VictorJuiz/thesis huggingface dataset:
Cardiac stem cell therapy for heart failure

Cardiovascular disease is a leading cause of death worldwide and becomes increasingly prevalent in the elderly population. Independent of etiopathogenesis, heart failure (HF) is the final common stage of numerous heart diseases. Cardiac stem cell (CSC) therapy has emerged as a promising cell-based strategy for treatment of HF. However, cell replacement is not able to fully restore a structurally damaged myocardium in advanced and end-stage HF. The objective of this project was to test the following hypotheses: that a bioengineered heart extracellular matrix (ECM) with preserved intact geometric structure could be generated using decellularization by coronary perfusion; and that autologous CSCs, to repopulate this ECM, could be isolated and expanded from the adult heart, with the caveat that autologous CSCs are depleted and impaired by both aging and chronic dilated cardiomyopathy. This will help to develop a possible therapeutic approach for advanced HF, using a combination of CSCs and engineering technique. Resident CSCs were isolated from explant-derived cells (EDCs) and expanded into cardiosphere-derived cells (CDCs) via cardiosphere formation. The CDCs expressed CSC markers (c-kit and Sca-1), pluripotent markers (Oct3/4 and Sox2), and the cardiac lineage-committed marker (Nkx2.5), and showed clonal expansion, self-renewal, and cardiomyogenic potential in vitro. In tissue engineering experiments, CDCs survived and proliferated within biomaterial alginate scaffolds for up to 7 weeks. An engineered bioartificial ECM scaffold was successfully produced from a whole rat heart using retrograde coronary perfusion and possessed an intact 3D architecture with functionally perfusable vascular network. Compared with ventricles, cultures derived from atria produced significantly higher number of c-kit+ and Sca-1+ CSCs (c-kit: 13% vs. 3.4%; Sca-1: 82% vs. 53%, respectively) and exhibited greater clonogenic and proliferative capacity. CDCs could be grown from young and aged mice, but the yield of CSCs significantly declined with age, as did cell migration and differentiation potential. In comparison to wild-type mice, atrial-CDCs from dystrophic mice showed no significant differences in CSC subpopulations and characteristics, despite confirmation of cardiac dysfunction using MRI. In conclusion, CDCs could be considered to be a viable cell candidate for cardiac therapy and may be used to treat HF at various stages, in combination with myocardial tissue engineering.

Keywords: cardiovascular disease
stem cell
tissue engineering
Advisor: Carr, C
Clarke, K
Cui, Z
Biological transport networks

Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system, and we can photograph their growth, digitize the network structure, and measure the movement of radio-tracers. Mycelial networks are more accessible than the transport networks of other multicellular organisms, but there are many open questions concerning the coordination of growth and transport within fungal networks. As osmotically driven water uptake is often distal from the growing margin, and aqueous fluids are effectively incompressible, we propose that growth induces mass flows across the mycelium, towards the growing regions. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimizing the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and cords that were predicted to carry large currents were significantly more likely to increase in size than cords with small currents.
We have also developed an efficient method for calculating the exact quantity of resource in each part of an arbitrary network, where the resource is lost or delivered out of the network at a given rate, while being subject to advection and diffusion. This method enabled us to model the spatial distribution of resource that emerges as a fungal network grows over time, and we found good empirical agreement between our model and experimental data gathered using radio-labelled tracers. Our results suggest that in well insulated fungal networks, growth-induced mass flow is sufficient to account for long distance transport. We conclude that active transport mechanisms may only be required at the very end of the transport pathway, near the growing tips. We also developed a simple model of glucose delivery through vascular networks, which indicates that increasing the number of blood vessels in a region can actually decrease the total rate of glucose delivery.

Keywords: Fungi
transport networks
advection-diffusion
Advisor: Maini, P
Lopez, E
Jones, N
Fricker, M
Magnetic resonance studies of proteins and model systems

This thesis discusses, employs and develops further applications of both Electron Paramagnetic Resonance (EPR) and Nuclear Magnetic Resonance (NMR) methodology in the study of a variety of biological systems.
Chemically Induced Dynamic Nuclear Polarization (CIDNP) is used to study the surface accessibility of Tryptophan and Tyrosine residues in the Equine Lysozyme-Oleic Acid complex (ELOA). It is believed that these amino acids may play a vital role in the interaction of this partially structured complex with cell walls leading to the apoptosis of the cell.
Double Electron-Electron Resonance (DEER) is an EPR technique that can be used to study the distance and, in some cases, the orientation between two paramagnetic centres on a nano-meter length scale. Attaching spin labels, such as Methane Thiosulphonate Spin Label (MTSL), to proteins, or by using spin active cofactors in proteins as innate spin labels, allows the measurement of distances within proteins or their complexes. In this thesis, model copper systems were initially studied in order to gain a better understanding of the orientational information obtainable from such spectra. The methodology developed from this project was applied to the protein−protein complexes of ferredoxin reductase−ferredoxin and ferredoxin−P450, three proteins that form a vital electron transport chain, leading to the catalytic hydroxylation of many small molecules. The structure of the docked P450−ferredoxin complex is the first experimentally determined structure of its type and thus is of considerable biochemical interest.
As part of the structural determination of the ferredoxin complexes, it was necessary to measure the relative orientation of the g-matrix with respect to the molecular structure. This was achieved using a combination of orientationally selective proton Electron Nuclear Double Resonance (ENDOR) and HYperfine Sublevel CORrElation (HYSCORE) spectroscopy.
The expansion of the DEER technique to measure an ever-increasing variety of systems has shown the limitations of the pulse sequences most frequently employed at present, particularly in relation to the measurement of many of the metal centres, which could be used as innate spin probes in protein systems. Methodological work has also been undertaken to examine possible solutions to circumvent some of these problems, namely low modulation depths and fast relaxation times. This has resulted in the development of two modifications to the existing techniques: Dead-time free three-pulse DEER and Repeated Excitations IN DEER (REINDEER). These techniques have been used to study of both synthetic model systems and also spin labelled proteins.

Keywords: electron paramagnetic resonance (EPR)
cytochrome P450
electron spin resonance (ESR)
chemically induced dynamic nuclear polarization (CIDNP)
double electron-electron resonance (DEER), ESR of metal centres
Advisor: Timmel, C
Hore, P
Colourings of random graphs

We study graph parameters arising from different types of colourings of random graphs, defined broadly as an assignment of colours to either the vertices or the edges of a graph.
The chromatic number X(G) of a graph is the minimum number of colours required for a vertex colouring where no two adjacent vertices are coloured the same. Determining the chromatic number is one of the classic challenges in random graph theory. In Chapter 3, we give new upper and lower bounds for the chromatic number of the dense random graph 𝒢(n,p)) where p ∈ (0,1) is constant. These bounds are the first to match up to an additive term of order o(1) in the denominator, and in particular, they determine the average colour class size in an optimal colouring up to an additive term of order o(1).
In Chapter 4, we study a related graph parameter called the equitable chromatic number. This is defined as the minimum number of colours needed for a vertex colouring where no two adjacent vertices are coloured the same and, additionally, all colour classes are as equal in size as possible. We prove one point concentration of the equitable chromatic number of the dense random graph 𝒢(n,m) with m = pn(n-1)/2, p &LT; 1-1/e2 constant, on a subsequence of the integers. We also show that whp, the dense random graph 𝒢(n,p) allows an almost equitable colouring with a near optimal number of colours.
We call an edge colouring of a graph G a rainbow colouring if every pair of vertices is joined by a rainbow path, which is a path where no colour is repeated. The least number of colours where this is possible is called the rainbow connection number rc(G). Since its introduction in 2008 as a new way to quantify how well connected a given graph is, the rainbow connection number has attracted the attention of a great number of researchers. For any graph G, rc(G)≥diam(G), where diam(G) denotes the diameter. In Chapter 5, we will see that in the random graph G(n,p), rainbow connection number 2 is essentially equivalent to diameter 2. More specifically, we consider G &Tilde; 𝒢(n,p) close to the diameter 2 threshold and show that whp rc(G) = diam(G) ∈ {2,3}. Furthermore, we show that in the random graph process, whp the hitting times of diameter 2 and of rainbow connection number 2 coincide.
In Chapter 6, we investigate sharp thresholds for the property rc(G)≤=r where r is a fixed integer. The results of Chapter 6 imply that for r=2, the properties rc(G)≤=2 and diam(G)≤=2 share the same sharp threshold. For r≥3, the situation seems quite different. We propose an alternative threshold and prove that this is an upper bound for the sharp threshold for rc(G)≤=r where r≥3.

Keywords: Graph colouring
Probabilistic combinatorics
Chromatic number
Random graph process
Equitable chromatic number
Rainbow connectivity
Random graphs
Advisor: Riordan, O
Styles of sovereignty: the relevance of Louis XIV to English royal iconography, 1689-1714

This thesis explores the influence of French royal image-making on English monarchies at the turn of the eighteenth century. It investigates the relevance of Louis XIV (r. 1643-1715) to English royal iconography during the reigns of William III (r. 1689-1702) and Queen Anne (r. 1702-1714) across a wide range of source material – from panegyric and portraiture, to medals, sculpture, and architecture. In doing so, it foregrounds the intricate interplay between political communication and different forms of artistic imagination in the early modern period.
The thesis conceptualises the relation between post-revolutionary English monarchical image-making and its French counterpart as one of contest with and emancipation from French influence. The specific political circumstances add a particular poignancy to the investigation of this narrative, as the almost continual crises which the English monarchy suffered at the time stand in sharp contrast with the (dynastic) stability of the French monarchy and its highly influential court culture. Despite these elements of rupture and contrast, however, the story of seventeenth-century English monarchical image-making is one of continuity in respect of its gradual disengagement from the French model. In contrast to his immediate predecessors, I contend, William's image-making presents him as Louis's competitor, rather than his imitator. In the course of William's reign, Louis's monarchical model thus turns from model to foil. This development evolves further in Queen Anne's reign, culminating in Louis's mort avant la lettre, as Anne's image-making dispenses with the Ludovican model both as model and as foil. English post-revolutionary image-making, I argue, not only mirrored, but actively contributed to the decline of the Ludovican model, whilst maintaining the figure of the monarch as central to public political discourse. Through the lens of monarchical image-making, therefore, this thesis offers a critical outlook onto late seventeenth-century Anglo-French political and artistic relations.

Advisor: Gerrard, C
Williams, W
Integrative imaging and electron cryo-tomography of viral transport mechanisms

To comprehensively understand a biological process or mechanism from molecule to cell it requires the combination of multiple techniques across a range of resolutions and scales. We currently rely on a variety of different approaches to highlight given aspects of biology that are then interlinked through interpretation. Intracellular transport is a process whereby vesicles and organelles are transported to different parts of cells with a precise spatial and temporal accuracy. This process is often hijacked by viruses, which utilize cellular machineries for active transport to and from the nucleus during their entry and egress. In this thesis I focus on the intracellular transport of adenoviruses, which are able to recruit and bind to the cytoskeletal motor, dynein, and use it to travel to the nucleus. I apply electron cryo-microscopy and fluorescence microscopy to elucidate the basis for this process, and link this to the behaviour of adenoviruses as they are recruited to microtubules. I then apply electron cryo-tomography to directly observe proteins in their native cellular environment. I discuss the ability of this technique to be utilized in the in situ determination of the structure of viruses as they infect a cell. I show that (i) in situ sub-volume averaging from single tomograms can guide and complement segmentation of biological features and (ii) that novel, transient processes can be imaged with high levels of detail. As a second example of transport in cells, I study the nuclear egress of herpesvirus capsids, utilizing a multi-modal approach in an attempt to characterize this process from cellular to molecular level, and ask how herpesviruses modulate the nuclear membrane during capsid egress into the cytosol. Finally, I discuss an emergent technique in the field of electron cryo-microscopy, the Volta phase plate, its potential application in molecular tomography, and how it may enhance our current ability to discern contextual molecular mechanism.

Advisor: Grünewald, K
Investigating past and present continental earthquakes with high-resolution optical imagery

Over the past few decades, remote sensing has emerged as a powerful tool for studying active faulting in continental regions. However, the commonly used remote sensing techniques, including radar interferometry, visual inspection of imagery, and image matching, cannot measure three-dimensional (3D) surface displacements in earthquakes, limiting our ability to investigate faulting. The improvement of very high-resolution (VHR) optical imaging systems (stereo in particular) in recent years has made it possible for earth scientists to measure 3D surface deformation remotely. In this thesis, I contribute to assessing the capability of VHR optical imagery, by determining earthquake deformation from four different types of earthquakes (different in sense of slip and date of the event). In the case of the 2010 Mw 7.2 El Mayor-Cucapah, Mexico earthquake, I show that digital elevation models (DEMs) derived from Pleiades stereo imagery are comparable to light detection and ranging (LiDAR) surveys, and differencing pre- and post-earthquake DEMs can measure 3D displacements, which will be very useful for studying future earthquakes. For the 2013 Mw 7.7 Balochistan, Pakistan earthquake, I determine the vertical motion from a post-earthquake Pleiades DEM and find constant fault kinematics throughout the Late Quaternary. This study has resolved a current controversy of the Balochistan earthquake, in which it has been argued that kinematics of the Hoshab fault switches between strike-slip and dip-slip. Applying historical aerial, KH-9 Hexagon spy satellite, SPOT-2 and modern SPOT-6 images to the 1978 Mw 7.3 Tabas-e-Golshan earthquake, I measure the coseismic and postseismic displacements, and show that the Tabas fold system in eastern Iran may exhibit characteristic slip behaviour. Combining Pleiades imagery, fieldwork and geological dating techniques, I determine slip in the 1556 Huaxian earthquake in China and the recurrence interval for similar events. These examples demonstrate the usefulness of high-resolution optical imagery in investigating past and present earthquakes.

Keywords: Continental Earthquakes
Optical Imagery
High Resolution
Active Tectonics
Faulting
Advisor: Parsons, B
Walker, R
Influence of the exchange symmetry beyond the exclusion principle

Since typically the physics of many body quantum systems is solely described and determined by pairwise interactions, the concept of reduced particle information is fundamentally relevant, particularly for indistinguishable particles. Determining the compatibility of r-particle reduced density operators (r-RDOs) with some N-particle state is known as the N-representability problem. The Pauli exclusion principle provides a set of necessary and sufficient conditions for the N-representability of fermionic 1-RDOs. However, pure N-representability requires a set of stricter conditions which are known as Generalised Pauli constraints (GPCs).
In this thesis we investigate the influence and significance of the GPCs beyond the well-explored and established relevance of the Pauli exclusion principle. In particular, we analytically study the (quasi-)pinning effect which corresponds to a saturation of the GPCs and imposes structural simplifications on the N-fermion state. So far, nothing is known about its origin and mechanisms. We will close this gap by analytically examining the dependence of quasipinning on the particle number, the dimensionality and the spin polarisation in a representative physical model system. Our results suggest the notion of a microscopic Pauli pressure which is a consequence of the competition between energy minimisation and antisymmetry, and drives the system towards the boundary of the allowed region. Furthermore, the relevance of quasipinning beyond the wellknown Pauli exclusion principle is evaluted by the Q-measure. The outcomes provide first direct evidence for the need to incorporate GPCs into the physical description.
To explore the role of the fermionic exchange symmetry beyond the Pauli exclusion principle from a more general perspective, we consider systems of hardcore bosons. Indeed, they exhibit a (lattice-based) exclusion principle, although their exchange symmetry is bosonic. Occupation numbers on oneparticle states other than the lattice basis can exceed one. We prove that the maximal occupation number is given by λmax = N/d(d - N + 1) where N, d are the numbers of particles and lattice sites. In addition, we derive necessary conditions for the N-representability of hardcore boson 1-RDOs and investigate the one-particle entropy boundaries. Finally, we present one-dimensional physical systems which macroscopically saturate λmax and exhibit (fractional) Bose-Einstein condensation.

Advisor: Vedral, V
Pneumococcal genomics and evolution

Streptococcus pneumoniae (the “pneumococcus”) is a global pathogen responsible for nearly a million deaths each year in children under the age of five. The polysaccharide capsule or serotype is the primary pneumococcal virulence factor and is encoded by the cps locus. The introduction of pneumococcal conjugate vaccines has led to a significant reduction in the prevalence of invasive diseases caused by vaccine serotypes and a concomitant reduction of vaccine serotypes recovered from the nasopharynx of healthy children, although the overall rates of carriage have remained constant due to the replacement of vaccine serotypes with non-vaccine serotypes. The increasing numbers of genomes from large well-characterised pneumococcal datasets allows for key biological questions related to the pneumococcus, such as capsular diversity, to be examined in unprecedented detail. This thesis describes the application of genomics to investigating important aspects of pneumococcal biology including the pan-genome, cps locus diversity and genomic regions potentially associated with invasive disease. The first part of the thesis described a Bayesian decision model for estimating bacterial core genomes. This model was applied to genome datasets from five different bacterial species. The same model was later used to estimate core genomes for four different pneumococcal carriage datasets. These estimated core genomes were then compared and revealed a very small shared core genome of 303 genes. The results also highlighted the unexpected diversity of a pneumococcal dataset from Thailand. The second part of the thesis examined the diversity of the cps locus starting with serogroup 6 and in particular the recently described novel serotype 6E. This analysis revealed that the majority of what had previously been described as serotype 6B pneumococci were in fact serotype 6E and serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to kill serotype 6E pneumococci. The analysis of cps loci was then extended to consider the diversity of 49 serotypes and included 5,405 genomes in the analyses. These analyses revealed several hybrid and putative novel serotypes. The final part of the thesis used a genome-wide association study to identify 89 candidate loci significantly associated with invasive disease. The results in this thesis showed that large numbers of genome sequences could provide a detailed insight into important aspects of pneumococcal biology.

Advisor: Brueggemann, A
Phenomenology and the self's measure: studies in subjectivity

The philosophical tradition has long understood subjectivity solely in reference to the self's place within the world and the powers of intentional transcendence which open it. Nowhere is this presupposition more apparent than in the thought of Husserl, Heidegger, Sartre, and Merleau-Ponty. Despite the precise differences among their respective philosophies of transcendence, each understands the self as little else than that which opens the exteriority of a world and is thereby exhausted and determined by it. Against this prevailing assumption that the self is a 'being-in-the-world', I contend that the essence of subjectivity instead consists in the unworldly interiority of life’s affective self-revelation. The studies that follow accordingly investigate five related aspects of subjectivity: the irreducibility of the self's individuality to society; the blow of vanity that reveals this inwardness; the resultant life that marshals and in turn deploys it; the power of the work of art to express it; and finally the promise of immortality that sustains it.

Keywords: self
god
Michel Henry
Kierkegaard
phenomenology
Advisor: Moore, A
Crowell, S