HIF-1α Contributes to Hypoxia-induced Invasion and Metastasis of Esophageal Carcinoma via Inhibiting E-cadherin and Promoting MMP-2 Expression

Hypoxia-inducible factor-1α (HIF-1α) has been found to enhance tumor invasion and metastasis, but no study has reported its action in esophageal carcinoma. The goal of this study was to explore the probable mechanism of HIF-1α in the invasion and metastasis of esophageal carcinoma Eca109 cells in vitro and in vivo. mRNA and protein expression of HIF-1α, E-cadherin and matrix metalloproteinase-2 (MMP-2) under hypoxia were detected by RT-PCR and Western blotting. The effects of silencing HIF-1α on E-cadherin, MMP-2 mRNA and protein expression under hypoxia or normoxia were detected by RT-PCR and Western blotting, respectively. The invasive ability of Eca109 cells was tested using a transwell chambers. We established an Eca109-implanted tumor model and observed tumor growth and lymph node metastasis. The expression of HIF-1α, E-cadherin and MMP-2 in xenograft tumors was detected by Western blotting. After exposure to hypoxia, HIF-1α protein was up-regulated, both mRNA and protein levels of E-cadherin were down-regulated and MMP-2 was up-regulated, while HIF-1α mRNA showed no significant change. SiRNA could block HIF-1α effectively, increase E-cadherin expression and inhibit MMP-2 expression. The number of invading cells decreased after HIF-1α was silenced. Meanwhile, the tumor volume was much smaller, and the metastatic rate of lymph nodes and the positive rate were lower in vivo. Our observations suggest that HIF-1α inhibition might be an effective strategy to weaken invasion and metastasis in the esophageal carcinoma Eca109 cell line

Supermassive Black Holes with High Accretion Rates in Active Galactic Nuclei. IV. Hβ\beta Time Lags and Implications for Super-Eddington Accretion

We have completed two years of photometric and spectroscopic monitoring of a large number of active galactic nuclei (AGNs) with very high accretion rates. In this paper, we report on the result of the second phase of the campaign, during 2013--2014, and the measurements of five new H$\beta$ time lags out of eight monitored AGNs. All five objects were identified as super-Eddington accreting massive black holes (SEAMBHs). The highest measured accretion rates for the objects in this campaign are $\dot{\mathscr{M}}\gtrsim 200$, where $\dot{\mathscr{M}}= \dot{M}_{\bullet}/L_{\rm Edd}c^{-2}$, $\dot{M}_{\bullet}$ is the mass accretion rates, $L_{\rm Edd}$ is the Eddington luminosity and $c$ is the speed of light. We find that the H$\beta$ time lags in SEAMBHs are significantly shorter than those measured in sub-Eddington AGNs, and the deviations increase with increasing accretion rates. Thus, the relationship between broad-line region size ($R_{_{\rm H\beta}}$) and optical luminosity at 5100\AA, $R_{_{\rm H\beta}}-L_{5100}$, requires accretion rate as an additional parameter. We propose that much of the effect may be due to the strong anisotropy of the emitted slim-disk radiation. Scaling $R_{_{\rm H\beta}}$ by the gravitational radius of the black hole, we define a new radius-mass parameter ($Y$) and show that it saturates at a critical accretion rate of $\dot{\mathscr{M}}_c=6\sim 30$, indicating a transition from thin to slim accretion disk and a saturated luminosity of the slim disks. The parameter $Y$ is a very useful probe for understanding the various types of accretion onto massive black holes. We briefly comment on implications to the general population of super-Eddington AGNs in the universe and applications to cosmology.Comment: 53 pages, 12 figures, 7 tables, accepted for publication in The Astrophysical Journa

Noise Performance Comparison of 1.5 um Correlated Photon Pair Generation in Different Fibers

In this paper, the noise performances of 1.5 um correlated photon pair generations based on spontaneous four wave-mixing in three types of fibers, i.e., dispersion shifted fiber, highly nonlinear fiber, and highly nonlinear microstructure fiber are investigated experimentally. Result of the comparison shows that highly nonlinear microstructure fiber has the lowest Raman noise photon generation rate among the three types of fibers while correlated photon pair generation rate is the same. Theoretical analysis shows that the noise performance is determined by the nonlinear index and Raman response of the material in fiber core. The Raman response raises with increasing doping level, however, the nonlinear index is almost unchanged with it. As a result, highly nonlinear microstructure fiber with pure silica core has the best noise performance and has great potential in practical sources of correlated photon pairs and heralded single photons.Comment: 10 pages, 6 figure

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment

Transcriptomic analyses of regenerating adult feathers in chicken

Transcriptome Expression Data. Table of mapped reads to Galgal4 transcripts for all 15 data sets. FPKM (Fragments per kilobase of exon per million fragments mapped): normalized transcript abundance values for each gene in the indicated tissues. (CSV 1314 kb

A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure

Noise Performance Comparison of 1.5 um Correlated Photon Pair Generation in Different Fibers

In this paper, the noise performances of 1.5 um correlated photon pair generations based on spontaneous four wave-mixing in three types of fibers, i.e., dispersion shifted fiber, highly nonlinear fiber, and highly nonlinear microstructure fiber are investigated experimentally. Result of the comparison shows that highly nonlinear microstructure fiber has the lowest Raman noise photon generation rate among the three types of fibers while correlated photon pair generation rate is the same. Theoretical analysis shows that the noise performance is determined by the nonlinear index and Raman response of the material in fiber core. The Raman response raises with increasing doping level, however, the nonlinear index is almost unchanged with it. As a result, highly nonlinear microstructure fiber with pure silica core has the best noise performance and has great potential in practical sources of correlated photon pairs and heralded single photons.Comment: 10 pages, 6 figure