Discovery of a Novel Scaffold as an Indoleamine 2,3‐Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid,Longamide B

Indoleamine 2,3‐dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1‐methyl‐tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.     

Electrical resistivity of Si3N4 ceramics with Yb2O3 additive

Si₃N₄ ceramics with excellent mechanical properties are used for heat dissipation substrates and so on. In order to improve their reliability and expand their application fields, it is desirable to understand and control the electrical properties of Si₃N₄ ceramics. In this study, the electrical resistivity of Si₃N₄ ceramics with Yb₂O₃ additive was investigated by applying various voltages at temperatures ranging from 25°C to 300°C. When Yb₂O₃ was added as a sintering aid to Si₃N₄ ceramics, a crystalline J-phase (Yb₄Si₂O₇N₂) was formed and their electrical resistivity was significantly lower than that of Y₂O₃ additive. The electrical resistivity of the Yb₂O₃-added ceramics decreased with an increase in temperature and applied voltage. Yb existed in multiple valence states, Yb²⁺ and Yb³⁺, in the Si₃N₄ ceramics and the decrease in the electrical resistivity can be attributed hopping conduction through the J-phase. The J-phase in the Si₃N₄ ceramics was observed to be continuous, and percolation analysis suggested that the J-phase formed an infinite cluster. Therefore, the decrease in the electrical resistivity of the Yb₂O₃-added Si₃N₄ ceramics was found mainly to result from the formation of an infinite cluster of J-phase, which exhibits hopping conduction.     

Advanced synthesis for monodisperse polymer nanoparticles in aqueous media with sub-millimolar surfactants

Highly monodisperse polystyrene nanoparticles with mean diameters of less than 100 nm are synthesized via aqueous emulsion polymerization using an amphoteric initiator (VA-057) in the presence of sub-millimolar concentrations of anionic surfactant. Since the net charge on the initiator is almost zero at neutral pH, the resultant latex particle size is mainly determined by surfactant adsorption. Polymerizations were performed in the presence of a range of anionic surfactants with differing critical micelle concentrations (CMC) by varying the concentrations of surfactant, initiator and monomer, and also the ionic strength. Sodium dodecyl benzene sulfonate (SDBS), sodium hexadecyl sulfate (SHS), and sodium octadecyl sulfate (SOS) have relatively low CMCs and so enable formation of highly monodisperse nanoparticles at relatively low (sub-millimolar) surfactant concentrations, C_S (i.e. below the CMC in each case). Empirically, it was found that the particle number, N_p, and coefficient of variation of the particle size, C_V, were strongly dependent on the C_S/CMC ratio: N_p increased almost in proportion with the square of this ratio, while the C_V exhibited a minimum at approximately C_S/CMC = 0.20. Higher ionic strength reduced the particle size, which is consistent with the above relationship because the addition of salt lowers the CMCs of ionic surfactants. Polymer latex particles produced using such formulations form highly regular, close-packed colloidal arrays.     

Thermal and optical properties of hyperbranched fluorinated polyimide/mesoporous SiO2 nanocomposites exhibiting high transparency and reduced thermo-optical coefficients

A series of hyper-branched polyimide (HBPI)/mesoporous SiO₂ nanocomposite films were prepared from a fluorinated anhydride (6FDA), a fluorinated triamine (TFAPOB), and mesoporous SiO₂ nanoparticles (NPs). The anhydride-terminated precursor of HBPI was functionalized using a coupling agent prior to mixing with SiO₂ NPs. The morphologies and thermal-optical properties of the nanocomposite films were investigated, with particular focus on their optical transparency, refractive indices (n), and thermo-optical (TO) coefficients. The absolute values of TO coefficients (|dn/dT|) of HBPI film (50.8 ppm/K) were significantly reduced to 13.4 ppm/K by homogeneous dispersion of 15 wt% of SiO₂ NPs. The HBPI/SiO₂ composite films exhibited high thermal stability without significant weight loss of up to 400 °C in air. The films also exhibited small coefficients of linear thermal expansion (CTEs) within the range 30–40 ppm/K. In addition, enhanced interfacial interactions between SiO₂ and HBPI significantly improve the optical transparency with cutoff wavelengths shorter than 450 nm. The refractive indices of HBPI/SiO₂ composite films were found to range from 1.477 to 1.502, which agrees well with the calculated values. This study shows that the incorporation of SiO₂ NPs in multi-functional HBPI matrix is a promising approach to prepare high performance thermally stable films for thermo-optic applications.     

Partially biobased polyamphiphile-bearing reactive epoxy groups in the side chains and its application to the hydrogel

Partially biobased polyamphiphile-bearing reactive epoxy groups in the side chains were obtained in 62–78 % yields by a radical copolymerization of limonene oxide (LO) and PEG methylacrylate (PEGA) with different feed ratios. Degree of LO incorporation into the copolymer was determined as 12–23 % by ¹H NMR spectroscopic analysis. The copolymer having LO unit:PEGA unit = 19:81 formed polymer associates in water, particle diameter of which was ranged mainly from 4 to 66 nm and hydrodynamic mean diameter was 12.3 nm. Its critical micelle concentration was determined as 0.53 g/L by fluorescence spectroscopic analysis. A cross-linking reaction of the epoxy groups in the side chains was conducted with 3.97 mol% (to the epoxy group) of branched poly(ethylene imine) as a cross-linker to give the corresponding hydrogel in 56 % yield. The hydrogel can absorb water as much as 13 times its own mass.     

Effect of wall wettability condition on drift-flux parameters in lead–bismuth two-phase flow in circular and annular bubble columns

Lead–bismuth two-phase flow in a cylindrical vessel and annulus was experimentally investigated by varying the surface wettability of the vessel wall. The test section used in this study was a cylindrical stainless vessel with/without inner sleeve to change the hydraulic diameter. Volume-averaged void fraction was measured by varying the surface wettability of the test section, which was enhanced by using a soldering flux. Measured void fraction was compared with existing two-phase flow correlations and with one-dimensional theoretical simulations assuming one-dimensional drift-flux model. From experimental results, measured distribution parameters of the lead–bismuth two-phase flow are much larger than that of ordinary two-phase flow regardless of the surface wettability. In the present work, the one-dimensional analysis was carried out for the cylindrical vessel to reproduce the distribution parameter. From the simulation results, predicted value for the cylindrical vessel showed good agreement with experimental results. However, in annulus, the distribution parameters in annulus were underestimated by the present model. It was suggested that, in case of annulus, steeper void fraction profile might be formed near the inner surface for poor wettability condition.     

Enzymatic Synthesis of 1‐Alkyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate Using a Novel Lysoplasmalogen‐Specific Phopholipase D

Many phospholipase Ds (PLDs) are known to catalyze transphosphatidylation as well as hydrolysis of phospholipids. Transphosphatidylation of lysoplasmalogen (LyPls)‐specific phospholipase D (LyPls‐PLD), which catalyzes hydrolysis of ether lysophospholipids such as LyPls and 1‐hexadecyl‐2‐hydroxy‐sn‐glycero‐3‐phosphocholine (Lyso‐PAF), still remains unclear. This study aims to reveal the transphosphatidylation activity of LyPls‐PLD, that is, the production of cyclic ether lysophospholipid. The enzymatic reaction is conducted in a buffer system, and the reaction products of a novel LyPls‐PLD from Thermocrispum sp. are investigated using mass spectrometry (MS). MS analyses demonstrate the reaction products to consist of 100% 1‐hexadecyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate (cLyPA) and choline from Lyso‐PAF; however, 1‐alkenyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate from 1‐O‐1′‐(Z)‐octadecenyl‐2‐hydroxy‐sn‐glycero‐3‐phosphocholine and 1‐O‐1′‐(Z)‐octadecenyl‐2‐hydroxy‐sn‐glycero‐3‐phosphoethanolamine is not produced. These results are expected to help in elucidating the catalytic mechanism of LyPls‐PLD, that is, the rate‐limiting step, and indicate LyPls‐PLD to be useful for the one‐pot synthesis of cLyPA. Practical Applications: A novel phospholipase D, LyPls‐PLD, can exclusively synthesize cLyPA from Lyso‐PAF using a one‐step enzymatic reaction without an organic solvent. cLyPA could be expected to show bioactivities similar to those of cyclic phosphatidic acid, which promotes normal cell differentiation, hyaluronic acid synthesis, antiproliferative activity in fibroblasts, and inhibitory activity toward cancer cell invasion and metastasis.     

Deoxidation of Ti Melt by Newly Developed Two-Step Plasma Arc Melting Process Using Hydrogen

Metallurgical and Materials Transactions B - A two-step plasma arc melting process, comprising a first step under Ar-30 pct H2 gas flow and the second step under Ar gas flow, has been...