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.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Annular‐ring slot antenna designs with circular polarization radiation

The design of a microstrip‐fed annular‐ring slot antenna (ARSA) with circular polarization (CP) radiation is initially studied. To obtain CP radiation with broad 3‐dB axial ratio (AR) bandwidth that can cover the WiMAX 2.3 GHz (2305–2320 MHz, 2345–2360 MHz) and WLAN 2.4 GHz (2400–2480 MHz) bands, a novel technique of extending an inverted L‐shaped slot from the bottom section of the annular‐ring is proposed. To suppress the harmonic modes induced by the CP ARSA, the technique of integrating a defected ground structure into the annular‐ring slot is further introduced. From the measured results, 10‐dB impedance bandwidth and 3‐dB AR bandwidth of 44.86 and 9.68% were achieved by the proposed harmonic suppressed CP ARSA. Furthermore, average gain and radiation efficiency of ～4.7 dBic and 71%, respectively, were also exhibited across the bands of interest. © 2014 Wiley Periodicals, Inc. Int J RF and Microwave CAE 25:337–345, 2015.     

中原油田岩石可钻性与声波时差关系研究

选取中原油田的大量岩心，采用常规岩石力学测试方法测定了岩石的可钻性、声波测试方法测定了岩石和岩屑声波时差，通过对测得的岩石可钻性级值和声波时差进行回归拟合，得出了中原油田岩石可钻性与声波时差的关系式。现场应用表明，该关系式较好地反映了中原油田地层岩石可钻性与声波时差的关系，可以在优选钻头时作为参考或直接应用。     

Modeling node mobility for reliable packet delivery in mobile ip networks

In this paper, we analyze node mobility for reliable packet delivery in mobile IP networks. In mobile IP, packets destined to roaming nodes are intercepted by their home agents and delivered via tunneling to their care of addresses (CoA). A mobile node may roam across multiple subnets. At each boundary crossing, a handoff is initiated such that the CoA is updated and a new tunnel is established. We consider both basic mobile IP handoff and smooth handoff. We find that reliable packet delivery in mobile IP networks can be modeled as a renewal process, because the retransmission over a new tunnel after each boundary crossing is independent of the previous history. We then derive the probability distribution of boundary crossings for each successful packet, based on which the packet reliable delivery time can be obtained. Our analytical model is derived based on a general distribution of residence time in a subnet and a general distribution of successful retransmission attempts in each subnet. The results can be readily applied to any distributions for both items. We also provide numerical examples to calculate the probability distribution of boundary crossings, and conduct simulations to validate our analytical results     

Dissolution processes,hydrolysis and condensation reactions during geopolymer synthesis: Part I—Low Si/Al ratio systems

Initial geopolymeric reaction processes governing dissolution of solid aluminosilicate particles in alkali solutions have been investigated using conventional experimental techniques, and the data analysed by speciation predictions of the partial charge model (PCM). For metakaolin powders activated with 5.0 M NaOH, solid-state nuclear magnetic resonance (NMR) spectra disclose the existence of monomeric [Al(OH)₄]⁻ species after two hours of dissolution, consistent with PCM predictions. However, no equivalent monomeric silicate species were observed for 5.0–10.0 M NaOH activator solutions characteristic of systems with nominal Si/Al ≤ 1. The apparent absence of monomeric silicate species suggest rapid condensation of silicate units with [Al(OH)₄]⁻ to generate aluminosilicate species, as indicated by the evolution of the shoulder at around −87 ppm in the ²⁹Si NMR spectra. Of the two possible stable silicate species [SiO₂(OH)₂]²⁻ and [SiO(OH)₃]⁻, the latter appears most likely to condense with [Al(OH)₄]⁻ to produce aluminosilicate oligomers, from which larger oligomers subsequently form through further condensation with [Al(OH)₄]⁻ leading to a gradual build up of aluminosilicate networks and a lowering of system alkalinity. This dissolution and hydrolysis sequence at the early stages of synthesis suggests a reaction path wholly consistent with predictions of the partial charge model.     

电力负荷削峰减载系统在珠钢电炉的应用

借助现场采集装置,在计算机上获取每一分钟的冶炼工艺电能需求量,显示当前15分钟时段已发生的电耗量,调整用户设定,实现需量自动刷新、报警和专家分析推荐后续用量;实现平稳用电并减少对电网冲击,同时降低电能最大需用量以减少成本。     

金属蒸气法制备聚合物固载Pd－Cu双金属原子簇

为了不使用任何还原剂而获得聚合物固载高分散零价双金属加氢催化剂，利用金属蒸气法制备了３种不同Ｐｄ／Ｃｕ质量比的聚合物固载双金属原子簇。透射电镜（ＴＥＭ）和Ｘ衍射（ＸＲＤ）测定表明，Ｐｄ－Ｃｕ原子簇粒度很小，平均直径小于３．０ｎｍ。Ｘ射线光电子能谱（ＸＰＳ）表明，Ｐｄ和Ｃｕ均为零价态。Ｐｄ－Ｃｕ原子簇在异丙叉加氢反应中具有很高的活性和选择性。这些结果提供了令人信服的证据，即金属蒸气法可用于在聚合物孔穴内直接而温和地置入小的零价金属原子簇，而且这样制备的聚合物固载金属原子簇很适合于催化应用。     

动态聚焦电子枪的模拟与实验研究

动态聚焦技术是为了满足大屏幕高分辨率彩色显像管及高分辨率彩色显示管的发展需求而产生的一项新技术。在本文中，作者首先提出了一种动态聚焦电子枪结构，进行了数值计算与分析，制作了动态聚焦电子枪并装管实验。通过对实验样管的测试与分析。证实该枪性能良好，动态聚集效果明显。