An automated workflow for patient-specific quality control of contour propagation

Contour propagation is an essential component of adaptive radiotherapy, but current contour propagation algorithms are not yet sufficiently accurate to be used without manual supervision. Manual review of propagated contours is time-consuming, making routine implementation of real-time adaptive radiotherapy unrealistic. Automated methods of monitoring the performance of contour propagation algorithms are therefore required. We have developed an automated workflow for patient-specific quality control of contour propagation and validated it on a cohort of head and neck patients, on which parotids were outlined by two observers. Two types of error were simulated-mislabelling of contours and introducing noise in the scans before propagation. The ability of the workflow to correctly predict the occurrence of errors was tested, taking both sets of observer contours as ground truth, using receiver operator characteristic analysis. The area under the curve was 0.90 and 0.85 for the observers, indicating good ability to predict the occurrence of errors. This tool could potentially be used to identify propagated contours that are likely to be incorrect, acting as a flag for manual review of these contours. This would make contour propagation more efficient, facilitating the routine implementation of adaptive radiotherap

Manganese Abundances in the Globular Cluster Omega Centauri

We present manganese abundances in 10 red-giant members of the globular cluster Omega Centauri; 8 stars are from the most metal-poor population (RGB MP and RGB MInt1) while two targets are members of the more metal rich groups (RGB MInt2 and MInt3). This is the first time Mn abundances have been studied in this peculiar stellar system. The LTE values of [Mn/Fe] in Omega Cen overlap those of Milky Way stars in the metal poor Omega Cen populations ([Fe/H] ~ -1.5 to -1.8), however unlike what is observed in Milky Way halo and disk stars, [Mn/Fe] declines in the two more metal-rich RGB MInt2 and MInt3 targets. Non-LTE calculations were carried out in order to derive corrections to the LTE Mn abundances. The non-LTE results for Omega Cen in comparison with the non-LTE [Mn/Fe] versus [Fe/H] trend obtained for the Milky Way confirm and strengthen the conclusion that the manganese behavior in Omega Cen is distinct. These results suggest that low-metallicity supernovae (with metallicities < -2) of either Type II or Type Ia dominated the enrichment of the more metal-rich stars in Omega Cen. The dominance of low-metallicity stars in the chemical evolution of Omega Cen has been noted previously in the s-process elements where enrichment from metal-poor AGB stars is indicated. In addition, copper, which also has metallicity dependent yields, exhibits lower values of [Cu/Fe] in the RGB MInt2 and MInt3 Omega Cen populations.Comment: Accepted for publication in the Ap

Using comparative genomics to reorder the human genome sequence into a virtual sheep genome

Using BAC-end sequences, a sparse marker map and the sequences of the human, dog and cow genomes, an accurate and detailed sub-gene level map of the sheep genome has been constructed

A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability

SN 2005bf: A possible transition event between type Ib/c supernovae and gamma-ray bursts

We present u′g′r′i′BV photometry and optical spectroscopy of the Type Ib/Ic SN 2005bf covering the first ∼100 days following discovery. The u′g′BV light curves displayed an unprecedented morphology among Type Ib/Ic supernovae, with an initial maximum some 2 weeks after discovery and a second, main maximum about 25 days after that. The bolometric light curve indicates that SN 2005bf was a remarkably luminous event, radiating at least 6.3 × 1042 ergs s -1 at maximum light and a total of 2.1 × 1049 ergs during the first 75 days after the explosion. Spectroscopically, SN 2005bf underwent a unique transformation from a Type Ic-like event at early times to a typical Type Ib supernova at later phases. The initial maximum in u′g′BV was accompanied by the presence in the spectrum of high-velocity (>14,000 km s-1) absorption lines of Fe II, Ca II, and H I. The photospheric velocity derived from spectra at early epochs was below 10,000 km s-1, which is unusually low compared with ordinary Type Ib supernovae. We describe one-dimensional computer simulations that attempt to account for these remarkable properties. The most favored model is that of a very energetic (2 × 1051 ergs), asymmetric explosion of a massive (8.3 M⊙) Wolf-Rayet WN star that had lost most of its hydrogen envelope. We speculate that an unobserved relativistic jet was launched producing a two-component explosion consisting of (1) a polar explosion containing a small fraction of the total mass and moving at high velocity and (2) the explosion of the rest of the star. At first, only the polar explosion is observed, producing the initial maximum and the high-velocity absorption-line spectrum resembling a Type Ic event. At late times, this fast-moving component becomes optically thin, revealing the more slowly moving explosion of the rest of the star and transforming the observed spectrum to that of a typical Type Ib supernova. If this scenario is correct, then SN 2005bf is the best example to date of a transition object between normal Type Ib/Ic supernovae and γ-ray bursts.Facultad de Ciencias Astronómicas y Geofísica

SN 2005bf: A Possible Transition Event Between Type Ib/c Supernovae and Gamma Ray Bursts

We present u'g'r'i'BV photometry and optical spectroscopy of the Type Ib/Ic SN 2005bf covering the first ~100 days following discovery. The u'g'BV light curves displayed a double-peaked morphology, which is among Type Ib/Ic supernovae. The bolometric light curve indicates that SN 2005bf was a remarkably luminous event. Spectroscopically, SN 2005bf underwent a unique transformation from a Type Ic-like event at early times to a typical Type Ib supernova at later phases. The initial maximum in u'g'BV was accompanied by the presence in the spectrum of high velocity absorption lines of Fe II, Ca II, and H I. The photospheric velocity derived from spectra at early epochs was unusually low compared with ordinary Type Ib supernovae. We describe one-dimensional computer simulations which attempt to account for these remarkable properties. The most favored model is that of a very energetic (2 x 10^{51} erg), asymmetric explosion of a massive (8.3 M_sun) Wolf-Rayet WN star that had lost most of its hydrogen envelope. We speculate that an unobserved relativistic jet was launched producing a two-component explosion consisting of 1) a polar explosion containing a small fraction of the total mass and moving at high velocity, and 2) the explosion of the rest of the star. At first, only the polar explosion is observed, producing the initial maximum and the high velocity absorption-line spectrum resembling a Type Ic event. At late times, this fast-moving component becomes optically-thin, revealing the slower-moving explosion of the rest of the star and transforming the observed spectrum to that of a typical Type Ib supernova. If this scenario is correct, then SN 2005bf is the best example to date of a transition object between normal Type Ib/Ic supernovae and gamma ray bursts.Comment: Accepted ApJ on 15 December 2005, 37 pages, 11 figures; minor changes after refereeing proces

Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells

The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals

Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences

Advances in the technologies and informatics used to generate and process large biological data sets (omics data) are promoting a critical shift in the study of biomedical sciences. While genomics, transcriptomics and proteinomics, coupled with bioinformatics and biostatistics, are gaining momentum, they are still, for the most part, assessed individually with distinct approaches generating monothematic rather than integrated knowledge. As other areas of biomedical sciences, including metabolomics, epigenomics and pharmacogenomics, are moving towards the omics scale, we are witnessing the rise of inter-disciplinary data integration strategies to support a better understanding of biological systems and eventually the development of successful precision medicine. This review cuts across the boundaries between genomics, transcriptomics and proteomics, summarizing how omics data are generated, analysed and shared, and provides an overview of the current strengths and weaknesses of this global approach. This work intends to target students and researchers seeking knowledge outside of their field of expertise and fosters a leap from the reductionist to the global-integrative analytical approach in research