Development and full validation of an LC–MS/MS methodology to quantify capmatinib (INC280) following intragastric administration to rats

A highly sensitive, specific and simple LC–MS/MS method for quantification of capmatinib (INC280) in rat plasma was presented. The LC–MS/MS method was validated in terms of specificity and selectivity, linearity, accuracy and precision, matrix effect, extraction recovery, dilution integrity, carryover and stability as per the US Food and Drug Administration's bioanalytical method validation guideline. The validated assay was applied for quantification of capmatinib from a pharmacokinetic study in rats following oral administration at the doses of 1.0, 3.0 and 9.0 mg/kg. The calibration curve ranges from 1 to 2000 ng/ml with desirable linearity and r² > 0.99. The intra- and inter-batch accuracies were within 99.24–103.59 and 97.76–102.83% with coefficients of variation 5.08–7.36 and 3.18–4.99%, respectively. No significant interference was observed by endogenous peak at the retention time of capmatinib and IS. The assay was free from any matrix effect and showed precise recovery across the calibration curve range, and samples were stable under all experimental conditions. The validated assay was successfully applied to analyze plasma samples of pharmacokinetic study in rat to determine the concentration of capmatinib. In summary, a novel method for analyzing capmatinib in rat plasma has been successfully validated and is now being utilized for quantification of capmatinib from pre-clinical studies.     

A new spirofluorene-based nonplanar PBI-dyad and its utilization in the film-based photo-production of singlet oxygen

Traditional photosensitizers are predominantly based on various types of polypyrrole macrocycles, which are generally used in homogeneous and/or suspension states. In the present study, a new non-polypyrrole-based photosensitizer(LW-PBI) was developed via the introduction of a nonplanar spirofluorene into a derivative of perylene bisimides(PBI) containing two longalkyl chains. Photophysical studies demonstrated that the compound shows good solubility in common organic solvents, great photochemical stability, and high absorption efficiency in the visible light region. Due to containing of two energetically matchable, independent fluorescent units, the compound as prepared displays strong tendency to form non-fluorescent chargeseparated states under light irradiation in polar solvents. Based on the merits, LW-PBI was examined for its catalytic property in the photo-production of singlet oxygen in film state. Luckily, the compound is an effective photosensitizer in the generation of the active oxygen species as verified by its unique reaction with uric acid(UA). Further studies revealed that the effective photoproduction of singlet oxygen can be also realized via the utilization of a tiny and low-price LED lamp as a light source and as a film support. Detailed studies on the application of the conceptual device as a medical instrument for photodynamic therapy(PDT) are in progress.     

A New Method for the Synthesis of Oligo-peptides

It was discovered that polypeptides were formed by self-assembly of N,O-bis(trimethylsilyl)amino acids with the assistance of O-phenylene phosphorochloridate.^[1] There were three steps involved in the self organization reactions, the activation of amino acid, the elongation of peptide chain and the termination of the chain reaction,among which the activation of amino acid -the formation of imino (alkyl)acetoxyphosphoranes was the key step. The formation process of the penta-coordinated phosphorus intermediates was showed in scheme 1.^[2,3,4] Through further studies of the mechanism of self-assembly reaction, it was found that carbonyl groups of the intermediates attacked by the neuclophilic groups were direct reson of the formation of peptides. However, the peptides in the solution were very difficult to be separated and analyzed.     

A Configurationally Tunable Perylene Bisimide Derivative-based Fluorescent Film Sensor for the Reliable Detection of Volatile Basic Nitrogen towards Fish Freshness Evaluation

Rapid and real-time mon itoring of food quality plays critical roles in the food industry and for the gen era I public health.Herei n,we specially synthesized a new perylene bisimide(PBI)derivative(PCB-EpE)composed of two PBI units and a rigid o-carborane linker,which was further employed in constructi ng a con ceptual fluoresce nt film sen sor for evaluati ng fish fresh ness.Photophysical studies indicate that PCB-EpE displays an open"Z-type"molecular configuration in chloroform and a closed"△-type"configuration in methyl cyclohexa ne.Comparatively,"Z-type"molecular configurati on possesses higher fluoresce nee qua ntum yield and is more sen sitive toward volatile basic nitrogen(VBN).     

新型氨基功能化碱性离子液体1-(2-氨基乙基)-3-甲基咪唑咪唑盐催化四类取代2-氨基-4H-色烯衍生物的合成

设计合成了阴阳离子均具有碱性位点的新型氨基功能化碱性离子液体1-(2-氨基乙基)-3-甲基咪唑咪唑盐([2-aemim]im,3),经ESIMS和1H NMR确定了结构.[2-aemim]im的碱性与氨基功能化的阳离子([2-amim]+)有关,但主要取决于咪唑阴离子(im-).TG-DSC分析显示[2-aemim]im具有高的热稳定性.将[2-aemim]im用于催化水相介质中芳香醛、丙二腈和酚的三组分一锅法反应制备2-氨基-4H-色烯衍生物,阴阳离子之间表现出协同促进催化作用.该催化剂具有高效和底物作用范围广的特点,应用不同的酚类及类似物,如1-萘酚、2-萘酚、间苯二酚和环己二酮,以高产率得到了相应的不同官能团取代的2-氨基-4H-苯并[h]色烯(4a～4e),2-氨基-4H-苯并[f]色烯(5a～se),2-氨基-4H-色烯(6a～6e)和2-氨基-4H-四氢色烯(7a～7e)四类2-氨基-4H-色烯衍生物.离子液体至少可以循环使用5次,催化活性无显著降低.     

供课堂用的大学物理演示软件

介绍了大学物理原理演示软件的内容、研制路线、功能及运行条件．     

Training Data Selection and Optimal Sensor Placement for Deep-Learning-Based Sparse Inertial Sensor Human Posture Reconstruction

Although commercial motion-capture systems have been widely used in various applications, the complex setup limits their application scenarios for ordinary consumers. To overcome the drawbacks of wearability, human posture reconstruction based on a few wearable sensors have been actively studied in recent years. In this paper, we propose a deep-learning-based sparse inertial sensor human posture reconstruction method. This method uses bidirectional recurrent neural network (Bi-RNN) to build an a priori model from a large motion dataset to build human motion, thereby the low-dimensional motion measurements are mapped to whole-body posture. To improve the motion reconstruction performance for specific application scenarios, two fundamental problems in the model construction are investigated: training data selection and sparse sensor placement. The problem of deep-learning training data selection is to select independent and identically distributed (IID) data for a certain scenario from the accumulated imbalanced motion dataset with sufficient information. We formulate the data selection into an optimization problem to obtain continuous and IID data segments, which comply with a small reference dataset collected from the target scenario. A two-step heuristic algorithm is proposed to solve the data selection problem. On the other hand, the optimal sensor placement problem is studied to exploit most information from partial observation of human movement. A method for evaluating the motion information amount of any group of wearable inertial sensors based on mutual information is proposed, and a greedy searching method is adopted to obtain the approximate optimal sensor placement of a given sensor number, so that the maximum motion information and minimum redundancy is achieved. Finally, the human posture reconstruction performance is evaluated with different training data and sensor placement selection methods, and experimental results show that the proposed method takes advantages in both posture reconstruction accuracy and model training time. In the 6 sensors configuration, the posture reconstruction errors of our model for walking, running, and playing basketball are 7.25°, 8.84°, and 14.13°, respectively.     

折射率失配对双光子三维光存储中像差的影响

双光子吸收三维光信息存储是实现高密度光存储的重要方法。三维数据写入过程中光束需经过两层不同的介质(如空气和存储材料),对像差和存储效果产生很大的影响,因此在理论和实验上分析系统各项光学参量对折射率失配引起的像差和存储效果的影响具有很大的意义。首先建立光学存储系统模型,在平行平板条件下,利用波像差函数推导展开,获得五项初级(赛德耳)像差,即球差、彗差、像散、场曲、畸变,然后对于存储材料在水平和倾斜两种情况下对初级像差进行模拟计算与分析,理论模拟与实验表明:物镜的数值孔径越大,像差随着存储深度增加而增大的速度就越快。     

31P NMR Spectral Evidence for the Hexacoordinated Phosphorus Intermediates in the Reaction of Oxyphosphorochloridate With Amino Acids

Abstract

The nucleophilic groups on the side chain of amino acid can attack phosphoryl to form high-coordinated phosphorus intermediate. which was similar to the active sits of the CAMP-enzyme system [1, 2]