SUMMARYIn this paper, the global method of di erential quadrature (DQ) is applied to solve three-dimensional Navier-Stokes equations in primitive variable form on a non-staggered grid. Two numerical approaches were proposed in this work, which are based on the pressure correction process with DQ discretization. The essence in these approaches is the requirement that the continuity equation must be satisÿed on the boundary. Meanwhile, suitable boundary condition for pressure correction equation was recommended. Through a test problem of three-dimensional driven cavity ow, the performance of two approaches was comparatively studied in terms of the accuracy. The numerical results were obtained for Reynolds numbers of 100, 200, 400 and 1000. The present results were compared well with available data in the literature. In this work, the grid-dependence study was done, and the benchmark solutions for the velocity proÿles along the vertical and horizontal centrelines were given.

Nitrate is necessary for agricultural productivity, but can cause considerable problems if released into aquatic systems. Agricultural land is the major source of nitrates in UK groundwater. Due to the long time-lag in the groundwater system, it could take decades for leached nitrate from the soil to discharge into freshwaters. However, this nitrate time-lag has rarely been considered in environmental water management. Against this background, this paper presents an approach to modelling groundwater nitrate at the national scale, to simulate the impacts of historical nitrate loading from agricultural land on the evolution of groundwater nitrate concentrations. An additional process-based component was constructed for the saturated zone of significant aquifers in England and Wales. This uses a simple flow model which requires modelled recharge values, together with published aquifer properties and thickness data. A spatially distributed and temporally variable nitrate input function was also introduced. The sensitivity of parameters was analysed using Monte Carlo simulations. The model was calibrated using national nitrate monitoring data. Time series of annual average nitrate concentrations along with annual spatially distributed nitrate concentration maps from 1925 to 2150 were generated for 28 selected aquifer zones. The results show that 16 aquifer zones have an increasing trend in nitrate concentration, while average nitrate concentrations in the remaining 12 are declining. The results are also indicative of the trend in the flux of groundwater nitrate entering rivers through baseflow. The model thus enables the magnitude and timescale of groundwater nitrate response to be factored into source apportionment tools and to be taken into account alongside current planning of land-management options for reducing nitrate losses.

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BTK kinase is a member of the TEC kinase family and is a key regulator of the B-cell Receptor (BCR)-mediated signaling pathway. It is important for B-cell maturation, proliferation, survival and metastasis. Pharmacological inhibition of BTK is clinically effective against a variety of B-cell malignances, such as MCL, CLL and AML. MNK kinase is one of the key downstream regulators in the RAF-MEK-ERK signaling pathway and controls protein synthesis via regulating the activity of eIF4E. Inhibition of MNK activity has shown moderate efficacy for AML cell lines proliferation. Through a structure-based drug design approach, we have discovered a selective and potent BTK/MNK dual kinase inhibitor (QL-X-138), which exhibits covalent binding to BTK and non-covalent binding to MNK. Compared to the BTK kinase inhibitor (PCI-32765) and the MNK kinase inhibitor (cercosporamide), QL-X-138 displays a stronger anti-proliferative effect against a variety of B-cell cancer cell lines, as well as AML and CLL primary patient cells. The agent can effectively arrest the growth of lymphoma and leukemia cells at the G0–G1 stage and can induce strong apoptotic cell death. These results demonstrated that simultaneous inhibition of BTK and MNK kinase activity might be a new therapeutic strategy for B-cell malignances.