The structure of graphite fluoride, (C2F)n has been investigated by X‐ray analyses, solid state 19F‐n.m.r., and electron microscopy for well characterized and crystallized samples obtained from natural graphite or HOPG (highly oriented pyrolytic graphite). On the basis of the present results and structural properties derived from previous works, (C2F)n has a layered structure of stage‐2 which belongs hexagonal to the system with C3h symmetry. Detailed discussions on the symmetry both for (CF)n and (C2F)n have led to possible stacking sequences each unit cell of graphite fluoride should require. The ideal structure of (C2F)n is a hexagonal crystal lattice with a = b = 2.5 Å; c = 16.2 Å, and a plausible stacking sequence of AB/B′A′/ with Ic (identity period) = 8.09 Å. The layered structure of (CF)n is of stage‐1 with A/A′/ stacking sequence.

Millisecond kinetics of photo-darkening/bleaching in xGe45Se55-(1−x)As45Se55 chalcogenide amorphous films J. Appl. Phys. 112, 053105 (2012) Analysis of sub-stoichiometric hydrogenated silicon oxide films for surface passivation of crystalline silicon solar cells J. Appl. Phys. 112, 054905 (2012) Phase evolution and room-temperature photoluminescence in amorphous SiC alloy J. Appl. Phys. 111, 103526 (2012) Resistive switching properties of amorphous Pr0.7Ca0.3MnO3 films grown on indium tin oxide/glass substrate using pulsed laser deposition method Silica glass with dispersed colloid Au particles was synthesized by ion implantation. Colloid Au particles were found to grow through an Ostwald ripening mechanism controlled by diffusion in the silica glass. The third-order nonlinear optical susceptibility xc3) of this glass was found to be proportional to the fourth power of the radius of the colloid particles or the fourth power of the absorption coefficient at the peak of a plasmon band when the total volume of the colloid particles was constant. Furthermore, x (3) of the glass was inversely proportional to the third power of the total volume of colloid particles when the absorption coefficient of the plasmon band was constant.

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Ischemia‐reperfusion injury (IRI) is believed to contribute to graft dysfunction after liver transplantation (LT). However, studies on IRI and the impact of early allograft dysfunction (EAD) in IRI grafts are limited. Histological IRI was graded in 506 grafts from patients who had undergone LT and classified based on IRI severity (no, minimal, mild, moderate, and severe). Of the 506 grafts, 87.4% had IRI (no: 12.6%, minimal: 38.1%, mild: 35.4%, moderate: 13.0%, and severe: 0.8%). IRI severity correlated with the incidence of EAD and graft survival at 6 months. Longer cold/warm ischemia time, recipient/donor hypertension, and having a male donor were identified as independent risk factors for moderate to severe IRI. Among 70 grafts with moderate to severe IRI, 42.9% of grafts developed EAD, and grafts with EAD had significantly inferior survival compared to grafts without EAD. Longer cold ischemia time and large droplet macrovesicular steatosis (≥20%) were identified as independent risk factors for EAD. Our study demonstrated that increased IRI severity was correlated with inferior short‐term graft outcomes. Careful consideration of IRI risk factors during donor‐recipient matching may assist in optimizing graft utilization and LT outcomes. Furthermore, identification of risk factors of IRI‐associated EAD may guide patient management and possible timely graft replacement.

Au microcrystal-doped glass films with high optical nonlinearity were prepared by the sol-gel method with dip-coating using NaAuCl4•E2H2O and tetraethyl or thosilicate (TEOS) as starting materials. The glass film with an Au/Si atomic ratio of 0.01 was successful ly prepared. The nonlinear susceptibility ƒÔ(3) of the film was 7.7•~10-9esu. Microcrystals with a radius of about 7A and of about 30A coexisted in the glass film. The nonlinear susceptibility of Au microcrystals itself in the film, ƒÔm(3), was 1.0•~10-7esu and was two times larger than that observed in Au-doped glasses pre pared by the melting method. Subsequent heat treat ment of the films at 1000•Ž changed the absorption spectra and decreased ƒÔ(3) by a factor of two. The atom ic ratio of Au/Si was able to be increased to 0.04.

Liver ischemia reperfusion injury (IRI) is an important problem in liver transplantation. Thrombomodulin (TM), an effective drug for disseminated intravascular coagulation, is also known to exhibit an anti-inflammatory effect through binding to the high-mobility group box 1 protein (HMGB-1) known as a proinflammatory mediator. We examined the effect of recombinant human TM (rTM) on a partial warm hepatic IRI model in wild-type (WT) and tolllike receptor 4 (TLR-4) KO mice focusing on the HMGB-1/TLR-4 axis. As in vitro experiments, peritoneal macrophages were stimulated with recombinant HMGB-1 protein. The rTM showed a protective effect on liver IRI. The rTM diminished the downstream signals of TLR-4 and also HMGB-1 expression in liver cells, as well as release of HMGB-1 from the liver. Interestingly, neither rTM treatment in vivo nor HMGB-1 treatment in vitro showed any effect on TLR-4 KO mice. Parallel in vitro studies have confirmed that rTM interfered with the interaction between HMGB-1 and TLR-4. Furthermore, the recombinant N-terminal lectin-like domain 1 (D1) subunit of TM (rTMD1) also ameliorated liver IRI to the same extent as whole rTM. Not only rTM but also rTMD1 might be a novel and useful medicine for liver transplantation. This is the first report clarifying that rTM ameliorates inflammation such as IRI in a TLR-4 pathway-dependent manner.Abbreviations: DIC, disseminated intravascular coagulation; dUTP, deoxyuridine triphosphate; Erk, extracellular signal-regulated kinase; GAPDH, glyceraldehyde-3-phosphate; HMGB-1, high-mobility group box 1 protein; IRF-3, interferon regulatory factor 3; IRI, ischemia reperfusion injury; JNK, c-Jun NH2-terminal kinase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MD-2, myeloid differentiation factor 2; Myd88, myeloid differentiation primary response 88; NF-jB, nuclear factor kappa B; NLRP-3, nod-like receptor protein 3; PI3K, phosphatidylinositol-3 0 -kinase; p-IjBa, phosphorylated inhibitory protein of NF-jB; qPCR, quantitative reverse-transcription polymerase chain reaction; rTMD1, recombinant N-terminal lectin-like domain 1 of thrombomodulin; rTM, recombinant human thrombomodulin; sALT, serum alanine aminotransferase; TLR-4, toll-like receptor 4; TM, thrombomodulin; TNF-a, tumor necrosis factor a; TUNEL, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling

ABSTRACT:To verify the availability of pharmacokinetic parameters in cynomolgus monkeys, hepatic availability (Fh) and the fraction absorbed multiplied by intestinal availability (FaFg) were evaluated to determine their contributions to absolute bioavailability (F) after intravenous and oral administrations. These results were compared with those for humans using 13 commercial drugs for which human pharmacokinetic parameters have been reported. In addition, in vitro studies of these drugs, including membrane permeability, intrinsic clearance, and p-glycoprotein affinity, were performed to classify the drugs on the basis of their pharmacokinetic properties. In the present study, monkeys had a markedly lower F than humans for 8 of 13 drugs. Although there were no obvious differences in Fh between humans and monkeys, a remarkable species difference in FaFg was observed. Subsequently, we compared the FaFg values for monkeys with the in vitro pharmacokinetic properties of each drug. No obvious FaFg differences were observed between humans and monkeys for drugs that undergo almost no in vivo metabolism. In contrast, low FaFg were observed in monkeys for drugs that undergo relatively high metabolism in monkeys. These results suggest that first-pass intestinal metabolism is greater in cynomolgus monkeys than in humans, and that bioavailability in cynomolgus monkeys after oral administration is unsuitable for predicting pharmacokinetics in humans. In addition, a rough correlation was also observed between in vitro metabolic stability and Fg in humans, possibly indicating the potential for Fg prediction in humans using only in vitro parameters after slight modification of the evaluation system for in vitro intestinal metabolism.Because the development of new drugs is a cost-and labor-intensive task, the selection of candidates with good pharmacokinetic profiles is becoming increasingly common. This practice minimizes the number of drug candidates dropped due to pharmacokinetic problems during the clinical phase (Wishart, 2007).When predicting human pharmacokinetics, the fraction absorbed (Fa), intestinal availability (Fg), and hepatic availability (Fh) are the main factors to consider. Fh prediction has become considerably accurate since several mathematical prediction models have been established, including the physiological model, well stirred model, parallel tube model, and dispersion model (Iwatsubo et al., 1996;Naritomi et al., 2001;De Buck et al., 2007). For FaFg, however, no quantitative prediction method has ever been established, although several qualitative prediction methods using human intestinal microsomes have been reported (Chiba et al., 1997;Shen et al., 1997;Fagerholm, 2007;Fisher and Labissiere, 2007;Yang et al., 2007). For these reasons, we have mainly used animal pharmacokinetic parameters to predict human FaFg in the drug discovery stage.It has been regarded as natural that monkey metabolism is the most similar to that of humans, and cynomolgus monkeys have been widely used in pharmacokinetic or drug-...