite measure using principal components analysis, is found to have a substantial impact upon inflation. Furthermore, the paper forecasts inflation over the 1 and 4 quarter horizon using a broad variety of forecasting models. The importance of an accurate, unbiased estimate of excess demand at the forecast origin is emphasized. Inference regarding the business cycle is integral to macroeconomics and this thesis aims to illustrate the importance of the output gap from a variety of angles.
Electron microscopy study of radiation damage in tungsten and alloys

The displacement damage induced by primary recoils of fusion neutrons in tungsten and alloys has been studied with self-ion irradiations, followed by damage characterization with electron microscopy. Tungsten and alloys (≤ 5 wt.% Re, Ta, V) were implanted with 2 MeV W+ ions over a dose range of 3.3×1017 - 2.5×1019 W+m-2 at temperatures ranging from 300 to 750°C. Dislocation loops of b = ½<111> (> 60%) and b = <100> were identified, and that ½<111> loops were found more thermally stable. Among loops that were large enough for nature determination, at least 50% were found to be of interstitial type, with larger fractions in high-temperature and high-dose conditions. The diameter of loops did not exceed 20 nm, with the majority being ≤ 5 nm. The loop number density varied between 1022 and 1023 m-3. The effects of ion dose, irradiation temperature, composition and grain orientation on damage microstructure were investigated.
In-situ irradiations (150 keV W+ ions) were carried out as a complement to the bulk implantations. Qualitative trends in loop size, geometry and nature with irradiation dose and temperature were similar to bulk irradiated specimens. Also, the dynamics of defects and their effects on the damage evolution were explored. In-situ annealing of irradiated thin foils was performed to investigate the thermal stability of radiation damage in tungsten. The majority of microstructure transformations were completed within 15 min of annealing. However, extended durations did favour the increase of loop size and the fraction of ½<111> loops.

Keywords: radiation damage
microscopy
tungsten
Advisor: Roberts, S
Jenkins, M
Politics, subjectivity and the public/private distinction

A critical investigation of the public/private distinction as it has been conceived in Anglo-American political thinking in the second half of the 20th century. A broadly held consensus has developed amongst many theorists that public/private does not refer to any single determinate distinction or relationship but rather to an often ambiguous range of related but analytically distinct conceptual oppositions. The argument of this thesis is that if we approach public/private in the search for analytic or conceptual clarity then this consensus is correct. Against this I propose that a number of the most dominant invocations of the distinction can be understood to express public/private as an irreducibly political dialectic that mediates the relationship between the subjective and objective side of social and political life. By locating these conceptually diverse invocations within a broader and more determinate framework of the historical development and contestation of the boundaries which establish the conditions for subjectivity, as the assertion of political agency, on the one hand, and which demarcate, police and defend these particular boundaries, as part of the objectively given character of social life and institutional organisation, on the other hand, then a more determinate character to public/private can be recognized. I then seek to explore the capacity of this model to capture and explain the peculiar post-war problematisation of public/private amongst a number of new left thinkers in Britain and America.

Keywords: Raphael Samuel
public sphere
Christopher Lasch
public/private
Habermas
Herbert Masrcuse
American New Left
Stuart Hall
civil society
political/non-poltical
intellectual history
private sphere
necessity/freedom
Hegel
Arendt
Liberalism
C Wright Mills
Marx
equality/liberty
political theory
Richard Sennett
British New Left
EP Thompson
Charles Taylor
Advisor: Frazer, E
Monoclonal antibodies to Ia glycoproteins from rat thymus and spleen

A fraction of rat thymocyte la glycoproteins was prepared by lentil lectin affinity chromatography and gel filtration in deoxycholate. Mice were immunized with these glycoproteins and cell lines secreting monoclonal antibody produced by cell fusion. Antibody from four cell lines, MRC OX 3, 4, 5 and 6, reacted with the thymus la glycoproteins. Analysis using a fluorescence activated cell sorter showed that these monoclonal antibodies bound to the majority of peripheral B lymphocytes, a subpopulation of thymocytes (18%) but did not significantly bind to peripheral T lymphocytes.
MRC OX 3 antibody detected a polymorphic antigenic determinant found on rat strains of the RT1 haplotype \ and y while MRC OX 4, 5 and 6 antibodies detected an antigenic determinant common to the rat strains of the RT1 haplotype a, c, 1, n, y. All four antibodies bound to mouse spleen cells and all detected polymorphic determinants. Studies on recombinant mouse strains suggested that the determinants recognized were coded by the I-A subregion of the tt-2 complex.
MRC OX 3 antibody also cross reacted with a polymorphic determinant on human lymphoblastoid cell lines. This antibody bound to cells which expressed the HLA-DRw specificities DRwl, DRw2 or DRw6 but did not bind to those cells which only expressed other HLA-DRw specificities. No significant binding of MRC OX 3 or 4 antibody to either normal or mitogen stimulated human peripheral leukocytes c:uld be detected.
MRC OX 4 antibody was used for affinity chromatography to purify la glycoproteins from rat spleen. The rat spleen la antigen was composed of two non-covalently bonded polypeptides of apparent molecular weight (unreduced) 30,000 and 24,000 as determined by polyerjryl amide gel electrophoresis in sodium dodecyl sulfate. The spleen la antigen had molecular characteristics indistinguishable from the thymus la glycoproteins.
The purified spleen la antigen partially inhibited the binding to lymph nod« cells of rat alloantibodies which detect la antigens linked to the RTi complex. The la absorbed alloantibodies still detected antigens found only on peripheral B lymphocytes. This binding could be completely inhibited by a further absorption with lymph node glycoproteins depleted of the MRC OX 4 la antigen. These results suggested that there were at least two separate rat la antigens. One antigen was detected by MRC OX 4 antibody while the remaining antigens were detected by the MRC OX 4 la absorbed alloantibodies.
From the same immunization another cell line was prepared called MRC OX 2 which secreted monoclonal antibody to a previously undefined thymus glycoprotein of 60,000 molecular weight. The MRC OX 2 antigen was found on all thymocytes and on brain tissue in equal amounts on the basis of wet tissue weight, and was also found on peripheral B lymphocytes in smaller amounts. Spleen, kidney and liver tissue had less than 10% of the antigen as compared to thymocyte or brain tissue.

Advisor: Williams, A
Unifying the epidemiological, ecological and evolutionary dynamics of Dengue

In under 6 decades dengue has emerged from South East Asia to become the most widespread arbovirus affecting human populations. Recent dramatic increases in epidemic dengue fever have mainly been attributed to factors such as vector expansion and ongoing ecological, climate and socio-demographic changes. The failure to control the virus in endemic regions and prevent global spread of its mosquito vectors and genetic variants, underlines the urgency to reassess previous research methods, hypotheses and empirical observations. This thesis comprises a set of studies that integrate currently neglected and emerging epidemiological, ecological and evolutionary factors into unified mathematical frameworks, in order to better understand the contemporary population biology of the dengue virus. The observed epidemiological dynamics of dengue are believed to be driven by selective forces emerging from within-host cross-immune reactions during sequential, heterologous infections. However, this hypothesis is mainly supported by modelling approaches that presume all hosts to contribute equally and significantly to the selective effects of cross-immunity both in time and space. In the research presented in this thesis it is shown that the previously proposed effects of cross-immunological reactions are weakened in agent-based modelling approaches, which relax the common deterministic and homogeneous mixing assumptions in host-host and host-pathogen interactions. Crucially, it is shown that within these more detailed models, previously reported universal signatures of dengue's epidemiology and population genetics can be reproduced by demographic and natural stochastic processes alone. While this contrasts with the proposed role of cross-immunity, it presents demographic stochasticity as a parsimonious mechanism that integrates, for the first time, multi-scale features of dengue's population biology. The implications of this research are applicable to many other pathogens, involving challenging new ways of determining the underlying causes of the complex phylodynamics of antigenically diverse pathogens.

Keywords: disease
albopictus
stochastic
ecology
aedes
meta-population
tropical
neglected
evolution
vector-born
multi-strain
urban
dengue fever
aegypti
epidemiology
dengue
flavivirus
Advisor: Recker, M
Indifference Pricing in a Basis Risk Model with Stochastic Volatility


The aim of this dissertation is to study exponential indifference pricing in a basis risk model of one tradable asset and one correlated non-tradable asset in which a claim on the non-tradable asset is hedged using the tradable asset. We extend this to incorporate stochastic volatilities for both assets, driven by a common stochastic factor, and look for the corresponding indifference price characterisation under such a model. We would also look at the optimal portfolio in hedging the claim on the non-tradable asset, the residual risk process and the payoff decomposition of the claim involving the indifference price process and a local martingale. Towards the end of the discussion, we would outline a procedure which one could use to obtain numerical results for the indifference price under this model.
Role of Notch ligands in tumour angiogenesis

The well conserved Notch signalling pathway plays a crucial role in vascular development and physiology. Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key notch ligands implicated in angiogenesis. Both ligands were shown to have opposite effects on vasculature. DLL4-Notch signalling inhibits sprouting resulting in fewer but better perfused blood vessels, promoting tumour growth. In contrast to DLL4, very little is known about JAG1- Notch signalling in tumour angiogenesis and its influence on tumour growth and progression. The overall aim of this work is to study the functional difference between DLL4 and JAG1-Notch signalling. The effects of murine DLL4 and murine JAG1 over-expression on tumour growth and angiogenesis was also investigated in a mouse U87 xenograft model. Firstly, the downstream target genes of DLL4 and JAG1-Notch signalling were established through microarray and QPCR. Angiogenic assays such as sprouting, network formation and migration assays were employed to study the functional effects of these two ligands in endothelial cells. The thesis firstly demonstrates that JAG1 has opposing effects on endothelial cells compared to DLL4 by increasing sprout coverage and network formation. JAG1 is less potent than DLL4 in stimulation of Notch target genes in primary endothelial cell (HUVEC) but both displayed equal potency in HMEC-1, an immortalised endothelial cell line. The growth of U87 cell lines which over-expressed murine DLL4 or murine JAG1 was slower compared to wild-type U87 cell line in vitro. JAG1- and DLL4- Notch signaling have different effects on vessel formation, which impacted on the tumour growth in vivo. Interestingly, tumours over-expressing mDLL4 had less but larger vessels compared to control, whereas mJAG1 produced more yet functional vessels; both tumours had significantly reduced pericyte coverage. Both U87 mDLL4 and mJAG1 over-expressing tumours showed increased resistance towards anti-VEGF therapy, compared to control tumours. Sensitivity to therapy was restored in combinational treatment with DBZ and bevacizumab. The mechanism behind the differential responsiveness of the Notch receptors to DLL4 or JAG1 ligands could either reflect modulation by fringes, a family of glycosyltransferases that regulate Notch signalling or by a positive feedback loop present for DLL4-Notch signalling only. Fringe was found to be abundantly expressed in endothelial cells and highly vascularised tumours. This work has highlighted some key novel differences between the two Notch Ligands.

Keywords: JAG1
DLL4
Angiogenesis
Advisor: Harris, A
Structural studies of integrin activation

Fundamental to cell adhesion and migration, integrins are large heterodimeric membrane proteins that link the extracellular matrix to the actin cytoskeleton. Uniquely, these adhesion receptors mediate inside-out signal transduction, whereby extracellular adhesion is activated from within the cell by talin, a large cytoskeletal protein that binds to the cytoplasmic tail of the β integrin subunit via its PTB-like F3 domain. Features of the interface between talin1 and small β3 fragments only have been described previously.
Through NMR studies of full-length integrin β tails, we have found that β tails differ widely in their interactions with different talin isoforms. The muscle-specific β1D/talin2 complex exhibited particularly high affinity, leading to the X-ray crystal structure of the β1D tail/talin2 F2-F3 complex. Further NMR and biological experiments demonstrated that integrin activation is induced by a concerted series of interactions between the talin F3 domain and the β tail and between the talin F2 domain and the cell membrane. Additional studies revealed the structural determinants of tight talin2/β1D binding and the basis of more general differences between β1 and β3 talin binding.
NMR studies were also performed on tyrosine-phosphorylated integrin tails binding to the PTB domains of talin1 and Dok1, an inhibitor of integrin activation; these revealed that phosphorylation can inhibit integrin activation by increasing the affinity of the β tail for talin competitors. Key residues governing this switch were identified, and proteins were engineered with reversed affinities, offering potentially useful biological tools. Taken together, these results reveal the remarkable complexity of structural features that enable talin and its competitors to mediate this important form of transmembrane signalling.

Keywords: integrins
NMR
cell adhesion
proteins
cell migration
structural biology
nuclear magnetic resonance
talin
Advisor: Campbell, I