187 research outputs found

    Giant tunnel-electron injection in nitrogen-doped graphene

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    International audienceScanning tunneling microscopy experiments have been performed to measure the local electron injection in nitrogen-doped graphene on SiC(000¯1) and were successfully compared to ab initio calculations. In graphene, a gaplike feature is measured around the Fermi level due to a phonon-mediated tunneling channel. At nitrogen sites, this feature vanishes due to an increase of the elastic channel that is allowed because of symmetry breaking induced by the nitrogen atoms. A large conductance enhancement by a factor of up to 500 was measured at the Fermi level by comparing local spectroscopy at nitrogen sites and at carbon sites. Nitrogen doping can therefore be proposed as a way to improve tunnel-electron injection in graphene

    MethCORR Modelling of Methylomes From Formalin-Fixed Paraffin-Embedded Tissue Enables Characterization and Prognostication of Colorectal Cancer

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    Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their methylation profiles. MethCORR is here applied to methylation profiles from 877 fresh-frozen/FFPE samples and comparative analysis identifies the same two subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicts relapse-free survival (HR = 2.66, 95%CI [1.67-4.22], P value < 0.001 (log-rank test)) than UICC tumor, node, metastasis (TNM) staging and microsatellite instability status are identified and validated using DNA methylation-specific PCR. The MethCORR approach is general, and may be similarly successful for other cancer types

    Aldebaran b's temperate past uncovered in planet search data

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    The nearby red giant Aldebaran is known to host a gas giant planetary companion from decades of ground-based spectroscopic radial velocity measurements. Using Gaussian Process-based Continuous Auto-Regressive Moving Average (CARMA) models, we show that these historic data also contain evidence of acoustic oscillations in the star itself, and verify this result with further dedicated ground-based spectroscopy and space-based photometry with the Kepler Space Telescope. From the frequency of these oscillations we determine the mass of Aldebaran to be 1.16±0.07M1.16 \pm 0.07 \, M_\odot, and note that this implies its planet will have been subject to insolation comparable to the Earth for some of the star's main sequence lifetime. Our approach to sparse, irregularly sampled time series astronomical observations has the potential to unlock asteroseismic measurements for thousands of stars in archival data, and push to lower-mass planets around red giant stars.Comment: 24 pages, 7 figures (including appendices); submitted to ApJL; paper text, figures, data, and code at https://github.com/farr/Aldebara

    Characterization of the LM5 pectic galactan epitope with synthetic analogues of β-1,4-d-galactotetraose

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    Plant cell wall glycans are important polymers that are crucial to plant development and serve as an important source of sustainable biomass. The study of polysaccharides in the plant cell wall relies heavily on monoclonal antibodies for localization and visualization of glycans, using e.g. Immunofluorescent microscopy. Here, we describe the detailed epitope mapping of the mab LM5 that is shown to bind to a minimum of three sugar residues at the non-reducing end of linear beta-1,4-linked galactan. The study uses de novo synthetic analogs of galactans combined with carbohydrate microarray and competitive inhibition ELISA for analysis of antibody-carbohydrate interactions

    Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis

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    <p>Abstract</p> <p>Background</p> <p>Approximately half of all human genes use alternative transcription start sites (TSSs) to control mRNA levels and broaden the transcriptional output in healthy tissues. Aberrant expression patterns promoting carcinogenesis, however, may arise from alternative promoter usage.</p> <p>Results</p> <p>By profiling 108 colorectal samples using exon arrays, we identified nine genes (<it>TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5</it>, and <it>SCIN</it>) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for <it>CHEK1, OSBPL1A</it>, and <it>TCF12 </it>in a subset of these cancer types.</p> <p>To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both <it>OSBPL1A </it>and <it>TRAK1</it>. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples.</p> <p>Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.</p> <p>Conclusions</p> <p>Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and <it>OSBPL1A </it>and <it>TRAK1 </it>were found to be regulated <it>in vitro </it>by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.</p
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