VictorJuiz/thesis huggingface dataset:
Time-efficient methods for non-invasive brain blood flow imaging using arterial spin labelling MRI

Accurate knowledge of brain tissue perfusion and clear visualisation of cerebral arteries are of great interest for the diagnosis and research of a range of diseases and conditions such as stroke, dementia, Moyamoya, and cancer, as well as in drug development. 15O-H20 PET imaging is considered the gold standard for measuring cerebral blood flow (CBF), while contrast-enhanced x-ray digital subtraction angiography is the gold standard for visualising cerebral arteries. However, both methods use ionising radiation and injectable contrast agents so carry some risks to the patient and are not appropriate for longitudinal monitoring or research.
There is growing interest in arterial spin labelling (ASL) magnetic resonance imaging (MRI), which uses magnetically labelled blood as an endogenous and freely diffusible tracer and can be flexibly used to visualise the arterial tree as well as to measure CBF. However, ASL is an intrinsically low SNR technique, requiring signal averaging and long scan times.
The main aim of this thesis is to improve the time-efficiency of ASL MRI perfusion and angiographic scans, increasing the accuracy and SNR of CBF measurements and vessel depiction in clinically relevant scan times.
First, a statistical framework was developed and validated for optimising multi- delay ASL perfusion protocol timings to improve the accuracy of CBF and arterial transit time measurements. This flexible framework can be targeted to improve the accuracy of specific parameters and provides a more informed method for designing ASL protocols.
Next, this framework was used to optimise and objectively compare a range of existing pseudo-continuous ASL (PCASL) perfusion protocol designs, including time- encoded preparations, from the literature and to explore novel protocol designs. These comparisons allowed the advantages and disadvantages of each approach to be explored, and recommendations about the best ASL experimental designs to be made.
Finally, the benefits of time-encoded PCASL preparations for ASL angiography were investigated. Angiography visualises the pass-through of labelled blood, in contrast to perfusion imaging which relies on the accumulation of labelled blood in tissue, and so the short label durations used in time-encoded PCASL have a greatly reduced impact on the magnitude of the ASL signal. A variable flip-angle approach was also used to remove signal discontinuities and demonstrate a significant SNR improvement over conventional PCASL angiography.

Keywords: pulse sequence development
PCASL
arterial spin labelling
magnetic resonance imaging
arterial spin labeling
angiography
time-encoded
perfusion imaging
Advisor: Okell, T
Chappell, M
The cellular response to atherogenic lipid

Atherosclerotic vascular disease is the leading cause of disease worldwide. It is an inflammatory condition affecting the arterial wall, and lesions are composed of vascular and immune cells. The purpose of this study is to understand how oxidised low density lipoprotein, a key risk factor for the development of atherosclerosis, affects immune and vascular cells involved in formation of the atherosclerotic lesion. Recent insights into the pathogenesis of atherosclerosis have highlighted changes in expression and activity of gene regulatory proteins (transcription factors) and epigenetic modifications, such as alterations in chromatin accessibility and histone marks, as important mechanisms of atherogenesis. To understand how these changes come about in atherosclerosis, genome-wide approaches have been used to investigate changes in gene expression, chromatin accessibility, and histone marks following exposure of primary human aortic endothelial cells, aortic vascular smooth muscle cells, CD4+ lymphocytes and CD14+ monocytes to oxidised low density lipoprotein.

Keywords: vascular smooth muscle
endothelial
atherosclerosis
chromatin
epigenetics
inflammation
histone modifications
monocytes
Advisor: O’Callaghan, C
Interactions of trypanosomatid Herpetomonas muscarum with dipteran Drosophila melanogaster

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). With resistance to both vector-targeted pesticides and trypanocidal drugs being reported, there is a need for novel transmission blocking strategies to be developed. Studies using the blood-feeding vectors themselves are not broadly accessible, as such, new model systems are being developed to unpick insect-trypanosmatids interactions. In this thesis the interactions between model dipteran Drosophila melanogaster and its own natural trypanosomatid Herpetomonas muscarum are investigated from the perspective of the parasite. This work describes the sequencing and annotation of the H. muscarum genome, which was shown to be highly syntenic to disease-causing trypanosomatids, especially with those of the Leishmania genus. Infections of D. melanogaster were shown to be confined to adults, where H. muscarum persisted in the crop and midgut of the flies for 3-4 days. RNA-sequencing analysis of infected flies showed that rapid, large-scale transcriptomic changes, associated with autophagy, nutrient acquisition and cell surface remodelling, are triggered in H. muscarum after ingestion by the fly. Much of the transcriptomic changes observed reflect what is known for disease-causing trypanosomatids. As such, several of the identified surface proteins are of interest as putative transmission blocking targets. Further characterisation of these genes will be greatly aided by genetic manipulation methods developed for H. muscarum as part of this work. This thesis has described multiple, evolutionarily conserved, trypanosomatid responses to ingestion by dipterans by using a Drosophila-Herpetomonas model. Future studies of these conserved responses will inform development of novel, broad-spectrum transmission blocking strategies.

Keywords: Leishmaniasis
Insect
Drosophila
Herpetomonas
Leishmania
Parasite
Trypanosomatid
Advisor: Ligoxygakis, P
Farr, H
Gull, K
Quantum Steenrod squares, related operations, and their properties

In this thesis, we generalise the Steenrod square on the cohomology of a topological space to a quantum Steenrod square on the quantum cohomology of a symplectic manifold. We prove quantum versions of the Cartan and Adem relations, and use the former to calculate the quantum Steenrod square for CPn, as well as more generally giving the means to compute the operation for all monotone toric varieties. We calculate the quantum Steenrod squares for two examples of blowups along a subvariety, in which a quantum correction of the Steenrod square on the blowup is determined by the classical Steenrod square on the subvariety. We then relate the quantum Steenrod square to Seidel's equivariant pair-of-pants product for open convex weakly monotone symplectic manifolds, using an equivariant version of the PSS isomorphism. We proceed similarly for Z/2-equivariant symplectic cohomology, using an equivariant version of the c*-map. We prove a symplectic Cartan relation, pointing out the difficulties in stating it. We will give some chain level calculations of the equivariant pair-of-pants product for T*Sn. We calculate the quantum Steenrod square for the negative line bundles O(-1) → CPm, and use this to calculate the equivariant pair-of-pants square by extending previous results due to Ritter. We finish with a brief sketch of further ideas, involving a Z/2-equivariant version of the Chas-Sullivan product and the Viterbo isomorphism.

Keywords: Gromov-Witten theory
Floer theory
Steenrod squares
Advisor: Ritter, A
Modelling an incremental theory of Lexical Functional Grammar

This thesis presents and tests an incremental theory of Lexical Functional Grammar (LFG) in an attempt to support researchers in formal grammar to engage with questions raised by experimental findings on language processing and artificial intelligence. Previous work on the incremental building of syntactic structure has concentrated on constituent structure, considering interactions between word class and phrase-structure rules. However, syntax in LFG is represented not only as constituent structure, but also as functional structure: a universal set of grammatical functions is included within the primitives of the theory.
The incremental theory presented here explores the role of grammatical functions as well as category and phrase-structure rules, to build representations of c-structure and f-structure. Universal and language-specific well-formedness constraints interact with lexical content to shape the process of incremental structural growth. The theory is then used to derive predictions about the impact of context on processing decisions.
The theory is tested computationally using a model built in the ACT-R computational cognitive architecture. The model’s production set assesses the combinatorial constraints that apply to lexical input in the context of previously processed material and builds structure accordingly. The combinatorial constraints are contained in lexical specifications stored in declarative, rather than procedural memory. As a result of this the model can use a single production set to process lexical input in English and Korean. The outputs of simulations show that the model is capable of building monoclausal and complex sentences in the two language. The model also simulates context-dependent variations in the parsing of identical strings. A language-independent proposal of the effect of prosodic breaks is included in the model, and this is used to simulate prosodic facilitation of the processing of complex syntax.

Advisor: Dalrymple, M
Diffusion MRI in premanifest Huntington's disease and early Parkinson's disease: tensor and tractography analyses

Huntington’s and Parkinson’s disease are neurodegenerative movement disorders that both affect the basal ganglia, a system of interconnected deep cerebral nuclei that receive converging input from various cortical areas through white matter tracts. Here we have used diffusion MRI to investigate changes in the tissue microstructure of the basal ganglia, as well as the white matter in presymptomatic/early Huntington’s and early Parkinson’s disease. In the presymptomatic Huntington’s disease group longitudinal sensitivity of diffusion MRI across presymptomatic stages was investigated. We also have investigated the connectivity of the basal ganglia with the cortex, and derived connectivity-based parcellations of the gobus pallidus, and subthalamic nucleus, two important hubs of the basal ganglia system, into motor, limbic, and associative territories.
In presymptomatic Huntington’s disease distinct longitudinal changes in the microstructure of the posterior part of the basal ganglia and the splenium of the corpus callosum, as revealed by diffusion tensor metrics, were detectable at different presymptomatic stages. Both patients with Huntington’s and Parkinson’s disease showed micro-structural alterations in the internal segment of the globus pallidus,and the posterior limb of the internal capsule, two important neuroanatomical structures of the basal ganglia system. Huntington's disease patients also showed marked decreases in their structural connectivity in the motor basal ganglia pathway, and the cortico-subthalamic hyperdirect pathway. The volumes of connectivity-based territories of the globus pallidus, pars interna, and subthalamic nucleus undergo disease-specific alterations that capture opposing effects in Huntington’s vs. Parkinson’s disease. Connectivity-based territories undergo disease-related changes in their coordinates that might be of clinical importance. Neuroimaging outcomes were found to be correlated with clinical questionnaire data.

Keywords: Parkinson's disease
subthalamic nucleus
neuroimaging
diffusion tensor MRI
Huntington's disease
magnetic resonance imaging
basal ganglia
globus pallidus
brain imaging
Advisor: Douaud, G
Jenkinson, M
Development of clinical prediction rules for reducing delays in the diagnosis of multiple myeloma

Background
Multiple myeloma is a type of blood cancer which starts at the bone marrow. Fifty percent of patients have more than three consultations in primary care before being referred to secondary care. This implies that myeloma patients can experience delays in the diagnosis which could contribute to the relatively poor prognosis. The aim of the thesis was to develop clinical prediction rules that could potentially reduce the time to diagnosis of myeloma patients.
Methods
The thesis comprises three main studies. The first is a systematic review which maps and quantifies the diagnostic pathway of myeloma patients. In the second study, the features of myeloma (symptoms and blood test abnormalities) were examined to identify which present the earliest. The most optimal combinations of blood tests for diagnosing myeloma were also examined. In the third study, a series of clinical prediction rules were developed and validated using the Clinical Research Datalink data that could be used to expedite the diagnosis of myeloma.
Results
Myeloma patients experience substantial delays with 50% experiencing a diagnostic interval greater than three months and 25% more than eight months. Early symptoms of myeloma include back pain, rib pain, chest pain and infections while fractures, weight loss and nausea manifest later in disease progression. For blood tests haemoglobin and inflammatory markers like Erythrocyte sedimentation rate (ESR) and plasma viscosity (PV) can become abnormal up to two years before diagnosis while values in calcium and creatinine manifest later. C-reactive protein is not a useful inflammatory marker for the diagnosis of myeloma. A combination of normal haemoglobin, either ESR or PV and calcium can rule out most myeloma cases. A clinical prediction rule containing demographics (age, gender, BMI), risk factors (MGUS) symptoms (nosebleeds, back pain, chest pain, rib pain) and the parameters of the full blood count (white cell count, haemoglobin, platelets and mean corpuscular volume) showed good discrimination (AUC: 0.84, 95% CI: 0.82-0.87, R^2: 0.57, 95% CI: 0.53-0.62 and D-statistic: 2.4, 95% CI: 2.2-2.6) and good calibration.
Conclusions
Myeloma patients experience substantial delays in their diagnosis. General practitioners should examine patients that present with myeloma related symptoms using a combination of a full blood count, an inflammatory marker (ESR or PV) and calcium. The clinical prediction rule developed can be useful when myeloma is not suspected and not all tests are ordered. The rule could be applied in the laboratory or on the electronic systems that general practitioners use, but further work is required before implementation.

Advisor: Van den Bruel, A
Oke, J
Noise, resistance, and intertext in Helmut Lachenmann's Dal niente (Interieur III) and Accanto

The following is in two parts: a thesis, and a portfolio of compositions. The thesis examines the centrality of noise, and related concepts of resistance and intertextuality, to the music and writings of Helmut Lachenmann. It begins by outlining the challenges posed by writing about noise in relation to Lachenmann but argues a historical case for its significance in the second chapter. The third chapter focuses on Dal niente (1970), suggesting that the piece maps noise and resistance from the empirical level of its sonic surface, to the more abstract level of its communicative ecology. This is read in the context of Lachenmann’s 1966 essay, ‘Klangtypen der neuen Musik’, and Heidegger’s theory of das Zeug. Chapter Four illustrates noise as a form of cultural resistance in Accanto (1975-76), which is read alongside ‘Zum problem des musikalisch Schönen heute’ (1976), ‘Bedingungen des Materials: Stichworte zur Praxis der Theoriebildung’ (1978) and ‘Vier Grundbestimmungen des Musikhörens’ (1979). Finally, I suggest the usefulness of intertextual theory as a critical framework within which to understand this mapping of noise and resistance, proposing a proximity between intertextuality and Lachenmann’s concept of dialectical structuralism.
The portfolio of compositions is also concerned with noise, but here noise is explored through its relationship with queerness: noise as queer and as queering / queerness as noise and as noisy. Through collaboration, notational experiments, installation, and a listening-based approach to electronic composition, these pieces investigate noise’s potential to create shared spaces of listening.

Advisor: Harry, M
Clarke, E
The poetic uses of Linnaean taxonomy from Erasmus Darwin to John Clare

This thesis challenges critical assumptions that Carl Linnaeus was a dulling if not malignant influence on Romantic poetry by exploring the ways in which Linnaean strategies of comparison and distinction, organisation and arrangement, enumeration and description find echoes in the poetry of Erasmus Darwin, William Wordsworth, and John Clare. As studies of Romantic science have proliferated in the last thirty years, research has investigated the gendered implications of the Linnaean system, as well as the imperial and commercial ramifications of botany’s global networks. Other accounts of Linnaean botany and poetry have preferred classificatory slippages rather than taxonomy’s possibilities. By contrast, this thesis argues that Linnaeus often looked at the natural world through a poetic lens, and that works such as his Philosophia botanica (1751) pay close attention to questions of language, an attention magnified by translations such as the Lichfield Botanic Society’s System of Vegetables (1783-5), which boasted Samuel Johnson as a consultant. Among the Lichfield Botanic Society’s three members was Erasmus Darwin, who produced the first thoroughly Linnaean poem, The Loves of the Plants (1789). Yet the poem’s reputation as a work of literary artifice has fallen alongside Linnaeus’s own sunken currency as the author of an ‘artificial’ system. On the other hand, William Wordsworth and John Clare have been regularly positioned as ‘natural’ poets in opposition to the ‘peeping’ botanist’s compulsion for prying and collecting. In doing so, critics have overlooked both poets’ Linnaean engagements. Challenging allegations of the imaginative failure of Linnaeus and his system, this thesis offers a reappraisal of Linnaeus and his reception in eighteenth and early nineteenth-century Britain. By offering a reconsideration of the period’s enthusiasm for Linnaeus and his system, it provides a more complex interpretation of Romantic responses to the natural world.

Advisor: Stafford, F
Correction of slice misalignment in cardiac MRI studies for the application of patient-specific geometry

Cardiac Magnetic Resonance (CMR) provides unique anatomical and functional information of the structures of the heart. To quantitatively assess cardiac functions, clinicians typically segment CMR slices in 2D. These can be used for 3D reconstructions allowing to better understand cardiovascular functions as well as predict different cardiac processes. These reconstructions can be used in the area of precision medicine or for shape analysis among populations, as well as serve as the input for biological simulations. However, CMR acquisition times usually necessitate slices to be acquired at different breath holds, which results in potential misalignment of the acquired slices. These artifacts cause any 3D model and subsequent evaluations to become distorted. Correcting for this spatial misalignment is required for accurate 3D reconstruction of the heart.
In order to go from cardiac imaging to the geometric definition of patient-specific anatomies, many steps must be taken to achieve accurate geometric representations. Imaging, segmentation, and meshing challenges make the generation of anatomically realistic volumetric meshes a complex task.
The main aim of this Thesis is to develop tools and methodologies to generate geometrically correct cardiac meshes in the presence of spatial misalignment between slices, to represent the anatomy of patients in a personalized manner.
Three main novel contributions are presented. The first concerns the development of a complete framework for the correction of translational and rotational misalignments between CMR slices, using only the information from the images, allowing the method to be used directly in the clinics. The method aligns the respective slices together by using the line intensities at their intersections. We introduce the normalized cross correlation of local phase vectors as a similarity measure making the method applicable to different CMR protocols, and perform a complete validation using manually traced contours, including the estimation of contouring errors. The second concerns the development of a 3D surface reconstruction method capable of dealing with typical cardiac segmentations which are non-parallel, crosssectional, sparse, heterogeneous, and non-coincidental contours. An evaluation of the method is performed and a parameter study achieve to tune the method parameters to cardiac applications. Finally a third methodology is presented which includes both prior works and incorporates the individual steps of segmentation, alignment and mesh reconstruction in one method. This method provides a fully automatic way to go from images to 3D personalized models.

Advisor: Grau, V
Zacur, E
Secularization as sacralization: religion and the formation of modern Chinese nationalism and nation-state, 1840-1939

This thesis investigates the nexus between religion and the formation of modern Chinese nationalism and nation-state. Recent scholarship has pointed out that the category “religion” is a crucial component of the secular project of modernization of the state and the enlightened elites outside the West. Being modern requires the state to separate itself from “religion,” defines as personal belief and freedom, and the society to eradicate the irrational aspect of religion that is “superstition.” The main focus in Chinese scholarship has been documenting the state-led secularization and forceful repression of Chinese religious life according to the alien hegemonic discourse of “religion,” “superstition,” “nation,” and “science.” Instead of uncovering the modern fate of Chinese religion, this study looks at the history of Chinese secularization from another angle, the perspective of the state. This thesis covers the period from 1858 to 1939 and seeks to address three questions: why is the modern concept of “religion” an issue for the Chinese state (imperial and post-imperial)? What is the role of “religion” in the formation of modern Chinese nationalism? What is the character of modern Chinese secularism and the nation-state? The study argues that the secularizing impulse of the Chinese state (imperial and early republican) was as much to do with the practical concerns of meeting the challenges posed by Christian missionary movements to state authority and the religious nationalisms of ethnic minorities in the borderlands as emanating from a coherent modernist project. It also discusses how the model of “religious citizenship” transmitted by Protestant missionaries and the State Shinto of Meiji Japan influenced the formation of modern Chinese nationalism and nation-state. Finally, the study argues that state secularization was at the same time a process of sacralization. Secularization is not simply a process of the triumph of science over religion but a creative as well as controversial boundary drawing exercise that involves defining certain ideology and practices as civil, hence public and mandatory, for the creation of the nation-state, and others as religious to be tolerated and protected by the state or superstitious to be criminalized and eradicated in the name of public order and progress.

Advisor: Haar, B