HCV治疗的新方法:RNA依赖的RNA聚合酶抑制剂

丙型肝炎病毒（hepatitis C virus,HCV）感染呈世界流行趋势,50%感染者转变为慢性肝炎,部分发展为肝硬化、肝细胞癌,给人类健康带来了极大危害.目前,没有疫苗研制成功,现有的HCV治疗药物普遍存在局限性,或者有一些药物没有发挥应有的作用.因此,开发新型、安全有效的抗HCV药物成为迫在眉睫的问题.NS5B蛋白是HCV复制的核心物质,具有RNA依赖的RNA聚合酶（RdRp）功能.研发有效的NS5B抑制剂,从而阻断病毒的复制,成为许多科研机构及制药公司的研究热点,有一些NS5B抑制剂已进入临床实验阶段.     

重组戊型肝炎病毒衣壳蛋白p239特异性吸附、侵入HepG2细胞并阻断野病毒对肝细胞的感染

戊型肝炎病毒(Hepatitis E virus,HEV)引起的戊型肝炎在临床症状上与甲肝相似,但病死率更高,妊娠晚期病死率可高达15%～25%[1].近年来,戊肝在世界各地暴发不断;而我国戊肝发病迅速增长,已经成为普遍流行、危害严重的疾病之一[2].     

棕背■在不同坡度林地的数量及预防幼林鼠害的意义

棕背(鼠平)(Clethrionomys rufocanus)是东北林区的优势鼠种,由于啃食树皮危害林木生长,在数量大发生年的秋末冬初更加严重,因此了解林地棕背(鼠平)数量变化规律,以便更有效地防治幼林鼠害,是很有意义的工作。棕背(鼠平)数量变化不仅与林分郁闭度有关(舒凤梅,1981),而且与林地坡度也有关。本文着重探讨不同坡度林地的棕背(鼠平)数量     

囊鼠某些摄食行为的观察(英文)

囊鼠是一种营地下单洞穴居的鼠类,广泛分布于加利福尼亚州的农田、牧场和森林,危害甚大。作者在实验室条件下对两种襄鼠(Thomomys bottae和Thomomys mazama)的某些摄食行为进行了观察,得到以下结论: 1.囊鼠的摄食行为有8个组成部分,即:(1)暴露洞口;(2)探察洞外动静;(3)将食物拖入洞内;(4)储藏食物;(5)反复在洞外搜索剩余食物;(6)推土堵洞;(7)尝试及摄食;(8)对粪便和尿的处理。     

海南省新发现的林业外来入侵害虫——水椰八角铁甲

报道了最近发生在海南省东方市华盛顿棕榈 (Washingtoniafilifera)上的林业外来入侵害虫—水椰八角铁甲Octodontanipae(Maulik) ;对其形态特征 ,发生与危害等进行了简要介绍 ,并提出了应对措施和建议。由于及时采取了适当的根除措施 ,目前该入侵种没发现蔓延、扩散。水椰八角铁甲目前仅有文献报道在马来西亚有分布 ,危害当地的椰树叶和梢     

两种贝类养殖环境特征污染物的筛选方法研究

采用Micro Tox Model500发光细菌毒性检测仪,对Cu、Pb、Cd、Hg、As、Cr、Zn、石油类、DDT、甲基对硫磷农药(MP)等10种贝类养殖环境污染物进行发光细菌抑制试验。对己知污染物的浓度与其相对应的发光强度进行回归分析,建立相关方程,求出相对发光度为50%时所对应污染物的浓度,即EC₅₀值,将其定义为相对毒性系数(RT),该值越小,表示污染物毒性越大。结果显示,上述10种污染物的相对毒性(RT)大小顺序为DDT>Hg>Cu=Zn>Cd>Cr>Pb=石油类>MP>As;结合两种贝类对上述污染物的生物富集系数(BCF),以RT/BCF值作为最终绝对毒性大小比较的指标,比值越小,危害影响越大,污染物应优先被选择作为环境特征污染物进行监测。经试验分析,缢蛏和泥蚶的养殖环境特征污染物的优先检测顺序分别为,缢蛏:Hg>Cd>Zn>Cu>As>Cr>Pb(椒江口),Cd>Pb>Cu(舟山海域),Cu>Zn>Cr>Pb(长江口);泥蚶:Cd>Pb>Cu(宁波、舟山海域),Cu>Cd>Pb(温州海域)。     

伪步甲危害在新疆草原不同地形梯度的空间分布特征

为揭示伪步甲危害在地形梯度上的差异, 探讨草原上不同地貌部位在伪步甲灾害发生过程中的作用, 在RS和GIS 支持下, 以国产ZY1-02C 卫星P/MS 和DEM(Digital Elevation Model)数据为基础, 运用ArcGIS 的空间叠加分析功能, 将遥感解译的数据与高程、坡度和坡向三个地形因子进行空间叠加分析, 对研究区草原伪步甲灾害分布现状的地形梯度空间分异进行了探讨。结果表明: 在高程和坡度梯度上, 伪步甲危害呈现出明显的分布规律, 即“中间高,两边低”, 分别在海拔1000 m-1200 m 和坡度3.3°-6.1° 范围内伪步甲危害最为严重; 而在坡向梯度上, 严重危害区随着坡向变化的分布趋势接近平缓, 在整个坡向范围内均有不同程度的分布。     

丙型肝炎病毒CS,NS3 NS4 区抗原融合基因的构建及其在大肠杆菌中的表达

丙型肝炎病毒是与输血有关的非甲非乙肝病毒[1];是全世界输血后获得性肝炎的重要病因之一,并与急慢性肝炎、肝硬化和肝癌有关.由于主要通过输血的传播,会给人民的身体健康尤其输血事业带来极大危害.     

应用环境微生物治理淡水湖泊微囊藻毒素污染的研究进展

近年来,随着水体富营养化程度的加剧,蓝藻水华现象时有发生,蓝藻及其释放的藻毒素对生态环境和人类健康构成严重威胁。在各种藻毒素中,以微囊藻毒素(Microcystins,MCs)毒性最强,对人类危害也最大,微囊藻毒素的化学性质相对稳定且难以通过常规水处理方法消除,因此如何有效去除环境中的MCs是国内外普遍关注的难题。研究发现自然界中的微生物能够有效降解和消除MCs污染,由此产生的环保技术极具应用价值。本文主要概述了微囊藻毒素的产生机理、化学结构以及毒性危害,总结了微囊藻毒素的自然分解过程以及微生物群落对微囊藻毒素的响应机制,重点分析了微生物群落在微囊藻毒素污染控制技术中的潜在应用,并对应用微生物技术治理微囊藻毒素污染的技术瓶颈提出了建议,以期加速微囊藻毒素微生物降解技术的完善和应用。     

中国鼩鼱亚科的系统分类和分布的评论(英文)

中国动物区系中的鼩(鼠青)类,或称赤齿鼩类,包括31个种;除此之外,东北省份还可能存在另外2个种。生物地理类群包括:1)东北寒温带针叶林(泰加)-Neomys fodiens,Sorex caecutiens,S.daphaenodon,S.gracillimus,S.isodon,S.mirabilis,S.roboratus,S.tundrensis以及S.unguiculatus;2)在山区针叶林中具有孤立居群的东北寒温带针叶林-Sorex minutissimus;3)中国喜马拉雅地区-Chimarrogale himalayica,Nectogale elegans,Sorex bedfordiae,s.thibetanus,Soriculus caudatus,S.leucops,S.macrurus,及S.nigrescens;4)中国特有种,或接近于特有种-Anourosorex squamipes,Blarinella quadraticauda,Chimarrogale styani,So-rex asper,S.cansulus,S.cylindricauda,S.excelsus,S.sinalis,Soriculus fumidus,S.hypsibius,S.lamula,S.parca,S.salenskii,及S.smithii。Sorex minutus的生物地理位置(仅见于天山)目前尚不清楚。     

On ordered subpopulations and population mortality at advanced ages

We consider hazard (mortality) rates in heterogeneous populations consisting of ordered (in the defined stochastic sense) subpopulations. This setting can be interpreted via the fixed frailty models with one or more frailty parameters. The shape of the hazard rate is of main interest in this paper. Specifically, the deceleration and leveling off in the hazard rates (mortality plateaus) are discussed and some examples of lifetime distributions that can result in asymptotically flat hazard rates are considered. These examples are based on vitality models when an organism’s initial vitality (resource) is ‘consumed’ in the course of life in accordance with a simple stochastic process (e.g., the Wiener process with drift or the gamma process).     

Application of high‐throughput mini‐bioreactor system for systematic scale‐down modeling,process characterization,and control strategy development

High‐throughput systems and processes have typically been targeted for process development and optimization in the bioprocessing industry. For process characterization, bench scale bioreactors have been the system of choice. Due to the need for performing different process conditions for multiple process parameters, the process characterization studies typically span several months and are considered time and resource intensive. In this study, we have shown the application of a high‐throughput mini‐bioreactor system viz. the Advanced Microscale Bioreactor (ambr15^TM), to perform process characterization in less than a month and develop an input control strategy. As a pre‐requisite to process characterization, a scale‐down model was first developed in the ambr system (15 mL) using statistical multivariate analysis techniques that showed comparability with both manufacturing scale (15,000 L) and bench scale (5 L). Volumetric sparge rates were matched between ambr and manufacturing scale, and the ambr process matched the pCO₂ profiles as well as several other process and product quality parameters. The scale‐down model was used to perform the process characterization DoE study and product quality results were generated. Upon comparison with DoE data from the bench scale bioreactors, similar effects of process parameters on process yield and product quality were identified between the two systems. We used the ambr data for setting action limits for the critical controlled parameters (CCPs), which were comparable to those from bench scale bioreactor data. In other words, the current work shows that the ambr15^TM system is capable of replacing the bench scale bioreactor system for routine process development and process characterization. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1623–1632, 2015     

Development of a versatile computer integrated control system for bioprocess controls

A general approach is described for the implementation of a networked multi-unit computer integrated control system. The use of data acquisition hardware and graphical programming tools alleviates tedious programming and maintains potency and flexibility. One application of the control system, the control of a mammalian cell perfusion culture based on a key nutrient glucose concentration, was demonstrated. The control system offers customized user interface for all process control parameters and allows the flexibility for continued improvement and implementation of new tailored functions. The temperature, pH, dissolved oxygen and glucose level were accurately controlled. This revised version was published online in June 2006 with corrections to the Cover Date.     

检验全流程数字化管理及质量控制体系的构建

通过对检验工作各环节流程、质控情况的分析,制定了新的检验业务管理及质量控制流程,并利用数字化技术对流程各环节进行系统实现。检验全流程数字化管理及质量控制体系的构建,有效提高了检验工作的效率与质量安全,进一步促进了医院医疗质量管理水平的提高。     

Costs of mass-producing the root weevil, Mogulones cruciger, a biological control agent for houndstongue (Cynoglossum officinale L.)

The cost of rearing the root-feeding weevil, Mogulones cruciger Herbst, to control the invasive weed houndstongue (Cynoglossum officinale L.) was determined for two managed production methods. Production in an insectary setting provides control over rearing and all adult weevils that emerge can be collected, but required facility investment and high labor input. Mass-rearing in a managed ‘field crop’ setting required less facilities and labor while the insects were multiplying, but capture of the emerged adults was challenging and labor intensive. Estimated per adult weevil production costs were $CDN 2.65 for the insectary approach, and from $CDN 0.10 to $CDN 0.14 for mass-rearing in the managed field crop setting. Even though collection of adult weevils in the field crop production system was challenging, commercial production of M. cruciger should consider use of this mass-rearing method because of its lower cost.     

瞳孔控制系统采样特性的中枢机制

本文以双脉冲光分眼刺激（ｄｉｃｈｏｐｔｉｃ ｓｔｉｍｕｌａｔｉｎｇ,双脉冲的第一脉冲光刺激一侧眼,第二脉冲光刺激另一侧眼）进行瞳孔采样特性研究。实验结果表明：当双脉冲之间的时间间隔较长时,瞳孔产生两次收缩反应;当时间间隔小于约０．６ｓ时,瞳孔只对第一个脉冲光刺激产生瞬态收缩,对第二个脉冲光刺激不产生反应。这不仅证实了单眼实验研究的结论：瞳孔系统不是在时间上连续进行控制,而是离散的采样控制,它对光刺     

Life expectancy for a class of life distributions having the "setting the clock back to zero" property

It is demonstrated that the expression for the life expectancy of an individual in biomedical investigations can be greatly simplified if the class of life distributions possesses what has been called the "setting the clock back to zero" property, studied previously by Raja Rao and Talwalker. It is shown that the Gompertzian growth process, Krane's family of life distributions, and the linear hazard exponential distribution have this property. To illustrate the use of this property, an individual's life expectancy is tabulated for several choices of the parameter values when the individual's life distribution belongs to a Gompertzian growth process. In addition, it is shown that a new survival model considered by Chiang and Conforti for the estimation of time to tumor has the "setting the clock back to zero" property. Its life expectancy is evaluated at any given time chi 0 using this property.     

Advanced control of glutathione fermentation process

A study was performed to understand the fermentation process for production of glutathione fermentation (GSH) with an improved strain of baker's yeast. Simultaneous utilization of sugar and ethanol has been found to be a key factor in the industrial process to produce GSH using Saccharomyces cerevisiae KY6186. Based on this observation, the optimal sugar feed profile for the fed-batch operation has been determined. A feedforward/feedback control system was developed to regulate the sugar feed rate so as to maximize GSH production yields. Using the feedforward/feedback control system and the on-line data of oxygen and ethanol concentration in exhaust gas, the successful scaleup to the production level was accomplished. An average of 40% improvement of glutathione production compared to a conventionally programmed control of exponential fed-batch operation was found in the new process. (c) 1992 John Wiley & Sons, Inc.     

Process-wide control and automation of an integrated continuous manufacturing platform for antibodies

Integrated continuous manufacturing is entering the biopharmaceutical industry. The main drivers range from improved economics, manufacturing flexibility, and more consistent product quality. However, studies on fully integrated production platforms have been limited due to the higher degree of system complexity, limited process information, disturbance, and drift sensitivity, as well as difficulties in digital process integration. In this study, we present an automated end-to-end integrated process consisting of a perfusion bioreactor, CaptureSMB, virus inactivation (VI), and two polishing steps to produce an antibody from an instable cell line. A supervisory control and data acquisition (SCADA) system was developed, which digitally integrates unit operations and analyzers, collects and centrally stores all process data, and allows process-wide monitoring and control. The integrated system consisting of bioreactor and capture step was operated initially for 4 days, after which the full end-to-end integrated run with no interruption lasted for 10 days. In response to decreasing cell-specific productivity, the supervisory control adjusted the loading duration of the capture step to obtain high capacity utilization without yield loss and constant antibody quantity for subsequent operations. Moreover, the SCADA system coordinated VI neutralization and discharge to enable constant loading conditions on the polishing unit. Lastly, the polishing was sufficiently robust to cope with significantly increased aggregate levels induced on purpose during virus inactivation. It is demonstrated that despite significant process disturbances and drifts, a robust process design and the supervisory control enabled constant (optimum) process performance and consistent product quality.     

Rats dying for mice: Modelling the competitor release effect

Abstract Introduced vertebrate predators are one of the most important threats to endemic species throughout a range of ecosystems, in particular on islands in biodiversity hot spots. Consequently, the reduction of predator numbers is considered a key conservation action in the management of many native vertebrates vulnerable to predators. It is now established that control attempts may affect non‐target species through trophic interactions, but little is known concerning their consequences on competitive relationships. We study a mathematical model mimicking the effects of controlling introduced species in the presence of their competitors. We used two competing rodents to illustrate our study: black rats, Rattus rattus, and mice, Mus musculus. Analyses of the model show that control of only one introduced species logically results in the dramatic increase of the overlooked competitor. We present empirical data that confirm our theoretical predictions. Less intuitively, this process, which we term ‘the competitor release effect’, may also occur when both introduced competitors are simultaneously controlled. In our setting, controlling both predators can promote their coexistence. This occurs as soon as the inferior competitor benefits from the differential effect of the simultaneous control of both competitors, that is, when the indirect positive effect of control (the removal of their competitors) exceeds its direct negative effect (their own removal). Both control levels and target specificity have a direct influence on the extent of this process: counter‐intuitively, the stronger and more specific the control, the greater the effect. The theoretical validation of the competitor release effect has important implications in conservation, especially for control management.