VictorJuiz/thesis huggingface dataset:
Molecular mechanisms of cholangiocarcinoma-cholangiocyte cell interactions in vitro

Cholangiocarcinoma is a highly aggressive cancer originating within the biliary tract. Whilst the role of the tumour microenvironment in CCA progression is well established, the function of surrounding cholangiocytes on CCA behaviour is often overlooked. Specifically, the effect of paracrine communication between cholangiocytes and cholangiocarcinoma cells has not been investigated previously. In this study, we provide evidence that cholangiocyte cells are a crucial paracrine modulator that influences the permissive or restrictive state to CCA progression.
Indirect co-culture of cholangiocarcinoma cells with cholangiocyte cells causes a significant decrease in CCA cell viability, migratory behaviour, and cell cycle progression, associated with a demonstratable switch in the gene and protein expression of the EMT markers E-cadherin, Slug, Snail, and Vimentin. Moreover, co-culture triggered a metabolic shift in CCA cells, with enhanced branched chain amino acid (BCAA) metabolism, as well as a transcriptomic shift resulting in increased cytokine signalling gene expression, recapitulated in the secretome.
In turn, cholangiocytes respond to this interaction with CCA cells, undergoing changes resulting in a growth advantage. Cholangiocytes experience an increase in creatine metabolism and ATP availability, linking to improved cell viability, increased cell cycle progression and reduced apoptosis, in conjunction with a reduction in gene and protein expression of p53 and apoptotic pathways.
Moreover, a high-throughput screen of epigenetic inhibitors successfully identified two targets, UNC0642 and SGC3027, for further development against CCA. More crucially, although effective against our CCA cell lines, co-culture with cholangiocytes caused a significant increase in IC50 value for these epigenetic inhibitors, implicating cholangiocyte cells in CCA chemoresistance.
We hypothesise the metabolic and genomic alterations triggered by this interaction contributes to CCA survival, invasiveness, and chemoresistance in the later stages of CCA development. Overall, our findings highlight the importance of cholangiocyte cells in modulating cholangiocarcinoma cells, impacting the development, progression, and treatment of cholangiocarcinoma.

Advisor: Kerr, D
Cai, S
Investigating the dynamic process of expressing breastmilk for very preterm infants and the influence of a relaxation intervention, with the aim of improving clinical recommendations

Background: Very preterm infants (born at less than 32 weeks of pregnancy) have higher morbidity and mortality than more mature infants. Even small increases in mother’s own milk quantity are associated with medium and long-term impacts on morbidity. Due to the infant’s oral immaturity, the mother must extract milk from the breasts (expressing), which is very challenging. Clinical recommendations to express 8-10 times per day are demanding and adherence is low. Relaxation has been identified as a promising intervention for lactation outcomes.
Aim: To investigate determinants of the quantity of breastmilk expressed by mothers of very preterm infants, focusing on relaxation interventions and expressing pattern.
Methods:
1) Systematic review and meta-analysis of relaxation interventions and milk yield.
2) A multi-centre, randomised, controlled trial. Mothers giving birth between 23+0 and 31+6 weeks of pregnancy were recruited. The intervention was a 12-minute guided relaxation recording. The primary outcome was the highest 24-hour milk quantity recorded at day 4, 14 or 21 after birth.
3) Exploratory analysis of expressing pattern and lactation outcomes.
Findings:
1) The systematic review included 1982 participants in 18 studies with heterogeneous relaxation interventions. There was moderate certainty evidence that relaxation increased breastmilk quantity by a moderate amount.
2) The randomised trial recruited the target 132 participants. Mean gestational age at birth was 27.8 weeks (SD 2.4). Adjusted mean difference in the primary outcome was 73.9g (95% CI –61.7 to 209.5). The majority of participants liked the intervention and found it relaxing. There were trends within the trial (sub-group analysis) and between trials (meta-regression) suggesting lower effect of relaxation on milk quantity with lower gestation at birth.
3) Less than a quarter of participants expressed eight or more times per day. Expressing frequency was positively associated with 24-hour milk yield (94.4g adjusted increase per session at three weeks after birth, 95% CI 62.7 to 126.2). Expressing eight or more times per day was associated with higher milk yield than expressing less than six times per day, but not compared to 6-7 times per day.
Conclusions: A weak recommendation can be made to offer relaxation interventions after very preterm birth. Many people value relaxation in this setting and there may be a small increase in milk quantity, which could be clinically important. Evidence for the recommendation to express 8-10 times per day is relatively weak, and this is difficult to achieve. These results can help improve individualised counselling for families.

Keywords: breastmilk
NICU
lactation
milk expression
neonatal intensive care unit
pumping
mother's own milk
relaxation therapy
infant
human milk
very premature
very preterm
neonate
relaxation
Advisor: Quigley, M
Hardy, P
Frances, O
Fewtrell, M
Nonparametric Involutive Markov Chain Monte Carlo: a MCMC algorithm for universal probabilistic programming

Probabilistic programming, the idea to write probabilistic models as computer programs, has proven to be a powerful tool for statistical analysis thanks to the computation power of built-in inference algorithms. Developing suitable inference algorithms that work for arbitrary programs in a Turing-complete probabilistic programming language (PPL) has become increasingly important. This thesis presents the Nonparametric Involutive Markov chain Monte Carlo (NP-iMCMC) framework for the construction of MCMC inference machines for nonparametric models that can be expressed in Turing-complete PPLs. Relying on the tree representable structure of probabilistic programs, the NP-iMCMC algorithm automates the trans-dimensional movement in the sampling process and only requires the specification of proposal distributions and mappings on fixed dimensional spaces which are provided by inferences like the popular Hamiltonian Monte Carlo (HMC). We gave a theoretical justification for the NP-iMCMC algorithm and put NP-iMCMC into action by introducing the Nonparametric HMC (NP-HMC) algorithm, a nonparametric variant of the HMC sampler. This NP-HMC sampler works out-of-the-box and can be applied to virtually all useful probabilistic models. We further improved NP-HMC by applying the techniques specified for NP-iMCMC to construct irreversible extensions that have shown significant performance improvements against other existing inference methods.

Keywords: HMC
MCMC
involutive MCMC
probabilistic programming
inference algorithm
Advisor: Ong, CH
Generating tools for the characterisation of cell surface proteins

Cell migration depends on cell surface molecules that work together to define the precise direction and position of the migrating cell. To understand the cells’ communication with their environment, the signaling networks that are formed between cell surface proteins are being explored. The determination of the structures of the individual proteins, as well as the complexes they form, is essential for the comprehension of these signaling networks. Recently, an interaction between the morphogen receptor Glypican 3 (GPC3) and the Uncoordinated-5 receptor D (Unc5D) was discovered. The crystal structure of the complex revealed an octamer of four GPC3 and four Unc5D molecules. Evidence in the literature about the two proteins points to a function of this newly discovered interaction in cell migration.
In my DPhil project, I developed tools to characterise the GPC3-Unc5D interaction and understand its role in cell migration. Nanobodies against GPC3 were characterised, and their effects on the GPC3-Unc5 interaction were investigated using biochemical, biophysical, and structural biology techniques. Two nanobodies were identified as potential research tools, one that enhances and one that inhibits the GPC3-Unc5 interaction. They were effectively employed in functional in vitro and in vivo experiments, which revealed the importance of the GPC3-Unc5 interaction in neuronal cell migration during cortical development and in neuroblastoma collective cell migration. In addition to the nanobodies, I also contributed to the design and characterisation of non-binding GPC3 and Unc5 mutants. These mutants were used as tools, together with the nanobodies, in functional experiments, and their contribution was critical for understanding the Unc5-GPC3 complex function in vivo.
In a side project during my DPhil, I worked on an adhesion G-protein coupled receptor (GPCR). This adhesion GPCR has functions in cell-cell communication through its intracellular signaling and adhesion properties, and data indicate its important role in the central nervous system development. In this project, I worked towards the structural characterisation of this adhesion GPCR and the protein construct design, expression and purification for this project are presented in this thesis.

Keywords: x-ray crystallography
uncoordinated-5 receptor (UNC5)
protein-protein interaction
nanobody
glypican-3 (GPC3)
Advisor: Seiradake, E
Higgins, M
British policy towards Israel and the Arab-Israeli dispute, 1951-1954

Written from the perspective of a student of British diplomatic history, rather than that of an orientalist, this thesis questions the unidimensional assumption, based mainly upon the literature about the Suez Crisis of 1956 and its origins, that the British, and Eden in particular, were more sympathetic to the Arab States, if not altogether hostile to Israel, in the early nineteen-fifties.
The method adopted in the writing of this thesis is thematic rather than chronological. Six principle themes have been selected, with the introduction and particularly the conclusion attempting to put the six chapters into a coherent whole. This thesis is based predominantly on the profusion of primary material available in the Public Record Office in London and the more modest quantity of documents in the Israel State Archives in Jerusalem.

Keywords: conflict
dispute
Great Britain
Arab-Israeli dispute
Arab-Israeli conflict
Israeli
Arab
Israel
Arab-Israeli
foreign relations
Advisor: Peele, G
How can GIS contribute to the development of 'Powerful Knowledge' in the Geography Curriculum?

This investigation examines Michael Young’s concept of powerful knowledge and considers whether Geographical information systems (GIS) present an opportunity for accessing such knowledge in the geography curriculum. The concept of powerful knowledge may produce fresh impetus to encourage more use of GIS in secondary education if the benefits are visible. To this end, the study also investigates the ease to which GIS tasks can be implemented in lessons. This small-scale evaluative project takes a class of year Nine students through a mapping exercise using ESRI’s ArcGIS interface, and then by way of questionnaires determines whether the knowledge accessed could be seen to be powerful, using Maude’s (2018) ideas as a framework. Similarly, interviews with a colleague establish whether such lessons could and should be incorporated into the syllabus more regularly. Results suggest that GIS and digital mapping allow pupils to access knowledge which could be considered powerful and that both practitioner and pupils enjoyed their completion. The project concludes by proposing that GIS activities be used more in geography lessons, whilst appreciating that some of the historical barriers to their implementation no longer exist.

Keywords: MLT
MLT 2021
Examining the extent and role of implicit bias within the religious education classroom

Implicit biases within education exist amongst both staff and students. The primary reasons for such biases exist due to the postcolonial condition, which has resulted in colonial influence that is systemically embedded amongst institutions such as schools. Within the context of the religious education classroom, using the Harvard Implicit Associations Test (IAT) education practitioners have the ability to measure and reduce the implicit biases demonstrated by staff and students. Students and staff tend to demonstrate implicit biases which demonstrate an automatic preference towards majority races and religions, but using decolonised models of curricula, staff have the potential to reduce such biases.

Keywords: MLT
MLT 2021
What impact does linking the affective dimensions of teaching to behavioural, cognitive and emotional engagement have on key stage four boys? 

Student engagement in a school context is often spoken about in a holistic sense rather than specific types of engagement. The aim of this practitioner research is to establish how breaking engagement into three different types - cognitive, behavioural and emotional - impacts on each type of engagement and engagement as a whole. This study investigates how the different engagement types interrelate through classroom-based strategy implementation and is measured through qualitative and quantitative data taken prior to and post strategy. The strategies applied are all dimensions that are within the control of the individual classroom teacher. This research will help practitioners and researchers to gain a further understanding into specific engagement types and strategies that can be used within the classroom and how to use them most effectively. The study found that increasing emotional engagement had the largest increase on engagement overall, whereas focussing solely on cognitive engagement can be detrimental to the other engagement types. The study took place in 2019, pre-pandemic, and the results may be different had the study been undertaken during, or following, the disruption of the pandemic.

Keywords: MLT
MLT 2021
In what ways does pupil consultation improve teaching and learning within a Humanities department?

The research investigates the opportunities that can arise for the improvement of teaching and learning through the use of student consultation. The key theme that emerges from the literature is that if it is implemented correctly, student consultation can bring many benefits to both teachers and students. This small-scale evaluation project was designed to understand if benefits could be seen through a pilot study in the Humanities department of my school over the course of an 8-week period. The research project was hampered by the impacts of COVID-19 and so only parts of the data collection could take place. Analysis was undertaken and links can be seen between the literature and the data collected with key themes emerging that often agreed with previous research. Students had constructive pieces of advice for the improvement of teaching strategies, prep setting strategies and marking and feedback, which suggests that if a complete research cycle was undertaken, positive strides could be made towards the improvement of teaching and learning.

Keywords: MLT
MLT 2021
Novel phosphorus precursors to group III-V semiconductor nanoparticles

The development of novel phosphorus precursors to group III-V semiconductor nanoparticles is described in this thesis. An overview of semiconductor nanoparticles, colloquially referred to as quantum dots (QDs), is presented in Chapter 1, including strategies for the preparation of InP QDs from typical phosphorus precursors.
Chapter 2 explores the reactivity of the parent phosphinecarboxamide (H2PC(O)NH2) in solution towards common InP QD precursors. The preparation of InP clusters and a novel N-functionalised phosphinecarboxamide using H2PC(O)NH2 is discussed. Both H2PC(O)NH2 and N-functionalised phosphinecarboxamides are found to be effective sources of PH3 in solution upon thermal decomposition in pyridine at 105oC.
Chapter 3 describes the use of an N-functionalised phosphinecarboxamide as a novel air-stable phosphorus precursor to core/shell In(Zn)P/ZnS QDs. A synthetic protocol is optimised to afford core/shell In(Zn)P/ZnS QDs with size-dependant photoluminescence emission maxima between 550 and 650 nm, with full width at half maxima (FWHM) between 68 and 128 nm.
Chapter 4 explores the reactivity of N-, N,N-, and P-functionalised phosphinecarboxamides in solution. The effect of phosphinecarboxamide side-chain functionalisation on reactivity is also discussed.
Finally, Chapter 5 discusses the use of functionalised phosphinecarboxamides for the preparation of In(Zn)P/ZnS QDs and the unique size control that they afford. Carboxylate functionalised phosphinecarboxamides are used to prepare core/shell In(Zn)P/ZnS QDs with size-dependant photoluminescence emission maxima between 550 and 620 nm and FWHM between 83 and 114 nm. Additionally, the unexpected use of a P-functionalised phosphinecarboxamide as an air-stable precursor to size-uniform InP QDs is described, which display a photoluminescence maximum at 546 nm and a FWHM of 75 nm.

Keywords: ZnS
characterisation
QDs
core shell
nanocrystal
InP
phosphinecarboxamide
indium phosphide
magic-sized clusters
phosphorus precursor
quantum dot
InP QD
heterostructured
seminconductor
zinc sulfide
air-stable phosphorus precursor
nanoparticle
synthesis
PH3
phosphine
shell
phosphaurea
air stable
InP/ZnS
clusters
precursor
photoluminescence
in-situ
Advisor: Davis, J
Goicoechea, J
Structural and biophysical study of the KlebC import mechanism

The cell envelope of Gram-negative bacteria hosts many different protein machineries. These protein machineries are used by bacteria to perform different functions, such as cell division and nutrient acquisition. TolC is a trimeric protein that anchors at the OM and extends into the periplasm. TolC is used as a channel forexporting protein toxins and xenobiotics out of the cell but is also hijacked by bacteriocins as an import channel. This unique double-sided function of TolC has drawn interest to understand its roles in different biological processes and apply them to combat increasingly serious global antimicrobial crisis. The exploitation of TolC by a group B bacteriocin, KlebC, was studied using biochemical, biophysical and structural methods. It was previously discovered that the Ton system, known for its role in nutrient acquisition, is required to uptake KlebC into cells. Although the interactions between different group B bacteriocins and their outer membrane receptors have been elucidated, there has been no published studies on the interaction between group B bacteriocins and periplasmic TonB. This study has successfully demonstrated binding between KlebC and TonB, by analytical size exclusion chromatography and isothermal titration calorimetry. A binding affinity of 66 μM was measured between KlebC and TonB. The structure of the complex waspredicted by Alphafold 2.0 and validated by mutational approaches. To fully understand the uptake mechanism of KlebC, the ternary KlebC translocon (KlebC-TolC-TonB) was assembled in nanodiscs. Grids, containing the KlebC translocon, wereoptimised for single-particle cryogenic electron microscopy data collection and analysis for future structure determination of the complex.

Keywords: bacteriocin
gram-negative bacteria cell envelope
Advisor: Kleanthous, C
Khalid, S
A qualitative examination of cybercriminal governance in China

Profit-driven cybercrime has evolved into a sophisticated industry, inflicting millions of dollars in losses on the world economy. However, limited research has been conducted on the extra-legal governance of this industry, particularly in China, one of the world's most prominent cybercrime hotspots. This study, based on comprehensive fieldwork in China from 2020 to 2022 and an analysis of both primary and secondary data, seeks to address this gap. It endeavours to answer the question: How is the cybercrime industry governed in China? In line with previous research on extra-legal governance, this study finds that Chinese cybercriminals have developed a series of private governance systems, encompassing both self-governance and third-party governance, to facilitate their business interactions. In addition, this study offered three main new findings that can be added to our understanding of extra-legal governance. Firstly, self-governance is notably effective in online marketplaces due to the swift transmission of information, thus diminishing the necessity for third-party governance in the cybercrime market and the use of violence. Secondly, cybercriminal firms tend to be less predatory than traditional criminal firms, likely attributed to the reduced need for territorial resources. Lastly, cybercriminals can relocate to countries where protectors are present and continue their illicit activities remotely, with protection being more likely offered when the inflicted harm does not impact the protector's own country’s residents, and the political and economic gains outweigh the costs. This availability of protection could potentially elucidate the ongoing global dispersion of cybercriminals.

Keywords: criminal governance
criminal cooperation
cybercrime
extra-legal governance
organised crime in China
Advisor: Varese, F
Lusthaus, J
How do we teach a knowledge rich primary science curriculum in an exciting way?

Research has shown that fewer pupils are choosing to pursue science in the later years of their education. One key reason for this is that pupils’ attitudes towards learning science become more negative. Debate exists about when this reported decline occurs, but some suggest that pupils’ attitudes to science begin to change towards the end of their primary education. One way to counteract this may be through teaching exciting lessons that are rich in scientific knowledge. This study interviewed year 5/6 pupils (ages 9-11), surveyed primary school teachers and conducted an intervention lesson series, which pupils were surveyed on, to explore ways of making knowledge rich science lessons exciting for pupils. Three task types were investigated during the intervention lesson series: talk tasks, inquiry-based learning and drama. The findings showed that all three task types made science lessons exciting for the pupils but to differing degrees, with drama tasks proving especially effective. This study also found that practical activities were highly important to both pupils and teachers for making science learning exciting, although it highlighted potential issues surrounding the effectiveness of how practical activities are used in science lessons. Issues surrounding the teaching of science such as time, space, resources and topics, were also raised and explored. The findings have impacted the future approach to science at the setting school.

Keywords: MLT
MLT 2021