Galactic Chemical Evolution and the abundances of lithium, beryllium and boron

A LiBeB evolution model including Galactic Cosmic Ray nucleosynthesis, the $\nu$-process, novae, AGB and C-stars is presented. We have included Galactic Cosmic Ray Nucleosynthesis (GCRN) in a complete Chemical Evolution Model that takes into account 76 stable isotopes from hydrogen to zinc. Any successful LiBeB evolution model should also be compatible with other observational constraints like the age-metallicity relation, the G-dwarf distribution or the evolution of other elements. At the same time, we have checked how different would be a model that took into account the last observations by Wakker et al. (1999) of metal-enriched clouds falling onto the disk, from a primordial infall model.Comment: 2 pages, 2 figures. To appear in `Cosmic Evolution' Conference at IAp, Paris 13-17 Nov 200

Asterias: a parallelized web-based suite for the analysis of expression and aCGH data

Asterias (\url{http://www.asterias.info}) is an integrated collection of freely-accessible web tools for the analysis of gene expression and aCGH data. Most of the tools use parallel computing (via MPI). Most of our applications allow the user to obtain additional information for user-selected genes by using clickable links in tables and/or figures. Our tools include: normalization of expression and aCGH data; converting between different types of gene/clone and protein identifiers; filtering and imputation; finding differentially expressed genes related to patient class and survival data; searching for models of class prediction; using random forests to search for minimal models for class prediction or for large subsets of genes with predictive capacity; searching for molecular signatures and predictive genes with survival data; detecting regions of genomic DNA gain or loss. The capability to send results between different applications, access to additional functional information, and parallelized computation make our suite unique and exploit features only available to web-based applications.Comment: web based application; 3 figure

Galactic Cosmic Rays from Superbubbles and the Abundances of Lithium, Beryllium, and Boron

In this article we study the galactic evolution of the LiBeB elements within the framework of a detailed model of the chemical evolution of the Galaxy that includes galactic cosmic ray nucleosynthesis by particles accelerated in superbubbles. The chemical composition of the superbubble consists of varying proportions of ISM and freshly supernova synthesized material. The observational trends of 6 LiBeB evolution are nicely reproduced by models in which GCR come from a mixture of 25% of supernova material with 75% of ISM, except for 6 Li, for which maybe an extra source is required at low metallicities. To account for 7 Li evolution several additional sources have been considered (neutrino-induced nucleosynthesis, nova outbursts, C-stars). The model fulfills the energetic requirements for GCR acceleration.Comment: 25 pages, 9 figures. Accepted for publication in the Astrophysical Journa

Using a structural and logics systems approach to infer bHLH–DNA binding specificity determinants

Numerous efforts are underway to determine gene regulatory networks that describe physical relationships between transcription factors (TFs) and their target DNA sequences. Members of paralogous TF families typically recognize similar DNA sequences. Knowledge of the molecular determinants of protein–DNA recognition by paralogous TFs is of central importance for understanding how small differences in DNA specificities can dictate target gene selection. Previously, we determined the in vitro DNA binding specificities of 19 Caenorhabditis elegans basic helix-loop-helix (bHLH) dimers using protein binding microarrays. These TFs bind E-box (CANNTG) and E-box-like sequences. Here, we combine these data with logics, bHLH–DNA co-crystal structures and computational modeling to infer which bHLH monomer can interact with which CAN E-box half-site and we identify a critical residue in the protein that dictates this specificity. Validation experiments using mutant bHLH proteins provide support for our inferences. Our study provides insights into the mechanisms of DNA recognition by bHLH dimers as well as a blueprint for system-level studies of the DNA binding determinants of other TF families in different model organisms and humans.National Institute of General Medical Sciences (U.S.) (DK068429)National Institute of General Medical Sciences (U.S.) (HG003985)European Union (PROSPECTS HEALTH-F4-2008-201648

Binary systems and their nuclear explosions

Peer ReviewedPreprin

Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspicion of RASopathy and children with multiple cafe-au-lait macules

Children with neurofibromatosis type 1 (NF1) may exhibit an incomplete clinical presentation, making difficult to reach a clinical diagnosis. A phenotypic overlap may exist in children with other RASopathies or with other genetic conditions if only multiple café-au-lait macules (CALMs) are present. The syndromes that can converge in these inconclusive phenotypes have different clinical courses. In this context, an early genetic testing has been proposed to be clinically useful to manage these patients. We present the validation and implementation into diagnostics of a custom NGS panel (I2HCP, ICO-IMPPC Hereditary Cancer Panel) for testing patients with a clinical suspicion of a RASopathy (n = 48) and children presenting multiple CALMs (n = 102). We describe the mutational spectrum and the detection rates identified in these two groups of individuals. We identified pathogenic variants in 21 out of 48 patients with clinical suspicion of RASopathy, with mutations in NF1 accounting for 10% of cases. Furthermore, we identified pathogenic mutations mainly in the NF1 gene, but also in SPRED1, in more than 50% of children with multiple CALMs, exhibiting an NF1 mutational spectrum different from a group of clinically diagnosed NF1 patients (n = 80). An NGS panel strategy for the genetic testing of these two phenotype-defined groups outperforms previous strategies.status: publishe