Terephthalamide derivatives as mimetics of helical peptides: disruption of the Bcl-x(L)/Bak interaction

A series of Bcl-x(L)/Bak antagonists, based on a terephthalamide scaffold, was designed to mimic the alpha-helical region of the Bak peptide. These molecules showed favorable in vitro activities in disrupting the Bcl-x(L)/Bak BH3 domain complex (terephthalamides 9 and 26, K(i) = 0.78 +/- 0.07 and 1.85 +/- 0.32 microM, respectively). Extensive structure-affinity studies demonstrated a correlation between the ability of terephthalamide derivatives to disrupt Bcl-x(L)/Bak complex formation and the size of variable side chains on these molecules. Treatment of human HEK293 cells with the terephthalamide derivative 26 resulted in disruption of the Bcl-x(L)/Bax interaction in whole cells with an IC(50) of 35.0 microM. Computational docking simulations and NMR experiments suggested that the binding cleft for the BH3 domain of the Bak peptide on the surface of Bcl-x(L) is the target area for these synthetic inhibitors.     

Determination of flumequine in channel catfish by liquid chromatography with fluorescence detection.

Rapid methods are described for determination of flumequine (FLU) residues in muscle and plasma of farm-raised channel catfish (Ictalurus punctatus). FLU residues were extracted from tissues with an acidified methanol solution, and extracts were cleaned up on C18 solid-phase extraction cartridges. FLU concentrations were determined by liquid chromatography (LC) using a C18 analytical column and fluorescence detection (excitation, 325 nm; emission, 360 nm). Mean recoveries of FLU from fortified muscle were 87-94% at 5 levels ranging from 10 to 160 ppb (5 replicates per level). FLU recoveries from fortified plasma were 92-97% at 5 levels ranging from 20 to 320 ppb. Limits of detection (signal-to-noise ratio, 3:1) for the method as described were 3 and 6 ppb for muscle and plasma, respectively. Relative standard deviations (RSDs) for recoveries were < or = 12%. Live catfish were dosed with 14C-labeled or unlabeled FLU to generate incurred residues. Recoveries of 14C residues throughout extraction and cleanup were 90 and 94% for muscle and plasma, respectively. RSDs for incurred FLU at 2 levels in muscle and plasma ranged from 2 to 6%. The identity of FLU in incurred tissues was confirmed by LC/mass spectrometry.     

On the oscillation of fourth order strongly superlinear and strongly sublinear dynamic equations

We establish some new criteria for the oscillation of fourth order nonlinear dynamic equations on a time scale. We investigate the case of strongly superlinear and the case of strongly sublinear equations subject to various conditions. Some examples are given here to illustrate our main results.     

Mixed nonlocal problem for a nonlinear singular hyperbolic equation

In this paper, we study a nonlocal mixed problem for a nonlinear hyperbolic equation. Based on some a priori estimates and some density arguments, we prove the well posedness of the associated linear problem. The existence and uniqueness of the weak solution of the nonlinear problem are then established by applying an iterative process based on the obtained results for the linear problem. Copyright © 2009 John Wiley & Sons, Ltd.     

Finite element method for the stress analysis of isotropic cylindrical helical spring

This paper presents an efficient two nodes finite element with six degrees of freedom per node, capable to model the total behaviour of a helical spring. The formulation, which includes the shear deformation effects, is based on the assumed forces hybrid approach. The resultant forces approximation verifies exactly the resultant equilibrium equations. The developed model proves its accuracy compared with other elements. This element permits to get the distribution of different stresses along the spring and through the wire surface by only one element.     

Modélisation de fissures elliptiques internes par hybridation de fonctions de poidsEmbedded elliptical cracks modeling with hybridization of weight functions

A method improving the evaluation of the stress intensity factor by hybridization of two weight functions is presented and applied to embedded elliptical cracks under various loadings. The hybridization consists in using one or the other function in the zone of the crack where it is the most efficient. The delimitation of the two zones is achieved after optimizing the axes ratio and the curvature radius of the crack. During this optimization we seek to reduce the effects of the singularities present in the weight functions as well as to take better into account the influence of the ellipse curvature. To cite this article: B. El Khalil Hachi et al., C. R. Mecanique 334 (2006).     

‘Universal’ inequalities for the eigenvalues of the Hodge de Rham Laplacian

We obtain ‘universal’ inequalities for the eigenvalues of the Laplacian acting on differential forms of a Euclidean compact submanifold. These inequalities generalize the Yang inequality concerning the eigenvalues of the Dirichlet Laplacian of a bounded Euclidean domain.      

Oscillation of second-order strongly superlinear and strongly sublinear dynamic equations

We establish some new criteria for the oscillation of second-order nonlinear dynamic equations on a time scale. We study the case of strongly superlinear and the case of strongly sublinear equations subject to various conditions.