Affinity of Cu+ for the copper-binding domain of the amyloid-β peptide of Alzheimer's disease

The role of metal ions in Alzheimer's disease etiology is unresolved. For the redox-active metal ions iron and copper, the formation of reactive oxygen species by metal amyloid complexes has been proposed to contribute to Alzheimer's disease neurodegeneration. For copper, reactive oxygen species are generated by copper redox cycling between its 1+ and 2+ oxidation states. Thus, the AβCu(I) complex is potentially a critical reactant associated with Alzheimer's disease etiology. Through competitive chelation, we have measured the affinity of the soluble copper-binding domain of the amyloid-β peptide for Cu(I). The dissociation constants are in the femtomolar range for both wild-type and histidine-to-alanine mutants. These results indicate that Cu(I) binds more tightly to monomeric amyloid-β than Cu(II) does, which leads us to propose that Cu(I) is a relevant in vivo oxidation state.     

Neue Cyclosporine aus Tolypocladium inflatum. Die Cyclosporine K–Z

Novel Cyclosporins from Tolypocladium inflatum. The Cyclosporins K–Z The fungus T. inflatum produces a plethora of oligopeptides, the cyclosporins, which exhibit remarkable biological activities. Cyclosporin A, the main metabolite, represents a potent immunosuppressant which opened new ways in the immunotherapy of bone marrow and organ transplantations. In addition to the already described cyclosporins A–I, we report now the isolation of the cyclosporins K–Z. The structural assignments of these novel congeners are based on chemical degradation, correlation reactions, mass spectra, and extensive analysis of ¹H- and ¹³C-NMR spectra. All cyclosporins are cyclic undecapeptides differing from each other by minor variations in the amino-acid sequence. Comparison of the immunosuppressive and antifungal effects furnished new information concerning structure-activity relationships.     

Construction d'un ensemble d-dominant sur un graphe en utilisant un critère donnéConstruction of a d-dominating set on a graph by using a given criterion

d-dominating sets in graphs are very important in system and network engineering. Their constructions is thus an important research topic. An heuristic which forms such sets by using a given criterion is proposed. We simplify the heuristic presented elsewhere. We extend it and prove the correctness of the extended heuristic. This heuristic has the advantage of being distributed and scalable. To cite this article: A. Delye de Clauzade de Mazieux et al., C. R. Mecanique 334 (2006).     

The cut cone III: On the role of triangle facets

The cut polytopeP _n is the convex hull of the incidence vectors of the cuts (i.e. complete bipartite subgraphs) of the complete graph onn nodes. A well known class of facets ofP _n arises from the triangle inequalities:x _ij +x _ik +x _jk ≤ 2 andx _ij -x _ik -x _jk ≤ 0 for 1 ≤i,j, k ≤n. Hence, the metric polytope M_n, defined as the solution set of the triangle inequalities, is a relaxation ofP _n . We consider several properties of geometric type for P_n, in particular, concerning its position withinM _n . Strengthening the known fact ([3]) thatP _n has diameter 1, we show that any set ofk cuts,k ≤ log₂ n, satisfying some additional assumption, determines a simplicial face ofM _n and thus, also, ofP _n . In particular, the collection of low dimension faces ofP _n is contained in that ofM _n . Among a large subclass of the facets ofP _n , the triangle facets are the closest ones to the barycentrum of P_n and we conjecture that this result holds in general. The lattice generated by all even cuts (corresponding to bipartitions of the nodes into sets of even cardinality) is characterized and some additional questions on the links between general facets ofP _n and its triangle facets are mentioned.     

Semiclassical results in the linear response theory

We consider a quantum system of non-interacting fermions at temperature T, in the framework of linear response theory. We show that semiclassical theory is an appropriate framework to describe some of their thermodynamic properties, in particular through asymptotic expansions in ? (Planck constant) of the dynamical susceptibilities. We show how the closed orbits of the classical motion in phase space manifest themselves in these expansions, in the regime where T is of the order of ?.     

A short large scale synthesis of (±) sarkomycin esters

(±) Sarkomycin ethyl ester has been prepared in four steps from ethyl acrylate.     

Stereochimie de la reaction de rupture par le brome de la liaision siliciumaryle du dimethyl-1,2 phenyl-1 silacyclopentane

Stereospecific synthesis of geometric isomers of 1,2-dimethyl-1-phenylsilacyclopentane is described. We demonstrate that brominolysis of the arylsilicon bond occurs with predominant inversion of configuration at the silicon atom of the silacyclopentane ring.     

Etudes stereochimiques dans la serie du silacyclopentane: synthese de dimethyl-1,2 alcoxy-1 silacyclopentanes a stereoisomere preferentiel

The stereoselective alcoholysis of 1,2-dimethyl-1-chlorosilacyclopentane and the catalytic alcoholysis of 1,2-dimethylsilacyclopentane are described.