VictorJuiz/thesis huggingface dataset:
Endothelial activation in experimental metastasis models

The majority of cancer related deaths occur due to the invasive growth of metastatic lesions. In the early stages of metastasis, circulating cell interact with the endothelial cells to establish at a distant site. In inflammation endothelial activation results in induction of adhesion molecules on the endothelium that participate in the homing of leukocytes. Because of the interactions of metastatic cells with the endothelium, the question was whether some of the characteristic molecules of endothelial activation were induced during metastasis.
In vivo pulmonary metastatic models were used to characterize the expression profile of endothelial activation. Immunohistochemistry identified VCAM-1 to be induced on the pulmonary endothelium following tumour cell arrest. VCAM-1 upregulation was not observed prior to tumour cells arrest or within the first hours. In contrast, tumour cell arrest appeared to be required for endothelial activation, arguing against a mechanism analogous to leukocyte homing. The upregulation of VCAM-1 upon tumour cell arrest corresponded with the initiation of platelet clot formation around the tumour cell and recruitment of leukocytes to the site, both previously shown to be essential for metastasis. Disruption of both phenomena, either through genetic or pharmacological manipulation, demonstrated that in contrast to the recruited leukocytes, platelets were involved in inducing endothelial activation.
Another protein investigated was VAP-1. In contrast to VCAM-1, central to VAP-1 adhesive function is its enzymatic activity. Blocking the functions of either molecule highlighted their role in facilitating the recruitment of the leukocyte population to the tumour cell. Disruption of which led to a significant attenuation of metastasis. While VCAM-1 and VAP-1 function appears critical in the early steps of metastasis, their inhibition had no effect at later stages of pulmonary colonization.

Keywords: pulmonary metastasis
endothelial activation
coagulation
metastasis
VAP-1
VCAM-1
Advisor: Muschel, R
Gil-Bernabe, A
Frustrated magnetism in the extended kagome lattice

The extended kagome lattice, composed of alternating kagome and triangular layers, provides a novel geometry for frustrated magnetism. In this thesis, we study the properties of Heisenberg spins with nearest-neighbour antiferromagnetic interactions on this lattice. In common with many other models of frustrated magnets, this system has highly degenerate classical ground states. It is set apart from other examples, however, by the strong interlayer correlations between triangular layer spins. We study the implications of such correlations in both the statics and dynamics.
We characterise classical ground states using a flux picture for a single layer of kagome spins, a theoretical description that sets geometrical bounds on correlations. We quantify the divergent but sub-extensive ground state degeneracy by a Maxwellian counting argument, and verify this calculation by analysing the energy eigenvalues of numerical ground states. We explore the ground state connectedness but do not reach firm conclusions on this issue. We use the self-consistent Gaussian approximation (SCGA) to calculate static spin correlations at finite temperature. The results of these calculations agree well with elastic neutron scattering experiments. We derive an expression for the effective interlayer interaction between kagome spins by integrating out the triangular lattice spins.
We use linear spinwave theory to compute the spin excitation spectrum numerically. This shows encouraging similarity with inelastic neutron scattering data on a single-crystal YBaCo4
O7
sample, for a wide range of wavevector and frequency. This agreement shows that our spin model is a reasonable description of the physics, and suggests that this numerical technique might be useful for other geometrically frustrated magnets.
We study the dynamics analytically using the stochastic SCGA recently developed for the pyrochlore lattice. For technical reasons, we apply this technique on a related model, the stacked kagome lattice, rather than on the extended kagome lattice itself. From this we find slow relaxation at low temperature, with a rate Γ ∼ T2 compared to the faster Γ ∼ T scaling for the pyrochlore. Strikingly, in simulations of the dynamics on the extended kagome lattice by numerical integration of the semiclassical equations of motion, we find two different relaxation rates. Kagome layer spins relax more quickly than the triangular layer spins, having Γ ∼ T.

Keywords: frustrated magnetism
condensed matter physics
frustration
Advisor: Chalker, J
Developing relations between heritage conservation and urban revitalization: lessons from China

The overall aim of this thesis is to further understanding of the developing relations between heritage conservation and urban revitalization, by following the on-going World Heritage List nomination process for the Grand Canal in China. A review of the history and current situation of heritage conservation and urban revitalization establishes several key gaps in knowledge, for example, the field of systematic heritage conservation is still left blank. Taking advantage of the opportunity to work with this on-going nomination, the project examines the nature and challenges of heritage conservation research and practice for a heritage property of large scale and complexity, in the form of four linked studies. A critique of the national level nomination process to date illustrates the complexity of the task, and concludes that systematic heritage conservation has not been established as a concentrated and nation-wide heritage conservation activity in China. Focusing on the municipal level nomination process to date through a case study of the city of Zhenjiang (and Yangzhou as a comparator) establishes key reasons why one city has been more successful than the other in its participation in the World Heritage List nomination. A second case study, of the Xi Jin Ferry area in Zhenjiang (Jiangsu Province), provides a fuller account of the ways in which heritage conservation can contribute to, and work with, urban revitalization. Drawing on the case of Xi Jin Ferry, a theoretically-informed, but practically-viable approach to linking heritage conservation and urban revitalization is developed which learns from the past and looks to the future. Building on the empirical research projects, a critique of existing approaches to heritage conservation of large, complex sites leads to a proposal for a 'Heritage System' framework which would facilitate future evaluations and improve the prospects for on-going management of the Grand Canal.

Keywords: Heritage Conservation
World Heritage
The Grand Canal
Urban Development
Advisor: Viles, H
Biodiversity and conservation of a cultural landscape in the Western Ghats of India

The effects of landscape modification on the diversity of three contrasting groups of organisms - trees, birds and macrofungi that are biologically and ecologically different - are presented in this study. Three competing heuristic frameworks - island biogeography, metapopulation theory and landscape ecology - which have been advanced to study the fragmented landscapes, are discussed. The most suitable framework for studying biodiversity of the three groups of organisms in landscapes that are modified but not fragmented, is determined. Two contrasting approaches to biodiversity conservation - strict protection, and community-based conservation - are assessed and the conditions where they are suitable are determined.
Methods were used for rapid assessment of biodiversity and evaluation of landscape structure in Kodagu district, in the Western Ghats of India, where few data are available on the distributions of trees, birds and macrofungi and where detailed spatial information is not easily accessible. The comparisons of diversity across the three groups of organisms were made based a maximum value that permitted calculation of rarefied species richness for all samples. The shaded coffee cultivation in the study area has been instrumental in maintaining a continuous cover of native trees, despite longterm management by humans. As an ecological consequence of high tree cover, recognised landscape measures such as patch area and isolation are inadequate for explaining the patterns of diversity in Kodagu, unlike in many other insularised fragmented landscapes. A slight climatic gradient and an increasing degree of human disturbance in patches farther from the contiguous forest reserve influence tree diversity, in addition to the isolation of the patches from the reserve. The intervening matrix of coffee plantations is not a strong barrier to the movements of many forestdwelling birds. The influence of landscape structure on moisture content of the air affects sporocarp production of macrofungi. The integrity of the surrounding landscape matrix has an influence on diversity of birds and macrofungi within patches.
There is no congruence in diversity of the three groups of organisms studied. It is inferred that their differences in biological and ecological characteristics as well as their ranges of dispersal are responsible for the distinct patterns of distribution in the landscape. It is proposed that the strategy for biodiversity conservation should consider landscape-level conservation in order to capture the range of biodiversity that exists outside the formal reserve network in Kodagu. While maintaining the integrity of the strictly protected forest reserve; of traditionally conserved sacred forests; and of privately owned coffee plantations is essential, conservation practice should emphasise the involvement of local communities in management of landscape rather than imposing biodiversity conservation by force.

Advisor: Brown, N
Transnationalism and the Ghanaian diaspora in the UK: regional inequalities and the developmental effects of remittances at the sub-national level

This thesis presents a sub-national comparative analysis of the nexus between migration and development using the case of two disparate migrant communities (from the Upper East and Eastern regions of Ghana) in the UK.
The aim is to examine how inherent socio-economic inequalities prior to emigration impact on emigrants’ migration patterns, experiences, transnational activities and, ultimately, development outcomes at the micro and meso levels in the sending country. I argue, in this thesis, that the focus by development economists and most migration researchers on national-level macro analysis, as well as ‘location specific’ or single-site sub-national analysis, of the centrality of remittances to the enhancement of development at ‘home’ masks important nuances that are revealed by a comparative sub-national analysis.
This study uses a case study approach, whereby two migrant communities are investigated in detail within their pre-migration contexts. This allows for a deeper understanding of how transnational migration practices and/or processes are influenced by, and influence their context. It examines regional socio-economic inequalities and the interconnections between migration stage, spatial scales and local development.
This is achieved through a fifteen-month fieldwork using multiple research methods (key-informant interviews, in-depth structured and semi-structured interviews, surveys, participant observation and library research) in order to corroborate and triangulate findings from different sources. The thesis takes a spatiotemporal perspective in the migration-development nexus debate. Respondents for this research include economic migrants and refugees/forced migrants.
Among others, I conclude that globalisation and access to effective, yet relatively cheap, technological and communications facilities have bolstered individualistic migratory decision making thus reducing the centrality of the family or household as the unit of analysis in the causes and consequences of migration discourses.
Overall, the thesis aims to contribute a new, broader, and more inclusive perspective to migration research by arguing that migration-development phenomena are better appreciated through a comprehensive approach that encompasses migrants and sending communities and underlines the relationship between the two within a sub-national context.

Keywords: remittances
diaspora
transnationalism
development
inequality
sub-national
Advisor: Daley, P
Rogers, A
Studies of Fc receptors mediating IgG transport

Suckling rats passively acquire immunity by receptor-mediated uptake of maternal immunoglobulin G (IgG) from colostrum and milk. Receptors for the Fc region of IgG mediate its internalisation at the brush borders of endothelial cells of the proximal small intestine. The first chapter of this thesis describes the development of our knowledge of this process and the progress which has been made toward purifying Fc receptors which mediate materno-foetal transmission of antibodies in other species. Chapter 2 describes the methods used to isolate intestinal brush borders from neonatal rats and the development of a radioligand binding assay for their Fc receptors. In chapter 3 the use of these methods to investigate the distribution of binding sites for IgG in the small intestine of young rats is described. Two classes of binding site are resolved by their affinities (K

Advisor: Rees, A
Mechanisms of induction and modulation of the pro-inflammatory cytokine interleukin-1beta

Interleukin (IL)-1beta is a powerful pro-inflammatory cytokine with important roles in directing both innate and adaptive immunity. As a result, its production is tightly controlled, with the synthesis of an inactive form (pro-IL-1beta) and the requirement of a second signal. This induces the formation of the inflammasome, a macromolecular complex which mediates the maturation of IL-1beta into the bioactive cytokine. Given its significance, it is important to identify mechanisms of IL-1beta induction and modulation.
Firstly, we describe serum amyloid A (SAA), an acute phase protein with immunomodulatory properties, as a novel inducer of IL-1beta. Using cells from genetically modified mice, the molecular mechanisms responsible were dissected, demonstrating the receptors TLR2 and NLRP3 as required for this effect. By instilling SAA into mice, we also show that SAA is able to induce IL-1beta production in vivo.
Invariant natural killer T (iNKT) cells have also been shown to be important modulators of immunity, mediating both pro- and anti-inflammatory responses. iNKT cells are non-conventional T lymphocytes which recognise glycolipid in the context of CD1d, with the ability to interact with immature antigen presenting cells in an autoreactive manner. We link the regulatory ability of iNKT cells with IL-1beta production, showing that a low activation signal leads to the induction of an IL-13-dominated cytokine profile, as well as weak engagement of the CD40-CD40L pathway. We show for the first time that through these mechanisms, iNKT cells are able to dampen the secretion of IL-1beta upon subsequent stimulation of dendritic cells.
We hypothesise that this effect of iNKT cells is important in controlling inflammatory responses in vivo, and demonstrate exacerbated IL-1beta production and inflammation during influenza virus infection of iNKT cell-deficient animals. This novel anti-inflammatory property of iNKT cells may be harnessed in the therapeutic intervention of inflammatory disorders.

Keywords: Influenza
iNKT cells
IL-1beta
Inflammasome
Serum Amyloid A
Advisor: Cerundolo, V
Proteomics-aided search for extracellular matrix signatures of colorectal hepatic metastases ex vivo

Hepatic metastases are one of the most dangerous consequences of colorectal cancer, and their occurrence often results in poor prognosis and death. There is a need to improve survival and quality of life for patients with colorectal liver metastases.
In this work, we utilised mass-spectrometry method to identify proteins characteristic of mouse colorectal liver metastasis matrisome and further confirmed the expression of some of them in liver metastasis by immunohistochemistry.
We showed ex vivo that S100-A11 and annexin A1 are significantly overexpressed in hepatic metastases according to two different mass-spectrometry approaches. Further, we demonstrated that both S100-A11 and annexin A1 are expressed by cancer cell lines MC38, Pan02, HCT116, HT29, and LoVo in culture. Also, using human xenografts in mice, we were able to identify the source of these proteins by mass-spectrometry. Obtained immunohistochemistry images suggest that S100-A11 and annexin A1 may for a complex within the tumour, which is in agreement with literature data. We next confirmed by immunohistochemistry that annexin A1 is markedly overexpressed in colorectal hepatic metastases, as well as in human liver metastases, as compared to adjacent healthy tissue. Finally, we found that CD45+ but not Ly6G+ or CD11b+ cells express annexin A1 in colorectal hepatic metastases.
Our findings indicate that S100-A11 and annexin A1 may play a role in colorectal liver metastases development. Further in-depth research is necessary to elucidate their impact on tumour biology.

Keywords: extracellular matrix
matrisome
cancer
proteomics
Advisor: Muschel, R
Lim, S
A protocol-based study of L2 problem-solving processes in Korean university students'  L2 English writing

Writing has increasingly been emphasised in EFL classrooms in recent years, and Korea is no exception to this trend. The literature indicates that L2 writers experience language problems and attempt to solve them while converting their thoughts into another language. At the moment when learners struggle with a linguistic feature, they become aware of their lack of linguistic knowledge, and try to resolve the problem either by employing their own previously acquired knowledge sources, or by trying to access external knowledge sources. This problem-solving process may occur repeatedly during the L2 writing process.
The aims of the current research are threefold: first, it investigates what Korean university learners of English notice while they are writing in L2; second, it attempts to examine what variables are related to and affect learners' noticing during the L2 problem-solving process and; third, the knowledge sources employed by learners when they face language problems are analysed. In order to achieve these aims, 108 English major students were recruited from three high ranked universities in Korea; think-aloud protocols and stimulated-recall interviews comprised the primary means of data collection. All participants were asked to do a writing task in L2 and to verbalise their thoughts while producing written text. Building on the data gathered from the writing task, stimulated recall interviews were carried out in order to identify the sources of knowledge employed to resolve language problems.
The results of quantitative data analysis showed that the 108 participants in this study noticed approximately five language problems while writing an L2 text for 20 minutes, and verbally expressed many more lexical episodes than grammatical episodes. Regarding the relations between learner-related variables and noticing during the L2 writing process, previous study abroad experience and L2 proficiency affected learners' noticing. It was also found that L2-based verbal working memory had an effect when learners notice language problems in L2 text production, while L1-based verbal working memory had no effect. Moreover, qualitative data analysis indicated that the participants employed various types of knowledge sources in order to solve lexical or grammatical problems. It was found that both explicit linguistic knowledge sources, such as previously acquired L1-L2 translation word pairs, aspects of word knowledge (i.e., form, meaning, or use), episodic memory or analogy, and implicit knowledge sources, such as intuition, were used during the L2 problem-solving process.
Based on these findings, possible implications for L2 writing teaching are discussed, stressing the importance of providing many writing opportunities for students, and suggestions for future research are presented.

Keywords: L2 English writing
L2 problem-solving processes
Advisor: Walter, C
The measurement of radical species of atmospheric importance

The measurement of radical species in the atmosphere has far reaching implications. For example, it is necessary to both understand and improve our knowledge of radicals in the atmosphere to better inform the models which in many cases are the best way of predicting future air quality and climate change. Although many of these models are often not fully representative of all the processes occurring, they are the current best estimate based on the knowledge available, and can be useful in informing and directing future policy. The numerous, varied and interlinked cycles in the atmosphere are complex and only by obtaining data on specific species can accurate concentrations be retrieved and fed back into the models to improve their accuracy.
This work is concerned with the development and application of an ultrasensitive absorption spectroscopy technique to the problem of detection of the peroxy radical, HO₂. Noise Immune Cavity Enhanced Optical Heterodyne Molecular Spectroscopy (NICE-OHMS) combines cavity enhancement techniques (in order to increase the path length) with frequency and wavelength modulation techniques (in order to reduce the noise).
Following a discussion of the current detection methods used by atmospheric scientists to accurately measure and quantitative concentrations, some preliminary work on the detection of ammonia by a simple cavity enhanced absorption setup is presented. Pressure broadening and shift results were obtained for a number of ammonia transitions in the near infrared region, broadened by He, Ne, Ar, Xe, O₂ and N₂.
The bulk of the work concentrates on the implementation of the NICE-OHMS technique, presenting the first results with the use of an external cavity diode laser and a ring shaped cavity. A sensitivity of 4 x 10⁻¹¹ cm⁻¹ Hz⁻1/2 is obtained on an individual rovibrational transition of methane at 6610.063 cm⁻¹, along with a selection of other data from the atmospherically important molecules methane, nitrogen dioxide and carbon dioxide, highlighting the broad wavelength range over which the instrument can operate. Finally, the NICE-OHMS technique is used to probe HO₂ radicals formed through the photolysis of a Cl₂/CH₃OH/O₂ mixture. Following the creation and detection of HO₂ radicals in the cavity, and based on the optimum sensitivity outlined above, a minimum concentration of 1 x 10⁹ molecules cm⁻³ has been demonstrated.

Keywords: spectroscopy
FM
radicals
NICE-OHMS
HO2
Advisor: Hancock, G
Ritchie, G