摘要：葡萄膜黑色素瘤（uveal melanoma）是成人眼内最常见的原发性恶性肿瘤，虽然其可以得到有效控制，但相当一部分病例（超过40%）最终会发生远处转移。转移性葡萄膜黑色素瘤仍是一种致死性疾病，但治疗手段和药物有限，且以原癌基因GNAQ或其旁系同源基因GNA11高频突变为特征。GNAQ/11突变后激活多条信号通路，主要包括PKC/MAPK,PI3K/AKT/mTOR和Hippo/YAP等。本文综述了GNAQ/11突变激活的主要信号通路，重点讨论了针对以上信号通路的新兴的靶向治疗药物和策略，并介绍了正在进行的临床试验的药物。

摘要：In order to meet the needs of various tasks of water conservancy project, tunnel excavation under the ground, called hydraulic tunnel. Hydraulic tunnel according to the functions of flood discharge, water diversion, irrigation, water supply, and the construction diversion tunnel of desilting emptying. Nowadays, water conservancy project on flood discharge runnel design requirements more and more high, so the factors taken into account the amount of spillway tunnel engineering, engineering cost, structure design and other factors to evaluate nature of the spillway tunnel is very important. Therefore, in actual construction, of spillway tunnel of optimization design, whether from the economic point of view, or from the point of view of safety and applicability are necessary. This article mainly from the overall layout of flood discharge tunnel, structure design and so on, and then discuss the optimization scheme.

摘要：With the development of economy, the adjustment of industrial structure, the improvement of people＇s living standard and the expansion of urbanization, the structure of the city has changed a lot. The proportion of industrial use of electricity decreased year by year, the proportion of household electricity, commercial electricity and public utilities increased year by year, the peak and valley change increased year by year. Therefore, the construction of hydropower project, to improve the current situation of the system of regulating the power grid, has a positive role in promoting. Reinforced rock fill dam with face slab in foreign countries has been built and at the dam more than 50m high dam more than 70 seats, of which more than 100m high dam 18. At present, Brazil estuary aliya rock fill dam is the highest dam in this kind of dam in the world, built in 1980, has been running well. Our reinforced rock fill dam with face slab design and construction technology in the introduction of digestion and absorption of foreign advanced experience in the foundation, the systemic research on a considerable scale. The design level and construction technology of the rock fill dam with face slab in our country have reached the international advanced level by the complete technology of the construction of the 100m level rock fill dam with face slab. This paper mainly from the rock fill dam with face slab, dam type selection and layout of water conservancy project comparison; dam profile design; detail dam; dam high determined; stability analysis; strength calculation; overflow capacity check aspects were studied.

摘要：针对梯级泵站系统运行效率普遍偏低、能耗损失较大等问题,建立了梯级泵站优化调度模型,引入了寻优能力强、搜索精度高的麻雀搜索算法(SSA),对算法中安全阈值和侦察者占比两参数进行了比选;据此提出了基于SSA算法的梯级泵站优化调度方法,并将其应用于密云水库调蓄工程中的三级泵站优化调度研究。结果表明,三种不同流量工况下,相较于现状方案,PSO及GA算法所得优化方案其系统运行效率可提升0.03%~0.18%,年运行成本可节省¥9,700~¥69,500。利用SSA算法所获优化方案在两项指标改进方面更为突出,可达到0.98%~1.20%的效率提升及¥369,000~¥443,900的年运行费用的节省,验证了SSA算法在梯级泵站优化调度中的可行性和高效性,可为梯级泵站优化调度提供一种合理可靠的方法。

摘要：为解决传统管理系统在应用中存在耗时长的问题,笔者提出一种基于数字孪生技术的网络运维管理系统,首先分析了基于数字孪生技术的网络运维管理系统硬件架构设计,进而分析了基于数字孪生技术的网络运维管理系统软件架构设计,最后进行了对比实验。实验结果证明,新的管理系统恢复网络运行环境正常运行的时间明显缩短,能够有效提高管理效率。

摘要：针对传统算法模型精度比较低的问题,提出了基于改进GLR算法的英语翻译智能识别模型。通过此算法创建用于标记规模上万个英汉单词的短语语料库,使短语能够自动搜索。另外,创建英语翻译智能识别模型,以数据的收集、处理和输出规划智能识别模型;有计划地对英语信号进行收集和处理,并且提取特征参数,实现英语翻译智能识别。对设计的英语翻译智能识别模型进行实验分析,记录实验数据。通过实验分析可知,设计的英语翻译识别模型精准度较高,能够满足英语翻译工作需求。

摘要：为实现引江济淮工程(安徽段)江水北送段的高效运行,以引江济淮工程江水北送段输水系统为研究对象,采用基于遗传算法构建的梯级泵站扬程优化分配模型,开展串联梯级泵站扬程优化分配研究。分别对设计和非设计工况下江水北送段输水系统的运行方案进行分析计算。计算结果表明:设计工况下优化后分配方案总效率较设计现状方案提高2.86%,说明模型优化后的方案可进一步提高梯级泵站的输水效率,为实现串联泵站输水系统科学、合理调度提供很好的科学支撑。

摘要：目的构建抑癌基因BAP1敲除的皮肤黑色素瘤细胞模型,筛选对BAP1缺失的皮肤黑色素瘤细胞具有选择性抑制活性的小分子化合物。方法选择表达野生型BAP1的皮肤黑色素瘤细胞利用CRISPR-Cas9系统敲除BAP1基因,获得与亲代细胞同基因型的BAP1敲除克隆,通过MTT法筛选化合物库中对BAP1敲除细胞具有选择性抑制活性的小分子化合物。通过挽救实验,明确BAP1敲除细胞对化合物的敏感性是否与BAP1蛋白缺失直接相关。流式细胞术检测化合物对细胞周期和凋亡的影响。Western blotting检测化合物对蛋白表达的影响。结果化合物库中的p53激活剂RITA选择性抑制BAP1敲除细胞的细胞活力。过表达野生型BAP1能够逆转BAP1敲除细胞对RITA的敏感性,而过表达去泛素化酶失活的突变型BAP1(C91S)没有挽救作用。与BAP1野生型对照细胞相比,BAP1敲除细胞对RITA引起的细胞周期阻滞和凋亡更为敏感(P<0.0001)。BAP1敲除增加了细胞p53蛋白的基础水平,而RITA处理后进一步增加p53蛋白表达(P<0.0001)。结论BAP1缺失导致皮肤黑色素瘤细胞对p53激活剂RITA敏感。BAP1的去泛素化酶活性与细胞对RITA的敏感性直接相关。BAP1敲除导致p53蛋白增加可能是细胞对RITA敏感的一个关键原因。

摘要：通过分析传统国有煤炭企业物资采购现状,阐述了推行物资采购电商化模式的背景意义,提出了基于B2B平台构建物资采购第三方服务平台的功能设计和中心架构,总结了山西焦煤集团的探索实践与应用效果,表明了物资采购电商化模式对深挖降本增效、打造充分竞争环境、实现内部协同联动、推动企业高质量发展的重要意义,为传统国有煤炭企业物资采购电商化模式建设提供了指导。

摘要：微党课是顺应当今时代需要的发展而产生的一种新型课程载体。高校党建工作队伍应该在积极转变工作思想观念以及提高自身党课素养的基础上,大力增进微党课设计能力以及管理能力,做好微党课的建设工作,在真正意义上全面提升高校大学生思想政治教育工作的效果。本文在诠释微党课的必要性与重要性前提之下,从微党课存在的问题出发,提出高校微党课教学创新建议,从而在今后的微党课工作中提高教学质量。