VictorJuiz/thesis huggingface dataset:
E-cadherin loss of function in the murine intestine
Keywords: E-cadherin
genetics
intestine
murine

E-cadherin (Cdh1), is a major component of epithelial adherens junctions, binds the Wnt pathway effector β-catenin and is lost at the invasive edge of colon cancers. Crypt stem cells give rise to 4 cell lineages that, with the exception of Paneth cells, travel along the crypt-villus axis over 3 days and are shed by anoikis. Gain of function of the Wnt pathway by a mutation in Adenomatous Polyposis Coli (Apc) disrupts enterocyte turnover to result in adenoma formation. Homozygote null Cdh1 is embryonic lethal, and heterozygote Cdh1 can promote Apc1638N induced adenoma formation, but we lack models that assess additional functions of Cdh1 in the adenoma to carcinoma transition. The aim of this thesis was to evaluate the effect of Cdh1 loss of function in the murine intestine, including in the setting of Wnt pathway activation. To do this, germline and intestinal specific conditional Cdh1 loss of function models were generated.
Conditional homozygous deletion of Cdh1 resulted in embryonic lethality using Villin-Cre. In adults, homozygous Cdh1 loss using the tamoxifen inducible Villin-CreERT2 led to intestinal inflammation, bacteraemia and disrupted crypt-villus architecture. Combined conditional homozygous deletion of Cdh1 and Apc resulted in Wnt pathway upregulation assessed by β-catenin immunolabelling. Strain dependent effects of Cdh1 heterozygosity were apparent on the Apc heterozygote background: ApcMin/&plus; Cdh1&plus;/- (C57BL/6J) had no effect on survival or adenoma phenotype compared to littermate ApcMin/&plus;; Cdh1+/fl increased adenoma burden in Apc&plus;/fl Vil-Cre animals (B6D2/C57BL/6J).
Low frequency recombination of Apcfl/fl using Lgr5-EGFP-IRES-CreERT2 bypasses the loss of heterozygosity event relied on in heterozygous Apc tumour models achieving a large adenoma burden within 4 weeks. Cdh1 loss did not alter survival or adenoma phenotype in this model, including the development of large caecal tumours. Immunolabelling of tumours from Apcfl/fl Cdh1fl/fl animals showed persistent E-cadherin protein expression, suggesting incomplete recombination or that double homozygote enterocytes failed to survive. In vitro adenoma culture was used to test whether E-cadherin loss was incompatible with enterocyte survival in the setting of Wnt activation. Apcfl/fl Cdh1&plus;/&plus; and Apcfl/fl Cdh1fl/fl adenoma were cultured in matrigel and treated with an adenovirus expressing Cre recombinase under a CMV promoter (Ad-Cre). Ad-Cre had no effect on Apcfl/fl Cdh1+/+ adenoma growth. Ad-Cre treated Apcfl/fl Cdh1fl/fl adenoma organoids showed cells where E‑cadherin loss resulted in Wnt pathway upregulation as assessed by nuclear β-catenin and Axin2 expression, and epithelial mesenchymal transition shown by upregulation of fibronectin, twist and vimentin. This work supports a role for E-cadherin in modulation of the Wnt pathway. Further investigation is required to define the cell adhesion versus Wnt regulatory functions of E-cadherin.
Quantum magnets with strong spin-orbit interaction probed via neutron and x-ray scattering
Keywords: Neutron Scattering
Resonant Magnetic X-ray Diffraction
Frustration
Spin-Orbital Singlet
Spin Orbit Coupling
Condensed Matter Physics
Kitaev Hamiltonian
2D TAF

This thesis presents details of x-ray and neutron scattering experiments used to probe quantum magnets with strong spin-orbit interaction. The first of these systems are the three-dimensional iridate compounds, in which the three-fold co-ordination of IrO6 octahedra has been theoretically hypothesized to stabilize anisotropic exchange between Ir4+ ions. This novel interaction between these spin-orbital entangled, Jeff=1/2 moments is described by a Hamiltonian first proposed by Kitaev, and would be the first physical realization of this Hamiltonian in a condensed matter system. This thesis details the determination of the structure of a new polytype within these compounds, the 'stripyhoneycomb' γ-Li2IrO3. Furthermore, through resonant magnetic x-ray diffraction experiments on single crystals of β-Li2IrO3 and γ-Li2IrO3, an incommensurate, non-coplanar structure with counter-rotating moments is found.
The counter-rotating moment structure is a rather counter-intuitive result, as it is not stabilizied by Heisenberg exchange between magnetic sites, however, the Kitaev exchange naturally accounts for this feature. As such, these experiments reveal, for the first time, systems which exhibit dominant Kitaev interactions. The ordering wavevector of both β- and γ-Li2IrO3 polytypes are found to be identical, suggesting that the same magnetic interactions are responsible for stabilizing magnetic order in both materials, despite their different lattice topologies. Following this, the spinel FeSc2S4 is considered. Here, despite the presence of strong exchange between Fe2+,/sup>, and the fact that these ions sit in a Jahn-Teller active environment, the system does not order in the spin or orbital degrees of freedom. A 'spin-orbital singlet' has been theoretically proposed to describe the groundstate of this system, and here inelastic neutron scattering (INS) is used to probe the resulting triplon excitations. This allows determination of microscopic parameters in the single ion and exchange Hamiltonians, and moreover experiments in external magnetic field reveal the true spin-and-orbital nature of these triplon excitations. Finally, Ba3CoSb2O9, a physical realization of the canonical triangular antiferromagnet model is explored with INS and the high energy excitations from the 120 degree magnetic structure are found to display significant differences from those calculated by linear spin wave theory, suggesting the presence of quantum dynamics not captured in the 1/S linear spin wave expansion.
Risk factors for violence in psychosis: meta-analysis and Cox regression analyses investigating the association of established and novel risk factors for violence
Keywords: violence
risk factors

Current treatment practice guidelines in a number of countries mandate the assessment of violence risk in all patients diagnosed with schizophrenia. Although more than 100 different instruments have been developed to facilitate the assessment of violence risk, few have been specifically validated for use in those with schizophrenia. Recent work instead suggests that these instruments are typically associated with lower predictive validity in samples with schizophrenia when compared to that achieved in diagnostically heterogeneous samples, leading to concerns that these instruments omit risk factors that may be specific to the prediction of violence risk in this population. The present thesis therefore aimed to investigate the predictive validity of a number of risk factors for violence in those with schizophrenia. Firstly, to identify key risk factors for violence, a meta-analysis was undertaken, finding that although a number of criminal history risk factors are strongly associated with violence risk, nonetheless a number of risk factors rarely assessed by existing violence risk assessment instruments were significantly associated with violence in those with schizophrenia; most notably a history of attempted suicide. Results of this review also suggested that although the criminal history domain is most strongly associated with violence risk, nonetheless, there is considerable variability in the magnitude of association for the individual risk factors. Study two therefore aimed to investigate this variability and found that a history of violence was most strongly associated with subsequent violence. Study three aimed to identify whether suicidal behaviour, which has rarely been considered risk factors for violence in previous work, incrementally contributes to the prediction of violence. A simple risk model composed of young age, comorbid substance use disorder, previous violence, and a history of suicidal threats, explained as much predictive validity, as measured by the area under the receiver operating characteristic curve, as established risk assessment instruments such as the HCR–20, LSI–R, PCL–R, and VRAG. Current risk assessment approaches may therefore need revision in light of these findings.
Effects of environmental change on plant performance and plant-herbivore interactions
Keywords: climate change
secondary metabolites
soil pollution
plant defence
habitat fragmentation
environment dependence
metal hyperaccumulation
conservation

Global environmental change fundamentally affects plants and their interactions with other species, and this has profound impacts on communities and ultimately ecosystems. In order to understand the mechanisms involved, we need to elaborate on the combined effects of different global change drivers on multiple levels of plant organization, including the biochemical level (production of defence compounds), the whole organism, the population, and the plant-herbivore interaction level. This thesis investigates (1) the combined effects of factors related to climate change and habitat fragmentation on Brassica nigra and (2) the effects of Zn soil pollution on the heavy metal hyperaccumulator Noccaea caerulescens at these different levels. Common garden and greenhouse experiments with B. nigra applied drought stress and elevated CO2 to examine climate change impacts, while crossing treatments (inbreeding and between-population outbreeding) were used to investigate habitat fragmentation effects. Heterosis was lost under drought stress, and there were several interactive effects of the experimental treatments that varied within and among populations. In a greenhouse experiment with N. caerulescens, plants were grown on soil with different amounts of zinc. Plants had greater herbivore resistance when grown on Zn-amended soil, and invested more in herbivore tolerance when grown on soil without added Zn. In general, the results indicate that factors related to global environmental change have complex and interactive effects on different levels of plant organization. The findings are discussed in terms of their implications for ecology, evolution and conservation.
‘Artlessness and artifice’: Byron and the historicity of poetic form.
Keywords: poetics
romanticism
Byron

This thesis examines the conscious amalgamation of conflicting forms in Byron’s verse, and how these forms strain to create meaning in the processes of his poetry. Through a series of close readings and critical engagements with other Romantic poets, I endeavour to show how Byron’s poetry is often a rich site of contention between revolutionary and conservative impulses; both in its style and subject matter, and more often than not, in the complicated relationship between them.
Beginning with Byron’s problematic place in the English Romantic canon, I attempt to lay a foundation for my claims that for all his mistrust of closed systems and predetermined positions there remained an urging desire to reconcile definitive artistic contour with internal form-developing process in many of his most intense poetic engagements. In his efforts at reconciling an awareness of the ever-moving provisional nature of subjectivity with a deep-rooted demand for evaluative permanence, Byron habitually employs a hybrid poetic idiom which seeks to be both timeless and time specific.
In many of his most distinctive compositions, Byron holds a so-called ‘High Romantic’ lyrical mode, in which meaning is immersed in a persistent flowing rhythm, in tension with an eighteenth-century rhetorical style in which the careful placement of weighty words offsets its continuity to striking effect. By bookending my enquiry with Byron’s penetrating discursive conflicts with the naïve lyrical impulses of Wordsworth’s blank verse and what he perceived as the rhetorical appropriations of Keats’s poetry, I wish to demonstrate that Byron’s poetry enacts a curious meeting of nature and culture by a refusal to cleave them.
The contribution of non-structrual components to the overall dynamic behaviour of concrete floor slabs
Keywords: concrete
dynamics

Prestressing and the advent of high strength materials enable the construction of more slender floor slabs with lower values of natural frequency and damping. Under certain circumstances, the vibrations due to forcing frequencies of normal human activities can be annoying to the occupants. Since the occupants are both the source and the sensor, the vibration cannot be isolated and must be controlled by the structural system. At present, there is a limited knowledge about the overall dynamic characteristics of such concrete slabs, including contributions from individual structural and non-structural components. An extensive programme of modal testing on a slender one-way spanning 50% scaled post-tensioned concrete slab is described. Testing was performed using electromagnetic shaker, instrumented hammer, heeldrop, and walking excitations, to determine full floor dynamic characteristics. The tests investigated the effect on vibration performance of the level of prestress, and of various non-structural additions, including vibration absorbers and effect of occupants. It was found that an increase in prestressing force increases natural frequency and decreases damping due to closing up of microcracks. A model is presented to reflect these changes in terms of effective second moment of area. Cantilever partition tests showed energy to dissipate by swaying, and full-height partitions were seen to act as line supports leading to a significant stiffening of the slab. Analytical models are derived for both forms of partitions. Tests with false floors showed a significantly higher increase in slab damping when the floor panels rested on the pedestals, as opposed to being rigidly fixed to them. Although the addition of viscoelastic screed layers were not seen to have great effect in damping, an analytical model is derived which shows the advantages of using such layers. A TMD system was designed and installed on the floor, using plywood sheets, which led to a reduction in vibration response by as much as 80%. A theoretical model is derived to represent the TMD results and a design criterion is suggested. Finally, the effect of human-structure interaction is investigated. An analytical model shows the natural frequency of the body to be 10.43Hz with a damping of 50%. Results are also reported of tests on a full-scale field slab, confirming some of the findings of the model slab experiments. Broadly, the results show that contrary to popular belief, merely the presence of non-structural components does not necessarily enhance the dynamic behaviour of the system. The design of these components and nature of their installation are important factors affecting their contribution to the overall floor vibrational behaviour.
Mucosal associated invariant T cells and related CD161 expressing T lymphocytes
Keywords: CD161
immunology
MAIT cells
T lymphocyte
MDR1

The C-type lectin CD161 is expressed by a large number of T lymphocytes, with approximately a quarter of both T cell receptor (TCR)αβ+ and TCRγδ+ T cells expressing this marker. Within CD8+ T cells, a large proportion of these are comprised of Mucosal Associated Invariant T (MAIT) cells, a novel innate-like lymphocyte subset characterised by expression of a semi-invariant TCR together with high levels of CD161 (CD161++). These cells display a phenotype reflective of type 17 CD4+ helper T cells (Th17), which are also hallmarked by CD161 expression. Both MAIT and Th17 cells arise from preprogrammed progenitors, identifiable within umbilical cord blood by expression of CD161. Thus, CD161 appears to identify cells of a pre-determined and distinct phenotype. Whether this reflects a common transcriptional programme, developmentally induced within these cells, and further whether this extends to other CD161 positive T cells, was examined here by mRNA microarray analysis. This analysis identified a shared transcriptional signature and common innate-like function of all CD161 expressing T lymphocytes, and independent of TCR expression or lineage. Furthermore, a population of CD8+ T lymphocytes expressing lower levels of CD161 which overlap phenotypically with CD161++CD8+ MAIT cells was identified by both mRNA microarray analysis and mass cytometry (CyTOF); the CD161+CD8+ T cell population. TCR repertoire analysis, flow cytometry and cell culture experiments were utilised to investigate the origin of this subset, and its phenotype and function in both health and disease investigated in depth. This revealed a pre-programmed, tissue-resident memory population with potent effector functions. Both CD161++ MAIT and CD161+CD8+ T cells expressed high levels of the drug efflux pump MDR1, previously described to confer drug resistance to certain malignant cells. The significance of expression of this pump was hence investigated to determine its potential affect on the success of a variety of clinical therapies.
Painful stories: the experience of pain and its narration in the Greek literature of the Imperial period (100-250)
Keywords: suffering
the body
Imperial Greek culture
ancient novels
pain
ancient art
ancient medicine

This research project investigates the relationship between pain and the practices of explaining and narrating it to others. Current scholarship argues that the representation of suffering became, during the Imperial period, an increasingly effective and popular strategy for cultivating authority and that this explains the success of Christian culture’s representation of itself as a community of sufferers. One criticism of this approach is that the experience of pain has often been assumed, rather than analysed. Here, I investigate the nature of pain by attending to its intimate relationship with language; pain was connected to the strategies used to communicate that experience to others. I will show that writers throughout the Imperial period were concerned with questions about how to communicate pain and how that act of communication shaped, managed, and alleviated the experience.
I investigate this culture along three axes. Part 1, ‘The Sublime Representation of Pain’, investigates the way different authors thought about the capacity of sublime language and rhetorical techniques such as enargeia to effectively communicate pain. I argue that for writers such as Longinus, the sublime offers an opportunity to replicate the traumatic experience of the pain sufferer in the audience or listener—pain is narrated to the audience through a traumatic communicative mode. Contrarily, I show how authors such as Plutarch and Galen were particularly concerned to desublimate the representation of pain, reducing the affective power of images of pain by promoting the audience’s conscious engagement with the text or representational medium. Part 2, ‘Medical Narratives’, examines a conflict between Galen and Aristides over the way language and narrative signified or referred to painful experiences. I show how both writers negotiate the way pain destroys and transcends ordered, structured, narrative by engaging in a process of narrative translation. I will illuminate the difference between scientific, diagnostic narratives which explain and rationalise pain experiences (in the case of Galen) and those which attempt to give witness to the nebulous, ineffable qualities of pain. In Part 3, ‘Narrating Cures’ I investigate ancient practices of psychotherapy. I show how various philosophical consolations were underpinned by an understanding of the power of pain to continually return and overwhelm the individual. I show further that the Greek romances engage in a type of talking cure: the novels use narration and story-telling to help assert the protagonists’ distance from their past traumatic experiences and, thus, allow the individual to overcome their painful past.
Towards a new theory of financial intermediation
Keywords: monetary economics
financial intermediation

This thesis includes three interconnected essays which, building on the work by Hart and Zingales (2011), lay down the foundations for a new theory of financial intermediation. The first essay explains the Hart and Zingales (HZ) framework and shows that their results are not general. In the HZ model, there is a lack of simultaneous double coincidence of wants, and future income is not pledgeable. This implies that agents need money to trade. However, holding money entails an opportunity cost that leads to a waste of resources. Because of this inefficiency, pecuniary externalities have welfare consequences that private price-taking agents fail to internalize. I find that HZ's result, whereby the market produces inefficiently high levels of liquidity, cannot be generalized, because the conflict between private and social incentives to create money depends on agents' preferences. In the second essay I construct a framework that explains the transactions, precautionary and speculative demand for money. Again, the welfare analysis indicates that, depending on individuals' preferences, the market may produce inefficiently high or low levels of liquidity. The results also evidence that the speculative demand for money exists only when households are risk averse in their wealth. In that case, private and social incentives to hold money are stronger, but the market produces insufficient means of payment relative to the social optimum. The third essay introduces active financial institutions, and examines the role played by moral hazard in the provision of and demand for liquidity. Limited liability and the non-contractibility of bank investment policy induce highly levered financial institutions to invest in an inefficient gambling asset. I find that, when the probability that banks gamble is non-zero, the primary goal of public intervention is to address the moral hazard problem by restricting the creation of liquidity. Several policies to address this inefficiency are discussed and analyzed.
Data analysis and results of the upgraded CRESST dark matter search
Keywords: limit
CRESST
dark matter
WIMP
neutralino
robust analysis
OxRop

CRESST has an established analysis procedure to evaluate the energy of the events it detects, in an attempt to detect WIMP dark matter. It was shown that unless eight classes of contaminant event were removed prior to this analysis, the output energy spectrum would be significantly biased. For both scientific and practical reasons, the removal process should be blind, and a series of cuts were developed to flag these events automatically, without removing any true events. An event simulation package was developed to optimise these cuts. It was shown that noise fluctuations could also reduce CRESST’s sensitivity, so a noise-dependent acceptance region was introduced to resolve this. The upgraded CRESST experiment included a new electronics system to provide heating and bias currents for 66 detectors. This system was integrated into the CRESST set-up, and it was shown that the electronics contributed no extra noise to the detectors. Data with an exposure of 50 kg days were analysed using the cuts and the noise-dependent acceptance. The cuts were successful, with no contaminant event retained and a live time reduction of just 2.3%. The data were used to set an upper limit on the WIMP-nucleon cross section for elastic scattering with a minimum of 6.3 × 10^(−7) pb at a WIMP mass of 61 GeV. This is a factor of 2.5 better than the previous best CRESST limit.