MASS SPECTROMETRY-BASED PERSONALIZED DRUG THERAPY

Personalized drug therapy aims to provide tailored treatment for individual patient. Mass spectrometry (MS) is revolutionarily involved in this area because MS is a rapid, customizable, cost-effective, and easy to be used high-throughput method with high sensitivity, specificity, and accuracy. It is driving the formation of a new field, MS-based personalized drug therapy, which currently mainly includes five subfields: therapeutic drug monitoring (TDM), pharmacogenomics (PGx), pharmacomicrobiomics, pharmacoepigenomics, and immunopeptidomics. Gas chromatography-MS (GC-MS) and liquid chromatography-MS (LC-MS) are considered as the gold standard for TDM, which can be used to optimize drug dosage. Matrix-assisted laser desorption ionization-time of flight-MS (MALDI-TOF-MS) significantly improves the capability of detecting biomacromolecule, and largely promotes the application of MS in PGx. It is becoming an indispensable tool for genotyping, which is used to discover and validate genetic biomarkers. In addition, MALDI-TOF-MS also plays important roles in identity of human microbiome whose diversity can explain interindividual differences of drug response. Pharmacoepigenetics is to study the role of epigenetic factors in individualized drug treatment. MS can be used to discover and validate pharmacoepigenetic markers (DNA methylation, histone modification, and noncoding RNA). For the emerging cancer immunotherapy, personalized cancer vaccine has effective immunotherapeutic activity in the clinic. MS-based immunopeptidomics can effectively discover and screen neoantigens. This article systematically reviewed MS-based personalized drug therapy in the above mentioned five subfields. © 2020 John Wiley & Sons Ltd. Mass Spec Rev     

MASS SPECTROMETRY ANALYSIS OF DRUGS OF ABUSE: CHALLENGES AND EMERGING STRATEGIES

Mass spectrometry has been the “gold standard” for drugs of abuse (DoA) analysis for many decades because of the selectivity and sensitivity it affords. Recent progress in all aspects of mass spectrometry has seen significant developments in the field of DoA analysis. Mass spectrometry is particularly well suited to address the rapidly proliferating number of very high potency, novel psychoactive substances that are causing an alarming number of fatalities worldwide. This review surveys advancements in the areas of sample preparation, gas and liquid chromatography-mass spectrometry, as well as the rapidly emerging field of ambient ionization mass spectrometry. We have predominantly targeted literature progress over the past ten years and present our outlook for the future. © 2020 Periodicals, Inc. Mass Spec Rev     

THE USE OF MASS SPECTROMETRY TO STUDY ZN-METALLOPROTEASE-SUBSTRATE INTERACTIONS

Zinc metalloproteases (ZnMPs) participate in diverse biological reactions, encompassing the synthesis and degradation of all the major metabolites in living organisms. In particular, ZnMPs have been recognized to play a very important role in controlling the concentration level of several peptides and/or proteins whose homeostasis has to be finely regulated for the correct physiology of cells. Dyshomeostasis of aggregation-prone proteins causes pathological conditions and the development of several different diseases. For this reason, in recent years, many analytical approaches have been applied for studying the interaction between ZnMPs and their substrates and how environmental factors can affect enzyme activities. In this scenario, mass spectrometric methods occupy a very important role in elucidating different aspects of ZnMPs-substrates interaction. These range from identification of cleavage sites to quantitation of kinetic parameters. In this work, an overview of all the main achievements regarding the application of mass spectrometric methods to investigating ZnMPs-substrates interactions is presented. A general experimental protocol is also described which may prove useful to the study of similar interactions. © 2020 John Wiley & Sons Ltd. Mass Spec Rev     

DESIGN AND PERFORMANCE OF TWO ORTHOGONAL EXTRACTION TIME-OF-FLIGHT SECONDARY ION MASS SPECTROMETERS FOR FOCUSED ION BEAM INSTRUMENTS

The design and performance of two orthogonal extraction time-of-flight mass spectrometers are reported that were adapted to existing focused ion beam microscopes for secondary ion mass spectrometry. The performances of these designs were compared to that of a prototype previously described by our group. The differences include newly designed transfer ion optics and in the use of a larger microscope chamber. The two new prototypes allow a mass resolving power of either 600 Th/Th (compact design) or 3000 Th/Th (high resolution design) while simultaneously achieving a lateral spatial resolution of less than 50 nm. The spectrometers and their performance (effective ion yield, mass resolving power, lateral, and depth resolution) are described and compared. Additionally, example applications are presented with multivariate statistical methods to visualize the data sets. Both time-of-flight mass analyzers use orthogonal extraction which avoids the need to pulse the primary ion beam, and the of use monoisotopic gallium to preserve the mass resolution. The goal of the design was a cost-effective accessory to augment typical focused ion beam-scanning electron microscopy applications as an alternative to the cost of a dedicated secondary ion mass spectrometer. The modified instrument allows excellent non destructive imaging and easy sample access, and benefits from the presence of complementary non destructive analytical and imaging techniques that exploit the presence of an electron microscope.     

TIG电弧传热传质过程的数值分析

以ＴＩＧ电弧为对象,建立了焊接电弧传热传质过程的完善数学模型,引入欧姆定律计算电流密度分布并用Ｋ－ε模型处理紊流问题。使用ＦＯＲＴＲＡＮ语言在ＳＵＮ工作站上进行了数值分析,得到了１００Ａ～３００Ａ电流下的流场分布、温度分布及电流分布等重要物理数据,且与重要的试验结果吻合良好。     

EXPERIMENTAL INVESTIGATION OF BEAM-TIP MASS AND PENDULUM SYSTEM UNDER RANDOM EXCITATION

This research deals with the dynamic response of a large flexible beam with a tip mass–pendulum system. The system is a conceptualisation of a vibration-absorbing device for large flexible structures with tip appendages. The response of the system to the wide-band random excitation is observed and analysed experimentally. The concept of the experiment is to determine the energy transfer between the beam and the pendulum due to the non-linear interaction of the modes of the system.The measurements include time history records, mean-square response curves of beam, and the pendulum for different response regimes. Also, sets of experiments were conducted to determine the autoparametric interaction between the two modes of the system in the neighbourhood of the autoparametric region. The outcome of this research reveals the scope and limitations of the beam–pendulum oscillator as a potential vibration-absorbing device in the applications where random disturbance occurs.     

CF_3CHClO化学反应动力学及其机理研究的理论计算与质谱测量(英文)

利用闪光光解 ( FP)将质谱学应用于气相光化学和动力学研究是从 1 957年开始的。由于能够用质谱法测定反应过程中各种不同的化学物种 ,探测反应物衰减和反应产物生长的动态速率 ,因此质谱法具有先进性和多用途。用于探测脉冲光解引起的反应物衰减和反应产物生长速率的质谱法 ,称为闪光光解时间分辨质谱法 ( FPTRMS)。在进行实验时 ,使用闪光光解时间分辨质谱法能够从实验中获得直接的和有价值的反应动力学和反应机理信息。但是 ,有时也会受到条件限制 ,例如 ,一些实验研究只能在有限的温度和气压范围内进行 ,而另一些实验研究并不是都能够单独提供反应机理信息 ,特别是对于复杂体系。理论研究 ,包括原始计算法 ,RRKM( Rice-Ramsperger-Kassel Model)计算法和数字模拟计算法都只不过是实验研究有效的辅助手段。在较宽的温度和气压范围内 ,原始计算法和RRKM计算法都能用来预示化学反应速率系数 ,还能够从理论研究获得反应机理的重要信息。然而 ,理论研究获得的结果的合理性和准确性 ,最终还必须由实验结果予以证实和修正。作为一个实际例子 ,本工作叙述了使用闪光光解时间分辨质谱法和理论计算法研究 CF3CHCl O官能团的反应动力学及其反应机理。     

微加速度计摆片质量的测量方法研究

梳齿式微机械加速度计摆片的质量是影响其性能的重要机械参数,获得实测值十分必要。提出一种基于开环频率响应试验和静态静电力试验求取摆片质量的方法,由加速度计的开环传递函数及摆片的力平衡方程,得到包含摆片质量的方程组,通过求解该方程组得出摆片的实际质量。对具体加速度计的试验结果表明,该方法能准确地估算摆片的实际质量,并能在制造现场使用,不需要特殊的测量环境和仪器设备,是一种简便而有效的试验方法。     

MASS SPECTROMETRY IN VIROLOGICAL SCIENCES

Virology, as a branch of the life sciences, discovered mass spectrometry (MS) to be the pivotal tool around two decades ago. The technique unveiled the complex network of interactions between the living world of pro- and eukaryotes and viruses, which delivered “a piece of bad news wrapped in protein” as defined by Peter Medawar, Nobel Prize Laureate, in 1960. However, MS is constantly evolving, and novel approaches allow for a better understanding of interactions in this micro- and nanoworld. Currently, we can investigate the interplay between the virus and the cell by analyzing proteomes, interactomes, virus-cell interactions, and search for the compounds that build viral structures. In addition, by using MS, it is possible to look at the cell from the broader perspective and determine the role of viral infection on the scale of the organism, for example, monitoring the crosstalk between infected tissues and the immune system. In such a way, MS became one of the major tools for the modern virology, allowing us to see the infection in the context of the whole cell or the organism. © 2019 John Wiley & Sons Ltd. Mass Spec Rev     

眼组织中缓释地塞米松药膜的HPLC/MS/MS测定方法研究

眼部手术后 ,在眼组织的前房中植入缓释地塞米松药膜以防术后感染。本实验采用液液萃取、液固萃取的方法来提取生物样品中的地塞米松药物 ,经液相色谱 /质谱 /质谱进行检测 ,样品中药物浓度在 1 0 8— 54μg/L范围内呈现良好的线性 (γ2 =0 .9995) ,最低检测浓度为 0 4 μg/L ,平均回收率大于 77%。用这一方法可高灵敏度、高选择性地应用于临床相关药物的动力学研究     

蜂窝式除湿转轮的传热传质数学模型及其试验验证

针对蜂窝式除湿转轮的结构特点以及波纹形通道的传热传质特性,建立了转轮除湿过程中的传热传质数学模型,用试验数据验证了其合理性。分析和讨论了传热传质过程中空气温湿度和干燥剂温度及其含水量的分布情况和特征。数值计算发现:在波纹形通道内沿再生空气方向存在一条空气含湿量峰值线,该峰值线向出口方向的迁移时间和峰值的大小决定了再生速度和再生效率。为了提高再生效率,应该尽可能加快再生空气含湿峰值向出口处的移动过程,提高其迁移速度,降低迁移时间。最后还对运行参数对再生空气出口含湿峰值的大小及其迁移时间的影响进行了讨论。     

多路换向阀的发展历程与研究展望

多路换向阀是工程机械液压系统中的关键部件之一。综述了多路换向阀的发展历程,分析了其发展背景及存在的关键问题。着重分析了最新的抗流量饱和技术、负流量控制技术和带电液负载敏感的负载口独立控制电液比例多路阀。展望了该领域今后的研究方向。     

大批量定制及其模型的研究

大批量定制是一种面向 2 1世纪的新的生产方式 ,其目的是解决长期困惑制造业的“两难”问题 ,就是既要使产品满足客户个性化的要求 ,又要使产品的成本和交货期与大批量生产的产品相同或相接近。本文讨论了大批量定制的背景 ,提出了面向大批量定制的集成产品和过程模型 ,并初步建立了一种大批量定制的数学模型。     

大批量定制原理

阐述大批量定制的外部多样化与内部多样化策略。对大批量定制的相似性原理、重用性原理、全局性原理进行研究,给出相似性的不同形式,论述相似性与重用性的关系,分析相似性与重用性的形成以及全局性改进过程,建立大批量定制总成本的原理模型。通过与完全定制生产、大批量生产的比较研究,提出基于相似性、重用性和全局性的大批量定制平均成本原理。阐述定制价值、定制成本、临界定制点、外部定制点和内部定制点的概念,在此基础上提出大批量定制的定制点原理。     

基于照片的实体建模方法的现状及展望

基于照片的实体建模方法指通过摄像、图像处理获得物体三维模型的方法。该方法源于计算机视觉,是一种方便快捷的三维建模方法。对基于照片的实体建模基础理论与方法进行了论述,并对目前国内外的研究动态进行了分析,提出了进一步研究的方向。     

ADVANCES IN HIGH-RESOLUTION MALDI MASS SPECTROMETRY FOR NEUROBIOLOGY

Research in the field of neurobiology and neurochemistry has seen a rapid expansion in the last several years due to advances in technologies and instrumentation, facilitating the detection of biomolecules critical to the complex signaling of neurons. Part of this growth has been due to the development and implementation of high-resolution Fourier transform (FT) mass spectrometry (MS), as is offered by FT ion cyclotron resonance (FTICR) and Orbitrap mass analyzers, which improves the accuracy of measurements and helps resolve the complex biological mixtures often analyzed in the nervous system. The coupling of matrix-assisted laser desorption/ionization (MALDI) with high-resolution MS has drastically expanded the information that can be obtained with these complex samples. This review discusses notable technical developments in MALDI-FTICR and MALDI-Orbitrap platforms and their applications toward molecules in the nervous system, including sequence elucidation and profiling with de novo sequencing, analysis of post-translational modifications, in situ analysis, key advances in sample preparation and handling, quantitation, and imaging. Notable novel applications are also discussed to highlight key developments critical to advancing our understanding of neurobiology and providing insight into the exciting future of this field. © 2020 John Wiley & Sons Ltd. Mass Spec Rev     

双哌嗪盐类化合物电子轰击离子化质谱研究(英文)

对 6个新合成的双哌嗪盐类化合物进行了电子轰击离子化质谱及其裂解规律的研究。研究表明 :通过降低电子轰击电流强度 ,该类化合物的电子轰击离子化质谱的准分子离子和特征碎片峰非常清晰。但 M+和 M2 +离子峰并未出现。在低电子能量条件下 ,发现了 [M-2 ]+,[M-R]+,[M-R-1 ]+,[M-2 R]+,甚至 [RX]+离子峰的存在。这些现象可能与分子内的 R+重排反应有关。进一步尝试提出该类化合物的电子轰击离子化质谱裂解规律 ,为该类化合物的质谱研究提供有用的信息。     

高速凸轮机构动力稳定性的分析与实验研究

文中对凸轮推杆系统的动力稳定性进行分析,在理论和实验的基础上建立了一种新的动力学模型,其中考虑了推杆的纵向和横向运动及其相互影响,导出了描述该系统的两个耦合的运动偏微分方程,经过简化得到一个描述推杆横向振动的变系数偏微分方程。应用Галеркин方法导出Hill方程组。根据Floquet理论,寻找Hill方程周期解存在之条件,得到临界频率方程,将此方程的求根问题转换为相应方阵的特征根求解的问题,简化了计算。在此基础上编制了计算程序,以确定动力不稳定区域。文中并以FG-1型柴油机的配气机构为例进行了理论计算和实验研究。     

等质量变刚度多层建筑剪切振动的摄动解

多层建筑振动时,沿竖向的变形以剪切为主.对于层数很多且又不分阶的建筑物,各层质量相差不大,而其刚度每层往往不同,因此可将多层建筑作为等质量变刚度的多层建筑.只考虑等质量变刚度的多层建筑剪切变形,由弹性振动理论得到其剪切固有振动微分方程,采用改进的摄动法研究多层建筑剪切固有振动.对求解变系数二阶齐次微分方程的摄动法进行改进,求得等质量变刚度多层建筑剪切固有振动的振型函数,得到确定等质量变刚度多层建筑剪切固有振动频率的特征方程.将分析结果与其他文献分析结果进行对比,算例表明改进摄动法不但计算过程简便,而且计算精度与Bessel函数法的计算精度非常接近.