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41.
分析了体系作战效能评估与优化的特点,基于“整体论”提出了将体系作战效能评估与优化划分为综合评估、分析、优化3个阶段的思路,针对3个阶段需要解决的实际问题,归纳总结了适用于解决各阶段问题的典型方法,并对比分析了不同方法的优缺点。针对“整体论”思想指导下体系作战效能评估与优化在实施中面临的实际困难,从综合应用框架设计、评估指标体系构建、试验推演模式创新等方面提出了下一步的研究方向,为体系作战效能评估与优化方法的有效落地提供了支撑。  相似文献   
42.
异构仿真网络是实况、虚拟和构造(live, virtual, and constructive, LVC)仿真的基础环境支撑,合理评估其可靠性在LVC仿真应用中具有重要作用。针对复杂网络可靠性评估难以获得精确解、效率不高的问题,提出一种考虑节点失效的LVC异构仿真网络蒙特卡罗评估方法。首先,基于异构网络自身特点及因子定理,对蜂窝网络和无线传感器网络进行等效转化;其次,运用可靠性保持缩减技术对转化的仿真网络进行缩减,提高算法效率和收敛速度;最后,依据不完全可靠节点转化原则,对简化网络可靠性进行蒙特卡罗模拟,实现LVC异构仿真网络连通可靠性的评估。计算结果表明,相比传统蒙特卡罗方法,所提方法在保证计算精度的同时,方差减小,运行负载较小,稳定性更好。  相似文献   
43.
Lin Z  Bei JX  Shen M  Li Q  Liao Z  Zhang Y  Lv Q  Wei Q  Low HQ  Guo YM  Cao S  Yang M  Hu Z  Xu M  Wang X  Wei Y  Li L  Li C  Li T  Huang J  Pan Y  Jin O  Wu Y  Wu J  Guo Z  He P  Hu S  Wu H  Song H  Zhan F  Liu S  Gao G  Liu Z  Li Y  Xiao C  Li J  Ye Z  He W  Liu D  Shen L  Huang A  Wu H  Tao Y  Pan X  Yu B  Tai ES  Zeng YX  Ren EC  Shen Y  Liu J  Gu J 《Nature genetics》2012,44(1):73-77
To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.  相似文献   
44.
Enucleated oocytes have the distinctive ability to reprogram somatic nuclei back to totipotency. Here, we investigate genome-scale DNA methylation patterns after nuclear transfer and compare them to the dynamics at fertilization. We identify specific targets for DNA demethylation after nuclear transfer, such as germline-associated promoters, as well as unique limitations that include certain repetitive element classes.  相似文献   
45.
46.
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development. Our findings establish that Cre/loxP-mediated tissue-specific gene knockout could be achieved using this BACK strategy and that canonical microRNAs play important roles in early embryonic development in zebrafish.  相似文献   
47.
Using an analogy in science and everyday life is a double-edged sword because they are accompanied by alternative ideas, in addition to scientific concepts. Schools and public education explain global warming by making a common analogy between this phenomenon and greenhouse effects (Chen in Philos Cogn Sci 105–114, 2012). Unfortunately, this analogy sometimes produces various incorrect explanatory mental models. To construct a correct understanding of global warming, it is necessary: first, to investigate the attributes of analogical reasoning; second, to understand these features by restructuring the greenhouse analogy; and third, to explore the problems and benefits of the greenhouse analogy. The characteristics of relations, rather than objects, must be mapped according to the principle of systematicity, but the public tends to preserve the attributes of the base domain, which is mapped relatively easily. In conclusion, certain facets of the prevailing greenhouse analogy cause a distorted public view of climate change. We must use the greenhouse analogy and yet simultaneously emphasize the relations and attributes highlighted and hidden in the analogy during evaluation.  相似文献   
48.
针对可修复备份多级管理模型当备件关键性不同时无法再使用边际效应法的问题,以舰艇编队索马里护航备件携带为研究背景,提出了一种基于备件关键性的初始库存优化方法。首先,建立了备件关键性影响因素的评价指标体系,针对其具有模糊性的特点,采用模糊层次分析法(fuzzy analytic hierarchy process,FAHP)分析了备件重要度指标之间的相对权重的关系,给出了模糊判断矩阵及其一致性的求解方法;其次,给出了基于蒙特卡罗仿真方法的备件关键性求解模型和流程;再次,改进了边际效应法,建立了基于备件关键性的舰艇备件库存优化模型;最后研究表明,基于FAHP和蒙特卡罗方法求解备件关键性的模型可以降低人为主观性的影响,操作简单且易于实现;将修正了的边际效应法用于求解备件初始库存,有重点针对关键性较高备件的同时也能兼顾一般。  相似文献   
49.
The utility F-box for protein destruction   总被引:3,自引:1,他引:2  
A signature feature of all living organisms is their utilization of proteins to construct molecular machineries that undertake the complex network of cellular activities. The abundance of a protein element is temporally and spatially regulated in two opposing aspects: de novo synthesis to manufacture the required amount of the protein, and destruction of the protein when it is in excess or no longer needed. One major route of protein destruction is coordinated by a set of conserved molecules, the F-box proteins, which promote ubiquitination in the ubiquitin-proteasome pathway. Here we discuss the functions of F-box proteins in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. We particularly emphasize the mechanisms whereby F-box proteins recruit specific substrates and regulate their abundance in the context of SCF E3 ligases. For some exceptions, we also review how F-box proteins function through non-SCF mechanisms.  相似文献   
50.
Chan TL  Yuen ST  Kong CK  Chan YW  Chan AS  Ng WF  Tsui WY  Lo MW  Tam WY  Li VS  Leung SY 《Nature genetics》2006,38(10):1178-1183
Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.  相似文献   
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