ORTHOGONAL DECOMPOSITIONS AND THEIR APPLICATIONS

It is well known that complex quaternion analysis plays an important role in the study of higher order boundary value problems of mathematical physics. Following the ideas given for real quaternion analysis, the paper deals with certain orthogonal decompositions of the complex quaternion Hilbert space into its subspaces of null solutions of Dirac type operator with an arbitrary complex potential. We then apply them to consider related boundary value problems, and to prove the existence and uniqueness as well as the explicit representation formulae of the underlying solutions

Two-loop stability of a complex singlet extended Standard Model

Motivated by the dark matter and the baryon asymmetry problems, we analyse a complex singlet extension of the Standard Model (SM) with a Z2 symmetry (which provides a dark matter candidate). After a detailed two-loop calculation of the renormalization group equations for the new scalar sector, we study the radiative stability of the model up to a high energy scale (with the constraint that the 126 GeV Higgs boson found at the LHC is in the spectrum) and find it requires the existence of a new scalar state mixing with the Higgs with a mass larger than 140 GeV. This bound is not very sensitive to the cut-off scale as long as the latter is larger than 10^10 GeV. We then include all experimental and observational constraints/measurements from collider data, dark matter direct detection experiments and from the Planck satellite and in addition force stability at least up to the GUT scale, to find that the lower bound is raised to about 170 GeV, while the dark matter particle must be heavier than about 50 GeV

A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets

Defining and cataloging exoplanets: The exoplanet.eu database

We describe an online database for extra-solar planetary-mass candidates, updated regularly as new data are available. We first discuss criteria for the inclusion of objects in the catalog: "definition" of a planet and several aspects of the confidence level of planet candidates. {\bf We are led to point out the conflict between sharpness of belonging or not to a catalogue and fuzziness of the confidence level.} We then describe the different tables of extra-solar planetary systems, including unconfirmed candidates (which will ultimately be confirmed, or not, by direct imaging). It also provides online tools: histogrammes of planet and host star data, cross-correlations between these parameters and some VO services. Future evolutions of the database are presented.Comment: Accepted in Astronomy and Astrophysics (revised version

MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights.

Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data analysis and interpretation. Here we introduce MetaboAnalyst version 5.0, aiming to narrow the gap from raw data to functional insights for global metabolomics based on high-resolution mass spectrometry (HRMS). Three modules have been developed to help achieve this goal, including: (i) a LC-MS Spectra Processing module which offers an easy-to-use pipeline that can perform automated parameter optimization and resumable analysis to significantly lower the barriers to LC-MS1 spectra processing; (ii) a Functional Analysis module which expands the previous MS Peaks to Pathways module to allow users to intuitively select any peak groups of interest and evaluate their enrichment of potential functions as defined by metabolic pathways and metabolite sets; (iii) a Functional Meta-Analysis module to combine multiple global metabolomics datasets obtained under complementary conditions or from similar studies to arrive at comprehensive functional insights. There are many other new functions including weighted joint-pathway analysis, data-driven network analysis, batch effect correction, merging technical replicates, improved compound name matching, etc. The web interface, graphics and underlying codebase have also been refactored to improve performance and user experience. At the end of an analysis session, users can now easily switch to other compatible modules for a more streamlined data analysis. MetaboAnalyst 5.0 is freely available at https://www.metaboanalyst.ca

Vitamin A affects flatfish development in a thyroid hormone signaling and metamorphic stage dependent manner

Vitamin A (VA) and retinoid derivatives are known morphogens controlling vertebrate development. Despite the research effort conducted during the last decade, the precise mechanism of how VA induces post-natal bone changes, and particularly those operating through crosstalk with the thyroid hormones (THs) remain to be fully understood. Since effects and mechanisms seem to be dose and time-dependent, flatfish are an interesting study model as they undergo a characteristic process of metamorphosis driven by THs that can be followed by external appearance. Here, we studied the effects of VA imbalance that might determine Senegalese sole (Solea senegalensis) skeletogenetic phenotype through development of thyroid follicles, THs homeostasis and signaling when a dietary VA excess was specifically provided during pre-, pro-or post-metamorphic stages using enriched rotifers and Artemia as carriers. The increased VA content in enriched live prey was associated to a higher VA content in fish at all developmental stages. Dietary VA content clearly affected thyroid follicle development, T3 and T4 immunoreactive staining, skeletogenesis and mineralization in a dose and time-dependent fashion. Gene expression analysis showed that VA levels modified the mRNA abundance of VA- and TH-specific nuclear receptors at specific developmental stages. Present results provide new and key knowledge to better understand how VA and TH pathways interact at tissue, cellular and nuclear level at different developmental periods in Senegalese sole, unveiling how dietary modulation might determine juvenile phenotype and physiology.Ministry of Education and Culture (MEC) of the Spanish Government [AGL2005-02478]; [SFRH/BPD/82049/2011]info:eu-repo/semantics/publishedVersio

How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids

Dystrophin is a large intracellular protein that prevents sarcolemmal ruptures by providing a mechanical link between the intracellular actin cytoskeleton and the transmembrane dystroglycan complex. Dystrophin deficiency leads to the severe muscle wasting disease Duchenne Muscular Dystrophy and the milder allelic variant, Becker Muscular Dystrophy (DMD and BMD). Previous work has shown that concomitant interaction of the actin binding domain 2 (ABD2) comprising spectrin like repeats 11 to 15 (R11-15) of the central domain of dystrophin, with both actin and membrane lipids, can greatly increase membrane stiffness. Based on a combination of SAXS and SANS measurements, mass spectrometry analysis of cross-linked complexes and interactive low-resolution simulations, we explored in vitro the molecular properties of dystrophin that allow the formation of ABD2-F-actin and ABD2-membrane model complexes. In dystrophin we identified two subdomains interacting with F-actin, one located in R11 and a neighbouring region in R12 and another one in R15, while a single lipid binding domain was identified at the C-terminal end of R12. Relative orientations of the dystrophin central domain with F-actin and a membrane model were obtained from docking simulation under experimental constraints. SAXS-based models were then built for an extended central subdomain from R4 to R19, including ABD2. Overall results are compatible with a potential F-actin/dystrophin/membrane lipids ternary complex. Our description of this selected part of the dystrophin associated complex bridging muscle cell membrane and cytoskeleton opens the way to a better understanding of how cell muscle scaffolding is maintained through this essential protein

H1 and H2 control design for polytopic continuous-time Markov jump linear systems with uncertain transition rates.

This paper investigates the problems of H1 and H2 state feedback control design for continuous-time Markov jump linear systems. The matrices of each operation mode are supposed to be uncertain, belonging to a polytope, and the transition rate matrix is considered partly known. By appropriately modeling all the uncertain parameters in terms of a multi-simplex domain, new design conditions are proposed, whose main advantage with respect to the existing ones is to allow the use of polynomially parameter-dependent Lyapunov matrices to certify the mean square closed-loop stability. Synthesis conditions are derived in terms of matrix inequalities with a scalar parameter. The conditions, which become LMIs for fixed values of the scalar, can cope with H1 and H2 state feedback control in both mode-independent and modedependent cases. Using polynomial Lyapunov matrices of larger degrees and performing a search for the scalar parameter, less conservative results in terms of guaranteed costs can be obtained through LMI relaxations. Numerical examples illustrate the advantages of the proposed conditions when compared with other techniques from the literature