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.     

灵敏度分析在惯导平台误差参数辨识中的应用

为了解决传统的惯导平台测漂方案下,惯导平台上陀螺安装误差角的系统级辨识精度不高的问题,对平台漂移的非线性模型进行了灵敏度分析,找出了影响陀螺安装误差角辨识精度的主要因素,进而提出了转台相对地面存在角速率条件下的改进辨识方案.仿真结果表明,在改进的辨识方案下误差角的辨识精度获得了显著提高.     

基于重复博弈的集群企业间社会关系构建分析

针对我国外生模式及混合内生模式集群中核心企业与依附企业间的主从支配关系,将核心企业与依附企业间的社会关系收益进行量化,讨论了核心企业与依附企业间的社会关系构建及维持的影响因素及内在机制.研究表明,核心企业与依附企业间的社会关系构建与维持取决于核心企业对双方社会关系价值的预期以及依附企业的市场价格;核心企业依据依附企业的市场价格来分割双方的社会关系收益;而依附企业可以通过提高自身的价值,获取更高的社会关系收益分割值,缔结和维持有利于自身和集群成长的社会关系.     

A partial robust optimization approach to inventory management for the offline-to-online problem under different selling prices

This study examines an optimal inventory strategy when a retailer markets a product at different selling prices through a dual-channel supply chain, comprising an online channel and an offline channel. Using the operating pattern of the offline-to-online (O2O) business model, we develop a partial robust optimization (PRO) model. Then, we provide a closed-form solution when only the mean and standard deviation of the online channel demand distribution is known and the offline channel demand follows a uniform distribution (partial robust). Specifically, owing to the good structural properties of the solution, we obtain a heuristic ordering formula for the general distribution case (i.e., the offline channel demand follows a general distribution). In addition, a series of numerical experiments prove the rationality of our conjecture. Moreover, after comparing our solution with other possible policies, we conclude that the PRO approach improves the performance of incorporating the internet into an existing supply chain and, thus, is able to adjust the level of conservativeness of the solution. Finally, in a degenerated situation, we compare our PRO approach with a combination of information approach. The results show that the PRO approach has more “robust” performance. As a result, a reasonable trade-off between robustness and performance is achieved.     

Genome-wide association studies of 14 agronomic traits in rice landraces

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ～ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ～ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.     

磁盘表面形貌对润滑剂分布及磁头／磁盘之间润滑剂转移的影响

磁盘表层润滑剂在磁头与磁盘之间转移会影响磁头飞行的稳定性．本文采用改进后的粗粒珠簧模型,运用分子动力学方法,研究了磁盘上类金刚石薄膜（diamondlikecarbon,DLC）层粗糙度和磁盘表面凸起对润滑剂在磁盘表面分布及磁头／磁盘之间润滑剂转移的影响．研究结果表明,DLC层粗糙度对润滑膜平均厚度及磁盘表层粗糙度的影响很小;磁盘表面凸起对磁盘表层润滑剂分布的影响明显．类金刚石薄膜层的粗糙度和磁盘表层凸起均可增加转移到磁头上的润滑剂的体积．但磁盘表层粗糙度对磁头／磁盘之间润滑剂转移量的影响明显低于由磁盘表层凸起导致的磁头／磁盘之间润滑剂的转移量．     

Genome-wide association study of flowering time and grain yield traits in a worldwide collection of rice germplasm

A high-density haplotype map recently enabled a genome-wide association study (GWAS) in a population of indica subspecies of Chinese rice landraces. Here we extend this methodology to a larger and more diverse sample of 950 worldwide rice varieties, including the Oryza sativa indica and Oryza sativa japonica subspecies, to perform an additional GWAS. We identified a total of 32 new loci associated with flowering time and with ten grain-related traits, indicating that the larger sample increased the power to detect trait-associated variants using GWAS. To characterize various alleles and complex genetic variation, we developed an analytical framework for haplotype-based de novo assembly of the low-coverage sequencing data in rice. We identified candidate genes for 18 associated loci through detailed annotation. This study shows that the integrated approach of sequence-based GWAS and functional genome annotation has the potential to match complex traits to their causal polymorphisms in rice.     

不确定性随机系统的输出反馈变结构滑模控制

研究了带有时变不确定性的It型随机系统的输出反馈镇定问题,采用变结构滑模控制(SMC)方法设计了镇定控制器.在系统的不确定性满足一定匹配条件的情况下,构造了对不确定性具有不变性以及参数不含噪声激励的滑模切换流形和变结构滑模控制律,分析和证明了滑模的可达性和闭环系统的稳定性,并给出了滑模控制律的参数选择条件.最后通过示例系统仿真实验证明了文中结果的正确性和有效性.     

基于连通图动态分裂的聚类算法

当前大部分的聚类算法都难以处理任意形状和大小、存在孤立点和噪音以及密度多变的簇,为此,文中提出了一种基于连通图动态分裂的聚类算法.首先构造数据集的l-连通图,然后采用动态分裂策略对l-连通图进行分割,把数据集分成多个互不相连的连通图子集,每个连通图子集为一类.实验结果表明,所提出的算法能够有效地解决任意形状和大小、存在孤立点和噪音以及密度多变的簇的聚类问题,具有广泛的适用性.