316 research outputs found
A multi-method approach to radial-velocity measurement for single-object spectra
The derivation of radial velocities from large numbers of spectra that
typically result from survey work, requires automation. However, except for the
classical cases of slowly rotating late-type spectra, existing methods of
measuring Doppler shifts require fine-tuning to avoid a loss of accuracy due to
the idiosyncrasies of individual spectra. The radial velocity spectrometer
(RVS) on the Gaia mission, which will start operating very soon, prompted a new
attempt at creating a measurement pipeline to handle a wide variety of spectral
types.
The present paper describes the theoretical background on which this software
is based. However, apart from the assumption that only synthetic templates are
used, we do not rely on any of the characteristics of this instrument, so our
results should be relevant for most telescope-detector combinations.
We propose an approach based on the simultaneous use of several alternative
measurement methods, each having its own merits and drawbacks, and conveying
the spectral information in a different way, leading to different values for
the measurement. A comparison or a combination of the various results either
leads to a "best estimate" or indicates to the user that the observed spectrum
is problematic and should be analysed manually.
We selected three methods and analysed the relationships and differences
between them from a unified point of view; with each method an appropriate
estimator for the individual random error is chosen. We also develop a
procedure for tackling the problem of template mismatch in a systematic way.
Furthermore, we propose several tests for studying and comparing the
performance of the various methods as a function of the atmospheric parameters
of the observed objects. Finally, we describe a procedure for obtaining a
knowledge-based combination of the various Doppler-shift measurements.Comment: 16 pages, 4 figure
Androstane-3β,5α,6β,17β-tetrol trihydrate
The title hydrated tetrol, C19H32O4·3H2O, was synthesized by stereoselective reduction of the compound 3β,5α,6β-trihydroxyandrostan-17-one. All rings are fused trans. The organic molecules are connected head-to-tail along the c axis via O—H⋯O hydrogen bonds. Layers of water molecules in the ab plane interconnect these chains. A quantum chemical ab initio Roothan Hartree–Fock calculation of the isolated molecule gives values for the molecular geometry close to experimentally determined ones, apart from the C—O bond lengths, whose calculated values are significantly smaller than the measured ones, probably a consequence of the involvement of the C—OH groups in the hydrogen-bonding network
Detergents and chaotropes for protein solubilization before two-dimensional electrophoresis
Because of the outstanding ability of two-dimensional electrophoresis to
separate complex mixtures of intact proteins, it would be advantageous to apply
it to all types of proteins, including hydrophobic and membrane proteins.
Unfortunately, poor solubility hampers the analysis of these molecules. As
these problems arise mainly in the extraction and isoelectric focusing steps,
the solution is to improve protein solubility under the conditions prevailing
during isoelectric focusing. This chapter describes the use of chaotropes and
novel detergents to enhance protein solubility during sample extraction and
isoelectric focussing, and discusses the contribution of these compounds to
improving proteomic analysis of membrane proteins
Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation
A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach
<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties
Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7.
Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release.
Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue.
Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7.
Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data
Systems biology-guided identification of synthetic lethal gene pairs and its potential use to discover antibiotic combinations
Mathematical models of metabolism from bacterial systems biology have proven their utility across multiple fields, for example metabolic engineering, growth phenotype simulation, and biological discovery. The usefulness of the models stems from their ability to compute a link between genotype and phenotype, but their ability to accurately simulate gene-gene interactions has not been investigated extensively. Here we assess how accurately a metabolic model for Escherichia coli computes one particular type of gene-gene interaction, synthetic lethality, and find that the accuracy rate is between 25% and 43%. The most common failure modes were incorrect computation of single gene essentiality and biological information that was missing from the model. Moreover, we performed virtual and biological screening against several synthetic lethal pairs to explore whether two-compound formulations could be found that inhibit the growth of Gram-negative bacteria. One set of molecules was identified that, depending on the concentrations, inhibits E. coli and S. enterica serovar Typhimurium in an additive or antagonistic manner. These findings pinpoint specific ways in which to improve the predictive ability of metabolic models, and highlight one potential application of systems biology to drug discovery and translational medicine
The Whereabouts of 2D Gels in Quantitative Proteomics
Two-dimensional gel electrophoresis has been instrumental in the development
of proteomics. Although it is no longer the exclusive scheme used for
proteomics, its unique features make it a still highly valuable tool,
especially when multiple quantitative comparisons of samples must be made, and
even for large samples series. However, quantitative proteomics using 2D gels
is critically dependent on the performances of the protein detection methods
used after the electrophoretic separations. This chapter therefore examines
critically the various detection methods (radioactivity, dyes, fluorescence,
and silver) as well as the data analysis issues that must be taken into account
when quantitative comparative analysis of 2D gels is performed
Rigorous and thorough bioinformatic analyses of olfactory receptor promoters confirm enrichment of O/E and homeodomain binding sites but reveal no new common motifs
<p>Abstract</p> <p>Background</p> <p>Mammalian olfactory receptors (ORs) are subject to a remarkable but poorly understood regime of transcriptional regulation, whereby individual olfactory neurons each express only one allele of a single member of the large OR gene family.</p> <p>Results</p> <p>We performed a rigorous search for enriched sequence motifs in the largest dataset of OR promoter regions analyzed to date. We combined measures of cross-species conservation with databases of known transcription factor binding sites and <it>ab initio </it>motif-finding algorithms. We found strong enrichment of binding sites for the O/E family of transcription factors and for homeodomain factors, both already known to be involved in the transcriptional control of ORs, but did not identify any novel enriched sequences. We also found that TATA-boxes are present in at least a subset of OR promoters.</p> <p>Conclusions</p> <p>Our rigorous approach provides a template for the analysis of the regulation of large gene families and demonstrates some of the difficulties and pitfalls of such analyses. Although currently available bioinformatics methods cannot detect all transcriptional regulatory elements, our thorough analysis of OR promoters shows that in the case of this gene family, experimental approaches have probably already identified all the binding factors common to large fractions of OR promoters.</p
Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation
A key step in heart development is the coordinated development of the atrioventricular canal (AVC), the constriction between the atria and ventricles that electrically and physically separates the chambers, and the development of the atrioventricular valves that ensure unidirectional blood flow. Using knock-out and inducible overexpression mouse models, we provide evidence that the developmentally important T-box factors Tbx2 and Tbx3, in a functionally redundant manner, maintain the AVC myocardium phenotype during the process of chamber differentiation. Expression profiling and ChIP-sequencing analysis of Tbx3 revealed that it directly interacts with and represses chamber myocardial genes, and induces the atrioventricular pacemaker-like phenotype by activating relevant genes. Moreover, mutant mice lacking 3 or 4 functional alleles of Tbx2 and Tbx3 failed to form atrioventricular cushions, precursors of the valves and septa. Tbx2 and Tbx3 trigger development of the cushions through a regulatory feed-forward loop with Bmp2, thus providing a mechanism for the co-localization and coordination of these important processes in heart development
Solubilization of Proteins in 2DE: An Outline
Protein solubilization for two-dimensional electrophoresis (2DE) has to break
molecular interactions to separate the biological contents of the material of
interest into isolated and intact polypeptides. This must be carried out in
conditions compatible with the first dimension of 2DE, namely isoelectric
focusing. In addition, the extraction process must enable easy removal of any
nonprotein component interfering with the isoelectric focusing. The constraints
brought in this process by the peculiar features of isoelectric focusing are
discussed, as well as their consequences in terms of possible solutions and
limits for the solubilization process
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