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.     

靶面激光光斑尺寸原位测量的研究

提供了一种简便易行的靶面激光光斑尺寸原位测量的方法。从高斯光束的横向光强分布特性出发,建立了激光烧蚀斑半径与辐照激光能量、光斑尺寸、烧蚀阈值间的关系式,模拟分析发现辐照激光光斑尺寸对烧蚀斑半径随辐照能量变化曲线有较大影响。对于脉宽为2 ms,波长为1064 nm的激光,实验测量了不同能量激光辐照下相纸烧蚀斑半径,并用推导出的关系式拟合测量数据,获得了靶面处光斑尺寸和样品烧蚀阈值。同时,也测量了不同位置处的光斑尺寸和样品烧蚀阈值,对高斯光束束腰位置和样品烧蚀阈值的光斑尺寸效应进行了验证。研究结果表明该技术结果可靠,简单高效。该技术可以为高能激光与固体物质相互作用的基础研究和激光加工等应用领域中实现简单方便地测量靶面光斑尺寸提供帮助。     

基于关键路径延时检测的自适应电压缩减技术

为了减小传统的最差情况设计方法引入的电压裕量,提出了一种变化可知的自适应电压缩减(AVS)技术,通过调整电源电压来降低电路功耗.自适应电压缩减技术基于检测关键路径的延时变化,基于此设计了一款预错误原位延时检测电路,可以检测关键路径延时并输出预错误信号,进而控制单元可根据反馈回的预错误信号的个数调整系统电压.本芯片采用SMIC180 nm工艺设计验证,仿真分析表明,采用自适应电压缩减技术后,4个目标验证电路分别节省功耗12.4％,11.3％,10.4％和11.6％.     

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.     

含煤盆地深层“超饱和”煤层气形成条件

中国深层煤层气资源丰富，但总体勘探和认识程度较低，尚未形成较为系统的深层煤层气地质理论。通过解剖分析准噶尔盆地白家海凸起和鄂尔多斯盆地临兴区块深层"超饱和"煤层气井的试气/生产动态，估算原地游离气的含气量，分析了深层"超饱和"煤层气的形成条件。研究表明：①深层"超饱和"煤层气储层中除吸附气外，还含有原地游离气，用常规试气方法可直接获得气流，煤层气的产出不明显依赖于排水降压；②埋藏超过一定深度，在煤阶和温度的综合作用下，煤的吸附能力将随埋深的继续增加而降低，煤层中吸附气的饱和度有增加的趋势，在达到吸附饱和后，出现原地游离气并形成"超饱和"煤层气，盆地深层具有"超饱和"煤层气形成的优势条件；③由于地温梯度和压力梯度的不同，不同盆地"超饱和"煤层气出现的临界深度不同，异常高压和异常高热流可以降低深层"超饱和"煤层气形成的临界深度；④深层"超饱和"煤层气开发具有大大缩短见气时间、充分利用地层能量和累积产水量低等优势，有望成为未来煤层气勘探开发的一个重要领域。     

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。     

低温低渗透砂岩油藏窜流大孔道深部封堵技术研究

所用堵剂为高强度的淀粉接枝聚丙烯酰胺交联凝胶SAMG-1,由<6%淀粉、4.5%-5.5%丙烯酰胺、0.003%-0.006%交联剂组成,35℃成胶时间受淀粉和交联剂用量控制,为18-20小时以上,成胶前黏度-100 mPa.s。该堵剂具有长期稳定性,在储层岩心中注入深度15 cm的堵剂,在35℃候凝48小时后及老化90天后,封堵强度分别为0.61和0.59 MPa/cm,封堵率分别为98.6%和98.1%。该堵剂优先进入高渗层,注入0.5 PV并成胶后,2组双填砂管组成的模型低、高渗管渗透率保留率分别为68.4%、0.7%和69.4%、0.0%。吉林扶余油田西一区+15-8.2区块有水井6口,油井13口,含水率达91.5%,注入水最快在5天内到达油井。报道了该区块整体深部调剖封堵窜流通道的情况,详细叙述了+15-9.2井施工中通过注入压力和井底回压控制注入流量,使堵剂陆续进入原生和次生孔道的工艺作业,该井设计注入堵剂92 m3。6口水井整体调剖后,油井产液量差别减小,产油量增加,有效期已超过了9个月,共增油843 t,含水平均下降3.87%。图7表1参8。