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.

Simulation based knowledge elicitation:effect of visual representation and model parameters

Since much knowledge is tacit, eliciting knowledge is a common bottleneck during the development of knowledge-based systems. Visual interactive simulation (VIS) has been proposed as a means for eliciting experts’ decision-making by getting them to interact with a visual simulation of the real system in which they work. In order to explore the effectiveness and efficiency of VIS based knowledge elicitation, an experiment has been carried out with decision-makers in a Ford Motor Company engine assembly plant. The model properties under investigation were the level of visual representation (2-dimensional, 2½-dimensional and 3-dimensional) and the model parameter settings (unadjusted and adjusted to represent more uncommon and extreme situations). The conclusion from the experiment is that using a 2-dimensional representation with adjusted parameter settings provides the better simulation-based means for eliciting knowledge, at least for the case modelled.

Metrics and models to support the development of hybrid information systems

The research described here concerns the development of metrics and models to support the development of hybrid (conventional/knowledge based) integrated systems. The thesis argues from the point that, although it is well known that estimating the cost, duration and quality of information systems is a difficult task, it is far from clear what sorts of tools and techniques would adequately support a project manager in the estimation of these properties. A literature review shows that metrics (measurements) and estimating tools have been developed for conventional systems since the 1960s while there has been very little research on metrics for knowledge based systems (KBSs). Furthermore, although there are a number of theoretical problems with many of the `classic' metrics developed for conventional systems, it also appears that the tools which such metrics can be used to develop are not widely used by project managers. A survey was carried out of large UK companies which confirmed this continuing state of affairs. Before any useful tools could be developed, therefore, it was important to find out why project managers were not using these tools already. By characterising those companies that use software cost estimating (SCE) tools against those which could but do not, it was possible to recognise the involvement of the client/customer in the process of estimation. Pursuing this point, a model of the early estimating and planning stages (the EEPS model) was developed to test exactly where estimating takes place. The EEPS model suggests that estimating could take place either before a fully-developed plan has been produced, or while this plan is being produced. If it were the former, then SCE tools would be particularly useful since there is very little other data available from which to produce an estimate. A second survey, however, indicated that project managers see estimating as being essentially the latter at which point project management tools are available to support the process. It would seem, therefore, that SCE tools are not being used because project management tools are being used instead. The issue here is not with the method of developing an estimating model or tool, but; in the way in which "an estimate" is intimately tied to an understanding of what tasks are being planned. Current SCE tools are perceived by project managers as targetting the wrong point of estimation, A model (called TABATHA) is then presented which describes how an estimating tool based on an analysis of tasks would thus fit into the planning stage. The issue of whether metrics can be usefully developed for hybrid systems (which also contain KBS components) is tested by extending a number of "classic" program size and structure metrics to a KBS language, Prolog. Measurements of lines of code, Halstead's operators/operands, McCabe's cyclomatic complexity, Henry & Kafura's data flow fan-in/out and post-release reported errors were taken for a set of 80 commercially-developed LPA Prolog programs: By re~defining the metric counts for Prolog it was found that estimates of program size and error-proneness comparable to the best conventional studies are possible. This suggests that metrics can be usefully applied to KBS languages, such as Prolog and thus, the development of metncs and models to support the development of hybrid information systems is both feasible and useful.

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.

A semantic web environment for component model

Component-based development (CBD) has become an important emerging topic in the software engineering field. It promises long-sought-after benefits such as increased software reuse, reduced development time to market and, hence, reduced software production cost. Despite the huge potential, the lack of reasoning support and development environment of component modeling and verification may hinder its development. Methods and tools that can support component model analysis are highly appreciated by industry. Such a tool support should be fully automated as well as efficient. At the same time, the reasoning tool should scale up well as it may need to handle hundreds or even thousands of components that a modern software system may have. Furthermore, a distributed environment that can effectively manage and compose components is also desirable. In this paper, we present an approach to the modeling and verification of a newly proposed component model using Semantic Web languages and their reasoning tools. We use the Web Ontology Language and the Semantic Web Rule Language to precisely capture the inter-relationships and constraints among the entities in a component model. Semantic Web reasoning tools are deployed to perform automated analysis support of the component models. Moreover, we also proposed a service-oriented architecture (SOA)-based semantic web environment for CBD. The adoption of Semantic Web services and SOA make our component environment more reusable, scalable, dynamic and adaptive.

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.

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.

Changing employment relation systems in Japan:cases of the Mitsubishi Chemical Group and the Federation of Shinkin Banks

Over the past decade or so a number of changes have been observed in traditional Japanese employment relations (ERs) systems such as an increase in non-regular workers, a move towards performance-based systems and a continuous decline in union membership. There is a large body of Anglo-Saxon and Japanese literature providing evidence that national factors such as national institutions, national culture, and the business and economic environment have significantly influenced what were hitherto three ‘sacred’ aspects of Japanese ERs systems (ERSs). However, no research has been undertaken until now at the firm level regarding the extent to which changes in national factors influence ERSs across firms. This article develops a model to examine the impact of national factors on ER systems; and analyses the impact of national factors at the firm level ER systems. Based on information collected from two different groups of companies, namely Mitsubishi Chemical Group (MCG) and Federation of Shinkin Bank (FSB) the research finds that except for a few similarities, the impact of national factors is different on Japanese ER systems at the firm level. This indicates that the impact of national factors varies in the implementation of employment relations factors. In the case of MCG, national culture has less to do with seniority-based system. Study also reveals that the national culture factors have also less influence on an enterprise-based system in the case of FSB. This analysis is useful for domestic and international organizations as it helps to better understand the role of national factors in determining Japanese ERSs.

Quasi-lossless data transmission with ultra-long Raman fibre laser based amplification

The project consists of an experimental and numerical modelling study of the applications of ultra-long Raman fibre laser (URFL) based amplification techniques for high-speed multi-wavelength optical communications systems. The research is focused in telecommunications C-band 40 Gb/s transmission data rates with direct and coherent detection. The optical transmission performance of URFL based systems in terms of optical noise, gain bandwidth and gain flatness for different system configurations is evaluated. Systems with different overall span lengths, transmission fibre types and data modulation formats are investigated. Performance is compared with conventional Erbium doped fibre amplifier based system to evaluate system configurations where URFL based amplification provide performance or commercial advantages.

Combining ERP systems with enterprise 2.0

The chapter discusses both the complementary factors and contradictions of adoption ERP-based systems with Enterprise 2.0. ERP is well known as IT's efficient business process management. Enterprise 2.0 supports flexible business process management, informal, and less structured interactions. Traditional studies indicate efficiency and flexibility may seem incompatible because they are different business objectives and may exist in different organizational environments. However, the chapter breaks traditional norms that combine ERP and Enterprise 2.0 in a single enterprise to improve both efficient and flexible operations simultaneously. Based on multiple case studies, the chapter analyzes the benefits and risks of the combination of ERP with Enterprise 2.0 from process, organization, and people paradigms. © 2013 by IGI Global.

Generalized Nets Model of an E-Learning System Software Architecture

The paper has been presented at the International Conference Pioneers of Bulgarian Mathematics, Dedicated to Nikola Obreshko ff and Lubomir Tschakaloff , Sofi a, July, 2006.

Analogical Reasoning Techniques in Intelligent Counterterrorism Systems

The paper develops a set of ideas and techniques supporting analogical reasoning throughout the life-cycle of terrorist acts. Implementation of these ideas and techniques can enhance the intellectual level of computer-based systems for a wide range of personnel dealing with various aspects of the problem of terrorism and its effects. The method combines techniques of structure-sensitive distributed representations in the framework of Associative-Projective Neural Networks, and knowledge obtained through the progress in analogical reasoning, in particular the Structure Mapping Theory. The impact of these analogical reasoning tools on the efforts to minimize the effects of terrorist acts on civilian population is expected by facilitating knowledge acquisition and formation of terrorism-related knowledge bases, as well as supporting the processes of analysis, decision making, and reasoning with those knowledge bases for users at various levels of expertise before, during, and after terrorist acts.

Parallelization of Logical Inference for Confluent Rule-based System

* This paper was made according to the program № 14 of fundamental scientific research of the Presidium of the Russian Academy of Sciences, the project 06-I-П14-052

Real-time high-resolution heterodyne-based measurements of spectral dynamics in fibre lasers

Conventional tools for measurement of laser spectra (e.g. optical spectrum analysers) capture data averaged over a considerable time period. However, the generation spectrum of many laser types may involve spectral dynamics whose relatively fast time scale is determined by their cavity round trip period, calling for instrumentation featuring both high temporal and spectral resolution. Such real-time spectral characterisation becomes particularly challenging if the laser pulses are long, or they have continuous or quasi-continuous wave radiation components. Here we combine optical heterodyning with a technique of spatiooral intensity measurements that allows the characterisation of such complex sources. Fast, round-trip-resolved spectral dynamics of cavity-based systems in real-time are obtained, with temporal resolution of one cavity round trip and frequency resolution defined by its inverse (85 ns and 24 MHz respectively are demonstrated). We also show how under certain conditions for quasi-continuous wave sources, the spectral resolution could be further increased by a factor of 100 by direct extraction of phase information from the heterodyned dynamics or by using double time scales within the spectrogram approach.