VictorJuiz/thesis huggingface dataset:
Paleovirology and the evolution of virus-host gene exchange
Keywords: Paleovirology
Horizontal gene transfer

Paleovirology is the study of viruses at large evolutionary timescales through the investigation of endogenous viral elements (EVEs) that are found in host genomes. EVEs are the result of a heritable, genomic integration of a viral genome in a host germline cell. The presence of retroviral sequences in animal genomes has been recognized since the 1970’s, but discoveries made in the last five years have revealed that viruses of all genome types can endogenise. Moreover, although most EVEs are non-functional relics, there are a number of examples of functional EVEs that are co-opted to benefit the host. There remain some methodological challenges in the identification and analysis of EVEs, and we have yet to fully understand the evolutionary processes involved in the rare instances of co-option. In this thesis, I develop novel techniques to identify and characterize large herpesviruses, which lead to the discovery of the first endogenous herpesvirus in the genome of the Philippine tarsier. The same methods were redeployed to identify a new family of dsDNA virus in the genome data of their hosts. Among the 15 different new species of virus, at least four viruses in four different host fish exhibit characteristic features of EVEs such as non-sense mutations and the accumulation of transposable elements. Moreover, more than half of the predicted genes in a full-length salmon virus have no detectable similarity to known genes. The second investigative theme of this thesis explored the idea that EVEs can sometimes be the result of adaptive gene transfer, and that this is the conceptual equivalent of viral genes that are host-derived. Considering a subset of rare, functional EVEs that act as antiviral genes, I developed an evolutionary framework to understand such gene transfers as a biological strategy within the evolutionary arms race between viruses and hosts. In viruses, I conducted a systematic genome-wide evolutionary analysis of host-derived genes, which revealed a consistent shift towards higher purifying selection when switching from host to virus genome. Finally, this thesis also considered the evolution of gene transfer between viruses, by investigating the intriguing history of a retroviral superantigen gene with similarity to genes in unrelated herpesviruses. Through the evolutionary reconstruction of a large group of mammalian EVEs, I was able to prove the independent horizontal gene transfer of superantigens from retroviruses to herpesviruses from two different donor lineages. This shows that viral gene capture can occur in an evolutionary manner, and demonstrates the utility of paleovirological methods in understanding the evolution of pathogenicity. Altogether, this thesis highlights the results of synthesizing methods from paleovirology with metagenomic techniques, demonstrating that genomic databases are themselves rich with novel viral biodiversity that hold key insights for virology, genomics and evolution.
The lived experience of inequality in post-apartheid South Africa: measuring exposure to socio-economic inequality at small area level.
Keywords: Residential segregation
Neighbourhood
South Africa
Inequality
Poverty
Lived experience of inequality

South Africa has undergone a remarkable political transformation since the birth of democracy in 1994, yet it remains plagued by extremely high levels of socio-economic inequality, violent crime and social unrest. Although inequality is often regarded as a major driver of many social problems, the evidence base concerning inequality in South Africa is relatively limited, consisting primarily of national level Gini coefficients or General Entropy measures based upon household income, expenditure or consumption data. In this thesis I argue that these broad national level measures say little about people's actual day-to-day lived experiences of inequality and how these individual experiences of inequality may be shaped by the local geographical areas in which people live and go about their daily lives. I construct a series of empirical measures of exposure to socio-economic inequality which reflect the socio-spatial environments in which people live. I argue that these new measures can be used as explanatory factors in the study of other social outcomes, both at an individual level (for example, individuals' attitudes) and at an area level (for example, rates of violent crime). Exposure to inequality is measured both from the perspective of the 'poor' population and the perspective of the 'non-poor' population and the measures are constructed and presented at small area level using the Datazone statistical geography. I analyse the spatial distribution of exposure to inequality and find that exposure to inequality is typically highest in urban neighbourhoods, particularly in the major metropolitan areas. I develop a measure of intensity of exposure in order to highlight areas with both high exposure and high levels of deprivation. I also present one example of how my new measures can be used to explore associations with other outcomes, specifically looking at the relationship between people’s lived experience of inequality and their attitudes towards inequality and redress.
Enhancing communication privacy using trustworthy remote entities
Keywords: Privacy
Trusted Computing
Trusted Third Party
Smart Energy Grid

Communication privacy is the property of a communication system that enables two or more distrusting participants to exchange information without compromising their privacy, with respect to internal and external adversaries. It encompasses aspects of anonymous communication as well as data privacy. A real-world example of the need for communication privacy is the smart energy grid, in which networked smart meters frequently measure energy consumption and communicate with grid operators. Privacy concerns arise from the possible inference of sensitive information from these measurements.
Using smart grid communication privacy as a case study, this thesis introduces the concept of the Trustworthy Remote Entity (TRE). The TRE is an intermediary between distrusting participants that performs privacy-enhancing computations on the exchanged information. Unlike cryptographic secure multiparty computation protocols, this approach does not increase participants' computational or communication complexity. In contrast to a trusted third party, this trustworthy entity uses trusted computing and remote attestation to establish attestation-based trust relationships. As a single-function system, the TRE requires only a minimal software Trusted Computing Base, thus minimizing its attack surface and making it an ideal candidate for security audits. Two research hypotheses are investigated: firstly that the TRE can be realized and used to enhance consumers' privacy in the smart grid, and secondly that the TRE concept can be formalized and used in other application domains.
This thesis confirms both hypotheses and, in doing so, presents five main contributions. Firstly, it proposes a new methodology for modelling and analysing communication privacy terms of unlinkability and undetectability, which is implemented in the CSP process algebra and used to enhance the Casper/FDR analysis tool. Secondly, it presents and analyses a new TRE-based smart grid communication architecture. Thirdly, it compares different TRE system architectures and evaluates a fully functional TRE prototype. Fourthly, it defines a new highly-scalable remote attestation protocol for establishing the TRE's trustworthiness. Finally, it formalizes the fundamental characteristics of the TRE concept and demonstrates how the TRE can be used to enhance communication privacy in location-based services and wireless network roaming.
Beyond corsairs: the British-Barbary relationship during the French revolutionary and Napoleonic wars
Keywords: Piracy
French Revolutionary War
Barbary States
Barbary
Barbary Pirates
Logistics
Royal Navy
Napoleonic War
Corsairs
North Africa
Pirates
supply

The North African Barbary States are usually dismissed as an unimportant, though bothersome, pirate base of little consequence in the late eighteenth and early nineteenth centuries. This thesis challenges that idea by providing qualitative and quantitative evidence of Barbary's role in trade and diplomacy during the French Revolutionary and Napoleonic Wars, especially as it affected Britain and how the British were able to carry out their military and political goals in the Mediterranean. The study is based on the correspondence between the British government and its military leaders in the region, the correspondence and reports generated by British consuls working in Barbary, import/export records, and a database tracking British shipping to and from North Africa during the conflict.
To the British, Barbary was not an irritation but an asset. Britain was able to manage Barbary's trade and foreign policy over the course of the twenty-three-year conflict. This was accomplished in two key ways: as a source of supplies for British forces and through the diplomatic role provided by Britain's extensive consul network. Though the North African states were neutral for the majority of both wars, Britain worked strenuously to maintain and increase its trade and diplomacy with Barbary for the benefit of the British armed forces. British trade with Barbary, supported by the British-Barbary diplomatic relationship, directly contributed to British successes in the Mediterranean and Iberian Peninsula.
Ligand hydration and bridging waters molecules
Keywords: Water
Drug Molecules
Hydration

Water is the most abundant molecule in biological systems and is ubiquitous in nature. Despite this prevalence, water has long been considered a backdrop for bio-processes. However, with increasing sophistication in experimental and computational methods, water has now been recognized to interact and influence the behaviour of biomolecules in complex, subtle, and essential ways. The structure of water is unique in that it is small yet able to form multiple hydrogen bonded interactions. Water molecules are thus ideally suited to bridge interactions on biomolecular surfaces. Specifically, they have been identified to play an important role in mediating protein-ligand interactions. A methodology for the inclusion of these mediating waters has often been stated to be a major challenge facing the field of rational drug design. While notable successes exist in the design of better binders using water molecules, no single method has been able completely predict the locations of water molecules and its propensity to interact with the binding ligand.
This thesis is intended to explore the possibilities of using the hydration of ligands as a pathway to study bridging water molecules in holo structures. To this end, a method of discretizing and scoring water-sites around ligands from their Molecular Dynamics (MD) simulation is first developed. This was then used to correlate the hydration shells of ligands with the locations of the bridging water molecules. Further, the hydration shell of ligands is used to improve WaterDock - a protocol to predict the locations of water molecules within binding sites. Finally, a comparison of MD is made with Empirical Potential Structure Refinement - a combined experimental and computational method that is often used to resolve the solvation structure of small molecules.
Epigenetic silencing of RASSF1A promotes tumourigenesis via alternative transcript expression, SFK activation and exosome secretion
Keywords: RASSF1
Cancer
YAP
Epigenetics
SRC
Exosomes

Loss of the tumour-suppressor gene RASSF1A upon promoter methylation is one of the most frequent events in sporadic human malignancies. Loss of RASSF1A is associated with progression and pathogenesis of solid tumours; and more aggressive clinical phenotype, leading to poor prognosis in breast, lung and colon cancers, amongst others. RASSF1A functions in a number of cellular processes, inducing apoptosis in response to DNA damage, cell cycle arrest and growth control. In tumours with RASSF1 promoter methylation, an alternative isoform, RASSF1C, is expressed and we find is able to bind and activate SRC. We also identify a novel tumour-suppressor role for RASSF1A, associating with the kinase inactivation of SRC. RASSF1C expression promotes SRC-dependent phosphorylation and internalisation of adherens junctions, leading to loss of cell-cell contacts and subsequent increase in cell motility, growth and invasiveness, both in vitro and in vivo. RASSF1C, via active SRC, mediates the phosphorylation of β-catenin and YAP1, promoting their nuclear localisation and association with the transcription factors TEAD1 and TBX3, resulting in the upregulation of anti-apoptotic and pro-survival genes. We show that RASSF1C expression leads to differential packaging and secretion of exosomes, modulating the communication between cancer cells and increasing their tumourigenicity. Finally, we find that cells expressing RASSF1C undergo phenotypic and transcriptional changes associated with the generation of cancer stem cells. We conclude that RASSF1C is an oncogene that plays a variety of roles in cell adhesion, invasion, survival and extracellular communication, resulting in increased tumourigenesis. These functions are inhibited by the tumour suppressor RASSF1A. This work highlights the association of the epigenetic inactivation of the RASSF1A gene with the more aggressive, metastatic tumours, and its relation to increased cancer outcome and risk.
Semiclassical transition state theory for chemical reactions
Keywords: semiclassical transition state theory

First-principles calculations of chemical reaction rate constants have useful applications in a variety of areas. Quantum reactive scattering approaches are the most accurate, but their computational costs scale significantly with system size. Semiclassical Transition State Theory (SCTST) constitutes a more efficient approach. In SCTST, rate constants are calculated from frequencies and anharmonic constants, which depend on the second, third, and fourth derivatives of the reaction's potential energy surface (PES) at the transition state. Further gains in efficiency can be achieved by calculating anharmonic constants for only a subset of degrees of freedom. SCTST can be improved by imposing more realistic behaviour of the reactant and product asymptotes of the potential barrier used in calculations.
This thesis investigates the accuracy of one- and two-dimensional SCTST in relation to accurate quantum scatteirng calculations performed on the same PESs. Calculations are performed for four H atom abstraction and exchange reactions: H + CH4, H + C2H6, H + cyc-C3H6, and CH3 + CH4. Two methods are presented for calculating frequencies and anharmonic constants from PESs developed previously for these reactions, which are defined in Jacobi coordinates. 2-D SCTST rate constants exhibit acceptable agreement with results from previous quantum scattering calculations. 1-D SCTST rate constants agree very well with 2-D results, although barrier corrections must be applied in the case of the CH3 + CH4 reaction. These corrections did not significantly improve the accuracy of other calculations. Agreement between 2-D and 1-D results suggests the validity of reducing the number of degrees of freedom considered in an SCTST calculation.
A practical ab initio approach is presented to facilitate evaluation of the accuracy of 1-D SCTST in relation to FD SCTST. Richardson extrapolation is discussed as an approach to improving the accuracy of purely numerical calculations of third and fourth derivatives. FD calculations for the H + CH4 and H + C2H6 reactions exhibit good agreement with previous results and with results from two different 1-D methods. The second of these methods requires only 4 single-point energy calculations in addition to those required for TST. The agreement of 1-D and FD results suggests the potential applicability of 1-D SCTST to larger systems.
Hotbeds of unrest and extremism: how social context influences political participation in the 21st century: Britain, from rioting to far right party membership
Keywords: political extremism
British politics
British National Party
London Riots 2011
far right

British politics at the start of the 21st century provide a good setting for examining factors associated with mobilisation for extremist politics. This thesis is concerned with the relationship between individuals' preferences, their local setting and political behaviour. With focus on two outcomes – participation in urban rioting and support for a far right party – this thesis is divided into two parts and consists of five research papers addressing different aspects of mobilisation.
In the first part we focus on urban disorder and examine police arrest records from the London riot of 2011. Much of the sociological literature has focused on variation in rioting across cities; here we examine variation within London by mapping the residential addresses of 1,620 rioters onto over 25,000 neighbourhoods. Our findings challenge the orthodoxy that rioting is not explained by deprivation or by disorganisation. Furthermore, we present evidence suggesting the importance of political grievances, in particular relations with the police, and examine the process of mobilisation to show that it was aided by spatial proximity and social similarity.
In the second part we look at factors associated with engagement with far right politics. We use individual attitudinal data from the British Election Study to examine whether concerns over immigration are associated with the actual experience of immigration in one's place of residence. The results suggest that local setting does play some role, although individual factors seem to be more important. Secondly, we use leaked British National Party membership list to map 12,536 far right supporters onto over 200,000 neighbourhoods in Britain. Our findings underline the importance of a larger geographic context, where some spatial configurations present particularly fertile grounds for the far right; we also report the relative unimportance of cultural threat and significance of the social distance. Lastly, we question the recently advocated 'legacy effect' and suggest that white flight mechanism may possibly be an alternative way of thinking about organisational continuity.
Blood pressure, atrial fibrillation and diabetes: evidence from observational and randomized analyses
Keywords: Epidemiology
Blood pressure

The subgroup-specific relationships between blood pressure (BP), risk of atrial fibrillation (AF) and risk of diabetes are unclear. These two chronic diseases have key epidemiologic and clinical similarities, are difficult to examine through traditional cohort studies, and are of high clinical and public health importance. Using observational analyses of electronic health records and meta-analyses of randomized trials, the relationships between blood pressure, atrial fibrillation and diabetes are investigated in this thesis. First, I show that blood pressure is modestly associated with risk of atrial fibrillation in a population free of cardiovascular disease [HR 1.21 95% confidence interval 1.19, 1.22 per 20 mm Hg higher systolic blood pressure (SBP)]. While a non-significant effect of BP lowering on AF in non-heart failure populations is observed in a meta-analysis of randomized trials, this randomized estimate is similar in magnitude to the observational association, suggesting that BP lowering may modestly lower the risk of AF. Second, I show that elevated BP is associated with a higher risk of incident diabetes (HR 1.76 CI 1.56, 198 per 20 mm Hg higher SBP), although the causality of this finding is unclear. Third, I demonstrate in both observational and randomized analyses that the relationship between blood pressure and cardiovascular events appears to be modified by achieved BP in type 2 diabetes, with attenuated proportional reductions at achieved SBP less than 130 mm Hg. However, I also show that BP lowering to levels lower than those recommended in current guidelines (&LT;130 mm Hg SBP) may lower the risk of stroke, renal disease and retinopathy. These findings are of clinical and public health importance, as they suggest that BP lowering therapy can be used to reduce the risk of AF, that elevated BP may be a risk factor for incident diabetes, and that BP lowering in type 2 diabetes to lower levels than currently recommended in guidelines may further reduce the burden of cardiovascular disease in diabetic populations.
The clinical applications of working memory training
Keywords: Worry
Working memory training
Neurodevelopmental disorders

Working memory is involved in a variety of cognitive tasks, with working memory capacity predicting an individual's ability to process information and focus attention on taskrelated information. Subsequently, recent research has investigated whether working memory capacity can be improved through training and whether improvements generalise to other cognitive, behavioural or emotional domains. This training is typically adaptive in nature, changing in difficulty according to participant ability, and can be completed in the participant’s home on a computer, giving it the potential to be an easily accessible intervention for a range of clinical populations.
The first paper presents a systematic review evaluating the effectiveness of computerised working memory training for individuals with neurodevelopmental disorders, which are often associated with working memory difficulties. The review found that to date, working memory training has been investigated in four neurodevelopmental disorders: attention deficit/hyperactivity disorder; autism spectrum disorder; intellectual disability and specific learning disorder. The findings indicate that although training appears to produce short-term improvements in the working memory capacity, this does not reliably generalise to other cognitive processes or disorder-specific symptoms.
The second paper presents a randomised controlled trial investigating the effects of working memory training for reducing worry in high-worriers. Working memory capacity limitations, and subsequent difficulties in attentional control, are believed to be central to the maintenance of worry. Participants were randomly assigned to complete 15 days of nonadaptive working memory training using a 1-back task, or adaptive working memory training using a n-back task. Training led to improvements in working memory capacity and worry symptoms post-training and at four-week follow-up, with improvements on the adaptive training task significantly correlating with improvements in working memory capacity and worry. These findings are discussed in terms of implications for clinical practice and future research, together with the limitations of the study.