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。     

搪瓷釜的使用维护与常用修补方法

介绍搪瓷釜的使用维护要点，简单介绍目前国内外常用的搪瓷釜修补方法，从用、管、修相结合出发来延长搪瓷釜的使用寿命。     

合成氨中置锅炉的修复

本文在分析中置锅炉失效原因的基础上，提出了详细的修复措施，为类似情况的设备修复提供了借鉴。     

发电设备的检修策略及可靠性管理研究

检修策略和可靠性管理是发电厂设备管理工作相辅相成的 2个方面 ,必须予以足够重视。目前要加大力度做好可靠性管理工作 ,建立可靠性管理系统为发电设备管理提供技术支持 ,为设备检修提供依据 ,以获得最佳的经济效益。     

水电站厂用接触器减振降噪的方法

指出水电站厂用接触器振动、噪音大对水电站正常运行的危害,分析其原因,以实例介绍解决方法,提出应重视对接触器的日常维护检修。     

A multi-agent architecture for dynamic scheduling of steel hot rolling

Steel production is a complex process and finding coherent and effective schedules for the wide variety of production steps, in a dynamic environment, is a challenging task. In this paper, we propose a multi-agent architecture for integrated dynamic scheduling of the hot strip mill (HSM) and the continuous caster. The scheduling systems of these processes have very different objectives and constraints, and operate in an environment where there is a substantial quantity of real-time information concerning production failures and customer requests. Each process is assigned to an agent which independently, seeks an optimal dynamic schedule at a local level taking into account local objectives, real-time information and information received from other agents. Each agent can react to real-time events in order to fix any problems that occur. We focus here, particularly, on the HSM agent which uses a tabu search heuristic to create good predictive–reactive schedules quickly. The other agents simulate the production of the coil orders and the real-time events, which occur during the scheduling process. When real-time events occur on the HSM, the HSM agent might decide whether to repair the current schedule or reschedule from scratch. To address this problem, a range of schedule repair and complete rescheduling strategies are investigated and their performance is assessed with respect to measures of utility, stability and robustness, using an experimental simulation framework.