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.     

Ab initio calculations of the NO2 fission for CL-20 conformers

NO₂ fission is regarded to be the most important initial decomposition process of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). In this study, four CL-20 conformers based on the ε-CL-20 were obtained after the optimization at m062x/cc-pvtz level, and the bond length, bond order and bond dissociation energy of the N-N bonds were examined to investigate the stability of these bonds. In addition, the rate constants and activation energy of the NO₂ fission were evaluated using the microcanonical variational transition state theory (μVT). The calculation results have shown that N-N bonds in the case of pseudo-equatorial and axial of nitro groups are the most stable and the least stable, respectively, by evaluating the bond length, bond order and minimum energy path (MEP). The NO₂ fission rate constants are affected by not only the stability of N-N bonds but also the repulsion forces from the other nitro groups, and the fission process for pseudo-equatorial positioning of nitro groups is easier to be accelerated due to the increase of the repulsion forces. The decomposition of CL-20 conformer may mainly originate from the fission of the pseudo-equatorial positioning of nitro groups, especially for CL-20 III conformer because of the significant low activation energy.     

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.     

Intrinsic dielectric behavior of Mg2TiO4 spinel ceramic

In the work, we focused on the intrinsic dielectric behavior of Mg₂TiO₄ spinel ceramic by P–V–L theory and infrared spectra analysis. Ti–O bonds have larger bond ionicity values, thus playing an important role in dielectric polarization. The theoretical dielectric constant was predicted by calculating the bond susceptibility of each chemical bond. Furthermore, Ti(1)–O bonds are responsible for the structural stability of Mg₂TiO₄ ceramic. Based on classical dispersion theory, permittivity and loss corresponding to each infrared active mode were quantified, and then the crucial contribution of low-frequency modes to intrinsic dielectric properties were determined.     

Effects of structural characteristics on microwave dielectric properties of low-loss (Zn1-xNix)ZrNbTaO8 ceramics

Low-loss (Zn_1-xNi_x)ZrNbTaO₈ (0.02?≤?x?≤?0.10) ceramics possessing single wolframite structure are initiatively synthesized by solid-state route. Based on the results of Rietveld refinement, complex chemical bond theory is used to establish the correlation between structural characteristics and microwave performance in this ceramic system. A small amount of Ni²⁺ (x?=?0.06) in A-site with the fixed substitution of Ta⁵⁺ in B-site can effectually raise the Q?×?f value of ZnZrNb₂O₈ ceramic, embodying a dense microstructure and high lattice energy. The dielectric constant and τ_f are mainly affected by bond ionicity and the average octahedral distortion. The (Zn_0.94Ni_0.06)ZrNbTaO₈ ceramic sample sintered at 1150?°C for 3?h exhibits an outstanding combination of microwave dielectric properties: ε_r =?27.88, Q?×?f?=?128,951?GHz, τ_f =?–39.9?ppm/°C. Thus, it is considered to be a candidate material for the communication device applications at high frequency.     

Effects of sintering in a high magnetic field on properties of vitrified bond and vitrified CBN composites

Vitrified bond CBN grinding wheels are being widely used due to their superior performance. Also, advantages of vitrified grinding wheels are high elastic modulus, stable chemical property, and low thermal expansion coefficient. Brittleness and low strength are key factors restricting the development of vitrified bond CBN grinding wheels. In this paper, the sintering in a high magnetic field was innovatively introduced into the manufacturing of vitrified bond CBN grinding wheels, and the effects of sintering in a high magnetic field on properties on vitrified bond and vitrified CBN composites were systematically investigated. Vitrified bond was characterized using three-point bending, scanning electron microscopy, X-ray diffraction. It was observed that microstructure of vitrified bond could be changed, grain orientation could be controlled and average grain size could be decreased in a high magnetic field, while vitrified bond strength could be simultaneously improved. High quality vitrified bond could be obtained by appropriately adjusting the strength and direction of high magnetic field. Results demonstrated that vitrified bond properties were improved when the magnetic field strength was 6?T. In order to highlight the high magnetic field effect on the vitrified CBN composites, the ordinary CBN abrasives and nickel plated CBN abrasives were used respectively. Microstructures, bending strengths of vitrified CBN composites were compared in different high magnetic fields. When the magnetic field strength was appropriate (less than 6?T), the binding characteristic of vitrified bond CBN composites with nickel plated CBN abrasives was greatly improved. The highest bending strength value of vitrified CBN composites was 79.5?MPa in 6?T high magnetic field.     

葛洲坝水利枢纽泄水建筑物进水口冲磨与修复

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。     

An application of chemometric techniques to analyze the effects of the wave function modifications on the intermolecular stretching frequencies of the hydrogen-bonded complexes

Factorial design and principal component models are used to determine how ab initio H-bond stretching frequencies depend on characteristics of the molecular orbital wave functions of acetylene–HX, ethylene–HX and cyclopropane–HX π-type hydrogen complexes with X=F, Cl, CN, NC and CCH. The results obtained for the three sets of complexes show that factorial design and principal component analyses complement each other. Factorial design calculations clearly show that these frequencies are affected mostly by inclusion of electron correlation on the calculation level. On average, their values are increased by about 25 cm⁻¹ due to a change from the Hartree–Fock (HF) to Möller–Plesset 2 (MP2) level. Valence, diffuse and polarization main effects as well as valence–diffuse, diffuse–correlation and polarization–correlation interaction effects are also important to better describe a factorial model to the H-bond stretching frequencies of these hydrogen complexes. This simplified model has been successful in reproducing the complete ab initio results, which correspond to two hundred and forty calculations. Principal component analyses applied only to hydrogen-bonded complexes whose experimental frequencies are known, has revealed that the six-dimensional original space can be accurately represented by a bidimensional space defined by two principal components. Its graphical representation reveals that the experimental intermolecular stretching frequencies are in closest agreement with the MP2/6–31+G and MP2/6–311+G ab initio results.