140 research outputs found

    The benefits of improved technologies in agricultural aviation

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    The results are present for a study of the economic benefits attributed to a variety of potential technological improvements in agricultural aviation. Part 1 gives a general description of the ag-air industry and discusses the information used in the data base to estimate the potential benefits from technological improvements. Part 2 presents the benefit estimates and provides a quantitative basis for the estimates in each area study. Part 3 is a bibliography of references relating to this study

    Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics

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    A molecular simulation pipeline for determining the mode of interaction of pleckstrin homology (PH) domains with phosphatidylinositol phosphate (PIP)-containing lipid bilayers is presented. We evaluate our methodology for the GRP1 PH domain via comparison with structural and biophysical data. Coarse-grained simulations yield a 2D density landscape for PH/membrane interactions alongside residue contact profiles. Predictions of the membrane localization and interactions of 13 PH domains reveal canonical, non-canonical, and dual PIP-binding sites on the proteins. Thus, the PH domains associate with the PIP molecules in the membrane via a highly positively charged loop. Some PH domains exhibit modes of interaction with PIP-containing membranes additional to this canonical binding mode. All 13 PH domains cause a degree of local clustering of PIP molecules upon binding to the membrane. This provides a global picture of PH domain interactions with membranes. The high-throughput approach could be extended to other families of peripheral membrane proteins

    Assembly and Test of a Support Structure for 3.6 m Long Nb3Sn Racetrack Coils”,

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    Abstract-The LHC Accelerator Research Program (LARP) is currently developing 4 m long Nb 3 Sn quadrupole magnets for a possible upgrade of the LHC Interaction Regions (IR). In order to provide a reliable test bed for the fabrication and test of long Nb 3 Sn coils, LARP has started the development of the long racetrack magnet LRS01. The magnet is composed of two 3.6 m long racetrack coils contained in a support structure based on an aluminum shell pre-tensioned with water-pressurized bladders and interference keys. For the phase-one test of the assembly procedure and loading operation, the structure was pre-stressed at room temperature and cooled down to 77 K with instrumented, solid aluminum "dummy coils". Mechanical behavior and stress homogeneity were monitored with strain gauges mounted on the shell and the dummy coils. The dummy coils were replaced with reacted and impregnated Nb 3 Sn coils in a second assembly procedure, followed by cool-down to 4.5 K and powered magnet test. This paper report on the assembly and loading procedures of the support structure as well as the comparison between strain gauge data and 3D model predictions

    Membrane Docking Geometry of GRP1 PH Domain Bound to a Target Lipid Bilayer: An EPR Site-Directed Spin-Labeling and Relaxation Study

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    The second messenger lipid PIP3 (phosphatidylinositol-3,4,5-trisphosphate) is generated by the lipid kinase PI3K (phosphoinositide-3-kinase) in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP3-specific pleckstrin homology (PH) domains to the membrane surface. Despite the broad importance of PIP3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i) PIP3 target lipid that provides specificity and affinity, and (ii) PS facilitator lipid that enhances the PIP3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral diffusion observed for PIP3-bound GRP1 PH domain on supported lipid bilayers

    Multiscale Simulations Suggest a Mechanism for the Association of the Dok7 PH Domain with PIP-Containing Membranes

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    Dok7 is a peripheral membrane protein that is associated with the MuSK receptor tyrosine kinase. Formation of the Dok7/MuSK/membrane complex is required for the activation of MuSK. This is a key step in the complex exchange of signals between neuron and muscle, which lead to neuromuscular junction formation, dysfunction of which is associated with congenital myasthenic syndromes. The Dok7 structure consists of a Pleckstrin Homology (PH) domain and a Phosphotyrosine Binding (PTB) domain. The mechanism of the Dok7 association with the membrane remains largely unknown. Using multi-scale molecular dynamics simulations we have explored the formation of the Dok7 PH/membrane complex. Our simulations indicate that the PH domain of Dok7 associates with membranes containing phosphatidylinositol phosphates (PIPs) via interactions of the β1/β2, β3/β4, and β5/β6 loops, which together form a positively charged surface on the PH domain and interact with the negatively charged headgroups of PIP molecules. The initial encounter of the Dok7 PH domain is followed by formation of additional interactions with the lipid bilayer, and especially with PIP molecules, which stabilizes the Dok7 PH/membrane complex. We have quantified the binding of the PH domain to the model bilayers by calculating a density landscape for protein/membrane interactions. Detailed analysis of the PH/PIP interactions reveal both a canonical and an atypical site to be occupied by the anionic lipid. PH domain binding leads to local clustering of PIP molecules in the bilayer. Association of the Dok7 PH domain with PIP lipids is therefore seen as a key step in localization of Dok7 to the membrane and formation of a complex with MuSK
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