To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-beta/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 ...and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-beta and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-beta and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins.
The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry.
The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions.
The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-beta/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.
GRB 130925A is a peculiar event characterized by an extremely long gamma-ray duration (\(\approx\)7 ks), as well as dramatic flaring in the X-rays for \(\approx\)20 ks. After this period, its X-ray ...afterglow shows an atypical soft spectrum with photon index $\Gamma$$\sim\(4, as observed by Swift and Chandra, until \)\approx 10^7\( s, when XMM-Newton observations uncover a harder spectral shape with \)\Gamma$$\sim$2.5, commonly observed in GRB afterglows. We find that two distinct emission components are needed to explain the X-ray observations: a thermal component, which dominates the X-ray emission for several weeks, and a non-thermal component, consistent with a typical afterglow. A forward shock model well describes the broadband (from radio to X-rays) afterglow spectrum at various epochs. It requires an ambient medium with a very low density wind profile, consistent with that expected from a low-metallicity blue supergiant (BSG). The thermal component has a remarkably constant size and a total energy consistent with those expected by a hot cocoon surrounding the relativistic jet. We argue that the features observed in this GRB (its ultralong duration, the thermal cocoon, and the low density wind environment) are associated with a low metallicity BSG progenitor and, thus, should characterize the class of ultralong GRBs.
We report on the achievement of a continuously tunable photonic molecule from an homoatomic to an heteroatomic condition. A complete control of the local mode tuning of two nominally identical ...photonic crystal microcavities on slab is obtained by a combination of different techniques. Homoatomic molecules are obtained by compensating the photonic disorder up to the standard condition of zero detuning between identical modes of the two cavities. Heteroatomic molecules are then realized by a large tuning of one of the two cavities, producing the condition of zero detuning between two modes of different polarization and spatial distribution. Clear modes anticrossing and hybridization is observed.
We systematically analyzed the relative contributions of frequency component elements of hemodynamic shear stress waveforms encountered in cardiovascular blood recirculating devices as to overall ...platelet activation over time. We demonstrated that high frequency oscillations are the major determinants for priming, triggering and yielding activated "prothrombotic behavior" for stimulated platelets, even if the imparted shear stress has low magnitude and brief exposure time. Conversely, the low frequency components of the stress signal, with limited oscillations over time, did not induce significant activation, despite being of high magnitude and/or exposure time. In vitro data were compared with numerical predictions computed according to a recently proposed numerical model of shear-mediated platelet activation. The numerical model effectively resolved the correlation between platelet activation and the various frequency components examined. However, numerical predictions exhibited a different activation trend compared to experimental results for different time points of a stress activation sequence. With this study we provide a more fundamental understanding for the mechanobiological responsiveness of circulating platelets to the hemodynamic environment of cardiovascular devices, and the importance of these environments in mediating life-threatening thromboembolic complications associated with shear-mediated platelet activation. Experimental data will guide further optimization of the thromboresistance of cardiovascular implantable therapeutic devices.
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