Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia

The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders.     

Thin gypsum panels

The present study was undertaken with a view to production of thin gypsum panels minus the outer cardboard as in gypsum wallboard, with strength and flexibility provided through reinforcement. Such a product can be handled by small plants, while the necessary materials are available or produced locally. A preliminary stage deal with incorporation of aggregates and reinforcement. The study proper had as its objectives: (1) Possible improvement in workability of the gypsum matrix through incorporation of polymers. (2) Improved bending strength, through high-strength reinforcement (glass fibre). (3) Examination of the effect of cut fibres, with a view to uniform two-way strength. The analysis of the results indicates that bending strength improved on admixture of a polymer (137%) and of glass fibres (175%). When both were used, the resulting strength showed synergistic effect: 29% over the arithmerical sum of the separate contributions.     

A New Level-Set Model for the Representation of Non-Smooth Geometries

In Starinshak et al. (J Comput Phys 262(1):1–16, 2014), we proposed a new level-set model for representing multimaterial flows in multiple space dimensions. Rather than associating each level-set function with the boundary of a material, the new model associates each level-set function with a pair of materials and the interface that separates them. In this paper, we extend the model to represent geometries with non-smooth boundaries. The model uses multiple level-set functions to describe the shape boundary, typically with one level-set function per smooth boundary segment. Sign information is collected from all level-set functions and a voting algorithm is used to determine the interior/exterior of the geometric shape. The model is well suited for representing boundaries with singularities; it offers significant improvement over standard level-set approaches, both in shape preservation and area conservation; and it eliminates the need for costly redistancing of the level-set function. Numerical examples illustrate the superior performance of the proposed model.     

Backbone cyclic peptide, which mimics the nuclear localization signal of human immunodeficiency virus type 1 matrix protein, inhibits nuclear import and virus production in nondividing cells

Here, we describe an application of the backbone cyclic (BC) proteinomimetic approach to the design and the synthesis of a BC peptide which functionally mimics the nuclear localization signal (NLS) region of the human immunodeficiency virus type 1 matrix protein (HIV-1 MA). On the basis of the NMR structure of HIV-1 MA, a library of BC peptides was designed and screened for the ability to inhibit nuclear import of NLS-BSA in digitonin-permeabilized HeLa and Colo-205 cultured cells. The screening yielded a lead compound (IC50 = 3 microM) which was used for the design of a second library. This library led to the discovery of a highly potent BC peptide, designated BCvir, with an IC50 value of 35 nM. This inhibitory potency is compared to a value of 12 microM exhibited by the linear parent HIV-1 MA NLS peptide. BCvir also reduced HIV-1 production by 75% in infected nondividing cultured human T-cells and was relatively resistant to tryptic digestion. These properties make BCvir a potential candidate for the development of a novel class of antiviral drugs which will be based on blocking nuclear import of viral genomes.