A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

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.     

电磁精细探测法在隐伏型导水地质裂缝勘探中的应用

针对传统隐伏型导水地质裂缝勘探方法存在勘测精度较差的问题,提出电磁精细探测法探析隐伏型导水地质裂缝。依照屏蔽系数、实测场强和理论场强数据绘制综合曲线图,通过该图获取隐伏型导水地质裂缝所处位置几何阴影范围,采用层析成像法得到网格化的工作面,获取隐伏型导水地质图像。通过图像直接观测隐伏型导水地质工作面裂缝所处位置,在此基础上,观测四个电磁场分量,采用正交电磁场分量计算介质视电阻率,依据计算视电阻率数值和视电阻率分布状态研究裂缝发育情况和裂缝富水程度。结果表明:采用该方法能较为精准地获取隐伏型导水地质裂缝位置。通过裂缝位置进一步检测出隐伏型导水地质裂缝最大发育高度为63.5 m。当视电阻数值不断增加时,隐伏型导水地质裂缝和裂缝富水性逐渐减小,与实际情况较为相符,说明该种方法探析效果较好。     

Three‐dimensional color prediction modeling of single‐ and double‐layered woven fabrics

In this research, the three‐dimensional structural and colorimetric modeling of three‐dimensional woven fabrics was conducted for accurate color predictions. One‐hundred forty single‐ and double‐layered woven samples in a wide range of colors were produced. With the consideration of their three‐dimensional structural parameters, three‐dimensional color prediction models, K/S‐, R‐, and L*a*b*‐based models, were developed through the optimization of previous two‐dimensional models which have been reported to be the three most accurate models for single‐layered woven structures. The accuracy of the new three‐dimensional models was evaluated by calculating the color differences ΔL*, ΔC*, Δh°, and ΔE_CMC(2:1) between the measured and the predicted colors of the samples, and then the error values were compared to those of the two‐dimensional models. As a result, there has been an overall improvement in color predictions of all models with a decrease in ΔE_CMC(2:1) from 10.30 to 5.25 units on average after the three‐dimensional modeling.     

Ferroelastic domain structure and phase transition in single-crystalline [PbZn1/3Nb2/3O3]1-x[PbTiO3]x observed via in situ x-ray microbeam

(1-x)Pb(Zn_1/3Nb_2/3)O₃-xPbTiO₃ ((1-x)PZN-xPT in short) is one of the most important piezoelectric materials. In this work, we extensively investigated (1-x)PZN-xPT (x = 0.07–0.11) ferroelectric single crystals using in-situ synchrotron μXRD, complemented by TEM and PFM, to correlate microstructures with phase transitions. The results reveal that (i) at 25 °C, the equilibrium state of (1-x)PZN-xPT is a metastable orthorhombic phase for x = 0.07 and 0.08, while it shows coexistence of orthorhombic and tetragonal phases for x = 0.09 and x = 0.11, with all ferroelectric phases accompanied by ferroelastic domains; (ii) upon heating, the phase transformation in x = 0.07 is Orthorhombic → Monoclinic → Tetragonal → Cubic. The coexistence of ferroelectric tetragonal and paraelectric cubic phases was in-situ observed in x = 0.08 above Curie temperature (T_C), and (iii) phase transition can be explained by the evolution of the ferroelectric and ferroelastic domains. These results disclose that (1-x)PZN-xPT are in an unstable regime, which is possible factor for its anomalous dielectric response and high piezoelectric coefficient.     

On stochastic comparisons of finite mixtures for some semiparametric families of distributions

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.     

Is the List of Incomplete Open Cubes Complete?

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.