VictorJuiz/thesis huggingface dataset:
Developing gene knockdown-replacement therapies for spinocerebellar ataxia type 7

For many dominant diseases, conventional treatment options are limited. This makes them attractive candidates for gene therapy, which may be directed to specifically silence a disease-causing allele. However, many mutations are not easily amenable to this technique, including nucleotide repeat expansions, which cause numerous neurodegenerative diseases such as Huntington’s disease and several Spinocerebellar Ataxias. Combined gene knockdown and replacement (K&R;) may present a more practical approach for such conditions, whereby the gene of interest is subject to mutation-independent non-allele-specific silencing and concurrently replaced with a functional copy. Artificial mimics of naturally occurring intronic microRNAs are theoretically ideal for this purpose, since they can be nested within the replacement gene. This thesis investigates the development of mimics of two different intronic miRNA systems (mirtron miR-1224 and the miR-106b cluster) to silence Ataxin-7 and to be incorporated into novel single K&R; constructs for testing in vitro. Artificial mirtrons and intronic miRNAs were successfully developed and shown to silence Ataxin-7 mRNA in numerous cell lines. An RNAi-resistant gene was developed and mirtrons could be successfully incorporated as introns. Patient-derived fibroblasts and iPSC-derived neuronal cells were investigated as models for testing of gene silencing therapies. This work suggests that mirtron-based K&R; is achievable, and warrants further investigation.

Keywords: miRNA
Mirtrons
Neurodegenerative disease
SCA7
Spinocerebellar Ataxia
Gene Therapy
Advisor: Wood, M
Patent races and market structure

This thesis is a theoretical study of relationships between patent races and market structure. The outcome of a patent race can be an important determinant of market structure. For example, whether or not a new firm enters a market may depend upon its winning a patent race against an incumbent firm already in that market. Moreover, market structure can be a major influence upon competition in a patent race. In the example, the asymmetry between incumbent and potential entrant has an effect upon their respective incentives in the patent race.
Chapter I discusses models of R and D with uncertainty. We show that, as the degree of correlation between the uncertainties facing rival firms increases, R and D efforts increase under some, but not all, conditions, and the number of active competitors falls. Chapter II discusses the approach of representing patent races as bidding games. We examine a model in which several incumbent firms compete with a number of potential entrants in a patent race, and ask whether the incumbents have an incentive to form a joint venture to deter entry. They do so if and only if the patent does not offer a major cost improvement. In Chapter III we examine the strategic interactions between competitors during the course of a race, in an attempt to clarify (for different types of race) the idea that a race degenerates when one player becomes 'far enough ahead' of his rivals, in a sense made precise. In Chapter IV we examine the evolution of market structure in a duopoly model when there is a sequence of patent races. The nature of competition in the product market is shown to determine whether one firm becomes increasingly dominant as industry leader, or whether there is 'action - reaction' between firms.
Free-space optical communications with retro-reflecting acquisition and turbulence compensation

Free-space optics (FSO), or wireless optical communications, has received extensive research due to its promise of practically limitless bandwidths. However, FSO has challenges yet to be met for a cost effective realisation. This D.Phil thesis explores a solution using a ferro-electric liquid crystal spatial light modulator (FLC SLM) and binary phase holograms to significantly reduce the hardware complexity of an FSO system with auto-alignment and turbulence compensation.
The theory of binary phase hologram is presented and extended to obtain a new algorithm that is suitable for a FLC SLM. The algorithm is able to be used in a demonstration system to broadcast data streams to multiple receivers, showing the capability of using FLC SLM to form any beam configuration. An FSO transmitter is then developed that uses retro-reflectors as markers for the receivers. The transmitter combines an imaging system with the FLC SLM as a reconfigurable beam steering system for acquiring the retro-reflector location. The FLC SLM is also used to reduce aberrations in the optics, resulting in a significant increase in the transmitted beam power density. The accuracy of the acquisition is measured to give a small steering error without the use of a closed loop controller.
An optical turbulence simulator, using the principals of binary phase hologram, is constructed to simulate optical beam propagation in turbulent conditions. The simulator accurately produces aberrations that have the same statistics with the theoretical prediction. Analysis of the phase distortion due to turbulence is performed and a wavefront sensorless turbulence compensation method based on the FLC SLM gives significant reduction in calculated bit error rates. New scintillation index derivation for multiple optical beams is described and then used to demonstrate further decrease in bit error rates.

Keywords: SLM
retroreflector
atmosphere
communication
turbulence
holography
optical
Advisor: O'Brien, D
Housing needs: power, subjectivity and public housing in England, 1920-1970

This thesis addresses two key questions: First, how did those involved in the provision of public housing in twentieth-century England conceptualise the people who they were providing houses for? Second, how did their ideas change over time?
These questions are important and need answering because, although there has been a great deal written about the history of public housing in England, there has up until now been very little thought given to the manner in which the council estate tenants themselves were actually identified and conceptualised as subjects in need of state-funded housing. My thesis begins to redress this imbalance by providing an overview of the changing forms and practices through which prospective tenants were conceptualised and acted upon by those in positions of power in England between 1920 and 1970. Using records from local authority archives, sociological surveys, architectural and town planning journals, central government publications, Mass Observation reports and tenant handbooks, and focusing primarily on council estates in London, Manchester and Sheffield, it shows how ideas about what prospective tenants needed from their homes changed dramatically over the course of this period, with the narrowly sanitary and biopolitical approaches of the 1920s and 1930s increasingly being challenged and complemented by a host of new ideas and discourses which placed far more emphasis upon the prospective tenant’s emotional, social and personal needs. As such, this thesis not only adds substantially to our understanding of the changes that took place in the English public housing sector between 1920 and 1970, but also adds to the burgeoning literature on questions of governmentality; contributing in the process to our understandings of modern modes of power.

Keywords: council housing
social housing
governmentality
welfare state
Britain
Advisor: Houlbrook, M
Studies of earthquakes and microearthquakes using near-field seismic and geodetic observations

The Centroid--Moment Tensor (CMT) method allows an optimal point-source description of an earthquake to be recovered from a set of seismic observations, and, for over 30 years, has been routinely applied to determine the location and source mechanism of teleseismically recorded earthquakes. The CMT approach is, however, entirely general: any measurements of seismic displacement fields could, in theory, be used within the CMT inversion formulation, so long as the treatment of the earthquake as a point source is valid for that data. We modify the CMT algorithm to enable a variety of near-field seismic observables to be inverted for the source parameters of an earthquake.
The first two data types that we implement are provided by Global Positioning System receivers operating at sampling frequencies of 1,Hz and above. When deployed in the seismic near field, these instruments may be used as long-period--strong-motion seismometers, recording displacement time series that include the static offset. We show that both the displacement waveforms, and static displacements alone, can be used to obtain CMT solutions for moderate-magnitude earthquakes, and that performing analyses using these data may be useful for earthquake early warning.
We also investigate using waveform recordings --- made by conventional seismometers deployed at the surface, or by geophone arrays placed in boreholes --- to determine CMT solutions, and their uncertainties, for microearthquakes induced by hydraulic fracturing. A similar waveform inversion approach could be applied in many other settings where induced seismicity and microseismicity occurs.

Keywords: GPS
geodesy
microseismicity
earthquakes
geophysics
Advisor: Woodhouse, J
Power is consuming the forest

The broad aim of this research is to further our understanding of the incorporation of nature into socio-political processes of transition within countries at war. The concomitant capitalist production of nature and construction of political power is examined through the case of forest exploitation in Cambodia. The thesis draws on political ecology, sociological theories of power, and political economic theories of commodity chains to explain the apparent failure of both the Cambodian government and the international community to employ logging revenues as a positive factor for 'peace and reconstruction'.
The main period of study extends from 1987 to 1998, during which Cambodia's protracted civil war ended. Timber represented over that period close to half of Cambodia's export earnings. However, this revenue largely escaped official taxation and reportedly fuelled the conflict, broadened wealth disparities, and deepened an environmental crisis. Rather than fully subscribing to this 'politics of plunder' story-line, this thesis examines the complexities of forestry practices, and flows of logging revenue, and analyses their relationship with the construction of political power throughout the process of transition.
This construction of political power is interpreted through a neopatrimonial model in which social actors' politico-economic strategies both influence, and are influenced by the transition process. In Cambodia during the period of study, these strategies reinforced a 'shadow state' politics, through which the political elite, in part responding to the demands of international markets and the political challenge of the UN-sponsored peace process, consolidated its power by reorganising productive networks outside formal governance. In turn, domestic and international actors through both discursive and material practices resisted these strategies. The case of logging in Cambodia is thus interpreted as a contested process of transforming nature and incorporating space into 'productive networks', as part of a broader political economy of power.
Retrieval of atmospheric structure and composition of exoplanets from transit spectroscopy

Recent spectroscopic observations of transiting exoplanets have permitted the derivation of the thermal structure and molecular abundances of H2O, CO, CO2, CH4, metallic oxides and alkali metals in these extreme atmospheres. Here, for the first time, a fully-fledged retrieval algorithm has been applied to exoplanet spectra to determine the thermal structure and composition. The development of a suite of radiative transfer and retrieval tools for exoplanet atmospheres is described, building upon an optimal estimation retrieval algorithm extensively used in solar system studies. Firstly, the collection of molecular line lists and the pre-tabulation of the absorption coefficients (k-distribution tables) for high temperature application are discussed. Secondly, the best-fit spectra for hot Jupiters are demonstrated and discussed case by case. Available sets of primary and secondary transit observations of exoplanets are used to retrieve atmospheric properties from these spectra, quantifying the limits of our knowledge of exoplanetary atmospheres based on the current quality of the data. The contribution functions and the vertical sensitivity to the molecules are fully utilised to interpret these spectra, probing the structure and composition of the atmosphere. Finally, the retrievals provide our best estimates of the thermal and compositional structure to date, using the covariance matrices to properly assess the degeneracy between different parameters and the uncertainties on derived quantities for the first time. This sheds light on the range of diverse interpretations offered by other authors so far, and allows us to scrutinise further atmospheric features by maximising the capability of the current retrieval algorithm and to demonstrate the need for broadband spectroscopy from future missions.

Keywords: exoplanets
hot Jupiters
optimal estimation
retrieval
transit spectroscopy
Advisor: Irwin, P
Fletcher, L
Phase separation in solutions of large spherical particles

The effect of large size ratios of solute to solvent on the critical properties and phase behaviour of binary mixtures of spherical particles is investigated using an "augmented van der Waals" equation of state. The equation used is essentially a van der Waals equation with an improved hard sphere repulsive term.
Molecular dynamics and constant-pressure Monte Carlo simulations of binary mixtures of hard spheres with different diameter ratios and mole fractions are undertaken to check the adequacy of the hard sphere equation. Good agreement is found, even for systems with large differences in size. Furthermore, many of the hard sphere mixtures exhibited a transition from a fluid to a solid phase at high densities.
Phase boundaries are calculated for model mixtures comprising spheres of different sizes between which there are long-ranged attractive forces. Particular attention is paid to the case in which the ratio of sizes is infinite. The systems show a wide variety of behaviour that includes liquid-liquid and gas-gas immiscibility, and the formation of negative azeotropes. Calculations investigating the effect of different attractive interactions between the small and large spheres show that as the magnitude of this interaction is increased, liquid-liquid immiscibility becomes the dominant feature of the phase diagram at moderate temperatures. The extent of liquid-liquid coexistence is greatest at large size differences. These model systems are shown to reproduce some of the behaviour of aqueous solutions of surfactants if it is assumed that the large spheres are models of the micelles and the small spheres models of the solvent molecules.
The properties of binary lattice mixtures of bifunctional molecules whose ends are chosen to mimic surfactant and solvent molecules are also briefly investigated, to determine the effect of the asymmetric surfactant molecule on the phase separation. Closed-loops emerge in the phase diagrams as the surfactant character of one of the species is increased.

Advisor: Rowlinson, J
Exploration, exploitation & complexity in biological evolution and self-assembly

Self-assembly --- by which ordered structures spontaneously emerge from disordered components --- and biological evolution --- by which Charles Darwin's "endless forms most beautiful" have emerged from the simple chemistry of prehistoric Earth --- may both be pictured as search processes on high-dimensional landscapes, defined respectively by the concepts of energy and fitness. The rich dynamics of these search processes will be studied in order to explain biologically observed features of self-assembly and evolution.
This study will introduce and analyse the behaviour of a model for a paradigmatic example of self-assembly, the icosahedral virus capsid, a symmetric structure formed from interacting protein subunits. Results for the thermodynamics and kinetics of model virus assembly will be presented, and the model will be extended to include complicating effects such as different subunit types and cellular crowding. A more general formalism for analysing self-assembling systems will then be introduced and used to suggest a well-defined complexity measure of universal applicability to self-assembled structures.
The biological evolution of simple self-assembling structures will be studied using genetic algorithms. The suitability of this modelling approach and its dependence on the many parameters involved will be investigated. Several active areas of enquiry in the field of evolution, including the evolution of complexity, the presence and effect of neutral networks, fluctuations in evolutionary time series and the emergence of symmetry will be investigated within this framework.
Throughout this study, we will use the picture of "exploration and exploitation": different approaches to performing optimisation on an unknown landscape, essentially corresponding to a random search and a hill-climbing approach respectively . We will show that, both in self-assembly and evolution, finding an optimal combination of these two approaches gives rise to many of the observed features in this study.

Keywords: landscapes
search processes
genetic algorithms
self-assembly
Evolutionary dynamics
Advisor: Louis, AA
St. Paul's Deuteronomy

Amid the recent turn to Paul’s reading of Scripture, the role Deuteronomy plays in his letters has generally been examined in individual citations without regard to the larger role Deuteronomy plays in Paul’s letters, or with an exclusive focus on either the theological or the ethical importance of Deuteronomy for Paul. In contrast, this study argues that Paul read Deuteronomy with three interlocking construals (as ethical authority, as theological authority, as an interpretation of Israel’s history), each equally basic. These construals can be combined to achieve a sense of the shape of Paul’s Deuteronomy as a whole. In order to ascertain and specify these construals, Paul’s engagement with Deuteronomy is examined as an instance of Jewish engagement with the book. Part I, therefore, supplies the historical conditions of Paul’s and other Jewish authors’ encounter with the scroll of Deuteronomy (Chap 2). On this basis, Part II proceeds to survey the major Jewish interpreters of Deuteronomy from the 3rd c. BCE to the 3rd c. CE (Chaps. 3-8). Because Paul is himself a Jewish author, this study foregoes the traditional bi-partite thesis division into “background” and Paul, opting instead to see Paul as one in a chain of Jews who turned to Deuteronomy to make sense of the present. These chapters thus also provide a sustained analysis of Deuteronomy’s broader effective history in Second Temple Jewish writings – and, in a few cases, beyond. In light of the range of interpretations to which Deuteronomy was susceptible, the concluding chapter examines what is distinctive about the shape of Paul’s Deuteronomy and what contribution this may make to debates on Pauline theology and to the study of Second Temple Jewish biblical interpretation.

Keywords: Second Temple Judaism
Apostle Paul
biblical interpretation
Deuteronomy
Old Testament in the New
Advisor: Bockmuehl, M
Analysis of atmospheric temperature and humidity from radio occultation measurements

Radio occultation measurements from global navigation satellite systems, such as the Global Positioning System (GPS), represent a new source of numerical weather prediction information.
Conventionally, radio occultation measurements are inverted using an Abel integral transform to obtain a profile of refractivity, and subsequently pressure, on geometric height levels via the hydrostatic relation. Although accurate temperature/water vapour retrievals are possible with a background estimate of water vapour/temperature, it is not possible to retrieve these quantities simultaneously using this method. Also, using this method, refractivity retrieval errors are introduced by assuming no horizontal structure local to ray periapsis (the spherical symmetry assumption), and the method is subject to 'first-guess' errors when the hydrostatic relation is initialised.
Results from an investigation into how departures from spherical symmetry affect the performance of the Abelian inverse method are presented. It is shown that realistic horizontal humidity inhomogeneities can compensate for or reinforce horizontal temperature inhomogeneities, and therefore are important to consider in both the forward and inverse modelling. Using the results from this experiment, regression coefficients are fitted in an effort to predict temperature and refractivity retrieval errors from the horizontal temperature and humidity structure local to the measurement. The largest contribution to the predicted errors is shown to be from the local parabolic component of the horizontal structure, but is found to predict only a small fraction of the total error.
A non-linear optimal estimation inverse method is presented with which it is possible to retrieve simultaneously profiles of temperature, humidity and surface pressure. Using this method, the measurements are assimilated with a priori information utilising error estimates of the a priori information and the measurements. The method implemented is validated using an ensemble of numerical simulations.
Real observations from the GPS/MET pilot experiment are used to retrieve profiles of temperature, humidity and surface pressure which are validated using collocated ECMWF and NMC model analyses, radiosondes, and the Abelian inversion results. Temperature and refractivity comparisons between the optimal estimate and results from the Abelian inverse method show good agreement at high latitudes for all altitudes, resolving small-scale structure not shown by the model analyses. At low latitudes there is good agreement above the tropopause, below which a temperature bias ensues between the Abelian inversion and all other correlative data. Retrieved values for water vapour and surface pressure compare well with model analyses and collocated radiosondes. Biases between the UKMO and the ECMWF model analyses are consistent with known differences between the two models at the time of the dataset.