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111.
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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In this paper, we consider the classical finite mixture model, which is an effective tool for modeling lifetime distributions for random samples from heterogeneous populations. We discuss new results on stochastic comparison for two finite mixtures when each of them is drawn from one of the following semiparametric families, i.e., proportional hazards, accelerated lifetime and proportional reversed hazards. 相似文献
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Correlation between instrumental texture and colour quality attributes with sensory analysis of selected cheeses as affected by fat contents
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A. Półtorak J. Wyrwisz M. Moczkowska M. Marcinkowska‐Lesiak A. Stelmasiak U. Ulanicka M. Zalewska A. Wierzbicka Da‐Wen Sun 《International Journal of Food Science & Technology》2015,50(4):999-1008
This study evaluated several physical and sensory parameters of different types of cheese available in the Polish market. The measurements of textural properties were conducted in an Instron universal testing machine, while the colour properties of cheeses were measured using a Minolta chromameter. The chemical composition was determined by means of the near‐infrared spectroscopy (NIRs). Moreover, a trained sensory panel was invited to assess the cheese texture‐related properties. Generally, cheeses with reduced fat content were characterised by higher hardness, adhesiveness, cohesiveness and elasticity. Texture‐related parameters of cheese with canola oil were comparable to that of most of full‐fat cheeses. The correlation analysis between physical and sensory attributes related to cheese textural properties indicated the potential applications of TPA, shear and penetration tests (r = 0.766, r = 0.75 and r = 0.765, respectively) for the evaluation of sensory properties related to the hardness. Meanwhile, the elasticity of cheese obtained from sensory evaluation was strongly correlated with the elasticity determined from the shear test (r = 0.722) and moderately correlated with the elasticity from penetration test (r = 0.588), indicating a need to refine the method of penetration test. In addition, cheeses exhibited higher meltability during convection heating at 230 °C than microwave heating. The values of meltability for cheese with reduced fat content were lower than those of full‐fat cheese. 相似文献
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Variations of Incomplete Open Cubes is the major project by the twentieth-century conceptual artist Sol LeWitt. In this paper we interpret the enumerative component of the project as embeddings of graphs. This formulation permits use of an algorithm to check the completeness of the list of the structures produced by the artist. Our conclusion is that the artist found the correct number of structures (that is, 122), but that his list contains a mistake in the presentation of a pair of incomplete cubes, a discovery that appears not to have been noted before. 相似文献
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