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A number of new pyrazolo[3,4-c] and [4,3-b]pyridine C-nucleosides, which can be viewed as 4- or 6-deazaformycin analogues were synthesized and examined as potential adenosine deaminase (ADA) inhibitors. The compounds were prepared through the condensation of a suitably substituted, lithiated 2- or 4-methylpyridine with tri-O-benzyl-d-ribonolactone, followed by borohydride reduction of the resulting hemiacetals, intramolecular Mitsunobu cyclisation of the derived diols, formation of the pyrazolopyridine ring system and subsequent removal of the protecting groups. These derivatives were designed on the structural basis provided by docking simulations performed within the enzyme catalytic site, however they demonstrated weak ADA inhibitory activity. Theoretical calculations assisted in the interpretation of the obtained biological data, thus providing guidance for rational structural modifications within this molecular scaffold.  相似文献   
2.
We study the Anisotropic Stormer Problem (ASP) and the Isosceles Three-Body Problem (IP), from the viewpoint of integrability, using Morales-Ramis theory and its generalization. The study of their integrability presents particular interest since they model important physical phenomena. Both problems can be reduced with respect to the S1 symmetry. Almeida and Stuchi [M.A. Almeida, T.J. Stuchi, Non-integrability of the anisotropic Stormer problem with angular momentum, Physica D 189 (2004) 219-233] proved that the reduced ASP is non-integrable for almost all values of the parameters. In this paper we establish the non-integrability (in the extended Liouville sense) of the remaining cases. The IP is a special case of the three-body problem and it can be considered as a generalization of the Sitnikov problem. Here we prove that the complexified reduced IP does not admit an additional independent meromorphic first integral.  相似文献   
3.
This paper reproduces the performance of a geometric average Spot Energy Index by investing only in a subset of stocks from the Dow Jones Composite Average, the FTSE 100 and Bovespa Composite indexes, and in two pools that include only energy-sector stocks from the US and the UK respectively. Daily data are used and the index-tracking problem for passive investment is addressed with two evolutionary algorithms – the differential evolution algorithm and the genetic algorithm. The performance of the suggested investment strategy is tested under three different scenarios: buy-and-hold, quarterly and monthly rebalancing, accounting for transaction costs where necessary.  相似文献   
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