Matrix interpretation of multiple orthogonality

In this work we give an interpretation of a (s(d + 1) + 1)-term recurrence relation in terms of type II multiple orthogonal polynomials.We rewrite this recurrence relation in matrix form and we obtain a three-term recurrence relation for vector polynomials with matrix coefficients. We present a matrix interpretation of the type II multi-orthogonality conditions.We state a Favard type theorem and the expression for the resolvent function associated to the vector of linear functionals. Finally a reinterpretation of the type II Hermite- Padé approximation in matrix form is given

The pH of the skin surface and its impact on the barrier function

The `acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e. g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e. g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases. Copyright (c) 2006 S. Karger AG, Base

Velocity tuning of friction with two trapped atoms

Our ability to control friction remains modest, as our understanding of the underlying microscopic processes is incomplete. Atomic force experiments have provided a wealth of results on the dependence of nanofriction on structure velocity and temperature but limitations in the dynamic range, time resolution, and control at the single-atom level have hampered a description from first principles. Here, using an ion-crystal system with single-atom, single-substrate-site spatial and single-slip temporal resolution we measure the friction force over nearly five orders of magnitude in velocity, and contiguously observe four distinct regimes, while controlling temperature and dissipation. We elucidate the interplay between thermal and structural lubricity for two coupled atoms, and provide a simple explanation in terms of the Peierls–Nabarro potential. This extensive control at the atomic scale enables fundamental studies of the interaction of many-atom surfaces, possibly into the quantum regime

Effects of interspecific gene flow on the phenotypic variance–covariance matrix in Lake Victoria Cichlids

Quantitative genetics theory predicts adaptive evolution to be constrained along evolutionary lines of least resistance. In theory, hybridization and subsequent interspecific gene flow may, however, rapidly change the evolutionary constraints of a population and eventually change its evolutionary potential, but empirical evidence is still scarce. Using closely related species pairs of Lake Victoria cichlids sampled from four different islands with different levels of interspecific gene flow, we tested for potential effects of introgressive hybridization on phenotypic evolution in wild populations. We found that these effects differed among our study species. Constraints measured as the eccentricity of phenotypic variance–covariance matrices declined significantly with increasing gene flow in the less abundant species for matrices that have a diverged line of least resistance. In contrast, we find no such decline for the more abundant species. Overall our results suggest that hybridization can change the underlying phenotypic variance–covariance matrix, potentially increasing the adaptive potential of such populations

Activity of Bdellovibrio Hit Locus Proteins, Bd0108 and Bd0109, Links Type IVa Pilus Extrusion/Retraction Status to Prey-Independent Growth Signalling

Bdellovibrio bacteriovorus are facultatively predatory bacteria that grow within gram-negative prey, using pili to invade their periplasmic niche. They also grow prey-independently on organic nutrients after undergoing a reversible switch. The nature of the growth switching mechanism has been elusive, but several independent reports suggested mutations in the hit (host-interaction) locus on the Bdellovibrio genome were associated with the transition to preyindependent growth. Pili are essential for prey entry by Bdellovibrio and sequence analysis of the hit locus predicted that it was part of a cluster of Type IVb pilus-associated genes, containing bd0108 and bd0109. In this study we have deleted the whole bd0108 gene, which is unique to Bdellovibrio, and compared its phenotype to strains containing spontaneous mutations in bd0108 and the common natural 42 bp deletion variant of bd0108. We find that deletion of the whole bd0108 gene greatly reduced the extrusion of pili, whereas the 42 bp deletion caused greater pilus extrusion than wild-type. The pili isolated from these strains were comprised of the Type IVa pilin protein; PilA. Attempts to similarly delete gene bd0109, which like bd0108 encodes a periplasmic/secreted protein, were not successful, suggesting that it is likely to be essential for Bdellovibrio viability in any growth mode. Bd0109 has a sugar binding YD- repeat motif and an N-terminus with a putative pilin-like fold and was found to interact directly with Bd0108. These results lead us to propose that the Bd0109/Bd0108 interaction regulates pilus production in Bdellovibrio (possibly by interaction with the pilus fibre at the cell wall), and that the presence (and possibly retraction state) of the pilus feeds back to alter the growth state of the Bdellovibrio cell. We further identify a novel small RNA encoded by the hit locus, the transcription of which is altered in different bd0108 mutation background

Multi-omics HeCaToS dataset of repeated dose toxicity for cardiotoxic & hepatotoxic compounds

The data currently described was generated within the EU/FP7 HeCaToS project (Hepatic and Cardiac Toxicity Systems modeling). The project aimed to develop an in silico prediction system to contribute to drug safety assessment for humans. For this purpose, multi-omics data of repeated dose toxicity were obtained for 10 hepatotoxic and 10 cardiotoxic compounds. Most data were gained from in vitro experiments in which 3D microtissues (either hepatic or cardiac) were exposed to a therapeutic (physiologically relevant concentrations calculated through PBPK-modeling) or a toxic dosing profile (IC20 after 7 days). Exposures lasted for 14 days and samples were obtained at 7 time points (therapeutic doses: 2-8-24-72-168-240-336 h; toxic doses 0-2-8-24-72-168-240 h). Transcriptomics (RNA sequencing & microRNA sequencing), proteomics (LC-MS), epigenomics (MeDIP sequencing) and metabolomics (LC-MS & NMR) data were obtained from these samples. Furthermore, functional endpoints (ATP content, Caspase3/7 and O2 consumption) were measured in exposed microtissues. Additionally, multi-omics data from human biopsies from patients are available. This data is now being released to the scientific community through the BioStudies data repository ( https://www.ebi.ac.uk/biostudies/ )

A note on the O(n)-storage implementation of the GKO algorithm

We propose a new O(n)-space implementation of the GKO-Cauchy algorithm for the solution of linear systems with Cauchy-like matrix. Despite its slightly higher computational cost, this new algorithm makes a more efficient use of the processor cache memory. Thus, for matrices of size larger than about 500-1000, it outperforms the existing algorithms. We present an applicative case of Cauchy-like matrices with non-reconstructible main diagonal. In this special instance, the O(n) space algorithms can be adapted nicely to provide an efficient implementation of basic linear algebra operations in terms of the low displacement-rank generators

Nucleolin, a Shuttle Protein Promoting Infection of Human Monocytes by Francisella tularensis

International audienceWe herein confirm the importance of nucleolin expression for LVS binding and its specificity as nucleolin is not involved in binding of another intracellular pathogen as L. monocytogenes or an inert particle. Association of nucleolin with F. tularensis during infection continues intracellularly after endocytosis of the bacteria. The present work therefore unravels for the first time the presence of nucleolin in the phagosomal compartment of macrophages

Tiotropium inhibits proinflammatory microparticle generation by human bronchial and endothelial cells

Tiotropium is a muscarinic antagonist that reduces the risk of acute exacerbations of chronic obstructive pulmonary disease, possibly through an as yet incompletely characterized anti-inflammatory activity. We hypothesized that muscarinic activation of bronchial epithelial cells and endothelial cells causes the release of proinflammatory microparticles and that tiotropium inhibits the phenomenon. Microparticle generation was assessed by a functional assay, by flow cytometry and by NanoSight technology. Immortalized bronchial epithelial cells (16HBE) and umbilical vein endothelial cells were treated with acetylcholine in the presence of varying concentrations of tiotropium. Intracellular calcium concentration, extracellular regulated kinase phosphorylation and chemokine content in the conditioned media were assessed by commercial kits. Acetylcholine causes microparticle generation that is completely inhibited by tiotropium (50 pM). Microparticles generated by acetylcholine-stimulated cells increase the synthesis of proinflammatory mediators in an autocrine fashion. Acetylcholine-induced upregulation of microparticle generation is inhibited by an inhibitor of extracellular regulated kinase phosphorylation and by a phospholipase C inhibitor. Tiotropium blocks both extracellular regulated kinase phosphorylation and calcium mobilization, consistent with the hypothesis that the drug prevents microparticle generation through inhibition of these critical pathways. These results might contribute to explain the effect of tiotropium in reducing acute exacerbations of chronic obstructive pulmonary disease