Generation of primary hepatocyte microarrays by piezoelectric printing

We demonstrate a single-step method for the generation of collagen and poly-l-Lysine (PLL) micropatterns on a poly(ethylene glycol) (PEG) functionalized glass surface for cell based assays. The method involves establishing a reliable silanization method to create an effective non-adhesive PEG layer on glass that inhibits cell attachment, followed by the spotting of collagen or PLL solutions using non-contact piezoelectric printing. We show for the first time that the spotted protein micropatterns remain stable on the PEG surface even after extensive washing, thus significantly simplifying protein pattern formation. We found that adherence and spreading of NIH-3T3 fibroblasts was confined to PLL and collagen areas of the micropatterns. In contrast, primary rat hepatocytes adhered and spread only on collagen micropatterns, where they formed uniform, well defined functionally active cell arrays. The differing affinity of hepatocytes and NIH-3T3 fibroblasts for collagen and PLL patterns was used to develop a simple technique for creating a co-culture of the two cell types. This has the potential to form structured arrays that mimic the in vivo hepatic environment and is easily integrated within a miniaturized analytical platform for developing high throughput toxicity analysis in vitro.

Dynamic simulation of chemical processes

This thesis describes the design and implementation of an interactive dynamic simulator called DASPRII. The starting point of this research has been an existing dynamic simulation package, DASP. DASPII is written in standard FORTRAN 77 and is implemented on universally available IBM-PC or compatible machines. It provides a means for the analysis and design of chemical processes. Industrial interest in dynamic simulation has increased due to the recent increase in concern over plant operability, resiliency and safety. DASPII is an equation oriented simulation package which allows solution of dynamic and steady state equations. The steady state can be used to initialise the dynamic simulation. A robust non linear algebraic equation solver has been implemented for steady state solution. This has increased the general robustness of DASPII, compared to DASP. A graphical front end is used to generate the process flowsheet topology from a user constructed diagram of the process. A conversational interface is used to interrogate the user with the aid of a database, to complete the topological information. An original modelling strategy implemented in DASPII provides a simple mechanism for parameter switching which creates a more flexible simulation environment. The problem description generated is by a further conversational procedure using a data-base. The model format used allows the same model equations to be used for dynamic and steady state solution. All the useful features of DASPI are retained in DASPII. The program has been demonstrated and verified using a number of example problems, Significant improvements using the new NLAE solver have been shown. Topics requiring further research are described. The benefits of variable switching in models has been demonstrated with a literature problem.

Studies on the generalisation of Gaussian processes and Bayesian neural networks

The assessment of the reliability of systems which learn from data is a key issue to investigate thoroughly before the actual application of information processing techniques to real-world problems. Over the recent years Gaussian processes and Bayesian neural networks have come to the fore and in this thesis their generalisation capabilities are analysed from theoretical and empirical perspectives. Upper and lower bounds on the learning curve of Gaussian processes are investigated in order to estimate the amount of data required to guarantee a certain level of generalisation performance. In this thesis we analyse the effects on the bounds and the learning curve induced by the smoothness of stochastic processes described by four different covariance functions. We also explain the early, linearly-decreasing behaviour of the curves and we investigate the asymptotic behaviour of the upper bounds. The effect of the noise and the characteristic lengthscale of the stochastic process on the tightness of the bounds are also discussed. The analysis is supported by several numerical simulations. The generalisation error of a Gaussian process is affected by the dimension of the input vector and may be decreased by input-variable reduction techniques. In conventional approaches to Gaussian process regression, the positive definite matrix estimating the distance between input points is often taken diagonal. In this thesis we show that a general distance matrix is able to estimate the effective dimensionality of the regression problem as well as to discover the linear transformation from the manifest variables to the hidden-feature space, with a significant reduction of the input dimension. Numerical simulations confirm the significant superiority of the general distance matrix with respect to the diagonal one.In the thesis we also present an empirical investigation of the generalisation errors of neural networks trained by two Bayesian algorithms, the Markov Chain Monte Carlo method and the evidence framework; the neural networks have been trained on the task of labelling segmented outdoor images.

Managerial cognitions in technological innovation processes:a study of interpretative processes

In this research, conceptualizations of the links between technological innovation and organizational change are explored and recommendations in the literature concerning such changes are reviewed and criticized. Such recommendations do not usually address the details of social interactions by which organizational changes take place. As a consequence, the issue of how these recommendations become relevant for the actors who would carry them out is not addressed. The complexity of organizational change processes highlights the role of actors' interpretations of organizational reality. Interpretations take place through the use of language in the interaction between actors. Theoretical contributions and recommendations concerning organizational changes should be seen therefore as discourses which contribute to these interpretations. They will influence the process of change only if they become relevant for organizational actors'. A method for analysing discourse in organizations is presented. It is used to identify the variety of discourses which are put forward in organizations, and to describe the structure of their distribution among actors. The structures of discourses in three companies suggest that knowledge about technological innovation processes becomes relevant to the extent that it contributes to political/discursive processes maintained by actors attempting to secure or change their role definitions. It follows that recommendations concerning planned organizational change should take into account these processes explicitly. It is therefore suggested that the analysis of discourse can be a valuable instrument for monitoring change processes. Suggestions for further research are made, concerning (i) the development of the method itself and its use in real situations (ii) the study of how discourse structures evolve over time and episodes of change.

Generation of nitric oxide and its protective and toxic actions in the gastrointestinal tract

Nitric oxide is a free-radical gas which can exert both protective and damaging effects. The objectives of the thesis were: (i) to investigate arginine metabolism in isolated rat gastric mucosal cells, (ii) to investigate the role of NO in the induction of ornithine decarboxylase in the rat gastric mucosa damaged by hypertonic saline in vivo, (iii) to expose primary cultures of guinea-pig gastric mucosal cells to oxidative challenge and an NO donor, and to investigate the response in terms of heat shock protein 72 (HSP 72) induction, and (iv) to investigate the induction of iNOS and the role of potential modulators of activity in gastric cell lines. Isolated rat gastric mucosal cells converted exogenous arginine to ornithine and citrulline. This metabolism of arginine was not affected by a range of NO synthase inhibitors, but was reduced by the arginase inhibitors NG-hydroxy-L-arginine and L-ornithine. Thus, the predominant pathway of arginine metabolism involves arginase and ornithine transcarbamoylase, not NO synthase. Pretreatment of rats with NG-nitro-L-arginine promoted activation of ornithine decarboxylase after intragastric hypertonic saline, but did not increase acid phosphatase release (damage). NO may therefore restrict activation of ornithine decarboxylase in response to damage. Exposure of primary cultures of guinea-pig gastric mucosal cells to S-nitroso-N-acetyl-penicillamine (SNAP) caused a concentration dependent induction of HSP 72, which was inhibited by an NO scavenger and blockade of transcription. The effect of SNAP was enhanced by decreasing the intracellular reduced thiol content with diethyl maleate, which itself also induced HSP 72 formation. Substantial amounts of NO may induce defensive responses in cells. Induction of iNOS was not detected in HGT-1 or AGS cells exposed to cytokines. Conclusions An arginase pathway may restrict availability of arginine for NO synthase in gastric mucosa or may be present to supply ornithine for polyamine synthesis. NO may modulate the response to damage of the stomach epithelium in vivo. Exogenous NO may induce a defensive response in gastric mucosal cells.

Generation of infrared surface plasmon resonances with high refractive index sensitivity utilizing tilted fiber Bragg gratings

We demonstrate the use of tilted fiber gratings to assist the generation of localized infrared surface plasmons with short propagation lengths and a sensitivity of d lambda/dn = 3365 nm in the aqueous index regime. It was also found that the resonances could be spectrally tuned over 1000 nm at the same spatial region with high coupling efficiency (in excess of 25 dB) by altering the polarization of the light illuminating the device.

Generation of spatial subharmonic gratings in the absence of photorefractive beam coupling

Using a new experimental geometry, we have proved for the first time that the generation of spatial subharmonic gratings in photorefractive crystals is not dependent on optical nonlinearity. We present results which confirm that the subharmonic gratings result from a parametric excitation of ultra low-frequency eigenmodes of a crystal by a time modulated fundamental grating.

Investigative framework for research into the design of manufacturing processes

This paper is based a major research project run by a team from the Innovation, Design and Operations Management Research Unit at the Aston Business School under SERC funding. International Computers Limited (!CL), the UK's largest indigenous manufacturer of mainframe computer products, was the main industrial collaborator in the research. During the period 1985-89 an integrated production system termed the "Modular Assembly Cascade'' was introduced to the Company's mainframe assembly plant at Ashton-under-Lyne near Manchester. Using a methodology primarily based upon 'participative observation', the researchers developed a model for analysing this manufacturing system design called "DRAMA". Following a critique of the existing literature on Manufacturing Strategy, this paper will describe the basic DRAMA model and its development from an industry specific design methodology to DRAMA II, a generic model for studying organizational decision processes in the design and implementation of production systems. From this, the potential contribution of the DRAMA model to the existing knowledge on the process of manufacturing system design will be apparent.

Delegation and employee work outcome:an examination of the cultural context of mediating processes in China

We used cultural self-representation theory to develop a model of the processes linking delegation to work outcomes. We tested this model with data from a sample of 171 subordinate-supervisor dyads from the People's Republic of China. Regression results revealed that organization-based self-esteem and perceived insider status fully mediated the influence of delegation on affective organizational commitment, task performance, and innovative behavior and partially mediated delegation's influence on job satisfaction. Furthermore, traditionality moderated the relationships between delegation and the mediators in such a way that the relationships were stronger for individuals lower rather than higher in traditionality. © Academy of Management Journal.

Generation of triangular-shaped optical pulses in normally dispersive fibre

We determine through numerical modelling the conditions for the generation of triangular-shaped optical pulses in a nonlinear, normally dispersive (ND) fibre and experimentally demonstrate triangular pulse formation in conventional ND fibre.

Proactive environmental systems:the next generation of environmental monitoring

In this article we envision factors and trends that shape the next generation of environmental monitoring systems. One key factor in this respect is the combined effect of end-user needs and the general development of IT services and their availability. Currently, an environmental (monitoring) system is assumed to be reactive. It delivers measurement data and computational results only if the user explicitly asks for it either by query or subscription. There is a temptation to automate this by simply pushing data to end-users. This, however, leads easily to an "advertisement strategy", where data is pushed to end-users regardless of users' needs. Under this strategy, the mere amount of received data obfuscates the individual messages; any "automatic" service, regardless of its fitness, overruns a system that requires the user's initiative. The foreseeable problem is that, unless there is no overall management, each new environmental service is going to compete for end-users' attention and, thus, inadvertently hinder the use of existing services. As the main contribution we investigate the nature of proactive environmental systems, and how they should be designed to avoid the aforementioned problem. We also discuss how semantics, participatory sensing, uncertainty management, and situational awareness link to proactive environmental systems. We illustrate our proposals with some real-life examples.

Evaluation of new processes for the preparation of iron by gas/solid phase systems

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Generation of spatial subharmonic gratings in the absence of photorefractive beam coupling

Using a new experimental geometry, we have proved for the first time that the generation of spatial subharmonic gratings in photorefractive crystals is not dependent on optical nonlinearity. We present results which confirm that the subharmonic gratings result from a parametric excitation of ultra low-frequency eigenmodes of a crystal by a time modulated fundamental grating.