Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
The radial velocity (RV) is a basic physical quantity that can be determined through the Doppler shift of the spectrum of a star. The precision of the RV measurement depends on the resolution of the ...spectrum we used and the accuracy of wavelength calibration. In this work, radial velocities of the Large Sky Area Multi-Object Fibre Spectroscopic Telescope-II (LAMOST-II) medium-resolution (R ∼ 7500) spectra are measured for 1,594,956 spectra (each spectrum has two wavebands) through matching with templates. A set of RV standard stars are used to recalibrate the zero point of the measurement, and some reference sets with RVs derived from medium-/high-resolution observations are used to evaluate the accuracy of the measurement. By comparing with reference sets, the accuracy of our measurement can get 0.0277 km s−1 with respect to radial velocities of standard stars. The intrinsic precision is estimated with the multiple observations of single stars, which can be achieved to 1.36 km s−1, 1.08 km s−1, and 0.91 km s−1 for the spectra at signal-to-noise levels of 10, 20, and 50, respectively.
Highlights • Regional and network functional changes could be seen in the early stage of SCI. • Functional changes were associated with clinical symptom severity in SCI patients. • Functional ...reorganization may reflect a compensatory role in the recovery of SCI.
Abstract
We present the second release of value-added catalogues of the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC DR2). The catalogues present values of radial velocity Vr, ...atmospheric parameters – effective temperature Teff, surface gravity log g, metallicity Fe/H, α-element to iron (metal) abundance ratio α/Fe (α/M), elemental abundances C/H and N/H and absolute magnitudes MV and $M_{K_{\rm s}}$ deduced from 1.8 million spectra of 1.4 million unique stars targeted by the LSS-GAC since 2011 September until 2014 June. The catalogues also give values of interstellar reddening, distance and orbital parameters determined with a variety of techniques, as well as proper motions and multiband photometry from the far-UV to the mid-IR collected from the literature and various surveys. Accuracies of radial velocities reach 5 km s−1 for the late-type stars, and those of distance estimates range between 10 and 30 per cent, depending on the spectral signal-to-noise ratios. Precisions of Fe/H, C/H and N/H estimates reach 0.1 dex, and those of α/Fe and α/M reach 0.05 dex. The large number of stars, the contiguous sky coverage, the simple yet non-trivial target selection function and the robust estimates of stellar radial velocities and atmospheric parameters, distances and elemental abundances make the catalogues a valuable data set to study the structure and evolution of the Galaxy, especially the solar-neighbourhood and the outer disc.
Previously, we reported that Akt inactivation determines the sensitivity of hepatocellular carcinoma (HCC) cells to bortezomib. In this study, we report that cancerous inhibitor of protein ...phosphatase 2A (CIP2A), a cellular inhibitor of protein phosphatase 2A (PP2A), mediates the apoptotic effect of bortezomib in HCC. Silencing PP2A by small interference RNA (siRNA) abolishes bortezomib-induced down-regulation of phospho-Akt and apoptosis. Bortezomib increases PP2A activity in sensitive HCC cells, including Sk-Hep1, Hep3B and Huh-7, but not in resistant PLC5 cells. Bortezomib down-regulates CIP2A in a dose- and time-dependent manner in all sensitive HCC cells, whereas no alterations in CIP2A were found in resistant PLC5 cells. Knockdown of CIP2A by siRNA restored bortezomib's effects on apoptosis and PP2A activity in PLC5 cells. Moreover, over-expression of CIP2A up-regulated phospho-Akt and protected Sk-Hep1 cells from bortezomib-induced apoptosis. It is significant that, ectopic expression of CIP2A decreased Akt-related PP2A activity, whereas silencing CIP2A increased this activity, indicating that CIP2A negatively regulates Akt-related PP2A activity in HCC cells, furthermore, our in vivo data showed that bortezomib down-regulates CIP2A and up-regulates PP2A activity in Huh-7 tumors, but not in PLC5 tumors. In conclusion, inhibition of CIP2A determines the effects of bortezomib on apoptosis and PP2A-dependent Akt inactivation in HCC.
The bilayer-based Antiferroelectric Tunneling Junction (AFTJ) with ferroelectric (FE) HfZrO 2 (HZO) and dielectric (DE) Al 2 O 3 demonstrates a current ratio of <inline-formula> <tex-math ...notation="LaTeX">> 100\times </tex-math></inline-formula>, a TER (tunneling electroresistance) of <inline-formula> <tex-math notation="LaTeX">> 50\times </tex-math></inline-formula>, multilevel states, <inline-formula> <tex-math notation="LaTeX">> 10^{4} </tex-math></inline-formula> sec retention, and a cycling endurance as high as 10 8 . The concept of tunneling current through DE in an antiferroelectric (AFE) system enhances the capacity to modulate the current/TER ratio and makes the AFTJ feasible for low-power crossbar eNVM (embedded nonvolatile memory) applications.
The 3D vertical ferroelectric tunneling junction (FTJ) of bilayer antiferroelectric (AFE) Hf 1-x Zr x O 2 (HZO) and Al 2 O 3 has been demonstrated for NAND-compatible feasibility. A bilayer-type FTJ ...is explored for the designs of the dielectric interlayer Al 2 O 3 0 nm to 4 nm and the ferroelectric type, while the current mechanism is revealed. The multilevel AFE-FTJ is exhibited for both the Program and Erase operations and realizes a synaptic device. High-density emerging memory and computing-in-memory (CiM) are in high demanded for the future era and can be feasible by the proposed vertical FTJ.
Abstract Background and purpose Radiomics provides opportunities to quantify the tumor phenotype non-invasively by applying a large number of quantitative imaging features. This study evaluates ...computed-tomography (CT) radiomic features for their capability to predict distant metastasis (DM) for lung adenocarcinoma patients. Material and methods We included two datasets: 98 patients for discovery and 84 for validation. The phenotype of the primary tumor was quantified on pre-treatment CT-scans using 635 radiomic features. Univariate and multivariate analysis was performed to evaluate radiomics performance using the concordance index (CI). Results Thirty-five radiomic features were found to be prognostic (CI > 0.60, FDR < 5%) for DM and twelve for survival. It is noteworthy that tumor volume was only moderately prognostic for DM (CI = 0.55, p -value = 2.77 × 10−5 ) in the discovery cohort. A radiomic-signature had strong power for predicting DM in the independent validation dataset (CI = 0.61, p -value = 1.79 × 10−17 ). Adding this radiomic-signature to a clinical model resulted in a significant improvement of predicting DM in the validation dataset ( p -value = 1.56 × 10−11 ). Conclusions Although only basic metrics are routinely quantified, this study shows that radiomic features capturing detailed information of the tumor phenotype can be used as a prognostic biomarker for clinically-relevant factors such as DM. Moreover, the radiomic-signature provided additional information to clinical data.
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