Epidemiological consequences of an incursion of highly pathogenic H5N1 avian influenza into the British poultry flock

Highly pathogenic avian influenza and in particular the H5N1 strain has resulted in the culling of millions of birds and continues to pose a threat to poultry industries worldwide. The recent outbreak of H5N1 in the UK highlights the need for detailed assessment of the consequences of an incursion and of the efficacy of control strategies. Here, we present results from a model of H5N1 propagation within the British poultry industry. We find that although the majority of randomly seeded incursions do not spread beyond the initial infected premises, there is significant potential for widespread infection. The efficacy of the European Union strategy for disease control is evaluated and our simulations emphasize the pivotal role of duck farms in spreading H5N1.     

Integrated continuous processing of proteins expressed as inclusion bodies: GCSF as a case study

Affordability of biopharmaceuticals continues to be a challenge, particularly in developing economies. This has fuelled advancements in manufacturing that can offer higher productivity and better economics without sacrificing product quality in the form of an integrated continuous manufacturing platform. While platform processes for monoclonal antibodies have existed for more than a decade, development of an integrated continuous manufacturing process for bacterial proteins has received relatively scant attention. In this study, we propose an end‐to‐end integrated continuous downstream process (from inclusion bodies to unformulated drug substance) for a therapeutic protein expressed in Escherichia coli as inclusion body. The final process consisted of a continuous refolding in a coiled flow inverter reactor directly coupled to a three‐column periodic counter‐current chromatography for capture of the product followed by a three‐column con‐current chromatography for polishing. The continuous bioprocessing train was run uninterrupted for 26 h to demonstrate its capability and the resulting output was analyzed for the various critical quality attributes, namely product purity (>99%), high molecular weight impurities (<0.5%), host cell proteins (<100 ppm), and host cell DNA (<10 ppb). All attributes were found to be consistent over the period of operation. The developed assembly offers smaller facility footprint, higher productivity, fewer hold steps, and significantly higher equipment and resin utilization. The complexities of process integration in the context of continuous processing have been highlighted. We hope that the study presented here will promote development of highly efficient, universal, end‐to‐end, fully continuous platforms for manufacturing of biotherapeutics. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:998–1009, 2017     

Combined use of periodic reaction field and coarse-grained molecular dynamics simulations. I. phospholipid monolayer systems

Abstract

A periodic reaction field based on a linear-combination-based isotropic periodic sum (LIPS) method was applied for coarse-grained molecular dynamics simulations of zwitterionic lipid systems. In phospholipid monolayer systems with various number of lipid molecules, the density profile, lipid orientation and surface tension were mainly calculated using the periodic reaction field and Ewald sum. The results from the periodic reaction field were almost equal to that from the Ewald sum. It is concluded that the periodic reaction field method has a great possibility to provide a high accuracy in determining coarse-grained zwitterionic lipid systems.     

人体动脉血气信号波浪式变化及连续动脉逐搏取血血气分析方法的建立*

目的: 建立动脉逐搏取血血气分析法,在人体实验中验证呼吸调控核心信号——PaO₂,PaCO₂和[H⁺]a是受呼吸影响的周期性、波浪式变化信号,而不是传统理念上误认的稳定水平信号。方法: 选择心功能正常、Allen试验阴性需要监测动脉血流动力学变化的患者6例。在左侧桡动脉穿刺,连接肝素化塑化管（3 mm×1 000 mm）,注满血液并计数血液注满所需心跳次数。用止血钳将塑化管钳闭成与心跳次数相对应的分段后,迅速置于冰水中,立即进行血气分析。选取每位患者的2个典型波浪式周期,用于分析2对最高-最低和最低-最高共4个测定值,取平均值。对相邻最高和最低值作统计学配对t检验。结果: 血液注满塑化管需要16±2次心跳,均覆盖超过2个呼吸周期。每个呼吸周期是5±0.6次心跳。PaO₂、PaCO₂、[H⁺]a和SaO₂都呈现出明显的波浪式变化（相邻高点与低点比较,P<0.05）,PaO₂、PaCO₂、[H⁺]a和SaO₂的波浪幅度分别是（11.28±1.13）mmHg,（1.77±0.89）mmHg,（1.14±0.35）nmol/L和（0.52±0.44）%;波浪幅度分别是其平均值的（7.7±1.1）%,（5.1±2.5）%,（3.1±1.0）%和（0.5±0.4）%。结论: 动脉延长管连续取血,按心跳次数分隔血样,血气分析法简单易行,为验证动脉血气受呼吸影响的周期性波浪式信号提供了可靠证据。本方法为原创,技术操作层面仍需提高熟练程度,增加志愿者和试验样本的数量进一步探索此类信号的临床检测可靠性及其与临床疾病的关系。     

混沌放电的可兴奋性细胞对外界刺激反应敏感的动力学机制

在大鼠损伤背根节神经元受到去甲肾上腺(NE)、四乙基胺(TEA)和高浓度钙等剌激的实验中,观察到非周期放电的神经元明显地比周期放电的神经元对外界刺激的反应敏感程度高。现有的结果表明许多非周期放电的神经元实际上表现为确定性的混沌运动,比如混沌尖峰放电、混沌簇放电以及整数倍放电等。以修正的胰腺B细胞Chay模型为例,通过对其分岔结构的分析和对构成混沌吸引子的基本骨架的不稳定周期轨道的计算,揭示了分岔、激变和混沌运动对参数敏感依赖性是该现象产生的动力学机制。同时指出以往使用平均发放率来刻划可兴奋性细胞放电活动存在的缺陷,提出了一种新的利用周期轨道信息的刻划方法。     

具有扩散的非自治两种群Lotka-Volterra模型的概周期问题

研究非自治两种群竞争系统,其中一种群可以在两个斑块之间扩散。而另一种群在一个斑块中,不能扩散。本文结合运用Liapunov函数,得到该系统唯一存在全局渐近稳定的正概周期解的条件．     

健康人心率变异性中的不稳定周期轨道

为刻划心脏节律存在的确定性动力学特征,运用不稳定周期轨道分析方法对健康青年人的RR间期时间序列数据进行分析。研究结果揭示健康人心脏节律中存在显著的不稳定周期轨道及不稳定周期轨道分级（周期1、周期2,周期3,周期4）现象,表明健康青年人心脏节律的动力学特性中包含着显著的确定性行为。通过跟踪不周期轨道随时间的演变,迹表明心脏节律的变化中存在着因有的非平稳性。     

一类具有随机周期移民扰动的非线性人口发展方程随机周期解的存在唯一性

本文给出了一类具有随机周期移民扰动的非线性m增生人口发展方程随机周期解的存在性和唯一性结论。     

模拟高海拔低氧对人体睡眠的影响

在模拟不同海拔高度的低氧条件暴露下,我们记录和测定了6名对象的睡眠生理各项指标。结果如下:在急性低氧暴露下所有对象均出现了睡眠障碍,主要是在夜间规定睡眠时间中觉醒期和觉醒次数增加,深睡眠期和快眼动期减少,睡眠各期的呼吸频率和心率增加。随着低氧暴露时间的延长和多次空气潜水后,各睡眠生理指标有向海平对照值水平发展的趋势。4500m以上的低氧暴露下,所有对象在睡眠中都有周期性呼吸现象出现,并影响体内的缺氧。     

草地螟(Loxostege sticticalis)周期性大发生与太阳黑子活动的相关性

草地螟Loxostege sticticalis L．是一种周期性大发生的农作物主要害虫,自新中国成立后已经3次大规模暴发成灾,但关于草地螟周期性大发生的原因还未见报道。利用国际通用的太阳黑子活动数据和我国草地螟大发生的历史记载进行相关性和相位分析的结果表明,我国草地螟大发生的周期性与对应的太阳黑子活动的奇数周期相关联。建国以来的3个大发生周期分别与对应的太阳黑子活动的第19、21周和第23周期在时间序列上表现出极高的同步性,尽管草地螟的发生为害程度与太阳黑子的活动强度之间相关性并不显著。根据这些结果,并结合太阳黑子活动周期的预测,草地螟在我国的第4个大发生周期很有可能开始于2017～2020年之间,并在2024—2025年间达到高峰。