Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes

Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with hypertelorism as the only feature. X-inactivation is proposed to explain the more severe outcome in heterozygous females, as this leads to functional mosaicism for cells with differing expression of EPHRIN-B1, generating abnormal tissue boundaries-a process that cannot occur in hemizygous males. Apparently challenging this model, males occasionally present with a more severe female-like CFNS phenotype. We hypothesized that such individuals might be mosaic for EFNB1 mutations and investigated this possibility in multiple tissue samples from six sporadically presenting males. Using denaturing high performance liquid chromatography, massively parallel sequencing and multiplex-ligation-dependent probe amplification (MLPA) to increase sensitivity above standard dideoxy sequencing, we identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5' untranslated region (UTR). Quantification by Pyrosequencing and MLPA demonstrated levels of mutant cells between 15 and 69%. The 5' UTR variant mutates the stop codon of a small upstream open reading frame that, using a dual-luciferase reporter construct, was demonstrated to exacerbate interference with translation of the wild-type protein. These results demonstrate a more severe outcome in mosaic than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females.

Are sustainable companies less risky and more profitable?

The purpose of this study was to determine whether there were significant differences in accounting indicators when comparing sustainable enterprises to other similar companies that are not considered as sustainable. The Corporate Sustainability Index of BM (São Paulo Stock, Commodities and Futures Exchange) was the criterion selected to break down the samples into sustainable and non-sustainable enterprises. The accounting indicators were separated into two kinds: risk (dividend payout, percentage growth of assets, financial leverage, current liquidity, asset size, variability of earnings, and accounting beta) and return (ROA, ROE, asset turnover, and net margin). We individually analyzed the companies in the energy sector, followed by those in the banking sector, as well as the entire ISE portfolio as of 2008/2009, including all the sectors. Mann-Whitney tests were performed in order to verify the difference of the means between the groups (ISE and non-ISE). The results, considering the method chosen and the time span covered by the study, indicate that there are no differences between sustainable companies and the others, when they are assessed by the accounting indicators used here.

A contribution for developing more efficient dynamic modelling algorithms of parallel robots

Parallel kinematic structures are considered very adequate architectures for positioning and orienti ng the tools of robotic mechanisms. However, developing dynamic models for this kind of systems is sometimes a difficult task. In fact, the direct application of traditional methods of robotics, for modelling and analysing such systems, usually does not lead to efficient and systematic algorithms. This work addre sses this issue: to present a modular approach to generate the dynamic model and through some convenient modifications, how we can make these methods more applicable to parallel structures as well. Kane’s formulati on to obtain the dynamic equations is shown to be one of the easiest ways to deal with redundant coordinates and kinematic constraints, so that a suitable c hoice of a set of coordinates allows the remaining of the modelling procedure to be computer aided. The advantages of this approach are discussed in the modelling of a 3-dof parallel asymmetric mechanisms.

The need of more rigorous assessments of marine species introductions: A counter example from the Brazilian coast

CAPES/PROCAD

Applying many-body expansion aiming to make ab in initio molecular dynamics more efficient

In this present work we present a methodology that aims to apply the many-body expansion to decrease the computational cost of ab initio molecular dynamics, keeping acceptable accuracy on the results. We implemented this methodology in a program which we called ManBo. In the many-body expansion approach, we partitioned the total energy E of the system in contributions of one body, two bodies, three bodies, etc., until the contribution of the Nth body [1-3]: E = E1 + E2 + E3 + …EN. The E1 term is the sum of the internal energy of the molecules; the term E2 is the energy due to interaction between all pairs of molecules; E3 is the energy due to interaction between all trios of molecules; and so on. In Manbo we chose to truncate the expansion in the contribution of two or three bodies, both for the calculation of the energy and for the calculation of the atomic forces. In order to partially include the many-body interactions neglected when we truncate the expansion, we can include an electrostatic embedding in the electronic structure calculations, instead of considering the monomers, pairs and trios as isolated molecules in space. In simulations we made we chose to simulate water molecules, and use the Gaussian 09 as external program to calculate the atomic forces and energy of the system, as well as reference program for analyzing the accuracy of the results obtained with the ManBo. The results show that the use of the many-body expansion seems to be an interesting approach for reducing the still prohibitive computational cost of ab initio molecular dynamics. The errors introduced on atomic forces in applying such methodology are very small. The inclusion of an embedding electrostatic seems to be a good solution for improving the results with only a small increase in simulation time. As we increase the level of calculation, the simulation time of ManBo tends to largely decrease in relation to a conventional BOMD simulation of Gaussian, due to better scalability of the methodology presented. References [1] E. E. Dahlke and D. G. Truhlar; J. Chem. Theory Comput., 3, 46 (2007). [2] E. E. Dahlke and D. G. Truhlar; J. Chem. Theory Comput., 4, 1 (2008). [3] R. Rivelino, P. Chaudhuri and S. Canuto; J. Chem. Phys., 118, 10593 (2003).