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81.
《Bioorganic & medicinal chemistry》2014,22(14):3739-3748
The fragment of 2-substituted-3-sulfonylaminobenzamide has been proposed to replace the fragment of 2-substituted-3-sulfonylaminopyridine in PI3K and mTOR dual inhibitors to design novel anticancer agents based on bioisostere. The combination of the fragment of 2-substituted-3-sulfonylaminobenzamide with the fragment of 2-aminobenzothiazole or 2-aminothiazolo[5,4-b]pyridine, or 2-amino[1,2,4]triazolo[1,5-a]pyridine produced the novel structures of anticancer agents. As a result, nineteen target compounds were synthesized and characterized. Their antiproliferative activities in vitro were evaluated via MTT assay against four human cancer cell lines including HCT-116, A549, MCF-7 and U-87 MG. The SAR of target compounds was preliminarily discussed. Compound 1g with potent antiproliferative activity was examined for its effect on the AKT and p-AKT473. The anticancer effect of 1g was evaluated in established nude mice HCT-116 xenograft model. The results suggested that compound 1g can block PI3K/AKT/mTOR pathway and significantly inhibit tumor growth. These findings strongly support our assumption that the fragment of benzamide can replace the pyridine ring in some PI3K and mTOR dual inhibitor to design novel anticancer agents. 相似文献
82.
Regional differences in the carbon isotopic compositions of teak from two monsoonal regimes of India
Inter and intra-annual carbon isotope compositions (δ13C) of several annual growth rings of teak trees from two monsoonal regimes from India were studied and compared with the corresponding oxygen isotopic (δ18O) variations. In teak from both the regimes, amplitudes of intra-annual δ13C were ∼2-3 times lower than that observed in δ18O. Seasonal cycle with lower δ13C values at the middle and higher at ring boundaries was observed for teak from central India, dominated by the southwest monsoon. Positive correlations of intra-annual δ13C values with the corresponding δ18O values of the same rings and with relative humidity (RH) of the concurrent period suggest a dominant role of RH in controlling δ13C values of teak from central India. Intra-annual δ13C variations of teak from southern India, receiving both the southwest and northeast monsoons, revealed an initial decreasing trend followed by an increasing trend before culminating in depleted 13C values at the end of the growing season. No correlation was observed between intra-annual δ13C and δ18O variations of teak trees from southern India. Regional differences in the climatology of δ13C of atmospheric CO2 or the lengths of growing season could be likely reasons for differing intra-annual δ13C variations of teak from the two climatic regimes. 相似文献
83.
P. S. Gill 《Biometrical journal. Biometrische Zeitschrift》1993,35(3):343-354
Design and analysis of field experiments in the presence of local and remote treatment effects are considered. The design criteria are optimality and balance for estimating local and remote effects. A nonlinear model, where remote effects are assumed to be proportional to the local effects, has been discussed. 相似文献
84.
85.
The present communication constitutes a global review on plant analgesic activity with special emphasis on those found in different parts of the world, including Brazil, which act on the central nervous system. One hundred and sixty six plants belonging to 79 families are reported. 相似文献
86.
Takashi Saitoh Jon Olav Vik Nils Chr. Stenseth Toshikazu Takanishi Shintaro Hayakashi Nobuo Ishida Masaaki Ohmori Toshio Morita Shigeru Uemura Masahiko Kadomatsu Jun Osawa Koji Maekawa 《Population Ecology》2008,50(2):159-167
We analysed the effects of Quercus crispula acorn abundance on the density dependence of the large Japanese wood mouse Apodemus speciosus using time series data (1992–2007). The data were obtained in a forest in northern Hokkaido, Japan, by live-trapping rodents
and directly counting acorns on the ground. Acorn abundance in one year clearly influenced the abundance of wood mice in the
following year in all models examined based on the Gompertz and Ricker model; in addition, the abundance of wood mice had
effects on the population. Acorn abundance influenced the strength of density dependence (intraspecific competition) of the
wood mouse population. When the abundance of acorns was high, density dependence was relaxed, and as a result the equilibrium
density at which the population growth rate decreased to zero became higher. Those effects of acorn abundance were regarded
as a nonlinear perturbation effect (sensu Royama 1992). The nonlinearity of density dependence was also detected; higher densities had stronger effects on population growth rates.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
87.
The importance of phylogenetic effects in controlling seed size variation at the macroevolutionary levels was examined using species of a well-defined, monophyletic family, the Leguminosae. A nested ANOVA was used to separate variance components at the various taxonomic levels such as subfamily, genus, and subgenus. Statistical significance was found at most of the taxonomic levels examined, which suggests that phylogeny as shown by the accepted taxonomy of the family, exerted a substantial influence over seed size variation. Thus, there appears to be a characteristic mean seed size for each genus and subgenus. The overall positive correlation between plant height and seed size was interpreted as a scaling of seed size to plant height. When the effect of plant height was controlled, the amount of variance changed to some extent across taxonomic levels, though resulting in no change in statistical significance at various taxonomic levels. This results indicate that phylogenetic effects in seed size variation among congeneric or consubgeneric groupings were largely independent of allometric effects. The patterns of variance components and intraclass correlation coefficients for seed size differed to some extent among subfamilies. The difference in those patterns among taxa will reflect evolutionary change more closely with larger sample sizes. A simple inverse relationship between seed size and number per fruit among related legume species was difficult to generalize. This was perhaps due to phylogenetic constraints on seed size and/or seed number (or ovule number). These results demonstrate that phylogeny and plant height affect seed size variation among related species. 相似文献
88.
89.
居住建筑能耗受建筑周边空间形态的直接影响,确定空间形态低碳效应及其最佳尺度将有助于实现县域城镇低碳转型。以浙江省长兴县、福建省连江县为例,共计选取49个具有代表性的居住建筑样本,采用GIS分析与数理统计相结合的方式,在居住建筑1800m半径范围内,以200m为间隔建立缓冲区,开展全年、最冷月份能耗期及最热月份能耗期建筑能耗与周边空间形态关联性的连续尺度研究。结果表明:(1)道路密度、开发密度、容积率均与建筑能耗呈正相关,但各指标对应的能耗时期、尺度范围有较大差异。(2)水面率、土地利用混合度是与建筑能耗相关的共性指标,但在不同地区的正负效应及尺度范围不同;(3)影响浙闽地区县域城镇最热月份能耗期能耗的关键形态因子为1000m-道路密度、800m-水面率、1600m-开放空间率;影响连江最冷月份能耗期能耗的关键形态因子为800m-水面率。(4)就控碳单元设置而言,长兴县可重点关注1000—1200m半径范围,连江县可重点关注800—1000m、1400m半径范围。(5)浙闽地区县域城镇特性指标为开放空间率,与最热月份能耗期建筑能呈负相关;长兴县特性指标为容积率、水岸密度,分别与全年、最冷... 相似文献
90.
《Molecular membrane biology》2013,30(8):397-421
AbstractRecent structures of the potassium channel provide an essential beginning point for explaining how the pore is gated between open and closed conformations by changes in membrane voltage. Yet, the molecular details of this process and the connections to transmembrane gradients are not understood. To begin addressing how changes within a membrane environment lead to the channel’s ability to sense shifts in membrane voltage and to gate, we performed double-bilayer simulations of the Kv1.2 channel. These double-bilayer simulations enable us to simulate realistic voltage drops from resting potential conditions to depolarized conditions by changes in the bath conditions on each side of the bilayer. Our results show how the voltage sensor domain movement responds to differences in transmembrane potential. The initial voltage sensor domain movement, S4 in particular, is modulated by the gating charge response to changes in voltage and is initially stabilized by the lipid headgroups. We show this response is directly coupled to the initial stages of pore domain motion. Results presented here provide a molecular model for how the pre-gating process occurs in sequential steps: Gating charge response, movement and stabilization of the S4 voltage sensor domain, and movement near the base of the S5 region to close the pore domain. 相似文献