VictorJuiz/thesis huggingface dataset:
Modelling oxygen transport and tissue damage in the human brain
Keywords: micro thrombi
oxygen transport
hypoxia
cell death
Green's function method
in silico trials
brain damage
cerebral blood flow
Ischaemic stroke
thrombus
microcirculation

Healthy brain function depends on continuous blood flow carrying oxygen and metabolites. Ischaemic stroke, caused by an occlusion in the cerebral artery that disrupts blood and oxygen supply and leads to irreversible tissue damage, is one of the leading causes of death and disability in the world.
To complement clinical trials to improve the functional outcomes of stroke patients, computational models have been developed to build a virtual platform (i.e. an in silico trial) to test the feasibility of new treatments. However, the role of the human cerebrovascular system in oxygen transport and tissue health remains poorly understood, which limits the utility of current brain models. Therefore, it is necessary to develop new models of oxygen transport and tissue damage for the human brain to improve our understanding of brain physiology and diseases.
This thesis first models oxygen transport in human capillary networks using a Green’s function method. The effects of microembolism on oxygen delivery are simulated to derive a quantitative relationship between tissue hypoxia and vessel blockage. In human cortical columns supplied by a single penetrating arteriole, oxygen transport is simulated after the arteriole tree is occluded by a 25 μm microthrombus to mimic a rodent experiment of microembolism. Reasonable agreement has been shown between simulations and experiments measuring the spatial correlation between hypoxic regions and occlusion sites.
A novel 3-state cell death model and a thrombus extravasation model are then proposed to simulate the irreversible tissue damage caused by cerebral microvascular occlusions. The cell death model is further developed to simulate brain tissue damage over time under different ischaemic conditions. A full in silico trial of ischaemic stroke can thus be built by coupling the cell death model with existing whole brain models of cerebral blood flow and ischaemic stroke.
Unconventional functions of MR1 restricted T-cells
Keywords: tissue repair functions of MAIT cells
MR1 based immunotherpay
MR1
regulatory functions of MAIT cells
MR1T
cancer immunotherapy
mucosal associated invariant T-cells
MR1 restricted T-cells
endogenous antigens
MAIT

The non-polymorphic MHC class I-related protein 1 (MR1) is an antigen presenting receptor that displays endogenous or microbial-derived metabolic intermediates. The commensal antigens, such as intermediates of the riboflavin synthesis pathway, are the most well understood so far and, these are known to activate mucosal associated invariant T (MAIT) cells. MAIT cells have been widely studied for their innate-like properties and, their strong pro-inflammatory and anti-microbial functions in response to TCR-dependent and TCR-independent signalling. These characteristics confers them with an important, but so far unclear, role in mucosal immunity and autoimmune diseases. Other non-MAIT MR1-restricted T (MR1T) cells have shown specificity to both commensal and endogenous antigens; however, we are still far from understanding the diversity in their functions, phenotype, antigenic specificity and, TCR repertoire.
In this thesis, we used RNAseq analysis to dissect the downstream effects of TCR-dependent and TCR-independent signals on their own and in combination. Our experiments revealed that while the inflammatory responses are tightly regulated and primarily driven by TCR-independent signalling, TCR-mediated activation elicit other unexpected functions related to homeostasis and tissue repair. These data provide a deeper insight on how MAIT cells balance inflammatory and protective functions at barrier sites under constant exposure to the microbiota.
We also explored MR1 as a target molecule for TCR-based immunotherapy against cancer disease. We hypothesised that the endogenous metabolic intermediates could be antigens of interest for the specific targeting of cells undergoing metabolic stress, such as transformed cancerous cells. In this thesis, we collaborated with Immunocore, a leader in TCR-based immunotherapies, to validate the role of MR1T cells in cancer disease and analysed the specificity of 2 new autoreactive MR1T cells. This work also proposes new methods to accelerate the discovery of antigens and TCR sequences in the unexplored field of MR1T cells.
Origami- and kirigami-adapted thick-panel folding
Keywords: compact folding
Hamiltonian circuit
uniform thickness
thick-panel kirigami
single-DoF assembly of 8Rs
spring-loaded hinges
collision-free deployment

This dissertation is concerned with folding rigid panels of uniform thickness into a compact volume and deploying it back to a continuous and flat surface in a predictable manner afterwards. This was achieved by either forming an assembly with a single degree-of-freedom (DoF) through special geometric designs of thick-panel kirigami or ensuring a collision-free deployment of a multiple-DoFs system through dynamics simulations. Four major findings of this dissertation were as follows. First, kirigami patterns were investigated to enable the folding of a chessboard-like array with identical panels into two stacks without any voids. Revolute joints (also known as hinges or rotational joints) and slits are placed to connect or disconnect panels according to a Hamiltonian circuit (HC) (Hamilton, 1856) that was drawn over the array. If multiple HCs were found, a method was proposed to select the ones that could be folded into two stacks. Physical prototypes were made to validate the designs. Secondly, simple spring-loaded hinges were used to synchronise the deployment of a multiple-DoF assembly resulting from the HC approach. An optimisation method was proposed to select the stiffness of hinges to ensure a collision-free deployment. Dynamic simulation of the deployment and collision detection method were incorporated into the optimisation process. By this approach, the trajectories of panels were sequenced to avoid collisions during the deployment, and the array was always deployed to a flat surface from packaged stacks, which were further validated by experiments. Thirdly, through special geometric designs, interlinked regular flat rigid panels of uniform thickness were folded into compact stacks with a single DoF. Kinematically the deployable structure is an assembly of several 8R closed chains. Although such a chain with eight rigid bodies and eight revolute joints would have two DoFs in general, a single-DoF assembly was created by combining them in a particular way. The bi-directional folding concept can be extended to fold an assembly consisting of an infinite number of panels. Not only can this work be directly applied to the design of future flat arrays, but is also important in the theory of mechanisms as the proposed assemblies are rare examples where a kinematic loop consisting of linkages of multiple DoFs possesses single mobility. Finally, a modular approach was proposed to fold arrays composing squares or the combination of squares and half-square triangles into a compact volume that is conforming to the shape of a CubeSat. The obtained arrays could possess a single DoF or a small number of DoFs.
Unsupervised learning of 3d objects in the wild
Keywords: unsupervised 3d learning

We live in a physical 3D world. Being able to perceive the world in 3D allows us to confidently navigate and perform sophisticated actions in it. Developing 3D perception systems is not only key to many AR and robotics applications, but also fundamental to the goal of visual understanding. However, most existing learning-based image understanding models process images simply as compositions of 2D patterns, ignoring the fact that images arise from a physical 3D world. Recent advances in differentiable rendering have opened new possibilities for learning physically-grounded disentangled 3D representations from raw images, marrying geometry with learning at last.
Learning 3D representations typically requires 3D supervision. This has previously come in the form of 3D labels, shape models, multi-views, or 2D geometric annotations, such as keypoints, masks and camera viewpoints. However, all of these are prohibitively expensive to collect on a large scale, which has become a major obstacle for learning 3D representations of general objects in the wild.
In this thesis, we explore the possibility of learning deformable 3D objects simply from raw casually recorded 2D image data “in the wild”, such as online photos and YouTube videos, without relying on heavy manual supervision. At the core of our approach is a Photo-Geometric Autoencoding framework that decomposes images into a set of physically-grounded photometric and geometric factors, including 3D shape, pose, shiny surface material, environment lighting and camera parameters, with the objective of recomposing them to reconstruct the input images through a differentiable renderer. In order to resolve the ambiguity in this highly ill-posed task, we propose to inject generic inductive biases to exploit the symmetries and regularities of the world. The resulting model is able to learn disentangled 3D priors of various deformable object categories, allowing for single-image inference at test time.
Bank failures: what failure? Distress, development, and supervision in Italian banking, 1926-1936
Keywords: financial development
bank failures
overbanking
banking supervision
banking crises
banking regulation
Great Depression

This dissertation studies the experience of Italian commercial banks between 1926 and 1936. To do so, it employs a mix of qualitative and quantitative methods. It presents a new database of banking distress, which includes not only outright bank failures but also those failures that were hidden and resolved behind the doors. This reconstruction is based on extensive archival research using the classified documents of Italian banking supervision (Archivio Storico della Banca d’Italia, and Archivio Centrale dello Stato). It reveals that the distress of small and medium banks was anything but negligible. Once distressed but resolved banks are considered, the magnitude of the crisis would be considered ‘systemic’ by today’s standards. It also shows important regional patterns: in terms of bankruptcies, Southern Italy suffered relatively more than the rest of the country. This thesis advances a new narrative on the causes of this crisis of Italian commercial banks. I argue that banking distress was not the outcome of a ‘bad credit boom’, but it is better understood as a process of ‘financial development gone wrong’. The 1920s were a crucial period of banking development for Italy, when the number of banks and branches expanded considerably. Coeval observers, however, considered this expansion as ill-fated. Regression analysis on bank balance sheets confirms their interpretation. The archival research conducted for this dissertation also sheds new light on banking supervision under the 1926 banking law – a law mostly known in the literature for having failed to prevent the failure of the big four universal banks in the 1930s. Using unexplored archival sources, this thesis documents in detail the functioning of banking supervision. I argue that, once the day-to-day functioning of the law is taken into account, the new regulation and its enforcement through supervision had a positive impact on small and medium commercial banks.
The assessment of surgeon-patient communication: An examination of validity

Keywords: MEA 2022
MEA

The ability to communicate competently is essential in medicine since it is integral to the provision of effective healthcare. This dissertation investigates how a surgeon’s communication skills are assessed within the context of Part B of the Membership of the Royal College of Surgeons (MRCS) examination. Through an exploration of perceived authenticity, this study examines if the communication skills component of the MRCS Part B is a valid reflection of clinical practice and whether it is a worthwhile assessment of surgeon-patient communication.
An online questionnaire was completed by 63 junior surgical trainees who sat the MRCS Part B between October 2018 and February 2022. In addition, semi-structured interviews were conducted with seven consultant surgeons and three senior surgical registrars, all of whom work in the UK’s National Health Service (NHS). The responses were analysed with descriptive statistics, inferential statistics, and inductive thematic analyses.
It was found that certain variables, such as the behaviour of simulated patients and the scenarios that frame the communication skills stations, shape how candidates communicate. Some candidates do not necessarily communicate in the exam as they communicate in clinical practice, which threatens the validity of the interpretations made and the actions taken based on the outcomes.
This study highlights several benefits of the communication skills component of the MRCS Part B, including its attempt to corroborate that a Core Surgical Trainee is competent to progress to Specialty Training. However, the impact on the patient must be brought to the forefront. If the exam confirms a candidate can communicate effectively, its outcomes must be valid to reflect this.
Graph geometry from effective resistances
Keywords: discrete curvature
effective resistance
network science
simplex geometry

The main subject of this thesis is the effective resistance — a measure of distance between the nodes of a graph which reflects how close or well- connected two nodes are, taking into account all paths between them and their interconnections.
The effective resistance has many other properties, however, and the contribution of this thesis is twofold. First, we provide a self-contained and unified exposition of some important but not well-known results on the effective resistance: the Fiedler–Bapat identity between Laplacian and resistance matrices and the graph–simplex correspondence. Second, we introduce and study two new applications of the effective resistance: a distance-based measure of variance for distributions on the nodes of a graph, and two resistance-based graph invariants p and σ2 which we interpret in the context of discrete curvature.
These contributions are unified in their geometric perspective on the effective resistance — ranging from the celebrated concept of resistance distance, to the lesser-known but far-reaching relation to simplex geometry and finally, a newly discovered relation to discrete curvature.
While the focus lies on developing the mathematical theory of effective resistances in a unified matrix-theoretic language, we also discuss many examples and some applications. In particular, the proposed measures of variance and covariance are readily applicable in practice to study functional data (signals, distributions, etc.) defined on graphs.
We hope that the exposition in this thesis will enable and stimulate further research on this fascinating subject and in particular on the theory of the resistance-based graph invariants p and σ2, the full depths of which still remain to be explored.
The role of microglia in activity-dependent neuronal network maturation and maintenance
Keywords: neuronal activity
brain development
Snap25
DREADD
microglia
sexual dimorphism

Neurons comprise only less than half of the nervous system, yet some of all those other cells have been largely ignored. Microglia are the tissue resident macrophages of the brain. These cells play a key role in shaping neuronal network formation during development and subsequently help to maintain a stable and healthy brain. After birth our brain contains overabundant neuronal connections and some of these must be refined and eliminated. Microglia scavenge the unnecessary connections via synaptic pruning and shape the neuronal network. Any abnormality in this interaction during neuronal network formation and maintenance can lead to a variety of neurodevelopmental disorders such as autism or schizophrenia. Yet, neither the risk factors underlying these disorders nor the mechanisms that regulate synaptic pruning in the developing brain are well understood.
My DPhil project tested the hypothesis that excitation or inhibition of specific neurons in a neuronal network changes microglial behaviour and dynamics leading to altered communication between microglia and neurons. Using a mouse model, I selectively removed parts of the Snap25 gene, and it produced a non-functioning protein in a subset of cortical layer 5 projection neurons and some hippocampal dentate gyrus neurons and thus also eradicated their ability to release synaptic vesicles in a regulated manner from around the time of birth in a chronic fashion. I observed that abolition of Snap25 expression reduced microglial activity and altered synaptic maturation. Also, it affected microglia-neuron communication by disrupting normal chemokine and phagocytic signalling. Lastly, I observed sex-specific changes in microglia-neuron communications, and this indicated that male mice were more sensitive to abolished Snap25-mediated release of synaptic vesicles during brain development. To test whether the same changes would apply for more acute silencing, I used chemogenetic manipulation to increase or reduce network activity of the same subpopulation of layer 5 and hippocampal neurons for hours rather than weeks. I observed that chronic synaptic and acute chemogenetic ‘silencing’ affects microglia in the same manner. Moreover, acute chemogenetic activation alters microglial morphology leading to retraction of processes and shift to a highly phagocytic active amoeboid form. Findings from my doctoral project suggest that interaction between microglia and neurons is bidirectional in an activity- dependent and sex-specific manner. Given the differential effects of synaptic ‘silencing’ on microglial cell morphology and activity in males and females, it would be interesting to speculate that microglia may contribute to the sex-specific effects of synaptic ‘silencing’ on microglia-neuron communications and synaptic maturation during development.
Profiling the 'Triple Crusade', c.1233-c.1241
Keywords: Valencia
Barons' Crusade
Latin East
Constantinople
Crusades

During the late 1230s, the Mediterranean saw crusades launched across its full breadth. From Muslim Valencia in the West, through Frankish Greece to the Holy Land, the Mediterranean saw redemptive war waged by Latin Christendom upon its neighbours, whether those neighbours be Muslims, as in Iberian or the Levant, or schismatics and heretics, as in the Balkans. Despite the success all three of these campaigns attained, they are often overlooked by crusade historians, perhaps due to the comparatively small sizes of the Greek and Outremer campaigns. This thesis contends all three campaigns warrant further investigation, both in order to reveal more about the campaigns themselves, and as exemplars from which to ground points of general resonance about crusading history. In undertaking this investigation, this thesis takes a broad approach to the expeditions using a wide range of sources, both chronicle and documentary, both Eastern and Western.
Tracing the expeditions thus from their inception in 1233 until their conclusion in 1241 achieves several distinct things. For one, given the special status of these three expeditions within the plethora of crusades called by Pope Gregory IX and the overlap in recruitment and participation witnessed between the three crusades, the connectivity between them is revealed. These were not simply coincidentally simultaneous events, but three equal parts of the same movement. That is why when approaching events, this thesis proposes the title “Triple Crusade”, replacing the heading of “Barons’ Crusade”. Secondly, taking a broad approach that includes oversight of all three campaigns allows fresh analysis of their preaching, financing and recruitment drives, advancing current knowledge on the subjects both in a specific and a general sense. Thirdly, taking a broad approach shows the actual expeditions took place within a much wider world than historians have previously allowed, with the influence of non-Latin agents key.
Interplay between oxygen sensing mechanisms and hepatitis B virus replication
Keywords: HBV
oxygen sensing
hypoxia
hepatitis B
hepatology
liver

Hepatitis B virus (HBV) preferentially replicates in the liver, a naturally hypoxic organ with an oxygen gradient from 8-4% in the periportal and pericentral regions, respectively. The hypoxia inducible factor (HIF) pathway is the most well studied mammalian oxygen sensing mechanism and is frequently perturbed by pathological states including infection and inflammation. However, the majority of in vitro studies have investigated HBV at atmospheric oxygen tensions (18%) where low oxygen sensing mechanisms are inactive and consequently their role in viral replication may be overlooked. Therefore, this thesis studied the interplay between HBV replication and oxygen sensing mechanisms.
Chronic hepatitis B (CHB) is associated with an increased expression of HIF gene transcripts. Further interrogation of a cohort of patients with CHB shows an association between inflammatory responses and HIF transcription. Importantly, this observation is not recapitulated in state-of-art in vitro, in vivo, and de novo HBV infection model systems.
HIF regulates target genes via HIF responsive elements (HREs), and the discovery of two evolutionarily conserved HREs in the HBV genome prompted experiments to understand the role of HIFs in viral replication. HIF siRNA silencing experiments in vitro and in vivo demonstrate a positive role for HIFs in regulating HBV replication.
As other oxygen sensing mechanisms have been identified in addition to the HIF pathway, further experiments assessed the role of hypoxia and HIF independent mechanisms in regulating HBV transcription. Data suggests that hypoxia positively regulates HBV transcription through both HIF dependent and independent mechanisms. Further investigations reveal that low oxygen downregulates the HBV host restriction factor Smc6 through HIF independent mechanisms. In addition, the cysteamine (2-aminoethanethol) dioxygenase oxygen sensing pathway regulated interleukin-32 may have anti-viral activities that are repressed under hypoxia.
Collectively, this thesis presents evidences demonstrating key regulatory interactions between HBV and hypoxia, revealing novel therapeutic directions.