摘要：Cyclic dinucleotides(CDNs) are known to activate stimulator of interferon genes(STING) and induce type I interferon responses, therefor possess great potentials to be of immunotherapeutic value for cancers and infectious diseases. However, the existence of different single nucleotide polymorphism(SNP) of human STING(hSTING) gene poses an obstacle to achieve broad-spectrum activation by CDNs. We reported here the design and synthesis of a total of 36 CDNs, representing all structural variations, that contain four bases(A, G, C, U) and two linkage directions(2′-5′-linked and 3′-5′-linked phosphodiester).Through systematic evaluation of IFN-β induction with a dual-luciferase reporter assay, we discovered that wild type hSTING and two isoforms(HAQ and AQ) showed strong response while hSTING-R232 H and R293 Q exhibited the relatively weak response to CDNs stimulation. For the first time, we found that the c[G(2′,5′)U(2′,5′)] showed excellent activity against all five hSTING variants even equivalent to the endogenous ligand c[G(2′,5′)A(3′,5′)]. Furthermore, we have also demonstrated that 3′-3′CDNs with two 3′-5′ phosphodiesters showed higher serum and hydrolase stability than 2′-2′ CDNs with two 2′-5′ phosphodiesters and 2′-3′ CDNs with one 2′-5′ and one 3′-5′ phosphodiester. It is very interesting to note that 2′-2′ CDNs has been found for the first time to show strong activity. These findings will stimulate our exploration for the new functional role of CDNs, and provide guidelines to design CDNs based hSTING targeted drugs.

摘要：文章对天津滨海国际机场二期扩建项目进行了介绍,结合机场外围配套道路规划,对机场现状对外交通状况进行分析,进而提出可实施性的交通疏解方案。

摘要：随着天津滨海国际机场二期扩建项目的实施,旅客吞吐量的增加,机场现有的客运道路已不能满足机场集疏运的要求。该文结合机场外围配套道路规划,对扩建后的机场对外交通状况进行分析,进而提出解决机场客运交通的配套道路方案。

摘要：天津南淀风景区是天津即将开发建设的北部新城的启动项目,该文通过对天津市南淀风景区的路网进行分析,细化了不同等级道路所承担的交通功能,并就如何结合规划路网的建设,解决好南淀风景区的对外交通组织进行了论述,并提出了建设时序建议。

摘要：存量规划背景下,深入挖掘存量建设用地资源是实现城市更新升级再发展的重要路径.本文以聊城市嘉明经济开发区为例,探索工业用地低效利用现象与成因,重点从宗地土地特征、建设特征、使用情况、经济效益、产业发展情况5个维度构建低效工业用地识别评价指标体系.基于评价结果制定从事前统筹到事中建设再到事后监测的全周期管理策略,进一步为低效工业用地的识别与高质量发展提供路径参考.

摘要：To improve magnetotelluric(MT)nonlinear inversion accuracy and stability,this work introduces the deep belief network(DBN)***,a network frame is set up for training in different 2D MT *** network inputs are the apparent resistivities of known models,and the outputs are the model *** optimal network structure is achieved by determining the numbers of hidden layers and network ***,the learning process of the DBN is implemented to obtain the optimal solution of network connection weights for known geoelectric ***,the trained DBN is verified through inversion tests,in which the network inputs are the apparent resistivities of unknown models,and the outputs are the corresponding model *** experiment results show that the DBN can make full use of the global searching capability of the restricted Boltzmann machine(RBM)unsupervised learning and the local optimization of the back propagation(BP)neural network supervised *** to the traditional neural network inversion,the calculation accuracy and stability of the DBN for MT data inversion are improved *** the tests on synthetic data reveal that this method can be applied to MT data inversion and achieve good results compared with the least-square regularization inversion.

摘要：敦煌版画最初是作为佛教的信仰和宣传用品的,但在其发展的过程中,为了迎合信众的精神需求,选择佛教与民众生存有关联的内容为题材,并含有中国民间美术的观念。敦煌版画的表现方法借用了民间美术的艺术语言,创造出了民族化的独特艺术形式。敦煌版画以当时最为先进的传播方式,在敦煌地区的社会各阶层中广泛流布,在中国民间美术发展史上有其重要的历史价值。

摘要：韩愈主张“文”、“道”并重,散文创作在艺术技巧及表现手法上颇具特点,“发言真率”和“抑遏蔽掩”两种笔法各臻化境。韩愈散文中“发言真率”之作,锋芒毕露,雄辩劲拔,文势如虹;运用“抑遏蔽掩”笔法则含蓄蕴藉,意味悠然,婉曲尽情。两种笔法都具有强烈的艺术感染力。

摘要：数字化、智能化、集成化、网络化是数字备用电源自动投切装置(简称备自投)的发展趋势,针对这一发展趋势,提出了一种新型的数字备自投装置整体解决方案,介绍了该装置的硬件设计、工作原理及几项关键技术。采用可编程逻辑的设计思想实现了灵活的备投方式;利用以太网方式实现了通信组网;利用全球定位系统(GPS)技术实现了硬件对时功能。该装置能自动跟踪变电站系统的运行方式,执行相应的备自投方案,保证供电持续可靠。

摘要：大学学科组织变革深受制度环境的影响,伴随着20世纪90年代我国高等教育管理体制改革的推行,院校合并成为创建世界一流大学的合法性途径,将艺术学科纳入建制成为清华大学向综合性大学发展的重要环节。与此同时,我国工业生产的繁荣加速了学科的制度化进程,工艺美术向现代设计的转向消解了中央工艺美术学院的组织合法性,创造了两校合并的制度环境。新成立的清华大学美术学院以“艺术与科学相结合”为逻辑起点,重塑新组织的合法性,完成了学科组织的再制度化。