An improved elastic-viscoplastic soil model

This paper develops an improved and accessible framework for modelling time-dependent behaviour of soils using the concepts of elasticity and viscoplasticity. The mathematical description of viscoplastic straining is formulated based on a purely viscoplastic and measurable phenomenon, namely creep. The resulting expression for the viscoplastic strain rates includes a measure of both effective stress and the corresponding volumetric packing of the soil particles. In this way, the model differs from some earlier viscoplastic models and arguably provides a better conceptual description of time-dependent behaviour. Analytical solutions are developed for the simulation of drained and undrained strain-controlled triaxial compression tests. The model is then used to back-analyze the measured response of normally consolidated to moderately overconsolidated specimens of a soft estuarine soil in undrained triaxial compression. The model captures aspects of soil behaviour that cannot be simulated using time-independent elastic–plastic models. Specifically, it can capture the dependence of stress–strain relationships and undrained shear strength on strain rate, the development of irrecoverable plastic strains at constant stress (creep), and the relaxation of stresses at constant strain

Finite element analysis of an embankment on a soft estuarine deposit using an elastic–viscoplastic soil model

A new elastic–viscoplastic (EVP) soil model has been used to simulate the measured deformation response of a soft estuarine soil loaded by a stage-constructed embankment. The simulation incorporates prefabricated vertical drains installed in the foundation soils and reinforcement installed at the base of the embankment. The numerical simulations closely matched the temporal changes in surface settlement beneath the centerline and shoulder of the embankment. More importantly, the elastic–viscoplastic model simulated the pattern and magnitudes of the lateral deformations beneath the toe of the embankment — a notoriously difficult aspect of modelling the deformation response of soft soils. Simulation of the excess pore-water pressure proved more difficult because of the heterogeneous nature of the estuarine deposit. Excess pore-water pressures were, however, mapped reasonably well at three of the six monitoring locations. The simulations were achieved using a small set of material constants that can easily be obtained from standard laboratory tests. This study validates the use of the EVP model for problems involving soft soil deposits beneath loading from a geotechnical structure.

FKBPL and Peptide Derivatives: Novel Biological Agents That Inhibit Angiogenesis by a CD44-Dependent Mechanism

Purpose: Antiangiogenic therapies can be an important adjunct to the management of many malignancies. Here we investigated a novel protein, FKBPL, and peptide derivative for their antiangiogenic activity and mechanism of action.

Experimental Design: Recombinant FKBPL (rFKBPL) and its peptide derivative were assessed in a range of human microvascular endothelial cell (HMEC-1) assays in vitro. Their ability to inhibit proliferation, migration, and Matrigel-dependent tubule formation was determined. They were further evaluated in an ex vivo rat model of neovascularization and in two in vivo mouse models of angiogenesis, that is, the sponge implantation and the intravital microscopy models. Antitumor efficacy was determined in two human tumor xenograft models grown in severe compromised immunodeficient (SCID) mice. Finally, the dependence of peptide on CD44 was determined using a CD44-targeted siRNA approach or in cell lines of differing CD44 status.

Results: rFKBPL inhibited endothelial cell migration, tubule formation, and microvessel formation in vitro and in vivo. The region responsible for FKBPL's antiangiogenic activity was identified, and a 24-amino acid peptide (AD-01) spanning this sequence was synthesized. It was potently antiangiogenic and inhibited growth in two human tumor xenograft models (DU145 and MDA-231) when administered systemically, either on its own or in combination with docetaxel. The antiangiogenic activity of FKBPL and AD-01 was dependent on the cell-surface receptor CD44, and signaling downstream of this receptor promoted an antimigratory phenotype.

Conclusion: FKBPL and its peptide derivative AD-01 have potent antiangiogenic activity. Thus, these agents offer the potential of an attractive new approach to antiangiogenic therapy.

Select Document: Sir George Radcliffe’s “Original of Government” (1639) and Absolutist Political Theory in Stuart Ireland

A seventeenth-century manuscript miscellany, which once belonged to Archbishop James Ussher of Armagh, contains a short treatise on the origins of government by Sir George Radcliffe. Radcliffe was legal assistant to Sir Thomas Wentworth, lord deputy of Ireland (from January 1640 earl of Strafford and lord lieutenant). The treatise insisted on the divine origin of all human political power and implied that the best form of government was absolute monarchy, in which the monarch was free of all human law and subject to divine restraint alone. It will be suggested below that the composition of this treatise can be dated to the summer of 1639. This introduction will offer an outline of Radcliffe’s education and political career, explain the genesis of his treatise on government, point out some pertinent aspects of its argument, and finally assess the document’s significance.