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.     

Regulation of sensory nerve conduction velocity of human bodies responding to annual temperature variations in natural environments

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.     

上水口环形吹氩对中间包内渣眼形成的影响

 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°。     

Stick-Breaking Dependent Beta Processes with Variational Inference

Neural Processing Letters - The beta processes (BP) is a powerful nonparametric tool in feature learning, which is often used as the prior of Bernoulli process for choosing features from a feature...     

Study of MW-scale biogas-fed SOFC-WGS-TSA-PEMFC hybrid power technology as distributed energy system: Thermodynamic,exergetic and thermo-economic evaluation

Advanced biogas power generation technology has been attracting attentions, which contributes to the waste disposal and the mitigation of greenhouse gas emissions. This work proposes and models a novel biogas-fed hybrid power generation system consisting of solid oxide fuel cell, water gas shift reaction, thermal swing adsorption and proton exchange membrane fuel cell (SOFC-WGS-TSA-PEMFC). The thermodynamic, exergetic, and thermo-economic analyses of this hybrid system for power generation were conducted to comprehensively evaluate its performance. It was found that the novel biogas-fed hybrid system has a gross energy conversion efficiency of 68.63% and exergy efficiency of 65.36%, indicating high efficiency for this kind of hybrid power technology. The market sensitivity analysis showed that the hybrid system also has a low sensitivity to market price fluctuation. Under the current subsidy level for the distributed biogas power plant, the levelized cost of energy can be lowered to 0.02942 $/kWh for a 1 MW scale system. Accordingly, the payback period and annual return on investment can reach 1.4 year and about 20%, respectively. These results reveal that the proposed hybrid system is promising and economically feasible as a distributed power plant, especially for the small power scale (no more than 2 MW).