VictorJuiz/thesis huggingface dataset:
Genomic epidemiology of meningococcal vaccine antigens in the United Kingdom

Vaccination against Neisseria meningitidis remains the optimal means to prevent invasive meningococcal disease (IMD), an important cause of septicaemia and meningitis disproportionately affecting infants and young children. Subcapsular protein-based vaccines were developed to offer broad protection against genetic lineages of meningococci responsible for endemic capsular group B IMD. As meningococci solely colonise the human oropharynx, the inherent variation in surface proteins potentially limits their efficacy as vaccine antigens. With increasing use of these vaccines worldwide, high-throughput genomic methods were required to analyse meningococcal protein diversity. The aims of this study were to determine the diversity and distribution of proteins in subcapsular protein-based vaccines Bexsero® and Trumenba® amongst meningococcal whole genome sequences (WGS) from disease and carriage isolates from the UK, 2010-2017. Using the principles underlying multilocus sequence typing, two novel genomic typing schemes were established on PubMLST.org Neisseria website. The Bexsero® Antigen Sequence Typing (BAST) and Outer Membrane Vesicle peptide Typing (OMVT) schemes were used to analyse ~3500 disease and ~650 carriage meningococcal WGS.
Using this comprehensive, national dataset, non-random distribution of BASTs and Bexsero® antigens was demonstrated, with a few variants occurring at high frequency. Strong, non-overlapping associations between OMVT clusters, BASTs, cc and genogroups were identified in disease and carriage meningococci, likely driven by host immune and metabolic selection. Understanding the population structure of subcapsular and outer membrane proteins has important implications when selecting antigens and variants for inclusion in existing or novel protein-based vaccines, for both meningococci and other Neisseria species, including gonococci. The development of BAST typing coincided with Bexsero® vaccine introduction into the UK infant immunisation programme and detailed pre-vaccine genomic surveillance provided estimations of vaccine coverage (58.3%-60.3%) and identified low incidence of exact antigenic variants. Both typing methods are rapid, scalable and open-source, with the potential to optimise vaccine development, reformulation and implementation worldwide.

Keywords: Invasive meningococcal disease
Genomic epidemiology
Molecular epidemiology
Neisseria meningitis
Protein-based vaccines
Genomics
Meningococci
Meningococcal vaccines
Bacteria
Vaccines
Whole genome sequencing
Genomic surveillance
Advisor: Maiden, M
Tang, C
Treatment planning &amp; targeting during shock wave therapy

Shock wave lithotripsy is a non-invasive procedure by which kidney stones are fragmented. Currently, many shock waves are delivered to the body that do not impact the stone, but do result in tissue trauma, mainly caused by cavitation. This work presents a monitoring system to reduce the number of shock waves delivered to the body, by tracking the target, and to detect cavitation throughout the procedure.
For the first goal, a circular array, housing twenty-two 0.5 MHz transducers that can be mounted around the aperture of a clinical lithotripter, was used to collect pulse-echo data, from which an acoustic triangulation algorithm was able to locate stones. The accuracy of the system in water was better than 4 mm in the lateral direction and better than 2 mm in the axial direction within ±15 mm of the focus—which is the variation that would be expected clinically. For the second goal, the acoustic pressure field of a shock wave therapy source was measured and its cavitation field was determined. Cavitation was localised using a conventional ultrasound probe and passive acoustic mapping. Bubbles were shown to grow, collapse, and rebound, and the characteristic times were determined. It was found that these parameters increased with the energy level and the pulse repetition frequency and that at the highest energy setting the characteristic time was 288 μs. Finally, the characteristic time of cavitation in an ex vivo pig kidney and for an artificial stone in water due to a clinical shock wave source was determined using passive acoustic mapping. The characteristic times in the pig kidney were shorter than for the stone, e.g. 560 μs in the kidney and 730 μs on the stone at EL 6. No significant correlation between cavitation on a stone that fractured well and a stone that fractured poorly could be determined.
The work in this thesis heralds an advance in current lithotripsy monitoring techniques that are based on B-mode and x-ray. Real-time tracking of the kidney stone and cavitation mapping throughout the treatment would limit the renal injury that routinely occurs during lithotripsy.

Keywords: Shock Wave Lithotripsy
Trilateration
Passive acoustic mapping
Shock Wave Therapy
Ultrasound
Cavitation
Advisor: Cleveland, R
‘The Chosen People’ and the ‘House of Many Mansions’: managing deep divisions in the Yishuv and Lebanon during the Mandate Period

This dissertation asks why Israel, a deeply divided society facing the same difficulties as other post-colonial states, was able to establish a stable democratic regime upon independence whereas its neighbour, Lebanon, with similar characteristics, established an unstable democracy. The question has wider implications for deeply divided post-colonial societies elsewhere and has gained greater currency in an age of civil strife and democratic retreat. By carefully tracing the political process that stretched from the advent of colonial power in the Middle East through the 1950s, this dissertation helps to explain how these two states came to follow divergent regime trajectories.
The key argument here is that during the mandate period, the community which would become the core of the Israeli state (known as the Yishuv) was able to develop a dominant vision of the state that guided post-independence policy and deactivated potentially destabilizing deep divisions. It was transformed from a vertically divided society into a horizontally divided society, making its regime less inclusive yet more stable. This development was aided by institutional mechanisms put in place by the British mandatory. In Lebanon, on the contrary, the mandatory power deepened and entrenched deep divisions. The institutional mechanisms put in place led to the multiplication of the number of politically relevant divisions in an already vertically divided society thus precluding the emergence of a shared vision of the state. The Lebanese state embraced diversity and protected minorities but its political system suffered from instability soon after attaining independence.

Advisor: Robins, P
Penslar, D
Machine learning for childhood pneumonia diagnosis

Pneumonia is the number one killer of children under the age of 5, causing more deaths than malaria, tuberculosis and HIV/AIDS combined. In 2015, over 920,000 children died of pneumonia and more than 95% of the incidence and 99% of subsequent mortality occurred in developing countries. Current gold standard diagnostic assessment of childhood pneumonia relies on the use of advanced tools (such as X-rays and blood culture) by a clinical expert who assesses and interprets a combination of clinical measurements. However, the shortage of clinical expertise and equipment in low-resource settings delay diagnosis, increasing the risk of mortality. This thesis investigates the role that machine learning could play in improving diagnosis of childhood pneumonia in low-resource settings.
Point-of-care devices such as a digital stethoscope and a pulse oximeter have become more affordable and hence abundant across the globe. The adoption of such devices, particularly in community settings, presents an opportunity to leverage information captured through their signals to provide early diagnosis for conditions such as childhood pneumonia. Hence, this thesis proposes a machine learning framework for the design of diagnostic models, built on a parsimonious set of symptoms which can be captured in a point-of-care setting, to deliver accurate and reproducible diagnosis of pneumonia. The approach is evaluated on three different datasets (with accuracy ranging between 81.8 – 97.9%), consistently outperforming diagnosis with the current gold standard guidelines for community diagnosis by the World Health Organisation.
A clinical study in Mumbai, India, is designed to capture a realistic dataset in a poor urban community and a resource-constrained hospital, where a mobile health toolkit including three point-of-care devices (a digital stethoscope, a pulse oximeter and a thermometer) is built to enable minimally trained users to capture essential health information. Diagnostic models developed on this rich dataset are seen to perform well when validated internally as well as generalise to other datasets from different geographies.
Finally, a set of tools for automated analysis of lung signals is proposed and validated on two big datasets, one from Peru and one from India. Combined with vital signs, information derived through this automated lung signal analysis was seen to outperform diagnosis via expert clinical annotation, delivering 81.3% sensitivity and 84.5% specificity.

Advisor: De Vos, M
Sisters and sisterhood: the Kenney sisters, suffrage and social reform c.1890-1970

This is the first thesis which offers a sustained study of working-class women who took part in the militant campaign for suffrage and remained loyal to the Pankhursts, not only during the campaign, but throughout their lives. Historians have often sought to demonstrate why working-class women would not be attracted to the Women’s Social and Political Union (WSPU), identifying political and practical barriers to participation in militancy. The original historiographical contribution of this thesis is to reverse this question, asking instead why working-class women would be attracted to the WSPU, through a case study of the Kenney sisters. It identifies the factors that enabled their activism, the opportunities that activism created for them, and the benefits they derived from participating in this organisation. This starting point positions working-class women as significant actors and autonomous agents in the militant suffrage movement, rather than passive pawns subject to manipulation by middle-class women. In focusing on a particular family, it also begins to bridge the surprising lack of research on suffrage families, extending recent research on the historical significance of siblings into a new context. However, this thesis also makes a substantial contribution to modern British history as well as to histories of suffrage, feminism, women and gender. It uses the Kenneys’ lived experiences to address questions of class and gender, politics and activism, and agency and identity in the early twentieth century. In doing so, it engages with broader historiographical themes including politicisation, networks and transnationalism. It is a history of education, literacy, religion, migration and social mobility as well as suffrage, and of teachers, theosophists, political activists, social reformers, friends and sisters as well as suffragettes.

Advisor: Paseta, S
Todd, S
Legal politics in the Libyan constitution-making process

Since the end of the Cold War, constitution-making has become a central element of post-conflict reconstruction, and state- and peace-building, more generally. Both scholars and practitioners assume that legal procedures and standards of constitution-making provide structures for resolving potentially violent political contest and debate, and thereby contribute to reconciliation and consensus finding. It is hoped that such processes will amplify commonality and strengthen democracy in a state. However, constitution-making processes in politically unstable countries often do not bring about the desired stability and security. As scholarly research in constitution-making has remained largely normative, there is still little detailed knowledge about why this is the case.
My thesis is an in-depth empirical analysis of the Libyan constitution-making process from 2014 to 2018. I describe the actors who are engaged in the constitution-making process and the ways in which the law, including constitutional law-making, is actually used and put to work in a post-conflict scenario. By analysing the Libyan process in this way, I highlight the open, provisional, and dynamic dimensions to constitution-making, and thereby contribute to an empirical understanding of these processes.
The Libyan example indicates that when societal conflict is high and the political landscape deeply divided, a constitution-making process is unlikely to solve conflicts through a redistribution of power or resources or the elaboration of a unitary vision for a state. On the contrary, since the idea of a constitution is to establish a high-level legal framework, constitution-making risks becoming a high-stakes arena of political conflict. This is what happened in Libya, developing into what I call legal politics. Understanding the dynamics of legal politics raises questions about the assumptions of those who advocate constitution-making in post-conflict situations and casts doubt on the technocratic vision that states can be built in a rational and orderly fashion.

Keywords: qualitative methods
Libya
ethnography
socio-legal studies
public law
empirical study
MENA
constitution-making
Advisor: Pirie, F
Towards dynamic pharmacophore models through the use of coarse grained molecular dynamic simulations

Computer aided drug design (CADD) plays a crucial role in the drug discovery pipeline e.g. in virtual screening of chemical databases, de novo drug design, and lead optimization. Due to the increased numbers of protein structures elucidated, structure-based methods for developing pharmacophore models have started gaining in popularity and are becoming of particular importance. There have been a number of studies combining such methods with the use of molecular dynamics (MD) simulations to model protein exibility. In this project, the development and application of a new methodology, based on coarse grained (CG) MD, through the use of the MARTINI forcefield, and employed to explore protein ligand interactions, will be presented. An overview of the history of CADD is presented, along with current computational fragment based methods available for exploring protein-ligand interactions. An overview of the theory and methods behind MD simulations both all atom and CG is also provided. In the first results chapter, the parametrization of MARTINI beads as pharmacophoric probes, the analysis protocol and the application of this method to a data set of water soluble targets of pharmacological interest is described. The results suggest that the pharmacophoric probes have the ability to identify protein-ligand interactions on the targets of interest. The probes are also able to identify the residues involved in forming ligand binding interactions, showing a particular accuracy in identifying "hotspot" interactions. In the second results chapter, the extension of the initial data set to a range of GPCRs is described. The results suggest that the pharmacophoric probes have the ability to accurately explore both the orthosteric and allosteric binding sites of the GPCR targets and accurately identify the interactions and residues involved in ligand binding. This is done without the need to embed the protein in a lipid bilayer. In the final results chapter, the application of the dynamic pharmacophoric probes to identifying PIP2 and cholesterol binding sites, on membrane proteins, is presented. The results suggest that the probes can indeed identify these binding sites, along with identifying the residues that are involved in binding the PIP2 head groups. This was also done without embedding the protein in a lipid bilayer, which is the usual practice for identifying lipid binding interactions, reducing the computational resource requirements.

Keywords: Coarse Grained
Molecular Dynamics
Computer Aided Drug Design
Advisor: Sansom, M
Stansfeld, P
Sands, Z
The productivity of unemployment: emerging forms of work and life in urban South Africa

With two-thirds of South Africa’s young people unemployed, mass joblessness is widely regarded as the country’s most pressing socio- economic crisis. This thesis examines young men’s everyday experiences of unemployment in South Africa. It challenges the dominant understanding of unemployment as a condition characterised by an absence – of income, something to do, or a place in society. Instead, this thesis offers an account of unemployment as an agentive and socially productive experience – punctuated by a multitude of actions, choices, and complex relations of inter-dependence. The findings of this thesis also challenge the assumption that unemployment is inevitably the result of a lack of jobs, showing instead that jobs at the bottom-end of the labour market are at times rejected in favor of alternative modes of socioeconomic life.
The thesis is based on twelve months of ethnographic research in Zandspruit, an informal settlement on the outskirts of northern Johannesburg. It offers a detailed account of the ways in which young men make a living outside of wage work. It argues that men’s alternative economic practices are not a last resort, as is often presumed, but rather an active attempt to guard themselves against succumbing to precarious and insecure wage employment. The thesis reveals how young men’s social position within the specific socio-spatial location of Zandspruit mediates their economic choices and work-related decisions while also reinforcing local inequalities. Finally, the thesis examines the wider social, existential, and political implications of such shifts in the historically close relationship between wage work and social order. The findings in this thesis confront a dominant discourse that propounds a ‘crisis of masculinity’ caused by unemployment. They do so by showcasing the diversity of ways young men negotiate their social obligations alongside the other demands in their lives.
By revealing the ways in which young men refuse wage work and socially, economically and politically navigate unemployment, this thesis contributes to current political and economic debates about (un)employment and inequality in South Africa – and beyond. In so doing, this thesis makes a case for re-thinking the normative centrality of work both in academic scholarship, and in our social policies and political visions of economic redress and emancipation.

Keywords: social stratification
marginality
inequality
youth politics
South Africa
gender
masculinity
unemployment
precarity
kinship
Advisor: Steinberg, J
Pratten, D
American modernism and the poetics of labour

This thesis argues for the relationship between the labour of the modernist poet and changes in working conditions and working culture in the twentieth century. Spanning the years 1903–1974, my research shows how modernist writers engaged with discussions around labour movements, labouring technologies, radical politics, and the relationship between work, race, and gender, and how this shaped how they conceived of their own writing as constituting a new kind of work. While accounts of modernism have stressed its aesthetic experimentalism, my dissertation is the first sustained analysis of how that experimental work emerged out of a growing awareness in literary culture of what labour in general meant. My dissertation thus presents a new reading of the formal innovations of U.S. modernist poetry—a reading grounded in historical research, theoretical thinking around labour, and close textual analysis.
The first chapter argues that Ezra Pound conceived of labour in ethical terms, as palliative or curative, and that this had determining effects on both his modernist aesthetics and Fascist politics. My second chapter looks at the impact of individualism and theories of collective labour on the poetry of Langston Hughes, especially the Constructivist aesthetics of his 1938 pamphlet A New Song. Chapter Three explores the relationship between experimental writing and activities deemed valueless by the gendered logic of capital in the experimental poetics of Gertrude Stein. Finally, my fourth chapter, on the Objectivist poets George Oppen, Lorine Niedecker, and Louis Zukofsky explores the residue of modernist labour in the post-war “golden age” of capitalism and the restructuring of work.
If modernism can be considered the major set of formal upheavals of the twentieth century, my dissertation offers a new historical and theoretical basis for those upheavals while also engaging in new readings of modernism’s diverse aesthetic experimentation. I suggest that modernist aesthetics are best conceived not as mere iconoclastic destruction of the past, but as attentiveness to the changing social and ethical role of labour in the twentieth century, when what it meant to be a worker, and a writer, was open to new interpretations and possibilities.

Advisor: Beasley, R
Lock correctness

Locks are a frequently used synchronisation mechanism in shared memory concurrent programs. They are used to enforce atomicity of certain code portions, avoid undefined behaviour due to data races, and hide weak memory effects of the underlying hardware architectures (i.e., they provide the illusion of interleaved execution). To provide these guarantees, the correct interplay of a number of subsystems is required. We distinguish between the application level, the transformation level, and the hardware level.
On the application level, the programmer is required to correctly use the locks. This amounts to avoiding data races, deadlocks, and other errors in using the locking primitives, such as unlocking a lock that is not currently held.
On the transformation level, the compiler needs to correctly optimise the program and correctly map its operations to machine code. This requires knowing, for example, when it is safe to move a code statement in a thread past a lock operation such that the resulting thread is a refinement of the original thread.
On the hardware level, the lock operations themselves need to be implemented correctly, by usage of low-level primitives such as memory fences and read-modifywrite operations. This requires knowing the relaxations of memory ordering that could occur on the target hardware, and the effect of the primitives that can be used to restore consistency (such as memory fences).
In this thesis, we address an aspect of each of the three levels of correctness mentioned above. On the application level, we provide a sound static approach for deadlock analysis of C/Pthreads programs. The approach is based on a contextand thread-sensitive abstract interpretation framework, and uses a lightweight dependency analysis to identify statements relevant to deadlock analysis. To quantify scalability, we have applied our approach to a large number of concurrent programs from the Debian GNU/Linux distribution.
On the transformation level, we provide a new theory of refinement between threads, which is phrased in terms of state transitions between lock operations. We show that the theory is more precise than existing approaches, and that its application in a compiler testing setting leads to large performance gains compared to a previous approach.
On the hardware level, we provide a toolchain to test the memory model of GPUs and the behaviour of code running on them. We automatically generate short concurrent code snippets that, when run on hardware, reveal interesting properties about the underlying memory model. These code snippets include idioms that typically appear in implementations of synchronisation operations. We further manually test several GPU locking primitives. Our testing has revealed surprising hardware behaviours and bugs in lock implementations.

Advisor: Kroening, D
Schrammel, P