Search

Abstract In this paper, the simulation–optimization method is used to study the optimal location of cutoff walls for seawater intrusion. The optimization model is based on minimizing the chlorine concentration of two water sources after 50 years. In order to reduce the computational complexity, a Kriging surrogate model simulation is coupled with the optimization model. Finally, a hypothetical case is used to evaluate the accuracy of the surrogate model and the performance of the optimization model. The results show that the outputs of the Kriging surrogate model and the variable density groundwater simulation model for the same cutoff wall design fit well, and the average relative error of the two outputs is only 2.2% which proves that it is feasible to apply the Kriging surrogate model to this problem. By solving the optimization model, the location of the cutoff wall which minimizes the sum of chlorine concentration of the two water sources after 50 years is obtained. This provides a stable and reliable method for the site selection of cutoff walls for future projects intended to prevent and control seawater intrusion.

High-cost remediation of groundwater pollution makes it important to obtain exact information about the source. This is quite difficult to achieve in naturally ill-posed inverse problems of this kind. If the aquifer parameters are also unknown, the problem becomes even more challenging. To address this difficulty, we propose the alternating direction genetic algorithm (ADGA) approach, together with modification of the order of magnitude of the decision variables, to increase the accuracy of the results and computational efficiency. Seven scenarios were designed to test the accuracy of the proposed approach in aquifer with different properties, number of pollution sources, parameters and measurement errors. The results show that combining the ADGA approach with modification of the order of magnitude of the decision variables for identifying both groundwater pollution source and aquifer parameters significantly increases the accuracy of estimated results. The NE value for the estimated results decreased from 9.81% to 58.44% for different cases, and computation time is about half decreased. In addition, the approach is applicable in situations where concentrations of observational data with measurement error, and for multiple source locations and non-uniform media. [ABSTRACT FROM AUTHOR]

Bromodomain‐containing protein 4 (BRD4) plays an extremely important physiological role in cancer, and the BRD4 inhibitors can effectively inhibit the proliferation of tumor cells. By taking BI‐2536 (PLK1 and BRD4 inhibitor) as the lead compound, sixteen novel BRD4 inhibitors with the 4,4‐difluoro‐1‐methyl‐N,6‐diphenyl‐5,6‐dihydro‐4H‐pyrimido[4,5‐b] [1,2,4] triazolo[4,3‐d] [1,4] diazepine‐8‐amine structure were designed and synthetized. Among the target compounds, compound 15h exhibited outstanding inhibition for BRD4‐BD1 (IC50 value of 0.42 μM) in the BRD4‐BD1 inhibitory activity assay. Additionally, cell growth inhibition assay demonstrated that compound 15h potently suppressed the proliferation of MV4‐11 cells (IC50 value of 0.51 μM). Besides, compound 15h induced apoptosis and G0/G1 cycle arrest in MV4‐11 leukemia cells effectively, and downregulated the expression of c‐Myc in a dose‐dependent manner. In summary, the optimal compound 15h is expected to become the clinical therapeutic drug for further research. [ABSTRACT FROM AUTHOR]