Isosteres of peptides: boron analogs as dipolar forms of α‐amino acids – a theoretical study

Modification of peptides to produce peptidomimetics is of great interest, with the aim of designing potent, selective, and metabolically stable analogs having certain conformational properties. Organoboranes have been reported in the literature with a wide range of therapeutic applications. One of the therapeutically important class of molecules is amine‐carboxyboranes derived from amino acids by replacement of the Cα atom of an amino acid/peptide by boron. The conformational preferences of these peptides, with respect to backbone ω, ?, and ψ torsion angles, have been investigated by theoretical calculations. The amide bond in these molecules has the same geometry in the ground and transition states as the natural peptides. However, the boron isosteres of glycine and alanine peptides are less structured than their natural derivatives, but are distinguished by structures with a positive value for the ? angle, which is normally disfavored for natural peptides. This property could be used to build peptides with a geometry not usually seen in natural peptides. Copyright © 2007 John Wiley & Sons, Ltd.     

A note on an SOR-like method for augmented systems

Golub et al. (2001, BIT, 41, 71–85) gave a generalizedsuccessive over-relaxation method for the augmented systems.In this paper, the connection between the SOR-like method andthe preconditioned conjugate gradient (PCG) method for the augmentedsystems is investigated. It is shown that the PCG method isat least as accurate (fast) as the SOR-like method. Numericalexamples demonstrate that the PCG method is much faster thanthe SOR-like method.     

A bio-mechanical model for coupling cell contractility with focal adhesion formation

Focal adhesions (FAs) are large, multi-protein complexes that provide a mechanical link between the cytoskeletal contractile machinery and the extracellular matrix. They exhibit mechanosensitive properties; they self-assemble upon application of pulling forces and dissociate when these forces are decreased. We rationalize this mechano-sensitivity from thermodynamic considerations and develop a continuum framework in which the cytoskeletal contractile forces generated by stress fibers drive the assembly of the FA multi-protein complexes. The FA model has three essential features: (i) the low and high affinity integrins co-exist in thermodynamic equilibrium, (ii) the low affinity integrins within the plasma membrane are mobile, and (iii) the contractile forces generated by the stress fibers are in mechanical equilibrium and change the free energies of the integrins. A general two-dimensional framework is presented and the essential features of the model illustrated using one-dimensional examples. Consistent with observations, the coupled stress fiber and FA model predict that (a) the FAs concentrate around the periphery of the cell; (b) the fraction of the cell covered by FAs increases with decreasing cell size while the total FA intensity increases with increasing cell size; and (c) the FA intensity decreases substantially when cell contractility is curtailed.     

The Small Index Property for Free Groups and Relatively Free Groups

1. Some groups with the small index property In this paper we shall use the methods of the paper [6] by Hodges,Hodkinson, Lascar and Shelah to show that the free group ofcountably infinite rank and certain relatively free groups ofcountably infinite rank have the small index property.     

A search for fractional electric charge in sea water

The magnetic levitation technique has been used to test for fractional electric charge in sea water, using steel balls coated with sea water residue by evaporation. The objective was to reach concentration levels below 1 g^?1 which might result from cosmic ray interactions. Four stages of increasing sensitivity are reported: (1) residue from direct evaporation of unprocessed sea water, (2) residue from sea water samples enriched by ion exchangen, (3) residue reduced by high temperature evaporation, and (4) hypothetical enrichment by dilution and separation of soluble residue. Stages 1–3 are based on the generally accepted preferential retention of fractional charge during evaporation, but stage 4 limits are subject to uncertainties in the enrichment process. No evidence for fractional charge was found in a total of about 130 samples tested in these four stages. Samples containing positive and negative ions were tested separately, and concentration limits are reported for each of the stages. Levels in the region 0.01–0.1g^?1 were reached in stage 3, and 0.001 g^?1 in stage 4.