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41.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
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Anna Enrico Wenjing Zhang Marie Lund Traulsen Elena Marzia Sala Paola Costamagna Peter Holtappels 《Journal of the European Ceramic Society》2018,38(7):2677-2686
Water-based sol-gel electrospinning is employed to manufacture perovskite oxide La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) nanofiber cathodes for intermediate-temperature solid oxide fuel cells. LSCF fibrous scaffolds are synthesized through electrospinning of a sol-gel solution employing water as the only solvent. Morphological characterizations demonstrate that the LSCF fibers have highly crystalline structure with uniform elemental distribution. After heat treatment, the average fiber diameter is 250 nm and the porosity of the nanofiber tissue is 37.5 %. The heat treated LSCF nanofibers are applied directly onto a Ce0.9Gd0.1O1.95 (CGO) electrolyte disk to form a symmetrical cell. Electrochemical characterization is carried out through electrochemical impedance spectroscopy (EIS) in the temperature range 550?°C–950?°C, and reproducibility of the electrochemical performance for a series of cells is demonstrated. At 650?°C, the average measured polarization resistance Rp is 1.0 Ω cm2. Measured performance decay is 1 % during the first 33?h of operation at 750?°C, followed by an additional 0.7 % over the subsequent 70?h. 相似文献
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Ugur Gezer Ebru E. Y?rüker Metin Keskin Cemil Burak Kulle Yoganiranjana Dharuman Stefan Holdenrieder 《International journal of molecular sciences》2015,16(12):29654-29662
Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination. 相似文献
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Iryna Smokovych Manja Krüger Michael Scheffler 《Journal of the European Ceramic Society》2019,39(13):3634-3642
Silica-based coating systems were developed using polymer derived ceramics (PDCs) technology. Ceramic composites on the base of a SiO2 and SiNO matrix and homogeneously distributed Mo5SiB2, SiB6, Si and B fillers were manufactured. The coating systems have low porosity and provide a high oxidation resistance up to 100 h at 800 °C and 1100 °C in air. The influence of temperature and atmosphere of pyrolysis on the polymer precursor, the volume fraction of filler materials on the chemical composition of compacts as well as their high-temperature oxidation protection was investigated. 相似文献
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Multibody System Dynamics - A recently developed index reduction method is applied to comparatively complicated underactuated mechanical systems in the context of inverse dynamics. The inverse... 相似文献