VictorJuiz/thesis huggingface dataset:
Investigating the nexus between chromatin and metabolism

Metabolism and epigenetics are tightly connected within the cell, as many chromatin-modifying enzymes use metabolites as co-factors or substrates, and the energetic state of the cell can drive the activation of several transcriptional programmes. This thesis examines the nexus between chromatin and metabolism, both at the systemic and cellular level, in two different projects. First, the impact on a panel of weight-loss drugs on the gut microbiome of obese rats is investigated through shotgun metagenomic sequencing. Results highlight a concomitant change in weight and gut microbiome composition following treatment with Sibutramine, which acts through inhibition of appetite.
A second project focuses on alterations induced by a gain-of-function mutation in the metabolic enzyme Isocitrate Dehydrogenase I (IDH1), which spurs production of the oncometabolite 2-hydroxyglutarate (2HG), in the context of glioma. Using an isogenic human glioma cell line (U87), either wild-type or bearing the R132H IDH1 mutation, an IDH1 inhibitor (GSK864) and a combination of multi-omics techniques, we characterize the metabolic and epigenetic alterations induced. Results suggest an uncoupling between metabolism, transcriptome and the epigenome, as treatment with an IDH1 inhibitor, while successfully rescuing the metabolic defect and promoting, upon a longer treatment, changes in gene expression, did not correct the epigenetic alterations.

Keywords: Chromatin
Epigenetics
Microbiome
Metabolism
NGS sequencing
Advisor: Mellor, J
Luminosity functions using new radio surveys

Galaxy evolution at radio wavelengths is often measured using luminosity functions which are commonly based on the luminosity (L) and redshift (z) of individual sources as well as the overall distribution for a sample. However, an important factor when K-correcting radio sources to their rest-frame luminosity is the spectral index (α). This is often assumed to be a constant value for the entire sample. In reality, there is a distributioninαwhich affects the rate at which sources drop below the flux limit of thesurvey. If not accounted for, the differing rates at which sources become unobservable can be mistaken as a genuine decline in source numbers and affect the evolution of the radio luminosity function (RLF).
To tackle this, I estimate RLFs incorporating theα-distribution for both active galactic nuclei (AGN) and star forming galaxies (SFGs). Data from the Low-Frequency Array (LOFAR) and the Very Large Array (VLA) are used to formulate 150 MHz RLFs for a sample of AGN. MeerKAT and VLA data are used to measure and model the 1.4 GHz RLFs for a sample of SFGs. Markov Chain Monte Carlo sampling is used to find parameters to fit models based onρ(L,z) andρ(L,z,α) for comparison.The main findings of this work are that the accurate modelling of theα-distribution has a significant effect on not only the shape of the RLF,but the value of the evolution parameter k, parameterised as (1 +z)k in pure evolution and pure density evolution. This is true for both AGN and SFGs.
The AGN RLF model has higher values of k when accounting for theα-distribution. Steep spectrum sources drop out of the flux limit of a survey earlier and therefore drive the RLF to evolve faster.
The SFG RLF model has lower values of k when α is accounted for, since high values of k are found to compensate for the absence ofαinformation.Since the aim of RLFs is to measure the evolution of galaxies, it is imperative that the α-distribution be included to obtain accurate estimates of the strength of any evolution.
Future work would aim to improve on this further through including an-other factor that affects the visibility of a source; the angular or projected linear size of the source. In this thesis, observations of the same field but using different antenna configurations have shown that high-resolution,long baseline imaging needs to be supplemented with short baseline observations to fully capture all scales of emission and all sources. Therefore, a radio telescope with an abundance of both short and long baselines is necessary. MeerKAT is such a telescope, as will be the SKA. Therefore, my work has set out the way forward for towards properly understanding the evolution of radio sources in the Universe.

Keywords: Radio Astronomy
Luminosity functions
active galactic nuclei
Star forming galaxies
AGN
interferometer
LOFAR
MeerKAT
VLA
Galaxy evolution
Advisor: Jarvis, M
Hierarchical modelling for financial data

Algorithmic trading has gained great popularity and has been heavily used by institutional investors. Such a trading system involves mathematical and statistical modelling that makes decisions to buy or sell financial securities by following automated trading instructions. In this thesis, we research machine learning based data-driven approaches to construct such trading rules.
We utilise deep learning models to predict stock price movements and develop trading strategies based on the derived signals. Instead of using hand-crafted features, we propose neural network architectures to extract nonlinear features from limit order books data. We expand this work to study Bayesian Deep Learning models and Quantile Regression, obtaining uncertainty estimates on predictive outputs. These uncertainty estimates can be used for position sizing to improve trading performance.
However, a mapping from predictive signals to trade positions is non-trivial to construct. To solve this problem, we research Reinforcement Learning algorithms to optimise a measure of expected utility of final wealth, directly outputting trade positions thus bypassing the explicit forecasting step. Reinforcement Learning algorithms are used to trade individual assets and, subsequently, we extend this end-to-end training framework to portfolio optimisation and directly maximise the Sharpe ratio for portfolios, maximising return per risk.

Keywords: Limit order books
Deep learning
Portfolio optimisation
Microstructure data
Reinforcement learning
Advisor: Zohren, S
Roberts, S
Ecology and evolution of protective microbes

Every host is colonized by a variety of microbes, some of which can protect their hosts from pathogen infection. Harbouring protective microbes (PMs) has evolutionary implications which often result in these microbes being costly for the host. Here I have investigated the evolutionary and ecological conditions under which the interaction between a host and a protective microbe are established. For this I have used populations of Caenorhabditis elegans worm hosts, bacteria possessing protective traits (Enterococcus faecalis) and pathogenic bacteria (Staphylococcus aureus). I have experimentally coevolved the host and protective microbe and infected the coevolving system at different intervals and host generations. Furthermore, I have investigated how host sex and mating status affects the interaction of the host with the surrounding bacteria. More generally, to assess how host dynamics are affected by protective microbes, I constructed SIR models in the absence and presence of the protective microbe. My results indicate that even the rare presence of the pathogen is enough to drive the evolution of microbe mediated protection, and that this is independent of the interval or initial pathogen presence. I find that both sexes use the benefits of the PM to increase their reproductive success, even though females invest more in egg production and males more in mate searching behaviour. The SIR models indicate that the protective microbe stabilises host dynamics under a range of different parameters once the cost-benefit ratio is greater than one. Overall these results suggest, that protective microbes have high potential to influence and stabilize host dynamics, even though the two host sexes might benefit differently from the provided protection.

Keywords: Host-Pathogen Interactions
Experimental Evolution
Protective microbes
Mathematical Modelling
Defensive Symbiosis
Sexual Immune Dimorphism
Advisor: Bonsall, M
Understanding P450 hydroxylation profiles

The enzymatic approach to C-H functionalisation is a promising field within contemporary organic chemistry that complements parallel advances with chemical reagents. The cytochrome P450BM3, refined through aeons of evolution, offers a sustainable and elegant methodology for achieving synthetically valuable hydroxylations at ubiquitous C-H sites. This opens the potential for new synthetic strategies, relying on early-, mid- or late-stage C-H functionalisation. Gaining a working understanding of the regioselectivity profiles arising from such hydroxylation reactions is key to the wider adoption of this as a reliable strategy for molecular assembly.
This thesis describes a practical computational workflow that aims to rationalise selected experimental results obtained in the Wong and Robertson groups for the enzymatic hydroxylation of a bicyclic lactone and a spirocyclic amine derivative. The workflow was developed through three stages of increasing sophistication, starting with an investigation of the validity of an existing MD/docking protocol then building towards a stable and reproducible computational platform. The final iteration involved the preparation in silico of specific enzyme mutants based on the X-ray crystal structure of the Wild Type P450BM3, then performing molecular dynamics (MD) relaxation of these mutants to relieve the structural strain introduced by the process of mutagenesis and to account for enzyme solvation. The MD process was repeated for each mutant to produce four independent replicas that were clustered by a specified RMSD criterion for rigid ensemble docking with separate energy-minimised substrate conformers. The resulting docking poses were classified by the Fe=O•••H angle and O•••H distance, highlighting positions prone to hydrogen abstraction.
This approach predicted site of metabolism differences between two highly selective mutants, each of which hydroxylates one of two adjacent C-H positions of an N-protected spirocyclic amine. A new tactic for knowledge-guided mutagenesis, that eliminates the undesired binding pockets, suggested by this computational model, has enabled Wong’s group to achieve > 90% regioselectivity, > 90% stereoselectivity and > 90% conversion rates for the hydroxylation of selected N-protected cyclic amines. Potential avenues of future research are proposed and evaluated in the context of ongoing work within the groups on the further refinement and practical application of this computational methodology.

Keywords: MD
Computational model
P450
Docking
SoM pediction
P450BM3
Advisor: Robertson, J
To what extent could a literature-based approach to character education improve pupil understanding of virtue

This is the presentation of a proposed study into the role of literature as an aid to develop character for secondary school children. Building on existing research this study expects that the literature will have a positive effect in providing valuable material for research into character development. The Background Character education as a field within educational research became popular in the mid-twentieth century. With the rise of positive psychology at the beginning of the twenty-first century there has been renewed interest in the area. Within the United Kingdom there have been two main centres of study into character: The Jubilee Centre, at the University of Birmingham and the Narnian Project, at the University of Leeds. These two centres have recently taken to the study of fictional literature as a resource to help with the development of virtue within children. The basis of using literature has long been a rich source of inspiration within religious communities and so this study, being held within the context of a Christian school, aims to add to these studies. Method The innovation of this study is in three parts: biography, diversity, and measurement. The study exclusively uses biographies as the basis of the literature as this sits within the historical culture of the school. The selection of the material aims to be inclusive of gender and cultural background so as to provide approachable role models to the pupils. This study also argues that a Life History approach can provide an alternative and rich source to data collection. The proposal of Life History is not a suggestion that it is a better approach than that of previous studies. The use of self-reporting, questionnaires, semi-structured interviews, have all had success. This study proposes the Life History approach as a supplementary method of understanding the success of literature-based models of character development. In this way this study is successful in developing this important field in educational research. Findings This study was unable to collect data due to the situation with COVID-19 and the lockdown of schools. However, using the findings of the two studies above and a wealth of literature in the field this study lays out clear hypotheses and methodology to demonstrate the value of such an approach to the existent literature.

Keywords: MLT
MLT2020
Thomas Buckingham : a critical edition with commentary of the first question of the Questiones super Sententias

Rather more information is currently available about the life and works of Thomas of Buckingham than there was only a few decades ago, when L'Abbé A,.de Poorter, describing a manuscript containing Buckingham's Questiones super Sententias, was limited to saying: "Buckingham is the author of the second piece: the questions reproduced in folios 45 to 79 belong to his Commentary on the Sentences of which there exists one specimen at Florence (Laurenz.) and another at Paris (Bibl. Nat.). We owe this information to the kindness of R.P. Pelster, S.J., who promises us more ample information about Buckingham.” That it is now possible to write a reasonably full biography - albeit one subject to certain limitations - is due to the considerable work of Michalski, Chenu, Emden, Pantin, Robson and Weisheipl, among others. They have brought to light a body of materials for his life which may be regarded as exhaustive, at least insofar as all likely - and many unlikely - sources of information have been consulted. Some of these items have been published, but the majority are known only in brief references.
Since, in common with most of his mediaeval contemporaries, Thomas of Buckingham has left the modern biographer a fragmentary corpus of materials from which to reconstruct his life, it is the nature of the materials themselves which justifies further attempts at reconstruction. As Robson has said of the materials for the life of Wyclif: "...the certain and authoritative sources for these years are so few and so stark that they permit, and even encourage, an assessment de novo." What is true of Wyclif, who has not lacked biographers, is at least equally true of Buckingham, for whose life the sources are even more limited and no less ambiguous, but who has received far less critical attention. But, if it is the fragmentary nature of the materials which prompts this enterprise, it follows that interpretation must be both careful and open; i.e. that a balanced assessment of the conclusions and inferences which may be drawn from the primary materials must be presented, with clear distinctions drawn between the information actually given and the conjectural links.
Continued in thesis ...

Keywords: Manuscripts
commentary
critical edition
Oxford
Questiones super Sententias
De contingentia futurorum
Thomas Buckingham
England
Theologians
A hydro-socio-legal conception of rights for water: addressing jurisprudential tensions to foster responsive legal regimes

In the space of ten years, a number of novel and unique legal developments have arisen in different jurisdictions around the world with one element in common: a declaration of the Rights of Nature, and a direct attribution of this jurisprudence to watercourses in their respective contexts. This thesis uses a hydro-socio-legal approach to analysing three of these developments as case-studies, identifying why they have occurred, the tensions involved, and the institutional and governance issues that they seek to address or are responding to. This work frames the analysis around an evaluation of environmental constitutionalism, and legal personhood, which informed their selection. This evaluation is prefaced by a prior discussion of key ideas in the theoretical discourse pertaining to the appropriate form of a right for non-human entities, and whether natural objects can have identifiable, and representable, interests. This work concludes that sufficient sophisticated recognition and processing of information about socio-hydrologies in respective contexts can innovate water law to enable responsive governance regimes, and the achievement of this depends on whether jurisdictions are prepared to open themselves to new approaches, legitimate stakeholder relationships with watercourses, and technological solutions that can enrich empirical understandings of fair resource allocation and utilisation for both nature and society.

Keywords: Socio-legal
Water law
Rights
Environmental law
Jurisprudence
Advisor: Grecksch, K
Kurkchiyan, M
Sticking with droplets: Mathematical models of capillary adhesion

A small amount of liquid trapped between two solid surfaces can pull them together because of the effects of surface tension. This effect is called capillary adhesion, and is thought to be important in many small-scale scenarios, including helping insects to adhere. In this thesis, we study aspects of capillary adhesion using mathematical modelling.
We begin by considering whether the forces generated through capillary adhesion with a fixed volume of liquid can be enhanced by splitting a liquid bridge into many smaller bridges. By carefully calculating the bridge shape (and when bridges can span a given gap), capillary adhesion of rough surfaces is shown to be significantly enhanced compared to smooth surfaces. It is also shown that roughness may lead to a steady-state resistance to shear, which is compared quantitatively to experiments in insects.
Next, we turn to study solid-solid contact in the presence of capillary adhesion. Equilibria are found for impermeable and permeable elastic spheres in contact with a flat, rigid substrate. When saturated, a porous sphere can naturally secrete its own adhering liquid as its pore space is compressed by deformation. Numerical results and scaling laws are found to describe the equilibria with and without an applied force; results without a force are compared to experiments on hydrogel beads in contact.
We then investigate in more detail the effect of surface deformation on capillary adhesion through a model of a thin membrane under tension. Calculating the equilibrium adhesion forces shows that an increase in adhesion of more than an order of magnitude can be achieved compared to a comparable undeformable system; this is supported by experimental results. The dynamics of adhesion are investigated via a lubrication model. The slow drainage of a liquid-filled dimple explains why adhesion may not always be achieved in practice unless sufficient time is allowed to adhere. We also investigate how the deformability may be exploited to detach in a controllable manner.
Finally, we study how detachment occurs using a dynamic two-dimensional model of a loaded plate attached to a rigid substrate by a liquid bridge. Using a linear stability analysis, the motion of the plate is shown to decouple into two modes — separation and tilting — with the tilting mode growing fastest. As the plate tilts it may contact the substrate, depending on the width of the plate. We characterize how plate width and initial condition may determine whether a plate ultimately detaches or adheres and show that tilting may lead to anomalous detachment: plates that should stick, detach.

Keywords: Capillary adhesion
Mathematical modelling
Elasto-capillarity
Fluid-structure interaction
Lubrication theory
Capillary forces
Surface tension
Microfluidics
Viscous flow
Advisor: Vella, D
Ensuring readiness for delivering new qualifications: The perspective of college curriculum leaders in post-16 education in Wales

This study considers the impact upon curriculum leaders in further education colleges in Wales of the introduction of new, nationally mandated, vocational qualifications. Drawing upon the introduction of new, Wales-only, qualifications in the area of Health and Social Care and Childcare in 2019, the study sought the views of curriculum leaders about the impact that those qualifications had upon them and their work. Three key research questions are addressed:
A. What factors do college curriculum leaders take into account before, and when, new qualifications are introduced in Wales?
B. How have curriculum leaders, in further education colleges in Wales, been impacted in their role by the introduction of new qualifications in Health and Social Care in 2019?
C. How, potentially, might the qualifications regulator, awarding bodies, senior leaders and other relevant bodies in Wales improve upon past practice in relation to ensuring the manageability, for further education colleges in Wales, of the second phase of qualification reform in 2021?
The research to underpin the study took place in late May and June 2020 and consisted of hour-long interviews with senior curriculum leaders from eight of the twelve further education colleges in Wales.
The key findings of the study are that it is essential for policy makers and qualification developers to engage with, and understand the needs of, the institutions who will be delivering the qualifications to learners, at a strategic and operational level rather than, solely, at a subject level. Nine key factors are identified as being of importance to curriculum leaders and clarification is provided about the timescales which need to be followed in order to underpin successful implementation. Lessons learned from the implementation of the first suite of vocational qualifications to be reformed under the aegis of the qualifications’ regulator for Wales since its establishment in 2015 are identified in time for improvements in the implementation phase of the second major suite.
The study occurred during the height of the COVID19 pandemic of 2020 and, as such, introduces an additional dimension to the consideration of the manageability of assessment in the context of a highly unusual set of circumstances and the lessons that might be learned from these.

Keywords: MEA
MEA 2020