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.     

Densification mechanism during reactive hot pressing of B4C-ZrO2 mixtures

The densification behaviors of pure B₄C and B₄C-ZrO₂ mixtures were compared during hot pressing. The results showed that in-situ formed ZrB₂ effectively enhanced the densification process of B₄C-ZrO₂ mixtures, more significantly during the intermediate stage. Within the relative density ranging from 0.75 to 0.90, the B₄C-15?wt%ZrO₂ mixture (B15Z) achieved the maximum densification rate as twice much as that of pure B₄C. The stress exponent n>3 indicated plastic deformation was the dominant densification mechanism of B15Z. The viscosities of plastic flow were evaluated using Murray-Rodger-William equation and the viscosity of B15Z was only a quarter of that in pure B₄C. The sintering activation energy was calculated to be 305.9?kJ/mol for pure B₄C and 197?kJ/mol for B15Z, respectively. It was proposed that the lower viscosity of plastic flow and activation energy accelerated the sliding and propagating motions of plastic flow, by which underlain the enhanced densification behaviors of B₄C-ZrO₂ mixtures.     

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.     

Modeling Impact of ROADM Intra-Node Add/Drop Contention on a Single Node Lightpath Blocking Performance

We propose an analytical model to evaluate the lightpath blocking performance for a single ROADM node with intra-node add/drop contention,in which the number of lightpaths that can be added/dropped with the same wavelength is limited by the add/drop contention factor.Different models of traffic load per nodal degree are considered to validate the effectiveness of the analytical model.The simulation results show that the proposed analytical model is effective in predicting the performance for different values of add/drop contention factor C and for variable offered loads at the node.The add/drop contention factor shows an important impact on the lightpath blocking performance and properly raising the contention factor can significantly improve the lightpath blocking performance.When the add/drop contention factor C exceeds a certain level,the performance of a ROADM with intra-node contention is close to that of a contentionless ROADM.     

酸碱理论及其在有机反应中的应用研究

酸碱反应无论是在无机化学还是有机化学中,都占有极高的地位,文章以综述的形式讨论酸碱理论及其在一些重要的有机反应中应用研究。     

汽车空调的操作和应用分析

2013年国内汽车产销量超过2000万台,汽车正在快速进入中国的千家万户,但大部分车主还缺乏对汽车空调知识的了解,夏天又是空调故障多发期,如果车主了解相关汽车空调知识,在实际应用中会达到事倍功半的效果,因此介绍了一般车型的空调结构、工作原理以及特殊气候下的调节。     

BIM技术在大型项目上的应用——以连云港民用机场迁建工程旅客过夜用房酒店为例

在国家政策和市场需求的双重推动下,BIM技术在国内建筑领域迎来快速发展阶段,从最初的概念普及,到能够局部应用,再到现在能够全过程应用,其趋势是十分明确的,但是在其发展的过程中仍然存在着不少问题,如传统技术与BIM技术深入融合问题,BIM技术如何解决工程施工现场实际问题等.本文主要研究BIM技术在连云港民用机场迁建工程旅客过夜用房酒店项目中的综合应用,从协同建模、碰撞检查、管线综合、施工图深化出图及漫游展示等方面着手,着重解决BIM技术在施工过程中应用的落地问题,从而达到提高效率,缩短工期,降低成本,提升质量的目标.     

Analysis of the ionospheric variability based on wavelet decomposition

In this work,the ionospheric variability is analyzed by applying the wavelet decomposition technique to the noontime fo F2,F10.7,interplanetary magnetic field(IMF)Bz,Ap,and lower thermospheric temperature at pressure of 10?4 h Pa in 2002.Results show that the variance of periodic oscillations in the ionosphere is largest in the 2–4-day period and declines with the increase of the period.The maximum variance of the periodic oscillations in solar irradiation is in the 16–32-day period.For geomagnetic activities,most of the variance is about equally distributed on intervals of periods shorter than 32 days.Variance distributions of IMF Bz and lower thermospheric temperature are similar to those of the ionosphere.They show the maximum in the 2–4-day period and decline with the increase of the period.By analyzing the distributions of the variances,the potential connections between the ionosphere and the external sources are discussed.