VictorJuiz/thesis huggingface dataset:
Single cell analysis of the adult neural stem cells of the lateral ventricle using a novel genetic marker

Canonically, adult neurogenesis occurs, in mammals, in two distinct regions of the brain—the subgranular zone of the dentate gyrus and the ventricular-subventricular zone (V-SVZ) of the lateral ventricle. The V-SVZ germinal niche is comprised, in part, by ependymal cells and the quiescent neural stem cells (NSCs) that lie near these cells. During neurogenesis, the quiescent NSCs change their transcriptional state and alter their cellular machinery to become activated NSCs. Together, quiescent and activated NSCs are also known as B-cells. B-cells generate transit amplifying cells, which then generate neuroblasts. Initially, it was believed that the function of V-SVZ neurogenesis was to populate the olfactory bulb with new neurons. However, recent work suggests that under disease and injury states it can lead to the formation of new striatal neurons.
Studying B-cells is important because although they were identified two decades ago, many important questions regarding their development, specification, and function remain unanswered. The fate of B-cells is specified at the time of their formation during embryonic development. This work suggested that there existed many different subpopulations of B-cells—each fated to generate different types of neurons in the adult mouse brain. However, the mechanism by which the B-cells are apportioned to the different subgroups still remains a mystery.
In this thesis, we demonstrate that a BAC-Penk-CRE transgenic line (which causes CRE expression in cells with an active pre-pro-Enkephalin promoter), generated in our lab and crossed to an appropriate reporter strain, labels a novel subgroup of B-cells, as well as previously identified subgroups of B-cells and neuroblasts. Using single-cell RNA sequencing, and other validation techniques, we show that this novel subgroup expresses the 5-Hydroxytryptamine Receptor 2C (5-HT2C receptor) and the prolactin receptor—which have been functionally correlated with B-cells, but B-cells expressing these receptors have never been captured and sequenced before. We also show that this novel subgroup expresses the KiR7.1 channel and the folate receptor. These findings are novel and exciting and will allow for the further study of the heterogeneity of B-cells and to investigate the many unanswered questions.
Finally, not only have we been able to validate the RNAseq data, but we also show that in a partial progressive model of Parkinson’s disease, cells expressing the BAC-Penk-CRE reporter increase their proliferation and can be found in the striatal parenchyma. Thereby demonstrating the functional importance of this group of V-SVZ stem cells.

Keywords: Single cell sequencing
Subventricular Zone
Neural Stem Cells
RNA sequencing
Neurogenesis
Advisor: Minichiello, L
Nerlov, C
Linking glucocorticoid action and hypoxia: a novel mechanism driving an adverse metabolic phenotype?

Obstructive sleep apnoea (OSA) is characterised by repeated cycles of reduced and complete obstruction of air flow occurring in sleep. This can result in decreased oxygen levels (hypoxia). OSA and states of glucocorticoid excess are both associated with metabolic diseases including fatty liver disease. Whether increased glucocorticoids are a feature of OSA and may contribute to the increased metabolic risk seen in OSA is unknown.
In vitro, patient and healthy volunteer studies were employed to assess adipose response to hypoxia. Further metabolic effects of acute and chronic intermittent hypoxia (AIH and CIH) were examined in healthy volunteers and rodents respectively. The AIH study incorporated glucocorticoid receptor (GR) blockade. The patient study also examined the effect of OSA on glucocorticoid availability.
Adipocytes were sensitive to extreme hypoxia in vitro although this was not seen in adipose biopsies from patients with OSA or in assessment of adipose function in AIH. AIH in man and CIH in rodents resulted in increased de novo lipogenesis (DNL). Sham CPAP was associated with increased urinary glucocorticoids. GR blockade limited adipose tissue fatty acid mobilisation but did not affect the metabolic impact of AIH on DNL.
Intermittent hypoxia drives DNL. OSA is associated with increased glucocorticoids. Despite this GR blockade was not protective against the effects of intermittent hypoxia in this model and is unlikely to be a useful therapeutic target therefore in patients with OSA.

Advisor: Hodson, L
Tomlinson, J
Optimizing Bayesian optimization

We are concerned primarily with improving the practical applicability of Bayesian optimization. We make contributions in three key areas.
We develop an intuitive online stopping criterion, allowing only as many steps as necessary to achieve the desired target to be taken. By combining this with intelligent online switching between acquisition functions and pure local optimization we are also able to substantially improve convergence to the local minimum associated with our final solution.
In cases where a continuum of reduced cost, but also reduced accuracy, evaluations are available we develop a Bayesian Optimization acquisition function to select both the location and cost of each evaluation. We achieve this with lower overheads than previous methods, translating to a real increase in performance. Part of this improvement is achieved by way of a new, more efficient, method for generating support points to sample the minimum of a Gaussian process. Further, in the case that the reduced cost estimates are unbiased we show that a practical solution cannot exist in most cases without also taking into consideration both computational overheads and a restriction on available resources. Given this knowledge we then develop a method which provides a viable solution in this setting.
Finally, we outline practical implementation details for Bayesian optimization which allow substantial reductions in the overhead costs without changing the theoretical properties of optimization. This is primarily achieved by use of adaptive quadrature to marginalize Gaussian process hyperparameters in place of the more common slice sampling approach.

Keywords: Bayesian Optimization
Gaussian Processes
Optimization
Advisor: Roberts, S
Osborne, M
Regional and basin scale modelling of hydro-ecology: potential impacts of climate change from a conservation perspective

The principal objective of this thesis has been to assess the potential impacts of climate change on hydro-ecology at the regional and basin scale, with particular reference to the associated effects these may have on conservation efforts. Different methodologies are required when considering climate-change impact at regional and basin scales. At the regional scale, the vulnerability of European HydroBasins was determined through the application of a 'top-down' methodology to climate assessment and incorporation of novel approaches in determining both catchment and species sensitivity and resilience to climate change. The congruence between existing European protected areas and catchments most vulnerable to climate change was explored, suggesting fewer than 25% of these catchments are currently adequately included. At the basin scale, a 'scenario-neutral' approach was adopted, and the sensitivity of four key hydro-ecological variables to perturbed climatic drivers identified on a catchment-by-catchment basis in the Thames Basin, UK. Linking these responses to Water Framework Directive thresholds of environmental quality and the application of UKCP09 probabilistic scenarios generated quantifiable estimates of potential ecological alteration under climate change. Protocols were developed to further aggregate these into whole basin summary maps, and congruence between existing protected areas and potential ecological alteration under climate change was explored. The results presented in this thesis should be used to a) re-design the European protected area network to better account for projected climate change, and b) explore the most effective management strategies in mitigating climate change within existing protected areas of the Thames Basin and identify high impact Priority River Habitats for conservation and restoration.

Keywords: Hydroecology
Scenario-Neutral Climatic Modelling
Europe
Climate Change
River Thames
Environmental Modelling
Freshwater Conservation
Advisor: Whitehead, PG
Gender differences in occupational preferences among young people: evidence from the UK

This thesis advances the understanding of gender differences in occupational preferences and job values among young people in the UK. There are two main aims; first, to provide an up-to-date description of gender differences. Second, to investigate how job values and occupational preferences are related, and to what extent gender differences are associated with parental education, mother, father, and sibling characteristics, or an individual’s own attitudes. My four chapters make several contributions to the literature. First, I explain the theoretical relevance of job values—the features of a job that are important to an individual, and describe differences by gender and parental education, in the UK and wider Europe. Second, I show how job values are associated with gender differences in preferences for science, technology, engineering and mathematics (STEM). Third, I examine the relationship between parental education and gender-typical occupational preferences and assess potential explanations for this. Fourth, I study the role of siblings, and whether preferences cluster within sibships. Overall, this thesis confirms the persistence of significant and substantial gender differences in occupational preferences in the UK. Gender differences in ratings on job values are small but important for occupational preferences; girls consistently value altruistic aspects of jobs highly and this discourages them from STEM aspirations. There are clear differences by parental education, with young people from a low parental education background more likely to have gender-typical aspirations. This is primarily due to the distribution of gender-typical occupations between occupational classes, and differences in the occupational class aspired to. Lastly, siblings do not significantly influence occupational preferences, either due to sibship composition, and/or through clustering of specific occupational preferences. Instead, the main between-family contrast is between only children and those who have siblings—the former are more likely to have gender-atypical aspirations.

Keywords: Gender
Preferences
UK
Young people
Aspirations
Advisor: Mills, C
Breen, R
Multi-scale CFD modelling towards resolving machined roughness

Recent advances in manufacturing technologies, such as additive manufacturing, have introduced the potential of selecting the roughness characteristics as a design parameter. Hence, the understanding and prediction of aerothermal effects of manufacturable (machined) micro-structures would be of paramount importance. So far, roughness has been largely considered as a stochastic attribute and, therefore, had been empirically modelled. Thus, the question arises of whether the shape and pattern of regular roughness and the fine flow structures around them require detailed resolution.
Initially, a systematic computational study is carried out on the aerothermal behaviour and impact of some discrete micro-structures. Micro-structure configurations are considered for a Reynolds number range typical for those roughness elements (Re<5000). Several RANS and LES analyses are performed to compare the behaviour in a well-established turbulent flow regime to a transitional one. The results highlight the significance of resolving such fine scales and their interactive wakes, as they are dependent on both the shape and the pattern of the micro-structures.
Considering the need for resolving both the geometric and flow fine scales efficiently, a new multi-scale approach, the novel Block Spectral Method, is adopted. This method aims to provide efficient resolution of the local spatial and temporal flow variations due to the large scale micro-structures. This resolution is provided without resorting to the modelling of every single micro-structure in detail, as a conventional large scale CFD simulation would demand, but still demonstrating similar time-accurate and time-averaged flow properties. The emphasis is then put into developing a parallelised solver of the method to enable tackling large problems. The present work also includes a first of the kind verification of the Block Spectral Method application to surfaces fitted with 3D micro-structures that promote unsteadiness in the flow.

Advisor: He, L
General-to-specific approaches for evaluating multi-step system forecasts

Multi-horizon forecasts from large scale models play important roles in ongoing policy debates across a wide range of disciplines. Although there are many ways to evaluate imperfect forecasts, we show the importance of taking a more general approach and considering the joint distributions over variables and horizons. Once a multi step system context is envisaged, potential singularities need to be addressed, as do tests of significant differences between the forecasts and assessments of the value of improved forecasts. These important issues are the focus of the thesis and are illustrated using applications in the fields of macroeconomics and climate.

Keywords: hurricanes
Covariance
log determinant
MSFE
GFESM
Advisor: Hendry, D
Castle, J
Restrictions on press freedom in Ethiopia: an historical analysis of Ethiopian laws and compliance with international law

This thesis offers a historical analysis of press law in Ethiopia and examines the extent to which the current legal framework for freedom of expression and press freedom complies with constitutional guarantees and international human rights conventions. Following the political transition in 1991, Ethiopia made perhaps a major stride with accession to the International Bill of Human Rights and adopting a new constitution which should have been a powerful foundation for securing freedom of expression and media freedom. However, the EPRDF regime that led the making of a new constitution and accession to the international human rights covenants earned itself the infamous reputation as one of the world’s leading jailer of journalists and predator of free press. At the heart of this paradox is the contradiction between constitutional guarantees for press freedom and restrictive subsidiary laws inherited from the past.
Contrary to commonly held assumptions that press freedom was introduced to Ethiopia in the 1991 political transition and accession to international human rights covenants, this thesis uncovers the emergence of press freedom in Ethiopia as well as its traditional foundations well before 1991 and the international covenants. However, the analysis also shows how several of the current repressive and restrictive laws are directly inherited from the imperial and military rule period laws which are inconsistent with international standards. Despite the new constitution, the current legal framework continues legal antecedents and a pattern of restrictive and repressive laws adopted by the successive imperial and the military regimes.
The historical analysis is critical for understanding the current laws. The thesis, therefore, documents the history of printing and press work in Ethiopia starting from the early traditional foundations to demonstrate freedom of expression as an indigenous concept and the birth of free press in Ethiopia at the beginning of the 20th century and the emergence of press restrictive laws in the 1930’s. Since then, there has been a persistent popular demand to reclaim press freedom which is initially heeded by the successive political regimes but systematically rolled back as the regimes consolidate political power. The thesis also identifies the necessary legislative reform to create an enabling legal environment for freedom of expression and press freedom in Ethiopia. The new political transition in Ethiopia since April 2018 offers yet another historical opportunity to implement this legislative reform.

Keywords: Freedom of Expression
Press Law
Media Law
Advisor: O'Regan, K
Essays in applied microeconomics

This thesis is made of three chapters. In Chapter 1 I investigate some of the potential effects of the interaction between minimum wages and job frictions on labour market outcomes in the UK. In a random search model with wage-posting and productivity dispersion across firms, under certain conditions, an increase in the minimum wage has stronger effects on separations between firms and workers facing relatively higher frictions than on separations between firms and workers facing relatively lower frictions. In this chapter, I test this prediction within two separate empirical settings, using two sources of UK data. I find some evidence that employment transitions of "high-friction" workers respond more strongly relative to the "low-friction" group’s.
In Chapter 2 I analyse voting behaviour of US House Democrats on two separate bills aimed at permanently repealing or reforming the estate tax. Existing analyses of politicians’ voting behaviour are consistent with a framework in which voting decisions result from the competing influences of politicians’ own ideology and interests, special interests, and the interests of their constituents. Recent analyses of roll-call votes in the US Congress suggest that local interests are more likely to influence political decisions when the issues at hand are prominent and when the stakes associated with them are clear. Making use of data on representatives’ wealth and personal characteristics, I am able to assess whether their private interests influence their voting behaviour. Further, I use data on campaign contributions and advertising, characteristics of electoral constituents, and measures of politicians’ ideology. My results confirm the predictive power of ideology and campaign contributions found elsewhere in the literature. I am not able to find clear evidence that local interests had an influence on voting behaviour. Finally, I find no evidence that politicians’ own wealth had an influence on their voting behaviour.
Chapter 3 is co-authored with Brian Bell and John Van Reenen. In this paper, we investigate whether moving to relative performance contracts has improved the alignment between CEO pay and performance. To address this, we use an original dataset on CEO contracts for almost 500 publicly listed UK companies. We find that pay responds more strongly to increases in firm performance than to decreases, and that this asymmetry is present only in weakly governed firms. Further, we find that CEO pay is still linked to positive random industry shocks. This result is due to the fact that failing awards in weakly governed firms are redesigned in ways that reduce the risks attached to them for the CEOs. These findings suggest that reforms to the formal structure of CEO pay contracts are unlikely to align incentives in the absence of strong shareholder governance.

Keywords: Minimum wage
Political economy
Incentives
Equity plans
Public choice
Firm monopsony power
Estate tax
Random search
CEO pay
Advisor: Bell, B
Stevens, M
Liberal organic democracy: a politics of active citizenship

This thesis outlines a new theory of democracy – Liberal Organic Democracy – that recovers the dynamic understanding of popular self-rule developed in the work of New Liberal theorists, and reconstructs it on much firmer philosophical foundations. It reframes the New Liberal principle of democratic self-realisation within a Wittgensteinian theory of language- and concept-use. And it advances an organic model of democracy grounded in the everyday practice of following a rule.
Early chapters of the thesis endeavour to reclaim New Liberal democratic thought from its current obscurity. The first chapter offers a detailed analysis of the ‘organic’ model of political development that shaped New Liberal demands for constitutional reform. Thereafter, the second chapter advances a new interpretation of Hobson’s democratic thought, acknowledging its theoretical limitations, while extolling the organic social ontology that grounds Hobson’s model of democracy in a framework of political engagement.
Subsequent chapters reframe this organic social ontology within a comprehensive philosophy of meaning. The third chapter begins the process of theoretical reconstruction by outlining a Wittgensteinian theory of rule-following practice. The fourth chapter maps the theory onto the normative claim that ‘every agent should have the opportunity to be understood’. And the fifth chapter illustrates the importance of the rule-following norm for politics, arguing that social development is defined by a holistic process of self-realisation.
The final chapters of the thesis apply this argument to political thought. The sixth chapter identifies three political characteristics that follow from the rule-following norm, and grounds meaningful democracy in a model of active citizenship. And the seventh chapter gestures towards a loose institutional framework for meaningful democratic rule. This theoretical model aims to democratise the development of political concepts: to uncover the holistic processes driving political engagement, and to demonstrate how they can be harnessed to the principle of democratic self-realisation.

Keywords: Wittgenstein
Hobson
New Liberal
Organic Democracy
Meaningful Democracy
Democratic Theory
Advisor: Leopold, D
Minimal models of quantum chaotic many-body systems

Phenomena in quantum chaotic systems such as spectral fluctuations are known to be described remarkably well by the random matrix theory (RMT) in small energy intervals and over large time scales. However, in exchange for analytical tractability, RMT has been constructed to leave out an important element of realistic physical systems { the notion of locality. Since quantum information propagates at a finite speed in a spatially-extended quantum chaotic system, there exists time scales before which RMT is effective. How do we describe the non-equilibrium quantum dynamics at intermediate timescales which are much longer than the local relaxation time but too short for RMT to apply? What are the signatures of many-body quantum chaotic systems beyond the description of RMT? In this thesis, we address these questions by analysing minimal models that incorporate a notion of locality and at the same time retain some analytical tractability of RMT.
More specifically, we study Floquet quantum circuits that are random in space but periodic in time. These circuits consist of local and random quantum gates that act on a q-state `spin' at each site. After a brief review of classical chaos, quantum chaos, and quantum circuits in Chapter 1, we present three main results. In Chapter 2, we formulate a diagrammatical approach for computing ensemble averages of observables over random unitary circuits, and derive exact results on spectral statistics and dynamical observables for a Floquet circuit in the large-q limit. In Chapter 3, we further investigate the spectral statistics in spatiallyextended many-body quantum chaotic systems by computing the spectral form factor K(t) analytically and numerically. We show that K(t) follows the RMT description at times longer than the Thouless time tTh and identify the scaling of tTh at the large-q limit of a Floquet circuit. In Chapter 4, we discuss eigenstate correlations for spatially-extended many-body quantum chaotic systems, in terms of the statistical properties of matrix elements of local observables. While the eigenstate thermalization hypothesis (ETH) is known to give an excellent description of these quantities, the phenomenon of scrambling and the butterfly effect imply structure beyond ETH. We determine analytically and verify numerically the universal form of this structure at long distances and small eigenvalue separations for Floquet systems.

Advisor: Chalker, J