Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens

Rho GTPases are common targets of bacterial toxins and type III secretion system effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the basis that they share a conserved WxxxE motif. In this study, we characterized six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of Citrobacter rodentium. We show that EspM2 triggers formation of global parallel stress fibres, TrcA and EspM1 induce formation of localized parallel stress fibres and EspM3 triggers formation of localized radial stress fibres. Using EspM2 and EspM3 as model effectors, we report that while substituting the conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp substitutions did not affect stress-fibre formation. We show, using dominant negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3 is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2 and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered phosphorylation of cofilin. These results suggest that the EspM effectors modulate actin dynamics by activating the RhoA signalling pathway

Modelling of photonic wire Bragg Gratings

Some important properties of photonic wire Bragg grating structures have been investigate. The design, obtained as a generalisation of the full-width gap grating, has been modelled using 3D finite-difference time-domain simulations. Different types of stop-band have been observed. The impact of the grating geometry on the lowest order (longest wavelength) stop-band has been investigated - and has identified deeply indented configurations where reduction of the stop-bandwidth and of the reflectivity occurred. Our computational results have been substantially validated by an experimental demonstration of the fundamental stop-band of photonic wire Bragg gratings fabricated on silicon-on-insulator material. The accuracy of two distinct 2D computational models based on the effective index method has also been studied - because of their inherently much greater rapidity and consequent utility for approximate initial designs. A 2D plan-view model has been found to reproduce a large part of the essential features of the spectral response of full 3D models

A generic contact detection framework for cylindrical particles in discrete element modelling

This paper aims to develop a generic framework for detecting contact between cylindrical particles in discrete element modelling based on a full exploitation of the axi-symmetrical property of cylinders. The main contributions include: (1) A four-parameter based local representative system is derived to describe the spatial relationship between two cylinders so that the 3D cylinder-cylinder intersection problem can be reduced to a series of 2D circle-ellipse intersections, which considerably simplifies the contact detection procedure. (2) A two-stage contact detection scheme is proposed in which no-overlap contact pairs are identified in the first overlap check stage, and then the actual overlap region is determined in the second resolution stage and represented by two schemes: the layered representation which is generic, and the edge representation which is numerically more efficient but less accurate. (3) The most significant contribution is the development of two theorems that establish a fundamental relationship between the contact point and contact normal of two contacting cylinders, offering a simple approach to determining the normal direction based on the contact point and vice versa. These theorems are valid not only for cylinders, but also for any axi-symmetrical shapes and their combinations. Some numerical issues are discussed. Numerical examples are presented to illustrate the capability and applicability of the proposed methodologies

A coupled 3D isogeometric and discrete element approach for modelling interactions between structures and granular matters

A three-dimensional (3D) isogeometric/discrete-element coupling method is presented for modelling contact/impact between structures and particles. This method takes advantages of the geometry smoothness and exactness of isogeometric analysis (IGA) for continuous solid media and the effectiveness and flexibility of the discrete element method (DEM) for particulate matters. The coupling procedure for handling interactions between IGA elements and discrete elements (DEs) includes global search, local search and interaction calculation. In the global search, the CGRID method is modified to detect potential contact pairs between IGA elements and DEs based on their bounding box representations. The strong convex hull property of a NURBS control mesh plays an important part in the bounding box representation of IGA elements. In the local search, the proposed approach treats each spherical DE centroid as a slave node and the contact surface of each IGA element as the master surface. The projection of a DE centroid onto an IGA element contact surface is solved by modifying the simplex method and Brent iterations. The contact force between an IGA element and a DE is determined from their penetration by using a (nonlinear) penalty function based method. The whole coupled system is solved by the explicit time integration within a updated Lagrangian scheme. Finally, three impact examples, including the impact of two symmetric bars, a tube onto a footing strip, and an assembly of granular particles to a tailor rolled blank, are simulated in elastic regime to assess the accuracy and applicability of the proposed method

Relativistic electrons produced by reconnecting electric fields in a laser-driven bench-top solar flare

Laboratory experiments have been carried out to model the magnetic reconnection process in a solar flare with powerful lasers. Relativistic electrons with energy up to megaelectronvolts are detected along the magnetic separatrices bounding the reconnection outflow, which exhibit a kappa-like distribution with an effective temperature of ~109 K. The acceleration of non-thermal electrons is found to be more efficient in the case with a guide magnetic field (a component of a magnetic field along the reconnection-induced electric field) than in the case without a guide field. Hardening of the spectrum at energies ≥500 keV is observed in both cases, which remarkably resembles the hardening of hard X-ray and γ-ray spectra observed in many solar flares. This supports a recent proposal that the hardening in the hard X-ray and γ-ray emissions of solar flares is due to a hardening of the source-electron spectrum. We also performed numerical simulations that help examine behaviors of electrons in the reconnection process with the electromagnetic field configurations occurring in the experiments. The trajectories of non-thermal electrons observed in the experiments were well duplicated in the simulations. Our numerical simulations generally reproduce the electron energy spectrum as well, except for the hardening of the electron spectrum. This suggests that other mechanisms such as shock or turbulence may play an important role in the production of the observed energetic electrons

Towards stochastic discrete element modelling of spherical particles with surface roughness: A normal interaction law

The current work is the first attempt towards establishing a stochastic discrete element modelling framework by developing a normal contact interaction law based on the classic Greenwood and Williamson (GW) model for spheres with rough surfaces. Two non-dimensional forms of the model that have a substantial impact on the computational efficiency are discussed and the theoretical relationship between the GW model and the Hertzian model for smooth spheres is formally established. Due to the inter-dependence between the contact pressure and deformation distributions in the model, a Newton-Raphson based iterative solution procedure is proposed to effectively and accurately obtain the contact force in terms of the overlap and two surface roughness parameters. The related key components of the procedure are addressed in detail. The numerical results obtained are first validated and then curve-fitted to derive an empirical formula as a new normal interaction law for spheres with surface roughness. The explicit nature of the new interaction law makes it readily be incorporated into the current discrete element modelling framework. A simple example is presented to illustrate the effect of surface roughness on the packing behaviour of a particle assembly

Prunella vulgaris: A comprehensive review of chemical constituents, pharmacological effects and clinical applications.

Prunella vulgaris (PV) is a perennial herb belonging to the Labiate family and is widely distributed in northeastern Asian countries such as Korea, Japan, and China. It is reported to display diverse biological activities including anti-microbial, anti-cancer, and anti-inflammation as determined by in vitro or in vivo studies. So far, about 200 compounds have been isolated from PV plant and majority of these have been characterized mainly as triterpenoids, sterols and flavonoids, followed by coumarins, phenylpropanoids, polysaccharides and volatile oils. This review summarizes and analyzes the current knowledge on the chemical constituents, pharmacological activities, mechanisms of action and clinical applications of the PV plant including its potential as a future medicinal plant. Although some of the chemical constituents of the PV plant and their mechanism of action have been investigated the biological activities of many of these remain unknown and further clinical trials are required to further enhance its reputation as a medicinal plant

The IASLC/ITMIG thymic epithelial tumors staging project: Proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/ Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification