Structure-Based Design,Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one ( 1 ). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide ( 25 ) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.     

Improved environmental stability,electrical and EMI shielding properties of vapor‐grown carbon fiber‐filled polyaniline‐based nanocomposite

An all polymeric electrically conductive thermoset adhesive resin system is prepared for future lightning strike protection applications. Polyaniline (PANI)‐based hybrid nano‐composite is prepared by incorporating high apparent‐density type vapor grown carbon fiber (VGCF‐H) as additional conductive filler. Electrical, mechanical and electromagnetic interference (EMI) shielding properties of PANI‐dodecylbenzene sulfonic acid (DBSA), and divinylbenzene (DVB) system are improved with addition of VGCF‐H. Different weight percentages of VGCF‐H in the PANI‐DBSA/DVB matrix, are studied, and their effect on composite's properties are investigated. Electrical conductivity up to 1.89 S/cm with the addition of 5 wt% VGCF‐H is achieved, which is almost 300% improvement compared with previous system. However, the maximum flexural modulus is obtained at 3 wt% of VGCF‐H. The change in the electronic structure of PANI with the addition of VGCF‐H is investigated using Fourier transform infrared (FT‐IR) analysis. Rheological study and Differential scanning calorimetry analysis were employed to show the effect of VGCF‐H concentration on curing profile of the nanocomposites. EMI shielding properties of the composite with and without VGCF‐H are measured in X‐band frequencies and compared. Composite with 5 wt% VGCF‐H has shown EMI shielding effectiveness about 51 dB in X‐band, which is higher than the composite without VGCF‐H (around 22 dB). POLYM. ENG. SCI., 59:956–963, 2019. © 2018 Society of Plastics Engineers     

Variable stage-independent double sampling plan with screening for acceptance quality loss limit inspection scheme

The quality loss suggested by Taguchi has been recognised as a new quality evaluation based on variable property instead of the quality evaluation based on traditional attribute property such as the proportion of nonconforming items. Some variable sampling inspection plans in order to assure the quality have been considered. As one of those sampling inspection plans, the single sampling plan with screening (SSPS) has been constructed for acceptance quality loss limit inspection scheme. Further, the repetitive group sampling plan with screening (RGSPS) has been developed for reducing the average total inspection (ATI). Although ATI by RGSPS has successfully been reduced in comparison with ATI by SSPS, RGSPS may sometimes increase the average sampling frequency (ASF) in return for reducing ATI. In this study, the stage-independent double sampling plan with screening (SIDSPS) based on the concept of the acceptance quality loss limit inspection scheme is proposed under the consideration of the trade-off between ATI and ASF. Through some numerical comparisons about ATI and ASF in SSPS, RGSPS, and SIDSPS, the usefulness of SIDSPS proposed in this study is confirmed.     

Do people with social anxiety feel anxious about interacting with a robot?

AI & SOCIETY - To investigate whether people with social anxiety have less actual and “anticipatory” anxiety when interacting with a robot compared to interacting with a person, we...     

Superconducting Coupling Nature at Grain Boundaries in Bi2Sr2CaCu2Ox Glass-Ceramics

Superconducting coupling nature at grain boundaries in Bi₂Sr₂CaCu₂O _x glass-ceramics consisting mainly of the low- T _c phase was first examined by measuring superconducting properties and temperature or ac field dependence of ac complex susceptibility. It was found from the ac loss peaks that superconducting coupling at grain boundaries was basically characterized by three types of weak links. The weak-link behaviors at grain boundaries depended strongly on cooling conditions after annealing and annealing time and temperature. Particularly, it was found that the weak links at grain boundaries were improved by prolonged annealing at 840°C. The furnace-cooled glass-ceramics obtained by annealing at 820° or 840°C for about 200 h exhibited a critical transport current density (77 K, zero magnetic field) of about 200 A/cm².     

Hydrogen-bond-assisted isotactic-specific radical polymerization of N-isopropylacrylamide with pyridine N-oxide

Radical polymerization of N-isopropylacrylamide (NIPAAm) in CHCl₃ at low temperatures in the presence of pyridine N-oxide (PNO) was investigated. An isotactic poly(NIPAAm) with meso diad content of 61% was successfully prepared at −60 °C in the presence of a two-fold amount of PNO. Thermodynamic analysis suggested that the isotactic-specificity was entropically induced, probably due to conformational fixation near the propagating chain-end through coordination by PNO.     

An estimation of friction from the indentation of metals by acute-angled conical indenters

The paper describes a method for estimating the coefficient of friction (COF) between sliding surfaces by an indentation of an acute-angled indenter. The COF estimated by the method is compared with the COF measured by a friction tester. The conical indenter, which is made of WC and has an apex angle of 45°, is used for the experiments. A micro-Vickers hardness tester is used for the indentation tests. The friction tester used is one of Bowden–Leben type. A copper and a 0.45% carbon steel are used for the indentation and sliding specimens. The estimation of the COF is based on the equilibrium equation of indentation, which takes the friction between the contacting surfaces of the indenter and the specimen into consideration. The results show that the estimated COF is approximately equal to the measured one. Based on the results, the validity of this method is discussed.     

Effects of photo-induced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on physical properties of cross-linked polyethylene in artificial hip joints

Osteolysis caused by wear particles from polyethylene in the artificial hip joints is a serious issue. We have used photo-induced radical graft polymerization to graft 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer onto the surface of cross-linked polyethylene (CLPE-g-MPC) in order to reduce friction and wear at the bearing surface of the joint. The physical and mechanical properties of CLPE and CLPE-g-MPC were not significantly different, expect that the friction coefficient of untreated CLPE cups was 0.0075, compared with 0.0009 for CLPE-g-MPC cup, an 88% reduction. After 3.0 × 10⁶ cycles in the hip joint simulator test, we could not observe any wear of CLPE-g-MPC cups. We concluded that the advantage of photo-induced radical graft polymerization technique was that the grafted MPC polymer gave a high lubricity only on the surface and has no effect on the bulk properties of the CLPE substrate.