Functional characterization of 21 CYP2C19 allelic variants for clopidogrel 2-oxidation.

Genetic variations in cytochrome P450 2C19 (CYP2C19) contribute to interindividual variability in the metabolism of therapeutic agents such as clopidogrel. Polymorphisms in CYP2C19 are associated with large interindividual variations in the therapeutic efficacy of clopidogrel. This study evaluated the in vitro oxidation of clopidogrel by 21 CYP2C19 variants harboring amino acid substitutions. These CYP2C19 variants were heterologously expressed in COS-7 cells, and the kinetic parameters of clopidogrel 2-oxidation were estimated. Among the 21 CYP2C19 variants, 12 (that is, CYP2C19.5A, CYP2C19.5B, CYP2C19.6, CYP2C19.8, CYP2C19.9, CYP2C19.10, CYP2C19.14, CYP2C19.16, CYP2C19.19, CYP2C19.22, CYP2C19.24 and CYP2C19.25) showed no or markedly low activity compared with the wild-type protein CYP2C19.1B. This comprehensive in vitro assessment provided insights into the specific metabolic activities of CYP2C19 proteins encoded by variant alleles, and this may to be valuable when interpreting the results of in vivo studies.

Thin film growth of Fe-based superconductors: from fundamental properties to functional devices. A comparative review.

Fe-based superconductors bridge a gap between MgB2 and the cuprate high temperature superconductors as they exhibit multiband character and transition temperatures up to around 55 K. Investigating Fe-based superconductors thus promises answers to fundamental questions concerning the Cooper pairing mechanism, competition between magnetic and superconducting phases, and a wide variety of electronic correlation effects. The question addressed in this review is, however, is this new class of superconductors also a promising candidate for technical applications? Superconducting film-based technologies range from high-current and high-field applications for energy production and storage to sensor development for communication and security issues and have to meet relevant needs of today's society and that of the future. In this review we will highlight and discuss selected key issues for Fe-based superconducting thin film applications. We initially focus our discussion on the understanding of physical properties and actual problems in film fabrication based on a comparison of different observations made in the last few years. Subsequently we address the potential for technological applications according to the current situation.

Detection of antiferromagnetic ordering in heavily doped LaFeAsO(1-x)H(x) pnictide superconductors using nuclear-magnetic-resonance techniques.

We studied double superconducting (SC) domes in LaFeAsO(1-x)H(x) by using 75As and 1H nuclear-magnetic-resonance techniques and unexpectedly discovered that a new antiferromagnetic (AF) phase follows the double SC domes on further H doping, forming a symmetric alignment of AF and SC phases in the electronic phase diagram. We demonstrated that the new AF ordering originates from the nesting between electron pockets, unlike the nesting between electron and hole pockets, as seen in the majority of undoped pnictides. The new AF ordering is derived from the features common to high-Tc pnictides; however, it has not been reported so far for other high-Tc pnictides because of their poor electron doping capability.

s-wave superconductivity in the noncentrosymmetric W3Al2C superconductor: an NMR study.

We report on a microscopic study of the noncentrosymmetric superconductor W3Al2C (withTc= 7.6 K), mostly by means of27Al- and13C nuclear magnetic resonance (NMR). Since in this material the density of states at the Fermi level is dominated by the tungsten's 5dorbitals, we expect a sizeable spin-orbit coupling (SOC) effect. The normal-state electronic properties of W3Al2C resemble those of a standard metal, but with a Korringa product 1/(T1T) significantly smaller than that of metallic Al, reflecting the marginal role played bys-electrons. In the superconducting state, we observe a reduction of the Knight shift and an exponential decrease of the NMR relaxation rate 1/T1, typical ofs-wave superconductivity (SC). This is further supported by the observation of a small but distinct coherence peak just belowTcin the13C NMR relaxation-rate, in agreement with the fully-gapped superconducting state inferred from the electronic specific-heat data well belowTc. The above features are compared to those of members of the same family, in particular, Mo3Al2C, often claimed to exhibit unconventional SC. We discuss why, despite the enhanced SOC, W3Al2C does not show spin-triplet features in its superconducting state and consider the broader consequences of our results for noncentrosymmetric superconductors in general.

Metamagnetic behavior and Kondo breakdown in heavy-fermion CeFePO.

We report that nonmagnetic heavy-fermion (HF) iron oxypnictide CeFePO with two-dimensional XY-type anisotropy shows a metamagnetic behavior at the metamagnetic field H(M)≃4 T perpendicular to the c axis and that a critical behavior is observed around H(M). Although the magnetic character is entirely different from that in other Ce-based HF metamagnets, H(M) in these metamagnets is linearly proportional to the inverse of the effective mass, or to the temperature where the susceptibility shows a peak. This finding suggests that H(M) is a magnetic field breaking the local Kondo singlet, and the critical behavior around H(M) is driven by the Kondo breakdown accompanied by the Fermi-surface instability.

Single crystal growth of nanoporous C12A7:e- by controlling melt state.

It has been known that electron doped 12CaO x 7Al2O3 (C12A7:e-, electride) single crystals, which are composed of a closed-packed periodic quantum dot structure, may be prepared by strong reduction of the precursor C12A7:O2-, but direct single crystal growth of the C12A7:e- from the melt state has never been achieved to date. We report the melt state of polycrystalline electride in pure dry Ar atmosphere at temperatures of 1290 approximately 1500 degrees C, which leads to the direct single crystal growth of the C12A7:e- from the melt. The electride single crystals with a diameter of 7 mm and a length of 43 mm have been grown by a floating zone method, where a polycrystalline electride feed and an electride single crystal seed rod were employed. The electron concentration in the crystal increased up to approximately 1.0 x 10(20) cm(-3) as the growth proceeded. The present findings suggest that electron-entrapped local structure may exist in the melt and the electrons may act as a template for the formation of C12A7 electride in the solidification process of the C12A7 lattice.

A novel red-emitting K2Ca(PO4)F:Eu2+ phosphor with a large Stokes shift.

We report a K2CaPO4F:Eu2+ phosphor with a new crystal structure. This phosphor has a large Stokes shift and converts near-ultraviolet light to red luminescence without absorption of other visible light. The mechanism was elucidated by applying a constrained density functional theory to the solved crystal structure.

Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity.

OBJECTIVE: The aim of this study was to identify the best sedation/analgesia protocol for laser photocoagulation (PC) of retinopathy of prematurity (ROP). STUDY DESIGN: This multicenter observational study included five hospitals, each using a specific sedation/analgesia protocol: local anesthesia with oxybuprocaine hydrochloride (Group L); intravenous pentazocine (Group P); intravenous fentanyl (Group F); air, oxygen and sevoflurane (AOS) inhalation (Group I). The groups were compared for pain responses, vital signs and adverse events. RESULTS: Heart rates and systemic blood pressures were elevated by PC in Groups L and P and Groups L, P and F, respectively. Moreover, poor analgesic efficacy was recognized in Groups L, P and F. In contrast, Group I experienced hypothermia, enteral feeding intolerance and apnea more frequently. CONCLUSION: From the viewpoint of sedation/pain relief, AOS anesthesia should be the best protocol. However, considering all the various factors together, the most reasonable one can be varied based on the patient's condition and hospital.

Superconductivity at 52 K in hydrogen-substituted LaFeAsO(1-x)Hx under high pressure.

The 1111-type iron-based superconductor LnFeAsO(1-x)Fx (Ln stands for lanthanide) is the first material with a Tc above 50 K, other than cuprate superconductors. Electron doping into LaFeAsO by H, rather than F, revealed a double-dome-shaped Tc-x diagram, with a first dome (SC1, 0.0550 K observed in RE-1111 compounds (RE: Pr, Sm, and Gd) at ambient pressure is the merging of SC1 and SC2.

Different calcium phosphate bioglass ceramics implanted in rabbit cortical bone. An interface study.

In order to study the interface of calcium phosphate bioglass ceramics, cylinders of standard size were implanted in the tibiae of rabbits. The materials were evaluated by radiography, light microscopy and microradiography. Bioceramics with hydroxyapatite surface give rise to a closer contact with new bone than calcium phosphate glass ceramics.

Comparison of calcium phosphate glass ceramics with apatite ceramics implanted in bone. An interface study--II.

In order to study bone tissue interaction on calcium phosphate glass ceramics and on apatite ceramics, cylinders of standard size were implanted in the tibiae of rabbits. The materials were evaluated by radiography, light microscopy and microradiography. Apatite ceramics gave rise to a very close contact with new bone. Glass with an apatite surface evoked bone growth similar to that for apatite ceramics but with a loose contact while glass without an apatite surface gave rise to porous remodelling of new bone without close contact to the implant.

Oxygen-related intrinsic defects in glassy SiO2: interstitial ozone molecules

Interstitial O3 molecules in 7.9 eV photon-irradiated silica are identified. Their optical absorption band at 4.8 eV nearly coincides with the 4.8 eV band of nonbridging oxygen hole centers. The O3-related band is distinguished by a smaller halfwidth (0.84 vs 1. 05 eV), by susceptibility to ultraviolet bleaching, by lack of correlation to the 1.9 eV luminescence band, and by rise of a singlet O2 luminescence band at 0.974 eV during photobleaching. This identification solves a long controversy on the nature of optical bands in silica and gives a tool for studying the mobility of atomic oxygen in SiO2.

Effects of growth conditions on thymidine nucleotide pools in Escherichia coli.

The cellular levels of thymidine nucleotide derived from [3H]thymine or [3H]thymidine were followed under various environmental conditions with a thymine-requiring mutant of Escherichia coli. It was shown that the pool sizes varied greatly with the growth conditions; that is, with growth temperature, inhibition of DNA synthesis of replacement of thymine with thymidine. In the strain used here, the level of compound X, presumably dTDP-sugar, was very much higher than those of other thymidine nucleotides. It is suggested that the conversion of thymine to thymidine is rate-limiting, while the conversions of thymidine to dTMP, and of dTMP to dTDP are more rapid than other steps in the salvage pathway of thymidine nucleotide.

Peroxidase-catalyzed generation of catechin oligomers that inhibit glucosyltransferase from Streptococcus sobrinus.

Oolong tea extract (OTE) and the purified polymeric polyphenols from OTE have been found to inhibit glucosyltransferase (GTase) of mutans streptococci. In view of the partial fermentation characteristic of oolong tea, we describe here an in vitro model reaction system to produce partially fermented products of D-(+)-catechin or green tea extract (GTE) using horseradish peroxidase. A dimeric catechin molecule was identified as dehydro-dicatechin A by instrumental analyses. The molecular size of some oligomeric catechins was estimated by the elution profile with HPLC. These catechin oligomers markedly inhibited GTase from Streptococcus sobrinus 6715. As the degree of polymerization of catechin or GTE increased, GTase was inhibited more effectively. These results suggest that polymeric polyphenols found in OTE are synthesized by partial fermentation due to oxidases/peroxidases present in tea leaves.

Synthesis of S-(carboxymethyl)-D-cysteine by 3-chloro-D-alanine chloride-lyase of pseudomonas putida CR 1-1.

S-(Carboxymethyl)-D-cysteine, which is an important component of semisynthetic cephalosporin, MT-141, was enzymatically synthesized. S-(Ethoxy-carbonyl-methyl)-D-cystein was synthesized from 3-chloro- D-alanine and ethyl thioglycolate by the beta-replacement reaction of 3-chloro-D-alanine chloride-lyase from Pseudomonas putida CR 1-1 and subsequently hydrolyzed by alkali. The synthesized S-(carboxymethyl)-D-cysteine was isolated from a large scale reaction mixture and identified physicochemically. The reaction conditions for the synthesis of S-(ethoxycarbonylmethyl)-D-cysteine were optimized using resting cells of P. putida CR 1-1.

Crossover between magnetism and superconductivity in LaFeAsO with low H-doping level.

By making a systematic study of the hydrogen-doped LaFeAsO system by means of dc resistivity, dc magnetometry, and muon-spin spectroscopy, we addressed the question of universality of the phase diagram of rare-earth-1111 pnictides. In many respects, the behaviour of LaFeAsO(1-x)H(x) resembles that of its widely studied F-doped counterpart, with H(-) realizing a similar (or better) electron doping in the LaO planes. In an x = 0.01 sample we found a long-range spin-density wave (SDW) order with TN = 119 K, while at x = 0.05 the SDW establishes only at 38 K and, below Tc = 10 K, it coexists at a nanoscopic scale with bulk superconductivity. Unlike the abrupt magnetic-superconducting transition found in the La-1111 compound, the presence of a crossover region makes the H-doped system qualitatively similar to other Sm-1111, Ce-1111, and Nd-1111 families.