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61.
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
62.
Yan Xiong Xianwu Du Mingyu Xiang Hao Wang Weimin Wang Zhengyi Fu 《Journal of the European Ceramic Society》2018,38(12):4167-4172
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. 相似文献
63.
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. 相似文献
64.
Baizhan Li Chenqiu Du Hong Liu Wei Yu Jie Zheng Meilan Tan Zhenxing Jin Wenjie Li Jing Wu Lu Chen Runming Yao 《Indoor air》2019,29(2):308-319
The extensive research interests in environmental temperature can be linked to human productivity / performance as well as comfort and health; while the mechanisms of physiological indices responding to temperature variations remain incompletely understood. This study adopted a physiological sensory nerve conduction velocity (SCV) as a temperature‐sensitive biomarker to explore the thermoregulatory mechanisms of human responding to annual temperatures. The measurements of subjects’ SCV (over 600 samples) were conducted in a naturally ventilated environment over all four seasons. The results showed a positive correlation between SCV and annual temperatures and a Boltzmann model was adopted to depict the S‐shaped trend of SCV with operative temperatures from 5°C to 40°C. The SCV increased linearly with operative temperatures from 14.28°C to 20.5°C and responded sensitively for 10.19°C‐24.59°C, while tended to be stable beyond that. The subjects’ thermal sensations were linearly related to SCV, elaborating the relation between human physiological regulations and subjective thermal perception variations. The findings reveal the body SCV regulatory characteristics in different operative temperature intervals, thereby giving a deeper insight into human autonomic thermoregulation and benefiting for built environment designs, meantime minimizing the temperature‐invoked risks to human health and well‐being. 相似文献
65.
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. 相似文献
66.
67.
M1080B无心外圆磨床砂轮及导轮宽度较窄,磨削轴承套圈外圆时,磨削效率低,托板架调整较为繁琐、皮带打滑、磨损较为严重。针对上述问题,提出了相应的解决办法,提高了磨削效率。 相似文献
68.
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. 相似文献
69.
70.
Hao Li Pengcheng Zhang Shengquan Yu Hongyu Yang Bin Tang Fuhai Li Shuren Zhang 《Ceramics International》2019,45(9):11639-11647
Mg2(Ti1-xSnx)O4 (x?=?0–1) ceramics were prepared through conventional solid-state method. This paper focused on the dependence of microwave dielectric properties on crystal structural characteristics via crystal structure refinement, Raman spectra study and complex chemical bond theory. XRD spectrums delineated the phase information of a spinel structure, and structural characteristic of these compositions were achieved with the help of Rietveld refinements. Raman spectrums were used to depict the correlations between vibrational phonon modes and dielectric properties. The variation of permittivity is ascribed to the Mg2(Ti1-xSnx)O4 average bond covalency. The relationship among the B-site octahedral bond energy, tetrahedral bond energy and temperature coefficient are discussed by defining on the change rate of bond energy and the contribution rate of octahedral bond energy. The quality factor is affected by systematic total lattice energy, and the research of XPS patterns illustrated that oxygen vacancies can be effectively restrained in rich oxygen sintering process. Obviously, the microwave dielectric properties of Mg2(Ti1-xSnx)O4 compounds were obtained (= 12.18, ?=?170,130?GHz, ?=??53.1?ppm/°C, x?=?0.2). 相似文献