Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome.

AIMS: Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel BrS SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C. The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (I(to)) was incorporated. A new mutation (C1850S) was identified in the Na(v)1.5 C-terminal domain. In HEK293 cells, mutant I(Na) density was decreased by 62% at -20 mV. Inactivation of mutant I(Na) was accelerated in a voltage-dependent manner and the steady-state inactivation curve was shifted by 11.6 mV towards negative potentials. No change was observed regarding activation characteristics. Altogether, these biophysical alterations decreased the availability of I(Na). In the simulations, the I(to) density necessary to precipitate repolarization differed minimally between the two genotypes. In contrast, the mutation greatly affected conduction across a structural heterogeneity and precipitated conduction block. CONCLUSION: Our data confirm that mutations of the C-terminal domain of Na(v)1.5 alter the inactivation of the channel and support the notion that conduction alterations may play a significant role in the pathogenesis of BrS

A Goal-Oriented Requirements Engineering Method for Business Processes

Abstract. The field of requirements engineering (RE) for business processes has grown during the last several years. As business processes are needed to fulfil organizational goals, the information captured in goal models provides a basis for designing business processes. Although research has started to explore how to transform goal models into business process models, current transformation methods need further research. This paper proposes a toolsupported method to model goals as part of the business requirements for business processes and to automatically generate business process design skeletons that respond to these business requirements

Supporting scenario-based requirements engineering

Scenarios have been advocated as a means of improving requirements engineering yet few methods or tools exist to support scenario based RE. The paper reports a method and software assistant tool for scenario based RE that integrates with use case approaches to object oriented development. The method and operation of the tool are illustrated with a financial system case study. Scenarios are used to represent paths of possible behavior through a use case, and these are investigated to elaborate requirements. The method commences by acquisition and modeling of a use case. The use case is then compared with a library of abstract models that represent different application classes. Each model is associated with a set of generic requirements for its class, hence, by identifying the class(es) to which the use case belongs, generic requirements can be reused. Scenario paths are automatically generated from use cases, then exception types are applied to normal event sequences to suggest possible abnormal events resulting from human error. Generic requirements are also attached to exceptions to suggest possible ways of dealing with human error and other types of system failure. Scenarios are validated by rule based frames which detect problematic event patterns. The tool suggests appropriate generic requirements to deal with the problems encountered. The paper concludes with a review of related work and a discussion of the prospects for scenario based RE methods and tools

Creating Requirements - Techniques and Experiences in the Policing Domain

Processes and techniques to discover and create requirements rather than elicit and acquire them from stakeholders have received relatively little attention in the requirements engineering literature. In contrast researchers in artificial intelligence and cognitive and social psychology have been researching creativity for some time. More recently we have applied their theories and models to requirements engineering. In this experience paper we report results and lessons learned from 2 creativity workshops undertaken with the UK's Police Information Technologies Organisation, in which theories and models of creativity informed creative thinking about requirements and opportunities for bio-metric technologies in policing. The main results are presented as lessons learned for the wider requirements engineering community

Exploring the Effectiveness of Normative i* Modelling: Results from a Case Study on Food Chain Traceability

This paper evaluates the effectiveness of an extension to i* modelling – normative i* modelling – during the requirements analysis for new socio-technical systems for food traceability. The i* focus on modelling systems as networks of heterogeneous, inter-dependent actors provides limited support for modelling system-wide properties and norms, such as laws and regulations, that also influence the specification of socio-technical systems. In this paper we introduce an extension to i* to model and analyse norms, then apply it to model laws and regulations applicable to European food traceability systems. We report an analysis of the relative strengths and weaknesses of this extended form of i* with its traditional forms, and use results to answer two research questions about the usefulness and usability of the i* modelling extension