VictorJuiz/thesis huggingface dataset:
Sleep physiology, circadian rhythms, and the risk for developing psychosis
Keywords: Sleep

Sleep and circadian rhythm disruption (SCRD) is frequently found to co-occur in psychotic disorders. This can include a range of phenotypes such as insomnia, circadian delays, deficits in sleep spindles, and sleep-dependent cognitive impairments. However, increasing evidence suggests that psychosis occurs across a continuum of severity within the general population, yet few studies have investigated sleep and circadian rhythms prior to clinical diagnosis. Furthermore, SCRD and psychosis are posited to share underlying neuropathologies and although increasing evidence implicates shared genetic influence, little is known of the shared environmental risk. This thesis investigates sleep and circadian rhythms at multiple levels, from their occurrence in the general population, their disruption in high risk individuals, and a focus on sleep spindle oscillations in the brain. Firstly, the relationship between subjective measures of sleep and circadian rhythms, risk factors for psychosis, and psychotic-like experiences (PLEs) were studied in a large population sample. All three were highly related, with a subset of risk factors showing a strong association to both PLEs and SCRD. Secondly, sleep and circadian rhythms were assessed in individuals at high risk for developing psychosis based upon having a high load of risk factors and sub-clinical psychotic symptoms. High risk individuals showed subjective SCRD but this was not reflected in objective measures assessed by actigraphy and polysomnography. A subset of high risk individuals further showed substantially later melatonin rhythms compared to a low risk group. Thirdly, high and low risk individuals were assessed for measures of declarative and procedural sleep dependent memory consolidation. High risk individuals showed no evidence for sleep dependent cognitive impairment but did show a potential sensitivity in performance to the amount of sleep, not seen in low risk individuals. Finally, recordings in the somatosensory cortex (SCx) of mice were used as a model to explore the spatio-temporal dynamics and functional significance of sleep spindles. Distinct highly localised spindle events were discovered in the anterior SCx, with their complete absence just a fraction of a millimetre away, and their occurrence of which coincided with unique responses to global vigilance states. Together, this work pioneers research into sleep and circadian phenotypes associated with both sub-clinical psychotic symptoms and risk factors for disease and furthers our knowledge of particular sleep processes which could collectively help us to understand why SCRD and psychosis develop.
Incremental generative models for syntactic and semantic natural language processing
Keywords: Dependency Parsing
Deep Learning
Semantic Parsing
Generative Models
Parsing
Language Modelling
Incremental Parsing

This thesis investigates the role of linguistically-motivated generative models of syntax and semantic structure in natural language processing (NLP). Syntactic well-formedness is crucial in language generation, but most statistical models do not account for the hierarchical structure of sentences. Many applications exhibiting natural language understanding rely on structured semantic representations to enable querying, inference and reasoning. Yet most semantic parsers produce domain-specific or inadequately expressive representations.
We propose a series of generative transition-based models for dependency syntax which can be applied as both parsers and language models while being amenable to supervised or unsupervised learning. Two models are based on Markov assumptions commonly made in NLP: The first is a Bayesian model with hierarchical smoothing, the second is parameterised by feed-forward neural networks. The Bayesian model enables careful analysis of the structure of the conditioning contexts required for generative parsers, but the neural network is more accurate. As a language model the syntactic neural model outperforms both the Bayesian model and n-gram neural networks, pointing to the complementary nature of distributed and structured representations for syntactic prediction. We propose approximate inference methods based on particle filtering. The third model is parameterised by recurrent neural networks (RNNs), dropping the Markov assumptions. Exact inference with dynamic programming is made tractable here by simplifying the structure of the conditioning contexts.
We then shift the focus to semantics and propose models for parsing sentences to labelled semantic graphs. We introduce a transition-based parser which incrementally predicts graph nodes (predicates) and edges (arguments). This approach is contrasted against predicting top-down graph traversals. RNNs and pointer networks are key components in approaching graph parsing as an incremental prediction problem. The RNN architecture is augmented to condition the model explicitly on the transition system configuration. We develop a robust parser for Minimal Recursion Semantics, a linguistically-expressive framework for compositional semantics which has previously been parsed only with grammar-based approaches. Our parser is much faster than the grammar-based model, while the same approach improves the accuracy of neural Abstract Meaning Representation parsing.
Physical phenomena in metal-organic frameworks: mechanical, vibrational, and dielectric response
Keywords: Vibrational Spectroscopy
Metal-Organic Frameworks
Terahertz Vibrations
Inelastic Neutron Scattering
Mechanical Properties
Density Functional Theory
Synchrotron Infrared Spectroscopy
Raman Spectroscopy
Response Properties
Dielectric Response

This thesis entails the utilisation of ab initio density functional theory (DFT) in conjunction with neutron and synchrotron spectroscopy to study the mechanical, vibrational, and dielectric response of metal-organic framework (MOF) materials at the molecular level. MOFs are crystalline materials with nanoscale porosity, which have garnered immense scientific and technological interest for a wide variety of innovative engineering applications.
One part of the thesis involves using low-frequency lattice vibrations to characterise the various physical motions that are possible for framework materials. These collective modes detected at terahertz (THz) frequencies have been used to reveal a broad range of exciting possibilities. New evidence has been established to demonstrate that THz modes are intrinsically linked to anomalous elasticity underpinning gate-opening and pore-breathing mechanisms, and to shear-induced phase transitions and the onset of structural instability. The phenomenon of molecular rotor mechanisms and trampoline-like motions are also observed, along with the first experimental confirmation of coordinated shear dynamics. Additionally, a new method to characterise the effects of temperature, and hence thermally-induced structural amorphisation is reported.
Finally, for the first time, the frequency-dependent (dynamic) dielectric response of MOF materials, across the extended infrared (IR) spectral region was reported. The results were obtained from experimental synchrotron radiation IR reflectivity and DFT to reveal the low-&kcy; dielectric response of MOFs and established structure-property trends that highlight them as promising systems for microelectronic device applications.
The role of lung tissue-resident memory T cells in protection against tuberculosis
Keywords: T cell immunology
Tuberculosis
BCG vaccine
Tissue-resident memory

Tuberculosis (TB) is a global health problem, which is proving extremely difficult to control in the absence of an effective vaccine. Bacille Calmette-Guérin (BCG), the only vaccine currently licensed against TB, demonstrates variable efficacy in humans and cattle. A greater understanding of what constitutes a protective host immune response is required in order to aid the development of improved vaccines. Tissue-resident memory T cells (TRM) are a recently-identified subset of T cells, which may represent an important aspect of protective immunity to TB. This thesis aims to characterise the role of lung TRM in BCG-induced protection against TB. In a mouse model, intravascular staining allowed discrimination between lung-vascular and lung-parenchymal T cells. Experiments demonstrated that BCG vaccination induced a population of antigen-specific lung-parenchymal CD4+ T cells, a putative tissue-resident population. This lung-parenchymal population was significantly increased in frequency following mucosal BCG vaccination, compared to systemic BCG vaccination. This correlated with enhanced protection against Mycobacterium tuberculosis (M.tb) infection in the lungs of mice receiving mucosal BCG, compared to those receiving systemic BCG. Mucosal BCG induced lung-parenchymal CD4+ T cells with enhanced proliferative capacity and a PD1+KLRG1- cell-surface phenotype, a memory-like phenotype associated with improved protection against M.tb infection. These cells may represent a BCG-induced lung TRM population responsible for the enhanced protection observed following mucosal BCG. Overall, this thesis highlights the potential of mucosal vaccination to elicit lung TRM and identifies this as a possible immunological mechanism underlying enhanced protection against M.tb infection. These cells may constitute an important target for future vaccination strategies.
Crustal structure, gravity anomalies and subsidence history of the Parnaíba cratonic basin, Northeast Brazil
Keywords: Sedimentary basin
Gravity modelling
Seismic refraction
Cratonic
Backstripping
Subsidence analysis
Seismic reflection

Cratonic basins cover more than 10% of Earth's continental surface area, yet their origin remains enigmatic. In this thesis a suite of new and legacy geophysical and geological data are integrated to constrain the origin of the Parnaíba basin, a cratonic basin in Northeast Brazil. These data include a 1400 km long, deep (20 s two-way travel time) seismic reflection profile, five +/- 110 km offset wide-angle split-spread receiver gathers, gravity anomaly, and well data.
In the centre of the basin, the depth to pre-Paleozoic basement is &Tilde; 3.3 km, a zone of midcrustal reflectivity (MCR) can be traced laterally for &Tilde; 250 km at depths between 17-25 km and Moho depth is &Tilde; 42 +/- 2 km. Gravity and P-wave modelling suggests that the MCR represents the upper surface of a high density (2985 kg m3) and Vp (6.7–7.0 km s-1) lower crustal body, likely of magmatic origin. Backstripping of well data shows a concave up decreasing tectonic subsidence, similar in form to that commonly observed in rift-type basins. It is shown, however, that the seismic and gravity data are inconsistent with an extensional origin. It is shown that an intrusive body in the lower crust that has loaded and flexed the surface of the crust, combined with sediment loading, provides a satisfactory fit to the observed gravity anomaly, sediment thickness and basin shape. A buried load model is also consistent with seismic data, which suggest that the Moho is as deep or deeper beneath the basin centre than its flanks and accounts for at least part of the tectonic subsidence through a viscoelastic stress relaxation that occurs in the lithosphere following load emplacement.
Comparative analysis of the Michigan and Congo basins shows gravity data from these basins is also consistent with a lower crustal mass excess, while subsidence analysis shows viscoelastic stress relaxation may also contribute to their early subsidence histories. However, unlike Parnaíba, both of these basins appear to have been subjected to secondary tectonic processes that obscure the primary 'cratonic basin' subsidence signals. Parnaíba basin, therefore, offers an excellent record for the investigation of cratonic basin formation.
Collaboration of Ezh2 and Runx1 inactivating mutations in malignant haematopoiesis
Keywords: Myelodysplastic syndrome
Leukaemia

Extensive efforts have shed light on the identity and biology of cancer stem cells, required and sufficient for the propagation of hematological malignancies and solid tumours. Much less is understood about the closely related issue as to the identity and properties of the normal stem and progenitor cells targeted by oncogenic lesions, and how the nature of the targeted cell might impact on the biology and clinical picture of the resulting cancer. To address this, we developed a mouse model allowing targeted inactivation of Ezh2 and Runx1 to different haematopoietic compartments. Inactivating mutations of EZH2 and RUNX1 frequently co-occur in haematological malignancies with markedly different phenotypes including myelodysplastic syndrome (MDS) and early thymic progenitor (ETP) leukaemia.
Inactivation of Ezh2 and Runx1 in adult haematopoietic stem cells (HSCs) resulted in perturbed haematopoiesis leading to development of an MDS-like disease. Unexpectedly, this MDS phenotype could be fully reproduced when Ezh2 and Runx1 inactivation was targeted to multipotent progenitors (MPPs) using Flt3-Cre. Furthermore, the disease was transplantable by MPPs, but not more committed progenitor populations, demonstrating that MDS tumour propagating potential is not exclusive to intrinsically self-renewing HSCs.
Targeting Ezh2 and Runx1 inactivation to early lympho-myeloid progenitors did not result in an MDS phenotype. These mice showed a marked expansion of ETPs within the thymus, combined with a block in thymocyte differentiation. These expanded ETPs displayed transcriptional features characteristic of ETP leukaemia, a treatment-resistant acute leukaemia subtype hypothesised to originate from ETPs. Combination of inactivation of Ezh2 and Runx1 in ETPs with the constitutively activating Flt3-ITD signalling mutation resulted in an aggressive lympho-myeloid acute leukaemia, which could be propagated by the expanded ETP population. These findings demonstrate the potential of lympho-myeloid progenitors such as ETPs to become leukaemia stem cells which propagate a disease retaining lympho-myeloid features.
We used this novel ETP leukaemia model to explore therapeutic targeting of Ezh2-inactivated ETP leukaemias using inhibitors of the bromodomain and extra terminal (BET) proteins. Aberrant transcription resulting from epigenetic changes induced by Ezh2 loss could be reversed by BET inhibitors, and these compounds showed therapeutic efficacy against both mouse and human ETP leukaemias in vitro and in vivo.
Melodic exchange and musical violence in the thirteenth-century jeu-parti
Keywords: jeu-parti
music analysis
trouvère
violence

The thirteenth-century jeu-parti was a sung debate between two or more poet singers. In the jeu-parti, singers exchanged stanzas composed to the same melody, rhyme scheme and syllable count. What else was exchanged in the composition, performance and inscription of the jeu-parti? Grounded in a definition of violence as the non-consensual deployment of power on a subject, this thesis investigates whether any modes of exchange in the jeu-parti were non-consensual, and therefore violent. The form of the jeu-parti has the potential for what Žižek calls ‘symbolic violence’, in which the structures and meaning of one trouvère’s song are appropriated and undermined by their opponent. This symbolic violence is discussed throughout the thesis. Several early jeux-partis are contrafacts of other trouvère songs. They were created in an aristocratic milieu that was deeply, and often violently, divided; contrafacture stages these aristocratic disputes and animates the form of the jeu-parti, which itself was created in a process of successive contrafacture. Later jeux-partis do not have the same context of aristocratic dispute, but are nevertheless a platform for symbolic violence. This is manifest in jeux-partis melodies, which are frequently tonally divided. In the interaction between textual structures and divided tonal structures, trouvères were able to enact symbolic violence against one another by subverting their opponent’s tonal arguments. Furthermore, the jeu-parti was performed and created in a cultural context that praised violent acts. Set against the cultural backdrop of chivalric literature and rituals, the disputatio, the trial by inquest, the tournament, the joust, and scientific and lyric definitions of sound as the product of a violent act, the jeu-parti was a genre through which violent practices could be praised, defined, and censured.
Beyond the politics of labelling: exploring the cessation clauses for Rwandan and Eritrean refugees through semiotics
Keywords: Rwanda
Politics
Forced Migration
Uganda
Eritrea
Refugees
Semiotics

Academics have for decades written on the need to interrogate the labels upon which the field of Refugee and Forced Migration Studies has been founded. At the centre of these discussions has been theorising around the 'integrity' and 'content' of the refugee label itself, with foundational texts expounding the need to take nothing about the meaning and purpose of this label for granted. This is evidently important in popular accounts, where the term's misuse fuels anti-immigrant sentiments and societal mistrust, as well as for the futures of these populations, as multiple interpretations of their status affect attempts to negotiate durable solutions to their plight. Without denying the importance of these theoretical accounts, or the incredibly rich literature that has emerged on account of them, this thesis suggests that much of the theorising on labelling to date has lacked a clear theoretical framework around which to structure otherwise critical observations vis-à-vis the performative and malleable characteristics of language.
It therefore introduces semiotic theories and methodologies as an approach for making sense of these manifold interpretations and their relationships to each other, and to explore what impacts this has on negotiations over refugees' futures. Associated theories are used to explain the controversial negotiations that surrounded the invocation of the Cessation Clause for Eritrean refugees in Sudan in 2002, and the ongoing attempts to apply Cessation to Rwandan refugees in Uganda. Both processes were mired by controversy, and yet almost no literature exists detailing when, why and how they unfolded as they did. Disaggregating the refugee 'label' through the semiotic frameworks provided by Saussure and Barthes helps explain the conceptual and spatial dissonance that plagued attempts to conclude these protracted refugee situations.
Through doing so, this thesis seeks to make three main contributions. First, it provides these extended accounts of how decisions to apply Cessation are arrived at, thereby filling an empirical gap in literature on this process. Second, it presents a heuristic framework rooted in linguistic theories to explain how certain words and objects – including the refugee label - can see their meanings transformed and bourgeon over time, the mechanisms through which this distortion occurs and is accommodated within discussions over the treatment of refugees, and the implications that the application of this theoretical framework has for how we understand particular incidents of decision-making within the refugee regime. Third, these theoretical approaches are shown to result in key challenges to how the role, content and function of the word refugee have been conceptualised to date.
The pathophysiological role of TDP-43 in amyotrophic lateral sclerosis due to C9orf72 mutations
Keywords: Amyotrophic Lateral Sclerosis
C9orf72
TDP-43
Motor Neuron Disease

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative condition that affects corticospinal and spinal motor neurons and leads to death within 30 months of symptom onset in half of all cases. It remains incurable and treatment is supportive. The genetic and molecular understanding of ALS has gone through a rapid expansion in recent years, notably with the discoveries of TDP-43, a heterogeneous ribonucleoprotein as a major component of neuronal inclusions in ALS, as well as the discovery of the C9orf72 hexanucleotide expansion as the most common genetic cause of this disease.
This first part of this thesis addresses the question of which of the various pathological hallmarks of the C9orf72 Hexanucleotide Repeat Expansion (HRE) in autopsy material correlates best with the clinical presentation. The main finding is that TDP-43 distribution, rather than C9orf72 RNA foci or dipeptide aggregation in the brain, corresponds best with the areas relevant to the clinical subtype of ALS-FTD. Subsequently the role of TDP-43 was investigated in induced pluripotent stem cell derived motor neurons, and no evidence of the hallmarks of TDP-43 dysfunction, were seen in this model of the disease. No mislocalisation is found on immunofluorescence, and biochemical analysis shows no differences in insoluble species between the patient and control cell lines. In the final section, RNA sequencing was used to study the transcriptome of a BAC transgenic mouse carrying a human M337V transgene expressed at low levels, to identify early presymptomatic differences in gene expression. Interestingly, no changes were found in genes known to be associated with ALS through mutations, and the constitutive nuclear functions of TDP-43 in the regulation of splicing was maintained, prior to the emergence of a clinical phenotype in the mouse. This favours a gain of function mechanism for TDP-43 mutations in ALS.
Extensions of Presburger arithmetic and model checking one-counter automata
Keywords: Presburger arithmetic
reachability problems
p-adic numbers
one-counter automata

This thesis concerns decision procedures for fragments of linear arithmetic and their application to model-checking one-counter automata. The first part of this thesis covers the complexity of decision problems for different types of linear arithmetic, namely the existential subset of the first-order linear theory over the p-adic numbers and the existential subset of Presburger arithmetic with divisibility, with all integer constants and coefficients represented in binary. The most important result of this part is a new upper complexity bound of NEXPTIME for existential Presburger arithmetic with divisibility. The best bound that was known previously was 2NEXPTIME, which followed directly from the original proof of decidability of this theory by Lipshitz in 1976. Lipshitz also gave a proof of NP-hardness of the problem in 1981. Our result is the first improvement of the bound since this original description of a decision procedure.
Another new result, which is both an important building block in establishing our new upper complexity bound for existential Presburger arithmetic with divisibility and an interesting result in its own right, is that the decision problem for the existential linear theory of the p-adic numbers is in the Counting Hierarchy CH, and thus within PSPACE. The precise complexity of this problem was stated as open by Weispfenning in 1988, who showed that it is in EXPTIME and NP-hard.
The second part of this thesis covers two problems concerning one-counter automata. The first problem is an LTL synthesis problem on one-counter automata with integer-valued and parameterised updates and with equality tests. The decidability of this problem was stated as open by Göller et al. in 2010. We give a reduction of this problem to the decision problem of a subset of Presburger arithmetic with divisibility with one quantifier alternation and a restriction on existentially quantified variables. A proof of decidability of this theory is currently under review.
The final result of this thesis concerns a type of one-counter automata that differs from the previous one in that it allows parameters only on tests, not actions, and it includes both equality and disequality tests on counter values. The decidability of the basic reachability problem on such one-counter automata was stated as an open problem by Demri and Sangnier in 2010. We show that this problem is decidable by a reduction to the decision problem for Presburger arithmetic.