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21.
    
DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295, which was discovered by screening for demethylating agents. {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295. MKN28 cells infected with EBV were sensitive to {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A, and CDC45 were significantly decreased by {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295 could up-regulate their expression. In conclusion, {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"MC180295\",\"term_id\":\"1885105835\",\"term_text\":\"MC180295\"}}MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle.  相似文献   
22.
    
Molecular dynamics (MD) simulations are powerful theoretical methods that can reveal biomolecular properties, such as structure, fluctuations, and ligand binding, at the level of atomic detail. In this review article, recent MD simulation studies on these biomolecular properties of the RNA-dependent RNA polymerase (RdRp), which is a multidomain protein, of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are presented. Although the tertiary structures of RdRps in SARS-CoV-2 and SARS-CoV are almost identical, the RNA synthesis activity of RdRp of SARS-CoV is higher than SARS-CoV-2. Recent MD simulations observed a difference in the dynamic properties of the two RdRps, which may cause activity differences. RdRp is also a drug target for Coronavirus disease 2019 (COVID-19). Nucleotide analogs, such as remdesivir and favipiravir, are considered to be taken up by RdRp and inhibit RNA replication. Recent MD simulations revealed the recognition mechanism of RdRp for these drug molecules and adenosine triphosphate (ATP). The ligand-recognition ability of RdRp decreases in the order of remdesivir, favipiravir, and ATP. As a typical recognition process, it was found that several lysine residues of RdRp transfer these ligand molecules to the binding site such as a “bucket brigade.” This finding will contribute to understanding the mechanism of the efficient ligand recognition by RdRp. In addition, various simulation studies on the complexes of SARS-CoV-2 RdRp with several nucleotide analogs are reviewed, and the molecular mechanisms by which these compounds inhibit the function of RdRp are discussed. The simulation studies presented in this review will provide useful insights into how nucleotide analogs are recognized by RdRp and inhibit the RNA replication.  相似文献   
23.
24.
新一代超小型DIP-IPM   总被引:1,自引:0,他引:1  
为了满足空调、洗衣机、冰箱等白色家电对高效、高性能的需要,三菱电机开发了新一代超小型第四代(Ver.4)双列直插封装的智能功率模块(Dual-In-linePackageIntelligentPowerModule,简称DIP-IPM)。本文首先分析了第四代超小型DIP-IPM内部电路的构成和功能,然后详细介绍了第四代DIP-IPM生产过程中的关键技术,包括无铅化、高热传导性绝缘片、chip-to-chip导线直接连接以及ASIC技术,最后与第三代(Ver.3)DIP-IPM进行了比较。  相似文献   
25.
The synthesis of solid solutions of (Ti,W,Cr)B2 from elemental reactants using the field-activated, pressure-assisted synthesis method and employing the SPS apparatus was investigated. The nature of the products depended on temperature; they were nearly pure solid solutions at 1900°C with minor amounts of β-WB. The product density and microhardness depended on the temperature of synthesis for the same value of applied pressure (64 MPa). Samples with the highest density (94%) corresponded to a hardness of 22.7 GPa. When annealed at 1500°C, the solid solutions decomposed, precipitating a (W,Ti,Cr)B2 phase in a spinodal form. In addition, β-WB precipitates in the form of thin (0.4–5.3 nm) layers were observed. They existed in a 60°/120° orientation to the (Ti,W,Cr)B2 matrix, in agreement with previous observations. Highly faceted, small (nanosized) pores associated with the β-WB precipitates were also observed.  相似文献   
26.
长久以来,北海道产大米的食味口碑一直不高,也未出现像“越光”一样全日本知名的优良食味品种,因此,自1980年开始历时28年,北海道立(现称道总研)农业试验场致力于粳稻优良食味品种快速研究项目的实施。为实现快速研发的目标,通过世代促进栽培法和花药培养法成功缩短了育种年限;采用扩大育种规模的方式,并利用优良食味、耐寒性等内外部有效基因培育兼具优良食味及早熟耐寒性的品种;初期世代开始主要通过分析大米的蛋白质含量、尤其是直链淀粉含量,中间世代则通过少量蒸饭的方式进行食味品鉴,选育出优良食味种系。在食味遗传基因的改良方面,先是集聚北海道优良食味的遗传基因培育出品种“雪光”,再经由北海道品种引进“越光”的优良食味遗传基因,之后以日本东北优良食味遗传基因品种“秋田小町”作为直接杂交母本,分别成功培育出品种“闪光397”和“星之梦”,其直链淀粉含量与以往多肥多产品种的22%相比降低了2%。在此基础之上,引进美国品种“国宝玫瑰”优良食味遗传基因的品种“七星”成功问世,其直链淀粉含量又降低了1%;以变异低直链淀粉种系“北海287号”为母本,成功培育出“梦美”,其直链淀粉含量15%~16%,粘度和软度俱佳,食味亦可与“越光”媲美。  相似文献   
27.
Bent pipe wall thinning has been often found at the elbow of the drain line and the high-pressure secondary feed-water bent pipe in nuclear reactors. Liquid droplet impingement (LDI) erosion could be regarded as one of the major causes and is a significant issue of the thermal hydraulics and structural integrity in aging and life extension for nuclear power plant safety. In this paper a computational methodology is established for simulation of LDI erosion using computational fluid dynamics (CFD) simulation and theoretical calculation. Two-phase flow numerical simulations are conducted for standard elbow geometry, typically with the pipe diameter of 170 mm. This computational fluid model is built up by incompressible Reynolds Averaged Navier–Stoke equations using standard k? turbulence model and the SIMPLE algorithm, and the numerical droplet model adopts the Lagrangian approach. The turbulence damping in vapor–droplets flow is theoretically analyzed by a damping function on the energy spectrum basis of single phase flow. Locally, a droplet impact angle function is employed to determine the overall erosion rate. Finally, the overall and local investigations are combined to purpose a general methodology of LDI erosion prediction procedure, which has been complemented into CFD code. Based on our more physical computational results, comparison with an available accident data was made to prove that our methodology could be an appropriate way to simulate and predict the bent pipe wall thinning phenomena.  相似文献   
28.
The development of a Water Cooled Ceramic Breeder (WCCB) Test Blanket Module (TBM) is being performed as one of the most important steps toward DEMO blanket in Japan. For the TBM testing and evaluation toward DEMO blanket, the module fabrication technology development by a candidate structural material, reduced activation martensitic/ferritic steel, F82H, is one of the most critical items from the viewpoint of realization of TBM testing in ITER. In Japan, fabrication of a real scale first wall, side walls, a breeder pebble bed box and assembling of the first wall and side walls have succeeded. Recently, the real scale partial mockup of the back wall was fabricated. The fabrication procedure of the back wall, whose thickness is up to 90 mm, was confirmed toward the fabrication of the real scale back wall by F82H. Important key technologies are almost clarified for the fabrication of the real scale TBM module mockup. From the view point of testing and evaluation, development of the technology of the blanket tritium recovery, development of advanced breeder and multiplier pebbles and the development of the blanket neutronics measurement technology are also performed. Also, tritium production and recovery test using D-T neutron in the Fusion Neutronics Source (FNS) facility has been started as the verification test of tritium production performance. This paper overviews the recent achievements of the development of the WCCB TBM in Japan.  相似文献   
29.
Ash-washing technology is a crucially important technology for removing radioactive Cs from contaminated ash. For that technology, Cs+ removal from the ash-washing solution by the adsorbent is necessary. This study was conducted to establish rapid preparation of appropriate adsorption columns for Cs+ uptake. A one-site model was not used for analysis because the model cannot accommodate sites with different adsorption speed. Results demonstrated that the adsorption behavior of the column filled with the granules of potassium copper hexacyanoferrate was well reproduced by a two-site adsorption model with parameters chosen through analysis of batch adsorption test results.  相似文献   
30.
Probabilistic fuel pin gap distributions within a wire-spaced fuel subassembly and sensitivities of the related uncertainties to fuel pin gaps are discussed. The analyses consist mainly of expressing a local fuel pin gap in terms of sensitivity functions of the related uncertainties and calculating the corresponding probabilistic distribution through taking all the possible combinations of the distribution of uncertainties. The results of illustrative calculations show that with the reliability level of 0.9987, the maximum deviation of the pin gap at the cladding hot spot of a center fuel subassembly is 8.05% from its nominal value and the corresponding probabilistic pin gap distribution is shifted to the narrower side due to the external confinement of a pin bundle with a wrapper tube.  相似文献   
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