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71.
传统的路侧被动限速方式对于特定的惩处区域以外缺少管控,间接导致车辆行为在时空上的不一致性甚至突变,影响了交通的通行效率与安全性。从车侧主动限速方式入手,提出主动限速效用评价与推荐方法,结合道路线形、交通流量、车型比例,开展多情景主动、被动限速交通仿真,利用安全间接分析模型及交通流运行状态,从安全与效率2个层面提取效用评价指标及其权重,采用集成学习方法进行预测分析。结果显示:主动限速方式相较于被动限速方式更有利于提高安全性和调节效率,而在主动限速方面,GBDT(gradient boosting decision tree)回归模型的预测稳定性和准确率更高(R2=0.984)。 相似文献
72.
火灾是威胁公共安全的主要灾害之一,火灾产生的高温和有毒有害烟气严重影响了疏散路径的选择。将深度强化学习引入到应急疏散仿真研究,针对多智能体环境提出了协作式双深度Q网络算法。建立随时间动态变化的火灾场景模型,为人员疏散提供实时的危险区域分布信息;对各自独立的智能体神经网络进行整合,建立多智能体统一的深度神经网络,实现所有智能体之间的神经网络和经验共享,提高整体协作疏散效率。结果表明:所提方法具有良好的稳定性和适应性,训练和学习效率得到提升,具有良好的应用价值。 相似文献
73.
74.
Patricio Atanes Inmaculada Ruz-Maldonado Ross Hawkes Bo Liu Min Zhao Guo Cai Huang Israa Mohammed Al-Amily Albert Salehi Stefan Amisten Shanta J. Persaud 《Cellular and molecular life sciences : CMLS》2018,75(16):3039-3050
Introduction
Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.Materials and methods
GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.Results
We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.Discussion
The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.75.
Lei Chen Cong-Fa Huang Yi-Cun Li Wei-Wei Deng Liang Mao Lei Wu Wen-Feng Zhang Lu Zhang Zhi-Jun Sun 《Cellular and molecular life sciences : CMLS》2018,75(11):2045-2058
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. 相似文献
76.
77.
Generation of CRISPR/Cas9-mediated gene-targeted pigs via somatic cell nuclear transfer 总被引:1,自引:1,他引:0
78.
Genome-wide association studies of 14 agronomic traits in rice landraces 总被引:20,自引:0,他引:20
Huang X Wei X Sang T Zhao Q Feng Q Zhao Y Li C Zhu C Lu T Zhang Z Li M Fan D Guo Y Wang A Wang L Deng L Li W Lu Y Weng Q Liu K Huang T Zhou T Jing Y Li W Lin Z Buckler ES Qian Q Zhang QF Li J Han B 《Nature genetics》2010,42(11):961-967
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. 相似文献
79.
80.
Ong CK Subimerb C Pairojkul C Wongkham S Cutcutache I Yu W McPherson JR Allen GE Ng CC Wong BH Myint SS Rajasegaran V Heng HL Gan A Zang ZJ Wu Y Wu J Lee MH Huang D Ong P Chan-on W Cao Y Qian CN Lim KH Ooi A Dykema K Furge K Kukongviriyapan V Sripa B Wongkham C Yongvanit P Futreal PA Bhudhisawasdi V Rozen S Tan P Teh BT 《Nature genetics》2012,44(6):690-693
Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA. 相似文献