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.     

Deterioration and Recovery of Metakaolin Blended Concrete Subjected to High Temperature

The deterioration and spalling frequency of metakaolin (MK) blended concrete subjected to high temperature is analyzed and compared with the equivalent silica fume (SF), fly ash (FA) and pure OPC concretes. Normal and high strength concrete mixes incorporating 0–20% MK were prepared and exposed to a series of high temperatures till 800°C. The residual compressive strength, porosity and pore size distribution were determined. It was found that after an increase in compressive strength at 200°C, the MK concrete suffered a more severe loss of compressive strength and permeability-related durability than the corresponding SF, FA, and pure OPC concretes at higher temperatures. Explosive spalling was observed in both normal and high strength MK concretes, and the frequency increased with higher MK contents. It is concluded that the dense micro-structure and low porosity are the main reasons of the poor performance of MK concrete at high temperature. The effect of post-fire curing on the strength and durability recovery of fire-damaged concrete was also investigated. The test results indicated that the post-fire curing, results in substantial strength and durability recovery, and its extent depends upon the types of concrete, exposure temperature, method, and duration of re-curing.     

The Effects of Sc Alloying in Y56Al24Ni10Co10 Glasses on the Local Atomic Structure

Using neutron diffraction and the pair density function analysis, the effect of Sc alloying for Y on the local atomic structure of Y_56-x Al₂₄Ni₁₀Co₁₀ was investigated. The replacement of Y with Sc significantly changes the local atomic structure of amorphous Y_56-x Al₂₄Ni₁₀Co₁₀ as it promotes the formation of nanocrystalline particles. By comparing the structure function in reciprocal space of three alloys with x = 0, 0.1, and 0.2 (in atomic percent), small Bragg peaks are observed that increase in intensity proportionate with the amount of Sc. In real space, the substitution of Sc for Y leads to a drastic structural contraction most likely resulting from efficient cluster packing.     

Atomic Bond Deficiency Defects in Amorphous Metals

Atomic bond deficiency (BD) is considered to be characteristic structural defects in amorphous metals. They are the necessary feature of local atomic configurations that facilitate various atomic transports under different driving forces. Compared with vacancies in crystalline solids, they are ??small?? in terms of their formation energies, volume costs, and elementary steps involved in atomic transport. This article reviews the authors?? recent efforts made to analyze how various local configurations containing BD are related to amorphous metal??s unique characteristics, such as glass transition, diffusion, shear flow, and structural relaxation.     

复杂功能超高层建筑的结构设计挑战

0引言 总部位于美国纽约的宋腾添玛沙帝工程顾问有限公司(Thornton Tomasetti lnc.,简称TT),是一个专长大型复杂结构设计的公司,其凭借专业实力,参与了世界前20个超高层建筑中近一半项目的结构设计,包括已建成的中国台湾台北市的世界金融中心(即台北101)、马来西亚吉隆坡的双子石油大厦、上海的恒隆广场和正在建设中的上海中心、芝加哥螺旋塔、平安国际金融中心等。     

Engineering and microstructure properties of contaminated marine sediments solidified by high content of incinerated sewage sludge ash

Management of incinerated sewage sludge ash(ISSA) and dredged contaminated marine sediments(CMSs) is a great challenge for Hong Kong and other coastal cities due to limited landfilling capacity.The present study investigates the use of high content(20% of sediment by mass) of ISSA in combination with cement/lime for solidification/stabilization(S/S) treatment of CMSs to provide a way to reuse the wastes as construction materials.The results showed that ISSA being a porous material was able to absorb a large amount of water rendering a more efficient solidification process of the marine sediment which normally had a very high water content(～80%).The S/S treatment improved the engineering properties of the sediment,but reduced the workability,especially for the lime-treated samples.Lime can be used to replace ordinary Portland cement(OPC) for better heavy metal immobilization and carbon emission reduction.The hardened sediment samples prepared with 10% of lime and 20% of ISSA could attain a strength of 1.6 MPa after 28 d of curing.In addition,leaching tests confirmed that there was no environmental risk induced by these stabilized materials.The formation of hydrated cementitious compounds including calcium silicate hydrate(C-S-H)/calcium aluminate silicate hydrate(C-A-S-H)/hydrocalumite/calcite was mainly responsible for the strength development in the ISSA/lime-treated sediments.     

Characterization of the deterioration of externally bonded CFRP-concrete composites using quantitative infrared thermography

Defects embedded in externally-bonded CFRP-concrete composite structures reduce the interfacial bond strength and durability. This paper classifies these defects into two types: flaws and delaminations. Flaws are formed during the first application of the CFRP strips onto the concrete surface due to poor workmanship. Delaminations are formed due to stress concentrations related to chemical/physical degradation of the binding layer. In this study, an aggressive environment was simulated by placing the specimens in water baths with elevated temperatures (40 °C and 60 °C). The sizes of the CFRP-flaws and delaminations were determined by (i) quantitative infrared thermography (QIRT) and (ii) processing of visual images after opening-up the CFRP by direct shear. Experimental results show that apparent flaw sizes determined by QIRT were in good agreement (88% accuracy) with actual flaw sizes determined by the image processing method. The results also show that flaws exhibited little change but the bonding layer showed significant deterioration after exposure to high water temperatures.     

Fluid-phase equilibria in binary systems containing an ionic liquid. Application of the Percus-Yevick-van der Waals equation of state

Following some simplifications to reduce the computational effort, the Percus-Yevick-van der Waals equation of state is used to calculate the isothermal total pressure of a binary liquid system containing one volatile nonelectrolyte liquid and one nonvolatile ionic liquid. Pure-component parameters a and b are found from pure-component enthalpy-of-vaporization and liquid-density data. The single binary parameter a₁₂ is obtained from Henry's constant for the nonelectrolyte in the ionic liquid. For 10 binary systems, calculated total pressures are in good agreement with experiment although in a few systems observed total pressures are slightly higher than those calculated in the region where the ionic liquid is dilute. Brief attention is given to a few binary systems with a miscibility gap.