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.     

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.     

合成氨中置锅炉的修复

本文在分析中置锅炉失效原因的基础上，提出了详细的修复措施，为类似情况的设备修复提供了借鉴。     

Examining a dimensional representation of depression and anxiety disorders' comorbidity in psychiatric outpatients with item response modeling.

The current study replicated, in a sample of 2,300 outpatients seeking psychiatric treatment, a previous study (R. F. Krueger & M. S. Finger, 2001) that implemented an item response theory approach for modeling the comorbidity of common mood and anxiety disorders as indicators along the continuum of a shared latent factor (internalizing). The 5 disorders examined were major depressive disorder, social phobia, panic disorder/agoraphobia, specific phobia, and generalized anxiety disorder. The findings were consistent with the prior research. First, a confirmatory factor analysis yielded sufficient evidence for a nonspecific factor underlying the 5 diagnostic indicators. Second, a 2-parameter logistic item response model showed that the diagnoses were represented in the upper half of the internalizing continuum, and each was a strongly discriminating indicator of the factor. Third, the internalizing factor was significantly associated with 3 indexes of social burden: poorer social functioning, time missed from work, and lifetime hospitalizations. Rather than the categorical system of presumably discrete disorders presented in DSM-IV, these 5 mood and anxiety disorders may be alternatively viewed as higher end indicators of a common factor associated with social cost. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bite and unconfirmed failures

Electronic BITE is poor at identifying hardware failure and in present design approaches tends to create the reviled ‘unconfirmed failure’. A different approach to BITE and unconfirmed failure could improve both operational performance and the cost of maintenance.     

The TDCPR Management Mode of Engineering Equipment

The Three Gorges Project is a very large project,and its structure is very complex.Interna-tional advanced engineering equipment is broadly used.The state of equipment running directly influ-ences project building qualities and limited time.According to the factud conditions of the Three Gor-ges Project,the characteristics of engineering equipment are analyzed.At the same time ,some theories about equipment management are induced ,and the TDCPR management mode of engineering equip-ment of the Three Gorges Project is put forwared in order to gain the aim of managing and using equip-ment well and speeding up the project construction.     

柳海矿运输大巷返修工程深部软岩支护设计研究

通过现场调查、室内试验以及理论分析,柳海矿运输大巷支护现状进行分析研究,总结破坏原因。根据现场工程地质条件、岩石特性和破坏特点,确定软岩变形力学机制为高应力膨胀性软岩,并提出采用预留刚隙柔层支护技术进行支护。     

Some results on generalized residual entropy

Shannon’s entropy plays an important role in the context of information theory. Since this entropy is not applicable to a system which has survived for some units of time, the concept of residual entropy has been developed in the literature. Here we generalize the residual entropy by choosing a convex function ? with ?(1) = 0. In this paper, some orderings and aging properties have been defined in terms of the generalized residual entropy function and their properties have been studied. Quite a few results available in the literature have been generalized and some distributions (viz. uniform, exponential, Pareto, power series, finite range) have been characterized through the generalized residual entropy.