Barbar Harmel to James Meredith (3 October 1962)

https://egrove.olemiss.edu/mercorr_pro/1211/thumbnail.jp

Palytoxin-induced Effects on Partial Reactions of the Na,K-ATPase

The interaction of palytoxin with the Na,K-ATPase was studied by the electrochromic styryl dye RH421, which monitors the amount of ions in the membrane domain of the pump. The toxin affected the pump function in the state P-E2, independently of the type of phosphorylation (ATP or inorganic phosphate). The palytoxin-induced modification of the protein consisted of two steps: toxin binding and a subsequent conformational change into a transmembrane ion channel. At 20°C, the rate-limiting reaction had a forward rate constant of 105 M−1s−1 and a backward rate constant of about 10−3 s−1. In the palytoxin-modified state, the binding affinity for Na+ and H+ was increased and reached values between those obtained in the E1 and P-E2 conformation under physiological conditions. Even under saturating palytoxin concentrations, the ATPase activity was not completely inhibited. In the Na/K mode, ∼50% of the enzyme remained active in the average, and in the Na-only mode 25%. The experimental findings indicate that an additional exit from the inhibited state exists. An obvious reaction pathway is a slow dephosphorylation of the palytoxin-inhibited state with a time constant of ∼100 s. Analysis of the effect of blockers of the extracellular and cytoplasmic access channels, TPA+ and Br2-Titu3+, respectively, showed that both access channels are part of the ion pathway in the palytoxin-modified protein. All experiments can be explained by an extension of the Post-Albers cycle, in which three additional states were added that branch off in the P-E2 state and lead to states in which the open-channel conformation is introduced and returns into the pump cycle in the occluded E2 state. The previously suggested molecular model for the channel state of the Na,K-ATPase as a conformation in which both gates between binding sites and aqueous phases are simultaneously in their open state is supported by this study

A method to manage the co-evolution of product an organization architectures.

International audienceComplex systems design and especially automotive design is facing continuous technological evolution that needs stronger integration. To tackle this issue, a method for modeling products and organizations architectures is presented. This method will be completed by a "management by uncertainty" tool to help managers anticipate the co-evolutions of project domains and properly structure these domains

Architecture des systèmes complexes : modélisation et pilotage par l'incertitude.

National audienceLa conception des systèmes complexes et plus précisément la conception de l'automobile fait face à des évolutions technologiques continues qu'il faut savoir intégrer et adapter. Dans cet article, nous proposons une méthode pour modéliser l'architecture des produits et des organisations et nous présentons brièvement ce que pourrait être un outil, basé sur pilotage par l'incertitude, permettant de faire coévoluer l'organisation et le produit dans le but d'atteindre un niveau de prestation donné

New hybrid quadrature schemes for weakly singular kernels applied to isogeometric boundary elements for 3D Stokes flow

This work proposes four novel hybrid quadrature schemes for the efficient and accurate evaluation of weakly singular boundary integrals (1/r kernel) on arbitrary smooth surfaces. Such integrals appear in boundary element analysis for several partial differential equations including the Stokes equation for viscous flow and the Helmholtz equation for acoustics. The proposed quadrature schemes apply a Duffy transform-based quadrature rule to surface elements containing the singularity and classical Gaussian quadrature to the remaining elements. Two of the four schemes additionally consider a special treatment for elements near to the singularity, where refined Gaussian quadrature and a new moment-fitting quadrature rule are used. The hybrid quadrature schemes are systematically studied on flat B-spline patches and on NURBS spheres considering two different sphere discretizations: An exact single-patch sphere with degenerate control points at the poles and an approximate discretization that consist of six patches with regular elements. The efficiency of the quadrature schemes is further demonstrated in boundary element analysis for Stokes flow, where steady problems with rotating and translating curved objects are investigated in convergence studies for both, mesh and quadrature refinement. Much higher convergence rates are observed for the proposed new schemes in comparison to classical schemes

Architecture des produits et des organisations : modélisation et pilotage par l'incertitude.

International audienceLa conception des systèmes complexes et plus précisément la conception de l'automobile fait face à des évolutions technologiques continues qu'il faut savoir intégrer et adapter. Dans cet article, nous proposons une méthode pour représenter l'architecture des produits et des organisations et nous présentons brièvement ce que pourrait être un outil, basé sur la gestion de l'incertitude, permettant de faire coévoluer l'organisation et le produit dans le but d'atteindre un niveau de prestation donné