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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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中间包上水口环形吹氩可以在塞棒周围形成清洗钢液的环形气幕,同时部分氩气泡随钢液进入上水口内,可以减少非金属夹杂物在水口内壁的黏附,起到防止水口堵塞的作用。然而,不合理的吹氩量会导致中间包内液面渣层受过强的气液羽流冲击而形成渣眼,使得钢液裸露并发生二次氧化,严重影响铸坯质量。采用标准 k ε 湍流模型研究中间包内流体流动,采用DPM模型和VOF模型耦合方法,研究上水口环形吹氩条件下渣眼的形成及演化规律。结果表明,上水口环形吹氩在塞棒周围形成较强的上升流,塞棒上部邻近区域存在多个涡流区;在钢液涡流的影响下,中间包液渣下层远离塞棒区域,上层向塞棒区域迁移;随着吹氩量的增大,平均湍动能增大,塞棒附近钢液速度逐渐增大,钢渣界面钢液速度先增大后减小,渣眼边缘钢液速度先增大后减小然后再增大,速度与垂直方向夹角逐渐减小;增大吹氩量,中间包熔池液面形成以塞棒为中心的渣眼,渣眼面积逐渐增大。试验条件下不产生渣眼的临界吹氩量为4.2 L/min,对应的钢渣界面最大速度为0.247 m/s,与垂直方向夹角为70°。 相似文献
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Qianglong He Aiyang Wang Chun Liu Weimin Wang Hao Wang Zhengyi Fu 《Journal of the European Ceramic Society》2018,38(7):2832-2840
B4C-TiB2-SiC composites were fabricated via hot pressing using ball milled B4C, TiB2, and SiC powder mixtures as the starting materials. The impact of ball milling on the densification behaviors, mechanical properties, and microstructures of the ceramic composites were investigated. The results showed that the refinement of the powder mixtures and the removal of the oxide impurities played an important role in the improvement of densification and properties. Moreover, the formation of the liquid phases during the sintering was deemed beneficial for densification. The typical values of relative density, hardness, bending strength, and fracture toughness of the composites reached 99.20%, 32.84?GPa, 858?MPa and 8.21?MPa?m1/2, respectively. Crack deflection, crack bridging, crack branching, and microcracking were considered to be the potential toughening mechanisms in the composites. Furthermore, numerous nano-sized intergranular/intragranular phases and twin structures were observed in the B4C-TiB2-SiC composite. 相似文献
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Chun Dong Hyun Rhim Geun Bae Youn Min Hye Deviana Deviana Lee Ji Eun Park Ji Chan Jeong Heondo 《Topics in Catalysis》2020,63(9-10):793-809
Topics in Catalysis - Fischer–Tropsch synthesis (FTS) is a promising way to produce clean liquid fuels and high value-added chemicals from low-value carbon-containing resources such as coal,... 相似文献
18.
Timothy Zurrer Kenneth Wong Jonathan Horlyck Emma C. Lovell Joshua Wright Nicholas M. Bedford Zhaojun Han Kang Liang Jason Scott Rose Amal 《Advanced functional materials》2021,31(9):2007624
The vast chemical and structural tunability of metal–organic frameworks (MOFs) are beginning to be harnessed as functional supports for catalytic nanoparticles spanning a range of applications. However, a lack of straightforward methods for producing nanoparticle-encapsulated MOFs as efficient heterogeneous catalysts limits their usage. Herein, a mixed-metal MOF, NiMg-MOF-74, is utilized as a template to disperse small Ni nanoclusters throughout the parent MOF. By exploiting the difference in Ni O and Mg O coordination bond strength, Ni2+ is selectively reduced to form highly dispersed Ni nanoclusters constrained by the parent MOF pore diameter, while Mg2+ remains coordinated in the framework. By varying the ratio of Ni to Mg in the parent MOF, accessible surface area and crystallinity can be tuned upon thermal treatment, influencing CO2 adsorption capacity and hydrogenation selectivity. The resulting Ni nanoclusters prove to be an active catalyst for CO2 methanation and are examined using extended X-ray absorption fine structure and X-ray photoelectron spectroscopy. By preserving a segment of the Mg2+-containing MOF framework, the composite system retains a portion of its CO2 adsorption capacity while continuing to deliver catalytic activity. The approach is thus critical for designing materials that can bridge the gap between carbon capture and CO2 utilization. 相似文献
19.
Koay Seong Chun Chan Ming Yeng Chou Pui May Tshai Kim Yeow Ong Thai Kiat Cheah Kean How 《乙烯基与添加剂工艺杂志》2020,26(1):10-16
Chrysanthemum flower is among one of the highly sought after and widely planted flower crops, in particular for cultural and religious ceremonies. However, the chrysanthemum stem and stalk have little value and usually discard as by‐product waste from floristry. The objective of this research is to investigate the potential value of utilizing chrysanthemum stem and stalk as reinforcing fillers for thermoplastic composites. In this study, 2‐mm thick composite sheet containing predefined formulations of polylactic acid (PLA), chrysanthemum waste filler (CWF) ranging from 15 to 60 phr, and maleated polyethylene (MAPE) coupling agent up to 5 phr were prepared with the aid of Haake internal mixer and compression molding. The effect of MAPE loading on tensile, thermal, and morphological properties of PLA/CWF composites was investigated. The findings revealed that PLA/CWF composite attained improved tensile modulus compared to the neat PLA, and the tensile modulus increases with higher concentration of CWF. However, both tensile strength and elongation at break reduces with increase loading of CWF. Overall, PLA/CWF composites with MAPE shows better performance compared to those without MAPE, where an optimum strength of 21.8 MPa can be achieved with 60 phr CW and 3 phr MAPE. The measured tensile strength is comparable to alternatives natural fiber thermoplastic composites demonstrating its potential to be used in non‐structurally demanding application. J. VINYL ADDIT. TECHNOL., 26:10–16, 2020. © 2019 Society of Plastics Engineers 相似文献
20.
Inam Ridha Ali Basiri Sudhakar Godeshala Md Zubair Ebne Rafique Deepanjan Ghosh Jason Williams Nikhilesh Chawla Jung Keun Lee Jacquelyn Kilbourne Yu Yao Kaushal Rege 《Advanced functional materials》2021,31(6):2007811
Poor strength, infection, leakage, long procedure times, and inflammation limit the efficacy of common tissue sealing devices in surgeries and trauma. Light-activated sealing is attractive for tissue sealing and repair, and can be facilitated by the generation of local heat following absorption of nonionizing laser energy by chromophores. Here, the inherent ability of biomaterials is exploited to absorb nonionizing, mid-infrared (midIR) light in order to engender rapid photothermal sealing and repair of soft tissue wounds. In this approach, the biomaterial simultaneously acts as a photothermal convertor as well as a biosealant, which dispenses the need for exogeneous light-absorbing nanoparticles or dyes. Biomechanical recovery, mathematical modeling, histopathology analyses, tissue strain mapping using digital imaging correlation, and visualization of the biosealant-tissue interface using hyperspectral imaging indicate superior performance of midIR sealing in live mice compared to conventional sutures and glue. The midIR-biosealant approach demonstrates rapid sealing of soft tissues, improves cosmesis, lowers potential for scarring, obviates safety concerns because of the nonionizing light used, and allows adoption of a wide diversity of biomaterials. Taken together, the studies demonstrate a novel advance both in biomaterials for surgical sealing along with the use of nonionizing midIR light, with high potential for clinical translation. 相似文献