Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

安全仪表系统设计的多目标优化

安全仪表系统在过程工业中日益受到更多关注,为满足安全仪表系统多目标优化问题对于安全完整性等级的综合要求,提出一种改进的多目标遗传优化方法.首先研究了安全仪表系统多目标优化中存在的问题,然后结合安全仪表系统优化问题的特殊性提出了一种更加适合用于安全仪表系统多目标优化的方法,最后将该方法应用于一个实例.结果表明:改进的方法能够解决安全仪表系统优化对于安全完整性等级要求的优化偏好问题,所得到的解比原有方法的解更具参考价值.     

Application of megasonic cleaner to sub-micron particles of SIL optical flying head

 As the demand for large capacity storage drives has increased, the flying height of near-field recording (NFR) sliders becomes as small as 100 nm for super high storage density. Accordingly contamination problems have been a concern of information storage industry because it may cause a serious damage to solid immersion lens (SIL) of optical flying head. Sub-micro contaminants in air bearing of the NFR slider may affect the flyability and stability of the optical slider. In addition, the cleaning of small particles becomes more difficult as the contaminant particle size decreases because the adhesion force increases very much as the particle size decreases. Recently developed high-frequency ultrasonic (megasonic) cleaning technique have made it possible to remove sub-micron particles less than 100 nm without surface erosion and many remarkable results have been reported. In this paper, the megasonic technique is applied and tested for the cleaning of the flying head of NFR drive. 1 MHz ultrasound with maximum 100 W was used to remove polystyrene latex (PSL) particles and alumina particles deposited on the surface of the slider. Effective cleaning performance was observed without any damages on the slider surface using optical microscope and AFM at different ultrasonic energy levels and cleaning times. Received: 20 June 2002 / Accepted: 9 September 2002     

安全系统的安全完整性水平及其选择

讨论安全完整性水平的概念、安全生命周期、安全完整性水平选择的定性、定量方法,介绍如何遵照功能安全的国际标准进行安全完整性水平选择.并结合一个具体实例,介绍了如何实现安全完整性水平选择的过程.     

火/气探测系统与安全仪表技术

火/气探测系统(FGS)是保护人员、环境及设备关键的安全部件,但火/气探测系统的产品、技术和设计基础与仪控系统不完全相同,因此国际上一直质疑是否应将FGS纳入安全仪表系统(SIS)及要求具有SIL2或SIL3安全完整性等级认证。本文综合TüV及ISA专家的视点从不同视角探讨如何妥善使用安全标准及技术并优化火/气探测设备布置以期获得最大的风险减轻效果。     

Probabilistic assessments in relationship with safety integrity levels by using Fault Trees

In this article, we study the assessment of safety integrity levels of safety-instrumented system by means of Fault Trees. We focus on functions with a low demand rate. For these functions, the appropriate measure of performance is the so-called probability of failure on demand (PFD) or probability of not functioning on demand. In order to calculate accurately the average PFD as per IEC 61508 standard, we introduce distributions for periodically tested components into Fault Tree models. We point out the specific problems raised by the assessment of safety integrity levels (SILs), which restrict the use of the formulae proposed in the standard. Among these problems there is the fact that SIL should be assessed by considering the time-dependent behavior of the system unavailability in addition to its average value. We check, on a simple pressure protection system, the results obtained by means of the Fault Tree approach against those obtained by means of stochastic Petri nets with predicates.     

LDPE装置管式反应器紧急泄压联锁系统可靠性分析

低密度高压聚乙烯(LDPE)装置反应系统的安全与紧急泄压系统的安全与可靠性密切相关。为评估紧急泄压安全联锁系统的安全要求及可靠性,采用精确的过程安全分析方法,对LDPE装置管式反应器紧急泄压联锁系统执行机构的冗余要求进行了分析。通过对泄压阀的开启及对泄压影响的研究,提出了LDPE反应器自分解泄压方程的修正模型,采用数值仿真方法研究了反应器内不同管段及全线自分解时紧急泄压阀开启数量、开启速度对反应泄压的关系。得出五取二以上的紧急泄压阀开启可以满足反应系统的紧急泄压要求。本研究结果确定了紧急泄压联锁系统执行机构的安全要求,为LDPE装置的联锁系统的安全完整性评估(SIL)提供了技术依据。文中还提出了反应过程的泄压系统设计要求,对提高装置的安全完整性具有借鉴意义。     

Beurteilungskriterien für sicherheitstechnische Prüfungen

Methods are presented which enable one to assess and compare the hazard potentials of different technical installations without the necessity of a detailed technical plant analysis. The basis is the energy content of the installation. In the case that energies with different impact mechanisms, e.g., pressure and heat, are to be compared, the probit method is used. In addition, the expected frequency of occurrence is included in the assessment. This is an approach which is already used in neighboring countries. It is foreseeable that it will gain importance in Germany as well. In the case of elevators the predator‐prey model is used to analyze the time series of accidents. The influence of errors in inspection and maintenance is put into evidence by comparison with the SIL classification.     

Clinsulf-Do法硫磺回收装置的安全仪表系统设计特点

结合硫磺回收装置项目的具体设计,重点介绍了德国LINDE公司的Clinsulf-Do硫磺回收工艺中安全仪表系统的控制思想,具体分析了该安全仪表系统各控制环节的设计特点,通过对该安全控制方案的介绍、分析,有助于人们认识Clinsulf-Do硫磺回收装置安全控制思想的先进性。     

石油化工装置中SIS的安全功能

对安全仪表系统SIS的发展和分级作了阐述，并结合了3取2系统及Fisher DVC6000智能阀门定位器对SIS的安全功能的实现作了分析。