VictorJuiz/thesis huggingface dataset:
Leveraging multiple sources of information to search continuous spaces
Keywords: informed bidirectional search
informed search
heuristics
sampling-based path planning
asymptotically optimal path planning

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.
Development of training and support for parents who perform specialist medical care at home
Keywords: home care
gastrostomy
schemas
psychology of learning
retrieval practice
medical complexity
family caregivers

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.
Numerical simulation of the internal structure of sand dunes
Keywords: computing fluid dynamic
cellular automaton
transverse dune
uni-directional wind regime
bi-modal wind regime
numerical simulation
linear dune
sand dune stratigraphy

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.
Scara5 as a cell fate determinant of osteoblasts and adipocytes
Keywords: Bone marrow cell differentiation
Osteoblast differentiation
Scavenger Receptors
Scara5
Bone marrow 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.
Developmentally regulated molecular programmes in human fetal
haematopoietic cells cooperate with MLL-AF4 to drive infant acute
lymphoblastic leukaemia
Keywords: CRISPR
human
haematopoiesis
leukaemia
cancer
MLL-rearranged ALL
MLL-AF4
infant
fetal

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.
Decoupling configurations from moduli spaces of manifolds
Keywords: Infinity operads
Operads
Mapping class groups
Configuration spaces
Homological stability
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.
Assessing how commercial data on food retail sales can be used to monitor industry-led changes in the food supply in the UK
Keywords: Public Health
Reformulation
Nutrition
Policy

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.
Follow the leader: collective cell migration in cancer and developmental biology
Keywords: asymptotic analysis
sensitivity analysis
neural crest cell
angiogenesis
contact guidance
collective cell migration
extracellular matrix remodelling
coarse graining
agent based model
multiscale modelling

Collective cell migration is an essential phenomenon in biology, occurring in diverse processes such as neural crest stem cell migration and angiogenesis (the formation of new blood vessels from pre-existing ones). One particular mode of collective cell migration involves two distinct phenotypes: leader cells, which migrate towards external biophysical signals, and follower cells, which move in response to leader-created cues. Mechanisms underpinning leader-follower migration remain poorly characterised in general, partly because they occur over multiple spatial and temporal scales. Mathematical modelling can address such issues, as it can be used to tractably evaluate different biological hypotheses, connect individual cell interactions to the behaviour of collectives, and guide the design of in vivo experiments. Open questions remain, however, regarding the validity of certain mathematical models and the conditions for which they accurately capture data from biological experiments.
In this thesis, we address different questions relating to leader-follower migration within the contexts of angiogenesis and neural crest cell migration. By comparing agent-based model simulations for angiogenesis to solutions from both a classical phenomenological framework and an alternative coarse-grained model, we identify parameter regimes for which the phenomenological framework accurately describes results of the other two systems. In doing so, we uncover implicit physical assumptions that underpin the continuum models. We also collaborate with experimental colleagues to develop a new agent-based model for cranial neural crest cell migration that incorporates cell remodelling of, and movement through, a naive extracellular matrix. We perform a global sensitivity analysis on the model and rank the mechanisms that most dominate collective cell behaviour. Further tests of this model suggest that migration is most efficient when leader and follower cell phenotypes are not identical. We conclude by providing, to our knowledge, the first detailed investigation of mechanisms that ensure robust neural crest cell migration.
The molecular epidemiology of bloodstream infections caused by non-Salmonella Gram-negative bacteria in a tertiary hospital in Nepal with focus on neonatal sepsis and Enterobacter species
Keywords: bloodstream infections
whole genome sequencing
epidemiology
antimicrobial resistance
Nepal
Enterobacter
Gram-negative bacteria
neonatal sepsis

Bloodstream infections (BSIs) are common cause of morbidity and mortality among patients of all age groups. Of particular concern is the increasing emergence and spread of antimicrobial resistance (AMR) in many Gram-negative bacteria (GNB) that cause BSIs. The aim of this thesis was to determine some of the epidemiological features of BSIs in a tertiary hospital in Nepal providing a specific focus on the molecular aspects of AMR, virulence, and variations in Enterobacter spp., a clinically important GNB associated with BSIs.
To better understand BSIs-causing non-Salmonella GNB and their AMR determinants in this setting, I conducted a retrospective surveillance study, accessing data from 2012 to 2018. I identified a high prevalence of multi-drug resistance (MDR) and several key AMR genes associated with predominant GNB pathogens. The neonatal intensive care unit (NICU) and the emergency room (ER) were the most prevalent hospital departments for BSIs. To gain an insight into the epidemiology of hospital-acquired (HA) BSIs and identify potential preventive measures, I conducted a further prospective study in the NICU. An increased isolation of Enterobacter spp. in the NICU during the study period suggested an outbreak, prompting an outbreak investigation of Enterobacter spp. isolates using whole genome sequencing (WGS). Identification of ER to having the highest burden of BSIs due to Enterobacter spp. demanded for an epidemiological research to understand the genomic determinants of virulence, AMR, and variations of Enterobacter spp.. To address this, I performed a comprehensive WGS analysis of Enterobacter spp. isolated in the ER.
The conclusion of my work is that BSIs due to antimicrobial resistant non-Salmonella GNB is an expanding problem in our hospital, highlighting the need for a continued AMR surveillance. I found that Enterobacter spp. was an emerging MDR pathogen causing BSIs in this hospital. The complex transmission dynamics of Enterobacter spp. observed in ER warranted for a more comprehensive genomic investigation complemented with demographic and clinical data of patients to better disaggregate the epidemiology of BSIs in ER.
The four elements of nature and narrative: from antiquity to neo-mythological Russian drama
Keywords: Drama
Mythology
Innokenty Annensky
Narratology
Intertextuality

The present thesis examines Russian twentieth-century drama composed by Innokenty Annensky, Valery Bryusov, Fyodor Sologub in the context of Classical, Medieval and contemporary philosophical and literary works, as well as in the context of visual art (archaeological, sculptural and numismatic evidence: Greek pottery and vase-painting, Greek and Roman coinage, Etruscan mirrors, Roman sarcophagi). In my thesis I adopt an intertextual approach to Russian drama in relation to Ancient Greek and Roman epic, dramatic, elegiac and mythographic traditions, which are represented as a single mythological hypertext. I attempt to show the applicability of a narratological approach to a manifestly non-narrative, i.e. performative genre, which inherits a narrative structure from the mythological plotline underlying it, and argue that a parallel system of four closely interconnected narrative elements underlies the hypertext of Annensky’s tragedies.
My thesis explores the main variants of artistic myth-making in Silver Age drama based on traditional mythological plots, projected onto contemporary life, the creation of individual systems of mythologemes and motifs, the use of temporal-chronological planes and causal-consecutive connections, and the functions of archetypal themes, images and characters (cosmos vs. chaos, hero vs. anti-hero, love vs. strife).
My thesis offers a basis for understanding Annensky’s mythological tetralogy as a cosmogonical universe based on the reception of Empedoclean principles, which accounts for the choice of mythological plots based on the four Classical elements of nature (earth, fire, water and air). Each of the four mythological dramas composed by Innokenty Annensky is conceptualised through an element, enabling the poet to explore problems of psychology and ethics by fusing the natural world with the human soul.
Using an aerosol human BCG infection model to define the early immune response in the lung and systemic circulation
Keywords: BCG
CHIM
Aerosol
Tuberculosis
Mucosal immunology
Innate immunology

There remains much that we do not understand about the interaction between Mycobacterium tuberculosis (M.tb) and the host immune response. Development of an effective vaccine is hampered by an incomplete understanding of the immunoprotective mechanisms, no biomarker of infection and no validated correlate of protection. Initial immune events driven by the innate system play an important role in the development of adaptive immunity and protection. This thesis describes the development of an aerosol BCG human infection challenge and demonstrates that this model is safe and well tolerated in BCG and M.tb naïve UK adults. This novel challenge model is then used to describe the initial innate and adaptive immune events at the site of infection, the airway parenchymal interface. The response is characterised by a local innate and adaptive lymphocytosis by day 7, and rapid upregulation of MHC-II antigen presentation differential gene expression pathways and Th1 effector function. There is a corresponding peak in antigen-specific IFN-y production at day 7 in the peripheral circulation, and improved mycobacterial growth control by peripheral blood mononuclear cells at day 14 on an ex-vivo functional assay. By describing underlying early immune responses to a mycobacterial airway infection in humans, this thesis provides an invaluable contribution to the field. This body of work has created a rich resource of early immune variables from which new hypotheses can be drawn for further investigation. Novel immune mechanisms, if correlated with growth control, could be used for rational tuberculosis vaccine design, to help tackle this pervasive disease.