Using a cDNA microarray screening approach, we have identified seven novel thrombin-responsive genes in human umbilical vein endothelial cells that were verifiable by Northern blot analysis. Among them CL-100, a dual-specificity phosphatase also known as MAP kinase phosphatase-1 (MKP-1), showed greatest induction by thrombin. Steady-state levels of CL-100 mRNA induction by thrombin peaked at 1 h and declined rapidly (t1 ⁄2 ϳ45 min). Induction by thrombin was protease-activated receptor-1-mediated, protein synthesis-independent, and transcriptionally regulated. Metabolic labeling followed by immunoprecipitation verified that the thrombininduced CL-100 mRNA was translated into protein. We found that both Src-kinase and p42/p44 ERK activity are critical for thrombin-induced CL-100 expression, whereas phosphatidylinositol 3-kinase and protein kinase C activity were not required. Antisense-mediated inhibition of CL-100 was shown to prolong thrombininduced ERK activity in endothelial cells, concomitant with an inhibition in thrombin-induced PDGF-A (platelet-derived growth factor A) and PDGF-B gene expression and an up-regulation in thrombin-induced VCAM-1 and E-selectin gene expression. Inhibition of ERK activation by PD98059 in endothelial cells was shown to potentiate thrombin-induced expression of PDGF-B (ϳ3-fold) while inhibiting thrombin-induced VCAM-1 and Eselectin gene expression by 60 and 70%, respectively. These results suggested that induced expression of the CL-100 phosphatase and its subsequent regulation of ERK activity play a key regulatory role in the thrombin signaling pathway and in the transcriptional regulation of pathologically important "endothelial cell activation genes."
The influence of the chemical mechanical planarization process on the 4o off-axis 4HN SiC removal rate for silicon carbide slurry produced by Cabot Microelectronics Corporation (CMC) has been studied. A detailed kinetic analysis was applied and the linearity of an Arrhenius-like activation energy plot suggests that the primary removal occurs from particles adhered to the pad surface.
Polishing of Silicon Carbide (SiC) seed crystals and substrates to achieve an extremely smooth, level surface, and an optically clear finish takes many surface finishing steps with very long processing times producing a significant amount of slurry waste and utilizing numerous lapping and polishing machines. This paper presents a newly developed cost-efficient SiC polishing process which reduces these operations to two surface finishing steps for achieving an optically clear finish on monocrystalline SiC material where the same size of diamond abrasives for lapping and polishing steps allows to carry out stock removal lapping and polishing processes on a single platform (machine) without concern of cross-contamination and making it as a very cost-efficient and high-throughput polishing process for SiC seed crystals and substrates.
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