The influence of geometry, surface character and flexibility on the permeation of ions and water through biological pores

A hydrophobic constriction site can act as an efficient barrier to ion and water permeation if its diameter is less than the diameter of an ion's first hydration shell. This hydrophobic gating mechanism is thought to operate in a number of ion channels, e.g. the nicotinic receptor, bacterial mechanosensitive channels (MscL and MscS) and perhaps in some potassium channels (e.g. KcsA, MthK, and KvAP). Simplified pore models allow one to investigate the primary characteristics of a conduction pathway, namely its geometry (shape, pore length, and radius), the chemical character of the pore wall surface, and its local flexibility and surface roughness. Our extended (ca. 0.1 \mu s) molecular dynamic simulations show that a short hydrophobic pore is closed to water for radii smaller than 0.45 nm. By increasing the polarity of the pore wall (and thus reducing its hydrophobicity) the transition radius can be decreased until for hydrophilic pores liquid water is stable down to a radius comparable to a water molecule's radius. Ions behave similarly but the transition from conducting to non-conducting pores is even steeper and occurs at a radius of 0.65 nm for hydrophobic pores. The presence of water vapour in a constriction zone indicates a barrier for ion permeation. A thermodynamic model can explain the behaviour of water in nanopores in terms of the surface tensions, which leads to a simple measure of "hydrophobicity" in this context. Furthermore, increased local flexibility decreases the permeability of polar species. An increase in temperature has the same effect, and we hypothesise that both effects can be explained by a decrease in the effective solvent-surface attraction which in turn leads to an increase in the solvent-wall surface free energy.Comment: Peer reviewed article appeared in Physical Biology http://www.iop.org/EJ/abstract/1478-3975/1/1/005

FM-track: a fiducial marker tracking software for studying cell mechanics in a three-dimensional environment

Tracking the deformation of fiducial markers in the vicinity of living cells embedded in compliant synthetic or biological gels is a powerful means to study cell mechanics and mechanobiology in three-dimensional environments. However, current approaches to track and quantify three-dimensional (3D) fiducial marker displacements remain ad-hoc, can be difficult to implement, and may not produce reliable results. Herein, we present a compact software package entitled “FM-Track,” written in the popular Python language, to facilitate feature-based particle tracking tailored for 3D cell micromechanical environment studies. FM-Track contains functions for pre-processing images, running fiducial marker tracking, and post-processing and visualization. FM-Track can thus aid the study of cellular mechanics and mechanobiology by providing an extensible software platform to more reliably extract complex local 3D cell contractile information in transparent compliant gel systems.https://www.sciencedirect.com/science/article/pii/S2352711019303474Published versio

The [alpha/Fe] Ratios in Dwarf Galaxies: Evidence for a Non-universal Stellar Initial Mass Function?

It is well established that the [alpha/Fe] ratios in elliptical galaxies increase with galaxy mass. This relation holds also for early-type dwarf galaxies, although it seems to steepen at low masses. The [alpha/Fe] vs. mass relation can be explained assuming that smaller galaxies form over longer timescales (downsizing), allowing a larger amount of Fe (mostly produced by long-living Type Ia Supernovae) to be released and incorporated into newly forming stars. Another way to obtain the same result is by using a flatter initial mass function (IMF) in large galaxies, increasing in this way the number of Type II Supernovae and therefore the production rate of alpha-elements. The integrated galactic initial mass function (IGIMF) theory predicts that the higher the star formation rate, the flatter the IMF. We have checked, by means of semi-analytical calculations, that the IGIMF theory, combined with the downsizing effect (i.e. the shorter duration of the star formation in larger galaxies), well reproduces the observed [alpha/Fe] vs. mass relation. In particular, we show a steepening of this relation in dwarf galaxies, in accordance with the available observations.Comment: 4 pages, 2 figures; to appear in the proceedings of the JENAM 2010 Symposium on Dwarf Galaxies (Lisbon, September 9-10, 2010

How directed is a directed network?

The trophic levels of nodes in directed networks can reveal their functional properties. Moreover, the trophic coherence of a network, defined in terms of trophic levels, is related to properties such as cycle structure, stability and percolation. The standard definition of trophic levels, however, borrowed from ecology, suffers from drawbacks such as requiring basal nodes, which limit its applicability. Here we propose simple improved definitions of trophic levels and coherence that can be computed on any directed network. We demonstrate how the method can identify node function in examples including ecosystems, supply chain networks, gene expression and global language networks. We also explore how trophic levels and coherence relate to other topological properties, such as non-normality and cycle structure, and show that our method reveals the extent to which the edges in a directed network are aligned in a global direction

Parameter uncertainty in forecast recalibration

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Ensemble forecasts of weather and climate are subject to systematic biases in the ensemble mean and variance, leading to inaccurate estimates of the forecast mean and variance. To address these biases, ensemble forecasts are post-processed using statistical recalibration frameworks. These frameworks often specify parametric probability distributions for the verifying observations. A common choice is the Normal distribution with mean and variance specified by linear functions of the ensemble mean and variance. The parameters of the recalibration framework are estimated from historical archives of forecasts and verifying observations. Often there are relatively few forecasts and observations available for parameter estimation, and so the fitted parameters are also subject to uncertainty. This artefact is usually ignored. This study reviews analytic results that account for parameter uncertainty in the widely used Model Output Statistics recalibration framework. The predictive bootstrap is used to approximate the parameter uncertainty by resampling in more general frameworks such as Non-homogeneous Gaussian Regression. Forecasts on daily, seasonal and annual time scales are used to demonstrate that accounting for parameter uncertainty in the recalibrated predictive distributions leads to probability forecasts that are more skilful and reliable than those in which parameter uncertainty is ignored. The improvements are attributed to more reliable tail probabilities of the recalibrated forecast distributions.Stefan Siegert was supported by the European Union Programme FP7/2007–2013 under grant agreement 3038378 (SPECS). Philip Sansom was supported by a grant from the National Oceanic and Atmospheric Administration (NOAA) NA12OAR4310086

An RUL-informed approach for life extension of high-value assets

The conventional approaches for life-extension (LE) of industrial assets are largely qualitative and focus only on a few indicators at the end of an asset’s design life. However, an asset may consist of numerous individual components with different useful lives and therefore applying a single LE strategy to every component will not result in an efficient outcome. In recent years, many advanced analytics techniques have been proposed to estimate the remaining useful life (RUL) of the assets equipped with sensor technology. This paper proposes a data-driven model for LE decision-making based on RUL values predicted on a real-time basis during the asset’s operational life. Our proposed LE model is conceptually targeted at the component, unit, or subsystem level; however, an asset-level decision is made by aggregating information across all components. Consequently, LE is viewed and assessed as a series of ongoing activities, albeit carefully orchestrated in a manner similar to operation and maintenance (O&M). The application of the model is demonstrated using the publicly available NASA C-MAPSS dataset for large commercial turbofan engines. This approach will be very beneficial to asset owners and maintenance engineers as it seamlessly weaves LE strategies into O&M activities, thus optimizing resources

Gating-like Motions and Wall Porosity in a DNA Nanopore Scaffold Revealed by Molecular Simulations

Recently developed synthetic membrane pores composed of folded DNA enrich the current range of natural and engineered protein pores and of nonbiogenic channels. Here we report all-atom molecular dynamics simulations of a DNA nanotube (DNT) pore scaffold to gain fundamental insight into its atomic structure, dynamics, and interactions with ions and water. Our multiple simulations of models of DNTs that are composed of a six-duplex bundle lead to a coherent description. The central tube lumen adopts a cylindrical shape while the mouth regions at the two DNT openings undergo gating-like motions which provide a possible molecular explanation of a lower conductance state observed in our previous experimental study on a membrane-spanning version of the DNT (ACS Nano 2015, 9, 1117-26). Similarly, the central nanotube lumen is filled with water and ions characterized by bulk diffusion coefficients while the gating regions exhibit temporal fluctuations in their aqueous volume. We furthermore observe that the porous nature of the walls allows lateral leakage of ions and water. This study will benefit rational design of DNA nanopores of enhanced stability of relevance for sensing applications, of nanodevices with tunable gating properties that mimic gated ion channels, or of nanopores featuring defined permeation behavior