Managing LTL properties in Event-B refinement

Refinement in Event-B supports the development of systems via proof based step-wise refinement of events. This refinement approach ensures safety properties are preserved, but additional reasoning is required in order to establish liveness and fairness properties. In this paper we present results which allow a closer integration of two formal methods, Event-B and linear temporal logic. In particular we show how a class of temporal logic properties can carry through a refinement chain of machines. Refinement steps can include introduction of new events, event renaming and event splitting. We also identify a general liveness property that holds for the events of the initial system of a refinement chain. The approach will aid developers in enabling them to verify linear temporal logic properties at early stages of a development, knowing they will be preserved at later stages. We illustrate the results via a simple case study

Visual assessment of heart rate variability patterns associated with neonatal infection in preterm infants

Early identification of neonatal sepsis may help reduce morbidity. From Heart Rate Variability (HRV) visually assessed in preterm infants, eight of nine recordings in babies with positive blood cultures had low HRV and six infants without positive cultures had normal HRV. Straightforward HRV display could help identify infection in infants

The taxonomist - an endangered race : a practical proposal for its survival

Background: Taxonomy or biological systematics is the basic scientific discipline of biology, postulating hypotheses of identity and relationships, on which all other natural sciences dealing with organisms relies. However, the scientific contributions of taxonomists have been largely neglected when using species names in scientific publications by not citing the authority on which they are based. Discussion: Consequences of this neglect is reduced recognition of the importance of taxonomy, which in turn results in diminished funding, lower interest from journals in publishing taxonomic research, and a reduced number of young scientists entering the field. This has lead to the so-called taxonomic impediment at a time when biodiversity studies are of critical importance. Here we emphasize a practical and obvious solution to this dilemma. We propose that whenever a species name is used, the author(s) of the species hypothesis be included and the original literature source cited, including taxonomic revisions and identification literature - nothing more than what is done for every other hypothesis or assumption included in a scientific publication. In addition, we postulate that journals primarily publishing taxonomic studies should be indexed in ISISM. Summary: The proposal outlined above would make visible the true contribution of taxonomists within the scientific community, and would provide a more accurate assessment for funding agencies impact and importance of taxonomy, and help in the recruitment of young scientists into the field, thus helping to alleviate the taxonomic impediment. In addition, it would also make much of the biological literature more robust by reducing or alleviating taxonomic uncertainty. Keywords: Taxonomy crisis; taxonomic impediment; impact factor; original species description; citation index; systematic

Interdisciplinary geographies of science

More than two decades into the “geographical” turn within science studies (Shapin, 1998, pp. 5–6), geographies of science are a vibrant interdisciplinary field of research. Based on exciting work by geographers, historians, sociologists, and anthropologists of science, the ideas that science has a geography and that scientific knowledge bears the marks of particular locations have themselves become accepted facts, at least within this community of scholars. Indeed, it can be argued that the meaning of scientific knowledge “takes shape in response to spatial forces at every scale of analysis—from the macropolitical geography of national regions to the microsocial geography of local cultures” (Livingstone, 2003, p. 4)...

Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer's Disease

There exists an urgent need for new target discovery to treat Alzheimer's disease (AD); however, recent clinical trials based on anti-Aβ and anti-inflammatory strategies have yielded disappointing results. To expedite new drug discovery, we propose reposition targets which have been previously pursued by both industry and academia for indications other than AD. One such target is the calcium-activated potassium channel KCa3.1 (KCNN4), which in the brain is primarily expressed in microglia and is significantly upregulated when microglia are activated. We here review the existing evidence supporting that KCa3.1 inhibition could block microglial neurotoxicity without affecting their neuroprotective phagocytosis activity and without being broadly immunosuppressive. The anti-inflammatory and neuroprotective effects of KCa3.1 blockade would be suitable for treating AD as well as cerebrovascular and traumatic brain injuries, two well-known risk factors contributing to the dementia in AD patients presenting with mixed pathologies. Importantly, the pharmacokinetics and pharmacodynamics of several KCa3.1 blockers are well known, and a KCa3.1 blocker has been proven safe in clinical trials. It is therefore promising to reposition old or new KCa3.1 blockers for AD preclinical and clinical trials

Signal Transduction and Pathogenic Modifications at the Melanocortin-4 Receptor: A Structural Perspective

The melanocortin-4 receptor (MC4R) can be endogenously activated by binding of melanocyte-stimulating hormones (MSH), which mediates anorexigenic effects. In contrast, the agouti-related peptide (AgRP) acts as an endogenous inverse agonist and suppresses ligand-independent basal signaling activity (orexigenic effects). Binding of ligands to MC4R leads to the activation of different G-protein subtypes or arrestin and concomitant signaling pathways. This receptor is a key protein in the hypothalamic regulation of food intake and energy expenditure and naturally-occurring inactivating MC4R variants are the most frequent cause of monogenic obesity. In general, obesity is a growing problem on a global scale and is of social, medical, and economic relevance. A significant goal is to develop optimized pharmacological tools targeting MC4R without adverse effects. To date, this has not been achieved because of inter alia non-selective ligands across the five functionally different MCR subtypes (MC1-5R). This motivates further investigation of (i) the three-dimensional MC4R structure, (ii) binding mechanisms of various ligands, and (iii) the molecular transfer process of signal transduction, with the aim of understanding how structural features are linked with functional-physiological aspects. Unfortunately, experimentally elucidated structural information is not yet available for theMC receptors, a group of class A G-protein coupled receptors (GPCRs). We, therefore, generated MC4R homology models and complexes with interacting partners to describe approximate structural properties associated with signaling mechanisms. In addition, molecular insights from pathogenic mutations were incorporated to discriminate more precisely their individual malfunction of the signal transfer mechanism