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For this study, the geological engineering features and possible failure modes of the Dabenliu quarry slope in the Jinping-I Hydropower Station were qualitatively analyzed before a method for setting viscous boundary and an algorithm for modeling pre-stressed cables were embedded into a DDA (Discontinuous Deformation Analysis) computer code to analyze the deformation of the slope under seismic loading. Our simulation results revealed that the middle and upper parts of the slope slipped along the bedding joints (interlayer shear zones) and that the lower part buckled and collapsed after the slope was excavated. This is a typical slipping–buckling failure mode characterized by upper-slipping followed by lower-buckling. Based on the distribution of the simulated internal force of the anchor cables, the reinforcement scheme was adjusted by strengthening the support for the middle and lower parts of the slope, whereas the length and pre-stress of the anchor cables were reduced for the upper part of the slope. The adjusted reinforcement scheme can ensure the stability of the slope under the action of a magnitude 7 earthquake, and the slope may lose stability with no evident collapse under the action of a magnitude 8 earthquake. Finally, the simulation results were verified via a comparison with the monitoring data regarding the slope. [ABSTRACT FROM AUTHOR]

In natural rock masses, the shapes of three‐dimensional (3‐D) blocks cut by arbitrary fracture networks may be very complex. Owing to the geometric complexity and difficulty of mesh discretization of 3‐D blocks and fracture facets, explicit consideration of fracture networks in flow analysis of fractured porous medium (FPM) is very challenging. Using the numerical manifold method based on independent covers (NMMIC), an FPM flow model was proposed that can deal with very complex 3‐D fracture networks. In this paper, the convergence of NMMIC was first demonstrated. The theoretical basis of the arbitrary refinement of computational meshes was proven. Moreover, three peculiarities of NMMIC meshes, that is, arbitrary shape, arbitrary connection, and arbitrary refinement of independent covers, were concluded. Finally, some two‐dimensional (2‐D) tunnel flow examples were analyzed and the numerical results were compared with the analytical results. 3‐D examples with complex fracture distributions were also analyzed. In addition, the computational scale of the developed program was tested by increasing the number of computational elements. The results show that our model can accurately analyze the groundwater flow of rocks surrounding tunnels with complex fracture distributions. [ABSTRACT FROM AUTHOR]

Metastasis accounts for 90% of cancer death worldwide, and effective therapeutic strategies are lacking. The aim of this work is to identify the key drivers in tumor metastasis and screen therapeutics for treatment of esophageal squamous cell carcinoma (ESCC). Gene Ontology analysis of The Cancer Genome Atlas (TCGA) gene expression datasets of ESCC patients with or without lympy metastasis identifies that TGFβ2 is highly enriched in the pathways essential for tumor metastasis and upregulates in the metastatic ESCC tumors. High TGFβ2 expression in ESCC correlates with metastasis and patient survival, and functionally contributes to tumor metastasis via activating extracellular signal‐regulated kinases (ERK) signaling. By screening of a library consisting of 429 bioactive compounds, imperatorin is verified as a novel TGFβ2 inhibitor, with robustly suppressive effect on tumor metastasis in multiple mice models. Mechanistically, direct binding of imperatorin and CREB1 inhibits phosphorylation, nuclear translocation of CREB1, and its interaction with TGFβ2 promoter, represses TGFβ2 expression and fibroblasts‐secreted CCL2, and then inactivates ERK signaling to block cancer invasion and abrogates the paracrine effects of fibroblasts on tumor angiogenesis and metastasis. Overall, the findings suggest the use of TGFβ2 as a diagnostic and prognostic biomarker and therapeutic target in ESCC, and supports the potential of imperatorin as a novel therapeutic strategy for cancer metastasis. [ABSTRACT FROM AUTHOR]

In the case of very complex geometric morphology in three-dimensional (3-d) calculation regions, the subdivision of finite element meshes tends to be very difficult or even impossible. This problem was especially dominant in the element subdivision of rock blocks cut by arbitrary fracture networks. This study proposed a directed simplex subdivision method of 2- and 3-d regions which can readily subdivide a complex region and automatically adapt to arbitrary variations of region boundaries. The directed simplex was employed as finite elements for the first time. When the nodes of 2-d simplex (triangle) were connected anticlockwise and the nodes of 3-d simplex (tetrahedron) were linked by the right hand screw rule, the finite element is treated as a positive element. Otherwise, it is treated as a negative element. However, some generated elements presented superposition, which was unallowable in the normal finite element method (FEM). Therefore, the superposition principle of positive and negative finite elements was proposed. Such superposition method can transform a normal FEM mesh into a positive-negative FEM mesh with maintaining its completeness and compatibility. Finally, 1-d, 2-d, and 3-d cases were used as examples to verify the validity of the proposed method. The completeness and compatibility of the positive-negative FEM and the normal FEM are consistent. The accuracy of these two methods differs due to the difference of nodal connection relationships, node numbers, and element sizes. However, as the mesh is refined, the calculated results tend to be consistent. [ABSTRACT FROM AUTHOR]