An operational research-based integrated approach for mass evacuation planning of a city

Large-scale disasters are constantly occurring around the world, and in many cases evacuation of regions of city is needed. ‘Operational Research/Management Science’ (OR/MS) has been widely used in emergency planning for over five decades. Warning dissemination, evacuee transportation and shelter management are three ‘Evacuation Support Functions’ (ESF) generic to many hazards. This thesis has adopted a case study approach to illustrate the importance of integrated approach of evacuation planning and particularly the role of OR/MS models. In the warning dissemination phase, uncertainty in the household’s behaviour as ‘warning informants’ has been investigated along with uncertainties in the warning system. An agentbased model (ABM) was developed for ESF-1 with households as agents and ‘warning informants’ behaviour as the agent behaviour. The model was used to study warning dissemination effectiveness under various conditions of the official channel. In the transportation phase, uncertainties in the household’s behaviour such as departure time (a function of ESF-1), means of transport and destination have been. Households could evacuate as pedestrians, using car or evacuation buses. An ABM was developed to study the evacuation performance (measured in evacuation travel time). In this thesis, a holistic approach for planning the public evacuation shelters called ‘Shelter Information Management System’ (SIMS) has been developed. A generic allocation framework of was developed to available shelter capacity to the shelter demand by considering the evacuation travel time. This was formulated using integer programming. In the sheltering phase, the uncertainty in household shelter choices (either nearest/allocated/convenient) has been studied for its impact on allocation policies using sensitivity analyses. Using analyses from the models and detailed examination of household states from ‘warning to safety’, it was found that the three ESFs though sequential in time, however have lot of interdependencies from the perspective of evacuation planning. This thesis has illustrated an OR/MS based integrated approach including and beyond single ESF preparedness. The developed approach will help in understanding the inter-linkages of the three evacuation phases and preparing a multi-agency-based evacuation planning evacuation

The effect of load on agent-based algorithms for distributed task allocation

Multi-agent algorithms inspired by the division of labour in social insects and by markets, are applied to a constrained problem of distributed task allocation. The efficiency (average number of tasks performed), the flexibility (ability to react to changes in the environment), and the sensitivity to load (ability to cope with differing demands) are investigated in both static and dynamic environments. A hybrid algorithm combining both approaches, is shown to exhibit improved efficiency and robustness. We employ nature inspired particle swarm optimisation to obtain optimised parameters for all algorithms in a range of representative environments. Although results are obtained for large population sizes to avoid finite size effects, the influence of population size on the performance is also analysed. From a theoretical point of view, we analyse the causes of efficiency loss, derive theoretical upper bounds for the efficiency, and compare these with the experimental results.

Reporter ion-based mass spectrometry approaches for the detection of non-enzymatic protein modifications in biological samples

Development of mass spectrometry techniques to detect protein oxidation, which contributes to signalling and inflammation, is important. Label-free approaches have the advantage of reduced sample manipulation, but are challenging in complex samples owing to undirected analysis of large data sets using statistical search engines. To identify oxidised proteins in biological samples, we previously developed a targeted approach involving precursor ion scanning for diagnostic MS3 ions from oxidised residues. Here, we tested this approach for other oxidations, and compared it with an alternative approach involving the use of extracted ion chromatograms (XICs) generated from high-resolution MSMS data using very narrow mass windows. This accurate mass XIC data methodology was effective at identifying nitrotyrosine, chlorotyrosine, and oxidative deamination of lysine, and for tyrosine oxidations highlighted more modified peptide species than precursor ion scanning or statistical database searches. Although some false positive peaks still occurred in the XICs, these could be identified by comparative assessment of the peak intensities. The method has the advantage that a number of different modifications can be analysed simultaneously in a single LC-MSMS run. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. Biological significance: The use of accurate mass extracted product ion chromatograms to detect oxidised peptides could improve the identification of oxidatively damaged proteins in inflammatory conditions. © 2013 Elsevier B.V.

Resource allocation in decentralised computational systems:an evolutionary market-based approach

We present a novel market-based method, inspired by retail markets, for resource allocation in fully decentralised systems where agents are self-interested. Our market mechanism requires no coordinating node or complex negotiation. The stability of outcome allocations, those at equilibrium, is analysed and compared for three buyer behaviour models. In order to capture the interaction between self-interested agents, we propose the use of competitive coevolution. Our approach is both highly scalable and may be tuned to achieve specified outcome resource allocations. We demonstrate the behaviour of our approach in simulation, where evolutionary market agents act on behalf of service providing nodes to adaptively price their resources over time, in response to market conditions. We show that this leads the system to the predicted outcome resource allocation. Furthermore, the system remains stable in the presence of small changes in price, when buyers' decision functions degrade gracefully. © 2009 The Author(s).

Mass spectrometry-based methods for identifying oxidized proteins in disease:advances and challenges

Many inflammatory diseases have an oxidative aetiology, which leads to oxidative damage to biomolecules, including proteins. It is now increasingly recognized that oxidative post-translational modifications (oxPTMs) of proteins affect cell signalling and behaviour, and can contribute to pathology. Moreover, oxidized proteins have potential as biomarkers for inflammatory diseases. Although many assays for generic protein oxidation and breakdown products of protein oxidation are available, only advanced tandem mass spectrometry approaches have the power to localize specific oxPTMs in identified proteins. While much work has been carried out using untargeted or discovery mass spectrometry approaches, identification of oxPTMs in disease has benefitted from the development of sophisticated targeted or semi-targeted scanning routines, combined with chemical labeling and enrichment approaches. Nevertheless, many potential pitfalls exist which can result in incorrect identifications. This review explains the limitations, advantages and challenges of all of these approaches to detecting oxidatively modified proteins, and provides an update on recent literature in which they have been used to detect and quantify protein oxidation in disease.

The redoxomics of PTEN: walking a fine line between damage and signaling:mass spectrometry-based approaches to study the effect of oxidation on PTEN function, structure, and protein-protein interactions

The research described in this PhD thesis focuses on proteomics approaches to study the effect of oxidation on the modification status and protein-protein interactions of PTEN, a redox-sensitive phosphatase involved in a number of cellular processes including metabolism, apoptosis, cell proliferation, and survival. While direct evidence of a redox regulation of PTEN and its downstream signaling has been reported, the effect of cellular oxidative stress or direct PTEN oxidation on PTEN structure and interactome is still poorly defined. In a first study, GST-tagged PTEN was directly oxidized over a range of hypochlorous acid (HOCl) concentration, assayed for phosphatase activity, and oxidative post-translational modifications (oxPTMs) were quantified using LC-MS/MS-based label-free methods. In a second study, GSTtagged PTEN was prepared in a reduced and reversibly H2O2-oxidized form, immobilized on a resin support and incubated with HCT116 cell lysate to capture PTEN interacting proteins, which were analyzed by LC-MS/MS and comparatively quantified using label-free methods. In parallel experiments, HCT116 cells transfected with a GFP-tagged PTEN were treated with H2O2 and PTENinteracting proteins immunoprecipitated using standard methods. Several high abundance HOCl-induced oxPTMs were mapped, including those taking place at amino acids known to be important for PTEN phosphatase activity and protein-protein interactions, such as Met35, Tyr155, Tyr240 and Tyr315. A PTEN redox interactome was also characterized, which identified a number of PTEN-interacting proteins that vary with the reversible inactivation of PTEN caused by H2O2 oxidation. These included new PTEN interactors as well as the redox proteins peroxiredoxin-1 (Prdx1) and thioredoxin (Trx), which are known to be involved in the recycling of PTEN active site following H2O2-induced reversible inactivation. The results suggest that the oxidative modification of PTEN causes functional alterations in PTEN structure and interactome, with fundamental implications for the PTEN signaling role in many cellular processes, such as those involved in the pathophysiology of disease and ageing.