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.     

Geopolymer concrete-filled pultruded composite beams – Concrete mix design and application

The limited research on the geopolymer concrete mix design for targeting a specific strength is identified an obstacle for their effective design and wide use. In this paper, a mix design procedure has been proposed for fly-ash based geopolymer concrete and its use as infill hybrid composite beam is investigated. Then, the structural performance of geopolymer concrete filled hybrid composite beam is investigated to determine their possible application in civil infrastructure. Firstly, a detailed procedure of mix design for fly-ash based geopolymer concrete is presented. Secondly, three hybrid beams filled with geopolymer concrete were prepared and tested in a four-point bending setup to evaluate their flexural modulus and modulus of rupture. Numerical and analytical evaluation of the behaviour of hybrid beam were performed and results showed a good agreement with the experimental investigation. Thirdly, the suitability of the beam for a composite railway sleeper is evaluated and compared with existing timber and composite sleepers. Finally, the beams’ performance in a ballast railway track is analysed using Strand7 finite element simulation software and the results showed that the new concept of using geopolymer concrete as infill to pultruded composite section satisfied the stiffness and strength requirements for a railway sleeper.     

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。     

Driver detection and recognition of lineside signals and signs at different approach speeds

A study was carried out using simulation to investigate driver responses to lineside signals and signs at various approach speeds. The objectives of the study were: (1) to find out whether train speed would significantly affect signal/sign reading; (2) to examine at which point certain types of signs or signals could be detected or recognised, and (3) to determine a speed cut-off level above which certain types of signs or signals are no longer recognisable or detectable. Fifty-seven train drivers from 12 Train Operating Companies in the UK participated in the trials. Twenty different types of lineside signs and ten types of signals were tested under six different approach speeds ranging from 100 to 350 km/h (62–218 mph). Driver performance measures were ‘time remaining to the signal/sign’ at the point of detection or recognition, and reading error rate. The results showed a significant influence of train speed on driver responses to lineside signals/signs and demonstrated a non-linear relationship between driver responses to signals/signs and approach speed. This has been used to estimate a maximum approach speed limit within which a specific signal or sign can be correctly detected or recognised. The findings and implications of the study are discussed in the paper.     

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。     

Scheduling railway traffic at a construction site

We consider the problem of rescheduling trains in the case where one track of a railway section consisting of two tracks in opposing directions is closed due to construction activities. After presenting an appropriate model for this situation we derive a polynomial algorithm for the subproblem of finding an optimal schedule with minimal latenesss if the subsequences of trains for both directions outside the construction site are fixed. Based on this algorithm we propose a local search procedure for the general problem of finding good schedules and report test results for some real world instances. Received: December 8, 1999 / Accepted: May 2, 2001