Surgery groups of the fundamental groups of hyperplane arrangement complements

Using a recent result of Bartels and Lueck (arXiv:0901.0442) we deduce that the Farrell-Jones Fibered Isomorphism conjecture in L-theory is true for any group which contains a finite index strongly poly-free normal subgroup, in particular, for the Artin full braid groups. As a consequence we explicitly compute the surgery groups of the Artin pure braid groups. This is obtained as a corollary to a computation of the surgery groups of a more general class of groups, namely for the fundamental group of the complement of any fiber-type hyperplane arrangement in the complex n-space.Comment: 11 pages, AMSLATEX file, revised following referee's comments and suggestions, to appear in Archiv der Mathemati

Structural and Magnetic Properties of Trigonal Iron

First principles calculations of the electronic structure of trigonal iron were performed using density function theory. The results are used to predict lattice spacings, magnetic moments and elastic properties; these are in good agreement with experiment for both the bcc and fcc structures. We find however, that in extracting these quantities great care must be taken in interpreting numerical fits to the calculated total energies. In addition, the results for bulk iron give insight into the properties of thin iron films. Thin films grown on substrates with mismatched lattice constants often have non-cubic symmetry. If they are thicker than a few monolayers their electronic structure is similar to a bulk material with an appropriately distorted geometry, as in our trigonal calculations. We recast our bulk results in terms of an iron film grown on the (111) surface of an fcc substrate, and find the predicted strain energies and moments accurately reflect the trends for iron growth on a variety of substrates.Comment: 11 pages, RevTeX,4 tar'd,compressed, uuencoded Postscript figure

Direct Selective Laser Sintering of Tool Steel Powders to High Density: Part B -The Effect on Microstructural Evolution

This paper describes recent progress on the Direct Selective Laser Sintering of M2 [Fe6W-5Mo-4Cr-2V-0.8C] high speed steel (HSS) and H13 [Fe-5Cr-1V-1Si-1.5Mo-0.4C] tool steel powders. Part B will focus on the microstructural evolution of laser scanned powder beds. It has been found that H13 powders are more amenable to Direct Selective Laser Sintering than M2 powders. Densities up to 90% are possible with H13 powder compared with 70% for M2. The relationship between alloy composition, microstructure, post-scanned density and scan conditions will be discussed for single track, single layer and multi-layer constructions.The research reported in this paper is a joint project between the Universities of Bradford, Leeds and Liverpool, funded by the UK Engineering and Physical Sciences Research Council under Grant Number GR/R32222.Mechanical Engineerin

Direct Selective Laser Sintering of Tool Steel Powders to High Density: Part A - Effects of Laser Beam Width and Scan Strategy

This paper describes progress on the Direct Selective Laser Sintering of M2 and H13 tool steel powders, comparing this with previous and further observations on stainless steel powders. The distinguishing feature is the melting of single tracks and layers in deep powder beds. The paper focuses on changing characteristics of the melt pool (mass, volume, aspect ratio, stability) and laser-powder interactivity as the laser beam width, power and scan speed change. It also compares the melt pool of neighbouring tracks during single layer construction. Simulations from a computer model to predict melt pool shape and dimension show reasonable agreement with experimental results at low scan speeds (0.5mm/s). But unexpected increases in melt depth above 1.0mm/s have been observed, suggesting higher values and more variability in laser absorptivity than expected, even approaching 1.0 for the CO2 laser radiation used in this work.Mechanical Engineerin

Breaking of general rotational symmetries by multi-dimensional classical ratchets

We demonstrate that a particle driven by a set of spatially uncorrelated, independent colored noise forces in a bounded, multidimensional potential exhibits rotations that are independent of the initial conditions. We calculate the particle currents in terms of the noise statistics and the potential asymmetries by deriving an n-dimensional Fokker-Planck equation in the small correlation time limit. We analyze a variety of flow patterns for various potential structures, generating various combinations of laminar and rotational flows.Comment: Accepted, Physical Review

Single stranded fully Modified-Phosphorothioate oligonucleotides can induce structured nuclear inclusions, alter nuclear protein localization and disturb the transcriptome In Vitro

Oligonucleotides and nucleic acid analogues that alter gene expression are now showing therapeutic promise in human disease. Whilst the modification of synthetic nucleic acids to protect against nuclease degradation and to influence drug function is common practice, such modifications may also confer unexpected physicochemical and biological properties. Gapmer mixed-modified and DNA oligonucleotides on a phosphorothioate backbone can bind non-specifically to intracellular proteins to form a variety of toxic inclusions, driven by the phosphorothioate linkages, but also influenced by the oligonucleotide sequence. Recently, the non-antisense or other off-target effects of 2′ O- fully modified phosphorothioate linkage oligonucleotides are becoming better understood. Here, we report chemistry-specific effects of oligonucleotides composed of modified or unmodified bases, with phosphorothioate linkages, on subnuclear organelles and show altered distribution of nuclear proteins, the appearance of highly stable and strikingly structured nuclear inclusions, and disturbed RNA processing in primary human fibroblasts and other cultured cells. Phosphodiester, phosphorodiamidate morpholino oligomers, and annealed complimentary phosphorothioate oligomer duplexes elicited no such consequences. Disruption of subnuclear structures and proteins elicit severe phenotypic disturbances, revealed by transcriptomic analysis of transfected fibroblasts exhibiting such disruption. Our data add to the growing body of evidence of off-target effects of some phosphorothioate nucleic acid drugs in primary cells and suggest alternative approaches to mitigate these effects

Radiative Corrections to One-Photon Decays of Hydrogenic Ions

Radiative corrections to the decay rate of n=2 states of hydrogenic ions are calculated. The transitions considered are the M1 decay of the 2s state to the ground state and the E1(M2) decays of the $2p_{1/2}$ and $2p_{3/2}$ states to the ground state. The radiative corrections start in order $\alpha (Z \alpha)^2$, but the method used sums all orders of $Z\alpha$. The leading $\alpha (Z\alpha)^2$ correction for the E1 decays is calculated and compared with the exact result. The extension of the calculational method to parity nonconserving transitions in neutral atoms is discussed.Comment: 22 pages, 2 figure

Integromic analysis of genetic variation and gene expression identifies networks for cardiovascular disease phenotypes

BACKGROUND - : Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. METHODS AND RESULTS - : We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P≤5×10) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7), which in turn may promote interindividual variation in phenotypes. CONCLUSIONS - : Using a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major

Background The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip. Objectives In this study, co-crystallography experiments with recombinant B. pseudomallei Mip (BpMip) protein and Mip inhibitors, biochemical analysis and computational modelling were used to predict the efficacy of lead compounds for broad-spectrum activity against other pathogens. Methods Binding activity of three lead compounds targeting BpMip was verified using surface plasmon resonance spectroscopy. The determination of crystal structures of BpMip in complex with these compounds, together with molecular modelling and in vitro assays, was used to determine whether the compounds have broad-spectrum antimicrobial activity against pathogens. Results Of the three lead small-molecule compounds, two were effective in inhibiting the PPIase activity of Mip proteins from Neisseria meningitidis, Klebsiella pneumoniae and Leishmania major. The compounds also reduced the intracellular burden of these pathogens using in vitro cell infection assays. Conclusions These results indicate that Mip is a novel antivirulence target that can be inhibited using small-molecule compounds that prove to be promising broad-spectrum drug candidates in vitro. Further optimization of compounds is required for in vivo evaluation and future clinical applications

Mangrove microniches determine the structural and functional diversity of enriched petroleum hydrocarbon-degrading consortia

In this study, the combination of culture enrichments and molecular tools was used to identify bacterial guilds, plasmids and functional genes potentially important in the process of petroleum hydrocarbon (PH) decontamination in mangrove microniches (rhizospheres and bulk sediment). In addition, we aimed to recover PH-degrading consortia (PHDC) for future use in remediation strategies. The PHDC were enriched with petroleum from rhizosphere and bulk sediment samples taken from a mangrove chronically polluted with oil hydrocarbons. Southern blot hybridization (SBH) assays of PCR amplicons from environmental DNA before enrichments resulted in weak positive signals for the functional gene types targeted, suggesting that PH-degrading genotypes and plasmids were in low abundance in the rhizosphere and bulk sediments. However, after enrichment, these genes were detected and strong microniche-dependent differences in the abundance and composition of hydrocarbonoclastic bacterial populations, plasmids (IncP-1 alpha, IncP-1 beta, IncP-7 and IncP-9) and functional genes (naphthalene, extradiol and intradiol dioxygenases) were revealed by in-depth molecular analyses [PCR-denaturing gradient gel electrophoresis and hybridization (SBH and microarray)]. Our results suggest that, despite the low abundance of PH-degrading genes and plasmids in the environmental samples, the original bacterial composition of the mangrove microniches determined the structural and functional diversity of the PHDC enriched.Deutsche Forschungsgemeinschaft [SM59/4-1, 4-2]; FAPERJ-Brazil; European Commission [003998, 211684]; Alexander-von-Humboldt-Stiftung; CONICET (Argentina)info:eu-repo/semantics/publishedVersio