Donor-strand exchange in chaperone-assisted pilus assembly revealed in atomic detail by molecular dynamics

Adhesive multi-subunit fibres are assembled on the surface of many pathogenic bacteria via the chaperone-usher pathway. In the periplasm, a chaperone donates a β-strand to a pilus subunit to complement its incomplete immunoglobulin-like fold. At the outer membrane, this is replaced with a β-strand formed from the N-terminal extension (Nte) of an incoming pilus subunit by a donorstrand exchange (DSE) mechanism. This reaction has previously been shown to proceed via a concerted mechanism, in which the Nte interacts with the chaperone:subunit complex before the chaperone has been displaced, forming a ternary intermediate. Thereafter, the pilus and chaperone β-strands have been postulated to undergo a strand swap by a ‘zip-in-zip-out’ mechanism, whereby the chaperone strand zips out, residue by residue, as the Nte simultaneously zips in. Here, molecular dynamics simulations have been used to probe the DSE mechanism during formation of the Salmonella enterica Saf pilus at an atomic level, allowing the direct investigation of the zip-inzip- out hypothesis. The simulations provide an explanation of how the incoming Nte is able to dock and initiate DSE due to inherent dynamic fluctuations within the chaperone:subunit complex. The chaperone donor-strand is shown to unbind from the pilus subunit residue by residue, in direct support of the zip-in-zip-out hypothesis. In addition, an interaction of a residue towards the Nterminus of the Nte with a specific binding pocket (P*) on the adjacent pilus subunit is shown to stabilise the DSE product against unbinding, which also proceeds by a zippering mechanism. Together, the study provides an in-depth picture of DSE, including the first insights into the molecular events occurring during the zip-in-zip-out mechanism

Pile and Pile Group Capacity: Some Findings from Centrifuge Tests

The London Geotechnical Centrifuge Centre at City University London is a major experimental research facility for the Geotechnical Engineering Research Group. Some findings from two recent doctoral research projects are presented. The projects were aimed at improving our understanding of piled foundations. Pile group behaviour was studied with particular emphasis in determining the efficiency and load capacity of non standard group arrangements. The project was related directly to a development in London UK in which high capacity foundations were constructed using a Perimeter group arrangement of minipiles since that was all that could be constructed given onerous site constraints. The centrifuge research gave new insights into how pile groups carry large loads and demonstrated that Perimeter group arrangements make much more efficient use of piles than Grid groups. The second project was again industry driven and demonstrated that modifying the profile of a pile shaft can give significant increase in capacity with relatively little additional pile material

З листування Л. Биковського з Є. Бачинським

У статті надається листування видатного бібліографа, історика Л. Биковського з визначним українським громадським і церковним діячем Є. Бачинським. листи написані в 1947–1952 рр.В статье представлена переписка выдающегося библиографа, историка Л. Быковского с выдающимся украинским общественным и церковным деятелем Е. Бачинским. Письма написаны в 1947-1952 гг.The article consists of correspondence of the outstanding bibliographer, historian L.Bykovskyi with the outstanding Ukrainian public and church figure Ye. Bachynskyi. Letters are written in 1947–1952

Linear Amplifier Breakdown and Concentration Properties of a Gaussian Field Given that its L2\bm{L^2}-Norm is Large

In the context of linear amplification for systems driven by the square of a Gaussian noise, we investigate the realizations of a Gaussian field in the limit where its $L^2$-norm is large. Concentration onto the eigenspace associated with the largest eigenvalue of the covariance of the field is proved. When the covariance is trace class, the concentration is in probability for the $L^2$-norm. A stronger concentration, in mean for the sup-norm, is proved for a smaller class of Gaussian fields, and an example of a field belonging to that class is given. A possible connection with Bose-Einstein condensation is briefly discussed.Comment: REVTeX file, 11 pages, 1 added paragraph in the introduction, 2 added references, minor modifications in the text and abstract, submitted to J. Stat. Phy

Research report: Summary of key state issues of FERC orders 888 and 889

The Federal Energy Regulatory Commission`s (FERC) Order 888 is perhaps the most important and far reaching FERC electricity order in decades. The consequences on the structure of the industry and how the industry is regulated are significant departures from past methods and regulatory philosophy. This will undoubtedly have a dramatic impact on the manner in which state public utility commissions, which are also undergoing or considering dramatic change, regulate their jurisdictional electric utilities. This report summarizes and discusses the actions that the FERC is taking and their profound repercussions on the industry and state commissions. The report is not a comprehensive summary of the entire order. Rather, it is intended to highlight the order`s more important features and discuss what this could mean for the states. The report is organized into eight sections; the first seven address Order 888 and the last section (section 8) addresses Order 889. Section 1 through 5 summarize and discuss the main features of Order 888. Section 6 (on jurisdiction) and Section 7 (on property rights) interpret the likely consequences of the order. Section 8, summarizes the FERC`s Open Access Same Time System (OASIS) and discusses some concerns about its real-world application

Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis

Electron Spin Relaxation in a Semiconductor Quantum Well

A fully microscopic theory of electron spin relaxation by the D'yakonov-Perel' type spin-orbit coupling is developed for a semiconductor quantum well with a magnetic field applied in the growth direction of the well. We derive the Bloch equations for an electron spin in the well and define microscopic expressions for the spin relaxation times. The dependencies of the electron spin relaxation rate on the lowest quantum well subband energy, magnetic field and temperature are analyzed.Comment: Revised version as will appear in Physical Review

Nanostructural characterization of geopolymers by advanced beamline techniques

This paper presents the outcomes of a series of beamline-based studies, the results of which are combined to provide a more detailed multiscale understanding of the structure and chemistry of geopolymer binders. The range of beamline-based characterization techniques which have been applied to the study of geopolymer binders is increasing rapidly; although no single technique can provide a holistic view of binder structure across all the length scales which are of importance in determining strength development and durability, the synergy achievable through the combination of multiple beamline techniques is leading to rapid advances in knowledge in this area. Studies based around beamline infrared and X-ray fluorescence microscopy, in situ and ex situ neutron pair distribution function analysis, and nano- and micro-tomography, are combined to provide an understanding of geopolymer gel chemistry, nano- and microstructure in two and three dimensions, and the influences of seeded nucleation and precursor chemistry in these key areas. The application of advanced characterization methods in recent years has brought the understanding of geopolymer chemistry from a point, not more than a decade ago, when the analysis of the detailed chemistry of the aluminosilicate binder gel was considered intractable due to its disordered (“X-ray amorphous”) nature, to the present day where the influence of key compositional parameters on nanostructure is well understood, and both gel structure and reaction kinetics can be manipulated through methods including seeding, temperature variation, and careful mix design. This paper therefore provides a review outlining the value of nanotechnology – and particularly nanostructural characterization – in the development and optimization of a new class of environmentally beneficial cements and concretes. Key engineering parameters, in particularly strength development and permeability, are determined at a nanostructural level, and so it is essential that gel structures can be analyzed and manipulated at this level; beamline-based characterization techniques are critical in providing the ability to achieve this goal