Data Assimilation Enhancements to Air Force Weathers Land Information System

The United States Air Force (USAF) has a proud and storied tradition of enabling significant advancements in the area of characterizing and modeling land state information. 557th Weather Wing (557 WW; DoDs Executive Agent for Land Information) provides routine geospatial intelligence information to warfighters, planners, and decision makers at all echelons and services of the U.S. military, government and intelligence community. 557 WW and its predecessors have been home to the DoDs only operational regional and global land data analysis systems since January 1958. As a trusted partner since 2005, Air Force Weather (AFW) has relied on the Hydrological Sciences Laboratory at NASA/GSFC to lead the interagency scientific collaboration known as the Land Information System (LIS). LIS is an advanced software framework for high performance land surface modeling and data assimilation of geospatial intelligence (GEOINT) information

Stability of amorphous solid dispersions: Impact of intermolecular drug-polymer interactions

It is well recognized that delivering a poorly water soluble drug as the amorphous form can be used as a strategy to improve the apparent solubility, thus potentially improving its dissolution rate and bioavailability. However, an amorphous drug will tend to convert to the thermodynamically more stable crystalline form over pharmaceutically relevant timescales. Dispersing the amorphous drug within a suitable carrier, for example a polymer, has been used as a strategy to delay or prevent the crystallization of the drug over the appropriate timescale. The goal of this study is to investigate specific interactions occurring at the molecular level in solid dispersions and to understand how polymers can disrupt molecular self-assembly leading to an amorphous solid in which crystallization is prevented for long time periods. In addition, the use of infrared spectroscopy was evaluated for its ability to help with the rational selection of polymers for solid dispersions. Long term solid state stability against crystallization, along with crystallization kinetics in solution were studied. This project will supply a rational model for designing amorphous formulations that have good solid state stability over a pharmaceutically relevant time scale, and result in the generation of a supersaturated solution upon dissolution that is maintained for a period of time long enough to increase bioavailability

DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3

International audiencePre–B and pre–T lymphocytes must orchestrate a transition from a highly proliferative state to a quiescent one during development. Cyclin D3 is essential for these cells’ proliferation, but little is known about its posttranslational regulation at this stage. Here, we show that the dual specificity tyrosine-regulated kinase 1A (DYRK1A) restrains Cyclin D3 protein levels by phosphorylating T283 to induce its degradation. Loss of DYRK1A activity, via genetic inactivation or pharmacologic inhibition in mice, caused accumulation of Cyclin D3 protein, incomplete repression of E2F-mediated gene transcription, and failure to properly couple cell cycle exit with differentiation. Expression of a nonphosphorylatable Cyclin D3 T283A mutant recapitulated these defects, whereas inhibition of Cyclin D:CDK4/6 mitigated the effects of DYRK1A inhibition or loss. These data uncover a previously unknown role for DYRK1A in lymphopoiesis, and demonstrate how Cyclin D3 protein stability is negatively regulated during exit from the proliferative phases of B and T cell development