A new radiation scheme has been developed for dynamic general-circulation modeling. An automatic determination of k-distribution parameters and a treatment of solar-terrestrial radiation interacting with gaseous and particulate matter are incorporated into the scheme by a technique that combines discrete ordinate and matrix operator methods. An accelerated scheme for cloud overlap is developed and tested. The resultant accuracy of the scheme is ?0.5 K/day to a 70-km height in clear sky better than that of the line-by-line calculation method.

Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is, therefore, a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin-binding protein by affinity purification using a biotinylated metformin analogue. Metformin directly bound to the C-terminal acidic tail of HMGB1. Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1 but not by HMGB1 lacking the acidic tail. In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody. In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1. Because HMGB1 plays a major role in inflammation, our results suggest possible new ways to manage HMGB1-induced inflammation.

The equilibrium hydrogen and oxygen isotope fractionations in ice-water system were determined under the con dition of comparatively slow rate of ice formation using mass spectrometric isotope analysis of coexisting ice and water. The values of hydrogen and oxygen isotope fractionation factors were determined to be1.0206•}0.0005and1.0028 •} 0.0001,respectively. 1.Introduction Determination of the equilibrium distri bution of hydrogen and oxygen isotopes in

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BACKGROUND AND PURPOSEUpon stimulation, neutrophils release their nuclear contents called neutrophil extracellular traps (NETs), which contain unfolded chromatin and lysosomal enzymes. NETs have been demonstrated to play a critical role in host defence, although the role of PGE 2 , a bioactive substance generated in inflammatory tissues, in the formation of NETs remains unclear. EXPERIMENTAL APPROACHThe effects of PGE 2 , agonists and antagonists of its receptors, and modulators of the cAMP-PKA pathway on the formation of NETs were examined in vitro in isolated neutrophils and in vivo in a newly established mouse model. KEY RESULTSPGE 2 inhibited PMA-induced NET formation in vitro through EP 2 and EP 4 Gαs-coupled receptors. Incubation with a cell-permeable cAMP analogue, dibutyryl cAMP, or various inhibitors of a cAMP-degrading enzyme, PDE, also suppressed NET formation. In the assay established here, where an agarose gel was s.c. implanted in mice and NET formation was detected on the surface of the gel, the extent of the NET formed was inhibited in agarose gels containing rolipram, a PDE4 inhibitor, and butaprost, an EP 2 receptor agonist. CONCLUSIONS AND IMPLICATIONSPGE 2 inhibits NET formation through the production of cAMP. These findings will contribute to the development of novel treatments for NETosis-related diseases. AbbreviationsBSA, bovine serum albumin;