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31.
32.
Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood‐Stage Antimalarial Compounds 下载免费PDF全文
Dr. Sandeep Sundriyal Dr. Nicholas A. Malmquist Dr. Joachim Caron Scott Blundell Dr. Feng Liu Xin Chen Nitipol Srimongkolpithak Prof. Jian Jin Prof. Susan A. Charman Prof. Artur Scherf Dr. Matthew J. Fuchter 《ChemMedChem》2014,9(10):2360-2373
Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1‐benzyl‐4‐piperidyl)[6,7‐dimethoxy‐2‐(4‐methyl‐1,4‐diazepin‐1‐yl)‐4‐quinazolinyl]amine (BIX01294; 1 ), a known human G9a inhibitor, together with its dose‐dependent effects on histone methylation in the malarial parasite. This work describes our initial medicinal chemistry efforts to optimise the diaminoquinazoline chemotype for antimalarial activity. A variety of analogues were designed by substituting the 2 and 4 positions of the quinazoline core, and these molecules were tested against Plasmodium falciparum (3D7 strain). Several analogues with IC50 values as low as 18.5 nM and with low mammalian cell toxicity (HepG2) were identified. Certain pharmacophoric features required for antimalarial activity were found to be analogous to the previously published SAR of these analogues for G9a inhibition, thereby suggesting potential similarities between the malarial and human HKMT targets of this chemotype. Physiochemical, in vitro activity, and in vitro metabolism studies were also performed for a select set of potent analogues to evaluate their potential as antimalarial leads. 相似文献
33.
Artur Lugmayr 《Multimedia Tools and Applications》2012,58(2):385-398
This article is based on the keynote held at the workshop on Events in Multimedia (EiMM09) that took place in conjunction
with the ACM Multimedia conference in Beijing in October 2009. The idea of the keynote was to develop and explain the idea
of ambient media in general, it is principles, and additionally relate ambient media to information theoretical approaches
such as Peirce’s categories, to the theories of decision making, and to theories discussing how smart objects can be made
‘smart’ by simulating the human mind. This article rounds up with practical examples underlining the presented ideas and theories. 相似文献
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Artur Glavic Jörg VoigtJörg Persson Yixi SuJürgen Schubert Joost de GrootWilli Zande Thomas Brückel 《Journal of Alloys and Compounds》2011,509(16):5061-5063
High quality thin films of TbMnO3 were grown by pulsed laser deposition on orthorhombicYAlO3 (1 0 0). The interface and surface roughness of a 55 nm thick film were probed by X-ray reflectometry and atomic force microscopy, yielding a roughness of 1 nm. X-ray diffraction revealed untwinned films and a small mosaic spread of 0.04° and 0.2° for out-of-plane and in-plane reflections, respectively. This high degree of epitaxy was also confirmed by Rutherford backscattering spectrometry. Using polarized neutron diffraction we could identify a magnetic structure with the propagation vector (0 0.27 0), identical to the bulk magnetic structure of TbMnO3. 相似文献
36.
This paper presents the Connectionist Inductive Learning and Logic Programming System (C-IL2P). C-IL2P is a new massively parallel computational model based on a feedforward Artificial Neural Network that integrates inductive learning from examples and background knowledge, with deductive learning from Logic Programming. Starting with the background knowledge represented by a propositional logic program, a translation algorithm is applied generating a neural network that can be trained with examples. The results obtained with this refined network can be explained by extracting a revised logic program from it. Moreover, the neural network computes the stable model of the logic program inserted in it as background knowledge, or learned with the examples, thus functioning as a parallel system for Logic Programming. We have successfully applied C-IL2P to two real-world problems of computational biology, specifically DNA sequence analyses. Comparisons with the results obtained by some of the main neural, symbolic, and hybrid inductive learning systems, using the same domain knowledge, show the effectiveness of C-IL2P. 相似文献
37.
Compared a new set of queen's norms (for responses to 100 words from the kent-rosanoff word association test) collected in kingston, canada with minnesota norms reported by D. S. Palermo and J. J. Jenkins (see pa, vol. 39:17) for the 1st 9 primaries plus a 10th category for all other responses. Out of the 20 words compared, 19 were significantly different. In the light of previous evidence, word associations seem to have both a time and a place specificity, but its degree does not appear to be attributable to environmental-cultural differences between canada and the united states. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
38.
Free-Sets: A Condensed Representation of Boolean Data for the Approximation of Frequency Queries 总被引:5,自引:4,他引:1
Jean-François Boulicaut Artur Bykowski Christophe Rigotti 《Data mining and knowledge discovery》2003,7(1):5-22
Given a large collection of transactions containing items, a basic common data mining problem is to extract the so-called frequent itemsets (i.e., sets of items appearing in at least a given number of transactions). In this paper, we propose a structure called free-sets, from which we can approximate any itemset support (i.e., the number of transactions containing the itemset) and we formalize this notion in the framework of -adequate representations (H. Mannila and H. Toivonen, 1996. In Proc. of the Second International Conference on Knowledge Discovery and Data Mining (KDD'96), pp. 189–194). We show that frequent free-sets can be efficiently extracted using pruning strategies developed for frequent itemset discovery, and that they can be used to approximate the support of any frequent itemset. Experiments on real dense data sets show a significant reduction of the size of the output when compared with standard frequent itemset extraction. Furthermore, the experiments show that the extraction of frequent free-sets is still possible when the extraction of frequent itemsets becomes intractable, and that the supports of the frequent free-sets can be used to approximate very closely the supports of the frequent itemsets. Finally, we consider the effect of this approximation on association rules (a popular kind of patterns that can be derived from frequent itemsets) and show that the corresponding errors remain very low in practice. 相似文献
39.
Andrzej Trybulec Artur Kornilowicz Adam Naumowicz Krystyna Kuperberg 《Journal of Automated Reasoning》2013,50(2):119-121
The collection of works for this special issue was inspired by the presentations given at the 2011 AMS Special Session on Formal Mathematics for Mathematicians: Developing Large Repositories of Advanced Mathematics. The issue features a collection of articles by practitioners of formalizing proofs who share a deep interest in making computerized mathematics widely available. 相似文献
40.