Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

Band Gap Modification of Diamond Photonic Crystals by Changing the Volume Fraction of the Dielectric Lattice

Photonic crystals with a diamond structure of epoxy lattices in which TiO₂-based ceramic particles are dispersed were fabricated by stereolithography. The periodicity of the lattice was designed to reflect electromagnetic waves in the gigahertz range. The volume fraction (β) of the dielectric lattice medium was modified from 14% to 33% by changing the rod diameter of the lattice. The photonic band gap was observed along Γ-L 〈111〉, Γ-X 〈100〉, and Γ-K 〈110〉 directions and the complete photonic band gap was formed at over β= 20%. The width of the forbidden gap increased gradually when the β increased over 14%, and reached 2.4 GHz at β= 33%. These results agreed with the band calculation using the plane wave expansion method.     

Polymerization of epoxide with aluminum complex/silanol catalyst. VII. Thermal and electrical properties of epoxy resin cured with the new catalyst

Curing catalyst for epoxy resins was newly found. The catalyst consists of aluminum complex and silanol. Lack of one component of the pair does not cure epoxy resins. The epoxy resins cured with the catalyst are characterized by excellent electrical properties, especially at high temperature, due to the absence of strong acid species in the cured epoxy resin matrix. Heat-resistant property of the resin was also excellent. These properties were compared with those of epoxy resin cured with commonly used BF₃ complex.     

Hydrolysis of human horny cells by alkaline protease: Morphological observation of the process

The interaction of highly purified alkaline protease fromBacillus sp. KSM-K16 with the horny cells of human skin contained in skin grime was directly visualized by electron microscopy. It became clear that the protease first penetrates the horny cells and then adsorbs, mainly onto the internal structure of the cells at the initial stage of hydrolysis, and directly hydrolyzes the keratin filaments, though the marginal band surrounding them retains its original shape. Then, hydrolysate produced from the keratin filaments flows out of the cell, and early in the hydrolysis process keratin filaments decrease and then disappear, leaving a marginal band, i.e., the cell turns to a hollow state. As a result, the remaining marginal band loses support from inside the cell, thus promoting cleavage and dispersion. Until this stage in the protease reaction, the remarkable liberation of hydrolysis products as water-soluble protein does not occur.     

Intrinsic Elastic, Dielectric, and Piezoelectric Losses in Lead Zirconate Titanate Ceramics Determined by an Immittance-Fitting Method

The material coefficients of "soft" and "hard" lead zirconate titanate (PZT) ceramics were determined as complex values by the nonlinear least-squares-fitting of immittance data measured for length-extensional bar resonators. The piezoelectric d -constant should be a complex value to obtain a best fitting between observed and calculated results. Because the elastic, dielectric, and piezoelectric losses determined in this process were not "intrinsic" losses, a calculation process to evaluate the "intrinsic" losses was proposed. It was confirmed that the intrinsic losses were smaller than the corresponding extrinsic losses. The intrinsic piezoelectric loss existed in both soft and hard PZTs; ∼50% of the loss of piezoelectric d -constant was derived from the elastic and dielectric losses. The most notable difference between the soft and hard PZTs was observed in their elastic losses.     

Microstructure and Thermal Shock Resistance of Molten Glass-Coated Carbon Materials Fabricated by Interfacial Control

Carbon substrates were coated completely with a molten silicate glass, where the wettability of carbon to glass was improved by infiltration and pyrolysis of perhydropolysilazane. Microstructures of the carbon–glass interface were dependent on P n ₂ during coating. Coating at lower P n ₂ induced the formation of cristobalite at the carbon–glass interface. When the coating was performed at higher P n ₂, the glass and carbon were strongly adhered, without the formation of cristobalite. Coating at higher P n ₂ improved the thermal shock resistance of the glass layer, because crack initiation was not induced by the phase transformation of cristobalite during the cooling process. In the case of coating at higher P n ₂, an oxynitride glass layer was formed at the glass subsurface by dissolution of N₂. A porous glass subsurface layer with uniform spherical micro-pores could be produced by soaking near the glass transition temperature in a steam environment. The porous layer with fine and homogeneous microstructure acts as a thermal shock absorbing layer, so that glass-coated carbon with a porous glass layer has excellent thermal shock resistance in addition to steam oxidation resistance.     

Radiation-induced polymerization of ethylene in pilot plant. III. Heavy-phase recycling process

Radiation-induced polymerization of ethylene using aqueous tert-butyl alcohol as medium was carried out in a large-scale pilot plant with a 50-liter central source-type reactor at a pressure of 105 to 395 kg/cm², temperature of 30° to 80°C, mean dose rate of 4.5 × 10⁴ to 1.9 × 10⁵ rads/hr, ethylene feed rate of 5.5 to 23.5 kg/hr, and medium feed rate of 21 to 102 l./hr. The space–time yield and molecular weight of the polymer were in the range of 4.7 to 16.8 g/l.-hr and 1.3 × 10⁴ to 8.9 × 10⁴, respectively. The space–time yield and molecular weight increased with mean residence time at 30°C, whereas at 80°C they became almost independent of the time. The space–time yield increased with pressure and dose rate, slightly decreased with temperature, and was maximum at ethylene molar fraction of 0.5. The polymer molecular weight increased with pressure and ethylene molar fraction, and decreased with dose rate and temperature. The total amount of deposited polymer on the reactor wall, source case wall, and scraping blades was usually less than 1 kg, which was negligibly small for the analysis of polymerization. Continuous discharge of the polymer slurry and production of fine-powder polyethylene were successfully carried out. In the central source-type reactor, a dose rate of 1.9 × 10⁵ rads/hr was obtained with a ⁶⁰Co source of ca. 12 kCi.     

Pulsed Electric Current Sintering of Silicon Nitride

Pulsed electric current sintering (PECS) has been used to densify α-Si₃N₄ powder doped with oxide additives of Y₂O₃ and Al₂O₃. A full density (>99%) was achieved with virtually no transformation to β-phase, resulting in a microstructure with fine equiaxed grains. With further holding at the sintering temperature, the α-to-β phase transformation took place, concurrent with an exaggerated grain growth of a limited number of elongated β-grains in a fine-grained matrix, leading to a distinct bimodal grain size distribution. The average grain size was found to obey a cubic growth law, indicating that the growth is diffusion-controlled. In contrast, the densification by hot pressing was accompanied by a significant degree of the phase transformation, and the subsequent grain growth gave a broad normal size distribution. The apparent activation energy for the phase transformation was as high as 1000 kJ/mol for PECS, almost twice the value for hot pressing (∼500 kJ/mol), thereby causing the retention of α-phase during the densification by PECS.     

Phase evolution and <110>-orientation mechanism in RTGG-processed BaTiO3 ceramics with electrical properties

The <110>-oriented BaTiO₃ ceramics were fabricated using BaCO₃ matrix and H_1.08Ti_1.73O₄.nH₂O (HTO) template particles, and the mechanism of BaTiO₃ phase formation was investigated. The dielectric, ferroelectric, and piezoelectric properties were also investigated. The transformation of the HTO phase into the TiO₂ bronze or TiO₂ (B) phase was observed at 600°C, where the BaTiO₃ nucleation was accompanied by the formation of a Ba₂TiO₄ phase. The TiO₂ phase reacted with the Ba₂TiO₄ phase at 800°C to give a BaTiO₃ phase, whereas its reaction with the BaTiO₃ resulted in the formation of BaTi₂O₅ phase that got decomposed into BaTiO₃ and Ba₆Ti₁₇O₄₀ phase at sintering temperature ≥1300°C. Sintering with samples’ embedding in BaTiO₃ powders prevented the formation of the Ba₆Ti₁₇O₄₀ secondary phase. The crystallographic orientation along the <110> direction (F₁₁₀) was developed by the epitaxial grain growth mechanism. In addition to the contribution of the grain-size increment for enhancing the F₁₁₀, the preservation of the platelike structure was also found to have a significant impact. The ceramics prepared by the embedded sintering (grain size ≈12.4 µm and F₁₁₀ = 83%) exhibited the room-temperature dielectric constant of 1708 and piezoelectric strain constant of 445 pm/V, which are higher than those of the BaTiO₃ ceramics with randomly oriented grains.     

Time Averaging Algorithms with Stopping Rules for Multi‐Agent Consensus with Noisy Measurements

A time averaging technique is introduced to consensus algorithms in networked multi‐agent systems under a noisy environment. Each agent communicates with its neighboring agents via a constant gain, while the time averaging states of the agents are considered as the values for agreement. The variation of the time averaging states then is evaluated at a specific number of iterations, where the number is given explicitly in terms of parameters related to the consensus accuracy and its probabilistic guarantee. This result establishes a rigorous stopping rule for the multi‐agent consensus with noisy measurements. Several results on this type of stopping rules are provided for undirected, directed, and time‐varying communication graphs. These theoretical results are illustrated through numerical examples.