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1.
Cho-Yi Chen Masaoki Kawasumi Tien-Yun Lan Chi-Lam Poon Yi-Sian Lin Pin-Jou Wu Yao-Chung Chen Bing-Hong Chen Cheng-Hsien Wu Jeng-Fan Lo Rueyhung Roc Weng Yi-Chen Sun Kai-Feng Hung 《International journal of molecular sciences》2021,22(1)
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. 相似文献
2.
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. 相似文献
3.
针对新闻文本领域,该文提出一种基于查询的自动文本摘要技术,更加有针对性地满足用户信息需求。根据句子的TF-IDF、与查询句的相似度等要素,计算句子权重,并根据句子指示的时间给定不同的时序权重系数,使得最近发生的新闻内容具有更高的权重,最后使用最大边界相关的方法选择摘要句。通过与基于TF-IDF、Text-Rank、LDA等六种方法的对比,该摘要方法ROUGE评测指标上优于其他方法。从结合评测结果及摘要示例可以看出,该文提出的方法可以有效地从新闻文档集中摘取核心信息,满足用户查询内容的信息需求。 相似文献
4.
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. 相似文献
5.
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. 相似文献
6.
葛洲坝水利枢纽泄水建筑物进水口冲磨与修复 总被引:2,自引:1,他引:1
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。 相似文献
7.
总结了HB - 3,HB - 4型钴钼触媒升温硫化过程及注意事项 ,简单介绍了使用情况 ,并针对出现的问题采取了一定措施 相似文献
8.
乌江洪家渡水电站坝址河谷深切300余m,硬质岩与软质岩相间分布,岸坡地形陡峻,软弱夹层发育,卸荷、崩塌等物理地质作用强烈。根据坝址地质条件与电站枢纽布置,工程存在:隧洞群进水口同向高边坡整体稳定问题;坝肩开挖、隧洞进出口开挖、厂房开挖及料场开挖等高边坡稳定问题;泄洪冲刷及雾化区1号、2号塌滑体高边坡稳定问题;王家渡堆料场、瓦房寨砂石系统高边坡稳定问题。因此,工程高边坡稳定问题是本工程的主要工程问题之一,但通过参建各方共同努力,本工程高边坡处理都取得了圆满成功。 相似文献
9.
搪瓷釜的使用维护与常用修补方法 总被引:2,自引:0,他引:2
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。 相似文献
10.