Development of In Vitro and In Vivo Evaluation Systems for Vitamin D Derivatives and Their Application to Drug Discovery

We have developed an in vitro system to easily examine the affinity for vitamin D receptor (VDR) and CYP24A1-mediated metabolism as two methods of assessing vitamin D derivatives. Vitamin D derivatives with high VDR affinity and resistance to CYP24A1-mediated metabolism could be good therapeutic agents. This system can effectively select vitamin D derivatives with these useful properties. We have also developed an in vivo system including a Cyp27b1-gene-deficient rat (a type I rickets model), a Vdr-gene-deficient rat (a type II rickets model), and a rat with a mutant Vdr (R270L) (another type II rickets model) using a genome editing method. For Cyp27b1-gene-deficient and Vdr mutant (R270L) rats, amelioration of rickets symptoms can be used as an index of the efficacy of vitamin D derivatives. Vdr-gene-deficient rats can be used to assess the activities of vitamin D derivatives specialized for actions not mediated by VDR. One of our original vitamin D derivatives, which displays high affinity VDR binding and resistance to CYP24A1-dependent metabolism, has shown good therapeutic effects in Vdr (R270L) rats, although further analysis is needed.     

Crystallographic analysis for acicular ferrite formation in low carbon steel weld metals

Inclusions contributing to acicular ferrite nucleation were investigated from a crystallographic point of view in low carbon low alloy steelweld metals. The samples from electro slag welding (ESW) and submerged arc welding (SAW) deposits with various cooling rates were prepared in this study. In those samples, intragranular acicular ferrite formation was observed from inclusions. The inclusions contributing to acicular ferrite formation were of multi-phase type consisting of amorphous phase, spinel type and MnS. They were surrounded by a Ti-enriched layer. It was confirmed by selected area diffraction patterns and energy-dispersive X-ray spectrometer analyses that the Ti-enriched layer was TiO. The acicular ferrite had a Baker–Nutting orientation relationship with the TiO layer on the inclusion surface. The misfit was 3.0% at the interface between the acicular ferrite and TiO. Therefore, it is considered that TiO on the inclusion surface contributes to the heterogeneous nucleation of acicular ferrite by small lattice misfit. However, themorphologies of ferrite growth which nucleated from inclusions were different in both samples. Whereas the growth of ferrites nucleated from TiO was enough in ESW, the size of nucleated ferrite in SAW was a few hundred millimetres in size. In the early stage of nucleation from TiO, ferrite had small deviation from Kurdjumov–Sachs orientation relationship (K–S relationship) in both ESW and SAW. However, there was a difference in the growth stage of ferrite. The ferrite orientations were gradually changed to fit to the K–S relationship in ESW. On the other hand, the nucleated ferrite in SAW stopped growing and the newly nucleated ferrite which had K–S relationship prior to austenite was formed adjacently because of large super cooling due to small heat input.     

Electron beam welding of aluminium alloy by wire feed method (1st Report).Effect of filler wire melting configuration on bead formation

The 5XXX series of non-heat-treatable aluminium alloys, widely used in modern industry, have the peculiarity that an area near the welding bead, which reaches a temperature higher than 230°C, suffers an annealing effect that causes a considerable decrease in yield strength. The present paper deals with the three-dimensional modelling, using general-use finite element software, of a classic experiment conducted in the past by Masubushi, using the GMAW process on aluminium alloy 5052 H32, in order to determine the thermal history, and transient and residual strain and stress. Finally, a method for modelling applicable to this material type is proposed, where the model is divided into three zones; one near the weld with the properties of aluminium in annealed state, another further away with the base metal properties, and a transitional zone with intermediate properties.     

Effect of REM addition of wire on CO2 gas shielded arc phenomenon

Carbon dioxide (CO₂) gas shielded arc welding is the main arc welding method, but it generates a large amount of spatter during welding. The root cause of spatter lies in the fact that the droplet undergoes repeated irregular shaking. To solve this problem, spatter generation modes were clarified and the effects of polarity and rare earth metal (REM) addition of the wire on CO₂ gas shielded arc welding were investigated. As a result, when welding is performed with an electrode negative (DCEN) polarity using REM added wire, it was found that a conical arc plasma is formed, and the droplet which is transferred from the wire tip to the molten pool is fine and continuous, in what is termed ‘spray transfer’. Thus, spatter generation was reduced to 10% of amount of the conventional CO₂ gas shielded arc welding (from 0.058 to 0.005g/s).     

Homology-Based Interactions between Small RNAs and Their Targets Control Dominance Hierarchy of Male Determinant Alleles of Self-Incompatibility in Arabidopsis lyrata

Self-incompatibility (SI) is conserved among members of the Brassicaceae plant family. This trait is controlled epigenetically by the dominance hierarchy of the male determinant alleles. We previously demonstrated that a single small RNA (sRNA) gene is sufficient to control the linear dominance hierarchy in Brassica rapa and proposed a model in which a homology-based interaction between sRNAs and target sites controls the complicated dominance hierarchy of male SI determinants. In Arabidopsis halleri, male dominance hierarchy is reported to have arisen from multiple networks of sRNA target gains and losses. Despite these findings, it remains unknown whether the molecular mechanism underlying the dominance hierarchy is conserved among Brassicaceae. Here, we identified sRNAs and their target sites that can explain the linear dominance hierarchy of Arabidopsis lyrata, a species closely related to A. halleri. We tested the model that we established in Brassica to explain the linear dominance hierarchy in A. lyrata. Our results suggest that the dominance hierarchy of A. lyrata is also controlled by a homology-based interaction between sRNAs and their targets.     

Delamination growth mechanisms in woven glass fiber reinforced polymer composites under Mode II fatigue loading at cryogenic temperatures

The purpose of this research is to characterize the cryogenic delamination growth behavior in woven glass fiber reinforced polymer (GFRP) composite laminates subjected to Mode II fatigue loading. Mode II fatigue delamination tests were performed at room temperature, liquid nitrogen temperature (77 K) and liquid helium temperature (4 K) using the four-point bend end-notched flexure (4ENF) test method, and the delamination growth rate data for the woven GFRP laminates were obtained. The energy release rate range was determined by the finite element method. Microscopic examinations of the specimen sections and fracture surfaces were also carried out. The present results are discussed to obtain an understanding of the fatigue delamination growth mechanisms in the woven GFRP laminates under Mode II loading at cryogenic temperatures.     

TEM/STEM Observation of ZrC Coating Layer for Advanced High-Temperature Gas-Cooled Reactor Fuel, Part II

The Japan Atomic Energy Agency (JAEA) has started to study and develop zirconium carbide (ZrC)-coated fuel particles for advanced high-temperature gas-cooled reactors. The ZrC coating layer has been fabricated at JAEA by chemical vapor deposition using a pyrolytic reaction of zirconium bromide. The microstructures of the ZrC layers, whose nominal deposition temperatures could be measured and controlled during the deposition process, were characterized by means of TEM and STEM. In the present study, three batches were prepared and compared with each other as well as the previous batches. The crystallographic orientation of ZrC with regard to the growth direction in the ZrC layers deposited at a constant temperature of 1630 K was different from that deposited at varying temperatures in the 1493–1823 K range. A thin layer of turbostratic carbon was observed at the boundary between pyrolytic carbon and ZrC in particles deposited at the highest temperature among those used in this study (the nominal temperature was 1769 K); no such structure was found in a batch deposited at a lower temperature (the nominal temperature was 1632 K). Therefore, precise control of temperature is shown to be critical to the formation of good ZrC coatings.     

Metastable precipitation in isothermally solidified YAG-alumina composites with off-eutectic composition

YAG-alumina composites with Al₂O₃-rich and YAG-rich compositions were prepared by annealing the hot-pressed composites at the eutectic temperature (1820°C) for 1 h followed by cooling down at 10 or 100°C/min in argon atmosphere. Microstructural observations of the solidified composites identified that metastable phase -Al₂O₃ precipitated in the Al₂O₃-rich specimens cooled down at both the cooling rates. For the solidified YAG-rich specimens, however, equilibrium phase -Al₂O₃ could not be reprecipitated, moreover, metastable YAlO₃ phase was formed at cooling rate of 100°C/min. Formation of the metastable phases in the solidified composites was attributed to the decreased melting temperature caused by the divorced eutectic precipitation and the metastable decomposition of YAG component in YAG-alumina eutectic melt during rapid solidification.     

Low Frequency Susceptibility of High-Density bcc Solid 3He in the Paramagnetic and Nuclear-Ordered States

We have measured the AC magnetic susceptibility and static magnetization of high-density bcc solid ³ He through the nuclear-ordering transition. The susceptibility in the paramagnetic state strongly depends on the frequency of the measuring field. Near the transition temperature a sharp peak in the real part of the AC susceptibility and an abrupt depression in the imaginary part are observed. The transition temperature indicated by the AC susceptibility is higher than that derived from static magnetization. We analyzed the new behavior in the susceptibility in terms of the spin relaxation between the Zeeman system and the exchange system. The relaxation time in the energy flow in the two systems is in the range of milliseconds in the paramagnetic state, and decreases drastically by two orders of magnitude in the ordered state. The relaxation time in the paramagnetic state is interpreted as due to exchange narrowing, while in the ordered state is explained to be the drift time of the spin wave limited by the size of the sample grown in the pores of the sintered silver. The ordering temperature is given as a function of molar volume in the entire range of the bcc phase.     

Influence of Y2O3 distribution on the rate of tetragonal to monoclinic phase transformation of yttria-stabilized zirconia during hydrothermal aging

Tetragonal to monoclinic phase transformation of yttria-stabilized zirconia, namely plasma-sprayed coatings and sintered bodies containing 4–8 mass % Y₂O₃ during hydrothermal aging was investigated with respect to Y₂O₃ distribution using 1 m area from electron probe microanalysis (EPMA) and 20 nm area from transmission electron microscopy (TEM) analysis. Phase transformation at 473 K was prevented only in plasma-sprayed coatings having more than 6.7 mass % Y₂O₃ in 20 nm microscopic area. Furthermore, it was confirmed influence of Y₂O₃ distribution on the rate constants of this phase transformation was observed at 368 K.