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.     

Extraction of Trivalent Rare Earths and Minor Actinides from Nitric Acid with N,N,N’,N’-Tetradodecyldiglycolamide (TDdDGA) by Using Mixer-Settler Extractors in a Hot Cell

Single-stage batch experiments to reveal the extraction properties of N,N,N’,N’-tetradodecyldiglycolamide (TDdDGA) for Y, La, Eu, Nd, and Am in nitric acid were carried out. The distribution ratios of Y, Eu, Nd, and Am exceeded 10 when the nitric acid concentration was 1–2 mol/dm³ (M), and the distribution ratio of La was 5.5 when the nitric acid concentration was 2 M. A continuous counter-current experiment using 0.1 M TDdDGA diluted with n-dodecane was performed using mixer-settler extractors installed in a hot cell. Nitric acid with a concentration of 2.1 M containing minor actinides (MAs: Am and Cm), rare earths (REs: Y, La, Nd, and Eu), and other fission products (Sr, Cs, Zr, Mo, Ru, Rh, and Pd) was fed to the extractor. TDdDGA effectively extracted MAs and REs from the feed, while other fission products were barely extracted. The extracted MAs and REs were back-extracted by bringing them in contact with 0.02 M nitric acid, and they were collected as the MA–RE fraction. The results indicated that more than 98% of Am and Cm in the feed were recovered in the MA–RE fraction. The proportions of Y, La, Nd, and Eu in the MA–RE fraction were 94.0%, 99.9%, 99.9%, and 86.9%, respectively.     

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     

Electromigration of sodium ions and electro-osmotic flow in water-saturated, compacted Na-montmorillonite

Sodium ions spiked with ²²Na as a tracer were migrated by electromigration and electro-osmosis in the water-saturated compacted Na-montmorillonite at dry densities 1.0×10³ kg m⁻³, under an electric potential gradient. Dissolved helium was also migrated by electro-osmosis in the montmorillonite. After migration, concentration profiles of the sodium ions and helium were obtained by γ-spectrometry and mass-spectrometric methods, respectively. From the profiles of both chemical species, not only migration due to electrokinetic phenomena but also mechanical dispersion was observed in the montmorillonite. The dispersion coefficients, D_i, and apparent migration rates, U_i^a, of ²²Na and helium were found in the compacted Na-montmorillonite at 1.0×10³ kg m⁻³. The migration of helium in the montmorillonite under an electric potential gradient reflects that of water because helium migrates as an electrically neutral species. The parameters D_He^m, U_He^a, and α_He correspond to those of water. The mechanical dispersion coefficients, D_Na^m, of ²²Na⁺ ions are much smaller than those of water obtained by helium. The dispersivity parameters, α_Na, for ²²Na⁺ obtained from these D_Na and U_Na^a values are 10⁻⁵ m and those for water (α_He) are 10⁻³ m. This indicates that ²²Na⁺ ions migrate in different spaces than water in the compacted montmorillonite under a potential gradient. This finding suggests that the migration of Na⁺ ions occurs in the interlayer and/or on the outer surfaces of the montmorillonite; whereas dissolved helium migrates in the pore water.     

Improvement of anode oxidation reaction of a fuel cell using ammonium formate with Pt‐Ir catalysis

We have attempted to develop high‐performance and safe fuel cells by using ammonium formate as a solid (powder) fuel. This solid fuel has the potential of safer transportability than liquid fuels such as methanol from the viewpoint of toxicity and flammability. In order to make use of some of the advantages of ammonium formate, we investigated the oxidation characteristics of ammonium formate with respect to a Pt electrode. Cyclic voltammograms indicate that ammonium formate has high oxidation activity with respect to a Pt electrode. We have also found that the oxidation of ammonium formate can be improved by the addition of Ir to Pt catalysts. It is highly likely that ammonium formate will be useful as a solid (powder) fuel for polymer electrolyte membrane (PEM) fuel cells. This new fuel will promote the development of safe fuel cells for PEM. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 174(4): 45–50, 2011; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.21043     

Properties of reactively sputtered IrOx for PZT electrode applications

Abstract

The use of IrO_x for electrodes in PbZr_xTi_1?xO₃ (PZT) capacitors for ferroelectric memory applications has proven to be advantageous in several respects. In comparison with Pt, IrO_x often exhibits improved fatigue and provides resistance to hydrogen induced degradation at elevated temperatures. Since IrO_x is often produced by sputtering in an oxygen containing environment, several forms of IrO_x can be produced depending on the process conditions. This work concentrates on an analysis of the DC reactive sputtering of IrO_x from an Ir metal target. As with other oxidizable metals, Ir exhibits a transition between metal and oxide mode sputtering when sputtered in oxygen containing atmospheres. Variations in the Ar/O₂ gas flow ratio were used to produce Ir and IrO_xfilms on both sides of the metal-to-oxide mode reactive sputtering transition. Changes in the IrO_x film properties were quantified by using a combination of metrics including X-ray diffraction, sheet resistance, and stress. It was found that the, IrO_x crystalline structure and other IrO_x properties could be directly related to the ferroelectric switching performance of PZT capacitors with IrO_xtop electrodes. A relationship between IrO_x deposition processes and resistance to etch induced damage of the ferroelectric properties was also observed.     

Intelligent combinatorial auctions of decentralized task assignment for AGV with multiple loading capacity

The need to have an efficient transportation system has attracted worldwide attention. Although there is increasing demand to implement distributed control system for industrial applications, there is still an unexplored potential of deploying distributed transportation system. This paper focuses on dynamic assignment of transportation requests to a fleet of vehicles in real time. We introduce an improved combinatorial auction methodology to accommodate the distributed task assignment procedure. Based on a multiagent architecture, each vehicle is represented by an intelligent agent that bids for task and plans its own schedule. On the other hand, the auctioneer has the objective of minimizing transportation tardiness. An automated guided vehicle (AGV) has been selected as the case study, and numerical experiments have been carried out. The result obtained shows that the improved task assignment approach is able to produce performance competitive to a conventional task assignment. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

Cost-Efficient Traffic Aggregation Employing Cross-Layer Shared Protection

Shared protection/restoration is a promising solution for reducing protection resources and is supported at each layer of the current multi-layer networks. Software-defined networking is expected to reduce equipment cost as well as operational cost by orchestrating these shared protection functionalities. However, although protection resource sharing improves link utilization, it sometimes increases the required equipment. Meanwhile, traffic re-aggregation at each layer is an important technique for low volume traffic to utilize the underlying link capacity more efficiently, but re-aggregation also makes it difficult to share protection resources with traffic at lower layers. In this paper, we present multi-layer network design strategy and method that reduce equipment cost by means of both traffic re-aggregation at each layer and protection resource sharing among multiple service traffic at different layers. The strategy first prioritizes traffic re-aggregation at each layer, and then maximally delegates shared protection to lower layers as long as it does not increase the required capacity at the lower layer. Evaluation results from the example three-layer networks confirm that the proposed method can effectively reduce equipment cost compared to the conventional design method. Cost reduction is achieved by leveraging shared protection functions at multiple layers.