VictorJuiz/thesis huggingface dataset:
Continuous monitoring during haemodialysis
Keywords: haemodialysis
intradialytic hypotension
blood pressure

Intradialytic Hypotension (IDH) is the commonest complication of maintenance haemodialysis and is associated with increased morbidity and mortality. However, there is no standardised definition of IDH, making comparisons between studies difficult.
This observational study with a total of 80 patients and over 600 dialysis sessions showed a poor correlation between symptoms and hypotension. Importantly, patients experienced low blood pressure without symptoms, so continuous intradialytic blood pressure monitoring is required to identify this asymptomatic group. In light of these findings, a revised definition of IDH is suggested. This study also aimed to identify predictors of IDH that could be detected in sufficient time to allow a mitigating intervention.
A novel non-invasive alternative for continuous blood pressure monitoring is introduced which uses intra-fistula pressure data from the sensors sited in the extracorporeal circuit of the dialysis machine. Results show that in the majority of patients, changes in intra-fistula pressure correlate with blood pressure measurements obtained by a standard oscillometric device.
To investigate whether IDH can be predicted, a photoplethysmogram (PPG) waveform was obtained from a pulse oximeter attached to the finger or ear. Continuous PPG monitoring of patients with IDH during dialysis demonstrated that some IDH episodes were predictable using the variation in the PPG baseline with respiration as a surrogate for low blood volume. Additionally, the area under the curve of the PPG waveform can be used as a surrogate for cardiac output and peripheral vascular tone, resulting in a reasonable predictor for potentially critical changes in blood pressure during dialysis.
Individually, the novel metrics described here are limited in their identification of IDH in all patients affected, but in combination they may be used to develop a multi-parameter predictive model. The relative merits of personalised versus population-based models are explored and a conclusion is drawn that personalised multi-parameter data fusion modelling for haemodialysis patients would be an important area for future work.
Quantum control of donor spins in silicon and their environment
Keywords: Donors in silicon
decoherence
spins

Donors in silicon, which combine an electron and nuclear spin, are some of the most promising candidates for quantum information. The electron spin has been proposed as a register with fast manipulation and the nuclear spin as a memory with long coherence times. However, this division reduces the complexity of the donor system, in particular behaviors emerging from their interaction. In natural silicon, there is also the presence of 29Si nuclear spins in the donor environment; though they are generally seen as a source of decoherence, they are quantum systems that can be investigated too. The main subject of this thesis is the study of the interactions between these various spins, using different methods to probe and control them.
I first concentrate on the coupling between the donor and the 29Si spins. This coupling can be perturbed by the application of dynamical decoupling on the donor electron spin, whose evolution can be made sensitive to the number of 29Si spins interacting together. I then propose an error correction scheme using the donor and 29Si spins, showing key requirements such as coherence times and methods for manipulation and initialization. Secondly, I focus on the donor itself, in a regime where the hyperfine and Zeeman couplings compete with each other. Here, the spin transitions can have different sensitivities to the magnetic environment, and can even be suppressed to first order, resulting in coherence times up to seconds with electron spin-like manipulation times. Controlling this sensitivity was also used to probe the effect of the donor on the 29Si spin bath evolution. Finally, I use electric fields to modulate the hyperfine coupling within the donor. I first characterize the spins’ sensitivity to the electric field, and then demonstrate electrical switching of the nuclear spin response to an external magnetic excitation.
Novel functional nano-coatings on glass by spray deposition
Keywords: Thin Film
Gold nanoparticles
Spray pyrolysis
Nanomaterials

Nanocomposite thin films with gold nanoparticles embedded in a host metal oxide prepared by spray pyrolysis deposition have been investigated. A single-step process has been developed using a one-pot solution containing precursors for both gold nanoparticles and host metal oxides. The films obtained display combined features of colouration, electrical conductivity and solar control. In this study two precursors for gold nanoparticles were used: preformed gold colloids and HAuCl4. Three metal oxide host materials, TiO2, SnO2 and ZnO, were investigated. These films were deposited at a substrate temperature of 200-600 °C. Powder X-ray diffraction analysis reveals the presence of metallic gold. SEM inspection typically showed particulate gold of 5-20 nm in diameter, distributed at the surface or within the host matrix. Optical spectroscopy showed an intense absorption in the visible region due to the characteristic surface plasmon resonance (SPR) effects of gold nanoparticles. The wavelength of the SPR peaks varies depending on the refractive index of surrounding host material which is significantly influenced by the substrate deposition temperature. On the other hand, SnO2 and ZnO, together with the introduction of dopants, were further investigated as suitable materials for transparent conducting oxides (TCO). SnO2:F films were found to attain very low electrical resistivity, while ZnO films exhibit higher transparency in the visible. A double layered structure with a TCO layer of SnO2:F on top of a layer embedded with gold nanoparticles has been employed to achieve the combined functionalities of conductivity and colouration. The electrical conductivity is significantly enhanced compared to a nanocomposite single layer film due to the introduction of the TCO top layer. In this thesis, spray pyrolysis deposition has demonstrated a simple and rapid approach to the production of a variety of thin films. It can be immediately integrated with current industrial coating equipment and scaled up for large-scale production process.
Curriculum tracking and the achievement ideology at an American urban public school
Keywords: achievement ideology
curriculum tracking
meritocracy
International Baccalaureate

This thesis presents a case study of how curriculum differentiation operates at Lincoln High School, an urban public school in the Midwestern United States with a highly regarded International Baccalaureate (IB) program. I use a mix of qualitative and quantitative methods to investigate the systems of beliefs and practices that structure Lincoln's tracking system.
Like many American high schools, Lincoln has rejected the traditional practice of assigning all students to overarching curriculum 'tracks' on the basis of their measured aptitude, instead allowing students to choose between courses covering different content at different levels of difficulty in most academic subjects. The school thus offers an excellent opportunity to examine within-school stratification in light of the declining popularity of traditional tracking and the increasing degree to which students control their own coursetaking. Within-school stratification is particularly worthy of continued attention because it qualifies the mythology of the American dream, which holds that schools give students from all backgrounds an opportunity to achieve upward social mobility. I use interviews, observations, and document analysis to explore how curriculum differentiation structures academic and social hierarchies at Lincoln, what teachers and students believe about how to achieve school success and upward mobility, and how Lincoln reconciles its egalitarian ideals with the continued existence of de facto tracking.
I argue that Lincoln's approach to curriculum differentiation strikes a tenuous balance between academic excellence and equity for all students. Although student choice dominates the course scheduling process, Lincoln's curriculum still bears many of the hallmarks of tracking: the IB structures a clear academic and social hierarchy of courses, and students tend to follow predictable patterns of coursetaking within each subject, with few opportunities for upward mobility. Nonetheless, teachers and students almost unanimously subscribe to the local achievement ideology, which holds that any student, regardless of prior academic achievement, can and should participate in the IB as long as he or she is willing to work hard. This radical promise of equal opportunity allows participants to characterize Lincoln as a force for equality and social justice. However, the school's continued reliance on sorting its students, even in the face of evidence that tracking reproduces racial and class inequalities, suggests that the achievement ideology serves primarily to legitimate stratification, not to undo it. These findings have important ramifications for research in tracking, detracking, and stratification, and for practice in all schools seeking to negotiate the tension between excellence and equity.
Structure and function of bacterial ion channels
Keywords: Kir channels
KirBac channels
structure-function
Ion channels

KirBac channels are prokaryotic homologs of eukaryotic inwardly-rectifying potassium channels, which have served as models for gaining insight into the structure of eukaryotic channels. This thesis focuses on the structure-function relationship in these channels. The first part of this study concerns a novel KirBac channel, KirBac9.2, which contains a unique amino acid sequence in the place of the canonical GYG selectivity filter. Although expressed and purified in a stable and functional form, the protein did not form well-diffracting crystals. Functional studies suggest that KirBac9.2 is non-selective for monovalent cations and a random mutagenesis screen identified a number of activatory mutants in the cytoplasmic domains of the channel. A full electrophysiological investigation of KirBac9.2 channel function is beyond the scope of this study. However, initial studies suggest that it is possible to record currents from KirBac9.2 channels reconstituted into lipid bilayers. The second part of this thesis investigates KirBac3.1, which is a classical KirBac channel containing the consensus GYG sequence for potassium selectivity. Five high resolution structures of a mutant channel are reported, which suggest a new feature in the gating mechanism of KirBac3.1 where a rotation of the cytoplasmic domains is linked to a change in the electrostatic environment of the cytoplasmic cavity. In addition, a functional study of the KirBac3.1 showed that the channel is highly pH sensitive.
The lives of Ovid: secrets, exile and galanterie in writing of the ‘Grand Siècle’  
Keywords: Life-writing
Madame de Villedieu
Galanterie
History and Criticism
Pierre Bayle and Historiography
La Querelle des Anciens et des Modernes
Ovid
Bussy-Rabutin.
Classical Reception
17th-Century French Literature
Anne de la Roche-Guilhen

This study examines the constructions and uses of the figure of Ovid in French writing of the second half of the seventeenth century, and explores how they were modulated by contemporary aesthetic and cultural concerns. As the influence of Ovid’s poetry made itself felt in various ways – in the mythopoeia of the Sun-King and the fashionable galant salons – interest in the story of Ovid’s life blossomed. This, I argue, was facilitated by new forms of ‘life-writing’, the nouvelle historique and histoire galante, and fuelled in unexpected ways by the escalating querelle des Anciens et des Modernes. Research has been done on the reception and influence of Ovid’s poetry in this period, but little attention has been paid to the figure of Ovid. This thesis offers a new perspective and, informed by recent renewed interest in life-writing, argues that analysis of biographical depictions is vital for establishing a coherent picture of the uses of Ovid in the ‘Grand Siècle’.
I explore a diverse range of textual descriptions of Ovid (Vies; prefatory material attached to translations and editions of his work; correspondence; dialogues des morts; biographical dictionaries and historical novels), organized according to their different, though intersecting, ways of writing about this poet. He was constructed as a historical figure, an author, a fictional character and a ‘parallèle’ – a point of identification or contrast for contemporary writers. Through close analysis of a multi-authored corpus, this thesis identifies and examines two instances of paradox: though an ancient poet, Ovid became emblematic of 'Moderne' movements and was used to explore aspects of galanterie; and, though his creative work was mobilized in the service of royal propaganda, Ovid, as a figure for the exiled poet, was also used to express anxieties about the sway of power and the machinations and pitfalls of the world of the court.
Effects of age on sleep and consolidation of motor learning
Keywords: consolidation
memory
learning
sleep
ageing

Background: Our ability to consolidate what we learn changes with age. However, little is known about the neurophysiological underpinnings of consolidation of motor learning in ageing. This is largely because studies have repeatedly demonstrated a deficit in sleep-dependent consolidation of motor learning in older adults. This thesis aims to reassess commonly held assumptions about consolidation in ageing, as well as to examine the neurophysiological and neurochemical mechanisms that support the learning and consolidation processes.
Methods: Most of the studies in this thesis are based on the design of a novel whole-hand task for use in older adults, which reduces dependency on fine motor skill. This thesis adopts a number of converging measures to examine learning and memory including electroencephalograhy (EEG), magnetic resonance spectroscopy (MRS), actigraphy recordings, as well as behavioural and self-reported measures of sleep.
Results: Findings show significant improvements in learning with the adapted motor task in older adults. Importantly, this task reveals significant sleep- dependent enhancements in older adults, which are comparable to those seen in younger controls. Functional changes in sleep architecture with ageing show overall decline in slow wave sleep. Sleep-dependent improvements were specifically associated with activity in stage 3 slow wave sleep and increased hemispheric differences regardless of age. Changes in GABA concentrations with learning on a visuomotor tracking task showed marked variability across participants, and no clear associations were found between GABA and consolidation.
Conclusion: The evidence presented in this thesis highlight the complex dynamics underlying sleep consolidation, and challenges a commonly held assumption about consolidation in older adults. Specifically, the studies presented here show that observed declines in motor consolidation with ageing may be contaminated by age-related deficits fine motor skill. By removing such kinematic constraints, it was possible to detect marked improvements in motor performance also in older adults despite age-related changes in sleep architecture.
Design and analysis of genome-wide association studies
Keywords: crohn's disease
genome-wide association study

Despite many years of effort, linkage and candidate gene association studies have yielded disappointingly few risk loci for common human diseases such as diabetes, auto-immune disorders and cancers. Large sample sizes, increased understanding of the patterns of correlation in genetic variation, and plunging genotyping costs have enabled genome-wide association studies, which have good power to detect common risk alleles of modest effect. I present an evaluation of SNP choice in study design and show that overall, despite substantial differences in genotyping technologies, marker selection strategies and number of markers assayed, the first generation platforms all offer good levels of genome coverage (∼ 70%). I next describe the largest such project undertaken to date, the Wellcome Trust Case Control Consortium, which consisted of 2000 cases from each of seven common diseases and 3000 shared controls. It identified nearly two dozen new associations. I demonstrate the importance of careful data quality control, including both standard and unorthodox analyses. I next focus on the association results therein for Crohn’s disease. I present a replication experiment in over 1000 additional Crohn’s patients which unambiguously confirmed six previously published loci and four new loci. Next I describe, in a general context, several issues impeding the combination of genome-wide scans, including data annotation, population structure and differences in genotyping platform. Each of these problems is shown to be tractable with available methods, provided that these methods are applied prudently. I present the results of a meta-analysis of three genome-wide scans for Crohn’s disease. The data showed a striking excess of significant associations, and a replication experiment involving over 4000 independent Crohn’s patients verified twenty new risk loci. Finally, I discuss the early success of genome-wide association and its consequences for further understanding the biology of human disease.
A study of the phenotype and function of HLA-C restricted CD8 T cells in HIV-1 infection
Keywords: HIV-1
HLA-C

A recent study showed that a polymorphism ~35kb upstream of the HLA-C gene (-35 SNP) correlates with host control of HIV-1 in Caucasians, with the minor allele (C) associating with significantly lower set point viral loads than the major allele (T). A link between viral load and HLA-C is suggested by linkage of the two SNP alleles with different HLA-C alleles and by the fact that HLA-C, in contrast to HLA-A and -B, is not down-regulated by HIV-1 Nef protein. In addition, the -35C variant has been shown to associate with higher HLA-C messenger RNA expression in EBV-transformed B cell lines. We initially propose that increased surface expression of HLA-C in subjects with the protective SNP leads to increased breadth and magnitude of HLA-C restricted T cell responses, explaining the decrease in viral load in these subjects.
This study initially investigates whether the -35 SNP correlates with the surface level of HLA-C using the monoclonal antibodies DT9, which recognises both HLA-C and HLA-E, and 3D12, which is specific for HLA-E. The lymphocytes from -35 CC subjects expressed a significantly higher level of surface HLA-C when compared to those from -35 TT subjects, but this difference in HLA-C expression can be attributed primarily to the very low expression of a single allelic product, HLA-Cw*07.
Increased surface HLA-C should translate to functional differences between CC and TT subjects. This study confirmed that HLA-C restricted CD8 T cell responses against HIV-1 do exist, even for HLA-Cw*07, but represent a minority of total T cell responses. They were detected in all -35 SNP genotypes but there were no functional differences, making it unlikely that the protective effect of this SNP on viral load set point could be accounted for solely by HLA-C restricted T cell responses.
Finally, a viral suppression assay was used to investigate the capacity of CD8 T cells to suppress HIV-1 replication in Caucasian and African subjects. We provide evidence that the -35 SNP effect on viral load is indeed T cell mediated. However, we suggest that the protective effect of the -35 SNP on viral load set point manifests as a result of linkage disequilibrium of this polymorphism with both favourable and unfavourable HLA-B and HLA-C alleles.
Chemical and biological studies on human oxygenases
Keywords: platform
2-oxoglutarate
prostate
demethylase
breast
non-haem
muscular dystrophy
chemical probe
KDM
translation
technology
cystic fibrosis
open
organasational capability
ribosome
collaboration
innovation
market
cancer
transcription
lung
OGFOD1
histone
epigenetics
iron
2OG
oxygenase

As depicted in Chapter I, 2-oxoglutarate- (2OG) dependent oxygenases are ubiquitous in living systems and display a wide range of cellular functions, spanning metabolism, transcription, and translation. Although functionally diverse, the 2OG oxygenases share a high degree of structural similarities between their catalytic sites. From a medicinal chemistry point of view, the combination of biological diversity and structural similarity presents a rather challenging task for the development of selective small molecules for functional studies in vivo.
The non-selective metal chelator 8-hydroxyquinoline (8HQ) was used as a template for the generation of tool compound I for the KDM4 subfamily of histone demethylases via application of the Betti reaction. Structural analogue II was used as the corresponding negative control (Figure A). These compounds were characterised in vitro against a range of 2OG oxygenases and subsequently used for studies in cells. I displays selectivity for KDM4 and increases the level of the H3K9me3 histone mark in cells. It has an effect on the post-translational modification pattern of histone H3, but not other histones, and reduces the viability of lung cancer cells, but not normal lung cells, derived from the same patient. I also stabilises hypoxia-inducable factor HIF in cells via a mechanism which seems to be independent from prolyl hydroxylase inhibition. This work is described in Chapters II and III.
The chemical biology research in epigenetics is complemented by qualitative analysis conducted in the social sciences at Said Business School. With a global view on how innovation occurs and may actively be fostered, Chapter IV focuses on the potential of epigenetics in drug discovery and how this process may actively be promoted within the framework of open innovation. Areas of focus include considerations of incremental and disruptive technology; how to claim, demarcate, and control the market; how knowledge brokering occurs; and insights about process, management, organisation, and culture of open innovation.
In contrast to the open-skies approach adopted for the development of a tool compound in Chapters II and III, a focused-library approach was taken for the generation of a tool compound for the OGFOD1 ribosomal prolyl hydroxylase. The development of a suitable in vitro activity assay for OGFOD1 in Chapter V enabled the development of lead compound III in Chapter VI. III is selective for OGFOD1 against the structurally closely related prolyl hydroxylase PHD2.