The use of erythrocytic and animal models in the study of protein phosphorylation

Phosphorylation processes are common post-transductional mechanisms, by which it is possible to modulate a number of metabolic pathways. Proteins are highly sensitive to phosphorylation, which governs many protein-protein interactions. The enzymatic activity of some protein tyrosine-kinases is under tyrosine-phosphorylation control, as well as several transmembrane anion-fluxes and cation exchanges. In addition, phosphorylation reactions are involved in intra and extra-cellular 'cross-talk' processes. Early studies adopted laboratory animals to study these little known phosphorylation processes. The main difficulty encountered with these animal techniques was obtaining sufficient kinase or phosphatase activity suitable for studying the enzymatic process. Large amounts of biological material from organs, such as the liver and spleen were necessary to conduct such work with protein kinases. Subsequent studies revealed the ubiquity and complexity of phosphorylation processes and techniques evolved from early rat studies to the adaptation of more rewarding in vitro models. These involved human erythrocytes, which are a convenient source both for the enzymes, we investigated and for their substrates. This preliminary work facilitated the development of more advanced phosphorylative models that are based on cell lines. © 2005 Elsevier B.V. All rights reserved.

A decision support system for supplier selection and order allocation in stochastic, multi-stakeholder and multi-criteria environments

Integrated supplier selection and order allocation is an important decision for both designing and operating supply chains. This decision is often influenced by the concerned stakeholders, suppliers, plant operators and customers in different tiers. As firms continue to seek competitive advantage through supply chain design and operations they aim to create optimized supply chains. This calls for on one hand consideration of multiple conflicting criteria and on the other hand consideration of uncertainties of demand and supply. Although there are studies on supplier selection using advanced mathematical models to cover a stochastic approach, multiple criteria decision making techniques and multiple stakeholder requirements separately, according to authors' knowledge there is no work that integrates these three aspects in a common framework. This paper proposes an integrated method for dealing with such problems using a combined Analytic Hierarchy Process-Quality Function Deployment (AHP-QFD) and chance constrained optimization algorithm approach that selects appropriate suppliers and allocates orders optimally between them. The effectiveness of the proposed decision support system has been demonstrated through application and validation in the bioenergy industry.

Advanced mean field methods:theory and practice

A major problem in modern probabilistic modeling is the huge computational complexity involved in typical calculations with multivariate probability distributions when the number of random variables is large. Because exact computations are infeasible in such cases and Monte Carlo sampling techniques may reach their limits, there is a need for methods that allow for efficient approximate computations. One of the simplest approximations is based on the mean field method, which has a long history in statistical physics. The method is widely used, particularly in the growing field of graphical models. Researchers from disciplines such as statistical physics, computer science, and mathematical statistics are studying ways to improve this and related methods and are exploring novel application areas. Leading approaches include the variational approach, which goes beyond factorizable distributions to achieve systematic improvements; the TAP (Thouless-Anderson-Palmer) approach, which incorporates correlations by including effective reaction terms in the mean field theory; and the more general methods of graphical models. Bringing together ideas and techniques from these diverse disciplines, this book covers the theoretical foundations of advanced mean field methods, explores the relation between the different approaches, examines the quality of the approximation obtained, and demonstrates their application to various areas of probabilistic modeling.

Advanced fibre gratings and their applications

This thesis describes a detailed study of advanced fibre grating devices using Bragg (FBG) and long-period (LPG) structures and their applications in optical communications and sensing. The major contributions presented in this thesis are summarised below. One of the most important contributions from the research work presented in this thesis is a systematic theoretical study of many distinguishing structures of fibre gratings. Starting from the Maxwell equations, the coupled-mode equations for both FBG and LPG were derived and the mode-overlap factor was analytically discussed. Computing simulation programmes utilising matrix transform method based on the models built upon the coupled-mode equations were developed, enabling simulations of spectral response in terms of reflectivity, bandwidth, sidelobes and dispersion of gratings of different structures including uniform and chirped, phase-shifted, Moiré, sampled Bragg gratings, phase-shifted and cascaded long-period gratings. Although the majority of these structures were modelled numerically, analytical expressions for some complex structures were developed with a clear physical picture. Several apodisation functions were proposed to improve sidelobe suppression, which guided effective production of practical devices for demanding applications. Fibre grating fabrication is the other major part involved in the Ph.D. programme. Both the holographic and scan-phase-mask methods were employed to fabricate Bragg and long-period gratings of standard and novel structures. Significant improvements were particularly made in the scan-phase-mask method to enable the arbitrarily tailoring of the spectral response of grating devices. Two specific techniques - slow-shifting and fast-dithering the phase-mask implemented by a computer controlled piezo - were developed to write high quality phase-shifted, sampled and apodised gratings. A large number of LabVIEW programmes were constructed to implement standard and novel fabrication techniques. In addition, some fundamental studies of grating growth in relating to the UV exposure and hydrogenation induced index were carried out. In particular, Type IIa gratings in non-hydrogenated B/Ge co-doped fibres and a re-generated grating in hydrogenated B/Ge fibre were investigated, showing a significant observation of thermal coefficient reduction. Optical sensing applications utilising fibre grating devices form the third major part of the research work presented in this thesis. Several experiments of novel sensing and sensing-demodulating were implemented. For the first time, an intensity and wavelength dual-coding interrogation technique was demonstrated showing significantly enhanced capacity of grating sensor multiplexing. Based on the mode-splitting measurement, instead of using conventional wavelength-shifting detection technique, successful demonstrations were also made for optical load and bend sensing of ultra-high sensitivity employing LPG structures. In addition, edge-filters and low-loss high-rejection bandpass filters of 50nm stop-band were fabricated for application in optical sensing and high-speed telecommunication systems

Buyer-supplier relationships in advanced manufacturing technology acquisition and implementation : a study in Malaysia

This thesis reports the results of research into the connections between transaction attributes and buyer-supplier relationships (BSR) in advanced manufacturing technology (AMT) acquisitions and implementation. It also examines the impact of the different patterns of BSR on performance. Specifically, it addresses the issues of how the three transaction attributes; namely level of complexity, level of asset specificity, and level of uncertainty, can affect the relationships between the technology buyer and suppler in AMT acquisition and implementation, and then to see the impact of different patterns of BSR on the two aspect of performance; namely technology and implementation performance. In understanding the pohenomena, the study mainly draws on and integrates the literature of transaction cost economics theory,buyer-supplier relationships and advanced manufacturing technology as a basis of theoretical framework and hypotheses development.data were gathered through a questionnaire survey with 147 responses and seven semi-structured interviews of manufacturing firms in Malaysia. Quantitative data were analysed mainly using the AMOS (Analysis of Moment Structure) package for structural equation modeling and SPSS (Statistical Package for Social Science) for analysis of variance (ANOVA). Data from interview sessions were used to develop a case study with the intention of providing a richer and deeper understanding on the subject under investigation and to offer triangulation in the research process. he results of the questionnaire survey indicate that the higher the level of technological specificity and uncertainty, the more firms are likely to engage in a closer relationship with technology suppliers.However, the complexity of the technology being implemented is associated with BSR only because it is associated with the level of uncertainty that has direct impact upon BSR.The analysis also provides strong support for the premise that developing strong BSR could lead to an improved performance. However, with high levels of transaction attribute, implementation performance suffers more when firms have weak relationships with technology suppliers than with moderate and low levels of transaction attributes. The implications of the study are offered for both the academic and practitioner audience. The thesis closes with reports on its limitations and suggestions for further research that would address some of these limitations.

On a distinction between casual and formative variable models:theoretical issues and practical implications for organizational researchers

Formative measurement has seen increasing acceptance in organizational research since the turn of the 21st Century. However, in more recent times, a number of criticisms of the formative approach have appeared. Such work argues that formatively-measured constructs are empirically ambiguous and thus flawed in a theory-testing context. The aim of the present paper is to examine the underpinnings of formative measurement theory in light of theories of causality and ontology in measurement in general. In doing so, a thesis is advanced which draws a distinction between reflective, formative, and causal theories of latent variables. This distinction is shown to be advantageous in that it clarifies the ontological status of each type of latent variable, and thus provides advice on appropriate conceptualization and application. The distinction also reconciles in part both recent supportive and critical perspectives on formative measurement. In light of this, advice is given on how most appropriately to model formative composites in theory-testing applications, placing the onus on the researcher to make clear their conceptualization and operationalisation.

Bridging large and small scales of water models using hybrid Molecular Dynamics/Fluctuating Hydrodynamics framework

This thesis presents a two-dimensional water model investigation and development of a multiscale method for the modelling of large systems, such as virus in water or peptide immersed in the solvent. We have implemented a two-dimensional ‘Mercedes Benz’ (MB) or BN2D water model using Molecular Dynamics. We have studied its dynamical and structural properties dependence on the model’s parameters. For the first time we derived formulas to calculate thermodynamic properties of the MB model in the microcanonical (NVE) ensemble. We also derived equations of motion in the isothermal–isobaric (NPT) ensemble. We have analysed the rotational degree of freedom of the model in both ensembles. We have developed and implemented a self-consistent multiscale method, which is able to communicate micro- and macro- scales. This multiscale method assumes, that matter consists of the two phases. One phase is related to micro- and the other to macroscale. We simulate the macro scale using Landau Lifshitz-Fluctuating Hydrodynamics, while we describe the microscale using Molecular Dynamics. We have demonstrated that the communication between the disparate scales is possible without introduction of fictitious interface or approximations which reduce the accuracy of the information exchange between the scales. We have investigated control parameters, which were introduced to control the contribution of each phases to the matter behaviour. We have shown, that microscales inherit dynamical properties of the macroscales and vice versa, depending on the concentration of each phase. We have shown, that Radial Distribution Function is not altered and velocity autocorrelation functions are gradually transformed, from Molecular Dynamics to Fluctuating Hydrodynamics description, when phase balance is changed. In this work we test our multiscale method for the liquid argon, BN2D and SPC/E water models. For the SPC/E water model we investigate microscale fluctuations which are computed using advanced mapping technique of the small scales to the large scales, which was developed by Voulgarakisand et. al.

Developing accurate models of the human airways

Objectives Particle delivery to the airways is an attractive prospect for many potential therapeutics, including vaccines. Developing strategies for inhalation of particles provides a targeted, controlled and non-invasive delivery route but, as with all novel therapeutics, in vitro and in vivo testing are needed prior to clinical use. Whilst advanced vaccine testing demands the use of animal models to address safety issues, the production of robust in vitro cellular models would take account of the ethical framework known as the 3Rs (Replacement, Reduction and Refinement of animal use), by permitting initial screening of potential candidates prior to animal use. There is thus a need for relevant, realistic in vitro models of the human airways. Key findings Our laboratory has designed and characterised a multi-cellular model of human airways that takes account of the conditions in the airways and recapitulates many salient features, including the epithelial barrier and mucus secretion. Summary Our human pulmonary models recreate many of the obstacles to successful pulmonary delivery of particles and therefore represent a valid test platform for screening compounds and delivery systems.

Advanced tilted fiber gratings and their applications

This thesis presents a detailed numerical analysis, fabrication method and experimental investigation on 45º tilted fiber gratings (45º-TFGs) and excessively tilted fiber gratings (Ex-TFGs), and their applications in fiber laser and sensing systems. The one of the most significant contributions of the work reported in this thesis is that the 45º-TFGs with high polarization extinction ratio (PER) have been fabricated in single mode telecom and polarization maintaining (PM) fibers with spectral response covering three prominent optic communication and central wavelength ranges at 1060nm, 1310nm and 1550nm. The most achieved PERs for the 45º-TFGs are up to and greater than 35-50dB, which have reached and even exceeded many commercial in-fiber polarizers. It has been proposed that the 45º-TFGs of high PER can be used as ideal in-fiber polarizers for a wide range of fiber systems and applications. In addition, in-depth detailed theoretical models and analysis have been developed and systematic experimental evaluation has been conducted producing results in excellent agreement with theoretical modeling. Another important outcome of the research work is the proposal and demonstration of all fiber Lyot filters (AFLFs) implemented by utilizing two (for a single stage type) and more (for multi-stage) 45º-TFGs in PM fiber cavity structure. The detailed theoretical analysis and modelling of such AFLFs have also been carried out giving design guidance for the practical implementation. The unique function advantages of 45º-TFG based AFLFs have been revealed, showing high finesse multi-wavelength transmission of single polarization and wide range of tuneability. The temperature tuning results of AFLFs have shown that the AFLFs have 60 times higher thermal sensitivity than the normal FBGs, thus permitting thermal tuning rate of ~8nm/10ºC. By using an intra-cavity AFLF, an all fiber soliton mode locking laser with almost total suppression of siliton sidebands, single polarization output and single/multi-wavelength switchable operation has been demonstrated. The final significant contribution is the theoretical analysis and experimental verification on the design, fabrication and sensing application of Ex-TFGs. The Ex-TFG sensitivity model to the surrounding medium refractive index (SRI) has been developed for the first time, and the factors that affect the thermal and SRI sensitivity in relation to the wavelength range, tilt angle, and the size of cladding have been investigated. As a practical SRI sensor, an 81º-TFG UV-inscribed in the fiber with small (40μm) cladding radius has shown an SRI sensitivity up to 1180nm/RIU in the index of 1.345 range. Finally, to ensure single polarization detection in such an SRI sensor, a hybrid configuration by UV-inscribing a 45º-TFG and an 81º-TFG closely on the same piece of fiber has been demonstrated as a more advanced SRI sensing system.

Exploring business models to provide a foundation for enhanced eye care services in high street optometric practice

High street optometric practices are for-profit businesses. They mostly provide sight testing and eye examination services and sell optical products, such as spectacles and contact lenses. The sight testing services are often sold at a vastly reduced price and profits are generated primarily through high margin spectacle sales, in a loss leading strategy. Published literature highlights weaknesses in this strategy as it forms a barrier to widening the scope of services provided within optometric practices. This includes specialist non-refraction based services, such as shared care. In addition this business strategy discourages investment in advanced diagnostic equipment and higher professional qualifications. The aim of this thesis was to develop a greater understanding of the traditional loss-leading strategy. The thesis also aimed to assess the plausibility of alternative business models to support the development of specialist non-refraction services within high street optometric practice. This research was based on a single independent optometric practice that specialises in advanced retinal imaging and offers a broad range of shared care services. Specialist non-refraction based services were found to be poor generators of spectacle sales likely due to patient needs and presenting concerns. Alternative business strategies to support these services included charging more realistic professional fees via cost-based pricing and monthly payment plans. These strategies enabled specialist services to be more self-sustainable with less reliance on cross-subsidy from spectacle sales. Furthermore, improving operational efficiency can increase stand-alone profits for specialist services.Practice managers may be reluctant to increase professional fees due to market pressures and confidence. However, this thesis found that patients were accepting of increased professional fees. Practice managers can implement alternative business models to enhance eye care provision in high street optometric practices. These alternative business models also improve revenues and profits generated via clinical services and improve patient loyalty.