VictorJuiz/thesis huggingface dataset:
Design of modulatory peptides against chemokines
Keywords: inflammation
chemokine
CCL8
evasin
peptide
tick

Chemotactic cytokines or chemokines are small signalling proteins responsible for the recruitment of leukocytes to sites of inflammation. Although, chemokines are critical to orchestrate effective immune response, many have been associated to several inflammatory disorders. Despite being recognised as therapeutic target, no efficient treatments targeting the chemokine network for inflammatory diseases are available to date. This is attributed with the complexity of the many and varied chemokine interactions with themselves, their receptors and glycosaminoglycans on extracellular matrix. Thus, the pharmaceutical industry dogma of “one molecule, one target” is rendered ineffective against this network. Evasins are small tick saliva proteins that can bind and neutralise several chemokines, therefore allowing the tick to feed on their host for days without sparking an immune response. The potential of Evasins as effective anti-inflammatory agents was proven in many pre-clinical disease models. The interest in Evasins led to the discovery of a novel Evasin, P672, that can bind a wide range of CC chemokines. This work describes the discovery of peptides inspired by the chemokine binding site of P672. These peptides were shown to neutralise several chemokines and exhibited in vivo anti-inflammatory activity. A novel generation of P672-inspired peptides were designed and exhibited multiple chemokine-binding properties with increased human plasma resistance. Finally, P672/chemokine interfaces were mapped using peptide display techniques informing on P672 binding sites and its mode of action to neutralise chemokines. This work demonstrates the exciting potential of utilising Evasin/chemokine interaction studies with informed mode of action as starting points for anti-inflammatory peptide development.
Generation and analysis of attack graphs on computer networks
Keywords: attack graphs
cybersecurity
network security

The complexity of computer network attacks requires a sophisticated understanding of network security. Attackers combine seemingly inconsequential vulnerabilities into damaging attacks. Attack graphs compactly represent the possible ways exploits can be combined in the network by attackers. Armed with an accurate, up-to-date and sufficiently-detailed attack graph model, network defenders could straightforwardly select the most critical vulnerabilities and weaknesses in their network, allowing them to perform the necessary actions to optimally mitigate the threat.
But attack graphs suffer from a number of problems that stand in the way. They rely heavily on data sources that were not intended to be used for this purpose, and have not been demonstrated to be reliable enough. Graphical models frequently suffer from complexity problems, and attack graphs are no exception. Once an attack graph is constructed, it requires analysis methods that are hard to verify, making any conclusions hard to justify.
In this thesis, I address each of these problems through a variety of theoretical methods. I begin by establishing a clear definition of attack graph, based on template-matching methods. This is used to provide a set of comparisons by which attack graph analysis techniques can be verified theoretically, demonstrating that some common analysis methods perform unreasonable assessments. From this basis, I examine the assumptions that underlie attack graph models, and propose two novel assumptions, the single-precondition assumption and the partitioned-preconditioned assumption. I also provide a motivating smart home example, together with a dataset of vulnerabilities.
I provide two independent contributions towards the generation and analysis of attack graphs; the first is a method to construct attack graphs without vulnerability data, making them easier to construct and allowing them to model zero-day vulnerabilities. The second is a method to parametrise attack graphs, enabling analysis to incorporate characteristics of the attacker and decisions of the defender, so that analysis can be performed across the full spectrum of possible attackers and defender decisions. Finally, these techniques are combined and presented with a collection of possible analysis methods, and applied to the smart home use case through a software implementation.
Efficient object detection and discovery for real-world robotics applications
Keywords: Generative models
Object discovery
Robot manipulation
Object representations
Variational autoencoders
Autonomous driving
Sparse convolutions
Representation learning
Image generation
Object detection

Robots need to interact with the world to complete practical tasks. This typically requires the interaction with objects, rendering object perception a fundamental capability in robotics. Real-world robotics applications provide particular challenges and opportunities for object perception. It is possible to utilise data from a variety of sensing modalities, such as cameras and lidar devices, but physical hardware constraints demand careful management of computational resources. Similarly, the need to respond to changing environmental conditions and task definitions requires robots to learn efficiently from limited human supervision. Efficiency in terms of computation and supervision are thus essential. To these ends, this thesis makes several contributions. Firstly, we develop Vote3Deep which is - to the best of our knowledge - the first method that performs efficient, native 3D object detection in real-world lidar point clouds with convolutional neural networks (CNNs). This is achieved by maintaining the natural sparsity inherent in the data throughout the CNN hierarchy and by leveraging an efficient, sparse convolution operation. Secondly, we present GENESIS which is - to the best of our knowledge - the first object-centric generative model that learns to decompose rendered images of simulated 3D environments into object-like components without supervision, while also being able to generate entire coherent scenes in an object-centric fashion. This is facilitated by an autoregressive prior that captures correlations between objects in the generative model, offering the potential of utilising GENESIS as an object-centric
world model'' for efficient skill acquisition. Given that we want to apply object-centric generative models in real-world applications, we finally develop GENESIS++ which utilises a novel algorithm for fully-differentiable clustering of instance embeddings to facilitate the symmetric inference of object representations. We show that GENESIS++ outperforms competitive baselines both on well-established simulated datasets and on challenging real-world datasets collected in the context of robotics applications.
Diaspora return to politics: from state collapse to a new federal Somalia and Somaliland, 1985–2018
Keywords: International organisations
Post-war reconstruction
Statebuilding
Somalia
Diaspora politics

African governments and their political structures are now increasingly constituted of returning diaspora. The thesis explores the international and domestic political processes through which diaspora return to politics and influence the Somali-speaking subnational and national administrations of the Republic of Somaliland, Puntland Member State of Somalia, and the Federal Government of Somalia from 1985 until 2018. These processes are traced across the three contexts and chronologically from the irredentist fight of the 1980s, through state formation and reconstruction processes after 1991, and up to contemporary politics. In each context, different historical and conflict legacies, state formation processes (including relationships with the international system) and internal elite pacts shape the opportunity structures for diaspora politicians to contest and influence politics. Divergences emerge in trends in leadership succession, including the rise and fall of diaspora administrations, as well as in the forms of alliance building and local resistance that emerge against periods of diaspora rule. This thesis is particularly concerned with how international actors and statebuilding agendas may confer undue legitimacy on diaspora politicians and empower them to challenge existing political arrangements and systems of clan governance. As such, this thesis contributes to key academic debates about clan politics and limited stateness, the symbolic valence of expertise, and the politics of state formation.
Applying genetic epidemiology to explore sex-specific causes, correlations and consequences of obesity
Keywords: PCOS
genome-wide association study
obesity
proteomics
GWAS
Mendelian randomization
polycystic ovary syndrome

Obesity has considerable consequences on global health. Yet, it is relatively unexplored if the causes and consequences of obesity and obesity-related diseases differ between men and women. The increased scope of genetic studies provides an opportunity to leverage genetic data to characterise sex-specific epidemiological relationships using methods less prone to reverse causation and confounding, such as Mendelian randomisation. Thus, I aimed to investigate the sex-specific causes and consequences of obesity using genetic epidemiology, as well as to identify potential disease-mediating genes in two common obesity-related female reproductive diseases: polycystic ovary syndrome and miscarriage.
In my first research chapter, I use Mendelian randomisation to investigate the sex-specific effects of obesity on leading causes of death from non-communicable diseases, before comparing the men- and women-specific effect estimates. My results indicate that the disease risk arising from obesity differs between the sexes for several diseases, including type 2 diabetes, renal failure, and chronic obstructive pulmonary disease.
I then proceed to perform sex-stratified genome-wide association studies of 2,623 unique proteins and compare the effect estimates of the genetic variants between the sexes. Using these data, I compare the effects of proteins on obesity and cardiometabolic diseases between men and women. My results in this chapter indicate that up to 15% of protein-associated genetic variants may have different effects in the two sexes. I further identify seven proteins with sexually heterogeneous effects on obesity in men versus women, including two proteins – kynureninase and N-terminal pro b-type natriuretic peptide – with seemingly opposite effects in men compared to women. However, sensitivity analyses indicated that my results may be affected by poor specificity in the original protein measurements.
Finally, in my third research chapter, I use colocalisation to highlight potential disease-mediating genes in polycystic ovary syndrome and recurrent miscarriage. While I was not able to identify any potential disease-mediating genes for recurrent miscarriage, I identify eleven genes and proteins with evidence of colocalising with risk of polycystic ovary syndrome.
My thesis demonstrates that causal relationships in cardiometabolic disease can differ between the sexes, and emphasises the importance of investigating sex-specific effects. Furthermore, my results highlight several genes and proteins that may contribute to obesity and obesity-related diseases. Although their clinical utility will need to be established in future studies, several of these genes and proteins hold promise for use as biomarkers or for targeting by drugs to improve the health of both men and women.
Neuromodulation in pain
Keywords: deep brain stimulation
dorsal root ganglion stimulation
pain
neuromodulation

Background
Chronic pain is one of the most debilitating disorders afflicting a wide cross-section of the global population. Unfortunately, conventional treatments for chronic pain have proven ineffective for a large subsection of this patient population, prompting the development of new therapeutic paradigms such as neuromodulation. Deep brain stimulation, dorsal root ganglion stimulation and non-invasive brain stimulation have emerged as useful tools in the therapeutic armamentarium for these medically refractory chronic pain patients. We sought to interrogate how these treatments might work and what insights can be gained into the neurophysiology of the pain experience through neuromodulation.
Methods
This thesis describes three categories of experiments into the neurophysiology of chronic pain. The first explored the mechanisms of dorsal root ganglion stimulation in the sensory, cognitive and affective dimensions of pain, as well as its potential to modulate the autonomic nervous system. The second interrogated the utility of non-invasive brain stimulation, transcranial direct current stimulation, to augment the supraspinal effects of dorsal root ganglion stimulation. The final experiment involved a retrospective analysis regarding the effectiveness stimulation frequency in deep brain stimulation for chronic pain and whether these treatments are dependent on underlying neural activity.
Results
1. There were significant neurophysiologic markers of pain (cortical theta activity) and pain relief (cortical beta activity) among dorsal root ganglion stimulation patients, with efficacy in modulating sensory, cognitive and autonomic indicators in chronic pain patients. The affective dimension of 3 pain revealed mixed results, however demonstrated features consistent with differences of emotional processing in chronic pain compared to healthy controls.
2. Transcranial direct current stimulation significantly enhanced the therapeutic efficacy of dorsal root ganglion stimulation on chronic pain in the acute setting and demonstrated augmentation of predetermined neurophysiologic indicators (cortical beta activity) of pain relief.
3. The efficacy of deep brain stimulation did not appear to be dependent on stimulation frequency. However, baseline local field potential recordings appear to be predictive of the ideal stimulation frequency to optimise analgesic effect in chronic pain patients.
Conclusion
This thesis provides novel evidence of the mechanisms of dorsal root ganglion stimulation and provides preliminary evidence of a synergistic effect between invasive and non-invasive neuromodulation in the treatment of chronic pain. We have also provided supportive evidence for the utility of physiologic biomarkers of pain in evaluating neuromodulatory therapies as a framework for personalising chronic pain treatments.
Narratives of confession in France from Musset to Zola
Keywords: Musset
confession
sand
novel
translation
nineteenth-century France
Zola
De Quincey

This thesis argues that the novel of confession was a highly significant genre in early-to-mid-nineteenth-century France. This genre has identifiable traits, which are echoed in multiple novels, and even, at times, parodied. The thesis analyses these traits through a close and comparative study of both canonical and non-canonical writers, including Jules Janin, Alfred de Musset, Frédéric Soulié, Xavier de Montépin, Champfleury, Arnould Frémy, Mme du Saule, Marie Garcia, George Sand and Émile Zola. It argues that the genre both draws on the models of autobiographical confession offered by St Augustine, Rousseau and De Quincey (translated into French by Musset in 1828), and engages in an irreverent dialogue with Catholic confession, around which a polemic was raging in the period. The thesis takes the story as far as 1865, a pivotal year in which Zola's La Confession de Claude — an uneasy hybrid between confessional discourse and what the Goncourts call enquête sociale — signals the end of a chapter in the genre's development.
The first chapter — 'The Transgression, or What is Confessed?' — argues that the novel of confession consistently breaks Catholic rules about sinning and redefines the sphere of confession away from wrongdoing towards suffering and selfhood. The second chapter — 'The Self, or Who is Confessing?' — argues that the novel of confession centres around protagonists who are unsure of their (emotional, and sometimes, actual) identity, presenting characters who are fragmented within themselves, often on the point of suicide or madness. Far from confession resolving these characters' problems of selfhood, it tends to fragment the self further. The third chapter — 'The Confession(s)' — argues that these novels repeatedly stage acts of confession, in both religious and secular contexts. In so doing, they invariably challenge the principles of both Catholic confession and autobiographical confession, consistently showing acts of confession that 'fail' according to the models from which they draw. The novel of confession is thus a disruptive genre, which unmakes the act by which it is defined.
Deeply religious nonbelief: countering the affective case against naturalism with embodied cognition
Keywords: emotion
embodied cognition
imagination
affect
naturalism
religious naturalism
wonder
narratology
embodied simulation
embodied metaphor

The Affective Case against Naturalism (ACAN) claims that naturalism cannot be emotionally satisfying. I argue that Religious Naturalism (RN) is concerned with developing meaningful myths founded on mainstream science; that my concept of affective embodied cognition (AEC) has an enabling role in that process; and that in doing so AEC overturns the ACAN.
The ACAN has deep roots but emerges starkly in critiques of the ‘disenchantment’ of modernism. It is challenged explicitly by RN, which owes debts to William James, John Dewey and George Santayana. I define AEC as a combination of ‘4EA’ cognition, embodied metaphor and embodied simulation, and build a model for analysing the affective processes engaged when consuming texts.
I show that AEC can counter the purportedly alienating character of scientific explanation by analysing the work of David Abram, and evaluate affective engagement with nonhuman entities. Abram exemplifies naturalist imaginaries that elevate the material, participating with the unseen and indeed unsensed. I then demonstrate how toggling between two distinct forms of attention dissected by Iain McGilchrist reveals how wonder and explanation can co-exist.
I concur with Mary Midgley and Lisa Sideris that scientific theories do not disclose specific human purposes, but show that once a purpose is chosen, AEC offers opportunities to align readers behind it. I also demonstrate that while some RN narratives are anthropocentric, alternative narrative plots with various affective topographies are available.
I review naturalist strategies to ease death anxiety, suggesting that the relation between direct perception and embodied simulation involves isomorphic material configurations. These entail imperfect reconstructions of those absent and their experiences. Finally, I propose that the origin and identity of all life on Earth in a supernova can be blended with the affectivity of the stellar, such that stars can serve as a focaliser upon which numerous naturalist ideas can hang.
The prologue to John in Ibn al-Ṭayyib's commentary on the Gospels
Keywords: Bible
Ibn al-Ṭayyib
prologue
al-Tayyib
John
Abū al-Faraj
commentaries
Gospels

The thesis presents a critical edition of the Arabic text (Chapter 2), annotated translation (Chapter 3) and analysis of various aspects of the Prologue to John in the Commentary on the Gospels by the Abbasid philosopher, doctor, theologian and Biblical exegate, Abii al-Faraj ‘Abd Allah ibn al-Tayyib (d. 1043/44). It is unquestionably the most influential work of Gospel exegesis in Arabic. The critical edition compares three mss, Paris ar. 85 and 86 (both c. 13th C), and BL or. 3201 (early 19th C). All three are of Egyptian provenance.
Chapter 4 analyses the differences between the original Eastern (‘Nestorian’) and later Miaphysite (‘Jacobite’) recensions, whilst Chapter 5 consists of a discussion of the exegetical sources for the Commentary(meaning that portion of it on the Prologue to John), concentrating on Theodore of Mopsuestia, Chrysostom, Moshe bar Kepha and Isho‘dad of Merv, only the last of whom has been established as a likely direct source. Unidentified intermediaries were established as being the sources for interpretations derived from the other exegetes. Close links were identified between the East- and West-Syriac exegetical traditions.
Chapter 6 discusses the technical terminology in (and beyond) the Commentary including, in particular, a substantial analysis of jawhar (substance) and ddhdt (essence), and terms relating to ‘person’ and hypostasis. Chapter 7 analyses the Biblical quotations in the Commentary, found to be translated from the Peshitta, and a discussion of the strong possibility of Ibn al-Tayyib's authorship of the Arabic Diatessaron There is also analysis of the Ge‘ez (Ethiopic) translation of the Commentary (Chapter 8).
A context for the Commentary is provided by a biography of the author (Chapter 1), based on a detailed analysis of the primary sources, along with a brief survey of his works. There is also a discussion of his relationship with Ibn Sinā.
The conclusion includes a discussion of Ibn al-Tayyib’s relationship to the Islamic tradition, which turns out to be far from obvious.
Radiation damage and transmutation in tungsten-alloys for nuclear fusion applications
Keywords: Atomistic Kinetic Monte Carlo
Radiation Induced Precipitation
Atom Probe Tomography
Tungsten Rhenium Osmium Alloys
Radiation Damage

In this work, the effect of neutron-induced radiation damage and transmutation on the microstructure of W is investigated. Samples irradiated in the High Flux Reactor to a dose of 1.67 dpa at 1173 K were characterised using a combination of atom probe tomography and electron microscopy based techniques. Characterisation showed a microstructure dominated by voids and precipitates rich in Re and Os atoms produced via transmutation. Voids were shown to be decorated with Re and Os. Samples with equivalent Re and Os concentrations were produced via arc melting by ACI alloys, and heavy-ion irradiated at Sandia National Laboratory, USA, to a peak dose of 1.7 dpa at 1173 K. Characterisation using APT and TEM was used to highlight key differences in the microstructure produced by ion and neutron irradiation, including a smaller average void size and weaker precipitate formation. The clusters observed under ion irradiation were smaller, more diffuse and consisted primarily of Os, with slight enrichment of Re measured using cluster analysis techniques. The clusters in the neutron irradiated ma- terial on the other hand were dense and comprised mainly of Re, but with a central Os rich core. Cluster analysis methods showed cluster compositions comparable to samples from the Joyo reactor, however, line profile analysis suggested that some of the clusters had a composition consistent with σ phase in the centre. Kinetic Monte Carlo simulations of W-Re showed that transport of Re to point defect sinks occurred via mixed interstitial defects. A new energy model including Os was developed in which more accurate vacancy interactions were modelled by introducing local vacancy concentration dependant interactions. Analysis of the binding energies showed that Re and Os bind strongly to vacancies, and that Os had the strongest binding. The new model was used to simulate the formation of voids in W under irradiation and forms the basis for further study of the phenomena observed experimentally in this thesis.