β-catenin activation down-regulates cell-cell junction-related genes and induces epithelial-to-mesenchymal transition in colorectal cancers

WNT signaling activation in colorectal cancers (CRCs) occurs through APC inactivation or β-catenin mutations. Both processes promote β-catenin nuclear accumulation, which up-regulates epithelial-to-mesenchymal transition (EMT). We investigated β-catenin localization, transcriptome, and phenotypic differences of HCT116 cells containing a wild-type (HCT116-WT) or mutant β-catenin allele (HCT116-MT), or parental cells with both WT and mutant alleles (HCT116-P). We then analyzed β-catenin expression and associated phenotypes in CRC tissues. Wild-type β-catenin showed membranous localization, whereas mutant showed nuclear localization; both nuclear and non-nuclear localization were observed in HCT116-P. Microarray analysis revealed down-regulation of Claudin-7 and E-cadherin in HCT116-MT vs. HCT116-WT. Claudin-7 was also down-regulated in HCT116-P vs. HCT116-WT without E-cadherin dysregulation. We found that ZEB1 is a critical EMT factor for mutant β-catenin-mediated loss of E-cadherin and Claudin-7 in HCT116-P and HCT116-MT cells. We also demonstrated that E-cadherin binds to both WT and mutant β-catenin, and loss of E-cadherin releases β-catenin from the cell membrane and leads to its degradation. Alteration of Claudin-7, as well as both Claudin-7 and E-cadherin respectively caused tight junction (TJ) impairment in HCT116-P, and dual loss of TJs and adherens junctions (AJs) in HCT116-MT. TJ loss increased cell motility, and subsequent AJ loss further up-regulated that. Immunohistochemistry analysis of 101 CRCs revealed high (14.9%), low (52.5%), and undetectable (32.6%) β-catenin nuclear expression, and high β-catenin nuclear expression was significantly correlated with overall survival of CRC patients (P = 0.009). Our findings suggest that β-catenin activation induces EMT progression by modifying cell-cell junctions, and thereby contributes to CRC aggressiveness

Drift-compensated low-noise frequency synthesis based on a cryoCSO for the KRISS-F1

Date of publication November 8, 2016; date of current version May 10, 2017.In this paper, we report on the implementation and stability analysis of a drift-compensated frequency synthesizer from a cryogenic sapphire oscillator (CSO) designed for a Cs/Rb atomic fountain clock. The synthesizer has two microwave outputs of 7 and 9 GHz for Rb and Cs atom interrogation, respectively. The short-term stability of these microwave signals, measured using an optical frequency comb locked to an ultrastable laser, is better than 5×10−15 at an averaging time of 1 s. We demonstrate that the short-term stability of the synthesizer is lower than the quantum projection noise limit of the Cs fountain clock, KRISS-F1(Cs) by measuring the short-term stability of the fountain with varying trapped atom number. The stability of the atomic fountain at 1 s averaging time reaches 2.5×10−14 at the highest atom number in the experiment when the synthesizer is used as an interrogation oscillator of the fountain. In order to compensate the frequency drift of the CSO, the output frequency of a waveform generator, in the synthesis chain, is ramped linearly. By doing this, the frequency stability of the synthesizer at an average time of one hour reaches a level of 10−16, which is measured with the fountain clock.Myoung-Sun Heo, Sang Eon Park, Won-Kyu Lee, Sang-Bum Lee, Hyun-Gue Hong, Taeg Yong Kwon, Chang Yong Park, Dai-Hyuk Yu, Giorgio Santarelli, Ashby Paul Hilton, Andre Nicholas Luiten, and John Gideon Hartnet

J/psi suppression at forward rapidity in Au+Au collisions at sqrt(s_NN)=39 and 62.4 GeV

We present measurements of the J/psi invariant yields in sqrt(s_NN)=39 and 62.4 GeV Au+Au collisions at forward rapidity (1.2<|y|<2.2). Invariant yields are presented as a function of both collision centrality and transverse momentum. Nuclear modifications are obtained for central relative to peripheral Au+Au collisions (R_CP) and for various centrality selections in Au+Au relative to scaled p+p cross sections obtained from other measurements (R_AA). The observed suppression patterns at 39 and 62.4 GeV are quite similar to those previously measured at 200 GeV. This similar suppression presents a challenge to theoretical models that contain various competing mechanisms with different energy dependencies, some of which cause suppression and others enhancement.Comment: 365 authors, 10 pages, 11 figures, 4 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Measurement of higher cumulants of net-charge multiplicity distributions in Au++Au collisions at sNN=7.7−200\sqrt{s_{_{NN}}}=7.7-200 GeV

We report the measurement of cumulants ($C_n, n=1\ldots4$) of the net-charge distributions measured within pseudorapidity ($|\eta|<0.35$) in Au$+$Au collisions at $\sqrt{s_{_{NN}}}=7.7-200$ GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g. $C_1/C_2$, $C_3/C_1$) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of $C_1/C_2 = \mu/\sigma^2$ and $C_3/C_1 = S\sigma^3/\mu$ can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy.Comment: 512 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. C as a Rapid Communication. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

L\'evy-stable two-pion Bose-Einstein correlations in sNN=200\sqrt{s_{_{NN}}}=200 GeV Au++Au collisions

We present a detailed measurement of charged two-pion correlation functions in 0%-30% centrality $\sqrt{s_{_{NN}}}=200$ GeV Au$+$Au collisions by the PHENIX experiment at the Relativistic Heavy Ion Collider. The data are well described by Bose-Einstein correlation functions stemming from L\'evy-stable source distributions. Using a fine transverse momentum binning, we extract the correlation strength parameter $\lambda$, the L\'evy index of stability $\alpha$ and the L\'evy length scale parameter $R$ as a function of average transverse mass of the pair $m_T$. We find that the positively and the negatively charged pion pairs yield consistent results, and their correlation functions are represented, within uncertainties, by the same L\'evy-stable source functions. The $\lambda(m_T)$ measurements indicate a decrease of the strength of the correlations at low $m_T$. The L\'evy length scale parameter $R(m_T)$ decreases with increasing $m_T$, following a hydrodynamically predicted type of scaling behavior. The values of the L\'evy index of stability $\alpha$ are found to be significantly lower than the Gaussian case of $\alpha=2$, but also significantly larger than the conjectured value that may characterize the critical point of a second-order quark-hadron phase transition.Comment: 448 authors, 25 pages, 11 figures, 4 tables, 2010 data. v2 is version accepted for publication in Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Medium modification of jet fragmentation in Au+Au collisions at sqrt(s_NN)=200 GeV measured in direct photon-hadron correlations

The jet fragmentation function is measured with direct photon-hadron correlations in p+p and Au+Au collisions at sqrt(s_NN)=200 GeV. The p_T of the photon is an excellent approximation to the initial p_T of the jet and the ratio z_T=p_T^h/p_T^\gamma is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au+Au collisions while a photon isolation cut is applied in p+p. I_ AA, the ratio of jet fragment yield in Au+Au to that in p+p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high z_T. The fragment yield at low z_T is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.Comment: 562 authors, 70 insitutions, 8 pages, and 3 figures. Submitted to Phys. Rev. Lett. v2 has minor changes to improve clarity. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm