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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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Archive for History of Exact Sciences - From Antiquity through the early modern period, the apparent motion of the Sun in longitude was simulated by the eccentric model set forth in Ptolemy’s...  相似文献   
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With the exponential development of mobile communications and the miniaturization of radio frequency transceivers, the need for small and low profile antennas at mobile frequencies is constantly growing. Therefore, new antennas should be developed to provide larger bandwidth and at the same time small dimensions. Although the gain in bandwidth performances of an antenna are directly related to its dimensions in relation to the wavelength, the aim is to keep the overall size of the antenna constant and from ...  相似文献   
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Tracking mobile nodes in dynamic and noisy conditions of industrial environments has provided a paradigm for many issues inherent in the area of distributed control systems in general and wireless sensor networks in particular. Due to the dynamic nature of the industrial environments, a practical tracking system is required that is adaptable to the changes in the environment. More specifically, given the limited resources of wireless nodes and the challenges created by harsh industrial environments there is a need for a technique that can modify the configuration of the system on the fly as new wireless nodes are added to the network and obsolete ones are removed. To address these issues, two cluster-based tracking systems, one static and the other dynamic, are proposed to organize the overall network field into a set of tracking zones, each composed of a sink node and a set of corresponding anchor nodes. To manage the wireless nodes activities and inter and intra cluster communications, an agent-based technique is employed. To compare the architectures, we report on a set of experiments performed in JADE (Java Agent Development Environment). In these experiments, we compare two agent-based approaches (dynamic and static) for managing clusters of wireless sensor nodes in a distributed tracking system. The experimental results corroborate the efficiency of the static clusters versus the robustness and effectiveness of the dynamic clusters.  相似文献   
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The weldability of the ZhS6U nickel-based superalloy, which is prone to solidification cracking during electron-beam welding(EBW) repair processes, was investigated. The effects of two different pre-weld heat-treatment cycles on the final microstructure before and after welding were examined. Welds were made on flat coupons using an EBW machine, and the two heat-treatment cycles were designed to reduce γ′ liquation before welding. Microstructural features were also examined by optical and scanning electron microscopy. The results showed that the change in the morphology and size of the γ′ precipitates in the pre-weld heat-treatment cycles changed the ability of the superalloy to release the tensile stresses caused by the matrix phase cooling after EBW. The high hardness in the welded coupons subjected to the first heat-treatment cycle resulted in greater resistance to stress release by the base alloy, and the concentration of stress in the base metal caused liquation cracks in the heat-affected zone and solidification cracks in the weld area.  相似文献   
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Based on the measurement of the released hydrogen gas pressure (PH2), the reaction kinetics between TiH2 powder and pure aluminum melt was studied at various temperatures. After cooling the samples, the interface of TiH2 powder and aluminum melt was studied. The results show that the 2 H PH2-time curves have three regions; in the first and second regions, the rate of reaction conforms zero and one order, respectively; in the third region, the hydrogen gas pressure remains constant and the rate of reaction reaches zero. The main factors that control the rate of reaction in the first and second regions are the penetration of hydrogen atoms in the titanium lattice and the chemical reaction between molten aluminum and titanium, respectively. According to the main factors that control the rate of reaction, three temperature ranges are considered for the reaction mechanism:(a) 700-750℃, (b) 750-800℃, and (c) 800-1000℃. In the first temperature range, the reaction is mostly under the control of chemical reaction; at the temperature range of 750 to 800℃, the reaction is controlled by the diffusion and chemical reaction; at the third temperature range (800-1000℃), the dominant controlling mechanism is diffusion.  相似文献   
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