Anti-Kdr Monoclonal antibody, clone Bwbt23b2 [PE]

Vascular endothelial growth factor A (VEGF) signals primarily through its cognate receptor VEGF receptor-2 (VEGFR-2) to control vasculogenesis and angiogenesis, key physiological processes in cardiovascular disease and cancer. In human umbilical vein endothelial cells (HUVECs), knockdown of protein kinase D-1 (PKD1) or PKD2 down-regulates VEGFR-2 expression and inhibits VEGF-induced cell proliferation and migration. However, how PKD regulates VEGF signaling is unclear. Previous bioinformatics analyses have identified binding sites for the transcription factor activating enhancer-binding protein 2 (AP2) in the VEGFR-2 promoter. Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2? to the VEGFR-2 promoter. Luciferase reporter assays with serial deletions of AP2-binding sites within the VEGFR-2 promoter revealed that its transcriptional activity negatively correlates with the number of these sites. Next we demonstrated that AP2? up-regulation decreases VEGFR-2 expression and that loss of AP2? enhances VEGFR-2 expression in HUVECs. In vivo experiments confirmed increased VEGFR-2 immunostaining in the spinal cord of AP2? knockout mouse embryos. Mechanistically, we observed that PKD phosphorylates AP2? at Ser(258) and Ser(277) and suppresses its nuclear accumulation. Inhibition of PKD activity with a pan-PKD inhibitor increased AP2? nuclear localization, and overexpression of both WT and constitutively active PKD1 or PKD2 reduced AP2? nuclear localization through a Ser(258)- and Ser(277)-dependent mechanism. Furthermore, substitution of Ser(277) in AP2? increased its binding to the VEGFR-2 promoter. Our findings uncover evidence of a molecular pathway that regulates VEGFR-2 expression, insights that may shed light on the etiology of diseases associated with aberrant VEGF/VEGFR signaling.

This paper presents a reduced-order model (ROM) for simulation of thermal stratification in reservoirs by combining the CE-QAUL-W2 (W2) and the proper orthogonal decomposition (POD) models. The Karkheh Dam Reservoir (KDR) was used as a case study where the water temperature (WT) simulated with W2 model provided the necessary information for the development of ROM. The main outputs of ROM, containing spatio-temporal patterns of WT variation in the KDR, were produced with the POD model. WT profiles of the KDR, simulated with both ROM and W2, were presented and compared. W2 calibration and verification results revealed a good agreement between the simulated vertical WT profiles and measured ones in the reservoir. The mean absolute errors (MAEs) for calibration and verification of WT profiles were 0.71 and 0.67 degrees C, respectively. The results also indicated a good agreement between the WT profiles simulated with the W2 and the ROM developed using the first 10 out of 3425 modes, as evidenced by a small absolute error (<0.5 degrees C). The agreement demonstrated that the performance of the developed ROM was comparable with that of the existing W2 while the new ROM was much simpler in model structure and thus easier to use than the W2 model.