The effect of anisotropic elasticity on the yielding characteristics of overconsolidated natural clay

Quantitative application of elastoplastic theory to the yielding behaviour of natural soils has always been uncertain. Part of the reason is that the theory was developed for reconstituted materials with isotropic structure, in contrast to natural soils that are usually anisotropic. The approach considered in this study assumes that pre-yielding behaviour is governed by the theory of linear anisotropic elasticity and that yield loci in the mean effective stress ( p') – deviator stress (q) plane are aligned approximately along the coefficient of earth pressure (K0) line. The assumption of a rotated yield locus associated with anisotropic elastic behaviour within the state boundary surface indicates that the elastic wall within the state boundary surface is inclined. The form of the state boundary surface has been determined mathematically in terms of anisotropic elastic and Cam-Clay soil parameters. Stress path tests were conducted on samples of Belfast Upper Boulder Clay removed from a depth of 28 m below ground surface. Good agreement was found between predicted and measured yield loci. The study also examined the influence of subsequent isotropic compression on the yielding characteristics of the natural clay. The indications are that the anisotropy developed during deposition disappears when the sample is loaded to a stress level at least twice the stress generated during the original deposition process. The methods developed in the paper have also been applied to test results reported previously on Winnipeg clay, and good agreement was obtained.

Lys(9) for Glu(9) substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39)

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLIP-l's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His(7) and Ala(8), can greatly improve resistance to this enzyme. Little research has assessed what effect Glu(9)-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu(9) of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue, (Lys(9))GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1 (9-36)amide. We investigated the in vivo antagonistic actions of (Lys(9))GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor. (C) 2004 Elsevier Inc. All rights reserved.

Determination of absolute configuration of conformationally flexible cis-dihydrodiol metabolites: Effect of diene substitution pattern on the circular dichroism spectra and optical rotations

Absolute configurations of a number of cis-dihydrodiols (cis-1,2-dihydroxy-3,5-cyclohexadienes), synthetically useful products of TDO-catalyzed dihydroxylations of 1,2- and 1,3-disubstituted benzene derivatives, have been determined by a comparison of calculated and experimental CD spectra and optical rotations and by methods involving X-ray crystallography, H-1 NMR spectra of diastereoisomeric derivatives, and by stereochemical correlations. The computations disclosed a significant effect of the substituents on conformational equilibria of cis-dihydrodiols and chiroptical properties of individual conformers. The assigned absolute configurations of cis-dihydrodiols have allowed the validity of a simple predictive model for TDO-catalyzed arene dihydroxylations to be extended.

Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2

Explaining the uniqueness of the acquired somatic JAK2 V617F mutation, which is present in more than 95% of polycythemia vera patients, has been a challenge. The V617F mutation in the pseudokinase domain of JAK2 renders the unmutated kinase domain constitutively active. We have performed random mutagenesis at position 617 of JAK2 and tested each of the 20 possible amino acids for ability to induce constitutive signaling in Ba/F3 cells expressing the erythropoietin receptor. Four JAK2 mutants, V617W, V617M, V617I, and V617L, were able to induce cytokine independence and constitutive downstream signaling. Only V617W induced a level of constitutive activation comparable with V617F. Also, only V617W stabilized tyrosine-phosphorylated suppressor of cytokine signaling 3 ( SOCS3), a mechanism by which JAK2 V617F overcomes inhibition by SOCS3. The V617W mutant induced a myeloproliferative disease in mice, mainly characterized by erythrocytosis and megakaryocytic proliferation. Although JAK2 V617W would predictably be pathogenic in humans, the substitution of the Val codon, GTC, by TTG, the codon for Trp, would require three base pair changes, and thus it is unlikely to occur. We discuss how the predicted conformations of the activated JAK2 mutants can lead to better screening assays for novel small molecule inhibitors.

Capital substitutability and weak sustainability revisited: The conditions for capital substitution in the presence of risk

The capital approach is frequently used to model sustainability. A development is deemed to be sustainable when capital is not reduced. There are different definitions of sustainability, based on whether or not they allow that different forms of capital may be substituted for each other. A development that allows for the substitution of different forms of capital is called weakly sustainable. This article shows that in a risky world and a risk-averse society even under the assumptions of weak sustainability the circumstances under which different forms of capital may be substituted are limited. This is due to the risk-reducing effect of diversification. Using Modern Portfolio Theory this article shows under which conditions substitution of different forms of capital increases risk for future generations.

Estimation of in situ stresses using anisotropic elasticity and suction measurements

Sampling and specimen preparation produce changes in mean effective stresses and pore water pressures, even with ‘perfect sampling’. The paper takes an existing simplified three-parameter cross-anisotropic elastic model and uses it to model these changes. The required ratio of cross-anisotropic parameters J/3G* can be obtained from standard CIU triaxial tests. If measurements are also made of suctions in unloaded specimens in the laboratory, then a combination of J/3G*, the measured suction, and the effective overburden pressure permits an estimation of the horizontal effective pressure and the K 0 ‘at rest’ coefficient. This can be helpful in numerical modelling that needs to start from in situ conditions, and in planning pressure levels for reconsolidation of clay specimens in the laboratory. Tests were done on Belfast Upper Boulder Clay from a depth of 28 m. Values of horizontal in situ effective stress estimated from these measurements compare favorably with conventional estimates of the ‘at rest’ coefficient K 0 and the overconsolidation ratio. Estimates of horizontal stress in London Clay were made using published data and the results compared with actual measurements. Again reasonable agreement was obtained.

Cycloalkenyl Halide Substitution Reactions of Enantiopure Arene cis-Tetrahydrodiols with Boron, Nitrogen and Phosphorus Nucleophiles

Enantiopure arene cis-tetrahydrodiols of bromobenzene and iodobenzene have been obtained in good yields, from chemoselective hydrogenation (rhodium-graphite) of the corresponding cis-dihydrodiol metabolites. Palladium-catalysed substitution of the halogen, by hydrogen, boron, nitrogen and phosphorus nucleophiles, in the acetonide derivatives, has yielded highly functionalised products for application in synthesis with potential as scaffolds for chiral ligands.

Reactivity difference between protolytic forms of some macrocyclic chromium(III) complexes in ligand substitution and electron transfer processes

The review provides insight into the mechanism of ligand substitution and electron transfer (from chromium(III) to iron(III)) by comparison of the reactivity of some tetraazamacrocyclic chromium(III) complexes in the conjugate acid-base forms. Use of two geometrical isomers made possible to estimate the influence of geometry and protolytic reactions in trans and cis position towards the leaving group on the rate enhancement. Studies on the reaction rates in different media demonstrated the role played by outer sphere interactions in a monodentate ligand substitution. (C) 2009 Published by Elsevier B.V.

THE ROLE OF SENSE OF CONTROL AND SOCIAL SUPPORT IN MEDIATING THE IMPACT OF PSYCHOLOGICAL DISTRESS - A TEST OF THE HYPOTHESIS OF FUNCTIONAL SUBSTITUTION

The purpose of this paper is to examine the manner in which beliefs relating to sense of control and perceived social support mediate the impact of objective circumstances on psychological distress. In particular it focuses on the nature of the interaction between such variables. The results provide no evidence favouring the displacement hypothesis whereby the benefits of social support involve costs in terms of independence. Consistent support, however, is found for the functional substitution hypothesis. The conclusion is unaffected by the introduction of distinctions relating to types of support and types of power.