VictorJuiz/thesis huggingface dataset:
Avian malaria in the montane tropics

Understanding the unequal distribution of life on earth is a fundamental goal of ecology and evolutionary biology. Past efforts to explain large-scale patterns in diversity have tended to focus on two broad classes of explanation, one invoking the importance of abiotic factors (i.e. climate and vegetation) and the other biotic (i.e. competition); but neither has proven entirely adequate. Parasites are a major but poorly understood component of life that may offer some answers. Yet despite widespread theoretical support and some empirical evidence, the role of parasites in explaining patterns in the diversity, distribution, and abundance of species remains largely untested in natural communities. In this thesis I use a mega-diverse elevation gradient of birds as a model system to study the role of avian malaria in explaining these macroecological patterns.
In the first data chapter I tested the extent to which patterns of infection across species is predictable. I found that the effects of host ecology and environment were weakly related to infection prevalence and were not consistent across different malaria lineages. Instead, I show that hosts coexisting with many close phylogenetic relatives consistently experience higher infection than evolutionarily distinct host species. In the second chapter I tested if parasite sharing may help explain these observed relationships and show that parasite sharing among host pairs declines with the time since divergence. Spatial contiguity between host pairs was also positively associated with parasite sharing. In the third chapter I tested how infection prevalence varies across species ranges in accordance with expected variation in host abundance. I show that birds are more likely to be infected at the centre of their elevation range, where host abundance is expected to be highest. Intriguingly, I also found that the incidence of host infection is unrelated to the position within the geographic range of the parasite. In the fourth data chapter, I tested whether parasites may regulate diversity by limiting geographic ranges of their hosts through ‘apparent competition’ in which a non-lethal parasite in a primary host, may be lethal in a secondary host. In support of this, I found that more observed bird ranges end at parasite infection zones than would be expected by chance.
Taken together, my results suggest that parasites may play a major role in shaping patterns in the distribution and diversity of species, over both ecological and evolutionary scales. This is likely to arise and be maintained by host parasite interactions in which distantly related hosts are less likely to be infected by local parasites than close relatives, thus promoting the build up of diversity locally. On the basis of my analyses, I conclude that across montane elevation gradients in birds, and across diversity gradients more generally, parasites are likely to play a crucial role in the origin and maintenance of high biological diversity
.

Keywords: parasite
community diversity
eccological uniqueness
avian malaria
host
phylogenetic uniqueness
Advisor: Tobias, J
Seddon, N
Hellgren, O
Suetonius on the emperor

A study of Suetonius' Lives of the Caesars as a gallery of portraits of Roman emperors. The object is to make sense of Suetonius' methods of depicting emperors as emperors and to ask what light is cast on contemporary perceptions of the role of the Emperor. In order to set the Caesars in context, the work is approached from three different angles, the literary, the social and the ideological.
The first part looks at the literary background of the Lives. The question here is of how far the rubric method and the actual choice of rubrics can be accounted for in terms of literary tradition as opposed to the author's understanding of what was significant about an emperor.
The second part considers the impact of the author's position in society on his presentation. An attempt is made to discover the viewpoint of one who was simultaneously an equestrian official and an antiquarian scholar. His view of society is related to his views of the emperor's place in society and his functions as an administrator.
The last part examines the relationship between his representation of the emperor and the ideals desiderated in or attributed to autocratic rulers. Discussion centres on the use of virtues and vices as categories of estimation and on their relationship to official and theoretical 'ideologies'. Since it is argued that Suetonius shares the views of other Roman sources, discussion of individual virtues and vices ranges far beyond the Caesars.
Characterisation of a novel group B oncolytic adenovirus, ColoAd1

Developing high potent oncolytic virus with multimodal antitumour capabilities is crucial for realizing the full potential of oncolytic virotherapy in cancer treatment. ColoAd1 is a novel replicating chimeric group B adenovirus recently bioselected from a large library of recombinant viruse. This thesis aims at evaluating the oncolysis ability of ColoAd1, characterization of its cellular activities and the corresponding responses from host tumour cells, elucidating the killing mechanism as well as exploring its potential applications in the advanced cancer therapy.
Among all oncolytic adenoviruses tested, ColoAd1 elicited the strongest cytotoxicity with a rapid killing kinetics in tumour cells. The virus displayed high infection efficiency, enhanced genome replication (compared to other adenoviruses) and strict selectively in tumour cells.The viral oncolysis also induced a bystander killing effect.
Investigation of the host cells responses during ColoAd1 oncolysis showed the virus mediated cell killing is not classic apoptosis but rather necrosis-like. The dying cells displayed the early cytoplasmic membrane leakage, falling intracellular ATP with a rise in calcium, disruption of the cell cycle and cellular DNA damage, with rapid release of progeny virions from the cell; on the other hand, ColoAd1-killing lacked the characteristic hallmarks of apoptosis. Autophagy may play a role in final execution of oncolysis but is not the main death mechanism. The cellular pathway involved in ColoAd1 oncolysis was further studied by using a panel of specific inhibitors. The results indicated the ColoAd1 mediated cell death is PARP- and RIP1- dependent and necroptosis could be the major death mechanism.
The highly oncolytic potency and special killing mechanism of ColoAd1 may have beneficial implication for advanced cancer therapies, including the possibility of circumventing drug resistance and invoking cancer immunotherapy.
The data in this thesis supported ColoAd1 as a novel potent oncolytic virus candidate. It promises to overcome the major drawbacks of Ad5 and therefore could have enhanced therapeutic efficacy in future clinical trial.

Keywords: group B
adenovirus
oncolysis
oncolytic viruses
Advisor: Seymour, L
Elucidating the role of GBA in the pathology of Parkinson's disease using patient derived dopaminergic neurons differentiated from induced pluripotent stem cells.

Heterozygous mutations in the glucocerebrosidase (GBA) gene represent the most common risk factor for Parkinson’s disease (PD), a disease in which midbrain dopaminergic neurons are preferentially vulnerable. However, the mechanisms underlying this association are still unknown, mostly due to the lack of an appropriate model of study. In this thesis, we aimed at elucidating the role of heterozygous GBA mutations in PD using a specific human induced pluripotent stem cell (hiPSC)-based model of disease.
First we developed a protocol for the efficient differentiation of hiPSCs into dopaminergic cultures, and extensively characterized the derived dopaminergic neurons which expressed multiple midbrain relevant markers and produced dopamine. Next we screened a clinical cohort of PD patients to identify carriers of GBA mutations of interest. Using for the first time hiPSCs generated from PD patients heterozygous for a GBA mutation (together with idiopathic cases and control individuals) we were able to efficiently derive dopaminergic cultures and identify relevant disease mechanisms. Upon differentiation into dopaminergic neuronal cultures, we observed retention of mutant glucocerebrosidase (GCase) protein in the endoplasmic reticulum (ER) with no change in protein levels, leading to upregulation of ER stress machinery and resulting in increased autophagic demand. At the lysosomal level, we found a reduction of GCase activity in dopaminergic neuronal cultures, and the enlargement of the lysosomal compartment in identified dopaminergic neurons suggesting a decreased capacity for protein clearance.
Together, these perturbations of cellular homeostasis resulted in increased release of α-synuclein and could likely represent critical early cellular phenotypes of Parkinson's disease and explain the high risk of heterozygous GBA mutations for PD.

Keywords: Parkinson's disease
heterozygous GBA-N370S
iPSC
dopaminergic neuron
Advisor: Wade-Martins, R
Unravelling the biological roles of charged carbohydrates

The phosphate and sulfate esters of carbohydrates are widespread in nature, where they partake in a variety of signalling roles. This thesis focuses on the involvement of trehalose-6-phosphate (Tre-6-P) in regulating plant growth, and the function of sulfated carbohydrates in the immune response.
In plants, Tre-6-P is a critical messenger that conveys environmental information for the control of metabolic state. Beneficial natural conditions lead to an increase in the in vivo concentration of Tre-6-P, which in turn triggers biosynthetic processes facilitating plant growth. However, the mechanism by which this effect is exerted is largely unknown. A thorough understanding of this fundamental signalling pathway could allow considerable improvements in agriculture. Recent evidence has found an interaction between Tre 6 P and a protein kinase system (SnRK1), mediated via an intermediary protein whose identity is unknown. Our efforts to identify this elusive protein are presented. Methodology is developed to allow the synthesis of Tre-6-P analogues for defining structure-activity relationships, with particular attention focused towards the desymmetrization of trehalose and the control of phosphate migrations. Tre-6-P is tethered to a solid phase resin allowing affinity extraction of putative intermediary factors. The 14-3-3 class of regulatory proteins is identified as a potential binding partner of Tre-6-P.
The mannose receptor (MR) is an essential element of the mammalian immune system. Expressed on macrophages, the protein can bind and internalize pathogens through their surface exposed carbohydrates. However, the receptor can also dimerize, upon which it is able to divalently bind to sulfated carbohydrates. The biological significance of this sulfate binding is poorly understood. Current hypotheses invoke a role for the sulfate mediated trafficking of MR dimers to areas of B-cell maturation for antigen presentation, thus linking the innate and adaptive defence mechanisms. In any case, the dimerization of the MR is an essential prerequisite for interaction with carbohydrate sulfates. Methodology is required to probe this dimerization on the surface of cells under their native conditions. In this thesis, we use fluorescence microscopy to study the binding of various probes to macrophage and endothelial liver derived cell lines. Results of our initial investigations are presented that show internalization of the probes. The use of FRET imaging to directly probe the presence of MR dimers is studied.

Keywords: PHOSPHATE
SULFATE
TREHALOSE
ORGANIC CHEMISTRY
TREHALOSE-6-PHOSPHATE
MALDI
CARBOHYDRATE CHEMISTRY
SnRK1
MANNOSE RECEPTOR
Advisor: Davis, B
Adults' responses to infant vocalisations: a neurobehavioural investigation

Infant vocalisations are uniquely salient sounds in the environment. They universally attract attention and compel the listener to respond with speed and care. They provide a wealth of information to parents about their infant’s needs and affective state. There is a scientific consensus that early parenting has a profound impact on child development. In particular, the sensitivity with which parents respond to their infant’s communicative cues has been shown to affect cognitive and socio-emotional outcomes. The mechanisms underlying such sensitivity are not well understood.
In this thesis, adults’ sensitivity to infant cues will be considered in terms of two components, the ‘promptness’ and ‘appropriateness’ of responses, as originally conceptualised by Bell and Ainsworth (1972). Promptness of responses is considered in terms of adults’ ability to move with speed and effort after listening to infant vocalisations. Appropriateness, on the other hand, is considered in terms of adults’ ability to differentiate between functionally significant parameters in infant vocalisations. The effect of modifiable environmental factors on the promptness and appropriateness of responses is also investigated. Finally, a focused investigation of the brain basis of responses to infant vocalisations is presented.
Overall, findings demonstrated that infant vocalisations undergo privileged, specialised processing in the adult brain. After hearing an infant cry, adults with and without depression were found to move with greater coordination and effort. Adults were also found to be attuned to subtle parameters in infant cries. This sensitivity was shown to be affected by two participant-level factors, depression and previous musical training. Furthermore, this sensitivity could be enhanced through intervention, as evidenced by findings from short-term, perceptual discrimination training. The notion of privileged processing of infant vocalisations is further supported by evidence of early discrimination of infant sounds in a survival-related subcortical brain structure.
Future directions for this work include directly relating current experimental measures of adults’ responses to infant cues with parental sensitivity to infant communication during dynamic interactions. Translating current findings into applied settings would require an investigation of the effects of factors such as musical and perceptual training on sensitivity to infant cues in at-risk populations, such as mothers and fathers with depression. Lastly, an increased understanding of the brain basis of adults’ sensitivity to infant cues will provide insight into our greatest challenge: parenting our young.

Keywords: deep brain stimulation
depression
vocalisations
local field potential
infant
parent
Advisor: Kringelbach, M
Stein, A
New detectors for electron microscopy

Detectors for Electron Microscopy have traditionally used a scintillator to generate photons from fast electrons, which are then detected by a sensor. However, in recent years direct detection has become an area of interest due to the potential improvements to detector performance.
In this thesis various aspects of direct detection are presented. I will begin with simulations of direct detectors based on Joy’s model of straight trajectories between Rutherford scattering events, where signal is generated by inelastic scattering events. The effects of microscope operating voltage, detector thickness, a surface electrically dead layer and diode depth on detector performance are presented.
A prototype detector was developed using the DUOS sensor, two thicknesses of the sensor were produced a 50μm thick detector and a 20μm thick detector. EBSD results are presented which show how the use of a reactive ion etch to reduce the dead layer thickness of a mechanically thinned sensor improve the detection efficiency of a sensor allowing EBSD work to be carried out at operating voltages as low as 5keV.
The MTF and DQE of both thicknesses of DUOS sensor are measured at 80kV and 200kV, which show that there is little difference between the two thicknesses at 80kV, but at 200kV the thinner detector shows an improved MTF. The results are then and compared with the equivalent simulated detectors. I show how the high frame rate of a detector and rigid and non-rigid registration can be used to improve image quality, resolving the {331} lattice spacing which is not visible with a simple summation of frames.
Detectors using gallium nitride rather than silicon as the base semiconductor are simulated. The MTF at the Nyquist frequency for a GaN detector is double that of a Si detector at an operating voltages of 80kV due to the smaller interaction volume of an electron in GaN. However, at higher voltages the improvement is much smaller as most electrons pass through the detector.

Keywords: Electron Microscopy
DQE
MTF
Detectors
Advisor: Kirkland, A
The Commission of Eastern Enquiry in Ceylon, 1822-1837

With the emegence of an empire, many of the devices and instruments adopted for the governance of England, were extended beyond the seas to the colonies. One such device was royal commissions of inquiry. Royal commissions, the origins of which in England have been traced as far back as the time of the Norman Conquest, were utilised by the administration in England from time to time to investigate particular problems in colonies, and suggest ways and means of solving them. In the first empire, the American settlements received bodies of somewhat similiar nature on some occasions, but their true value was displayed only when the second empire was being founded. During the turbulent years of the French and Napoleonic wars the empire was continuously extended, but only after peace was established did it become possible for the ministers in England to take stock of the empire which had been acquired. What were the purposes of the empire, what were the nature and the conditions of the colonies conquered, in what manner should this new empire of a diverse and amorphous character be governed, were some of the numerous questions which faced them through the following years. These clearly emphasised above all the need to obtain information about the colonies. The information provided by their Governors did not prove to be adequate, and there was no possibility of officials at home acquiring the much needed information. To resolve the problem, they fell back upon the age old method: royal commissions of inquiry.
[Please see pdf. for full abstract.]
Degree completion in the UK: individual, institutional and contextual factors that explain students’ chances of educational success in British universities

Degree completion is as important as participation in higher education. To date, most of the research on this subject has investigated the association between socio-economic background and academic preparation to explain lower rates or non-completion. This thesis explores the role that individual, institutional and contextual factors have on degree completion chances.
The first empirical chapter uses an individual-level longitudinal dataset to study the role that attainment on entry and socio-economic background have on students’ chances of completion. The chapter finds that attainment on entry significantly affects students’ chances of degree completion. It also reveals, however, that attainment on entry does not completely explain the socio-economic differences in degree completion chances in the system.
The second empirical chapter examines the role that institutions have on students’ chances of degree completion. Like the first chapter, this one draws on the individual-level longitudinal dataset. Although the analyses discover institutional effects, they show them to have a small effect on the system.
The third empirical chapter examines the role that teaching has on the probability that students complete their degrees in higher education. The findings show that teaching has a small but significant effect on students’ chances of degree completion. Teaching effects take place only at the most selective institutions of the system.
The final empirical chapter examines the role that unemployment has on students’ decisions to complete a university degree. Using data from the Labour Force Survey, the research finds that higher unemployment rates have a positive effect on students’ chances of degree completion. This thesis contributes to the field by showing that stratification of higher education also translates to degree completion. The results confirm that selectivity and institutional effects are strongly associated. In addition, they show that where the institutional framework is concerned, there is a gradient for class effect in educational outcomes.

Keywords: Educational inequalities
Higher Education
Advisor: Mills, C
Comparing stochastic discrete and deterministic continuum models of cell migration

Multiscale mathematical modelling is one of the major driving forces behind the systems biology revolution. The inherently interdisciplinary nature of its study and the multiple spatial and temporal scales which characterise its dynamics make cell migration an ideal candidate for a systems biology approach. Due to its ease of analysis and its compatibility with the type of data available, phenomenological continuum modelling has long been the default framework adopted by the cell migration modelling community. However, in recent years, with increased computational power, complex, discrete, cell-level models, able to capture the detailed dynamics of experimental systems, have become more prevalent. These two modelling paradigms have complementary advantages and disadvantages. The challenge now is to combine these two seemingly disparate modelling regimes in order to exploit the benefits offered by each in a comprehensive, multiscale equivalence framework for modelling cell migration.
The main aim of this thesis is to begin with an on-lattice, individual-based model and derive a continuum, population-based model which is equivalent to it in certain limits. For simple models this is relatively easy to achieve: beginning with a one-dimensional, discrete model of cell migration on a regular lattice we derive a partial differential equation for the evolution of cell density on the same domain. We are also able to simply incorporate various signal sensing dynamics into our fledgling equivalence framework. However, as we begin to incorporate more complex model attributes such as cell proliferation/death, signalling dynamics and domain growth we find that deriving an equivalent continuum model requires some innovative mathematics. The same is true when considering a non-uniform domain discretisation in the one-dimensional model and when determining appropriate domain discretisations in higher dimensions. Higher-dimensional simulations of individual-based models bring with them their own computational challenges. Increased lattice sites in order to maintain spatial resolution and increased cell numbers in order to maintain consistent densities lead to dramatic reductions in simulation speeds. We consider a variety of methods to increase the efficiency of our simulations and derive novel acceleration techniques which can be applied to general reaction systems but are especially useful for our spatially extended cell migration algorithms.
The incorporation of domain growth in higher dimensions is the final hurdle we clear on our way to constructing a complex discrete-continuum modelling framework capable of representing signal-mediated cell migration on growing (possibly non-standard) domains in multiple dimensions.

Keywords: continuum
discrete
equivalence framework
cell migration
stochastic
position-jump
non-uniform domain
deterministic
Advisor: Maini, P
Baker, R
Erban, R