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Voltage-gated Na(+) channels underlie the electrical activity of most excitable cells, and these channels are the targets of many antiarrhythmic, anticonvulsant, and local anesthetic drugs. The channel pore is formed by a single polypeptide chain, containing four different, but homologous domains that are thought to arrange themselves circumferentially to(More)
Problem orientation is gaining interest as a way of approaching the development of software intensive systems, and yet, a significant example that explores its use is missing from the literature. In this paper, we present the basic elements of Problem Oriented Software Engineering (POSE), which aims at bringing both nonformal and formal aspects of software(More)
Formal approaches to development are widely acknowledged to have difficulty in the validation of real-world requirements; in contrast, non-formal approaches find it difficult to identify the formal structures in requirements that are useful in a solution. That the problems that computing treats are embedded in the real world with solutions being an(More)
Problem frames provide a means of analyzing and decomposing problems. They emphasise the world outside of the computer, helping the developer to focus on the problem domain, instead of drifting into inventing solutions. However, even modestly complex problems can force us into detailed consideration of the architecture of the solution. This is counter to(More)
Jackson's Problem Frames provide a means of analysing and decomposing problems. They emphasise the world outside the computer helping the developer to focus on the problem domain instead of drifting into inventing solutions. The intention is to delay consideration of the solution space until a good understanding of the problem is gained. In contrast, early(More)
This paper presents a framework for understanding Problem Frames. The semantics places Problem Frames within the framework for Requirements Engineering of Zave and Jackson, and its subsequent formaliza-tion in the Reference Model of Gunter et al. It distinguishes between problem frames, context diagrams and problem diagrams, and allows us to formally define(More)
The language of causation is natural for the specification of requirements for complex systems. The paper provides a vocabulary of causal specification expressions, suitable for describing and analysing such systems. The notation is given a syntax and partial semantics. It covers many of the commonly-used modes of causal language including necessary and(More)
The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of(More)