ABSTRACT
The modern European climatic regime is peculiar, due to its unitary winter but diverse summer climates and a pronounced Mediterranean climate in the south. However, little is known on its evolution in the deep time. Here we reconstruct the European summer climate conditions in the Tortonian (11.62-7.246 Ma) using plant fossil assemblages from 75 well-dated sites across Europe. Our results clearly show that the Tortonian Europe mainly had humid to subhumid summers and no arid climate has been conclusively detected, indicating that the summer-dry Mediterranean-type climate has not yet been established along most of the Mediterranean coast at least by the Tortonian. More importantly, the reconstructed distribution pattern of summer precipitation reveals that the Tortonian European must have largely been controlled by westerlies, resulting in higher precipitation in the west and the lower in the east. The Tortonian westerly wind field appears to differ principally from the trade wind pattern of the preceding Serravallian (13.82-11.62 Ma), recently deduced from herpetofaunal fossils. Such a shift in atmospheric circulation, if ever occurred, might result from the development of ice caps and glaciers in the polar region during the Late Miocene global cooling, the then reorganization of oceanic circulation, and/or the Himalayan-Tibetan uplift.
ABSTRACT
Synthesis and SAR of substituted pyrrolotriazine-4-one analogues as Eg5 inhibitors are described. Many of these analogues displayed potent inhibitory activities in the Eg5 ATPase and A2780 cell proliferation assays. In addition, pyrrolotriazine-4-one analogue 26 demonstrated in vivo efficacy in an iv P388 murine leukemia model. Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein.
