Suppression and summation in contrast gain control for human vision

Over the last ten years our understanding of early spatial vision has improved enormously. The long-standing model of probability summation amongst multiple independent mechanisms with static output nonlinearities responsible for masking is obsolete. It has been replaced by a much more complex network of additive, suppressive, and facilitatory interactions and nonlinearities across eyes, area, spatial frequency, and orientation that extend well beyond the classical recep-tive field (CRF). A review of a substantial body of psychophysical work performed by ourselves (20 papers), and others, leads us to the following tentative account of the processing path for signal contrast. The first suppression stage is monocular, isotropic, non-adaptable, accelerates with RMS contrast, most potent for low spatial and high temporal frequencies, and extends slightly beyond the CRF. Second and third stages of suppression are difficult to disentangle but are possibly pre- and post-binocular summation, and involve components that are scale invariant, isotropic, anisotropic, chromatic, achromatic, adaptable, interocular, substantially larger than the CRF, and saturated by contrast. The monocular excitatory pathways begin with half-wave rectification, followed by a preliminary stage of half-binocular summation, a square-law transducer, full binocular summation, pooling over phase, cross-mechanism facilitatory interactions, additive noise, linear summation over area, and a slightly uncertain decision-maker. The purpose of each of these interactions is far from clear, but the system benefits from area and binocular summation of weak contrast signals as well as area and ocularity invariances above threshold (a herd of zebras doesn't change its contrast when it increases in number or when you close one eye). One of many remaining challenges is to determine the stage or stages of spatial tuning in the excitatory pathway.

Cells, surfaces and adhesion

This thesis concerns cell adhesion to polymer surfaces with an experimental emphasis on hydrogels. The thesis begins with a review of the literature and a synthesis of recent evidence to describe the process of cell adhesion in a given situation. The importance of understanding integrin-adhesion protein interactions and adhesion protein-surface interactions is emphasised. The experimental chapters describe three areas of investigation. Firstly, in vitro cell culture techniques are used to explore a variety of surfaces including polyethylene glycol methacrylate (PEGMA) substituted hydrogels, sequence distribution modified hydrogels and worn contact lenses. Cell adhesion to PEGMA substituted gels is found to decrease with increases in polyethylene oxide chain length and correlations are made between sequence distribution and adhesion. Worn contact lenses are investigated for their cell adhesion properties in the presence of antibodies to specific adhesion proteins, demonstrating the presence of vitronectin and fibronectin on the lenses. The second experimental chapter addresses divalent cation regulation of integrin mediated cell adhesion. Several cell types and various cations are used. Zinc, previously not regarded as an important cation in the process, is found to inhibit 3T3 cell adhesion to vitronectin that is promoted by other divalent cations. The final experimental chapter concerns cell adhesion and growth on macroporous hydrogels. A variety of freeze-thaw formed porous gels are investiated and found generally to promote cell growth rate.Interpenetrating networkbased gels (IPN) are made porous by elution of dextrin particles of varying size and loading density. These materials provide the basis for synthetic cartilage. Cartilage cells (chondrocytes) plated onto the surface of the porous IPN materials maintain a rounded shape and hence phenotypic function when a critical pore size and density is achieved. In this way, a prospective implant, made porous at the perpendicular edges contacting natural cartilage can be both mechanically stabilised and encourage the maintenance of normal matrix production at the tissue interface.

Translation elongation factor 1A is essential for regulation of the actin cytoskeleton and cell morphology

The binding of eukaryotic translation elongation factor 1A (eEF1A) to actin is a noncanonical function that may link two distinct cellular processes, cytoskeleton organization and gene expression. Using the yeast Saccharomyces cerevisiae, we have established an in vivo assay that directly identifies specific regions and residues of eEF1A responsible for actin interactions and bundling. Using a unique genetic screen, we isolated a series of eEF1A mutants with reduced actin bundling activity. These mutations alter actin cytoskeleton organization but not translation, indicating that these are separate functions of eEF1A. This demonstrates for the first time a direct consequence of eEF1A on cytoskeletal organization in vivo and the physiological significance of this interaction.

TRial of an Educational intervention on patients' knowledge of Atrial fibrillation and anticoagulant therapy, INR control, and outcome of Treatment with warfarin (TREAT)

Background Atrial fibrillation (AF) patients with a high risk of stroke are recommended anticoagulation with warfarin. However, the benefit of warfarin is dependent upon time spent within the target therapeutic range (TTR) of their international normalised ratio (INR) (2.0 to 3.0). AF patients possess limited knowledge of their disease and warfarin treatment and this can impact on INR control. Education can improve patients' understanding of warfarin therapy and factors which affect INR control. Methods/Design Randomised controlled trial of an intensive educational intervention will consist of group sessions (between 2-8 patients) containing standardised information about the risks and benefits associated with OAC therapy, lifestyle interactions and the importance of monitoring and control of their International Normalised Ratio (INR). Information will be presented within an 'expert-patient' focussed DVD, revised educational booklet and patient worksheets. 200 warfarin-naïve patients who are eligible for warfarin will be randomised to either the intervention or usual care groups. All patients must have ECG-documented AF and be eligible for warfarin (according to the NICE AF guidelines). Exclusion criteria include: aged < 18 years old, contraindication(s) to warfarin, history of warfarin USE, valvular heart disease, cognitive impairment, are unable to speak/read English and disease likely to cause death within 12 months. Primary endpoint is time spent in TTR. Secondary endpoints include measures of quality of life (AF-QoL-18), anxiety and depression (HADS), knowledge of AF and anticoagulation, beliefs about medication (BMQ) and illness representations (IPQ-R). Clinical outcomes, including bleeding, stroke and interruption to anticoagulation will be recorded. All outcome measures will be assessed at baseline and 1, 2, 6 and 12 months post-intervention. Discussion More data is needed on the clinical benefit of educational intervention with AF patients receiving warfarin. Trial registration ISRCTN93952605

A longitudinal study of the diffusion of the ISO/IEC information resource dictionary system standard (IRDS.)

The IRDS standard is an international standard produced by the International Organisation for Standardisation (ISO). In this work the process for producing standards in formal standards organisations, for example the ISO, and in more informal bodies, for example the Object Management Group (OMG), is examined. This thesis examines previous models and classifications of standards. The previous models and classifications are then combined to produce a new classification. The IRDS standard is then placed in a class in the new model as a reference anticipatory standard. Anticipatory standards are standards which are developed ahead of the technology in order to attempt to guide the market. The diffusion of the IRDS is traced over a period of eleven years. The economic conditions which affect the diffusion of standards are examined, particularly the economic conditions which prevail in compatibility markets such as the IT and ICT markets. Additionally the consequences of the introduction of gateway or converter devices into a market where a standard has not yet been established is examined. The IRDS standard did not have an installed base and this hindered its diffusion. The thesis concludes that the IRDS standard was overtaken by new developments such as object oriented technologies and middleware. This was partly because of the slow development process of developing standards in traditional organisations which operate on a consensus basis and partly because the IRDS standard did not have an installed base. Also the rise and proliferation of middleware products resulted in exchange mechanisms becoming dominant rather than repository solutions. The research method used in this work is a longitudinal study of the development and diffusion of the ISO/EEC IRDS standard. The research is regarded as a single case study and follows the interpretative epistemological point of view.

Investigating Turkey's national innovation and learning system

The national systems of innovation (NIS) approach focuses on the patterns and the determinants of innovation processes from the perspective of nation-states. This paper reports on continuing work on the application of an NIS model to the development of technological capability in Turkey. Initial assessment of the literature shows that there are a number of alternative conceptualisations of NIS. An attempt by the Government to identify a NIS for Turkey shows the main actors in the system but does not pay sufficient attention to the processes of interactions between agents within the system. An operational model should be capable of representing these processes and interactions and assessing the strengths and weaknesses of the NIS. For industrialising countries, it is also necessary to incorporate learning mechanisms into the model. Further, there are different levels of innovation and capability in different sectors which the national perspective may not reflect. This paper is arranged into three sections. The first briefly explains the basics of the national innovation and learning system. Although there is no single accepted definition of NIS, alternative definitions reviewed share some common characteristics. In the second section, an NIS model is applied to Turkey in order to identify the elements, which characterise the country’s NIS. This section explains knowledge flow and defines the relations between the actors within the system. The final section draws on the “from imitation to innovation” model apparently so successful in East Asia and assesses its applicability to Turkey. In assessing Turkey’s NIS, the focus is on the automotive and textile sectors.

Strategy and control systems:a framework for analysis

This research explores the links between the strategies adopted by companies and the mechanisms used to control the organisation. This is not seen as a one way process with the control system following from the strategy but rather as an interactive process between the control systems, the environment and the business strategy. The main proposition of the research, derived from a review of the relevant literature, is that the dimensions of Business Pro-Activity and Environmental Change provide a plausible explanation of the reasons why companies need to adopt different strategies in order to be successful in different markets. A model is proposed which links these dimensions with the business strategy, organisational structure, strategic planning system and management control systems. The model is used as a framework for analysing four companies in order to further our understanding of these interactions and the mechanisms which act to both promote and resist change. Whilst it is not suggested that the model in its present form is a perfect instrument it has, during the course of this research, proved to be an appropriate framework for analysing the various mechanisms used by four companies to formulate and implement their strategies. The research reveals that these should not be viewed independently but as a balanced system.

The impact of the introduction of visual display terminals on the job characteristics, job satisfaction and well-being of users in government offices

The proliferation of visual display terminals (VDTs) in offices is an international phenomenon. Numerous studies have investigated the health implications which can be categorised into visual problems, symptoms of musculo-skelctal discomfort, or psychosocial effects. The psychosocial effects are broader and there is mixed evidence in this area. The inconsistent results from the studies of VDT work so far undertaken may reflect several methodological shortcomings. In an attempt to overcome these deficiencies and to broaden the model of inter-relationships a model was developed to investigate their interactions and Ihc outputs of job satisfaction, stress and ill health. The study was a two-stage, long-term investigation with measures taken before the VDTs were introduced and the same measures taken 12 months after the 'go-live' date. The research was conducted in four offices of the Department of Social Security. The data were analysed for each individual site and in addition the total data were used in a path analysis model. Significant positive relationships were found at the pre-implementation stage between the musculo-skeletal discomfort, psychosomatic ailments, visual complaints and stress. Job satisfaction was negatively related to visual complaints and musculo-skeletal discomfort. Direct paths were found for age and job level with variety found in the job and age with job satisfaction and a negative relationship with the office environment. The only job characteristic which had a direct path to stress was 'dealing with others'. Similar inter-relationships were found in the post-implementation data. However, in addition attributes of the computer system, such as screen brightness and glare, were related positively with stress and negatively with job satisfaction. The comparison of the data at the two stages found that there had been no significant changes in the users' perceptions of their job characteristics and job satisfaction but there was a small and significant reduction in the stress measure.

Chemical synthesis of DNA and RNA containing thio-substituted bases and their post-synthetic modifications

Modified oligonucleotides containing sulphur group have been useful tools for studies of carcinogenesis, protein or nucleic acid structures and functions, protein-nucleic acid interactions, and for antisense modulation of gene expression. One successful example has been the synthesis and study of oligodeoxynucleotides containing 6-thio-2'-deoxyguanine. 6-Thio-2-deoxyguanosine was first discovered as metabolic compound of 6- mercaptopurine (6-MP). Later, it was applied as drug to cure leukaemia. During the research of its toxicity, a method was developed to use the sulphur group as a versatile position for post-synthetic modification. The advantage of application of post-synthetic modification lies in its convenience. Synthesis of oligomers with normal sequences has become routine work in most laboratories. However, design and synthesis of a proper phosphoramidite monomer for a new modified nucleoside are always difficult tasks even for a skilful chemist. Thus an alternative method (post-synthetic method) has been invented to overcome the difficulties. This was achieved by incorporation of versatile nucleotides into oligomers which contain a leaving group, that is sufficiently stable to withstand the conditions of synthesis but can be substituted by nucleophiles after synthesis, to produce, a series of oligomers each containing a different modified base. In the current project, a phosphoramidite monomer with 6-thioguanine has been successfully synthesised and incorporated into RNA. A deprotection procedure, which is specific for RNA was designed for oligomers containing 6-thioguanosine. The results were validated by various methods (UV, HPLC, enzymatic digestion). Pioneer work in utilization of the versatile sulphur group for post-synthetic modification was also tested. Post-synthetic modification was also carried out on DNA with 6- deoxythioguanosine. Electrophilic reagents with various functional groups (alphatic, aromatic, fluorescent) and bi-functional groups have been attached with the oligomers.

Studies of molecular interactions using physical techniques

The investigations described in this thesis concern the molecular interactions between polar solute molecules and various aromatic compounds in solution. Three different physical methods were employed. Nuclear magnetic resonance (n.m.r.) spectroscopy was used to determine the nature and strength of the interactions and the geometry of the transient complexes formed. Cryoscopic studies were used to provide information on the stoichiometry of the complexes. Dielectric constant studies were conducted in an attempt to confirm and supplement the spectroscopic investigations. The systems studied were those between nitromethane, chloroform, acetonitrile (solutes) and various methyl substituted benzenes. In the n.m.r. work the dependence of the solute chemical shift upon the compositions of the solutions was determined. From this the equilibrium quotients (K) for the formation of each complex and the shift induced in the solute proton by the aromatic in the complex were evaluated. The thermodynamic parameters for the interactions were obtained from the determination of K at several temperatures. The stoichiometries of the complexes obtained from cryoscopic studies were found to agree with those deduced from spectroscopic investigations. For most systems it is suggested that only one type of complex, of 1:1 stiochiometry, predominates except that for the acetonitrile-benzene system a 1:2 complex is formed. Two sets of dielectric studies were conducted, the first to show that the nature of the interaction is dipole-induced dipole and the second to calculate K. The equilibrium quotients obtained from spectroscopic and dielectric studies are compared. Time-averaged geometries of the complexes are proposed. The orientation of solute, with respect to the aromatic for the 1:1 complexes, appears to be the one in which the solute lies symmetrically about the aromatic six-fold axis whereas for the 1:2 complex, a sandwich structure is proposed. It is suggested that the complexes are formed through a dipole-induced dipole interaction and steric factors play some part in the complex formation.

Acquisition and management of technology in Malaysian companies

This thesis is about the acquisition and diffusion of imported technology. Writers in the field of technology development in developing countries have always recognised that technical progress depends on the diffusion of imported technology and its applications to the provision of products and processes (Rosemberg, 1982). Despite the massive importation of technology by Malaysian companies, little effort has been made to study and understand the diffusion system in local companies. This study analyses: The problems associated with the acquisition of technology, highlighting the technology strategies adopted by the suppliers of technology; the diffusion pattern and key characteristics of the diffusion process; and major factors affecting the diffusion of technology. The policy implications are examined and the framework to manage the diffusion process within the enterprises is suggested. The findings indicated that the diffusion process is not one of passive acceptance but involves systematic efforts to acquire and diffuse the imported technology. A strong system of diffusion in companies had enabled a rapid diffusion of imported technology resulting in higher levels of technical capability. On the other hand, weakness in the company's diffusion system led to limited diffusion and slow technical progress. Characteristics of diffusion system are analysed and discussed extensively. The thesis attempts to develop the idea of `in-house system of diffusion' associated with the acquisition and development of imported technology. It argues for the development ofa stronger theoretical framework on the diffusion and development of technology particularly in countries like Malaysia which relies extensively on the importation of foreign technology.

Alginates as therapeutic and drug delivery systems

Alginate is widely used as a viscosity enhancer in many different pharmaceutical formulations. The aim of this thesis is to quantitatively describe the functions of this polyelectrolyte in pharmaceutical systems. To do this the techniques used were Viscometry, Light Scattering, Continuous and Oscillatory Shear Rheometry, Numerical Analysis and Diffusion. Molecular characterization of the Alginate was carried out using Viscometry and Light Scattering to determine the molecular weight, the radius of gyration, the second virial coefficient and the Kuhn statistical segment length. The results showed good agreement with similar parameters obtained in previous studies. By blending Alginate with other polyelectrolytes, Xanthan Gum and 'Carbopol', in various proportions and with various methods of low and high shear preparation, a very wide range of dynamic rheological properties was found. Using oscillatory testing, the parameters often varied over several decades of magnitude. It was shown that the determination of the viscous and elastic components is particularly useful in describing the rheological 'profiles' of suspending agent blends and provides a step towards the non-empirical formulation of pharmaceutical disperse systems. Using numerical analysis of equations describing planar diffusion, it was shown that the analysis of drug release profiles alone does not provide unambiguous information about the mechanism of rate control. These principles were applied to the diffusion of Ibuprofen in Calcium Alginate gels. For diffusion in such non-Newtonian systems, emphasis was placed on the use of the elastic as well as the viscous component of viscoelasticity. It was found that the diffusion coefficients were relatively unaffected by increases in polymer concentration up to 5 per cent, yet the elasticities measured by oscillatory shear rheometry were increased. This was interpreted in the light of several theories of diffusion in gels.

Properties and performance of polymer modified cements and mortars

Polymer modified cements and mortars have become popular for use as patch repair materials. General evidence suggests that these materials offer considerable improvements compared to traditional mortars although the mechanisms for this are not fully understood. This work elucidates the factors which govern some properties and performance of different polymer systems. In view of the wide range of commercial systems available, investigations concentrated on the use of three of the most commonly available groups of polymers. These were: (1) Styrene Butadiene Rubber (SBR), (2) Acrylics and, (3) Ethylene Vinyl Acetates (EVA). The later two were in the form of both emulsions and redispersible powders. Experiments concentrated on: (1) Rheological behaviour of polymer modified cement pastes; (2) Workability of polymer modified mortars; (3) Influence of curing conditions on the pore size distribution and diffusion of chloride ions; (4) Bond strength of polymer modified cement and mortar patches; and (5) Microscopic examination and semi-quantitative analyses of the bulk and interfacial microstructures. The following main conclusions were reached: (1) The addition of polymer emulsions have a considerable influence on the workability of fresh cement pastes, the extent of this depending on the type of system used. (2) The rheological parameters of fresh polymer modified mortars can be established using a two-point workability test which may be used when comparing the properties of different systems at constant workability. (3) Curing conditions affect the properties of polymer modified systems and a wet/dry curing regime was essential for good adhesion of these materials to mortar substrates. (4) In contrast, the wet/dry curing regime resulted in a curing affected zone at the surface of patch materials. This can result in a much coarser pore structure and enhanced diffusion of e.g. chloride ions. (5) The microstructure of polymer modified systems was very different compared with the unmodified cement/mortar and varied depending on curing conditions.

Ground cracking and frost heaving associated with chilled gas pipeline operations in Britain

This thesis investigates the soil-pipeline interactions associated with the operation of large-diameter chilled gas pipelines in Britain, these are frost/pipe heave and ground cracking. The investigation was biased towards the definition of the mechanism of ground cracking and, the parameters which influence its generation and subsequent development, especially its interaction with frost heave. The study involved a literature review, questionnaire, large-scale test and small-scale laboratory model experiments. The literature review concentrated on soil-pipeline interactions and frost action, with frost/pipe heave often reported but ground cracking was seldom reported. A questionnaire was circulated within British Gas to gain further information on these interactions. The replies indicated that if frost/pipe heave was reported, ground cracking was also likely to be observed. These soil-pipeline interactions were recorded along 19% of pipelines in the survey and were more likely along the larger diameter, higher flow pipelines. A large-scale trial along a 900 mm pipeline was undertaken to assess the soil thermal, hydraulic and stress regimes, together with pipe and ground movements. Results indicated that cracking occurred intermittently along the pipeline during periods of rapid frost/pipe heave and ground movement and, that frozen annulus growth produced a ground surface profile was approximated by a normal probability distribution curve. This curve indicates maximum tensile strain directly over the pipe centre. Finally a small-scale laboratory model was operated to further define the ground cracking mechanism. Ground cracking was observed at small upward ground surface movement, and with continued movement the ground crack increased in width and depth. At the end of the experiments internal soil failure planes slanting upwards and away from the frozen annulus were noted. The suggested mechanism for ground cracking involved frozen annulus growth producing tensile strain in the overlying unfrozen soil, which when sufficient produced a crack.

From postgraduate student to published writer:discourse variation and development in TESOL

This thesis is part of a project whose overall aim is to assist participants on an MSc TESOL course who wish to begin to publish articles in the field to do so. The project, which is undertaken within a naturalistic paradigm, has two intimately related and mutually constitutive strands: one descriptive, one interventionist. The descriptive strand consists of an analytical model of the TESOL article genre, and it is instantiated in this thesis. The interventionist strand consists of a series of pedagogic interactions and materials intended to assist project participants formulate a text suitable for publication within the target genre, and it is reported on in this thesis. I begin the thesis by looking in detail at the research approach which characterises the project. I then attempt to explain the situational context of the work and to position it within the context of other research in the areas of discourse community membership, academic genres, genre learning and academic enculturation. Having thus contextualised the work, I next attempt a detailed exploration of the problems of postgraduate students in TESOL when first attempting to write in the TESOL article genre: this exploration is undertaken from both a linguistic and a pedagogic perspective. Then in subsequent chapters, both a linguistic and a pedagogic response to these problems are proposed: the first consisting of an analytical model of the target genre, the second consisting of a series of pedagogic interactions and materials. The relationships between the two lines of response are also examined in some detail. Then in the final part of the thesis, I report feedback from the interventionist strand and attempt to conduct an evaluation of the whole project to date. Criteria for evaluation are proposed and examined in some detail in the context of the research approach of the project. The concluding chapter is a brief discussion of future directions for this work.