Incremental Construction of Large Specifications: Case Study and Techniques

The RODIN project is an EU-funded project concerned with the provision of methods and tools for rigorous development of complex software-based systems. Ultimately, through the development of open-source tools and techniques, the project aims to make formal methods more appealing and accessible to industry. The project is driven by a number of case studies, each of which is designed to exercise the technology being developed and create methodologies for the future. In this paper we focus on the methodologies being developed in one of the case studies (the CDIS subset). This case study is based on a commercial air traffic information system that was developed using formal methods 14 years ago, and it is still in operation today. The key goals of our approach are to improve the comprehensibility of large specifications and to achieve a complete mechanical proof of consistency

Redevelopment of an industrial case study using Event-B and Rodin

CDIS is a commercial air traffic information system that was developed using formal methods 15 years ago by Praxis, and it is still in operation today. This system is an example of an industrial scale system that has been developed using formal methods. In particular, the functional requirements of the system were specified using VVSL -- a variant of VDM. A subset of the original specification has been chosen to be reconstructed on the Rodin platform based on the new Event-B formalism. The goal of our reconstruction was to overcome three key difficulties of the original formalisation, namely the difficulty of comprehending the original specification, the lack of any mechanical proof of the consistency of the specification and the difficulty of dealing with distribution and atomicity refinement. In this paper we elucidate how a new formal notation and tool can help to overcome these difficulties

Prenatal programming of neuroendocrine reproductive function

It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the “prenatal programming” of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be “shaped” both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent “normal function”. The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on reproductive potential

Modelling and Refinement in CODA

This paper provides an overview of the CODA framework for modelling and refinement of component-based embedded systems. CODA is an extension of Event-B and UML-B and is supported by a plug-in for the Rodin toolset. CODA augments Event-B with constructs for component-based modelling including components, communications ports, port connectors, timed communications and timing triggers. Component behaviour is specified through a combination of UML-B state machines and Event-B. CODA communications and timing are given an Event-B semantics through translation rules. Refinement is based on Event-B refinement and allows layered construction of CODA models in a consistent way.Comment: In Proceedings Refine 2013, arXiv:1305.563

The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae

Neutrophils play an important role in the innate immune response to infection with Streptococcus pneumoniae, the pneumococcus. Pneumococci are phagocytosed by neutrophils and undergo killing after ingestion. Other cellular processes may also be induced, including autophagy and the formation of neutrophil extracellular traps (NETs), which may play a role in bacterial eradication. We set out to determine how these different processes interacted following pneumococcal infection of neutrophils, and the role of the major pneumococcal toxin pneumolysin in these various pathways. We found that pneumococci induced autophagy in neutrophils in a type III phosphatidylinositol-3 kinase dependent fashion that also required the autophagy gene Atg5. Pneumolysin did not affect this process. Phagocytosis was inhibited by pneumolysin but enhanced by autophagy, while killing was accelerated by pneumolysin but inhibited by autophagy. Pneumococci induced extensive NET formation in neutrophils that was not influenced by pneumolysin but was critically dependent on autophagy. While pneumolysin did not affect NET formation, it had a potent inhibitory effect on bacterial trapping within NETs. These findings show a complex interaction between phagocytosis, killing, autophagy and NET formation in neutrophils following pneumococcal infection that contribute to host defence against this pathogen

Integrating Formal Methods with Informal Digital Hardware Development

This paper presents some results from an industrial project to develop high-integrity digital hardware by integrating formal methods with a more traditional informal approach. The ultimate goal of the project team was to produce sythesisable VHDL that could be proven to meet given requirements for an embedded controller. The burden was on the formal methods experts to integrate themselves into the team. This paper describes the formal approach that was developed as a result

Strategies and plans for implementing e-learning at the University of Zululand

University of Zululand presentation at the Colloquium, Developmental study towards effective practices in technology-assisted learning: Reflections 2009, held on 23 November 2009 at the University of Johannesburg

Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa

Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic fibrosis (CF) and other chronic lung diseases. Cytokines of the IL-17 family have been proposed as important in the host response to P. aeruginosa infection through augmenting antibacterial immune responses, although their pro-inflammatory effect may contribute to lung damage that occurs as a result of chronic infection. We set out to explore the role of IL-17 in the host response to chronic P. aeruginosa infection. We used a murine model of chronic pulmonary infection with CF-related strains of P. aeruginosa. We demonstrate that IL-17 cytokine signaling is essential for survival and prevention of chronic infection at 2 weeks post-inoculation using two different P. aeruginosa strains. Following infection, there was a marked expansion of cells within mediastinal lymph nodes, comprised mainly of innate lymphoid cells (ILCs); ∼90% of IL-17 producing cells had markers consistent with Group 3 ILCs. A smaller percentage of IL-17+ cells had markers consistent with a B1 phenotype. In lung homogenates 14 days following infection, there was a significant expansion of IL-17+ cells – about 50% of these were CD3+, split equally between CD4+ Th17 cells and γδ T cells, while the CD3- IL-17+ cells were almost exclusively Group 3 ILCs. Further experiments with B cell deficient mice showed that B cell production of IL-17 or natural antibodies did not provide any defence against chronic P. aeruginosa infection. Thus, IL-17 rather than antibody is a key element in host defence against chronic pulmonary infection with P. aeruginosa

Delegation to Independent Regulators and the Ratchet Effect

Dynamic principal-agent settings with asymmetric information but no commitment are well known to create a ratchet effect. Here, the most efficient agents must be provided with extra 'information rent' as an incentive to relinquish their informational advantage over an uninformed principal; this causes welfare to fall. We study this problem in the case of regulatory procurement and show that delegation by the government to an independent regulator whose preferences differ from the government's can overcome this inefficiency, and we provide 'conservative' conditions under which this happens. Our solution reflects several aspects of many modern regulatory settings: government commitment to a particular regulator, the provision of independence to that regulator, and heterogeneity across available regulators. Our results also provide an analogy with the literatures on the benefits of delegation to independent principals in other settings, such as monetary policy, financial regulation and trade and hence contribute to this broader research agenda.delegation; ratchet effect; procurement