VictorJuiz/thesis huggingface dataset:
Big data approaches to microbial genomics


Alongside tremendous challenges in infectious diseases, like the rise of antimicrobial resistance and the coronavirus disease pandemic, the 21st century is also witness to the big data revolution, which offers opportunities to design methodology capable of addressing these great challenges. Whilst developing tools there are two competing philosophies of how to gain insight from big data: The modelling approach, where the natural data generating mechanism is approximated by statistical inference, and the algorithmic approach, where general-purpose algorithms are tuned to capture hidden structure in the data for prediction. The aim of the thesis is to contribute existing infectious disease problems, by motivating, designing, and applying the correct big data methodology, whilst facilitating future use through generating applications can be easily re-purposed. I first design a machine learner that can predict the source of Campylobacteriosis 33% more accurately than the previous most commonly used methods. Our method broadens the data input spectrum to captures of whole genomes, which uniquely allows assigning sources to individual samples showing a shift in host affinity of one of the most common lineages of Campylobacter jejuni. Based on the individual prediction of the machine learner,I infer which genetic changes are associated with host specificity by conducting a genome-wide association study. I find fluoroquinolone resistant genes pre-adapting chicken isolates to infection for humans and polyphosphate pathway associated genes to distinguish adaption to chicken and ruminant niche. For the study of COVID-19 risk, I conduct a machine learning prediction of very severe forms of the disease, hospitalisation, and susceptibility, whilst also inferring risk factors for all phenotypes by applying Bayesian model averaging. I re-discover commonly defined risk factors describing socio-economic standing, ill health and ethnicity whilst discovering more novel factors like previous lung injury predisposing very severe COVID-19 and bring order to the wealth of published COVID-19 risk studies. In the closing arguments I give limitations of my work and give recommendations on how the developed tools can be re-applied to make big data research more accessible. I also expand how statistical inference and machine learning prediction can be used in unison to tap into the potential of big data to address the foremost infectious disease challenges of our time.

Keywords: genomics
machine learning
bioinformatics
Advisor: Wilson, DJ
Clifton, D
Exploiting sulfinate coupling partners for the preparation of diversely functionalised heterocycles

In the following thesis, sulfinates have been exploited for the formation of di(hetero)arylmethanes and bi(hetero)aryls, either by being formed in situ or through a straightforward synthetic sequence.
Chapter 1 discusses previously developed desulfinative cross-coupling methodologies, an overview of the application of sulfinate salts in synthetic chemistry, and cross-coupling reactions to construct C(sp2)- C(sp3) bonds.
Chapter 2 details the route development for the synthesis of benzyl sulfinate starting materials.
Chapter 3 presents a palladium catalysed C(sp2)- C(sp3) desulfinative cross-coupling to form di(hetero)arylmethanes from benzyl sulfinates and heteroaryl halides.
Chapter 4 demonstrates further developments to the palladium catalysed C(sp2)- C(sp3) desulfinative cross-coupling to form di(hetero)arylmethanes, through a one-pot protocol. The benzyl sulfinate is formed in situ before entering the cross-coupling step. This methodology avoids problematic preparation and storage of unstable benzyl sulfinates, allowing a wider variety of di(hetero)arylmethanes to be accessed.
Chapter 5 describes practical and safety improvements made to the palladium catalysed C(sp2)- C(sp2) desulfinative cross-coupling process, to form bi(hetero)aryls on large scale.
Chapter 6 concludes the work and evaluates potential avenues for future research.
Chapter 7 details the experimental procedures and data.

Keywords: sulfinate
reductive coupling
diarylmethane
palladium
cross-coupling
catalysis
desulfinative
Advisor: Willis, M
Supramolecular halogen bonding and photo-responsive transmembrane anion transporters

This thesis describes the design, synthesis and testing of novel anion host architectures which exploit hydrogen, halogen, and chalcogen bonding for the purpose of selective and stimuli-responsive anion transport across lipid bilayer membranes.
Chapter 1 introduces the field of anion supramolecular chemistry, with particular focus on areas of relevance to this thesis, namely transmembrane anion transport.
Chapter 2 describes the design, synthesis and testing of monodentate halogen and hydrogen bonding anion transporters.
Chapter 3 describes the design, synthesis and testing of bidentate halogen and chalcogen bonding anion transporters with non-protonophoric activity and carriers with higher denticity.
Chapter 4 describes the design, synthesis and testing of photo-caged, stimuli-responsive anion transporters.
Chapter 5 describes the experimental procedures used within this research and details the characterisation of compounds presented in Chapters 2–4.
Chapter 6 summarises and concludes this thesis.
The Appendix holds all the original data for the 1H NMR titration experiments and the anion transport assays.

Keywords: anion recognition
anion binding
chloride
transmembrane transport
HPTS
chalcogen bonding
halogen bonding
Advisor: Langton, M
Beer, P
Family language policy and Chinese-English bilingualism: an exploratory study of Beijing families

Family language policy (FLP) studies language ideology, management, and practice among family members in the home domain. Although English is a global lingua franca and the fever for English learning has persisted in China for decades, there has been little research on how mainland Chinese parents perceive, manage, and practice English language learning and use for their children. This study aims to learn how some Chinese parents perceive Chinese-English bilingualism, manage English learning for their children, and practice English use with their children. With a mixed methods design, this study recruited 26 parents of primary school children in Beijing for the questionnaire and three of the 26 parents for the semi-structured interview. The children (aged 6 to 12) went to a Chinese monolingual primary school where they learned English as a foreign language (EFL). Results show that the parents had highly positive attitudes toward their children’s Chinese-English bilingual development, but they were unable to communicate with their children in English at home due to their limited English proficiency. As a result, the parents sought alternative methods to help develop and improve their children’s English skills. The findings reveal an ideology-practice gap among these Beijing parents and significant barriers to parent-child communication in English at home.

Keywords: Chinese-English bilingualism
family language policy
parental language ideology
Crosslinguistic influence in L3 acquisition: a systematic review

Crosslinguistic influence (CLI) denotes the facilitative and/or negative influence from a bilingual’s L1 to their L2 and vice versa (e.g., Sharwood Smith & Kellerman, 1986). Most studies on CLI target simultaneous bilinguals (Serratrice, 2013), and have found that certain variables like language dominance (operationalised as the societal language) affect the presence of CLI in this population (Van Dijk et al., 2021). A less investigated but growing area of CLI research explores the acquisition of a third or further language(s) (L3/Ln) (Puig-Mayenco, et al., 2020). The fact that many children across the globe speak two languages/dialects from birth and/or at an early age (OECD, 2014), in turn making learning an L3 a more prevalent occurrence, highlights the importance of focusing more on CLI in the L3 context. Furthermore, estimates indicate that over 15% of the population are multilingual. Drawing on 27 studies, this systematic review therefore investigates the effect of CLI and learner/language specific variables (such as language proficiency) which may interact with this process, across linguistic domains including phonology and lexis. Furthermore, in focusing on successive/sequential bilinguals (referring to those who have had a gap between learning their L1 and L2), this review intends to clearly target L3 learning, as in simultaneous bilinguals there may be no distinction between an L1 and L2 (instead referred to as 2L1), therefore challenging whether additional languages would in fact be L3s. Evidence of CLI was found in 26 of the 27 studies, albeit to varying degrees, with a variety of linguistic domains and features represented in the research. The data extracted from these studies contained a mixture of results, but CLI was found to be on the whole more facilitative. Major observations from this review include the ongoing challenges researchers face with terminological discrepancies. This work carries importance for both academic and non-academic audiences: from a theoretical perspective, understanding what variables underpin CLI in L3/Ln can develop the research community’s current understanding of the cognitive experiences of multilinguals; from a pedagogical perspective, assessing what we do know about CLI in L3/Ln acquisition through a robust review can inform learning and teaching practices among learners and educators alike. Despite a trend of monolingualism in the UK due to the lingua franca status of English, multilingual individuals are increasingly becoming the norm rather than the exception worldwide, and this should be reflected in current research.

Keywords: systematic review
multilingualism
L3 acquisition
crosslinguistic influence
Advisor: Faitaki, F
Hedgehog Acyltransferase: Structure, Function and Inhibition

The Hedgehog signalling pathway is essential for mammalian development. Errors in Hedgehog signalling resulting in loss of function during development, lead to a variety of congenital diseases, including holoprosencephaly, brachydactyly and disorders of sex development. In adults, Hedgehog signalling is largely dormant, and aberrant Hedgehog signalling has been implicated in cancers of various organs. As such, the Hedgehog signalling pathway is an important anti-cancer drug target and drugs against the Smoothened cell-surface receptor, which relays the Hedgehog signal across the receiving cell membrane, have proven useful in treatment in the clinic. A critical step in this pathway is the maturation of the sonic Hedgehog (SHH) morphogen. SHH undergoes a unique maturation process in which it is expressed as a 45 kDa pre-protein with N-terminal “hedge” and C-terminal “hog” domains. The C-terminal hog domain has homology to intein domains and induces autocleavage and concomitant addition of a cholesterol moiety at the C-terminus of the “hedge” domain. The N-terminal amine of the hedge fragment is palmitoylated to yield a dually-lipidated N-terminal SHH signalling fragment – the mature morphogen. SHH palmitoylation is catalysed by Hedgehog acyltransferase (HHAT), an integral membrane enzyme, located in the endoplasmic reticulum membrane. This thesis explores the structure-function relationship of HHAT and its interaction with the SHH morphogen. In Chapter 3, the expression of HHAT and production of a high quality sample for structural studies is discussed. Creation and characterisation of single-chain camelid antibody fragments (nanobodies) against HHAT for use in structural studies is covered in Chapter 4. In Chapter 5 the structure of HHAT is presented and the binding mode of the acyl-donor substrate is discussed. Furthermore, structural information is confirmed through mutagenesis assays. In Chapter 6, the interaction of HHAT with the acyl-receiving substrate, SHH, is explored through the use of biophysical approaches to identify the SHH binding site. The final chapter, Chapter 7, covers the determination of the structure of HHAT in complex with inhibitor compounds and discusses the mode of inhibition. Overall, this work provides a basis for the function of HHAT, details the HHAT structure and explores HHAT inhibition at the structural level.

Keywords: Structural biology
Cryo-electron microscopy
Nanobodies
Membrane proteins
Acyltransferase
Hedgehog signalling
Inhibitor
Drug discovery
Advisor: Siebold, C
Redfield, C
Living standards and market integration in the rural economy of Roman Britain

Rural non-élites (i.e. ‘peasant producers’) are thought to have comprised 50–95% of the Roman population, and yet, because they are seen as having operated largely at subsistence, models of ancient economic development see them as having had little effect on the wider economy. The spread of commercial excavation regulations across Britain (and in other parts of the former Roman world) has created a growing body of evidence pertaining to rural settlement and economy. Economic historians and archaeologists alike have used these data to make arguments about the Roman economy—but continue to debate whether or not excavated rural sites should be seen as representative of the ancient settlement landscape at all.
This thesis examines data from four microregions in Southern Britain, arguing, first, that the new archaeological data available since the passing of PPG16 provide representative samples of sites up and down the socio-economic spectrum. Second, it argues that farm sites of all statuses were integrated into local, regional, and supra-regional markets to a degree typically not recognised in current economic models of the Roman agricultural economy. The variegated landscape revealed by commercial excavations demonstrates that this integration was the result of the complex interaction of multiple macro- and micro-economic factors—changes in consumer culture (beginning in the Late Iron Age), expanding markets, and site status alongside institutional changes (taxation)—that fostered widespread integration in the Roman world. These data suggest that models of the Roman ‘peasantry’ and the wider economy must be re-theorised to accommodate changes in rural demand, as well as production, as a possible factor in economic change.

Keywords: Roman Britain
Roman agriculture
peasant economies
peasant consumption
rural consumption
Roman peasants
Roman archaeology
ancient economy
rural archaeology
Roman economy
Advisor: Wilson, A
Human photoreceptor signals

The first stage in the human response to light is the sensing of light by the five classes of photoreceptors in the retina: the three cone classes (short- [S], medium- [M], and long- [L] wavelength sensitive), the rods, and the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). Signals from these five photoreceptor classes drive the full range of visual and non-visual light-mediated neural mechanisms, from the perception of movement and colour, to the pupillary light reflex and circadian entrainment. In traditional models of the function and interaction between these photoreceptors, cones are thought to be the primary drivers of daytime vision, rods the drivers of visual functions in low-light levels, while ipRGCs feed into the internal clock, driving the non-visual effects of light.
Such accounts may give the impression that understanding the retinal inputs to light mediated mechanisms is a fully solved problem, yet there are still many unanswered questions. For example, while cones and ipRGCs are known to both feed into control of the pupillary light reflex, little is understood about the post-receptoral pathways that combine cone and ipRGC input, and whether interactions between cones and ipRGCs feed into other light-mediated mechanisms. Models of retinal inputs to vision also fail to take into account the large degree of individual variation between observers, particularly in the case of colour vision. Furthermore, it is unclear how our visual system is able to solve the computational challenges of using the filtered and downsampled information conveyed by the photoreceptor signals as cues to guide our interactions with the external world.
This thesis presents a range of new methodologies, both in terms of custom-built equipment and experimental design, and novel analytical approaches, to study, characterize, and quantify retinal inputs in ways that have previously been unachievable. It presents new technical capabilities in stimulus generation and control to enable new tests of the photoreceptor inputs to vision. Overall, the primary focus of this thesis is the novel characterization of the biological and physiological factors that influence the first stages of vision and non-visual light mediated neural mechanisms.

Advisor: Smithson, H
Spitschan, M
Champions of the crowd: aediles in Roman society

This thesis provides a social history of the plebeian and curule aedileships of the Roman republic. It examines the relationship between aediles and the Roman people, both in the idealized form described by the Roman aristocracy and from the perspective of the aediles' audience, the 'crowd'. To do this, it looks at where aediles interacted with the people, how they communicated, and which groups of people they interacted with. It asks several questions usually unasked in studies devoted to the constitution of republican Rome. How did Rome’s politicians communicate ideas to the people and their peers? In what spaces did they interact? What did Rome's politicians think the social role of a magistracy was, or ought to be? And, more elusively, what did the Roman people expect of their magistrates?
The thesis is divided into three sections. The first provides a topography of the aedileship of the republic, allowing us to see where aediles opted to interact with the Roman people. The purpose of this section is to set the scene and to map attested aedilician theatres of interaction. The second section looks at how the aristocracy spoke and wrote about the aedileship. It analyses how some Roman aristocrats expected aediles to act, and how they imagined the people expected them to act. The final section investigates the question of popular expectations further. It examines the interactions that an aedile could anticipate having during his year of office. It questions how aediles comported themselves before the Roman people. Men who held the aedileship were expected, both by their peers and the people at large, to perform on the public stage and interact with the people in a distinctive, aedilician, way.

Keywords: elections
aediles
aedileship
magistracy
politics
Rome
Advisor: Bispham, E
Forgotten Men: Post-war memory of Indian Prisoners of War of the Japanese in World War Two

During the Second World War some sixty-seven thousand Indian personnel of the British Indian Army were captured by Imperial Japanese forces, including a large number at the surrender of Singapore in February 1942. This thesis examines why these colonial Prisoners of War were largely forgotten in the post-war period, and therefore represents a case study in the formation of British wartime historical memory. It does so by addressing three questions, relating to the impact of evidence that some Indian prisoners were disloyal, the role of British colonial propaganda, and the unavailability of important documentary sources. It argues that the process of forgetting can be understood in terms of three active memory practices, namely: suppression; obscuration; and selection. Examples of how each of these have impacted British memory of Indian prisoners are provided within the thesis. These practices acted in a colonial context within which a pertinent element was a “Myth of loyalty”, namely the idea that, whatever may have occurred in captivity, most Indian prisoners stayed fundamentally loyal to the British. Newly available sources, in particular records from British Military Intelligence, allow a reassessment of such narratives. The thesis consists of an Introduction, four thematic chapters, and a conclusion. The first thematic chapter examines British responses to the loss and recovery of Indian prisoners. The second chapter examines how the experiences of Indian prisoners were remembered. The third examines how those Indian prisoners who fought against British forces later in the war, were often marginalised and forgotten in British accounts. While the fourth reviews post-war war-crimes trials of Japanese military personnel where the victims were Indian prisoners, the focus being the effect on trial outcomes of British suppression of knowledge regarding Indian prisoners. Throughout, the emphasis is on the role of forgetting in the management of unpalatable truths.

Keywords: British Indian Army
Memory
Prisoners of War
World War Two
Indian National Army
Advisor: Khan, Y
Executing Mary Queen of Scots : strategies of representation in early modern Scotland

This thesis examines a series of sixteenth- and early seventeenth-century texts that respond to the 1567 deposition of Mary Queen of Scots. As these texts argue about her character or her sovereignty, they illustrate how Mary became the centre of an ideological debate in which those men whose representation of the Queen prevailed might direct the course of political or religious history.
The thesis employs a range of interpretative tools to uncover how cultural references, discursive choices, and clandestine publishing ventures function to discredit or to defend Mary. The first three chapters focus on seminal texts dating from 1567 to 1571: Robert Sempill’s satirical poetry, George Buchanan’s Detectioun (1571), and John Leslie’s Defence (1569) and Historie of Scotland (1570).
Working for Mary’s political opponents, Sempill and Buchanan demonise the Queen by manipulating literary and cultural traditions such as Senecan tragedy, medieval poetic fopoi, and the speculum principis. Their rhetorical strategies collaborate with burgeoning Scottish and English print culture - broadsides tacked to market crosses, for instance - to create the illusion of a widespread populist uprising against Mary. In response, her primary advocate John Leslie, the Bishop of Ross, transforms moral into political debate, stridently proclaiming Mary’s title to English throne and writing aversion of Scottish national history sympathetic to her cause. These texts use familiar narrative patterns to authenticate specific views of Mary, demonstrating how systems of language and representation can be enlisted to justify or to challenge political change.
The final chapter turns to Sir James Melville’s Memoirs (1603), a retrospective of sixteenth-century court politics written as James I accedes to the English crown. Melville must account for the conflicts between earlier texts, and his depiction of Mary, especially as revealed through substantive alterations made to his holograph manuscript, illustrates a cautious desire to recover her reputation in order to preserve a legacy for her politically successful son. The Memoirs thus register a growing ambivalence that emerges largely from the complexity of the Queen’s textual representation.
Privileging the form and strategy of arguments about Mary over the question of her guilt or innocence, this project, unlike previous studies, lays bare the operations of a culture that found in her the source of its most pressing concerns - about female rule, religious change, popular sovereignty, and versions of national history.

Keywords: Mary, Queen of Scots
rulers
Queen of Scots
16th century
sixteenth century
queens
Mary Stuart
Scotland
execution
deposition
representation
Advisor: Mapstone, S