Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.     

Crystallographic characteristics and microwave dielectric properties of Ni-modified MgTa2O6 ceramics

Ni²⁺ modified MgTa₂O₆ ceramics with a trirutile phase and space group P4₂/mnm were obtained. The correlations between crystallographic characteristics and microwave dielectric performance of MgTa₂O₆ ceramics were systematically studied based on the chemistry bond theory (PVL theory) for the first time. The results indicate that the introduction of Ni²⁺ causes a change in polarizability and the Mg–O bond ionicity, which contributes to the variation of dielectric constant. Moreover, the lattice energy, and packing fraction, full width at half maximum of the Raman peak of Ta–O bond, as the quantitative characterization of crystallographic parameters, regulate the dielectric loss of MgTa₂O₆ ceramics in GHz frequency band. In addition, the study of sintering behavior shows that the densification and micromorphology are the crucial factors affecting the microwave dielectric performance. Typically, Ni²⁺ doping on the A-site of MgTa₂O₆ can effectively promote the Q × f values to 173,000 GHz (at 7.43 GHz), which ensures its applicability in 5G communication technology.     

Structural Cues for Understanding eEF1A2 Moonlighting

Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.     

Flow state monitoring of gas-water two-phase flow using multi-Gaussian mixture model based on canonical variate analysis

As a highly complex and time-varying process, gas-water two-phase flow is commonly encountered in industries. It has a variety of typical flow states and transition flow states. Accurate identification and monitoring of flow states is not only beneficial to further study of two-phase flow but also helpful for stable operation and economic efficiency of process industry. Combining canonical variate analysis (CVA) and Gaussian mixture model (GMM), a strategy called multi-CVA-GMM is proposed for flow state monitoring in gas-water two-phase flow. CVA is used to extract flow state features from the perspective of correlation between historical data and future data, which solves the cross correlation and temporal correlation of multi-sensor measurement data. GMM calculates the possibility that the current flow state belongs to each typical flow pattern and judges the current flow state by probability indicators. It is conducive to follow-up use of Bayesian inference probability and Mahalanobis distance-based (BID) indicator for flow state monitoring, which avoids repeated traversal of multiple CVA-GMM models and improves the efficiency of the monitoring process. The probability indicators can also be used to analyze transition flow states. The method combining the probabilistic idea of GMM with the deterministic idea of multimodal modeling can accurately identify the current flow state and effectively monitor the evolution of flow state. The multi-CVA-GMM method is validated by using the measured data of the horizontal flow loop of gas-water two-phase flow experimental facility, and its effectiveness is proved.     

Investigation of crystal characteristics,Raman spectra,and microwave dielectric properties of Mg1-xZnxTa2O6 ceramics

Mg_(1-x)Zn_xTa₂O₆ (x = 0.00?0.08) dielectric ceramics were synthesized via the traditional solid-state reaction method. We used XRD and Rietveld refinement to demonstrate that a pure Mg_(1-x)Zn_xTa₂O₆ phase with trirutile structure was formed. Zn²⁺ substitution helped to decrease the Raman full width at half width of the A_1g mode at 703 cm^?1, which resulted in an increase in the order and rigidity of the TaO₆ octahedron, this in turn contributed to improving the Q×f values. Additionally, the introduction of Zn²⁺ significantly promoted grain growth and increased the dense, and the molecular polarizability, these factors lead to a higher permittivity. Moreover, enhanced Ta-O bond energy resulted in a more stable TaO₆ octahedron in the Mg_(1?x)Zn_xTa₂O₆ system, which contributed to enhanced τ_f values via substitution of Zn²⁺ doped on the A-site. Correspondingly, the microwave dielectric properties were significantly improved for 0.04-doped samples, obtaining: ε_r = 27, Q × f = 185,000 GHz (at 7.47 GHz), τ_f =32 ppm/°C.     

Impedance matching optimization of SiCf/Si3N4–SiOC composites for excellent microwave absorption properties

SiC fiber reinforced ceramic matrix composites (SiC_f-CMCs) are considered to be one of the most promising materials in the electromagnetic (EM) stealth of aero-engines, which is expected to achieve strong absorption and broad-band performance. Multiscale structural design was applied to SiC_f/Si₃N₄–SiOC composites by construction of micro/nanoscale heterogeneous interfaces and macro double-layer impedance matching structure. SiC_f/Si₃N₄–SiOC composites were fabricated by using SiC fibers with different conductivities and SiOC–Si₃N₄ matrices with gradient impedance structures to improve impedance matching effectively. Owing to its unique structure, SiC_f/Si₃N₄–SiOC composites (A3-composites) achieved excellent EM wave absorption performance with a minimum reflection coefficient (RC_min) of ?25.1 dB at 2.45 mm and an effective absorption bandwidth (EAB) of 4.0 GHz at 2.85 mm in X-band. Moreover, double-layer SiC_f/Si₃N₄–SiOC with an improved impedance matching structure obtained an RC_min of ?56.9 dB and an EAB of 4.2 GHz at 3.00 mm, which means it can absorb more than 90% of the EM waves in the whole X-band. The RC is less than ?8 dB at 2.6–2.8 mm from RT to 600 °C in the whole X-band, displaying excellent high-temperature absorption performance. The results provide a new design opinion for broad-band EM absorbing SiC_f-CMCs at high temperatures.     

Quasi-static compressive behaviour of aluminium cenosphere syntactic foams

In this paper, cenosphere particles embedded in AA2014 aluminium matrix are used to fabricate syntactic foam by stir casting method. The particle size is about 100?µm and foam density is about 1990?kg?m^?3. Compression tests at strain rate 0.001/s are performed on foam samples to characterise their mechanical properties which are then used in numerical analysis on commercial finite element analysis software ABAQUS/CAE with isotropic elastic-plastic material model. Experimental and numerical results show good conformity in deformation behaviour with elastic and plateau zones showing average deviations less than 5% and 20%, respectively. Foams showed high yield stress and energy absorption capabilities that can be useful in making blast and impact resistant structures.     

面向电信承载网的监控系统设计与实现

面对电信承载网连接的日益增长的海量终端设备，运营商需要结合网络拓扑对终端设备产生的数据进行高效的汇聚统计、异常分析、故障定位处理等操作。针对已有系统存在的操作困难、分析效率低等问题，设计与实现了一个面向电信承载网的高效监控系统，提供实时与离线数据分析和多维可视化分析的能力。对网管、认证、终端等系统及设备采集的数据进行结构化存储，对采集的数据进行拓扑相关性和时间序列方法分析，根据分析结果实现基于动态阈值控制的异常实时告警、定位等操作，并提供多维度可视化分析对网络状态进行实时监控。实际应用结果表明，该系统性能优异，具有良好交互性，能较好地满足承载网运维人员业务分析需求。     

Design and validation of robotic bionic eye with multiple flexible ropes parallel mechanism inspired by oculomotor law

Producing a stable and agile bionic eye for visual image acquisition in robotics is a challenging task. In this paper, we design a bionic eye with mirror-symmetric distribution and cross-connection of flexible ropes. This mechanism is based on oculomotor law and the physiological structure of the extraocular muscles (EOMs). Specifically, the basic structural parameters are determined by Listing’s law, and the unique connection of the flexible ropes can realize the functions of the recti and oblique muscles. Furthermore, to mimic the trochlea structure, a pulley mechanism is constructed to permit the free movement of the flexible ropes. Through simulation and physical experiments, it is demonstrated that the bionic eye mechanism can move with agility under the structural parameters. The experimental results indicate that the proposed bionic eye mechanism has a superior motion accuracy of 2.798 mm, which is 6.7% of the maximum motion distance, and the repeatable accuracy of the mechanism can up to 0.210 mm.