In many dynamic open systems, agents have to interact with one another to achieve their goals. Here, agents may be self-interested, and when trusted to perform an action for another, may betray that trust by not performing the action as required. In addition, due to the size of such systems, agents will often interact with other agents with which they have little or no past experience. There is therefore a need to develop a model of trust and reputation that will ensure good interactions among software agents in large scale open systems. Against this background, we have developed TRAVOS (Trust and Reputation model for Agent-based Virtual OrganisationS) which models an agent's trust in an interaction partner. Specifically, trust is calculated using probability theory taking account of past interactions between agents, and when there is a lack of personal experience between agents, the model draws upon reputation information gathered from third parties. In this latter case, we pay particular attention to handling the possibility that reputation information may be inaccurate.

We have studied two misfolded oligomeric forms of the protein HypF-N, which show similar morphologies but very different toxicities. We measured over 80 intermolecular distance-dependent parameters for each oligomer type using FRET, in conjunction with solution- and solid-state NMR and other biophysical techniques. The results indicate that the formation of a highly organised hydrogen bonded core in the toxic oligomers results in the exposure of a larger number of hydrophobic residues than in the nontoxic species, causing the former to form aberrant interactions with cellular components.

Background: Antimicrobial peptides (AMPs) have the potential to act against multiple pathogenic targets.Results: AMPs that maintain conformational flexibility are more potent against multiple pathogens and less hemolytic.Conclusion: Antimicrobial action and hemolysis proceed via differing mechanisms.Significance: The potency, selectivity, and ability of AMPs to reach intracellular pathogens can be modulated using general principles.

This research aims to develop a model of trust and reputation that will ensure good interactions amongst software agents in large scale open systems in particular. The following are key drivers for our model: (1) agents may be self-interested and may provide false accounts of experiences with other agents if it is beneficial for them to do so; (2) agents will need to interact with other agents with which they have no past experience. Against this background, we have developed TRAVOS (Trust and Reputation model for Agent-based Virtual OrganisationS) which models an agent's trust in an interaction partner. Specifically, trust is calculated using probability theory taking account of past interactions between agents. When there is a lack of personal experience between agents, the model draws upon reputation information gathered from third parties. In this latter case, we pay particular attention to handling the possibility that reputation information may be inaccurate.

Cationic amphipathic histidine rich peptides demonstrate differential nucleic acid binding capabilities at neutral and acidic pH and adopt conformations at acidic pH that enable interaction with endosomal membranes, their subsequent disordering and facilitate entry of cargo to the cell cytosol. To better understand the relative contributions of each stage in the process and consequently the structural requirements of pH responsive peptides for optimal nucleic acid transfer, we used biophysical methods to dissect the series of events that occur during endosomal acidification. Far-UV circular dichroism was used to characterise the solution conformation of a series of peptides, containing either four or six histidine residues, designed to respond at differing pH while a novel application of near-UV circular dichroism was used to determine the binding affinities of the peptides for both DNA and siRNA. The peptide induced disordering of neutral and anionic membranes was investigated using (2)H solid-state NMR. While each of these parameters models key stages in the nucleic acid delivery process and all were affected by increasing the histidine content of the peptide, the effect of a more acidic pH response on peptide self-association was most notable and identified as the most important barrier to further enhancing nucleic acid delivery. Further, the results indicate that Coulombic interactions between the histidine residues modulate protonation and subsequent conformational transitions required for peptide mediated gene transfer activity and are an important factor to consider in future peptide design.