The development and applications of the combined use of NMR and ultrasound

The objective of the research carried out in this report was to observe the first ever in-situ sonochemical reaction in the NMR Spectrometer in the megahertz region of ultrasound. Several reactions were investigated as potential systems for a sonochemical reaction followed by NMR spectroscopy. The primary problem to resolve when applying ultrasound to a chemical reaction is that of heating. Ultrasound causes the liquid to move and produces 'hot spots' resulting in an increase in sample temperature. The problem was confronted by producing a device that would counteract this effect and so remove the need to account for heating. However, the design of the device limited the length of time during which it would function. Longer reaction times were required to enable observations to be carried out in the NMR spectrometer. The fIrst and most obvious reactions attempted were those of the well-known ultrasonic dosimeter. Such a reaction would, theoretically, enable the author to simultaneously observe a reaction and determine the exact power entering the system for direct comparison of results. Unfortunately, in order to monitor the reactions in the NMR spectrometer the reactant concentrations had to be signifIcantly increased, which resulted in a notable increase in reaction time, making the experiment too lengthy to follow in the time allocated. The Diels-Alder Reaction is probably one of the most highly investigated reaction systems in the field of chemistry and it was this to which the author turned her attention. Previous authors have carried out ultrasonic investigations, with considerable success, for the reaction of anthracene with maleic anhydride. It was this reaction in particular that was next attempted. The first ever sonochemically enhanced reaction using a frequency of ultrasound in the megahertz (MHz) region was successfully carried out as bench experiments. Due to the complexity of the component reactants the product would precipitate from the solution and because the reaction could only be monitored by its formation, it was not possible to observe the reaction in the NMR spectrometer. The solvolysis of 2-chloro-2-methylpropane was examined in various solvent systems; the most suitable of which was determined to be aqueous 2-methylpropan-2-ol. The experiment was successfully enhanced by the application of ultrasound and monitored in-situ in the NMR spectrometer. The increase in product formation of an ultrasonic reaction over that of a traditional thermal reaction occurred. A range of 1.4 to 2.9 fold improvement was noted, dependent upon the reaction conditions investigated. An investigation into the effect of sonication upon a large biological molecule, in this case aqueous lysozyme, was carried out. An easily observed effect upon the sample was noted but no explanation for the observed effects could be established.

Improved message passing for inference in densely connected systems

An improved inference method for densely connected systems is presented. The approach is based on passing condensed messages between variables, representing macroscopic averages of microscopic messages. We extend previous work that showed promising results in cases where the solution space is contiguous to cases where fragmentation occurs. We apply the method to the signal detection problem of Code Division Multiple Access (CDMA) for demonstrating its potential. A highly efficient practical algorithm is also derived on the basis of insight gained from the analysis. © EDP Sciences.

Expert systems for vendor selection

The survival of organisations, especially SMEs, depends, to the greatest extent, on those who supply them with the required material input. This is because if the supplier fails to deliver the right materials at the right time and place, and at the right price, then the recipient organisation is bound to fail in its obligations to satisfy the needs of its customers, and to stay in business. Hence, the task of choosing a supplier(s) from a list of vendors, that an organisation will trust with its very existence, is not an easy one. This project investigated how purchasing personnel in organisations solve the problem of vendor selection. The investigation went further to ascertain whether an Expert Systems model could be developed and used as a plausible solution to the problem. An extensive literature review indicated that very scanty research has been conducted in the area of Expert Systems for Vendor Selection, whereas many research theories in expert systems and in purchasing and supply management chain, respectively, had been reported. A survey questionnaire was designed and circulated to people in the industries who actually perform the vendor selection tasks. Analysis of the collected data confirmed the various factors which are considered during the selection process, and established the order in which those factors are ranked. Five of the factors, namely, Production Methods Used, Vendors Financial Background, Manufacturing Capacity, Size of Vendor Organisations, and Suppliers Position in the Industry; appeared to have similar patterns in the way organisations ranked them. These patterns suggested that the bigger the organisation, the more importantly they regarded the above factors. Further investigations revealed that respondents agreed that the most important factors were: Product Quality, Product Price and Delivery Date. The most apparent pattern was observed for the Vendors Financial Background. This generated curiosity which led to the design and development of a prototype expert system for assessing the financial profile of a potential supplier(s). This prototype was called ESfNS. It determines whether a prospective supplier(s) has good financial background or not. ESNS was tested by the potential users who then confirmed that expert systems have great prospects and commercial viability in the domain for solving vendor selection problems.

WASOP, a qualitative methodology for waste minimization: systems thinking, HAZOP principles and nuclear waste

Purpose – The international nuclear community continues to face the challenge of managing both the legacy waste and the new wastes that emerge from ongoing energy production. The UK is in the early stages of proposing a new convention for its nuclear industry, that is: waste minimisation through closely managing the radioactive source which creates the waste. This paper proposes a new technique (called waste and source material operability study (WASOP)) to qualitatively analyse a complex, waste-producing system to minimise avoidable waste and thus increase the protection to the public and the environment. Design/methodology/approach – WASOP critically considers the systemic impact of up and downstream facilities on the minimisation of nuclear waste in a facility. Based on the principles of HAZOP, the technique structures managers' thinking on the impact of mal-operations in interlinking facilities in order to identify preventative actions to reduce the impact on waste production of those mal-operations.' Findings – WASOP was tested with a small group of experienced nuclear regulators and was found to support their qualitative examination of waste minimisation and help them to work towards developing a plan of action. Originality/value – Given the newness of this convention, the wider methodology in which WASOP sits is still in development. However, this paper communicates the latest thinking from nuclear regulators on decision-making methodology for supporting waste minimisation and is hoped to form part of future regulatory guidance. WASOP is believed to have widespread potential application to the minimisation of many other forms of waste, including that from other energy sectors and household/general waste.

The impact of the performance measurement systems in setting the 'direction' in the University of Warwick

This paper presents a case study examining the role of performance measurement systems in setting organizational ‘direction’. There is a growing concern in the existing literature to link the development of organizational ‘direction’ with performance measurement systems. Furthermore, the alignment between organizational ‘direction’, strategy and performance measurement is an area of increasing interest for both academics and practitioners. However, there is no adequate research recorded in the literature on the use of the performance measurement systems and the potential impact that performance measurement can have in setting the organizational ‘direction’. This study reports the findings of a case study from one of the leading academic institutions in the UK, the University of Warwick, presenting the main characteristics of its performance measurement system and attempting to explain the connection with setting the university’s ‘direction’.

A comparison of variational and Markov chain Monte Carlo methods for inference in partially observed stochastic dynamic systems

In recent work we have developed a novel variational inference method for partially observed systems governed by stochastic differential equations. In this paper we provide a comparison of the Variational Gaussian Process Smoother with an exact solution computed using a Hybrid Monte Carlo approach to path sampling, applied to a stochastic double well potential model. It is demonstrated that the variational smoother provides us a very accurate estimate of mean path while conditional variance is slightly underestimated. We conclude with some remarks as to the advantages and disadvantages of the variational smoother. © 2008 Springer Science + Business Media LLC.

The properties of advanced alumimium alloy systems

2XXX and 7XXX series aluminium alloys have been the accepted materials for airframe construction for many decades. However, only minor improvements in properties have been possible by the development of these alloys since the early 1970's. The constant need to reduce weight in aircraft has therefore led to a resurgence in the research for higher performance aluminium alloys. The reason for this investigation was to evaluate possible alternatives for the existing conventional aluminium alloy 2014 for aircraft wheel applications. Three new technologies in alloy development were considered: a metal matrix composite, an aluminium-lithium alloy and a powder metallurgical alloy. The basic mechanical properties of these advanced materials have already been established to an extent, but their fatigue behaviour has yet to be fully understood. The purpose of this work was to investigate the fatigue properties of the materials concerned, in both air and an aerated 3.5% NaCl solution, and compare these properties to 2014-T6. As well as the basic mechanical properties, fatigue crack propagation data is presented for all of the materials concerned. Additionally, fatigue crack initiation data is presented for the aluminium-lithium alloy and 2014. The D.C. electrical potential method was used to monitor crack growth. Of the materials investigated, the most promising was the aluminium-lithium alloy. However, short transverse properties need to be increased and the commercial cost of the material needs to be decreased before it can be considered as a direct replacement for 2014 for aircraft structural applications. It was considered that the cost of the powder metallurgical alloy would limit its further use. The metal matrix composite material proved to be unsuitable for most ambient temperature applications

Dispersion managed soliton systems

Dispersion managed solitons have been discovered to have some remarkable properties which indicate an outstanding opportunity for exploitation in transmission systems. This paper will review and interpret these discoveries and discuss the potential for WDM of these solitons for both long distance systems and for the upgrade of the installed fibre base.

Vaccine adjuvant systems: enhancing the efficacy of sub-unit protein antigens

Vaccination remains a key tool in the protection and eradication of diseases. However, the development of new safe and effective vaccines is not easy. Various live organism based vaccines currently licensed, exhibit high efficacy; however, this benefit is associated with risk, due to the adverse reactions found with these vaccines. Therefore, in the development of vaccines, the associated risk-benefit issues need to be addressed. Sub-unit proteins offer a much safer alternative; however, their efficacy is low. The use of adjuvanted systems have proven to enhance the immunogenicity of these sub-unit vaccines through protection (i.e. preventing degradation of the antigen in vivo) and enhanced targeting of these antigens to professional antigen-presenting cells. Understanding of the immunological implications of the related disease will enable validation for the design and development of potential adjuvant systems. Novel adjuvant research involves the combination of both pharmaceutical analysis accompanied by detailed immunological investigations, whereby, pharmaceutically designed adjuvants are driven by an increased understanding of mechanisms of adjuvant activity, largely facilitated by description of highly specific innate immune recognition of components usually associated with the presence of invading bacteria or virus. The majority of pharmaceutical based adjuvants currently being investigated are particulate based delivery systems, such as liposome formulations. As an adjuvant, liposomes have been shown to enhance immunity against the associated disease particularly when a cationic lipid is used within the formulation. In addition, the inclusion of components such as immunomodulators, further enhance immunity. Within this review, the use and application of effective adjuvants is investigated, with particular emphasis on liposomal-based systems. The mechanisms of adjuvant activity, analysis of complex immunological characteristics and formulation and delivery of these vaccines are considered.

Biomass-based small and micro combined heat and power (CHP) systems:application and status in the United Kingdom

This chapter discusses the current state of biomass-based combined heat and power (CHP) production in the UK. It presents an overview of the UK's energy policy and targets which are relevant to the deployment of biomass-based CHP and summarises the current state for renewable, biomass and CHP. A number of small-scale biomass-based CHP projects are described while providing some indicative capital costs for combustion, pyrolysis and gasification technologies. For comparison purposes, it presents an overview of the respective situation in Europe and particularly in Sweden, Finland and Denmark. There is also a brief comment about novel CHP technologies in Austria. Finally it draws some conclusions on the potential of small-scale biomass CHP in the UK. © 2011 Woodhead Publishing Limited All rights reserved.

A structural method for the design of fault tolerant distributed control systems

Distributed digital control systems provide alternatives to conventional, centralised digital control systems. Typically, a modern distributed control system will comprise a multi-processor or network of processors, a communications network, an associated set of sensors and actuators, and the systems and applications software. This thesis addresses the problem of how to design robust decentralised control systems, such as those used to control event-driven, real-time processes in time-critical environments. Emphasis is placed on studying the dynamical behaviour of a system and identifying ways of partitioning the system so that it may be controlled in a distributed manner. A structural partitioning technique is adopted which makes use of natural physical sub-processes in the system, which are then mapped into the software processes to control the system. However, communications are required between the processes because of the disjoint nature of the distributed (i.e. partitioned) state of the physical system. The structural partitioning technique, and recent developments in the theory of potential controllability and observability of a system, are the basis for the design of controllers. In particular, the method is used to derive a decentralised estimate of the state vector for a continuous-time system. The work is also extended to derive a distributed estimate for a discrete-time system. Emphasis is also given to the role of communications in the distributed control of processes and to the partitioning technique necessary to design distributed and decentralised systems with resilient structures. A method is presented for the systematic identification of necessary communications for distributed control. It is also shwon that the structural partitions can be used directly in the design of software fault tolerant concurrent controllers. In particular, the structural partition can be used to identify the boundary of the conversation which can be used to protect a specific part of the system. In addition, for certain classes of system, the partitions can be used to identify processes which may be dynamically reconfigured in the event of a fault. These methods should be of use in the design of robust distributed systems.

Dispersion aspects of periodically amplified soliton transmission systems

This thesis presents improvements to optical transmission systems through the use of optical solitons as a digital transmission format, both theoretically and experimentally. An introduction to the main concepts and impairments of optical fibre on pulse transmission is included before introducing the concept of solitons in optically amplified communications and the problems of soliton system design. The theoretical work studies two fibre dispersion profiling schemes and a soliton launch improvement. The first provides superior pulse transmission by optimally tailoring the fibre dispersion to better follow the power, and hence nonlinearity, decay and thus allow soliton transmission for longer amplifier spacings and shorter pulse widths than normally possible. The second profiling scheme examines the use of dispersion compensating fibre in the context of soliton transmission over existing, standard fibre systems. The limits for solitons in uncompensated standard fibre are assessed, before the potential benefits of dispersion compensating fibre included as part of each amplifier are shown. The third theoretical investigation provides a simple improvement to the propagation of solitons in a highly perturbed system. By introducing a section of fibre of the correct length prior to the first system amplifier span, the soliton shape can be better coupled into the system thus providing an improved "average soliton" propagation model. The experimental work covers two areas. An important issue for soliton systems is pulse sources. Three potential lasers are studied, two ring laser configurations and one semiconductor device with external pulse shaping. The second area studies soliton transmission using a recalculating loop, reviewing the advantages and draw-backs of such an experiment in system testing and design. One particular example of employing the recirculating loop is also examined, using a novel method of pulse shape stabilisation over long distances with low jitter. The future for nonlinear optical communications is considered with the thesis conclusions.

Strategic development process and complex adaptive systems

The two areas of theory upon which this research was based were „strategy development process?(SDP) and „complex adaptive systems? (CAS), as part of complexity theory, focused on human social organisations. The literature reviewed showed that there is a paucity of empirical work and theory in the overlap of the two areas, providing an opportunity for contributions to knowledge in each area of theory, and for practitioners. An inductive approach was adopted for this research, in an effort to discover new insights to the focus area of study. It was undertaken from within an interpretivist paradigm, and based on a novel conceptual framework. The organisationally intimate nature of the research topic, and the researcher?s circumstances required a research design that was both in-depth and long term. The result was a single, exploratory, case study, which included use of data from 44 in-depth, semi-structured interviews, from 36 people, involving all the top management team members and significant other staff members; observations, rumour and grapevine (ORG) data; and archive data, over a 5½ year period (2005 – 2010). Findings confirm the validity of the conceptual framework, and that complex adaptive systems theory has potential to extend strategy development process theory. It has shown how and why the strategy process developed in the case study organisation by providing deeper insights to the behaviour of the people, their backgrounds, and interactions. Broad predictions of the „latent strategy development? process and some elements of the strategy content are also possible. Based on this research, it is possible to extend the utility of the SDP model by including peoples? behavioural characteristics within the organisation, via complex adaptive systems theory. Further research is recommended to test limits of the application of the conceptual framework and improve its efficacy with more organisations across a variety of sectors.

Liposomes:Formulation and characterisation as contrast agents and as vaccine delivery systems

Liposome systems are well reported for their activity as vaccine adjuvants; however novel lipid-based microbubbles have also been reported to enhance the targeting of antigens into dendritic cells (DCs) in cancer immunotherapy (Suzuki et al 2009). This research initially focused on the formulation of gas-filled lipid coated microbubbles and their potential activation of macrophages using in vitro models. Further studies in the thesis concentrated on aqueous-filled liposomes as vaccine delivery systems. Initial work involved formulating and characterising four different methods of producing lipid-coated microbubbles (sometimes referred to as gas-filled liposomes), by homogenisation, sonication, a gas-releasing chemical reaction and agitation/pressurisation in terms of stability and physico-chemical characteristics. Two of the preparations were tested as pressure probes in MRI studies. The first preparation composed of a standard phospholipid (DSPC) filled with air or nitrogen (N2), whilst in the second method the microbubbles were composed of a fluorinated phospholipid (F-GPC) filled with a fluorocarbon saturated gas. The studies showed that whilst maintaining high sensitivity, a novel contrast agent which allows stable MRI measurements of fluid pressure over time, could be produced using lipid-coated microbubbles. The F-GPC microbubbles were found to withstand pressures up to 2.6 bar with minimal damage as opposed to the DSPC microbubbles, which were damaged at above 1.3 bar. However, it was also found that DSPC-filled with N2 microbubbles were also extremely robust to pressure and their performance was similar to that of F-GPC based microbubbles. Following on from the MRI studies, the DSPC-air and N2 filled lipid-based microbubbles were assessed for their potential activation of macrophages using in vitro models and compared to equivalent aqueous-filled liposomes. The microbubble formulations did not stimulate macrophage uptake, so studies thereafter focused on aqueous-filled liposomes. Further studies concentrated on formulating and characterising, both physico-chemically and immunologically, cationic liposomes based on the potent adjuvant dimethyldioctadecylammonium (DDA) and immunomodulatory trehalose dibehenate (TDB) with the addition of polyethylene glycol (PEG). One of the proposed hypotheses for the mechanism behind the immunostimulatory effect obtained with DDA:TDB is the ‘depot effect’ in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. The depot effect has been suggested to be primarily due to their cationic nature. Results reported within this thesis demonstrate that higher levels of PEG i.e. 25 % were able to significantly inhibit the formation of a liposome depot at the injection site and also severely limit the retention of antigen at the site. This therefore resulted in a faster drainage of the liposomes from the site of injection. The versatility of cationic liposomes based on DDA:TDB in combination with different immunostimulatory ligands including, polyinosinic-polycytidylic acid (poly (I:C), TLR 3 ligand), and CpG (TLR 9 ligand) either entrapped within the vesicles or adsorbed onto the liposome surface was investigated for immunogenic capacity as vaccine adjuvants. Small unilamellar (SUV) DDA:TDB vesicles (20-100 nm native size) with protein antigen adsorbed to the vesicle surface were the most potent in inducing both T cell (7-fold increase) and antibody (up to 2 log increase) antigen specific responses. The addition of TLR agonists poly(I:C) and CpG to SUV liposomes had small or no effect on their adjuvanticity. Finally, threitol ceramide (ThrCer), a new mmunostimulatory agent, was incorporated into the bilayers of liposomes composed of DDA or DSPC to investigate the uptake of ThrCer, by dendritic cells (DCs), and presentation on CD1d molecules to invariant natural killer T cells. These systems were prepared both as multilamellar vesicles (MLV) and Small unilamellar (SUV). It was demonstrated that the IFN-g secretion was higher for DDA SUV liposome formulation (p<0.05), suggesting that ThrCer encapsulation in this liposome formulation resulted in a higher uptake by DCs.

Increased potential of a cationic liposome-based delivery system:enhancing stability and sustained immunological activity in pre-clinical development

The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.