LC–MS–MS Study of the Pharmacokinetics of a 9-β-Dihydro-9,10-O-acetal Derivative of Docetaxel in Rats and Beagle Dogs

SHR110008 is a representative 9-β-dihydro-9,10-O-acetal taxane with greater anticancer activity and less toxicity than docetaxel. To support a preclinical study of its pharmacokinetics and to predict the effect of 9-β-dihydro-9,10-O-acetal modification on its pharmacokinetic properties, we have developed a sensitive and rapid liquid chromatographic–tandem mass spectrometric method for quantitative analysis of SHR110008 in rat and dog plasma. Plasma was extracted with ethyl acetate. The analytes were separated on a 150 × 4.6 mm i.d., 5 μm particle, reversed-phase C₁₈ column with 90:10 (v/v) methanol–0.1% formic acid as mobile phase at a flow rate of 0.3 mL min⁻¹. Detection was performed by triple-quadrupole tandem mass spectrometry in selected reaction monitoring (SRM) mode with an electrospray ionization source. The precursor-to-product ion transition m/z 933 → 142 was used. The method was validated for accuracy and precision, and linearity in the two matrices was good. Lower limits of quantification (LLOQ) in rat and dog plasma were 5 and 2 ng mL⁻¹, respectively. There were no stability-related problems in the procedure for analysis of SHR110008. The method was successfully used in a preclinical study of the pharmacokinetics of SHR110008 in rats and beagle dogs. The pharmacokinetics of SHR110008 were non-linear in rats and dogs. The elimination half-life ranged from 5.18 to 7.32 h for the rats and from 6.42 to 8.42 h for the dogs.

     

Brualdi-Anstee猜想的反例

1980年,Brualdi和Anstte独立地提出了下述 猜想:设的R,R,S,S是非负整向量,则存在矩阵A∈u(R,S),B∈u(R,S)使A B∈u(R R,S S)的充要条件是u(R,S),u(R,S) 和u(R R ,S S)均非空。     

Vibration characteristics of a hydraulic generator unit rotor system with parallel misalignment and rub-impact

The object of this research aims at the hydraulic generator unit rotor system. According to fault problems of the generator rotor local rubbing caused by the parallel misalignment and mass eccentricity, a dynamic model for the rotor system coupled with misalignment and rub-impact is established. The dynamic behaviors of this system are investigated using numerical integral method, as the parallel misalignment, mass eccentricity and bearing stiffness vary. The nonlinear dynamic responses of the generator rotor and turbine rotor with coupling faults are analyzed by means of bifurcation diagrams, Poincaré maps, axis orbits, time histories and amplitude spectrum diagrams. Various nonlinear phenomena in the system, such as periodic, three-periodic and quasi-periodic motions, are studied with the change of the parallel misalignment. The results reveal that vibration characteristics of the rotor system with coupling faults are extremely complex and there are some low frequencies with large amplitude in the 0.3–0.4× components. As the increase in mass eccentricity, the interval of nonperiodic motions will be continuously moved forward. It suggests that the reduction in mass eccentricity or increase in bearing stiffness could preclude nonlinear vibration. These might provide some important theory references for safety operating and exact identification of the faults in rotating machinery.     

Linguistic modelling and information coarsening based on prototype theory and label semantics

The theory of prototypes provides a new semantic interpretation of vague concepts. In particular, the calculus derived from this interpretation results in the same calculus as label semantics proposed by Lawry. In the theory of prototypes, each basic linguistic label L has the form ‘about P’, where P is a set of prototypes of L and the neighborhood size of the underlying concept is described by the word ‘about’ which represents a probability density function δ on [0,+∞). In this paper we propose an approach to vague information coarsening based on the theory of prototypes. Moreover, we propose a framework for linguistic modelling within the theory of prototypes, in which the rules are concise and transparent. We then present a linguistic rule induction method from training data based on information coarsening and data clustering. Finally, we apply this linguistic modelling method to some benchmark time series prediction problems, which show that our linguistic modelling and information coarsening methods are potentially powerful tools for linguistic modelling and uncertain reasoning.     

Design of thermo-optic tunable optical filter based on Si/Air DBR and polymer Fabry–Perot microcavity in SOI

An integrated tunable optical filter (TOF) based on thermo-optic effect in silicon on insulator (SOI) rib waveguide is designed and simulated. The device is comprised of two high refractivity contrast Si/Air stacks, functioning as high reflectivity of DBRs (distributed Bragg reflectors) and separating by a variable refractive index polymer Fabry–Perot (F–P) cavity. The designed device exhibits Q = 24077, FWHM = 0.065 nm and finesse = 566. Wavelength tuning is achieved through thermal modulation of refractive variation of the cavity. As the cavity polymer is heated, the refractive index of the cavity decreases. When the temperature of cavity polymer changes within 105, the central wavelength gets a continuous 35 nm shift from 1530 nm to 1565 nm, which can operate the whole C-band in the WDM (wavelength division multiplexing) networks. Moreover, by calculating, the tuning sensitivity is about 0.33 nm/°C. Owing to the compact size and excellent characteristics of integration, the proposed component has a promising utilization in spectroscopy and optical communication.     

模糊技术在可靠性工程中的应用

本文主要介绍模糊集合理论和技术在可靠性工程中的应用现状及其发展趋势，尤其是在系统故障诊断，故障树分析（ＦＴＡ）系统可靠性分配，人的可靠性，软件可靠性，结构可靠性以及系统安全性工程中的应用和技术关键，并从工程应用的需要出发针对存在问题预测和提出各种解决途径。     

An unstructured finite volume model for dam‐break floods with wet/dry fronts over complex topography

A robust, well‐balanced, unstructured, Godunov‐type finite volume model has been developed in order to simulate two‐dimensional dam‐break floods over complex topography with wetting and drying. The model is based on the nonlinear shallow water equations in hyperbolic conservation form. The inviscid fluxes are calculated using the HLLC approximate Riemann solver and a second‐order spatial accuracy is achieved by implementing the MUSCL reconstruction technique. To prevent numerical oscillations near shocks, slope‐limiting techniques are used for controlling the total variation of the reconstructed field. The model utilizes an explicit two‐stage Runge–Kutta method for time stepping, whereas implicit treatments for friction source terms. The novelties of the model include the flux correction terms and the water depth reconstruction method both for partially and fully submerged cells, and the wet/dry front treatments. The proposed flux correction terms combined with the water depth reconstruction method are necessary to balance the bed slope terms and flux gradient in the hydrostatical steady flow condition. Especially, this well‐balanced property is also preserved in partially submerged cells. It is found that the developed wet/dry front treatments and implicit scheme for friction source terms are stable. The model is tested against benchmark problems, laboratory experimental data, and realistic application related to dam‐break flood wave propagation over arbitrary topography. Numerical results show that the model performs satisfactorily with respect to its effectiveness and robustness and thus has bright application prospects. Copyright © 2010 John Wiley & Sons, Ltd.     

Thermally assisted switching in FePt single-domain particles with a Gaussian distribution of temperature

Magnetic nanoscale systems,including nanodots,nanofibers,nanowires and nanoparticles,are currently attracting great interest due to their interesting physical and promising applications in various fields,such as magnetic recording,sensors,target drugs and catalysts,as well as others.To achieve ultrahigh recording density,the method of heat assisted magnetic recording(HAMR) has been introduced.In this work,with the help of a Monte Carlo method,the mechanisms of thermally assisted magnetization switching in F...     

An Improved K-Means Algorithm Based on Evidence Distance

The main influencing factors of the clustering effect of the k-means algorithm are the selection of the initial clustering center and the distance measurement between the sample points. The traditional k-mean algorithm uses Euclidean distance to measure the distance between sample points, thus it suffers from low differentiation of attributes between sample points and is prone to local optimal solutions. For this feature, this paper proposes an improved k-means algorithm based on evidence distance. Firstly, the attribute values of sample points are modelled as the basic probability assignment (BPA) of sample points. Then, the traditional Euclidean distance is replaced by the evidence distance for measuring the distance between sample points, and finally k-means clustering is carried out using UCI data. Experimental comparisons are made with the traditional k-means algorithm, the k-means algorithm based on the aggregation distance parameter, and the Gaussian mixture model. The experimental results show that the improved k-means algorithm based on evidence distance proposed in this paper has a better clustering effect and the convergence of the algorithm is also better.