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.     

基于残差决策的自动飞行控制系统远程实时故障诊断

针对自动飞行控制系统结构复杂、关联部件众多,发生故障时诊断时间长,从而影响飞机运行效率的问题,提出一种基于飞机通信寻址报告系统(ACARS)的远程实时故障诊断方案。首先,分析自动飞行控制系统的故障特点,设计搭建检测滤波器;然后,利用ACARS数据链实时发送的自动飞行控制系统的关键信息进行相关部件的残差计算,并根据残差决策算法进行故障诊断及定位;最后,针对不同故障部件残差间的差异大、决策门限无法统一的缺点,提出基于二次差值的残差决策改进算法,减缓了检测对象的整体变化趋势,降低了随机噪声和干扰的影响,避免了将瞬态故障诊断为系统故障的情况。实验仿真结果表明,基于二次差值的改进残差决策算法避免了多决策门限的复杂性,在采样时间为0.1 s的情况下,故障检测所需时间大约为2 s,故障检测时间大幅降低,有效故障检测率大于90%。     

Liner services network design and fleet deployment with empty container repositioning

Transportation demand of shipping container fluctuates due to the seasonality of international trade, thus, every 3–6 months, the liner company has to alter its current liner shipping service network, redeploy ships and design cargo routes with the objective of minimizing the total cost. To solve the problem, the paper presents a mixed integer linear program model. The proposed model incorporates several relevant constraints, such as weekly frequency, the transshipment of cargo between two or more service routes, and transport time. Extensive numerical experiments based on realistic date of Asia–Europe–Oceania shipping operations show that the proposed model can solve real-case problems efficiently by CPLEX. The results demonstrate that the model can reduce ship’s capacity consumption and raise ships’ capacity utilization.     

机载通信电台通电老炼检测系统设计与实现

为保证航材备件的完好率，解决仓储机载通信电台长期不通电导致的装备性能下降甚至出现故障的问题，综合运用自动测试、虚拟仪器、面向信号设计等技术，以计算机为核心，以PXI仪器、GPIB仪器为依托，以多种总线接口为纽带，构建了一种可靠性高、通用性好、操作简便、可扩展性强的自动化通电老炼平台。通过在航材仓库中使用，证明该电台老炼检测系统降低了仓储通信电台的失效率，提高了仓储电台的完好率。     

嵌入式实时操作系统内核混合代码的自动化验证框架

"如何构造高可信的软件系统"已成为学术界和工业界的研究热点.操作系统内核作为软件系统的基础组件，它的安全可靠是构造高可信软件系统的重要环节.为了确保操作系统内核的安全可靠，将形式化方法引入到操作系统内核验证中，提出了一个自动化验证操作系统内核的框架.该验证框架包括：（1）分别对C语言程序和混合语言程序（C语言和汇编语言）进行验证；（2）在混合语言程序验证中，为汇编程序建立抽象模型，并将C语言程序和抽象模型粘合形成基于C语言验证工具可接收的验证模型；（3）从规范中提取性质，基于该自动验证工具，对性质完成自动验证；（4）该框架不限于特定的硬件架构.成功地运用该验证框架对两种不同硬件平台的嵌入式实时操作系统内核μC/OS-II进行了验证.结果显示：利用该框架在对两个不同的硬件平台上内核验证时，框架的可重复利用率很高，高达到88%，虽然其抽象模型需要根据不同的硬件平台进行重构.在对基于这两种平台的操作系统内核验证中，分别发现了10~12处缺陷.其中，在ARM平台上两处与硬件相关的问题被发现.实验表明，该方法对不同硬件平台的同一个操作系统分析验证具有一定的通用性.     

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.     

基于查询的新闻多文档自动摘要技术研究

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。     

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.     

Moderate lameness leads to marked behavioral changes in dairy cows

Lameness is one of the most prevalent diseases affecting the welfare of cows in modern dairy production. Lameness leads to behavioral changes in severely lame cows, which have been investigated in much detail. For early detection of lameness, knowledge of the effects of moderate lameness on cow behavior is crucial. Therefore, the behavior of nonlame and moderately lame cows was compared on 17 Swiss dairy farms. On each farm, 5 to 11 nonlame (locomotion score 1 of 5) and 2 to 7 moderately lame (locomotion score 3 of 5) cows were selected for data collection in two 48-h periods (A, B) separated by an interval of 6 to 10 wk. Based on visual locomotion scoring, 142 nonlame and 66 moderately lame cows were examined in period A and 128 nonlame and 53 moderately lame cows in period B. Between these 2 periods, the cows underwent corrective hoof trimming. Lying behavior, locomotor activity, and neck activity were recorded by accelerometers (MSR145 data logger, MSR Electronics GmbH, Seuzach, Switzerland), and feeding and rumination behaviors by noseband sensors (RumiWatch halter, ITIN + HOCH GmbH, Liestal, Switzerland). Furthermore, visits to the brush and the concentrate feeder, and the milking order position were recorded. In comparison with nonlame cows, moderately lame cows had a longer lying duration, a longer average lying bout duration, and a greater lateral asymmetry in lying duration. Average locomotor activity, locomotor activity during 1 h after feed delivery or push-ups, and average neck activity were lower in moderately lame cows. Eating time and the number of eating chews (jaw movements) were reduced in moderately lame compared with nonlame cows, whereas no effect of moderate lameness was evident for ruminating time, number of ruminating chews and boluses, and average number of ruminating chews per bolus. Moderately lame cows visited the concentrate feeder and the brush less frequently, and they were further back in the milking order compared with nonlame cows. In conclusion, nonlame and moderately lame cows differed in a biologically relevant way in many of the behavioral variables investigated in this study. Therefore, the use of these behavioral changes seems to be promising to develop a tool for early lameness detection.