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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.
介绍了全电动注塑机的特色,综述了国内外全电动注塑机在精密注塑、智能注塑、高效注塑和绿色注塑方面的研究进展,并对全电动注塑机在汽配电子行业中的应用作了简单介绍。对双电机同步控制技术的逐渐成熟为全电动注塑机实现大型化提供了助力,全电动注塑机高效、精密、智能、节能、环保的优势在汽配电子行业显示了很好的应用前景。  相似文献   
3.
Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.  相似文献   
4.
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   
5.
通过多步法合成了离子型含双苯并三氮唑环的目标分子,4,4'-{苯-1,3-二基二[(1E)-3-羰基丙-1-烯-1,3-二基]}二[2-(2H-苯并三唑-2-基)苯醇酸]二钾。在室温条件下,目标分子在3.5%(质量)NaCl/DMSO(二甲基亚枫)混合溶液 (体积比:40/60) 中能够发生分子自组装产生纳-微米级的自聚集体。通过傅里叶变换红外光谱 (FT-IR)、拉曼光谱和X射线光电子能谱 (XPS) 的表征,证实了所形成的目标分子自聚集体能够对铜表面产生强烈的化学吸附作用,在铜表面形成自组装膜。利用电化学方法测定了目标分子自聚集体吸附在铜表面形成自组装膜后,在3.5%(质量)NaCl溶液中的缓蚀性能。结果表明目标分子自聚集体在NaCl溶液中能高效地抑制铜腐蚀。  相似文献   
6.
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   
7.
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   
8.
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   
9.
Cables to moving parts on a linear actuator in production machines, such as pick-and-place machines, are a source of unreliability owing to the possible breaking of a cable. They further reduce the positioning precision of the actuator owing to additional forces. Slotted waveguide systems for rail vehicles based on 2.4 GHz transmission frequency are well known, but transmitters/receivers and waveguides are bulky. The paper reports on the reduction in size of the equipment, adapted to 5.8 GHz using a commercial off-the-shelf RadioLan communication module. Further, the efficient termination of the wave-guide and a new way to reduce standing-wave effects is also discussed.  相似文献   
10.
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   
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