Open-access liquid chromatography/mass spectrometry in a drug discovery environment

The use of open-access mass spectrometry to monitor synthetic chemistry reactions, and also the integrity and purity of new chemical entities, has been a part of the medicinal chemist's tool-box for more than 5 years. Originally in our group at Wyeth Research there were two open-access methods available to the chemists, flow injection analysis (FIA) and liquid chromatography/mass spectrometry (LC/MS). The FIA method was approximately 3 min long, while the LC/MS method was approximately 20 min long (including an 8 min gradient). Within the first 2 years, the total number of open-access analyses increased by approximately 125%. It is interesting, however, that the number of LC/MS analyses increased by more than 285%. This is attributed to the fact that the chemists began using the LC/MS data to monitor reactions and also to check final product integrity and purity. In addition, the number of chemists performing parallel synthesis reactions has increased; thus, individual chemists can produce sample sets of up to 100 vials. This paper describes the implementation of new methodology, which accommodates the need for much faster run times and also the ability to acquire alternating positive and negative ion spectra within the same run. In addition, the instrument has been configured to e-mail the resulting processed data report to the submitting chemist. Several methods have been developed, including structure elucidation using in-source collision-induced dissociation (CID) and night-time analysis. The LC/MS methods for this system are described herein and are applicable to both industrial and academic synthetic chemistry optimization efforts.     

Microstructure and ferroelectric properties of r.f. magnetron sputtering derived PZT thin films deposited on interlayer (PbO/TiO2)

Lead zirconate titanate (PZT) thin films were deposited on Pt/Ti/SiO₂/Si and interlayer/Pt/Ti/SiO₂/Si substrate by radio frequency (r.f.) magnetron sputtering with a Pb_1.1Zr_0.53Ti_0.47O₃ target. The crystallization of the PZT thin films was formed only by substrate temperature. When interlayer (PbO/TiO₂) was inserted between the PZT thin film and the Pt electrode, the grain growth and processing temperature of the PZT thin films were considerably improved. Compared to PZT/Pt structure, the dielectric constant and polarization properties of the PZT/interlayer/Pt structure were fairly improved. In particular, PZT/interlayer/Pt at the substrate temperature of 400 °C showed prevalent ferroelectric properties (_r=475.97, tanδ=0.0591, P_r=23 μC/cm²). As a result of an X-ray photoelectron spectroscopy (XPS) depth-profile analysis, it was found that PZT/interlayer/Pt deposited only by substrate temperature without the post-annealing process via r.f. magnetron sputtering method remained independent of each other regardless of substrate temperatures.     

Hazard in reaction of titanium raw materials with sulphuric acid

The reaction of ilmenite titanium raw material with sulphuric acid was investigated in ‘hazard’ type calorimetric system. The investigations show the essential influence of initial temperature, particle size distribution and concentration of sulphuric acid on rate and heat power of reaction and determine the limits of safety of the process and also its efficiency.     

A unified set of proposals for control and design of high speed data networks

In this paper we articulate our philosophy and approach to the design and control of high speed data networks. The object is to put into perspective and to explain the coordination of various isolated pieces of detailed technical analyses that have been reported in several recent papers. In the process we summarize what we have learnt in our recent work and, also, we give indications of the direction of our future work. Our scheme integrates feedback and open loop control. The feedback control is exercised by sliding windows; access controllers regulate bursty sources. All our design proposals are rooted in asymptotic analyses; the justification for asymptotics comes from the largeness of the parameters, such as propagation delay, speed, window size, buffer size, and the number of virtual circuits. This analysis makes a strong case for operating in a specific moderate usage regime, and adaptive dynamic windowing algorithms are given that make this happen; moreover, when in this regime, buffers may be sized aggressively small without jeopardizing performance and the simplicity of the retransmission protocol. The topics in the paper are: model of communication, results on the steady-state behavior of the basic model, access control, small buffers and retransmission protocols, dynamic adaptive windows, bursty sources, and contrast with previous work.I. Mitrani's work was done while AT&T Bell Laboratories.     

实验室安全环保意识的调查与分析——以中山大学化学类专业学生为例

A survey about students' laboratory safety and environmental protection consciousness was performed in the freshmen majored in chemistry at Sun Yat-Sen University. Results showed that laboratory safety and environmental protection consciousness of most students' are weak. After analyzing the reasons, we put forward some suggestions. Cultivating students' laboratory safety and environmental protection consciousness should be carried out from several aspects such as emphasizing and regulating from school level, training in laboratory teaching, maintaining good cultural atmosphere of laboratory, as well as providing perfect laboratory safety and environmental protection facilities. We should guide students to actively learn knowledge and skills of laboratory safety and environmental protection in order to develop their good behavior and raise their consciousness.     

中国进口食品安全风险评估的统计学方法

近年来,随着对外贸易的快速发展和人民生活水平的不断提高,我国已经成为食品进口大国。运用科学的方法优化检验资源配置,强化对进口食品安全的风险管理,是一个关系到人民福社的重大问题。国际上通行的做法是对不同种类的食品和检测项目的潜在风险进行评估,并根据评估结果制定有针对性的监督抽检计划,使得更多的检验资源可以投入到对高风险产品和项目的监管中去。我国在这方面的管理实践才刚刚起步,急需建立一套符合我国食品进口自身特点和管理需求的风险评价模型和相应的估计方法。本文借鉴了其它国家的相关做法,并结合我国进口食品的管理需求和历史检测数据的特点,制定了一套完整的风险评价和估计方法。     

Trichothecenes in Food and Feed,Relevance to Human and Animal Health and Methods of Detection: A Systematic Review

Trichothecene mycotoxins are sesquiterpenoid compounds primarily produced by fungi in taxonomical genera such as Fusarium, Myrothecium, Stachybotrys, Trichothecium, and others, under specific climatic conditions on a worldwide basis. Fusarium mold is a major plant pathogen and produces a number of trichothecene mycotoxins including deoxynivalenol (or vomitoxin), nivalenol, diacetoxyscirpenol, and T-2 toxin, HT-2 toxin. Monogastrics are sensitive to vomitoxin, while poultry and ruminants appear to be less sensitive to some trichothecenes through microbial metabolism of trichothecenes in the gastrointestinal tract. Trichothecene mycotoxins occur worldwide however both total concentrations and the particular mix of toxins present vary with environmental conditions. Proper agricultural practices such as avoiding late harvests, removing overwintered stubble from fields, and avoiding a corn/wheat rotation that favors Fusarium growth in residue can reduce trichothecene contamination of grains. Due to the vague nature of toxic effects attributed to low concentrations of trichothecenes, a solid link between low level exposure and a specific trichothecene is difficult to establish. Multiple factors, such as nutrition, management, and environmental conditions impact animal health and need to be evaluated with the knowledge of the mycotoxin and concentrations known to cause adverse health effects. Future research evaluating the impact of low-level exposure on livestock may clarify the potential impact on immunity. Trichothecenes are rapidly excreted from animals, and residues in edible tissues, milk, or eggs are likely negligible. In chronic exposures to trichothecenes, once the contaminated feed is removed and exposure stopped, animals generally have an excellent prognosis for recovery. This review shows the occurrence of trichothecenes in food and feed in 2011–2020 and their toxic effects and provides a summary of the discussions on the potential public health concerns specifically related to trichothecenes residues in foods associated with the exposure of farm animals to mycotoxin-contaminated feeds and impact to human health. Moreover, the article discusses the methods of their detection.     

具有高安全性和有效性的Ⅱ期两阶段临床试验

Ⅱ期临床试验的主要目的是对药物治疗的安全性和有效性进行评估.针对具有高安全性的Ⅱ期两阶段临床试验,给出小样本量下关于安全性和有效性的精确检验方法,并证明最大Ⅰ类错误概率与Ⅱ类错误概率分别在原假设和备择假设的边界处达到.在期望样本量最小原则下,给出最优两阶段设计的构造方法和常用设计表,供实际应用选用.     

The Acceleration Severity Index in the impact of a vehicle against permanent road equipment support structures

The acceleration Severity Index (ASI), described in European Standard EN12767 (The passive safety of support structures for road equipment. Requirements, classification and the test method) is regarded as the most important indicator of impact on the occupants. The requirements for experiments are described, having in mind that the results depend on many factors. One of them is the selection of a vehicle to be used in the crash test. To perform numerical vehicle crash simulation, the finite-element models of permanent road equipment support structures were developed using the LS Dyna software available. To examine the response of the vehicle upon the impact, the acceleration severity index curves were calculated and visualised in Matlab.     

Retrovirus-mediated transduction of a cytosine deaminase gene preserves the stemness of mesenchymal stem cells

Human mesenchymal stem cells (MSCs) have emerged as attractive cellular vehicles to deliver therapeutic genes for ex-vivo therapy of diverse diseases; this is, in part, because they have the capability to migrate into tumor or lesion sites. Previously, we showed that MSCs could be utilized to deliver a bacterial cytosine deaminase (CD) suicide gene to brain tumors. Here we assessed whether transduction with a retroviral vector encoding CD gene altered the stem cell property of MSCs. MSCs were transduced at passage 1 and cultivated up to passage 11. We found that proliferation and differentiation potentials, chromosomal stability and surface antigenicity of MSCs were not altered by retroviral transduction. The results indicate that retroviral vectors can be safely utilized for delivery of suicide genes to MSCs for ex-vivo therapy. We also found that a single retroviral transduction was sufficient for sustainable expression up to passage 10. The persistent expression of the transduced gene indicates that transduced MSCs provide a tractable and manageable approach for potential use in allogeneic transplantation.