VictorJuiz/thesis huggingface dataset:
Molecular biology of X-chromosome disease

Genomic clones were isolated and characterized using the human monoamine oxidase A (MAOA) cDNA to screen a phage library, constructed from a human 4X cell line (48, XXXX). The genomic contig derived from overlapping phage clones showed that the size of the MAOA gene is over 80 kb. Exon-containing fragments from these phage clones were subcloned and sequenced. The data from this showed that the MAOA gene consists of 15 exons.
A YAC (yeast artificial chromosome) isolated using the MAOA cDNA was characterized. This YAC was found to contain both the MAOA and the MAOB genes. Using PFGE (pulsed-field gel electrophoresis) to investigate the YAC, it was found that the MAOA and the MAOB genes are located within 50 kb and adjacent to each other. The two genes are localized in a 3'-to-3' fashion, suggesting their expression may be regulated independently. The analysis of the homology shown by the two genes clearly demonstrated that they were derived from duplication of a common ancestral gene. A CpG island was discovered to be associated with the 5' end of both genes.
A restriction map of -2.5 Mb of genomic DMA around the MAO genes was generated by PFGE. Long-range mapping defined the physical relationship between the marker L1.28 and the MAO genes as L1.28_MAOA_MAOB.
A number of genetic diseases have been linked to the Xp11.3 region. Strong linkage was known to exist between the Norrie disease locus and L1.28. Studies showed that some of the Norrie patients have deletions encompassing the region which contains L1.28 as well as the MAO genes. Another YAC isolated by using L1.28 as the probe was also characterized.
A phage library was constructed from the L1.28 YAC and the end clones were isolated. Studies on some of the Norrie deletion patients showed that the proximal end clone of the YAC was retained in one of the deletion patients. Previous studies had shown that the Norrie disease locus was also localized proximal to the 5' end of the MAOB gene. The combined information placed the disease locus to an interval of 240 kb within the YAC.
More phage clones were characterized in order to define further the region for the Norrie locus which was finally localized within 160 kb. A YAC fragment of 160 kb was isolated and used to screen two human retinal cDNA libraries. Among the cDNAs isolated, one group was found to be deleted in some of the Norrie patients previously without any known deletion, which established their candidacy as the transcripts of the Norrie disease locus. Further characterization of the candidate gene showed that it is conserved across species. The expression of the gene was detected in various tissues. The homology shared between the NDP gene and some of the growth factor binding proteins suggests its role in neural cell proliferation and differentiation.

Advisor: Edwards, J
Regularity and uniqueness in the calculus of variations

This thesis is about regularity and uniqueness of minimizers of integral functionals of the form
F(u) := ∫Ω F(∇u(x)) dx;
where F∈C2(RNn) is a strongly quasiconvex integrand with p-growth, Ω⊆RnRn is an open bounded domain and u∈W1,pg(Ω,RN) for some boundary datum g∈C1,α(‾Ω, RN).
The first contribution of this work is a full regularity result, up to the boundary, for global minimizers of F provided that the boundary condition g satisfies that ΙΙ∇gΙΙLP < ε for some ε > 0 depending only on n;N, the parameters given by the strong quasiconvexity and p-growth conditions and, most importantly, on an arbitrary but fixed constant M > 0 for which we require that ΙΙ∇gΙΙO,α < M. Furthermore, when the domain Ω is star-shaped, we extend the regularity result to the case of W1,p-local minimizers.
On the other hand, for the case of global minimizers we exploit the compactness provided by the aforementioned regularity result to establish the main contribution of this thesis: we prove that, under essentially the same smallness assumptions over the boundary condition g that we mentioned above, the minimizer of F in W1,pg is unique. This result appears in contrast to the non-uniqueness examples previously given by Spadaro [Spa09], for which the boundary conditions are required to be suitably large.

Keywords: integral functionals
minimizers
Advisor: Kristensen, J
The Geopolitics of Ethnic Relations in Russia

Ethnic relations are an important feature of contemporary Russia. This is especially true in the North Caucasus where ongoing insecurity combined with a depressed economy has led to growing Russian nationalism, xenophobia, and fears over immigration. In Stavropol’skii krai, the only ethnic Russian dominated territory in the North Caucasus Federal District, the situation is especially acute. In this thesis I investigate how the geopolitics of ethnic relations in Stavropol’skii krai, as part of the wider North Caucasus situation, impact on the everyday life of citizens in Stavropol’. I do this through employing an eclectic methodology, including both qualitative and quantitative techniques.
Through four research papers, I explore how the built urban environment, through the politics of naming place (for example, street names and monuments), has become a space through which ethnic identity can be (re)produced and contested. I show how ethnic relations are (re)presented and performed in Stavropol’ through the Den’ kraya celebration, a performance that is based on a Soviet-era idealised framing of ethnic relations, and one which is open to challenge. I explore how in summer 2007 ethnic relations turned violent as ethnic Russian and non-ethnic Russian citizens rioted, and I attempt to explain the geopolitics surrounding this. Finally, I show how everyday ethnic relations have turned increasingly violent in Stavropol’ since 1991, drawing on reports from non-governmental organisations and independent researchers. I situate this research within the context of the changing ethnic geography of the krai since 1991. Together, this research represents a geopolitics of ethnic relations in Stavropol’skii krai.

Keywords: Russia; North Caucasus; Ethnic Relations; Geopolitics
Advisor: Pallot, J
Increasing statistical power and generalizability in genomics microarray research

The high-throughput technologies developed in the last decade have revolutionized the speed of data accumulation in the life sciences. As a result we have very rich and complex data that holds great promise to solving many complex biological questions. One such technology that is very well established and widespread is DNA microarrays, which allows one to simultaneously measure the expression levels of tens of thousands of genes in a biological tissue. This thesis aims to contribute to the development of statistics that allow the end users to obtain robust and meaningful results from DNA microarrays for further investigation. The methodology, implementation and pragmatic issues of two important and related topics – sample size estimations for designing new studies and meta-analysis of existing studies – are presented here to achieve this aim. Real life case studies and guided steps are also given. Sample size estimation is important at the design stage to ensure a study has sufficient statistical power to address the stated objective given the financial constraints. The commonly used formula for estimating the number of biological samples, its short-comings and potential amelioration are discussed. The optimal number of biological samples and number of measurements per sample that minimizes the cost is also presented. Meta-analysis or the synthesis of information from existing studies is very attractive because it can increase the statistical power by making comprehensive and inexpensive use of available information. Furthermore, one can also easily test the generalizability of findings (i.e. the extent of results from a particular valid study can be applied to other circumstances). The key issues in conducting a meta-analysis for microarrays studies, a checklist and R codes are presented here. Finally, the poor availability of raw data in microarray studies is discussed here with recommendations for authors, journal editors and funding bodies. Good availability of data is important for meta-analysis in order to avoid biased results and for sample size estimation.

Keywords: genomics
sample size
genetics
statistics
meta-analysis
microarray
Advisor: Altman, D
Holmes, C
Measuring laminar burning velocities

The laminar burning velocity of a fuel is the rate of normal propagation of a 1D flame front relative to the movement of the unburned gas. This is a fundamental property of a fuel that affects many aspects of its combustion behaviour. Experimental values are required to validate kinetic simulations, and also to provide input for models of flashback, minimum ignition energy and turbulent combustion. Burning velocity affects burn duration and consequently power output in spark ignition engines. Burning velocities are affected by pressure, temperature, equivalence ratio, residuals, additives, and stretch rates. The constant volume vessel has been used as it is considered both the most versatile and accurate method of measuring laminar burning velocities. An existing combustion vessel and oven were refurbished and new systems built for fuel injection, ignition, experiment control, data acquisition and high speed schlieren photography. An existing multi-zone model was used to allow calculation of burning velocity from pressure and schlieren data, allowing the user to select data uncorrupted by heat transfer or cellularity. A twelve term correlation for burning velocity was validated using methane modelling data. The chosen data from all the experiments was then fitted to the correlation. Methane, n-butane, n-heptane, iso-octane, toluene, ethylbenzene and ethanol were tested over a wide range of initial pressures (0.5, 1, 2 and 4 barA), temperatures (289-450 K) and equivalence ratios (0.7-1.4). For liquid fuels, tests with real residuals at mole fractions of up to 0.3 were also conducted. Stoichiometric mixture tests were performed at two initial temperatures (380 and 450 K) and the same four initial pressures. For mixtures of iso-octane and ethylbenzene, percentage volumes of 12.5, 25, 50 and 75% iso-octane were tested. It was found that the the percentage of iso-octane affected burning velocity non-linearly. For iso-octane/ethanol, a single 50:50% mixture was tested.

Keywords: residuals
combustion
flame speeds
laminar burning velocities
Advisor: Stone, R
Advances in the theory of electrochemical methods

This thesis is concerned with dynamic electrochemistry experiments in which faradaic processes are driven by the application of potential to an electrode immersed in an electrolyte solution. In particular, experimental methods are considered which could be used to study electrochemical systems in a more informative way if the processes occurring at the electrode were better understood. The work develops the theoretical models which describe these experiments, and details the approximations made in each model and the conditions under which they are appropriate. Numerical simulations are reported which demonstrate how the models can be used to infer quantitative details of chemical behaviour from experimentally recorded data. The first system studied in detail is linear sweep voltammetry at a microband electrode array. The diffusional behaviour of an electroactive species is shown to depend on the configuration of the microband array and on the potential scan rate used. Details are given on how experimental conditions can be optimised for the study of electrochemical systems. The next area of work develops the theory of nanoparticle-modified electrodes. Experiments are considered in which an electron transfer reaction is catalysed only at the site of the nanoparticles, whilst the supporting planar electrode remains electrochemically inert. Numerical simulations show how the current measured at these modified electrodes depends on the size and shape of the particles, on the distribution of the particles on the electrode surface, and on the timescale of the experiment. The final theme of work is on electrochemical experiments in poorly conducting solutions. A theoretical model is developed which takes into account the effects of an electric field on the mass transport of electroactive species and on the charge transfer kinetics at the electrode. The model is then used to rationalise the unusual current behaviour that is observed in the anodic stripping of thallium from an amalgam.

Keywords: microband electrode arrays
computational electrochemistry
partially supported voltammetry
nanoparticle modified electrodes
Advisor: Compton, R
Analysis of artificial chromosomes in human embryonic stem cells

The development of safe and efficient gene delivery systems in pluripotent human embryonic stem cells (hESc) is essential to realising their full potential for basic and clinical research. The purpose of this study was to develop an efficient, non-integrating gene expression system in pluripotent hESc using human artificial chromosomes (HAC). Similar to endogenous chromosomes, HAC are capable of gene expression, replication and segregation during cell division. Unlike retroviral-mediated gene delivery vectors, HAC do not integrate into the host genome and can encompass large genomic regions for the delivery of multiple genes. Despite the advantages HAC offer, their use has been limited due to laborious cloning procedures and poor transfection efficiencies, and thus only studied in immortalised and tumour-derived human cell lines. In this study, the high transduction efficiency of herpes simplex virus type-1 (HSV-1) amplicons was utilised to overcome the described difficulties and delivered HAC vectors into pluripotent hESc. Analysis of stable hESc clones showed that de novo gene-expressing HAC were present at high frequencies ranging from 10-70% of metaphases analysed, without integrating into the genome. The established HAC contained an active centromere, and were stably maintained without integration or loss in the absence of selection for 90 days. Stable HAC-containing hESc clones retained their pluripotency as demonstrated by neuronal differentiation, in vitro germ layer and teratoma formation assays. HAC gene expression persisted, with some variation, post-differentiation in the various deriving cell types. This is the first report of successful de novo HAC formation in hESc for gene expression studies. These findings show potential for delivering high-capacity genomic constructs safely and efficiently into pluripotent cells for the purpose of genetic manipulation and ultimately patient-specific somatic gene therapy.

Keywords: Human embryonic stem cells
Chromosomal analysis
Gene therapy
Genetic manipulation
Herpes simplex virus type 1 (HSV-1) amplicon
Human artificial chromosomes (HAC)
Advisor: Larin Monaco, Z
Attrition of particulate solids

Attrition occurs during the transport and storage of particles and leads to loss of material through dust formation and to environmental pollution. Standard tests are all specifically designed to cater for particular needs and are often indicators of relative hardness than of attrition rates. Since little progress has been made into understanding the mechanisms of attrition, the purpose here is to study one of the basic processes that determines the rate of grinding. The aim is thus to establish a fundamental framework within which past work and future developments can be assessed.
An annular attrition cell was designed, constructed and commissioned to permit one of the mechanisms of attrition, namely that in failure zones of deforming solids, to be considered in isolation. Sample weights of 100 gm were more than sufficient and the results were found to be reproducible, systematic and generally independent of sample size.
Several close-sized material in the size range 250-2000 µm of various shapes were studied including different grades of sodium chloride, sodium carbonate and molecular sieve beads. The mode of attrition, bodily fracture or surface grinding, was easily verified by microscopic examination of attrited product. Results followed Gwyn's empirical law W = Kp tm where W denotes the weight fraction attrited, t time and Kp , m are characterising parameters.
The reliable data permitted the development of simple kinetic models. One supposes first order loss of coarse material, another that attrition rate is dependent on radius reduction. It may be argued that the former applies to a fracturing mechanism, the latter to a surface grinding process. The first order approach has to be modified to allow for the initial high rate of attrition; the second model may be reduced to the Gwyn form.
The attrition cell is useful in characterising materials; it should, in future, permit assessment of equipment performance.

Advisor: Bridgwater, J
The politics of high rise housing in Britain

This research analyses an area of public housing construction .policy in Britain, the building of high riee flats (defined as those in blocks of five or more storeys).
The national political process on the issue involved central government subsidy policy (which encouraged local authorities to build high until 1967), and the influence of the design professions, the construction industry and the national local government system on trends in high flat construction. The policy was largely confined to inner urban areas, where the operation of the 1947 planning system within an anachronistic local government structure forced local authorities to try to meet their housing needs in situ. High rise became characterized as a 'technological shortcut to social change' by production interests, and pursued despite its relative unpopularity and considerably greater costs. A weak structure of Ministry cost controls combined with the provision of strong subsidy incentives (both premissed upon inaccurate expectations of local authorities' response), resulted in considerable over-building of high rise and a major change in the balance of public housing construction policy. Contractual pressure on local authorities and central government by large national construction firms can be seen as the basic dynamic of the high rise housing boom.
The local level political process on high rise is examined in case studies of three widely differing areas - Newham, Birmingham and Bristol. Ths development of housing construction policies in these areas was essentially similar, ana largely explicable in terms of non-local, structural influences, Ebcplanations of policy change in terms of the system of actors in each locality proved inadequate, despite the importance of some distinctive local factors.
Theoretically the study offers little support to pluralist or elite approaches. 'Mew Pluralist' thsory emerges as descriptively accurate but normatively optimistic, and the neo-Kandrrdst critique is found to have relevance at points.
Evaluating forcings in an ensemble of paleo-climate models

This thesis presents the initial results from climateprediction.net's paleo-experiments. A grand ensemble of paleo-climate models was successfully designed and executed using this distributed computing approach. The physical parameters, initial conditions and boundary conditions were perturbed in two sets of experiments distributed to the general public. The paleo - focus period is the mid-Holocene, i.e. ~6000 years before present, due to its relative climatic stability and the abundance of geological evidence. Attempting to simulate climates that were substantially different from today provides an opportunity to evaluate model skill. A set of robust 6kyBP climatological features were established to benchmark the climate model against in order to assess the model’s abilities. Two experiments were distributed: in the first experiment the boundary conditions in the 6kyBP models took on the standard Paleoclimate Modelling Intercomparison Project (PMIP) values with altered orbital configuration as the main forcing on the climate.
In a second experiment the local boundary conditions in Eastern North America (ENA) were also perturbed in the 6kyBP models to include an expanded Hudson Bay and land ice. The results highlight strengths and weaknesses in the model and stresses the importance of high quality paleo-observations.
The models simulate the broad-scale features of the mid-Holocene climate reasonably well, though the model performance decreases when the benchmarks are inspected more closely. A relationship between the climate sensitivity, i.e. the equilibrium temperature response to doubling of pre-industrial CO2 concentrations, and the 6kyBP East Asian monsoonal moisture budget is found. This provides a climate sensitivity range of 2.5-6.1°C.
The ENA boundary condition experiment concludes that the perturbations brought the climate models to a closer agreement with the geological records.
A sensitivity experiment perturbing the North African vegetation cover emphasises the importance of vegetation feedbacks in relation to the 6kyBP northwards expansion of the monsoon.

Keywords: paleo-climates
GCM ensemble
climate sensitivity
Advisor: Allen, M
Henderson, G
Valdes, P
High resolution infrared spectroscopy of jet-cooled molecules

The development and implementation of a high resolution, direct absorption, rapidscanning infrared diode laser spectrometer incorporating a supersonic jet expansion source is described. High sensitivity is achieved by directly modulating absorption signals at frequencies in excess of 50 kHz, enabling their separation from lower frequency mechanical and diode 1/f noise. This is accomplished by rapidly scanning the diode laser across a small frequency window (~0.5-1.5cm-1) synchronously with a pulsed supersonic expansion in a time period of 1 or 2 ms. Absorptions appear as small attenuations in the overall variation of the laser mode power across the scan window. This background profile is removed by recording the laser power without gas pulsing and subtracting. Relative frequency calibration is effected by simultaneously recording the spectrum of a reference gas and the interference fringes of an etalon. Absorption signals are recorded by means of a fast 12-bit analog-to-digital converter operating at 1 MHz. This is housed within a dedicated PC microprocessor which performs spectrometer control, data coaddition, signal processing and spectrum calibration functions.
The spectrometer has been used to measure the infrared spectra of two weakly bound complexes, CO-OCS and Ne-SiH4. The infrared absorption spectrum of CO-OCS was measured in the 5μm region of the OCS ν3 asymmetric stretch. In addition microwave spectra of CO-OCS and two isotopomers 13CO-OCS and CO-OC34S have been recorded using a pulsed nozzle microwave Fourier transform spectrometer. The lines have been fitted to a Watson S reduction Hamiltonian yielding rotational, quartic and (for the ground states) sextic centrifugal distortion constants. A T-shaped structure is determined and this is rationalised by a simple potential model incorporating a distributed multipole analysis of the electrostatic charge distribution, distributed dispersion contribution and a cylindrical hard-core repulsion.
The infrared spectrum of Ne-SiH4 was recorded in the vicinity of the SiH4 ν3 triply degenerate stretching vibration centred at 2189.19 cm-1. Ne-SiH4 is only the second atomspherical top complex to be successfully recorded and analysed. The complex exhibits an intermolecular potential with considerably smaller anisotropy than its argon analogue Ar-SiH4. Consequently the SiH4 unit is almost free to rotate within the complex, resulting in novel Coriolis interaction between the angular momentum of the SiH4 unit and that of the overall complex. Individual bands are fitted to Coriolis interaction Hamiltonians, and the band centres for all the transitions of the complex are fitted to an anisotropic intermolecular potential.
Finally, applications of the spectrometer to the study of air sensitive compounds and species generated by electric discharge sources are considered.

Advisor: Brown, J