Mutations inducing divergent shifts of constitutive activity reveal different modes of binding among catecholamine analogues to the beta(2)-adrenergic receptor.

1. We compared the changes in binding energy generated by two mutations that shift in divergent directions the constitutive activity of the human beta(2) adrenergic receptor (beta(2)AR). 2. A constitutively activating mutant (CAM) and the double alanine replacement (AA mutant) of catechol-binding serines (S204A, S207A) in helix 5 were stably expressed in CHO cell lines, and used to measure the binding affinities of more than 40 adrenergic ligands. Moreover, the efficacy of the same group of compounds was determined as intrinsic activity for maximal adenylyl cyclase stimulation in wild-type beta(2)AR. 3. Although the two mutations had opposite effects on ligand affinity, the extents of change were in both cases largely correlated with the degree of ligand efficacy. This was particularly evident if the extra loss of binding energy due to hydrogen bond deletion in the AA mutant was taken into account. Thus the data demonstrate that there is an overall linkage between the configuration of the binding pocket and the intrinsic equilibrium between active and inactive receptor forms. 4. We also found that AA mutation-induced affinity changes for catecholamine congeners gradually lacking ethanolamine substituents were linearly correlated to the loss of affinity that such modifications of the ligand cause for wild-type receptor. This indicates that the strength of bonds between catechol ring and helix 5 is critically dependent on the rest of interactions of the beta-ethanolamine tail with other residues of the beta(2)-AR binding pocket.

Modes of acquisition of health literacy skills in informal learning contexts

In this article we try to analyze the learning processes of health literacy skills in informal contexts. We intend to broaden the understanding of the learning process beyond the formal contexts, thus contributing to the elucidation of health professionals on how individuals acquire and manage their knowledge in health matters. Given our goal, we use an analytic corpus constituted by one hundred autobiographical narratives written between 2006 and 2011, in educational contexts but with recognized potential for use in different scientific fields, including health. The results reveal the existence of three different types of modes of learning health literacy skills in informal context: : i) learning that takes place in action, in achieving daily tasks; ii) learning processes that result from problem solving; iii) learning that occurs in an unplanned manner, resulting from accidental circumstances and, in some cases, devoid of intentionality.

Convention de Londres du 21 mai 1833, suivie de la convention conclue, à Mayence, le 31 mars 1831, relativement à la navigation du Rhin

[Traité. 1833-05-21. Londres (français)]

Testing Spatial Autocorrelation in Weighted Networks : the Modes Permutation Test

In a weighted spatial network, as specified by an exchange matrix, the variances of the spatial values are inversely proportional to the size of the regions. Spatial values are no more exchangeable under independence, thus weakening the rationale for ordinary permutation and bootstrap tests of spatial autocorrelation. We propose an alternative permutation test for spatial autocorrelation, based upon exchangeable spatial modes, constructed as linear orthogonal combinations of spatial values. The coefficients obtain as eigenvectors of the standardised exchange matrix appearing in spectral clustering, and generalise to the weighted case the concept of spatial filtering for connectivity matrices. Also, two proposals aimed at transforming an acessibility matrix into a exchange matrix with with a priori fixed margins are presented. Two examples (inter-regional migratory flows and binary adjacency networks) illustrate the formalism, rooted in the theory of spectral decomposition for reversible Markov chains.

L'art de naviguer : contenant toutes les reigles, secrets, & enseignemens necessaires à la bonne navigation ([Reprod.]) / de M. Pierre de Medina ; traduict de Castillan en François, avec augmentation & illustration de plusieurs figures et annotations par Nicolas de Nicolai,...

Collection : French books before 1601 ; 69.4

Recueil d'appareils à vapeur employés aux travaux de navigation et de chemins de fer / par A. Castor,... ; par M. Baude,...

Comprend : Rapport sur les travaux de fondation du pont du Rhin ...

Carte Phisique [sic] Administrative et Routière de la France donnant la Belgique et une partie de la Hollande : Indiquant les Relais de Poste, les Eaux Thermales et la Navigation Intérieure / par A. Beaupré

Échelle(s) : [ca 1:1 754 000], 10 Myriamètres [ = 5,7 cm]

Carte générale des Îles Britanniques contenant l'Angleterre, l'Écosse et l'Irlande : indiquant les principales routes, les canaux de navigation, les chemins de fer exécutés et en cours d'exécution dans la Grande-Bretagne / par J. Andriveau ; le burin par Piat ; écrit par Arnoul

Échelle(s) : [ca 1:1 4640 000], échelle de 25 lieues communes de France [= 7,6 cm]