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51.
Wallace IM Urbanus ML Luciani GM Burns AR Han MK Wang H Arora K Heisler LE Proctor M St Onge RP Roemer T Roy PJ Cummins CL Bader GD Nislow C Giaever G 《Chemistry & biology》2011,18(10):1273-1283
Preselection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened ~81,000 compounds in Saccharomyces cerevisiae and identified ~7500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. These data were used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes, we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the ~7500 growth-inhibitory molecules have been made commercially available and the computational model and filter used are provided. 相似文献
52.
Synthesis of a novel class of multinucleate pyrimidine chalcogen (S/Se/Te) derivatives has been successfully attempted for the first time by the selective substitution of chlorine at the C-2 position of 2,4-dichloropyrimidine with nucleophilic dichalcogenide anion E22− (E = S, Se, Te) to afford bis[4-chloro-2-pyrimidyl] dichalcogenide. The highly electrophilic nature of 2,4-dichloropyrimidine compared to aryl chlorides has been further exploited to prepare a variety of 4-chloro-2-(arylchalcogenyl) pyrimidine compounds by substituting the chlorine exclusively at the C-2 position of 2,4-dichloropyrimidine with a variety of chalcogen bearing aryl anions ArE− (Ar = phenyl, 1-naphthyl, p-tolyl, 4,6-dimethyl-2-pyrimidyl, 2-pyridyl, 4-methyl-2-pyridyl). All the newly prepared symmetrical and unsymmetrical pyrimidyl chalcogen compounds have been thoroughly characterized with the help of various spectroscopic techniques viz., NMR (1H, 13C, 77Se), FT-IR and mass spectrometry (in representative cases). The crystal structures of 4-chloro-2-(phenylselanyl) pyrimidine and 2-(p-tolylselanyl)-4-chloropyrimidine have been determined by X-ray crystallography. 相似文献
53.
The activation of nuclear factor-kappa B1 (NFkB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFkB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in γ-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFκB1. Overexpression of miR-9 down-regulated the level of NFκB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFκB1, although there was no canonical target site for let-7g in the NFκB1 3' untranslated region. From these results, we conclude that the expression of miR-9 and let-7g could enhance the efficiency of radiotherapy for lung cancer treatment through the inhibition of NFκB1. 相似文献
54.
For an integer k ≥ 2, kth‐order slant Toeplitz operator Uφ [1] with symbol φ in L∞(??), where ?? is the unit circle in the complex plane, is an operator whose representing matrixM = (αij ) is given by αij = 〈φ, zki–j〉, where 〈. , .〉 is the usual inner product in L2(??). The operator Vφ denotes the compression of Uφ to H2(??) (Hardy space). Algebraic and spectral properties of the operator Vφ are discussed. It is proved that spectral radius of Vφ equals the spectral radius of Uφ, if φ is analytic or co‐analytic, and if Tφ is invertible then the spectrum of Vφ contains a closed disc and the interior of the disc consists of eigenvalues of infinite multiplicities. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
55.
M. J. Adamovich M. M. Aggarwal Y. A. Alexandrov R. Amirikas N. P. Andreeva Z. V. Anzon R. Arora F. A. Avetyan S. K. Badyal A. M. Bakich et al. 《Zeitschrift fur Physik C Particles and Fields》1995,65(3):421-429
The mechanism for producing slow, target associated particles in high energy heavy ion collisions is investigated. It is shown that the same mechanism which was proposed for hadron induced interactions is likely to appear also for heavy-ion reactions. The results indicate however a much weaker correlation between impact parameter and yield of slow particles. 相似文献
56.
2,2′‐Dipyridyl‐3,3′‐dipyridyl,5,5′‐dipyridyl‐diselenides have been synthesized by a convenient method employing non‐cryogenic conditions. Various bromopyridines (2‐Bromopyridine, 2,5‐dibromopyridines and 2,3,5‐Tribromopyridines) undergo selective monobromine–magnesium exchange to yield the corresponding pyridyl magnesium chlorides at room temperature upon treatment with iPrMgCl. The resulting pyridyl magnesium chloride is quenched with elemental selenium, which upon further oxidation affords the above diselenides in good yields. The compounds prepared using this methodology have been characterized by elemental analysis, IR, NMR (1H, 13C, 77Se) and mass spectral analysis. The molecular structure of 2,2′,5,5′‐Tetrabromo‐3,3′‐dipyridyldiselenide has been established by single‐crystal X‐ray diffraction analysis. It exists as a dimeric form due to the non‐bonding interactions between the selenium of one pyridine moiety and the hydrogen of the other. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
57.
RF SQUID behaviour has been observed at 77 K in YBaCuO thick films prepared by screen printing technique. A hole shunted with
a microbridge type of geometry is patterned manually for observing rf SQUID behaviour. Flux noise spectrum is also studied
and it is found to depend on the quality of the film. The spectral density of the flux noise in the white noise region is
1.7×10−3 Φ0/√Hz at 77 K. 相似文献
58.
Glasses with composition xGeO2.(0.30−x)M2O.0.70B2O3 (M=Li, K) containing 2.0 mol% of V2O5 have been prepared in the range 0.00≤x≤0.15 by normal melt quenching method. Electron paramagnetic resonance (EPR), optical transmission and absorption spectra and dc conductivity of these glasses have been studied. Spin Hamiltonian parameters (SHPs) of VO2+ ions, dipolar hyperfine coupling parameter, P, Fermi contact interaction parameter, K and molecular orbital coefficients (α2 and γ2) have been calculated. In GeO2·Li2O·B2O3 glasses there is no change in the tetragonality of the V4+O6 complex and the size of 3dxy orbit also remains unchanged with increase in GeO2 content. In GeO2·K2O·B2O3 glasses, there is an increase in the tetragonality of the V4+O6 complex and the 3dxy orbit expands with increase in GeO2 content. Values of the theoretical optical basicity, Λth, have also been reported. Optical band gap decreases with increase in GeO2 content. The dc conductivity of these glasses decreases and the activation energy increases with increase in GeO2:M2O ratio. 相似文献
59.
60.
We consider the time evolution of a class of stochastic systems of finite size with polynomial nearest neighbor transition rates. We obtain analytical expressions for the first passage time (FPT) and its moments. We show that the mean FPT, averaged over a uniform initial distribution, shows a simple asymptotoc behavior with the system size and the parameters of the transition rates. 相似文献