Isolation, purification, and full NMR assignments of cyclopamine from Veratrum californicum

The Hedgehog signaling pathway is essential for embryogenesis and for tissue homeostasis in the adult. However, it may induce malignancies in a number of tissues when constitutively activated, and it may also have a role in other forms of normal and maladaptive growth. Cyclopamine, a naturally occurring steroidal alkaloid, specifically inhibits the Hedgehog pathway by binding directly to Smoothened, an important Hedgehog response element. To use cyclopamine as a tool to explore and/or inhibit the Hedgehog pathway in vivo, a substantial quantity is required, and as a practical matter cyclopamine has been effectively unavailable for usage in animals larger than mice.

Centrifuge modelling-based verification of response spectra design methods for some vulnerable structures

Residential RC framed structures suffered heavily during the 2001 Bhuj earthquake in Gujarat, India. These types of structures also saw severe damage in other earthquakes such as the 1999 Kocaeli earthquake in Turkey and 921 Ji-Ji earthquake in Taiwan. In this paper the seismic response of residential structures was investigated using physical modelling. Idealised soft storey and top heavy, two degrees of freedom (2DOF) portal frame structures were developed and tested on saturated and dry sand models at 25 g using the Schofield Centre 10-m Beam Centrifuge. It was possible to recreate observed field behaviour using these models. As observed in many of the recent earthquakes, soft storey structures were found to be particularly vulnerable to seismic loads. Elastic response spectra methods are often used in the design of simple portal frame structures. The seismic risk of these structures can be significantly increased due to modifications such as removal of a column or addition of heavy water tanks on the roof. The experimental data from the dynamic centrifuge tests on such soft storey or top-heavy models was used to evaluate the predictions obtained from the response spectra. Response spectra were able to predict seismic response during small to moderate intensity earthquakes, but became inaccurate during strong earthquakes and when soil structure interaction effects became important. Re-evaluation of seismic risk of such modified structures is required and time domain analyses suggested by building codes such as IBC, UBC or NEHRP may be more appropriate. © Springer 2006.