Influence of CYP3A5 polymorphism on tacrolimus blood concentrations in renal transplant patients

Objective Tacrolimus is an immunosuppressive drug with narrow therapeutic range and wide interindividual variation in its pharmacokinetics. Tacrolimus is a substrate of cytochrome P450(CYP)3A5. The aim of this study was to evaluate whether the A6986G polymorphism is associated with tacrolimus concentration /dose ratio. Methods Fifty-two Chinese renal transplant patients were enrolled in this study. Their body weight, dosage and concentration of tacrolimus were observed. CYP3A5 genotype was determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results A significant association was found between tacrolimus levels per dose/kg/d and CYP3A5 gene A6986G polymorphism (P<0.001). The CYP3A5 * 3 * 3 patients have a significantly higher tacrolimus level/dose than CYP3A5 * 1 * 1 and CYP3A5 * 1 * 3. Conclusions CYP3A5 gene A6986G polymorphism is associated with tacrolimus pharmacokinetics and dose requirements. Pharmacogenetic methods could be employed prospectively to help the dose selection and to individualize immunosuppressive therapy according to the result. Foundation item: Project (03GZ3072) supported by the Science and Technology Department of Hunan Province; project (2004035206) supported by the China Postdoctoral Foundation and project (30300383) supported by the National Natural Sciences Foundation of China     

Direct adaptive control of nonminimum phase systems using integralaction

A direct adaptive control scheme is proposed for nonminimum-phase systems in which controller parameters are estimated from the recursive least-squares algorithm and additional auxiliary parameters are obtained from the proposed polynomial identity. A local convergence is guaranteed without any extra condition. Integral action is incorporated into the adaptive controller to eliminate the steady-state error and to satisfy a condition of the unique solution for the polynomial identity. The control law used in this scheme is based on the set-point-on-I-only proportional-integral-derivative (PID) structure     

Re-examination of analytical models for microwave scattering from deciduous leaves

This paper presents an examination of classical scattering models for radar cross sections of deciduous leaves, such as the generalised Rayleigh-Gans (GRG) model and the physical optics (PO) model. The PO model employs the resistive sheet approximation in this study. The validity regions of the analytical models for microwave scattering from deciduous leaves are investigated by comparison with the precise numerical results of the method of moment. It was found that the GRG and PO models extend their validity regions for estimating the scattering amplitudes as the thickness of a lossy dielectric disk decreases. The GRG and PO models can be used alternatively for computing the scattering matrices of natural deciduous leaves at microwave frequencies regardless of the size of the leaves, because of the very small thickness of the leaves (0.2-0.4 mm)     

Efficient and stable field emission from the oxidized porous polysilicon using Pt/Ti multilayer electrode

The field emission characteristics of an oxidized porous polysilicon (OPPS) were investigated with a Pt/Ti multilayer electrode, which showed highly efficient and stable electron emission characteristics compared with those of conventional Au/NiCr electrodes. The thin Ti layer played an important role in promoting the adhesion of Pt to SiO₂ surface and the distribution of the electric field on the OPPS surface. Additionally, the Ti layer efficiently blocked the diffusion of emitter metal, which resulted in more reliable emission characteristics.     

Effects of gallia additions on sintering behavior of gadolinia-doped ceria

The effects of gallia additions on the sintering behavior of gadolinia-doped ceria were systematically investigated from the following aspects: the variation in sintered density, the variation in grain size, and the existing forms of Ga₂O₃ in CeO₂.Sintered density increased with increasing Ga₂O₃ content up to 5 mol.% and then it decreased with further addition of Ga₂O₃. Grain size also increased with increasing Ga₂O₃ content up to 5 mol.% and then decreased with further addition of Ga₂O₃. Decrease in grain size was caused by a pinning effect of Ga₂O₃ precipitation at grain boundaries. Lattice constant decreased with increasing Ga₂O₃ content up to 5 mol.%. This decrease will be due to the substitution of smaller Ga³⁺ ions for Ce⁴⁺ ions in the CeO₂ structure. According to the results obtained from scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses, the solubility limit of Ga₂O₃ in Ce_0.8Gd_0.2O_1.9 ceramics can be estimated to be nearly 5 mol.%. The addition of Ga₂O₃ up to the solubility limit was found to promote the sintering properties of Gd₂O₃-doped CeO₂.     

基于移动代理的安全研究

移动代理计算模式较传统的分布式计算模式有明显的优势,而伴随它有诸多安全问题出现,这使得它没有得到十分广泛的应用。本文针对代理自身的安全问题,分析了代理可能受到的攻击,并提出了一个安全方案。     

Synthesis and characterization of a series of star-branched poly(ε-caprolactone)s with the variation in arm numbers and lengths

A series of star-branched poly(ε-caprolactone)s (SPCLs) was synthesized with structural variation of the arm numbers and lengths through ring-opening polymerization under bulk condition. Arm numbers were varied to be 3, 4, and 6 by using multifunctional initiating cores such as trimethylol propane, pentaerythritol, and dipentaerythritol, respectively. The lengths of the poly(ε-caprolactone) arms were varied by controlling the molar ratio of monomer-to-initiating hydroxyl group molar ratio ([CL]₀/[-OH]₀=5, 10, 15). Molecular weights were determined by both ¹H NMR end-group analysis and MALDI-TOF mass spectrometry, which gave reasonably consistent values. On the contrary, the GPC method failed to give accurate values of molecular weight of SPCLs due to the discrepancy with the linear standard. The branching architecture of SPCLs was evaluated by the branching ratio, g, which is the ratio of the mean-square radius of SPCL to that of liner counterpart, linear poly(ε-caprolactone) (LPCL), which is of the same chemistry and having the same molecular weight. The radii of gyration of SPCLs and LPCLs were determined using small-angle X-ray scattering (SAXS) from the initial slopes of Zimm plots, represented as 1/I(q) vs q² with I(q) and q being the scattered intensity and scattering vector, respectively. The g values were observed to decrease with increasing arm numbers, indicating more compact molecular structure for SPCLs with higher arm numbers, while no such effect was observed for arm length variation. Thermal properties as well as the degree of crystallinity of SPCLs were found to be also dependent on structural variations. The melting points and the degradation temperatures were observed to increase with increasing arm lengths but with constant arm number. On the other hand, arm number variation with constant arm length gave no such changes to the thermal transitions of SPCLs. However, for the SPCLs with equivalent molecular weights, the degree of crystallinity was found to decrease with increasing arm numbers.     

Protein binding study of isoflavone, perillyl alcohol and S-ibuprofen by high-performance frontal analysis

High-performance frontal analysis (HPFA) was used for a protein binding study of isoflavones (daidzein, genistin, and genistein), enantiomers of perillyl alcohol and S-ibuprofen to human serum albumin (HSA). The analyses were performed on a Develosil and Inertsil 100-Diol-5 column (10 cm×4.6mm). Sodium phosphate solution (pH 7.4, ionic strength 0.17) was used as the mobile phase at a flow rate of 1 ml/min. To ensure the drug to be eluted as a trapezoidal peak with a plateau, injection volumes were each fixed up the zonal profile with an evident plateau appears. The unbound drug concentration was determined from a plateau height of the plateau region after that experimental data were fitted by Scatchard equation. The binding constants (K) and total binding affinities (nK) of drugs to HSA were calculated, respectively.