Experimental investigation of shear deformation in laboratory prepared layered soil specimens

The purpose of this study was to identify and describe the shear deformation mechanisms and structures of laboratory prepared layered soil specimens. Soil specimens made of alternating layers of sand and clay were produced in the laboratory with different layering schemes and layering geometries. Layering schemes are groups of specimens with similar layering geometries. Layering geometries refers to the number of layers of sand and clay, thicknesses of the layers and the layer positions within the specimen. The specimens were sheared perpendicular to layering using a specially designed deformation apparatus and their deformation mechanisms and deformation structures were identified and described. The descriptions of the deformation structures were used to compare the deformation of specimens within and between layering schemes; The study showed that as the sand layer thickness of the specimens increased, the sand deformation structures became more complex. The sand deformation structures, shear bands, did not appear to form in specimens with very thin sand layers, but, as the sand layer thickness increased, secondary shear bands, primary shear bands and tertiary shear bands formed; As the clay percentage of the specimen increased, the clay deformation structures became more complex. In specimens with a low clay percentage, slip lines and step structures were formed. As the clay content increased, clay smears and double clay smears were formed. Specimens with higher clay contents generally required more local strain to form clay deformation structures and have narrower shear zones than specimens with a lower clay content

Mechanical properties of tuffaceous rocks under triaxial conditions

Yucca Mountain has been designated as a potential site for a high level nuclear waste repository. Part of the site characterization program is an investigation of the mechanical properties of the tuffs which comprise Yucca Mountain. The study tested specimens of TCw tuff in triaxial compression to observe the effects of confining pressure, saturation, strain rate, and anisotropy on the compressive strengths and Young\u27s Moduli of the specimens. Test results have shown that increasing the confining pressure increased the compressive strength and generally increased the Young\u27s Modulus. Saturation appears to lower both the compressive strength and Young\u27s Modulus of the specimens. Increasing strain rates increase the compressive strengths, but lowers the Young\u27s Modulus values. There appears to be a stiffness anisotropy where the specimens are stiffer perpendicular to the orientation of the the lithophysal cavity orientation. Correlations with porosity have shown as increase in porosity generally lowers both the compressive strength and the Young\u27s Modulus of the specimens. From the triaxial tests, the Mohr-Coulomb strength parameters have also been determined. A comparison between the strengths and modulus values from this study, values from previous studies and the suggested values reveal that the values computed for this study are generally lower than the previously published data. The dicrepancy may be due to sample and specimen differences between the studies

Discovery and Preclinical Characterization of the Cyclopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of the Hepatitis C Virus NS5B Polymerase

Described herein are structure–activity relationship studies that resulted in the optimization of the activity of members of a class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors. Subsequent iterations of analogue design and syntheses successfully addressed off-target activities, most notably human pregnane X receptor (hPXR) transactivation, and led to significant improvements in the physicochemical properties of lead compounds. Those analogues exhibiting improved solubility and membrane permeability were shown to have notably enhanced pharmacokinetic profiles. Additionally, a series of alkyl bridged piperazine carboxamides was identified as being of particular interest, and from which the compound BMS-791325 (<b>2</b>) was found to have distinguishing antiviral, safety, and pharmacokinetic properties that resulted in its selection for clinical evaluation