A Review of Distributed Electric Propulsion Concepts for Air Vehicle Technology

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Overcoming High Energy Backgrounds at Pulsed Spallation Sources

Instrument backgrounds at neutron scattering facilities directly affect the quality and the efficiency of the scientific measurements that users perform. Part of the background at pulsed spallation neutron sources is caused by, and time-correlated with, the emission of high energy particles when the proton beam strikes the spallation target. This prompt pulse ultimately produces a signal, which can be highly problematic for a subset of instruments and measurements due to the time-correlated properties, and different to that from reactor sources. Measurements of this background have been made at both SNS (ORNL, Oak Ridge, TN, USA) and SINQ (PSI, Villigen, Switzerland). The background levels were generally found to be low compared to natural background. However, very low intensities of high-energy particles have been found to be detrimental to instrument performance in some conditions. Given that instrument performance is typically characterised by S/N, improvements in backgrounds can both improve instrument performance whilst at the same time delivering significant cost savings. A systematic holistic approach is suggested in this contribution to increase the effectiveness of this. Instrument performance should subsequently benefit.Comment: 12 pages, 8 figures. Proceedings of ICANS XXI (International Collaboration on Advanced Neutron Sources), Mito, Japan. 201

Management of the anticoagulated trauma patient in the emergency department: A survey of current practice in England and Wales

Objective The aim of this study was to investigate current management of the anticoagulated trauma patient in the emergency departments (EDs) in England and Wales. Methods A survey exploring management strategies for anticoagulated trauma patients presenting to the ED was developed with two patient scenarios concerning assessment of coagulation status, reversal of international normalised ratio (INR), management of hypotension and management strategies for each patient. Numerical data are presented as percentages of total respondents to that particular question. Results 106 respondents from 166 hospitals replied to the survey, with 24% of respondents working in a major trauma unit with a specialist neurosurgical unit. Variation was reported in the assessment and management strategies of the elderly anticoagulated poly-trauma patient described in scenario one. Variation was also evident in the responses between the neurosurgical and non-neurosurgical units for the headinjured, anticoagulated trauma patient in scenario two. Conclusion The results of this study highlight the similarities and variation in the management strategies used in the EDs in England and Wales for the elderly, anticoagulated trauma patient. The variations in practice reported may be due to the differences evident in the available guidelines for these patients

Identification and assessment of cardiolipin interactions with E. coli inner membrane proteins

Integral membrane proteins are localized and/or regulated by lipids present in the surrounding bilayer. While bacteria have relatively simple membranes, there is ample evidence that many bacterial proteins bind to specific lipids, especially the anionic lipid cardiolipin. Here, we apply molecular dynamics simulations to assess lipid binding to 42 different Escherichia coli inner membrane proteins. Our data reveal an asymmetry between the membrane leaflets, with increased anionic lipid binding to the inner leaflet regions of the proteins, particularly for cardiolipin. From our simulations, we identify >700 independent cardiolipin binding sites, allowing us to identify the molecular basis of a prototypical cardiolipin binding site, which we validate against structures of bacterial proteins bound to cardiolipin. This allows us to construct a set of metrics for defining a high-affinity cardiolipin binding site on bacterial membrane proteins, paving the way for a heuristic approach to defining other protein-lipid interactions

PyLipID : A Python package for analysis of protein-lipid interactions from MD simulations

Lipids play important modulatory and structural roles for membrane proteins. Molecular dynamics simulations are frequently used to provide insights into the nature of these protein–lipid interactions. Systematic comparative analysis requires tools that provide algorithms for objective assessment of such interactions. We introduce PyLipID, a Python package for the identification and characterization of specific lipid interactions and binding sites on membrane proteins from molecular dynamics simulations. PyLipID uses a community analysis approach for binding site detection, calculating lipid residence times for both the individual protein residues and the detected binding sites. To assist structural analysis, PyLipID produces representative bound lipid poses from simulation data, using a density-based scoring function. To estimate residue contacts robustly, PyLipID uses a dual-cutoff scheme to differentiate between lipid conformational rearrangements while bound from full dissociation events. In addition to the characterization of protein–lipid interactions, PyLipID is applicable to analysis of the interactions of membrane proteins with other ligands. By combining automated analysis, efficient algorithms, and open-source distribution, PyLipID facilitates the systematic analysis of lipid interactions from large simulation data sets of multiple species of membrane proteins

Relative affinities of protein–cholesterol interactions from equilibrium molecular dynamics simulations

Specific interactions of lipids with membrane proteins contribute to protein stability and function. Multiple lipid interactions surrounding a membrane protein are often identified in molecular dynamics (MD) simulations and are, increasingly, resolved in cryo-electron microscopy (cryo-EM) densities. Determining the relative importance of specific interaction sites is aided by determination of lipid binding affinities using experimental or simulation methods. Here, we develop a method for determining protein–lipid binding affinities from equilibrium coarse-grained MD simulations using binding saturation curves, designed to mimic experimental protocols. We apply this method to directly obtain affinities for cholesterol binding to multiple sites on a range of membrane proteins and compare our results with free energies obtained from density-based equilibrium methods and with potential of mean force calculations, getting good agreement with respect to the ranking of affinities for different sites. Thus, our binding saturation method provides a robust, high-throughput alternative for determining the relative consequence of individual sites seen in, e.g., cryo-EM derived membrane protein structures surrounded by an array of ancillary lipid densities

LipIDens : simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins

Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities

Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of three new genome-wide association studies (GWAS) and one prior scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of nine promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; $P=2.33x10^{-21}$), rs2523607 at 6p21.33 (HLA-B; $2.40x10^{-10}$), rs79480871 at 2p23.3 (NCOA1; $P=4.23x10^{-8}$), and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; $P=9.98x10^{-13}$ and $P=3.63x10^{-11}$, respectively). These data provide substantial new evidence for genetic susceptibility to this B-cell malignancy, and point towards pathways involved in immune recognition and immune function in the pathogenesis of DLBCL

Flight envelope protection using flap hinge moment measurement

An experimental investigation of the sensitivity of flap hinge moment to airfoil surface contamination was conducted at the University of Illinois at Urbana-Champaign Aerodynamics Research Lab. Tests were conducted on two airfoil models, an NACA 3415 and an NACA 23012, at Reynolds numbers of 1.8 × 106 and 1.0 × 106. The effects of six different simulated contamination configurations on the performance characteristics of both airfoils were tested. These configurations consisted of glaze ice, rime ice, two severities of distributed leading-edge roughness, three-dimensional leading-edge damage, and three-dimensional upper-surface damage. Additionally, the effects of flap deflection and trim tab deflection on the unsteady hinge moment were studied. Results from this study found that large increases in Ch.StDev often occurred at the same angle of attack as Cl,max. By correlating regions of separated flow observed in Cp distributions and fluorescent-oil flow visualizations to Ch,StDev at discrete angles of attack, it was determined that regions of boundary-layer separation were the primary driver for large increases in unsteadiness in the hinge moment. It was also found that the unsteady hinge moment had negligible dependence on trim tab deflection. The response of Ch,StDev was dependent on the stalling characteristics of the airfoil model. Of all of the contamination configurations tested, the two simulated ice cases had the largest effect on the performance of the airfoils. For the distributed leading-edge roughness cases, the larger roughness elements had a larger effect on the performance than the smaller roughness elements, but the Ch,StDev response of both roughness cases were comparable. While the 3D simulated damage cases did not significantly affect the lifting characteristics of either model, the magnitude of the Ch,StDev response of the 3D simulated damage case was comparable to the 2D contamination cases. Additionally, the large increase in Ch,StDev occurred prior to stall due to localized regions of separated flow that resulted from the simulated damage