The Mystery of Two Straight Lines in Bacterial Genome Statistics. Release 2007

In special coordinates (codon position--specific nucleotide frequencies) bacterial genomes form two straight lines in 9-dimensional space: one line for eubacterial genomes, another for archaeal genomes. All the 348 distinct bacterial genomes available in Genbank in April 2007, belong to these lines with high accuracy. The main challenge now is to explain the observed high accuracy. The new phenomenon of complementary symmetry for codon position--specific nucleotide frequencies is observed. The results of analysis of several codon usage models are presented. We demonstrate that the mean--field approximation, which is also known as context--free, or complete independence model, or Segre variety, can serve as a reasonable approximation to the real codon usage. The first two principal components of codon usage correlate strongly with genomic G+C content and the optimal growth temperature respectively. The variation of codon usage along the third component is related to the curvature of the mean-field approximation. First three eigenvalues in codon usage PCA explain 59.1%, 7.8% and 4.7% of variation. The eubacterial and archaeal genomes codon usage is clearly distributed along two third order curves with genomic G+C content as a parameter.Comment: Significantly extended version with new data for all the 348 distinct bacterial genomes available in Genbank in April 200

A Gibbs approach to Chargaff's second parity rule

Chargaff's second parity rule (CSPR) asserts that the frequencies of short polynucleotide chains are the same as those of the complementary reversed chains. Up to now, this hypothesis has only been observed empirically and there is currently no explanation for its presence in DNA strands. Here we argue that CSPR is a probabilistic consequence of the reverse complementarity between paired strands, because the Gibbs distribution associated with the chemical energy between the bonds satisfies CSPR. We develop a statistical test to study the validity of CSPR under the Gibbsian assumption and we apply it to a large set of bacterial genomes taken from the GenBank repository.Comment: 16 page

Interaction between galectin-3 and cystinosin uncovers a pathogenic role of inflammation in kidney involvement of cystinosis.

Inflammation is involved in the pathogenesis of many disorders. However, the underlying mechanisms are often unknown. Here, we test whether cystinosin, the protein involved in cystinosis, is a critical regulator of galectin-3, a member of the β-galactosidase binding protein family, during inflammation. Cystinosis is a lysosomal storage disorder and, despite ubiquitous expression of cystinosin, the kidney is the primary organ impacted by the disease. Cystinosin was found to enhance lysosomal localization and degradation of galectin-3. In Ctns-/- mice, a mouse model of cystinosis, galectin-3 is overexpressed in the kidney. The absence of galectin-3 in cystinotic mice ameliorates pathologic renal function and structure and decreases macrophage/monocyte infiltration in the kidney of the Ctns-/-Gal3-/- mice compared to Ctns-/- mice. These data strongly suggest that galectin-3 mediates inflammation involved in kidney disease progression in cystinosis. Furthermore, galectin-3 was found to interact with the pro-inflammatory cytokine Monocyte Chemoattractant Protein-1, which stimulates the recruitment of monocytes/macrophages, and proved to be significantly increased in the serum of Ctns-/- mice and also patients with cystinosis. Thus, our findings highlight a new role for cystinosin and galectin-3 interaction in inflammation and provide an additional mechanistic explanation for the kidney disease of cystinosis. This may lead to the identification of new drug targets to delay cystinosis progression

Far-field approximation for hydrodynamic interactions in parallel-wall geometry

A complete analysis is presented for the far-field creeping flow produced by a multipolar force distribution in a fluid confined between two parallel planar walls. We show that at distances larger than several wall separations the flow field assumes the Hele-Shaw form, i.e., it is parallel to the walls and varies quadratically in the transverse direction. The associated pressure field is a two-dimensional harmonic function that is characterized by the same multipolar number m as the original force multipole. Using these results we derive asymptotic expressions for the Green's matrix that represents Stokes flow in the wall-bounded fluid in terms of a multipolar spherical basis. This Green's matrix plays a central role in our recently proposed algorithm [Physica A xx, {\bf xxx} (2005)] for evaluating many-body hydrodynamic interactions in a suspension of spherical particles in the parallel-wall geometry. Implementation of our asymptotic expressions in this algorithm increases its efficiency substantially because the numerically expensive evaluation of the exact matrix elements is needed only for the neighboring particles. Our asymptotic analysis will also be useful in developing hydrodynamic algorithms for wall-bounded periodic systems and implementing acceleration methods by using corresponding results for the two-dimensional scalar potential.Comment: 28 pages 5 figure

On local linearization of control systems

We consider the problem of topological linearization of smooth (C infinity or real analytic) control systems, i.e. of their local equivalence to a linear controllable system via point-wise transformations on the state and the control (static feedback transformations) that are topological but not necessarily differentiable. We prove that local topological linearization implies local smooth linearization, at generic points. At arbitrary points, it implies local conjugation to a linear system via a homeomorphism that induces a smooth diffeomorphism on the state variables, and, except at "strongly" singular points, this homeomorphism can be chosen to be a smooth mapping (the inverse map needs not be smooth). Deciding whether the same is true at "strongly" singular points is tantamount to solve an intriguing open question in differential topology

Hydrodynamic Coupling of Two Brownian Spheres to a Planar Surface

We describe direct imaging measurements of the collective and relative diffusion of two colloidal spheres near a flat plate. The bounding surface modifies the spheres' dynamics, even at separations of tens of radii. This behavior is captured by a stokeslet analysis of fluid flow driven by the spheres' and wall's no-slip boundary conditions. In particular, this analysis reveals surprising asymmetry in the normal modes for pair diffusion near a flat surface.Comment: 4 pages, 4 figure

Controllability on infinite-dimensional manifolds

Following the unified approach of A. Kriegl and P.W. Michor (1997) for a treatment of global analysis on a class of locally convex spaces known as convenient, we give a generalization of Rashevsky-Chow's theorem for control systems in regular connected manifolds modelled on convenient (infinite-dimensional) locally convex spaces which are not necessarily normable.Comment: 19 pages, 1 figur

Many-particle hydrodynamic interactions in parallel-wall geometry: Cartesian-representation method

This paper describes the results of our theoretical and numerical studies of hydrodynamic interactions in a suspension of spherical particles confined between two parallel planar walls, under creeping-flow conditions. We propose a novel algorithm for accurate evaluation of the many-particle friction matrix in this system--no such algorithm has been available so far. Our approach involves expanding the fluid velocity field into spherical and Cartesian fundamental sets of Stokes flows. The interaction of the fluid with the particles is described using the spherical basis fields; the flow scattered with the walls is expressed in terms of the Cartesian fundamental solutions. At the core of our method are transformation relations between the spherical and Cartesian basis sets. These transformations allow us to describe the flow field in a system that involves both the walls and particles. We used our accurate numerical results to test the single-wall superposition approximation for the hydrodynamic friction matrix. The approximation yields fair results for quantities dominated by single particle contributions, but it fails to describe collective phenomena, such as a large transverse resistance coefficient for linear arrays of spheres

Incorporating prior knowledge improves detection of differences in bacterial growth rate

BACKGROUND: Robust statistical detection of differences in the bacterial growth rate can be challenging, particularly when dealing with small differences or noisy data. The Bayesian approach provides a consistent framework for inferring model parameters and comparing hypotheses. The method captures the full uncertainty of parameter values, whilst making effective use of prior knowledge about a given system to improve estimation. RESULTS: We demonstrated the application of Bayesian analysis to bacterial growth curve comparison. Following extensive testing of the method, the analysis was applied to the large dataset of bacterial responses which are freely available at the web-resource, ComBase. Detection was found to be improved by using prior knowledge from clusters of previously analysed experimental results at similar environmental conditions. A comparison was also made to a more traditional statistical testing method, the F-test, and Bayesian analysis was found to perform more conclusively and to be capable of attributing significance to more subtle differences in growth rate. CONCLUSIONS: We have demonstrated that by making use of existing experimental knowledge, it is possible to significantly improve detection of differences in bacterial growth rate

Component-Based Real-Time Operating System for Embedded Applications

Acceptance rate: 37%, Rank (CORE): AInternational audienceAs embedded systems must constantly integrate new functionalities, their developement cycles must be based on high-level abstractions, making the software design more flexible. CBSE provides an approach to these new requirements. However, low-level services provided by operating systems are an integral part of embedded applications, furthermore deployed on resource-limited devices. Therefore, the expected benefits of CBSE must not impact on the constraints imposed by the targetted domain, such as memory footprint, energy consumption, and execution time. In this paper, we present the componentization of a legacy industry-established Real-Time Operating System, and how component-based applications are built on top of it. We use the Think framework that allows to produce flexible systems while paying for flexibility only where desired. Performed experimentions show that the induced overhead is negligeable