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.

Experts:the knowledge and power of expertise

In this book, Stehr and Grundmann outline the theoretical significance and practical importance of the growing stratum of experts, counsellors and advisors in contemporary society, and claim that the growing spectrum of knowledge-based occupations has led to the pluralisation of expertise. As decision makers in organizations and private citizens, for various reasons, increasingly seek advice from experts, the authors examine the nature of expert activity, and suggest that the role of experts needs to be distinguised from other roles such as professionals, scientists, or intellectuals. Experts, they argue, perform knowledge based activities that mediate between the context of knowledge creation and application. Existing approaches tend to restrict the role of the expert to scientists, or to conflate the roles of professionals with experts. In avoiding such restrictions, this book sets out a framework to understanding the growing role of expertise in a better way. Experts provides thought-provoking discussion that will be of interest to postgraduate students and academics working within the fields of social theory, knowledge, and consumption.

Business processes and knowledge management

Knowledge has been a subject of interest and inquiry for thousands of years since at least the time of the ancient Greeks, and no doubt even before that. “What is knowledge” continues to be an important topic of discussion in philosophy. More recently, interest in managing knowledge has grown in step with the perception that increasingly we live in a knowledge-based economy. Drucker (1969) is usually credited as being the first to popularize the knowledge-based economy concept by linking the importance of knowledge with rapid technological change in Drucker (1969). Karl Wiig coined the term knowledge management (hereafter KM) for a NATO seminar in 1986, and its popularity took off following the publication of Nonaka and Takeuchi’s book “The Knowledge Creating Company” (Nonaka & Takeuchi, 1995). Knowledge creation is in fact just one of many activities involved in KM. Others include sharing, retaining, refining, and using knowledge. There are many such lists of activities (Holsapple & Joshi, 2000; Probst, Raub, & Romhardt, 1999; Skyrme, 1999; Wiig, De Hoog, & Van der Spek, 1997). Both academic and practical interest in KM has continued to increase throughout the last decade. In this article, first the different types of knowledge are outlined, then comes a discussion of various routes by which knowledge management can be implemented, advocating a process-based route. An explanation follows of how people, processes, and technology need to fit together for effective KM, and some examples of this route in use are given. Finally, there is a look towards the future.

Regional benchmarking in a global context:knowledge, competitiveness, and economic development

Benchmarking exercises have become increasingly popular within the sphere of regional policy making. However, most exercises are restricted to comparing regions within a particular continental bloc or nation.This article introduces the World Knowledge Competitiveness Index (WKCI), which is one of the very few benchmarking exercises established to compare regions across continents.The article discusses the formulation of the WKCI and analyzes the results of the most recent editions.The results suggest that there are significant variations in the knowledge-based regional economic development models at work across the globe. Further analysis also indicates that Silicon Valley, as the highest ranked WKCI region, holds a unique economic position among the globe’s leading regions. However, significant changes in the sources of regional competitiveness are evolving as a result of the emergence of new regional hot spots in Asia. It is concluded that benchmarking is imperative to the learning process of regional policy making.

Expert systems for fault analysis

The initial aim of this research was to investigate the application of expert Systems, or Knowledge Base Systems technology to the automated synthesis of Hazard and Operability Studies. Due to the generic nature of Fault Analysis problems and the way in which Knowledge Base Systems work, this goal has evolved into a consideration of automated support for Fault Analysis in general, covering HAZOP, Fault Tree Analysis, FMEA and Fault Diagnosis in the Process Industries. This thesis described a proposed architecture for such an Expert System. The purpose of the System is to produce a descriptive model of faults and fault propagation from a description of the physical structure of the plant. From these descriptive models, the desired Fault Analysis may be produced. The way in which this is done reflects the complexity of the problem which, in principle, encompasses the whole of the discipline of Process Engineering. An attempt is made to incorporate the perceived method that an expert uses to solve the problem; keywords, heuristics and guidelines from techniques such as HAZOP and Fault Tree Synthesis are used. In a truly Expert System, the performance of the system is strongly dependent on the high quality of the knowledge that is incorporated. This expert knowledge takes the form of heuristics or rules of thumb which are used in problem solving. This research has shown that, for the application of fault analysis heuristics, it is necessary to have a representation of the details of fault propagation within a process. This helps to ensure the robustness of the system - a gradual rather than abrupt degradation at the boundaries of the domain knowledge.

Optical fibre sensors and their applications in the industrial weighing and aerospace industries

This thesis presents the design, fabrication and testing of novel grating based Optical Fibre Sensor (OFS) systems being interrogated using “off the shelf” interrogation systems, with the eventual development of marketable commercial systems at the forefront of the research. Both in the industrial weighing and aerospace industries, there has been a drive to investigate the feasibility of using optical fibre sensors being deployed where traditionally their electrical or mechanical counterparts would traditionally have been. Already, in the industrial weighing industry, commercial operators are deploying OFS-based Weigh-In-Motion (WIM) systems. Likewise, in the aerospace industry, OFS have been deployed to monitor such parameters as load history, impact detection, structural damage, overload detection, centre of gravity and the determination of blade shape. Based on the intrinsic properties of fibre Bragg gratings (FBGs) and Long Period Fibre Gratings (LPFGs), a number of novel OFS-based systems have been realised. Experimental work has shown that in the case of static industrial weighing, FBGs can be integrated with current commercial products and used to detect applied loads. The work has also shown that embedding FBGs in e-glass, to form a sensing patch, can result in said patches being bonded to rail track, forming the basis of an FBG-based WIM system. The results obtained have been sufficiently encouraging to the industrial partner that this work will be progressed beyond the scope of the work presented in this thesis. Likewise, and to the best of the author’s knowledge, a novel Bragg grating based systems for aircraft fuel parameter sensing has been presented. FBG-based pressure sensors have been shown to demonstrate good sensitivity, linearity and repeatability, whilst LPFG-based systems have demonstrated a far greater sensitivity when compared to FBGs, as well the advantage of being potentially able to detect causes of fuel adulteration based on their sensitivity to refractive index (RI). In the case of the LPFG-based system, considerable work remains to be done on the mechanical strengthening to improve its survivability in a live aircraft fuel tank environment. The FBG system has already been developed to an aerospace compliant prototype and is due to be tested at the fuel testing facility based at Airbus, Filton, UK. It is envisaged by the author that in both application areas, continued research in this area will lead to the eventual development of marketable commercial products.

Engineering liposomal systems to develop solubility enhancing technology

This research primarily focused on identifying the formulation parameters which control the efficacy of liposomes as delivery systems to enhance the delivery of poorly soluble drugs. Preliminary studies focused on the drug loading of ibuprofen within vesicle systems. Initially both liposomal and niosomal formulations were screened for their drug-loading capacity: liposomal systems were shown to offer significantly higher ibuprofen loading and thereafter lipid based systems were further investigated. Given the key role cholesterol is known to play within the stability of bilayer vesicles. the optimum cholesterol content in terms of drug loading and release of poorly soluble drugs was then investigated. From these studies a concentration of 11 total molar % of cholesterol was used as a benchmark for all further formulations. Investigating the effect of liposomc composition on several low solubility drugs, drug loading was shown to be enhanced by adopting longer chain length lipids. cationic lipids and. decreasing drug molecular weight. Drug release was increased by using cationic lipids and lower molecular weight of drug; conversely, a reduction was noted when employing longer chain lipids thus supporting the rational of longer chain lipids producing more stable liposomes, a theory also supported by results obtained via Langmuir studies· although it was revealed that stability is also dependent on geometric features associated with the lipid chain moiety. Interestingly, reduction in drug loading appeared to be induced when symmetrical phospholipids were substituted for lipids constituting asymmetrical alkyl chain groups thus further highlighting the importance of lipid geometry. Combining a symmetrical lipid with an asymmetrical derivative enhanced encapsulation of a hydrophobic drug while reducing that of another suggesting the importance of drug characteristics. Phosphatidylcholine liposornes could successfully be prepared (and visualised using transmission electron microscopy) from fatty alcohols therefore offering an alternative liposomal stabiliser to cholesterol. Results obtained revealed that liposomes containing tetradecanol within their formulation shares similar vesicle size, drug encapsulation, surface charge. and toxicity profiles as liposomes formulated with cholesterol, however the tetradecanol preparation appeared to release considerably more drug during stability studies. Langmuir monolayer studies revealed that the condensing influence by tetradecanol is less than compared with cholesterol suggesting that this reduced intercalation by the former could explain why the tetradecanol formulation released more drug compared with cholesterol formulations. Environmental scanning electron microscopy (ESEM) was used to analyse the morphology and stability of liposomes. These investigations indicated that the presence of drugs within the liposomal bilayer were able to enhance the stability of the bilayers against collapse under reduced hydration conditions. In addition the presence of charged lipids within the formulation under reduced hydration conditions compared with its neutral counterpart. However the applicability of using ESEM as a new method to investigate liposome stability appears less valid than first hoped since the results are often open to varied interpretation and do not provide a robust set of data to support conclusions in some cases.

The development of an expert system for the identification anodic coating process defects as a contribution to the dissemination of anodizing technology

Initially this thesis examines the various mechanisms by which technology is acquired within anodizing plants. In so doing the history of the evolution of anodizing technology is recorded, with particular reference to the growth of major markets and to the contribution of the marketing efforts of the aluminium industry. The business economics of various types of anodizing plants are analyzed. Consideration is also given to the impact of developments in anodizing technology on production economics and market growth. The economic costs associated with work rejected for process defects are considered. Recent changes in the industry have created conditions whereby information technology has a potentially important role to play in retaining existing knowledge. One such contribution is exemplified by the expert system which has been developed for the identification of anodizing process defects. Instead of using a "rule-based" expert system, a commercial neural networks program has been adapted for the task. The advantages of neural networks over 'rule-based' systems is that they are better suited to production problems, since the actual conditions prevailing when the defect was produced are often not known with certainty. In using the expert system, the user first identifies the process stage at which the defect probably occurred and is then directed to a file enabling the actual defects to be identified. After making this identification, the user can consult a database which gives a more detailed description of the defect, advises on remedial action and provides a bibliography of papers relating to the defect. The database uses a proprietary hypertext program, which also provides rapid cross-referencing to similar types of defect. Additionally, a graphics file can be accessed which (where appropriate) will display a graphic of the defect on screen. A total of 117 defects are included, together with 221 literature references, supplemented by 48 cross-reference hyperlinks. The main text of the thesis contains 179 literature references. (DX186565)

State-of-the-art in lean design engineering:a literature review on white collar lean

Lean is usually associated with the ‘operations’ of a manufacturing enterprise; however, there is a growing awareness that these principles may be transferred readily to other functions and sectors. The application to knowledge-based activities such as engineering design is of particular relevance to UK plc. Hence, the purpose of this study has been to establish the state-of-the-art, in terms of the adoption of Lean in new product development, by carrying out a systematic review of the literature. The authors' findings confirm the view that Lean can be applied beneficially away from the factory; that an understanding and definition of value is key to success; that a set-based (or Toyota methodology) approach to design is favoured together with the strong leadership of a chief engineer; and that the successful implementation requires organization-wide changes to systems, practices, and behaviour. On this basis it is felt that this review paper provides a useful platform for further research in this topic.

Knowledge management in knowledge intensive service networks:a strategic management approach

Purpose – The main purpose of this paper is to analyze knowledge management in service networks. It analyzes the knowledge management process and identifies related challenges. The authors take a strategic management approach instead of a more technology-oriented approach, since it is believed that managerial problems still remain after technological problems are solved. Design/methodology/approach – The paper explores the literature on the topic of knowledge management as well as the resource (or knowledge) based view of the firm. It offers conceptual insights and provides possible solutions for knowledge management problems. Findings – The paper discusses several possible solutions for managing knowledge processes in knowledge-intensive service networks. Solutions for knowledge identification/generation, knowledge application, knowledge combination/transfer and supporting the evolution of tacit network knowledge include personal and technological aspects, as well as organizational and cultural elements. Practical implications – In a complex environment, knowledge management and network management become crucial for business success. It is the task of network management to establish routines, and to build and regularly refresh meta-knowledge about the competencies and abilities that exist within the network. It is suggested that each network partner should be rated according to the contribution to the network knowledge base. Based on this rating, a particular network partner is a member of a certain knowledge club, meaning that the partner has access to a particular level of network knowledge. Such an established routine provides strong incentives to add knowledge to the network's knowledge base Originality/value – This paper is a first attempt to outline the problems of knowledge management in knowledge-intensive service networks and, by so doing, to introduce strategic management reasoning to the discussion.

Transition of legacy systems to semantically enabled applications:TAO method and tools

Despite expectations being high, the industrial take-up of Semantic Web technologies in developing services and applications has been slower than expected. One of the main reasons is that many legacy systems have been developed without considering the potential of theWeb in integrating services and sharing resources.Without a systematic methodology and proper tool support, the migration from legacy systems to SemanticWeb Service-based systems can be a tedious and expensive process, which carries a significant risk of failure. There is an urgent need to provide strategies, allowing the migration of legacy systems to Semantic Web Services platforms, and also tools to support such strategies. In this paper we propose a methodology and its tool support for transitioning these applications to Semantic Web Services, which allow users to migrate their applications to Semantic Web Services platforms automatically or semi-automatically. The transition of the GATE system is used as a case study. © 2009 - IOS Press and the authors. All rights reserved.

Graduate employability, 'soft skills' versus 'hard' business knowledge:a European study

There is a growing awareness in the UK and mainland Europe of the importance of higher education to the development of a knowledge-based economy. European universities are increasingly required to produce highly mobile graduates able to respond to the ever-changing needs of the contemporary workplace. Following the Bologna Declaration (19991. 19 June 1999 . “The European Higher Education Area” (Bologna Declaration), Joint Declaration of the European Ministers of Education, Bologna, higher education across Europe has expanded rapidly. This has resulted in questions being raised about the quality of the graduate labour market and the ability of graduates to meet the needs of employers. This paper analyses graduate and employer perspectives of graduate employability in four European countries (UK, Austria, Slovenia and Romania). In doing so it adds to current debates in this area.

Competing for knowledge:creating, connecting and growing

With the buzzwords of knowledge-based economy and knowledge-driven economy, policy-makers, as well as journalists and management consultants, are pushing forward a vision of change that transforms the way advanced economies work. Yet little is understood about how the knowledge-based economy differs from the old, traditional economy. It is generally agreed that the phenomenon has grown out of the branch of economic thought known as new growth theory. Digesting up-to-date thinking in economics, management, innovation studies and economic geography, this significant volume provides an account of these developments and how they have transformed advanced economies.

Goal-based modeling of dynamically adaptive system requirements

Self-adaptation is emerging as an increasingly important capability for many applications, particularly those deployed in dynamically changing environments, such as ecosystem monitoring and disaster management. One key challenge posed by Dynamically Adaptive Systems (DASs) is the need to handle changes to the requirements and corresponding behavior of a DAS in response to varying environmental conditions. Berry et al. previously identified four levels of RE that should be performed for a DAS. In this paper, we propose the Levels of RE for Modeling that reify the original levels to describe RE modeling work done by DAS developers. Specifically, we identify four types of developers: the system developer, the adaptation scenario developer, the adaptation infrastructure developer, and the DAS research community. Each level corresponds to the work of a different type of developer to construct goal model(s) specifying their requirements. We then leverage the Levels of RE for Modeling to propose two complementary processes for performing RE for a DAS. We describe our experiences with applying this approach to GridStix, an adaptive flood warning system, deployed to monitor the River Ribble in Yorkshire, England.

Combining ERP systems with enterprise 2.0

The paper discusses both the complementary factors and contradictions of adoption ERP based systems with enterprise 2.0. ERP is well known as its' efficient business process management. Also the high failure rate the system implementation is famous as well. According to [1], ERP systems could achieve efficient business performance by enabling a standardized business process design, but at a cost of flexibility in operations. However, enterprise 2.0 supports flexible business process management, informal and less structured interactions [3],[4],[21]. Traditional researcher claimed efficiency and flexibility may seem incompatible in that they are different business objectives and may exist in different organizational environments. However, the paper will break traditional norms that combine ERP and enterprise 2.0 in a single enterprise to improve both efficient and flexible operations simultaneously. Based on the multiple cases studies, four cases presented different attitudes on usage ERP systems and enterprise social systems. Based on socio-technical theory, the paper presents in-depth analysis benefits of combination ERP with enterprise 2.0 for these firms.