Massive Star Formation in Luminous Infrared Galaxies: Giant HII Regions and their relation to Super Star Clusters

We have used HST/NICMOS H-band narrow-band Pa-alpha (at rest 1.87micron) images to identify star clusters and HII regions respectively in a sample of 8 luminous infrared galaxies (LIRGs). These observations have revealed the presence of a large population of super star clusters (SSC) and bright HII regions. A significant fraction of the HII regions shows H-alpha luminosities above that of 30 Doradus, the prototypical giant HII region. The excess of extremely luminous HII regions in LIRGs has been confirmed by comparison with normal galaxies observed at similar spatial resolutions. Despite the large numbers of identified star clusters and HII regions in LIRGs, we only find a small fraction of coincidences, between 4% and 30%. Using synthesis models we have reproduced the relative fractions of young HII regions, intermediate and old star clusters observed in Arp299 and the central region NGC3256 using a Salpeter IMF and instantaneous star formation. HII regions with no detected near-infrared cluster counterpart (25-39%) represent the youngest sites of star formation, with ages of up to approximately 5Myr and mostly intermediate mass (~10^5Msun) ionizing clusters. For these two galaxies, and within the present detection threshold we can only detect coincidences (4-10%) between an HII region and a near-infrared star cluster for the most massive star clusters (~10^6Msun) during the first 7Myr of their evolution. The identified near-infrared SSCs with no detectable Pa-alpha emission represent the ``old'' population (53-66% of the detected sources), with ages of between 7 and 20-40Myr. Older clusters possibly created in this or previous episodes of star formation are likely to exist in these systems but cannot be identified with the present detection threshold. (Abridged)Comment: Accepted for publication in AJ (July issue). Figure 2 not included. Go to: http://nicmos2.as.arizona.edu/~aalonso/work/papers/lirghii_v2.ps for a complete version of pape

Current methods for automated filtering of multiple sequence alignments frequently worsen single-gene phylogenetic inference

Phylogenetic inference is generally performed on the basis of multiple sequence alignments (MSA). Because errors in an alignment can lead to errors in tree estimation, there is a strong interest in identifying and removing unreliable parts of the alignment. In recent years several automated filtering approaches have been proposed, but despite their popularity, a systematic and comprehensive comparison of different alignment filtering methods on real data has been lacking. Here, we extend and apply recently introduced phylogenetic tests of alignment accuracy on a large number of gene families and contrast the performance of unfiltered versus filtered alignments in the context of single-gene phylogeny reconstruction. Based on multiple genome-wide empirical and simulated data sets, we show that the trees obtained from filtered MSAs are on average worse than those obtained from unfiltered MSAs. Furthermore, alignment filtering often leads to an increase in the proportion of well-supported branches that are actually wrong. We confirm that our findings hold for a wide range of parameters and methods. Although our results suggest that light filtering (up to 20% of alignment positions) has little impact on tree accuracy and may save some computation time, contrary to widespread practice, we do not generally recommend the use of current alignment filtering methods for phylogenetic inference. By providing a way to rigorously and systematically measure the impact of filtering on alignments, the methodology set forth here will guide the development of better filtering algorithms

Current Methods for Automated Filtering of Multiple Sequence Alignments Frequently Worsen Single-Gene Phylogenetic Inference

Phylogenetic inference is generally performed on the basis of multiple sequence alignments (MSA). Because errors in an alignment can lead to errors in tree estimation, there is a strong interest in identifying and removing unreliable parts of the alignment. In recent years several automated filtering approaches have been proposed, but despite their popularity, a systematic and comprehensive comparison of different alignment filtering methods on real data has been lacking. Here, we extend and apply recently introduced phylogenetic tests of alignment accuracy on a large number of gene families and contrast the performance of unfiltered versus filtered alignments in the context of single-gene phylogeny reconstruction. Based on multiple genome-wide empirical and simulated data sets, we show that the trees obtained from filtered MSAs are on average worse than those obtained from unfiltered MSAs. Furthermore, alignment filtering often leads to an increase in the proportion of well-supported branches that are actually wrong. We confirm that our findings hold for a wide range of parameters and methods. Although our results suggest that light filtering (up to 20% of alignment positions) has little impact on tree accuracy and may save some computation time, contrary to widespread practice, we do not generally recommend the use of current alignment filtering methods for phylogenetic inference. By providing a way to rigorously and systematically measure the impact of filtering on alignments, the methodology set forth here will guide the development of better filtering algorithm

A modular safety system for an insulin dose recommender: A feasibility study

Background: Delivering insulin in type 1 diabetes is a challenging, and potentially risky, activity; hence the importance of including safety measures as part of any insulin dosing or recommender system. This work presents and clinically evaluates a modular safety system that is part of an intelligent insulin dose recommender platform developed within the EU-funded PEPPER project. Methods: The proposed safety system is composed of four modules which use a novel glucose forecasting algorithm. These modules are: predictive glucose alerts and alarms; a predictive low-glucose basal insulin suspension module; an advanced rescue carbohydrate recommender for resolving hypoglycaemia; and a personalised safety constraint applied to insulin recommendations. The technical feasibility of the proposed safety system was evaluated in a pilot study including eight adult subjects with type 1 diabetes on multiple daily injections over a duration of six weeks. Glycaemic control and safety system functioning were compared between the two-weeks run-in period and the end-point at eight weeks. A standard insulin bolus calculator was employed to recommend insulin doses. Results: Overall, glycaemic control improved over the evaluated period. In particular, percentage time in the hypoglycaemia range (<3.0mmol/l) significantly decreased from 0.82 (0.05-4.79) % at run-in to 0.33 (0.00-0.93) % at endpoint (p=0.02). This was associated with a significant increase in percentage time in target range (3.9-10.0mmol/l) from 52.8 (38.3-61.5) % to 61.3 (47.5-71.7) % (p=0.03). There was also a reduction in number of carbohydrate recommendations. Conclusion: A safety system for an insulin dose recommender has been proven to be a viable solution to reduce the number of adverse events associated to glucose control in type 1 diabetes

Obscured star formation in the central region of the dwarf galaxy NGC5253

We present HST/NICMOS observations (1.1-2.2micron) and 1.9-4.1micron spectroscopy of the central region of the dwarf galaxy NGC5253. The HST/NICMOS observations reveal the presence of a nuclear double star cluster separated by 0.3-0.4arcsec or 6-8pc (for a distance d=4.1Mpc). The double star cluster, also a bright double source of Pa-alpha emission, appears to be coincident with the double radio nebula detected at 1.3cm. The eastern near-infrared star cluster (C1) is identified with the youngest optical cluster, whereas the western star cluster (C2), although it is almost completely obscured in the optical, becomes the brightest star cluster in the central region of NGC 5253 at wavelengths longer than 2micron. Both clusters are extremely young with ages of approximately 3.5 million years old. C2 is more massive than C1 by a factor of 6 to 20 (M(C2)= 7.7 x 10^5 - 2.6 x 10^6Msun, for a Salpeter IMF in the mass range 0.1-100Msun). Analysis of the circumnuclear spectrum excluding C1 and C2, as well as of a number of other near-infrared selected clusters with a range of (young) ages, suggests that the star formation was triggered across the central regions of the galaxy. We have also modelled the nuclear UV to mid-infrared spectral energy distribution (SED) of NGC5253 and found that the infrared part is well modelled with a highly obscured (A_V= 17mag) young starburst with a stellar mass consistent with our photometric estimates for C1 and C2. The SED model predicts a moderately bright polycyclic aromatic hydrocarbon (PAH) feature at 3.3micron that is not detected in our nuclear L-band spectrum. NGC5253's low metallicity and a top-heavy IMF likely combine to suppress the 3.3micron PAH emission that is commonly seen in more massive starburst systems.Comment: Accepted for publication in ApJ. High quality versions of Figures 1 and 2 are available upon reques

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

SGC - Structural Biology and Human Health: A New Approach to Publishing Structural Biology Results

The Structural Genomics Consortium (SGC) is a not-for-profit, public-private partnership established to deliver novel structural biology knowledge on proteins of medical relevance and place this information into the public domain without restriction, spearheading the concept of "Open-Source Science" to enable drug discovery. The SGC is a major provider of structural information focussed on proteins related to human health, contributing 20.5% of novel structures released by the PDB in 2008. In this article we describe the PLoS ONE Collection entitled 'Structural Biology and Human Health: Medically Relevant Proteins from the SGC'. This Collection contains a series of articles documenting many of the novel protein structures determined by the SGC and work to further characterise their function. Each article in this Collection can be read in an enhanced version where we have integrated our interactive and intuitive 3D visualisation platform, known as iSee. This publishing platform enables the communication of complex structural biology and related data to a wide audience of non-structural biologists. With the use of iSee as the first example of an interactive and intuitive 3D document publication method as part of PLoS ONE, we are pushing the boundaries of structural biology data delivery and peer-review. Our strong desire is that this step forward will encourage others to consider the need for publication of three dimensional and associated data in a similar manner. © 2009 Lee et al