VictorJuiz/thesis huggingface dataset:
Mechanisms of immunoglobulin deactivation by Streptococcus pyogenes
Keywords: EndoS
glycobiology
antibodies
Streptococcus pyogenes
biophysics
immunology
structural biology
IdeS
IgG

The bacteria Streptococcus pyogenes produces a multitude of proteins which interact with and alter the functions of the host immune system. Two such proteins, Endoglycosidase S (EndoS) and Immunoglobulin G-degrading enzyme from S. pyogenes (IdeS) are able to specifically alter the effector functions of immunoglobulin G (IgG). EndoS is a glycoside hydrolase which removes the conserved N-linked glycan from IgG Fc whereas IdeS is a cysteine protease that cleaves the exible protein hinge of IgG. The activity of both proteins results in the reduced ability of IgG to elicit immune responses through Fc receptor binding and complement activation. Amongst other applications, both EndoS and IdeS are actively being explored as new therapeutics for IgG-mediated autoimmune diseases. Given the therapeutic potential of EndoS and IdeS, experiments were designed to investigate the structural and functional characteristics of these enzymes in an effort to understand their specficity for and activity against IgG.
Here, bioinformatic and biophysical characterisation of EndoS identified subdomains outside of the catalytic domain which contribute to glycoside hydrolase activity. The substrate specificity of EndoS was also explored and showed that EndoS hydrolyses a broad range of glycans from the IgG scaffold. EndoS was also shown to have activity against alternative glycoprotein substrates, however, this non-specific activity was negligible in the context of whole serum. The effect of EndoS-mediated deglycosylation on the structure of the IgG Fc domain was explored using both X-ray crystallography and small-angle X-ray scattering. Small angle X-ray scattering was also used to characterise both EndoS and IdeS in complex with IgG Fc. Solution-state models of each complex were produced providing preliminary data towards how these enzymes interact with IgG. Overall, the results presented here contribute to our understanding of these enzymes which is of importance as they go forward into clinical applications.
Automotive combustion modelling and control
Keywords: combustion
diesel
FPGA
control
modelling
automotive

This thesis seeks to bring together advances in control theory, modelling and controller hardware and apply them to automotive powertrains. Automotive powertrain control is dominated by PID controllers, look-up tables and their derivatives. These controllers have been constantly refined over the last two decades and now perform acceptably well. However, they are now becoming excessively complicated and time consuming to calibrate. At the same time the industry faces ever increasing pressure to improve fuel consumption, reduce emissions and provide driver responsiveness. The challenge is to apply more sophisticated control approaches which address these issues and at the same time are intuitive and straightforward to tune for good performance by calibration engineers.
This research is based on a combustion model which, whilst simplified, facilitates an accurate estimate of the harmful NOx and soot emissions. The combustion model combines a representation of the fuel spray and mixing with charge air to give a time varying distribution of in-cylinder air and fuel mixture which is used to calculate flame temperatures and the subsequent emissions.
A combustion controller was developed, initially in simulation, using the combustion model to minimise emissions during transient manoeuvres. The control approach was implemented on an FPGA exploiting parallel computations that allow the algorithm to run in real-time. The FPGA was integrated into a test vehicle and tested over a number of standard test cycles demonstrating that the combustion controller can be used to reduce NOx emissions by over 10% during the US06 test cycle.
A further use of the combustion model was in the optimisation of fuel injection parameters to minimise fuel consumption, whilst delivering the required torque and respecting constraints on cylinder pressure (to preserve engine integrity) and rate of increase in cylinder pressure (to reduce noise).
Incremental modelling for verified communication architectures
Keywords: communication protocols
verification
theorem proving

Modern computer systems are advancing from multi-core to many-core designs and System-on-chips (SoC) are becoming increasingly complex while integrating a great variety of components, thus constituting complex distributed systems. Such architectures rely on extremely complex communication protocols to exchange data with required performance. Arguing formally about the correctness of communication is an acknowledged verification challenge.
This thesis presents a generic framework that formalises the idea of incremental modelling and step-wise verification to tackle this challenge: to control the overall complexity, features are added incrementally to a simple initial model and the complexity of each feature is encapsulated into an independent modelling step. Two main strategies reduce the verification effort. First, models are constructed with verification support in mind and the verification process is spread over the modelling process. Second, generic correctness results for framework components allow the verification to be reduced to discharging local assumptions when a component is instantiated. Models in the framework are based on abstract state machines formalised in higher order logic using the Isabelle theorem prover.
Two case studies show the utility and breadth of the approach: the ARM AMBA Advanced High-performance Bus protocol, an arbiter-based master-slave bus protocol, represents the family of SoC protocols; the PCI Express protocol, an off-chip point-to-point protocol, illustrates the application of the framework to sophisticated, performance-related features of current and future on-chip protocols.
The presented methodology provides an alternative to the traditional monolithic and post-hoc verification approach.
Study of High Energy Density Matter through Quantum Molecular Dynamics and Time Resolved X-ray Scattering
Keywords: Warm dense matter
Non-equilibrium plasmas
Molecular Dynamics
Density functional theory

The warm dense matter regime (WDM), defined by temperatures of a few electron volts and densities comparable with solids, is a complex state of matter where multi-body particle correlations and quantum effects play an important role in determining the overall structure and equation of state. The study of WDM states represents the laboratory analogue of the astrophysical environments found in the cores of planets and in the crusts of old stars, but also has practical applications for controlled thermonuclear fusion.
Time resolved X-ray diffraction is used to study the temporal evolution of a sample from solid state towards WDM, either after irradiation with an intense proton/electron beam, in carbon samples, or direct laser illumination, in thin gold nanofoils. The electron-ion equilibration time is extracted through the use of the two-temperature model and in highly excited carbon shown to be longer than previously thought, this is attributed to strong ion-ion coupling screening the interaction (coupled mode theory).
Calculation of the dynamic ion-ion structure factor is performed using orbital-free density functional theory (OF-DFT) and shown to compare well with Kohn-Sham DFT in both the static and dynamic cases. Experimental verification of these results is vital and measurement of the microscopic dynamics of warm dense aluminium have been successfully demonstrated through inelastic X-ray scattering. Using the self-seeded beam at the linear coherent light source (LCLS) scattering at a small momentum exchange allowed the first direct measurement of ion acoustic waves in WDM. This data provides the basis for a direct experimental test of many dense plasma theories through direct comparison with the ion-ion dynamic structure factor.
Towards a theory of adjudication: some issues of method and principle
Keywords: Natural Law
Adjudication
Judicial Duty
Jurisprudence
Methodology
Thomas Aquinas
John Finnis

A sound theory of adjudication and of judicial duty requires or presupposes a sound theory of law and of legal argument. Jurisprudential inquiry is properly grounded not in reflections on conceptual properties of law but in reflections on human goods and needs as understood in a morally articulated theory of practical reason and compactly expressed in the normative concept of the common good. Such reflections confirm that law exists, in its central case, as a means to various types of authoritative co-ordination solutions. The underdetermined nature of (a) the positive requirements of practical reasonableness and the common good and of (b) the appropriate means of enforcing compliance and remedying non-compliance with either these requirements or the determinate negative precepts of practical reasonableness entails that a practically necessary aspect of the positive law’s role is constituting the requirements of justice, i.e. of what is due to whom generally and in particular situations (including situations where an injustice has been or is alleged to have been done). As a distinct and practically necessary mode of legal co-ordination for the common good, adjudication, in its central case, answers litigated questions of justice by applying all relevant law in accordance with the legal system’s practice of legal argument. Thus adjudication is performed by authoritative law-applying institutions precisely because it is about answering questions of justice, and not despite that fact. Theories of law developed on the assumption that it is possible to understand the ‘what’ of law without reliance on any moral judgments deny any practically necessary connection between (a) the promotion of justice and the common good and (b) the nature of law, in its central case, and, hence, the adjudicative application of the law. In the absence of this connection a judicial duty to do justice according to law is unintelligible.
Confronting the juggernaut of extraction: local, national and transnational mobilisation against the Phulbari coal mine in Bangladesh
Keywords: mining
protests
displacement
environment
national interest

A massive open-cast coal mine was proposed for Phulbari in 1994, with the support of the government and international financial organisations. Threatened by displacement, the apparently powerless community mobilised against the mine. Allied with the national and the transnational activist organisations, they successfully stopped the mine. This remarkable success is the subject of the thesis.
This resistance is compared quantitatively with the incidence of protests in 397 other mines in the South Asia. Predictors of protest include density of population, proportion of area under forest cover, and ownership by a multinational company. These factors alone would predict a high probability of protest in Phulbari. To understand how the resistance unfolded and why it was successful, the thesis relies on ethnographic evidence. I conducted participant observation and interviewed sixty-four individuals in Phulbari and Dhaka in Bangladesh and in London.
Mobilisation against the mine can be explained in part by dialogic framing. Local challengers continuously opposed the dominant discourse of development. Crucially, they shifted their identity to legitimize their opposition to the mine by tagging it with nationalism. As a result, local resistance established links with national left-wing activists. Mobilisation culminated in a mass march of 70,000 in 2006, which was fired on by government forces, with several casualties. Repression failed to quail the resistance. Continued mobilisation was motivated by emotional responses like anger, and facilitated by cultural practices like the obligatory funeral procession.
Media reports of the repression catapulted the resistance on to the global stage. This alone is not sufficient to explain the formation of a transnational alliance against the mine. This was maintained by the presence of a large community of Bangladeshi living in Britain, and the mediating role of the left-wing activists in Bangladesh; both groups could translate between locals and western NGOs. This transnational coalition impeded the mining company by targeting international financial organisations, Western governments, the government of Bangladesh, and investors in London. As a result, the company’s share price has collapsed and there seems little prospect of the project proceeding.
Signal compatibility as a modulatory factor for audiovisual multisensory integration
Keywords: crossmodal correspondences
audition
vision
Multisensory integration
psychophysics

The physical properties of the distal stimuli activating our senses are often correlated in nature; it would therefore be advantageous to exploit such correlations to better process sensory information. Stimulus correlations can be contingent and readily available to the senses (like the temporal correlation between mouth movements and vocal sounds in speech), or can be the results of the statistical co-occurrence of certain stimulus properties that can be learnt over time (like the relation between the frequency of acoustic resonance and the size of the resonator). Over the last century, a large body of research on multisensory processing has demonstrated the existence of compatibility effects between individual features of stimuli from different sensory modalities. Such compatibility effects, termed crossmodal correspondences, possibly reflect the internalization of the natural correlation between stimulus properties.
The present dissertation assesses the effects of crossmodal correspondences on multisensory processing and reports a series of experiments demonstrating that crossmodal correspondences influence the processing rate of sensory information, distort perceptual experiences and lead to stronger multisensory integration. Moreover, a final experiment investigating the effects of contingent signals’ correlation on multisensory processing demonstrates the key role of temporal correlation in inferring whether two signals have a common physical cause or not (i.e., the correspondence problem). A Bayesian framework is proposed to interpret the present results whereby stimulus correlations, represented on the prior distribution of expected crossmodal co-occurrence, operate as cues to solve the correspondence problem.
Probabilistic bias in genotype-phenotype maps
Keywords: biological evolution
Probability
RNA
information theory

Among the most fundamental features shared by all organisms is the mapping of information encoded in genotypes (genetic material) to generate phenotypes (biological structures, functions, and traits). Hence, elucidating the structure of genotype-phenotype (GP) maps is important for understanding evolution and biology.
While it is known that often GP maps are highly degenerate with many different genotypes adopting the same phenotype, the distribution of genotypes over phenotypes is less well studied. In this thesis we investigate the question of the distribution of genotypes over phenotypes, or put differently the distribution of neutral set sizes (NSS), where a neutral set is the collection of all genotypes in a GP map which map to the same phenotype. We focus on examining phenotypic bias in GP maps, where some phenotypes have disproportionally large NSS as compared to others. We find phenotypic bias to be ubiquitous in the broad range of GP maps that we analyse, from the genetic code up to molecular RNA to a model of neuronal connections, and hence we hypothesise bias to be a common property of GP maps. Further, we also consider the implications that this bias has for evolutionary outcomes, and we argue that bias is a significant influencing factor in determining evolutionary outcomes.
Finally, we propose a method to predict a phenotype's NSS via estimating the phenotype's structural complexity, without using detailed knowledge about the specifics of the relevant GP map. We achieve this via a novel application of algorithmic information theory and especially Levin's coding theorem.
Conspicuous silences: implicature and fictionality in the Victorian novel
Keywords: implicature
Victorian literature
stylistics
pragmatics
fictionality
the novel

This dissertation examines the central use of implicature within the Victorian novel. 'Implicature' denotes a communicative strategy in which a reader must infer the primary meaning of an utterance from that utterance's relationship to its context, rather than 'decode' explicitly presented information. While all communications rely on implicature to an extent, the novels examined in this thesis contain large gaps in their explicit narration and rely primarily on implicature to communicate central elements of their plots. If readers do not recognise these texts' implicatures, the texts will often appear incoherent: their implicatures must be acknowledged in order for the text to be understood. Because little has been said about the central role implicature can play in fictional narration, this thesis contributes to interpretations of these novels that are currently being discussed in Victorian literary scholarship, as well as literary pragmatic debates about the use of implicature within fictional texts.
The dissertation's secondary aim is to examine the implicatures which may be generated by the author's exploitation of certain reader assumptions. It focuses on the reader's potential assumption of narratorial omniscience, and relates it to the reader assumption of the narrative's fictionality. This secondary emphasis contributes to literary pragmatic conceptions of fictionality, and contributes to narratological discussions of narratorial omniscience.
Chapter One examines represented illegitimate pregnancies in Victorian novels, and illustrates implicature's use as a politeness strategy. It explains how this use of implicature is called for by the novels' fictional and Victorian contexts. Chapter Two discusses implicatures which communicate characters' semiconscious romantic desires, and relates these representations to Victorian discourses on the unconscious and narratological scholarship on consciousness representation. Chapter Three discusses the central use of implicature in sensation fiction to create narrative 'puzzles', and connects the ensuing playful, sometimes offensive tone to these implicatures' satire of the realist mode.
Development and application of nickel stable isotopes as a new geochemical tracer
Keywords: stable isotopes
method development
geochemical applications
nickel

In this thesis, I have developed a new methodology for the accurate determination of mass-dependent variations in nickel (Ni) isotope compositions. Nickel is initially separated in a three-column ion-exchange procedure, and the purified solutions are analysed by multi-collector inductively coupled plasma mass spectrometry (MCICPMS) using a double-spike technique. Using this methodology, I have measured the first Ni isotope ratios for a wide variety of natural geological samples. Significant Ni isotope variations were observed, with an overall spread in delta 60Ni-values of -0.9 to 2.5 permil. In igneous rocks Ni isotopes appear to be largely homogeneous, with only small variations (0.2 permil) between different rock types. Weathering of silicate rocks does on the other hand appear to cause significant fractionation of Ni isotopes, probably producing an isotopically heavy riverine input to the ocean. A heavy isotope signature is also visible in hydrogenetic ferromanganese crusts, with surface scrapings from globally distributed crusts show an average delta 60Ni-value of 1.65 permil. However, the variation in these samples is over 1.5 permil, likely reflecting local sources or biological processes, or alternatively indicating a heterogeneous Ni isotopic composition of the ocean. Organic-rich sediments also show heavy isotopic compositions, which are possibly transferred to the crude oils originating in these types of sediments. The only significant reservoir of light Ni isotopes found during this project are sulphides from magmatic systems. Overall, this thesis demonstrates the potential of this system as a powerful new tracer for a variety of geochemical processes.
Multimode absorption spectroscopy of CO and CO2 gas mixtures
Keywords: spectroscopy
gas sensing
exhaust gas

The development of multimode absorption spectroscopy (MUMAS) for multi-species detec- tion and its potential for process control or environmental monitoring is reported. The simultaneous detection of CO and CO2 is demonstrated in a proof-of-principle experiment for applications in industrially relevant gas species monitoring. The technique of MUMAS is extended to the near infrared in order to detect these and other industrially relevant species.
A laser was designed and constructed to emit a multimode spectrum in the region of 1.57um to take advantage of the spectral overlap of the second vibrational overtone of CO and the combination band 3ν1 + ν3 of CO2. The laser consisted of a semi-confocal cavity employing an Er:Yb glass chip as the gain medium. The laser was pumped by a 1W laser diode at 980nm and emitted up to 30mW in a bandwidth of 180GHz. The laser emitted between 6-10 modes depending upon the selective cavity length. Mode spacings varied between 18GHz to 33GHz with an individual mode linewidth of less than 8MHz. The laser modes were simultaneously scanned using a piezo-electric transducer (PZT) in order to modulate the cavity length at frequencies between 1Hz and 10Hz.
A system for linearizing the MUMAS spectra with respect to frequency was devised based on a transmission spectra of a confocal Fabry-Perot etalon. Refinements to the MUMAS fitting code were developed to improve the computational efficiency. An initial demonstration of MUMAS on a known gas mixture of CO and CO2 was per- formed. The ratio of CO:CO2 concentrations in the gas mixture was measured with an accuracy of 0.4% which was within the supplier’s quoted uncertainty.
MUMAS is then applied to the detection of CO and CO2 concentrations in exhaust gas produced by a 1.3 litre 4-cylinder turbo-charged spark ignition engine. Relative and absolute concentrations were derived from MUMAS signals and values compared to measurements using a 4-gas analyser. Concentrations of CO and CO2 were measured using MUMAS to a precision of 0.17% and 0.23% respectively compared to less than 0.1% for the 4-gas analyser. Ratios of CO and CO2 were determined with a precision of 0.28 using MUMAS compared to 0.11 with the 4-gas analyser. The detection limit of CO was found to be 1486ppm in these circumstances.
Finally a discussion is presented of potential improvements arising from wavelength mod- ulation spectroscopy and cavity enhancement techniques.