<div>Abstract<p>The Akt and mitogen-activated protein kinase (MAPK) pathways have been implicated in tumor cell survival and contribute to radiation resistance. However, the molecular basis for link between MAPK and Akt in cell survival response to radiation is unclear. Here, we show that c-Src-Rac1-p38 MAPK pathway signals Akt activation and cell survival in response to radiation. Ionizing radiation triggered Thr<sup>308</sup> and Ser<sup>473</sup> phosphorylation of Akt. Exposure of cells to radiation also induced p38 MAPK and c-Jun NH<sub>2</sub>-terminal kinase activations. Inhibition of c-Jun NH<sub>2</sub>-terminal kinase suppressed radiation-induced cell death, whereas inhibition of p38 MAPK effectively increased sensitivity to radiation. Interestingly, inhibition of p38 MAPK completely attenuated radiation-induced Ser<sup>473</sup> phosphorylation of Akt but did not affect Thr<sup>308</sup> phosphorylation. Conversely, overexpression of p38 MAPK enhanced Ser<sup>473</sup> phosphorylation of Akt in response to radiation. In addition, inhibition of p38 MAPK failed to alter phosphoinositide 3-kinase and phosphoinositide-dependent protein kinase activities. Ectopic expression of RacN17, dominant-negative form of Rac1, inhibited p38 MAPK activation and Ser<sup>473</sup> phosphorylation of Akt. Following exposure to radiation, c-Src was selectively activated among Src family tyrosine kinases. Inhibition of c-Src attenuated Rac1 and p38 MAPK activations and Ser<sup>473</sup> phosphorylation of Akt. Our results support the notion that the c-Src-Rac1-p38 MAPK pathway is required for activation of Akt in response to radiation and plays a cytoprotective role against radiation in human cancer cells. (Mol Cancer Res 2008;6(12):1872–80)</p></div>
Nanostructured semiconducting metal oxides offer an extremely high surface/volume ratio which have detecting sensitivity of part per million and even below, dynamic range and decrease the response time by more than 10-fold in comparison with thin film materials. Motivated by the recent development in fabricating and synthesizing nano-sized metal oxides, we have used an electrospinning method to produce semiconducting ZnO nanofibers for advanced environmental sensing. ZnO/PVP composite fiber mats were directly electrospun onto a SiO2/Si at 120oC, then calcined at 600oC. Polycrystalline wurtzite ZnO nanofibers of diameter in 35~70 nm were obtained. The CO gas sensing performances have been evaluated in a CO concentration range of 10~25 ppm. The resistances of ZnO nanofibers were observed to decrease upon exposure to CO. This is attributed to the reducing nature of CO, which reacts with O- to release an extra electron
Abstract This work presents the design, fabrication and microwave performance of distributed analog phase shifter (DAPS) fabricated on (Ba,Sr)TiO3 (BST) thin films for X-band applications. Ferroelectric BST thin films were deposited on MgO substrates by pulsed laser deposition. The DAPS consists of high impedance coplanar waveguide (CPW) and periodically loaded tunable BST interdigitated capacitors (IDC). In order to reduce the insertion loss of DAPS and to remove the alteration of unloaded CPW properties according to an applied dc bias voltage, BST layer under transmission lines were removed by photolithography and RF-ion milling. The measured results are in good agreement with the simulated results at the frequencies of interest. The measured differential phase shift based on BST thin films was 24° and the insertion loss decreased from −1.1 dB to −0.7 dB with increasing the bias voltage from 0 to 40 V at 10 GHz. Keywords: Ferroelectric thin films distributed analog phase shifter coplanar waveguide interdigitated capacitor phased array antenna
High power microwave properties of the ferroelectric phase shifters have been studied to reduce the effect of the nonlinear response of ferroelectrics under high power microwave with an applied dc bias field of 0 - 40 kV/cm. The Ba 0.6 Sr 0.4 TiO 3 ferroelectric films were prepared on (001) MgO single crystals by pulsed laser deposition. Coplanar waveguide (CPW) phase shifters were fabricated from 2 w m thick Au layer to reduce metal loss. The fabricated CPW phase shifters exhibited more than 100° of differential phase at 10 GHz with a 40 kV/cm dc bias field between ground and center conductors. Furthermore, the CPW phase shifter showed a constant differential phase shift with microwave power range from m 10 to +30 dBm. Microwave power and/or dc bias field dependant responses of phase shifters are presented in the paper.
Allogenic myoblast transplantation (AMT) is under investigation for treatment of severe genetic myopathies. Data regarding the role of cyclosporine (CsA) and FK-506 in AMT have shown that CsA is less effective than FK-506. For this study, we investigated mechanisms of CsA toxicity during AMT and showed that a high level of reactive oxygen species (ROS) generated by CsA, mediated partly by inhibition of the peptidylprolyl-cis-trans-isomerase (PPIase)-like activity of cyclophilin A (CypA), blocked differentiation and induced apoptosis at an early stage of muscle differentiation. Inhibition of the PPIase-like activity of CypA alone also blocked muscle differentiation. However, CsA toxicity did not depend on the inhibition of calcineurin activity during muscle differentiation. Together, these data suggest that CsA-mediated inhibition of the PPIase-like activity of CypA and the high level of ROS generation contributed to the low efficacy of CsA in AMT. In addition, we showed that a reduction of oxidative stress protected cells from CsA-induced apoptosis, and myoblasts that had survived after preexposure to CsA not only proliferated and differentiated reversibly but also gained resistance to subsequent CsA exposure. Thus, administration of antioxidants or overexpression of CypA either exogenously or endogenously during CsA treatment has the potential to improve the success of this treatment in AMT.
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