Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of navitoclax

The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax-d8, was achieved with a Waters Acquity UPLC BEH C₁₈ column using isocratic flow over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5–5,000 ng/ml and proved to be accurate (89.5–104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at −70°C was at least 43 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose.     

Coordination and extraction properties of new bis- and tetrakis(diphenylphosphoryl)-substituted pyrazines towards f-block elements

2,3-Bis- and 2,3,5,6-tetrakis(diphenylphosphoryl)-substituted pyrazines have been synthesized from the corresponding polychloropyrazines and ethyl diphenylphosphinite. They may serve as new N,O-bidentate organophosphorus ligands for extraction and recovery of f-block metal ions from nitric acid solutions.     

Observation of unusual Griffith’s phase behavior in quadruple perovskite oxide CaCu3Mn4O12 (CCMO) synthesized through chemical route

The CaCu₃Mn₄O₁₂ (CCMO) ceramic was successfully synthesized through the chemical route. The phase formation was confirmed by the X-ray diffraction pattern. Thermogravimetric (TGA), FT-IR, SEM, TEM, EDX, and XPS analysis were performed for investigation of the thermal behavior, phase identification, microstructural analysis, elemental analysis and oxidation state of the CCMO ceramic respectively. FT-IR spectra confirmed the existence of MnO₆ octahedral in body-centered cubic (BCC) complex perovskite oxide that resembles the CaCu₃Ti₄O₁₂ structure. The average particle size was observed by TEM in the range between 100 and 200 nm. AFM shows the average roughness of the surface was found to be in the range of 30 ± 5 nm. XPS and EDX studies confirmed the purity and oxidation state of the CCMO ceramic. The synthesized material shows very interesting unique Griffith’s phase (T_G) results that arise disorder in magnetic susceptibility in which ferromagnetic transition was to be observed in the paramagnetic region.     

Metabolites identification of oil palm roots infected with Ganoderma boninense using GC–MS-based metabolomics

An approach to metabolomics profiling of non-infected and Ganoderma boninense (G. boninsense) infected oil palm roots crude extracts that utilize gas chromatography-mass spectrometry (GC–MS) and multivariate statistics of principal component analysis (PCA) have been tested. This combination has provided a rapid approach in investigating the changes in the metabolite variations of non-infected and infected oil palm roots at 14 and 30 days post-infection. The extracts were prepared by using 80% (v/v) of methanol. In identifying the metabolites responsible for each differentiation, PCA model was generated in loading bi-plot. Dimethyl benzene-1,4-dicarboxylate, methyl 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate, ergost-5-en-3-ol, (3β), stigmast-5-en-3-ol, (3β), stigmasterol, methyl hexadecanoate, methyl (9Z,12Z)-octadeca-9,12-dienoate, methyl octadecanoate, 2-(hydroxymethyl)-2-nitropropane-1,3-diol, methyl (Z)-octadec-6-enoate and (E)-icos-5-ene were found more abundant in G. boninense infected roots than in non-infected roots. Steroidal compounds and fatty acid derivatives which has been determined in the non-infected and G. boninense infected roots regulate a variety of responses to the G. boninense. The abundant of these metabolites in G. boninense infected roots are due to the crucial roles in pathogen defence.     

Stochastic method to control Mycobacterium tuberculosis epidemic

We study the origin of TB (tuberculosis) epidemic and complex distributions of various populations of TB infection within the stochastic framework. The stochastic nature of this disease infection could be linked to the stochastic behaviour at genome level which is exhibited in SNP (single nucleotide polymorphism) distributions of experimentally identified hotspot driver genes. Our results show the emergence of random clusters, and well-defined discrete domains of the respective species populations in the model driven by demographic stochasticity and intrinsic complex species interaction. The multifractal analysis of the time series of the species populations indicate that TB epidemic could be mainly caused by contact communication and is directional. We propose that any TB epidemic may have high chance of approximately periodic recurrence and can be controlled by optimizing some of the parameters involved in the system modelling.     

中国聚变工程实验堆真空室超压保护系统中爆破片的选型与计算

参照相关标准，对聚变装置真空室超压保护系统(VVPSS)中爆破片进行了选型。结合VVPSS的工作要求，完成了爆破片的设计计算，初步得到爆破片直径为882mm，厚度为1mm。利用有限元分析软件对多种型号爆破片进行结构分析比较，最终选用了反拱环向开缝型爆破片。对最终选定的爆破片进行优化设计，使其达到设计要求。     

On the integrability aspects of nonparaxial nonlinear Schrödinger equation and the dynamics of solitary waves

The integrability nature of a nonparaxial nonlinear Schrödinger (NNLS) equation, describing the propagation of ultra-broad nonparaxial beams in a planar optical waveguide, is studied by employing the Painlevé singularity structure analysis. Our study shows that the NNLS equation fails to satisfy the Painlevé test. Nevertheless, we construct one bright solitary wave solution for the NNLS equation by using the Hirota's direct method. Also, we numerically demonstrate the stable propagation of the obtained bright solitary waves even in the presence of an external perturbation in a form of white noise. We then numerically investigate the coherent interaction dynamics of two and three bright solitary waves. Our study reveals interesting energy switching among the colliding solitary waves due to the nonparaxiality.     

Prediction of resolvent mode shapes in supersonic turbulent boundary layers

This work applies resolvent analysis to compressible zero-pressure-gradient turbulent boundary layers with freestream Mach numbers between 2 and 4, focusing exclusively on large scale motions in the outer region of the boundary layer. We investigate the effects of Mach number on predicted flow structures, and in particular, look at how such effects may be attributed to changes in mean properties. By leveraging the similarity between the compressible and incompressible resolvent operators, we show that the shape of the streamwise velocity and temperature components of resolvent response modes in the compressible regime can be approximated by applying ideas from wavepacket pseudospectral theory to a simple scalar operator. This gives a means of predicting the shape of resolvent mode components for compressible flows without requiring the singular value decompositions of discretized operators. At a Mach number of 2, we find that accurate results are obtained from this approximation when using the compressible mean velocity profile. At Mach numbers of 3 and 4, the quantitative accuracy of these predictions is improved by also considering a local effective Reynolds number based on the local mean density and viscosity.     

HL-2M偏滤器结构动力学分析

 用有限元软件分析了动载荷作用下的偏滤器结构动力学响应。通过对动力学和静力学计算结果的对比，确定载荷的动态放大因子。计算结果表明，所设计的偏滤器结构在瞬态电磁力载荷作用下能满足设计准则的要求。     

基于像差特征分析的变焦光学系统装调

提出了一种基于像差特征分析的变焦系统共轴性装调方法。针对某型20倍变焦光学系统的装调，在分析变焦光学系统装调要求的基础上，通过采用光学定心加工技术，提高变焦系统各镜组内光学元件的同轴度；采用Zygo干涉仪，检测变焦系统在长短焦位置的像差特性分布；借助CodeV软件仿真计算各光学元件在系统中的公差灵敏度分布，并确定产生像差影响的敏感光学元件；在中心偏测量仪上，完成最终光学系统像质的调整。此外，还设计了一种变焦光学系统各动组间同轴度调试装置，对变焦相机主镜筒机械内孔轴线与直线导轨的平行性进行了精确测量，保证了动组组元光轴的同轴精度。装调结果表明:变焦系统成像质量有明显改善，像面一致性得到保证，长短焦轴上传递函数值分别优于技术要求值0.45和0.55，长短焦轴外0.7视场传递函数值优于0.25和0.35，实现了高精度装调，验证了该方法的可靠性。