K-FLOW : Knowledge management in the extended manufacturing enterprise

This paper discusses knowledge management in the extended manufacturing enterprise. It was presented at the e-business and e-work conference in 2002. K-FLOW is a project co-funded by the European Commission, in the GROWTH Programme, whose aim is to develop a Software platform and a set of supporting methodologies for managing knowledge in an Extended Manufacturing Enterprise (EME). Principal elements considered in an EME are: plant production stations, design office stations, customers and suppliers. The main objective is to provide to workers of the EME, the right knowledge, at the right place, in the right form, at the right time. The expected benefits for the EME are: to earn competitiveness, to improve production, productivity and quality rates, service, and reduce costs, lead time and time to market by co-ordinating activities amongst different actors that improve the overall performance of the EME. The societal objectives are: to improve the working conditions, quality of work and workers’ skills, and reduce the environmental impact of the production processes

Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack

About 20% of patients with ischaemic stroke have a preceding transient ischaemic attack, which is clinically defined as focal neurological symptoms of ischaemic origin resolving spontaneously. Failure to diagnose transient ischaemic attack is a wasted opportunity to prevent recurrent disabling stroke. Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of a specific test. New diagnostic tools are thus needed, in particular for radiologically silent cases, which correspond to the recommended tissue-based definition of transient ischaemic attack. As endothelial activation is a hallmark of cerebrovascular events, we postulated that this may also be true for transient ischaemic attack, and that it would be clinically relevant to develop non-invasive in vivo imaging to detect this endothelial activation. Using transcriptional and immunohistological analyses for adhesion molecules in a mouse model, we identified brain endothelial P-selectin as a potential biomarker for transient ischaemic attack. We thus developed ultra-sensitive molecular magnetic resonance imaging using antibody-based microparticles of iron oxide targeting P-selectin. This highly sensitive imaging strategy unmasked activated endothelial cells after experimental transient ischaemic attack and allowed discriminating transient ischaemic attack from epilepsy and migraine, two important transient ischaemic attack mimics. We provide preclinical evidence that combining conventional magnetic resonance imaging with molecular magnetic resonance imaging targeting P-selectin might aid in the diagnosis of transient ischaemic attack

GpIb -VWF blockade restores vessel patency by dissolving platelet aggregates formed under very high shear rate in mice

International audienceInteractions between platelet glycoprotein (Gp) IIb/IIIa and plasma proteins mediate platelet cross-linking in arterial thrombi. However, GpIIb/IIIa inhibitors fail to disperse platelet aggregates after myocardial infarction or ischemic stroke. These results suggest that stability of occlusive thrombi involves additional and as-yet-unidentified mechanisms. In the present study, we investigated the mechanisms driving platelet cross-linking during occlusive thrombus formation. Using computational fluid dynamic simulations and in vivo thrombosis models, we demonstrated that the inner structure of occlusive thrombi is heterogeneous and primarily determined by the rheological conditions that prevailed during thrombus growth. Unlike the first steps of thrombus formation, which are GpIIb/IIIa-dependent, our findings reveal that closure of the arterial lumen is mediated by GpIbα-von Willebrand Factor (VWF) interactions. Accordingly, disruption of platelet cross-linking using GpIbα-VWF inhibitors restored vessel patency and improved outcome in a mouse model of ischemic stroke, although the thrombi were resistant to fibrinolysis or traditional antithrombotic agents. Overall, our study demonstrates that disruption of GpIbα-VWF interactions restores vessel patency after occlusive thrombosis by specifically disaggregating the external layer of occlusive thrombi, which is constituted of platelet aggregates formed under very high shear rates