VictorJuiz/thesis huggingface dataset:
Key transcriptional regulators of neutrophil function in inflammation
Keywords: inflammation
innate immunity
neutrophils
transcription factor
gene expression

Neutrophils are important effector cells in innate immunity, possessing a wide range of effector functions, including reactive oxygen species (ROS) production, phagocytosis and chemotaxis. These properties enable neutrophils to rapidly respond to stimulation and orchestrate protective immunity. Currently, the transcriptional regulatory networks underlying neutrophil activation and function remain largely unexplored. Of note, there is partial understanding of transcription factors (TFs) that act as key regulators to control neutrophil development and inflammatory responses. Neutrophils undergo tightly controlled genomic and transcriptional changes while transitioning between bone marrow, blood, and tissue sites. However, the molecular mechanisms underlining neutrophil function during inflammation have yet to be fully elucidated. To determine the transcription factor networks that shape these responses, we have undertaken integrated transcriptional and chromatin analyses of neutrophils during acute inflammation and revealed distinct sets of putative transcription factors (TFs) associated with control of neutrophil differentiation and inflammatory responses.
To investigate the regulatory role of the selected TFs in neutrophils, I utilised HoxB8 myeloid progenitors as a model system for in vitro production of neutrophils and generated stable knockout lines for JUNB, RELB, IRF5, RFX2, KLF6, and RUNX1 in Hoxb8 myeloid progenitors, using the CRISPR/Cas9 mediated system. Additionally, I have demonstrated the importance of RUNX1, KLF6 in neutrophil differentiation. RUNX1, KLF6 deletion in HoxB8 progenitors caused a block in neutrophil differentiation and produced lower levels of mature neutrophils. KLF6 and RUNX1 deficient neutrophils also displayed impaired transmigration properties. Consistent with findings in the Hoxb8 in vitro model, conditional deletion of RUNX1 in myeloid populations produced lower mature neutrophils in the bone marrow.
To validate the functional role of the selected TFs in neutrophil activation, I examined the consequence of CEBPβ, RELB, IRF5, JUNB knockouts on neutrophil effector functions, such as phagocytosis, cytokine production, generation of ROS, formation of NETs and bacterial killing. I found that RELB, IRF5, JUNB knockout significantly affect the ability of neutrophils to produce inflammatory mediators. JUNB and RELB also contribute to neutrophil phagocytosis, ROS generation and NETosis.
Agents and learning in foreign policy-making: the EU's involvement in the Moldova protracted conflict, 2002-2019
Keywords: policy change
frozen conflict
Transnistria
EU foreign policy
policy instrument
Moldova
policy learning
lesson learning

This thesis seeks to analyze how the EU learns, and in particular, how the EU learns in its foreign policy-making in protracted conflicts. Through a case study analysis of Moldova’s protracted conflict with the Transnistrian de facto breakaway state between 2002-2019, I examine the conditions through which learning is facilitated and leads to policy change in the EU. Using my original Theoretical Model of Learning – an adapted model building on previous learning theories looking at learning as a constitutive process – I analyze the adjustment of goals, instruments, and processes in policy to examine how the EU learns, who are the agents involved, and where learning takes place. A qualitative analysis is conducted of 150 official documents and 8 elite interviews. The project identifies conditions under which learning and policy change impact EU foreign policy towards Moldova, and how it has evolved between 2002-2019 in diffusing lessons learned from the individual, to the organizational levels. I argue theories of learning thus far have failed to account not only for the constituent levels of policy reflection informing the learning process, but also in illustrating the nuanced forms in which learning can manifest, often in reaction to external political shocks. I assert the prevalent conditions impacting EU learning are twofold: The presence of agents of change on-the-ground where policy diffusion is buttressed; and engagement of local agents through bestowment of issue ownership, as it balances policy learning entrenchment at the organizational level.
The reactivity of strained carbocycles
Keywords: reactivity
strain
electronic structure
chemistry

The idea that increasing a reaction driving force will increase its rate is a central principle of chemistry. This principle has been used to great effect for the design of ‘strain-release’ reactions, in which a driving force is provided by building strain energy into the reactant. However, strain release alone is unable to account for the contrasting reactivity of even the simplest of systems, such as cyclopropane and cyclobutane which release near-identical amounts of strain energies but display stark differences in their rates of ring-opening. In this Thesis, the dominance of strain release is challenged by introducing the concept of electronic delocalisation to enhance reactivity: a more delocalised bond will be easier to break, and therefore incur a lower activation barrier to its cleavage resulting in a faster reaction rate. This idea is first explored through a computational study of the electronic structure and reactivity of [1.1.1]propellane (Chapter 2), before the importance of delocalisation is explored in the development of a new synthesis of alpha-chiral bicyclo[1.1.1]pentanes – important motifs in drug discovery (Chapter 3). The relationship between reaction rate, strain release and delocalisation is then quantified through the development of a predictive model for the reactivity of small rings in general (Chapter 4), where three-membered rings are found to be unique in their ability to cause delocalisation-enabled reactivity. In summary, this Thesis introduces a framework to better understand the relationship between ring strain and reactivity, and in doing so guide synthetic efforts towards new reaction design.
Operando characterisations of all-solid-state batteries
Keywords: Li dendrite
all-solid-state batteries
electro-chemo-mechanical models
battery degradation
X-ray computed tomography

The work in this thesis is focused on the mechanistic investigations of all-solid-state battery degradation associated with a lithium metal anode, via the development of operando characterisation techniques, and ultimately enabling the reliable application of lithium metal anode in all-solid-state batteries.
In Chapter 3, the interfacial degradation with the Li metal anode on Li stripping is explored. The void formation is recognised as a form of interfacial degradation that leads to voltage polarisation, local current flux enhancement, and ultimately failure of the cell. The evolution of voids in response to the passage of current is characterised, quantitatively analysed, and with the effects from stack pressure and cycling temperature determined.
Chapter 4 explores the solid electrolyte cracking and dendrite formation as a response to Li plating towards the Li metal anode. The spallation is observed as a way of cracking in solid electrolyte associated with the transverse crack that propagates across the whole cell. The crack propagation and the distribution of lithium inside the crack is tracked as function of the charge passed. The propagation process of Li dendrite and its implication are discussed.
In Chapter 5, models are proposed to explain the dendrite initiation and propagation in all-solid-state batteries based on experimental observations. The assumptions and predictions of the models are explored and discussed. Guided by the models, effective approaches are explored to improve the performance the all-solid-state batteries.
"Good wood on crowdpleasers": humour publications in the Ming Wanli period
Keywords: publishing
compiling practices
Aizi
early modern China
late imperial China
book history
Su Shi
late-Ming book culture
humour compilations
Ming China
jestbooks
humour
textual categorisation
jokes
anthropomorphic biography
paratexts
Master Ai

Joke and humour publications are a severely understudied area of the world of late-Ming book culture. Taking imprints from the Wanli reign period (1573–1620) as a starting point, this dissertation undertakes a preliminary investigation into late-Ming humour compilations. It looks at the publication of humour as a historical phenomenon, rather than from a literary standpoint, to see how this group of books fitted into the publishing and intellectual scene of their day. Towards this aim, the dissertation leans mostly upon the paratextual materials of humour publications, such as prefaces, titles and annotations. These were spaces in which compilers and publishers communed with their faceless, anticipated readership, and as such can be used to yield information about how these compilations were viewed on both sides. Experimenting by temporarily putting aside modern notions of “the joke” in favour of contemporaneous terms used by the publications themselves, the dissertation sketches the boundaries around a broader genre of ‘humour compilations’, thereby reconstructing a genre of publications that were connected in the eyes of Ming publishers and readers, yet has been obscured by subsequent systems of categorisation. It spotlights the ambivalence that surrounded humour as an appropriate topic for publication and the measures taken by compilers and publishers to counter such attitudes. The dissertation also sheds light upon how this group of texts identified with and drew upon precedents from previous dynasties and developed its own set of traditions through an in-depth look at the Ming sequels to the Aizi (“Master Ai”) tradition of Warring States-themed humour, which originated in the Song period. A preliminary discussion on the ‘Dongpo vogue’ in late-Ming publishing reveals the omnipresence of Song dynasty literatus Su Shi in Ming humour publications while simultaneously demonstrating how this group of texts reflected and interacted with the fashions and concerns of the times.
Charge transfer reactions between rare gas ions and polar molecules
Keywords: inverse kinetic isotope effect
coulomb crystals
cold chemistry

Charge transfer reactions between rare gas Xe+, Kr+ or Ar+ ions and polar molecules are investigated. The reactions are undertaken within the cold and controlled environment of Ca+ Coulomb crystals at temperatures lower than 300 K, spanning 194-260 K. Both fully hydrogenated and fully deuterated ammonia and water reactants are employed, with all of these neutral species known to be present in interstellar environments.
Inverse kinetic isotope effects (KIEs) are reported for the ammonia charge transfer reactions, with the deuterated molecules reacting at a faster rate than the hydrogenated species. The magnitude of the effect depends on the identity of the rare gas species; the strongest effect is observed for the Xe+ ions. Capture theory models, which are frequently used to describe ion-molecule interactions, fail to predict these findings. Further, the experimentally measured rate coefficients are suppressed in comparison to classical and quantum capture theory predictions, indicating that the reactions are not capture limited. With the aid of high-level ab initio calculations, a tentative explanation is proposed, suggesting that properties of the reaction complex (such as its lifetime) may give rise to the observed inverse KIEs.
No inverse KIE-indeed, no isotope effects at all-are observed for the water charge transfer reactions, with the measured reaction rate coefficients being in good agreement with capture theory models.
As this thesis will discuss, capture theory models do not always successfully predict the behaviour of ion-molecule reactions. In the absence of experimental data, capture theory models are often employed in astrochemical databases to predict the behaviour of ion-molecule reactions. This work highlights the assumptions underpinning the widespread use of capture theories in astrochemical modelling, and proposes that there is a need for further work to establish when capture theory models can be reliably used to predict the behaviour of ion-molecule reactions.
The role of social media as evidence in asylum procedures in Iceland
Keywords: asylum procedure
digitising borders
social media monitoring
refugees
surveillance
migration

The role of technology in border control has grown steadily in recent years. While smart border technology has become commonplace in many states, the increasing popularity of social media amongst migrant populations offers immigration authorities unprecedented opportunities to access publicly available data on asylum applicants. Although this novel vetting technique has been criticised by human rights activists as invasive and unfair, little academic research exists on the extent to which social media content is exploited as a source of evidence in asylum procedures. The purpose of this study is to address this gap by examining how social media and open-source data shapes the evidentiary assessment in asylum cases in Iceland. Based on eight in-depth interviews with Icelandic immigration officials and legal representatives of asylum applicants, I examine the extent to which social media analyses are carried out and their relevance compared to other sources of evidence. The findings of the study suggest that while social media analysis is used on a regular basis in asylum procedures in Iceland, caseworkers face various structural, personal and bureaucratic hurdles in practice. It is argued herein that due to personal experiences and attitudes towards social media, caseworkers generally consider the evidentiary value of social media too weak to be routinely turned into direct evidence.
Probing and restoring disrupted thalamocortical interactions during Parkinson's disease and essential tremor
Keywords: essential tremor
thalamocortical dynamics
closed-loop neuromodulation
Parkinson's disease

Parkinson’s disease (PD) and Essential Tremor (ET) are two movement disorders where impaired motor function can lead to severe disability. In conjunction with motor impairments, both disorders display augmented frequency-specific activity patterns across brain networks that converge at the thalamocortical (TC) level. In treating motor symptoms, the available therapies for PD and ET modulate these pathologically increased activity patterns. However, therapeutic interventions can also lead to the disruption of physiological brain activity and cause undesirable secondary effects. A major challenge delaying the development of selective neuromodulatory therapies is our limited understanding of the impact of neural activity on function and dysfunction. This thesis contributes to addressing this knowledge gap by probing the TC network dynamics that underlie aberrant synchrony in PD, and by exploring ways of restoring motor function in ET through temporally-specific perturbations of tremor-related TC interactions. By using a combination of tools that span from computational modelling, signal analysis and closed-loop stimulation algorithms we have found that: 1) transient events of high-power beta synchrony in PD are promoted by synaptic dynamics across the TC circuit; 2) the temporal patterning of beta activity in PD is mediated by unit and ensemble dynamic changes in TC temporal alignment; 3) phase-specific stimulation (Cagnan et al., 2017a) can bring kinetic and postural tremor control in ET patients with stable tremor properties, and 4) closed-loop algorithms using online estimates of phase and amplitude to trigger median nerve stimulation might be more effective in yielding tremor suppression in ET patients. Overall, the findings of this thesis contribute to the fields of neuroscience and neurotechnology by deepening our understanding on the dynamics of pathological neural synchrony and shedding light on the key features underlying the efficacy of selective neuromodulatory therapies.
Having meanings in view: groundwork for a substantive account of rule-following
Keywords: McDowell
meaning
normativity
Merleau-Ponty
action
intentionality
Wittgenstein
rule-following

The present work is an attempt to lay the groundwork for an account of rule-following that is both philosophically substantive and partially reductive. It is philosophically substantive in contrast with the kind of discourses that exemplify a quietist approach to philosophy. It is partially reductive inasmuch as it proposes to reconstruct the phenomena of rule-following, linguistically or conceptually shaped meaning, and understanding out of materials that do not presuppose either, though without depriving itself altogether of properly intentional resources.
Ultimately, the present work aims to answer two questions: (i) which feature of signs are we responsive to in cases of rule-following? and (ii) what is the relation between these signs and our responses to them in such cases? It does so, not in sterile isolation from any historical anchorage, but through a critical engagement with the writings of three authors: McDowell, Merleau-Ponty and Wittgenstein. It is, we could say, an attempt at constructive philosophy which takes form in dialogue.
Supervoxel-based image registration and analysis with application to lung cancer
Keywords: supervoxels
image registration
ventilation estimation
lung cancer
image analysis

Lung diseases, including lung cancer, are amongst the largest burdens to healthcare systems worldwide. Improving the extraction of information from imaging data has the potential to provide more accurate diagnosis and more effective treatment. For example, assessing regional lung function could guide more effective radiotherapy treatment to spare well-functioning parts of the lungs. One meaningful regional representation is achieved by locally clustering similar image voxels together using the concept of supervoxels, which allows for bulk regional processing and analysis, whilst removing redundant information. This thesis aims to lay further foundations for supervoxel-based image analysis by presenting novel deformable lung image registration frameworks, as well as a method to estimate lung ventilation using supervoxels.
We demonstrate how a supervoxel-based image representation can be combined with graph cuts as a discrete optimisation-based approach to provide effcient and accurate 3D deformable image registration. Our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation field, allows us to model `sliding motion'. Applying this method to lung image registration results in highly accurate image registration and anatomically plausible estimations of the deformations.
The resulting deformation fields might be further applied to estimate lung ventilation maps. We present a novel approach for estimating regional lung ventilation from dynamic lung CT imaging. Our method combines a supervoxel-based image representation with deformable image registration, performed between peak breathing phases, during which we track changes in intensity for a number of layers of previously extracted supervoxels. Such a region-based approach is expected to be physiologically more consistent with lung anatomy than methods relying on voxel-wise relationships.
Our work also presents novel approaches for performing more accurate hyperpolarised 129Xenon MRI (XeMRI) analysis. We propose a multimodal lung image registration enhanced with personalised motion model approach derived from lung 4DCT. The approach with a prior motion model is particularly important for regions where there is not enough information to reliably drive the registration process, as in the case of XeMRI and proton density MRI (pMRI) to CT registration. Subsequently we introduce a framework for breathing motion correction of the dynamic sequence of XeMRI using a lung atlas-based approach. Such a method for the breathing motion correction is expected to facilitate the analysis of temporal lung ventilation.
Anatomical visions: medical illustrations and (r)evolutionary bodies in the visual arts of modern China, 1851–1937
Keywords: Body
Anatomy
Art
Modern China
Medical Illustrations
Evolutionary Theories

This dissertation examines anatomy, body imagery, and the modern visual information revolution in China from the late nineteenth to early twentieth century. Whereas scholarship on the advent of translated modernity in China has focused predominantly on the roles of literature and political thought, this dissertation argues that the veritable explosion of body imagery in China’s art and visual culture against the preexisting visual tradition points to a significant transformation in which the human body became a central object of visualisation and knowledge production. This seismic shift hinged on the plural anatomical visions of the body in a cultural space of Chinese intellectuals’ sustained epistemological and aesthetic quests to see the previously unseen. Their dialogues with European anatomical imagery in medicine and science occurred simultaneously with their engagement with Western aesthetic body imagery. As representations of the physical body increasingly became a site of cultural identity projection, anatomical imagery intersected with disparate discourses of the body such as gender and subjectivity, beauty and aesthetics, science and evolution, and nation and modernity themselves, collectively amounting to a new modern Chinese visualisation of the body politic.
Chapter One traces plural visions of anatomy beginning with the arrival of systematic Western anatomical imagery and the naturalistic visual world of Darwinian evolution theories in late-Qing China. It sets up the intellectual framework within which the image-making and knowledge-making about the body are examined in the interrelated webs of emerging medical-scientific knowledge, new aesthetic modes of representation, and changing political imperatives in an age of revolutions. The remaining four chapters each examine a separate body trope through in-depth case studies. Chapter Two considers the anatomical womb, through which reproduction was rendered knowable both medically and aesthetically. Chapter Three considers exposed body surfaces and the controversial issue of nudity, shedding light on an essential link between anatomy and art in the formulation of the nude in modern China. Chapter Four examines how the bodily representation of the Chinese masses coalesced around the figure of the hand in tandem with their emergence as a socio-political force, situating the imagery in Haeckelian ecology and inter-communist visual culture. The fifth and final chapter explores how the dead body was rendered anatomically visible as a leitmotif of martyrdom in the age of nationalism, war, and revolution.