VictorJuiz/thesis huggingface dataset:
Short pulse x-ray generation in synchrotron radiation sources
Keywords: x-ray
beam dynamics
accelerator
synchrotron radiation
short pulses

This thesis describes an investigation into the performance of different schemes for generating short x-rays pulses via synchrotron radiation emission. A review is given of the methods that have been previously proposed for this task. From this review, three leading schemes are selected for in-depth investigations, each of which explores the boundary of what is presently achievable in accelerator-based light sources.
The first scheme generates short x-ray pulses by operating an electron storage ring in a quasi-isochronous state using a ‘low-alpha’ lattice. High and low emittance lattices are developed, studied through simulation and then implemented on the Diamond storage ring. Beam dynamics and bunch length measurements are presented for a variety of machine conditions, and an assessment is made of the minimum practically achievable bunch length for stable user operation. Radiation pulses of 1 ps r.m.s. are demonstrated using this scheme.
The second and third schemes investigate performance limits for a linac-based light source through numerical simulations. The first of these generates ultra-short pulses by passing a highly compressed electron bunch through a long undulator to radiate in the ‘single-spike’ regime. A comparison is made with theoretical predictions for the required electron bunch length to operate in this way, which highlights the need for accurate start-to-end simulations. The final scheme generates ultra-short x-ray pulses through laser manipulation of the electron bunches. The modulated electrons pass through a long undulator with tapered gap, such that only the centre of the modulated portion experiences high free-electron laser (FEL) gain. A method to enhance the FEL output from this scheme using a wavelength filter and grating-compressor is investigated. The sensitivity of the two schemes to jitter sources is determined, and it is demonstrated both schemes are capable of generating GW-level, fully coherent sub-fs soft x-ray pulses. Such pulses would open up the development of time-resolved science to new regimes.
Computerised analysis of fetal heart rate
Keywords: genetic algorithms
Fetal heart rate
decision support system
signal loss

This thesis presents a comprehensive work on computerised analysis of fetal heart rate (FHR) features, including feature extraction, feature selection, analysis of influencing factors and setting up/validation of a computerised decision support system.
Firstly, a novel feature – pattern readjustment – was extracted and tested. Clinical data were used to train a Support Vector Machine (SVM) to detect pattern readjustment. Then, the association of pattern readjustment and adverse labour outcome was investigated. The validation results with clinical experts show that the pattern readjustment can be accurately detected, while the study on labour outcome shows that the feature is related to fetal acidemia at birth.
Secondly, Genetic Algorithms were employed as a feature selection method to select a best subset of FHR features and to use them to predict fetal acidemia with linear and nonlinear SVM. The diagnostic power of the classifier output using selected features was tested on the total set of 7,568 cases. As the classifier output increases, there is a consistent increase of the risk of fetal acidemia.
Thirdly, an important influencing factor on FHR features - signal loss – was investigated. A bivariate model was built to estimate error based on signal loss. Validation results show that the bivariate model can accurately predict the error generated by signal loss. The influence of signal loss on labour outcome classification was also investigated.
Finally, a computerised decision support system to estimate the risk of fetal acidemia was set up based on the above studies. The system was validated using new retrospective data. Validation results show that the system is capable of predicting adverse labour outcome and providing timely decision support. It is the first time an intrapartum computerised FHR decision support system has been built and validated on this size of dataset. With further improvements, such a system could be implemented clinically in the long term.
An edition with commentary of the Batrachomyomachia
Keywords: Batrachomyomachia
Hellenistic
textual criticism
parody
Ancient Greek
mice
Homer
frogs

The thesis consists of three main sections: the Introduction, the text (with apparatus), and the Commentary.
The Introduction begins with a survey of the available evidence for the poem’s date and authorship, before moving on to consider its generic affiliations and influences, focusing on two particular areas: its links with the ill-defined genre of παρῳδία, and its relationship to animal-narratives elsewhere in ancient literature (particularly fable) and visual art. This is followed by a detailed analysis of the poem’s style and metre, a brief tour of its Nachleben up to the 13th century, and a summary of the notoriously tangled manuscript tradition.
The text is new, and differs substantially from both that of Allen (in the OCT) and of West (the most recent English edition). The apparatus, as explained in more detail on p. 117, is somewhere between the two: it takes into account the readings of only nine MSS from the 80-100 extant, and does not attempt to represent every single textual variation even among these nine, but it is much fuller than the minimalist apparatus of the Loeb. It aims to provide a useful source for scholars interested in the poem’s many and serious textual cruces, while remaining more succinct and user-friendly than the dense and sometimes baffling apparatus of Ludwich’s monumental 1896 edition. The text is followed by an English prose translation: this makes no claims to beauty, and is simply intended as a relatively literal guide to the sense of the Greek.
The Commentary, finally, is twofold. Any commentary on the Batrachomyomachia will inevitably spend much space and ink on purely textual issues, and on the fundamental task of unearthing meaning from the dizzying range of wild and nonsensical variants available. Interspersed with these textual points, however, this commentary includes considerations of the poem not as a mechanics problem but as a sophisticated Hellenistic work of art – exploring its intertextualities, its characterisation, its dramatic effects, its dry sense of humour, and subjecting it to the serious literary analysis it has often been denied.
Role of the NMB0342-NMB0348 locus in meningococcal pathogenesis and investigation of NMB0345 as a vaccine candidate
Keywords: bacterial meningitis

Neisseria meningitidis is the most common cause of bacterial meningitis in the Western world and the second leading cause of mortality in 1-5 year-olds in the United Kingdom. A signature-tagged mutagenesis screen of approximately 3,000 insertional mutants of a serogroup B isolate of N. meningitidis, C311⁺, identified 73 genes required for pathogenesis in an infant rat model of meningococcal septicaemia. Homology-based searches indicate that two of the genes identified, NMB0342 and NMB0345, have homologues in other pathogenic bacteria and exist within a potential operon of seven genes (NMB0342-NMB0348). NBM0342 is a homologue of ispA (intracellular septation protein) of Shigella flexneri, required for effective intercellular spread and plaque formation in epithelial cells. NMB0345 is a homologue of cbf, a Campylobacter jejuni gene that encodes a 29 kDa protein which is a major antigenic peptide. PCR and Southern analyses of genes in the NMB0342-NMB0348 locus show that they are conserved across a wide range of pathogenic isolates and serogroups of N. meningitidis. However, these genes are present only in a subset of commensal strains. N. meningitidis mutants with transpoon insertions in NMB0342 and NMB0345 are highly attenuated when directly competed with the wild-type bacterium in the infant rat model of infection. Mutations have been introduced into other genes within the locus and the resulting mutants analyzed for their ability to cause systemic disease. Mutants with transpoon insertions in the NMB0343 and NMB0344 genes are significantly attenuated, while mutants with insertions in NMB0347 and NMB0348 are attenuated to a lesser degree. Complementation of the NMB0342 mutation by ectopic chromosomal integration of a wild-type copy of NMB0342 almost completely restores the virulence of the bacterium. In vitro cell-culture analyses and microscopic analysis of mutants in association with host cells demonstrate that a mutant with a transpoon insertion in NMB0345 is significantly reduced in its adherence to Chang epithelial cells compared to the wild-type bacterium. Whole blood and serum-sensitivity assays show that the NMB0342 and NMB0345 mutants are highly serum-sensitive compared to the wild-type bacterium. Preliminary experiments have demonstrated that immunization of mice with recombinant NMB0345 protein confers protection against challenge with the serogroup B isolate MC58. In vitro assays demonstrate that recombinant NMB0345 is an active peptidyl polyl cistrans isomerase (PPIase). Together, the results from these investigations support a role for genes of the NMB0342-NMB0348 locus in the pathogenesis of N. meningitidis infections. Further investigation is needed to assess the potential of NMB0345 as a vaccine candidate.
The role of ubiquitylation in regulating apurinic/apyrimidinic endonuclease 1
Keywords: Genome Stability
APE1
UBR3
Ubiquitylation
Apurinic/Apyrimidinic Endonuclease 1
Base Excision Repair
DNA damage repair

Apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA repair factor involved in the DNA base excision repair (BER) pathway that is required for the maintenance of genome stability. In this pathway, APE1 cleaves DNA at an abasic site to generate a DNA single strand break, allowing for repair completion by a DNA polymerase and a DNA ligase. High levels of APE1 have been observed in multiple cancer types however it is not understood if this contributes to cancer onset and development. What is known is that these cancers tend to display increased resistance to DNA damaging treatments and APE1 is therefore considered a key target for inhibition in the treatment of APE1-overexpressing cancers. Considering the relevance of modulating APE1 levels in disease and cancer treatment, very little is known about how cellular APE1 levels are regulated. Our lab has previously shown that the levels of the BER factors Pol β, XRCC1 and DNA Lig IIIα are regulated by ubiquitylation-mediated proteasomal degradation. The aim of this doctoral thesis was therefore to determine if ubiquitylation also regulates APE1 stability in cells. I present evidence that APE1 is ubiquitylated in cells and have identified the UBR3 E3 ligase that is responsible for this activity. Using mouse embryonic fibroblasts generated from Ubr3 knockout mice, I demonstrate that UBR3 regulates APE1 cellular levels. I furthermore show that a loss of cellular UBR3 leads to the formation of DNA double strand breaks and genome instability.
Quantum simulation using ultracold atoms in two-dimensional optical lattices
Keywords: optical lattices
quantum simulation
ultracold atoms
strongly correlated systems

Ultracold atoms in optical lattices can be used to model condensed matter systems. They provide a clean, tuneable system which can be engineered to reach parameter regimes that are not accessible in condensed matter systems. Furthermore, they provide different techniques for probing the properties of these systems.
This thesis presents an experimental and theoretical study of ultracold atoms in optical lattices for quantum simulation of two-dimensional systems.The first part of this thesis describes an experiment with a Bose-Einstein condensate of 87Rb loaded into a two-dimensional optical lattice. The beams that generate the optical lattice are controlled by acousto-optic deflection to provide a flexible optical lattice potential. The use of a dynamic ‘accordion’ lattice with ultracold atoms, where the spacing of the lattice is increased in both directions from 2.2 to 5.5 μm, is described. This technique allows an experiment such as quantum simulations to be performed with a lattice spacing smaller than the resolution limit of the imaging system, while allowing imaging of the atoms at individual lattice sites by subsequent expansion of the optical lattice. The optical lattice can also be rotated, generating an artificial magnetic field. Previous experiments with the rotating optical lattice are summarised, and steps to reaching the strongly correlated regime are discussed.
The second part of this thesis details numerical techniques that can be used to describe strongly correlated two-dimensional systems. These systems are challenging to simulate numerically, as the exponential growth in the size of the Hilbert space with the number of particles means that they can only be solved exactly for very small systems. Recently proposed correlator product states [Phys. Rev. B 80, 245116 (2009)] provide a numerically efficient description which can be used to simulate large two-dimensional systems. In this thesis we apply this method to the two-dimensional quantum Ising model, and the Bose-Hubbard model subject to an artificial magnetic field in the regime where fractional quantum Hall states are predicted to occur.
Comparing the radiological anatomy, electrophysiology, and behavioral roles of the pedunculopontine and subthalamic nuclei in the normal and parkinsonian brain
Keywords: deep brain stimulation
Parkinson's disease
pedunculopontine nucleus
gait analysis
diffusion tensor imaging
local field potential
oscillations
posture
basal ganglia
subthalamic nucleus

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and DBS of the pedunculopontine nucleus (PPN) have been shown to be effective surgical therapies for Parkinson’s disease (PD). To better understand the PPN and STN as DBS targets for PD, this research compares the anatomy, electrophysiology, and motor control roles of these nuclei. PPN and STN connections were examined in vivo in human subjects and in the non-human primate using probabilistic diffusion tractography. Both the PPN and STN were connected with each other and with the motor cortex (M1) and basal ganglia. After studying these anatomical connections in primates, their functional significance was further explored in an anesthetized rat model of PD. Examination of the electrophysiological relationship between the PPN and basal ganglia in the presence of slow cortical oscillatory activity suggested that excitatory input from the STN may normally modulate PPN spike timing but that inhibitory oscillatory input from the basal ganglia output nuclei has a greater effect on PPN spike timing in the parkinsonian brain. To examine transmission and modulation of oscillatory activity between these structures at higher frequencies, LFP activity was recorded from the PPN and STN in PD patients performing simple voluntary movements. Movement-related modulation of oscillatory activity predominantly occurred in the α (8-12 Hz) and low β (12-20 Hz) frequencies in the STN but in the high β (20-35 Hz) frequencies in the PPN, supporting observations from rodent studies suggesting that oscillatory activity is not directly transmitted from the STN to the PPN in PD. Finally, to better understand the roles of the STN and PPN in large-scale movement, the effects of STN and PPN DBS on gait abnormalities in PD patients were studied. DBS of the STN appeared to improve gait by optimising executive gait control while DBS of the PPN appeared to restore autonomic gait control. These results have several implications for DBS patient selection, surgical targeting, and for understanding the mechanisms underlying DBS efficacy.
A conception of equality of opportunity
Keywords: luck
fairness
equality

This thesis defends a conception of equality of opportunity. It comes in two parts. The first part elaborates the conception. It begins by clarifying the concept of equality of opportunity, showing it to be made up of four basic elements: a distributive pattern, a set of subjects, an opportunity obstacle and a distributive object. The conception I build from these elements explains the value of the distributive pattern, equality, in terms of a concern for fairness, takes persons as its subject and takes well-being as its object. The conception presented is partial, rather than comprehensive, in that it does not include a detailed account of an opportunity obstacle. The conception of equality of opportunity that I present can also be characterised as a luck egalitarian principle. My aim in elaborating the conception is to show that it has intuitive appeal; it constitutes a pro tanto moral principle.
The second part of the thesis examines the implications of luck egalitarianism in two contexts. It begins by examining the context of gifts, arguing that although luck egalitarianism is highly restrictive with respect to the freedom to give this only confirms that it is a merely pro tanto moral principle. It continues by examining the context of markets, arguing that luck egalitarianism makes intuitively correct judgments in several specified cases. My aim in applying luck egalitarianism is to show that its implications do not give us reason to reject its initial intuitive appeal. I examine luck egalitarianism generally, rather then the partial conception I elaborate, to allow for the possibility that my earlier arguments are wrong in some respect. Overall, I hope the arguments presented provide reasons to accept the conception presented as morally valuable.
Moving beyond boundaries: an exploration into the relationship between politics and dance
Keywords: dance; politics; political theory

This thesis looks into the relationship between dance and politics. It argues that dance is both a method of intervening in other symbolic languages and a system of inscription that is intertwined in that moment of intervention. Dance as a political language has a subversive potential; it can challenge verbal political statements.
In the thesis I work with and against Jacques Rancière’s interpretation of politics as re-distribution of the sensible and with Aletta Norval’s reading of Rancière’s conception of democracy as egalitarian inscription which I expand and read as egalitarian embodied inscription. I show that Rancière’s focus on politics as rupture disables the recognition inscription as continuity. I show that dance enables a reading of politics as both rupture and continuity, an intervention that leaves traces that endure after it ends. Through a genealogy of the concept of the Dionysian I show that philosophers and dance practitioners alike have read dance as both subversive and affirmative, an intervention and a system of inscription that acts independently of spoken discourse. I show that Isadora Duncan created the first political moment in modern dance as a re-distribution of the sensible; at the same time although she created egalitarian embodied inscription she did not leave a codified system of movement, and did not contradict her politics in spoken language. I show that Martha Graham created the second moment of re-distribution of the sensible in which she created a codified movement language that subverted politics in spoken words. Finally, I revisit Rancière’s work and bind his discussion of human rights with the problematic of the tension between rupture and continuity. I re-read both these arguments with my interpretation of dance as political and argue that it yields a reading of dance as enabling the creation of human rights claims. Dance is both subversive and affirmative.
Role and regulation of MITF in melanocytes and melanoma
Keywords: melanoma
DNA
MITF

One key to understanding how cells integrate and how they respond to diverse stimuli in order to direct a transcriptional response is knowing how a transcription factor may be directed to an appropriate subset of its target genes. One mechanism with which this may be achieved is by modulation of the transcription factor’s post-translational modification status. The microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage, and it is also a lineage addiction gene in melanoma. Low or high levels of MITF expression induce a reversible cell cycle arrest. Invasive behaviour is characteristic of low MITF expression; differentiation a product of high MITF activity; and moderate levels of MITF expression promote proliferation. A major, unaddressed problem is how DNA binding by MITF may be differentially directed such that it regulates either a proliferation-associated or a differentiation-associated gene expression programme appropriate to the cellular microenvironment. This thesis explores the function and regulation of the signalling pathways controlling novel post-translational modifications of MITF. One such modification, in the DNA binding domain of MITF, defines a key switch that controls MITF’s DNA binding affinity and specificity. Moreover, a novel set of MITF target genes are revealed that extend its control beyond pigmentation and cell cycle regulation to implicate MITF as an overall regulator of cell behaviour in the melanocyte lineage.
Genome scale metabolic models of plant tissues
Keywords: maintenance costs
genome scale metabolic model
arabidopsis
diel metabolism

The aim of this thesis was to explore the use of genome-scale metabolic models to predict metabolic fluxes in plant tissues. Results from this thesis showed that the application of constraint-based modelling, namely flux balance analysis, to an Arabidopsis genome-scale metabolic model gave accurate predictions of metabolic fluxes in heterotrophic cell culture and in photosynthetic leaves. Two major factors important for the accuracy of model predictions were highlighted from the study: 1) the inclusion of energetic costs for transports and cellular maintenance in terms of ATP and NADPH; 2) consideration of the interactions between light and dark metabolism in modelling photosynthetic leaves.
This study began with the construction of a well-curated and compartmented genome-scale metabolic model of Arabidopsis. Using the model, cellular maintenance costs in a heterotrophic cell culture under control and two stress conditions were estimated in terms of ATP and reductant usage. The results suggested that the cells were not stressed under hyperosmotic conditions. Comparisons between model predictions and experimentally estimated flux maps showed that the inclusion of transport and maintenance costs was important for obtaining accurate model flux predictions.
To model leaf metabolism over a day-night cycle, a diel modelling framework was developed which took into account the interactions between light and dark metabolism. Numerous known features of metabolism in a C3 leaf were predicted such as the nocturnal accumulation of citrate utilised for diurnal glutamate and glutamine synthesis and the operation of an incomplete TCA cycle during the day. Using the Arabidopsis genome-scale metabolic model and the diel modelling framework, the operation of the CAM cycle was predicted as a direct consequence of blocking the CO2 exchange with the external air during the day to simulate closure of the stomata. Comparisons between model predictions of C3 and various subtypes of CAM leaves suggested that photon and nitrogen use efficiencies are unlikely to be the driving forces for the evolution of CAM plants under the current atmospheric CO2 concentration.
Finally, the model was utilised to predict the changes in metabolic fluxes, in particular fluxes through various routes of alternative electron flow, in a C3 leaf with varying light intensity, nitrogen availability and at different stages of leaf development. From the model flux predictions, it was shown that constraint-based modelling can be utilised to elucidate the distinct metabolic roles of enzymes in different subcellular compartments and the tissue-specific use of distinct forms of enzymes with different coenzyme specificities.