Unified QSAR & network‐based computational chemistry approach to antimicrobials. II. Multiple distance and triadic census analysis of antiparasitic drugs complex networks

In the previous work, we reported a multitarget Quantitative Structure‐Activity Relationship (mt‐QSAR) model to predict drug activity against different fungal species. This mt‐QSAR allowed us to construct a drug–drug multispecies Complex Network (msCN) to investigate drug–drug similarity (González‐Díaz and Prado‐Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species–species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt‐QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series; the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug–drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug–drug msCN and species–species mdsCN with random networks. We also introduced here the inverse methodology to construct species–species msCN based on a mt‐QSAR model. Last, we reported the first substructural analysis of drug–drug msCN using Triadic Census Analysis (TCA) algorithm. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010     

Triggered alternans in an ionic model of ischemic cardiac ventricular muscle

It has been known for several decades that electrical alternans occurs during myocardial ischemia in both clinical and experimental work. There are a few reports showing that this alternans can be triggered into existence by a premature ventricular contraction. Detriggering of alternans by a premature ventricular contraction, as well as pause-induced triggering and detriggering, have also been reported. We conduct a search for triggered alternans in an ionic model of ischemic ventricular muscle in which alternans has been described recently: a one-dimensional cable of length 3 cm, containing a central ischemic zone 1 cm long, with 1 cm segments of normal (i.e., nonischemic) tissue at each end. We use a modified form of the Luo-Rudy [Circ. Res. 68, 1501-1526 (1991)] ionic model to represent the ventricular tissue, modeling the effect of ischemia by raising the external potassium ion concentration ([K(+)](o)) in the central ischemic zone. As [K(+)](o) is increased at a fixed pacing cycle length of 400 ms, there is first a transition from 1:1 rhythm to alternans or 2:2 rhythm, and then a transition from 2:2 rhythm to 2:1 block. There is a range of [K(+)](o) over which there is coexistence of 1:1 and 2:2 rhythms, so that dropping a stimulus from the periodic drive train during 1:1 rhythm can result in the conversion of 1:1 to 2:2 rhythm. Within the bistable range, the reverse transition from 2:2 to 1:1 rhythm can be produced by injection of a well-timed extrastimulus. Using a stimulation protocol involving delivery of pre- and post-mature stimuli, we derive a one-dimensional map that captures the salient features of the results of the cable simulations, i.e., the {1:1-->2:2-->2:1} transitions with {1:1<-->2:2} bistability. This map uses a new index of the global activity in the cable, the normalized voltage integral. Finally, we put forth a simple piecewise linear map that replicates the {1:1<-->2:2} bistability observed in the cable simulations and in the normalized voltage integral map. (c) 2002 American Institute of Physics.     

Localized states in polymeric molecules III The electronic structure of polyacetylene

The Transfer Matrix approach is used to treat the relaxed defect problem in trans-polyacetylene. We use a particular choice of parametrization for the hopping integrals, which is related to the existence of solitons in this material, to discuss its electronic structure. We obtain closed expressions for the density of states and for the wavefunctions associated to the localized state at any site of the chain.     

Controllable soliton emission from a Bose-Einstein condensate

We demonstrate, through numerical simulations, the controllable emission of matter-wave bursts from a Bose-Einstein condensate in a shallow optical dipole trap. The process is triggered by spatial variations of the scattering length along the trapping axis. In our approach, the outcoupling mechanisms are atom-atom interactions and thus, the trap remains unaltered. Once emitted, the matter wave forms a robust soliton. We calculate analytically the parameters for the experimental implementation of these matter-wave bursts of solitons.     

Stabilized two-dimensional vector solitons

In this Letter, we introduce the concept of stabilized vector solitons as nonlinear waves constructed by the addition of mutually incoherent fractions of Townes solitons that are stabilized under the effect of a periodic modulation of the nonlinearity. We analyze the stability of these new kinds of structures and describe their behavior and formation in Manakov-like interactions. Potential applications of our results in Bose-Einstein condensation and nonlinear optics are also discussed.     

Diastereoselective conjugate reduction with samarium diiodide: asymmetric synthesis of methyl (2S,3R)-N-acetyl-2-amino-2,3-dideuterio-3-phenylpropionate

A highly diastereoselective conjugate reduction using SmI2 and D2O has been demonstrated on a homochiral benzylidene diketopiperazine template, giving methyl (2S,3R)-N-acetyl-2-amino-2,3-dideuterio-3-phenylpropionate in 93% de and 90% ee after deprotection, hydrolysis and N-acetylation.     

Minimalist molecular model for nanopore selectivity

Using a simple model it is shown that the cost of constraining a hydrated potassium ion inside a narrow nanopore is smaller than the cost of constraining the smaller hydrated sodium ion. The former allows for a greater distortion of its hydration shell and can therefore maintain a better coordination. We propose that in this way the larger ion can go through narrow pores more easily. This is relevant to the molecular basis of ion selective nanopores and since this mechanism does not depend on the molecular details of the pore, it could also operate in all sorts of nanotubes, from biological to synthetic.     

Effects of temperature on the relaxation to equilibrium and stationary nonequilibrium states of some Langevin systems

We investigate the effects of temperature on the properties of the time relaxation to equilibrium and nonequilibrium steady states of correlation functions of some Langevin harmonic systems. We consider commonly used dissipative and conservative Langevin dynamics, and show that the time relaxation rate depends on the temperature in the case of thermal reservoirs at different temperatures connected to the system, but it does not happen in the case of relaxation to equilibrium, i.e., if all the heat bath are at the same temperature. Our formalism maps the initial stochastic problem on a noncanonical quantum field theory, and the calculations of the relaxation rates are based on a perturbative analysis. We argue to show the reliability of the perturbative computation.     

Inversion of the Bessel potential operator in weighted variable Lebesgue spaces

We study the inversion problem of the Bessel potential operator within the frameworks of the weighted Lebesgue spaces with variable exponent. The inverse operator is constructed by using approximative inverse operators. This generalizes some classical results to the variable exponent setting.