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- Deryck, M., et al.
(author)
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Legislation in the Knowledge Base Paradigm : Interactive Decision Enactment for Registration Duties
- 2019
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In: Proceedings - 13th IEEE International Conference on Semantic Computing, ICSC 2019. - : Institute of Electrical and Electronics Engineers Inc.. - 9781538667835 ; , s. 174-177
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Conference paper (peer-reviewed)abstract
- Recently, a prototype for an interactive decision enactment system for notaries was developed. This prototype follows the Knowledge Base Paradigm (KBP): it consists of purely declarative domain knowledge, to which various logical inference methods can be applied. This paper extends that work in two ways. First, we experimentally validate the claim that the KBP leads to highly maintainable software. Second, we extend the number of additional logical inferences, which allows us to address a number of usability concerns. This provides further evidence for the claim that the KBP is indeed a viable method of developing interactive software systems. The resulting interactive decision enactment prototype is a fully generic system, that can be applied to other domains with minimal effort.
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2. |
- Shigeto, Makoto, et al.
(author)
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GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation
- 2015
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In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:12, s. 4714-4728
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Journal article (peer-reviewed)abstract
- Strategies aimed at mimicking or enhancing the action of the incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives insulin secretion in pancreatic islets. Here, we examined the mechanisms by which GLP-1 stimulates insulin secretion in mouse and human islets. We found that GLP-1 enhances GSIS at a half-maximal effective concentration of 0.4 pM. Moreover, we determined that GLP-1 activates PLC, which increases submembrane diacylglycerol and thereby activates PKC, resulting in membrane depolarization and increased action potential firing and subsequent stimulation of insulin secretion. The depolarizing effect of GLP-1 on electrical activity was mimicked by the PKC activator PMA, occurred without activation of PKA, and persisted in the presence of PKA inhibitors, the K-ATP channel blacker tolbutamide, and the L-type Ca2+ channel blacker isradipine; however, depolarization was abolished by lowering extracellular Na+. The PKC-dependent effect of GLP-1 on membrane potential and electrical activity was mediated by activation of NW-permeable TRPM4 and TRPM5 channels by mobilization of intracellular Ca2+ from thapsigargin-sensitive Ca2+ stores. Concordantly, GLP-1 effects were negligible in Trpm4 or Trpm5 KO islets. These data provide important insight into the therapeutic action of GLP-1 and suggest that circulating levels of this hormone directly stimulate insulin secretion by beta cells.
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