Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7

Point mutations in the genes encoding the skeletal muscle isoforms of tropomyosin can cause a range of muscle diseases. The amino acid substitution of Arg for Pro residue in the 90th position (R90P) in γ-tropomyosin (Tpm3.12) is associated with congenital fiber type disproportion and muscle weakness. The molecular mechanisms underlying muscle dysfunction in this disease remain unclear. Here, we observed that this mutation causes an abnormally high Ca²⁺-sensitivity of myofilaments in vitro and in muscle fibers. To determine the critical conformational changes that myosin, actin, and tropomyosin undergo during the ATPase cycle and the alterations in these changes caused by R90P replacement in Tpm3.12, we used polarized fluorimetry. It was shown that the R90P mutation inhibits the ability of tropomyosin to shift towards the outer domains of actin, which is accompanied by the almost complete depression of troponin’s ability to switch actin monomers off and to reduce the amount of the myosin heads weakly bound to F-actin at a low Ca²⁺. These changes in the behavior of tropomyosin and the troponin–tropomyosin complex, as well as in the balance of strongly and weakly bound myosin heads in the ATPase cycle may underlie the occurrence of both abnormally high Ca²⁺-sensitivity and muscle weakness. BDM, an inhibitor of myosin ATPase activity, and W7, a troponin C antagonist, restore the ability of tropomyosin for Ca²⁺-dependent movement and the ability of the troponin–tropomyosin complex to switch actin monomers off, demonstrating a weakening of the damaging effect of the R90P mutation on muscle contractility.     

TEM and DFT investigation of CVD TiN/κ-Al2O3 multilayer coatings

This paper investigates the interfacial structure in hot-wall CVD TiN/κ-Al₂O₃ multilayer coatings using both HREM and DFT modeling. Two multilayers with different thicknesses of the TiN layers (50 and 600 nm) separating the κ-Al₂O₃ layers are analyzed. The general microstructure of the two multilayers is relatively similar. The TiN layer in the thicker TiN/κ-Al₂O₃ coating is thick enough to be several TiN grains high. This means that epitaxial columns, which are often found in the thinner TiN/κ-Al₂O₃ coatings, are not present. However, the orientation relationships at the TiN/κ-Al₂O₃ interfaces are the same in both multilayers. The HREM investigations show that κ-Al₂O₃ (001) planes can grow directly on flat (111) TiN faces, without any other phases or detectable amounts of impurities, such as sulphur, present. Where the TiN layers are more curved, γ-Al₂O₃ can be grown, at least partly stabilized by the cube-on-cube orientation relationship between γ-Al₂O₃ and the underlying TiN. The DFT calculations show very similar adsorption strengths for an O monolayer positioned on Ti-terminated TiC(111) and TiN(111) surfaces, with preferred adsorption in the fcc site. O adsorption on N-terminated TiN(111) is much weaker, with preferred adsorption in the top site. Calculated elastic-energy contributions yield a higher stability for κ-Al₂O₃ on TiN(111) than on TiC(111) and a higher stability for κ-Al₂O₃ than for α-Al₂O₃ on both TiC and TiN. This indicates that the observed higher stability of κ-Al₂O₃ on TiC(111) than on TiN(111) is not due to the lattice mismatch, while the preferred epitaxial growth of κ-Al₂O₃ over α-Al₂O₃ can be partly attributed to the mismatch.     

LabVIEW 7 Express平台上的液压测试系统

为了满足工程实践对先进液压测试技术的需要，研究了基于美国NI公司最新推出的LabVIEW 7 Express虚拟仪器开发平台的液压测试系统的软硬件结构，介绍了测试系统实现网络通讯、数据库链接和多种编程语言联合作业的方法，提出了现代液压测试系统的技术方案。     

STUDY OF INTERFACES AND SURFACES OF YBa_2Cu_3O_(7-x)-Ag

Interfaces and surfaces of YBa_2Cu_3O_(7-x)(YBCO)-Ag have been studied by SEM-EDXand AES.No effect of Ag on 123 structure in X-ray diffraction pattern was observedfor 0.4 mol Ag doped YBCO.AES analysis indicated that Ag segregated on surfaceof YBCO and resulted in decrease of YBCO-metal lead resistance.In addition,solutionand segregation of Ag as elemental state were often appeared on interfaces and surfacesof high temperature annealed YBCO,whether elemental Ag or compound Ag_2O andAgNO_3 adopted as doping material.     

LD7铝合金时效工艺的研究

通过试验系统地研究了ＬＤ７铝合金的单级和两级时效工艺。结果表明，与传统的单级时效相比，两级时效在不降低室温强度，硬度的前提下，可显著提高合金的电导率及高温性能。     

锡磷青铜合金水平连铸工艺参数的优化

铸造锡磷青铜合金组织中存在显微缩松、枝晶偏析和反偏析是冷加工报废的主要原因.通过连铸工艺参数的正交实验,建立了轧制成材率与主要工艺参数之间的神经网络描述,网络模型与遗传算法结合对工艺参数的组合进行了优化,改善了铸坯的组织,提高了轧制带材成材率.     

Influence of expandable graphite on fire resistance and water resistance of flame-retardant coatings

Expandable graphite (EG) coating and ammonium polyphosphate-pentaerythritol-melamine (APP-PER-MEL) coating were prepared. Thermal degradation and char formation of the coatings were investigated by differential thermal analysis (DTA), thermogravimetry (TG), X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The results have shown that the anti-oxidation and fire-resistant properties of expandable graphite coating containing EG with size of 74 μm are better than those of APP-PER-MEL coating. The static immersion test was applied to study water resistance of the coatings, and the fire protection test and mechanical test were used to analyse heat insulation and mechanical properties of coatings before and after water immersion. The fire-resistant and mechanical properties of APP-PER-MEL coating were severely damaged by water immersion, whereas EG coating containing 8.5% EG with size of 74 μm could retain the good fire resistance even after 500 h water immersion.     

Oxygen transport in ferrite-based ceramic membranes: Effects of alumina sintering aid

Moderate additions of Al₂O₃ to strontium ferrite-based mixed conductors, such as SrFe_0.7Al_0.3O_3−δ and La_0.2Sr_0.8Fe_0.8Ga_0.2O_3−δ with the composition close to the solid solution formation limits, make it possible to improve ceramics sinterability, to increase oxygen permeability and to decrease thermal expansion. These effects are associated with the segregation of alumina-rich phases, primarily SrAl₂O₄, and the formation of A-site cation-deficient perovskite. The improved properties of the SrFe_0.7Al_0.3O₃-based material were used to fabricate high-quality tubular membranes for methane conversion reactors. Similar enhancement in sinterability is also observed for another promising parent material of mixed-conducting membranes, La_0.5Sr_0.5FeO_3−δ. However, extensive dissolution of Al³⁺ cations in the iron sublattice, creation of A-site vacancies and changing the La:Sr concentration ratio all lead to decreasing ionic transport in La_0.5Sr_0.5FeO_3−δ. As a result, additions of either Al₂O₃ or SrAl₂O₄ have a deteriorating influence on the oxygen permeation fluxes through La_0.5Sr_0.5FeO₃-based ceramics.     

Enhancement by SO2 of initial activity for selective catalytic reduction of NO with CH3OH over \gamma-alumina

The effect of SO₂ on catalytic activity for NO reduction to N₂ by methanol in excess oxygen over $\gamma$ -alumina has been investigated. SCR activity increased initially upon exposure of a fresh $\gamma$ -alumina catalyst to SO₂ which is attributed to formation of Brønsted acid sites. Longer exposure to SO₂ leads to a decline in catalytic activity to a lower steady-state NO_x reduction activity which is independent of the SO₂ content in the feed gas.