VictorJuiz/thesis huggingface dataset:
A commentary on Silius Italicus Book 1

The main part of the thesis is a commentary on Silius Italicus Book 1, concentrating on the poet's attempts to blend history into epic. Close scrutiny of his language reveals his awareness of the problems involved in writing historical epic, as he varies his diction and conventions at different stages of the book. The commentary also examines his manipulation of the historical tradition.
Excursus 1, The Structure, examines Silius' solution of the largescale problem of shaping his historical raw material into a poem that conformed to the conventions of proportion and harmony. It is suggested that he did not seek unity through a hero or by thematic means, but by superimposing a coherent pattern on to the events of the war.
Excursus 2, The Gods, investigates Silius' decision to retain the traditional epic divine apparatus. It is argued that such a decision is intelligible and not to be summarily dismissed as misguided. Any "failure" of the divine apparatus in Silius is a matter of practice, not of theory.
Climate change adaptation and tourism in the Mexican Caribbean

The Mexican Caribbean tourism sector is highly exposed to hurricane activity, yet coastal tourism is also a major driver influencing regional biophysical and social vulnerability to climate risks. Drawing on a political ecology approach and a vulnerability assessment, this study asks how experiences with extreme hurricane events in the Mexican Caribbean shape climate change adaptation in the regional tourism sector. This study uses multiple methods, scales and field sites to (a) examine how biophysical vulnerability to extreme hurricanes affects the tourism sector, (b) explain the changing conditions of social vulnerability linked to hurricane damage in the tourism sector and (c) assess the present and future opportunities and obstacles for adaptation planning.
The main findings show that the region is experiencing a phase of unprecedented high intensity hurricanes. It is uncertain, however, whether changes in hurricane activity exceed natural multi-decadal variability. Tourism is one major driver of land use changes which have resulted in some of the world’s fastest increase in coastal urban sprawl. Most tourism infrastructure is located in areas with the greatest exposure to hurricanes. Hurricane Wilma which hit the region in 2005 is the most expensive natural disaster in the history of the Mexican insurance industry. Hotels have showed a high ability to recover operations after hurricanes. There is a high penetration of insurance ownership in hotels and there is substantial mobilization of public and private financial and human resources during hurricane disasters. Hotel responses to hurricanes, however, tend to be reactive and autonomous. One important consequence of hurricanes is that hoteliers in the interest to reduce operational costs, fire those workers with the weakest labour rights. Thus, hotel workers suffer from ‘double exposure’, a situation where hotel workers are confronted with the consequences of climate change while simultaneously suffering the consequences of globalization and neoliberal policies which have reduced the power of unions and weakened access to social security. The Mexican government has created a national climate change strategy and its operational programme which has led to the consolidation of an adaptation organizational structures at the national and state levels. I conclude, however, that adaptation planning may not result in the necessary actions on the ground since local actors are not well integrated yet into such efforts.
This study shows the importance of regional adaptation research that takes into account perspectives from both the physical and social sciences. This study highlights the importance of interactions between local actors, the larger socioeconomic and political economy context to inform adaptation planning and policy.

Keywords: tourism
adaptation to climate change
climate change policy
Latin America
Mexican Caribbean
climate change
Mexico
Advisor: Liverman, D
Tompkins, E
New developments in the interpretation of dendrochronology as applied to oak building timbers

The ring-width data for 3313 oak samples with complete sapwood were studied from mainland Britain, together with 1067 additional samples from various other European locations. Regression analysis of the material showed that there was a relationship between the number of sapwood rings, the mean ring width of the heartwood, and to a lesser degree the number of heartwood rings present. A method of producing models using datasets where complete sapwood was available was devised, which produced individual felling date ranges for each sample. One model was found to be suitable for all of England and Wales from the Roman period to the present, and produced a success rate of 96%, with 94% of the samples tested giving a felling date range narrower than the 36-year empirically calculated range previously used.
Analysis in the variation of felling dates within individual phases of construction found a significant proportion of timbers had been stock-piled. A method was developed of combining individual felling date ranges using Bayesian methodology, and allowing for the possibility of stockpiling, dramatically reducing the usual empirically-derived felling date range. This reduction was as much as 90%, depending on the number of samples combined. Testing of this procedure with independent data has achieved a 95% success rate. Samples exhibiting extreme or sudden changes in growth rate were found to be unsuitable, as well as those from cathedrals due to their exceptionally long periods of construction.
The comparison of over 100 examples of dendrochronologically-dated buildings with independent dating evidence showed a good correlation between felling and construction dates. Analysis of these demonstrated that most structures were erected in less than half a year, and usually during the summer season.
The combination of the various aspects of this research has resulted in a better understanding of how medieval buildings were constructed, and allows an improved interpretation of tree-ring dates, including both precise and estimated felling date ranges.

Advisor: Professor Christopher Ramsey, J
Studies of rare gas halide lasers

This thesis presents the results of a study of the mechanisms responsible for limiting the laser pulse duration obtainable in xenon chloride lasers which are excited by UV-preionized, self-sustained gas discharges.
The xenon chloride laser system, the principal emission band of which is centred around 308 nm, belongs to the class of high pressure gas lasers known as 'rare-gas halides'(RGH). RGH lasers are now well known for their high peak power output at a number of wavelengths from 193 nm to 353 nm in the ultraviolet region of the spectrum. To date, however, they have only been operated in the pulsed mode with laser pulse durations of ~1000 ns for devices employing electron beam excitation and ~30 ns for devices employing transverse discharge excitation. There is no a priori kinetic limitation which prevents RGH lasers from operating in the CW mode, and an attempt to extend the duration of the laser pulse would enable the quality of laser output to be improved.
The laser pulse duration of a discharge excited XeCl* laser was extended by about one order of magnitude - to 270 ns FWHM - by the use of a distributed resistance electrode to stabilize the discharge. The typical gas mixture used in the laser was ~2 atm of Ne (buffer gas), ~25 mbar of Xe, and 2.5 mbar of HC1. However, the laser pulse duration obtained was considerably shorter than the 500 ns duration, 2000 A peak current, discharge excitation pulse.
The cause of this difference between the duration of the laser output pulse and the discharge current pulse was found by carrying out a comprehensive parametric study of the laser, combined with a detailed spectroscopic analysis and the results of a semi-empirical computer model. Two interrelated factors were identified as being responsible for the short duration of the laser output: namely, a temporal collapse of the discharge volume and a spatially non-uniform depletion of the HCl within this volume. The experimental results presented here contradict an earlier theory which ascribed the onset of discharge instabilities in RGH lasers to step-wise ionization of the minority rare gas atoms, and which attributed stability enhancement properties to the electronegative halogen gases used in RGH lasers.

Advisor: Webb, C
Dimensions of powerlessness

This inquiry into the nature of political powerlessness begins with a definition which posits that Q is politically powerless to the extent that it is unable to promote and defend its interests within authoritative processes of value allocation. Political powerlessness is said to derive from Q's lack of relevant power resources; and from T's exploitation of this deficiency through its exercise of power over Q. Contrary to pluralist assumptions, it is argued that T may exercise political power over Q both within and beyond formal arenas of value allocation: the determining factor is not where political power is exercised, but rather that it prevents Q from satisfying its interests within these authoritative arenas.
The above hypotheses are tested for their validity and utility by being applied to the experiences of the post-war agricultural work force in England. In particular, the study asks whether farmworkers' workplace powerlessness, as identified by Howard Newby in 'The Deferential Worker' (Penguin, Harmondsworth, 1979), has been compensated for by their Union's promotion and defence of agricultural workers' occupational interests at the formal, political level.
Part One provides a theoretical, historical and descriptive setting for the empirical study. Part Two determines the extent to which the efforts of the Union and of its external political allies to influence the relevant value allocating institutions have resulted in the successful promotion and defence of farmworkers' objective interests. These interests are defined as: earning high wages (Chapter Four); living in housing which is independent from employment (Chapter Five); and ensuring a reasonable standard of occupational health and safety (Chapter Six).
The study shows that the farmworkers' Union has been largely unable to compensate for its members' industrial weakness by taking political action. The Union's political powerlessness is attributed chiefly to its lack of relevant power resources; and to its resulting vulnerability to power exercises both within and beyond the formal political arena, all of which have weakened the Union within that arena. It is suggested finally that the Union's recent merger with the Transport and General Workers' Union provides farmworkers with access to new power resources which may allow for greater success in the future promotion of farmworkers' occupational interests.
Exon skipping peptide-pmos for correction of dystrophin in mouse models of duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal, muscle-wasting disorder due to mutations/deletions in the dystrophin gene. Whilst improvements in palliative care have increased the life expectancy of patients, cardiomyopathy and respiratory complications are still the leading causes of death. A potential therapy for the treatment of DMD is antisense oligonucleotides (AOs), which modulate dystrophin pre-mRNA splicing to restore the dystrophin reading frame and generate a truncated functional protein. Conjugation of AOs to cell penetrating peptides (CPP), such as Pip5e-, significantly improves delivery to skeletal muscles and to the heart, which is imperative given the impact of cardiomyopathy to mortality. However, it should be noted that the contribution of skeletal muscles, such as the core respiratory muscle, the diaphragm, in dystrophic cardiopulmonary function is poorly understood.
The specific aims of the work in this thesis were to (i) understand the effect of the diaphragm on cardiac function using magnetic resonance imaging (MRI), (ii) screen a number of derivatives of Pip5e (Pip6) in an effort to discover further promising peptides and define the properties integral to heart penetrating capacity, and (iii) assess whether Pip6-PMOs restore cardiac function (MRI) following a repeat, low dose regimen. In short, the specific restoration of dystrophin in the diaphragm of the dystrophic mouse model, the mdx mouse, did not improve cardiac function, highlighting the importance of a body-wide therapy. The screening of multiple Pip5e-PMO derivatives revealed 3 promising peptides with improved cardiac splicing capacity; however, serial deletions of amino acids from the central core resulted in the diminution of dystrophin restoration, possibly due to a reduction in hydrophobicity. Finally, the Pip6-PMO treatment regimen substantially restored dystrophin protein (28% in heart) and stabilised cardiac function, even with an increased work load. In conclusion, this study illustrates the importance of a body-wide treatment, such as the CPP strategy (Pip-PMO). These Pip-PMO conjugates demonstrate high dystrophin restoration in a number of muscles, including cardiac muscle, and have a beneficial effect on cardiac function.

Keywords: magnetic resonance imaging
Duchenne muscular dystrophy
antisense-olignucleotide
Advisor: Wood, M
Hammond, S
Essays in labour and behavioural economics

The entire literature on adverse selection in the labour market spawned by Greenwald (1986, Review of Economic Studies, 63(3)) has been built, somewhat unwittingly, on the assumption that firms forget the type of a worker after the worker quits. In many contexts, this assumption is implausible. The first three chapters of this thesis therefore explore an alternative approach to modelling labour markets with asymmetric information by assuming firms will never forget a worker's type.
The first chapter turns the standard Greenwald result on its head by showing that if the worker knows her own type and productivity is unchanging, the possibility of competitive wage offers from fully-informed previous employers means that adverse selection will never persist. Job changing frictions can cause a semi-separating equilibrium where the more productive workers have their type revealed whilst the least productive workers receive a pooling payoff. But even where asymmetric information persists there is no adverse selection because job changing frictions shield potential employers from the winner's curse. The second chapter investigates the robustness of the non-persistence of adverse selection result where previous employers are asymmetrically informed. The result is found to be robust where firms bid for the worker under a closed but not an open auction. The third chapter finds that, if workers are not sure of their exact value to their employer, there will be an adversely selected stream of job changers in equilibrium, even as the probability of a worker quitting for exogenous reasons approaches zero. Less able workers are quickly revealed as such, whilst more able workers have their type revealed gradually.
The fourth substantive chapter of this thesis investigates the widely observed paradox that, despite what traditional economics would lead us to believe, there can be such a thing as too much choice. The model provides a formal theoretical explanation for this phenomenon using the regret theory of Loomes and Sugden (1982, Economic Journal, 92(368)). When options are few it is shown that enlarging the choice set improves welfare, but when options are many, a "less is more" phenomenon emerges. In some cases, excess search options can decrease search.

Advisor: Malcomson, J
Epistasis in complex human traits

Epistasis (gene-gene interaction) is a universal component of common complex genetic traits. The identification and characterization of epistatic interactions are crucial to a full understanding of the complex genetic mechanisms that underlie human disease. The aim of this thesis is to examine epistasis in non-parametric linkage analysis of human complex traits, with an emphasis on the affected sibling pair (ASP) study design.
Following an overview of approaches that model and detect epistasis in linkage analysis of human complex traits, I present an extension of a two-locus nonparametric linkage method in ASPs. The new two-locus approach, Merloc, jointly models pair-wise interactions between susceptibility loci in different types of affected relative pairs and estimates of the most likely underlying genetic model for a pairwise interaction, implemented to genome-wide applications. To test the performance of the approach, Merloc was compared to two multilocus non-parametric conditional linkage approaches. Power and type I error rates under null, single-locus, and twolocus genetic models of epistasis and heterogeneity indicated that Merloc outperformed the other methods.
The method was applied to type 2 diabetes data to assess the evidence for epistasis between two susceptibility loci. Significant evidence for epistasis was obtained supporting previous findings from conditional interaction analysis. A search through the space of parametric two-locus models indicated that nine two-locus models best approximated the pair-wise interaction.
Genome-wide strategies to detect epistasis were also examined in this thesis and the simultaneous search for genome-wide interactions was explored in detail. Two-dimensional (2D) linkage scans were performed using Merloc in three complex traits, essential hypertension, autism, and type 2 diabetes. Several peaks were detected in the two-dimensional likelihood surfaces with genome-wide suggestive evidence for linkage. Extensive simulations were used to examine the distribution of the test statistic under the null hypothesis in the context of two-dimensional linkage scans.
Finally, two main extensions of this approach were considered - linkage approaches to examine more than two loci, and extending the method in this study to include a test of association.

Advisor: Farrall, M
MiR-215 regulates differentiation in colorectal cancer stem cells

Since the initial description of cancer stem cells (CSCs) as a self-renewing subpopulation of malignant cells with tumor-initiating capacity, a growing body of evidence has supported the existence of CSCs in virtually every tumor type. Our previous work in colorectal cancer has identified the transcription factor CDX1 as a key regulator of colorectal CSC differentiation. CDX1 expression is frequently lost in colorectal cancer, resulting in more aggressive, poorly differentiated tumors with higher proportions of CSCs. Many miRNAs have been implicated in tumor suppression and carcinogenesis, but the roles of miRNAs in differentiation, particularly in colorectal cancer, remain poorly understood. We began by identifying miRNAs downstream of CDX1 by using high-throughput small-RNA sequencing to profile miRNA expression in two pairs of colorectal cancer cell lines with stable CDX1 overexpression or knockdown. Validation of candidates identified by RNAseq in a larger cell line panel revealed miR-215 to be most significantly correlated with CDX1 expression. ChIP-qPCR and promoter reporter assays confirmed that CDX1 directly transactivates miR-215 transcription. MiR-215 is depleted in FACS-enriched CSCs compared to unsorted samples. Overexpression of miR-215 in poorly-differentiated, highly clonogenic cell lines causes growth arrest and a dramatic decrease in colony formation. miR-215 knockdown using a miRNA sponge causes an increase in clonogenicity and impairs differentiation in CDX1-high cell lines. Indeed, the effects of CDX1 expression on both gene expression and colony morphology can be attenuated by miR-215 inhibition, indicating that miR-215 is a functional mediator of CDX1. Microarray studies following miR-215 overexpression indicate that miR-215 induces terminal differentiation-associated growth arrest, due in part to direct silencing of BMI1 expression and de-repression of BMI1 target genes including CDKN1A. Our work situates miR-215 as a link between CDX1 expression and BMI1 repression that governs differentiation in colorectal cancer. We further characterize another miRNA-transcription factor axis in colorectal cancer, and we identify the novel miR-3189-3p as a potent effector of cell death with potential therapeutic implications.

Keywords: colorectal cancer
cancer stem cells
RNA biology
microRNAs
p53
Advisor: Bodmer, W
Miscible flow through porous media

This thesis is concerned with the modelling of miscible fluid flow through porous media, with the intended application being the displacement of oil from a reservoir by a solvent with which the oil is miscible. The primary difficulty that we encounter with such modelling is the existence of a fingering instability that arises from the viscosity and the density differences between the oil and solvent. We take as our basic model the Peaceman model, which we derive from first principles as the combination of Darcy’s law with the mass transport of solvent by advection and hydrodynamic dispersion. In the oil industry, advection is usually dominant, so that the Péclet number, Pe, is large. We begin by neglecting the effect of density differences between the two fluids and concentrate only on the viscous fingering instability. A stability analysis and numerical simulations are used to show that the wavelength of the instability is proportional to Pe^−1/2, and hence that a large number of fingers will be formed. We next apply homogenisation theory to investigate the evolution of the average concentration of solvent when the mean flow is one-dimensional, and discuss the rationale behind the Koval model. We then attempt to explain why the mixing zone in which fingering is present grows at the observed rate, which is different from that predicted by a naive version of the Koval model. We associate the shocks that appear in our homogenised model with the tips and roots of the fingers, the tip-regions being modelled by Saffman-Taylor finger solutions. We then extend our model to consider flow through porous media that are heterogeneous at the macroscopic scale, and where the mean flow is not one dimensional. We compare our model with that of Todd & Longstaff and also models for immiscible flow through porous media. Finally, we extend our work to consider miscible displacements in which both density and viscosity differences between the two fluids are relevant.

Keywords: viscous fingering
enhanced oil recovery
Saffman-Taylor
miscible
Advisor: Ockendon, J
Farmer, C