VictorJuiz/thesis huggingface dataset:
Indefinite causal orders in thermodynamics and from time superpositions

This thesis is concerned with the use of indefinite causal orders (ICOs) for thermodynamic tasks, and a new context in which these exotic causal structures might arise — from superpositions in time. I propose a thermodynamic refrigeration cycle which uses indefinite causal orders to achieve non-classical cooling. The cycle cools a cold reservoir while consuming purity in a control qubit. I first show that the application to an input state of two identical thermalising channels of temperature T in an indefinite causal order can result in an output state with a temperature not equal to T. This result allows the construction of the refrigeration cycle. I investigate its properties and show that thermodynamically, the result is compatible with unitary quantum mechanics in the circuit model, but could not be achieved classically. This result suggests the development of a new class of thermodynamic resource theories in which operations are allowed to be performed in an indefinite causal order. I proceed to detail a simulation of the protocol using the IBM cloud quantum computing service, which is open to all users of the internet. The simulation, which is itself a quantum refrigerator, shows that the refrigeration cycle is robust to noise and can be implemented on Noisy Intermediate-Scale Quantum (NISQ) devices. This represents the development of a promising new test-bed for ICO protocols. Finally, the possibility for ICOs to arise from superpositions in time is considered. A new formalism, developed to analyse such superpositions, is applied to the case of two events which have a quantum uncertainty associated with their times. It is shown that these events can be used as triggers which enable an ICO. The fact that such commonplace phenomena can give rise to indefinite causal orders suggests that they might be much more common in nature than is typically understood.

Keywords: quantum refrigeration
indefinite causal orders
quantum thermodynamics
superpositions in time
Advisor: Vedral, V
Civic honourability in Western Asia Minor from the late Attalid dynasty to the early Principate, 188 BCE to 98 CE

This is a study of the impact of Roman imperialism on the public honorific culture of the Greek cities of western Asia Minor, 188 BCE to 98 CE. It is concerned with the way that local civic languages of power, framed in the terms of reciprocal benefaction and gift- exchange, adapted to changing political structures, as Rome succeeded the earlier Seleukid and Attalid regimes. This entails relating a mass of archaeological realia for public civic discourse, as embodied in several hundred inscribed honorific decrees, statue-base inscriptions, and public dedicatory inscriptions, to known historical and political contexts, thereby composing a diachronic history of discursive and ideological change and continuity tied to specific chronological and regional boundaries. Of the five chapters, Chapters 1, 2, and 4 chart the influence of high political change. The post-Seleukid era, 188-29 BCE, witnesses an overarching Roman dominance conceived in terms of universal euergetism that affects both late Attalid euergetic self-presentation and the honorific status of local citizens, who become plenipotentiary intermediaries with Roman power. Under the principate the autocratic power of the emperor channels the ambitions of local citizens into the imperial cult, which becomes an arena for elite giving at the provincial and local levels, and encourages honorific hierarchisation and titularisation. Chapters 3 and 5 examine developments in internal political culture across these two periods. Euergetic activity in relation to gymnasia and local cults in the decades after 188 is traceable to anxieties over local identity and growing socio-economic imbalance between citizens and non-citizens; this is exacerbated in the 1st century by the presence of resident Romans, and deepening wealth inequalities, thereby giving prominence to wealth and familial descent as arguments for civic honourability. The result is a subtle change in ethos, as honorific monuments by the early empire emphasise the honorand’s memorability rather than exemplarity.

Keywords: Euergetism
epigraphy
Asia Minor
honorific culture
Advisor: Kuhn, C
Leveraging multiple sources of information to search continuous spaces

Path planning algorithms can solve the problem of finding paths through continuous spaces. This problem appears in a wide range of applications, from navigating autonomous robots to automating assessments of surgical tolerances. The performance requirements on these algorithms tend to become more demanding as the problems they are applied to become more sophisticated. This simultaneous increase in performance requirements and application complexity calls for new approaches to the path planning problem and makes it an active area of research in robotics and beyond.
This thesis demonstrates how different types of information can be leveraged to solve the path planning problem more effectively. Optimization-specific information can guide the search towards high-quality solutions, environment-specific information can exploit incremental information about the surroundings, and intent-specific information can directly align the search of a problem with its priorities.
These three types of information are leveraged in this thesis by integrating advanced graph-search techniques in sampling-based path planning algorithms. The resulting planners, Advanced BIT* (ABIT*), Adaptively Informed Trees (AIT*), and Effort Informed Trees (EIT*), are theoretically shown to be almost-surely asymptotically optimal and experimentally demonstrated to outperform existing planners on diverse problems in abstract, robotic, and biomedical domains.

Keywords: informed bidirectional search
informed search
heuristics
sampling-based path planning
asymptotically optimal path planning
Advisor: Gammell, J
Developing viral vectored vaccines for MAGE-expressing tumours

The MAGE-type antigen family represent excellent targets for a therapeutic cancer vaccine. However, numerous attempts to develop effective MAGE-targeting cancer vaccines to date have shown poor induction of specific CD8+ T-cell responses and little clinical efficacy. In this study, a novel vaccination strategy based on a heterologous prime-boost with recombinant Chimpanzee Adenovirus (ChAdOx1) and Modified vaccinia Ankara (MVA) viral vectors was assessed for its potential in targeting MAGE-expressing tumours. The immunogenicity and anti-tumour efficacy of vaccination with ChAdOx1/MVA encoding the murine MAGE-type antigen P1A was evaluated in pre-clinical murine models. Heterologous prime-boost with ChAdOx1/MVA encoding P1A induced a very strong P1A-specific CD8+ T-cell response in DBA/2 and BL/6 mice and demonstrated good therapeutic efficacy in the P1A-expressing 15V4T3 tumour model. Many tumours are poorly infiltrated by tumour-specific CD8+ T-cells, which is believed to underlie the unresponsiveness of many patients to recently developed immunotherapies such as immune checkpoint blockade. Vaccination was seen to greatly increase the magnitude of P1A-specific CD8+ T-cell infiltrate into the tumour and synergised with anti-PD-1 blockade to provide improved control of tumour growth and increased survival. ChAdOx1/MVA vectors encoding the human MAGE-type antigens MAGE-A3 and NY-ESO-1 were also constructed and their immunogenicity evaluated in mice with the view to translation of this strategy to the clinical setting. A prime with ChAdOx1 encoding a dual-antigen MAGE-A3/NY-ESO-1 fusion construct was seen to induce high magnitude CD8+ T-cells to both antigens, which could be boosted further still against either antigen of choice with an MVA vector encoding either MAGE-A3 or NY-ESO-1 alone. Overall, these results strongly indicate that ChAdOx1/MVA is an efficient vaccination strategy for generating MAGE-type antigen-specific CD8+ T-cell responses and that vaccination in combination with PD-1 blockade has high therapeutic potential for treating cancer patients with MAGE-expressing tumours.

Advisor: Leung, C
Van den Eynde, B
Pugh, C
Development of training and support for parents who perform specialist medical care at home

Complex medical care is now performed by families at home, and is no longer solely the domain of healthcare professionals working in hospitals. Parents caring for children with serious or chronic conditions perform a range of medical procedures for their children, including caring for children with feeding tubes and children who need support with breathing (children dependent on long-term ventilation). This thesis examines the challenges and risks of complex medical care for children at home, and explores how best to train and prepare parents to provide this care, drawing upon relevant psychological theory and the lived experience of families. The first section of the thesis explores the clinical issues: Chapters 3 and 4 examine the safety concerns of clinicians who support families at home through analyses of incident reporting data, and Chapters 5 and 6 explore the experiences of parents caring for children with complex medical needs through interviews and surveys. This first section reveals a clear need to improve training and support for families. The second section (Chapters 7-9) consists of a series of experiments on how findings from psychology could inform the development of training interventions for parents caring for children with gastrostomies (a type of feeding tube). There was a significant benefit of supplementary videos and images on parents’ learning, but limited benefit of retrieval practice. Schema-enhanced training had a detrimental impact on performance in a test of knowledge. In the final section (Chapters 10 and 11) I develop and evaluate a package of training and support for parents caring for children with feeding tubes which has now been implemented across Oxfordshire and the Thames Valley. The training package consists of a library of videos to support families from referral for a gastrostomy through to the first few years caring for their child at home. Survey data from families and clinicians confirm the value of the library of videos for educating and empowering families.

Keywords: home care
gastrostomy
schemas
psychology of learning
retrieval practice
medical complexity
family caregivers
Advisor: Vincent, C
Yeung, N
Numerical simulation of the internal structure of sand dunes

The internal sedimentary structure of aeolian sand dunes has long been considered as an indicator of the paleo environment evolution. Traditional methods (e.g. digging, radar) for studying the internal structure have been restricted by the time and space coverage and data continuity. This thesis deploys a cellular automaton (CA) approach to investigate wind regime controls on the dune dynamic and the corresponding internal stratigraphy. The sand dune CA selected is coupled with a lattice gas (LG) --- a discrete Computing Fluid Dynamic (CFD) model to ‘generate’ the wind flow instantaneously adapted to the dune topography. In the dune CA, each sand grain cell is enabled with a activation time property to construct the full set of chronology records. The two ‘simplest’ wind regimes (i.e. unimodal and bimodal) are investigated.
For unimodal winds, scenarios are run on transverse dunes to identify controls of wind speeds and directions. High wind speeds or more crest-normal angles tend to trigger high grain flow magnitude and bury thicker strata whilst the preservation time within the dune body is short.
For bimodal regimes, firstly the fundamental dune evolution pattern and the stratigraphy are identified. With extension of a slip face from the dune crest to the lee slope plinth, the previous stoss slope gets buried, separating two sequences of grain flow strata and forming chronology gaps in age-depth profiles. Secondly the linear dune lateral migration potentials and elongation dynamics are investigated under bimodal winds. For established linear dunes, the lateral migration speeds, directions and the deposition pattern are highly sensitive to tiny (smaller than one degree) changes of wind directions. The sideways moving stratigraphy is either formed by avalanche in the lee or by accumulation of sand on the windward surface. For elongating linear dunes, the stratigraphy is featured by bidirectional strata buried as a core beneath active sand layers. Growth of the core and the whole dune both are influenced by geometries of the bimodal wind regimes, including wind cycle durations, wind directionality and asymmetry of the wind regime.

Keywords: computing fluid dynamic
cellular automaton
transverse dune
uni-directional wind regime
bi-modal wind regime
numerical simulation
linear dune
sand dune stratigraphy
Advisor: Wiggs, G
Bailey, R
Scara5 as a cell fate determinant of osteoblasts and adipocytes

Bone loss disorders associated with an imbalance in osteoblast and adipocyte differentiation, such as osteoporosis, are fast-growing health challenges in our aging populations. Cell fate differentiation shifts towards fat-storing adipocytes at the expense of bone-forming osteoblasts resulting in bone loss and increased fat mass. There is published evidence that murine models lacking specific scavenger receptors show alterations in bone and metabolic phenotypes. Herein, mice lacking scavenger receptor class A member 5 (Scara5) exhibited significantly greater bone mass and markedly reduced bone marrow adipose tissue than control WT animals. This was consistent with in vitro differentiation of Scara5-deficient (Scara5-/-) bone marrow stromal cells (BMSCs), showing a reduction in adipocyte differentiation and an increase in osteoblast bone nodule formation. The underlying mechanism was investigated using recombinant SCARA5 and bone-related ligands, including ferritin, HMGB1, and WNT-related proteins. These in vivo and in vitro findings underscore the crucial role of Scara5 in BMSC lineage allocation and demonstrate that Scara5 is a negative regulator of bone mass and osteogenesis. Additionally, Scara5-/- animals carried leaner body mass and a smaller percentage of subcutaneous inguinal fat than the age and sex-matched controls. This project proposes Scara5 as an important modulator of bone and adipocyte formation, which could be reciprocally manipulated as a potential therapeutic target for body fat and bone formation.

Keywords: Bone marrow cell differentiation
Osteoblast differentiation
Scavenger Receptors
Scara5
Bone marrow adipocytes
Advisor: Horwood, N
Platt, N
Sabokbar, A
Developmentally regulated molecular programmes in human fetal
haematopoietic cells cooperate with MLL-AF4 to drive infant acute
lymphoblastic leukaemia

Although advances in the treatment of childhood acute lymphoblastic leukaemia (ALL) mean that about 90% of children with ALL are now leukaemia-free 5 years on from their diagnosis, the prognosis for the subset of ALL that occurs within the first year of life, referred to as infant ALL, remains dismal. The most common genetic driver of infant ALL is a chromosomal translocation that leads to rearrangement of the Mixed Lineage Leukaemia (MLL) gene. In infant ALL, the MLL-rearrangement invariably arises in utero, and this single mutational hit in fetal life is sufficient to give rise to a leukaemia that is uniquely aggressive and treatment-refractory, even when compared to leukaemia in older children with the same MLL-rearrangement. The reasons for disparate outcomes in patients of different ages with identical driver mutations are unknown. Moreover, the contribution of the particular human fetal haematopoietic progenitor in which the translocation occurs remains unexplored. In this DPhil project, I aimed to address the hypothesis that fetal-specific gene expression programmes cooperate with the most common MLL-rearrangement in infants, MLL-AF4, to initiate and maintain infant ALL. I further aimed to identify the human fetal haematopoietic progenitor(s) that provide the permissive cellular context for leukaemia initiation. I found that CRISPR/Cas9 editing of primary human fetal liver (FL) cells to produce an MLL-AF4/t(4;11) chromosomal translocation gave rise to a leukaemia that replicated the aggressive phenotypic features of infant ALL, designated CRISPRMLL-AF4+ ALL. Using direct comparison of the transcriptomes of human fetal and adult haematopoietic progenitor cells, I identified a fetal-specific gene signature and further showed that CRISPRMLL-AF4+ ALL and MLL-AF4 infant ALL patients, but not MLL-AF4 childhood ALL patients, maintain the expression of these fetal genes. Finally, I found that, in-keeping with the B-ALL phenotype of MLL-AF4 infant ALL, lymphoid primed progenitors provided the most permissive cellular context to give rise to CRISPRMLL-AF4+ ALL.

Keywords: CRISPR
human
haematopoiesis
leukaemia
cancer
MLL-rearranged ALL
MLL-AF4
infant
fetal
Advisor: Roberts, I
Roy, A
Milne, T
Decoupling configurations from moduli spaces of manifolds

We consider moduli spaces of d-dimensional manifolds with embedded particles and discs. In such a moduli space, the location of the particles and discs is constrained by the d-dimensional manifold. We will compare this moduli space with the moduli space of d-dimensional manifolds in which the location of such decorations is no longer constrained, i.e. the decorations are decoupled. We generalise work by Bodigheimer–Tillmann for oriented surfaces and obtain new results for surfaces with different tangential structures as well as to higher dimensional manifolds. We also provide a generalisation of this result to moduli spaces with more general submanifold decorations and specialise in the case of decorations being unparameterised unlinked circles.
The moduli space of oriented surfaces with one boundary component can be made into a topological monoid with the operation of gluing surfaces along a section of their boundary. This operation can be extended to the spaces of configurations on surfaces with labels. We show that the group completion of this monoid splits as a product of the group completion of the moduli space of oriented surfaces and labelled configuration spaces of points in infinite Euclidean space. We further generalise this result for the configuration spaces on surfaces with partially summable labels, where particles are allowed to collide whenever their labels are summable.
The final project consists of endowing normalized cacti with the structure of an infinity-operad by showing that its existing composition laws are associative up to all higher homotopies. The higher homotopies are encoded by a new topological operad of bracketed trees which we relate both to an enrichment of the dendroidal category and to the Boardman-Vogt W-construction on the operad of operads.

Keywords: Infinity operads
Operads
Mapping class groups
Configuration spaces
Homological stability
Moduli spaces of manifolds
Advisor: Tillmann, U
Assessing how commercial data on food retail sales can be used to monitor industry-led changes in the food supply in the UK

Introduction: A poor diet is one of the leading causes of morbidity and premature mortality around the world. National and international policymakers recognise that changing the food supply is a crucial part in changing the diets of a population, yet there are few established methods to monitor the actions of food manufacturers and retailers.
Aim: The overarching aim of this thesis was to develop and apply a new method pairing food sales data and nutrition composition data to allow the nature of the food supply to be quantified and monitored over time. Method: A systematic review identified potential sources of food sales data. A cross comparison data study, led to the selection of Euromonitor as the most appropriate source for food sales data with nutrition composition data collected from supermarket websites by commercial company Brand View. The sales data and nutrition information were paired based on product name, brand name and category. This unique method was then applied in two ways: first, by analysing the changes in the sugar content of selected food and drinks in the UK between 2015 and 2018 in the context of the UK Government’s 20% sugar reduction targets and soft drinks industry levy (SDIL); and second by applying a nutrient profiling model to the top 10 UK companies’ product portfolios, to develop a benchmarking tool based on the healthiness of companies’ products.
Results: Analysis showed that the sales-weighted mean sugar content of soft drinks fell by 34% between 2015 and 2018, from 4.4g/100ml to 2.9g/100ml. The total volume of sugars 2 sold from soft drinks decreased by 30%, from 15.5g per capita per day to 10.8g, a reduction of 4.7g. There was a much smaller decrease in the mean sugar content or sugar sales from food products included in the sugar reduction strategy. The total volume sales of sugar from the included categories fell by 8%, equating to 1.7g per capita per day with marked differences across food categories. However, there has been no significant change between 2015 and 2018 in the overall nutrient profiling score for the top 10 food and drink companies in the UK. In 2018, the sales-weighted mean score of all food and drinks was 65, below the score of 70 which can be considered ‘healthy’. No individual company had an overall score of above 70. There was little change in the number of individual products classified as healthy, although the proportion of total sales classified as healthy increased from 38% to 46%.
Discussion: This thesis provides novel insights into how companies have responded to Government public health policies, including the sugar reduction programme. A new method has been developed in this thesis that has the potential to be used continually to monitor the nutritional composition of the food supply, to evaluate which companies are making efforts to improve public health nutrition and to monitor the pace of change.

Keywords: Public Health
Reformulation
Nutrition
Policy
Advisor: Rayner, M
Jebb, S
Scarborough, P