VictorJuiz/thesis huggingface dataset:
The importance of electron transfer in determining properties of [NiFe]-hydrogenases

[NiFe] hydrogenases are microbial metalloenzymes that catalyse the reversible interconversion between molecular hydrogen and protons with high selectivity and efficiency. The catalytic properties of different [NiFe] hydrogenases vary according to the physiological roles they each play, yet all seem to be based upon an almost identical catalytic site architecture. Through efforts to understand the structural and mechanistic basis for the differing properties of [NiFe] hydrogenases, it has become increasingly evident that electron transfer to and from the active site, mediated by a set of Iron-Sulphur clusters, influences to a significant extent the observed catalytic properties of different hydrogenases. Here we present a comprehensive study of E. coli Hyd-1, an O2-tolerant hydrogenase, by PFE with a focus on the properties that are characteristic of O2-tolerant enzymes: overpotential requirement, lack of H2 production, low KH2M, and high Eswitch.
We show that Hyd-1 catalysis can be made reversible by increasing the equilibrium potential for the reaction through changes in substrate concentration, and that electron transfer into and out of the enzyme molecule, rather than active site properties, is responsible for the characteristics of overpotential and bias in Hyd-1. We present a set of experiments with Hyd-2 from E. coli in which surface-exposed cysteine residues are specifically introduced near the distal and medial Iron-Sulphur clusters to act as points of attachment for photosensitizer molecules, and a study of the kinetics of electron injection from photoexcited molecules to the enzyme and subsequent absorbance changes attributed to transient redox changes at the active site. We are able to show lightdependent H2 production from a Hyd-2 + photosensitizer system. Finally, we present the first purification of the formate-hydrogen lyase (FHL) complex from E. coli, the complex responsible for H2-production by this organism during fermentation, and we provide a characterisation of the complex by EPR and PFE. The properties of Hyd-3, the hydrogenase subunit of the FHL, seem to differ from those observed previously for other [NiFe] hydrogenases.

Keywords: enzyme chemistry
protein film electrochemistry
enzyme catalysis
Advisor: Armstrong, F
Assessing the risk and consequence of engineered nano-scale zinc oxide in phytological and bacterial systems

With the increased usage and production of engineered nanoparticles (ENPs), entry into the environment and hence contact with plant root systems is inevitable. Nano zinc oxide (nZnO) is widely used in commercial products, such as sunscreens, paints and coatings due to its high antimicrobial properties and wide electrical band-gap. Disposal down drains and into greywater leads to particle entry into the environment via waste water systems. Here, ENPs could potentially interact with plant root systems, which may lead to uptake, translocation and accumulation within plant tissues, and in the case of edible crops have consequences on human health. This study aimed to identify mechanisms of toxicity by employing whole-cell biosensors in conjunction with model bacteria and plant species. Furthermore, zeta potential (ZP), particle size, reactive oxygen species (ROS) release and solubility of the particles were determined and linked to both plant and bacterial toxicity. In Escherichia coli bacteria, it was demonstrated that growth inhibition from nano-scale ZnO treatment was similar to that from the bulk-scale ZnO and ionic zinc treatments, with the concentrations leading to 50 % inhibition (IC50) demonstrated to be 251, 282 and 298 mg/L for bulk, nano-scale and ZnSO4, respectively. It was demonstrated that the mode of nZnO toxicity in E. coli was bacteriostatic rather than bacteriotoxic. In barley plants, biomass was negatively impacted by up to 50 %, and significantly more zinc was able to enter root tissues as a result of hydroponic nZnO treatment, with 47 mg/L zinc detected in root tissues after 7 days treatment with 500 mg/L nZnO. Comparison of particle characteristics revealed that ROS, solubility, ZP, size and concentration were involved in toxicity, with ZP (charge) identified as a key parameter in both plant and bacterial toxicity.

Keywords: biosensors
plants
microbiology
nanotechnology
environment
crops
ZnO
bacteria
Advisor: Thompson, I
Smith, A
The role of hypoxia-inducible factor in systemic human physiology

This thesis summarizes a research programme on the role of hypoxia-inducible factor (HIF) and its 2alpha subunit in systemic human physiology. Experiments were performed to assess the role of HIF in the regulation of skeletal muscle metabolism, cardiac anatomy, function and energy metabolism, and in cardiopulmonary physiology. Patients with different genetic mutations affecting the HIF pathway were recruited for each main study.
Chapter 1 presents an overview of human physiological responses to hypoxia in a historical perspective, with particular attention to the areas of human physiology that are relevant for the studies presented in the experimental chapters. Chapter 1 also presents a summary of the HIF pathway and the novel findings presented in this thesis.
Chapter 2 illustrates the methods used to perform the experiments.
Chapter 3 investigates skeletal muscle metabolism, cardiac anatomy, function and energy metabolism in patients with Chuvash polycythaemia, who have mildly elevated levels of HIF, associated with a mutation in von Hippel-Lindau gene, at whole body level. Chapter 3 shows major abnormalities associated with HIF pathway alterations in skeletal muscle energy metabolism, especially in conditions of metabolic stress such as during exercise and digestion of a meal.
Chapter 4 shows that patients with Chuvash polycythaemia also have small hearts and reduced cardiac energy levels.
Chapter 5 explores cardiopulmonary abnormalities in patients with gain-of-function mutations specifically in HIF-2alpha subunit; these patients are polycythaemic like patients with Chuvash polycythaemia. Observed abnormalities include pulmonary hypertension, elevated heart rate, cardiac output, ventilation, and the increment in pulmonary blood pressure in response to moderate hypoxia.
Chapter 6 presents results from experiments in patients with classic von Hippel- Lindau disease, who are not usually polycythaemic. However, some degree of haploinsufficiency was observed in their neutrophils, suggesting a pseudo-hypoxic phenotype. Chapter 6 shows that von Hippel-Lindau disease is not associated with major cardiopulmonary abnormalities.
Overall, the research reported in this thesis presents original experimental evidence for the effects of alterations in the HIF pathway on human physiology.

Keywords: physiology human hypoxia
Advisor: Robbins, PA
Dorrington, KL
James Joyce and the rhetoric of translation

This thesis examines theories of translation which are explicit in the themes and implicit in the rhetorical uses of form in the work of Joyce, with a focus on the French translations of Ulysses and Finnegans Wake produced with his collaboration between 1921 and 1931. Philosophies of translation from Jerome through Benjamin plus work in translation theory by Even-Zohar and Toury inform this study of the ethics both of translating and of being translated in the modernist idiom. In identifying a translation ethic arising out of the modernist aesthetic, the thesis postulates a rhetoric of translation by analogy with Booth's The Rhetoric of Fiction. To this end, key issues in translation studies are addressed: the critical status of the authorized collaborative translation; accounting in translation for persuasive (versus purely expressive) functions of literary works as text types; translation strategy as a contribution to the debate between essentialism or universal grammar and cultural relativism; the translation imagined as a frame narrative, and the translator as an implied frame narrator of varying invisibility and reliability; and translation as a model of cognitive processes such as reading, understanding, memory, and the growth of consciousness. Via a combination of descriptive, historical, and textual study, this set of topics in translation is shown to explain many thematic and technical preoccupations of Joyce - just as Joyce proves to be an ideal case for descriptive translation studies, not in spite but by virtue of his notional untranslatability. The thesis also seeks to contribute to Joyce studies proper: to an understanding of how Joyce's fiction both does and does not depart from conventions of western narrative; to a portrait of the implied author and undramatized narrator in Ulysses; to an appreciation of translation both broadly and narrowly defined as a recurrent theme in his work; and to a recognition of the influence of Joyce's many contemporary translators and their languages, cultures, and personalities upon his own innovating uses of language and narrative.

Advisor: Paulin, T
Evolutionary debunking arguments in ethics

I consider whether evolutionary explanations can debunk our moral beliefs. Most contemporary discussion in this area is centred on the question of whether debunking implications follow from our ability to explain elements of human morality in terms of natural selection, given that there has been no selection for true moral beliefs. By considering the most prominent arguments in the literature today, I offer reasons to think that debunking arguments of this kind fail. However, I argue that a successful evolutionary debunking argument can be constructed by appeal to the suggestion that our moral outlook reflects arbitrary contingencies of our phylogeny, much as the horizontal orientation of the whale’s tail reflects its descent from terrestrial quadrupeds.
An introductory chapter unpacks the question of whether evolutionary explanations can debunk our moral beliefs, offers a brief historical guide to the philosophical discussion surrounding it, and explains what I mean to contribute to this discussion. Thereafter follow six chapters and a conclusion. The six chapters are divided into three pairs. The first two chapters consider what contemporary scientific evidence can tell us about the evolutionary origins of morality and, in particular, to what extent the evidence speaks in favour of the claims on which debunking arguments rely. The next two chapters offer a critique of popular debunking arguments that are centred on the irrelevance of moral facts in natural selection explanations. The final chapters develop a novel argument for the claim that evolutionary explanations can undermine our moral beliefs insofar as they show that our moral outlook reflects arbitrary contingencies of our phylogeny. A conclusion summarizes my argument and sets out the key questions that arise in its wake.

Keywords: Meta-ethics; evolution; epistemology; moral epistemology;
Advisor: Bykvist, K
Hawthorne, J
Energy transport in open quantum systems

This thesis is concerned with modelling the dynamics of open quantum systems in several different contexts. Of principal interest is the manner in which the environment can modify, or even dominate, a system’s quantum behaviour in order to facilitate the transport of energetic excitations.
In the first research chapter, a time-local, non-Markovian quantum master equation is derived in a variationally defined reference frame, for networks of two-level systems coupled to bosonic environments. The predictions of this master equation are then compared with those derived using both weak-coupling and polaron approximations. The variational master equation is found to agree with these standard approaches in their regimes of validity, whilst interpolating between them in intermediate parameter regimes.
The second research chapter focusses on the dynamics of a superconducting double quantum dot embedded in a resonant circuit. The device is considered in a regime where the ground state consists of a coherent spatial superposition of a single Cooper pair, which can be excited by a variety of interactions with the environment. The relevant transition rates are calculated and the processes responsible are identified. A numerical simulation of the system is then used to explain experimental data, and show that for certain parameters a significant fraction of excitations occur via absorption of photons from the environment.
The final chapter considers a model for an olfactory receptor, in which odorant molecules are recognised by their vibrational modes. Electron transfer occurs in the receptor, dependent on the presence of a vibrational mode of the right frequency. A quantum master equation for the system is derived, and the resulting dynamics is compared to earlier semi-classical treatments. The behaviour of the receptor is found to be sensitive not only to the frequency of the vibrational mode, but also to the character of the surrounding environment. Increased dissipation on the odorant mode, as well as the presence of higher frequencies in the environment is found to improve the frequency resolution of the receptor.

Keywords: Open quantum systems
quantum biology
Advisor: Vedral, V
The revolution's echoes : music and political culture in Conakry, Guinea

This thesis is an ethnographic study of music and authoritarianism in Conakry, Guinea. Representations in the scholarly and popular literature often emphasize African music as a site for resistance and oppositional politics, while musicians who support the state are seen as tools of propaganda. In this thesis, I examine instead the choices and subjectivities of musicians who sing for an authoritarian state. As I show, musicians in Conakry, across genres and generations, rarely express dissent and overwhelmingly adopt cautious and conservative positions towards the state. I describe these stances as operating within a politics of silence that has emerged over the past half-century of authoritarian rule in Guinea, deriving from norms of ambiguity and secrecy in Mande culture. I begin in Chapter One by considering the foundational moment of the Guinean Cultural Revolution to examine how music became intertwined with a political culture of control under the regime of Guinea’s first president Sékou Touré. In Chapters Two, Three and Four I then investigate the legacy of the Revolution in shaping musical practice in Conakry today. My analysis is based on ethnographic research conducted in 2009, following a military coup d’état. I use the particular circumstances of the post-coup moment in 2009 as a lens through which to understand the ongoing legacy of authoritarianism on Conakry’s musical and political landscape. I consider the afterlife of musical nationalism as musicians from the Revolution seek to find a place in the post-nationalist state; anxieties about praise-singing and music professionalization that have sharpened since the Revolution’s end; and the politics of youth music as young people negotiate between ideals of protest and the quiet accommodation of power. As I argue, silence is a form of agency for musicians in Conakry as they attempt to negotiate the complexities of life in an authoritarian state.

Keywords: Ethnomusicology
politics
West Africa
Advisor: Stokes, M
Towards a trusted grid architecture

The malicious host problem is challenging in distributed systems such as grids and clouds. Rival organisations may share the same physical infrastructure. Administrators might deliberately or accidentally compromise users' data.
The thesis concerns the development of a security architecture that allows users to place a high degree of trust in remote systems to process their data securely. The problem is tackled through a new security layer that ensures users' data can only be accessed within a trusted execution environment. Access to encrypted programs and data is authorised by a key management service using trusted computing attestation. Strong data integrity and confidentiality protection on remote hosts is provided by the job security manager virtual machine.
The trusted grid architecture supports the enforcement of digital rights management controls. Subgrids allow users to define a strong trusted boundary for delegated grid jobs. Recipient keys enforce a trusted return path for job results to help users create secure grid workflows. Mandatory access controls allow stakeholders to mandate the software that is available to grid users.
A key goal of the new architecture is backwards compatibility with existing grid infrastructure and data. This is achieved using a novel virtualisation architecture where the security layer is pushed down to the remote host, so it does not need to be pre-installed by the service provider. A new attestation scheme, called origin attestation, supports the execution of unmodified, legacy grid jobs. These features will ease the transition to a trusted grid and help make it practical for deployment on a global scale.

Keywords: virtualization
virtualisation
cloud
grid
trusted computing
security
Advisor: Martin, A
Interaction of oxygen and nitrogen impurities with dislocations in silicon single-crystals

An experimental technique based on the immobilisation of dislocations by segregation of impurity atoms to the dislocation core (dislocation locking) has been developed and used to investigate the critical conditions for slip occurrence in Czochralski-grown and nitrogen-doped floating-zone-grown silicon crystals.
The accumulation of nitrogen and oxygen impurities along a dislocation and the resulting dislocation locking effect has been investigated in silicon samples subjected to different annealing conditions. In particular, the stress needed to unlock the dislocations after their decoration by impurities has been measured as a function of annealing duration and temperature.
The approach used in this study has allowed the determination of new diffusivity data for oxygen and nitrogen in silicon in the technologically important range of temperatures 350-850°C. No other data covering such wide temperature range are available in the literature.
In addition to transport properties, the binding energy of an impurity atom to a dislocation in silicon has been deduced from the experimental data in the case of oxygen and nitrogen impurities. A discussion in terms of the impurity species responsible for transport (monomers or dimers) and dislocation locking is also presented.
The role of oxide precipitates in the generation of glide dislocation loops and the parameters affecting the occurrence of slip have been investigated in silicon samples containing precipitates of different sizes and different morphologies.
The fundamental parameters deduced in this work have been used to develop a numerical model to investigate the effect of different heat treatments on the mechanical properties of silicon wafers containing a controlled distribution of impurities. This model has then been used to simulate real wafer processing conditions during device fabrication to show how they may be modified to increase dislocation locking. It is hoped that these results will have relevance to how wafers are processed in order to minimise or eliminate dislocation multiplication and consequent warpage.

Keywords: nitrogen
silicon
precipitation
oxygen
dislocation
diffusivity
Advisor: Wilshaw, P
Achieving a mass-scale transition to clean cooking in India to improve public health

This research provides policy-relevant insights into how a mass-scale, equitable transition to the use of Advanced Biomass (cook) Stoves (ABSs) can be achieved in India, with the aim of improving public health, especially for women and children. The research uses socio-technical systems to provide a characterisation of transition processes, and governance to explain issues of power influencing transition. A review of previous government cook-stove programmes in India and China highlights governance shortcomings in the former, in particular a lack of functional links between layers of administration and poor engagement with community institutions and cooks. Primary data from West Bengal and Karnataka highlighted sophisticated, skilful, flexible and culturally context specific cooking practices. Reasons for apparent low demand for improved stoves, characterised as lock-in, are found to include a combination of risk aversion and habits, lack of affordability, low awareness of the health consequences, as well as a mis-match between the normative priorities of policy makers – currently health- and those of cooks. It is found that the majority of polluting emissions within households - as well as greenhouse gases - from cooking derive from poorer households. A sectoral carbon offset strategy is proposed as a means of funding subsidies for ABSs and programme support measures. Several large corporations have invested significant sums in technology development, community outreach and dissemination, resulting in sales of over 600,000 ABSs. Reasons for their involvement appear mixed. Their market-based activities have generally not reached poor households and there are questions about their ability to build viable businesses in this highly dispersed and heterogeneous sector. A fundamental dichotomy is highlighted between large, centralised cooking programmes and the diverse, complex and changing reality of cooking activities, beliefs and behaviours on the ground. The research concludes that functional multi-level and multi-actor governance structures would be required to achieve a mass-scale transition to clean cooking using ABSs, with a lead role for the public sector. A key component of future success will involve building structures that ensure the agency of cooks and account for their socio-cultural cooking practices in the processes of technology and programme design and implementation.

Keywords: socio-technical system
stove
India
equity
poverty
cooking
women
governance
children
climate change
health
Advisor: Boardman, B
Liverman, D
The efficacy and safety of aspirin in individuals with and without diabetes:  A collaborative meta-analysis of individual participant data from randomised trials

Background: Whether aspirin is of net clinical benefit for the primary prevention of vascular events in those at high risk, such as some people with diabetes, is uncertain.
Methods: Individual participant data from 26 randomised trials (123,361 individuals, 760,000 person-years) assessing aspirin versus control in people with and without diabetes were included. Major outcomes included serious vascular events (SVE: myocardial infarction, stroke or vascular death) and major extracranial bleeding (MEB).
Findings: In the primary prevention setting, aspirin reduced SVE (0.65% vs 0.71% per year; relative risk (RR) 0.90 [95% confidence interval (CI) 0.85-0.96]; p=0.0006) and increased MEB (0.10% vs 0.07% per year; RR 1.52 [95% CI 1.30-1.78]; p<0.0001). These proportional effects were similar in people with and without diabetes (χ21=0.74, p=0.39 and χ21=1.00, p=0.32 respectively). Estimated absolute effects of aspirin according to diabetes status and vascular risk suggested that some people, particularly those with diabetes and 5-year risk >5%, may derive net clinical benefit in the primary prevention setting. At a 5-year risk level of 5-10%, for example, people without diabetes might have a 1.6% (95% CI 1.1-2.1) reduction in 5-year SVE balanced against a 0.5% (95% CI 0.3-0.8) increase in 5-year MEB. In comparison, people with diabetes and 5-year risk of 5-10% might have a 1.7% (95% CI 1.2-2.2) reduction in 5-year SVE balanced against a 0.3% (95% CI 0.1-0.4) increase in 5-year MEB. Even if an approximate halving of baseline vascular risk by modern preventative measures such as statins is factored in before aspirin therapy is considered, aspirin may still have a worthwhile net clinical benefit in such people at least at moderate vascular risk.
Interpretation: Some people without previous disease but at higher vascular risk, such as people with diabetes and 5-year risk >5%, may derive net clinical benefit from aspirin. Further direct randomised evidence in these individuals will help clarify the balance of risks and benefits.

Keywords: aspirin
Cardiovascular disease
diabetes
randomised trials
Advisor: Baigent, C
Emberson, J