VictorJuiz/thesis huggingface dataset:
Cadmium isotope fractionation in seawater: driving mechanisms and palaeoceanographic applications

The global marine distributions of Cd and phosphate are closely correlated, which has led to Cd being considered as a marine micronutrient. Recent developments in Cd stable isotope mass spectrometry have revealed that Cd uptake by phytoplankton causes isotopic fractionation in the open ocean and in culture. The explanation for this nutrient-like behaviour is unknown as there is only one identified biochemical function for Cd, an unusual Cd/Zn carbonic anhydrase (CdCA1). This thesis investigates why Cd appears to act as an algal nutrient by performing subcellular analyses of microorganisms genetically-modified to express the CdCA1 gene. It was found that CdCA1 was not a significant contributor to whole-cell Cd isotope compositions. Instead, a large proportion of the internalized Cd is sequestered into cell membranes with a similar direction and magnitude of Cd isotopic fractionation as seen in surface seawater. This observation is explained if Cd is mistakenly imported with other divalent metals and subsequently managed by binding within the cell to avoid toxicity. This result implies that surface seawater Cd isotope compositions, if captured by an appropriate archive, may be invaluable for reconstructions of past marine productivity. The role of environmental factors in modulating the inorganic partitioning of Cd isotopes into calcite was investigated through a series of laboratory analogue experiments. In seawater, the light isotopes of Cd are always preferred in calcite. The magnitude of fractionation showed no response to temperature, ambient [Mg], or precipitation rate. To further identify suitable palaeaoceanographic archives, the Cd isotopic composition of a suite of modern deep-sea corals were investigated. It was found that the Cd/Ca and Cd isotope composition of coralline calcium carbonate followed the predicted trend for closed-system Rayleigh fractionation in the calcifying space. The lack of isotopic offsets between some corals and seawater will simplify the application of Cd isotopes in deep-sea corals -- and potentially other marine calcifying organisms that vacuolize seawater prior to calcium carbonate precipitation -- to palaeoceanography.

Keywords: Cadmium Isotope
Isotope Fractionation
Cadmium
Seawater
Trace Metal
Advisor: Henderson, G
Rickaby, R
Semi-synthesis and biological evaluations of tunicamycin lipid analogues and investigation of the tunicamycin biosynthetic pathway

Tunicamycins are potent antimicrobial agents but are also toxic to mammalian cells, which render them clinically impractical to use to treat infectious diseases. Instead, they have been used extensively as biochemical tools to study the N-linked glycosylation of proteins. However, despite such a routine application, their inhibitory mechanisms are still not clear. The central objective of this thesis was to develop novel tunicamycin analogues that are non-toxic to eukaryotic cells that could serve as potential antimicrobial drug candidates. We hypothesised that if we retain the lipid character of tunicamycin structure and modify the GlcNAc moiety then the antimicrobial activity would be retained but the tunicamycins inhibitory action towards GPT would be abolished, thus diminishing tunicamycins cytotoxicity towards mammalian cells.
I - Semi-synthesis of the Tunicamycin Core Scaffolds and Lipid Analogues
Semi-synthetic strategies were devised for isolating tunicamycin core scaffolds and for the selective addition of lipid chains at the 10'-N and 2"-N positions of tunicamycin, yielding the first library of novel tunicamycin lipid analogues.
II - Biological Evaluations of the Tunicamycin Core Scaffolds and Lipid Analogues
For the first time, the antibacterial activity of tunicamycins was shown to be dependent on the presence of a lipid chain. The tunicamycin core scaffolds were shown to lack antibacterial activity and cytotoxicity. More importantly, the library of tunicamycin lipid analogues with lipid chain length from seven to twelve carbons showed titrated antibacterial activity profile. Furthermore, the tunicamycin lipid analogues were not only found to have potent antibacterial and anti-M. tuberculosis activities but were non-cytotoxic compared to tunicamycins. The relative therapeutic index calculated for the tunicamycin lipid analogues was up to several thousand folds more than tunicamycins.
III - Investigation of the tunB and tunF Knockout in the tun Gene Cluster
The tunB and tunF single knockout mutations were made in the tun gene cluster by PCR-targeting and then heterologously expressed in S. coelicolor. The tunB knockout successfully abolished tunicamycin biosynthesis and showed evidence by MS the first existence of exo-glycal intermediates in sugar biology, further supporting the discovery of TunA as a novel NDP-sugar 5,6-dehydrogenase.
IV - Investigation of the TunD and TunE Enzymatic Activities in Tunicamycin Biosynthetic Pathway
The recapitulation of TunD glycosyltransferase and TunE deacetylase activities in vitro were attempted. Recombinant TunD was refolded from insoluble TunD inclusion bodies, while TunE was isolated in small quantities. However, no TunD and TunE activities were found using proposed intermediates. The co-translation of the tun gene cluster and the formation of multi-protein complex are proposed to be involved in the tunicamycin biosynthesis.

Keywords: Streptomyces
biosynthesis
antimicrobial
antibiotic
natural product
Tunicamycin
Advisor: Davis, B
Tuning the dimensionality and interactions in transition metal oxides: a μSR study

This thesis is concerned with how the physical properties of transition metal oxides change due to chemical substitution or intercalation. Experiments using the muon-spin relaxation and rotation (μSR) techniques were carried out at the ISIS Facility (UK) and the Paul Scherrer Institute (CH). In conjunction with the μSR results, the results of heat capacity and magnetic susceptibility experiments are used to provide complementary information on the same samples. Investigations of the properties of the layered triangular lattice magnets NaNiO2 and LiNiO2 are presented. For NaNiO2, all three experimental techniques are used to provide a full survey of the thermodynamic and magnetic properties of this compound. For LiNiO2, μSR studies of notionally stoichiometric and Mg-doped samples were carried out. These showed that Mg doping causes a significant change in the magnetic dynamics of the material, but neither sample exhibits long-range magnetic order. The magnetic ordering of the extensively studied perovskite compounds LaTiO3 and YTiO3 is investigated using μSR. The results were in agreement with previous neutron diffraction studies of the two compounds, but clarified the orientation of the magnetic moments in LaTiO3. It was also possible to make a detailed comparison between the μSR results and those of dipole field calculations of the magnetic field at possible muon stopping sites, allowing these to be deduced and compared with results in other well characterized transition metal oxides. The two titanium chain compounds NaTiSi2O6 and TiOCl exhibit spin gap formation at unusually high temperatures due to unconventional dimerization mechanisms. A model allowing the comparison of X-ray diffraction data, dimerization, and the magnitude of the spin gap is proposed. This is tested against both magnetic susceptibility and μSR data for both compounds. For NaTiSi2O6 both experimental techniques are in reasonable agreement, whereas in TiOCl the results are conclusively different. The origin of this disparity in TiOCl is explored. The intercalation of organic chain molecules into Bi based high-temperature superconductors has previously been demonstrated to extend the interlayer spacing by a factor of up to three without changing the superconducting transition temperature. μSR is used to investigate the London penetration depth, as a function of interlayer spacing, of two series of such samples. The results show a simple trend corresponding to a constant density of superconducting electron pairs in each layer. The consequences of this result are discussed in the context of previously identified scaling relations between superconducting parameters. Results of experiments excluding the possibility of magnetic order and muon-organic radical formation in these samples are presented, as well a preliminary study of the field distributions in a mosaic of intercalated crystallites.

Keywords: muon spin rotation
superconductivity
transition metal oxide
magnetism
Advisor: Blundell, S
Hybrid tractability of constraint satisfaction problems with global constraints

A wide range of problems can be modelled as constraint satisfaction problems (CSPs), that is, a set of constraints that must be satisfied simultaneously. Constraints can either be represented extensionally, by explicitly listing allowed combinations of values, or intensionally, whether by an equation, propositional logic formula, or other means. Intensionally represented constraints, known as global constraints, are a powerful modelling technique, and many modern CSP solvers provide them. We give examples to show how problems that deal with product configuration can be modelled with such constraints, and how this approach relates to other modelling formalisms.
The complexity of CSPs with extensionally represented constraints is well understood, and there are several known techniques that can be used to identify tractable classes of such problems. For CSPs with global constraints, however, many of these techniques fail, and far fewer tractable classes are known. In order to remedy this state of affairs, we undertake a systematic review of research into the tractability of CSPs. In particular, we look at CSPs with extensionally represented constraints in order to understand why many of the techniques that give tractable classes for this case fail for CSPs with global constraints. The above investigation leads to two discoveries.
First, many restrictions on how the constraints of a CSP interact implicitly rely on a property of extensionally represented constraints to guarantee tractability. We identify this property as being a bound on the number of solutions in key parts of the instance, and find classes of global constraints that also possess this property. For such classes, we show that many known tractability results apply. Furthermore, global constraints allow us to treat entire CSP instances as constraints. We combine this observation with the above result, and obtain new tractable classes of CSPs by dividing a CSP into smaller CSPs drawn from known tractable classes.
Second, for CSPs that simply do not possess the above property, we look at how the constraints of an instance overlap, and how assignments to the overlapping parts extend to the rest of the problem. We show that assignments that extend in the same way can be identified. Combined with a new structural restriction, this observation leads to a second set of tractable classes.
We conclude with a summary, as well as some observations about potential for future work in this area.

Keywords: constraint programming
global constraints
configuration
complexity
tractability
hypergraph
Advisor: Jeavons, P
Gottlob, G
The problems and possibilities for interns of gaining access to experienced teachers' craft knowledge

This thesis is concerned with the problems and possibilities of student teachers' access to the professional craft knowledge of practitioners within the Oxford Internship Scheme. The study builds on previous research by Brown and Mclntyre (1986, 1988, 1993), and is set within the wider context of recent research on teachers' thinking and on student teachers learning from experienced teachers.
The investigation reported in this thesis is broadly conceived as an action research study, focusing on the theoretical and practical questions raised by the attempt to institutionalise student teachers' access to experienced teachers' craft knowledge within a PGCE programme. A number of investigations were conducted over a period of two years and together they consistute preliminary studies in the light of which the research problem was revised and developed. The main study investigated the effectiveness of plans for enabling interns (student teachers within the Oxford scheme) to gain access to teachers' craft knowledge.
Post-lesson conversations between interns and experienced teachers were audio-taped and content analysed. The main finding from the content analysis is that it is possible for student teachers to access experienced teachers craft knowledge through the adoption of procedures broadly similar to those used by Brown and Mclntyre (1993) when interviewing teachers following observation of their teaching.
Semi-structured interviews were conducted separately with a sample of the interns and teachers involved. Analysis of these interviews focuses on teachers' and interns' interpretations of the conversations, on this general approach to learning about teaching, on the use which interns made of craft knowledge they accessed, and on wider views about acquiring the knowledge needed for teaching. Further analysis of six cases explores the relationships between the two sets of interviews and the content analysis of the conversations.
The concluding chapter explores implications of the research findings for the accessibility of teachers' craft knowledge, wider issues about the conditions necessary for the potential of school-based initial teacher education to be realised, and future research in the field.
On the specification and analysis of secure transport layers

The world is becoming strongly dependent on computers, and on distributed communication between computers. As a result of this, communication security is important, sometimes critically so, to many day-to-day activities. Finding strategies for discovering attacks against security protocols and for proving security protocols correct is an important area of research. An increasingly popular technique that is used to simplify the design of security protocols is to rely on a secure transport layer to protect messages on the network, and to provide protection against attackers. In order to make the right decision about which secure transport layer protocols to use, and to compare and contrast different secure transport protocols, it is important that we have a good understanding of the properties that they can provide. To do this, we require a means to specify these properties precisely. The aim of this thesis is to improve our understanding of the security guarantees that can be provided by secure transport protocols. We define a framework in which one can capture security properties. We describe a simulation relation over specifications based on the events performed by honest agents. This simulation relation allows us to compare channels; it also allows us to specify the same property in different ways, and to conclude that the specifications are equivalent. We describe a hierarchy of confidentiality, authentication, session and stream properties. We present example protocols that we believe satisfy these specifications, and we describe which properties we believe that the various modes of TLS satisfy. We investigate the effects of chaining our channel properties through a trusted third party, and we prove an invariance theorem for the secure channel properties. We describe how one can build abstract CSP models of the secure transport protocol properties. We use these models to analyse two single sign-on protocols for the internet that rely on SSL and TLS connections to function securely. We present a new methodology for designing security protocols which is based on our secure channel properties. This new approach to protocol design simplifies the design process and results in a simpler protocol.

Keywords: secret
confidential
channel
security
authenticated
authentication
computer security
secrecy
confidentiality
secure transport layer
Advisor: Lowe, G
Breeding biology and feeding ecology of Black guillemots

Since 1974 a population study of Black Guillemots has been conducted on Flatey Island, NW Iceland. The main aspects are summarized below.
Population numbers and distribution. The population has been censused several years, also those of 20 islets near Flatey. Information was collected on past status. Great changes have occurred since turn of the century. Last major change began in 1967; the population started increasing of such a scale that it can only have resulted from massive immigration. These changes are thought to be due to rats and Mink.
Attendance and population structure. Data was gathered on timing of spring return to nesting areas, status of attending birds, sex ratio, area and nest-site fidelity, pair-bond maintenance, and post-breeding departure. Special attention has been given to the problem of censusing birds attending nesting areas.
Breeding biology. Breeding biology variables were quantified and studied on a seasonal basisj;timing of laying, clutch size, interval between eggs, egg size, reproductive output, lengths of incubation and nestling periods. Supernormal clutch and brood experiments were conducted. I looked at length of replacement time of lost clutches, factors influencing timing of laying, its effect and that of clutch and egg size on breeding performance. Egg and chick losses were analyzed. Many interesting population phenomena seem to have been associated with the unusually rapid population increase.
Feeding ecology. Analyses were made of prey taken, feeding rhythm and areas, and factors influencing feeding rate and prey selection. Some information was collected on share of the sexes in feeding chicks, and kleptoparasitism. Study was made of chick growth, fledging condition and postfledging survival.
Population dynamics. About 3300 birds were ringed, providing basis for determining age at maturity, adult survival, and mortality. Pre-breeding survival was calculated using data from ringing schemes. A population model was constructed for the population, showing magnitude of immigration. Ringing provided data on dispersal.

Advisor: Perrins, C
Mathematical and computational modelling of tissue engineered bone in a hydrostatic bioreactor

In vitro tissue engineering is a method for developing living and functional tissues external to the body, often within a device called a bioreactor to control the chemical and mechanical environment. However, the quality of bone tissue engineered products is currently inadequate for clinical use as the implant cannot bear weight. In an effort to improve the quality of the construct, hydrostatic pressure, the pressure in a fluid at equilibrium that is required to balance the force exerted by the weight of the fluid above, has been investigated as a mechanical stimulus for promoting extracellular matrix deposition and mineralisation within bone tissue. Thus far, little research has been performed into understanding the response of bone tissue cells to mechanical stimulation.
In this thesis we investigate an in vitro bone tissue engineering experimental setup, whereby human mesenchymal stem cells are seeded within a collagen gel and cultured in a hydrostatic pressure bioreactor. In collaboration with experimentalists a suite of mathematical models of increasing complexity is developed and appropriate numerical methods are used to simulate these models. Each of the models investigates different aspects of the experimental setup, from focusing on global quantities of interest through to investigating their detailed local spatial distribution. The aim of this work is to increase understanding of the underlying physical processes which drive the growth and development of the construct, and identify which factors contribute to the highly heterogeneous spatial distribution of the mineralised extracellular matrix seen experimentally.
The first model considered is a purely temporal model, where the evolution of cells, solid substrate, which accounts for the initial collagen scaffold and deposited extracellular matrix along with attendant mineralisation, and fluid in response to the applied pressure are examined. We demonstrate that including the history of the mechanical loading of cells is important in determining the quantity of deposited substrate. The second and third models extend this non-spatial model, and examine biochemically and biomechanically-induced spatial patterning separately. The first of these spatial models demonstrates that nutrient diffusion along with nutrient-dependent mass transfer terms qualitatively reproduces the heterogeneous spatial effects seen experimentally. The second multiphase model is used to investigate whether the magnitude of the shear stresses generated by fluid flow, can qualitatively explain the heterogeneous mineralisation seen in the experiments. Numerical simulations reveal that the spatial distribution of the fluid shear stress magnitude is highly heterogeneous, which could be related to the spatial heterogeneity in the mineralisation seen experimentally.

Keywords: numerical simulation
hydrostatic pressure
bone
mathematical modelling
tissue engineering
multiphase model
Advisor: Whiteley, J
Waters, S
James, O
Income splitting, settlements and avoidance: taxing the family on business profits

In a progressive income tax system with an individual tax unit, high-rate taxpayers have an incentive to split income with lower-rate family members to minimise the family’s total tax burden. This raises equity and neutrality concerns. Adopting a spousal tax unit limits the gains from income splitting, but the individual is the better choice on privacy, autonomy, equality, definitional, marriage neutrality and work incentive grounds. Once the individual is chosen as the income tax unit, the control model provides a strong policy basis for attributing both earned and unearned income to individuals. Income splitting, however, undermines this model as well as the individual tax unit.
This thesis focuses on the UK’s approach to income-splitting in family businesses. The relevant UK income tax rules, particularly the settlements provisions, are inadequate for the task. Various possible reforms are examined. Incorporating a transfer pricing or ‘reasonableness’ test into the settlements provisions would strengthen these rules, but would make taxpayer compliance with an uncertain regime even more difficult. Another option is to expand the scope of employment tax by moving the borderline between employees and the self-employed or companies. Deeper structural reforms could be made to enhance the neutrality of taxation on different legal forms of economic activity. This would reduce the incentives to incorporate for tax savings, including from income splitting. Integration of income tax and NICs is one such option; a dual income tax is another. A TAAR or GAAR also could be pursued. Ultimately, some combination of these various reform options could provide a partial solution to this challenging issue.

Keywords: family taxation
husband and wife
income splitting
settlements
Advisor: Freedman, J