13C NMR study of isoxazolines and isoxazolidines in the thiophene and benzo[b]thiophene S-oxide and S,S-dioxide series

The ¹³C NMR spectra were recorded for isoxazolines and isoxazolidines from 2,4,6-trimethylbenzonitrile oxide or α-phenyl-N-phenyl nitrone as dipolarophiles with the thiophene and benzo[b]thiophene S-oxide and S,S-dioxide series. The effects of the isoxazoline or isoxazolidine groups are not very different. Owing to the electronegativity of the oxygen atom, the main influence arises from the regioselectivity of the addition to the carbon atoms located at the α or β position from SO or SO₂.     

The computation of regionalized short-run marginal costs of electricity: The ARCOMALT model

Generation operation models, giving expected values of marginal fuel and failure costs, have been developed at EDF since about fifteen years. In order to study the regionalization of the future tariffs, we have recently developed a model for computing short-run marginal costs including not only generation but also the interconnection network. We shall first deal below with the necessary reduction of the general problem of optimization of the interconnection network operation before explaining how we solve the reduced problem.The French 400 kV interconnection network enables more than hundred plants to deliver electricity to consumers through more than hundred main nodes. The optimization of the operation has been examined for network planning and has led to a separation between shortage cases (for which additional outage due to the network is minimized) and normal cases (for which economic dispatching, taking into losses account, is established). In order to deal with these two cases with ARCOMALT, and to be able to introduce the randomness of all the variables concerned, we have reduced the number of nodes to about a dozen, which will be justified by both technical and economic reasons. It will also be shown that a good way to represent the interconnection network, from an economic point of view, is to let the various regions exchange electricity at marginal cost (either fuel or failure cost) with a transaction cost (a polynome, the degree of shich will be discussed) and bounds on exchange capacities.The reduced problem is neither linear (both criteria and constraints are not) nor of a small size, so that usual methods cannot be applied. Graph theory cannot be used in this case because it is a problem with variable gains related to the links, and not a problem with fixed gains related to the nodes (which could be solved). It will be proved that, using the additive properties of the criteria, the main problem can be decomposed into smaller sub-problems and the optimal size of these sub-problems being the 3 nodes-problem. Finally, the relaxation method, which proceeds in two steps, is described: a rough solution is first obtained through a primal approach before using a dual approach to complete the computation of the marginal costs.     

Finite-amplitude disturbances in self-gravitating media. II

This paper deals with finite-amplitude axisymmetric disturbances in a self-gravitating fluid column of finite radius R. It is shown that the cutoff wavelength λ_nl above which gravitational breakup occurs now depends on the relative amplitude $\text{?}\text{R}$ of the initial perturbation. Actually, for small-but finite-amplitude disturbances, $\text{λ}{}_{\mathrm{nl}}\text{=}\text{λ}{}_{\mathrm{l}}\text{(1 ? 0.34368}\text{?}{}^2\text{R}{}^2\text{)}$, where λ_l ( = 5.8898R) designates the cutoff wavelength predicted in the linear approximation.     

Substituted thiazolamide coupled to a redox delivery system: a new gamma-secretase inhibitor with enhanced pharmacokinetic profile

Inhibition of gamma-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce pathogenic A beta peptides, is an attractive approach for the treatment of Alzheimer's disease. We have designed a new gamma-secretase thiazolamide inhibitor bearing a dihydronicotinoyl moiety as Redox Delivery System which allows specific delivery of the drug to the brain. Through, on the one hand, A beta peptide production measurements by specific in vitro assays (gamma-secretase Cell Free assay and Cell Based assay on HEK 293 APP transfected cells) and, on the other hand, pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent gamma-secretase inhibitory activity in vitro. From the obtained results, it is expected that drug will be mainly delivered to the CNS with low diffusion in the peripheral tissues. Consequently the side effects of this gamma-secretase inhibitor on the immune cells could be reduced.     

Introducing variable cell shape methods in field theory simulations of polymers

We propose a new method for carrying out field-theoretic simulations of polymer systems under conditions of prescribed external stress, allowing for shape changes in the simulation box. A compact expression for the deviatoric stress tensor is derived in terms of the chain propagator, and it is used to monitor changes in the box shape according to a simple relaxation scheme. The method allows fully relaxed, stress free configurations to be obtained even in nontrivial morphologies, and it enables the study of morphology transitions induced by external stresses.     

Roughness analysis of the cracked surfaces of a face centered cubic alloy

Intergranular and transgranular fracture surfaces obtained in a face centered cubic alloy are studied using 3D maps reconstructed by scanning electron microscopy stereo imaging. The roughness exponents measured in the intergranular and transgranular surfaces, respectively, zeta = 0.83 +/- 0.05 and zeta = 0.75 +/- 0.05, are in agreement with the universal roughness value of 3D fractures. However, the slightly smaller value related to the transgranular surface could be a consequence of crystallographic transgranular zones disseminated on the surface whose roughness exponent zeta = 0.65 +/- 0.07 is close to the one usually measured on 2D fractures.     

Synthesis of ether oligomers

[structure: see text] Hydroxyaromatic aldehydes and ketones were used as building blocks to prepare ether oligomers. An iterative two-step protocol involving Mitsunobu coupling and carbonyl reduction provided a protecting-group-free route with high yields. Activity screening of an 84-member library against proteases led to the discovery of micromolar inhibitors for trypsin, chymotrypsin, and subtilisin.     

New 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidinium alkaloids (phloeodictynes) from the New Caledonian shallow-water haplosclerid sponge Oceanapia fistulosa. Structural elucidation from mainly LC-tandem-MS-soft-ionization techniques and discovery of antiplasmodial activity

We report here on new 6-hydroxy-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidinium alkaloids, belonging to the phloeodictyne family, isolated from the haplosclerid sponge Oceanapia[=Phloeodictyon]fistulosa(Bowerbank, 1873) from New Caledonian shallow waters. Online LC-ESI-MS analysis, coupled to tandem fragmentation experiments on the crude alkaloid mixture, allowed us to clarify their flat structures, including structural isomers. At least 25 different components, of which 17 are new members with variable terminus and length chains, were characterised, besides less abundant analogues bearing a thioethylguanidine side chain. Crude mixtures and HPLC enriched fractions proved active against chloroquine-resistant Plasmodium falciparum, with IC(50) values ranging from 0.6 to 6 microM, while cytotoxicity against human A-549 cell line was low. This makes these alkaloids a good prospect as leads for novel antimalarial agents.