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.

Adapting populations of agents

We control a population of interacting software agents. The agents have a strategy, and receive a payoff for executing that strategy. Unsuccessful agents become extinct. We investigate the repercussions of maintaining a diversity of agents. There is often no economic rationale for this. If maintaining diversity is to be successful, i.e. without lowering too much the payoff for the non-endangered strategies, it has to go on forever, because the non-endangered strategies still get a good payoff, so that they continue to thrive, and continue to endanger the endangered strategies. This is not sustainable if the number of endangered ones is of the same order as the number of non-endangered ones. We also discuss niches, islands. Finally, we combine learning as adaptation of individual agents with learning via selection in a population. © Springer-Verlag Berlin Heidelberg 2003.

Evolutionary market agents and heterogeneous service providers:achieving desired resource allocations

In future massively distributed service-based computational systems, resources will span many locations, organisations and platforms. In such systems, the ability to allocate resources in a desired configuration, in a scalable and robust manner, will be essential.We build upon a previous evolutionary market-based approach to achieving resource allocation in decentralised systems, by considering heterogeneous providers. In such scenarios, providers may be said to value their resources differently. We demonstrate how, given such valuations, the outcome allocation may be predicted. Furthermore, we describe how the approach may be used to achieve a stable, uneven load-balance of our choosing. We analyse the system's expected behaviour, and validate our predictions in simulation. Our approach is fully decentralised; no part of the system is weaker than any other. No cooperation between nodes is assumed; only self-interest is relied upon. A particular desired allocation is achieved transparently to users, as no modification to the buyers is required.

Methods of Adaptive Extraction and Analysis of Knowledge for Knowledge-base Construction and Fast Decision Making

An approach for knowledge extraction from the information arriving to the knowledge base input and also new knowledge distribution over knowledge subsets already present in the knowledge base is developed. It is also necessary to realize the knowledge transform into parameters (data) of the model for the following decision-making on the given subset. It is assumed to realize the decision-making with the fuzzy sets’ apparatus.

Adaptive Routing and Multi-Agent Control for Information Flows in IP-Networks

The principles of adaptive routing and multi-agent control for information flows in IP-networks.

Adaptive power and rate control for QoS guarantee of DSRC based collaborative road safety applications

In this paper we propose an adaptive power and message rate control method for safety applications at road intersections. The design objectives are to firstly provide guaranteed QoS support to both high priority emergency safety applications and low priority routine safety applications and secondly maximize channel utilization. We use an offline simulation based approach to find out the best possible configurations of transmit power and message rate for given numbers of vehicles in the network with certain safety QoS requirements. The identified configurations are then used online by roadside access points (AP) adaptively according to estimated number of vehicles. Simulation results show that this adaptive method could provide required QoS support to safety applications and it significantly outperforms a fixed control method. © 2013 International Information Institute.

Bimodal adaptive hypermedia and interactive multimedia a web-based learning environment based on Kolb's theory of learning style

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

British Double Agents and Operation Fortitude: A New Perspective

On June 6th, 1944, Allied forces stormed the beaches of Normandy as a part of Operation Overlord, the Allied invasion of France. While they experienced pockets of stiff resistance, Allied troops sustained far fewer casualties than they had expected. The reason for this was due to Operation Fortitude, a deception mission that intended to fool Hitler about the time and location of the Allied invasion mission. The use of double agents by British Intelligence services was essential for the effective execution of Fortitude. The story of the double agents goes beyond their success during Fortitude. Double agents were initially recruited as German agents, but key agents immediately turned themselves in to British authorities upon reaching the nation. These agents decided to become involved with British Intelligence due to broader circumstances that were happening in Europe. The emergence of Fascist regimes disrupted the political landscape of Europe and led to widespread condemnation from political and social spheres. Their development as double agents became crucial to their effectiveness during Operation Fortitude. Their successful infiltration of German Intelligence allowed them to convince Hitler and German High Command that the main Allied invasion force would come at the Pas de Calais instead of Normandy. The result was that the Allies met an unprepared German defense force on D-Day and were able to advance past the beaches. The work of the double agents during Fortitude saved thousands of Allied lives and was vital to the success of Operation Overlord.

Bimodal adaptive hypermedia and interactive multimedia a web-based learning environment based on Kolb's theory of learning style

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Disaster preparedness, adaptive politics and lifelong learning: a case of Japan

Preparedness for disaster scenarios is progressively becoming an educational agenda for governments because of diversifying risks and threats worldwide. In disaster-prone Japan, disaster preparedness has been a prioritised national agenda, and preparedness education has been undertaken in both formal schooling and lifelong learning settings. This article examines the politics behind one prevailing policy discourse in the field of disaster preparedness referred to as ‘the four forms of aid’ – ‘kojo [public aid]’, ‘jijo [self-help]’, ‘gojo/kyojo [mutual aid]’. The study looks at the Japanese case, however, the significance is global, given that neo-liberal governments are increasingly having to deal with a range of disaster situations whether floods or terrorism, while implementing austerity measures. Drawing on the theory of the adaptiveness of neo-liberalism, the article sheds light on the hybridity of the current Abe government’s politics: a ‘dominant’ neo-liberal economic approach – public aid and self-help – and a ‘subordinate’ moral conservative agenda – mutual aid. It is argued that the four forms of aid are an effective ‘balancing act’, and that kyojo in particular is a powerful legitimator in the hybrid politics. The article concludes that a lifelong and life-wide preparedness model could be developed in Japan which has taken a social approach to lifelong learning. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Cultural Heritage and Mobile Robotics Technologies

This paper reviews current research works at the authors’ Institutions to illustrate how mobile robotics and related technologies can be used to enhance economical fruition, control, protection and social impact of the cultural heritage. Robots allow experiencing on-line, from remote locations, tours at museums, archaeological areas and monuments. These solutions avoid travelling costs, increase beyond actual limits the number of simultaneous visitors, and prevent possible damages that can arise by over-exploitation of fragile environments. The same tools can be used for exploration and monitoring of cultural artifacts located in difficult to reach or dangerous areas. Examples are provided by the use of underwater robots in the exploration of deeply submerged archaeological areas. Besides, technologies commonly employed in robotics can be used to help exploring, monitoring and preserving cultural artifacts. Examples are provided by the development of procedures for data acquisition and mapping and by object recognition and monitoring algorithms.

Agents and SCT based self* control architecture for production systems

Otto-von-Guericke-Universität Magdeburg, Fakultät für Maschinenbau, Dissertation, 2016

Control of citrus black spot (Guignardia citricarpa) by biological control agents and other alternative products.

2007