VictorJuiz/thesis huggingface dataset:
Stochastic modelling and simulation in cell biology

Modelling and simulation are essential to modern research in cell biology. This thesis follows a journey starting from the construction of new stochastic methods for discrete biochemical systems to using them to simulate a population of interacting haematopoietic stem cell lineages.
The first part of this thesis is on discrete stochastic methods. We develop two new methods, the stochastic extrapolation framework and the Stochastic Bulirsch-Stoer methods. These are based on the Richardson extrapolation technique, which is widely used in ordinary differential equation solvers. We believed that it would also be useful in the stochastic regime, and this turned out to be true.
The stochastic extrapolation framework is a scheme that admits any stochastic method with a fixed stepsize and known global error expansion. It can improve the weak order of the moments of these methods by cancelling the leading terms in the global error. Using numerical simulations, we demonstrate that this is the case up to second order, and postulate that this also follows for higher order. Our simulations show that extrapolation can greatly improve the accuracy of a numerical method.
The Stochastic Bulirsch-Stoer method is another highly accurate stochastic solver. Furthermore, using numerical simulations we find that it is able to better retain its high accuracy for larger timesteps than competing methods, meaning it remains accurate even when simulation time is speeded up. This is a useful property for simulating the complex systems that researchers are often interested in today.
The second part of the thesis is concerned with modelling a haematopoietic stem cell system, which consists of many interacting niche lineages. We use a vectorised tau-leap method to examine the differences between a deterministic and a stochastic model of the system, and investigate how coupling niche lineages affects the dynamics of the system at the homeostatic state as well as after a perturbation. We find that larger coupling allows the system to find the optimal steady state blood cell levels. In addition, when the perturbation is applied randomly to the entire system, larger coupling also results in smaller post-perturbation cell fluctuations compared to non-coupled cells.
In brief, this thesis contains four main sets of contributions: two new high-accuracy discrete stochastic methods that have been numerically tested, an improvement that can be used with any leaping method that introduces vectorisation as well as how to use a common stepsize adapting scheme, and an investigation of the effects of coupling lineages in a heterogeneous population of haematopoietic stem cell niche lineages.

Keywords: higher-order stochastic methods
Stochastic simulation
population dynamics
stem cells
tau-leap
Advisor: Burrage, K
Erban, R
Looking for life

This dissertation challenges the adequacy of three interrelated foci of twentieth- century Protestant Pauline interpretation. Interpreters regularly: (1) distinguish Paul's theology from his ethics, (2) emphasise his preaching as the sole or primary vehicle for gospel proclamation and divine revelation, and (3) deny that Paul engages in reasoned, ethical reflection. This study offers a new proposal for understanding how Paul does theology and ethics as a former Pharisee and first-century pastoral theologian a Christian community-builder with an apocalyptic (i.e. revelatory) perspective.
Paul integrates Christian thinking and living, combining what interpreters frequently separate as theology and ethics. This becomes evident in Paul's complex process of theological, moral reasoning for which we have coined the phrase 'theo-ethical reasoning'. This characterisation captures both the divine and human elements of Paul's behavioural reasoning grounded in the revelation of the risen Christ to Paul and in Paul. According to theo-ethical reasoning, Paul associates specific acts of Christ-conforming conduct with the power of God that becomes manifest in community experiences of new life. Since this reasoning often lies beneath the surface of the texts, the study explores the underlying logic of Paul's arguments. This highlights the consistent pattern of reasoning by which Paul analyses and responds to behavioural issues.
The study also argues that Paul encourages his churches to practise spiritual discernment by engaging in theo-ethical reasoning a dialogical, comparative process of reasoned reflection on the links between behaviour and experience. In this practice of looking for life, the Spirit leads community members to associate experiences of new life with conduct that conforms to Christ's cruciform pattern of self-giving love for others. This correlation grounds both Paul's proclamation of Jesus Christ by word and deed and believers' faith in the power of God. We conclude that theo-ethical reasoning lies at the centre of Paul's religion.

Advisor: Morgan, t
The cost-effectiveness and efficiency of intrapartum maternity care in England

Background
High quality evidence on the cost-effectiveness of planned birth in alternative settings (at home, in a midwifery unit or an obstetric unit) has been lacking, and is a priority area for maternity policy.
Aim
To provide evidence about the efficiency of the configuration of maternity care in England and to estimate the cost-effectiveness of alternative settings for intrapartum care for ‘low risk’ women, thereby providing guidance for commissioners, clinicians and for pregnant women and their families.
Methods
A literature review of existing evidence was followed by four stand-alone empirical studies using different methods to determine the efficiency and cost-effectiveness of alternative settings for intrapartum care. Data from the Birthplace in England Programme of Research were analysed to explore whether there are differences in the efficiency of maternity units when they are stratified according to the type and scale of unit. Incremental cost-effectiveness ratios were used to estimate the short-term cost-effectiveness of different planned settings for birth for ‘low risk’ women and to develop a template for the design of decision-analytic models to estimate life-long cost-effectiveness for the mother and baby dyad.
Findings
The larger obstetric units (OUs) tended to be more efficient than the smaller OUs. Less than half of free-standing midwifery units (FMUs) were operating at full efficiency.
The cost of intrapartum and after birth care, and associated related complications, was less for births planned at home, in a free standing midwifery unit (FMU), or in an alongside midwifery unit (AMU) compared with planned births in an obstetric unit (OU).
Planned birth in a FMU or in an AMU compared with an OU will generate incremental cost savings but with uncertainty surrounding the outcomes for the baby. Planned birth in all non-OU settings generated incremental cost savings and improved outcomes for mothers. For ‘low risk’ women having a second or subsequent birth, planned birth at home was found to be the most cost-effective option.

Keywords: health economics
Advisor: Brocklehurst, P
Petrou, S
Redshaw, M
Modernization and social stratification in Iceland

Some myths of Icelandic society are examined and empirically tested in this thesis. The myths are variants of two basic themes: firstly, the idea that the Icelandic social structure is funda- mentally unique, and, secondly, the belief that the contemporary society is exceptionally egalitarian in many respects. The uniqueness theme is reflected upon by maintaining an international comparative perspective throughout the presentation, and by examining the characteristics and degree of modernization in Icelandic society. In relation to the equality theme, some important aspects of socio-economic advantages are examined. Opportunities of individuals and class formation are also assessed, and then the analysis moves to the level of organizations and labour market relations, i.e., to unionism, conflict, and inflation.
The findings seriously question or discard the themes which are considered. Thus, we show that Iceland has modernized to a very high level, sharing most of the basic social structural features which have been found to produce a "family resemblance" amongst advanced societies. Iceland is also found to have an inequality structure with familiar characteristics. The degree of income inequality seems to be on level with the Scandinavian societies, but when other related advantages are also considered, such as welfare and security aspects, the net outcome is that inequality appears to be greater in Iceland. Upward mobility has been extensive, mainly due to changes in the occupational structure, but the patterns are fairly typical.
The structure of the industrial relations system has signifi- cant affinities with comparable Scandinavian systems, but the level of industrial conflict has been extensive in Iceland. Inflation has similarly prevailed at a very high level for a long period. By relating inflation to distributional conflicts and the inequality structure, we offer a novel interpretation of this outstanding characteristic.
Lastly, the relatively poor showing in the welfare league arid the intense distributional conflicts are explained by relating them to the distribution of political power in the society. Unlike the Scandinavian societies, Iceland has not been dominated by a large social-democratic party. The conservative Independence Party is the largest political party in the country and it has been the dominant force in governments for most of the post-war period.
Studies in the reception of Pindar in Hellenistic poetry

This thesis examines the reception of Pindar in Hellenistic poetry. More specifically it examines texts of three major Hellenistic poets: Theocritus of Syracuse, Callimachus of Cyrene and Posidippus of Pella. The texts discussed have been selected on the basis of two principles: (i) genre and (ii) subject matter. They include texts that inscribe themselves in the tradition of encomiastic, and more specifically, Pindaric poetry either through the generic discourse which they partake in or through the employment of myths that Pindar had used in his own odes. Throughout the thesis it is argued that the connections with Pindaric passages are carried out on the basis of ‘allusions’ which are picked up by the readers. This term is employed to describe one of the ways in which intertextuality functions. Following the model of Conte and Barchiesi, the discussion insists on the distinction between allusions to specific Pindaric passages and allusions to epinician generic motifs that can best be illustrated through Pindaric passages. The aim of the discussion for each case of textual correspondence suggested is to describe the means whereby this connection is suggested to the reader and to propose a ‘meaning’ for it. In this sense, equal emphasis is given to the detailed examination of all texts that partake in the intertextual connection suggested, i.e. to Pindaric and Hellenistic alike.

Keywords: intertextuality
Posidippus
Hellenistic poetry
Theocritus
Genre theory
Pindar's reception
ancient readers
Pindar
Callimachus
Reception theory
P. Horak 4
Advisor: Hutchinson, G
Neglected issues in the epidemiology of vascular disease

Vascular disease is the leading cause of global disease burden, but substantial gaps in our knowledge regarding family history of vascular disease, peripheral arterial disease (PAD) and acute aortic disease persist. Prospective, population-based data in these neglected areas may be useful in diagnosis, risk prediction, prognosis and clinical management of vascular disease.
The Oxford Vascular Study (OXVASC) is an ongoing prospective, population-based study of vascular disease in all territories in Oxfordshire, UK, which started in 2002. The study population comprises all 91,106 individuals registered with nine general practices. Multiple overlapping methods of “hot” and “cold” pursuit are used to identify all patients with acute vascular events.
I have shown that patients with acute coronary syndromes (ACS) and a history of myocardial infarction (MI) in both parents are 6 times more likely to have siblings with MI than those ACS patients with no parental history of MI, whereas, parental stroke does not predict stroke in siblings among TIA/stroke patients. Maternal history of MI is more common in women than men with ACS. Premature maternal MI is strongly associated with premature MI in females and males. I have also shown that maternal stroke is more common than paternal stroke in female ACS patients, and that family history of stroke is as common in patients with ACS as in patients with TIA/stroke. However, I showed that these associations between family history and MI or stroke cannot be explained by disease localisation or disease severity on coronary angiography.
In both primary and secondary prevention settings, PAD indicates a high risk of future events. I have shown that, although acute PAD events account for only 7% of acute vascular events at 1 year, they account for 12% of acute vascular deaths. Acute peripheral arterial events are more aggressive in terms of risk factor profile, mortality and morbidity than other vascular disease. Half of patients with incident PAD had history of vascular disease. Incidence and severity of PAD events generally increases with age, and severity of disease predicts mortality.
I have shown that incidence of ruptured abdominal aortic aneurysm (RAAA) and aortic dissection increased steeply with age, and 5-year mortality rates were 74% and 65% for RAAA and aortic dissection respectively. I have also shown that the true population-based incidence of acute aortic dissection is similar to previous estimates of incidence, implying that it is accurately diagnosed and coded, and that retrospective data analysis produces valid estimates of incidence.

Keywords: cardiovascular disease
peripheral arterial disease
stroke
family history
epidemiology
Advisor: Rothwell, P
Processing and properties of nanostructured solid-state energy storage devices

A scalable spray processing technique was used to fabricate carbon nanotube (CNT)-based film electrodes and solid-state supercapacitors. The sprayed CNT-based electrodes comprised a randomly interconnected meso-porous network with a high electrical conductivity. Layer-by-layer (LbL) deposition of functionalised and oppositely charged single-wall carbon nanotubes (SWNTs) increased the electrode density and improved charging and discharging kinetics when compared with carboxylic functionalised only SWNT electrodes. The capacitance was further increased to 151 F g-1 at 2 mV s-1 and 120 F g-1 at 100 mV s-1 after vacuum and H2 heat treatments that removed the functional groups, and resulted in a hybrid microstructure of SWNTs and multi-layer graphene sheets from unzipped SWNTs.
Flexible solid-state supercapacitors were fabricated by directly spraying multi-wall carbon nanotube (MWNT)-based aqueous suspensions onto both sides of a Nafion membrane and dried. A single cell with MWNT-only electrodes had a capacitance of 57 F g-1 per electrode at 2 mV s-1 and 44 F g-1 at 150 mV s-1. Cells with MWNT/ionomer electrodes showed a higher H+ mobility and a lower charge transfer resistance, and the capacitance increased to 145 F g-1 at 2 mV s-1 and 91 F g-1 at 150 mV s-1.
Finally, MWNT/TiO2 nanoparticle/ionomer hybrid electrodes were used in the same solid-state supercapacitor configuration and provided a capacitance of 484 F g-1 per electrode at 5 mV s-1 and 322 F g-1 at 100 mV s-1. A qualitative model of the charge storage mechanism was developed, where TiO2 promoted H+ ions via redox reactions that fed protons into the proton-conducting ionomer coating over the MWNTs (in which the TiO2 was embedded), while electrons were readily conducted through the MWNT scaffold. This solid-state supercapacitor provided both attractive energy (31.8 Wh kg-1) and power (14.9 kW kg-1) densities, where such high energy density is difficult to achieve for MWNTs alone and such high power density is difficult for metal oxides alone, especially in the solid state.

Keywords: Processing
Nanostructure
Energy Storage
Advisor: Grant, P
Situational awareness in autonomous vehicles: learning to read the road

This thesis is concerned with the problem of situational awareness in autonomous vehicles. In this context, situational awareness refers to the ability of an autonomous vehicle to perceive the road layout ahead, interpret the implied semantics and gain an awareness of its surrounding - thus reading the road ahead.
Autonomous vehicles require a high level of situational awareness in order to operate safely and efficiently in real-world dynamic environments. A system is therefore needed that is able to model the expected road layout in terms of semantics, both under normal and roadwork conditions.
This thesis takes a three-pronged approach to this problem: Firstly, we consider reading the road surface. This is formulated in terms of probabilistic road marking classification and interpretation. We then derive the road boundaries using only a 2D laser and algorithms based on geometric priors from Highway Traffic Engineering principles. Secondly, we consider reading the road scene. Here, we formulate a roadwork scene recognition framework based on opponent colour vision in humans. Finally, we provide a data representation for situational awareness that unifies reading the road surface and reading the road scene. This thesis therefore frames situational awareness in autonomous vehicles in terms of both static and dynamic road semantics - and detailed formulations and algorithms are discussed.
We test our algorithms on several benchmarking datasets collected using our autonomous vehicle on both rural and urban roads. The results illustrate that our road boundary estimation, road marking classification, and roadwork scene recognition frameworks allow autonomous vehicles to truly and meaningfully read the semantics of the road ahead, thus gaining a valuable sense of situational awareness even at challenging layouts, roadwork sites, and along unknown roadways.

Keywords: scene interpretation
autonomous driving
scene recognition
intelligent transport systems
Advisor: Newman, P
Role of delta-like 4 in solid tumours and response to radiation therapy

Delta-like ligand 4 (DLL4) is a ligand for the Notch family of receptors. DLL4 is an important regulator of angiogenesis and DLL4 blockade promotes non-productive angiogenesis and delays tumour growth. The aim of this thesis was to investigate the effects of anti-DLL4 therapy in solid tumours in combination with a clinically relevant dose of ionising radiation (5 Gy; IR) and to analyse alterations in the Notch pathway induced by the treatments. Combining both treatments resulted in a greater than additive tumour growth delay in LS174T tumours, compared to either treatment alone. DLL4 blockade dysregulated vasculature and increased necrosis in LS174T and HCT-15 (DLL4-expressing and negative cell lines respectively) tumours within 3 days after treatment, but no changes were observed with IR alone. Additionally, combined IR and anti-DLL4 treatment of FaDu tumours (another DLL4-negative cell line) by our colleagues, also resulted in a supra-additive growth delay. These results show that combining IR with DLL4 blockade is an effective strategy for prolonging tumour growth delay and suggest that the stroma/vasculature provide the main therapeutic target for the anti-DLL4 therapy. Analysis of Notch pathway shows that IR upregulated Jag1 in tumour cells, and may inhibit Notch and downregulate DLL4 in the stroma. These changes may potentially affect tumour vessels and response to anti-DLL4 therapy. In vitro, anti-DLL4 therapy induced proliferation in quiescent contact-inhibited endothelial cells and also appeared to abrogate IR-induced inhibition of migration. These results suggest that DLL4 may be important in maintaining vessel quiescence and that IR may in part decrease migration through Notch signalling. Combining IR and DLL4 blockade to target tumour growth is an effective and well tolerated strategy and warrants further validation and refinement to be translated into clinical practice.

Keywords: tumour microenvironment
DLL4
Delta-like 4
radiotherapy
Notch
tumour angiogenesis
radiation therapy
tumour vasculature
Advisor: Harris, A
Muschel, R
Malaria pre-erythrocytic stage vaccines: targeting antigen combinations

Consistent efficacy in human clinical trials has been achieved by two leading malaria vaccine candidates encoding either the P. falciparum circumsporozoite (CSP) or thrombospondin-related adhesion (TRAP) proteins. However, protection in humans relies on high antibody (Ab) titers or potent T cells, respectively, when these antigens are used individually. Therefore, a concurrent induction of both anti-CSP antibodies and TRAP-specific T cells may further improve the protective efficacy associated with these immunogens.
This thesis investigates the protective potential associated with CSP and TRAP combination vaccines by employing a pre-clinical Plasmodium berghei (P. berghei) mouse malaria challenge model. Depletion of CD4+ and CD8+ T cells indicated that protection by the CSP antigen relied solely on antibodies while TRAP protected through CD8+ T cell responses. Moreover, the administration of relatively small amount of anti-CSP monoclonal antibodies (mAb) substantially enhanced the sub-optimal protection elicited by TRAP. A way to maximize both, anti-CSP antibodies by adenovirus/protein (Ad-P) prime-boost vaccinations and anti-TRAP T cell responses using adenovirus/modified vaccinia strain Ankara (Ad-M), was explored. Combination of the two approaches stimulated optimal humoral and cellular responses that afforded sterile protection in the C57BL/6 animal model. Additional analyses of the effector functions of Abs indicated that the efficacy of this vaccine relied on a two-stage attack against the parasite: anti-CS antibodies reduced the number of sporozoites reaching the liver, thus decreasing the number of infected hepatocytes required to be eliminated by the dual action of natural killer (NK) cells and CD8+ T cells. These proof-of-concept studies using a wild-type (wt) P. berghei challenge model allowed progression towards the development of human malaria Plasmodium vivax (P. vivax) vaccines using PvCSP and PvTRAP antigens. The immunogenicity of PvCSP and PvTRAP-based vaccine candidates was assessed in multiple mouse strains. Additionally, transgenic (tg) P. berghei parasites expressing P. vivax genes were generated and used to demonstrate the protective efficacy of Ad-P PvCSP and Ad-M PvTRAP vaccines.

Keywords: CSP
infectious diseases
malaria
TRAP
P. berghei
vaccinology
P. vivax
immunology
Advisor: Hill, A
Reyes-Sandoval, A