51,234 research outputs found

    Rapamycin induces transactivation of the EGFR and increases cell survival.

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    The mammalian target of rapamycin (mTOR) signaling network regulates cell growth, proliferation and cell survival. Deregulated activation of this pathway is a common event in diverse human diseases such as cancers, cardiac hypertrophy, vascular restenosis and nephrotic hypertrophy. Although mTOR inhibitor, rapamycin, has been widely used to inhibit the aberrant signaling due to mTOR activation that plays a major role in hyperproliferative diseases, in some cases rapamycin does not attenuate the cell proliferation and survival. Thus, we studied the mechanism(s) by which cells may confer resistance to rapamycin. Our data show that in a variety of cell types the mTOR inhibitor rapamycin activates extracellularly regulated kinases (Erk1/2) signaling. Rapamycin-mediated activation of the Erk1/2 signaling requires (a) the epidermal growth factor receptor (EGFR), (b) its tyrosine kinase activity and (c) intact autophosphorylation sites on the receptor. Rapamycin treatment increases tyrosine phosphorylation of EGFR without the addition of growth factor and this transactivation of receptor involves activation of c-Src. We also show that rapamycin treatment triggers activation of cell survival signaling pathway by activating the prosurvival kinases Erk1/2 and p90RSK. These studies provide a novel paradigm by which cells escape the apoptotic actions of rapamycin and its derivatives that inhibit the mTOR pathway

    Non-Gaussianity from Lifshitz Scalar

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    A Lifshitz scalar with the dynamical critical exponent z = 3 obtains scale-invariant, super-horizon field fluctuations without the need of an inflationary era. Since this mechanism is due to the special scaling of the Lifshitz scalar and persists in the presence of unsuppressed self-couplings, the resulting fluctuation spectrum can deviate from a Gaussian distribution. We study the non-Gaussian nature of the Lifshitz scalar's intrinsic field fluctuations, and show that primordial curvature perturbations sourced from such field fluctuations can have large non-Gaussianity of order f_NL = O(100), which will be detected by upcoming CMB observations. We compute the bispectrum and trispectrum of the fluctuations, and discuss their configurations in momentum space. In particular, the bispectrum is found to take various shapes, including the local, equilateral, and orthogonal shapes. Intriguingly, all integrals in the in-in formalism can be performed analytically.Comment: 17 pages, 15 figures, v2: published in JCA

    Dual-mode mechanical resonance of individual ZnO nanobelts

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    ©2003 American Institute of Physics. The electronic version of this article is the complete one and can be found online at: http://link.aip.org/link/?APPLAB/82/4806/1DOI:10.1063/1.1587878The mechanical resonance of a single ZnO nanobelt, induced by an alternative electric field, was studied by in situ transmission electron microscopy. Due to the rectangular cross section of the nanobelt, two fundamental resonance modes have been observed corresponding to two orthogonal transverse vibration directions, showing the versatile applications of nanobelts as nanocantilevers and nanoresonators. The bending modulus of the ZnO nanobelts was measured to be ~52 GPa and the damping time constant of the resonance in a vacuum of 5×10–8 Torr was ~1.2 ms and quality factor Q = 500
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