Inscription of in-fibre photonic devices by an infrared femtosecond laser

In this work, a point by point method for the inscription of fibre Bragg gratings using a tightly focused infrared femtosecond laser is implemented for the first time. Fibre Bragg gratings are wavelength-selective, retro-reflectors which have become a key component in optical communications as well as offering great potential as a sensing tool. Standard methods of fabrication are based on UV inscription in fibre with a photosensitive core. Despite the high quality of the gratings, a number of disadvantages are associated with UV inscription, in particular, the requirements of a photosensitive fibre, the low thermal stability and the need to remove the protective coating prior to inscription. By combining the great flexibility offered by the point by point method with the advantages inherent to inscription by an infrared femtosecond laser, the previous disadvantages are overcome. The method here introduced, allows a fast inscription process at a rate of ~1mm/s, gratings of lengths between 1cm and 2cm exhibiting reflections in excess of 99%. Physical dimensions of these gratings differ significantly from those inscribed by other methods, in this case the grating is confined to a fraction of the cross section of the core, leading to strong and controllable birefringence and polarisation dependent loss. Finally, an investigation of the potential for their exploitation towards novel applications is carried out, devices such as directional bend sensors inscribed in single-mode fibre, superimposed but non-overlapping gratings, and single-mode, single-polarisation fibre lasers, were designed, fabricated and characterised based on point by point femtosecond inscription.

The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells

Tissue transglutaminase (TG2) can induce post-translational modification of proteins, resulting in protein cross-linking or incorporation of polyamines into substrates, and can also function as a signal transducing G protein. The role of TG2 in the formation of insoluble cross-links has led to its implication in some neurodegenerative conditions. Exposure of pre-differentiated SH-SY5Y cells to the Parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) resulted in significant dose-dependent reductions in TG2 protein levels, measured by probing Western blots with a TG2-specific antibody. Transglutaminase (TG) transamidating activity, on the other hand, monitored by incorporation of a polyamine pseudo-substrate into cellular proteins, was increased. Inhibitors of TG (putrescine) and TG2 (R283) exacerbated MPP+ toxicity, suggesting that activation of TG2 may promote a survival response in this toxicity paradigm.

The cellular response to transglutaminase-cross-linked collagen

Collagen, type I, is a highly abundant natural protein material which has been cross-linked by a variety of methods including chemical agents, physical heating and UV irradiation with the aim of enhancing its physical characteristics such as mechanical strength, thermal stability, resistance to proteolytic breakdown, thus increasing its overall biocompatibility. However, in view of the toxicity of residual cross-linking agents, or impracticability at large scales, it would be more useful if the collagen could be cross-linked by a milder, efficient and more practical means by using enzymes as biological catalysts. We demonstrate that on treating native collagen type I (from bovine skin) with both tissue transglutaminase (TG2; tTG) and microbial transglutaminase (mTG; Streptoverticillium mobaraense) leads to an enhancement in cell attachment, spreading and proliferation of human osteoblasts (HOB) and human foreskin dermal fibroblasts (HFDF) when compared to culture on native collagen. The transglutaminase-treated collagen substrates also showed a greater resistance to cell-mediated endogenous protease degradation than the native collagen. In addition, the HOB cells were shown to differentiate at a faster rate than on native collagen when assessed by measurement of alkaline phosphatase activity and osteopontin expression. © 2005 Elsevier Ltd. All rights reserved.

Enzymatic stabilization of gelatin-based scaffolds

The definitive goal of this research is to develop protein-based scaffolds for use in soft tissue regeneration, particularly in the field of dermal healing. The premise of this investigation was to characterize the mechanical properties of gelatin cross-linked with microbial transglutaminase (mTGase) and to investigate the cytocompatibility of mTGase cross-linked gelatin. Dynamic rheological analysis revealed a significant increase in the storage modulus and thermal stability of gelatin after cross-linking with mTGase. Static, unconfined compression tests showed an increase in Young's modulus of gelatin gels after mTGase cross-linking. A comparable increase in gel strength was observed with 0.03% mTGase and 0.25% glutaraldehyde cross-linked gelatin gels. In vitro studies using 3T3 fibroblasts indicated cytotoxicity at a concentration of 0.05% mTGase after 72 h. However, no significant inhibition of cell proliferation was seen with cells grown on lower concentrations of mTGase cross-linked gelatin substrates. The mechanical improvement and cytocompatibility of mTGase cross-linked gelatin suggests mTGase has potential for use in stabilizing gelatin gels for tissue-engineering applications.

Synthesis and evaluation of novel ligands for quantum dot stabilisation and polymerisation studies

This thesis describes the design and synthesis of a variety of functionalised phosphine oxides and sulfides, based on the structure of trioctylphosphine oxide, synthesised for the purpose of surface modification of quantum dots. The ability of the ligands to modify the surface chemistry via displacement of the original hexadecylamine capping layer of quantum dots was evaluated. Finally the surface modified quantum dots were investigated for enhancement in their inherent properties and improved compatibility with the various applications for which they were initially designed. Upon the commencement of research involving quantum dots it became apparent that more information on their behaviour and interaction with the environment was required. The limits of the inherent stability of hexadecylamine capped quantum dots were investigated by exposure to a number of different environments. The effect upon the stability of the quantum dots was monitored by changes in the photoluminescence ability of their cores. Subtle differences between different batches of quantum dots were observed and the necessity to account for these in future applications noted. Lastly the displacement of the original hexadecylamine coating with the "designer" functionalised ligands was evaluated to produce a set of conditions that would result in the best possible surface modification. A general procedure was elucidated however it was discovered that each displacement still required slight adjustment by consideration of the other factors such as the difference in ligand structure and the individuality of the various batches of quantum dots. This thesis also describes a procedure for the addition of a protective layer to the surface of quantum dots by cross-linking the functionalised ligands bound to the surface via an acyclic diene metathesis polymerisation. A detailed description of the problems encountered in the analysis of these materials combined with the use of novel techniques such as diffusion ordered spectroscopy is provided as a means to overcome the limitations encountered. Finally a demonstration of the superior stability, upon exposure to a range of aggressive environments of these protected materials compared with those before cross-linking provided physical proof of the cross-linking process and the advantages of the cross-linking modification. Finally this thesis includes the presentation of initial work into the production of luminescent nanocrystal encoded resin beads for the specific use in solid phase combinatorial chemistry. Demonstration of the successful covalent incorporation of quantum dots into the polymeric matrices of non-functionalised and functionalised resin beads is described. Finally by preliminary work to address and overcome the possible limitations that may be encountered in the production and general employment of these materials in combinatorial techniques is given.

Making political films politically?:the film-making practice of Jean-Luc Godard

This thesis attempts to re-examine the work of Jean-Luc Godard and in particular the claims which have been made for it as the starting-point for a revolutionary cinema.This re-examination involves, firstly, a critical summary of the development of Structuralist thinking, from its origins in linguistics, with Saussure, through to its influence on Marxism, with Althusser. It is this `Structural Marxism' which prepared the ground for a view of Godard as a revolutionary film-maker so its influences on film theory in the decade after 1968 is traced in journals such as Cahiers du Cinéma and Screen and in the work of their editors and contributors. Godard's relationship with such theories was a complex one and some of the cross-breeding is revealed in a brief account of his own ideas about his film-making. More important, however is his practice as a committed `political' film-maker between 1968 and 1972 which is analysed in terms of the responses it makes to the cultural opportunities offered in the period after the revolutionary situation of May 1968. The severe problems revealed by that analysis may be partially resolved in Godard's greatest `political' achievement Tout va bien, but a comparative analysis proves that in earlier `a-political' films such as Vivre sa vie, he was creating more meaningful and perhaps even more revolutionary art, whose formal experimentation is more organically linked to its subject and whose ability to communicate ideas far oustrips the later work. In conclusion some indications are suggested of a more fruitful basis for Marxist theories of art than Structural variants, seeking a non-formalist approach in the work of Marx, of Trotsky, of Brecht and Lukacs.

Collaborative enterprise governance : sustainable management of inter-firm R&D relationships in the German car industry

This research reports on the appropriate governance, i.e. design and management, of inter-firm R&D relationships in order to achieve sustainable competitive success for the whole partnership as well as its individual members. An exploratory study in the German automotive industry using inductive Grounded Theory was conducted. This involved data collection via 28 semi-structured interviews with 16 companies in order to form a set of 35 tentative propositions that have been validated via a questionnaire survey receiving 110 responses from 52 companies. The research has resulted in the consolidation of the validated propositions into a novel concept termed Collaborative Enterprise Governance. The core of the concept is a competence based contingency framework that helps decision makers in selecting the most appropriate governance strategy (i.e. sourcing strategy) for an inter-firm R&D relationship between a buyer and its supplier. Thereby, the concept does not draw on whole company-to-company connectivity. It rather conceptualises an inter-firm relationship to be composed of autonomous cross-functional units of the individual partner companies that contribute value to a particular joint R&D project via the possession of task specific competencies. The novel concept and its elements have been evaluated in a focus group with industrial experts of the German automotive industry and revealed positive effects on the sustainable competitive success of the whole partnership and the individual partner companies. However, it also showed that current practice does not apply the right mechanisms for its implementation and hence guidelines for practitioners and decision makers involved in inter-firm R&D collaboration in the automotive industry are offered on how to facilitate the implementation and usage of the Collaborative Enterprise Governance philosophy.

An investigation into the network structures of eThylene propylene terpolymer elastomers

A series of ethylene propylene terpolymer vulcanizates, prepared by varying termonomer type, cure system, cure time and cure temperature, are characterized by determining the number and type of cross-links present. The termonomers used represent the types currently available in commercial quantities. Characterization is carried out by measuring the C1 constant of the Mooney Rivlin Saunders equation before and after treatment with the chemical probes propane-2-thiol/piperidine and n-hexane thiol/piperidine, thus making it possible to calculate the relative proportions of mono-sulphidic, di-sulphidic and poly- sulphidic cross-links. The cure systems used included both sulphur and peroxide formulations. Specific physical properties are determined for each network and an attempt is made to correlate observed changes in these with variations in network structure. A survey of the economics of each formulation based on a calculated efficiency parameter for each cure system is included. Values of C1 are calculated from compression modulus data after the reliability of the technique when used with ethylene propylene terpolymers had been established. This is carried out by comparing values from both compression and extension stress strain measurements for natural rubber vulcanizates and by assessing the effects of sample dimensions and the degree of swelling. The technique of compression modulus is much more widely applicable than previously thought. The basic structure of an ethylene propylene terpolymer network appears to be independent of the type of cure system used ( sulphur based systems only), the proportions of constituent cross-links being nearly constant.

A study of the scattering of fast neutrons in large samples

In the present work, the elastic scattering of fast neutrons from iron and concrete samples were studied at incident neutron energies of 14.0 and 14.4 Mev, using a neutron spectrometer based on the associated particle time-of-flight technique. These samples were chosen because of their importance in the design of fusion reactor shielding and construction. Using the S.A.M.E.S. accelerator and the 3 M v Dynamitron accelerator at the Radiation Centre, 14.0 and 14.4 Mev neutrons were produced by the T(d, n)4He reaction at incident deuteron energies of 140 keV and 900 keV mass III ions respectively. The time of origin of the neutron was determined by detecting the associated alpha particles. The samples used were extended flat plates of thicknesses up to 1.73 mean free paths for iron and 2.3 mean free paths for concrete. The associated alpha particles and fast neutrons were detected by means of a plastic scintillator mounted on a fast focused photomultiplier tube. The differential neutron elastic scattering cross-sections were measured for 14 Mev neutrons in various thicknesses of iron and concrete in the angular range from zero to 90°. In addition, the angular distributions of 14.4 Mev neutrons after passing through extended samples of iron were measured at several scattering angles in the same angular range. The measurements obtained for the thin sample of iron were compared with the results of Coon et al. The differential cross-sections for the thin iron sample were also analyzed on the optical model using the computer code RAROMP. For the concrete sample, the angular distribution of the thin sample was compared with the cross-sections calculated from the major constituent elements of concrete, and with the predicted values of the optical model for those elements. No published data could be found to compare with the results of the concrete differential cross-sections. In the case of thick samples of iron and concrete, the number of scattered neutrons were compared with a phenomological calculation based on the continuous slowing down model. The variation of measured cross-sections with sample thickness were found to follow the empirical relation σ = σ0 eαx. By using the universal constant "K", good fits were obtained to the experimental data. In parallel with the work at 14.0 and 14.4 Mev, an associated particle time-of-flight spectrometer was investigated which used the 2H(d,n)3He reaction for 3.02 Mev neutron energy at the incident deuteron energy of 1 Mev.

Possibilities and limitations of coded aperture imaging

We have simulated the performance of various apertures used in Coded Aperture Imaging - optically. Coded pictures of extended and continuous-tone planar objects from the Annulus, Twin Annulus, Fresnel Zone Plate and the Uniformly Redundant Array have been decoded using a noncoherent correlation process. We have compared the tomographic capabilities of the Twin Annulus with the Uniformly Redundant Arrays based on quadratic residues and m-sequences. We discuss the ways of reducing the 'd. c.' background of the various apertures used. The non-ideal System-Point-Spread-Function inherent in a noncoherent optical correlation process produces artifacts in the reconstruction. Artifacts are also introduced as a result of unwanted cross-correlation terms from out-of-focus planes. We find that the URN based on m-sequences exhibits good spatial resolution and out-of-focus behaviour when imaging extended objects.

Failure analysis of cold-formed steel sections

The purlin-sheeting system has been the subject of numerous theoretical and experimental investigations over the past 30 years, but the complexity of the problem has led to great difficulty in developing a sound and general model. The primary aim of the thesis is to investigate the failure behaviours of cold-formed zed and channel sections for use in purlin-sheeting systems. Both the energy method and finite strip method are used to develop an approach to investigate cold-formed zed and channel section beams with partial-lateral restraint from the metal sheeting when subjected to a uniformly distributed transverse load. The stress analysis of cold-formed zed and channel section beams with partially-lateral restraint from the metal sheeting when subjected to a uniformly distributed transverse load is investigated firstly by using the analytical model based on the energy method in which the restraint actions of the sheeting are modelled by using two springs representing the translational and rotational restraints. The numerical results have showed that the two springs have significantly different influences on the stresses of the beams. The influence of the two springs has also been found to depend on the anti-sag bar and the position of the loading line. A novel method is presented for analysing the elastic local buckling behaviour of cold-formed zed and channel section beams with partial-lateral restraint from metal sheeting when subjected to a uniformly distributed transverse load, which is carried out by inputting the cross sectional stresses with the largest compressive stress into the finite strip analysis. By using the presented novel method, individual influences of warning stress, partially lateral restraints from the sheeting and the dimensions of the cross section and position of the loading line on the buckling behaviour are investigated.

Mathematical modelling of patient risks in a hospital environment, using multiple regression analysis

The aim of this research work was primarily to examine the relevance of patient parameters, ward structures, procedures and practices, in respect of the potential hazards of wound cross-infection and nasal colonisation with multiple resistant strains of Staphylococcus aureus, which it is thought might provide a useful indication of a patient's general susceptibility to wound infection. Information from a large cross-sectional survey involving 12,000 patients from some 41 hospitals and 375 wards was collected over a five-year period from 1967-72, and its validity checked before any subsequent analysis was carried out. Many environmental factors and procedures which had previously been thought (but never conclusively proved) to have an influence on wound infection or nasal colonisation rates, were assessed, and subsequently dismissed as not being significant, provided that the standard of the current range of practices and procedures is maintained and not allowed to deteriorate. Retrospective analysis revealed that the probability of wound infection was influenced by the patient's age, duration of pre-operative hospitalisation, sex, type of wound, presence and type of drain, number of patients in ward, and other special risk factors, whilst nasal colonisation was found to be influenced by the patient's age, total duration of hospitalisation, sex, antibiotics, proportion of occupied beds in the ward, average distance between bed centres and special risk factors. A multi-variate regression analysis technique was used to develop statistical models, consisting of variable patient and environmental factors which were found to have a significant influence on the risks pertaining to wound infection and nasal colonisation. A relationship between wound infection and nasal colonisation was then established and this led to the development of a more advanced model for predicting wound infections, taking advantage of the additional knowledge of the patient's state of nasal colonisation prior to operation.

Spelling acquisition in English and Italian:a cross-linguistic study

We examined the spelling acquisition in children up to late primary school of a consistent orthography (Italian) and an inconsistent orthography (English). The effects of frequency, lexicality, length, and regularity in modulating spelling performance of the two groups were examined. English and Italian children were matched for both chronological age and number of years of schooling. Two-hundred and seven Italian children and 79 English children took part in the study. We found greater accuracy in spelling in Italian than English children: Italian children were very accurate after only 2 years of schooling, while in English children the spelling performance was still poor after 5 years of schooling. Cross-linguistic differences in spelling accuracy proved to be more persistent than the corresponding ones in reading accuracy. Orthographic consistency produced not only quantitative, but also qualitative differences, with larger frequency and regularity effects in English than in Italian children.

A copper-hydrogen peroxide redox system induces dityrosine cross-links and chemokine oligomerisation

The activity of the chemoattractant cytokines, the chemokines, in vivo is enhanced by oligomerisation and aggregation on glycosaminoglycan (GAG), particularly heparan sulphate, side chains of proteoglycans. The chemokine RANTES (CCL5) is a T-lymphocyte and monocyte chemoattractant, which has a minimum tetrameric structure for in vivo activity and a propensity to form higher order oligomers. RANTES is unusual among the chemokines in having five tyrosine residues, an amino acid susceptible to oxidative cross-linking. Using fluorescence emission spectroscopy, Western blot analysis and LCMS-MS, we show that a copper/H2O2 redox system induces the formation of covalent dityrosine cross-links and RANTES oligomerisation with the formation of tetramers, as well as higher order oligomers. Amongst the transition metals tested, namely copper, nickel, mercury, iron and zinc, copper appeared unique in this respect. At high (400 µM) concentrations of H2O2, RANTES monomers, dimers and oligomers are destroyed, but heparan sulphate protects the chemokine from oxidative damage, promoting dityrosine cross-links and multimer formation under oxidative conditions. Low levels of dityrosine cross-links were detected in copper/H2O2-treated IL-8 (CXCL8), which has one tyrosine residue, and none were detected in ENA-78 (CXCL5), which has none. Redox-treated RANTES was fully functional in Boyden chamber assays of T-cell migration and receptor usage on activated T-cells following RANTES oligomerisation was not altered. Our results point to a protective, anti-oxidant, role for heparan sulphate and a previously unrecognised role for copper in chemokine oligomerisation that may offer an explanation for the known anti-inflammatory effect of copper-chelators such as penicillamine and tobramycin.

Organizing innovation:complementarities between cross-functional teams

Cross-functional teams play a potentially important part in the innovation process enabling knowledge sharing, the development of trust and overcoming spatial and organizational barriers. Using a supermodularity approach, we focus on potential complementarities which may arise when cross-functional teams are used in different elements of the innovation process in UK and German manufacturing plants. Using optimal combinations of cross-functional teams in the innovation process increases innovation success in the UK by 29.5 per cent compared to 9.5 per cent in Germany. Patterns of complementarity are complex, however, but are more uniform in the UK than in Germany. The most uniform complementarities are between product design and development and production engineering, with little synergy evident between the more technical phases of the innovation process and the development of marketing strategy. In strategic terms, our results suggest the value of using cross-functional teams for the more technical elements of the innovation process but that the development of marketing strategy should remain the domain of specialists.