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101.
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Grant RM Hamer D Hope T Johnston R Lange J Lederman MM Lieberman J Miller CJ Moore JP Mosier DE Richman DD Schooley RT Springer MS Veazey RS Wainberg MA 《Science (New York, N.Y.)》2008,321(5888):532-534
After disappointing results from all efficacy trials conducted to date, the field of microbicides research now faces substantial challenges. Poor coordination among interested parties and the choice of nonvalidated scientific targets for phase III studies have hampered progress and created mistrust about the use of microbicides as a method to prevent HIV-1 sexual transmission. Although new promising strategies are available, there will need to be serious reappraisals of how decisions are made to advance the next generations of candidates into clinical trials, and the use of appropriate animal models in this process will be critical. 相似文献
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Grimm V Revilla E Berger U Jeltsch F Mooij WM Railsback SF Thulke HH Weiner J Wiegand T DeAngelis DL 《Science (New York, N.Y.)》2005,310(5750):987-991
Agent-based complex systems are dynamic networks of many interacting agents; examples include ecosystems, financial markets, and cities. The search for general principles underlying the internal organization of such systems often uses bottom-up simulation models such as cellular automata and agent-based models. No general framework for designing, testing, and analyzing bottom-up models has yet been established, but recent advances in ecological modeling have come together in a general strategy we call pattern-oriented modeling. This strategy provides a unifying framework for decoding the internal organization of agent-based complex systems and may lead toward unifying algorithmic theories of the relation between adaptive behavior and system complexity. 相似文献
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Nanominerals, mineral nanoparticles, and Earth systems 总被引:4,自引:0,他引:4
Hochella MF Lower SK Maurice PA Penn RL Sahai N Sparks DL Twining BS 《Science (New York, N.Y.)》2008,319(5870):1631-1635
Minerals are more complex than previously thought because of the discovery that their chemical properties vary as a function of particle size when smaller, in at least one dimension, than a few nanometers, to perhaps as much as several tens of nanometers. These variations are most likely due, at least in part, to differences in surface and near-surface atomic structure, as well as crystal shape and surface topography as a function of size in this smallest of size regimes. It has now been established that these variations may make a difference in important geochemical and biogeochemical reactions and kinetics. This recognition is broadening and enriching our view of how minerals influence the hydrosphere, pedosphere, biosphere, and atmosphere. 相似文献
108.
Zong-li HU Ph D Xu-qing CHEN Guo-ping CHEN Li-juan LÜ Grierson Donald 《中国农业科学(英文版)》2007,6(4):406-413
The purpose of this study is to explore the influence of co-suppressing tomato ACC oxidase Ⅰ on the expression of fruit ripening-related and pathogenesis-related protein genes, and on the biosynthesis of endogenous ethylene and storage ability of fruits. Specific fragments of several fruit ripening-related and pathogenesis-related protein genes from tomato (Lycopersicon esculentum) were cloned, such as the l-aminocyclopropane-1-carboxylic acid oxidase 1 gene (LeAC01), 1- aminocyclopropane-l-carboxylic acid oxidase 3 gene (LeAC03), EIN3-binding F-box 1 gene (LeEBF1), pathogenesis-related protein 1 gene (LePR1), pathogenesis-related protein 5 gene (LePR5), and pathogenesis-related protein osmotin precursor gene (LeNP24) by PCR or RT-PCR. Then these specific DNA fragments were used as probes to hybridize with the total RNAs extracted from the wild type tomato Ailsa Craig (AC++) and the LeAC01 co-suppression tomatoes (V1187 and T4B), respectively. At the same time, ethylene production measurement and storage experiment of tomato fruits were carded out. The hybridization results indicated that the expression of fruit ripening-related genes such as LeACO3 and LeEBF1, and pathogenesis-related protein genes such as LePR1, LePR5, and LeNP24, were reduced sharply, and the ethylene production in the fruits, wounded leaves decreased and the storage time of ripening fruits was prolonged, when the expression of LeACO1 gene in the transgenic tomato was suppressed. In the co-suppression tomatoes, the expression of fruit ripening-related and pathogenesis-related protein genes were restrained at different degrees, the biosynthesis of endogenous ethylene decreased and the storage ability of tomato fruits increased. 相似文献
109.
Steed PM Tansey MG Zalevsky J Zhukovsky EA Desjarlais JR Szymkowski DE Abbott C Carmichael D Chan C Cherry L Cheung P Chirino AJ Chung HH Doberstein SK Eivazi A Filikov AV Gao SX Hubert RS Hwang M Hyun L Kashi S Kim A Kim E Kung J Martinez SP Muchhal US Nguyen DH O'Brien C O'Keefe D Singer K Vafa O Vielmetter J Yoder SC Dahiyat BI 《Science (New York, N.Y.)》2003,301(5641):1895-1898
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands. 相似文献
110.
Abelson JF Kwan KY O'Roak BJ Baek DY Stillman AA Morgan TM Mathews CA Pauls DL Rasin MR Gunel M Davis NR Ercan-Sencicek AG Guez DH Spertus JA Leckman JF Dure LS Kurlan R Singer HS Gilbert DL Farhi A Louvi A Lifton RP Sestan N State MW 《Science (New York, N.Y.)》2005,310(5746):317-320
Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS. 相似文献