1,144 research outputs found

    The expression of RUNX3 in colorectal cancer is associated with disease stage and patient outcome

    Get PDF
    RUNX3 is believed to have tumour suppressor properties in several cancer types. Inactivation of RUNX3 has been shown to occur by methylation-induced transcriptional silencing and by mislocalization of the protein to the cytoplasm. The aim of this study was to examine the clinical significance of RUNX3 expression in a large series of colorectal cancers using immunohistochemistry and tissue arrays. With advancing tumour stage, expression of RUNX3 in the nucleus decreased, whereas expression restricted to the cytoplasmic compartment increased. Nuclear RUNX3 expression was associated with significantly better patient survival compared to tumours in which the expression of RUNX3 was restricted to the cytoplasm (P=0.025). These results support a role for RUNX3 as a tumour suppressor in colorectal cancer

    Evidence of High Harmonics from Echo-Enabled Harmonic Generation for Seeding X-Ray Free Electron Lasers

    Get PDF
    Echo-enabled harmonic generation free electron lasers hold great promise for the generation of fully coherent radiation in x-ray wavelengths. Here we report the first evidence of high harmonics from the echo-enabled harmonic generation technique in the realistic scenario where the laser energy modulation is comparable to the beam slice energy spread. In this experiment, coherent radiation at the seventh harmonic of the second seed laser is generated when the energy modulation amplitude is about 2-3 times the slice energy spread. The experiment confirms the underlying physics of echo-enabled harmonic generation and may have a strong impact on emerging seeded x-ray free electron lasers that are capable of generating laserlike x rays which will advance many areas of science

    Macroscopic transport by synthetic molecular machines

    Get PDF
    Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with—and perform physical tasks in—the macroscopic world represents a significant hurdle for molecular nanotechnology. Here we describe a wholly synthetic molecular system that converts an external energy source (light) into biased brownian motion to transport a macroscopic cargo and do measurable work. The millimetre-scale directional transport of a liquid on a surface is achieved by using the biased brownian motion of stimuli-responsive rotaxanes (‘molecular shuttles’) to expose or conceal fluoroalkane residues and thereby modify surface tension. The collective operation of a monolayer of the molecular shuttles is sufficient to power the movement of a microlitre droplet of diiodomethane up a twelve-degree incline.

    Measurement of the Transverse-Longitudinal Cross Sections in the p (e,e'p)pi0 Reaction in the Delta Region

    Get PDF
    Accurate measurements of the p(e,e?p)pi0 reaction were performed at Q^2=0.127(GeV/c)^2 in the Delta resonance energy region. The experiments at the MIT-Bates Linear Accelerator used an 820 MeV polarized electron beam with the out of plane magnetic spectrometer system (OOPS). In this paper we report the first simultaneous determination of both the TL and TL? (``fifth" or polarized) cross sections at low Q^{2} where the pion cloud contribution dominates the quadrupole amplitudes (E2 and C2). The real and imaginary parts of the transverse-longitudinal cross section provide both a sensitive determination of the Coulomb quadrupole amplitude and a test of reaction calculations. Comparisons with model calculations are presented. The empirical MAID calculation gives the best overall agreement with this accurate data. The parameters of this model for the values of the resonant multipoles are |M_{1+}(I=3/2)|= (40.9 \pm 0.3)10^{-3}/m_pi, CMR= C2/M1= -6.5 \pm 0.3%, EMR=E2/M1=-2.2 \pm 0.9%, where the errors are due to the experimental uncertainties.Comment: 10 pages, 3 figures, minor corrections and addition

    Relativistic effects and two-body currents in 2H(e,ep)n^{2}H(\vec{e},e^{\prime}p)n using out-of-plane detection

    Full text link
    Measurements of the 2H(e,ep)n{^2}H(\vec{e},e^{\prime}p)n reaction were performed using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator and with the out-of-plane magnetic spectrometers (OOPS). The longitudinal-transverse, fLTf_{LT} and fLTf_{LT}^{\prime}, and the transverse-transverse, fTTf_{TT}, interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q2^2=0.15 (GeV/c)2^2. On comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions, and the importance of the two-body meson-exchange currents and isobar configurations. We demonstrate that these effects can be disentangled and studied by extracting the interference response functions using the novel out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio

    Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer

    Get PDF
    Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series
    corecore