Verification and Control of Partially Observable Probabilistic Real-Time Systems

We propose automated techniques for the verification and control of probabilistic real-time systems that are only partially observable. To formally model such systems, we define an extension of probabilistic timed automata in which local states are partially visible to an observer or controller. We give a probabilistic temporal logic that can express a range of quantitative properties of these models, relating to the probability of an event's occurrence or the expected value of a reward measure. We then propose techniques to either verify that such a property holds or to synthesise a controller for the model which makes it true. Our approach is based on an integer discretisation of the model's dense-time behaviour and a grid-based abstraction of the uncountable belief space induced by partial observability. The latter is necessarily approximate since the underlying problem is undecidable, however we show how both lower and upper bounds on numerical results can be generated. We illustrate the effectiveness of the approach by implementing it in the PRISM model checker and applying it to several case studies, from the domains of computer security and task scheduling

Verification and control of partially observable probabilistic systems

We present automated techniques for the verification and control of partially observable, probabilistic systems for both discrete and dense models of time. For the discrete-time case, we formally model these systems using partially observable Markov decision processes; for dense time, we propose an extension of probabilistic timed automata in which local states are partially visible to an observer or controller. We give probabilistic temporal logics that can express a range of quantitative properties of these models, relating to the probability of an event’s occurrence or the expected value of a reward measure. We then propose techniques to either verify that such a property holds or synthesise a controller for the model which makes it true. Our approach is based on a grid-based abstraction of the uncountable belief space induced by partial observability and, for dense-time models, an integer discretisation of real-time behaviour. The former is necessarily approximate since the underlying problem is undecidable, however we show how both lower and upper bounds on numerical results can be generated. We illustrate the effectiveness of the approach by implementing it in the PRISM model checker and applying it to several case studies from the domains of task and network scheduling, computer security and planning

Evaluation of state-of-the-art technologies in industrial coal use and pollution control

Issued as Final report, Project no. A-382

Advanced flight control system study

A fly by wire flight control system architecture designed for high reliability includes spare sensor and computer elements to permit safe dispatch with failed elements, thereby reducing unscheduled maintenance. A methodology capable of demonstrating that the architecture does achieve the predicted performance characteristics consists of a hierarchy of activities ranging from analytical calculations of system reliability and formal methods of software verification to iron bird testing followed by flight evaluation. Interfacing this architecture to the Lockheed S-3A aircraft for flight test is discussed. This testbed vehicle can be expanded to support flight experiments in advanced aerodynamics, electromechanical actuators, secondary power systems, flight management, new displays, and air traffic control concepts

Genome-scale approaches to strengthen Neisseria gonorrhoeae epidemiological and antimicrobial resistance surveillance

Neisseria gonorrhoeae is the human pathogen responsible for the sexually transmitted disease gonorrhoea, whose burden remains a major public health concern. This bacterium has shown an extraordinary ability to develop antimicrobial resistance (AMR) to multiple classes of antimicrobials, with the advent of reaching a “superbug” status. With no available vaccine, managing gonorrhoea infections demands effective preventive measures, antibiotic treatments and epidemiological surveillance. National and international surveillance programmes are increasingly promoting the application of whole-genome sequencing (WGS) data to track N. gonorrhoeae circulation and the emergence and spread of AMR. The major goal of the PhD dissertation was to strengthen N. gonorrhoeae epidemiological and AMR surveillance using WGS. Particularly, we disclose the major AMR trends observed in Portugal throughout 16 years, by reporting data from the National Laboratory Network for Neisseria gonorrhoeae Collection (PTGonoNet), hosted at the Portuguese National Institute of Health (NIH). Using WGS data from across Europe, we report a comprehensive WGS-based genogroup assignment for N. gonorrhoeae. These genogroups represent main circulating lineages and were correlated with other typing techniques and linked to specific AMR signatures. Using a dynamic gene-by-gene approach, we performed the first genome-scale study of N. gonorrhoeae in Portugal, highlighting the genetic diversity of circulating strains, as well as potential transmission chains, which is essential to support epidemiological investigation. Finally, we evaluated a culture-independent strategy to obtain WGS data directly from clinical samples and its suitability for epidemiological surveillance and AMR detection. The findings presented in this dissertation constituted a turning point to consolidate the genomic epidemiology of gonococci in Portugal through the implementation of a WGS-based surveillance methodology in the Portuguese NIH. Ultimately, this work enhances N. gonorrhoeae surveillance by promoting the prospective monitoring of genogroup frequency and geographic spread, towards more oriented Public Health actions to control the spread of N. gonorrhoeae AMR.Neisseria gonorrhoeae é o agente patogénico humano que causa a doença sexualmente transmissível gonorreia, constituindo um problema de saúde publica. Esta bactéria tem capacidade de adquirir resistência antimicrobiana (RAM) a múltiplas classes de antibióticos. Sem vacina, o controlo da gonorreia exige medidas preventivas e tratamentos antimicrobianos eficazes, assim como vigilância epidemiológica. Programas nacionais e internacionais estão a promover progressivamente a aplicação da sequenciação total do genoma (WGS) para monitorizar a circulação de N. gonorrhoeae e a emergência e propagação de RAM. O principal objetivo desta dissertação foi o de contribuir para o fortalecimento da vigilância epidemiológica e de RAM em N. gonorrhoeae recorrendo a WGS. As principais tendências de RAM em Portugal ao longo de 16 anos foram identificadas, beneficiando dos dados colhidos pela Rede Nacional de Vigilância Laboratorial de Estirpes de Neisseria gonorrhoeae (PTGonoNET), sediada no Instituto Nacional de Saúde, Doutor Ricardo Jorge, I.P. (INSA). Através de dados de WGS Europeus, reportamos uma classificação de N. gonorrhoeae em genogrupos, os quais representam as suas principais linhagens em circulação, correlacionando-se com outras técnicas de tipagem e com perfis específicos de RAM. Aplicando uma abordagem gene-a-gene, efetuou-se o primeiro estudo à escala do genoma para N. gonorrhoeae em Portugal, revelando-se a diversidade genética das estirpes em circulação, assim como possíveis cadeias de transmissão, de forma a promover e/ou suportar a investigação epidemiológica. Finalmente, avaliou-se um método independente da cultura para obter dados de WGS diretamente de amostras clínicas e a sua aplicação para a vigilância epidemiológica e na deteção de RAM. Os resultados apresentados nesta tese constituem um ponto de viragem para a consolidação da epidemiologia genómica dos gonococos em Portugal com a implementação de uma metodologia de vigilância baseada em WGS no Laboratório de Referência no INSA. Por ultimo, este trabalho contribui para o fortalecimento da vigilância de N. gonorrhoeae promovendo a monotorização da frequência e propagação geográfica de genogrupos e contribuindo para ações de Saúde Pública mais orientadas para controlar a propagação de RAM de N. gonorrhoeae