VictorJuiz/thesis huggingface dataset:
Insights into epigenetic modulation from computational studies
Keywords: Quantum Mechanics
Molecular Dynamics
Epigenetics
DFT

Histone monomers are proteins found in the nucleosome, which contain tail domains that can be post-translationally modified as part of epigenetic modulation. The accumulation of these chemical groups on histone amino acid residues such as lysine, alter the flexibility of the nucleosome, influencing how transcriptional machinery binds to DNA. As a result, epigenetic regulation has large impacts on gene activation and repression, which can be exploited by cancerous cells to proliferate in hypoxic and dense tumour conditions. Subsequently, research to elucidate the chemical mechanisms driving the enzymes responsible for reading, writing, and erasing these post-translational modifications (PTMs) gained increasing attention in recent decades. In contribution to this field, the work presented here discusses the use of computational chemistry techniques, such as quantum mechanics (QM) and molecular dynamics (MD) simulations, to shed light on the underlying behaviour of the PTM substrates and epigenetic receptors. Chapter 1 will introduce the relevant protein families, computational theory, and previous pioneering work in the field. In Chapter 2, an in-depth analysis using several in silico approaches to optimise a 5-isoxazolylbenzimidazole inhibitor (Fig. 1, blue) and bromodomain cation–π interaction is discussed, followed by details of a large-scale study exploring all the available crystallographic PDB data containing an analogous interaction. Chapter 3 characterizes the enthalpic landscape of the rate-determining step for demethylation of epigenetic eraser Fe(II)-αKG substrates, such as DNA nucleobase 1-methyladenine, using a combination of ab initio and DFT calculations. Chapters 4, 5, and 6 discuss the results of work performed in collaboration with experimental groups. MD simulations are employed in Chapter 4 to understand the effects on recognition after altering trimethyllysine, the natural substrate of several epigenetic readers, by shortening and lengthening its side chain or inverting the backbone stereochemistry (Fig. 1, green). In Chapter 5, the wild type substrate is kept constant while the aromatic cage of the reader proteins is mutated and examined using MD simulations (Fig. 1, orange). A different application of modelling modified lysines is applied in Chapter 6, which discusses the results of a collaboration to understand the role of carbamyl-lysine in a novel degradation mechanism of carbapenem, an antibiotic of the last resort.
Moderating effects of education on the problem behavior trajectories of high SES children: a secondary data analysis of the Millennium Cohort Study
Keywords: Latent growth curve modeling
Student-teacher relationships
Millennium Cohort Study
Problem behavior
Structural equation modeling

The purpose of this study is to find the potential moderating effects of student-teacher relationships on the problem behavior trajectories of children using the Millennium Cohort Study (MCS), a nationally representative longitudinal survey following the development of over 19,000 UK children. Latent growth curve (LGC) modeling within the Structural Equation Modeling (SEM) was employed with an analytic sample of 11,796 children. First, findings suggest that children’s problem behavior decreases linearly over time, but that significant levels of individual variations exist across children. Second, the findings also show that children with higher initial problem behavior levels at age three display steeper drops in problem behavior over time than those who have low initial levels of problem behavior. Third, student-teacher relationships and problem behavior have a transactional and negative relationship. Implications for teachers, policy makers, and early intervention designers to improve children’s socio-emotional development and lifelong outcomes, and study limitations are further discussed.
Grassroots informatisation: the internet and everyday information seeking practices in rural and urban China
Keywords: everyday life
China
mixed methods
information seeking practices

Contemporary China has seen a proliferation of Information and Communication Technologies (ICTs). Part of this transformation is that mobile technologies have rapidly become widely used among rural and working-class Chinese populations. Meanwhile, the dichotomy between online and offline has become less distinct compared to the early years of Internet development, leading to a convergence between the Internet and traditional sources of information. Previous research on these topics has primarily focused on the Internet’s disruptive role in challenging the Chinese authority of Party- state or on the co-evolution of Chinese civil society and government. However, it is unclear without substantial empirical evidence how the rapid development of ICTs has influenced the routine and mundane lives of ordinary Chinese people. These routine practices, however, are fundamental to understanding the impact of the Internet on Chinese society and economy. The study of information practices in everyday life offers a way to understand how ICTs complement or displace traditional information sources. Instead of studying savvy Chinese Internet users in major cities, this research aims to understand how the Internet fits into the everyday lives of rural and working-class Chinese users. Through extensive fieldwork in Central China, this research studies how rural and working-class users have adapted to digital technologies, how ICTs satisfy or fail to meet daily information needs, and whether digital technologies have caused disruptions in information seeking practices. The research takes a bottom-up perspective in studying how the Internet is embedded in everyday information seeking practices. In terms of methods, the research employs both a quantitative approach including surveys and qualitative data such as interviews and focus group studies. By detailing how the Internet changes information seeking practices in everyday life, the thesis contributes insights to understanding the challenges and opportunities brought about by various social divides and divides in information seeking practices.
Breaking gender code: visibility, power, and gender in creative coding cultures
Keywords: hacakthons
programming
sexism
computing
stack overflow
gender
technology
women
teachnology

This project is a radically multidisciplinary examination of how gender intervenes in programming culture. Through three studies, I level a feminist challenge to the meritocracy of technology. I show how gender norms prescribe individual capacity for action, perpetuating “natural” masculine ability. By reviewing existing scholarship, I show how academia has perpetuated the narrative of a gendered difference. I explore how computational studies have quantified success and attributed women's lack of representation to feminine behavior as opposed to categorical discrimination.
In Study I, I conduct a survey into the perceptions of gender stereotypes in sites that afford anonymity. Comparing Reddit, Twitter, and 4chan, I show that gender norms dictate perceptions of hostility and technical knowledge. The exploratory analysis finds male-dominated spaces are socially read as hostile, even for men. Study II examines gender on Stack Overflow. I combine computational approaches with a non-binary inference of gender to analyse how gendered identity dictates interaction. Using social network analysis, I find that even in anonymity communities are organised by gender. I also show that the inferred gender of a user can be predicted by how they are spoken to. I conclude that Stack Overflow obscures rampant sexism behind narratives of being hostile to new users. In Study III, I observe gender performance and boundary-making at hackathons. I participate in the coding competitions to the fullest extent, programming alongside my teammates for an intensive 24-hour period. Through the sharing of memes and ironic jokes, I show that gender is the mediator of legitimate technical knowledge. I delineate how masculinity is embodied in tech start-ups and geeks to define femininity as incompatible with computers. Overall, this feminist project conducts a social structural analysis to reveal that sexism is fundamental to technology culture.
A scalable cooperative game theoretic framework for coalitional energy management
Keywords: energy management
energy storage
Shapley value
clustering
cooperative game theory
sampling
nucleolus
energy markets
prosumers

The advances in distributed energy resources (DER) propelled power networks worldwide to transition from a unidirectional model to a bidirectional one, under which uncertain and intermittent renewable generation cause load balancing issues. Energy storage as flexible resources have the potential to mitigate the stress on the network, and local energy markets emerged in recent years to encourage efficient management of these resources. However, the formulation of a market scheme that incentivizes such operation by offering profit for all the participants remains an unresolved challenge. This thesis proposes the novel application of cooperative game theory to coalitional energy management, which extends existing cooperative theoretic frameworks to the energy storage operation. The proposed scheme is then proven to have a non-empty core, ensuring the existence of a payoff allocation that incentivizes participation in the grand coalition of all participants.
This thesis focuses on two main payoff allocations: the Shapley value and the nucleolus.
The Shapley value is a commonly used payoff allocation in cooperative game theory, but is highly computationally complex. This thesis proposes a novel multi-step sampling method based on optimal stratified sampling for estimating the Shapley value, and demonstrates its effectiveness to improve the scalability of the proposed scheme. It is shown, however, that the Shapley value is not necessarily stabilizing, meaning that given the payoffs based on the Shapley value, some participants may choose to defect from the grand coalition and form smaller coalitions for higher profits.
The nucleolus, albeit a less commonly used payoff allocation in cooperative game theory, is proven to be stabilizing, preventing defection from the grand coalition. Similarly, the computation time of the nucleolus increases exponentially with the number of participants, strictly limiting the size of this scheme. This thesis proposes a new strategy which incorporates clustering techniques to estimate the nucleolus at reduced computation times, where a novel marginal contribution profile is constructed as the clustering features. While maintaining a high estimation accuracy, it is shown to easily scale up the scheme from less than 15 participants to over 100, a well applicable number of load buses in a real distribution feeder.
Algorithms and modelling for large-scale Bayesian data analysis
Keywords: Markov chain Monte Carlo methods
Monte Carlo methods
Deep generative modelling
Normalising flows
Bayesian statistics

Bayesian statistics has emerged as a leading paradigm for the analysis of complicated datasets and for reasoning and making predictions under uncertainty. However, the framework faces significant difficulties when it is applied at scale. As datasets grow larger, simulation-based approaches to inference become unviably expensive. As models become more complex, the naïve application of traditional inference methods does not always produce valid predictions. And as Bayesian methods are applied to more complicated phenomena, it is often unclear how even to write down a suitable model on which to perform inference in the first place.
This thesis presents three pieces of work aimed at addressing these problems. We describe a Markov chain Monte Carlo method whose cost per iteration does not necessarily scale linearly with the size of the dataset when applied to Bayesian big-data posteriors. We provide a rigorous analysis of this method including precise conditions under which it yields a performance benefit over standard Metropolis--Hastings. We next provide an asymptotic analysis of nested Monte Carlo schemes that are required for certain complex Bayesian models such as probabilistic programs, along with prescriptions to ensure their consistency under well-specified conditions. Finally, we consider the task of learning models from data automatically using deep generative models. We identify a limitation of normalising flow models, which are defined to be homeomorphisms and so must preserve the topology of the prior. We propose a new family of deep generative models to address this, and demonstrate its benefits empirically across a variety of datasets.
Effective representations for road scene understanding with scalable learning
Keywords: autonomous vehicles
perception
autonomous driving
scalable learning
semantic segmentation

Autonomous vehicles require an accurate understanding of the scene for safe operation in real-world driving scenarios. This thesis examines and offers effective representations for road scene understanding based on in-situ perception, which can be employed directly for planning and decision making in a variety of complex urban environments and under wide-ranging environmental conditions.
A common, versatile scene representation is the pixel-wise semantic segmentation obtained by deep neural networks. However, this representation is limited in its direct usefulness for several reasons. Firstly, the pixel-wise semantic segmentation does not naturally support the high-level reasoning required for complex driving manoeuvres. This thesis resolves that limitation by focussing on a hierarchical, graph-based representation, the scene graph, which combines segmented entities and object-centric perception in bird's-eye view at a suitable abstraction level for decision making. The road markings are a crucial prerequisite in this representation as their underlying meaning dictates the desired driving behaviour. Secondly, semantic segmentation often lacks this semantic understanding of the road markings due to the inordinate cost of labelling adequate training data. Instead, this thesis presents and compares a model-driven and data-driven approach for self-supervised road marking classification. Whereas the former leverages additional sensor modalities and domain knowledge, the latter employs state-of-the-art image-to-image translation techniques to synthesize training data. Thirdly, semantic segmentation is commonly performed in the front-facing perspective, which does not explicitly encode distances or directly link to the vehicle's action space. We tackle this problem by learning an improved bird's-eye-view mapping, called "boosted IPM", which aids scene graph generation in real-world scenarios.
In addressing the above, we introduce scalable, self-supervised learning techniques by employing design principles such as transfer learning, leveraging domain knowledge, and data synthesis. Furthermore, we improve the robustness of the representations under wide-ranging environmental conditions by image restoration and learning appearance-invariant representations. The presented methodologies serve as a valuable starting point to devise effective and efficient representations for road scene understanding based on in-situ perception in real-world scenarios.
CP violation in B->Dh decays where D->Ksh'h'
Keywords: LHCb
B Physics
CP Violation
Flavour Physics
Particle Physics
CKM Triangle

This thesis presents a measurement of the Cabibbo-Kobayashi-Maskawa angle gamma using B->DK and B->Dpi decays, where the D meson decays to one of the final states KsPiPi and KsKK. The measurement relies on the distribution of signal decays over the phase space of the D decay, analysed using a model-independent method based on strong-phase measurements by the CLEO and BESIII collaborations. The measurement is performed using proton-proton collision data collected by the LHCb experiment during the full Run 1 and 2 of the Large Hadron Collider, corresponding to a total integrated luminosity of 8.7 inverse femtobarn at centre-of-mass energies of 7, 8, and 13 TeV. The measurement determines that gamma equals 68.7 degrees (plus 5.2 degrees, minus 5.1degrees defined the 1sigma confidence band), with an alternative solution corresponding to gamma+180 degrees. This is the most precise stand-alone measurement of gamma to date, and achieves a precision that is comparable to all earlier measurements of gamma combined.
The thesis also presents a phenomenological study of the impact of neutral kaon CP violation and material interaction on gamma measurements with B+/- -> Dh decays where the D meson decays in the final states KsPiPi and KsKK. The existing literature at the outset of the thesis work had estimated the potential bias to be O(1 degree) in B->DK decays and to scale with 1/r_B. This suggests potentially large biases for a measurement with B->Dpi decays, since r_B(Dpi) is much smaller than r_B(DK). However, the thesis argues that the actual impact is an order of magnitude smaller, as long as the CP-violation observables are determined based on the phase-space distribution of signal decays. This is demonstrated in a number of numerical studies that take the geometries of the LHCb and Belle II detectors into account.
Profiling primitive haematopoietic progenitors in the vertebrate embryo
Keywords: Developmental biology
Haematopoiesis
Zebrafish

The primitive wave of haematopoiesis provides an initial circulatory system used during vertebrate embryonic development. During the primitive wave, lateral plate mesoderm cells, expressing the transcription factor Scl, contribute to both blood and vasculature progenitors. Scl protein is required for the development of all blood lineages in zebrafish, while in mice Scl knockout results in prenatal fatalities due to complete absence of early haematopoiesis. The highly dynamic nature and small cell number of primitive haematopoietic progenitors have to date hindered in depth in vivo studies of this developmentally crucial population. Using genome-wide profiling of scl-expressing progenitors in zebrafish I have shown that early primitive haematopoietic programmes at the anterior and posterior of the embryos, are distinct at the level of both transcriptional and chromatin landscapes. I have identified characteristic anterior and posterior transcriptional signatures and associated putative cis-regulatory modules, correlating with divergent biological functions in these populations.
In particular, I have characterised the cellular heterogeneity, identifying spatially and transcriptionally distinct sub-populations within the anterior scl-expressing cells in vivo. I have identified regulatory programmes underlying development of anterior vascular and haematopoietic progenitors, and identified a cell subpopulation co-expressing key regulators of both lineages, possibly accounting for the developmental plasticity within the system. Here, scl-expressing haematopoietic progenitor populations were profiled at unparalleled temporal and spatial resolution, obtaining full genome-wide description of early vertebrate primitive haematopoiesis in vivo. This work provides comprehensive framework for analysis of gene regulatory interactions and exploration of novel factors and putative regulatory elements involved in this process.
Searches for B → Dμ+μ− decays and test-beam studies of TORCH detector prototypes
Keywords: Physics
LHCb
Flavour Physics
Particle Physics
Particle Detectors

Two complementary pieces of research, linked by the LHCb experiment, are presented. The first uses 8.7 fb−1 of LHCb data to search for a set of rare decays in the B → Dμ+μ- family: B0 → D0μ+μ−, B0 → D0J/ψ , Bs0 → D0μ+μ-, Bs0 → D0J/ψ, B+ → Ds+μ+μ−, B+ → Ds+J/ψ, and Bc+ → Ds+μ+μ-. Although no signals are observed, the following world-best upper limits are set on the branching ratios at the 95% confidence level:
B(B0 → D0μ+μ-) < 6.1 × 10−8,
B(B0 → D0J/ψ) < 1.4 × 10−6,
B(Bs0 → D0μ+μ-) < 1.8 × 10−7,
B(Bs0 → D0J/ψ) < 1.4 × 10−6,
B(B+ → Ds+μ+μ-) < 3.2 × 10−8,
B(B+ → Ds+J/ψ) < 3.5 × 10−7,
and (fc/fu).B(Bc+ → Ds+μ+μ-) < 9.6 × 10−8,
where fc and fu are the probabilities that a b quark will hadronize into a Bc+ or B+ mesons respectively. Additionally, the branching ratio of the previously-observed Bc+ → Ds+J/ψ decay is measured to be
(fc/fu).B(Bc+ → Ds+J/ψ ) = (1.63 ± 0.15 ± 0.13) × 10−5,
where the first error is statistical and the second systematic.
The second piece of research details test-beam studies of novel time-of-flight detector for a future upgrade of LHCb, prototypes of the so-called TORCH detector. Three test-beam campaigns have been undertaken, two with a small- scale demonstrator and one with a half-sized LHCb module. Single-photon time resolutions better than 100 ps have been measured; a plan of future work required to reach the target 70 ps is discussed. The photon-counting efficiency of the half- sized demonstrator is also presented. A deficit of photons compared to the LHCb benchmark is seen, however with MCP-PMT photon detectors of improved quantum efficiency, photon yields close to requirement should be anticipated.
Language prosody as a resource in musical composition
Keywords: prosody
spectralism
composition techniques
music
inspiration
orchestration
music analysis
composition

This dissertation explores the notion of prosody and its relationship to musical composition. The linguistic study of prosody is concerned with the energy, rhythms and intonations of speech patterns and how these impact on the meaning of utterances. It is clear that there are considerable correspondences between the prosodic elements of language (its rhythms, stresses and intonations) and music; it is by far the closest element of language to musical sound (as opposed to semantic or even pragmatic meaning). The study of prosody reveals many of the features of any speaker's emotional or expressive state, in the same way that we infer emotional content in music from the performance of a work. But what of the relationship between prosody and composition? The link between prosody and musical composition has been very significant at particular moments in history yet there is a lack of any thorough scholarship on this connection. This dissertation aims to address this lack of research.
With these ideas in mind, over the four chapters of the thesis, I provide an overview of the connections between prosody and music composition, and examine some current psycho-linguistic work on the subject (Chapter 1). I then turn to the way in which prosody has provided compositional resources by attending to a number of case studies, which reflect a changing but persistent role for prosody in composition (Chapter 2). In Chapter 3, I reflect on my own compositional approach using prosody as a resource, before a final discussion chapter.