VictorJuiz/thesis huggingface dataset:
Genome engineering and gene drive in the mosquito aedes aegypti

Genetic control strategies are a novel method for reducing populations of pest insects such as the yellow fever mosquito Aedes aegypti, a major vector of several important arboviral diseases. This thesis describes efforts to develop new tools to engineer the Ae. aegypti genome and to better understand existing tools, and furthermore to use these to engineer a gene drive system in Ae. aegypti. The piggyBac transposon was found to be extremely stable in the germline of Ae. aegypti, and transposons engineered into the germline could not be remobilized with either an endogenous or exogenous source of piggyBac transposase. Conversely, somatic remobilization of piggyBac transposons was found to be readily detectable in the presence of a source of active transposase, the first report of such remobilization in Ae. aegypti. Toward new tools for genome engineering, the site-specific integrase from the phage φC31 was successfully used to promote exchange between a transgene cassette inserted into the genome of Ae. aegypti and a cassette in a plasmid vector, in the first demonstration of recombinase mediated cassette exchange technology in a pest insect species. The integrases from phages φRV1 and Bxb1 were not found to be active in the germline of the mosquito. Finally, development of a gene drive system in Ae. aegypti using an RNAi-mediated killer-rescue mechanism was attempted. Tissue-specific expression of tTAV-regulated-toxic effectors genes, using the promoter regions of the blood meal induced genes Carboxypeptidase A-1, 30Kb and Vitellogenin A, was possible, but sex-specificity was not achieved. A blood meal inducible lethal phenotype was not possible using the chosen promoters, with expression of the effectors either leading to death in early development or to a sublethal phenotype. RNAi against tTAV fused to the Mnp fragment of the dengue virus’ genome was tissue specific, but was found to be highly effective in the fat body suggesting that the Vitellogenin A was the best candidate for the engineering of killer-rescue systems in the mosquito.

Keywords: mosquito
genetic engineering
sterile insect technique
RNAi
Aedes
dengue fever
transposons
piggybac
gene drive
aegypti
Advisor: Sinkins, S
Pipelining - an approach for machine vision

Much effort has been spent over the last decade in producing so called "Machine Vision" systems for use in robotics, automated inspection, assembly and numerous other fields. Because of the large amount of data involved in an image (typically ¼ MByte) and the complexity of many algorithms used, the processing times required have been far in excess of real time on a VAX-class serial processor. We review a number of image understanding algorithms that compute a globally defined "state", and show that they may be computed using simple local operations that are suited to parallel implementation. In recent years, many massively parallel machines have been designed to apply local operations rapidly across an image. We review several vision machines. We develop an algebraic analysis of the performance of a vision machine and show that, contrary to the commonly-held belief, the time taken to relay images between serial streams can exceed by far the time spent processing. We proceed to investigate the roles that a variety of pipelining techniques might play. We then present three pipelined designs for vision, one of which has been built. This is a parallel pipelined bit slice convolution processor, capable of operating at video rates. This design is examined in detail, and its performance analysed in relation to the theoretical framework of the preceeding chapters. The construction and debugging of the device, which is now operational in its hardware is detailed.

Advisor: Brady, M
Tense and aspect in Old Japanese

This thesis analyses the nine main tense–aspect constructions in Old Japanese in more detail than ever before, exploiting the research possibilities created by the Oxford Corpus of Old Japanese. The commitment to close textual reading and the interpretation of examples in context that is characteristic of traditional Japanese scholarship is combined with a determination to explain the distributional data revealed by the Corpus. Large samples are used to produce quantitative semantic analyses, allowing a new perspective on multifunctional constructions from both synchronic and diachronic perspectives. All findings are placed within the wider perspective of cross-linguistic studies of tense and aspect, an approach often missing in Old Japanese scholarship.
This thesis is the most comprehensive analysis of Old Japanese tense and aspect to date. Some traditional conclusions are challenged, and light is shed on many previously unexplained phenomena. Resultative constructions are discovered to be even more pervasive in Japanese than previously thought, with at least five of the nine con-structions I look at hypothesized to have begun as resultative constructions. In most cases these constructions have broadened to also denote ongoing activities, another characteristic of Japanese. This thesis thereby contributes to the cross-linguistic understanding of resultative constructions, and to the question of the validity and nature of the distinction between activities and states. It also shows the potential of an exemplar-based model of linguistic storage, which is seen to be a powerful tool for explaining both the multifunctionality of grammatical constructions and semantic change.

Keywords: Nara period
aspect
Japanese
historical linguistics
tense
Old Japanese
linguistics
classical Japanese
semantics
corpus linguistics
Advisor: Frellesvig, B
Microphysical modelling of aerosols in the ORAC retrieval

This thesis describes an investigation of, and improvements to, the microphysical modelling of aerosols in the Oxford-Rutherford Appleton Laboratory Aerosol and Clouds retrieval (ORAC), which is used to obtain aerosol properties from measurements by the Advanced Along Track Scanning Radiometer (AATSR). Modelling decisions determine the light scattering properties of the aerosol classes which in turn alter the retrieved aerosol properties: aerosol optical depth, and effective radius.
The maritime, mineral dust, urban, and biomass burning aerosol classes were first investigated, and then improvements implemented. Major additions to the scheme include the ability to model non-spherical dust as spheroids, soot as fractal aggregates, and to coat spherical particles with an extra layer of differing refractive index (whose thickness can be modified by ambient relative humidity where necessary). Output from aerosol retrievals containing these new models is presented.
Modelling of marine aerosol was found to be adequate, but an improvement in the relative humidity assumptions led to an average 5 % increase in aerosol optical depth (AOD). Modelling of mineral dust aerosols has been dramatically altered by the addition of non-spherical dust and hygroscopic particles, leading to increases in measured AOD of over 100 % during dust events, compared to the previous model. Measurement of biomass burning aerosol has been tested with an `ageing' aerosol scheme, leading to increases in over-land measured AOD of 0.14 (~50 % increase). With such significant changes in AOD, representation of aerosol light scattering properties is seen to be important factor in the accuracy of the ORAC scheme.
Finally, a method of optimising the placement of detectors in an aerosol measurement device is presented.

Keywords: satellite retrieval
aerosol microphysics
atmospheric physics
Advisor: Grainger, R
On learning assumptions for compositional verification of probabilistic systems

Probabilistic model checking is a powerful formal verification method that can ensure the correctness of real-life systems that exhibit stochastic behaviour. The work presented in this thesis aims to solve the scalability challenge of probabilistic model checking, by developing, for the first time, fully-automated compositional verification techniques for probabilistic systems. The contributions are novel approaches for automatically learning probabilistic assumptions for three different compositional verification frameworks.
The first framework considers systems that are modelled as Segala probabilistic automata, with assumptions captured by probabilistic safety properties. A fully-automated approach is developed to learn assumptions for various assume-guarantee rules, including an asymmetric rule Asym for two-component systems, an asymmetric rule Asym-N for n-component systems, and a circular rule Circ. This approach uses the L* and NL* algorithms for automata learning.
The second framework considers systems where the components are modelled as probabilistic I/O systems (PIOSs), with assumptions represented by Rabin probabilistic automata (RPAs). A new (complete) assume-guarantee rule Asym-Pios is proposed for this framework. In order to develop a fully-automated approach for learning assumptions and performing compositional verification based on the rule Asym-Pios, a (semi-)algorithm to check language inclusion of RPAs and an L*-style learning method for RPAs are also proposed.
The third framework considers the compositional verification of discrete-time Markov chains (DTMCs) encoded in Boolean formulae, with assumptions represented as Interval DTMCs (IDTMCs). A new parallel operator for composing an IDTMC and a DTMC is defined, and a new (complete) assume-guarantee rule Asym-Idtmc that uses this operator is proposed. A fully-automated approach is formulated to learn assumptions for rule Asym-Idtmc, using the CDNF learning algorithm and a new symbolic reachability analysis algorithm for IDTMCs.
All approaches proposed in this thesis have been implemented as prototype tools and applied to a range of benchmark case studies. Experimental results show that these approaches are helpful for automating the compositional verification of probabilistic systems through learning small assumptions, but may suffer from high computational complexity or even undecidability. The techniques developed in this thesis can assist in developing scalable verification frameworks for probabilistic models.

Keywords: Computational learning
Assume-guarantee reasoning
Compositional verification
Probabilistic model checking
Advisor: Kwiatkowska, M
Foundations of practical reason

This thesis is an examination of the foundations of practical reason. Building on the later work of Wittgenstein, I argue for a subjectivist view of moral judgment and of judgments about reasons for action. On this view, moral judgments and judgments about reasons for action can be true or false, but they are not objective.
The argument for this view has the form of an inference to the best explanation. Using a distinction between primary and secondary qualities, I suggest that moral judgments and judgments about reasons for action should not be construed as referring to an ethical or normative reality that exists independently of us. There are ethical facts and facts about our reasons, but these facts arise as the result of our involvement in a linguistic practice. This provides a new way of accounting for these judgments that differs both from moral realism and expressivism.
The view of reasons that emerges is closely related to, but not identical with, reasons internalism as described by Bernard Williams. I reject his argument in favour of internalism and provide a new and independent argument to support this view of our reasons. In the course of spelling out that argument, I show why internalism as described by Williams should be modified, and why this does not commit us to externalism.
In the final chapters, I show that there is an important parallel between our practical predicament and the account of our epistemic condition as portrayed by Wittgenstein. The inference to the best explanation is completed by considering a number of objections to subjectivism that are based on the idea that a subjectivist account of moral judgment and of reasons fails to do justice to the ethical phenomena. I reject these objections, and suggest that a subjectivist can both be reflectively aware of his subjectivism and continue to live well.

Advisor: Child, B
A study of alpha particle widths in light nuclei using elastic alpha particle scattering

Elastic alpha particle scattering has been used to examine two different aspects of the nuclear wavefunction: to determine alpha cluster strengths in 19F and to investigate the isospin mixing amplitudes in the wavefunctions of T = 3/2 states in 19F and the first 0+; T = 2 state in 40Ca.
Yield curves of gamma rays and elastically scattered alpha particles from fourteen resonances in the 15N(α,γ) 19F and 15N(α, α0) 15N reactions have been simultaneously determined. The bombarding energies range from 4.465 to 8.105 MeV and the excitation energies from 7.538 to 10.411 MeV. The alpha decay widths and total widths of the compound nuclear states populated in these resonant reactions were determined using an R-matrix analysis. Five of the states in 19F have been identified as members of alpha or triton cluster bands and the widths of these states are compared with cluster model calculations.
A technique has been developed to measure small alpha widths in regions of high level density. The gamma rays from a resonance are used to define the energy region to be searched, since weak alpha particle resonances are not immediately apparent, and the beam energy is then automatically modulated to scan repeatedly the energy region of interest. High resolution was required to separate neighbouring resonances when the level density was high and this was acheived by using a differentially cryopumped windowless gas target.
Three of the resonances studied in the (α + 15N) reaction were isospin forbidden. The alpha decay width of the first 5/2; T = 3/2 state in 19F has been measured and the result is in agreement with the width predicted by Wormald et al [WOR69] from a radiative alpha capture study. The 9.926 MeV state has been proposed as a candidate for the first 9/2 ; T = 3/2 and the value for the alpha width obtained from these elastic scattering experiments supports this assignment.
The first 0 + ;T = 2 state in 40Ca was also studied as an isopsin forbidden resonance in the 36 Ar(α,α0 )36Ar reaction. The alpha decay width and the total width of this state has been determined. The systematics of T = 2 states in A = 4N nuclei is discussed in connection with this measurement since data are now available on all such nuclei up to mass 44.

Advisor: Allen, K
Induction of anti-apoptotic factors by cutaneous Human Papillomaviruses

Human Papillomaviruses (HPVs) are small DNA viruses which specifically infect keratinocytes at different body sites. An association between cutaneous Squamous Cell Carcinoma (SCC) formation, UV irradiation and infection with a high-risk subset of cutaneous HPVs has been postulated although the underlying molecular mechanisms by which HPV may play a role in SCC development are not yet fully elucidated. Expression of the viral E6 oncoprotein has been shown to interfere with DNA damage responses and inhibit UV induced apoptosis, suggesting HPV can contribute to early stages in tumourigenesis. Here, expression of E6 from HPV types 5, 8, 10, 18 and 77 was shown to reduce UV- or Fas-induced apoptosis, and the changes in a range of intracellular apoptotic regulators were investigated. Additionally, the subject of cutaneous SCCs, in contrast to HPV-associated anogenital cancers, not harboring HPV DNA in every tumor cell was explored. Results herein show that expression of E6 from skin cancer-associated HPV types 5 and 8 induced the secretion of factors that were able to inhibit UV-induced apoptosis in non-HPV expressing cell lines and primary human keratinocytes. The anti-apoptotic effect of HPV E6 expression was found to be mediated in part by upregulation of Osteoprotegerin (OPG) and Interleukin 6 (IL6). Purified OPG and IL6, when added to cells together, but not individually, reduced apoptosis following UV irradiation. Evidence is shown that OPG and IL6 inhibit the extrinsic and intrinsic apoptotic pathways respectively. Furthermore immunohistochemistry of HPV-typed SCC sections shows that IL6 protein is up-regulated in HPV positive tumors compared to HPV-negative cancers. To further test the effects of HPV5E6 expression, in combination with UV irradiation, on primary human keratinocytes microarray studies were performed. These findings support the hypothesis that a small number of HPV infected cells influence UV induced apoptosis in the skin and contribute to tumourigenesis.

Keywords: Human papillomavirus
apoptosis
ultraviolet
Advisor: Storey, A
Financial benchmark tracking problems under a stochastic linear quadratic control framework

In this thesis we analyse the problem of tracking a financial benchmark via trading a portfolio of a small number of assets on a finite time horizon. The development of general stochastic linear quadratic control (SLQ) theory in recent years allows us to study this investment problem using this approach. We formulate the problem under the SLQ control framework and derive an optimal feedback control solution using stochastic Riccati equations and an accompanying equation. We then apply our theory to benchmark problems involving tracking a continuously compounded given growth rate and a stock market index to obtain novel solutions. An outline of how we might implement the model in practice is also given.
The impact of radio-AGN on star formation across cosmic time

This thesis presents a detailed study of the impact of radio-AGN on star formation and the interstellar medium (ISM) of galaxies across cosmic time. To do this, this thesis uses far-IR/sub-mm data from the Herschel Space Observatory. I create a well-selected sample of 1599 radio sources using the NRAO VLA Sky Survey (NVSS) and Faint Images of the Radio Sky at Twenty-Centimeters (FIRST) data in combination with the UKIRT Infrared Deep Sky Survey - Large Area Survey (UKIDSS - LAS) data. I find that the far-IR luminosities and dust temperatures of radio galaxies are lower in comparison to those of non-radio-detected galaxies. This luminosity deficit grows with increasing stellar mass. I argue that the reasons for these differences is probably due to indirect radio-AGN feedback, i.e. radio jets mechanically heat the halo-environment, preventing external sources of cold gas from entering the host and forming stars. The far-IR luminosity and dust temperature is found to decrease as a function of radio source size. I find the most likely explanation for this is jet-induced star formation while the jets are confined to the ISM. Finally, a method for identifying reliable high-z, star-bursting radio sources in the H-ATLAS is described with which statistically significant studies of radio-jet induced star formation may be undertaken.

Keywords: Galaxy Evolution
Radio-AGN
Star formation
Far-IR
Advisor: Rigopoulou, D
Rawlings, S
Phosphorus nutrition of mycorrhizal plants. A mathematical model

Arbuscular mycorrhizas, mutualistic symbiotic associations between plant roots and soil fungi, provide an important pathway for phosphorus nutrition of many plants. We are interested in understanding the mechanisms that control and influence this pathway by means of a mathematical model. The scope of this dissertation was to develop a spatially explicit and dynamic model for solute uptake by a mycorrhizal root. To do so, we developed approximate analytical solutions for solute uptake by a single cylindrical hypha based on the standard assumption that the soil can be regarded as continuum as well as based on the assumption that a hypha grows inside individual soil pores. There is up to an order of magnitude of difference between these solutions. This highlights the fact that experiments on the single hyphal scale are needed. Furthermore, we developed a model for fungal growth which we used for upscaling uptake by a single hypha to a fungal colony scale. The result was introduced as sink term in a classical single root uptake model. The differences in calculated total uptake between the different versions of the sink term were large. Our simulation results confirm that mycorrhizas provide the root with a big spatial advantage to access non-mobile solutes in soil. They also confirm that under certain conditions, mycorrhizal fungi may dominate solute uptake completely.
Synthesis of the ABC fragment of pectenotoxin-4

This thesis details the application of two synthetic methodologies, developed by the Donohoe group, to the synthesis of the ABC fragment of pectenotoxin-4, a macrolide marine natural product that consists of 19 stereogenic centres, three tetrahydrofuran rings, one spiroketal and one bicyclic ketal embedded within a 26-membered macrocycle.
Pivotal to the developed synthetic route was the utilisation of an unprecedented cascade osmium catalysed oxidative cyclisation for the construction of two THF rings (the BC ring system). After successfully developing a model system for the synthesis of the AB anomeric 6,5 spiroketal, which involved the employment of a hydride shift initiated oxo carbenium ion formation followed by intramolecular spiroketalisation, the developed system was then applied to the fully elaborated synthesis of the ABC fragment.
The synthesis of the ABC fragment of pectenotoxin-4 was completed in 20 linear steps, with an overall yield of 3.3%.

Keywords: catalysis
spiroketals
natural products
cyclization
pectenotoxin
Advisor: Donohoe, T
Rural and urban perpectives on population mobility in France

Migration studies are both extensive and fragmentary, reflecting a wide variety of aims and methodology. In recent years an abstract statistical approach has dominated migration study which tends to concentrate on the distance and direction of migrants. This thesis aims to extend this approach to investigate more fully the structural variables of the migration environment. The study of the migration context is supplemented by analysis of the characteristics of migrants drawn from a sample survey of heads of households in Grenoble; to give a more complete and balanced picture of the complexity of migration.
The examination of net migration balances has been extended to study the spatial pattern of migration by Principal Components Analysis of gross flows at a national level. Factors of the migration environment selected for further study were demography, agriculture and amenities. Agricultural improvement is seen to act as an intervening variable between population pressure and outmigration in the early years of this century, while in more recent years the level of available amenities appears the dominant factor influencing migration.
The department of Isère was selected for further study because of the presence within it of the rapidly growing city of Grenoble which in the post-war period emerges as a focus for migrants of national importance. Furthermore the diversity of the natural environment within Isère provides a variety of source and destination areas. The areas of population loss were studied by means of Automatic Interaction Detection which determined the factors important in explaining out-migration and provided a basis for the classification of those areas. The types of origin and destination areas are related to the characteristics of the migrants themselves, drawn from a sample of individual census returns from the 1968 census. The varied environments within Isère and France as a whole produce different types of migrants with varying characteristics and aspirations; who seek out different areas of the city in which to settle. The characteristics of the migrants are drawn from a sample survey of individual census returns from the 1968 census.