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Mammalian protease-activated-receptor-1 and -2 (PAR1 and PAR2) are activated by proteases found in the flexible microenvironment of a tumor and play a central role in breast cancer. We propose in the present study that PAR1 and PAR2 act together as a functional unit during malignant and physiological invasion processes. This notion is supported by assessing pro-tumor functions in the presence of short hairpin; shRNA knocked-down hPar2 or by the use of a truncated PAR2 devoid of the entire cytoplasmic tail. Silencing of hPar2 by shRNA-attenuated thrombin induced PAR1 signaling as recapitulated by inhibiting the assembly of Etk/Bmx or Akt onto PAR1-C-tail, by thrombin-instigated colony formation and invasion. Strikingly, shRNA-hPar2 also inhibited the TFLLRN selective PAR1 pro-tumor functions. In addition, while evaluating the physiological invasion process of placenta extravillous trophoblast (EVT) organ culture, we observed inhibition of both thrombin or the selective PAR1 ligand; TFLLRNPNDK induced EVT invasion by shRNA-hPar2 but not by scrambled shRNA-hPar2. In parallel, when a truncated PAR2 was utilized in a xenograft mouse model, it inhibited PAR1–PAR2-driven tumor growth in vivo. Similarly, it also attenuated the interaction of Etk/Bmx with the PAR1-C-tail in vitro and decreased markedly selective PAR1-induced Matrigel invasion. Confocal images demonstrated co-localization of PAR1 and PAR2 in HEK293T cells over-expressing YFP-hPar2 and HA-hPar1. Co-immuno-precipitation analyses revealed PAR1-PAR2 complex formation but no PAR1-CXCR4 complex was formed. Taken together, our observations show that PAR1 and PAR2 act as a functional unit in tumor development and placenta-uterus interactions. This conclusion may have significant consequences on future breast cancer therapeutic modalities and improved late pregnancy outcome.  相似文献   
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Cellular and Molecular Life Sciences - Hematopoietic system transports all necessary nutrients to the whole organism and provides the immunological protection. Blood cells have high turnover,...  相似文献   
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天牛(鞘翅目Coleoptera:天牛科Cerambycidae)为树木重要的钻蛀性害虫.本文研究了伊朗西北部Arasbaran生物圈保护区及邻近地区的天牛种类,采集鉴定了5个亚科26属33种,提供了一些种类的植物寄主.  相似文献   
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An integrated semiconductor device enabling non-optical genome sequencing   总被引:4,自引:0,他引:4  
The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.  相似文献   
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The focus of this paper is to address a novel control technique for stability and transparency analysis of bilateral telerobotic systems in the presence of data loss and time delay in the communication channel. Different control strategies have been reported to compensate the effects of time delay in the communication channel;however, most of them result in poor performance under data loss. First, a model for data loss is proposed using a finite series representation of a set of periodic continuous pulses.To improve the performance and data reconstruction, a holder circuits is also introduced. The passivity of the overall system is provided via the wave variable technique based on the proposed model for the data loss. The stability analysis of the system is then derived using the Lyapunov theorem under the time delay and the data loss. Finally, experimental results are given to illustrate the capability of the proposed control technique.  相似文献   
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Do long‐run equilibrium relations suggested by economic theory help to improve the forecasting performance of a cointegrated vector error correction model (VECM)? In this paper we try to answer this question in the context of a two‐country model developed for the Canadian and US economies. We compare the forecasting performance of the exactly identified cointegrated VECMs to the performance of the over‐identified VECMs with the long‐run theory restrictions imposed. We allow for model uncertainty and conduct this comparison for every possible combination of the cointegration ranks of the Canadian and US models. We show that the over‐identified structural cointegrated models generally outperform the exactly identified models in forecasting Canadian macroeconomic variables. We also show that the pooled forecasts generated from the over‐identified models beat most of the individual exactly identified and over‐identified models as well as the VARs in levels and in differences. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   
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1 Results The synthesis, physical characterization and electrochemical analysis of Pt particles prepared using the surface oxidized carbon nanotubes prepared by chemically anchoring Pt onto the surface of the CNTs with 2.0 mol/L HNO3 by refluxing for 10 h to introduce surface functional groups.The particles of Pt are synthesized by reduction with sodium borohydride of H2PtCl6. The electro-oxidation of liquid methanol of this catalyst as a thin layer on glassy carbon electrode is investigated at room te...  相似文献   
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