VictorJuiz/thesis huggingface dataset:
The Aza-Bohlmann cyclisation and the synthesis of Pandanus alkaloids

Bohlmann et al. reported the oxidative spirocyclisation of 2-(ω-hydroxyalkyl)furans under Clauson-Kaas conditions to furnish 1,6-dioxaspiro[4.5]dec-3-enes, thereafter termed the “Bohlmann cyclisation.” This thesis describes the development of an analogous aza-Bohlmann cyclisation. Treatment of 2-(ω-aminoalkyl)furans with m-CPBA or singlet oxygen generates hydroxy- or methoxybutenolides, respectively, which undergo spirocyclisation upon treatment with H₂SO₄ to generate [4.4]- and [4.5]-spiroaminoacetals.
The axial/equatorial preferences of N-sulfonylspiroaminoacetals featuring a 3-O-isovaleryl or 3-O-benzyl substituent are described. Acid-catalysed equilibration revealed that in acetonitrile the axial isomer is thermodynamically favoured for both substrates.
The first total synthesis of the spiroaminoacetal alkaloid pandamarilactone-1 is discussed, via an aza-Bohlmann cyclisation, in 13 steps and 3% overall yield from 4-pentyn-1-ol.

Keywords: Furan
oxidative spirocyclisation
spiroaminal
spiroaminoacetal
Advisor: Robertson, J
Base excision repair of radiation-induced DNA damage in mammalian cells

A specific feature of ionising radiation is the formation of clustered DNA damage, where two or more lesions form within one to two helical turns of the DNA induced by a single radiation track. The complexity of ionising radiation-induced DNA damage increases with increasing ionisation density and it has been shown that complex DNA damage has reduced efficiency of repairability. In mammalian cells, base excision repair (BER) is the predominant pathway for the repair of non-DSB clustered DNA lesions and is split into two sub-pathways known as short patch (SP) BER and long patch (LP) BER. SP-BER is the predominant pathway, especially in the repair of isolated DNA lesions. However, LP-BER is thought to play a greater role in the repair of radiation-induced clustered lesions. In this study, cell lines were generated stably expressing the fluorescently tagged BER proteins, XRCC1-YFP (marker for SP-BER) or FEN1-GFP (marker for LP-BER). The recruitment and loss of XRCC1-YFP and FEN1-GFP to sites of DNA damage induced by both ultrasoft X-ray (USX), a form of low linear energy transfer (LET) radiation, and near infrared (NIR) laser microbeam irradiation (‘mimic’ high LET radiation) was visualised in real-time and the decay kinetics of the fluorescently-tagged proteins determined. The half-life of fluorescence decay of FEN1-GFP following USX irradiation was longer than that of XRCC1-YFP, indicating that LP-BER is a slower process than SP-BER. Additionally, the fluorescence decay of XRCC1-YFP after NIR laser microbeam irradiation was fitted by bi-exponential decays with a fast component and a slow component, reflecting the involvement of XRCC1 in the repair of different types of DNA damage. In contrast to USX irradiation, where the XRCC1-YFP fluorescence decay reached background levels by 20 min, XRCC1-YFP still persisted at some of the NIR laser induced DNA damage sites even after 4 hours. This is consistent with the fact that the laser induces more complex damage that presents a major challenge to the repair proteins, persisting for much longer than the simple damage caused by low LET USX irradiation. Persistent, unrepaired DNA damage can potentially lead to mutations and replication-induced DSBs if it persists into S-phase. PARP1 inhibition reduced the recruitment of XRCC1 to DNA damage sites. However, a considerable amount of XRCC1 was still detected at the DNA damage sites, leading to the conclusion that there is a subset of DNA damage that requires XRCC1 but not PARP1 for repair. Understanding how clustered damage is repaired by the BER pathway can aid the design of future therapies which can be used in combination with radiotherapy to enhance the radiosensitisation effect. Knockdown of FEN1 was investigated and found to radiosensitise A549 (adenocarcinoma) cells, possibly as a result of an excess of unrepaired radiation-induced lesions requiring LP-BER for repair, although FEN1 knockdown alone induced cell death in non-cancerous BEAS-2B cells.

Keywords: ionising radiation
Base excision repair
XRCC1
clustered DNA damage
FEN1
Advisor: O'Neill, P
Lomax, M
The stereospecific formation of 1,2-cis glycosides via allyl-mediated intramolecular aglycon delivery

This thesis describes investigations into the possibility and scope of allylderived intramolecular aglycon delivery as a tool for the stereospecific formation of 1,2-cis glycosides. The three-step procedure involves isomerisation of the 2-O-allyl protection of a glycosyl donor, followed by iodonium-mediated tethering to an aglycon alcohol. Activation of the donor induces intramolecular delivery of the aglycon, to afford the 1,2-cis glycoside.
The synthesis of ten glycosyl donors, including gluco-, manno- and rhamnopyranosyl and glucofuranosyl donors, as selenoglycosides, thioglycosides and glycosyl fluorides, is described.
Isomerisation was carried out in excellent yield in all cases using a catalyst derived from Wilkinson's catalyst.
The scope of N-Iodosuccinimide-mediated tethering is described. Attempted tethering to a selenoglycoside resulted in activation of the donor. Tethering to a thiomethyl glycoside was successful for unhindered alcohols, but sluggish for secondary carbohydrates, and activation of the donor became competitive in these cases. The use of glycosyl fluorides gave good tethering yields for many alcohols, including secondary carbohydrates. For hindered alcohols, tethering of succinimide became competitive, resulting in reduced yields.
Examples of high-yielding tethering reactions using a novel source of iodonium ion are reported. A large excess of aglycon was unnecessary for good yields to be obtained. A 'reverse' tethering approach, whereby a donor with a free 2-hydroxyl is tethered to the isomerised allyl group of an aglycon, was found to be effective using this reagent.
In all cases, activation gave stereospecific glycosylation, furnishing the 1,2-cis glycosides. Other glycosylated products still bearing functionality derived from the tether, including mixed acetals and enol ethers, were cleaved by acid treatment, affording further 1,2-cis glycoside. Slightly lower glycosylation yields were obtained in the rhamno and glucofurano systems. Investigations into the glycosylation mechanism were also undertaken.
The stereospecific synthesis of the Glc 3 Man N-glycan tetrasaccharide via an iterative tethering and allyl-mediated intramolecular glycosylation strategy is reported.

Advisor: Fairbanks, A
Thought, perception and the creative act: a study of the work of four contemporary French poets: Pierre Alferi, Valère Novarina, Anne Portugal and Christophe Tarkos

In this thesis I suggest that the work of the four contemporary poets studied manifests the vital role perceptual experience plays in the creation of literary texts. I engage primarily in the analysis of particular texts in order to argue for a shift in critical focus away from the explicit manipulation or exteriorization of the physical aspects of poetry (for example versification and explicit visual presentation) in order to concentrate on the role sensory aspects of thought play within it. Emphasis is therefore put on the way these poets draw from sensory experience, and the effect this has on the way their poetry functions. A shift away from traditional critical vocabulary is considered necessary in part due to the fact that discussions of the physical aspects of poetry often carry with them a variety of preconceptions concerning the nature of language, thought and the thinking subject. The tendency to pose dividing lines between mind and body, word and image, the physical and non-physical aspects of language has characterized the history of Western thought, and neither literature nor literary criticism have been exempt from the conceptual presuppositions inherent in such binary systems. Here, I consider how the work of Pierre Alferi, Valère Novarina, Anne Portugal and Christophe Tarkos transcends such dualisms, using the analysis of specific works to develop a critical approach that reflects their exploration of the ambiguity of the boundaries that separate different sorts of experience and means of expression. The thesis is therefore structured around the development of three concepts, ‘pensée-vue’, ‘pensée-voix’ and ‘pensée-toucher’, inspired directly by the texts studied, that are intended to indicate the vital role different forms of perception play in both the creation and experience of poetic texts. It is hoped that the development of an approach that emphasizes the connection between thought, perception and creativity will suggest the fertility of a shift in critical focus in domains beyond that of contemporary French poetry.

Keywords: language
poetry
contemporary
French
thought
creativity
perception
Advisor: Sheringham, M
Social and psychological factors affecting the impact of painful chronic illness upon mental health

This thesis is a report of a study on patients suffering one of two painful chronic illnesses (rheumatoid arthritis (RA) or migraine), and attempts to discover possible determinants of psychological reactions to long term painful illness.
One hundred and sixty chronically ill individuals were interviewed, (80 migraine and 80 RA sufferers). In keeping with other evidence, the extent of psychological disturbance was found to be higher for chronically ill individuals than for general population samples. There were no zero order correlations between reported pain and psychological distress. Age and length of suffering have often been cited as possible factors influencing mood state, but no evidence was found for this in the data gained in this survey.
The results provide no evidence for the use of coping strategies as a method of adapting to the demands of the painful chronic illnesses studied here. Beliefs in control over illness have been posited as possible factors that may influence psychological state, and were measured in this research using a health locus of control scale. However locus of control scores were not found to be associated with mood state, although, in keeping with other research, scores were found to be associated with age and social class, with both lower social class and older sufferers scoring higher on externality than those from higher social classes, or whom were younger.
The strongest association was found between aspects of subjective health status and mood state. The major finding of this study is that patients assessment of their own health state, in both illnesses, is the major factor associated with psychological state.

Advisor: Argyle, M
Applications of Malliavin calculus to the pricing and hedging of Bermudan options

The pricing of Bermudan options, which give the holder the right to buy or sell an underlying asset at a predetermined price and at a discretely spaced number of times prior to maturity, can be based on a deterministic method or on a probabilistic one. Deterministic methods such as finite differences lose their efficiency as the dimension of the problem increases, and they are therefore known to suffer from the "curse of dimensionality". Probabilistic methods enable us to overcome this problem by using Monte Carlo simulations. One particular method is the Malliavin pricing and hedging algorithm, which uses representation formulas for conditional expectation and its derivative to approximate the price and delta of a Bermudan option. This paper specifically deals with how the powerful tools of Malliavin calculus are applied in the derivation of such representation formulas, and looks at how the latter are subsequently used in the pricing and hedging algorithm. Key words: Bermudan option, dynamic programming principle, Malliavin derivative operator, Skorohod integral, first and second variational processes, representation formula, localizing function.
Identifying vital sign abnormality in acutely-ill patients

The Emergency Department (ED) provides the first line of care for anyone seeking treatment for an urgent problem caused by an accident or illness . Physiological observations in the ED are a required part of patient care, and are used to monitor a patient's condition. Manual observations are recorded regularly by nursing staff, using a Track and Trigger (T&T;) system, in which higher scores indicate greater physiological abnormality.
An observational study at the John Radcliffe Hospital, Oxford, was conducted to assess the effectiveness of T&T; in the ED. Retrospective analysis showed that the effectivenessof T&T; was limited by poor completion, and incorrect calculation of T&T; scores. In response, we computed a retrospective, fully completed, scoring system which showedvery clear improvements in both sensitivity and specificity.
In addition to nurse observations, higher acuity ED patients have their vital signs continuously monitored by bedside monitors. However, the alerts generated by the monitors are routinely ignored due to their high false alert rate. We investigated whether a baseline data fusion model and two alternative techniques, weighted Parzen windows and Support Vector Machines, could identify events relating to vital sign abnormality while keeping the number of false alerts to a minimum. The performance of each model was assessed by calculating its sensitivity and specificity. However, it was not possible to select an optimal model, due to the difficulty in assessing the relative importance of maximising true alertsand minimising false alerts.
In the final part of this thesis, two limitations of the data fusion models are highlighted. Firstly, missing data is not handled coherently within the current models, and secondly the models do not make use of temporal information. One method of addressing both of these issues, Gaussian processes, was considered. Using this method, a novel framework was derived that allowed for alerts to be generated even when there is uncertainty in the vital sign values.

Keywords: Monitoring
Machine Learning
Patient
Data Fusion
Advisor: Tarassenko, L
Alumina based nanocomposites by precipitation

This project addressed two main problems pertaining to Al2O3-FeAl2O4 nanocomposites developed via solid state precipitation: the mechanisms for precipitation in ceramic solid solution via reduction reaction, and the mechanisms for the improved mechanical properties and wear resistance of the developed Al2O3-FeAl2O4 nanocomposites.
A model was proposed for precipitation in ceramic solid solutions via reduction reactions (the PRCS model). The thermodynamics of reduction reactions during aging treatments under various atmospheres were calculated and discussed relative to the second phase precipitate formation. Attempts were made to measure the corresponding diffusion kinetics using a new theory developed here based on volume fraction profiles of second phase particles in the aged samples. It was found that the measured apparent oxygen vacancy diffusivities conform well to the oxygen vacancy grain boundary diffusion coefficients reported in the literature, and the measured apparent matrix diffusivity conforms well to the Fe3+ ion matrix diffusion coefficients reported in literature. Based on the thermodynamics calculations, diffusion kinetics and some essential mechanisms that were discussed, the PRCS model was proposed. This has two aspects: macroscopic and microscopic. The macroscopic aspect of PRCS model was mainly used to explain the general aspects of microstructure and the distribution of intergranualar second phase particles. The microscopic aspect of the PRCS model was mainly used to explain the precipitation of intragranualar nanoparticles.
The mechanical properties, thermal residual stress and wear resistance of selected Al2O3-FeAl2O4 nanocomposites were measured. The results revealed that the Al2O3-FeAl2O4 possessed improved fracture toughness (by around 46%), flexural strength (by around 30%) and abrasive wear resistance (by a factor of around 5) with respect to monolithic alumina. Several mechanisms were proposed to explain the improvements in both mechanical properties and wear resistance. Compressive residual stress was found in the surface layer of Al2O3-FeAl2O4 nanocomposites due to the thermal expansion coefficient mismatch between surface layer and bulk parts. Such residual stress was also interpreted as the main reason for the improvements in both mechanical properties and wear resistance.

Keywords: nanocomposites
alumina
precipitation
mechanical properties
diffusion
Advisor: Todd, RI
A Framework for the semantic representation of energy policies related to electricity generation

Energy models are optimisation tools which aid in the formulation of energy policies. Built on mathematics, the strength of these models lie in their ability to process numerical data which in turn allows for the generation of an electricity generation mix that incorporates economic and the environmental aspects.
Nevertheless, a comprehensive formulation of an electricity generation mix should include aspects associated with politics and society, an evaluation of which requires the consideration of non-numerical qualitative information. Unfortunately, the use of energy models for optimisation coupled with the evaluation of information other than numerical data is a complicated task.
Two prerequisites must be fulfilled for energy models to consider political and societal aspects. First, the information associated with politics and society in the context of energy policies must be identified and defined. Second, a software tool which automatically converts both quantitative and qualitative data into mathematical expressions for optimisation is required.
We propose a software framework which uses a semantic representation based on ontologies. Our semantic representation contains both qualitative and quantitative data. The semantic representation is integrated into an Optimisation Modelling System which outputs a model consisting of a set of mathematical expressions. The system uses ontologies, engineering models, logic inference and linear programming.
To demonstrate our framework, a Prototype Energy Modelling System which accepts energy policy goals and targets as inputs and outputs an optimised electricity generation mix has been developed. To validate the capabilities of our prototype, a case study has been conducted. This thesis discusses the framework, prototype and case study.

Keywords: Energy Models
Knowledge Representation
Ontology
Advisor: Bañares-Alcántara, R
Computational modelling of vascular interventions: endovascular device deployment

Minimally invasive vascular interventions with stent deployment have become a popular alternative to conventional open surgery in the treatment of many vascular disorders. However, the high initial success rates of endovascular repairs have been overshadowed by reported complications that cause re-interventions and, in the worst case, morbidity and mortality. The dangerous complications could be mitigated by better choice of device design and by the appropriate positioning of the implant inside the vessel. However, there is currently no possibility for the interventionist to predict the resulting position and the expanded shape of the device for a given patient, before the actual procedure, within the clinical setting.
Motivated by this unmet clinical need and the lack of suitable methods, this thesis develops a methodology for modelling virtual deployment of implantable devices inside patient vessels, that features fast computational execution times and can be used in clinical practice. This novel deployment method was developed based on a spring-mass model and was tested in different deployment scenarios, expanding stents inside vessels in the order of seconds. Further, the performance of the novel method was optimised by calibrating a set of parameters with the help of a genetic algorithm, which utilises the outcomes of a finite element analysis as a learning reference. After the calibration, the developed stenting method demonstrated acceptable accuracy as compared to the "gold standard" of the finite element simulation. Finally, on a real patient case, 4 alternative stenting scenarios were investigated by comparing the subsequent blood flow conditions, via computational haemodynamics. The obtained results suggested that device design, dimensions, stiffness and positioning have important implications on the post-procedural haemodynamics of the vessel. Ultimately, the presented results can play a transformative role in aiding clinical decision-making and also give rise to overall improvements in implant design and deployment procedure.

Keywords: Virtual stenting
FEA
Stent deployment
Modelling
Genetic algorithm
Advisor: Ventikos, Y
Dislocations in semiconductors

A set of codes with 3D periodic boundary conditions has been developed to model dislocations in semiconductors. Several schemes have been used to investigate the atomic structure of dislocations; classical potentials incorporated in a Molecular Dynamics framework, a tightbinding k-space scheme and ab initio pseudopotential codes developed at Cambridge and Edinburgh.
An error has been detected in previous work that modelled dislocations using periodic boundary conditions. It is demonstrated, for the 90° and 30° Shockley partials, that a mismatch at the periodic boundaries leads to erroneous atomic and particularly electronic structures. A new approach is proposed which through its geometry obviates this problem.
The Stillinger Weber potential has been found to predict a completely new type of reconstruction for the 90° partial. Recent work by other authors confirms this and predicts significantly different results to earlier work. A thorough investigation has been made into the bonding processes involved in the core of the 90° partial. This study has involved reproducing much of the earlier work to understand why there has been such poor agreement between various authors. The reconstruction of the 90° partial is found to involve a symmetry lowering displacement intimately connected to its electronic structure. The band-gap is predicted to be clear of states, except for the possibility of shallow states at both band edges, which contradicts the findings of the most recent work on this partial by other authors.
The interaction of phosphorous with the 90° partial has been studied using the tightbinding model. The Hamiltonian has been parameterised by comparing the predictions to an earlier ab initio cluster method study. Good qualitative agreement with the ab initio work is obtained, including the prediction of a strong dislocation locking effect by phosphorous. Preliminary studies on the unreconstructed 30° partial show that phosphorous is strongly bound to the three-fold coordinated sites resulting in no states in the indirect band-gap.
The modelling of interstitial copper at the core of the 90° partial has been initiated. The ab initio codes have been used and new silicon and copper pseudopotentials tested. The first attempt to model copper located interstitially in the core was not successful and the reasons for this have been identified. However, it is evident from this investigation that the neutral copper strongly repels and does not form bonds with the surrounding silicon atoms.
A review is given of two techniques that have been developed to obtain the thermally averaged structure and concentration of vacancies at dislocations, together with a preliminary investigation on the Frank partial.

Advisor: Sutton, A