87 research outputs found
Functional Implications of Structure-Based Sequence Alignment of Proteins in the Extracellular Pectate Lyase Superfamily
Recommended from our members
Protection and fault detection for Lawrence Berkeley Laboratory neutral beam sources
Testing of TFTR neutral beam (NB) sources has begun at the LBL Neutral Beam System Test Facility (NBSTF). Operation at 120 kV, 65 A, 0.5 sec should be achieved soon. Because NB sources spark down frequently during conditioning, the main accelerating (accel) power supply must be interrupted within a few microseconds to avoid degrading the voltage holding capability, or even the damaging, of the NB source. A variety of improper magnitudes and/or ratios of voltages, currents, and times can occur and must be recognized as fault conditions in order to initiate a prompt interruption of the accel power supply. This paper discusses in detail the key signals which must be monitored and the manner in which they are processed in fault detector circuitry for safe operation of LBL NB sources. The paper also reviews the more standard interlocks and protective features recommended for these sources
Recommended from our members
Effect of Axial Loading on Quench Performance in Nb3Sn Magnets
A series of tests has been performed at Lawrence Berkeley National Laboratory (LBNL) and Fermi National Accelerator Laboratory (FNAL) with the goal of assessing the influence of coil axial pre-load on Nb{sub 3}Sn magnet training. The tests involved two subscale Nb{sub 3}Sn magnets: SQ02, a quadrupole magnet fabricated as part of the US LHC Accelerator Research Program (LARP), and SD01, a dipole magnet developed in collaboration between CEA/Saclay and LBNL. Both magnets used similar Nb{sub 3}Sn flat racetrack coils from LBNL Subscale Magnet Program, and implemented an axial support system composed of stainless steel end-plates and aluminum rods. The system was designed to withstand full longitudinal electro-magnetic forces and provide controllable preloads. Quench performances, training, and quench locations have been recorded in various axial loading conditions. Test results are reported
Multiscale Simulations Suggest a Mechanism for the Association of the Dok7 PH Domain with PIP-Containing Membranes
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
Membrane Docking Geometry of GRP1 PH Domain Bound to a Target Lipid Bilayer: An EPR Site-Directed Spin-Labeling and Relaxation Study
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
Insulin signalling and the regulation of glucose and lipid metabolism
The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62568/1/414799a.pd
Recommended from our members
Assembly and Test of SQ01b, a Nb3Sn Quadrupole Magnet for the LHC Accelerator Research Program
The US LHC Accelerator Research Program (LARP) consists of four US laboratories (BNL, FNAL, LBNL, and SLAC) collaborating with CERN to achieve a successful commissioning of the LHC and to develop the next generation of Interaction Region magnets. In 2004, a large aperture Nb{sub 3}Sn racetrack quadrupole magnet (SQ01) has been fabricated and tested at LBNL. The magnet utilized four subscale racetrack coils and was instrumented with strain gauges on the support structure and directly over the coil's turns. SQ01 exhibited training quenches in two of the four coils and reached a peak field in the conductor of 10.4 T at a current of 10.6 kA. After the test, the magnet was disassembled, inspected with pressure indicating films, and reassembled with minor modifications. A second test (SQ01b) was performed at FNAL and included training studies, strain gauge measurements and magnetic measurements. Magnet inspection, test results, and magnetic measurements are reported and discussed, and a comparison between strain gauge measurements and 3D finite element computations is presente
On the controlling factors for the variability of carbon dioxide flux in a heterogeneous urban environment
Local heterogeneity of CO2 sources and sinks is a key factor for the variability of carbon dioxide flux (FC) in urban areas. Information on the urban structure around a site, especially the related emission characteristics, is thus of great importance to the understanding of observed FC. Strong spatially confined sources like major roads inhibit a direct correlation of FC to area-averaged features of the urban structure and may lead to a heavily biased signal. Four years of FC measured at Basel Aeschenplatz, Switzerland, are analysed with respect to the controlling factors and the cause for variability on different time scales. The source area is segregated into equal sectors to address heterogeneous emission patterns. Residential areas to the east are bordered by business areas and major roads to the west, which leads to a fundamental dependence of FC on wind direction. Besides, its diurnal course is explainable with traffic emissions while its annual course follows heating-related combustion emissions. Vegetation fraction is rather considered to be an indicator for urban land use types (residential/business) and the attributable emission characteristics than to be a measure for biological sink effects. Inter-annual variability occurs as a result of anomalies in wind direction patterns or air temperature. Average yearly FC is 16.4 µmol m–2s–1 with slight variations (±0.55 µmol m–2s–1) over the 4 years. It likely originates from an average of 70% traffic and 30% heating-related emissions with significant sectoral differences. As a continuous measure for the emissions of each sector, the expected CO2 flux (eFC) per sector is introduced, leading to an enhanced comparability. Relating sectoral eFC instead of FC to urban surface fractions of buildings and vegetation results in a better agreement (also with data from other studies)
Structure-based multiple alignment of extracellular pectate lyase sequences
International audienc
- …