VictorJuiz/thesis huggingface dataset:
The clinical and molecular epidemiology of Streptococcus agalactiae in Kenya: maternal colonisation and perinatal outcomes
Keywords: neonate
streptococcus
Kenya
stillbirth

Two cellular processes of central importance to cancer and neurodegeneration are apoptosis and cellular senescence. Both are a means of cellular suicide that are utilized in time- and context-dependent manners and have important evolutionary purposes. However, they are also the drivers of many deleterious processes underlying cancer and neurodegeneration. Many of the cellular responses to aging and age-related diseases, including apoptosis and senescence, converge on the tumor suppressor pathway, p53.
Here I examine the molecular basis for loss of cell polarity and accelerated cell death mediated by apoptosis stimulating protein of p53 2 (ASPP2) in neurodegeneration. In this study we find that ASPP2 mediates STAT1Linduced apoptosis. Lipopolysaccharide (LPS) induces ASPP2 mRNA expression in vitro. Also, LPS induces nuclear ASPP2 in vivo at the blood-cerebral spinal fluid-barrier (BCSFB), the brain's barrier to inflammation. Consistent with ASPP2's role as a gatekeeper to inflammation, ASPP2 mutant mouse brains possess enhanced neuroinflammation. Elevated ASPP2 expression is also observed in mouse models and human neuroinflammatory disease tissue in astrocytes. The identification of ASPP2 as a novel transcriptional target of STAT1 and the observed increase in ASPP2 expression in both mouse and human neuroinflammatory disorders, suggests that the identified STAT1/ASPP2 pathway may connect tumor suppression and cell polarity to neuroinflammation.
Additionally, I investigate the regulation of cellular senescence by p53 isoforms as a means to enhance neuroprotection of astrocytes in chronic neurodegenerative diseases, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Here we report that p53 isoforms, Δ133p53 and p53β, are endogenous regulators of cellular senescence in the central nervous system (CNS). Δ133p53 functions as a dominant-negative regulator of full-length (FL)Lp53 and represses senescence, while p53β as a co-activator of FLLp53, promotes senescence. In neurodegenerative disease brain tissue, FLL53 and p53β are upregulated while Δ133p53 is downregulated. We demonstrate that Δ133p53 and p53β directly regulate astrocyte senescence, including the release of key neurotoxic proL inflammatory cytokines such as ILL6 and ILL1β. Also, we show that the p53 isoform switch that occurs during aging and neurodegeneration promotes neuronal toxicity using coL culture experiments with human iPSC-derived motor neurons and human astrocytes. We also demonstrate that astrocyte senescence can be rescued through overexpression of Δ133p53, revealing a promising therapeutic approach to delay or inhibit the progression of neurodegeneration.
Studying marcomolecular transitions by NMR and computer simulations
Keywords: NMR spin-relaxation
NMR
MD simulations
NMR dynamics

Macromolecular transitions such as conformational changes and protein-protein association underlie many biological processes. Conformational changes in the N-terminal domain of the transmembrane protein DsbD (nDsbD) were studied by NMR and molecular dynamics (MD) simulations. nDsbD supplies reductant to biosynthetic pathways in the oxidising periplasm of Gram-negative bacteria after receiving reductant from the C-terminal domain of DsbD (cDsbD). Reductant transfer in the DsbD pathway happens via protein-protein association and subsequent thiol-disulphide exchange reactions. The cap loop shields the active-site cysteines in nDsbD from non-cognate oxidation, but needs to open when nDsbD bind its interaction partners. The loop was rigid in MD simulations of reduced nDsbD. More complicated dynamics were observed for oxidised nDsbD, as the disulphide bond introduces frustration which led to loop opening in some trajectories. The simulations of oxidised and reduced nDsbD agreed well with previous NMR spin-relaxation and residual dipolar coupling measurements as well as chemical shift-based torsion angle predictions. NMR relaxation dispersion experiments revealed that the cap loop of oxidised nDsbD exchanges between a major and a minor conformation. The differences in their conformational dynamics may explain why oxidised nDsbD binds its physiological partner cDsbD much tighter than reduced nDsbD. The redox-state dependent interaction between cDsbD and nDsbD is thought to enhance turnover. NMR relaxation dispersion experiments gave insight into the kinetics of the redox-state dependent interaction. MD simulations identified dynamic encounter complexes in the association of nDsbD with cDsbD. The mechanism of the conformational changes in the transport cycle of LacY were also investigated. LacY switches between periplasmic open and cytoplasmic open conformations to transport sugars across the cell membrane. Two mechanisms have been proposed for the conformational change, a rocker-switch mechanism based on rigid body motions and an “airlock” like mechanism in which the transporter would switch conformation via a fully occluded structure. In MD simulations using the novel dynamics importance sampling approach such a fully occluded structure was found. The simulations argued against a strict “rocker-switch” mechanism.
The Roman de la Rose: nature, sex, and language in thirteenth-century poetry and philosophy
Keywords: usury
ethics
philosophy
artificial
science
rhetoric
sodomy
Roman de la rose
Aristotle
Guillaume de Lorris
poetry
nature
Jean de Meun
dialectic

Jean de Meun's continuation of the Roman de la rose (The Romance of the Rose), written in Paris in the 1270s, presents a vast amount of philosophy and natural science in vernacular poetry, while engaging thoroughly with contemporary, local philosophical and institutional debates. Taking this into consideration, this study investigates how the Rose depends for its meaning on questions around human nature, natural philosophy, and the philosophy of language that were being discussed and debated in the University of Paris at the time of its composition. It suggests a reading of the poem as a work of philosophy that uses Aristotelian ideas of nature and what is natural to present a moral framework – at times explicitly, at times implicitly – within which to assess and critique human behaviour. The concepts of the unnatural and the artificial are used to discuss sin and its effects on sexuality – a key concern of the Rose – and on language. The Rose is shown to present itself as artificial and compromised, yet nevertheless capable of leading imperfect and compromised humans to moral behaviour and towards knowledge which can only ever be imperfect. It is read as a presenting a rhetorical kind of philosophy that is sui generis and that appeals to human desire as well as to the intellect. The specific issue of usury and its relation to avarice is examined, studying contemporary theological and philosophical treatments of the question, in order to illustrate similarities and contrasts in the Rose's theoretical methodology to more orthodox modes of philosophical enquiry. Finally, the poem's valorisation of pleasure and of the perversity inherent in artificial productions is explored to show how poetry, though deviating from the strictures of dialectical language, is nevertheless productive and generative.
Fast model predictive control
Keywords: active set methods
robust model predictive control
dynamic programming

This thesis develops efficient optimization methods for Model Predictive Control (MPC) to enable its application to constrained systems with fast and uncertain dynamics. The key contribution is an active set method which exploits the parametric nature of the sequential optimization problem and is obtained from a dynamic programming formulation of the MPC problem. This method is first applied to the nominal linear MPC problem and is successively extended to linear systems with additive uncertainty and input constraints or state/input constraints. The thesis discusses both offline (projection-based) and online (active set) methods for the solution of controllability problems for linear systems with additive uncertainty. The active set method uses first-order necessary conditions for optimality to construct parametric programming regions for a particular given active set locally along a line of search in the space of feasible initial conditions. Along this line of search the homotopy of optimal solutions is exploited: a known solution at some given plant state is continuously deformed into the solution at the actual measured current plant state by performing the required active set changes whenever a boundary of a parametric programming region is crossed during the line search operation. The sequence of solutions for the finite horizon optimal control problem is therefore obtained locally for the given plant state. This method overcomes the main limitation of parametric programming methods that have been applied in the MPC context which usually require the offline precomputation of all possible regions. In contrast to this the proposed approach is an online method with very low computational demands which efficiently exploits the parametric nature of the solution and returns exact local DP solutions. The final chapter of this thesis discusses an application of robust tube-based MPC to the nonlinear MPC problem based on successive linearization.
Rules, reasons, and acceptance
Keywords: rules
reasons
acceptance

In law as well as in ordinary life, it matters what rules societies have; but what does it mean for a society to have a rule? HLA Hart’s famous answer is that for a society to have a rule is for there to be a certain social practice in that society, consisting of an external, behavioural aspect and an internal, attitudinal aspect. Hart’s ‘practice theory’ dominates thinking in jurisprudence about social rules, but, I argue, there are serious problems with it. It would be better to adopt what I call the ‘acceptance theory’.
In the early chapters of this thesis, I argue that the practice theory is both overinclusive and underinclusive. It is overinclusive because Hart’s description of the ‘internal aspect’ is too general. It is underinclusive because the ‘external aspect’ is unnecessary. Once these criticisms are taken into account, what remains of the practice theory is the idea that a society has a rule because its members have a certain attitude. I spend much of this thesis determining the features of this attitude.
Ultimately, I focus on the attitude known as “acceptance” in the philosophy of action. Acceptance of a proposition simulates belief in that proposition, though it may be held independently of that belief. I argue that a person or society has a rule when that person, or that society’s members, accept that some action ought to be performed, whatever their beliefs about the matter. This theory incorporates the plausible core of the practice theory, while avoiding its problems.
Resilience and emotional distress in young people: risk, promotive and cultural factors
Keywords: socioecological
low and middle income countries
emotional distress
risk factors
clinical psychology
protective factors
resilience
cultural differences
adolescents
youth
promotive factors
systematic review

Resilience, as a trait, process or outcome, is the negation of an undesirable outcome or of an expected maladjustment in the context of an adversity. Young people represent a developmental stage in which there is a vulnerability to experience deleterious outcomes during adversity. The literature on risk and promotive factors for resilience in youth is compounded by narrative reviews which have not applied a rigorous search methodology and which have failed to operationalise resilience. To date, the majority of research in resilience for emotional distress has focussed on data collected in high income countries. The first paper presents a systematic review of the literature on risk and promotive factors for trait resilience in youth. The findings indicate that there are differences in the magnitude of association between trait resilience and various risk and promotive factors, which were conceptualised into biological, intrapersonal, interpersonal and environmental factors. The largest body of evidence reviewed pertained to intrapersonal risk and promotive factors for trait resilience. Factors predicting trait resilience were also identified. Implications for future research include addressing the methodological and sampling limitations of the reviewed studies. The second paper presents an empirical study investigating factors within a microsystem which differentiate adolescents with resilience for emotional distress and those vulnerable to emotion distress in India (N = 967) and in Peru (N = 606). Factors which predict low emotional distress in each country and factors which differentiate between low emotional distress Indian and Peruvian adolescents were additionally investigated. A cross-sectional exploratory investigation of secondary data was employed. The findings suggest that the profile of low vulnerability for emotional distress differs between different cultural contexts and contribute to an extraordinarily limited evidence-base in low and middle income contexts. Extensive additional research is required to delineate culturally-specific profiles of resilience for emotional distress in a bid to develop culturally-sensitive treatment targets.
Nutrient assimilation and amino acid utilisation in Pseudomonas syringae
Keywords: pseudomonas syringae
microbiology

The aim of this study was to increase understanding of amino acid utilisation and amino acid permease (aa_permease) genes in the plant pathogen Pseudomonas syringae, which inhabits the nutrient-limited environment of the plant surface and intracellular apoplast. aa_permease genes are significantly reduced in P. syringae genomes compared to non plant-pathogenic Pseudomonas. Accordingly, this work demonstrates that P. syringae can utilise a restricted number of amino acids for growth compared to non plant-pathogenic Pseudomonas. The remaining aa_permease genes in Pseudomonas syringae pv. tomato are annotated as transporting GABA, ethanolamine, proline and aromatic amino acids. Sequence analyses, phylogenetic analyses, chemotaxis assays and gene expression analyses supported the functional annotations of the GABA, ethanolamine and aromatic aa_permeases, but showed that expression of the proline permease was specifically induced by histidine, which suggests that this encodes a histidine transporter. Expression of the GABA and histidine permeases was also induced in the presence of tomato apoplast, indicating that these amino acids may be assimilated during apoplast colonisation. P. syringae pv. tomato exhibited chemotaxis towards tomato apoplast and several constituent amino acids, which may be important for invasion of the apoplast from the plant surface. Uptake of several amino acids including GABA and histidine appeared to be negatively affected in alkaline media. The aa_permeases use electrochemical potential energy to transport substrates and this mechanism may be affected by pH. The plant apoplast becomes increasingly alkaline during infection and this may select against the retention of particular transporters in P. syringae. As GABA is an abundant amino acid in the apoplast and can be used by P. syringae strains for growth, the growth of P. syringae pv. tabaci was monitored in transgenic tobacco plants with increased GABA. Although growth was similar in all plants, significantly fewer symptoms and more callose deposition was observed upon infection.
Strong correlations in ultracold atomic gases
Keywords: entanglement
strongly correlated systems
optical lattices
macroscopic superposition states
quantum information science
ultracold bosons

In this thesis we investigate strongly-correlated states of ultracold bosonic atoms in rotating ring lattices and arrays of double-well potentials. In the first part of the thesis, we study the tunneling dynamics of ultracold bosons in double-well potentials. In the non-interacting limit single-particle transitions dominate, while in the interaction-dominated regime correlated tunneling of all particles prevails. At intermediate times of the many-particle flopping process correlated states occur, but the timescales of these processes increase dramatically with the number of particles. Using an array of double-well potentials, a large number of such few-particle superposition states can be produced in parallel. In the second part of the thesis, we study the effects of rotation on ultracold bosons confined to one-dimensional ring lattices. We find that at commensurate filling there exists a critical rotation frequency, at which the ground state of the weakly-interacting gas is fragmented into a macroscopic superposition of different quasi-momentum states. We demonstrate that the generation of such superposition states using slightly non-uniform ring lattices has several practical advantages. Moreover, we show that different quasi-momentum states can be distinguished in time-of-flight absorption imaging and propose to probe correlations via the many-body oscillations induced by a sudden change in the rotation frequency. Finally, we compare these macroscopic superposition states to those occurring in superconducting quantum interference devices. In the third part of the thesis, we demonstrate the creation of entangled states with ultracold bosonic atoms by dynamical manipulation of the shape of the lattice potential. To this end, we consider an optical superlattice that allows both the splitting of each site into a double-well potential and the variation of the height of the potential barrier between the sites. We show how to use this array of double-well potentials to perform entangling operations between neighboring qubits encoded on the Zeeman levels of the atoms. As one possible application, we present a method of realizing a resource state for measurement-based quantum computation via Bell-pair measurements. In the final part of the thesis, we study ultracold bosons on a two-dimensional square lattice in the presence of an effective magnetic field and point out a couple of features this system has in common with ultracold bosons in one-dimensional rotating ring lattices.
Facilitating visual target  identification using non-visual cues
Keywords: perception
audition
visual search
multisensory integration
attention
vision

The research presented in this thesis was designed to investigate whether and how the temporal synchrony and spatial congruence of non-visual cues with visual targets could work together to improve the discrimination and identification of visual targets in neurologically-healthy adult humans. The speed and accuracy of participants’ responses were compared following the presence or absence of temporally synchronous and/or spatially congruent or incongruent auditory, vibrotactile, and audiotactile cues in the context of dynamic visual search and rapidly-masked visual target identification. The understanding of the effects of auditory, vibrotactile, and audiotactile cues derived from these laboratory-based tasks was then applied to an air traffic control simulation involving the detection and resolution of potential conflicts (represented as visual targets amidst dynamic and cluttered visual stimuli). The results of the experiments reported in this thesis demonstrate that, in the laboratory-based setting, temporally synchronous and spatially informative non-visual cues both gave rise to significant improvements in participants’ performance, and the combination of temporal and spatial cuing gave rise to additional improvements in visual target identification performance. In the real-world setting, however, only the temporally synchronous unimodal auditory and bimodal audiotactile cues gave rise to a consistent facilitation of participants’ visual target detection performance. The mechanisms and accounts proposed to explain the effects of spatial and temporal cuing, namely multisensory integration and attention, are examined and discussed with respect to the observed improvements in participants’ visual target identification performance.
p-block hydrogen storage materials
Keywords: Solid-State
p-Block
Hydrogen
EPR
Diffraction
ESR
Synchrotron
Hydrides
Storage
Crystallography
Alanates
Milling

The development of a clean hydrogen economy will aid a smooth transition from fossil fuels which is required to stem the environmental impact and economic instability caused by oil dependency. For vehicular application, in addition to being cheap and safe, a commercial hydrogen store must contain a certain weight percentage of hydrogen to provide a reasonable range (~300 miles). It must also be able to release hydrogen under near-ambient conditions (80-120°C) and have a reasonable cycling capacity (~1000 cycles). The primary motivation of this thesis is to gain a fundamental understanding into the sorption processes of hydrogen on carbon- and aluminium-based materials to improve their hydrogen storage capacity. The sorption processes of hydrogen on mechanically milled graphite have been investigated, primarily using Electron Spin Resonance Spectroscopy and Inelastic Neutron Scattering. An investigation into the storage properties of tetrahydroaluminates, primarily NaAlH4 and LiAlH4, is performed in the presence and absence of a catalyst, and a new phase of NaAlH4 is observed prior to its decomposition. Variable temperature neutron and synchrotron diffraction, in conjunction with gravimetric and mass spectroscopy data were obtained for several mixtures of tetrahydroaluminates and alkali amides and the hydrogen desorption processes are shown to be quite different from the constituent materials. The structure of Ca(AlH4)2 has been experimentally determined for the first time and a complete set of equations describing its decomposition pathway is given.
Investigating the regulation and functioning of RNT-1 and BRO-1 in C. elegans
Keywords: proliferation
C. elegans
enhancers
differentiation
development
stem cells
niche
seam cells

The stem cell-like seam cells of the nematode, Caenorhabditis elegans, represent a tractable and powerful model for studying stem cell biology. rnt-1, the worm homologue of the mammalian RUNX family of transcription factors, together with the CBFβ homologue bro-1, is essential for the proliferation of the seam cells. RUNX genes and CBFβ are important regulators of stem cell development in mammals, and are associated with a variety of cancers. The worm seam cell model offers an opportunity to examine how these genes function in stem cell biology. The aim of this work was to shed light on the genetic network in which bro-1 and rnt-1 function, and to reveal the identity of regulators of these genes as well the downstream targets of the bro-1/rnt-1 pathway.
Here, a number of genes that interact with bro-1 and rnt-1 have been identified. ELT-1, a GATA transcription factor, is shown to be a direct regulator of bro-1. Findings which show that the MEIS gene unc-62 acts upstream of bro-1/rnt-1 and regulates the symmetry of seam cell divisions are also presented. The seam cell marker, scm::gfp, is widely used in studies of the seam cells; here the results of an investigation into its identity and functional links are described. In addition, the mechanism underlying spatial regulation of rnt-1 was examined; this led to the discovery of distinct tissue-specific enhancer modules within an intron of this gene. Finally, interactions between pal-1 and bro-1/rnt-1 are reported and described.
Together, these findings provide a framework for furthering our understanding of the mechanisms and genes associated with the functioning of bro-1 and rnt-1 in the worm.