VictorJuiz/thesis huggingface dataset:
Evaluation of the immunological mechanisms induced by mycobacteria and the potential effect this may have on immunity induced by tuberculosis vaccines
Keywords: Mycobacterium tuberculosis
non-tuberculous mycobacteria
bacillus calmette-geurin
T cells
adaptive immunity
pulmonary tuberculosis

The efficacy of Bacille-Calmette Guerin (BCG) vaccination in protection against pulmonary tuberculosis (TB) is highly variable between populations. One possible explanation is increased exposure of certain populations to non-tuberculous mycobacteria (NTM). Given the variable efficacy of BCG an improved vaccine against TB is required. The novel TB vaccine MVA85A has shown promising results, however, the immunogenicity of the vaccine is reduced when it is administered in the Expanded Programme on Immunisation (EPI) schedule. This thesis aims to explore: (A) the effect of exposure to NTM on the level of protection afforded by BCG vaccination against Mycobacterium tuberculosis (M. tb) and (B) the immunological mechanisms behind EPI interference with MVA85A.
The effect of M. avium (MA) exposure via systemic and oral routes on the efficacy of BCG was tested using M. tb aerosol infection in a mouse model. The adaptive immune response was profiled in BCG vaccinated mice with and without exposure to MA pre- and post- M. tb infection. The results showed BCG efficacy could be enhanced by exposure to dead MA by a systemic route; T helper 1 and T helper 17 responses were associated with increased protection. In contrast, BCG efficacy may have been reduced by exposure to live MA by the oral route; T helper 2 and regulatory T cells were associated with reduced protection.
To answer the second aim MVA85A was co-administered to mice with aluminium adjuvants or aluminium-containing vaccines to replicate the effect of co-administration in the EPI schedule; the adaptive immune response was profiled. T helper 2 and regulatory T cell responses induced by aluminium-containing vaccines were associated with a reduction in the immunogenicity of MVA85A.
Image formation mechanisms in three-dimensional aberration-corrected scanning transmission electron microscopy
Keywords: scanning transmission electron microscopy

This thesis considers the theory and calculations of image formation mechanisms for various modes of three-dimensional imaging in aberration-corrected scanning transmission electron microscopy. Discrete tomography is used to determine and refine the three-dimensional structure of molecular nanowire bundles. The structure determination is expedited by the use of annular dark-field imaging, an incoherent imaging mode which provides directly interpretable images. The development of spherical aberration correctors and the subsequent reduction in probe sizes, including the depth of field, has made optical depth sectioning a feasible technique. The localisation in three dimensions of substitutional impurity atoms in zone-axis imaging is discussed. Both the channelling of the probe and the pre-focussing effect of the atomic column play an important role in determining the depth response of the impurity atom. Interband scattering within a sample is shown to be influential in imaging crystals containing dislocations and optical depth sectioning is explored as a possible option for overcoming surface relaxation effects in the imaging of screw dislocations end-on. The possibility of extending the optical depth sectioning approach using aberration-corrected scanning confocal electron microscopy is discussed. The coherent and incoherent imaging modes, involving elastically and inelastically scattered electrons respectively, are investigated.
Constructing an international market for carbon trading: an institutional perspective
Keywords: institutional political economy
climate policy
carbon markets

Mitigating climate change requires the collaborative and international management of a range of socio-economic processes that produce greenhouse gas emissions. Governments in a number of regions are developing carbon markets to mitigate climate change by limiting the production of greenhouse gases. This thesis examines the construction of carbon markets in the United States and Europe to understand what role these markets play in mitigating climate change. Using a relational economic geography framework and institutional theory, I frame the markets into two components: 1) the regulatory structures which give the markets existence and bound their rules of operation, and 2) the financial and service components which operationalized the markets. Within these components, I investigate four specific facets of market development: complementarity, spacetime, design vs. path dependence and institutional development. The study is conducted through close dialogue and case studies of organization in London, New York and Chicago as well as interviews with policymakers in Washington D.C. Sacramento, and San Francisco. I find that the regulatory components of the market are built both by regulatory agencies and private organizations such as legal firms. Political path dependence constrains the development of the regulatory framework of the carbon markets. The financial service components are constructed in existing financial service centers such as London and New York by directly adopting expertise, products, services and infrastructure from other markets. With respect to the spacetime construction of markets, I find that carbon markets are being adapted to management in existing time zones, with a seamless transaction of activity between North America, Europe and Asia. However, the nature of spacetime within the markets is changing; the markets now manage non-spacetime. In sum, the carbon markets are constructed as a social institution which mitigates greenhouse gas production by communicating and widely disseminating the value of the absence of emissions.
Sound propagation in an urban environment
Keywords: source localisation
acoustics

This thesis concerns the modelling of sound propagation in an urban environment. For most of the thesis a point source of sound source is assumed, and both 2D and 3D geometries are considered. Buildings are modelled as rigid blocks, with the effects of surface inhomogeneities neglected. In the time-harmonic case, assuming that the wavelength is short compared to typical lengthscales of the domain (street widths and lengths), ray theory is used to derive estimates for the time-averaged acoustic power flows through a network of interconnecting streets in the form of integrals over ray angles. In the impulsive case, the propagation of wave-field singularities in the presence of obstacles is considered, and a general principle concerning the weakening of singularities when they are diffracted by edges and vertices is proposed. The problem of switching on a time-harmonic source is also studied, and an exact solution for the diffraction of a switched on plane wave by a rigid half-line is obtained and analysed. The pulse diffraction theory is then applied in a study of the inverse problem for an impulsive source, where the aim is to locate an unknown source using Time Differences Of Arrival (TDOA) at multiple receivers. By using reflected and diffracted pulse arrivals, the standard free-space TDOA method is extended to urban environments. In particular, approximate source localisation is found to be possible even when the exact building distribution is unknown.
The induced mean flow of surface, internal and interfacial gravity wave groups
Keywords: Stokes drift
surface waves
interfacial waves
internal waves

Although the leading-order motion of waves is periodic - in other words backwards and forwards - many types of waves including those driven by gravity induce a mean flow as a higher-order effect. It is the induced mean flow of three types of gravity waves that this thesis examines: surface (part I), internal (part II) and interfacial gravity waves (part III). In particular, this thesis examines wave groups. Because they transport energy, momentum and other tracers, wave-induced mean flows have important consequences for climate, environment, air traffic, fisheries, offshore oil and other industries. In this thesis perturbation methods are used to develop a simplified understanding of the physics of the induced mean flow for each of these three types of gravity wave groups. Leading-order estimates of different transport quantities are developed.
For surface gravity wave groups (part I), the induced mean flow consists of two compo- nents: the Stokes drift dominant near the surface and the Eulerian return flow acting in the opposite direction and dominant at depth. By considering subsequent orders in a separation of scales expansion and by comparing to the Fourier-space solutions of Longuet-Higgins and Stewart (1962), this thesis shows that the effects of frequency dis- persion can be ignored for deep-water waves with realistic bandwidths. An approximate depth scale is developed and validated above which the Stokes drift is dominant and below which the return flow wins: the transition depth. Results are extended to include the effects of finite depth and directional spreading.
Internal gravity wave groups (part II) do not display Stokes drift, but a quantity analogous to Stokes transport for surface gravity waves can still be developed, termed the “divergent- flux induced flow” herein. The divergent-flux induced flow it itself a divergent flow and induces a response. In a three-dimensional geometry, the divergent-flux induced flow and the return flow form a balanced circulation in the horizontal plane with the former transporting fluid through the centre of the group and the latter acting in the opposite direction around the group. In a two-dimensional geometry, stratification inhibits a balanced circulation and a second type of waves are generated that travel far ahead and in the lee of the wave group. The results in the seminal work of Bretherton (1969b) are thus validated, explicit expressions for the response and return flow are developed and compared to numerical simulations in the two-dimensional case.
Finally, for interfacial wave groups (part III) the induced mean flow is shown to behave analogously to the surface wave problem of part I. Exploring both pure interfacial waves in a channel with a closed lid and interacting surface and interfacial waves, expressions for the Stokes drift and return flow are found for different configurations with the mean set-up or set-down of the interface playing an important role.
Deformation studies near hard particles in a superalloy
Keywords: dislocation density
crystal plasticity finite element
Nickel superalloys
high-resolution EBSD
strain analysis

Superalloys have performed well as blade and disc materials in turbine engines due to their exceptional elevated temperature strength, high resistance to creep, oxidation and corrosion as well as good fracture toughness. This study explores the use of a relatively new technique of strain measurement, high resolution electron backscatter diffraction (HR-EBSD) to measure local deformation fields. The heart of the HR-EBSD technique lies in comparing regions in EBSD patterns from a strained region of a sample to those in a pattern from an unstrained region. This method was applied to study the elastic strain fields and geometrically necessary dislocation density (GND density) distribution near hard carbide particles in a nickel-based superalloy MAR-M-002.
Significant thermal strains were initially induced by thermal treatment, which included a final cooling from the ageing temperature of 870°C. Elastic strains were consistent with a compressive radial strain and tensile hoop strain that was expected as the matrix contracts around the carbide. The mismatch in thermal expansion coefficient of the carbide particles compared to that of the matrix was sufficient to have induced localized plastic deformation in the matrix leading to a GND density of 3 × 1013 m–2 in regions around the carbide. These measured elastic strain and GND densities have been used to help develop a crystal plasticity finite element model in another research group and some comparisons under thermal loading have also been examined.
Three-point bending was then used to impose strain levels within the range ±12% across the height of a bend bar sample. GND measurements were then made at both carbide-containing and carbide-free regions at different heights across the bar. The average GND density increases with the magnitude of the imposed strain (both in tension and compression), and is markedly higher near the carbide particles. The higher GND densities near the carbides (order of 1014 per m2) are generated by the large strain gradients produced around the plastically rigid inclusion during monotonic mechanical deformation with some minor contribution from the pre-existing residual deformation from thermal loading. A method was developed of combining the local EBSD measurements with FE modelling to set the average residual strains within the mapped region even when a good strain free reference point was unavailable.
Cyclic loading was then performed under four point loading to impose strain levels of about ±8% across the height of bend bar samples. Similar measurements as in the case of monotonic deformation were made at several interruptions to fatigue loading. Observations from the cyclic loading such as slip features, carbide cracking, GND density accumulation have been explored around carbide particles, at regions away from them and near a grain boundary.
A critical edition, with introduction and commentary, of the libretto texts of  Montagu Slater and Benjamin Britten's Peter Grimes 
Keywords: George Crabbe
Montagu Slater
Peter Grimes
Benjamin Britten

A definitive text of the libretto of Benjamin Britten's opera Peter Grimes is here presented. The process by which it was created is revealed in detail. All the extant versions are collated and significant differences between them displayed. For the first time the scenarios written by Britten and his partner Peter Pears and the first surviving draft versions of scenes by the librettist Montagu Slater are published in full. Additions to the draft and final libretto texts and revisions throughout this process by Slater, Britten, producer Eric Crozier and, in the final scene, poet Ronald Duncan, are clarified and a critique provided. Marked differences in stage directions between the libretto texts and music scores are shown and versions selected or created which offer the best indicative detail for performance practice. The edited text is similarly enriched by the inclusion of performance indicators from various sources added by Britten, Pears and the work's first conductor, Reginald Goodall.
The edition is introduced by three 'Perspectives' sections which consider (1) Britten's relationship with Slater and working practice with librettists; (2) the relationship of the work to its original source, George Crabbe's poem The Borough, the difference in the portrait and treatment of the character Peter Grimes and the reasons for the difference; and (3) the particular contribution and features of Slater's writing. Thereafter follow an account of the rationale, principles and practice of the edition and introductions to every scene in which the use of source material, the evolution of the text, the plot development and performance issues of the scene, the presentation of characters and the set are delineated, the latter with reference to photographs of the original set hitherto unpublished.
The end of Richelieu
Keywords: Richelieu; French History; Louis XIII; political conspiracy; Spanish History; Olivares; Philip IV; noble culture; nobility; rebellion; Bouillon; Guise; Soissons; Cinq-Mars; Anne of Austria; court culture

Cardinal Richelieu is traditionally accredited with defeating the power of the grands, the upper echelon of the French nobility, as part of his supposedly successful project for monarchical absolutism. Modern historians have recast Richelieu as a nobleman of his time, who advanced himself within the social and political hierarchies through marriage alliances and patronage. He therefore worked hard to forge alliances with the grands rather than trying to destroy them. Yet his ministry was riven by persistent noble conspiracies and rebellions, which have gone largely without systematic investigation. This study examines the nature and causes of that unrest during Richelieu’s final six years, offering a radical re-assessment of the opposition and the politics of the period. Noble conspiracy was not just a by-product of government by a first minister, but reflected the factional nature of Richelieu’s approach. Factional rivalry was exacerbated by the emergence, after 1638, of a struggle for the anticipated regency. After this, Richelieu took a more hostile approach to his adversaries, forcing them to adopt strong countermeasures in order to preserve their positions.
Richelieu’s opponents were surprisingly successful in asserting their independence. As well as enjoying widespread domestic support, they allied with the Habsburg powers to engineer military rebellion, posing a major threat to the Cardinal and undermining the war effort against Spain. The Spanish set their stall out for a long-term war, expecting that Richelieu’s opponents would eventually gain power and negotiate peace on more flexible terms. The ability of the grands to re-assert themselves was still a dominant characteristic of French politics. Richelieu’s legacy, on his death in 1642, was a highly volatile political situation in which success was still a long way off for France. These findings suggest the catalytic impact of Habsburg power on France’s internal divisions, which should consequently be seen as integral to the forging of the ancien régime.
Sandstone weathering, Electrical Resistivity Tomography, and the deterioration of San Rock Art in the Golden Gate Highlands National Park, South Africa
Keywords: sandstone
rock art
tafoni
weathering

Electrical Resistivity Tomography (ERT) is a novel technique which can be used to build up a 2D pseudo-section of resistivity distribution of a porous material. Here, it is used to visualise internal moisture regimes by measuring the resistivity distribution of transects within sandstone, inferring that high resistivity equals low moisture content and vice versa. This method was used to perform two intermediate complexity laboratory tests; the first one to determine high-resolution, multi-scale drying patterns of sandstone, the second to determine capillary ingress of moisture within a sandstone block and the influence of temperature on moisture distribution. It was found that moisture behaviour showed far more complex patterns than previously acknowledged. A new model is therefore proposed which describes the influence of increased near-surface temperatures on capillary rise. This series of tests bridge the gap between field observations and mathematical models, as well as confirm the validity of ERT as a geomorphological tool.
This research was continued by investigating the role of internal moisture in sandstone weathering using the Golden Gate Highlands National Park (GGHNP), South Africa as a case study. The ERT data was correlated with Equotip (rock surface hardness) and Protimeter (rock surface saturation) measurements. Seven sites were investigated, which showed that there is a non-linear correlation between rock surface hardness and internal moisture patterns. In addition, annual change measurements confirmed that the fluctuating patterns of internal moisture can be correlated to strengthening or weakening of the rock surface. This research therefore proposes two new conceptual weathering models. The first correlates ‘optimal moisture content’ to rock surface strength. The second correlates the development of shelters and changing weathering patterns to the non-linear interaction between case hardening and internal moisture. This new approach to sandstone weathering can be incorporated into conservation methods, as rock surface loss is one of the main causes of the San Rock Art deterioration observed in the GGHNP.
Regulation of human RNA polymerase II CTD modifications
Keywords: Transcription
RNA Polymerase
C-terminal domain
RPAP2
Integrator
PP1
Gene regulation

Transcription of human protein-coding genes and most small nuclear RNA genes is mediated by RNA Polymerase II (Pol II). During a cycle of transcription, Pol II recruits a variety of factors that facilitate transcription elongation, RNA processing and termination, through its long, unstructured C-terminal domain (CTD). The CTD in humans comprises 52 tandem heptapeptide repeats with the consensus sequence Y1S2P3T4S5P6S7. Each amino acid of the heptapeptide can be chemically modified, which influences the recruitment of other protein factors to the transcription machinery. Not all enzymes that modify the CTD have been discovered. Recent studies have identified a novel CTD phosphatase: RPAP2 in humans and its yeast homologue Rtr1, which dephosphorylate phospho-Ser5 of the heptapeptide repeats. RPAP2 has been shown to stimulate 3' end cleavage of nascent snRNAs through recruitment of the Integrator complex, and unpublished work suggests the involvement of RPAP2 in regulating vertebrate developmental programs. However, the exact mechanisms that regulate the function of human RPAP2, and thus impact on CTD modification, are not well-understood.
This thesis presents a novel mechanism whereby RPAP2 recruits protein phosphatase 1 (PP1) to snRNA genes, where PP1 is postulated to activate P-TEFb to phosphorylate Ser2 of the CTD. At the same time, P-TEFb may have a role in activating the phosphatase activity of RPAP2. Furthermore, RPAP2 itself is shown to be recruited to a number of gene promoters by the RPRD1A protein, which also stimulates its phosphatase activity. RPAP2 was shown to have another role in regulating transcription termination: by recruiting the Integrator complex, which is shown here to mediate termination of snRNA genes, and by a so far unknown mechanism on a long protein-coding gene. An attempt was made to purify and crystallise the human RPAP2 to obtain a crystal structure, however the crystallisation trials were not successful. Finally, a correlation was found in human embryonic stem cells and induced pluripotent stem cells between low levels of RPAP2 and high levels of CTD Ser5P, suggesting a potential involvement of RPAP2 in regulating transcription at a key developmental stage.
The results presented here contribute to the understanding of human transcriptional mechanisms and the numerous interactions within the transcription machinery. In particular, the mechanism of terminating the transcription of snRNA genes is identified. An interesting possibility is the regulation of development and stem cell differentiation by RPAP2; however the exact pathways by which this occurs are yet to be discovered.