Parametrization of nanoparticles: development of full-particle nanodescriptors.

While metal oxide nanoparticles (NPs) are one of the most commonly used nanomaterials, the theoretical models used to analyze and predict their behavior have been mostly based on just the chemical composition or the extrapolation from small metal oxide clusters' calculations. In this study, a set of novel, theoretical full-particle descriptors for modeling, grouping or read-across of metal oxide NP properties and biological activity was developed based on the force-field calculation of the potential energies of whole NPs. The capability of these nanodescriptors to group the nanomaterials acoording to their biological activity was demonstrated by Principal Component Analysis (PCA). The grouping provided by the PCA approach was found to be in good accordance with the algal growth inhibition data of well characterized nanoparticles, synthesized and measured inside the consortia of the EU 7FP framework MODERN project.

In silico exploratory study using structure-activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay.

The mutagenic potential of chemicals is a cause of growing concern, due to the possible impact on human health. In this paper we have developed a knowledge-based approach, combining information from structure-activity relationship (SAR) and metabolic triggers generated from the metabolic fate of chemicals in biological systems for prediction of mutagenicity in vitro based on the Ames test and in vivo based on the rodent micronucleus assay. In the first part of the work, a model was developed, which comprises newly generated SAR rules and a set of metabolic triggers. These SAR rules and metabolic triggers were further externally validated to predict mutagenicity in vitro, with metabolic triggers being used only to predict mutagenicity of chemicals, which were predicted unknown, by SARpy. Hence, this model has a higher accuracy than the SAR model, with an accuracy of 89% for the training set and 75% for the external validation set. Subsequently, the results of the second part of this work enlist a set of metabolic triggers for prediction of mutagenicity in vivo, based on the rodent micronucleus assay. Finally, the results of the third part enlist a list of metabolic triggers to find similarities and differences in the mutagenic response of chemicals in vitro and in vivo.

No time to lose--high throughput screening to assess nanomaterial safety.

Nanomaterials hold great promise for medical, technological and economical benefits. Knowledge concerning the toxicological properties of these novel materials is typically lacking. At the same time, it is becoming evident that some nanomaterials could have a toxic potential in humans and the environment. Animal based systems lack the needed capacity to cope with the abundance of novel nanomaterials being produced, and thus we have to employ in vitro methods with high throughput to manage the rush logistically and use high content readouts wherever needed in order to gain more depth of information. Towards this end, high throughput screening (HTS) and high content screening (HCS) approaches can be used to speed up the safety analysis on a scale that commensurate with the rate of expansion of new materials and new properties. The insights gained from HTS/HCS should aid in our understanding of the tenets of nanomaterial hazard at biological level as well as assist the development of safe-by-design approaches. This review aims to provide a comprehensive introduction to the HTS/HCS methodology employed for safety assessment of engineered nanomaterials (ENMs), including data analysis and prediction of potentially hazardous material properties. Given the current pace of nanomaterial development, HTS/HCS is a potentially effective means of keeping up with the rapid progress in this field--we have literally no time to lose.

Identification of coherent structures in turbulent shear flows with a fuzzy artmap neural network.

An implementation of a Fuzzy Artmap neural network is used to detect and to identify (recognise) structures (patterns) embedded in the velocity field of a turbulent wake behind a circular cylinder. The net is trained to recognise both clockwise and anticlockwise eddies present in the u and v velocity fields at 420 diameters downstream of the cylinder that generates the wake, using a pre-processed part of the recorded velocity data. The phase relationship that exists between the angles of the velocity vectors of an eddy pattern is used to reduce the number of classes contained in the data, before the start of the training procedure. The net was made stricter by increasing the vigilance parameter within the interval [0.90, 0.95] and a set of net-weights were obtained for each value. Full data files were scanned with the net classifying patterns according to their phase characteristics. The net classifies about 27% of the recorded signals as eddy motions, with the strictest vigilance parameter and without the need to impose external initial templates. Spanwise distances (homogeneous direction of the flow) within the centres of the eddies identified suggest that they form pairs of counter-rotating vortices (double rollers). The number of patterns selected with Fuzzy Artmap is lower than that reported for template matching because the net classifies eddies according to the recirculating pattern present at the core or central region, while template matching extends the region over which correlation between data and template is performed. In both cases, the topology of educed patterns is in agreement.

[Hypothalamic-hypophyseal-gonadal axis in chronic alcoholic patients]. / Estudio del eje hipotálamo-hipofisario-gonadal en pacientes alcohólicos cronicos.

Eleven male chronic alcoholics without cirrhosis but with clinical features of alcoholism were studied. Ten healthy men of similar age served as controls. After suppressing hormone (FSH), luteinizing hormone (LH), 17-beta-oestradiol (E2) and testosterone were determined in basal conditions and after administration of clomiphene citrate in each case. Basal levels of FSH, LH and E2 were higher and the testosterone level lower in the alcoholic group. After stimulation, there was no difference in gonadal hormone levels between both groups, suggesting a normal hypothalamic-pituitary axis with an adequate gonadal response.

[Hypothalamic-hypophyseal-gonadal axis in patients with liver cirrhosis of alcoholic origin]. / Estudio del eje hipotálamo-hipofisario-gonadal en pacientes con cirrosis hepática de etiología alcohólica.

Plasma levels of testosterone, 17-beta-oestradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone were estimated in 19 males with alcoholic cirrhosis and in 10 healthy age matched controls in basal conditions and after administration of clomiphene citrate. The gonadal hormone response is normal in the cirrhotic group after stimulation with clomiphene citrate, suggesting a normal functional reserve of the gonad of the cirrhotic patients. It is emphasized the direct damage that the alcohol produces in the Leydig cell.