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101.
Andrew M.K. Pennell James B. Aggen Subhabrata Sen Wei Chen Yuan Xu Edward Sullivan Lianfa Li Kevin Greenman Trevor Charvat Derek Hansen Daniel J. Dairaghi J.J. Kim Wright Penglie Zhang 《Bioorganic & medicinal chemistry letters》2013,23(5):1228-1231
A novel series of CCR1 antagonists based on the 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanone scaffold was identified by screening a compound library utilizing CCR1-expressing human THP-1 cells. SAR studies led to the discovery of the highly potent and selective CCR1 antagonist 14 (CCR1 binding IC50 = 4 nM using [125I]-CCL3 as the chemokine ligand). Compound 14 displayed promising pharmacokinetic and toxicological profiles in preclinical species. 相似文献
102.
The molecular mechanisms leading to asexuality remain little understood despite their substantial bearing on why sexual reproduction is dominant in nature. Here, we examine the role of hybridization in the origin and spread of obligate asexuality in Daphnia pulex, arguably the best‐documented case of contagious asexuality. Obligately parthenogenetic (OP) clones of D. pulex have traditionally been separated into ‘hybrid’ (Ldh SF) and ‘nonhybrid’ (Ldh SS) forms because the lactase dehydrogenase (Ldh) locus distinguishes the cyclically parthenogenetic (CP) lake dwelling Daphnia pulicaria (Ldh FF) from its ephemeral pond dwelling sister species D. pulex (Ldh SS). The results of our population genetic analyses based on microsatellite loci suggest that both Ldh SS and SF OP individuals can originate from the crossing of CP female F1 (D. pulex × D. pulicaria) and backcross with males from OP lineages carrying genes that suppress meiosis specifically in female offspring. In previous studies, a suite of diagnostic markers was found to be associated with OP in Ldh SS D. pulex lineages. Our association mapping supports a similar genetic mechanism for the spread of obligate parthenogenesis in Ldh SF OP individuals. Interestingly, our study shows that CP D. pulicaria carry many of the diagnostic microsatellite alleles associated with obligate parthenogenesis. We argue that the assemblage of mutations that suppress meiosis and underlie obligate parthenogenesis in D. pulex originated due to a unique historical hybridization and introgression event between D. pulex and D. pulicaria. 相似文献
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以小时为步长的大兴安岭兴安落叶松林地表可燃物含水率预测模型 总被引:2,自引:0,他引:2
应用时滞平衡含水率法(包括Nelson和Simard两种)及气象要素回归法,以小时为步长对大兴安岭地区阳坡上部落叶松林下地表细小死可燃物进行动态含水率测定,分析了不同郁闭度林分的预测误差.结果表明:以小时为步长的可燃物含水率预测方法适用于大兴安岭地区的典型落叶松林分,Simard法预测平均绝对误差为1.1%,平均相对误差为8.5%,低于Nelson法和传统的气象要素回归法,接近同类研究的误差范围;同一坡度、坡位上,不同郁闭度下的可燃物含水率变化差异较大,使用以小时为步长的可燃物含水率预测方法,应根据不同地区林分和地点选择合适的平衡含水率模型,或建立基于林分的可燃物含水率模型. 相似文献
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The regional specialization of brain function has been well documented in the mouse and fruitfly. The expression of regulatory factors in specific regions of the brain during development suggests that they function to establish or maintain this specialization. Here, we focus on two such factors—the Drosophila cephalic gap genes empty spiracles (ems) and orthodenticle (otd), and their vertebrate homologues Emx1/2 and Otx1/2—and review novel insight into their multiple crucial roles in the formation of complex sensory systems. While the early requirement of these genes in specification of the neuroectoderm has been discussed previously, here we consider more recent studies that elucidate the later functions of these genes in sensory system formation in vertebrates and invertebrates. These new studies show that the ems and Emx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective olfactory systems. Moreover, they demonstrate that the otd and Otx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective visual systems. Based on these recent experimental findings, we discuss the possibility that the olfactory and visual systems of flies and mice share a common evolutionary origin, in that the conserved visual and olfactory circuit elements derive from conserved domains of otd/Otx and ems/Emx action in the urbilaterian ancestor. 相似文献
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Sen Jia Thomas Lansdall-Welfare Saatviga Sudhahar Cynthia Carter Nello Cristianini 《PloS one》2016,11(2)
Feminist news media researchers have long contended that masculine news values shape journalists’ quotidian decisions about what is newsworthy. As a result, it is argued, topics and issues traditionally regarded as primarily of interest and relevance to women are routinely marginalised in the news, while men’s views and voices are given privileged space. When women do show up in the news, it is often as “eye candy,” thus reinforcing women’s value as sources of visual pleasure rather than residing in the content of their views. To date, evidence to support such claims has tended to be based on small-scale, manual analyses of news content. In this article, we report on findings from our large-scale, data-driven study of gender representation in online English language news media. We analysed both words and images so as to give a broader picture of how gender is represented in online news. The corpus of news content examined consists of 2,353,652 articles collected over a period of six months from more than 950 different news outlets. From this initial dataset, we extracted 2,171,239 references to named persons and 1,376,824 images resolving the gender of names and faces using automated computational methods. We found that males were represented more often than females in both images and text, but in proportions that changed across topics, news outlets and mode. Moreover, the proportion of females was consistently higher in images than in text, for virtually all topics and news outlets; women were more likely to be represented visually than they were mentioned as a news actor or source. Our large-scale, data-driven analysis offers important empirical evidence of macroscopic patterns in news content concerning the way men and women are represented. 相似文献
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