6,955 research outputs found

    Phosphorylation of nucleophosmin at threonine 234/237 is associated with HCC metastasis

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    Hepatocellular carcinoma (HCC) is frequently complicated by the occurrence of intrahepatic and extrahepatic metastases, leading to poor prognosis. To improve the prognosis for HCC patients, there is an urgent need to understand the molecular mechanisms of metastasis in HCC. Since protein Serine/Threonine phosphorylation emerges to be an important posttranslational modification critical in signaling process associated with cell proliferation, survival and metastasis, we employed a pair of primary tumor-derived and corresponding lung-metastatic counterparts (PLC/PRF/5-PT and PLC/PRF/5-LM) and aimed to identify these changes using CelluSpot Serine/Threonine kinase peptide array. Upon analysis, we found phosphorylated level of nucleophosmin (NPM) at Threonine 234/237 (p-NPM-Thr234/237) had remarkably high level in metastatic HCC cells (PLC-LM) than the corresponding primary HCC cell line (PLC-PT). Similar observation was observed in another match primary and their metastatic counterparts (MHCC-97L and MHCC-97H). By immunohistochemical staining, p-NPM-Thr234/237 was consistently found to be preferentially expressed in metastatic HCCs when compared with primary HCC in 28 HCC cases (p < 0.0001). By overexpressing Flag-tagged NPM and its phosphorylation site mutant (Thr234/237A) into low p-NPM-Thr234/237 expressing cells (Hep3B and Huh7) using a lentiviral based approach, we demonstrated that p-NPM-Thr234/237 is critical in invasion and migration of HCC cells, and this effect was mediated by cyclin-dependent kinase 1 (CDK1). Wild-type NPM was found to physically interact with a metastatic gene, ROCK2, and defective in Thr234/237 phosphorylation decreased its binding affinity, resulting in decrease in ROCK2 mediated signaling pathway. Identification of CDK1/p-NPM/ROCK2 signaling pathway provides a novel target for molecular therapy against HCC metastasis.published_or_final_versio

    Evidence for solar cycles in a late Holocene speleothem record from Dongge Cave, China

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    The association between solar activity and Asian monsoon (AM) remains unclear. Here we evaluate the possible connection between them based on a precisely-dated, high-resolution speleothem oxygen isotope record from Dongge Cave, southwest China during the past 4.2 thousand years (ka). Without being adjusted chronologically to the solar signal, our record shows a distinct peak-to-peak correlation with cosmogenic nuclide 14C, total solar irradiance (TSI) and sunspot number (SN) at multi-decadal to centennial timescales. Further cross-wavelet analyses between our calcite δ18O and atmospheric 14C show statistically strong coherence at three typical periodicities of ~80, 200 and 340 years, suggesting important roles of solar activities in modulating AM changes at those timescales. Our result has further indicated a better correlation between our calcite δ18O record and atmospheric 14C than between our record and TSI. This better correlation may imply that the Sun–monsoon connection is dominated most likely by cosmic rays and oceanic circulation (both associated to atmospheric 14C), instead of the direct solar heating (TSI)

    Remifentanil ameliorates intestinal ischemia-reperfusion injury

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    Parity Doubling and the S Parameter Below the Conformal Window

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    We describe a lattice simulation of the masses and decay constants of the lowest-lying vector and axial resonances, and the electroweak S parameter, in an SU(3) gauge theory with Nf=2N_f = 2 and 6 fermions in the fundamental representation. The spectrum becomes more parity doubled and the S parameter per electroweak doublet decreases when NfN_f is increased from 2 to 6, motivating study of these trends as NfN_f is increased further, toward the critical value for transition from confinement to infrared conformality.Comment: 4 pages, 5 figures; to be submitted to PR

    Ultrafast changes in lattice symmetry probed by coherent phonons

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    The electronic and structural properties of a material are strongly determined by its symmetry. Changing the symmetry via a photoinduced phase transition offers new ways to manipulate material properties on ultrafast timescales. However, in order to identify when and how fast these phase transitions occur, methods that can probe the symmetry change in the time domain are required. We show that a time-dependent change in the coherent phonon spectrum can probe a change in symmetry of the lattice potential, thus providing an all-optical probe of structural transitions. We examine the photoinduced structural phase transition in VO2 and show that, above the phase transition threshold, photoexcitation completely changes the lattice potential on an ultrafast timescale. The loss of the equilibrium-phase phonon modes occurs promptly, indicating a non-thermal pathway for the photoinduced phase transition, where a strong perturbation to the lattice potential changes its symmetry before ionic rearrangement has occurred.Comment: 14 pages 4 figure

    Topological Interactions in Warped Extra Dimensions

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    Topological interactions will be generated in theories with compact extra dimensions where fermionic chiral zero modes have different localizations. This is the case in many warped extra dimension models where the right-handed top quark is typically localized away from the left-handed one. Using deconstruction techniques, we study the topological interactions in these models. These interactions appear as trilinear and quadrilinear gauge boson couplings in low energy effective theories with three or more sites, as well as in the continuum limit. We derive the form of these interactions for various cases, including examples of Abelian, non-Abelian and product gauge groups of phenomenological interest. The topological interactions provide a window into the more fundamental aspects of these theories and could result in unique signatures at the Large Hadron Collider, some of which we explore.Comment: 40 pages, 10 figures, 2 tables; modifications in the KK parity discussion, final version at JHE

    A Tale of Two Current Sheets

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    I outline a new model of particle acceleration in the current sheet separating the closed from the open field lines in the force-free model of pulsar magnetospheres, based on reconnection at the light cylinder and "auroral" acceleration occurring in the return current channel that connects the light cylinder to the neutron star surface. I discuss recent studies of Pulsar Wind Nebulae, which find that pair outflow rates in excess of those predicted by existing theories of pair creation occur, and use those results to point out that dissipation of the magnetic field in a pulsar's wind upstream of the termination shock is restored to life as a viable model for the solution of the "σ\sigma" problem as a consequence of the lower wind 4-velocity implied by the larger mass loading.Comment: 17 pages, 6 figures, Invited Review, Proceedings of the "ICREA Workshop on The High-Energy Emission from Pulsars and their Systems", Sant Cugat, Spain, April 12-16, 201

    Correlation of liver stiffness and histological features in healthy persons and in patients with occult hepatitis B, chronic active hepatitis B, or hepatitis B cirrhosis

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    OBJECTIVES: Liver stiffness measurement using transient elastography has become a popular tool to assess liver fibrosis. The aim of this study was to determine liver stiffness values and histological features in healthy subjects and in patients with chronic hepatitis B (CHB).METHODS: A total of 157 people were included (28 healthy subjects and 18 patients with occult hepatitis B infection, 102 with active CHB, and 9 with end-stage hepatitis B cirrhosis). Histology and liver stiffness measurements were obtained from all patients.RESULTS: The median liver stiffness in healthy subjects and in occult hepatitis B, active hepatitis B, and end-stage cirrhosis patients was 4.6, 4.2, 8.7, and 33.8 kPa, respectively. In healthy subjects and in patients with occult hepatitis B infection, none had significant fibrosis on histology, and all had liver stiffness 7.2 kPa. In patients with active CHB, 32 (31%) had liver stiffness 11.0 kPa, but only four (12%) had cirrhosis on histology. Using liver stiffness to predict cirrhosis in this group had a sensitivity of 100%, a specificity of 69%, a positive predictive value of 10%, and a negative predictive value of 100%. All nine patients with end-stage liver cirrhosis had liver stiffness 11.0 kPa. The overall area under the ROC curve (AUROC) for diagnosing cirrhosis using a cutoff of 11.3 kPa was 0.89.CONCLUSIONS: Liver stiffness measurement has an overall good diagnostic accuracy with excellent negative predictive value. However, in active CHB with elevated alanine aminotransferase (ALT) levels, the positive predictive value for diagnosing cirrhosis is poor, and further studies are needed to optimize the use of transient elastography in this important group. © 2010 by the American College of Gastroenterology.postprin

    Logarithmic Corrections to Extremal Black Hole Entropy from Quantum Entropy Function

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    We evaluate the one loop determinant of matter multiplet fields of N=4 supergravity in the near horizon geometry of quarter BPS black holes, and use it to calculate logarithmic corrections to the entropy of these black holes using the quantum entropy function formalism. We show that even though individual fields give non-vanishing logarithmic contribution to the entropy, the net contribution from all the fields in the matter multiplet vanishes. Thus logarithmic corrections to the entropy of quarter BPS black holes, if present, must be independent of the number of matter multiplet fields in the theory. This is consistent with the microscopic results. During our analysis we also determine the complete spectrum of small fluctuations of matter multiplet fields in the near horizon geometry.Comment: LaTeX file, 52 pages; v2: minor corrections, references adde
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