Topological structural alerts modulations of mammalian cell mutagenicity for halogenated derivatives.

Genotoxicity is a key toxicity endpoint for current regulatory requirements regarding new and existing chemicals. However, genotoxicity testing is time-consuming and costly, and involves the use of laboratory animals. This has motivated the development of computational approaches, designed to predict genotoxicity without the need to conduct laboratory tests. Currently, many existing computational methods, like quantitative structure-activity relationship (QSAR) models, provide limited information about the possible mechanisms involved in mutagenicity or predictions based on structural alerts (SAs) do not take statistical models into account. This paper describes an attempt to address this problem by using the TOPological Substructural MOlecular Design (TOPS-MODE) approach to develop and validate improved QSAR models for predicting the mutagenicity of a range of halogenated derivatives. Our most predictive model has an accuracy of 94.12%, exhibits excellent cross-validation and external set statistics. A reasonable interpretation of the model in term of SAs was achieved by means of bond contributions to activity. The results obtained led to the following conclusions: primary halogenated derivatives are more mutagenic than secondary ones; and substitution of chlorine by bromine increases mutagenicity while polyhalogenation decreases activity. The paper demonstrates the potential of the TOPS-MODE approach in developing QSAR models for identifying structural alerts for mutagenicity, combining high predictivity with relevant mechanistic interpretation.

Quantum conductance steps in solutions of multiwalled carbon nanotubes.

We have prepared solutions of multiwalled carbon nanotubes in Aroclor 1254, a mixture of polychlorinated biphenyls. The solutions are stable at room temperature. Transport measurements were performed using a scanning-tunneling probe on a sample prepared by spin coating the solution on gold substrates. Conductance steps were clearly seen. A histogram of a high number of traces shows maximum peaks at integer values of the conductance quantum G(0)=2e(2)/h, demonstrating ballistic transport at room temperature along the carbon nanotube over distances longer than 1.4 microm.

Stretched exponential relaxation for growing interfaces in quenched disordered media.

We study the relaxation for growing interfaces in quenched disordered media. We use a directed percolation depinning model introduced by Tang and Leschhorn for 1+1 dimensions. We define the two-time autocorrelation function of the interface height C(t('),t) and its Fourier transform. These functions depend on the difference of times t-t(') for long enough times, this is the steady-state regime. We find a two-step relaxation decay in this regime. The long time tail can be fitted by a stretched exponential relaxation function. The relaxation time tau(alpha) is proportional to the characteristic distance of the clusters of pinning cells in the direction parallel to the interface and it diverges as a power law. The two-step relaxation is lost at a given wavelength of the Fourier transform, which is proportional to the characteristic distance of the clusters of pinning cells in the direction perpendicular to the interface. The stretched exponential relaxation is caused by the existence of clusters of pinning cells and it is a direct consequence of the quenched noise.

Fluctuations of the correlation dimension at metal-insulator transitions.

We investigate numerically the inverse participation ratio, P(2), of the 3D Anderson model and of the power-law random banded matrix (PRBM) model at criticality. We found that the variance of lnP(2) scales with system size L as sigma(2)(L) = sigma(2)(infinity)-AL(-D(2)/2d), with D(2) being the correlation dimension and d the system dimension. Therefore the concept of a correlation dimension is well defined in the two models considered. The 3D Anderson transition and the PRBM transition for b = 0.3 (see the text for the definition of b) are fairly similar with respect to all critical magnitudes studied.

[Hyperthyroidism as a cause of irreversible dilated myocardiopathy]. / Hipertiroidismo como causa de miocardiopatía dilatada irreversible.

We describe the case of a young man with Graves Basedow's Disease as the unique cause of congestive heart failure, which after several months of antihyperthyroid therapy not very strictly followed, underwent heart transplantation due to severe ventricular and diastolic disfunction. The relationship between thyroid hypertension and cardiomyopathy is reviewed.