A new numerical method for the analysis of monolithic seepage problems with complex drainage systems in a groundwater recharge area for a hydropower station in China

After construction of a dam impounding water in a reservoir, a monolithic seepage field develops in the surrounding rock mass. Here, a new finite element method is proposed for determining the shape and characteristics of the 3D monolithic seepage field including the free surface, considering complex drainage systems consisting of densely-spaced drainage holes and drainage galleries. To this end, the previously proposed virtual flux method is improved by a refined numerical integration scheme and a regularized Heaviside function for distinguishing the subregions below and above the free surface within a particular finite element. Leakage and overflow drainage holes are modeled as internal boundaries. The proposed numerical method is verified by an academic example, for which the analytical solution is available. Finally, the numerical simulation of the seepage field developing in the vicinity of a high dam and underground power house, constructed in the context of a hydropower plant project in China is used to show its application to a problem in engineering practice.</p

miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level

<p>Abstract</p> <p>Background</p> <p>miR-15a and miR-16-1(miR-15a/16-1) have been implicated as tumor suppressors in chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemic cells. However the mechanism of inhibiting the proliferation of leukemic cells is poorly understood.</p> <p>Methods</p> <p>K562 and HL-60 cells were transfected with pRS-15/16 or pRS-E, cell growth were measured by CCK-8 assay and direct cell count. Meanwhile WT1 protein and mRNA level were measured by Western blotting and quantitative real-time PCR.</p> <p>Results</p> <p>In this study we found that over-expression of miR-15a/16-1 significantly inhibited K562 and HL-60 cells proliferation. Enforced expression of miR-15a/16-1 in K562 and HL-60 cells significantly reduced the protein level of WT1 but not affected the mRNA level. However enforced expression of miR-15a/16-1 can not reduce the activity of a luciferase reporter carrying the 3'-untranslated region(3'UTR) of WT1. Silencing of WT1 by specific siRNA suppressed leukemic cells proliferation resembling that of miR-15a/16-1 over-expression. Anti-miR-15a/16-1 oligonucleotides (AMO) reversed the expression of WT1 in K562 and HL-60 cells. Finally, we found a significant inverse correlation between miR-15a or miR-16-1 expression and WT1 protein levels in primary acute myeloid leukemia (AML) blasts and normal controls.</p> <p>Conclusions</p> <p>These data suggest that miR-15a/16-1 may function as a tumor suppressor to regulate leukemic cell proliferation potentially by down-regulating the WT1 oncogene. However WT1 is not directly targeted by miR-15a/16-1 through miRNA-mRNA base pairing, therefore more study are required to understand the mechanism by which miR-15a/16-1 downregulate WT1.</p