The volume flux group and nonpositive curvature

We show that every closed nonpositively curved manifold with non-trivial volume flux group has zero minimal volume, and admits a finite covering with circle actions whose orbits are homologically essential. This proves a conjecture of Kedra-Kotschick-Morita for this class of manifolds.Comment: 6 pages, final version, to appear in Ann. Global Analysis and Geometr

AGMIAL: implementing an annotation strategy for prokaryote genomes as a distributed system

We have implemented a genome annotation system for prokaryotes called AGMIAL. Our approach embodies a number of key principles. First, expert manual annotators are seen as a critical component of the overall system; user interfaces were cyclically refined to satisfy their needs. Second, the overall process should be orchestrated in terms of a global annotation strategy; this facilitates coordination between a team of annotators and automatic data analysis. Third, the annotation strategy should allow progressive and incremental annotation from a time when only a few draft contigs are available, to when a final finished assembly is produced. The overall architecture employed is modular and extensible, being based on the W3 standard Web services framework. Specialized modules interact with two independent core modules that are used to annotate, respectively, genomic and protein sequences. AGMIAL is currently being used by several INRA laboratories to analyze genomes of bacteria relevant to the food-processing industry, and is distributed under an open source license

Entropies, volumes, and Einstein metrics

We survey the definitions and some important properties of several asymptotic invariants of smooth manifolds, and discuss some open questions related to them. We prove that the (non-)vanishing of the minimal volume is a differentiable property, which is not invariant under homeomorphisms. We also formulate an obstruction to the existence of Einstein metrics on four-manifolds involving the volume entropy. This generalizes both the Gromov--Hitchin--Thorpe inequality and Sambusetti's obstruction.Comment: This is a substantial revision and expansion of the 2004 preprint, which I prepared in spring of 2010 and which has since been published. The version here is essentially the published one, minus the problems introduced by Springer productio

A simple proof of Perelman's collapsing theorem for 3-manifolds

We will simplify earlier proofs of Perelman's collapsing theorem for 3-manifolds given by Shioya-Yamaguchi and Morgan-Tian. Among other things, we use Perelman's critical point theory (e.g., multiple conic singularity theory and his fibration theory) for Alexandrov spaces to construct the desired local Seifert fibration structure on collapsed 3-manifolds. The verification of Perelman's collapsing theorem is the last step of Perelman's proof of Thurston's Geometrization Conjecture on the classification of 3-manifolds. Our proof of Perelman's collapsing theorem is almost self-contained, accessible to non-experts and advanced graduate students. Perelman's collapsing theorem for 3-manifolds can be viewed as an extension of implicit function theoremComment: v1: 9 Figures. In this version, we improve the exposition of our arguments in the earlier arXiv version. v2: added one more grap

AGMIAL: implementing an annotation strategy for prokaryote genomes as a distributed system

We have implemented a genome annotation system for prokaryotes called AGMIAL. Our approach embodies a number of key principles. First, expert manual annotators are seen as a critical component of the overall system; user interfaces were cyclically refined to satisfy their needs. Second, the overall process should be orchestrated in terms of a global annotation strategy; this facilitates coordination between a team of annotators and automatic data analysis. Third, the annotation strategy should allow progressive and incremental annotation from a time when only a few draft contigs are available, to when a final finished assembly is produced. The overall architecture employed is modular and extensible, being based on the W3 standard Web services framework. Specialized modules interact with two independent core modules that are used to annotate, respectively, genomic and protein sequences. AGMIAL is currently being used by several INRA laboratories to analyze genomes of bacteria relevant to the food-processing industry, and is distributed under an open source license

Three Essential Ribonucleases—RNase Y, J1, and III—Control the Abundance of a Majority of Bacillus subtilis mRNAs

Bacillus subtilis possesses three essential enzymes thought to be involved in mRNA decay to varying degrees, namely RNase Y, RNase J1, and RNase III. Using recently developed high-resolution tiling arrays, we examined the effect of depletion of each of these enzymes on RNA abundance over the whole genome. The data are consistent with a model in which the degradation of a significant number of transcripts is dependent on endonucleolytic cleavage by RNase Y, followed by degradation of the downstream fragment by the 5′–3′ exoribonuclease RNase J1. However, many full-size transcripts also accumulate under conditions of RNase J1 insufficiency, compatible with a model whereby RNase J1 degrades transcripts either directly from the 5′ end or very close to it. Although the abundance of a large number of transcripts was altered by depletion of RNase III, this appears to result primarily from indirect transcriptional effects. Lastly, RNase depletion led to the stabilization of many low-abundance potential regulatory RNAs, both in intergenic regions and in the antisense orientation to known transcripts

BaSysBio: Towards an understanding of dynamic transcriptional regulation at global scale in bacteria: a systems biology approach

9th International Conference on Systems Biology, ICSB 2008, 22-28 August, Goteborg, SwedenBaSysBio adopts a systems biology approach in which quantitative experimental data will be generated for each step of the information flow and will fuel computational modelling. High throughput technologies (living cell arrays, tiling DNA microarrays, MDLC proteomics and quantitative metabolomics) will be developed in conjunction with new computational modelling concepts to facilitate the understanding of biological complexity. Models will simulate the cellular transcriptional responses to environmental changes and their impact on metabolism and proteome dynamics. The iterative process of simulations and model-driven targeted experiments will generate novel hypotheses about the mechanistic nature of dynamic cellular responses, unravel emerging systems properties and ultimately provide an efficient roadmap to tackle novel, pathogenic organismsN

Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence