Liposomal vaccine delivery systems

INTRODUCTION: Liposomes remain at the forefront of drug and vaccine design owing to their well-documented abilities to act as delivery vehicles. Nevertheless, the concept of liposomes as delivery vehicles is not a new one, with most works focusing on their use for the delivery of genes and drugs. However, in the last 10 years a significant amount of research has focused on using liposomes as vaccine adjuvants, not only as an antigen delivery vehicle but also as a tool to increase the immunogenicity of peptide and protein antigens. AREAS COVERED: This paper reviews liposomal adjuvants now in vaccine development, with particular emphasis on their adjuvant mechanism and how specific physicochemical characteristics of liposomes affect the immune response. The inclusion of immunomodulators is also discussed, with prominence given to Toll-like receptor ligands. EXPERT OPINION: The use of liposomes as vaccine delivery systems is evolving rapidly owing to the combined increase in technological advances and understanding of the immune system. Liposomes that contain and deliver immunostimulators and antigens are now being developed to target diseases that require stimulation of both humoral and cell-mediated immune responses. The CAF liposomal system, described in detail in this review, is one liposomal model that shows such flexibility.

The growing importance of inter-company collaboration

Guest editorial: This special issue has been drawn from papers that were published as part of the Second European Conference on Management of Technology (EuroMOT) which was held at Aston Business School (Birmingham, UK) 10-12 September 2006. This was the official European conference for the International Association for Management of Technology (IAMOT); the overall theme of the conference was “Technology and global integration.” There were many high-calibre papers submitted to the conference and published in the associated proceedings (Bennett et al., 2006). The streams of interest that emerged from these submissions were the importance of: technology strategy, innovation, process technologies, managing change, national policies and systems, research and development, supply chain technology, service and operational technology, education and training, small company incubation, technology transfer, virtual operations, technology in developing countries, partnership and alliance, and financing and investment. This special issue focuses upon the streams of interest that accentuate the importance of collaboration between different organisations. Such organisations vary greatly in character; for instance, they may be large or small, publicly or privately owned, and operate in manufacturing or service sectors. Despite these varying characteristics they all have something in common; they all stress the importance of inter-organisational collaboration as a critical success factor for their organisation. In today's global economy it is essential that organisations decide what their core competencies are what those of complementing organisations are. Core competences should be developed to become a bases of differentiation, leverage and competitive advantage, whilst those that are less mature should be outsourced to other organisations that can claim to have had more recognition and success in that particular core competence (Porter, 2001). This strategic trend can be observed throughout advanced economies and is growing strongly. If a posteriori reasoning is applied here it follows that organisations could continue to become more specialised in fewer areas whilst simultaneously becoming more dependent upon other organisations for critical parts of their operations. Such actions seem to fly in the face of rational business strategy and so the question must be asked: why are organisations developing this way? The answer could lie in the recent changes in endogenous and exogenous factors of the organisation; the former emphasising resource-based issues in the short-term, and strategic positioning in the long-term whilst the later emphasises transaction costs in the short-term and acquisition of new skills and knowledge in the long-term. For a harmonious balance of these forces to prevail requires organisations to firstly declare a shared meta-strategy, then to put some cross-organisational processes into place which have their routine operations automated as far as possible. A rolling business plan would review, assess and reposition each organisation within this meta-strategy according to how well they have contributed (Binder and Clegg, 2006). The important common issue here is that an increasing number of businesses today are gaining direct benefit from increasing their levels of inter-organisational collaboration. Such collaboration has largely been possible due to recent technological advances which can make organisational structures more agile (e.g. the extended or the virtual enterprise), organisational infra-structure more connected, and the sharing of real-time information an operational reality. This special issue consists of research papers that have explored the above phenomenon in some way. For instance, the role of government intervention, the use of internet-based technologies, the role of research and development organisations, the changing relationships between start-ups and established firms, the importance of cross-company communities of practice, the practice of networking, the front-loading of large-scale projects, innovation and the probabilistic uncertainties that organisations experience are explored in these papers. The cases cited in these papers are limited as they have a Eurocentric focus. However, it is hoped that readers of this special issue will gain a valuable insight into the increasing importance of collaborative practices via these studies.

Strategy, IT and dynamic change in enterprises

This paper explores the importance of collaboration between different types of organizations within an enterprise. To achieve successful collaboration requires both endogenous and exogenous factors of each organization to be considered and a shared meta-strategy supported by shared cross-organizational processes and technology. A rolling business plan would periodically review, assess and reposition each organization within this meta-strategy according to how well they have contributed. We show that recent technological advances have made organizational structures more agile, organizational infra-structure more connected and the sharing of real-time information an operational reality; we also discuss the challenges and risks.

The impact of e-business infusion on channel coordination, conflict and reseller performance

Manufacturer–reseller interactions are becoming more technology-enabled as channels of distribution increasingly utilize e-business tools on the Internet. This research examines the performance consequences for resellers as these technological advances are applied to distribution activities between channel members. Using a sample of 216 resellers of computer products, the research explores the impact of e-business tools in 2 areas of manufacturer–reseller interactions: supply tasks and demand tasks. The results suggest that e-business in supply tasks increases relationship coordination between manufacturer and reseller, whereas e-business in demand tasks increases coordination as well as conflict within the channel dyad. The increase of conflict constitutes a potential “dark side” of e-business in channel relationships that may provide an explanation for e-business implementation failures and negative returns on investment in technology.

The frontier approach to the measurement of productivity and technical efficiency

In 1957, Farrell proposed to measure technical (in)efficiency as the realised deviation from a frontier isoquant. Since then, the research has developed several methods to derive the production frontier and it has also extended its scope in applying frontier techniques to the measurement of total factor productivity. In this paper, I present the core techniques for the measurement of technical efficiency and productivity based on the notion of frontier and introduce the more recent technological advances in the field.

A biological-inspired support frame for an artificial cornea

Bilateral corneal blindness represents a quarter of the total blind, world-wide. The artificial cornea in assorted forms, was developed to replace opaque non-functional corneas and to return sight in otherwise hopeless cases that were not amenable to corneal grafts; believed to be 2% of corneal blind. Despite technological advances in materials design and tissue engineering no artificial cornea has provided absolute, long-term success. Formidable problems exist, due to a combination of unpredictable wound healing and unmanageable pathology. To have a solid guarantee of reliable success an artificial cornea must possess three attributes: an optical window to replace the opaque cornea; a strong, long term union to surrounding ocular tissue; and the ability to induce desired host responses. A unique artificial cornea possesses all three functional attributes- the Osteo-odonto-keratoprosthesis (OOKP). The OOKP has a high success rate and can survive for up to twenty years, but it is complicated both in structure and in surgical procedure; it is expensive and not universally available. The aim of this project was to develop a synthetic substitute for the OOKP, based upon key features of the tooth and bone structure. In doing so, surgical complexity and biological complications would be reduced. Analysis of the biological effectiveness of the OOKP showed that the structure of bone was the most crucial component for implant retention. An experimental semi-rigid hydroxyapatite framework was fabricated with a complex bone-like architecture, which could be fused to the optical window. The first method for making such a framework, was pressing and sintering of hydroxyapatite powders; however, it was not possible to fabricate a void architecture with the correct sizes and uniformity of pores. Ceramers were synthesised using alternative pore forming methods, providing for improved mechanical properties and stronger attachment to the plastic optical window. Naturally occurring skeletal structures closely match the structural features of all forms of natural bone. Synthetic casts were fabricated using the replamineform process, of desirable natural artifacts, such as coral and sponges. The final method of construction by-passed ceramic fabrication in favour of pre-formed coral derivatives and focused on methods for polymer infiltration, adhesion and fabrication. Prototypes were constructed and evaluated; a fully penetrative synthetic OOKP analogue was fabricated according to the dimensions of the OOKP. Fabrication of the cornea shaped OOKP synthetic analogue was also attempted.

Influence of microbial antigen formulation and delivery route on the immune response

Recent technological advances have resulted in the production of safe subunit and synthetic small peptide vaccines. Unfortunately, these vaccines are weakly or non-immunogenic in the absence of an immunological adjuvant (agents that can induce strong immunity to antigens). In addition, in order to prevent and/or control infection at the mucosal surface, stimulation of the mucosal immune system is essential. This may be achieved via the common mucosal immune system by exposure to antigen at a mucosal surface remote from the area of infection. Initial studies investigated the potential of multiple emulsions in effecting oral absorption and the subsequent immune responses to a lipopolysaccharide vaccine (LPS) after immunisation. Nasal delivery of LPS was carried out in parallel work using either aqueous solution or gel formulations. Tetanus toxoid vaccine in simple solution was delivered to guinea pigs as free antigen or entrapped in DSPC liposomes. In addition, adsorbed tetanus toxoid vaccine was delivered nasally free or in an aerosil gel formulation. This work was extended to investigate guinea pigs immunised by various mucosal routes with a herpes simplex virus subunit vaccine prepared from virus infected cells and delivered in gels, multiple emulsions and liposomes. Comparable serum antibody responses resulted but failed to produce enhanced protection against vaginal challenge when compared to subcutaneous immunisation with alhydrogel adjuvanted vaccine. Thus, immunisation of the mucosal surface by these methods may have been inadequate. These studies were extended in an attempt to protect against HSV genital challenge by construction of an attenuated Salmonella typhimurium HWSH aroA mutant expressing a cloned glycoprotein D-l gene fused to the Es-cherichia coli lac z promoter. Preliminary work on the colonisation of guinea pigs with S. typhimurium HWSH aroA mutants were carried out, with the aim of using the guinea pig HSV vaginal model to investigate protection.

The application of contact mechanics to the numerical simulation of particulate material

Particulate solids are complex redundant systems which consist of discrete particles. The interactions between the particles are complex and have been the subject of many theoretical and experimental investigations. Invetigations of particulate material have been restricted by the lack of quantitative information on the mechanisms occurring within an assembly. Laboratory experimentation is limited as information on the internal behaviour can only be inferred from measurements on the assembly boundary, or the use of intrusive measuring devices. In addition comparisons between test data are uncertain due to the difficulty in reproducing exact replicas of physical systems. Nevertheless, theoretical and technological advances require more detailed material information. However, numerical simulation affords access to information on every particle and hence the micro-mechanical behaviour within an assembly, and can replicate desired systems. To use a computer program to numerically simulate material behaviour accurately it is necessary to incorporte realistic interaction laws. This research programme used the finite difference simulation program `BALL', developed by Cundall (1971), which employed linear spring force-displacement laws. It was thus necessary to incorporate more realistic interaction laws. Therefore, this research programme was primarily concerned with the implementation of the normal force-displacement law of Hertz (1882) and the tangential force-displacement laws of Mindlin and Deresiewicz (1953). Within this thesis the contact mechanics theories employed in the program are developed and the adaptations which were necessary to incorporate these laws are detailed. Verification of the new contact force-displacement laws was achieved by simulating a quasi-static oblique contact and single particle oblique impact. Applications of the program to the simulation of large assemblies of particles is given, and the problems in undertaking quasi-static shear tests along with the results from two successful shear tests are described.

Visual performance of the human eye with soft hydrophilic contact lenses

The recording of visual acuity using the Snellen letter chart is only a limited measure of the visual performance of an eye wearing a refractive aid. Qualitative in addition to quantitative information is required to establish such a parameter: spatial, temporal and photometric aspects must all be incorporated into the test procedure. The literature relating to the correction of ametropia by refractive aids was reviewed. Selected aspects of a comparison between the correction provided by spectacles and contact lenses were considered. Special attention was directed to soft hydrophilic contact lenses. Despite technological advances which have produced physiologically acceptable soft lenses, there still remain associated with this recent form of refractive aid unpredictable visual factors. Several techniques for vision assessment were described, and previous studies of visual performance were discussed. To facilitate the investigation of visual performance in a clinical environment, a new semi-automated system was described: this utilized the presentation of broken ring test stimuli on a television screen. The research project comprised two stages. Initial work was concerned with the validation of the television system, including the optimization of its several operational variables. The second phase involved the utilization of the system in an investigation of visual performance aspects of the first month of regular daily soft contact lens wear by experimentally-naive subjects. On the basis of the results of this work an ‘homoeostatic’ model has been proposed to represent the strategy which an observer adopts in order to optimize his visual performance with soft contact lenses.

Overcoming barriers to membrane protein structure determination

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

Towards standardization of UV eye protection:what can be learned from photodermatology?

While knowledge about standardization of skin protection against ultraviolet radiation (UVR) has progressed over the past few decades, there is no uniform and generally accepted standardized measurement for UV eye protection. The literature provides solid evidence that UV can induce considerable damage to structures of the eye. As well as damaging the eyelids and periorbital skin, chronic UV exposure may also affect the conjunctiva and lens. Clinically, this damage can manifest as skin cancer and premature skin ageing as well as the development of pterygia and premature cortical cataracts. Modern eye protection, used daily, offers the opportunity to prevent these adverse sequelae of lifelong UV exposure. A standardized, reliable and comprehensive label for consumers and professionals is currently lacking. In this review we (i) summarize the existing literature about UV radiation-induced damage to the eye and surrounding skin; (ii) review the recent technological advances in UV protection by means of lenses; (iii) review the definition of the Eye-Sun Protection Factor (E-SPF®), which describes the intrinsic UV protection properties of lenses and lens coating materials based on their capacity to absorb or reflect UV radiation; and (iv) propose a strategy for establishing the biological relevance of the E-SPF. © 2013 John Wiley & Sons A/S.

The development of a symptom questionnaire for assessing virtual reality viewing using a head-mounted display

ABSTRACT: Purpose. Virtual reality devices, including virtual reality head-mounted displays, are becoming increasingly accessible to the general public as technological advances lead to reduced costs. However, there are numerous reports that adverse effects such as ocular discomfort and headache are associated with these devices. To investigate these adverse effects, questionnaires that have been specifically designed for other purposes such as investigating motion sickness have often been used. The primary purpose of this study was to develop a standard questionnaire for use in investigating symptoms that result from virtual reality viewing. In addition, symptom duration and whether priming subjects elevates symptom ratings were also investigated. Methods. A list of the most frequently reported symptoms following virtual reality viewing was determined from previously published studies and used as the basis for a pilot questionnaire. The pilot questionnaire, which consisted of 12 nonocular and 11 ocular symptoms, was administered to two groups of eight subjects. One group was primed by having them complete the questionnaire before immersion; the other group completed the questionnaire postviewing only. Postviewing testing was carried out immediately after viewing and then at 2-min intervals for a further 10 min. Results. Priming subjects did not elevate symptom ratings; therefore, the data were pooled and 16 symptoms were found to increase significantly. The majority of symptoms dissipated rapidly, within 6 min after viewing. Frequency of endorsement data showed that approximately half of the symptoms on the pilot questionnaire could be discarded because <20% of subjects experienced them. Conclusions. Symptom questionnaires to investigate virtual reality viewing can be administered before viewing, without biasing the findings, allowing calculation of the amount of change from pre- to postviewing. However, symptoms dissipate rapidly and assessment of symptoms needs to occur in the first 5 min postviewing. Thirteen symptom questions, eight nonocular and five ocular, were determined to be useful for a questionnaire specifically related to virtual reality viewing using a head-mounted display.

Shannon capacity of nonlinear communication channels

The exponentially increasing demand on operational data rate has been met with technological advances in telecommunication systems such as advanced multilevel and multidimensional modulation formats, fast signal processing, and research into new different media for signal transmission. Since the current communication channels are essentially nonlinear, estimation of the Shannon capacity for modern nonlinear communication channels is required. This PhD research project has targeted the study of the capacity limits of different nonlinear communication channels with a view to enable a significant enhancement in the data rate of the currently deployed fiber networks. In the current study, a theoretical framework for calculating the Shannon capacity of nonlinear regenerative channels has been developed and illustrated on the example of the proposed here regenerative Fourier transform (RFT). Moreover, the maximum gain in Shannon capacity due to regeneration (that is, the Shannon capacity of a system with ideal regenerators – the upper bound on capacity for all regenerative schemes) is calculated analytically. Thus, we derived a regenerative limit to which the capacity of any regenerative system can be compared, as analogue of the seminal linear Shannon limit. A general optimization scheme (regenerative mapping) has been introduced and demonstrated on systems with different regenerative elements: phase sensitive amplifiers and the proposed here multilevel regenerative schemes: the regenerative Fourier transform and the coupled nonlinear loop mirror.

A cloud-based farm management system:architecture and implementation

Recent technological advances have paved the way for developing and offering advanced services for the stakeholders in the agricultural sector. A paradigm shift is underway from proprietary and monolithic tools to Internet-based, cloud hosted, open systems that will enable more effective collaboration between stakeholders. This new paradigm includes the technological support of application developers to create specialized services that will seamlessly interoperate, thus creating a sophisticated and customisable working environment for the end users. We present the implementation of an open architecture that instantiates such an approach, based on a set of domain independent software tools called "generic enablers" that have been developed in the context of the FI-WARE project. The implementation is used to validate a number of innovative concepts for the agricultural sector such as the notion of a services' market place and the system's adaptation to network failures. During the design and implementation phase, the system has been evaluated by end users, offering us valuable feedback. The results of the evaluation process validate the acceptance of such a system and the need of farmers to have access to sophisticated services at affordable prices. A summary of this evaluation process is also presented in this paper. © 2013 Elsevier B.V.

Optical information capacity processing

The never-stopping increase in demand for information transmission capacity has been met with technological advances in telecommunication systems, such as the implementation of coherent optical systems, advanced multilevel multidimensional modulation formats, fast signal processing, and research into new physical media for signal transmission (e.g. a variety of new types of optical fibers). Since the increase in the signal-to-noise ratio makes fiber communication channels essentially nonlinear (due to the Kerr effect for example), the problem of estimating the Shannon capacity for nonlinear communication channels is not only conceptually interesting, but also practically important. Here we discuss various nonlinear communication channels and review the potential of different optical signal coding, transmission and processing techniques to improve fiber-optic Shannon capacity and to increase the system reach.