VictorJuiz/thesis huggingface dataset:
Hydroxylysine glycosides of corneal collagen

The universally found thin and uniform features of collagen fibrils constituting the corneal stroma (Craig and Parry, 1981), are essential for corneal transparency (Goldman et at., 1968). Corneal collagen contains more hydroxylysine glycoside than most collagens. In relation to the 'D stagger' arrangement of collagen molecules in the fibril, it was postulated that an excess of hydroxylysine - glycoside occurring in the 'overlap' region may limit fibril growth in the lateral direction by steric hindrance (Morgan et al., 1970).
The ultimate aim of this work was to pinpoint the sites of hydroxylysine-glycosides in the corneal collagen molecule, bearing in mind their location with respect to the fibril gap/overlap structure. Determination of hydroxylysine-glycosides were carried out on an automated amino acid analyser with the much reduced total analysis time of 1¼ hours per sample, using a two - buffer elution system developed during this work. Cyanogen bromide peptides αl CBS, αl CB7 and αl CBS were isolated and shown to contain 1.0, 0.97 and 1.21 residues of hydroxylysine-glycoside respectively per peptide.
It was also proven beyond doubt that peptide αl CBS has a higher electrophoretic mobility on SDS gels than peptide αl CB7, pointing to mistakes found in the literature.
In the 271 residue peptide αl CB7, analysis of tryptic and V8 - protease peptides led to the discovery of seven glycoside sites, the major site being at lysyl position 684 (numbers from start of αl[I] helical sequence). This lysyl position was found to be 46% hydroxylysine-glycoside, being 34% glucosylgalactosyl- hydroxylysine and 12% galactosylhydroxylysine. Of position 564, 17% was hydroxylysine-glycoside while of the other positions 573, 603, 648, 657 and 756, between 5% and 12% was hydroxylysine glycoside. In relation to the fibril gap/overlap structure, position 756 is in an overlap zone and position 564 is just inside one. Positions 573 and 684 are just inside a gap zone which also contains the other glycoside sites. Another possible site at position 729 was not found to contain hydroxylysine nor therefore, any glycoside.
These findings are discussed with respect to the possible role of hydroxylysine glycosides in limiting collagen fibril diameter. Comparisons of the amino acid sequences around the seven glycoside sites however gave no clues as to what makes some lysyl residues more susceptible to modification than others. The possible reasons for the high extent of lysyl modification in the cornea are also discussed.

Advisor: Harding, J
On auxiliary variables and many-core architectures in computational statistics

Emerging many-core computer architectures provide an incentive for computational methods to exhibit specific types of parallelism. Our ability to perform inference in Bayesian statistics is often dependent upon our ability to approximate expectations of functions of random variables, for which Monte Carlo methodology provides a general purpose solution using a computer. This thesis is primarily concerned with exploring the gains that can be obtained by using many-core architectures to accelerate existing population-based Monte Carlo algorithms, as well as providing a novel general framework that can be used to devise new population-based methods.
Monte Carlo algorithms are often concerned with sampling random variables taking values in X whose density is known up to a normalizing constant. Population-based methods typically make use of collections of interacting auxiliary random variables, each of which is in X, in specifying an algorithm. Such methods are good candidates for parallel implementation when the collection of samples can be generated in parallel and their interaction steps are either parallelizable or negligible in cost. The first contribution of this thesis is in demonstrating the potential speedups that can be obtained for two common population-based methods, population-based Markov chain Monte Carlo (MCMC) and sequential Monte Carlo (SMC).
The second contribution of this thesis is in the derivation of a hierarchical family of sparsity-inducing priors in regression and classification settings. Here, auxiliary variables make possible the implementation of a fast algorithm for finding local modes of the posterior density. SMC, accelerated on a many-core architecture, is then used to perform inference for a range of prior specifications to gain an understanding of sparse association signal in the context of genome-wide association studies.
The third contribution is in the use of a new perspective on reversible MCMC kernels that allows for the construction of novel population-based methods. These methods differ from most existing methods in that one can make the resulting kernels define a Markov chain on X. A further development is that one can define kernels in which the number of auxiliary variables is given a distribution conditional on the values of the auxiliary variables obtained so far. This is perhaps the most important methodological contribution of the thesis, and the adaptation of the number of particles used within a particle MCMC algorithm provides a general purpose algorithm for sampling from a variety of complex distributions.

Keywords: Markov chain Monte Carlo
Bayesian Inference
Sequential Monte Carlo
Advisor: Holmes, C
Cardiac stem cell therapy for infarcted rat hearts

Infarction irreversibly damages the heart, with formation of an akinetic scar that may lead to heart failure. Endogenous cardiac stem cells (CSCs) are a promising candidate cell source for restoring lost tissue and thereby preventing heart failure. CSCs would be most beneficial if administered soon after infarction, thus the aim of this project was to optimize CSC culture conditions to enhance their therapeutic potential for myocardial infarction. CSCs were isolated and expanded in vitro via the formation of cardiospheres to give cardiosphere-derived cells (CDCs). Neonatal rat CDCs were found to be heterogenous, containing cells expressing the cardiac stem cell marker, c-Kit, pluripotent cell markers, Oct-4, Sox 2, Klf-4 and Nanog, and early cardiac specific differentiation markers, Nkx 2.5 and GATA 4. Administration of CDCs to the infarcted rat heart increased the cardiac ejection fraction by 9%, capillary density by 9% and reduced scar volume by 33%, compared to the non-treated group. The proliferation rates and the expression of c-Kit were significantly decreased in CSCs isolated from aged rats and after extended culture in vitro, so, CSC culture was optimized using hypoxic preconditioning. Under hypoxia, CDC proliferation rates were 1.7-fold greater, and larger cardiosphere clusters were formed. Hypoxic CDCs had an increased cardiac stem cell population, in that c-Kit was increased by 220% and CD90 and CD105 were decreased by 55% and 35%, respectively, compared to normoxic CDCs. Further, hypoxia induced the expression of CXCR-4 (~3.2-fold), EPO (~3.0-fold) and VEGF (~1.5-fold), indicating that hypoxic preconditioning may stimulate stem cell homing and neovascularization in the infarcted myocardium. Notably, hypoxic CDCs were able to switch to anaerobic glycolytic metabolism and had approximately 80% lower oxygen consumption, suggesting that they may be better adapted to survive within the hypoxic infarct scar, compared with normoxic CDCs. Culture of CDCs with hypoxia-mimicking prolyl-4-hydroxylase inhibitors (PHDIs) using DMOG, BIC and a novel compound, EDBA, induced similar effects to hypoxic culture by increasing c-Kit, EPO, VEGF, CXCR-4, decreasing CD90 and CD105 and increasing glycolytic metabolism. However, PHDI treatment for 24 hours did not alter CDC proliferation rates and cells died after 24 hours. In conclusion, CDCs are a potential cell source for therapy after myocardial infarction and their therapeutic potential can be enhanced using hypoxia or PHDI-preconditioning techniques.

Keywords: cardiac stem cell therapy
myocardial infarction
prolyl-4-hydroxylase inhibitors
hypoxic stem cell culture
Advisor: Clarke, K
Davies, K
Carr, C
Modelling human decision under risk and uncertainty

Humans are unique in their ability to flexibly and rapidly adapt their behaviour and select courses of action that lead to future reward. Several ‘component processes’ must be implemented by the human brain in order to facilitate this behaviour. This thesis examines two such components; (i) the neural substrates supporting action selection during value- guided choice using magnetoencephalography (MEG), and (ii) learning the value of environmental stimuli and other people’s actions using functional magnetic resonance imaging (fMRI). In both situations, it is helpful to formally model the underlying component process, as this generates predictions of trial-to-trial variability in the signal from a brain region involved in its implementation.
In the case of value-guided action selection, a biophysically realistic implementation of a drift diffusion model is used. Using this model, it is predicted that there are specific times and frequency bands at which correlates of value are seen. Firstly, there are correlates of the overall value of the two presented options, and secondly the difference in value between the options. Both correlates should be observed in the local field potential, which is closely related to the signal measured using MEG. Importantly, the content of these predictions is quite distinct from the function of the model circuit, which is to transform inputs relating to the value of each option into a categorical decision.
In the case of social learning, the same reinforcement learning model is used to track both the value of two stimuli that the subject can choose between, and the advice of a confederate who is playing alongside them. As the confederate advice is actually delivered by a computer, it is possible to keep prediction error and learning rate terms for stimuli and advice orthogonal to one another, and so look for neural correlates of both social and non-social learning in the same fMRI data. Correlates of intentional inference are found in a network of brain regions previously implicated in social cognition, notably the dorsomedial prefrontal cortex, the right temporoparietal junction, and the anterior cingulate gyrus.

Keywords: action
magnetoencephalgraphy
functional magnetic resonance imaging
decision
model
cortex
reward
learning
reinforcement
choice
biophysical
Advisor: Behrens, T
Assessing the uses of 230Th, 232Th and 231Pa as proxies in the past and modern ocean

Thorium-230 and protactinium-231 have been widely used as proxies of oceanic processes in both modern and past marine environment. Their application as such proxies is, however, limited by sparse data from the modern ocean with which to characterize their distribution and behavior. This thesis aims to provide such data and to assess their uses as oceanic proxies for ocean circulation, sediment dissolution, and modern dust input. Twelve profiles of dissolved 230Th, 231Pa and 232Th obtained on a meridional GEOTRACES section in the Southwest Atlantic confirm the expected transport and fractionation of 231Pa from 230Th by deep ocean circulation out of the modern Atlantic. There is however neither a water mass dependence nor progressive change as water masses age, which challenges the use of sedimentary 231Pa/230Th to assess past flow in the South Atlantic. Decreases of 230Th and 231Pa observed in near-bottom water indicate enhanced sea-floor removal in regions where nepheloid layers are present. In a second study of sedimentary nuclides concentration, high-resolution 230Thxs profiles from sediment in Southeast Atlantic exhibit increasing 230Thxs concentrations from core-top to a depth of ∼3 cm followed by relatively constant values at greater depth, suggestive of sediment dissolution in the upper sediment core. This observation suggests the use of 230Thxs to quantify sediment dissolution. Combined with sediment composition measurements, 230Thxs also provides an assessment of which constituents are dissolving from the sediment. (231Pa/230Th)xs ratios do not appear to be affected by sediment dissolution. A third study, in the tropical Atlantic Ocean, combines water-column measurements of 230Th, 232Th with coeval aerosol measurements, and allows assessment and improvement of the use of 232Th to quantify dust input to the surface ocean. 232Th-derived dust flux increases from 0.43 g/m2/yr at low latitude in the South Atlantic to 10.70 g/m2/yr at higher latitude in the North Atlantic, and broadly agree with a model of dust input. The data presented in this thesis have expanded the dataset of 230Th, 232Th and 231Pa in the Atlantic Ocean, and provide an insight into future uses of these nuclides as oceanic proxies.

Keywords: Th isotopes
ocean proxies
ocean circulation
dust input
sediment dissolution
231Pa
Advisor: Henderson, G
Thomas, A
Characteristics of plasma turbulence in the Mega Amp Spherical Tokamak

Turbulence is a major factor limiting the achievement of better tokamak performance as it enhances the transport of particles, momentum and heat which hinders the foremost objective of tokamaks. Hence, understanding and possibly being able to control turbulence in tokamaks is of paramount importance, not to mention our intellectual curiosity of it. We take the first step by making measurements of turbulence using the 2D (8
radial imes
4
poloidal channels) beam emission spectroscopy (BES) system on the Mega Amp Spherical Tokamak (MAST). Measured raw data are statistically processed, generating spatio-temporal correlation functions to obtain the physical characteristics of the turbulence such as spatial and temporal correlation lengths as well as its motion. The reliability of statistical techniques employed in this work is examined by generating and utilizing synthetic 2D BES data. The apparent poloidal velocity of fluctuating density patterns is estimated using the cross-correlation time delay method. The experimental results indicate that the poloidal motion of fluctuating density patterns in the lab frame arises because the patterns are advected by the strong toroidal plasma flows while the patterns are aligned with the background magnetic fields which are not parallel to the flows. Furthermore, various time scales associated with the turbulence are calculated using statistically estimated spatial correlation lengths and correlation times of turbulence. We find that turbulence correlation time, the drift time associated with ion temperature or density gradients, the ion streaming time along the magnetic field line and the magnetic drift time are comparable and possibly scale together suggesting that the turbulence, determined by the local equilibrium, is critically balanced. Finally, we argue that we have produced a critical manifold in the experimentally obtained local equilibrium parameter space separating dominant turbulent transport from a non-turbulent or weakly turbulent state. It shows that the inverse ion-temperature-gradient scale length is correlated inversely with q/arepsilon
(safety factor/inverse aspect ratio) and positively with the plasma rotational shear. Practically, this means that we can attain the stiffer ion-temperature-gradient, thus hotter plasma core, without increasing the rotational shear.

Keywords: critical balance
plasma
turbulence
BES
transport stiffness
fusion
Advisor: Schekochihin, A
Field, A
A thermodynamic approach to constitutive modelling of concrete using damage mechanics and plasticity theory

Recent advances in computational mechanics have opened the potential of carrying out the analysis and design of concrete structures in a realistic manner with the use of nonlinear concrete models. This encourages the development of more capable and realistic constitutive models, based on a rigorous approach, for the analysis and design of concrete structures. This research focuses on the development of a thermodynamic approach to constitutive modelling of concrete, with emphasis on the rigour and consistency both in the formulation of constitutive models, and in the identification of model parameters based on experimental tests. The key feature of the thermodynamic framework used in this study is that all behaviour of the defined model can be derived from two specified energy potentials. In addition, the derivation of a constitutive model within this framework merely follows procedures established beforehand. The proposed constitutive model here is based on continuum damage mechanics, in combination with plasticity theory, hence enabling the macroscopic material behaviour observed in experiments to be appropriately modelled. Damage-induced softening is the cause of many problems in numerical failure simulations based on conventional continuum mechanics. The resolution of these problems requires an appropriate special treatment for the constitutive modelling which, in this study, is based on nonlocal theory, and realized through the nonlocality of energy terms in the damage loading functions. For practical applications in structural analysis, the model requires a minimum number of parameters, which can be identified from experimental tests. All the above features of the model have been incorporated in a unified and consistent thermodynamic approach, which also distinguish the approach from existing ones. Numerical implementation and application are important parts of the study. A suitable implicit scheme is adapted here for the integration of the nonlocal rate constitutive equations. For the solution of systems of nonlinear algebraic equations in finite element analysis, the arc-length method in combination with local constraint equations employing dominant displacements is implemented, and proves its reliability in this study. Application of the proposed constitutive models in the analysis and design of concrete structures is straightforward, with several numerical examples showing the practical aspects of the proposed modelling.

Keywords: isotropic damage
constitutive modelling
plasticity theory
concrete
Advisor: Houlsby, G
Structural and electrophysiological analysis of Hepatitis C Virus p7

Infection with the hepatitis C virus (HCV) has a big impact on global health. It is estimated that approximately 3 % of the world’s population carry HCV, putting more than 200 million people at risk of developing severe liver disease, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The HCV encoded viroporin p7 forms ion channels that are crucial for the assembly and secretion of infectious viruses, making it a potential drug target. Its hydrophobic nature makes p7 notoriously difficult to investigate in an untagged native form. A previously determined 16 Å electron microscopy single-particle reconstruction in detergent showed a hexameric, flower-shaped p7 protein. In conjunction with one hexameric and several monomeric p7 solution state NMR structures published, this constitutes the currently available structural information framework. An E. coli expression system is introduced, which is especially adapted to express isotopically labeled p7. For the first time, suitable solution-state NMR conditions at physiological pH and temperature were identified that gave rise to high quality spectra suitable to interrogate iminosugar drug interactions with untagged isotopically labeled J4 p7 (C27S) solubilised in detergent. A novel secondary structure topology was observed and preliminary iminosugar binding sites were determined. Further, a DIB (droplet interface bilayer) system to analyse p7 ion channel function was established, which is suitable to elucidate how inhibitors act on p7 genotypes and how different lipids influence the ion channel function of p7. The p7 oligomeric state was further investigated using native gel analysis, showing that isolates representing HCV genotypes 1 - 6 form oligomeric complexes. An ion channel defective dibasic mutant implicated in severely compromising viral fitness is also shown for the first time to form an oligomer, implicating that it is not an assembly problem that leads to the abrogated function.

Keywords: NMR
iminosugar
p7
viroporin
Hepatitis C Virus
Advisor: Zitzmann, N
Planning the Soviet everyday: Reimagining the city, home and material culture of developed socialism

This thesis explores professional visions for the planning of everyday life during the period of developed socialism. Considering a wide range of disciplinary literature, including architecture, urban planning, design and sociology, this thesis analyses how professionals imagined residential and domestic life in an urbanised and technologically advanced socialist society. Continuing the narrative of Khrushchev’s modernising programme to reform everyday life (byt) into the post-Khrushchev period, the thesis follows professionals of the last two Soviet decades who criticised the rationalising and collectivising planning paradigm inaugurated during the preceding decades. Professionals argued that this paradigm had produced a dehumanised and alienating everyday environment in the city and the home.
After setting out the theoretical framework and the historical context of developed socialism, the first empirical section addresses urban residential life. It focuses on the microdistrict planning unit to illustrate how professionals, disillusioned with functionalist planning, searched for ways to humanise the city and adapt it to the behaviours and needs of urban residents. Part two investigates shifting professional views on the home and the everyday processes associated with it, such as cooking and cleaning. No longer seen as a utilitarian space in which everyday processes transpire, the home came to be understood as a personal and emotionally resonant place. Part three focuses on material culture, investigating evolving views on consumption and aesthetics. It illustrates how professionals endeavoured to rehabilitate the object world and align it with populist preferences while nonetheless maintaining a commitment to technological and forward-looking principles. In contributing to the scholarly understanding of developed socialism, this thesis contends that the 1970s-1980s saw experts embrace individual agency and popular sentiments. This turn did not, however, signify a turn towards individualism or de-politicised malaise: professionals maintained their utopian aspirations to engineer and control everyday life.

Keywords: architecture
design history
urban planning
developed socialism
Soviet Union
Advisor: Pallot, J
McDowell, L