VictorJuiz/thesis huggingface dataset:
Hypoxia-induced chromatin  changes and ATM signalling 
Keywords: hypoxia
DNA replication
chromatin
ATM
DNA damage response

The DNA damage response (DDR) is a complex signalling cascade triggered in response to stress, in an attempt to maintain genomic integrity. Components of this pathway, such as ATM-mediated signalling, have been proposed to act as a barrier in the early stages of tumourigenesis. Regions of low oxygen concentrations (hypoxia) occur in most solid tumours and are associated with a poor prognostic outcome. Here, we investigated the DDR induced following hypoxia-induced replication stress in an attempt to decipher the mechanism of ATM activation in response to physiological stresses that do not induce DNA damage. We hypothesized that hypoxia-mediated chromatin changes could impact on ATM signalling. We have characterised H3 methylation in response to hypoxia and found oxygen dependent changes in H3K9me3, including both global and replication fork associated increases in this histone modification. Importantly, we have found that decreases in H3K9me3 result in loss or attenuation of ATM activation. Notably, in a background of replication stress and increased H3K9me3, ATM inhibition or loss leads to accumulation of DNA damage and a significant decrease in replication rates in hypoxia. We propose that when replication stress occurs in the presence of hypoxia-induced chromatin changes, ATM activation is facilitated by the induction of H3K9me3. In this context, we propose a novel and stress specific role for ATM-mediated signalling in maintaining replication and preventing the generation of DNA breaks that may compromise genomic integrity. Moreover, the biological consequences of the hypoxia-induced chromatin context and in particular hypoxia-induced H3K9me3 include the repression of APAK, a negative regulator of p53. Activation of p53 is a key consequence of the hypoxia-induced DDR. Here we found that SETDB1, one of the H3 methyltransferases induced by hypoxia, mediates APAK repression. We propose that H3K9me3 plays a role in regulating APAK expression to allow optimal induction of p53 dependent apoptosis in hypoxic conditions suggesting a further role for H3K9me3 in facilitating DDR signalling in hypoxia. Together, these data suggest that the hypoxic chromatin context is critical for the role of the DDR as a barrier to tumourigenesis and predict that altering the chromatin landscape in combination with DNA damaging therapies would be efficacious in the treatment of hypoxic tumours.
Aspects of exchangeable coalescent processes
Keywords: site frequency spectrum
cumulants
exchangeable coalescents
hydrodynamic limit

In mathematical population genetics a multiple merger n-coalescent process, or Λ n-coalescent process, {Πn(t) t ≥ 0} models the genealogical tree of a sample of size n (e.g. of DNA sequences) drawn from a large population of haploid individuals. We study various properties of Λ coalescents. Novel in our approach is that we introduce the partition lattice as well as cumulants into the study of functionals of coalescent processes. We illustrate the success of this approach on several examples.
Cumulants allow us to reveal the relation between the tree height, Tn, respectively the total branch length, Ln, of the genealogical tree of Kingman’s n-coalescent, arguably the most celebrated coalescent process, and the Riemann zeta function. Drawing on results from lattice theory, we give a spectral decomposition for the generator of both the Kingman and the Bolthausen-Sznitman n-coalescent, the latter of which emerges as a genealogy in models of populations undergoing selection.
Taking mutations into account, let Mj count the number of mutations that are shared by j individuals in the sample. The random vector (M1,...,Mn-1), known as the site frequency spectrum, can be measured from genetical data and is therefore an important statistic from the point of view of applications. Fu worked out the expected value, the variance and the covariance of the marginals of the site frequency spectrum. Using the partition lattice we derive a formula for the cumulants of arbitrary order of the marginals of the site frequency spectrum.
Following another line of research, we provide a law of large numbers for a family of Λ coalescents. To be more specific, we show that the process {#Πn(t), t ≥ 0} recording the number #Πn(t) of individuals in the coalescent at time t, coverges, after a suitable rescaling, towards a deterministic limit as the sample size n grows without bound. In the statistical physics literature this limit is known as a hydrodynamic limit. Up to date the hydrodynamic limit was known for Kingman’s coalescent, but not for other Λ coalescents. We work out the hydrodynamic limit for beta coalescents that come down from infinity, which is an important subclass of the Λ coalescents.
Sub-imperialism in crisis? South Africa's government-business-media complex and the geographies of resistance
Keywords: Geopolitics
South African Politics
Political Geography
Human Geography
Regional Studies
Southern Africa
Imperial Geopolitics
Global South

This study develops a geographic theory relating to sub-imperial states and resistance to them. The theory is centred on what can be called the government-business-media (GBM) complex, whilst resistance to such states is characterised as counter-imperialist discourses. The theory is applied primarily to South Africa’s (SA’s) interactions with the Southern African Development Community (SADC) region. The aim is to assess the state of SA’s sub-imperialism and evaluate the claim that this sub-imperialism is in crisis. The research findings are based on media material drawn from, and interviews conducted in, Botswana, Zambia and SA.
The thesis outlines how sub-imperialism should be regarded as a distinct analytical and theoretical phenomenon. It explores the theoretical context in which the GBM complex and counter-imperialist discourses may be viewed. Using this theoretical framework, the study then traces the historical geographical development of SA’s GBM complex. Building on this, the thesis identifies and examines regional responses and attitudes to SA’s post-apartheid political, business and cultural-media engagement with the region, by analysing counter-imperialist discourses to SA during this period. In order to assess the current state of SA’s sub-imperialism, case studies were taken from the following four areas which cover crucial aspects of SA’s post-apartheid engagement with the region: SA’s parastatal expansion (Eskom); SA’s peacemaking role (Zimbabwe); SA’s state-driven rhetoric of multiculturalism and tolerance (xenophobia); and SA’s hosting of mega-events (2010 Football World Cup). In each of these areas the intended geopolitical and geoeconomic discourses of the GBM complex, and the corresponding responses in the region, are investigated. It is concluded that there is a discrepancy between the intended discourses of the GBM complex and the responses from the region, giving rise to counter-imperialist discourses. These discourses support the claim that SA’s sub-imperialism is in crisis.
Optical spectroscopy of a single GaAs quantum ring
Keywords: Optical spectroscopy
Localization

Given their unique structural properties, quantum rings (QRs) structures have recently been of particular interest for investigating quantum interference which is called the neutral charged exciton optical Aharonov-Bohm (AB) effect. A delocalized wavefunction around the rim is a prerequisite for the AB effect, but asymmetry and anisotropy seem to have been overlooked in the spectroscopy of QRs. In this thesis, the presence of a localized state in a single GaAs QR is presented.
Issues of control and causation in quantum information theory
Keywords: quantum computing
self-replication
quantum state transfer
constructor theory

Issues of control and causation are central to the Quantum Theory of Computation. Yet there is no place for them in fundamental laws of Physics when expressed in the prevailing conception, i.e., in terms of initial conditions and laws of motion.
This thesis aims at arguing that Constructor Theory, recently proposed by David Deutsch to generalise the quantum theory of computation, is a candidate to provide a theory of control and causation within Physics. To this end, I shall present a physical theory of information that is formulated solely in constructor-theoretic terms, i.e., in terms of which transformations of physical systems are possible and which are impossible. This theory solves the circularity at the foundations of existing information theory; it provides a unifying relation between classical and quantum information, revealing the single property underlying the most distinctive phenomena associated with the latter: the unpredictability of the outcomes of some deterministic processes, the lack of distinguishability of some states, the irreducible perturbation caused by measurement and the existence of locally inaccessible information in composite systems (entanglement).
This thesis also aims to investigate the restrictions that quantum theory imposes on copying-like tasks. To this end, I will propose a unifying, picture-independent formulation of the no-cloning theorem. I will also discuss a protocol to accomplish the closely related task of transferring perfectly a quantum state along a spin chain, in the presence of systematic errors. Furthermore, I will address the problem of whether self-replication (as it occurs in living organisms) is compatible with Quantum Mechanics. Some physicists, notably Wigner, have argued that this logic is in fact forbidden by Quantum Mechanics, thus claiming that the latter is not a universal theory. I shall prove that those claims are invalid and that the logic of self-replication is, of course, compatible with Quantum Mechanics.
Contribution of monocytes to immunopathology during influenza A virus infection
Keywords: immunology
influenza
monocyte

This thesis investigates the role of monocytes in mouse and human influenza A virus (IAV) infection and questions how they contribute to immunopathology. I first show in mice that Ly6Chi monocytes are dominant immune cells in the lungs during severe IAV infection. Comparison of the gene expression profiles in lungs of severe or mild IAV infection revealed enrichment of genes related to monocyte recruitment in severe disease, which were more rapidly expressed than in mild infection. There was also less representation of M2 macrophage polarisation genes in lungs during severe disease.
In human IAV infection, inflammatory monocytes and neutrophilic MDSCs were higher in fresh blood samples in severe compared to mild disease; but only monocyte frequency was specific to IAV infection. There were less IL-10 producing monocytes and more IL-6+TNFα- producing monocytes in severe compared to mild infection, and HLA-DR was markedly reduced on these monocytes. Increase in monocytes, but not neutrophilic MDSC, was sustained throughout infection and into recovery. Frequency of monocytes correlated with differentiation states of CD8+ T cells, and there was a negative association between iNKT cells and inflammatory monocytes in blood.
Focusing on the interaction between iNKT cells and monocytes, I questioned if monocyte number and function were regulated by iNKT cells. Using iNKT deficient mice (Jα18-/-) and deriving monocytes from blood and lungs following IAV infection and comparing to wild-type mice, I showed that iNKT cells influenced diverse monocyte characteristics including apoptosis, M1/M2 polarisation and inflammasome activation. Induction of monocyte apoptosis by activated iNKT cells was investigated in vitro as a possible mechanism by which activated iNKT cells controlled monocyte numbers.
This thesis established the role of monocytes in IAV immunopathology and provides a rationale for further studies in amelioration of monocyte number in severe IAV infection.
A high order Discontinuous Galerkin - Fourier incompressible 3D Navier-Stokes solver with rotating sliding meshes for simulating cross-flow turbines
Keywords: Large Eddy Simulation (LES)
turbulence
Arbitrary Lagrangian-Eulerian
cross-flow turbines (wind and tidal turbines)
Incompressible Navier-Stokes
Direct Numerical Simulation (DNS)
High order discontinuous Galerkin
sliding meshes

This thesis details the development, verification and validation of an unsteady unstructured high order (≥ 3) h/p Discontinuous Galerkin - Fourier solver for the incompressible Navier-Stokes equations on static and rotating meshes in two and three dimensions. This general purpose solver is used to provide insight into cross-flow (wind or tidal) turbine physical phenomena.
Simulation of this type of turbine for renewable energy generation needs to account for the rotational motion of the blades with respect to the fixed environment. This rotational motion implies azimuthal changes in blade aero/hydro-dynamics that result in complex flow phenomena such as stalled flows, vortex shedding and blade-vortex interactions. Simulation of these flow features necessitates the use of a high order code exhibiting low numerical errors. This thesis presents the development of such a high order solver, which has been conceived and implemented from scratch by the author during his doctoral work.
To account for the relative mesh motion, the incompressible Navier-Stokes equations are written in arbitrary Lagrangian-Eulerian form and a non-conformal Discontinuous Galerkin (DG) formulation (i.e. Symmetric Interior Penalty Galerkin) is used for spatial discretisation. The DG method, together with a novel sliding mesh technique, allows direct linking of rotating and static meshes through the numerical fluxes. This technique shows spectral accuracy and no degradation of temporal convergence rates if rotational motion is applied to a region of the mesh. In addition, analytical mappings are introduced to account for curved external boundaries representing circular shapes and NACA foils.
To simulate 3D flows, the 2D DG solver is parallelised and extended using Fourier series. This extension allows for laminar and turbulent regimes to be simulated through Direct Numerical Simulation and Large Eddy Simulation (LES) type approaches. Two LES methodologies are proposed.
Various 2D and 3D cases are presented for laminar and turbulent regimes. Among others, solutions for: Stokes flows, the Taylor vortex problem, flows around square and circular cylinders, flows around static and rotating NACA foils and flows through rotating cross-flow turbines, are presented.
Experimental philosophy and armchair philosophy
Keywords: experimental philosophy
intuitions

Experimental Philosophers argue that the credibility of armchair methodology is undermined by recent empirical findings that show that people's intuitive judgments about thought experiments vary systematically with a host of factors, such as cultural or socioeconomic background. In this thesis, I argue that the experimentalists’ sceptical challenge (ESC) must be understood and evaluated as a philosophical—specifically epistemological—claim, and not as (experimental philosophers maintain) a “merely methodological” claim. To that end, I (1) summarize the findings of experimental philosophy, (2) articulate a formalization of ESC on behalf of experimental philosophers, (3) distinguish ESC from traditional forms of scepticism, and explain why traditional responses to intuition scepticism fail to adequately address it; (4) argue that ESC suffers from a threat of incoherence, drawing on results of a survey on people’s meta-intuitions about the significance of divergence; (5) suggest that the proponent of ESC, in defending the coherence of his own position, opens up the possibility of parallel defences on behalf of armchair philosophy; and (6) lay out possible epistemological considerations that the armchair philosopher can use to defend her traditional methodology against the experimentalist’s challenge.
Livelihoods under stress: household assets and responses to environmental change in the Mekong Delta, Vietnam
Keywords: Migration
Vietnam
Resettlement
Livelihoods
Vulnerability
Environmental Change

This thesis is a response to broad stroked claims that climate change and sea-level rise will cause mass displacements in areas such as the Mekong Delta. Instead, I argue for a more nuanced approach to understanding vulnerability and household response measures in contexts of environmental stress, and highlight the importance of deciphering differentiations of vulnerability across households of varying characteristics. I propose that in this way, by empirically understanding differentiated household vulnerabilities and response measures to stress rather than focusing on one type of stressor (environmental change) and response (migration), we would be better positioned to holistically address the root causes of vulnerability.
To this end, I take a micro household-level approach, using an asset vulnerability framework, to assess the role of various household assets in mediating vulnerability and resilience in the rural Mekong Delta context. As a result, we are able to understand the interactions of numerous elements, including the effects of environmental stress and mobility decision-making processes, within the context of household asset profiles, which are in turn shaped by the broader political ecology.
The main findings of this study furthermore include the ‘counterintuitive’ role of environmental stress, where it is found to be one of many stressors, often paling in comparison to the pressure of others. In the process of analysing resettlement outcomes, we encounter the process of vulnerability shifts, whereby some vulnerabilities are alleviated while others are increased as a result of resettlement. Finally, in terms of the link between environmental change and migration, a direct relationship is found to be tenuous. Instead, the key drivers, deterrents, and facilitators of migration are identified, pointing to the significance of assets and their role in shaping mobility decisions and outcomes for households. This leads us to not only think about those who move, but also those who do not have the option to move as a result of their poor asset profiles.
Spatial correlation models for cell populations
Keywords: spatial correlation models
population models
cell biology

Determining the emergent behaviour of a population from the interactions of its individuals is an ongoing challenge in the modelling of biological phenomena. Many classical models assume that the spatial location of each individual is independent of the locations of all other individuals. This mean-field assumption is not always realistic; in biological systems we frequently see clusters of individuals develop from uniform initial conditions. In this thesis, we explore situations in which the mean-field approximation is no longer valid for volume-excluding processes on a regular lattice. We provide methods which take into account the spatial correlations between lattice sites, thus more accurately reflecting the system's behaviour, and discuss methods which can provide information as to the validity of mean-field and other approximations.
Thatcher's economists: ideas and opposition in 1980s Britain
Keywords: privatisation
economic policy
Margaret Thatcher
1980s
Thatcherite
Government Economic Service
economists
history of economic thought
Thatcher
privatization
economic ideas

This thesis is an historical study of the formation of Thatcherite economic thinking and policymaking with a particular focus upon investigating the part played by economic ideas and economists in Thatcherism. While some economists and economic ideas are closely associated with Thatcherism, Thatcherites were hostile to the bulk of Britain’s economists residing in universities and in the Government Economic Service and skeptical of the usefulness of economic theory in policymaking. Thatcherites thought that British academic and government economists supported a ‘Keynesian consensus’ which was purported to have been in operation since the Second World War and had allegedly retarded Britain’s growth from a quasi-mythical free-enterprise Victorian high-point. However, Thatcherites were keen to win the ‘battle of ideas’ and became eager ‘buyers’ of economic ideas – Keith Joseph particularly – in a ‘marketplace in economic ideas’ which developed over the 1960s, 1970s and 1980s. Yet, Thatcherites were not suddenly converted to neoliberal economic thinking by the marketplace in economic ideas. Instead, Thatcherites pragmatically sought out ideas which could be adopted and adapted in combination with long-standing ideological beliefs which were hostile to the size and role of the state and in favour of ‘sound money.’ Thatcherite economic thinking developed to include sometimes contradictory strands of supply-side economics, Austrian economics, monetarism/rational expectations and public choice economics but also contained, particularly for Margaret Thatcher, elements of ‘businessmen’s economics’ and ‘housewife economics.’ A case study of privatisation policy illustrates the point that pre-existing Thatcherite thinking, such as the desire to ‘roll back the state’, provided the core underlying rationale for economic policies. Yet, Thatcherites were also able to use a jumbled amalgam of economic ideas such as Austrian and neoclassical economics to promote secondary objectives such as introducing competition when conditions were judged as favourable by Thatcherites.
Design of a system to support policy formulation for sustainable biofuel production
Keywords: fuzzy set theory
sustainability
decision support system
biofuels
analytical hierarchy process
fuzzy AHP
multi criteria decision making (MCDM)

The increased demand for biofuels is expected to put additional strain on the available agricultural resources while at the same time causing environmental degradation. Hence, new energy policies need to be formulated and implemented in order to meet global energy needs while reducing the impact of biofuels farming and production.
This research focuses on proving a decision support system which can aid the formulation of policies for the sustainable biofuel production. The system seeks to address policy formulation that requires reconciliation of the qualitative aspects of decision making (such as stakeholder’s viewpoints) with quantitative data, which often may be imprecise. To allow this, based on: Fuzzy logic and Multi Criteria Decision Making (MCDM) in the form of Analytical Hierarchy Process (AHP). Using these concepts, three software functionalities, “Options vs. Fuzzy Criteria Matrix”, “Analytical Hierarchy Process” and “Fuzzy AHP” were developed. These were added within the framework of pre-existing base software, Compendium (developed by the Open University, UK).
A number of case study based models have been investigated using the software. These models made use of data from the Philippines and India in order to pinpoint suitable land and crop options for these countries. The models based on AHP and Fuzzy AHP were very successful in identifying suitable crop options for India by capturing both the stakeholder viewpoints and quantitative data. The software functionalities are very effective in scenario planning and selection of policies that would be beneficial in achieving a desired future scenario. The models further revealed that the newly developed software correctly identified many of the important issues in a consistent manner.