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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.
A series of anionic conjugated polyelectrolytes (CPEs) is synthesized based on poly(fluorene-co-phenylene) by varying the side-chain ionic density from two to six per repeat units (MPS2-TMA, MPS4-TMA, and MPS6-TMA). The effect of MPS2, 4, 6-TMA as interlayers on top of a hole-extraction layer of poly(bis(4-phenyl)-2,4,6-trimethylphenylamine (PTAA) is investigated in inverted perovskite solar cells (PeSCs). Owing to the improved wettability of perovskites on hydrophobic PTAA with the CPEs, the PeSCs with CPE interlayers demonstrate a significantly enhanced device performance, with negligible device-to-device dependence relative to the reference PeSC without CPEs. By increasing the ionic density in the MPS-TMA interlayers, the wetting, interfacial defect passivation, and crystal growth of the perovskites are significantly improved without increasing the series resistance of the PeSCs. In particular, the open-circuit voltage increases from 1.06 V for the PeSC with MPS2-TMA to 1.11 V for the PeSC with MPS6-TMA. The trap densities of the PeSCs with MPS2,4,6-TMA are further analyzed using frequency-dependent capacitance measurements. Finally, a large-area (1 cm2) PeSC is successfully fabricated with MPS6-TMA, showing a power conversion efficiency of 18.38% with negligible hysteresis and a stable power output under light soaking for 60 s.  相似文献   
3.
Peer-to-Peer Networking and Applications - P2P-TV is a TV system that receives content through a peer-to-peer network. Content is stored in the distributed manner then to be serviced to users, and...  相似文献   
4.
Tricalcium silicate (C3S) and hydroxyapatite (HAp) composites were fabricated through the sol-gel process. The aim of this research is to improve the biocompatibility of C3S through HAp addition and study the potential of using this as coating materials. The composites (HAp/C3S) were characterised by Fourier transform infrared spectrometry, thermal gravity-differential thermal analysis and X-ray diffraction. The working and setting times of cement pastes were tested using Gillmore needle. Mechanical properties were examined by nanoindentation and material testing system. In vitro biocompatibility of the materials were studied by cell attachment and viability of L929 and MG-63 cells. HAp/C3S as a coating material on gelatin film were measured with the surface roughness and imaged by scanning electron microscope. With the addition of HAp, no undesirable free CaO was detected with the synthesis by the sol-gel preparation. The pH values of HAp added groups were between 7.54 and 8.76, which were much lower than pure C3S group (pH?=?11.75). For in vitro studies, the presence of HAp could effectively enhance the cell attachment and viability of both L929 and MG-63 cells grown in the extract or directly on the composites. However, the mechanical properties of the composites were impaired as compared to pure C3S. Lastly, HAp/C3S cement could be evenly coated on gelatin film. HAp is successfully demonstrated to improve C3S biocompatibility with this new composites HAp/C3S. C-75 (75% C3S and 25% HAp), in particular, has good biocompatibility, relatively high compressive strength and can be uniformly coated onto gelatin film. Thus, C-75 is a promising material for further investigation as a coating on other biopolymers.  相似文献   
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6.
Mobile software applications have to cope with a particular environment that involves small size, limited resources, high autonomy requirements, competitive business models and many other challenges. To provide development guidelines that respond to these needs, several practices have been introduced; however, it is not clear how these guidelines may contribute to solve the issues present in the mobile domain. Furthermore, the rapid evolution of the mobile ecosystem challenges many of the premises upon which the proposed practices were designed. In this paper, we present a survey of the literature on software assurance practices for mobile applications, with the objective of describing them and assessing their contribution and success. We identified, organized and reviewed a body of research that spans in three levels: software development processes, software product assurance practices, and software implementation practices. By carrying out this literature survey, we reviewed the different approaches that researchers on Software Engineering have provided to address the needs that raise in the mobile software development arena. Moreover, we review the evolution of these practices, identifying how the constant changes and modernization of the mobile execution environment has impacted the methods proposed in the literature. Finally, we introduced discussion on the application of these practices in a real productive setting, opening an area for further research that may determine if practitioners have followed the proposed assurance paradigms.  相似文献   
7.
This paper presents an integrated passive damping approach in hybrid metal-CFRP parts for structural applications. In this concept a viscoelastic material is embedded in the joint zone of the hybrid component. To examine the connection strength single-lap-joint specimens were produced and tested and the influence of the used material combinations, different surface structures, and different process parameters i.e. the moment of cross-linking were evaluated. Afterwards, the metal-CFRP hybrids were tested in quasi-static tests to assess their connection strength and failure behaviour. Dynamic cyclic tensile tests with step-wise increased loading conditions were performed to determine the specimens damping behaviour and to estimate their fatigue performance. Finally, these results are compared to a state of the art metal-CFRP hybrid with rivets connecting both materials.  相似文献   
8.
In this paper, we consider the classical finite mixture model, which is an effective tool for modeling lifetime distributions for random samples from heterogeneous populations. We discuss new results on stochastic comparison for two finite mixtures when each of them is drawn from one of the following semiparametric families, i.e., proportional hazards, accelerated lifetime and proportional reversed hazards.  相似文献   
9.
This study presents a back-analysis of geotechnical parameters on prefabricated vertical drain improved ground at a site in the Mekong Delta. Various time?settlement behaviors that reflected different clay thicknesses and loading patterns were observed. The total surface settlement behavior at several monitoring locations was simulated using an updated exponential method that considered staged construction. The analyzed results were validated by substituting the values into a theoretical solution for radial consolidation. The estimated theoretical behaviors were comparable with the monitored behaviors. The geotechnical parameters were back-analyzed by applying the previously analyzed results to various theoretical and empirical formulas. However, the use of extensometer data that were installed at large intervals produced different values of the geotechnical properties. Furthermore, finite element analysis supported the back-analyzed total settlement behaviors and nearly disregarded the application of the geotechnical properties that were obtained using either surface or subsurface settlement data. However, settlements and excess pore pressures in the sublayers were not successfully predicted even when the geotechnical properties were adjusted. Thus, subsurface instruments that can be installed closely in thick clay deposits are required to reliably reevaluate the variations in geotechnical properties along a certain depth.  相似文献   
10.
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