115 research outputs found

    A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-α therapy

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    BACKGROUND: Survivin is a member of the inhibitor-of-apoptosis (IAP) family which is widely expressed by many different cancers. Overexpression of survivin is associated with drug resistance in cancer cells, and reduced patient survival after chemotherapy and radiotherapy. Agents that antagonize the function of survivin hold promise for treating many forms of cancer. The purpose of this study was to investigate whether a cell-permeable dominant-negative survivin protein would demonstrate bioactivity against prostate and cervical cancer cells grown in three dimensional culture.RESULTS: A dominant-negative survivin (C84A) protein fused to the cell penetrating peptide poly-arginine (R9) was expressed in E. coli and purified by affinity chromatography. Western blot analysis revealed that dNSurR9-C84A penetrated into 3D-cultured HeLa and DU145 cancer cells, and a cell viability assay revealed it induced cancer cell death. It increased the activities of caspase-9 and caspase-3, and rendered DU145 cells sensitive to TNF-&alpha; via by a mechanism involving activation of caspase-8.CONCLUSIONS: The results demonstrate that antagonism of survivin function triggers the apoptosis of prostate and cervical cancer cells grown in 3D culture. It renders cancer cells sensitive to the proapoptotic affects of TNF-&alpha;, suggesting that survivin blocks the extrinsic pathway of apoptosis. Combination of the biologically active dNSurR9-C84A protein or other survivin antagonists with TNF-&alpha; therapy warrants consideration as an approach to cancer therapy.<br /

    Learning for Expressive Task-Related Sentence Representations

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    NLP models learn sentence representations for downstream tasks by tuning a model which is pre-trained by masked language modeling. However, after tuning, the learned sentence representations may be skewed heavily toward label space and thus are not expressive enough to represent whole samples, which should contain task-related information of both sentence inputs and labels. In this work, we learn expressive sentence representations for supervised tasks which (1). contain task-related information in the sentence inputs, and (2). enable correct label predictions. To achieve this goal, we first propose a new objective which explicitly points out the label token space in the input, and predicts categories of labels via an added [MASK] token. This objective encourages fusing the semantic information of both the label and sentence. Then we develop a neighbor attention module, added on a frozen pre-trained model, to build connections between label/sentence tokens via their neighbors. The propagation can be further guided by the regularization on neighborhood representations to encourage expressiveness. Experimental results show that, despite tuning only 5% additional parameters over a frozen pre-trained model, our model can achieve classification results comparable to the SOTA while maintaining strong expressiveness as well.Comment: 12 pages, 2 figure

    Effect of Roughness on Shear Characteristics of the Interface between Silty Clay and Concrete

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    In order to study the effect of roughness on the mechanical parameters of silty clay-concrete interface, and to explore the applicability of silicon piezoresistive sensor to test the interface pressure, a large-scale direct shear test system was used to carry out experimental research on the shear characteristics of silty clay-concrete interface under different roughness conditions. Based on silicon piezoresistive sensor, the shear characteristics of silty clay-concrete interface are analyzed. The results show that the silicon piezoresistive sensor has excellent performance in measuring the interface pressure and can accurately obtain the shear characteristics of the silty clay-concrete interface. The roughness has a significant influence on the shear strength, shear stiffness, and other mechanical properties of the prefabricated pile-soil interface. With the increase of roughness, interface shear strength, interface friction angle, shear stiffness coefficient, and interface residual shear stress all show an increasing trend, with the maximum increase of 37.0%. The interface adhesion decreased first and then increased with the increase of roughness, with an increase of 23.7%. The test results can provide reference for the engineering practice of jacked pile

    Ultimate Load Tests on Bearing Behavior of Large-Diameter Bored Piles in Weathered Rock Foundation

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    Based on the vertical compressive static load test and pile mechanics test of three large diameter bored piles (one of the test piles was treated with postgrouting) in granite gneisses foundation, the bearing capacity, deformation characteristics, and influencing factors of the single pile under the limit state are analyzed and compared with the recommended values of survey report and the recommended values of current codes. By comparing the measured and theoretical values of pile axial force, the bearing capacity of cast-in-place pile under normal and limit conditions is analyzed. The experimental results show that the Q-s curve of large-diameter rock-socketed mud wall retaining bored pile with a length-diameter ratio of 25–33 and rock-socketed depth of 5–8 d shows a rapid growth. After grouting treatment, the ultimate compressive bearing capacity of single pile is improved, the maximum settlement is reduced by 6.6%, the rebound rate is reduced by 11.1%, and the settlement effect of controlling pile top is not significant. The bearing capacity and deformation characteristics of the three test piles are less affected by length-diameter ratio and rock-socketed depth. For postgrouting piles, the ratio of frictional resistance of rock-socketed segment and the ratio of pile lateral resistance are less affected by length-diameter ratio and rock-socketed depth, while, for postgrouting piles, the ratio of pile lateral resistance is more affected by rock-socketed depth. The pile end resistance ratio of the three test piles is significantly affected by the rock-socketed depth, whether or not the pile side postgrouting treatment is carried out
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