VictorJuiz/thesis huggingface dataset:
Standardisation and variation in Latin orthography and morphology (100 BC - AD 100)

The period 100 BC – AD 100 is often seen by scholars as the time when the 'standard' form of educated Latin was established. Standardisation, according to some, was the defining process for the fixing of written language and written norms. Once established, these written norms, we are led to believe, remained unchanged for the rest of the Antiquity.
This study addresses this alleged standardisation of Latin in 100 BC – AD 100 by studying variations in spelling and morphology. Elimination of variation is a central part of establishing a standard language, while continuing variation characterises lack of standardisation. By studying variation in a diachronic perspective, therefore, we are able to assess the evidence for standardisation or lack thereof.
Complete standardisation can be achieved mainly in spelling: therefore, the study of spelling is central for determining the existence of any standardisation movement. The first part of the thesis is dedicated to studying spelling variation in high-register formal inscriptions, where standardisation ought to be most evident. We discuss variation of the type maximus/maxumus, variant spellings ei and i for /ī/ and variation between assimilated and non-assimilated spelling of prefixes. A separate chapter addresses the spelling reform of Claudius. The second part of the thesis focuses on cases of morphological variation in literary and non-literary texts (variation between quis and quibus in the dat./abl. pl. and variation between active and deponent forms of verbs).
The study of these cases of variation should add to our knowledge of language development in this period and provide a basis on which to begin a reassessment of standardisation in Latin. Language attitudes of literary authors and authors of nonliterary texts, which are relevant for the question of standardisation, will also be considered. My overall conclusion is that it is easy to exaggerate the importance of any standardising, and that it is important not to mix up uncontrolled linguistic change, which is a phenomenon of any language, and change, or fixing, that is the result of the conscious and deliberate efforts of language purists.

Keywords: Latin language
Latin linguistics
history of Latin
Advisor: Adams, J
Statistical analysis of Likert data on attitudes

Researchers interested in measuring people's underlying attitudes towards an object (e.g., abortion) often collect Likert data by administering a survey. Likert data consist of surveyees' responses to statements about the object, where responses fall into ordered categories running from 'Strongly agree' to 'Strongly disagree' or into a 'Don't Know / Can't Choose' category. Two examples of Likert data are used for illustrative purposes. The first dataset was collected by the author from American and British graduate students at Oxford University and contains items measuring underlying abortion attitudes. The second dataset was taken from British and American responses to the 1995 National Identity Survey (NIS) and contains items measuring underlying national pride and immigration attitudes.
A model for Likert data and underlying attitudes is introduced. This model is more principled than existing models. It treats people's underlying attitudes as latent variables, and it specifies a relationship between underlying attitudes and responses that is consistent with attitudinal research. Further, the formal probability model for responses allows people's interpretation of the response categories to differ. The model is fitted by maximising an appropriate likelihood.
Variants of the model are used to analyse Likert data in three contexts; in each, the method using our model compares favourably to existing methods. First, the model is used to visualise the structure underlying the abortion attitude data. This method of visualization produces more sensible plots than analogous multivariate data visualization methods. Second, the model is used to select the statements whose responses (in the abortion attitude data) best reflect underlying abortion attitudes. Our method of statement selection more closely adheres to attitude researchers' stated aims than popular methods based on sample correlations. Third, the model is used to investigate how underlying national pride varies with nationality in the NIS data and also how underlying abortion attitude varies with gender, religious status, and nationality in the abortion attitude data. Unlike methods currently used by social scientists to model the relationship between attitudes and covariates, our method controls for the effects of differing response category interpretation. As a result, inferences about group differences in underlying attitudes are more robust to group differences in response category interpretation.

Keywords: attitudes
attitude measurement
Likert scale
Likert data
Advisor: Ripley, B
Investigating the N-linked glycan specificity of bacterial endo-beta-N-acetylglucosaminidase S

Endoglycosidase (Endo) S, secreted by bacterial pathogen Streptococcus pyogenes, is an important immunomodulatory enzyme which specifically hydrolyses the functionally important N-linked complex biantennary glycan found at Asn297 on the CH2 domain of fragment crystallisable (Fc) on human immunoglobulin G (IgG). Deglycosylation of IgG Fc leads to complete loss of binding to cellular Fcγ receptors (FcγRs) thus abolishing antibody dependent cellular cytoxicity (ADCC) and prolonging bacterial survival. Here, the N-linked glycan specificity of Endo S was further investigated using unnatural Nlinked glycans. Recombinant Endo S was expressed and purified and its specificity for different N-linked oligo-, high-mannose, and complex type glycans was studied using MALDI-TOF analysis. Furthermore, Endo S specificity for core fucosylated N-linked complex glycans on human IgG was also investigated. These studies revealed that Nlinked oligo- and high-mannose glycans are resistant to Endo S hydrolysis and that the presence of α-1,6 linked fucose in the chitobiose core is not essential for Endo S activity. These studies further revealed that the N-linked glycan specificity of Endo S is reciprocal to that of other known endoglycosidases namely Endo A and Endo H. Taken together, the resistance of these engineered N-linked oligo- and high-mannose glycans on IgG to Endo S digestion opens up the possibility of using these antibodies as a potential therapeutic for autoimmune diseases.

Keywords: specificity
IgG
Endo S
Streptococcus pyogenes
Advisor: Davis, B
Non-parametric workspace modelling for mobile robots using push broom lasers

This thesis is about the intelligent compression of large 3D point cloud datasets. The non-parametric method that we describe simultaneously generates a continuous representation of the workspace surfaces from discrete laser samples and decimates the dataset, retaining only locally salient samples. Our framework attains decimation factors in excess of two orders of magnitude without significant degradation in fidelity.
The work presented here has a specific focus on gathering and processing laser measurements taken from a moving platform in outdoor workspaces. We introduce a somewhat unusual parameterisation of the problem and look to Gaussian Processes as the fundamental machinery in our processing pipeline. Our system compresses laser data in a fashion that is naturally sympathetic to the underlying structure and complexity of the workspace. In geometrically complex areas, compression is lower than that in geometrically bland areas. We focus on this property in detail and it leads us well beyond a simple application of non-parametric techniques. Indeed, towards the end of the thesis we develop a non-stationary GP framework whereby our regression model adapts to the local workspace complexity.
Throughout we construct our algorithms so that they may be efficiently implemented. In addition, we present a detailed analysis of the proposed system and investigate model parameters, metric errors and data compression rates. Finally, we note that this work is predicated on a substantial amount of robotics engineering which has allowed us to produce a high quality, peer reviewed, dataset - the first of its kind.

Keywords: non-stationary
Iterative Closest Point
3D mapping
laser
range sensing
dataset
point cloud
mobile robotics
Gaussian Process
online representation
Advisor: Newman, P
Active mountain-building in Mongolia and Iran

In this thesis I use a multi-disciplinary approach to investigate two areas of active mountain-building within the Alpine-Himalayan belt: the Altai range in western Mongolia, and the Zagros mountains in southern Iran. I begin by studying a clustered earthquake sequence that struck a previously unrecognised fault zone in the NW Altai mountains in 2003. By combining seismology and field observations with satellite radar interferometry (InSAR), I attempt to unravel the detailed history of faulting in time and space. Differences between body-wave and InSAR-based models prevent me from matching individual seismic events with individual fault segments, and I explore the cause of these discrepancies. In the following two chapters, I establish late Quaternary slip-rates on major right-lateral and thrust faults in the eastern part of the Altai. In particular, I explore the use of in situ-produced cosmogenic Be-10 and Optically Stimulated Luminescence (OSL) for dating offset alluvial fans and river terraces. My results suggest that faulting has migrated toward the eastern margin of the range from the high, interior Altai, presumably in response to stresses introduced by topography. In the final, main chapter, I investigate a link between buried reverse faulting and surface folding in the Zagros Simply Folded Belt. Using surface displacements measured with InSAR, I show that a major anticline on Qeshm Island was uplifted during an earthquake in 2005. However, the pattern of uplift is discordant with the growth of neighbouring folds, preventing us from establishing a simple connection between faulting and folding. All in all, my work demonstrates the importance of using several techniques in parallel when studying regions of active continental deformation.

Keywords: faulting
Earthquakes
tectonics
Advisor: Parsons, B
Walker, R
England, P
On the significance of neutral spaces in adaptive evolution

Evolutionary dynamics arise from the interplay of mutation and selection. Fundamentally, these two processes operate at different levels: Mutations modify genetic information (the genotype), which is passed from parent to offspring. Selection is triggered by variation in reproductive success, which depends on the physical properties (the phenotype) of an organism and its environment. Thus the genotype-phenotype map determines if and how mutations can lead to selection. The aim of this dissertation is to incorporate this map explicitly into a theoretical description of evolutionary dynamics. The first part of the analysis presented here is concerned with the static properties of simple models of these maps, which are studied using exhaustive enumeration. The two most important observations are phenotypic bias – some phenotypes are realized by many more genotypes than most other phenotypes – and the existence of neutral spaces – genotypes with the same phenotype can often be reached from each other by single mutational steps.
The remainder of the dissertation provides a theoretical description of evolutionary dynamics on and across neutral spaces. Two different mean-field approximations lead to simple analytic results for the first discovery of alternative phenotypes, highlighting the importance of phenotypic bias: Rare phenotypes are hard to find by evolutionary search. These results are used to discuss the relationship of robustness, the ability to withstand mutational change, and evolvability, the ability to create variation through mutation. Several types of fluctuations beyond the mean-field limit are studied, both theoretically and in simulations. The discrete structure of genotype spaces can lead to strong correlations in the spectra of phenotypes produced, increasing the probability that a particular phenotype is fixed in the population quickly after its discovery. Structural correlations between genotypes can increase the effect of phenotypic bias, while the qualitative features of the mean-field description remain valid. All these results highlight that neutral spaces impact evolutionary dynamics in many non-trivial ways, in particular by favouring phenotypes of high accessibly, but comparably low fitness over those phenotypes that are highly fit, but very hard to discover.

Keywords: genotype-phenotype map
evolvability
evolutionary dynamics
mutational robustness
Advisor: Louis, A
Investigation of the effects of IGF-1 receptor blockade on  chemoresistance of advanced melanoma

Advanced melanoma poses a major therapeutic challenge, and despite the development of recent promising therapeutic agents, resistance to treatment remains a problem. Until recently, despite low response rates, alkylating agents dacarbazine and temozolomide (TMZ) were the standard of care for the treatment of advanced melanoma. The cytotoxic effects of these agents relies upon the formation of alkylated base lesions such as O6-methylguanine (O6MeG), which is repaired by a protein implicated in TMZ resistance called O6-methylguanine-DNA methyltransferase (MGMT). Failure to resolve such alkylated bases results in DNA replication-associated double-strand breaks (DSBs). The type 1 insulin-like growth factor receptor (IGF-1R) mediates a number of characteristics common to cancers, including proliferation and survival, and evidence suggests it may also contribute to resistance to many anticancer agents. The aims of this study were to test whether melanoma cells could be sensitized to TMZ by small molecule IGF1R inhibitors, and to explore the mechanism of any chemosensitization. This study found an association between basal IGF1R phosphorylation and in vitro TMZ resistance in seven MGMT-proficient melanoma cell lines, suggesting that IGF1R activation may be linked with TMZ resistance. Furthermore, IGF1R inhibition caused dose-dependent sensitization of melanoma cells to TMZ, regardless of BRAF mutation status. This reduction in cell survival was not accompanied by an increase in apoptosis, but rather Chk2 activation and an accumulation of cells in the G2/M phase of the cell cycle, suggesting a possible effect of IGF1R inhibition on DNA repair. IGF1R depletion was found to increase MGMT protein levels and activity, but this effect was not seen in IGF1R inhibited cells. In addition, IGF1R inhibition was not epistatic with MGMT inhibition, and IGF1R inhibition reduced survival of TMZ treated MGMT-null cells. This suggested that TMZ sensitization by IGF1R inhibition was independent of MGMT. IGF1R inhibition did however cause an increase in the accumulation of TMZ-induced RPA foci, and delay in resolution of RAD51 foci. Together with the finding that IGF1R inhibition reduced survival in PARP inhibited melanoma cells, these results suggested that IGF1R inhibition influenced DSB repair by homologous recombination. Finally, the combination of IGF1R inhibition with TMZ was tested in a mouse model and was found to be tolerable. TMZ or IGF-1R inhibitor alone caused minor reduction in melanoma xenograft growth rates (rate reduction by 13% and 25% respectively), while combination treatment caused supra-additive growth delay (72%) that was significantly different from other treatment groups (p<0.05). The findings of this study suggest IGF1R inhibition as a possible option in overcoming alkylating drug resistance in melanoma.

Keywords: alkylating agent
melanoma
IGF-1 receptor
chemotherapy
resistance
Advisor: Macaulay, V
Middleton, M
The distribution and dispersion of herpetofauna in lowland farmland: with a focus on the common toad (Bufo bufo)

Concern over unexplained population declines in the common toad (Bufo bufo) has led to it being recognised as a priority species for conservation research. The general consensus among herpetologists is that the most important cause of the declines seen as part of a global amphibian extinction crisis is habitat loss and degradation.
The aim of thesis is to investigate the effect of habitat availability and quality on common toad populations in the United Kingdom, with a particular emphasis on the effect of land under agricultural use. I use occupancy modelling, resource selection function modelling and genetic techniques to determine the effects of both terrestrial and aquatic habitat on common toads. Based on my findings, I consider the impacts of habitat at local, landscape and national scales.
My research revealed the importance of pond density and presence of woodland in increasing relative probability of toad occurrence in the terrestrial habitat (Chapters 2 and 3) and the importance of water quality, woodland coverage and available terrestrial habitat coverage in determining common toad presence in ponds. The isolating effect of urban areas is demonstrated in Chapter 4 where Isolation By Barriers (IBB) explains genetic distance between common toad breeding populations better than Isolation By Distance (IBD). In Chapter 5 I again use the resource selection function for terrestrial habitat use developed in Chapter 3, to investigate the importance of terrestrial habitat availability in determining pond use by common toads at a national scale.
In my concluding chapter, I make recommendations for management and further research including consideration of potential interactions between the effect of habitat loss, fragmentation and degradation with other potential causes of common toad decline.

Keywords: habitat
Bufo bufo
agri-environment schemes
farmland
conservation
Advisor: Macdonald, D
High repetition rate tunable lasers

Copper vapour laser (CVL) pumped dye lasers offer a source of high power, kilohertz repetition rate, tunable narrow-bandwidth radiation suitable for many spectroscopic applications in the visible and infra-red. Furthermore, the nonlinear frequency conversion of CVL-pumped dye laser radiation extends the wavelength range of these laser sources into the blue and ultra-violet.
A series of experimental investigations have been undertaken to gain a physical understanding of the fundamental parameters necessary for the optimization of the CVL-pumping of dye lasers. Issues addressed include the influence of the CVL cavity design, the pump beam polarization and geometry, the dye oscillator cavity design, the choice of grating materials, and the dye flow rate. A model based on the rate equation analysis of the kinetic processes relevant to optical amplification in dye lasers has been developed, and the results have been used to design amplifiers with extraction efficiencies in excess of 45 %.
As a result of the aforementioned investigations, three commercially available pulsed dye lasers have been successfully optimized for CVL-pumping for the first time. Once modified, these dye lasers have typically shown conversion efficiencies in excess of 20%, with frequency bandwidths as narrow as 800MHz, and beam qualities approaching the diffraction limit.
The theory of second harmonic generation is reviewed, and a suite of corresponding computer models have been developed to form the basis for a coherent experimental investigation of UV generation using the CVL and CVL-pumped dye lasers. CVL SHG has been demonstrated in jS-barium borate (BBO) and lithium triborate (LBO), with SHG efficiencies in excess of 18% realized for the CVL 511nm line in BBO. For the first time, an experimental comparison of spherically and elliptically focused second harmonic generation has been undertaken. Optimized elliptical focusing is found to be up to 30% more efficient than using conventional spherical focusing in agreement with theoretical predictions.
The superior divergence and transverse coherence of CVL-pumped dye lasers, in comparison to those of the CVL, is reflected in the SHG efficiencies achieved in BBO, LBO and lithium iodate. Conversion efficiencies approaching 40% have been demonstrated in lithium iodate, with harmonic conversion coefficients approaching 2400mW/W2 realized at low input powers. The Boyd and Kleinman theory of SHG with focused Gaussian beams is found to provide an excellent description of SHG with CVL-pumped dye laser radiation, and accurately predicts the optimum strength of focusing and harmonic conversion coefficient. For the first time, sum frequency mixing (SFM) of the CVL with a dye laser has been demonstrated, and found to provide a potentially efficient source for tunable UV radiation.
Finally, the application of CVL-pumped dye lasers to resonant ionization mass spectrometry and tropospheric hydroxyl (OH) radical detection is discussed, and the spectroscopic potential of a frequency doubled CVL-pumped dye is demonstrated by recording the absorption spectrum of OH at 308nm.

Advisor: Webb, C
The within- and among-host evolution of chronically-infecting human RNA viruses

This thesis examines the evolutionary biology of the RNA viruses, a diverse group of pathogens that cause significant diseases. The focus of this work is the relationship between the processes driving the evolution of virus populations within individual hosts and at the epidemic level. First, Chapter One reviews the basic biology of RNA viruses, the current state of knowledge in relevant topics of evolutionary virology, and the principles that underlie the most commonly used methods in this thesis. In Chapter Two, I develop and test a novel framework to estimate the significance of phylogeny-trait association in viral phylogenies. The method incorporates phylogenetic uncertainty through the use of posterior sets of trees (PST) produced in Bayesian MCMC analyses. In Chapter Three, I conduct a comprehensive analysis of the substitution rate of hepatitis C virus (HCV) in within- and between-host data sets using a relaxed molecular clock. I find that within-host substitution rates are more rapid than previously appreciated, that heterotachy is rife in within-host data sets, and that selection is likely to be a primary driver. In Chapter Four I apply the techniques developed in Chapter Two to successfully detect compartmentalization between peripheral blood and cervical tissues in a large data set of human immunodeficiency virus (HIV) patients. I propose that compartmentalization in the cervix is maintained by selection. I extend the framework developed in Chapter Two in Chapter Five and explore the Type II error of the statistics used. In Chapter Six I review the findings of this thesis and conclude with a general discussion of the relationship between within- and among-host evolution in viruses, and some of the limitations of current techniques.

Keywords: within-host evolution
evolution
computational biology
phylogenetics
virology
molecular evolution
Advisor: Pybus, O