VictorJuiz/thesis huggingface dataset:
Dissecting human haematopoietic progenitors
Keywords: haematopoietic progenitors
Haematopoiesis
Stem Cell Research
blood stem cells
Biomedical Sciences

Human haematopoiesis resembles a complex hierarchy, however most intermediate stages are only poorly defined. Efforts to characterise human progenitors have been inconsistent and failed to integrate previous knowledge. Furthermore, characterisation of normal progenitors has important implications in acute myeloid leukaemia (AML) biology. We previously established that leukaemic stem cells (LSCs) resemble the immunophenotypic progenitor compartments more closely than the stem cell fraction. Therefore, I set out to characterise human stem and progenitor cells (HSCPs) on phenotypic, molecular and functional level to complete the picture of human haematopoiesis.
I purified HSPCs based on their immunophenotype from adult bone marrow (BM) and umbilical cord blood (CB) to investigate steady state and neonatal haematopoiesis. To define differentiation potentials, HSPCs were subjected to functional in vitro assays on bulk and clonal level. Limit dilution assays were used to determine the frequency of cells with multiple differentiation potentials. RNA sequencing revealed underlying lineage priming and specific gene expression signatures.
I successfully characterized the incompletely defined Lin-CD34+CD38-CD45RA+ fraction in BM and CB, containing a CD10lo lymphoid-primed multipotent progenitor (LMPP) with T cell, B cell, NK cell, granulocytic and monocytic differentiation potential, and succeeded in placing it in the haematopoietic hierarchy with relation to similar lympho-myeloid progenitors defined by other groups.
This research lays the foundation to characterise early human progenitors with a comprehensive toolkit on a phenotypic, molecular and functional level. Findings from this thesis might provide knowledge about potential targets in LSCs.
Explaining the policies of the Baltic States towards Russia, 1994-2010
Keywords: Russia
foreign policy
Baltic states
energy
security

Despite their similar size, material resources, shared geopolitical conditions and common history, the three Baltic states of Estonia, Latvia, and Lithuania have pursued remarkably different policies towards Russia in the 1994-2010 period. Complex patterns of differentiation are evident across issue areas and over time.
Given the static structural similarities between the Baltic states, how can we explain their divergent policies towards Russia and the change in these policies over time? This puzzle informs the central research question of this study: Why did Estonian, Latvian, and Lithuanian foreign policies towards Russia diverge in the 1994 to 2010 period?
This work analyses the foreign policy of the Baltic states using typologies based on two axes: cooperative/adversarial and pragmatic/principled. Relying primarily on the liberal approach to international relations, the theoretical framework identifies six independent variables: the left/right political orientation of the government, instrumental usage of principled policies, the ethnic factor, business interests, membership in the EU and NATO, and, finally, Moscow’s own policies. It suggests that these factors played causal roles in determining Baltic policy towards Russia. Three case studies on the oil and gas sectors, as well as historical tensions, provide the empirical evidence to trace and explain the differentiated pathways of Baltic foreign policies.
The empirical analysis provides evidence to argue that due to domestic political differences Lithuania pursued the most adversarial and principled policy towards Russia. Estonia, by way of contrast, pursued cooperative and pragmatic policies regarding energy issues. On political questions, however, it maintained a principled and adversarial stance, though this was less pronounced that that of Lithuania. Finally, Latvia pursued moderately principled and relatively adversarial energy policies placing it in between Lithuania and Estonia. With regard to history, Estonia’s and particularly Latvia’s policies experienced a notable evolution from adversarial and principled to more cooperative and pragmatic policies. In sum, this work demonstrates that the typologies of Baltic policies differed across sectors and experienced both divergence and at times convergence in rhetoric if not policies.
Coherent unsteadiness in film cooling
Keywords: Film Cooling
Coherent Unsteadiness
Turbomachinery

Film cooling is vital for the cooling of the blades and vanes in the high temperature environment of a jet engine high pressure turbine stage. Previous research into film cooling has typically concentrated on its time-mean performance. However, results from other studies upon more simplified geometries, suggest that coherent unsteadiness is likely to also be present in film cooling flows. The research presented in this thesis, therefore, aims to characterise what coherent unsteadiness, if any, is present within film cooling flows.
Cylindrical and shaped cooling holes, located upon the pressure surface of a turbine blade within a large scale linear cascade, have been investigated. A blowing ratio range of 0.5 to 2.0 has been investigated, with either a plenum or perpendicular crossflow at the cooling hole inlet. Particle Image Velocimetry, high speed photography and Hot Wire Anemometry have been used to investigate the jet downstream of both cooling holes. The impact of crossflow at the hole inlet upon the flowfield inside both cooling holes has been investigated using Hot Wire Anemometry and a further numerical model solved by applying TBLOCK.
The results presented in the current thesis, show the existence of two coherent unsteady structures in the jet downstream of both the cylindrical and the shaped holes. These structures are called shear layer vortices and hairpin vortices, and their formation is dependent on the velocity difference across the jet shear layer. Inside the cooling hole coherent hairpin vortices also appear to occur, with their formation dependent on the direction and magnitude of the crossflow at the hole inlet. The coherent unsteadiness presented here is shown for the first time for film cooling flows, and recommendations to build on the current study, in what is potentially an interesting research area, are made at the end of this thesis.
Modelling embankment breaching due to overflow
Keywords: embankments
fluid dynamics
unsaturated soil
Navier-Stokes
breach
erosion

Correct modelling of embankment breach formation is essential for an accurate assessment of the associated flood risk. Modelling breach formation due to overflow requires a thorough understanding of the geotechnical processes in unsaturated soils as well as erosion processes under supercritical flow conditions. This thesis describes 1D slope stability analysis performed for unsaturated soils whose moisture content changes with time. The analysis performed shows that sediment-laden gravity flows play an important role in the erosion behaviour of embankments. The thesis also describes a practical, fast breach model based on a simplified description of the physical processes that can be used in modelling and decision support frameworks for flooding. To predict the breach hydrograph, the rapid model distinguishes between breach formation due to headcut erosion and surface erosion in the case of failure due to overflow. The model also predicts the breach hydrograph in the case of failure due to piping. The assumptions with respect to breach flow modelling are reviewed, and result in a new set of breadth-integrated Navier-Stokes equations, that account for wall shear stresses and a variable breadth geometry. The vertical 2D flow field described by the equations can be used to calculate accurately the stresses on the embankment during the early stages of breach formation. Pressure-correction methods are given for solving the 2D Navier-Stokes equations for a variable breadth, and good agreement is found when validating the flow model against analytical solutions.
Investigating the relationship between reading comprehension and semantic skill in children with English as an Additional Language: a focus on idiom comprehension
Keywords: EAL
idiom
vocabulary
reading

The current study builds upon previous UK EAL research by i. sampling EAL children who do not struggle with reading comprehension and ii. investigating participants’ semantic ability at the word, sentence and discourse levels. Four groups of 9-10 year old children were recruited: EAL Average Readers; EL1 Average Readers; EAL Above Average Readers; EL1 Above Average Readers. At the word level, EL1 participants significantly outperformed EAL participants on 2 out of 6 vocabulary measures administered (TOWK Expressive Vocabulary and Multiple Contexts). The results of an idiom comprehension measure (ICM) showed that EAL and EL1 participants did not differ in their ability to engage in semantic analysis or in inference from context (semantic ability at the sentence and at the discourse levels respectively). The EL1 Above Average group alone were able to use prior experience with English language idioms to their advantage when answering the ICM. For the EAL participants, relationships between performance on the TOWK Expressive Vocabulary and Multiple Contexts and on the ICM are stronger than for the EL1 participants. The relationships between performance on the ICM and on a measure of reading comprehension are also stronger for EAL than for EL1 participants. These results suggest the following: i. it is important to develop the vocabulary abilities of EAL children, as the relationships between word-level semantic skills and sentence/discourse level semantic skills are stronger for EAL children than for their EL1 peers; ii. the relationships between the knowledge and skills measured by the ICM (i.e. prior knowledge of English language idioms; semantic analysis; inference from context) and reading comprehension are stronger for EAL than for EL1 children, suggesting the importance of a comprehensive approach to the semantic development of EAL children.
Through the vale of darkness history in South Malakula, Vanuatu
Keywords: Oceana
Museum
Christianity

The thesis is a multi-vocal and localized history of the destruction of ancient Malakulan society through depopulation, migration and conversion, of the salvation of some people who gathered around Christian communities, and of the relationship of these people and their descendants to the places they have left and to the communities in which they now live.
The thesis brings a historical perspective to Vanuatu anthropology. Compared to earlier work in anthropological history in the Pacific by Sahlins, Dening and Bronwen Douglas, the main innovation in method is that all historical statements are set in their context, emphasizing the multiplicity of view points and revealing the significance of even minor variations which refer to important local issues, from land disputes to conversion to Christianity. Innovative use is made of funerary inscriptions, local maps and court archives, reflecting local forms of historical literacy.
The research is part of a growing interest in Christianity in Oceania, after a long neglect by anthropologists. This is the first historical anthropology of Vanuatu and perhaps Melanesia to consider the long-term social impact of the dramatic depopulation that accompanied the colonial expansion of Europeans. The abandonment of the interior of the island of Malakula and the weakening of traditional links with other islands have reduced the social space of Malakula to the original zone of contact with Europeans, the coastal areas and nearby small islands. I argue that Christianity allowed the people of Malakula to create a new form of sociality in response to these events.
The new society has its own time and space organized around the nuclear family meal and Sunday service, which were the two cornerstones of the conversion process, symbolizing the abandonment of former ritual activities and of the segregation of cooking fires according to ritual status. This process of cultural adaptation continues with the appropriation by villagers of the historical perspective of official courts favouring material evidence and legalistic principles in land disputes.
Earlier research on Vanuatu was dominated by the themes of 'kastom', a discourse on tradition opposed to Western ways, and of the rootedness of people in place. This double emphasis is linked to the fact that most fieldwork in the country was done in the 1970s before a fifteen years ban on foreign research after Independence in 1980. In the context of the struggle for Independence and the restitution of alienated land, Vanuatu people needed to emphasize indigenous values and attachment to land. Today, priorities on the ground have changed and new types of discourses have come to the fore emphasizing conversion to Christianity and adopting new concepts reflecting a shift in preoccupation from recovering colonial land to the relation between indigenous Christian migrants and original owners.
Ethnic fragmentation and social expenditure: notions of social solidarity and membership and the challenges of ethnic diversity
Keywords: multiculturalism
solidarity
political economy.
social expenditure
welfare state
ethnic fragmentation
citizenship

Does ethnic fragmentation negatively affect social expenditure? In this thesis, I examine why this research question, only partially tackled by the political economy literature, is also central for the social policy field. Using a sample of 156 countries, and controlling for variables that social policy theory postulate as essential to explain welfare provision, I offer evidence that higher levels of ethnic fragmentation lead to lower levels of social expenditure. On that basis, I present a theoretical framework that explores how this relationship can be explained. Ethnic fragmentation is presented as a variable that complicates the development of social solidarity and the notions of shared identity, and shifts social mobilisation from issues of economic redistribution towards ethno-cultural recognition. I also conduct a second series of statistical analysis that show that there is evidence to support the previous propositions. Additionally, using a different confirmatory test, I explore the correspondence between the levels of de-commodification that 18 welfare states provide, and the principles of blood descent (jus sanguinis) or civic ties (jus solis) that their respective national laws favour. The findings show that the welfare regimes with the most de-commodifying provision tend to favour ethno-cultural principles. Finally, I emphasize that the probable effects of ethnic fragmentation in an increasingly multicultural world, with its tendencies to put social integration and differentiation issues back on the agenda, are not a prediction of erosion of the welfare state, but an important element to take into account in the creation and robustness of shared identities and notions of common belonging when designing social policy.
Internal visions, external changes: Russian religious philosophy 1905-1940
Keywords: Russia
philosophy
emigre
theology

This thesis tests the hypothesis that between 1905 and 1940 Russian religious philosophy changed, and that this can be gauged by looking at how the meanings of four ideas (all-unity, sobornost', Sophia and Godmanhood) changed in that time. By looking at religious philosophy through these ideas we can better understand the intellectual climate of the period. The proposal that Russian religious philosophy should be considered a coherent school of thought and the hypothesis that it would be useful to look at its four central ideas are raised and challenged. The theory that a 'discourse' of religious philosophy united texts in this period is examined, and it is concluded that discourse theory can act as an aid in analysis of religious philosophy. Religious philosophy before the Revolution, the history of the Revolution and its influence on philosophy are examined and its productivity is explored. Post-revolutionary Russian religious thought focusing on the experience of exile is also examined, concluding that the political and social upheaval that Russians were subjected to in the first half of the twentieth century added to and complicated the meaning of the Revolution. Themes of isolation and exclusion become more prevalent in emigration, and religious philosophy also becomes more theological. The findings of this research are (1) that changes within religious philosophy took place and can be detected through the careful study of the ideas that make up this philosophy; (2) that these changes can only partially be attributed to external circumstances because internal constraints also affected the capacity of these ideas to change; (3) that these changes were part of a decline in production, popularity or relevance of religious philosophy; and (4) that it is possible to explain why certain areas of their use remained relevant while others became obsolete.
Preparation and characterisation of encapsulation magnetic metal iron oxide nanoparticles
Keywords: magnetic
magnetite
ferromagnetic
superparamagnetic
maghemite

One of the most challenging goals in nanoparticle research is to develop successful protocols for the large-scale, simple and possibly low-cost preparation of morphologically pure nanoparticles with enhanced properties. The work presented in this thesis was focused on the synthesis, characterisation and testing of magnetic nanoparticles and their potential applications. There are a number of magnetic nano-materials prepared for specific applications such as metal oxide nanoparticles encapsulated with various porous materials including Fe₃O₄/Fe₂O₃ coated with soft bio-organic materials such as glycol chitosan and bovine serum albumin and hard materials such as silica (SiO₂) and zinc sulphide (ZnS). The preparation of these materials was achieved principally by bottom-up methods with different approaches including micro-emulsion, precipitation, electrostatic and thermolysis processes.
The thesis also presents the uses of various analytical techniques for characterising different types of nano-materials including Attenuated Total Reflection Fourier Transformer Infrared Vibrational Spectroscopy (ATR-FTIR), Ultraviolet Visible- Near Infrared (UV-Vis-NIR) Spectroscopy, Zeta Potentiometric Surface Charge Analysis, Superconducting Quantum Interference Device (SQUID) and Vibration Sample Magnetometry (VSM) for magnetic analysis and powder X-Ray Diffraction (XRD) for crystallographic pattern analysis.
There are many applications of magnetic nanoparticles, including nano-carriers for biological and catalytic reagents. The magnetic nanoparticles can facilitate separation in order to isolate the carriers from solution mixtures as compared to many inefficient and expensive classic methods, which include dialysis membrane, electrophoresis, ultracentrifugation, precipitation and column separation methods.
There are six key chapters in this thesis: the first chapter introduces the up-to-date literature regarding magnetic nano-materials. The uses of magnetic nano-materials in drug binding and for protein separation are discussed in the second and third chapters. The fourth chapter presents the use of magnetic nanoparticle in conjunction with a photo-catalytic porous overlayer for the photo-catalytic reduction of organic molecules. The fifth chapter describes different analytical techniques used for the characterisation of nanoparticles and the underlying principles and the experimental details are also given. The sixth chapter summarises the results and provides an overview of the work in a wider context of future applications of magnetic nanoparticles.
The requirement for endothelial cell tetrahydrobiopterin in health and disease
Keywords: vascular disease
endothelial function
hypertension
Tetrahydrobiopterin
nitric oxide synthase

Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) function and nitric oxide (NO) generation. Augmentation of BH4 levels can prevent eNOS uncoupling and improve endothelial dysfunction in vascular disease states. However, the physiological requirement for de-novo endothelial cell BH4 biosynthesis in eNOS function remains unclear. We generated a novel mouse model with endothelial cell-specific deletion of GCH1, encoding GTP cyclohydrolase 1, an essential enzyme for BH4 biosynthesis, to test the cell-autonomous requirement for endothelial BH4 biosynthesis under physiological conditions and disease states in vivo.
Mice with a floxed GCH1 allele (GCH1fl/fl) were crossed with Tie2cre mice to delete GCH1 in endothelial cells. GCH1fl/flTie2cre mice demonstrated reduced NO bioactivity and significantly greater O2•- production. GCH1fl/flTie2cre aortas and mesenteric arteries had impaired endothelium-dependent vasodilatations to acetylcholine. Endothelium-dependent vasodilatations in GCH1fl/flTie2cre aortas were in part mediated by NOS-derived hydrogen peroxide, through soluble guanylate cyclase. GCH1fl/flTie2cre mice had higher systemic blood pressure than wild-type littermates, which was normalised by the NOS inhibitor, L-NAME.
In a lipopolysaccharide (LPS)-induced systemic inflammation model, GCH1fl/flTie2cre mice were partially protected against LPS-induced vascular dysfunction and hypotension compared to wild-type littermates. In the angiotensin II (Ang-II)-induced hypertension model, chronic Ang II infusion with a sub-pressor dose caused hypertension in GCH1fl/flTie2cre mice but did not alter blood pressure in wild-type littermates. Abdominal aortic aneurysms (AAA) in response to Ang II infusion were observed in GCH1fl/flTie2cre but not in wild-type mice. In pregnancy, GCH1fl/flTie2cre mice exhibited a loss of NOS-derived NO mediated vasodilatation, impaired uterine vascular adaptation, increased blood pressure and fetal growth restriction.
Taken together, these studies reveal that endothelial cell GCH1 and BH4 biosynthesis play a pivotal role in vascular function and blood pressure regulation in health and disease. Therefore, targeting vascular GCH1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of vascular dysfunction in patients with hypertension, AAA formation, septic shock and preeclampsia.