Gravitational effective action at second order in curvature and gravitational waves

We consider the full effective theory for quantum gravity at second order in curvature including non-local terms. We show that the theory contains two new degrees of freedom beyond the massless graviton: namely a massive spin-2 ghost and a massive scalar field. Furthermore, we show that it is impossible to fine-tune the parameters of the effective action to eliminate completely the classical spin-2 ghost because of the non-local terms in the effective action. Being a classical field, it is not clear anyway that this ghost is problematic. It simply implies a repulsive contribution to Newton’s potential. We then consider how to extract the parameters of the effective action and show that it is possible to measure, at least in principle, the parameters of the local terms independently of each other using a combination of observations of gravitational waves and measurements performed by pendulum type experiments searching for deviations of Newton’s potential

THE NOVEL ORAL HSP90 INHIBITOR NVP-HSP990 EXHIBITS POTENT AND BROAD-SPECTRUM ANTI-TUMOR ACTIVITIES IN VITRO AND IN VIVO

A novel oral Hsp90 inhibitor, NVP-HSP990, has been developed and characterized in vitro and in vivo. In vitro, NVP-HSP990 exhibits single digit nM IC50 values on three of the Hsp90 isoforms (Hsp90α, Hsp90β, and GRP94) and 320 nM IC50 on the fourth (TRAP-1), with selectivity against unrelated enzymes, receptors and kinases. In c-Met amplified GTL-16 gastric tumor cells, NVP-HSP990 dissociated the Hsp90-p23 complex, depleted client protein c-Met and induced Hsp70. NVP-HSP990 potently inhibited the growth of human cell lines and primary patient samples from a variety of tumor types. In vivo, NVP-HSP990 exhibits drug-like pharmaceutical and pharmacological properties with high oral bioavailability. In the GTL-16 xenograft model, a single oral administration of 15 mg/kg of NVP-HSP990 induced sustained downregulation of c-Met and upregulation of Hsp70. In repeat dosing studies NVP-HSP990 treatment resulted in tumor growth inhibition of GTL-16 and other human tumor xenograft models driven by well defined oncogenic Hsp90 client proteins. On the basis of its pharmacological profile and broad spectrum anti-tumor activities, clinical trials have been initiated to evaluate NVP-HSP990 in advanced solid tumors

The first Cenozoic Equisetum from New Zealand

Equisetum is described for the first time from Cenozoic deposits of New Zealand. The fossils derive from two early to earliest middle Miocene assemblages in South Island, New Zealand. The fossils are ascribed tentatively to subgenus Equisetum based on their possession of whorled branch scars, but they cannot be assigned with confidence to a formal species. The decline of equisetaleans, otherwise unknown from the Cenozoic of the New Zealand-Australian-Antarctic domain, was possibly a consequence of severe environmental changes – particularly, abrupt shifts in the temperature and soil moisture regime – experienced by this region in the Neogene, coupled with competition from opportunistic angiosperms.Additional funding from US National Science Foundation (project #1636625)</p

Design, Structure Activity Relationship and in vivo Characterization of the Clinical Candidate NVP-HSP990

From a commercial hit (1), a novel dihydroquinazolinone scaffold was developed. The SAR of the series was developed which led to the selection of NVP-HSP990 as a clinical candidate