VictorJuiz/thesis huggingface dataset:
Structured membranes for biomedical and tissue engineering applications

Although biological/biomedical membranes may look like two-dimensional (2D) assemblies, depending on their functions, they may have detailed and complex configurations in their 3rd dimension. In such cases, three-dimensional (3D)-printing—as a process of layer-by-layer deposition of materials—can provide an effective and unique methodology for manufacturing of such membranes.
In this regard, 3D-printing of biocompatible hydrogels needed for fabrication of cell-free soft membranes with proper surgical handling is challenging, due to the rheological characteristics of hydrogels. This dissertation introduces and examines a newly developed generic hydrogel ink that can address such difficulties due to its several properties, including:
1) The ink is compatible with most biomedical applications in terms of the biomaterial composition and provides the appropriate cell attachment for different cell types.
2) It is easily printable without rheological complexities.
3) It is relatively inexpensive, making it appropriate for clinical use by different patients.
Using our developed printing protocol, we employed this ink for 3D-printing of structured soft thin and thick membranes for different biomedical purposes. More specifically, three applications were examined. The first application involves a structured 3D-printed membrane with the design criteria suitable for guided tissue regeneration (GTR). Its bio-stability, mechanical strength, surgical handling and in vitro biocompatibility were fully characterized and successfully evaluated for GTR application.
Reconstruction of ocular surface/conjunctival defects, using the 3D-printed membrane produced by the generic ink, is the second application that was examined. Both in vitro and in vivo (rabbit model) studies were performed to evaluate the function of the 3D-printed membrane in comparison to the amniotic membrane, which is a conventional membrane used in reconstruction of ocular surface/conjunctival defects. The use of the 3D-printed membrane indicates some advantages, including predictable degradation pattern, higher goblet cell density on the healed epithelium, reduced scar tissue formation and less inflammation.
Cartilage regeneration is the third application considered for the membranes printed by this ink. For this purpose, a new knee plug was developed, and a 3D-printed membrane was fabricated with the specific design criteria for assembling in the plug. The physical analyses and the in vitro examinations confirm the suitability of the fabricated membrane for cartilage regeneration.
Finally, the limitations and capabilities of the produced ink for future works are discussed at the end of the thesis.

Keywords: Tissue engineering
3D-printed membranes
3D-Printing
Membranes
Advisor: Cui, Z
Ye, H
Tradition in the theological thought of Basil of Caesarea: context and connotations

My thesis is an analysis of Basil’s appeals to tradition in his theological works, with a focus on Against Eunomius and, most importantly, On the Holy Spirit. The work begins with an analysis of Against Eunomius, focusing primarily on the context of the work, the influences on Basil’s thought and arguments in the treatise, and Basil’s attempt to refute Eunomius’ appeal to tradition. I have then traced ideas of tradition from Against Eunomius to On the Holy Spirit, and established the context of and purpose for the publication of the latter in 375 against Eustathius of Sebaste. Establishing the necessity of tradition for Basil’s argument in On the Holy Spirit, I have broken down the jargon and reconstructed the exact nature of the “non-scriptural tradition” to which he appeals. Following this, I have analysed the context to consider whether this idea of non-scriptural tradition is an innovation, or a development of both Christian and Hellenistic influence (though of course the two are indelibly linked in the fourth-century Christian tradition). The latter appears to be the case. The final task has been establishing how this idea of tradition fits into Basil’s theological epistemology. I argue, based on the tradition’s apparent equality in establishing knowledge of divine things with Scripture, that Basil takes a holistic view of the Christian experience, in that all aspects of it have hidden within the (in Basil’s eyes) undeniable truth of God as Trinity. To me, this holistic view is a natural product of his ascetic beliefs.
The scholarship on Basil’s idea of tradition has, since the works of Hanson and De Mendieta in the mid-60s, been scant and cursory, with most generally agreeing with the pronouncements of De Mendieta on the matter. However, though De Mendieta’s work is of significant value, it is very much a product of its time in the discipline of Patrology – the last fifty years have transformed the study of the early church, especially the fourth century. Both this, and the previous focus on On the Holy Spirit alone – often in far too small a space to explore the particularities of Basil’s language, context and influences, and the theological implications of non-scriptural tradition – mean that, in my view, a new and more focussed study is very much required.

Keywords: Patristics
Eustathius of Sebaste
Early Christianity
Eunomius
Basil of Caesarea
Tradition
Ancient Philosophy
Theology
Late Antiquity
Advisor: Edwards, M
Structural basis of centrosome assembly in flies

Centrosomes are the main microtubule-organising centres in many animal cells. They consist of a pair of centrioles surrounded by a dense mass of protein known as the pericentriolar material. As the cell enters mitosis, this pericentriolar material expands dramatically in a process called centrosome maturation. In flies, the protein Centrosomin (Cnn) assembles into a network that acts as a scaffold for the recruitment of the hundreds of other proteins making up a mature centrosome. Cnn network formation is known to depend on phosphorylation of a central region within Cnn. However, it is unclear how Cnn assembles into a network and how this process is controlled.
In this thesis it is shown that Cnn network formation in vitro depends on an interaction between the conserved C-terminus of Cnn and the phospho-regulated central region. The crystal structure of part of this central region is solved, revealing that it forms a dimer of α-helical hairpins that are sterically incompatible with binding of the Cnn C-terminus. The structure is therefore proposed to constitute an “inactive” state. Furthermore, the structure suggests a mechanism wherein phosphorylation acts by disrupting the hairpin fold, thereby exposing the Cnn C-terminus binding site and hence allowing formation of an “assembly-competent” state where the Cnn C-terminus is bound. In addition, the calcium-binding protein Calmodulin is shown to crosslink the Cnn C-terminus in crystallo. However, Calmodulin inhibits network assembly of Cnn constructs in solution, possibly by preventing the assembly-competent state from forming a network. Taken together, this thesis draws on structural and functional data to provide important atomic-level insights into the mechanism of mitotic centrosome assembly in flies.

Keywords: centrosome
Cnn
PCM
mitosis
Calmodulin
Plk1
Centrosomin
centriole
Advisor: Raff, J
Lea, S
Flexibility in avian migration across scales

Migratory birds form a network of organisms that connect the world, serving as indicators of ecosystem health and biodiversity on a hemispheric scale. Unfortunately, avian migrants are threatened by the rapidly increasing pressures of global change. Understanding the capabilities of migratory birds to respond to established and emerging challenges requires knowledge of the complex interactions among individuals, populations, species, and natural and built environments. In this thesis, I surveyed the drivers of bird migration across scales. I focused on the contributions of the innate migratory program, birds’ responses to environmental cues and conditions, and the influence of human activity on migratory behavior. First, I investigated birds’ innate migratory programs. I demonstrated that stonechats (genus Saxicola) possess inherited programs that vary among taxa according to migratory tendency, but also readily interact with environmental factors to influence migratory phenotypes (Chapter 1). Next, I combined field and laboratory studies to show that ongoing responses to climate change in a long-distance migrant, the pied flycatcher (Ficedula hypoleuca), involve not only phenotypic plasticity, but microevolutionary change as well (Chapter 2). I then shifted to a wild context and examined the migration of the Eurasian blackcap (Sylvia atricapilla) across its European range, illustrating two different ways that natural selection can act on migratory strategies (Chapter 3). Expanding to a continental perspective, I showed that migratory flexibility is important not only on evolutionary timescales, but also to enable short-term responses to variable environmental conditions during active migratory flights—and that these responses are predictable enough to reliably forecast avian movements (Chapter 4). Finally, I focused on human impacts on migration, showing that artificial light at night can drastically affect migratory journeys (Chapter 5). Human activity can impact not only migrants’ in-flight behaviors, but also their broader ecology (Chapter 6). Overall, this thesis shows that the flexibility we observe in migratory birds stems from a range of sources, innate and external, and that variation in migratory phenotypes may be key to responding to environmental change.

Keywords: forecasting
light pollution
global change
bird migration
movement
Advisor: Sheldon, B
Clegg, S
Vectorial problems: sharp Lipschitz bounds and borderline regularity

This thesis is devoted to the proof of fine regularity properties of solutions to a broad class of variational problems including models from geometry, material science, continuum mechanics and particle physics. Our starting point is the analysis of the behavior of manifold-constrained minima to certain non-homogeneous functionals: under sharp assumptions, we prove that they are regular everywhere, except on a negligible, "singular" set of points. The presence of the singular set is in general unavoidable. Looking at minima as solutions to the associated Euler-Lagrange system does not help: it presents an additional component generated by the curvature of the manifold having critical growth in the gradient variable. For instance, sphere-valued harmonic maps satisfy in a suitably weak sense
−∆u = |Du|2u.
This turns out to be an insurmountable obstruction to regularity. It is then natural to consider general systems of type
− div a(x, Du) = f (0.0.1)
and study how the features of f and of the partial map x 7→ a(x, z) influence the regularity of solutions. In this respect, we are able to cover non-linear tensors with exponential type growth conditions as well as with unbalanced polynomial growth: we prove everywhere Lipschitz regularity for vector-valued solutions to (0.0.1) under optimal assumptions on forcing term and space-depending coefficients, [76]. When the system in (0.0.1) has the Double Phase structure:
− div (|Du|p−2Du + a(x)|Du|q−2Du)= − div (|F|p−2F + a(x)|F| q−2F)
0 ≤ a(·) ∈ C0,α, 1 ≤ q/p ≤ 1 + α/n,
we complete the Calderón-Zygmund theory started in [62] by dealing with the delicate borderline case
q/p = 1 + α/n,
which has been left open so far. Finally, we propose a new approach to the analysis of variational integrals with (p, q)-growth based on convex duality.

Keywords: nonautonomous functionals
Regularity
nonuniform ellipticity
Advisor: Kristensen, J
Radiocarbon dating Late Pleistocene megafauna in southern Europe

In the last 100,000 years, mainland Europe lost over a dozen large mammal species. These were part of a global extinction event that occurred during heightened climatic variability and the expansion of modern humans. The role of these two factors in driving the extinctions has been debated for decades. To move the debate forward, precise and accurate chronological estimates of fossils are needed to link species to climatic events and human activities. Unfortunately many fossil chronology datasets are small, contain unreliable dates, and are not spatially representative.
This poor temporal constraint is in part due to the challenges of radiocarbon dating Pleistocene bone. Radiocarbon dating requires sufficient collagen to be extracted from a bone sample. Heat and aridity both degrade collagen, so faunal specimens from southern European sites in particular often fail to produce sufficient collagen. This has resulted in a dearth of reliable dates from the Mediterranean and an incomplete picture of when and where fauna disappeared in Europe. Resolving southern European faunal histories is particularly important as southern Europe has been posited as both the region species retracted to prior to extinction and where the earliest modern humans arrived in Europe.
This thesis tested approaches to improving sampling and pretreatment for radiocarbon dating poorly-preserved bone. It then produced new radiocarbon dates from three carnivore species in southern Europe: cave lions, cave hyenas, and leopards. These dates were combined with critically evaluated radiocarbon dates to model extinctions and interactions between fauna, climate, and modern humans using both established and novel modelling tools.
Key methodological results found sample preservation could vary dramatically within sites and even individual bones. Proposed alternatives to the standard ABA pretreatment produced lower-quality collagen but sometimes produced yields where ABA did not, presenting an opportunity for further purification. Critical evaluation of radiocarbon datasets was important, as inclusion of less-robust dates altered some model results.
Models were inconclusive on the still-small leopard dataset but suggested both cave lions and hyenas went extinct in southern Europe earlier than northern Europe. Time series analysis of OxCal kernel density estimate models suggested observational densities of hyenas lagged human densities and cave lions lagged climate changes, while Bayesian spatial extinction models estimated that both species went extinct in mid-latitude Europe at the last glacial maximum and terminal Pleistocene, respectively. A ‘pincer effect’ is suggested to interpret these results, where modern humans limited species’ ability to shift ranges during glacial expansions. These results are compared to other Pleistocene extinctions and discussed in relation to ecological theories.

Advisor: Devièse, T
Higham, T
Adaptive optics retinal imaging in patients with retinal disease

High-resolution in vivo retinal imaging with an adaptive optics scanning laser ophthalmoscope (AOSLO) allows visualisation of degenerative changes at the cellular level. The improvement in resolution with this type of imaging when compared to conventional retinal imaging technologies has made the use of cell-specific imaging biomarkers possible. With the development of new therapies for retinal disease, cell-specific biomarkers of disease are becoming increasingly important for monitoring treatment outcomes. This thesis aims to investigate the AOSLO as a clinical tool and to develop fully automated image processing and analysis pipelines for AOSLO images from patients with retinal disease.
Participants with Stargardt disease were investigated using multimodal conventional clinical imaging and high-resolution in vivo retinal imaging. Hyper-reflective spots, that were termed discrete hyper-reflective foci, were identified in AOSLO images in areas of retinal degeneration. We hypothesize that they may be cellular in nature and could represent cellular debris related to ongoing retinal degeneration. To optimise AOSLO image quality in patients with retinal disease, recommendations for future participant selection criteria and AOSLO image acquisition protocols are described.
Reference frames are used to measure and correct intraframe eye motion in order to produce averaged AOSLO images with a high signal to noise ratio. A fully automated algorithm for reference frame selection was developed and validated using synthetic data simulating normal retinae. Although the results did not show a significant difference between selected reference frames, averaged images generated using the developed algorithm were significantly better when compared to the default method used for reference frame selection with the Oxford AOSLO. We hypothesise that the improvement in averaged images may be due to clustering of spatially overlapping frames that occurs in the developed algorithm, which may lead to an improvement in the subsequent step of eye motion correction.
A deep learning approach for automated cone identification in AOSLO images of the photoreceptor mosaic was developed and validated. There was good agreement between the developed convolutional neural network (CNN), trained with synthetic and real data, and the current gold standard of manual marking. The developed CNN also marginally outperformed the results of current state-of-the-art automated cone detection algorithms. Although high-resolution in vivo retinal imaging provides substantial advantages over conventional clinical imaging, a number of technical, image processing and image analysis related challenges need to be overcome to promote its widespread clinical application.

Keywords: High-resolution retinal imaging
AOSLO
Adaptive optics
Retinal imaging
Image analysis
Advisor: Downes, S
Smithson, H
Young, L
Aspects of string model building and heterotic/F-theory duality

In this thesis, we develop tools for model building in heterotic string theory and F-theory. We focus in particular on heterotic line bundle models and their F-theory duals. The first reason for this is that line bundle models are particularly fruitful models for phenomenology, and the second reason is that they provide a convenient background in which to make progress in studying heterotic/F-theory duality for more general features.
In the first two parts of this thesis, we focus on transferring unique model building advantages between the heterotic and F-theory descriptions, via heterotic/F-theory duality. In the first part, we lay groundwork by analysing the interplay between phenomenological constraints and the requirement of an F-theory dual, for heterotic line bundle models. We describe the required geometries in detail and construct many examples. We also describe the constraints on the line bundle sums, and perform a systematic search for phenomenologically interesting models, finding several hundred.
In the second part, we first develop in detail the F-theory dual picture of heterotic line bundle models. The spectral cover description is inappropriate, so we first conjecture the details of the duality. We then verify various aspects, including gauge groups, spectra, supersymmetry conditions, and anomaly conditions, and we treat some interesting subtleties. Using knowledge of this duality, we then develop the F-theory perspective on a well-known but little-utilised aspect of heterotic model building: heterotic NS5-branes, including stacks and intersections. We describe the dual geometry to various NS5-brane configurations, including singular transitions between configurations. We make heavy use of toric geometry and find many pleasing correspondences between the toric data and the NS5-brane configuration.
In the third part, we develop methods to determine closed-form expressions for line bundle cohomology. We focus on the simpler case of complex surfaces as a step towards understanding the case of Calabi-Yau manifolds. These surfaces can also be used as bases for elliptic three- folds, and their cohomology lifted via the Leray spectral sequence. We derive index expressions for all line bundle cohomology on del Pezzo and Hirzebruch surfaces, and give methods to derive similar formulae on any compact tori surface, using a form of Zariski decomposition. We also discuss general methods to determine formulae on generic spaces, and in a companion paper we construct machine learning networks for this purpose.

Advisor: Lukas, A
Unconventional superconductivity and Majorana modes

In this thesis superconductivity with unconventional pairing symmetries arising from repulsive interactions is investigated. Anyonic quasiparticles within the subclass of chiral p-wave superconductors are also examined.
In Chapter 2 we study weak-coupling superconductivity in a repulsive Hubbard model on the tetragonal lattice. With the weak-coupling approximation we establish the superconducting phase diagram as the out-of-plane hopping strength and electron filling is varied. For four Fermi surface topologies we identify a total of five types of p- and d-wave ground state orders, several of which have accidental line nodes and break time-reversal symmetry.
The weak-coupling scheme is adapted to strontium ruthenate (Sr2RuO4) in Chapter 3. We compute and compare odd- and even-parity superconducting order parameters using a realistic three-dimensional band structure. Two superconducting phases are identified: a helical p-wave spin triplet and a d-wave spin singlet phase. Both orders are roughly found to be compatible with specific heat data and recent nuclear magnetic resonance measurements [A. Pustogow et al., Nature 574, 72 (2019)]. We suggest that a d-wave order is likely involved in the superconducting phase, although certain experiments appear to remain incompatible with this conclusion.
In Chapter 4 we describe anyonic (Majorana) quasiparticles in chiral p-wave superconductors at temperatures non-negligible compared to the superconducting gap. We consider the impact of thermally occupying in-gap vortex states on the hybridisation of two Majorana modes. The hybridisation, reflecting the state of the qubit defined by the two Majorana modes, is found to decay algebraically with temperature just above the first-excited state energy scale. In novel iron-based superconductors our results suggest that there is an appreciable temperature range in which qubit read-out can be achieved via the inter-vortex force derived from the hybridisation.

Keywords: Topological superconductivity
Majorana modes
Strontium ruthenate
Unconventional superconductivity
Hubbard model
Advisor: Simon, SH
Confinement and mobility in artificial lipid bilayer interfaces

All biological components are enclosed by membranes. Interfaces formed between membranes enable the transport of matter, information and energy between these components, but also serve as functional platforms for other processes. In these interfaces, membrane components such as lipids and proteins are recruited, sequestered and segregated to accomplish a range of operations. Often, sections of membranes are excised or inserted via transient interface formation. Due to the complexity of these processes, artificial models which represent reduced systems are used to understand the underlying physical, chemical and biological mechanisms. This thesis initiates an investigation into two key behaviours of membrane interfaces. Namely, the effects of substrates and intermembrane spacing on membrane mobility are studied using DNA linkers to alter the interactions between two model membranes; and the organisation of membrane components is studied using an artificial construct designed to mimic the structural properies of the membrane-deforming protein clathrin.

Keywords: clathrin
GUV-SLB interfaces
DNA-lipid interactions
DNA origami
Artificial bilayer interfaces
Advisor: Wallace, M