Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Model repair — aligning process models to reality

Process mining techniques relate observed behavior (i.e., event logs) to modeled behavior (e.g., a BPMN model or a Petri net). Process models can be discovered from event logs and conformance checking techniques can be used to detect and diagnose differences between observed and modeled behavior. Existing process mining techniques can only uncover these differences, but the actual repair of the model is left to the user and is not supported. In this paper we investigate the problem of repairing a process model w.r.t. a log such that the resulting model can replay the log (i.e., conforms to it) and is as similar as possible to the original model. To solve the problem, we use an existing conformance checker that aligns the runs of the given process model to the traces in the log. Based on this information, we decompose the log into several sublogs of non-fitting subtraces. For each sublog, either a loop is discovered that can replay the sublog or a subprocess is derived that is then added to the original model at the appropriate location. The approach is implemented in the process mining toolkit ProM and has been validated on logs and models from several Dutch municipalities.     

Investigation on the effectiveness of the repair method 8.3 “Corrosion protection by increasing the electrical resistivity” in chloride-containing concrete Part 2: Chloride redistribution in concrete after application of a system sealing surface protective coating

This DFG-funded research project aimed to gain a better understanding of the mechanisms of the W-Cl repair principle within the framework of fundamental investigations, to contribute to the creation of the necessary basis for a broader application of the repair principle in practice. The focus was on the development of a model to describe the chloride redistribution after the application of a system sealing surface protective coating. On the basis of Fick's second law of diffusion, a mathematical model with a self-contained analytical solution was developed, with the help of which the chloride redistribution after application of a system sealing surface protective coating can be calculated under the idealized assumption of complete water saturation of the concrete. Furthermore, the influence of the dehydration of the concrete, expected as a result of the application of the repair principle W-Cl, on the chloride redistribution was investigated. On the basis of laboratory tests and numerical simulations, material-specific reduction functions were developed to quantify the relationship between the chloride diffusion coefficient and the ambient humidity.     

Preventive replacement policies with time of operations,mission durations,minimal repairs and maintenance triggering approaches

When a mission arrives at a random time and lasts for a duration, it becomes an interesting problem to plan replacement policies according to the health condition and repair history of the operating unit, as the reliability is required at mission time and no replacement can be done preventively during the mission duration. From this viewpoint, this paper proposes that effective replacement policies should be collaborative ones gathering data from time of operations, mission durations, minimal repairs and maintenance triggering approaches. We firstly discuss replacement policies with time of operations and random arrival times of mission durations, model the policies and find optimum replacement times and mission durations to minimize the expected replacement cost rates analytically. Secondly, replacement policies with minimal repairs and mission durations are discussed in a similar analytical way. Furthermore, the maintenance triggering approaches, i.e., replacement first and last, are also considered into respective replacement policies. Numerical examples are illustrated when the arrival time of the mission has a gamma distribution and the failure time of the unit has a Weibull distribution. In addition, simple case illustrations of maintaining the production system in glass factories are given based on the assumed data.     

葛洲坝水利枢纽泄水建筑物进水口冲磨与修复

葛洲坝水利枢纽工程已运行20余年，近年水下检查中发现泄水建筑物进水口存在不同程度的冲磨，有些已威胁到建筑物安全运行，分析冲磨原因和探讨修复材料和手段是非常重要的，本文就此问题提出一些看法和建议供参考。     

石化企业实时数据管理引擎设计与实现

实时数据管理系统是流程企业控制信息网络与管理信息网络平滑集成的基础，为两者的数据通讯提供桥梁。介绍了笔者在炼油化工C企业IMS建设中的实时数据管理引擎设计与开发，具有其先进性与实用性。     

基于服务器端会话追踪的Web查询服务的研究

在探讨了Web查询服务的典型模型后,论文阐述了服务器端会话追踪机制的实现方式,设计了基于服务器端会话追踪的Web查询服务的典型解决方案。该设计方案可以较为安全地保存和维护客户的上下文信息,可靠地跟踪用户查询所处的状态,有效地实现有状态的Web查询服务。     

基于SIP的宽带实时多媒体通信研究与实现

介绍了会晤创建协议(SIP)，提出了基于SIP的应用系统——SRMCS，针对该实时多媒体通信系统，分析了其音频模块的实现和背景噪音的处理、视频模块的实现和视频的流畅播放，并就实时多媒体通信系统的关键问题——视、音频同步给出了可行的解决方案，最后还探讨了本系统中信令流和媒体流的传输方式。     

基于JSP技术的Web网站安全性研究

通过对基于JSP技术的Web网站的体系结构的介绍．从Web服务器安全、JSP脚本编程及数据库安全等几方面分析研究了web网站存在的安全问题，并探讨了web网站开发时应采取的安全措施。     

铁路远程网络维护的有效方法--呼叫回拨

本文阐述了网络远程维护人员进行网络维护时比较有用的三种有效方法的原理及其设置 ,较好地解决了故障排除的时间和网络维护成本的矛盾。