Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors

Separating the natural and anthropogenic air-sea flux of CO2: The Indian Ocean

We estimate the natural and anthropogenic components of the air-sea flux of CO2in the Indian Ocean. The increase in atmospheric CO2driven by human activity has caused the air-sea CO2disequilibrium, and consequently the flux, to increase significantly over the industrial era. We estimate the flux in the year 1780 to be approximately 0.2 Gt/ yr, increasing by 0.26 Gt/yr to 0.5 Gt /yr in 2000. The estimate of the natural (preindustrial) flux is highly sensitive to uncertainties in modern-day CO2disequilibrium measurements. By contrast, the estimate of the anthropogenic flux is only weakly sensitive to these measurements. Copyright 2004 by the American Geophysical Union

Separating the natural and anthropogenic air-sea flux of CO2: The Indian Ocean

We estimate the natural and anthropogenic components of the air-sea flux of CO2in the Indian Ocean. The increase in atmospheric CO2driven by human activity has caused the air-sea CO2disequilibrium, and consequently the flux, to increase significantly over the industrial era. We estimate the flux in the year 1780 to be approximately 0.2 Gt/ yr, increasing by 0.26 Gt/yr to 0.5 Gt /yr in 2000. The estimate of the natural (preindustrial) flux is highly sensitive to uncertainties in modern-day CO2disequilibrium measurements. By contrast, the estimate of the anthropogenic flux is only weakly sensitive to these measurements. Copyright 2004 by the American Geophysical Union

The impact of remineralization depth on the air-sea carbon balance

As particulate organic carbon rains down from the surface ocean it is respired back to carbon dioxide and released into the oceans interior. The depth at which this sinking carbon is converted back to carbon dioxideknown as the remineralization depthdepends on the balance between particle sinking speeds and their rate of decay. A host of climate-sensitive factors can affect this balance, including temperature, oxygen concentration, stratification, community composition and the mineral content of the sinking particles. Here we use a three-dimensional global ocean biogeochemistry model to show that a modest change in remineralization depth can have a substantial impact on atmospheric carbon dioxide concentrations. For example, when the depth at which 63% of sinking carbon is respired increases by 24 m globally, atmospheric carbon dioxide concentrations fall by 10-27 ppm. This reduction in atmospheric carbon dioxide concentration results from the redistribution of remineralized carbon from intermediate waters to bottom waters. As a consequence of the reduced concentration of respired carbon in upper ocean waters, atmospheric carbon dioxide is preferentially stored in newly formed North Atlantic Deep Water. We suggest that atmospheric carbon dioxide concentrations are highly sensitive to the potential changes in remineralization depth that may be caused by climate change. © 2009 Macmillan Publishers Limited. All rights reserved