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：目的:探讨下前牙缺失伴间隙不足采用种植单端固定桥修复的临床效果。方法:选取下前牙缺失,拟行种植义齿修复的单端及双端固定桥病例30例,收集并记录制取模型前种植体动度数据,以及戴入修复体后0、3、6、12月种植体PD值、附着水平及GCF体积变化值,通过数据整理分析探讨下前牙种植体单端固定桥的临床效果。结果:下前牙单端种植桥及双端种植桥组间比较PD值、附着水平、GCF体积变化无统计学差异,同种设计组内比较,差异不具有统计学意义。结论:对于下前牙缺失伴间隙不足不能进行双种植体修复的病例,采用单端种植桥设计后合理设计修复体,其后期具有较稳定的临床效果,降低损伤及患者经济负担,值得临床推广应用。

摘要：Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the *** elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains *** this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature ***,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic ***,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the ***,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain *** conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.

摘要：对于直线感应加速器的束位置探测,钮扣电极这种电容耦合型探测器是一种新的束流诊断手段。本文介绍了钮扣电极的工作原理,以及在研究这种探测器能否应用于直线感应加速器过程中,它的最初设计和根据实验结果对设计进行的改进。改进后的设计基本能够正确反映束流波形并且对束位置的测量精度达到亚毫米量级,在实验中得到了较理想的结果,证明钮扣电极可以用于电子直线感应加速器的强脉冲束位置探测。

摘要：为研究Q值法和RMR法围岩分级在隧道工程中的应用,选取国内外多座代表性铁路隧道,采用Q值法、RMR法分别对同里程掌子面进行围岩等级划分,和指标取值研究,并将其围岩分级结果与其他文献实测数据进行统一拟合,对Q值法、RMR法与BQ法围岩级别结果间关系进行探讨。研究表明,Q值法和RMR法中指标大多数为定性指标,实际应用中应熟悉各指标多途径获取方法和注意事项;Q值法和RMR法中各指标参数取值较为复杂,提出常遇工况下建议的各指标取值;Q值和[BQ]值间符合指数函数关系,RMR值和[BQ]值间符合线性函数,Q值和RMR值间关系符合对数函数关系;提出Q值法、RMR法与BQ法围岩级别划分对应关系表,可用于指导海外项目隧道工程设计和施工。

摘要：本文介绍了自行设计的土样剪切波速超声测试装置与测试方法,与扭剪三轴仪相结合,测试了多组干砂试样的剪切波速。检验了量测系统的可靠性。探讨了试件的边界条件及震相识别等问题。试验测得的干砂在不同固结压力下的剪切波速,与Hardin公式吻合良好,表明所研制的测试装置及测试方法是可行的。

摘要：在平原型水库反推入库流量过程中,存在明显的噪声干扰,导致传统的洪水预报方法精度下降。对此,提出一种结合卷积神经网络(CNN)与双向长短期记忆神经网络(BiLSTM)的入库洪水预报模型,该模型采用CNN的卷积层挖掘入库洪水数据中的深层特征信息,并赋予不重要特征较低的权重,以便模型更加专注于对目标任务关键的特征信息。此外,利用BiLSTM处理流量序列中的长期依赖问题,通过其遗忘门有选择性地过滤掉权重较低的特征信息,实现对入库洪水过程的准确预测。最后,基于不同预见期评估所构建模型在安徽省合肥市大房郢水库入库洪水预报中的精准度。结果表明,4 h预见期下CNN-BiLSTM模型在入库洪水预报中具有更高的预报精度,相比BiLSTM模型和新安江(XAJ)模型,其确定性系数(D_(DC))分别提升9.9%、39.0%,均方根误差(R_(RMSE))和相对偏差(B_(BIAS))分别降低34.6%、17.1%和148.6%、20.6%。研究成果可为反推入库流量过程的平原型水库入库洪水预报提供新思路和技术支持。

摘要：We present a design of indirect-drive pulse shape for inertial confinement fusion ignition capsules using laser energy 1.6 MJ with a moderate gain （~10） on the Shenguang 1V laser facility. The trade-off fuel compression （pressure） for resistance to the hydrodynamic instability （HI） in the recent high-foot （HF） implosion campaign [Dittrieh T t et al Phys. Rev. Lett. 112 （2014）055002] is recovered. The proposed design modifies the ＂main＂ pulse shape, which features a decompression-recompression step for the fuel shell resulting in higher areal density than that of the ＂simple＂ HF design, and thereby approaches the conditions required for ignition avoiding at the expense of more laser energy while holding the HI under control.

摘要：A series of 3-substituedmethylenethiochroman-4-ones was designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, MS, IR, UV and elemental analysis. The results of their anticancer activity studies show that almost all 3-chloromethylenethiochroman-4-ones exhibit high anticancer activities and their activities are all better than reference cisplatin. Their IC50 against cancer cells is in a range of 0.80―9.17 μg/mL. Thus they could be promising candidates for anticancer drugs. However, compound 5 has no activity against cancer cells, thus chloromethylene at the 3 position of thiochroman-4-ones seems to play an important role in observed anticancer activities.

摘要：We report the design of a wide-range energy material beamline(E-line) with multiple experimental techniques at the Shanghai Synchrotron Radiation *** undulators consisted of an elliptically polarizing undulator and in-vacuum undulator that generate the soft and hard X-rays, respectively. The beamline covered a wide energy range from 130 to 18 ke V with both a high photon flux([ 10^(12) phs/s with exit silt 30 lm in soft X-ray and [ 5 9 10^(12) phs/s in hard X-ray within 0.1%BW bandwidth) and promising resolving power(maximum E/DE [ 15,000 in soft X-ray with exit silt 30 lm and [6000 in hard X-ray). Moreover, the beam spots from the soft and hard X-rays were focused to the same sample position with a high overlap ratio, so that the surfaces, interfaces, and bulk properties were characterized in situ by changing the probing depth.