VictorJuiz/thesis huggingface dataset:
Multiscale modelling of fluid and drug transport in vascular tumours

Understanding the perfusion of blood and drugs in tumours is fundamental to foreseeing the efficacy of treatment regimes and predicting tumour growth. In particular, the dependence of these processes on the tumour vascular structure is poorly established. The objective of this thesis is to derive effective equations describing blood, and drug perfusion in vascular tumours, and specifically to determine the dependence of these on the tumour vascular structure. This dependence occurs through the interaction between two different length scales - that which characterizes the structure of the vascular network, and that which characterizes the tumour as a whole. Our method throughout is to use homogenization as a tool to evaluate this interaction. In Chapter 1 we introduce the problem. In Chapter 2 we develop a theoretical model to describe fluid flow in solid tumours through both the vasculature and the interstitium, at a number of length scales. Ultimately we homogenize over a network of capillaries to form a coupled porous medium model in terms of a vascular density. Whereas in Chapter 2 it is necessary to specify the vascular structure to derive the effective equations, in Chapter 3 we employ asymptotic homogenization through multiple scales to derive the coupled equations for an arbitrary periodic vascular network. In Chapter 4, we extend this analysis to account for advective and diffusive transport of anticancer drugs delivered intravenously; we consider a range of reaction properties in the interstitium and boundary conditions on the vascular wall. The models derived in Chapters 2–4 could be applied to any drug type and treatment regime; to demonstrate their potential, we simulate the delivery of vinblastine in dorsal skinfold chambers in Chapter 5 and make quantitative predictions regarding the optimal treatment regime. In the final Chapter we summarize the main results and indicate directions for further work.

Keywords: tumour biology
homogenization
vascular networks
Advisor: Chapman, SJ
Interpretation in the arts and the social sciences

This thesis makes a contribution to the debate about the status of the social sciences. Many philosophers have argued that the social sciences are unlike the natural sciences because they involve a kind of interpretative inquiry which has no parallel in the natural sciences. Stronger versions of this argument suggest that the social sciences are dominated or exhausted by interpretation. In many cases, this stronger claim is supported by an appeal to an analogy between interpretation in the social sciences and interpretation in the arts.
The claim of this thesis is that the analogy between interpretation in the arts and the social sciences is not as strong as it is often thought to be. Works of art can be subjected to several distinct kinds of interpretation. Not all of these different kinds have analogues in the social sciences. In particular, conceptions of interpretation which allow for multiple incompatible interpretations of a single artwork have no corollary in the social sciences.
By questioning the analogy between interpretation in the two fields, I seek to develop a limited version of naturalism in the philosophy of social science. That is, I argue that there are similarities and points of contact between the social sciences and the natural sciences. This position is strengthened by a further argument: that those who have opposed naturalism have tended to rely on an outdated and overly-rigid view of the what the natural sciences are like.
The naturalism I defend is limited because it accepts that there are differences between the natural and social sciences, including the fact that there is a role (but not a dominating role) for interpretation in the social sciences.

Advisor: Newton-Smith, W
Polycomb group proteins recruitment during mouse development

Polycomb proteins are a group of repressor proteins that form multiprotein complexes, Polycomb repressor complexes (PRC) that mediate gene silencing. Two major complexes that have been widely studied are PRC1 and PRC2.Both complexes have enzymatic activities that modify specific histone residues, monoubiquitination of H2AK119 (H2AK119u1) and methylation of H3K27 (H3K27me3) respectively, and it is thought that this is the basis for their silencing activity. The basis for recruitment of PcG proteins in mammalian systems remains to be fully elucidated. A key concept is the hierarchical model explaining co-occupancy of PRC1 and PRC2 at target loci. Here it is proposed that a chromodomain in the protein polycomb (Pc), a core PRC1 subunit, recognises the H3K27me3 histone modification catalysed by PRC2. Although some observations appear inconsistent with this idea it is nevertheless widely accepted.
In this study the Ink4b-Arf-Ink4a locus was used as a model to study PcG recruitment both by examining PcG localization and by setting up a reporter system that could be used to screen for novel regulators of PcG recruitment. The former analysis revealed that Exon E2, which is shared between Ink4a and Arf is strongly bound by PcG proteins, suggesting it as a good candidate for a recruitment centre. However, deletion of exon E2 does not inhibit the recruitment of PcG to other regulatory regions within the locus. In the latter study P1-derived artificial chromosome (PAC) recombineering was used to produce a modified PAC in which fluorescent marker proteins replaced endogenous Ink4a and Arf open reading frames. This will provide a useful tool for screening for factors that contribute to Ink4a-Arf activation including PcG recruitment factors.
Preliminary data from the lab indicated that global levels of PRC1 mediated H2AK119u1 are largely unaffected in cells lacking H3K27me3, an unexpected outcome based on the hierarchical recruitment model. Chromatin immunoprecipitation (ChIP) was carried out on Eed mutant (H3K27me3 depleted) ESCs and consistent with the hierarchical model, occupancy of the core PRC1 proteins RING1B and MEL18 was strongly reduced. However, H2AK119u1 was clearly detectable at target loci, suggesting PRC1 recruitment independent of H3K27me3. Genome wide analysis of RING1B occupancy substantiated this conclusion, demonstrating significant RING1B levels at polycomb target loci in Eed-/- ESCs.
From this study it can be concluded that PRC1 and PRC2 are recruited independently to sites that they co-occupy. Additionally evidence is provided that the primary function of H3K27me3 is to increase the residency of PRC1 at target loci and thereby to contribute to the stability of PRC1 mediated silencing.

Advisor: Brockdorff, N
Credibility, speculation and the speed of trade liberalization with an application to Kenya

This thesis studies the causes and consequences of the credibility problem in trade liberalization, with a special reference to African economies. The two necessary conditions for credibility are found to be macroeconomic compatibility and time-consistency, while the sufficient conditions are more difficult to identify. A lack of credibility is typically probabilistic as private agents may be uncertain about the government's intentions, or the future terms of trade.
The first part of the thesis develops a theory of economic behaviour in the absence of credibility. Due to private responses, incredibility creates a welfare cost which may arise from (i) non optimal intertemporal substitution in consumption, (ii) accumulation of stocks of imports, (iii) insufficient relocation of factors, and (iv) deferral of investment. A simple consumption model and two production models are used to assess the magnitude of the welfare cost and to derive a cost curve as a function of the probability of default. A non-monotonic curve with kinks emerges.
Many standard results concerning the speed of liberalization change drastically when the assumption of full credibility is relaxed. Containing consumption costs would typically call for a gradual reform to reduce the incentive to accumulate inventories, while, from the production point of view, a big bang or initial overshooting are preferable. Gradualism is preferable when (i) reserves may otherwise be depleted by speculative imports, forcing the government to abandon the reform, (ii) only incremental devaluation is possible, or (iii) the level of the implicit tariff is unknown.
The second part examines how liberalization episodes can be identified empirically using a quantitative measure of trade policy. The average implicit tariff index, which is the ratio of the domestic deflator to the world price index, is derived for Kenya. As the domestic deflator appears to be biased, a hypothetical implicit tariff index is derived from a Linear Expenditure System. Further, the other empirical study quantifies the social cost of incredibility during four Kenyan reforms. Three hypotheses are tested: (i) speculative accumulation of imports, (ii) deferral of investment, and (iii) increased liquidity in response to perceived uncertainty about future trade policy. The highest welfare cost was incurred during the 1980 reform which was not coordinated with exchange rate management and was therefore incompatible.
The energy heterologue: the EU-Russia energy dialogue, 2000-2012

The EU-Russia Energy Dialogue was launched in October 2000. Its goal was a binding energy agreement between Russia and the European Union, and possibly a wider political partnership. Today, however, the Energy Dialogue seems all but forgotten. How and why did the EU-Russia Energy Dialogue fail to define and create a legally binding energy partnership?
There is scant literature about the Energy Dialogue. To the limited extent that the literature addresses the failure, it identifies either ideational, political, economic, geo- economic or institutional variables. But this separation is artificial. To bridge this divide I have developed a novel analytical framework using narratives and Bakhtin’s theory of dialogue. In this respect, the thesis is ideational or constructivist. However, unlike conventional constructivist accounts, which tend to downplay politics, this account emphasises power and conflict: Not dialogue as dual meaning, but many meanings, or ‘heterologue’. Narratives, as opposed to variables, are always in flux.
To answer the how question: The dialogue failed because it could not forge a common narrative for the EU-Russia energy trade. Russia sought investment, whereas the EU wanted legal reform. Yet, the Energy Dialogue was a heterologue of conflicting narratives, both between and within Russia and the EU. I have coined six narrative clusters, used as Weberian ideal types: The ‘EUropean’, ‘EU15/25/27’, ‘Euro-Asian’, ‘Dual State’, ‘Statist’ and ‘Post-Imperial’ narratives.
To answer the why question: Narratives unfold in time-space, and the initial misgivings were exacerbated by pre-existing narrative divergences (chapter 1), but also by subsequent political (chapter 2), business (chapter 3), geo-economic (chapter 4) and legal developments (chapter 5) – all influenced by the ebbs and flows of world oil prices. Thus, the failure of the Energy Dialogue was never pre-determined, or caused by a singular factor or event. It was shaped in the multidimensional, unfolding time-space of Russo-European relations.

Keywords: Energy Dialogue
Russia
EU
Energy
Advisor: Zielonka, J
The design of inducement prize contests for research and innovation

Inducement prize contests, where a monetary prize is offered for a specified technological achievement, are increasingly popular means of incentivising research and innovation. Such prizes are often modelled by the rent-seeking Tullock contest, or an all-pay auction. However, the direct application of such models can overlook some particular features of technological competition. This thesis addresses three such features.
The first model notes that preliminary prizes are often part of contest designs. A two-round Tullock model is used to investigate a potential motivation for offering such prizes when contestants have different productivities. A designer can identify and purchase the rights to the more productive technology where the award of the preliminary prize is conditional on the winner licensing his technology to other contestants. In this way, endowing a preliminary round results in the potential for increased second round productivity, but at the cost of a reduced second round prize. Such a structure is optimal when the productivities are sufficiently different.
In the second model, it is noted that expenditures in inducement prize contests are often too large to be explained by the cash prize alone. There usually exists a final consumer application of the research. This chapter examines how different types of prizes arise by considering the informational content of winning and the effect this has on quality differentiation in when there is an established quality leader. A purely informational 2 prize influences investment decisions and also the qualities offered in the market. The main result is that some prizes may aim to select the highest quality firm as often as possible, whereas other prizes may aim to reward the entrant only if a significant improvement in quality is made.
In the third model, prizes are not the only instruments available to contest designers. In particular, subsidy of spending may be possible. This chapter uses an intuitive interpretation of the Tullock contest to offer a matching-funds instrument to a budget constrained principal. It is shown that symmetric prize/subsidy contest designs may be optimal even in the context of contestant asymmetry, in contrast to most existing contest design models. It is also shown that if only one subsidy is offered, it is always to the weaker contestant. The role of contest accuracy in these findings is also considered

Keywords: Contests
Research and development
Economics
Prizes
Innovation
Advisor: Meyer, M
Local structure/property relationships in functional materials

It is increasingly being realised that localised deviations from the average structure can play an important role in a material's properties, and hence an understanding of these deviations is essential when constructing a coherent picture of a system. In this thesis, both neutron and X-ray total scattering data have been collected and used to reveal information on three canonical systems: the high-temperature superconductor YBa2Cu3O7-x; the parent compound of the colossal magnetoresistive manganites, LaMnO3; and the oldest known magnetic material, Fe3O4. Reverse Monte Carlo refinements-using the RMCProfile implementation of the algorithm-have been used as the principal analysis technique, and the functionality of the RMCProfile program has been extended to allow the refinement of magnetic systems involving substitutional disorder. For YBa2Cu3O7-x, the focus of this thesis is on the apical Cu{O bond length. This is shown to have a bimodal distribution, but correlations in the displacements of both atoms disguise this fact in the average structure, thus resolving the apparent controversy that had existed between local- and average-structure probes. LaMnO3 displays (what was thought to be) a simple order{disorder transition that results in the Jahn-Teller distortion becoming invisible in the average structure above ~ 750 K. Here it is shown that in fact the transition is more complicated, and involves a change in the symmetry of the Jahn-Teller distortion, whereby the long Mn-O bonds move from being opposite one another in the octahedra to being adjacent to one another. This new distortion still breaks the degeneracy of the system, and is consistent with a wide range of existing observations. Finally the low temperature structure of Fe3O4 is examined using the updated RMCProfile code. The refinements show sensitivity to local structure variations, producing a bimodal Fe atom bond valence distribution. In addition, the refined magnetic spin configuration is presented, providing the first detailed description of the low-temperature magnetic structure. It is found to be a canted ferrimagnet, and appears to be consistent with Cc symmetry.

Keywords: manganites
canonical systems
superconductors
magnetism
Advisor: Goodwin, A
Study of two mouse mutants to identify novel neurodegenerative pathways

Neurodegenerative disorders (NDD) are an ever-increasing burden on healthcare; consequently, elucidating the mechanisms underlying neurodegeneration (ND) is critical for the development of effective treatments for these diseases. In order to unravel the molecular pathways underlying movement disorders and identify new genes involved in ND, two ataxic mouse mutants characterised by cell death in the cerebellum were studied in detail using a combination of in vitro and in vivo techniques. The robotic mouse demonstrated the key role of a transcription factor, Af4, in Purkinje cell (PC) survival and how only small changes in the levels of a single transcriptional cofactor could deleteriously affect normal cerebellum function. Expression array studies of the robotic PCs revealed the first confirmed targets of Af4-mediated transcription, including insulin-like growth factor 1 (Igf-1). It was demonstrated that Igf-1 is critical for PC survival, highlighting the role of the IGF-1 signalling pathway as a potential therapeutic target for the treatment of cerebellar ataxia in humans. Detailed analysis of the bella mutant demonstrated that ataxia and apoptotic cerebellar degeneration is caused by loss of the oxidative resistance 1 (Oxr1) gene. In vitro modelling experiments went on to show that the levels of this previously uncharacterised gene are critical for controlling the sensitivity of neuronal cells to oxidative stress (OS). Moreover, this study showed that Oxr1 was up-regulated both in human and pre-symptomatic mouse models of amyotrophic lateral sclerosis (ALS), demonstrating that Oxr1 was an early marker of ROS defence, prior to pathology, and potentially a novel neuroprotective factor in NDD. Preliminary interaction studies show that Oxr1 is likely to be a multi-functional protein that forms complexes with proteins known to be mutated in NDD. Thus, the study of both the robotic and the bella mouse has demonstrated the value of the phenotype-driven approach to investigate novel neurodegenerative pathways.

Keywords: oxidative stress
neurodegeneration
transcription factor
ENU
mouse mutants
Advisor: Davies, K
Some problems in algebraic topology

In his thesis we are concerned with certain numerical invariants of homotopy type akin to the Lusternik-Schnirelmann category and cocategory. In a series of papers I. Bernstein, T. Ganea, and P.J. Hilton developed the concepts of the category and weak category of a topological space. They also considered the related concepts of conilpotency and cup product length of a space and the weak category of a map. Later T. Ganea gave another definition of category and weak category (which we shall write as G-cat and G-wcat) in terms of vibrations and cofibrations and hence this dualizes easily in the sense of Eckmann-Hilton. We find the relationships between these invariants and then find various examples of spaces which show that the invariants are all different except cat and G-cat. The results are contained in the following theorem. The map e:B−>OmegaSigmaB is the natural embedding. All the invariants are normalized so as to take the value 0 on contractible spaces. THEOREM Let B have the homotopy type of a simply connected CW-complex, then catB=G−catBgeqG−wcatBgeqwcatBgeqwcategeqconilBgeqcup−longB and furthermore all the inequalities can occur. All the examples are spaces of the form B=Sqcupalphaen where alphainpin−1(Sq). When B is of this form, we obtain conditions for the category and the weak categories of B to be less than or equal to one of the terms of Hopf invariants of alpha. We use these conditions to prove the examples. We then prove the dual theorem concerning the relationships between the invariants cocategory, weak cocategory, nilpotency and Whitehead product length. THEOREM Let A be countable CW-complex, then cocatAgeqwcocatAgeqnilAgeqW−longA and furthermore all the inequalities can occur. The proof is not dual to the first theorem, though the examples we use to show that the inequalities can exist are all spaces with two non-zero homotopy groups. The most interesting of these examples is the space A with 2 non-zero homotopy groups, mathbbZ in dimension 2 and mathbbZ4 in dimension 7 with k-invariant u4inH8(mathbbZ,2;mathbbZ4). This space is not an H-space, but has weak cocategory 1. The condition wcocatAleq1 is equivalent to the fact that d is homotopic to 0 in the fibration D−d−>A−e−>OmegaSigmaA. In order to show that wcocat A = 1 we have to calculate to cohomology ring of OmegaSigmaK(mathbbZ,2). The method we use to do this is the same as that used to calculate the cohomology ring of OmegaSigmaSn+1 using James' reduced product construction. Finally we show that for the above space A the fibration OmegaA−g−>AS−f−>A has a retraction ho such that hocircg is homotopic to 1 even though A is not an H-space.

Keywords: MSC2010: 55P45
Hopf invariant
Lusternik-Schnirelmann
category
Whitehead product
nilpotency
fibration
cocategory
Advisor: James, I
The particle spectra of confining field theories

Massive QED (Schwinger model) for one and two fermion species in 1+1 dimensions is studied using Hamiltonian lattice techniques. Bound-state masses are calculated as strong-coupling expansions in inverse powers of the dimensionless coupling constant. Various Pade approximant methods for extracting continuum predictions from these are compared.
The non-relativistic limit of both lattice theories is the lattice linear potential model. This can be solved exactly. It is used to test convergence of the sequence of Pade approximants. The investigation is continued for the ordinary Schwinger model. At all coupling strengths, the best continuum estimates for bound-state masses come from values of the Pade approximants at non-zero lattice spacing.
Two different lattice formulations of the two-species Schwinger model are studied. Both have a restoration of chiral SU(2) symmetry as the fermion mass vanishes. The corresponding symmetric vacuum is too complicated to do a perturbative calculation beyond second order, where the low-lying states are those of a Heisenberg antiferromagnetic chain, in qualitative agreement with the continuum theory.
Strong-coupling expansions are carried out to high orders about the unsymmetric vacua of the massive theories. Continuum estimates for bound-state masses are compared. For weak coupling their convergence is understood in terms of the linear potential model. But for strong coupling convergence is slow; neither lattice can account for the whole particle spectrum, though each treats part of it well.
Matrix methods are studied in an attempt to obtain better convergence from low-order calculations. Strong-coupling expansions for the Hamiltonian matrix in a non-degenerate subspace are extrapolated to zero lattice spacing using matrix Pade approximants. Improved continuum estimates ore obtained from the scalar mass matrix of the ordinary Schwinger model, but not from the pseudoscalar mass matrix.

Advisor: Sinclair, D