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.     

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.     

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     

New anti-ablation candidate for carbon/carbon composites: Preparation,composition and ablation behavior of Y2Hf2O7 coating under an oxyacetylene torch

Y₂Hf₂O₇ possesses low thermal conductivity and high melting point, which make it promising for a new anti-ablation material. For evaluating the thermal stability and the potential applications of Y₂Hf₂O₇ on anti-ablation protection of C/C composites, Y₂Hf₂O₇ ceramic powder was synthesized by solution combustion method and Y₂Hf₂O₇ coating was prepared on the surface of SiC coated C/C composites using SAPS. Results shown that the coating exhibits good ablation resistance under the heat flux of 2.4?MW/m² with the linear and mass ablation rates are 0.16?μm?s^?1 and ?0.028?mg?s^?1, respectively, after ablation for 40?s. With the prolonging of the ablation time, the increasing thermal stress causes the increase of cracks. Moreover, the chemical erosion from SiO₂ and the physical volatilization of low temperature molten products aggravate failure of the Y₂Hf₂O₇ coating.     

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.     

Experimental study on the permeability and self-healing capacity of geosynthetic clay liners in heavy metal solutions

Geosynthetic clay liners (GCLs), which have a very low permeability to water and a considerably high self-healing capacity, are widely used in liner systems of landfills. In this study, a series of experimental tests were carried out under complex conditions on typical commercial GCLs from China. In particular, the effects of pH values and lead ions (Pb²⁺) were tested in addition to other factors. The swelling properties of natural bentonite encapsulated between geotextile components in the GCLs were tested first. The swelling capacity was reduced rapidly at pH values < 3 and concentrations of Pb²⁺ >40 mM. Permeability tests on GCLs with different concentrations of lead ions were then performed by using the self-developed multi-link flexible wall permeameter, and data showed that increases in lead ion concentrations greatly improved the permeability. Finally, self-healing capacity tests were conducted on needle-punched GCLs under different levels of damage. Results showed that the GCLs have a good self-healing capacity with small diameter damage holes (2 mm, close to three times the original aperture), but with a damage aperture larger than 15% of the sample area, the self-healing capacity could not prevent leakage; hence, in certain situations it will be necessary to repair the damage to meet the anti-seepage requirement.