NF-kappaB transcription factors regulate the expression of tissue factor (TF), a principal initiator of the coagulation cascade. Dominant among them is the p50/p65 heterodimer. Here we report that Andrographolide (Andro; a p50 inhibitor) and genetic deletion of p50 attenuated TF activity in stimulated endothelial cells and monocytes/macrophages. Results of the electrophoretic mobility "supershift" assay and chromatin immunoprecipitation demonstrated the direct interaction of the p50/p65 heterodimer with the NF-kappaB site of the human TF promoter. Andro-treated and p50 null mice both exhibited blunted TF expression and reduced venous thrombosis, which were recapitulated by an anti-murine TF antibody in vivo. Our findings thus indicate that regulation of TF by NF-kappaB transcription factor p50 is essential for the pathogenesis of deep vein thrombosis and suggest that specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and perhaps treating venous thrombosis.

The discovery of ubiquitous habitable extrasolar planets, combined with revolutionary advances in instrumentation and observational capabilities, has ushered in a renaissance in the search for extra-terrestrial intelligence (SETI). Large scale SETI activities are now underway at numerous international facilities. The Five-hundred-meter Aperture Spherical radio Telescope (FAST) is the largest single-aperture radio telescope in the world, well positioned to conduct sensitive searches for radio emission indicative of exo-intelligence. SETI is one of the five key science goals specified in the original FAST project plan. A collaboration with the Breakthrough Listen Initiative has been initiated in 2016 with a joint statement signed both by Dr. Jun Yan, the then director of the National Astronomical Observatories, Chinese Academy of Sciences (NAOC), and Dr. Peter Worden, the Chairman of the Breakthrough Prize Foundation. In this paper, we highlight some of the unique features of FAST that will allow for novel SETI observations. We identify and describe three different signal types indicative of a technological source, namely, narrow-band, wide-band artificially dispersed, and modulated signals. We here propose observations with FAST to achieve sensitivities never before explored.