螺栓连接大变形梁非线性振动特性的实验研究

柔性机械臂、大型可展开天线等机械结构的动作精度受运动过程中大变形几何非线性和连接处接触非线性的影响十分显著。以含螺栓连接结构的大变形梁作为研究对象，针对动力学建模和振动特性开展了实验研究，通过数值计算验证了实验发现的非线性振动特性。搭建了含螺栓连接柔性大变形梁的实验台架，开展了敲击和正弦激振的实验测试。实验结果表明，螺栓连接的柔性梁较连续梁的（无螺栓连接）模态频率降低，阻尼增加，反映出随着激励能量增大，模态频率降低的非线性模态特征。改变螺栓连接位置会显著影响结构的模态频率，其变化规律可由求解线性矩阵特征值定性反映。     

Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma

The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4⁺ and CD8⁺ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1⁺ and Tim3⁺ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy.     

Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

Ni~(26+)离子态分辨光复合过程的R矩阵理论研究

利用基于相对论R矩阵理论的DARC程序系统计算了Ni 25+离子基态1s22s(2S1/2)和激发态1s22p(2P1/2,2P3/2)的光电离截面,并通过细致平衡原理获得了统一的光复合过程(即辐射复合和双电子复合)态分辨的截面,计算结果给出了辐射复合与双电子复合过程间的干涉效应.为了标识和分析KLL共振能区所有的共振峰,基于相对论组态相互作用理论(RCI)的FAC程序被用来计算共振峰的能量、强度及其相关的双激发态的辐射、俄歇跃迁几率以及共振宽度等.利用统一的光复合截面进一步得到了KLL双电子复合过程的伴线强度,并与孤立共振近似下FAC的计算结果以及以前的理论和实验结果进行了比较,对存在的一致性和偏差进行了分析和讨论.     

General mechanisms of drought response and their application in drought resistance improvement in plants

Plants often encounter unfavorable environmental conditions because of their sessile lifestyle. These adverse factors greatly affect the geographic distribution of plants, as well as their growth and productivity. Drought stress is one of the premier limitations to global agricultural production due to the complexity of the water-limiting environment and changing climate. Plants have evolved a series of mechanisms at the morphological, physiological, biochemical, cellular, and molecular levels to overcome water deficit or drought stress conditions. The drought resistance of plants can be divided into four basic types-drought avoidance, drought tolerance, drought escape, and drought recovery. Various drought-related traits, including root traits, leaf traits, osmotic adjustment capabilities, water potential, ABA content, and stability of the cell membrane, have been used as indicators to evaluate the drought resistance of plants. In the last decade, scientists have investigated the genetic and molecular mechanisms of drought resistance to enhance the drought resistance of various crops, and significant progress has been made with regard to drought avoidance and drought tolerance. With increasing knowledge to comprehensively decipher the complicated mechanisms of drought resistance in model plants, it still remains an enormous challenge to develop water-saving and drought-resistant crops to cope with the water shortage and increasing demand for food production in the future.     

青藏铁路含保温夹层路基厚度与地温关系的研究

通过对青藏铁路风火山段含有保温夹层的路基建立均匀介质分层纯导热模型并运用分层近似解法求出冻土表层的温度函数,结合Lachenbruch给出的冻土层的理论温度表达式,得到了路基填料层、保温层、地表年平均温度与正弦变化温度的振幅比三者之间的隐式方程,并应用该方程对三者之间的关系进行了分析.     

含砂雾封层在桥面铺装工程中的应用

结合含砂雾封层在国道205桥面铺装上的应用,深入分析了含砂雾封层的防水、防老化作用机理,本文系统总结了国道205桥面雾封层施工质量的控制要点,并对施工前后封层各项性能指标进行跟踪检测,分析结果表明采取含砂雾封层措施确实能对桥面早期微裂缝进行有效封水,延缓桥面病害的发生,延长沥青路面的使用寿命。     

基于改进灰狼算法优化SVR的航天侦察装备效能评估

定量评估航天侦察装备效能是武器装备体系建设的重要环节之一, 对装备发展和作战应用具有重要的现实意义。针对评估样本数据少、效能在多指标因素影响下变化规律非线性等条件下的效能评估问题, 提出一种基于改进灰狼(improved grey wolf optimizer, IGWO)算法优化的支持向量回归机(support vector regression, SVR)评估方法(IGWO-SVR)。引入反向学习策略及余弦非线性收敛因子改进灰狼优化算法收敛性能及全局寻优能力, 并将其应用于基于支持SVR效能评估参数的优化。基于航天侦察装备特点, 构建评估指标体系及航天侦察装备效能评估模型。最后, 通过对一定作战想定背景下航天侦察装备效能进行仿真评估, 验证了所提方法的合理性及优化模型的有效性。     

Junctional adhesion molecule-A: functional diversity through molecular promiscuity

Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell–cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Nevertheless, JAM-A is involved in a variety of biological processes. The functional diversity of JAM-A resides to a large part in a C-terminal PDZ domain binding motif which directly interacts with nine different PDZ domain-containing proteins. The molecular promiscuity of its PDZ domain motif allows JAM-A to recruit protein scaffolds to specific sites of cell–cell adhesion and to assemble signaling complexes at those sites. Here, we review the molecular characteristics of JAM-A, including its dimerization, its interaction with scaffolding proteins, and the phosphorylation of its cytoplasmic domain, and we describe how these characteristics translate into diverse biological activities.