Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer

Background Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. Results Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. Conclusion We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer.

Lateral distortional buckling tests of a new hollow flange channel beam

The LiteSteel beam (LSB) is a new hollow flange channel section developed by OneSteel Australian Tube Mills using their patented dual electric resistance welding and automated continuous roll-forming process. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. The LSBs are commonly used as flexural members in buildings. However, the LSB flexural members are subjected to lateral distortional buckling, which reduces their member moment capacities. Unlike the commonly observed lateral torsional buckling of steel beams, the lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist, and cross sectional change due to web distortion. An experimental study including more than 50 lateral buckling tests was therefore conducted to investigate the behaviour and strength of LSB flexural members. It included the available 13 LSB sections with spans ranging from 1200 to 4000 mm. Lateral buckling tests based on a quarter point loading were conducted using a special test rig designed to simulate the required simply supported and loading conditions accurately. Experimental moment capacities were compared with the predictions from the design rules in the Australian cold-formed steel structures standard. The new design rules in the standard were able to predict the moment capacities more accurately than previous design rules. This paper presents the details of lateral distortional buckling tests, in particular the features of the lateral buckling test rig, the results and the comparisons. It also includes the results of detailed studies into the mechanical properties and residual stresses of LSBs.

Diffusion of corporate governance practices : the Dutch response to pressures for shareholder value

As part of a larger literature focused on identifying and relating the antecedents and consequences of diffusing organizational practices/ideas, recent research has debated the international adoption of a shareholder-value-orientation (SVO). The debate has financial economists characterizing the adoption of an SVO as performance-enhancing and thus inevitable, with behavioral scientists disputing both claims, invoking institutional differences. This study seeks to provide some resolution to the debate (and advance current understanding on the diffusion of practices/ideas) by developing a socio-political perspective that links the antecedents and consequences of an SVO. In particular, we introduce the notion of misaligned elites and misfitted practices in our analysis of how and why differences in the technical and cultural preferences of major owners will influence a firm’s adoption and (un)successful implementation of an SVO among the largest 100 corporations in the Netherlands from 1992-2006. We conclude with a discussion of the implications of our perspective and our findings for future research on corporate governance and the diffusion of organizational practices/ideas.

Asymptotic and numerical results for a model of solvent-dependent drug diffusion through polymeric spheres

A model for drug diffusion from a spherical polymeric drug delivery device is considered. The model contains two key features. The first is that solvent diffuses into the polymer, which then transitions from a glassy to a rubbery state. The interface between the two states of polymer is modelled as a moving boundary, whose speed is governed by a kinetic law; the same moving boundary problem arises in the one-phase limit of a Stefan problem with kinetic undercooling. The second feature is that drug diffuses only through the rubbery region, with a nonlinear diffusion coefficient that depends on the concentration of solvent. We analyse the model using both formal asymptotics and numerical computation, the latter by applying a front-fixing scheme with a finite volume method. Previous results are extended and comparisons are made with linear models that work well under certain parameter regimes. Finally, a model for a multi-layered drug delivery device is suggested, which allows for more flexible control of drug release.

Natural convection flow with combined buoyancy effects due to thermal and mass diffusion in a thermally stratified media

We present here a numerical study of laminar doubly diffusive free convection flows adjacent to a vertical surface in a stable thermally stratified medium. The governing equations of mass, momentum, energy and species are non-dimensionalized. These equations have been solved by using an implicit finite difference method and local non-similarity method. The results show many interesting aspects of complex interaction of the two buoyant mechanisms that have been shown in both the tabular as well as graphical form.

Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix

Uncontrolled fibroblast growth factor (FGF) signaling can lead to human diseases, necessitating multiple layers of self-regulatory control mechanisms to keep its activity in check. Herein, we demonstrate that FGF9 and FGF20 ligands undergo a reversible homodimerization, occluding their key receptor binding sites. To test the role of dimerization in ligand autoinhibition, we introduced structure-based mutations into the dimer interfaces of FGF9 and FGF20. The mutations weakened the ability of the ligands to dimerize, effectively increasing the concentrations of monomeric ligands capable of binding and activating their cognate FGF receptor in vitro and in living cells. Interestingly, the monomeric ligands exhibit reduced heparin binding, resulting in their increased radii of heparan sulfate-dependent diffusion and biologic action, as evidenced by the wider dilation area of ex vivo lung cultures in response to implanted mutant FGF9-loaded beads. Hence, our data demonstrate that homodimerization autoregulates FGF9 and FGF20's receptor binding and concentration gradients in the extracellular matrix. Our study is the first to implicate ligand dimerization as an autoregulatory mechanism for growth factor bioactivity and sets the stage for engineering modified FGF9 subfamily ligands, with desired activity for use in both basic and translational research.