VictorJuiz/thesis huggingface dataset:
Multiomic investigation on the relationship between metabolism and gene expression

Cellular metabolism and gene expression are proposed to be highly integrated but a detailed mechanistic understanding of this relationship is lacking. The central metabolite, acetyl-CoA, is the substrate for histone acetylation and increases in levels of acetyl-CoA are associated with increased histone acetylation and active gene expression. How histone acetylation leads to upregulated gene expression and how the altered patterns of gene expression subsequently influence cellular metabolism is not fully understood. This work addresses the ‘acetylation-recruitment’ hypothesis: that the upregulated histone acetylation in response to the increased acetyl-CoA can recruit a bromodomain containing chromatin remodelling complex to activate gene expression, which can further regulate cellular metabolism. To facilitate this study, a growth phenomenon in budding yeast, S.cerevisiae, known as the YMC (yeast metabolic cycle) is exploited. In the YMC, yeast cells exhibit highly synchronized and periodic oscillations between the high and low oxygen consumption states, associated with cycling levels of acetyl-CoA, histone acetylation and transcripts. To link histone acetylation to cycling transcripts, the role of various bromodomain containing proteins in maintaining the YMC is tested and the Rsc2 isoform of the RSC complex is identified as important. By comparing the temporal profiles of transcripts between the wild-type and the rsc2Δ strain, it is found that the expression of genes having histone H3 acetylation at their promoters is significantly more likely to be dependent on the RSC complex. Furthermore, ACO2 is identified and verified as a gene associated with the upregulation of oxygen consumption and also a downstream target of the acetylation-RSC-recruitment pathway. Finally, two new techniques have been developed with the aim of addressing the question about the relationship between transcription and transcripts during the YMC and how this relates to metabolism. One is ultralow background NET-seq, which reduces the percentage of background signals in a yeast NETseq library from 32% to 0.7%. The other is size-fractionated NET-seq, which can map transcription start sites for both coding and noncoding transcription units.

Advisor: Mellor, J
Rural, remote, raiya: Social differentiation on the pastoralist periphery in Turkana, Kenya

In places formerly characterised by the economic and political predominance of mobile pastoralists, the rise of urban centres can dramatically alter the social landscape, with both positive and negative consequences for herders. While many studies describe the processes (e.g. sedentarisation and commercialisation) affecting pastoralism as a livelihood system, there are fewer accounts of the divisions that emerge when these effects are unequally experienced by different people within that system. Through an ethnography of development- induced social differentiation in Turkana, Kenya, this study examines the ways that herders perceive, make sense of, and respond to their changing circumstances.
Many herders in contemporary Turkana refer to themselves as raiya, a word derived from the Swahili term for ‘civilian’ or ‘subject’ but reworked through historical encounters between rural Turkana-speaking communities and various agents of “development”, including missionaries, international agencies, and the state. This term takes on different connotations for differently-positioned speakers: Formally educated urbanites describe the raiya as rural people who “lack” education, development, and global awareness, while rural herders use the term with pride to describe their toughness, pastoral knowledge, and adherence to customary practices (ng’italio). To explore the meaning of raiya – as both an exonym applied by urban dwellers and an endonym adopted by the rural periphery – and its implications for social stratification, I conducted 18 months of fieldwork between 2015 and 2016 along a rural-to- urban transect.
Using the concept of the cultural archive (James 1988), I discuss how herders draw on notions from an idealised nomadic past to distinguish themselves as raiya. This is manifested in explicit descriptions of “tradition” (etal), but also in everyday performances of style, skilled livelihood practices, and attunement to the remote landscapes in the borderlands where they live. However, while the notion of raiya makes explicit reference to conventional binaries – distinguishing rural/traditional/non-literate herders from their urban/modern/educated counterparts – I argue that the flexibility of its more implicit meanings has made it useful in negotiating relationships across these dichotomies. This is especially important as herders manage kinship obligations and political relations with educated elites. The future prospects for herders in Turkana are not a matter of their persistence as pastoralists or their adherence to conservative tradition, but the particular ways that they re-articulate kinship and political relations with elites, who are increasingly untethered from the pastoralist moral economy as urban opportunities reduce their reliance on the family herd.

Keywords: Stratification
Turkana
Pastoralists
Kenya
Pastoralism
Nomadism
Urbanisation
Advisor: Hsu, E
Turton, D
Senior military officers, politics, and the country estate in Britain, c. 1700-1750

This thesis investigates how senior military officers (generals and admirals) in the army and navy interacted with and integrated into elite society in late Stuart and early Georgian Britain both during their years of active service and afterwards. A valuable tool with which to analyse these officers is the country estate, the basis of the landed elite’s political, economic, social, and cultural power. This thesis therefore explores the acquisition and development of country estates, and officers’ political participation in Parliament, at court, and in the political and social life of their localities. This raises and helps to answer important questions about how senior military officers in the first half of the eighteenth century used their country estates, and what social, cultural, and political activities they engaged in. Examining these issues is crucial to understanding the place of senior military officers in Britain during this period, and consequently aspects of elite society more generally.
This thesis brings together multiple historiographical traditions, with architectural and garden history playing important roles alongside social and political approaches. It is therefore a highly interdisciplinary piece of research which draws on many different strands of scholarship. The purpose in this study of the country estate (and other houses and properties where relevant) is therefore to act as a medium through which to discuss wider issues such as estate acquisition and development, material culture, patronage and personal relationships, and senior officers’ wider interaction with politics. The latter could take many forms, be that jostling for a peerage, a place at court, membership of the House of Commons or Lords, or cultivating a family interest in a local parliamentary seat.

Keywords: Early Georgian Britain
Military officers
Country estates
Late Stuart Britain
Advisor: Smith, H
Grain boundary engineering in Ni-based alloys: processing, mechanisms and effect on mechanical properties

The property of polycrstalline nickel alloys are crucially dependent upon grain boundaries, as they are the strength limiting sites at high temperatures. Engineering of grain boundary structure and phases can be effective means of pursuing optimum properties of a component. Grain boundary morphologies are known to have critical impact on time dependent deformation, such as creep and fatigue. However, the reason for such an improvement is only understood qualitatively, the mechanisms of its formation or strengthening are not well understood. Roles of second phase particles on mechanical properties, such as carbides and borides, are still in an open debate. The present research tackled the questions from a fundamental perspective. The results accomplished have gained a deep understanding on the underlying science and satisfied industrial interests. This is achieved by carefully controlled experimentation and advanced characterisation. First, grain boundary morphologies are shown to be sensitive to the heat treatment that is given, and intergranular phases are proven to be responsible for obtaining serrated boundaries. Next, mechanical response between different grain boundary structures are distinctive, which is further elucidated by strain and tomography analysis. Last, minor element additions showed drastic improvement of creep life by redecoration of grain boundary phases. Overall, the thesis presents the mechanistic study of grain boundary structures, which is thoroughly investigated through the processing parameters on alteration of second phase particles and its influence on mechanical properties.

Keywords: Carbide
HR-EBSD
Creep
Ni-based superalloy
Cavitation
Grain boundary engineering
TKD
Advisor: Wilkinson, A
Reed, R
Revelation and the intuition of dualism

There is a broad consensus among philosophers that when we think about the nature of consciousness, there is a persistent and plausibly widespread intuition of dualism – a belief or a disposition to believe that consciousness is nonphysical. This dissertation addresses the intuition of dualism and what explains it. The main body of the dissertation focuses on expounding a rational explanation of our dualistic intuition by drawing on what is known as the ‘thesis of revelation’ in the philosophy of mind, the claim that the essences of phenomenal properties are revealed in phenomenal experiences. The thesis of revelation, as I clarify, is incompatible with physicalism. Furthermore, as I argue, it is part of our ordinary conception of experience and its intuitiveness is what underlies our intuition of dualism. In my dissertation, I also defend the thesis of revelation from existing and potential objections.
The dissertation is divided into three main parts. Part I introduces the theme of the dissertation (chapter 1), elucidates the intuition of dualism (chapter 2), and critically assesses a number of candidate explanations of the intuition (chapter 3). Part II is dedicated to sharpening our understanding of revelation (chapter 4), clarifying its alleged incompatibility with standard versions of physicalism (chapter 5), and putting forward a linguistic argument for its intuitiveness (chapter 6). Discussion of these issues helps to bring forth a rational explanation for the intuition of dualism in terms of the intuitiveness of revelation (chapter 7). The issues of whether similar intuitions of distinctness can arise in other areas and of what explains the intuitiveness of revelation are also addressed (chapter 7). Parts I and II complete the main narrative of the dissertation. Part III deals with some further issues regarding revelation. It addresses objections against the revelation argument against physicalism and the thesis of revelation itself (chapter 8). It also provides a preliminary defence of property dualism, a position compatible with revelation, from the exclusion problem (chapter 9).

Keywords: dualism
qualia
consciousness
revelation
physicalism
Advisor: Davies, M
Rodriguez-Pereyra, G
Studies in magnon spintronics

This thesis is a thesis of two halves. The first investigates the Spintronic idea of generating charge-decoupled spin currents in metallic systems, whereas the second contains discussions on the topic of Magnon Computing.
Chapters 2 and 3 investigate the relevance of the ‘old knowledge’ of Magnetic Resonance to the modern-day research field of Spintronics. A model based on the Overhauser Effect is presented that explains microscopically how a pure spin current can be generated in a metallic bilayer system, and an experiment is proposed to explore this model, which is dubbed the ‘Overhauser Spin Battery’.
Chapter 3 contains details of all three aspects of the Spin Battery experimental process - that of sample fabrication, sample experimentation, and a presentation of the results. The results support the model presented in Chapter 2, and suggest that the Overhauser Spin Battery can indeed be used to generate pure spin currents.
Chapter 4 looks at the problem of how information is encoded into magnonic streams. A simple device for converting between amplitude modulated (AM) and phase modulated (PM) signals is demonstrated. Potential novel applications of this device are also considered.
Chapter 5 investigates methods of separating magnonic signals of differing frequencies that have been transmitted down a single waveguide simultaneously, which is known as multiplexing. It was determined that heterodyning is a viable method for extracting signals from a multiplexed data stream, and that it is applicable to both AM and PM signals. Quadrature phase-shift keying is shown to be a valid method for doubling the information transmitted down a magnonic waveguide, and a discussion is presented about how the principles of phase-shift keying could be applied to wider questions in Magnon Computing.
Chapter 6 summarises the key ideas and results of the thesis, and considers some further experiments that may be of interest.

Keywords: Magnon
Magnonics
Spin Battery
Spintronics
Advisor: Gregg, J
Dissecting the mechanisms underlying adolescent-onset schizophrenia using patient-derived cells

Schizophrenia is a complex mental disorder with unknown causes. It is widely accepted that the disease has a strong genetic basis and a root in neurodevelopment. To investigate the mechanisms at the cellular and molecular levels of schizophrenia, we collected blood, nasal and skin primary tissues from a cohort of patients with adolescent-onset schizophrenia and healthy controls. Whole exome sequencing revealed genetic variants associated with multiple pathways including cell adhesion and postsynaptic signalling. Patient-derived primary olfactory ecto-mesenchymal stem cells had significantly reduced adhesion and elevated levels of stress responses. Total protein expression profiling showed significantly downregulated EIF signalling, mTOR pathway and cytoskeleton regulation, resulting in reduced global protein synthesis, impaired stress response and dysregulated cytoskeleton dynamics. These observations highly agreed with previously studies on adult-onset schizophrenia, suggesting common disease mechanisms. Induced neurons, reprogrammed from skin fibroblasts via induced pluripotent stem cells, did not reveal obvious differences on neurite outgrowth and spine morphologies. Further studies are required to investigate the synaptic signal transmission of the induced neurons. This study demonstrated the use of human-specific systems to study disease mechanisms and highlighted the potential to discover dynamic disease-associated cellular and molecular phenotypes, as well as some technical challenges.

Advisor: Szele, F
Neural networks for inference, inference for neural networks

Bayesian statistics is a powerful framework for modeling the world and reasoning over uncertainty. It provides a principled method for representing our prior knowledge, and updating that knowledge in the light of new information. Traditional Bayesian statistics, however, has been limited to simple models. Two of the main limiting factors for this are the expressiveness and flexibility of the probability distributions used, and the computational restrictions in performing inference and model learning. In this thesis, we consider how neural networks (NNs) can be used to assist with both of these problems. In particular, we will look at how NNs can assist in the inference process and how we can perform inference over flexible NN models.
NNs are helpful for Bayesian inference in generative models. They are useful for producing the flexible variational families required for successful variational inference (VI), as well as learning distributed representations of model variables for guiding the distributional relationships of the model. Inference, on the other hand, is useful for quantifying uncertainty in NN discriminative models. For instance, with "Bayesian NNs" one can use inference to learn a distribution over the NNs parameters and hence quantify our uncertainty over the model's predictions. However, this increased flexibility in modeling and inference comes with challenges in inference and representation.
We present three pieces of original work in this thesis towards solving these challenges. We produce an algorithm for constructing the factorization of variational approximations in an optimal way to improve the fidelity and scalability of VI. We develop a framework for distributed Bayesian learning that is particularly useful for large Bayesian NNs and is less prone to the stale gradient of non-Bayesian approaches. We finish by considering an example of how Bayesian inference can be applied to NNs in a non-standard context by reinterpreting the problem of estimating NN robustness as an inference problem.

Keywords: variational autoencoders
variational inference
deep generative models
probabilistic programming
Advisor: Mudigonda, P
Teh, Y
Untangled: species identification of silks by protein mass spectrometry

Historical records and archaeological findings suggest the commercial use of wild silks in the ancient Middle East and Europe before the dissemination of Chinese silk. However, scientific analysis of archaeological textiles is often hindered by their physical durability and the analytical capacity of conventional microscopic methods, and thus limitations of accurate identification have resulted in many controversies. This research aims to promote the comprehensive understanding of silk, by providing literature reviews in the entomological, historical and physico-chemical aspects of the material. On this foundation, the experimental works were designed to establish the potential methods of protein mass spectrometry of silk fibroins. The objectives of the experiments were to distinguish and to identify the different species of silk. Firstly, a study on the solubilisation of silk fibroins using domesticated and wild silk species was implemented. Then the development of analytical protocols for the protein mass spectrometry of silk fibroins followed, employing peptide sequencing using tandem mass spectrometry as the primary tool of analysis. The resulting analytical protocol enabled the identification and distinction between seven different types of fresh silk samples of Bombyx, Antheraea and Samia silks. Furthermore, it was also effective in the identification of silks in severely degraded archaeological textiles. Although in its emerging stages, this research could offer a new, accurate and reliable approach to the identification of silks, and a way to resolve past and future disputes of archaeological textile attributions.

Advisor: Pollard, AM
NextBASS: a new low-frequency CMB foregrounds instrument

The Next Band All-Sky-Survey (NextBASS) is an instrument capable of measuring the diffuse Galactic Foregrounds continuously in frequency between 7 to 30 GHz, in both temperature and polarisation. Still currently in the design phase, NextBASS will obtain a resolution of ≤ 1◦, using a 6m cross-Dragone telescope with two bands, a single feed operating at 7 – 15 GHz and a 33-feed array of corrugated feed horns for 15 – 30 GHz. NextBASS will achieve a raw sensitivity of ≈ 9.4µKdeg for band-1, and ≈ 1.7µKdeg for in band-2. This sensitivity estimate is based on a conceptual 5 year survey, modelled with the atmospheric conditions and a visible sky fraction mirroring those of the Llano de Chajnantor Observatory. The receiver and digital back-end technologies will use continuous wave stabilisation with a low-bit and fast sampling ADC, and digitalsignal-processing performed in an FPGA. Using single pixel forecasting simulations with Bayesian parametric fitting methods, I demonstrate that NextBASS is capable of measuring a synchrotron spectral curvature term. Furthermore, NextBASS has the potential to detect the presence of a 1% polarised AME component, in regions of sky where the AME amplitude is bright comparative to other foregrounds. NextBASS will improve constraints on the diffuse foreground parameters and help remove bias on the cosmic microwave background B-mode amplitude. This thesis focuses on the motivations behind NextBASS by assessing its impact through single pixel forecasting, along with a full proof of concept, detailing the antenna and feed horn designs and developing a receiver model. The final performance of the combined optical and receiver system is capable of achieving beam efficiencies of over 96% in a 1◦ beam, yielding TSYS ≤ 34 K for all frequencies, and a cross-polarisation of less than -35 dB across the band.

Advisor: Jones, M
How to approach high-cost credit: beyond freedom and protection

The regulation of consumer credit poses several challenges for governments; they need to ensure a fair balance between the enforcement of parties’ mutually agreed promises on one hand, and protection of consumers with lesser bargaining power on the other. This is a particularly important and difficult balance in relation to high-cost credit, commonly referred to as ‘payday lending’. These financial products have received considerable media attention recently, specifically concerning the challenges of regulating this type of lending. The public interest has not been replicated in the academic arena, and the subject remains relatively under-researched. There are two particular gaps of note. First, inadequate analysis of the relevant philosophical concepts which has resulted in an oversimplistic approach to regulation. Second, a lack of engagement in, and awareness of, the high-cost credit market and who are using these financial products. This thesis takes steps to fill both these gaps. The first section considers the concepts of freedom, protection and social minimums to gain a deeper understanding of high-cost credit. This involves an analysis of the three concepts, including their meaning, limitations, history and rationale, and examples of the concepts in our legal system. The thesis then utilises qualitative empirical research to develop an accurate and representative debtor profile. The research was conducted through a series of in-depth interviews with a wide range of people in the high-cost credit industry. The taxonomy developed from this research is used to evaluate the needs of each class of borrower, assess the role of the three relevant concepts, and analyse the appropriateness of current and past legal responses. The result of these steps is to raise a number of further relevant questions. The final section of the thesis therefore addresses these questions, recommending some initial practical steps and identifying what is necessary to take each forward.

Advisor: Chen-Wishart, M