Scaffolding Reflection: Prompting Social Constructive Metacognitive Activity in Non-Formal Learning

The study explores the effects of three different types of non-adaptive, metacognitive scaffolding on social, constructive metacognitive activity and reflection in groups of non-formal learners. Six triads of non-formal learners were assigned randomly to one of the three scaffolding conditions: structuring, problematising or epistemological. The triads were then asked to collaboratively resolve an ill-structured problem and record their deliberations. Evidence from think-aloud protocols was analysed using conversational and discourse analysis. Findings indicate that epistemological scaffolds produced more social, constructive metacognitive activity than either of the two other scaffolding conditions in all metacognitive activities except for task orientation, as well as higher quality interactions during evaluation and reflection phases. However, participants appeared to be less aware of their activities as forming a strategic, self-regulatory response to the problem. This may indicate that for learning transfer, it may be necessary to employ an adaptive, facilitated reflection on learners' activities

New conserved structural fields for supercooled liquids

By considering Voronoi tessellations of the configurations of a fluid, we propose two new conserved fields, which provide structural information not fully accounted for by the usual 2-point density field fluctuations (structure factor). One of these fields is scalar and associated to the Voronoi cell volumes, whereas the other one, termed the "geometrical polarisation", is vectorial, related to the very local anisotropy of the configurations. We study the static and dynamical properties of these fields in the supercooled regime of a model glass-forming liquid. We show in particular that the geometrical polarisation is both statically correlated to the force field and contrary to it develops a plateau regime when the temperature is lowered. We attribute this behaviour to the microsopic disorder of the underlying inherent structures (IS) which dictate the dynamics on time scales larger than the true microscopic time, in the strong supercooled regime. In this respect, this work raises the issue of to what extent the inter IS dynamics, intrinsically anisotropic and collective (cf. T.B. Schr{\o}der et al. {\it J. of Chem. Phys.}, {\bf 112}, 9834 (2000)), could be related to their polarisation field.Comment: submitted to EPJE the 09/30/201

Characterization and Targeting of Thromboxane Receptor Dimerization: A Gateway to Novel Therapeutic Developments

Thromboxane A2 (TXA2) contributes to cardiovascular disease (CVD) by activating platelets and vascular smooth muscle cell constriction and proliferation. Despite their preclinical efficacy, pharmacological antagonists of the TXA2 receptor (the TP), a G protein-coupled receptor (GPCR), have not been clinically successful, raising interest in novel approaches to modifying TP function. We sought to examine molecular mechanisms underlying auto-upregulation of the TP in response to agonist activation. We first determined a lack of agonist-induced TP mRNA modulation, focusing our attention on post-translational TP regulation. GPCR dimerization contributes to post-translational regulation of receptor expression and function, therefore we characterized how TP forms dimers with itself (homodimerization) or other related receptors (heterodimerization) and defined the relative affinities. To determine how disruption of TP dimerization impacts its regulation and function, we targeted a GxxxGxxxL helical interaction motif, reportedly involved in transmembrane protein-protein interactions between other membrane proteins and GPCRs, that is located in the human TP\u27s (α isoform) 5th transmembrane domain. We determined that disruption of this motif suppressed TP agonist-induced Gq signaling and TPα homodimerization, but not its cell surface expression, ligand affinity or Gq association. Heterodimerization of TPα with the functionally opposing receptor for prostacyclin (the IP) shifts TPα to signal via the IP-Gs cascade contributing to prostacyclin\u27s restraint of TXA2 function. Interestingly, and in contrast to the TPα homodimer, disruption of the TPα-TM5 GxxxGxxxL motif did not modify either TPα-IP heterodimerization or its Gs-cAMP signaling. Our study indicates that distinct regions of the TPα receptor direct its homo- and hetero- dimerization and normal homodimerization appears necessary for efficient TPα-Gq activation. Targeting the TPα-TM5 GxxxGxxxL domain may allow development of biased TPα- homodimer antagonists that avoid suppression of TPα-IP heterodimer\u27s predicted beneficial IP-like effects. Such novel therapeutics may prove superior in CVD compared to non-selective suppression of all TP functions with TXA2 biosynthesis inhibitors or traditional TP antagonists