Prehistoric pathways to Anthropocene adaptation: Evidence from the Red River Delta, Vietnam.

Over the past twenty years, government advisory bodies have placed increasing emphasis on the need for adaptive measures in response to the effects of human-induced climate change. Integrated Assessment Models (IAMs), which incorporate macroeconomic and climate variables, feature prominently in advisory content, though they rarely draw on data from outside strictly constrained hypothetical systems. This has led to assertions that they are not well-suited to approximate complex systemic human-environment processes. Modular, interdisciplinary approaches have offered a way to address this shortcoming; however, beyond climate records, prehistoric data continue to be under-utilised in developing such models. In this paper we highlight the contribution that archaeology and palaeoecology can make to the development of the next generation IAMs that are expected to enhance provision for more local and pro-active adaptations to future climate change. We present data from one of Southeast Asia's most heavily developed river deltas: the Red River (Song Hong) Delta, in Vietnam and localised analysis from the Tràng An Landscape Complex World Heritage Site, on the delta's southern margin. Comparison is made between Shared Socio-economic Pathways (SSP) 5-8.5 and SSP2-4.5 emission projection models and the Mid-Holocene inundation of the Red River Basin. We highlight the value to taking a scientific long view of coastal evolution through an illustrative set of eight research foci where palaeo-data can bring new and localised empirical data to bear on future risk management planning. We proceed to demonstrate the applicability of palaeoenvironmental, zooarchaeological and historical evidence to management and the development of sustainable conservation strategies using Tràng An as a case study. In so doing, we further highlight the importance of knowledge exchange between scientific, corporate, non-governmental, local, and state stakeholders to achieve tangible results on the ground.

Discovery of a 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (MK-2461) inhibitor of c-Met kinase for the treatment of cancer.

c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes. In recent years, research into this area has highlighted c-Met as an attractive cancer drug target, triggering a number of approaches to disrupt aberrant c-Met signaling. Screening efforts identified a unique class of 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one kinase inhibitors, exemplified by 1. Subsequent SAR studies led to the development of 81 (MK-2461), a potent inhibitor of c-Met that was efficacious in preclinical animal models of tumor suppression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase. This report details the development of 81 and provides a description of its unique biochemical properties.