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.     

豫西雷门沟钼矿水文地质条件分析及涌水量预测

豫西熊耳山雷门沟钼矿床位于东秦岭多金属成矿带东段,是已探明的超大型斑岩型钼矿,前人研究程度高、地质成果丰硕,但对矿床开采技术条件方面研究较少。本次通过地质调查工程、水文地质试验等方法,从水文地质角度,对雷门沟钼矿床水文地质条件进行研究,填补了该方面的空白,丰富了研究成果；采用水文地质比拟法预测未来矿坑最大排水量2613 m³/d,经实践检验结果较为可靠；总结的采坑排水量预测方法、含水层特点、矿床充水因素以及防治水措施,以期对该区域水文地质工作具有参考价值。     

Thermoplastic and low dielectric constants polyimides based on BPADA-BAPP

ABSTRACT

The thermoplastic and low dielectric constants polyimides were introduced. The polyimides were prepared by pyromellitic dianhydride (PMDA) or 4,4?-(4,4?-Isopropylidenediphenoxy)diphthalic anhydride (BPADA) as anhydride monomer and 4,4?-oxydianiline (ODA) or 2,2-bis(4-(4-aminephenoxy)phenyl)propane (BAPP) as amine monomer. The polyimides were well characterized by FT-IR, thermogravimetric analysis, dynamic thermomechanical analysis, dielectric measurement, and tensile test. The dielectric constants were 2.32–2.95 compared with 3.10 of ODA-PMDA polyimide, while partly polyimides were thermoplastic. The results indicated anhydride monomers, containing lateral methyl groups, made polyimides become thermoplastic. The results of molecular simulations via Materials Studio also proved this conclusion.     

Preparation and electrochromism of pyrochlore-type tungsten oxide film

Pyrochlore-type WO_3 powder was synthesized via hydrothermal method using aqueous sodium tungstate solution and oxalic acid as raw materials. The as-prepared powder was made into a soliquoid,from which films were made by dip coating process with indium-tin oxide(ITO).The obtained films were characterized by thermogravimetric and differential thermal analysis(TG-DTA), X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM), cyclic voltammetry(CV), chronoamperometry(CA) and ultravioletvisible(UV-Vis) absorption. Results show that the crystal of the pyrochlore-type WO_3 powder is perfect. When the calcination temperature rises from room temperature to500 ℃,the pyrochlore-type structure first becomes deformed, then it is destroyed and turns into amorphous phase,finally it will completely convert to WO_3 with a monoclinic structure. Electrochemical and optical tests demonstrate that the film calcined at 300 ℃ exhibits the best electrochromic performance and has a coloration efficiency of up to 68.5 cm~2 C~(-1) at 884 nm.     

Synergistic flame retardant effects of activated carbon and molybdenum oxide in poly(vinyl chloride)

The synergistic effects of activated carbon (AC) and molybdenum oxide (MoO₃) in improving the flame retardancy of poly(vinyl chloride) (PVC) were investigated. The effects of AC, MoO₃ and their mixture with a mass ratio of 1:1 on the flame retardancy and smoke suppression properties of PVC were studied using the limiting oxygen index and cone calorimeter tests. It was found that the flame retardancy of the relatively cheaper AC was slightly weaker than that of MoO₃. In addition, the incorporation of AC and MoO₃ greatly reduced the total heat release and improved smoke suppressant property of PVC composites. When the total content of AC and MoO₃ was 10 phr, PVC/AC/MoO₃ had the lowest peak heat release rate and peak smoke production rate values of 173.80 kW m^?2 and 0.1472 m² s^?1, which represented reductions of 47.3 and 59.9%, respectively, compared with those of PVC. Furthermore, thermogravimetric analysis and gel content tests were used to analyze the flame retardant mechanism of AC and MoO₃, with results showing that AC could promote early crosslinking in PVC. Char residue left after heating at 500 °C was analyzed using scanning electron microscopy and Raman spectroscopy, and the results showed that MoO₃ produced the most compact char, with the smallest and most organized carbonaceous microstructures. © 2017 Society of Chemical Industry     

A novel bio‐based phthalonitrile resin derived from catechin: synthesis and comparison of curing behavior with petroleum‐based counterpart

The development of bio‐based thermosetting resins with good thermal stability can potentially afford sustainable polymers as replacements for petroleum‐based polymers. We report a practical route to a novel catechin‐based phthalonitrile resin precursor (CA‐Ph), which contains free phenolic hydroxyl groups that result in ‘self‐curing’ at elevated temperatures to afford a thermostable polymer. Comparison of the performance of this CA‐Ph resin with that of a conventional petroleum‐based bisphenol A phthalonitrile resin (BPA‐Ph; containing 5 wt% of the curing agent 4,4′‐diaminodiphenylsulfone) revealed that CA‐Ph exhibits a lower melting point and curing temperature. Cured CA‐Ph resin retains 95% of its weight at 520 °C under a nitrogen atmosphere, which compares favorably with results obtained for BPA‐Ph resin that retains 95% of its weight at a lower temperature of 484 °C. Kinetic results indicated that the curing reactions of both CA‐Ph and BPA‐Ph systems follow an autocatalytic mechanism. These results suggest that catechin is a useful bio‐based feedstock for the preparation of self‐curing and thermally stable phthalonitrile resins for advanced technological applications. © 2017 Society of Chemical Industry     

Using electroencephalogram to continuously discriminate feelings of personal thermal comfort between uncomfortably hot and comfortable environments

Thermal comfort is an important factor for the design of buildings. Although it has been well recognized that many physiological parameters are linked to the state of thermal comfort or discomfort of humans, how to use physiological signal to judge the state of thermal comfort has not been well studied. In this paper, the feasibility of continuously determining feelings of personal thermal comfort was discussed by using electroencephalogram (EEG) signals in private space. In the study, 22 subjects were exposed to thermally comfortable and uncomfortably hot environments, and their EEG signals were recorded. Spectral power features of the EEG signals were extracted, and an ensemble learning method using linear discriminant analysis or support vector machine as a sub-classifier was used to build the discriminant model. The results show that an average discriminate accuracy of 87.9% can be obtained within a detection window of 60 seconds. This study indicates that it is feasible to distinguish whether a person feels comfortable or too hot in their private space by multi-channel EEG signals without interruption and suggests possibility for further applications in neuroergonomics.     

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.     

黄浦江下游吴淞口站低潮位重现期研究

黄浦江为感潮河流,低潮位重现期的确定对黄浦江航道的设计具有重要意义。为了准确估计黄浦江低潮位的重现期,以黄浦江下游吴淞口站年最低潮位序列为例,在对样本进行三性审查的基础上,分别采用传统的数理统计方法和时变矩方法进行水文频率分析。结果表明:吴淞口站年最低潮位序列在1996年发生了变异;还现修正后的序列服从位置参数线性时变的GEV模型,低潮位存在缓慢的上升趋势;一致性条件下百年一遇低潮位约为0.261 m,在非一致性条件下其重现期增大为150 a。非一致性条件下的重现期增大说明黄浦江现有的航道设计标准偏安全,航道通航保证率提高。