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Sample records for aero vehicles cavs

  1. Aero-Assisted Pre-Stage for Ballistic and Aero-Assisted Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Ustinov, Eugene A.

    2012-01-01

    A concept of an aero-assisted pre-stage is proposed, which enables launch of both ballistic and aero-assisted launch vehicles from conventional runways. The pre-stage can be implemented as a delta-wing with a suitable undercarriage, which is mated with the launch vehicle, so that their flight directions are coaligned. The ample wing area of the pre-stage combined with the thrust of the launch vehicle ensure prompt roll-out and take-off of the stack at airspeeds typical for a conventional jet airliner. The launch vehicle is separated from the pre-stage as soon as safe altitude is achieved, and the desired ascent trajectory is reached. Nominally, the pre-stage is non-powered. As an option, to save the propellant of the launch vehicle, the pre-stage may have its own short-burn propulsion system, whereas the propulsion system of the launch vehicle is activated at the separation point. A general non-dimensional analysis of performance of the pre-stage from roll-out to separation is carried out and applications to existing ballistic launch vehicle and hypothetical aero-assisted vehicles (spaceplanes) are considered.

  2. Vehicle Health Management Communications Requirements for AeroMACS

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Clements, Donna J.; Apaza, Rafael D.

    2012-01-01

    As the development of standards for the aeronautical mobile airport communications system (AeroMACS) progresses, the process of identifying and quantifying appropriate uses for the system is progressing. In addition to defining important elements of AeroMACS standards, indentifying the systems uses impacts AeroMACS bandwidth requirements. Although an initial 59 MHz spectrum allocation for AeroMACS was established in 2007, the allocation may be inadequate; studies have indicated that 100 MHz or more of spectrum may be required to support airport surface communications. Hence additional spectrum allocations have been proposed. Vehicle health management (VHM) systems, which can produce large volumes of vehicle health data, were not considered in the original bandwidth requirements analyses, and are therefore of interest in supporting proposals for additional AeroMACS spectrum. VHM systems are an emerging development in air vehicle safety, and preliminary estimates of the amount of data that will be produced and transmitted off an aircraft, both in flight and on the ground, have been prepared based on estimates of data produced by on-board vehicle health sensors and initial concepts of data processing approaches. This allowed an initial estimate of VHM data transmission requirements for the airport surface. More recently, vehicle-level systems designed to process and analyze VHM data and draw conclusions on the current state of vehicle health have been undergoing testing and evaluation. These systems make use of vehicle system data that is mostly different from VHM data considered previously for airport surface transmission, and produce processed system outputs that will be also need to be archived, thus generating additional data load for AeroMACS. This paper provides an analysis of airport surface data transmission requirements resulting from the vehicle level reasoning systems, within the context of overall VHM data requirements.

  3. Fractional Order Modeling of Atmospheric Turbulence - A More Accurate Modeling Methodology for Aero Vehicles

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2014-01-01

    The presentation covers a recently developed methodology to model atmospheric turbulence as disturbances for aero vehicle gust loads and for controls development like flutter and inlet shock position. The approach models atmospheric turbulence in their natural fractional order form, which provides for more accuracy compared to traditional methods like the Dryden model, especially for high speed vehicle. The presentation provides a historical background on atmospheric turbulence modeling and the approaches utilized for air vehicles. This is followed by the motivation and the methodology utilized to develop the atmospheric turbulence fractional order modeling approach. Some examples covering the application of this method are also provided, followed by concluding remarks.

  4. Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2015-01-01

    Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  5. Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2010-01-01

    Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  6. Propulsion System Dynamic Modeling of the NASA Supersonic Concept Vehicle for AeroPropulsoServoElasticity

    NASA Technical Reports Server (NTRS)

    Kopasakis, George; Connolly, Joseph W.; Seiel, Jonathan

    2016-01-01

    A summary of the propulsion system modeling under NASA's High Speed Project (HSP) AeroPropulsoServoElasticity (APSE) task is provided with a focus on the propulsion system for the low-boom supersonic configuration developed by Lockheed Martin and referred to as the N+2 configuration. This summary includes details on the effort to date to develop computational models for the various propulsion system components. The objective of this paper is to summarize the model development effort in this task, while providing more detail in the modeling areas that have not been previously published. The purpose of the propulsion system modeling and the overall APSE effort is to develop an integrated dynamic vehicle model to conduct appropriate unsteady analysis of supersonic vehicle performance. This integrated APSE system model concept includes the propulsion system model, and the vehicle structural aerodynamics model. The development to date of such a preliminary integrated model will also be summarized in this report

  7. Propulsion System Dynamic Modeling of the NASA Supersonic Concept Vehicle for AeroPropulsoServoElasticity

    NASA Technical Reports Server (NTRS)

    Kopasakis, George; Connolly, Joseph W.; Seidel, Jonathan

    2014-01-01

    A summary of the propulsion system modeling under NASA's High Speed Project (HSP) AeroPropulsoServoElasticity (APSE) task is provided with a focus on the propulsion system for the lowboom supersonic configuration developed by Lockheed Martin and referred to as the N+2 configuration. This summary includes details on the effort to date to develop computational models for the various propulsion system components. The objective of this paper is to summarize the model development effort in this task, while providing more detail in the modeling areas that have not been previously published. The purpose of the propulsion system modeling and the overall APSE effort is to develop an integrated dynamic vehicle model to conduct appropriate unsteady analysis of supersonic vehicle performance. This integrated APSE system model concept includes the propulsion system model, and the vehicle structural-aerodynamics model. The development to date of such a preliminary integrated model will also be summarized in this report.

  8. Quantification of epistemic uncertainty in re-usable launch vehicle aero-elastic design

    NASA Astrophysics Data System (ADS)

    King, Jason M.; Grandhi, Ramana V.; Benanzer, Todd W.

    2012-04-01

    Due to the inherent natural variability of parameters with re-usable launch vehicles, design without consideration of reliability measures may be unreliable and vulnerable to failure. Generally, in preliminary air vehicle design little information is known regarding design variable uncertainties, therefore requiring a technique that can quantify epistemic uncertainties. Evidence theory is employed to accomplish this task resulting in a reliability bound of belief and plausibility. Due to the discontinuous nature of the belief and plausibility function it is necessary to implement a continuous function known as plausibility decision to be used to calculate sensitivities that can be implemented in a gradient-based reliability-based design optimization algorithm. This research develops a new plausibility decision approximation that calculates sensitivities with respect to uncertain variables without introducing extra computational cost or numerical integration. This new metric was demonstrated in a sensitivity analysis of the aero-elastic flutter reliability of a re-usable launch vehicle's wing.

  9. Highly flexible flight vehicle aeroelastic and aero-viscoelastic flutter issues

    NASA Astrophysics Data System (ADS)

    Merrett, Craig G.; Hilton, Harry H.

    2012-11-01

    Aeroelastic and aero-viscoelastic phenomena arising from the high flexibility of modern flight vehicles are examined, and governing relations are formulated and solved. In particular, the time dependent flight velocities associated with maneuvers and with in-plane bending are considered, which necessitate new derivations of the Theodorsen function, unsteady aerodynamic relations and equations of motion. Under these conditions, simple harmonic motion (SHM) is no longer achievable and different flutter criteria based directly on motion stability are presented. The viscoelastic problem is formulated in terms of integral partial differential equations with variable nonlinear coefficients. Their solutions and evaluations are discussed in detail. One interesting departure from linear responses emerged, which indicates flutter in one bending while the other bending mode and the torsional are both stable. A detailed and extended treatment of these subjects may be found in [1].

  10. Propulsion System Dynamic Modeling for the NASA Supersonic Concept Vehicle: AeroPropulsoServoElasticity

    NASA Technical Reports Server (NTRS)

    Kopasakis, George; Connolly, Joseph; Seidel, Jonathan

    2014-01-01

    A summary of the propulsion system modeling under NASA's High Speed Project (HSP) AeroPropulsoServoElasticity (APSE) task is provided with a focus on the propulsion system for the low-boom supersonic configuration developed by Lockheed Martin and referred to as the N+2 configuration. This summary includes details on the effort to date to develop computational models for the various propulsion system components. The objective of this paper is to summarize the model development effort in this task, while providing more detail in the modeling areas that have not been previously published. The purpose of the propulsion system modeling and the overall APSE effort is to develop an integrated dynamic vehicle model to conduct appropriate unsteady analysis of supersonic vehicle performance. This integrated APSE system model concept includes the propulsion system model, and the vehicle structural-aerodynamics model. The development to date of such a preliminary integrated model will also be summarized in this report.propulsion system dynamics, the structural dynamics, and aerodynamics.

  11. Advanced Aero-Propulsive Mid-Lift-to-Drag Ratio Entry Vehicle for Future Exploration Missions

    NASA Technical Reports Server (NTRS)

    Campbell, C. H.; Stosaric, R. R; Cerimele, C. J.; Wong, K. A.; Valle, G. D.; Garcia, J. A.; Melton, J. E.; Munk, M. M.; Blades, E.; Kuruvila, G.; Picetti, D. J.; Hassan, B.; Kniskern, M. W.

    2012-01-01

    vehicle stage return, thus making ideas reality. These paradigm shifts include the technology maturation of advanced flexible thermal protection materials onto mid lift-to-drag ratio entry vehicles, the development of integrated supersonic aero-propulsive maneuvering, and the implementation of advanced asymmetric launch shrouds. These paradigms have significant overlap with launch vehicle stage return already being developed by the Air Force and several commercial space efforts. Completing the realization of these combined paradigms holds the key to a high-performing entry vehicle system capability that fully leverages multiple technology benefits to accomplish NASA's Exploration missions to atmospheric planetary destinations.

  12. Aero-optical effects of an optical seeker with a supersonic jet for hypersonic vehicles in near space.

    PubMed

    Guo, Guangming; Liu, Hong; Zhang, Bin

    2016-06-10

    The aero-optical effects of an optical seeker with a supersonic jet for hypersonic vehicles in near space were investigated by three suites of cases, in which the altitude, angle of attack, and Mach number were varied in a large range. The direct simulation Monte Carlo based on the Boltzmann equation was used for flow computations and the ray-tracing method was used to simulate beam transmission through the nonuniform flow field over the optical window. Both imaging displacement and phase deviation were proposed as evaluation parameters, and along with Strehl ratio they were used to quantitatively evaluate aero-optical effects. The results show that aero-optical effects are quite weak when the altitude is greater than 30 km, the imaging displacement is related to the incident angle of a beam, and it is minimal when the incident angle is approximately 15°. For reducing the aero-optical effects, the optimal location of an aperture should be in the middle of the optical window.

  13. Aero-optical effects of an optical seeker with a supersonic jet for hypersonic vehicles in near space.

    PubMed

    Guo, Guangming; Liu, Hong; Zhang, Bin

    2016-06-10

    The aero-optical effects of an optical seeker with a supersonic jet for hypersonic vehicles in near space were investigated by three suites of cases, in which the altitude, angle of attack, and Mach number were varied in a large range. The direct simulation Monte Carlo based on the Boltzmann equation was used for flow computations and the ray-tracing method was used to simulate beam transmission through the nonuniform flow field over the optical window. Both imaging displacement and phase deviation were proposed as evaluation parameters, and along with Strehl ratio they were used to quantitatively evaluate aero-optical effects. The results show that aero-optical effects are quite weak when the altitude is greater than 30 km, the imaging displacement is related to the incident angle of a beam, and it is minimal when the incident angle is approximately 15°. For reducing the aero-optical effects, the optimal location of an aperture should be in the middle of the optical window. PMID:27409034

  14. Modeling simulation of the thermal radiation for high-speed flight vehicles' aero-optical windows

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Zhang, Liqin; Guo, Mingjiang

    2015-10-01

    When high-speed flight vehicles fly in the atmosphere, they can generate serious aero-optical effect. The optical window temperature rises sharply because of aerodynamic heating. It will form radiation interference that can lead infrared detectors to producing non-uniform radiation backgrounds, decreasing system SNR and detection range. Besides, there exits temperature difference due to uneven heating. Under the thermo-optical and elastic-optical effects, optical windows change into inhomogeneous mediums which influence the ray propagation. In this paper, a model of thermal radiation effect was built by a finite element analysis method. Firstly, the optical window was divided into uniform grids. Then, radiation distribution on the focal planes at different angles of the window's normal line and optical axis was obtained by tracing light rays of each grid. Finally, simulation results indicate that radiation distribution reflects the two directions-the length and width-of temperature distribution, and the change of angle causes the center of radiation distribution to shift to one direction of the image surface under the same window temperature.

  15. Advanced Models for Prediction of High Altitude Aero-Thermal Loads of a Space Re-entry Vehicle

    NASA Astrophysics Data System (ADS)

    Votta, R.; Schettino, A.; Bonfiglioli, A.

    2011-05-01

    The analysis of the rarefaction effects in predicting the main aero-thermal loads of a Space re-entry vehicle is presented. It is well known that the Navier-Stokes equations fail in rarefied regimes and other approaches must be used. In the present paper different configurations have been simulated by using the Direct Simulation Monte Carlo method. Moreover, slip flow boundary conditions have been implemented in a Navier-Stokes code in order to extend the validity of the continuum approach to the transitional flow regime. Finally, bridging formulas for high altitude aerodynamics of winged bodies have been used. Firstly, two simple geometries have been analysed, specifically designed to study the phenomenon of shock wave boundary layer interaction: a hollow cylinder flare, for which some experiments are available; and a blunt-nosed flat plate/flap model designed and tested at the Italian Aerospace Research Centre. The other configurations taken into account are, respectively, an experimental winged re-entry vehicle and a capsule, for which global aerodynamic coefficients and local wall heating have been determined with different approaches. The Navier-Stokes code with slip flow boundary conditions has shown good predicting capabilities compared with experiments in the hollow cylinder flare case; however, for the winged vehicle and capsule cases, the CFD results are not fully satisfactory and the Monte Carlo method remains the most reliable approach, together with the bridging formula, that provides good results for the aerodynamic coefficients.

  16. Advanced Aero-Propulsive Mid-Lift-to-Drag Ratio Entry Vehicle for Future Exploration Missions

    NASA Astrophysics Data System (ADS)

    Campbell, C. H.; Sostaric, R. R.; Cerimele, C. J.; Wong, K. A.; Valle, G. D.; Garcia, J. A.; Melton, J. E.; Munk, M. M.; Blades, E.; Kuruvila, G.; Picetti, D. J.; Hassan, B.; Kniskern, M. W.

    2012-06-01

    Advanced mid-L/D entry vehicles can provide performance advantages significant to mid-term robotic and human missions. Preliminary simulations with new paradigms show transonic Mach vehicle staging possible for retro-propulsion, descent and landing.

  17. Aerodynamic characteristics of generalized bent biconic bodies for aero-assisted, orbital-transfer vehicles

    NASA Technical Reports Server (NTRS)

    Davies, C. B.; Park, C.

    1983-01-01

    A method was developed to generate the surface coordinates of body shapes suitable for aeroassisted, orbital-transfer vehicles (AOTVs) by extending bent biconic geometries. Lift, drag, and longitudinal moments were calculated for the bodies using Newtonian flow theory. These techniques were applied to symmetric and asymmetric aerobraking vehicles, and to an aeromaneuvering vehicle with high L/D. Results for aerobraking applications indicate that a 70 deg, fore half cone angle with a spherically blunted nose, rounded edges, and a slight asymmetry would be appropriate. Moreover, results show that an aeromaneuvering vehicle with L/D 2.0, and with sufficient stability, is feasible.

  18. Hypersonic airbreathing vehicle conceptual design (focus on aero-space plane)

    NASA Technical Reports Server (NTRS)

    Hunt, James L.; Martin, John G.

    1989-01-01

    The airbreathing single stage to orbit (SSTO) vehicle design environment is variable-rich, intricately networked and sensitivity intensive. As such, it represents a tremondous technology challenge. Creating a viable design will require sophisticated configuration/synthesis and the synergistic integration of advanced technologies across the discipline spectrum. In design exercises, reductions in the fuel weight-fraction requirements projected for an orbital vehicle concept can result from improvements in aerodynamics/controls, propulsion efficiencies and trajectory optimization; also, gains in the fuel weight-fraction achievable for such a concept can result from improvements in structural design, heat management techniques, and material properties. As these technology advances take place, closure on a viable vehicle design will be realizable.

  19. Aero-thermo-dynamic analysis of the Spaceliner-7.1 vehicle in high altitude flight

    NASA Astrophysics Data System (ADS)

    Zuppardi, Gennaro; Morsa, Luigi; Sippel, Martin; Schwanekamp, Tobias

    2014-12-01

    SpaceLiner, designed by DLR, is a visionary, extremely fast passenger transportation concept. It consists of two stages: a winged booster, a vehicle. After separation of the two stages, the booster makes a controlled re-entry and returns to the launch site. According to the current project, version 7-1 of SpaceLiner (SpaceLiner-7.1), the vehicle should be brought at an altitude of 75 km and then released, undertaking the descent path. In the perspective that the vehicle of SpaceLiner-7.1 could be brought to altitudes higher than 75 km, e.g. 100 km or above and also for a speculative purpose, in this paper the aerodynamic parameters of the SpaceLiner-7.1 vehicle are calculated in the whole transition regime, from continuum low density to free molecular flows. Computer simulations have been carried out by three codes: two DSMC codes, DS3V in the altitude interval 100-250 km for the evaluation of the global aerodynamic coefficients and DS2V at the altitude of 60 km for the evaluation of the heat flux and pressure distributions along the vehicle nose, and the DLR HOTSOSE code for the evaluation of the global aerodynamic coefficients in continuum, hypersonic flow at the altitude of 44.6 km. The effectiveness of the flaps with deflection angle of -35 deg. was evaluated in the above mentioned altitude interval. The vehicle showed longitudinal stability in the whole altitude interval even with no flap. The global bridging formulae verified to be proper for the evaluation of the aerodynamic coefficients in the altitude interval 80-100 km where the computations cannot be fulfilled either by CFD, because of the failure of the classical equations computing the transport coefficients, or by DSMC because of the requirement of very high computer resources both in terms of the core storage (a high number of simulated molecules is needed) and to the very long processing time.

  20. Attitude Control for an Aero-Vehicle Using Vector Thrusting and Variable Speed Control Moment Gyros

    NASA Technical Reports Server (NTRS)

    Shin, Jong-Yeob; Lim, K. B.; Moerder, D. D.

    2005-01-01

    Stabilization of passively unstable thrust-levitated vehicles can require significant control inputs. Although thrust vectoring is a straightforward choice for realizing these inputs, this may lead to difficulties discussed in the paper. This paper examines supplementing thrust vectoring with Variable-Speed Control Moment Gyroscopes (VSCMGs). The paper describes how to allocate VSCMGs and the vectored thrust mechanism for attitude stabilization in frequency domain and also shows trade-off between vectored thrust and VSCMGs. Using an H2 control synthesis methodology in LMI optimization, a feedback control law is designed for a thrust-levitated research vehicle and is simulated with the full nonlinear model. It is demonstrated that VSCMGs can reduce the use of vectored thrust variation for stabilizing the hovering platform in the presence of strong wind gusts.

  1. Design and performance analysis of an aero-maneuvering orbital-transfer vehicle concept

    NASA Technical Reports Server (NTRS)

    Menees, G. P.

    1985-01-01

    Systems requirements for design-optimized, lateral-turn performance were determined for reusable, space-based applications and low-Earth orbits involving large multiple plane-inclination changes. The aerothermodynamic analysis is the most advanced available for rarefield-hypersonic flow over lifting surfaces at incidence. The effects of leading-edge bluntness, low-density viscous phenomena, and finite-rate flow-field chemistry and surface catalysis are accounted for. The predicted aerothermal heating characteristics are correlated with thermal-control and flight-performance capabilities. The mission payload capacity for delivery, retrieval, and combined operations was determined for round-trip sorties extending to polar orbits. Recommendations are given for future design refinements. The results help to identify technology issues required to develop prototype operational vehicles.

  2. Modeling, Analysis, and Control of a Hypersonic Vehicle with Significant Aero-Thermo-Elastic-Propulsion Interactions: Elastic, Thermal and Mass Uncertainty

    NASA Astrophysics Data System (ADS)

    Khatri, Jaidev

    This thesis examines themodeling, analysis, and control system design issues for scramjet powered hypersonic vehicles. A nonlinear three degrees of freedom longitudinal model which includes aero-propulsion-elasticity effects was used for all analyses. This model is based upon classical compressible flow and Euler-Bernouli structural concepts. Higher fidelity computational fluid dynamics and finite element methods are needed for more precise intermediate and final evaluations. The methods presented within this thesis were shown to be useful for guiding initial control relevant design. The model was used to examine the vehicle's static and dynamic characteristics over the vehicle's trimmable region. The vehicle has significant longitudinal coupling between the fuel equivalency ratio (FER) and the flight path angle (FPA). For control system design, a two-input two-output plant (FER - elevator to speed-FPA) with 11 states (including 3 flexible modes) was used. Velocity, FPA, and pitch were assumed to be available for feedback. Aerodynamic heat modeling and design for the assumed TPS was incorporated to original Bolender's model to study the change in static and dynamic properties. De-centralized control stability, feasibility and limitations issues were dealt with the change in TPS elasticity, mass and physical dimension. The impact of elasticity due to TPS mass, TPS physical dimension as well as prolonged heating was also analyzed to understand performance limitations of de-centralized control designed for nominal model.

  3. AeroMACS System Characterization and Demonstrations

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Apaza, Rafael D.; Dimond, Robert P.

    2013-01-01

    The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past three years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

  4. AeroMACS System Characterization and Demonstrations

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Apaza, Rafael D.; Dimond, Robert P.

    2013-01-01

    This The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past 3 years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

  5. AeroMACS system characterization and demonstrations

    NASA Astrophysics Data System (ADS)

    Kerczewski, R. J.; Apaza, R. D.; Dimond, R. P.

    This The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past three years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

  6. Numerical modeling of separated flows at moderate Reynolds numbers appropriate for turbine blades and unmanned aero vehicles

    NASA Astrophysics Data System (ADS)

    Castiglioni, Giacomo

    Flows over airfoils and blades in rotating machinery, for unmanned and micro-aerial vehicles, wind turbines, and propellers consist of a laminar boundary layer near the leading edge that is often followed by a laminar separation bubble and transition to turbulence further downstream. Typical Reynolds averaged Navier-Stokes turbulence models are inadequate for such flows. Direct numerical simulation is the most reliable, but is also the most computationally expensive alternative. This work assesses the capability of immersed boundary methods and large eddy simulations to reduce the computational requirements for such flows and still provide high quality results. Two-dimensional and three-dimensional simulations of a laminar separation bubble on a NACA-0012 airfoil at Rec = 5x104 and at 5° of incidence have been performed with an immersed boundary code and a commercial code using body fitted grids. Several sub-grid scale models have been implemented in both codes and their performance evaluated. For the two-dimensional simulations with the immersed boundary method the results show good agreement with the direct numerical simulation benchmark data for the pressure coefficient Cp and the friction coefficient Cf, but only when using dissipative numerical schemes. There is evidence that this behavior can be attributed to the ability of dissipative schemes to damp numerical noise coming from the immersed boundary. For the three-dimensional simulations the results show a good prediction of the separation point, but an inaccurate prediction of the reattachment point unless full direct numerical simulation resolution is used. The commercial code shows good agreement with the direct numerical simulation benchmark data in both two and three-dimensional simulations, but the presence of significant, unquantified numerical dissipation prevents a conclusive assessment of the actual prediction capabilities of very coarse large eddy simulations with low order schemes in general

  7. Aero-optimum hovering kinematics.

    PubMed

    Nabawy, Mostafa R A; Crowther, William J

    2015-08-07

    Hovering flight for flapping wing vehicles requires rapid and relatively complex reciprocating movement of a wing relative to a stationary surrounding fluid. This note develops a compact analytical aero-kinematic model that can be used for optimization of flapping wing kinematics against aerodynamic criteria of effectiveness (maximum lift) and efficiency (minimum power for a given amount of lift). It can also be used to make predictions of required flapping frequency for a given geometry and basic aerodynamic parameters. The kinematic treatment is based on a consolidation of an existing formulation that allows explicit derivation of flapping velocity for complex motions whereas the aerodynamic model is based on existing quasi-steady analysis. The combined aero-kinematic model provides novel explicit analytical expressions for both lift and power of a hovering wing in a compact form that enables exploration of a rich kinematic design space. Good agreement is found between model predictions of flapping frequency and observed results for a number of insects and optimal hovering kinematics identified using the model are consistent with results from studies using higher order computational models. For efficient flight, the flapping angle should vary using a triangular profile in time leading to a constant velocity flapping motion, whereas for maximum effectiveness the shape of variation should be sinusoidal. For both cases the wing pitching motion should be rectangular such that pitch change at stroke reversal is as rapid as possible.

  8. Aero-optimum hovering kinematics.

    PubMed

    Nabawy, Mostafa R A; Crowther, William J

    2015-08-01

    Hovering flight for flapping wing vehicles requires rapid and relatively complex reciprocating movement of a wing relative to a stationary surrounding fluid. This note develops a compact analytical aero-kinematic model that can be used for optimization of flapping wing kinematics against aerodynamic criteria of effectiveness (maximum lift) and efficiency (minimum power for a given amount of lift). It can also be used to make predictions of required flapping frequency for a given geometry and basic aerodynamic parameters. The kinematic treatment is based on a consolidation of an existing formulation that allows explicit derivation of flapping velocity for complex motions whereas the aerodynamic model is based on existing quasi-steady analysis. The combined aero-kinematic model provides novel explicit analytical expressions for both lift and power of a hovering wing in a compact form that enables exploration of a rich kinematic design space. Good agreement is found between model predictions of flapping frequency and observed results for a number of insects and optimal hovering kinematics identified using the model are consistent with results from studies using higher order computational models. For efficient flight, the flapping angle should vary using a triangular profile in time leading to a constant velocity flapping motion, whereas for maximum effectiveness the shape of variation should be sinusoidal. For both cases the wing pitching motion should be rectangular such that pitch change at stroke reversal is as rapid as possible. PMID:26248884

  9. Technologies for the National Aero-Space Plane

    NASA Astrophysics Data System (ADS)

    Rausch, Vincent L.; Morris, Charles E. K., Jr.

    1992-08-01

    Technologies for SSTO and hypersonic atmospheric cruise flight being developed in the context of the National Aero-Space Plane (NASP) program are discussed. Emphasis is given to research in aerothermodynamics, propulsion, fuel technology, structures and materials, vehicle management systems, and CVD and instrumentation tools. Brief attention is also given to the X-30 vehicle and to long-term applications of NASP technologies.

  10. Aero-optics measurement system for the AEDC aero-optics test facility

    NASA Astrophysics Data System (ADS)

    Crosswy, F. L.; Havener, A. G.

    1991-02-01

    A fundamental problem associated with hypersonic, endoatmospheric, optically guided vehicles for interception of ballistic reentry vehicles is target image degradation caused by the complex flow field of the intercept vehicle. The image degradation mechanisms are collectively referred to as aero-optics (AO) effects. The AEDC aero-optics measurement system provides the hardware, software, techniques, and expertise for measurement of the fundamental AO effects parameters in a ground test facility. The AO measurement system is presently configured for use in AEDC Tunnel C, a continuous flow hypersonic wind tunnel. AO effects measurements are based upon image analysis, image jitter, and holographic interferometry techniques. The primary purpose of this report is to provide hardware descriptions for the imaging and holography systems and their associated data acquisition and data reduction systems. Information is also provided in the appendixes, which describe several AO measurements technology advances in various stages of development.

  11. Aero dopes and varnishes

    NASA Technical Reports Server (NTRS)

    Britton, H T S

    1927-01-01

    Before proceeding to discuss the preparation of dope solutions, it will be necessary to consider some of the essential properties which should be possessed of a dope film, deposited in and on the surface of an aero fabric. The first is that it should tighten the material and second it should withstand weathering.

  12. Aero-Assisted Spacecraft Missions Using Hypersonic Waverider Aeroshells

    NASA Astrophysics Data System (ADS)

    Knittel, Jeremy

    This work examines the use of high-lift, low drag vehicles which perform orbital transfers within a planet's atmosphere to reduce propulsive requirements. For the foreseeable future, spacecraft mission design will include the objective of limiting the mass of fuel required. One means of accomplishing this is using aerodynamics as a supplemental force, with what is termed an aero-assist maneuver. Further, the use of a lifting body enables a mission designer to explore candidate trajectory types wholly unavailable to non-lifting analogs. Examples include missions to outer planets by way of an aero-gravity assist, aero-assisted plane change, aero-capture, and steady atmospheric periapsis probing missions. Engineering level models are created in order to simulate both atmospheric and extra-atmospheric space flight. Each mission is parameterized using discrete variables which control multiple areas of design. This work combines the areas of hypersonic aerodynamics, re-entry aerothermodynamics, spacecraft orbital mechanics, and vehicle shape optimization. In particular, emphasis is given to the parametric design of vehicles known as "waveriders" which are inversely designed from known shock flowfields. An entirely novel means of generating a class of waveriders known as "starbodies" is presented. A complete analysis is performed of asymmetric starbody forms and compared to a better understood parameterization, "osculating cone" waveriders. This analysis includes characterization of stability behavior, a critical discipline within hypersonic flight. It is shown that asymmetric starbodies have significant stability improvement with only a 10% reduction in the lift-to-drag ratio. By combining the optimization of both the shape of the vehicle and the trajectory it flies, much is learned about the benefit that can be expected from lifting aero-assist missions. While previous studies have conceptually proven the viability, this work provides thorough quantification of the

  13. National aero-space plane: Flight mechanics

    NASA Technical Reports Server (NTRS)

    Mciver, Duncan E.; Morrell, Frederick R.

    1990-01-01

    The current status and plans of the U.S. National Aero-Space Plane (NASP) program are reviewed. The goal of the program is to develop technology for single stage, hypersonic vehicles which use airbreathing propulsion to fly directly to orbit. The program features an X-30 flight research vehicle to explore altitude-speed regimes not amenable to ground testing. The decision to build the X-30 is now scheduled for 1993, with the first flight in the late 1990's. The flight mechanics, controls, flight management, and flight test considerations for the X-30 are discussed.

  14. Aero/structural tailoring of engine blades (AERO/STAEBL)

    NASA Technical Reports Server (NTRS)

    Brown, K. W.

    1988-01-01

    This report describes the Aero/Structural Tailoring of Engine Blades (AERO/STAEBL) program, which is a computer code used to perform engine fan and compressor blade aero/structural numerical optimizations. These optimizations seek a blade design of minimum operating cost that satisfies realistic blade design constraints. This report documents the overall program (i.e., input, optimization procedures, approximate analyses) and also provides a detailed description of the validation test cases.

  15. Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion.

    PubMed

    Drobinskaya, Irina; Neumaier, Felix; Pereverzev, Alexey; Hescheler, Jürgen; Schneider, Toni

    2015-05-01

    Peptide-hormone secretion is partially triggered by Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) and gene inactivation of Zn2+-sensitive Cav2.3-type VGCCs is associated with disturbed glucose homeostasis in mice. Zn2+ has been implicated in pancreatic islet cell crosstalk and recent findings indicate that sudden cessation of Zn2+ supply during hypoglycemia triggers glucagon secretion in rodents. Here we show that diethyldithiocarbamate (DEDTC), a chelating agent for Zn2+ and other group IIB metal ions, differentially affects blood glucose and serum peptide hormone level in wild-type mice and mice lacking the Cav2.3-subunit. Fasting glucose and glucagon level were significantly higher in Cav2.3-deficient compared to wild-type mice, while DEDTC Zn2+-chelation produced a significant and correlated increase of blood glucose and serum glucagon concentration in wild-type but not Cav2.3-deficient mice. Glucose tolerance tests revealed severe glucose intolerance in Zn2+-depleted Cav2.3-deficient but not vehicle-treated Cav2.3-deficient or Zn2+-depleted wildtype mice. Collectively, these findings indicate that Cav2.3 channels are critically involved in the Zn2+-mediated suppression of glucagon secretion during hyperglycemia. Especially under conditions of Zn2+ deficiency, ablation or dysfunction of Cav2.3 channels may lead to severe disturbances in glucose homeostasis. PMID:25603538

  16. AeroSpace Days 2013

    NASA Video Gallery

    At the eighth annual AeroSpace Days, first mom in space, Astronaut AnnaFisher, and Sen. Louise Lucas, interacted with students from Mack BennJr. Elementary School in Suffolk, Va. through NASA’s...

  17. Hypersonic Interplanetary Flight: Aero Gravity Assist

    NASA Technical Reports Server (NTRS)

    Bowers, Al; Banks, Dan; Randolph, Jim

    2006-01-01

    The use of aero-gravity assist during hypersonic interplanetary flights is highlighted. Specifically, the use of large versus small planet for gravity asssist maneuvers, aero-gravity assist trajectories, launch opportunities and planetary waverider performance are addressed.

  18. AeroDyn Theory Manual

    SciTech Connect

    Moriarty, P. J.; Hansen, A. C.

    2005-01-01

    AeroDyn is a set of routines used in conjunction with an aeroelastic simulation code to predict the aerodynamics of horizontal axis wind turbines. These subroutines provide several different models whose theoretical bases are described in this manual. AeroDyn contains two models for calculating the effect of wind turbine wakes: the blade element momentum theory and the generalized dynamic-wake theory. Blade element momentum theory is the classical standard used by many wind turbine designers and generalized dynamic wake theory is a more recent model useful for modeling skewed and unsteady wake dynamics. When using the blade element momentum theory, various corrections are available for the user, such as incorporating the aerodynamic effects of tip losses, hub losses, and skewed wakes. With the generalized dynamic wake, all of these effects are automatically included. Both of these methods are used to calculate the axial induced velocities from the wake in the rotor plane. The user also has the option of calculating the rotational induced velocity. In addition, AeroDyn contains an important model for dynamic stall based on the semi-empirical Beddoes-Leishman model. This model is particularly important for yawed wind turbines. Another aerodynamic model in AeroDyn is a tower shadow model based on potential flow around a cylinder and an expanding wake. Finally, AeroDyn has the ability to read several different formats of wind input, including single-point hub-height wind files or multiple-point turbulent winds.

  19. Structures technology applications for the National AeroSpace Plane

    NASA Technical Reports Server (NTRS)

    Little, T. E.

    1992-01-01

    The National AeroSpace Plane (NASP) presents a unique set of very complex structural problems that challenge our computational capabilities. Complex analyses are required in the conceptual design phase to achieve sufficient accuracy to address the extreme load conditions and to adequately evaluate vehicle weight. The computational capability must be available to perform these analyses in a rapid manner to accommodate the design process.

  20. 2005 PathfinderPlus Aero-Elastic Research Flight

    NASA Technical Reports Server (NTRS)

    Navarro, Robert

    2005-01-01

    This viewgraph presentation describes the 2005 Pathfinder along with an investigation of its aeroelastic responses. The contents include: 1) HALE Class of Vehicles; 2) Aero-elastic Research Flights Overall Objective; 3) General Arrangement; 4) Sensor Locations; 5) NASA Ramp Operations; 6) Lakebed Operations; 7) 1st Flight Data Set; 8) Tool development / data usage; 9) HALE Tool Development & Validation; 10) Building a HALE Foundation; 11) Compelling Needs Drive HALE Efforts; and 12) Team Photo

  1. Aero-thermal analysis of lifting body configurations in hypersonic flow

    NASA Astrophysics Data System (ADS)

    Kumar, Sachin; Mahulikar, Shripad P.

    2016-09-01

    The aero-thermal analysis of a hypersonic vehicle is of fundamental interest for designing its thermal protection system. The aero-thermal environment predictions over several critical regions of the hypothesized lifting body vehicle, including the stagnation region of the nose-cap, cylindrically swept leading edges, fuselage-upper, and fuselage-lower surfaces, are discussed. The drag (Λ=70°) and temperature (Λ=80°) minimized sweepback angles are considered in the configuration design of the two hypothesized lifting body shape hypersonic vehicles. The main aim of the present study is to analyze and compare the aero-thermal characteristics of these two lifting body configurations at same heat capacity. Accordingly, a Computational Fluid Dynamics simulation has been carried out at Mach number (M∞=7), H=35 km altitude with zero Angle of Attack. Finally, the material selection for thermal protection system based on these predictions and current methodology is described.

  2. Considerations for Improving the Capacity and Performance of AeroMACS

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Kamali, Behnam; Apaza, Rafael D.; Wilson, Jeffrey D.; Dimond, Robert P.

    2014-01-01

    The Aeronautical Mobile Airport Communications System (AeroMACS) has progressed from concept through prototype development, testing, and standards development and is now poised for the first operational deployments at nine US airports by the Federal Aviation Administration. These initial deployments will support fixed applications. Mobile applications providing connectivity to and from aircraft and ground-based vehicles on the airport surface will occur at some point in the future. Given that many fixed applications are possible for AeroMACS, it is necessary to now consider whether the existing capacity of AeroMACS will be reached even before the mobile applications are ready to be added, since AeroMACS is constrained by both available bandwidth and transmit power limitations. This paper describes some concepts that may be applied to improve the future capacity of AeroMACS, with a particular emphasis on gains that can be derived from the addition of IEEE 802.16j multihop relays to the AeroMACS standard, where a significant analysis effort has been undertaken.

  3. Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

    PubMed Central

    Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

    2015-01-01

    Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

  4. Regulation of aldosterone secretion by Cav1.3.

    PubMed

    Xie, Catherine B; Shaikh, Lalarukh Haris; Garg, Sumedha; Tanriver, Gizem; Teo, Ada E D; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B; Azizan, Elena A B; Brown, Morris J

    2016-01-01

    Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3. PMID:27098837

  5. Regulation of aldosterone secretion by Cav1.3

    PubMed Central

    Xie, Catherine B.; Haris Shaikh, Lalarukh; Garg, Sumedha; Tanriver, Gizem; Teo, Ada E. D.; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B.; Azizan, Elena A. B.; Brown, Morris J.

    2016-01-01

    Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3. PMID:27098837

  6. Differential zinc permeation and blockade of L-type Ca2+ channel isoforms Cav1.2 and Cav1.3.

    PubMed

    Park, So-Jung; Min, Se-Hong; Kang, Ho-Won; Lee, Jung-Ha

    2015-10-01

    Certain voltage-activated Ca2+ channels have been reported to act as potential zinc entry routes. However, it remains to be determined whether zinc can permeate individual Ca2+ channel isoforms. We expressed recombinant Ca2+ channel isoforms in Xenopus oocytes and attempted to record zinc currents from them using a two-electrode voltage clamp method. We found that, in an extracellular zinc solution, inward currents arising from zinc permeation could be recorded from Xenopus oocytes expressing L-type Cav1.2 or Cav1.3 isoforms, but not from oocytes expressing Cav2.2, Cav2.3, Cav3.1, or Cav3.2. Zinc currents through Cav1.2 and Cav1.3 were blocked by nimodipine, but enhanced by (±)Bay K8644, supporting the finding that zinc can permeate both L-type Cav1.2 and Cav1.3 channel isoforms. We also examined the blocking effects of low concentrations of zinc on Ca2+ currents through the L-type channel isoforms. Low micro-molar zinc potently blocked Ca2+ currents through Cav1.2 and Cav1.3 with different sensitivities (IC50 for Cav1.2 and Cav1.3=18.4 and 34.1 μM) and de-accelerated the activation and inactivation kinetics in a concentration-dependent manner. Notably, mild acidifications of the external zinc solution increased zinc currents through Cav1.2 and Cav1.3, with the increment level for Cav1.3 being greater than that for Cav1.2. In overall, we provide evidence that Cav1.2 and Cav1.3 isoforms are capable of potentially functioning as zinc permeation routes, through which zinc entry can be differentially augmented by mild acidifications.

  7. High-Temperature Adhesives for Thermally Stable Aero-Assist Technologies

    NASA Technical Reports Server (NTRS)

    Eberts, Kenneth; Ou, Runqing

    2013-01-01

    Aero-assist technologies are used to control the velocity of exploration vehicles (EVs) when entering Earth or other planetary atmospheres. Since entry of EVs in planetary atmospheres results in significant heating, thermally stable aero-assist technologies are required to avoid the high heating rates while maintaining low mass. Polymer adhesives are used in aero-assist structures because of the need for high flexibility and good bonding between layers of polymer films or fabrics. However, current polymer adhesives cannot withstand temperatures above 400 C. This innovation utilizes nanotechnology capabilities to address this need, leading to the development of high-temperature adhesives that exhibit high thermal conductivity in addition to increased thermal decomposition temperature. Enhanced thermal conductivity will help to dissipate heat quickly and effectively to avoid temperature rising to harmful levels. This, together with increased thermal decomposition temperature, will enable the adhesives to sustain transient high-temperature conditions.

  8. Exome Array Analysis Identifies CAV1/CAV2 as a Susceptibility Locus for Intraocular Pressure

    PubMed Central

    Chen, Fei; Klein, Alison P.; Klein, Barbara E. K.; Lee, Kristine E.; Truitt, Barbara; Klein, Ronald; Iyengar, Sudha K.; Duggal, Priya

    2015-01-01

    Purpose. Intraocular pressure (IOP) is an important clinical parameter in the evaluation of ocular health. Elevated IOP is a major risk factor for primary open-angle glaucoma (POAG). The goal of this study was to identify rare and less common variants that influence IOP. Methods. We performed an exome array analysis in a subset of 1660 individuals from a population-based cohort, the Beaver Dam Eye Study. Associations with IOP were tested on 45,849 single nucleotide variants and 12,390 autosomal genes across the genome. Results. Intraocular pressure was suggestively associated with novel variants located in FAR2 at 12p11.22 (rs4931170, P = 1.2 × 10−5), in GGA3 at 17q25.1 (rs52809447, P = 6.7 × 10−5), and in PKDREJ at 22q13.31 (rs7291444, P = 7.4 × 10−5). Gene-based analysis found suggestive associations between IOP and the genes HAP1, MTBP, FREM3, and PHF12. We successfully replicated the associations with GAS7 (P = 7.4 × 10−3) for IOP, and also identified a previously reported POAG locus in the CAV1/CAV2 region to be associated with IOP (P = 3.3 × 10−3). This association was confirmed in a meta-analysis with three published genome-wide association studies (Pcombined = 4.0 × 10−11). Conclusions. Our results suggest that novel genetic variants and genes with multiple, less common variants may play a role in the control of IOP. The implication of the caveolin genes, CAV1/CAV2, as a common genetic factor influencing both IOP variations and POAG may provide new insights of the underlying mechanism leading to glaucoma and glaucomatous visual field loss. PMID:25525164

  9. Resolution requirements for aero-optical simulations

    SciTech Connect

    Mani, Ali Wang Meng; Moin, Parviz

    2008-11-10

    Analytical criteria are developed to estimate the error of aero-optical computations due to inadequate spatial resolution of refractive index fields in high Reynolds number flow simulations. The unresolved turbulence structures are assumed to be locally isotropic and at low turbulent Mach number. Based on the Kolmogorov spectrum for the unresolved structures, the computational error of the optical path length is estimated and linked to the resulting error in the computed far-field optical irradiance. It is shown that in the high Reynolds number limit, for a given geometry and Mach number, the spatial resolution required to capture aero-optics within a pre-specified error margin does not scale with Reynolds number. In typical aero-optical applications this resolution requirement is much lower than the resolution required for direct numerical simulation, and therefore, a typical large-eddy simulation can capture the aero-optical effects. The analysis is extended to complex turbulent flow simulations in which non-uniform grid spacings are used to better resolve the local turbulence structures. As a demonstration, the analysis is used to estimate the error of aero-optical computation for an optical beam passing through turbulent wake of flow over a cylinder.

  10. PV-1 IS NEGATIVELY REGULATED BY VEGF IN THE LUNG OF CAV-1, BUT NOT CAV-2, NULL MICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An N-glycosylated 60-kDa PV-1 protein that binds heparin was detected in mouse lung from a single mRNA transcript. In the absence of disulfide bond reduction PV-1 is detected as a dimer or large molecular weight oligomer. In the lung of Cav-1, but not Cav-2, null mice the amount of PV-1 protein is d...

  11. Ontogenic Changes and Differential Localization of T-type Ca2+ Channel Subunits Cav3.1 and Cav3.2 in Mouse Hippocampus and Cerebellum

    PubMed Central

    Aguado, Carolina; García-Madrona, Sebastián; Gil-Minguez, Mercedes; Luján, Rafael

    2016-01-01

    T-type calcium (Ca2+) channels play a central role in regulating membrane excitability in the brain. Although the contributions of T-type current to neuron output is often proposed to reflect a differential distribution of T-type channel subtypes to somato-dendritic compartments, their precise subcellular distributions in central neurons are not fully determined. Using histoblot and high-resolution immunoelectron microscopic techniques, we have investigated the expression, regional distribution and subcellular localization of T-type Cav3.1 and Cav3.2 channel subunits in the adult brain, as well as the ontogeny of expression during postnatal development. Histoblot analysis showed that Cav3.1 and Cav3.2 proteins were widely expressed in the brain, with mostly non-overlapping patterns. Cav3.1 showed the highest expression level in the molecular layer (ml) of the cerebellum (Cb), and Cav3.2 in the hippocampus (Hp) and the ml of Cb. During development, levels of Cav3.1 and Cav3.2 increased with age, although there were marked region- and developmental stage-specific differences in their expression. At the cellular and subcellular level, immunoelectron microscopy showed that labeling for Cav3.1 was present in somato-dendritic domains of hippocampal interneurons and Purkinje cells (PCs), while Cav3.2 was present in somato-dendritic domains of CA1 pyramidal cells, hippocampal interneurons and PCs. Most of the immunoparticles for Cav3.1 and Cav3.2 were either associated with the plasma membrane or the intracellular membranes, with notable differences depending on the compartment. Thus, Cav3.1 was mainly located in the plasma membrane of interneurons, whereas Cav3.2 was mainly located in the plasma membrane of dendritic spines and had a major intracellular distribution in dendritic shafts. In PCs, Cav3.1 and Cav3.2 showed similar distribution patterns. In addition to its main postsynaptic distribution, Cav3.2 but not Cav3.1 was also detected in axon terminals establishing

  12. Ontogenic Changes and Differential Localization of T-type Ca(2+) Channel Subunits Cav3.1 and Cav3.2 in Mouse Hippocampus and Cerebellum.

    PubMed

    Aguado, Carolina; García-Madrona, Sebastián; Gil-Minguez, Mercedes; Luján, Rafael

    2016-01-01

    T-type calcium (Ca(2+)) channels play a central role in regulating membrane excitability in the brain. Although the contributions of T-type current to neuron output is often proposed to reflect a differential distribution of T-type channel subtypes to somato-dendritic compartments, their precise subcellular distributions in central neurons are not fully determined. Using histoblot and high-resolution immunoelectron microscopic techniques, we have investigated the expression, regional distribution and subcellular localization of T-type Cav3.1 and Cav3.2 channel subunits in the adult brain, as well as the ontogeny of expression during postnatal development. Histoblot analysis showed that Cav3.1 and Cav3.2 proteins were widely expressed in the brain, with mostly non-overlapping patterns. Cav3.1 showed the highest expression level in the molecular layer (ml) of the cerebellum (Cb), and Cav3.2 in the hippocampus (Hp) and the ml of Cb. During development, levels of Cav3.1 and Cav3.2 increased with age, although there were marked region- and developmental stage-specific differences in their expression. At the cellular and subcellular level, immunoelectron microscopy showed that labeling for Cav3.1 was present in somato-dendritic domains of hippocampal interneurons and Purkinje cells (PCs), while Cav3.2 was present in somato-dendritic domains of CA1 pyramidal cells, hippocampal interneurons and PCs. Most of the immunoparticles for Cav3.1 and Cav3.2 were either associated with the plasma membrane or the intracellular membranes, with notable differences depending on the compartment. Thus, Cav3.1 was mainly located in the plasma membrane of interneurons, whereas Cav3.2 was mainly located in the plasma membrane of dendritic spines and had a major intracellular distribution in dendritic shafts. In PCs, Cav3.1 and Cav3.2 showed similar distribution patterns. In addition to its main postsynaptic distribution, Cav3.2 but not Cav3.1 was also detected in axon terminals establishing

  13. Ontogenic Changes and Differential Localization of T-type Ca2+ Channel Subunits Cav3.1 and Cav3.2 in Mouse Hippocampus and Cerebellum

    PubMed Central

    Aguado, Carolina; García-Madrona, Sebastián; Gil-Minguez, Mercedes; Luján, Rafael

    2016-01-01

    T-type calcium (Ca2+) channels play a central role in regulating membrane excitability in the brain. Although the contributions of T-type current to neuron output is often proposed to reflect a differential distribution of T-type channel subtypes to somato-dendritic compartments, their precise subcellular distributions in central neurons are not fully determined. Using histoblot and high-resolution immunoelectron microscopic techniques, we have investigated the expression, regional distribution and subcellular localization of T-type Cav3.1 and Cav3.2 channel subunits in the adult brain, as well as the ontogeny of expression during postnatal development. Histoblot analysis showed that Cav3.1 and Cav3.2 proteins were widely expressed in the brain, with mostly non-overlapping patterns. Cav3.1 showed the highest expression level in the molecular layer (ml) of the cerebellum (Cb), and Cav3.2 in the hippocampus (Hp) and the ml of Cb. During development, levels of Cav3.1 and Cav3.2 increased with age, although there were marked region- and developmental stage-specific differences in their expression. At the cellular and subcellular level, immunoelectron microscopy showed that labeling for Cav3.1 was present in somato-dendritic domains of hippocampal interneurons and Purkinje cells (PCs), while Cav3.2 was present in somato-dendritic domains of CA1 pyramidal cells, hippocampal interneurons and PCs. Most of the immunoparticles for Cav3.1 and Cav3.2 were either associated with the plasma membrane or the intracellular membranes, with notable differences depending on the compartment. Thus, Cav3.1 was mainly located in the plasma membrane of interneurons, whereas Cav3.2 was mainly located in the plasma membrane of dendritic spines and had a major intracellular distribution in dendritic shafts. In PCs, Cav3.1 and Cav3.2 showed similar distribution patterns. In addition to its main postsynaptic distribution, Cav3.2 but not Cav3.1 was also detected in axon terminals establishing

  14. NFBD1/MDC1 regulates Cav1 and Cav2 independently of DNA damage and p53.

    PubMed

    Wilson, Kathleen A; Colavito, Sierra A; Schulz, Vincent; Wakefield, Patricia Heffernan; Sessa, William; Tuck, David; Stern, David F

    2011-06-01

    NFBD1/MDC1 is involved in DNA damage checkpoint signaling and DNA repair. NFBD1 binds to the chromatin component γH2AX at sites of DNA damage, causing amplification of ataxia telangiectasia-mutated gene (ATM) pathway signaling and recruitment of DNA repair factors. Residues 508-995 of NFBD1 possess transactivation activity, suggesting a possible role of NFBD1 in transcription. Furthermore, NFBD1 influences p53-mediated transcription in response to adriamycin. We sought to determine the role of NFBD1 in ionizing radiation (IR)-responsive transcription and if NFBD1 influences transcription independently of p53. Using microarray analysis, we identified genes altered upon NFBD1 knockdown. Surprisingly, most NFBD1 regulated genes are regulated in both the absence and presence of IR, thus pointing toward a novel function for NFBD1 outside of the DNA damage response. Furthermore, NFBD1 knockdown regulated genes mostly independent of p53 knockdown. These genes are involved in pathways including focal adhesion signaling, carbohydrate metabolism, and insulin signaling. We found that CAV1 and CAV2 mRNA and protein levels are reduced by both NFBD1 knockdown and knockout independently of IR and p53. NFBD1-depleted cells exhibit some similar phenotypes to Cav1-depleted cells. Furthermore, like Cav1-depletion, NFBD1 shRNA increases Erk phosphorylation. Thus, Cav1 could act as a mediator of the DNA-damage independent effects of NFBD1 in mitogenic signaling.

  15. NFBD1/MDC1 Regulates Cav1 and Cav2 Independently of DNA Damage and p53

    PubMed Central

    Wilson, Kathleen A.; Colavito, Sierra A.; Schulz, Vincent; Wakefield, Patricia Heffernan; Sessa, William; Tuck, David; Stern, David F.

    2014-01-01

    NFBD1/MDC1 is involved in DNA damage checkpoint signaling and DNA repair. NFBD1 binds to the chromatin component γH2AX at sites of DNA damage, causing amplification of ataxia telangiectasia-mutated gene (ATM) pathway signaling and recruitment of DNA repair factors. Residues 508–995 of NFBD1 possess transactivation activity, suggesting a possible role of NFBD1 in transcription. Furthermore, NFBD1 influences p53-mediated transcription in response to adriamycin. We sought to determine the role of NFBD1 in ionizing radiation (IR)–responsive transcription and if NFBD1 influences transcription independently of p53. Using microarray analysis, we identified genes altered upon NFBD1 knockdown. Surprisingly, most NFBD1 regulated genes are regulated in both the absence and presence of IR, thus pointing toward a novel function for NFBD1 outside of the DNA damage response. Furthermore, NFBD1 knockdown regulated genes mostly independent of p53 knockdown. These genes are involved in pathways including focal adhesion signaling, carbohydrate metabolism, and insulin signaling. We found that CAV1 and CAV2 mRNA and protein levels are reduced by both NFBD1 knockdown and knockout independently of IR and p53. NFBD1-depleted cells exhibit some similar phenotypes to Cav1-depleted cells. Furthermore, like Cav1-depletion, NFBD1 shRNA increases Erk phosphorylation. Thus, Cav1 could act as a mediator of the DNA-damage independent effects of NFBD1 in mitogenic signaling. PMID:21551225

  16. Determinants in CaV1 Channels That Regulate the Ca2+ Sensitivity of Bound Calmodulin*

    PubMed Central

    Halling, D. Brent; Georgiou, Dimitra K.; Black, D. J.; Yang, Guojun; Fallon, Jennifer L.; Quiocho, Florante A.; Pedersen, Steen E.; Hamilton, Susan L.

    2009-01-01

    Calmodulin binds to IQ motifs in the α1 subunit of CaV1.1 and CaV1.2, but the affinities of calmodulin for the motif and for Ca2+ are higher when bound to CaV1.2 IQ. The CaV1.1 IQ and CaV1.2 IQ sequences differ by four amino acids. We determined the structure of calmodulin bound to CaV1.1 IQ and compared it with that of calmodulin bound to CaV1.2 IQ. Four methionines in Ca2+-calmodulin form a hydrophobic binding pocket for the peptide, but only one of the four nonconserved amino acids (His-1532 of CaV1.1 and Tyr-1675 of CaV1.2) contacts this calmodulin pocket. However, Tyr-1675 in CaV1.2 contributes only modestly to the higher affinity of this peptide for calmodulin; the other three amino acids in CaV1.2 contribute significantly to the difference in the Ca2+ affinity of the bound calmodulin despite having no direct contact with calmodulin. Those residues appear to allow an interaction with calmodulin with one lobe Ca2+-bound and one lobe Ca2+-free. Our data also provide evidence for lobe-lobe interactions in calmodulin bound to CaV1.2. PMID:19473981

  17. Overview of NASA Glenn Research Center Programs in Aero-Heat Transfer and Future Needs

    NASA Technical Reports Server (NTRS)

    Gaugler, Raymond E.

    2002-01-01

    This presentation concentrates on an overview of the NASA Glenn Research Center and the projects that are supporting Turbine Aero-Heat Transfer Research. The principal areas include the Ultra Efficient Engine Technology (UEET) Project, the Advanced Space Transportation Program (ASTP) Revolutionary Turbine Accelerator (RTA) Turbine Based Combined Cycle (TBCC) project, and the Propulsion & Power Base R&T - Smart Efficient Components (SEC), and Revolutionary Aeropropulsion Concepts (RAC) Projects. In addition, highlights are presented of the turbine aero-heat transfer work currently underway at NASA Glenn, focusing on the use of the Glenn-HT Navier- Stokes code as the vehicle for research in turbulence & transition modeling, grid topology generation, unsteady effects, and conjugate heat transfer.

  18. Aerosciences, Aero-Propulsion and Flight Mechanics Technology Development for NASA's Next Generation Launch Technology Program

    NASA Technical Reports Server (NTRS)

    Cockrell, Charles E., Jr.

    2003-01-01

    The Next Generation Launch Technology (NGLT) program, Vehicle Systems Research and Technology (VSR&T) project is pursuing technology advancements in aerothermodynamics, aeropropulsion and flight mechanics to enable development of future reusable launch vehicle (RLV) systems. The current design trade space includes rocket-propelled, hypersonic airbreathing and hybrid systems in two-stage and single-stage configurations. Aerothermodynamics technologies include experimental and computational databases to evaluate stage separation of two-stage vehicles as well as computational and trajectory simulation tools for this problem. Additionally, advancements in high-fidelity computational tools and measurement techniques are being pursued along with the study of flow physics phenomena, such as boundary-layer transition. Aero-propulsion technology development includes scramjet flowpath development and integration, with a current emphasis on hypervelocity (Mach 10 and above) operation, as well as the study of aero-propulsive interactions and the impact on overall vehicle performance. Flight mechanics technology development is focused on advanced guidance, navigation and control (GN&C) algorithms and adaptive flight control systems for both rocket-propelled and airbreathing vehicles.

  19. Aero-Engine Condition Monitoring Based on Support Vector Machine

    NASA Astrophysics Data System (ADS)

    Zhang, Chunxiao; Wang, Nan

    The maintenance and management of civil aero-engine require advanced monitor approaches to estimate aero-engine performance and health in order to increase life of aero-engine and reduce maintenance costs. In this paper, we adopted support vector machine (SVM) regression approach to monitor an aero-engine health and condition by building monitoring models of main aero-engine performance parameters(EGT, N1, N2 and FF). The accuracy of nonlinear baseline models of performance parameters is tested and the maximum relative error does not exceed ±0.3%, which meets the engineering requirements. The results show that SVM nonlinear regression is an effective method in aero-engine monitoring.

  20. Results of the AEROS satellite program: Summary

    NASA Technical Reports Server (NTRS)

    Lammerzahl, P.; Rawer, K.; Roemer, N.

    1980-01-01

    Published literature reporting aeronomic data collected on two AEROS missions is summarized. The extreme ultraviolet solar radiation and other significant parameters of the thermosphere/ionosphere were investigated. Kinetic pressure, the quantity of atomic nitrogen, and partial densities of helium, oxygen, nitrogen, argon, and atomic nitrogen were determined. The thermal electron population, superthermal energy distribution, plasma density, ion temperature, and composition according to ion types were measured. The chief energy supply in the thermosphere was calculated. Aeronomic calculations showing that variations in the parameters of the ionosphere cannot be correlated with fluctuations of extreme ultraviolet solar radiation were performed. The AEROS data were compared with data from S3-1, ISIS, and AE-C satellites. Models of the thermosphere and ionosphere were developed.

  1. Transient aero-thermal simulations for TMT

    NASA Astrophysics Data System (ADS)

    Vogiatzis, Konstantinos

    2014-08-01

    Aero-thermal simulations are an integral part of the design process for the Thirty Meter Telescope (TMT). These simulations utilize Computational Solid-Fluid Dynamics (CSFD) to estimate wind jitter and blur, dome and mirror seeing, telescope pointing error due to thermal drift, and to predict thermal effects on performance of components such as the primary mirror segments. Design guidance obtained from these simulations is provided to the Telescope, Enclosure, Facilities and Adaptive Optics groups. Computational advances allow for model enhancements and inclusion of phenomena not previously resolved, such as transient effects on wind loading and thermal seeing due to vent operation while observing or long exposure effects, with potentially different flow patterns corresponding to the beginning and end of observation. Accurate knowledge of the Observatory aero-thermal environment will result in developing reliable look-up tables for effective open loop correction of key active optics system elements, and cost efficient operation of the Observatory.

  2. AeroValve Experimental Test Data Final Report

    SciTech Connect

    Noakes, Mark W.

    2014-09-01

    This report documents the collection of experimental test data and presents performance characteristics for the AeroValve brand prototype pneumatic bidirectional solenoid valves tested at the Oak Ridge National Laboratory (ORNL) in July/August 2014 as part of a validation of AeroValve energy efficiency claims. The test stand and control programs were provided by AeroValve. All raw data and processing are included in the report attachments.

  3. PREFACE: 9th International Symposium on Cavitation (CAV2015)

    NASA Astrophysics Data System (ADS)

    Farhat, M.; Müller, A.

    2015-12-01

    It is our pleasure and privilege to welcome all the participants of the 9th International Symposium on Cavitation (CAV2015) to Lausanne. Since its initiation in 1986 in Sendai, Japan, the CAV symposium has grown to become the world's foremost event dedicated to cavitation. Hosted by EPFL (Ecole Polytechnique Fédérale de Lausanne) and staged at the SwissTech Convention Center, CAV2015 is a unique opportunity to exchange with leading scientists and industry experts about the latest advances in theoretical modelling, numerical simulation and experimentation related to cavitation phenomena with a special emphasis on practical applications. The topics covered by CAV2015 include cavitation in ¬fluid machinery and fuel systems, bubble dynamics, cavitation erosion, advanced numerical simulation, sonochemistery, biomedicine and experimental techniques. CAV2015 will also host an exhibition of leading providers of state of the art measurement equipment, including high-speed imaging systems, non-intrusive velocimetry, pressure sensors, as well as numerical solvers. We have accepted over 190 papers, which will be presented in four parallel sessions. The proceedings will appear in the open access Journal of Physics: Conference Series (JPCS), which is part of the IOP Conference Series. All published papers are fully citable and upon publication will be free to download in perpetuity. We would like to thank all the reviewers for their great help during the selection process. We will also propose six plenary speakers to highlight cavitation issues in different fields. Finally, we would like to warmly thank our sponsors for their valuable support and the local Organizing Committee for the efforts in setting up this important event. We look forward to seeing you in Lausanne!

  4. Automated and Cooperative Vehicle Merging at Highway On-Ramps

    DOE PAGES

    Rios-Torres, Jackeline; Malikopoulos, Andreas A.

    2016-08-05

    Recognition of necessities of connected and automated vehicles (CAVs) is gaining momentum. CAVs can improve both transportation network efficiency and safety through control algorithms that can harmonically use all existing information to coordinate the vehicles. This paper addresses the problem of optimally coordinating CAVs at merging roadways to achieve smooth traffic flow without stop-and-go driving. Here we present an optimization framework and an analytical closed-form solution that allows online coordination of vehicles at merging zones. The effectiveness of the efficiency of the proposed solution is validated through a simulation, and it is shown that coordination of vehicles can significantly reducemore » both fuel consumption and travel time.« less

  5. Alternative Splicing Generates a Novel Truncated Cav1.2 Channel in Neonatal Rat Heart*

    PubMed Central

    Liao, Ping; Yu, Dejie; Hu, Zhenyu; Liang, Mui Cheng; Wang, Jue Jin; Yu, Chye Yun; Ng, Gandi; Yong, Tan Fong; Soon, Jia Lin; Chua, Yeow Leng; Soong, Tuck Wah

    2015-01-01

    L-type Cav1.2 Ca2+ channel undergoes extensive alternative splicing, generating functionally different channels. Alternatively spliced Cav1.2 Ca2+ channels have been found to be expressed in a tissue-specific manner or under pathological conditions. To provide a more comprehensive understanding of alternative splicing in Cav1.2 channel, we systematically investigated the splicing patterns in the neonatal and adult rat hearts. The neonatal heart expresses a novel 104-bp exon 33L at the IVS3-4 linker that is generated by the use of an alternative acceptor site. Inclusion of exon 33L causes frameshift and C-terminal truncation. Whole-cell electrophysiological recordings of Cav1.233L channels expressed in HEK 293 cells did not detect any current. However, when co-expressed with wild type Cav1.2 channels, Cav1.233L channels reduced the current density and altered the electrophysiological properties of the wild type Cav1.2 channels. Interestingly, the truncated 3.5-domain Cav1.233L channels also yielded a dominant negative effect on Cav1.3 channels, but not on Cav3.2 channels, suggesting that Cavβ subunits is required for Cav1.233L regulation. A biochemical study provided evidence that Cav1.233L channels enhanced protein degradation of wild type channels via the ubiquitin-proteasome system. Although the physiological significance of the Cav1.233L channels in neonatal heart is still unknown, our report demonstrates the ability of this novel truncated channel to modulate the activity of the functional Cav1.2 channels. Moreover, the human Cav1.2 channel also contains exon 33L that is developmentally regulated in heart. Unexpectedly, human exon 33L has a one-nucleotide insertion that allowed in-frame translation of a full Cav1.2 channel. An electrophysiological study showed that human Cav1.233L channel is a functional channel but conducts Ca2+ ions at a much lower level. PMID:25694430

  6. Expression and Pharmacology of Endogenous Cav Channels in SH-SY5Y Human Neuroblastoma Cells

    PubMed Central

    Sousa, Silmara R.; Vetter, Irina; Ragnarsson, Lotten; Lewis, Richard J.

    2013-01-01

    SH-SY5Y human neuroblastoma cells provide a useful in vitro model to study the mechanisms underlying neurotransmission and nociception. These cells are derived from human sympathetic neuronal tissue and thus, express a number of the Cav channel subtypes essential for regulation of important physiological functions, such as heart contraction and nociception, including the clinically validated pain target Cav2.2. We have detected mRNA transcripts for a range of endogenous expressed subtypes Cav1.3, Cav2.2 (including two Cav1.3, and three Cav2.2 splice variant isoforms) and Cav3.1 in SH-SY5Y cells; as well as Cav auxiliary subunits α2δ1–3, β1, β3, β4, γ1, γ4–5, and γ7. Both high- and low-voltage activated Cav channels generated calcium signals in SH-SY5Y cells. Pharmacological characterisation using ω-conotoxins CVID and MVIIA revealed significantly (∼ 10-fold) higher affinity at human versus rat Cav2.2, while GVIA, which interacts with Cav2.2 through a distinct pharmacophore had similar affinity for both species. CVID, GVIA and MVIIA affinity was higher for SH-SY5Y membranes vs whole cells in the binding assays and functional assays, suggesting auxiliary subunits expressed endogenously in native systems can strongly influence Cav2.2 channels pharmacology. These results may have implications for strategies used to identify therapeutic leads at Cav2.2 channels. PMID:23536870

  7. Aero-optics overview. [laser applications

    NASA Technical Reports Server (NTRS)

    Gilbert, K. G.

    1980-01-01

    Various aero-optical phenomena are discussed with reference to their effect on airborne high energy lasers. Major emphasis is placed on: compressibility effects induced in the surrounding flow field; viscous effects which manifests themselves as aircraft boundary layers or shear layers; inviscid flow fields surrounding the aircraft due to airflow around protuberance such as laser turret assemblies; and shocks, established whenever local flow exceeds Mach one. The significant physical parameters affecting the interaction of a laser beam with a turbulent boundary layer are also described.

  8. High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.

    PubMed

    Wright, N; Jackson, F R; Niezgoda, M; Ellison, J A; Rupprecht, C E; Nel, L H

    2013-08-28

    Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine. PMID:23867013

  9. High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.

    PubMed

    Wright, N; Jackson, F R; Niezgoda, M; Ellison, J A; Rupprecht, C E; Nel, L H

    2013-08-28

    Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine.

  10. Aeronautical Satellite-Assisted Process for Information Exchange Through Network Technologies (Aero-SAPIENT) Conducted

    NASA Technical Reports Server (NTRS)

    Zernic, Michael J.

    2002-01-01

    Broadband satellite communications for aeronautics marries communication and network technologies to address NASA's goals in information technology base research and development, thereby serving the safety and capacity needs of the National Airspace System. This marriage of technology increases the interactivity between airborne vehicles and ground systems. It improves decision-making and efficiency, reduces operation costs, and improves the safety and capacity of the National Airspace System. To this end, a collaborative project called the Aeronautical Satellite Assisted Process for Information Exchange through Network Technologies, or Aero-SAPIENT, was conducted out of Tinker AFB, Oklahoma, during November and December 2000.

  11. Turbofan Volume Dynamics Model for Investigations of Aero-Propulso-Servo-Elastic Effects in a Supersonic Commercial Transport

    NASA Technical Reports Server (NTRS)

    Connolly, Joseph W.; Kopasakis, George; Lemon, Kimberly A.

    2010-01-01

    A turbofan simulation has been developed for use in aero-propulso-servo-elastic coupling studies, on supersonic vehicles. A one-dimensional lumped volume approach is used whereby each component (fan, high-pressure compressor, combustor, etc.) is represented as a single volume using characteristic performance maps and conservation equations for continuity, momentum and energy. The simulation is developed in the MATLAB/SIMULINK (The MathWorks, Inc.) environment in order to facilitate controls development, and ease of integration with a future aero-servo-elastic vehicle model being developed at NASA Langley. The complete simulation demonstrated steady state results that closely match a proposed engine suitable for a supersonic business jet at the cruise condition. Preliminary investigation of the transient simulation revealed expected trends for fuel flow disturbances as well as upstream pressure disturbances. A framework for system identification enables development of linear models for controller design. Utilizing this framework, a transfer function modeling an upstream pressure disturbance s impacts on the engine speed is developed as an illustrative case of the system identification. This work will eventually enable an overall vehicle aero-propulso-servo-elastic model

  12. A near optimal guidance algorithm for aero-assisted orbit transfer

    NASA Astrophysics Data System (ADS)

    Calise, Anthony J.; Bae, Gyoung H.

    The paper presents a near optimal guidance algorithm for aero-assited orbit plane change, based on minimizing the energy loss during the atmospheric portion of the maneuver. The guidance algorithm makes use of recent results obtained from energy state approximations and singular perturbation analysis of optimal heading change for a hypersonic gliding vehicle. This earlier work ignored the terminal constraint on altitude needed to insure that the vehicle exits that atmosphere. Thus, the resulting guidance algorithm was only appropriate for maneuvering reentry vehicle guidance. In the context of singular perturbation theory, a constraint on final altitude gives rise to a difficult terminal boundary layer problem, which cannot be solved in closed form. This paper will demonstrate the near optimality of a predictive/corrective guidance algorithm for the terminal maneuver. Comparisons are made to numerically optimized trajectories for a range or orbit plane angles.

  13. A near optimal guidance algorithm for aero-assisted orbit transfer

    NASA Technical Reports Server (NTRS)

    Calise, Anthony J.; Bae, Gyoung H.

    1988-01-01

    The paper presents a near optimal guidance algorithm for aero-assited orbit plane change, based on minimizing the energy loss during the atmospheric portion of the maneuver. The guidance algorithm makes use of recent results obtained from energy state approximations and singular perturbation analysis of optimal heading change for a hypersonic gliding vehicle. This earlier work ignored the terminal constraint on altitude needed to insure that the vehicle exits that atmosphere. Thus, the resulting guidance algorithm was only appropriate for maneuvering reentry vehicle guidance. In the context of singular perturbation theory, a constraint on final altitude gives rise to a difficult terminal boundary layer problem, which cannot be solved in closed form. This paper will demonstrate the near optimality of a predictive/corrective guidance algorithm for the terminal maneuver. Comparisons are made to numerically optimized trajectories for a range or orbit plane angles.

  14. An overview of aeroelasticity studies for the National Aero-Space Plane

    NASA Technical Reports Server (NTRS)

    Ricketts, Rodney H.; Noll, Thomas E.; Whitlow, Woodrow, Jr.; Huttsell, Lawrence J.

    1993-01-01

    The National Aero-Space Plane (NASP), or X-30, is a single-stage-to-orbit vehicle that is designed to takeoff and land on conventional runways. Research in aeroelasticity was conducted by the NASA and the Wright Laboratory to support the design of a flight vehicle by the national contractor team. This research includes the development of new computational codes for predicting unsteady aerodynamic pressures. In addition, studies were conducted to determine the aerodynamic heating effects on vehicle aeroelasticity and to determine the effects of fuselage flexibility on the stability of the control systems. It also includes the testing of scale models to better understand the aeroelastic behavior of the X-30 and to obtain data for code validation and correlation. This paper presents an overview of the aeroelastic research which has been conducted to support the airframe design.

  15. A proposed university/industry/government cooperative aero educational program

    NASA Technical Reports Server (NTRS)

    Brodsky, R. F.

    1975-01-01

    A program is proposed to provide mutual aid between the beleaguered Aero Engineering degree-granting departments in the United States and United States industry/government. It is proposed that any accrued cost differentials be supported by the latter groups, although all programs proposed will provide true mutual assistance. The program suggested is designed to provide assured industrial experience for Aero faculty members, combat engineering obsolescence for industry engineers, provide assured summer work for Aero undergraduates, encourage industry/government input in curriculum and course planning, and funnel significant laboratory devices into the university system.

  16. Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

    PubMed Central

    Naranjo, David; Wen, Hua; Brehm, Paul

    2015-01-01

    The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

  17. Generic method for aero-optic evaluations.

    PubMed

    Frumker, Eugene; Pade, Offer

    2004-06-01

    The effect of aerodynamic flow on the performance of an airborne optical system is becoming a critical issue in the development of electro-optic systems. A novel technique for aero-optic calculations that is based on commercially available software is presented. The optically relevant data from the computational fluid dynamics results are transformed into an index-of-refraction field and introduced as an input to the optical code. The data do not necessarily have to be presented in analytical form; instead it is introduced in a most general form as a discrete set of values located at a nonuniform grid of points. The modified quadratic Shepard method has been adopted for data interpolation, enabling a simple interface with virtually any software output. Several numerical simulations that demonstrate the technique are presented. PMID:15181800

  18. Generic method for aero-optic evaluations.

    PubMed

    Frumker, Eugene; Pade, Offer

    2004-06-01

    The effect of aerodynamic flow on the performance of an airborne optical system is becoming a critical issue in the development of electro-optic systems. A novel technique for aero-optic calculations that is based on commercially available software is presented. The optically relevant data from the computational fluid dynamics results are transformed into an index-of-refraction field and introduced as an input to the optical code. The data do not necessarily have to be presented in analytical form; instead it is introduced in a most general form as a discrete set of values located at a nonuniform grid of points. The modified quadratic Shepard method has been adopted for data interpolation, enabling a simple interface with virtually any software output. Several numerical simulations that demonstrate the technique are presented.

  19. Aeronautical Mobile Airport Communications System (AeroMACS)

    NASA Technical Reports Server (NTRS)

    Budinger, James M.; Hall, Edward

    2011-01-01

    To help increase the capacity and efficiency of the nation s airports, a secure wideband wireless communications system is proposed for use on the airport surface. This paper provides an overview of the research and development process for the Aeronautical Mobile Airport Communications System (AeroMACS). AeroMACS is based on a specific commercial profile of the Institute of Electrical and Electronics Engineers (IEEE) 802.16 standard known as Wireless Worldwide Interoperability for Microwave Access or WiMAX (WiMax Forum). The paper includes background on the need for global interoperability in air/ground data communications, describes potential AeroMACS applications, addresses allocated frequency spectrum constraints, summarizes the international standardization process, and provides findings and recommendations from the world s first AeroMACS prototype implemented in Cleveland, Ohio, USA.

  20. Venom peptides as a rich source of cav2.2 channel blockers.

    PubMed

    Sousa, Silmara R; Vetter, Irina; Lewis, Richard J

    2013-02-01

    Ca(v)2.2 is a calcium channel subtype localized at nerve terminals, including nociceptive fibers, where it initiates neurotransmitter release. Ca(v)2.2 is an important contributor to synaptic transmission in ascending pain pathways, and is up-regulated in the spinal cord in chronic pain states along with the auxiliary α2δ1 subunit. It is therefore not surprising that toxins that inhibit Ca(v)2.2 are analgesic. Venomous animals, such as cone snails, spiders, snakes, assassin bugs, centipedes and scorpions are rich sources of remarkably potent and selective Ca(v)2.2 inhibitors. However, side effects in humans currently limit their clinical use. Here we review Ca(v)2.2 inhibitors from venoms and their potential as drug leads. PMID:23381143

  1. Aero-optical jitter estimation using higher-order wavefronts

    NASA Astrophysics Data System (ADS)

    Whiteley, Matthew R.; Goorskey, David J.; Drye, Richard

    2013-07-01

    Wavefront measurements from wind tunnel or flight testing of an optical system are affected by jitter sources due to the measurement platform, system vibrations, or aero-mechanical buffeting. Depending on the nature of the testing, the wavefront jitter will be a composite of several effects, one of which is the aero-optical jitter; i.e., the wavefront tilt due to random air density fluctuations. To isolate the aero-optical jitter component from recent testing, we have developed an estimation technique that uses only higher-order wavefront measurements to determine the jitter. By analogy with work done previously with free-stream turbulence, we have developed a minimum mean-square error estimator using higher-order wavefront modes to compute the current-frame tilt components through a linear operation. The estimator is determined from computational fluid dynamics evaluation of aero-optical disturbances, but does not depend on the strength of such disturbances. Applying this technique to turret flight test data, we found aero-optical jitter to be 7.7±0.8 μrad and to scale with (ρ/ρSL)M2 (˜1 μrad in the actual test cases examined). The half-power point of the aero-optical jitter variance was found to be ˜2u∞/Dt and to roll off in temporal frequency with a power law between f and f.

  2. Aero-servo-viscoelasticity theory: Lifting surfaces, plates, velocity transients, flutter, and instability

    NASA Astrophysics Data System (ADS)

    Merrett, Craig G.

    Modern flight vehicles are fabricated from composite materials resulting in flexible structures that behave differently from the more traditional elastic metal structures. Composite materials offer a number of advantages compared to metals, such as improved strength to mass ratio, and intentional material property anisotropy. Flexible aircraft structures date from the Wright brothers' first aircraft with fabric covered wooden frames. The flexibility of the structure was used to warp the lifting surface for flight control, a concept that has reappeared as aircraft morphing. These early structures occasionally exhibited undesirable characteristics during flight such as interactions between the empennage and the aft fuselage, or control problems with the elevators. The research to discover the cause and correction of these undesirable characteristics formed the first foray into the field of aeroelasticity. Aeroelasticity is the intersection and interaction between aerodynamics, elasticity, and inertia or dynamics. Aeroelasticity is well suited for metal aircraft, but requires expansion to improve its applicability to composite vehicles. The first is a change from elasticity to viscoelasticity to more accurately capture the solid mechanics of the composite material. The second change is to include control systems. While the inclusion of control systems in aeroelasticity lead to aero-servo-elasticity, more control possibilities exist for a viscoelastic composite material. As an example, during the lay-up of carbon-epoxy plies, piezoelectric control patches are inserted between different plies to give a variety of control options. The expanded field is called aero-servo-viscoelasticity. The phenomena of interest in aero-servo-viscoelasticity are best classified according to the type of structure considered, either a lifting surface or a panel, and the type of dynamic stability present. For both types of structures, the governing equations are integral

  3. The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells.

    PubMed

    Taylor, Jackson; Pereyra, Andrea; Zhang, Tan; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Kuan, Pei-Fen; Delbono, Osvaldo

    2014-06-23

    Voltage-gated calcium channel (Cav) β subunits are auxiliary subunits to Cavs. Recent reports show Cavβ subunits may enter the nucleus and suggest a role in transcriptional regulation, but the physiological relevance of this localization remains unclear. We sought to define the nuclear function of Cavβ in muscle progenitor cells (MPCs). We found that Cavβ1a is expressed in proliferating MPCs, before expression of the calcium conducting subunit Cav1.1, and enters the nucleus. Loss of Cavβ1a expression impaired MPC expansion in vitro and in vivo and caused widespread changes in global gene expression, including up-regulation of myogenin. Additionally, we found that Cavβ1a localizes to the promoter region of a number of genes, preferentially at noncanonical (NC) E-box sites. Cavβ1a binds to a region of the Myog promoter containing an NC E-box, suggesting a mechanism for inhibition of myogenin gene expression. This work indicates that Cavβ1a acts as a Cav-independent regulator of gene expression in MPCs, and is required for their normal expansion during myogenic development. PMID:24934157

  4. The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells

    PubMed Central

    Taylor, Jackson; Pereyra, Andrea; Zhang, Tan; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Kuan, Pei-Fen

    2014-01-01

    Voltage-gated calcium channel (Cav) β subunits are auxiliary subunits to Cavs. Recent reports show Cavβ subunits may enter the nucleus and suggest a role in transcriptional regulation, but the physiological relevance of this localization remains unclear. We sought to define the nuclear function of Cavβ in muscle progenitor cells (MPCs). We found that Cavβ1a is expressed in proliferating MPCs, before expression of the calcium conducting subunit Cav1.1, and enters the nucleus. Loss of Cavβ1a expression impaired MPC expansion in vitro and in vivo and caused widespread changes in global gene expression, including up-regulation of myogenin. Additionally, we found that Cavβ1a localizes to the promoter region of a number of genes, preferentially at noncanonical (NC) E-box sites. Cavβ1a binds to a region of the Myog promoter containing an NC E-box, suggesting a mechanism for inhibition of myogenin gene expression. This work indicates that Cavβ1a acts as a Cav-independent regulator of gene expression in MPCs, and is required for their normal expansion during myogenic development. PMID:24934157

  5. Towards an Aero-Propulso-Servo-Elasticity Analysis of a Commercial Supersonic Transport

    NASA Technical Reports Server (NTRS)

    Connolly, Joseph W.; Kopasakis, George; Chwalowski, Pawel; Sanetrik, Mark D.; Carlson, Jan-Renee; Silva, Walt A.; McNamara, Jack

    2016-01-01

    This paper covers the development of an aero-propulso-servo-elastic (APSE) model using computational fluid dynamics (CFD) and linear structural deformations. The APSE model provides the integration of the following two previously developed nonlinear dynamic simulations: a variable cycle turbofan engine and an elastic supersonic commercial transport vehicle. The primary focus of this study is to provide a means to include relevant dynamics of a turbomachinery propulsion system into the aeroelastic studies conducted during a vehicle design, which have historically neglected propulsion effects. A high fidelity CFD tool is used here for the integration platform. The elastic vehicle neglecting the propulsion system serves as a comparison of traditional approaches to the APSE results. An overview of the methodology is presented for integrating the propulsion system and elastic vehicle. Static aeroelastic analysis comparisons between the traditional and developed APSE models for a wing tip detection indicate that the propulsion system impact on the vehicle elastic response could increase the detection by approximately ten percent.

  6. T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels.

    PubMed

    Matza, Didi; Badou, Abdallah; Klemic, Kathryn G; Stein, Judith; Govindarajulu, Usha; Nadler, Monica J; Kinet, Jean-Pierre; Peled, Amnon; Shapira, Oz M; Kaczmarek, Leonard K; Flavell, Richard A

    2016-01-01

    The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) α1S subunits during calcium entry after TCR stimulation. High expression levels of Cav1.1 channels were detected in activated T cells. Sequencing and cloning of Cav1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Cav1.1 muscle counterpart. Overexpression studies using cloned T cell Cav1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Cav1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Cav1.1 channels are controlled by TCR signaling. PMID:26815481

  7. T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels

    PubMed Central

    Matza, Didi; Badou, Abdallah; Klemic, Kathryn G.; Stein, Judith; Govindarajulu, Usha; Nadler, Monica J.; Kinet, Jean-Pierre; Peled, Amnon; Shapira, Oz M.; Kaczmarek, Leonard K.; Flavell, Richard A.

    2016-01-01

    The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) α1S subunits during calcium entry after TCR stimulation. High expression levels of Cav1.1 channels were detected in activated T cells. Sequencing and cloning of Cav1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Cav1.1 muscle counterpart. Overexpression studies using cloned T cell Cav1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Cav1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Cav1.1 channels are controlled by TCR signaling. PMID:26815481

  8. Aero-Thermo-Dynamic Mass Analysis

    NASA Astrophysics Data System (ADS)

    Shiba, Kota; Yoshikawa, Genki

    2016-07-01

    Each gas molecule has its own molecular weight, while such a microscopic characteristic is generally inaccessible, and thus, it is measured indirectly through e.g. ionization in conventional mass analysis. Here, we present a novel approach to the direct measurement of molecular weight through a nanoarchitectonic combination of aerodynamics, thermodynamics, and mechanics, transducing microscopic events into macroscopic phenomena. It is confirmed that this approach can provide molecular weight of virtually any gas or vaporizable liquid sample in real-time without ionization. Demonstrations through analytical calculations, numerical simulations, and experiments verify the validity and versatility of the novel mass analysis realized by a simple setup with a flexible object (e.g. with a bare cantilever and even with a business card) placed in a laminar jet. Owing to its unique and simple working principle, this aero-thermo-dynamic mass analysis (AMA) can be integrated into various analytical devices, production lines, and consumer mobile platforms, opening new chapters in aerodynamics, thermodynamics, mechanics, and mass analysis.

  9. Aero-Thermo-Dynamic Mass Analysis.

    PubMed

    Shiba, Kota; Yoshikawa, Genki

    2016-07-14

    Each gas molecule has its own molecular weight, while such a microscopic characteristic is generally inaccessible, and thus, it is measured indirectly through e.g. ionization in conventional mass analysis. Here, we present a novel approach to the direct measurement of molecular weight through a nanoarchitectonic combination of aerodynamics, thermodynamics, and mechanics, transducing microscopic events into macroscopic phenomena. It is confirmed that this approach can provide molecular weight of virtually any gas or vaporizable liquid sample in real-time without ionization. Demonstrations through analytical calculations, numerical simulations, and experiments verify the validity and versatility of the novel mass analysis realized by a simple setup with a flexible object (e.g. with a bare cantilever and even with a business card) placed in a laminar jet. Owing to its unique and simple working principle, this aero-thermo-dynamic mass analysis (AMA) can be integrated into various analytical devices, production lines, and consumer mobile platforms, opening new chapters in aerodynamics, thermodynamics, mechanics, and mass analysis.

  10. Modular Aero-Propulsion System Simulation

    NASA Technical Reports Server (NTRS)

    Parker, Khary I.; Guo, Ten-Huei

    2006-01-01

    The Modular Aero-Propulsion System Simulation (MAPSS) is a graphical simulation environment designed for the development of advanced control algorithms and rapid testing of these algorithms on a generic computational model of a turbofan engine and its control system. MAPSS is a nonlinear, non-real-time simulation comprising a Component Level Model (CLM) module and a Controller-and-Actuator Dynamics (CAD) module. The CLM module simulates the dynamics of engine components at a sampling rate of 2,500 Hz. The controller submodule of the CAD module simulates a digital controller, which has a typical update rate of 50 Hz. The sampling rate for the actuators in the CAD module is the same as that of the CLM. MAPSS provides a graphical user interface that affords easy access to engine-operation, engine-health, and control parameters; is used to enter such input model parameters as power lever angle (PLA), Mach number, and altitude; and can be used to change controller and engine parameters. Output variables are selectable by the user. Output data as well as any changes to constants and other parameters can be saved and reloaded into the GUI later.

  11. Aero-Thermo-Dynamic Mass Analysis.

    PubMed

    Shiba, Kota; Yoshikawa, Genki

    2016-01-01

    Each gas molecule has its own molecular weight, while such a microscopic characteristic is generally inaccessible, and thus, it is measured indirectly through e.g. ionization in conventional mass analysis. Here, we present a novel approach to the direct measurement of molecular weight through a nanoarchitectonic combination of aerodynamics, thermodynamics, and mechanics, transducing microscopic events into macroscopic phenomena. It is confirmed that this approach can provide molecular weight of virtually any gas or vaporizable liquid sample in real-time without ionization. Demonstrations through analytical calculations, numerical simulations, and experiments verify the validity and versatility of the novel mass analysis realized by a simple setup with a flexible object (e.g. with a bare cantilever and even with a business card) placed in a laminar jet. Owing to its unique and simple working principle, this aero-thermo-dynamic mass analysis (AMA) can be integrated into various analytical devices, production lines, and consumer mobile platforms, opening new chapters in aerodynamics, thermodynamics, mechanics, and mass analysis. PMID:27412335

  12. Aero-Thermo-Dynamic Mass Analysis

    PubMed Central

    Shiba, Kota; Yoshikawa, Genki

    2016-01-01

    Each gas molecule has its own molecular weight, while such a microscopic characteristic is generally inaccessible, and thus, it is measured indirectly through e.g. ionization in conventional mass analysis. Here, we present a novel approach to the direct measurement of molecular weight through a nanoarchitectonic combination of aerodynamics, thermodynamics, and mechanics, transducing microscopic events into macroscopic phenomena. It is confirmed that this approach can provide molecular weight of virtually any gas or vaporizable liquid sample in real-time without ionization. Demonstrations through analytical calculations, numerical simulations, and experiments verify the validity and versatility of the novel mass analysis realized by a simple setup with a flexible object (e.g. with a bare cantilever and even with a business card) placed in a laminar jet. Owing to its unique and simple working principle, this aero-thermo-dynamic mass analysis (AMA) can be integrated into various analytical devices, production lines, and consumer mobile platforms, opening new chapters in aerodynamics, thermodynamics, mechanics, and mass analysis. PMID:27412335

  13. Cost effective aero-photogrammetry toys at active volcanoes: On the use of drones, balloons and kites

    NASA Astrophysics Data System (ADS)

    Walter, Thomas R.

    2014-05-01

    The availability of aerial photographs allows spatial mapping of flows and fractures, generation of digital elevation models and other change detection. Therefore aerial photographs significantly improve our understanding of volcanic processes. The common problem is the lack of available data for most volcanoes, and the lack of systematic and chronologic repeat surveys. This work summarizes the current state of knowledge and technical implementations that currently revolutionize the field of aero-photogrammetry. By the use of unmanned vehicles, such as octocopters, helicopters and small airplanes, photo data can be acquired from almost any place at distances up to kilometres from the operator. Moreover, by the use of helium balloons, kites or their hybrid helikites, near field aero-photographs are obtained. In combination with modern stitching procedures and computer vision algorithms, the positioning of the camera and the digital elevation model of the ground can be extracted, and the active volcano and its eruption cloud be imaged from almost any perspective. This field is increasingly gaining flexibility, as lightweight cameras are available from visible, infrared and other spectral bands. Here example data are provided from volcanoes that are difficult to access by regular airplanes, showing the strengths and the limits of these new aero-photogrammetry toys.

  14. Vibration modelling and verifications for whole aero-engine

    NASA Astrophysics Data System (ADS)

    Chen, G.

    2015-08-01

    In this study, a new rotor-ball-bearing-casing coupling dynamic model for a practical aero-engine is established. In the coupling system, the rotor and casing systems are modelled using the finite element method, support systems are modelled as lumped parameter models, nonlinear factors of ball bearings and faults are included, and four types of supports and connection models are defined to model the complex rotor-support-casing coupling system of the aero-engine. A new numerical integral method that combines the Newmark-β method and the improved Newmark-β method (Zhai method) is used to obtain the system responses. Finally, the new model is verified in three ways: (1) modal experiment based on rotor-ball bearing rig, (2) modal experiment based on rotor-ball-bearing-casing rig, and (3) fault simulations for a certain type of missile turbofan aero-engine vibration. The results show that the proposed model can not only simulate the natural vibration characteristics of the whole aero-engine but also effectively perform nonlinear dynamic simulations of a whole aero-engine with faults.

  15. Environmental perspectives of Phragmites australis (Cav.) Trin. Ex. Steudel

    NASA Astrophysics Data System (ADS)

    Srivastava, Jatin; Kalra, Swinder J. S.; Naraian, Ram

    2014-09-01

    Extensive research is being conducted worldwide to find alternative and efficient systems to lessen the impacts of climate change and reduce environmental pollution. The genus Phragmites has proven ability to mitigate the environmental pollution of its surroundings. Common reed ( Phragmites australis (Cav.) Trin. Ex. Steudel), a graminaceous plant of cosmopolitan nature, has been extensively studied especially for the mitigation of environmental contamination. The capability of common reed to grow well at extreme environmental conditions such as elevated CO2 and high temperature is conferred by several factors such as change of carbon trapping mechanism (from C3 to C4 and vice versa), microbial association and biochemical adaptations. P. australis has been a most preferred unique plant system, especially in ecological engineering for improving the quality of wastewater. This paper reviews the current state of knowledge regarding the suitability of Phragmites australis for environmental remediation and summarizes recent advancements in our understanding of this grass.

  16. Influence of altitude on aero-optic imaging deviation.

    PubMed

    Xu, Liang; Cai, Yuanli

    2011-06-20

    Aero-optic imaging deviation is a kind of aero-optic effect. It characterizes the image position displacement on an imaging plane. This paper studies the influence of altitude on aero-optic imaging deviation. The Reynolds-averaged Navier-Stokes solver provided in FLUENT was used for flow computations. The Runge-Kutta method based ray tracing was adopted for optics calculations. The orthogonal array was brought in for the experiment arrangement. Four representative suites of imaging deviations and imaging deviation slopes were obtained in the altitude range of 10-60 km. The results show that as altitude increases, the imaging deviation decreases, and the imaging deviation slope approaches zero from a negative value. PMID:21691360

  17. Aero-Structural Interaction, Analysis, and Shape Sensitivity

    NASA Technical Reports Server (NTRS)

    Newman, James C., III

    1999-01-01

    A multidisciplinary sensitivity analysis technique that has been shown to be independent of step-size selection is examined further. The accuracy of this step-size independent technique, which uses complex variables for determining sensitivity derivatives, has been previously established. The primary focus of this work is to validate the aero-structural analysis procedure currently being used. This validation consists of comparing computed and experimental data obtained for an Aeroelastic Research Wing (ARW-2). Since the aero-structural analysis procedure has the complex variable modifications already included into the software, sensitivity derivatives can automatically be computed. Other than for design purposes, sensitivity derivatives can be used for predicting the solution at nearby conditions. The use of sensitivity derivatives for predicting the aero-structural characteristics of this configuration is demonstrated.

  18. In-flight aero-optics of turrets

    NASA Astrophysics Data System (ADS)

    De Lucca, Nicholas; Gordeyev, Stanislav; Jumper, Eric

    2013-07-01

    Recent in-flight aero-optical measurements from the Airborne Aero-Optics Laboratory are provided, along with instrumentation and experimental set-up. Results of an extensive survey of the aero-optical environment at different viewing angles, for both flat-window and conformal-window turrets at different subsonic and low transonic speeds below M=0.65, are presented, compared and extensively discussed. A comparison between two turret geometries, hemisphere-on-cylinder and hemisphere only, plus the statistical analysis of wavefronts at different viewing angles, are also presented and discussed. Additionally, dynamics of a local shock appearing on the conformal-window turret at transonic Mach number are discussed.

  19. DEMONSTRATION BULLETIN: CAV-OX ULTRAVIOLET OXIDATION PROCESS MAGNUM WATER TECHNOLOGY

    EPA Science Inventory

    The CAV-OX® technology (see Fig- ure 1) destroys organic contaminants, including chlorinated hy- drocarbons, in water. The process uses hydrogen peroxide, hy- drodynamic cavitation, and ultraviolet (UV) radiation to photolyze and oxidize organic compounds present in water at ...

  20. The Cav3.2 T-type calcium channel regulates temporal coding in mouse mechanoreceptors

    PubMed Central

    Wang, Rui; Lewin, Gary R

    2011-01-01

    Abstract In mammals there are three types of low-voltage-activated (LVA) calcium channels, Cav3.1, Cav3.2 and Cav3.3, which all give rise to T-type Ca2+currents. T-type Ca2+currents have long been known to be highly enriched in a sub-population of medium-sized sensory neurones in the dorsal root ganglia (DRG). However, the identity of the T-type-rich sensory neurones has remained controversial and the precise physiological role of the Cav3.2 calcium channel in these sensory neurones has not been directly addressed. Here we show, using Cav3.2−/− mutant mice, that these channels are essential for the normal temporal coding of moving stimuli by specialized skin mechanoreceptors called D-hair receptors. We show that D-hair receptors from Cav3.2−/− fire approximately 50% fewer spikes in response to ramp-and-hold displacement stimuli compared to wild type receptors. The reduced sensitivity of D-hair receptors in Cav3.2−/− mice is chiefly due to an increase in the mechanical threshold and a substantial temporal delay in the onset of high-frequency firing to moving stimuli. We examined the receptive properties of other cutaneous mechanoreceptors and Aδ- and C-fibre nociceptors in Cav3.2−/− mice, but found no alteration in their mechanosensitivity compared to Cav3.2+/+ mice. However, C-fibre nociceptors recorded in Cav3.2−/− mutant mice displayed a small but statistically significant reduction in their spiking rate during noxious heat ramps when compared to C-fibres in control mice. The T-type calcium channel Cav3.2 is thus not only a highly specific marker of D-hair receptors but is also required to maintain their high sensitivity and above all to ensure ultra rapid temporal detection of skin movement. PMID:21486775

  1. Analysis of Cav1.2 and Ryanodine Receptor Clusters in Rat Ventricular Myocytes

    PubMed Central

    Scriven, David R.L.; Asghari, Parisa; Schulson, Meredith N.; Moore, Edwin D.W.

    2010-01-01

    We analyzed the distribution of ryanodine receptor (RyR) and Cav1.2 clusters in adult rat ventricular myocytes using three-dimensional object-based colocalization metrics. We found that ∼75% of the Cav1.2 clusters and 65% of the RyR clusters were within couplons, and both were roughly two and a half times larger than their extradyadic counterparts. Within a couplon, Cav1.2 was concentrated near the center of the underlying RyR cluster and accounted for ∼67% of its size. These data, together with previous findings from binding studies, enable us to estimate that a couplon contains 74 RyR tetramers and 10 copies of the α-subunit of Cav1.2. Extradyadic clusters of RyR contained ∼30 tetramers, whereas the extradyadic Cav1.2 clusters contained, on average, only four channels. Between 80% and 85% of both RyR and Cav1.2 molecules are within couplons. RyR clusters were in the closest proximity, with a median nearest-neighbor distance of 552 nm; comparable values for Cav1.2 clusters and couplons were 619 nm and 735 nm, respectively. Extradyadic RyR clusters were significantly closer together (624 nm) and closer to the couplons (674 nm) than the couplons were to each other. In contrast, the extradyadic clusters of Cav1.2 showed no preferential localization and were broadly distributed. These results provide a wealth of morphometric data that are essential for understanding intracellular Ca2+ regulation and modeling Ca2+ dynamics. PMID:21156134

  2. Protein kinase A modulation of CaV1.4 calcium channels

    PubMed Central

    Sang, Lingjie; Dick, Ivy E.; Yue, David T.

    2016-01-01

    The regulation of L-type Ca2+ channels by protein kinase A (PKA) represents a crucial element within cardiac, skeletal muscle and neurological systems. Although much work has been done to understand this regulation in cardiac CaV1.2 Ca2+ channels, relatively little is known about the closely related CaV1.4 L-type Ca2+ channels, which feature prominently in the visual system. Here we find that CaV1.4 channels are indeed modulated by PKA phosphorylation within the inhibitor of Ca2+-dependent inactivation (ICDI) motif. Phosphorylation of this region promotes the occupancy of calmodulin on the channel, thus increasing channel open probability (PO) and Ca2+-dependent inactivation. Although this interaction seems specific to CaV1.4 channels, introduction of ICDI1.4 to CaV1.3 or CaV1.2 channels endows these channels with a form of PKA modulation, previously unobserved in heterologous systems. Thus, this mechanism may not only play an important role in the visual system but may be generalizable across the L-type channel family. PMID:27456671

  3. Protein kinase A modulation of CaV1.4 calcium channels

    NASA Astrophysics Data System (ADS)

    Sang, Lingjie; Dick, Ivy E.; Yue, David T.

    2016-07-01

    The regulation of L-type Ca2+ channels by protein kinase A (PKA) represents a crucial element within cardiac, skeletal muscle and neurological systems. Although much work has been done to understand this regulation in cardiac CaV1.2 Ca2+ channels, relatively little is known about the closely related CaV1.4 L-type Ca2+ channels, which feature prominently in the visual system. Here we find that CaV1.4 channels are indeed modulated by PKA phosphorylation within the inhibitor of Ca2+-dependent inactivation (ICDI) motif. Phosphorylation of this region promotes the occupancy of calmodulin on the channel, thus increasing channel open probability (PO) and Ca2+-dependent inactivation. Although this interaction seems specific to CaV1.4 channels, introduction of ICDI1.4 to CaV1.3 or CaV1.2 channels endows these channels with a form of PKA modulation, previously unobserved in heterologous systems. Thus, this mechanism may not only play an important role in the visual system but may be generalizable across the L-type channel family.

  4. A Survey on the Coordination of Connected and Automated Vehicles at Intersections and Merging at Highway On-Ramps

    SciTech Connect

    Malikopoulos, Andreas

    2016-01-01

    Connected and automated vehicles (CAVs) have the potential to improve safety by reducing and mitigating traffic accidents. They can also provide opportunities to reduce trans- portation energy consumption and emissions by improving traffic flow. Vehicle communication with traffic structures and traffic lights can allow individual vehicles to optimize their operation and account for unpredictable changes. This paper summarizes the developments and the research trends in coordination with the CAVs that have been reported in the literature to date. Remain- ing challenges and potential future research directions are also discussed.

  5. A survey on the coordination of connected and automated vehicles at intersections and merging at highway on-ramps

    DOE PAGES

    Rios-Torres, Jackeline; Malikopoulos, Andreas A.

    2016-09-07

    Connected and automated vehicles (CAVs) have the potential to improve safety by reducing and mitigating traffic accidents. They can also provide opportunities to reduce transportation energy consumption and emissions by improving traffic flow. Vehicle communication with traffic structures and traffic lights can allow individual vehicles to optimize their operation and account for unpredictable changes. This paper summarizes the developments and the research trends in coordination with the CAVs that have been reported in the literature to date. In conclusion, remaining challenges and potential future research directions are also discussed.

  6. Overview of NASA Power Technologies for Space and Aero Applications

    NASA Technical Reports Server (NTRS)

    Beach, Raymond F.

    2014-01-01

    To achieve the ambitious goals that NASA has outlined for the next decades considerable development of power technology will be necessary. This presentation outlines the development objectives for both the space and aero applications. It further looks at the various power technologies that support these objectives and examines drivers that will be a driving force for future development.

  7. Optimization of Return Trajectories for Orbital Transfer Vehicle between Earth and Moon

    NASA Technical Reports Server (NTRS)

    Funase, Ryu; Tsuda, Yuichi; Kawaguchi, Jun'ichiro

    2007-01-01

    In this paper, optimum trajectories in Earth Transfer Orbit (ETO) for a lunar transportation system are proposed. This paper aims at improving the payload ratio of the reusable orbital transfer vehicle (OTV), which transports the payload from Low Earth Orbit (LEO) to Lunar Low Orbit (LLO) and returns to LEO. In ETO, we discuss ballistic flight using chemical propulsion, multi-impulse flight using electrical propulsion, and aero-assisted flight using aero-brake. The feasibility of the OTV is considered.

  8. The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions.

    PubMed

    Marschallinger, Julia; Sah, Anupam; Schmuckermair, Claudia; Unger, Michael; Rotheneichner, Peter; Kharitonova, Maria; Waclawiczek, Alexander; Gerner, Philipp; Jaksch-Bogensperger, Heidi; Berger, Stefan; Striessnig, Jörg; Singewald, Nicolas; Couillard-Despres, Sebastien; Aigner, Ludwig

    2015-12-01

    L-type voltage gated Ca(2+) channels (LTCCs) are widely expressed within different brain regions including the hippocampus. The isoforms Cav1.2 and Cav1.3 have been shown to be involved in hippocampus-dependent learning and memory, cognitive functions that require proper hippocampal neurogenesis. In vitro, functional LTCCs are expressed on neuronal progenitor cells, where they promote neuronal differentiation. Expression of LTCCs on neural stem and progenitor cells within the neurogenic regions in the adult brain in vivo has not been examined so far, and a contribution of the individual isoforms Cav1.2 and Cav1.3 to adult neurogenesis remained to be clarified. To reveal the role of these channels we first evaluated the expression patterns of Cav1.2 and Cav1.3 in the hippocampal dentate gyrus and the subventricular zone (SVZ) in adult (2- and 3-month old) and middle-aged (15-month old) mice on mRNA and protein levels. We performed immunohistological analysis of hippocampal neurogenesis in adult and middle-aged Cav1.3(-/-) mice and finally addressed the importance of Cav1.3 for hippocampal function by evaluating spatial memory and depression-like behavior in adult Cav1.3(-/-) mice. Our results showed Cav1.2 and Cav1.3 expression at different stages of neuronal differentiation. While Cav1.2 was primarily restricted to mature NeuN(+) granular neurons, Cav1.3 was expressed in Nestin(+) neural stem cells and in mature NeuN(+) granular neurons. Adult and middle-aged Cav1.3(-/-) mice showed severe impairments in dentate gyrus neurogenesis, with significantly smaller dentate gyrus volume, reduced survival of newly generated cells, and reduced neuronal differentiation. Further, Cav1.3(-/-) mice showed impairment in the hippocampus dependent object location memory test, implicating Cav1.3 as an essential element for hippocampus-associated cognitive functions. Thus, modulation of LTCC activities may have a crucial impact on neurogenic responses and cognition, which should be

  9. Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity.

    PubMed

    Jorquera, Gonzalo; Altamirano, Francisco; Contreras-Ferrat, Ariel; Almarza, Gonzalo; Buvinic, Sonja; Jacquemond, Vincent; Jaimovich, Enrique; Casas, Mariana

    2013-03-01

    An important pending question in neuromuscular biology is how skeletal muscle cells decipher the stimulation pattern coming from motoneurons to define their phenotype as slow or fast twitch muscle fibers. We have previously shown that voltage-gated L-type calcium channel (Cav1.1) acts as a voltage sensor for activation of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P₃]-dependent Ca(2+) signals that regulates gene expression. ATP released by muscle cells after electrical stimulation through pannexin-1 channels plays a key role in this process. We show now that stimulation frequency determines both ATP release and Ins(1,4,5)P₃ production in adult skeletal muscle and that Cav1.1 and pannexin-1 colocalize in the transverse tubules. Both ATP release and increased Ins(1,4,5)P₃ was seen in flexor digitorum brevis fibers stimulated with 270 pulses at 20 Hz, but not at 90 Hz. 20 Hz stimulation induced transcriptional changes related to fast-to-slow muscle fiber phenotype transition that required ATP release. Addition of 30 µM ATP to fibers induced the same transcriptional changes observed after 20 Hz stimulation. Myotubes lacking the Cav1.1-α1 subunit released almost no ATP after electrical stimulation, showing that Cav1.1 has a central role in this process. In adult muscle fibers, ATP release and the transcriptional changes produced by 20 Hz stimulation were blocked by both the Cav1.1 antagonist nifedipine (25 µM) and by the Cav1.1 agonist (-)S-BayK 8644 (10 µM). We propose a new role for Cav1.1, independent of its calcium channel activity, in the activation of signaling pathways allowing muscle fibers to decipher the frequency of electrical stimulation and to activate specific transcriptional programs that define their phenotype.

  10. Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity.

    PubMed

    Jorquera, Gonzalo; Altamirano, Francisco; Contreras-Ferrat, Ariel; Almarza, Gonzalo; Buvinic, Sonja; Jacquemond, Vincent; Jaimovich, Enrique; Casas, Mariana

    2013-03-01

    An important pending question in neuromuscular biology is how skeletal muscle cells decipher the stimulation pattern coming from motoneurons to define their phenotype as slow or fast twitch muscle fibers. We have previously shown that voltage-gated L-type calcium channel (Cav1.1) acts as a voltage sensor for activation of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P₃]-dependent Ca(2+) signals that regulates gene expression. ATP released by muscle cells after electrical stimulation through pannexin-1 channels plays a key role in this process. We show now that stimulation frequency determines both ATP release and Ins(1,4,5)P₃ production in adult skeletal muscle and that Cav1.1 and pannexin-1 colocalize in the transverse tubules. Both ATP release and increased Ins(1,4,5)P₃ was seen in flexor digitorum brevis fibers stimulated with 270 pulses at 20 Hz, but not at 90 Hz. 20 Hz stimulation induced transcriptional changes related to fast-to-slow muscle fiber phenotype transition that required ATP release. Addition of 30 µM ATP to fibers induced the same transcriptional changes observed after 20 Hz stimulation. Myotubes lacking the Cav1.1-α1 subunit released almost no ATP after electrical stimulation, showing that Cav1.1 has a central role in this process. In adult muscle fibers, ATP release and the transcriptional changes produced by 20 Hz stimulation were blocked by both the Cav1.1 antagonist nifedipine (25 µM) and by the Cav1.1 agonist (-)S-BayK 8644 (10 µM). We propose a new role for Cav1.1, independent of its calcium channel activity, in the activation of signaling pathways allowing muscle fibers to decipher the frequency of electrical stimulation and to activate specific transcriptional programs that define their phenotype. PMID:23321639

  11. Composition and Antidiarrheal Activity of Bidens odorata Cav.

    PubMed Central

    Zavala-Mendoza, Daniel; Alarcon-Aguilar, Francisco J.; Pérez-Gutierrez, Salud; Escobar-Villanueva, M. Carmen; Zavala-Sánchez, Miguel A.

    2013-01-01

    The antidiarrheal effects of chloroform, methanol, and aqueous extracts of Bidens odorata Cav. were investigated at doses of 200 mg/kg on castor-oil-induced diarrhea. The chloroform extract of B. odorata (CBO) reduced diarrhea by 72.72%. The effect of CBO was evaluated on mice with diarrhea induced by castor oil, MgSO4, arachidonic acid, or prostaglandin E2. CBO inhibited the contraction induced by carbachol chloride on ileum (100 µg/mL) and intestinal transit (200 mg/kg) in Wistar rats. The active fraction of CBO (F4) at doses of 100 mg/kg inhibited the diarrhea induced by castor oil (90.1%) or arachidonic acid (72.9%) but did not inhibit the diarrhea induced by PGE2. The active fraction of F4 (FR5) only was tested on diarrhea induced with castor oil and inhibited this diarrhea by 92.1%. The compositions of F4 and FR5 were determined by GC-MS, and oleic, palmitic, linoleic, and stearic acids were found. F4 and a mixture of the four fatty acids inhibited diarrhea at doses of 100 mg/kg (90.1% and 70.6%, resp.). The results of this study show that B. odorata has antidiarrheal effects, as is claimed by folk medicine, and could possibly be used for the production of a phytomedicine. PMID:24282432

  12. Physicochemical properties of tamarillo (Solanum betaceum Cav.) hydrocolloid fractions.

    PubMed

    Gannasin, Sri Puvanesvari; Adzahan, Noranizan Mohd; Hamzah, Mohd Yusof; Mustafa, Shuhaimi; Muhammad, Kharidah

    2015-09-01

    Tamarillo (Solanum betaceum Cav.) is an underutilised fruit in Malaysia. The fruit, however, contains good proportions of soluble fibre, protein, starch, anthocyanins and carotenoids. Amongst the fruits, only tamarillo mesocarp contains both polar (anthocyanins) and non-polar (carotenoids) pigments. The ability to retain both polar and non-polar pigments in the mesocarp could be related to the unique properties of its hydrocolloids. To understand the pigment-hydrocolloid interaction in the fruit, information on the physicochemical characteristics of the hydrocolloids is required. Therefore, hydrocolloids from the anthocyanin-rich seed mucilage fraction of the tamarillo and its carotenoid-rich pulp fraction were extracted and characterised. Water and 1% citric acid were used to extract the seed mucilage hydrocolloid while 72% ethanol and 20mM HEPES buffer were used for pulp hydrocolloid extraction. Seed mucilage hydrocolloid was primarily composed of arabinogalactan protein-associated pectin whereas pulp hydrocolloid was composed of hemicellulosic polysaccharides with some naturally interacting proteins and neutral polysaccharides. PMID:25842340

  13. Nonlinear Dynamic Modeling of a Supersonic Commercial Transport Turbo-Machinery Propulsion System for Aero-Propulso-Servo-Elasticity Research

    NASA Technical Reports Server (NTRS)

    Connolly, Joseph W.; Kopasakis, George; Carlson, Jan-Renee; Woolwine, Kyle

    2015-01-01

    This paper covers the development of an integrated nonlinear dynamic model for a variable cycle turbofan engine, supersonic inlet, and convergent-divergent nozzle that can be integrated with an aeroelastic vehicle model to create an overall Aero-Propulso-Servo-Elastic (APSE) modeling tool. The primary focus of this study is to provide a means to capture relevant thrust dynamics of a full supersonic propulsion system by using relatively simple quasi-one dimensional computational fluid dynamics (CFD) methods that will allow for accurate control algorithm development and capture the key aspects of the thrust to feed into an APSE model. Previously, propulsion system component models have been developed and are used for this study of the fully integrated propulsion system. An overview of the methodology is presented for the modeling of each propulsion component, with a focus on its associated coupling for the overall model. To conduct APSE studies the de- scribed dynamic propulsion system model is integrated into a high fidelity CFD model of the full vehicle capable of conducting aero-elastic studies. Dynamic thrust analysis for the quasi-one dimensional dynamic propulsion system model is presented along with an initial three dimensional flow field model of the engine integrated into a supersonic commercial transport.

  14. Nonlinear Dynamic Modeling of a Supersonic Commercial Transport Turbo-Machinery Propulsion System for Aero-Propulso-Servo-Elasticity Research

    NASA Technical Reports Server (NTRS)

    Connolly, Joe; Carlson, Jan-Renee; Kopasakis, George; Woolwine, Kyle

    2015-01-01

    This paper covers the development of an integrated nonlinear dynamic model for a variable cycle turbofan engine, supersonic inlet, and convergent-divergent nozzle that can be integrated with an aeroelastic vehicle model to create an overall Aero-Propulso-Servo-Elastic (APSE) modeling tool. The primary focus of this study is to provide a means to capture relevant thrust dynamics of a full supersonic propulsion system by using relatively simple quasi-one dimensional computational fluid dynamics (CFD) methods that will allow for accurate control algorithm development and capture the key aspects of the thrust to feed into an APSE model. Previously, propulsion system component models have been developed and are used for this study of the fully integrated propulsion system. An overview of the methodology is presented for the modeling of each propulsion component, with a focus on its associated coupling for the overall model. To conduct APSE studies the described dynamic propulsion system model is integrated into a high fidelity CFD model of the full vehicle capable of conducting aero-elastic studies. Dynamic thrust analysis for the quasi-one dimensional dynamic propulsion system model is presented along with an initial three dimensional flow field model of the engine integrated into a supersonic commercial transport.

  15. Human-Vehicle Interface for Semi-Autonomous Operation of Uninhabited Aero Vehicles

    NASA Technical Reports Server (NTRS)

    Jones, Henry L.; Frew, Eric W.; Woodley, Bruce R.; Rock, Stephen M.

    2001-01-01

    The robustness of autonomous robotic systems to unanticipated circumstances is typically insufficient for use in the field. The many skills of human user often fill this gap in robotic capability. To incorporate the human into the system, a useful interaction between man and machine must exist. This interaction should enable useful communication to be exchanged in a natural way between human and robot on a variety of levels. This report describes the current human-robot interaction for the Stanford HUMMINGBIRD autonomous helicopter. In particular, the report discusses the elements of the system that enable multiple levels of communication. An intelligent system agent manages the different inputs given to the helicopter. An advanced user interface gives the user and helicopter a method for exchanging useful information. Using this human-robot interaction, the HUMMINGBIRD has carried out various autonomous search, tracking, and retrieval missions.

  16. National Aero-Space Plane (NASP) program

    NASA Technical Reports Server (NTRS)

    Tank, Ming H.

    1991-01-01

    A program to develop the technology for reusable airbreathing hypersonic/transatmospheric vehicles is addressed. Information on the following topics is presented in viewgraph form: (1) the National Aerospace Plane (NASP) program schedule; (2) the NASP program organization; (3) competitive strategy; (4) propulsion options; (5) wind tunnel data available for NASP; (6) ground track of envelope expansion; and (7) altitude vs. Mach number. A NASP/Space Shuttle comparison, NASP configuration matrix, and the propulsion concept of a high speed scramjet are also briefly addressed.

  17. Sensitivity Analysis for Coupled Aero-structural Systems

    NASA Technical Reports Server (NTRS)

    Giunta, Anthony A.

    1999-01-01

    A novel method has been developed for calculating gradients of aerodynamic force and moment coefficients for an aeroelastic aircraft model. This method uses the Global Sensitivity Equations (GSE) to account for the aero-structural coupling, and a reduced-order modal analysis approach to condense the coupling bandwidth between the aerodynamic and structural models. Parallel computing is applied to reduce the computational expense of the numerous high fidelity aerodynamic analyses needed for the coupled aero-structural system. Good agreement is obtained between aerodynamic force and moment gradients computed with the GSE/modal analysis approach and the same quantities computed using brute-force, computationally expensive, finite difference approximations. A comparison between the computational expense of the GSE/modal analysis method and a pure finite difference approach is presented. These results show that the GSE/modal analysis approach is the more computationally efficient technique if sensitivity analysis is to be performed for two or more aircraft design parameters.

  18. Advanced selective plating with AeroNikl solutions

    NASA Astrophysics Data System (ADS)

    Smith, Gary W.

    1989-03-01

    This paper presents the latest technical data on nickel deposits on complex areas of engine components, obtained by the selective (brush) plating of nickel sulfamate solutions (AeroNikl-250, -400, and -575). Current applications for these coatings, and advancements in application technology, are described. Particular attention is given to a controlled velocity gap plating process developed for high-speed selective deposition in bores.

  19. Aerosol Comparisons Between Observations and Models: AeroCom and ABC

    NASA Technical Reports Server (NTRS)

    Chin, Mian; Schulz, Michael; Kinne, Stefan

    2011-01-01

    I will represent the AeroCom community to the Atmospheric Brown Cloud (ABC) workshop. I will summarize the activities and results from AeroCom Phase I activities in the past 8 years and introduce the new results and activities in the current AeroCom Phase II. We hope to coordinate some activities with the ABC community to share model output and data access for model evaluations, comparisons, and assessment.

  20. Improvement of the AeroClipper system for cyclones monitoring

    NASA Astrophysics Data System (ADS)

    Vargas, André; Philippe, Duvel Jean

    2016-07-01

    The AeroClipper developed by the French space agency (Centre National d'Études Spatiales, CNES) is a quasi-lagrangian device drifting with surface wind at about 20-30m above the ocean surface. It is a new and original device for real-time and continuous observation of air-sea surface parameters in open ocean remote regions. This device enables the sampling of the variability of surface parameters in particular under convective systems toward which it is attracted. The AeroClipper is therefore an ideal instrument to monitor Tropical Cyclones (TCs) in which they are likely to converge and provide original observations to evaluate and improve our current understanding and diagnostics of TCs as well as their representation in numerical models. In 2008, the AeroClipper demonstrates its capability to be captured by an Ocean Indian cyclone, as two models have converged, without damages, in the eye of Dora cyclone during the 2008 VASCO campaign. This paper will present the improvements of this balloon system for the international project 'the Year of Maritime Continent'.

  1. Minimum energy-loss guidance for aero-assisted orbital plane change

    NASA Technical Reports Server (NTRS)

    Hull, D. G.; Giltner, J. M.; Speyer, J. L.; Mapar, J.

    1984-01-01

    Minimum energy-loss guidance for the aero-assisted plane change of an orbiting vehicle is developed and applied to the plane change of a circular orbit. First, trajectories which minimize the fuel required to change the orbital plane are computed for a realistic vehicle. From these trajectories, it is observed that the fuel weight is minimized if the velocity at exit from the atmosphere is maximized. Next, for the atmospheric turn, approximate optimal controls (angle of attack and bank angle) which maximize the exit velocity are derived. Finally, the minimum-fuel problem is resolved using optimal guidance for the atmospheric part of the trajectory, and the optimization problem reduces to a one-dimensional parameter minimization. Successful plane changes up to 40 deg are demonstrated. Optimal guidance requires up to 14 percent more fuel than the 'true' optimum but only 50 percent of the fuel required by the single-impulse maneuver. Finally, the guidance law developed here is implementable because only algebraic manipulations are required.

  2. Cacna1c (Cav1.2) Modulates Electroencephalographic Rhythm and Rapid Eye Movement Sleep Recovery

    PubMed Central

    Kumar, Deependra; Dedic, Nina; Flachskamm, Cornelia; Voulé, Stephanie; Deussing, Jan M.; Kimura, Mayumi

    2015-01-01

    Study Objectives: The CACNA1C gene encodes the alpha 1C (α1C) subunit of the Cav1.2 voltage-dependent L-type calcium channel (LTCC). Some of the other voltage-dependent calcium channels, e.g., P-/Q-type, Cav2.1; N-type, Cav2.2; E-/R-type, Cav2.3; and T-type, Cav3.3 have been implicated in sleep modulation. However, the contribution of LTCCs to sleep remains largely unknown. Based on recent genome-wide association studies, CACNA1C emerged as one of potential candidate genes associated with both sleep and psychiatric disorders. Indeed, most patients with mental illnesses have sleep problems and vice versa. Design: To investigate an impact of Cav1.2 on sleep-wake behavior and electroencephalogram (EEG) activity, polysomnography was performed in heterozygous Cacna1c (HET) knockout mice and their wild-type (WT) littermates under baseline and challenging conditions (acute sleep deprivation and restraint stress). Measurements and Results: HET mice displayed significantly lower EEG spectral power than WT mice across high frequency ranges (beta to gamma) during wake and rapid eye movement (REM) sleep. Although HET mice spent slightly more time asleep in the dark period, daily amounts of sleep did not differ between the two genotypes. However, recovery sleep after exposure to both types of challenging stress conditions differed markedly; HET mice exhibited reduced REM sleep recovery responses compared to WT mice. Conclusions: These results suggest the involvement of Cacna1c (Cav1.2) in fast electroencephalogram oscillations and REM sleep regulatory processes. Lower spectral gamma activity, slightly increased sleep demands, and altered REM sleep responses found in heterozygous Cacna1c knockout mice may rather resemble a sleep phenotype observed in schizophrenia patients. Citation: Kumar D, Dedic N, FLachskamm C, Voulé S, Deussing JM, Kimura M. Cacna1c (Cav1.2) modulates electroencephalographic rhythm and rapid eye movement sleep recovery. SLEEP 2015;38(9):1371–1380. PMID

  3. Purkinje cell-specific ablation of Cav2.1 channels is sufficient to cause cerebellar ataxia in mice.

    PubMed

    Todorov, Boyan; Kros, Lieke; Shyti, Reinald; Plak, Petra; Haasdijk, Elize D; Raike, Robert S; Frants, Rune R; Hess, Ellen J; Hoebeek, Freek E; De Zeeuw, Chris I; van den Maagdenberg, Arn M J M

    2012-03-01

    The Cacna1a gene encodes the α(1A) subunit of voltage-gated Ca(V)2.1 Ca(2+) channels that are involved in neurotransmission at central synapses. Ca(V)2.1-α(1)-knockout (α1KO) mice, which lack Ca(V)2.1 channels in all neurons, have a very severe phenotype of cerebellar ataxia and dystonia, and usually die around postnatal day 20. This early lethality, combined with the wide expression of Ca(V)2.1 channels throughout the cerebellar cortex and nuclei, prohibited determination of the contribution of particular cerebellar cell types to the development of the severe neurobiological phenotype in Cacna1a mutant mice. Here, we crossed conditional Cacna1a mice with transgenic mice expressing Cre recombinase, driven by the Purkinje cell-specific Pcp2 promoter, to specifically ablate the Ca(V)2.1-α(1A) subunit and thereby Ca(V)2.1 channels in Purkinje cells. Purkinje cell Ca(V)2.1-α(1A)-knockout (PCα1KO) mice aged without difficulties, rescuing the lethal phenotype seen in α1KO mice. PCα1KO mice exhibited cerebellar ataxia starting around P12, much earlier than the first signs of progressive Purkinje cell loss, which appears in these mice between P30 and P45. Secondary cell loss was observed in the granular and molecular layers of the cerebellum and the volume of all individual cerebellar nuclei was reduced. In this mouse model with a cell type-specific ablation of Ca(V)2.1 channels, we show that ablation of Ca(V)2.1 channels restricted to Purkinje cells is sufficient to cause cerebellar ataxia. We demonstrate that spatial ablation of Ca(V)2.1 channels may help in unraveling mechanisms of human disease.

  4. Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology

    PubMed Central

    Stanika, Ruslan; Campiglio, Marta; Pinggera, Alexandra; Lee, Amy; Striessnig, Jörg; Flucher, Bernhard E.; Obermair, Gerald J.

    2016-01-01

    Dendritic spines are the postsynaptic compartments of glutamatergic synapses in the brain. Their number and shape are subject to change in synaptic plasticity and neurological disorders including autism spectrum disorders and Parkinson’s disease. The L-type calcium channel CaV1.3 constitutes an important calcium entry pathway implicated in the regulation of spine morphology. Here we investigated the importance of full-length CaV1.3L and two C-terminally truncated splice variants (CaV1.342A and CaV1.343S) and their modulation by densin-180 and shank1b for the morphology of dendritic spines of cultured hippocampal neurons. Live-cell immunofluorescence and super-resolution microscopy of epitope-tagged CaV1.3L revealed its localization at the base-, neck-, and head-region of dendritic spines. Expression of the short splice variants or deletion of the C-terminal PDZ-binding motif in CaV1.3L induced aberrant dendritic spine elongation. Similar morphological alterations were induced by co-expression of densin-180 or shank1b with CaV1.3L and correlated with increased CaV1.3 currents and dendritic calcium signals in transfected neurons. Together, our findings suggest a key role of CaV1.3 in regulating dendritic spine structure. Under physiological conditions it may contribute to the structural plasticity of glutamatergic synapses. Conversely, altered regulation of CaV1.3 channels may provide an important mechanism in the development of postsynaptic aberrations associated with neurodegenerative disorders. PMID:27708393

  5. Divergent control of Cav-1 expression in non-cancerous Li-Fraumeni syndrome and human cancer cell lines

    PubMed Central

    Sherif, Zaki A.; Sultan, Ahmed S.

    2013-01-01

    Li-Fraumeni syndrome (LFS) is primarily characterized by development of tumors exhibiting germ-line mutations in the p53 gene. Cell lines developed from patients of a LFS family have decreased p53 activity as evidenced by the absence of apoptosis upon etoposide treatment. To test our hypothesis that changes in gene expression beyond p53 per se are contributing to the development of tumors, we compared gene expression in non-cancerous skin fibroblasts of LFS-affected (p53 heterozygous) vs. non-affected (p53 wild-type homozygous) family members. Expression analysis showed that several genes were differentially regulated in the p53 homozygous and heterozygous cell lines. We were particularly intrigued by the decreased expression (~88%) of a putative tumor-suppressor protein, caveolin-1 (Cav-1), in the p53-mutant cells. Decreased expression of Cav-1 was also seen in both p53-knockout and p21-knockout HTC116 cells suggesting that p53 controls Cav-1 expression through p21 and leading to the speculation that p53, Cav-1 and p21 may be part of a positive auto-regulatory feedback loop. The direct relationship between p53 and Cav-1 was also tested with HeLa cells (containing inactive p53), which expressed a significantly lower Cav-1 protein. A panel of nonfunctional and p53-deficient colon and epithelial breast cancer cell lines showed undetectable expression of Cav-1 supporting the role of p53 in the control of Cav-1. However, in two aggressively metastasizing breast cancer cell lines, Cav-1 was strongly expressed suggesting a possible role in tumor metastasis. Thus, there is a divergent control of Cav-1 expression as evidenced in non-cancerous Li-Fraumeni syndrome and some aggressive human cancer cell lines. PMID:23114650

  6. Dynamic modal analysis of transonic Airborne Aero-Optics Laboratory conformal window flight-test aero-optics

    NASA Astrophysics Data System (ADS)

    Goorskey, David J.; Drye, Richard; Whiteley, Matthew R.

    2013-07-01

    We discuss spatial-temporal characterizations of recent in-flight Airborne Aero-Optics Laboratory wavefront measurements at transonic speeds (Mach 0.65) with a conformal window turret as a function of turret pointing angle. Using both proper orthogonal decomposition and dynamic mode decomposition modal analysis methods, the flow dynamics are characterized. The conformal window wavefronts show shock formation between 85 deg and 90 deg and shear layer formation at a considerably lower turret aft pointing angle than would be expected at subsonic speeds without shock. At larger aft pointing angles, shear layer vortex roll-up dynamics dominate the aero-optical disturbances. In particular, the spatially and temporally periodic vortices grow in width and magnitude while the corresponding oscillation frequency drops with increasing look-back angle, thus maintaining a near constant vortex convection speed equal to about 0.6 times the free-stream velocity. From these results, a modified form of the aero-optics frequency scaling relation is proposed that yields a Strouhal number independent of turret look-back angle in the portion of the flow dominated by such Kelvin-Helmholtz shear layer vortices.

  7. Alternative Splicing in CaV2.2 Regulates Neuronal Trafficking via Adaptor Protein Complex-1 Adaptor Protein Motifs

    PubMed Central

    Macabuag, Natsuko

    2015-01-01

    N-type voltage-gated calcium (CaV2.2) channels are expressed in neurons and targeted to the plasma membrane of presynaptic terminals, facilitating neurotransmitter release. Here, we find that the adaptor protein complex-1 (AP-1) mediates trafficking of CaV2.2 from the trans-Golgi network to the cell surface. Examination of splice variants of CaV2.2, containing either exon 37a (selectively expressed in nociceptors) or 37b in the proximal C terminus, reveal that canonical AP-1 binding motifs, YxxΦ and [DE]xxxL[LI], present only in exon 37a, enhance intracellular trafficking of exon 37a-containing CaV2.2 to the axons and plasma membrane of rat DRG neurons. Finally, we identify differential effects of dopamine-2 receptor (D2R) and its agonist-induced activation on trafficking of CaV2.2 isoforms. D2R slowed the endocytosis of CaV2.2 containing exon 37b, but not exon 37a, and activation by the agonist quinpirole reversed the effect of the D2R. Our work thus reveals key mechanisms involved in the trafficking of N-type calcium channels. SIGNIFICANCE STATEMENT CaV2.2 channels are important for neurotransmitter release, but how they are trafficked is still poorly understood. Here, we describe a novel mechanism for trafficking of CaV2.2 from the trans-Golgi network to the cell surface which is mediated by the adaptor protein AP-1. Alternative splicing of exon 37 produces CaV2.2-exon 37a, selectively expressed in nociceptors, or CaV2.2-exon 37b, which is the major splice isoform. Our study reveals that canonical AP-1 binding motifs (YxxΦ and [DE]xxxL[LI]), present in exon 37a, but not 37b, enhance intracellular trafficking of exon 37a-containing CaV2.2 to axons and plasma membrane of DRG neurons. Interaction of APs with CaV2.2 channels may also be key underlying mechanisms for differential effects of the dopamine D2 receptor on trafficking of CaV2.2 splice variants. PMID:26511252

  8. Research on the aero-thermal effects by 3D analysis model of the optical window of the infrared imaging guidance

    NASA Astrophysics Data System (ADS)

    Xu, Bo; Li, Lin; Zhu, Ying

    2014-11-01

    Researches on hypersonic vehicles have been a hotspot in the field of aerospace because of the pursuits for higher speed by human being. Infrared imaging guidance is playing a very important role in modern warfare. When an Infrared Ray(IR) imaging guided missile is flying in the air at high speed, its optical dome suffers from serious aero-optic effects because of air flow. The turbulence around the dome and the thermal effects of the optical window would cause disturbance to the wavefront from the target. Therefore, detected images will be biased, dithered and blurred, and the capabilities of the seeker for detecting, tracking and recognizing are weakened. In this paper, methods for thermal and structural analysis with Heat Transfer and Elastic Mechanics are introduced. By studying the aero-thermal effects and aero-thermal radiation effects of the optical window, a 3D analysis model of the optical window is established by using finite element method. The direct coupling analysis is employed as a solving strategy. The variation regularity of the temperature field is obtained. For light with different incident angles, the influence on the ray propagation caused by window deformation is analyzed with theoretical calculation and optical/thermal/structural integrated analysis method respectively.

  9. Variation in seed traits and germination potential of Solanum elaeagnifolium Cav. Following its invasion in Greece

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Solanum elaeagnifolium Cav. (Silverleaf nightshade) is presently considered to be one of the worst agricultural weeds around the world including the Mediterranean basin. Plant’s native range is considered to be an area expanding from Southern US to Northern Mexico. Introduced unintentionally from so...

  10. CAV-OX CAVITATION OXIDIATION PROCESS - MAGNUM WATER TECHNOLOGY, INC. - APPLICATIONS ANALYSIS REPORT

    EPA Science Inventory

    This report evaluates the ability of the CAV-OX cavitation oxidation process to remove volatile organic compounds (VOC) present in aqueous wastes. This report also presents economic data based on the Superfund Innovative Technology Evaluation (SITE) Program demonstration and nine...

  11. CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease

    PubMed Central

    Bhat, Shambhu; Dao, David T.; Terrillion, Chantelle E.; Arad, Michal; Smith, Robert J.; Soldatov, Nikolai M.; Gould, Todd D.

    2012-01-01

    One of the most consistent genetic findings to have emerged from bipolar disorder genome wide association studies (GWAS) is with CACNA1C, a gene that codes for the α1C subunit of the Cav1.2 voltage-dependent L-type calcium channel (LTCC). Genetic variation in CACNA1C have also been associated with depression, schizophrenia, autism spectrum disorders, as well as changes in brain function and structure in control subjects who have no diagnosable psychiatric illness. These data are consistent with a continuum of shared neurobiological vulnerability between diverse—Diagnostic and Statistical Manual (DSM) defined—neuropsychiatric diseases. While involved in numerous cellular functions, Cav1.2 is most frequently implicated in coupling of cell membrane depolarization to transient increase of the membrane permeability for calcium, leading to activation and, potentially, changes in intracellular signaling pathway activity, gene transcription, and synaptic plasticity. Cav1.2 is involved in the proper function of numerous neurological circuits including those involving the hippocampus, amygdala, and mesolimbic reward system, which are strongly implicated in psychiatric disease pathophysiology. A number of behavioral effects of LTCC inhibitors have been described including antidepressant-like behavioral actions in rodent models. Clinical studies suggest possible treatment effects in a subset of patients with mood disorders. We review the genetic structure and variation of CACNA1C, discussing relevant human genetic and clinical findings, as well as the biological actions of Cav1.2 that are most relevant to psychiatric illness. PMID:22705413

  12. Roscovitine inhibits CaV3.1 (T-type) channels by preferentially affecting closed-state inactivation.

    PubMed

    Yarotskyy, Viktor; Elmslie, Keith S

    2012-02-01

    T-type calcium channels (Ca(V)3) play an important role in many physiological and pathological processes, including cancerogenesis. Ca(V)3 channel blockers have been proposed as potential cancer treatments. Roscovitine, a trisubstituted purine, is a cyclin-dependent kinase (CDK) inhibitor that is currently undergoing phase II clinical trials as an anticancer drug and has been shown to affect calcium and potassium channel activity. Here, we investigate the effect of roscovitine on Ca(V)3.1 channels. Ca(V)3.1 channels were transiently expressed in human embryonic kidney 293 cells, and currents were recorded by using the whole-cell patch-clamp technique. Roscovitine blocks Ca(V)3.1 channels with higher affinity for depolarized cells (EC₅₀ of 10 μM), which is associated with a negative shift in the voltage dependence of closed-state inactivation. Enhanced inactivation is mediated by roscovitine-induced acceleration of closed-state inactivation and slowed recovery from inactivation. Small effects of roscovitine were also observed on T-channel deactivation and open-state inactivation, but neither could explain the inhibitory effect. Roscovitine inhibits Ca(V)3.1 channels within the therapeutic range (10-50 μM) in part by stabilizing the closed-inactivated state. The ability of roscovitine to block multiple mediators of proliferation, including CDKs and Ca(V)3.1 channels, may facilitate its anticancer properties. PMID:22088954

  13. Ca(V)1.3-driven SK channel activation regulates pacemaking and spike frequency adaptation in mouse chromaffin cells.

    PubMed

    Vandael, David H F; Zuccotti, Annalisa; Striessnig, Joerg; Carbone, Emilio

    2012-11-14

    Mouse chromaffin cells (MCCs) fire spontaneous action potentials (APs) at rest. Ca(v)1.3 L-type calcium channels sustain the pacemaker current, and their loss results in depolarized resting potentials (V(rest)), spike broadening, and remarkable switches into depolarization block after BayK 8644 application. A functional coupling between Ca(v)1.3 and BK channels has been reported but cannot fully account for the aforementioned observations. Here, using Ca(v)1.3(-/-) mice, we investigated the role of Ca(v)1.3 on SK channel activation and how this functional coupling affects the firing patterns induced by sustained current injections. MCCs express SK1-3 channels whose tonic currents are responsible for the slow irregular firing observed at rest. Percentage of frequency increase induced by apamin was found inversely correlated to basal firing frequency. Upon stimulation, MCCs build-up Ca(v)1.3-dependent SK currents during the interspike intervals that lead to a notable degree of spike frequency adaptation (SFA). The major contribution of Ca(v)1.3 to the subthreshold Ca(2+) charge during an AP-train rather than a specific molecular coupling to SK channels accounts for the reduced SFA of Ca(v)1.3(-/-) MCCs. Low adaptation ratios due to reduced SK activation associated with Ca(v)1.3 deficiency prevent the efficient recovery of Na(V) channels from inactivation. This promotes a rapid decline of AP amplitudes and facilitates early onset of depolarization block following prolonged stimulation. Thus, besides serving as pacemaker, Ca(v)1.3 slows down MCC firing by activating SK channels that maintain Na(V) channel availability high enough to preserve stable AP waveforms, even upon high-frequency stimulation of chromaffin cells during stress responses. PMID:23152617

  14. 48 CFR 1852.235-70 - Center for AeroSpace Information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Center for AeroSpace... SPACE ADMINISTRATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1852.235-70 Center for AeroSpace Information. As prescribed in 1835.070(a), insert...

  15. 48 CFR 1852.235-70 - Center for AeroSpace Information.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Center for AeroSpace... SPACE ADMINISTRATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1852.235-70 Center for AeroSpace Information. As prescribed in 1835.070(a), insert...

  16. 48 CFR 1852.235-70 - Center for AeroSpace Information.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Center for AeroSpace... SPACE ADMINISTRATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1852.235-70 Center for AeroSpace Information. As prescribed in 1835.070(a), insert...

  17. Similar molecular determinants on Rem mediate two distinct modes of inhibition of CaV1.2 channels

    PubMed Central

    Puckerin, Akil A.; Chang, Donald D.; Subramanyam, Prakash; Colecraft, Henry M.

    2016-01-01

    ABSTRACT Rad/Rem/Rem2/Gem (RGK) proteins are Ras-like GTPases that potently inhibit all high-voltage-gated calcium (CaV1/CaV2) channels and are, thus, well-positioned to tune diverse physiological processes. Understanding how RGK proteins inhibit CaV channels is important for perspectives on their (patho)physiological roles and could advance their development and use as genetically-encoded CaV channel blockers. We previously reported that Rem can block surface CaV1.2 channels in 2 independent ways that engage distinct components of the channel complex: (1) by binding auxiliary β subunits (β-binding-dependent inhibition, or BBD); and (2) by binding the pore-forming α1C subunit N-terminus (α1C-binding-dependent inhibition, or ABD). By contrast, Gem uses only the BBD mechanism to block CaV1.2. Rem molecular determinants required for BBD CaV1.2 inhibition are the distal C-terminus and the guanine nucleotide binding G-domain which interact with the plasma membrane and CaVβ, respectively. However, Rem determinants for ABD CaV1.2 inhibition are unknown. Here, combining fluorescence resonance energy transfer, electrophysiology, systematic truncations, and Rem/Gem chimeras we found that the same Rem distal C-terminus and G-domain also mediate ABD CaV1.2 inhibition, but with different interaction partners. Rem distal C-terminus interacts with α1C N-terminus to anchor the G-domain which likely interacts with an as-yet-unidentified site. In contrast to some previous studies, neither the C-terminus of Rem nor Gem was sufficient to inhibit CaV1/CaV2 channels. The results reveal that similar molecular determinants on Rem are repurposed to initiate 2 independent mechanisms of CaV1.2 inhibition. PMID:27115600

  18. An experimental study of aero-optical aberration and dithering of supersonic mixing layer via BOS

    NASA Astrophysics Data System (ADS)

    Zhao, Yuxin; Yi, Shihe; Tian, Lifeng; He, Lin; Cheng, Zhongyu

    2010-01-01

    The optical performance of supersonic mixing layer is heavily deteriorated by the aero-optical aberration and dithering of coherent structures, but current measuring methods limit the spatiotemporal resolution in relevant studies. A high resolution whole-field aero-optical aberration and dithering measuring method based on the Background Orient Schlieren (BOS) technique was studied. The systematic structure, sensitivity and resolution of BOS are analyzed in this paper. The aero-optical aberration and dithering of streamwise structures in supersonic mixing layers were quantificationally studied with BOS. The aberration field of spanwise structures revealed the ribbon-like aberration structures, which heavily restrict the optical performance of a mixing layer. The quantifications of aero-optical aberration and dithering are very important in studying aero-optical performance of supersonic mixing layer.

  19. Optimization of Aero Engine Acceleration Control in Combat State Based on Genetic Algorithms

    NASA Astrophysics Data System (ADS)

    Li, Jie; Fan, Ding; Sreeram, Victor

    2012-03-01

    In order to drastically exploit the potential of the aero engine and improve acceleration performance in the combat state, an on-line optimized controller based on genetic algorithms is designed for an aero engine. For testing the validity of the presented control method, detailed joint simulation tests of the designed controller and the aero engine model are performed in the whole flight envelope. Simulation test results show that the presented control algorithm has characteristics of rapid convergence speed, high efficiency and can fully exploit the acceleration performance potential of the aero engine. Compared with the former controller, the designed on-line optimized controller (DOOC) can improve the security of the acceleration process and greatly enhance the aero engine thrust in the whole range of the flight envelope, the thrust increases an average of 8.1% in the randomly selected working states. The plane which adopts DOOC can acquire better fighting advantage in the combat state.

  20. Interference Analysis Status and Plans for Aeronautical Mobile Airport Communications System (AeroMACS)

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Wilson, Jeffrey D.

    2010-01-01

    Interference issues related to the operation of an aeronautical mobile airport communications system (AeroMACS) in the C-Band (specifically 5091-5150 MHz) is being investigated. The issue of primary interest is co-channel interference from AeroMACS into mobile-satellite system (MSS) feeder uplinks. The effort is focusing on establishing practical limits on AeroMACS transmissions from airports so that the threshold of interference into MSS is not exceeded. The analyses are being performed with the software package Visualyse Professional, developed by Transfinite Systems Limited. Results with omni-directional antennas and plans to extend the models to represent AeroMACS more accurately will be presented. These models should enable realistic analyses of emerging AeroMACS designs to be developed from NASA Test Bed, RTCA 223, and European results.

  1. Future NASA Power Technologies for Space and Aero Propulsion Applications

    NASA Technical Reports Server (NTRS)

    Soeder, James F.

    2015-01-01

    To achieve the ambitious goals that NASA has outlined for the next decades considerable development of power technology will be necessary. This presentation outlines the development objectives for both space and aero applications. It further looks at the various power technologies that support these objectives and examines drivers that will be a driving force for future development. Finally, the presentation examines what type of non-traditional learning areas should be emphasized in student curriculum so that the engineering needs of the third decade of the 21st Century are met.

  2. Hypersonic Interceptor Performance Evaluation Center aero-optics performance predictions

    NASA Astrophysics Data System (ADS)

    Sutton, George W.; Pond, John E.; Snow, Ronald; Hwang, Yanfang

    1993-06-01

    This paper describes the Hypersonic Interceptor Performance Evaluation Center's (HIPEC) aerooptics performance predictions capability. It includes code results for three dimensional shapes and comparisons to initial experiments. HIPEC consists of a collection of aerothermal, aerodynamic computational codes which are capable of covering the entire flight regime from subsonic to hypersonic flow and include chemical reactions and turbulence. Heat transfer to the various surfaces is calculated as an input to cooling and ablation processes. HIPEC also has aero-optics codes to determine the effect of the mean flowfield and turbulence on the tracking and imaging capability of on-board optical sensors. The paper concentrates on the latter aspects.

  3. AeroVironment technician checks a Helios solar cell panel

    NASA Technical Reports Server (NTRS)

    2000-01-01

    A technician at AeroVironment's Design Development Center in Simi Valley, California, checks a panel of silicon solar cells for conductivity and voltage. The bi-facial cells, fabricated by SunPower, Inc., of Sunnyvale, California, are among 64,000 solar cells which have been installed on the Helios Prototype solar-powered aircraft to provide power to its 14 electric motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights above 50,000 feet altitude with the aid of a regenerative fuel cell-based energy storage system now under development in 2003.

  4. Overview of additive manufacturing activities at MTU aero engines

    NASA Astrophysics Data System (ADS)

    Bamberg, Joachim; Dusel, Karl-Heinz; Satzger, Wilhelm

    2015-03-01

    Additive Manufacturing (AM) is a promising technology to produce parts easily and effectively, just by using metallic powder or wire as starting material and a sophisticated melting process. In contrast to milling or turning technologies complex shaped and hollow parts can be built up in one step. That reduces the production costs and allows the implementation of complete new 3D designs. Therefore AM is also of great interest for aerospace and aero engine industry. MTU Aero Engines has focused its AM activities to the selective laser melting technique (SLM). This technique uses metallic powder and a laser for melting and building up the part layer by layer. It is shown which lead part was selected for AM and how the first production line was established. A special focus is set on the quality assurance of the selective laser melting process. In addition to standard non-destructive inspection techniques a new online monitoring tool was developed and integrated into the SLM machines. The basics of this technique is presented.

  5. Phosphorylation of Cav1.2 on S1928 uncouples the L-type Ca2+ channel from the β2 adrenergic receptor.

    PubMed

    Patriarchi, Tommaso; Qian, Hai; Di Biase, Valentina; Malik, Zulfiquar A; Chowdhury, Dhrubajyoti; Price, Jennifer L; Hammes, Erik A; Buonarati, Olivia R; Westenbroek, Ruth E; Catterall, William A; Hofmann, Franz; Xiang, Yang K; Murphy, Geoffrey G; Chen, Chao-Ye; Navedo, Manuel F; Hell, Johannes W

    2016-06-15

    Agonist-triggered downregulation of β-adrenergic receptors (ARs) constitutes vital negative feedback to prevent cellular overexcitation. Here, we report a novel downregulation of β2AR signaling highly specific for Cav1.2. We find that β2-AR binding to Cav1.2 residues 1923-1942 is required for β-adrenergic regulation of Cav1.2. Despite the prominence of PKA-mediated phosphorylation of Cav1.2 S1928 within the newly identified β2AR binding site, its physiological function has so far escaped identification. We show that phosphorylation of S1928 displaces the β2AR from Cav1.2 upon β-adrenergic stimulation rendering Cav1.2 refractory for several minutes from further β-adrenergic stimulation. This effect is lost in S1928A knock-in mice. Although AMPARs are clustered at postsynaptic sites like Cav1.2, β2AR association with and regulation of AMPARs do not show such dissociation. Accordingly, displacement of the β2AR from Cav1.2 is a uniquely specific desensitization mechanism of Cav1.2 regulation by highly localized β2AR/cAMP/PKA/S1928 signaling. The physiological implications of this mechanism are underscored by our finding that LTP induced by prolonged theta tetanus (PTT-LTP) depends on Cav1.2 and its regulation by channel-associated β2AR. PMID:27103070

  6. Phosphorylation of Cav1.2 on S1928 uncouples the L-type Ca2+ channel from the β2 adrenergic receptor.

    PubMed

    Patriarchi, Tommaso; Qian, Hai; Di Biase, Valentina; Malik, Zulfiquar A; Chowdhury, Dhrubajyoti; Price, Jennifer L; Hammes, Erik A; Buonarati, Olivia R; Westenbroek, Ruth E; Catterall, William A; Hofmann, Franz; Xiang, Yang K; Murphy, Geoffrey G; Chen, Chao-Ye; Navedo, Manuel F; Hell, Johannes W

    2016-06-15

    Agonist-triggered downregulation of β-adrenergic receptors (ARs) constitutes vital negative feedback to prevent cellular overexcitation. Here, we report a novel downregulation of β2AR signaling highly specific for Cav1.2. We find that β2-AR binding to Cav1.2 residues 1923-1942 is required for β-adrenergic regulation of Cav1.2. Despite the prominence of PKA-mediated phosphorylation of Cav1.2 S1928 within the newly identified β2AR binding site, its physiological function has so far escaped identification. We show that phosphorylation of S1928 displaces the β2AR from Cav1.2 upon β-adrenergic stimulation rendering Cav1.2 refractory for several minutes from further β-adrenergic stimulation. This effect is lost in S1928A knock-in mice. Although AMPARs are clustered at postsynaptic sites like Cav1.2, β2AR association with and regulation of AMPARs do not show such dissociation. Accordingly, displacement of the β2AR from Cav1.2 is a uniquely specific desensitization mechanism of Cav1.2 regulation by highly localized β2AR/cAMP/PKA/S1928 signaling. The physiological implications of this mechanism are underscored by our finding that LTP induced by prolonged theta tetanus (PTT-LTP) depends on Cav1.2 and its regulation by channel-associated β2AR.

  7. Semaphorin 3A induces CaV2.3 channel-dependent conversion of axons to dendrites

    PubMed Central

    Nishiyama, Makoto; Togashi, Kazunobu; von Schimmelmann, Melanie J.; Lim, Chae-Seok; Maeda, Shin-ichi; Yamashita, Naoya; Goshima, Yoshio; Ishii, Shin; Hong, Kyonsoo

    2012-01-01

    Polarized neurites, axons and dendrites, form the functional circuitry of the nervous system. Secreted guidance cues often convert the polarity of neuron migration and neurite outgrowth by regulating ion channels. Here, we show that secreted semaphorin 3A (Sema3A) converts the neurite identity of Xenopus spinal commissural interneurons (xSCINs) by activating CaV2.3 channels (CaV2.3). Sema3A treatment converted the identity of axons of cultured xSCINs to that of dendrites by recruiting functional CaV2.3. Inhibition of Sema3A signalling prevented both the expression of CaV2.3 and acquisition of the dendrite identity, and inhibition of CaV2.3 function resulted in multiple axon-like neurites of xSCINs in the spinal cord. Furthermore, Sema3A-triggered cGMP production and PKG activity induced, respectively, the expression of functional CaV2.3 and the dendrite identity. These results reveal a novel mechanism by which a guidance cue controls the identity of neurites during nervous system development. PMID:21602796

  8. Thermomechanical repository and shaft response analyses using the CAVS (Cracking And Void Strain) jointed rock model: Draft final report

    SciTech Connect

    Dial, B.W.; Maxwell, D.E.

    1986-12-01

    Numerical studies of the far-field repository and near-field shaft response for a nuclear waste repository in bedded salt have been performed with the STEALTH computer code using the CAVS model for jointed rock. CAVS is a constitutive model that can simulate the slip and dilatancy of fracture planes in a jointed rock mass. The initiation and/or propagation of fractures can also be modeled when stress intensity criteria are met. The CAVS models are based on the joint models proposed with appropriate modifications for numerical simulations. The STEALTH/CAVS model has been previously used to model (1) explosive fracturing of a wellbore, (2) earthquake effects on tunnels in a generic nuclear waste repository, (3) horizontal emplacement for a nuclear waste repository in jointed granite, and (4) tunnel response in jointed rock. The use of CAVS to model far-field repository and near-field shaft response was different from previous approaches because it represented a spatially oriented approach to rock response and failure, rather than the traditional stress invariant formulation for yielding. In addition, CAVS tracked the response of the joint apertures to the time-dependent stress changes in the far-field repository and near-field shaft regions. 28 refs., 21 figs., 11 tabs.

  9. Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels

    PubMed Central

    Moreno, Claudia M; Dixon, Rose E; Tajada, Sendoa; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Santana, Luis F

    2016-01-01

    CaV1.3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it is widely assumed that individual CaV1.3 channels behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report the results of super-resolution imaging, optogenetic, and electrophysiological measurements that refute this long-held view. We found that the short channel isoform (CaV1.3S), but not the long (CaV1.3L), associates in functional clusters of two or more channels that open cooperatively, facilitating Ca2+ influx. CaV1.3S channels are coupled via a C-terminus-to-C-terminus interaction that requires binding of the incoming Ca2+ to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca2+ currents as a consequence of their higher open probabilities, leading to increased firing rates in rat hippocampal neurons. We propose that cooperative gating of CaV1.3S channels represents a mechanism for the regulation of Ca2+ signaling and electrical activity. DOI: http://dx.doi.org/10.7554/eLife.15744.001 PMID:27187148

  10. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

    PubMed Central

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S.; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-01-01

    The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. PMID:25981458

  11. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle.

    PubMed

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-08-15

    The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. PMID:25981458

  12. Deletion of the L-type Calcium Channel CaV1.3 but not CaV1.2 Results in a Diminished sAHP in Mouse CA1 Pyramidal Neurons

    PubMed Central

    Gamelli, Amy E.; McKinney, Brandon C.; White, Jessica A.; Murphy, Geoffrey G.

    2009-01-01

    Trains of action potentials in CA1 pyramidal neurons are followed by a prolonged calcium-dependent post-burst afterhyperpolarization (AHP) that serves to limit further firing to a sustained depolarizing input. A reduction in the AHP accompanies acquisition of several types of learning and increases in the AHP are correlated with age-related cognitive impairment. The AHP develops primarily as the result of activation of outward calcium-activated potassium currents; however the precise source of calcium for activation of the AHP remains unclear. There is substantial experimental evidence suggesting that calcium influx via voltage-gated L-type calcium channels (L-VGCCs) contributes to the generation of the AHP. Two L-VGCC subtypes are predominately expressed in the hippocampus, CaV1.2 and CaV1.3, however it is not known which L-VGCC subtype is involved in generation of the AHP. This ambiguity is due in large part to the fact that at present there are no subunit-specific agonists or antagonists. Therefore, using mice in which the gene encoding CaV1.2 or CaV1.3 was deleted, we sought to determine the impact of alterations in levels of these two L-VCGG subtypes on neuronal excitability. No differences in any AHP measure were seen between neurons from CaV1.2 knockout mice and controls. However, the total area of the AHP was significantly smaller in neurons from CaV1.3 knockout mice as compared to neurons from wildtype controls. A significant reduction in the amplitude of the AHP was also seen at the 1 sec time point in neurons from CaV1.3 knockout mice as compared to those from controls. Reductions in both the area and 1 sec amplitude suggest the involvement of calcium influx via CaV1.3 in the slow AHP (sAHP). Thus, the results of our study demonstrate that deletion of CaV1.3, but not CaV1.2, significantly impacts the generation of the sAHP. PMID:20014384

  13. CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies.

    PubMed

    Scalco, Renata Siciliani; Gardiner, Alice R; Pitceathly, Robert D S; Hilton-Jones, David; Schapira, Anthony H; Turner, Chris; Parton, Matt; Desikan, Mahalekshmi; Barresi, Rita; Marsh, Julie; Manzur, Adnan Y; Childs, Anne-Marie; Feng, Lucy; Murphy, Elaine; Lamont, Phillipa J; Ravenscroft, Gianina; Wallefeld, William; Davis, Mark R; Laing, Nigel G; Holton, Janice L; Fialho, Doreen; Bushby, Kate; Hanna, Michael G; Phadke, Rahul; Jungbluth, Heinz; Houlden, Henry; Quinlivan, Ros

    2016-08-01

    Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n = 6). Symptoms included myalgia (n = 7), exercise intolerance (n = 7) and episodes of rhabdomyolysis (n = 2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients; however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series, immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other "typical" features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes. PMID:27312022

  14. Miga Aero Actuator and 2D Machined Mechanical Binary Latch

    NASA Technical Reports Server (NTRS)

    Gummin, Mark A.

    2013-01-01

    Shape memory alloy (SMA) actuators provide the highest force-to-weight ratio of any known actuator. They can be designed for a wide variety of form factors from flat, thin packages, to form-matching packages for existing actuators. SMA actuators can be operated many thousands of times, so that ground testing is possible. Actuation speed can be accurately controlled from milliseconds to position and hold, and even electronic velocity-profile control is possible. SMA actuators provide a high degree of operational flexibility, and are truly smart actuators capable of being accurately controlled by onboard microprocessors across a wide range of voltages. The Miga Aero actuator is a SMA actuator designed specifically for spaceflight applications. Providing 13 mm of stroke with either 20- or 40-N output force in two different models, the Aero actuator is made from low-outgassing PEEK (polyether ether ketone) plastic, stainless steel, and nickel-titanium SMA wires. The modular actuator weighs less than 28 grams. The dorsal output attachment allows the Aero to be used in either PUSH or PULL modes by inverting the mounting orientation. The SPA1 actuator utilizes commercially available SMA actuator wire to provide 3/8-in. (approx. =.1 cm) of stroke at a force of over 28 lb (approx. = .125 N). The force is provided by a unique packaging of the single SMA wire that provides the output force of four SMA wires mechanically in parallel. The output load is shared by allowing the SMA wire to slip around the output attachment end to adjust or balance the load, preventing any individual wire segment from experiencing high loads during actuation. A built-in end limit switch prevents overheating of the SMA element following actuation when used in conjunction with the Miga Analog Driver [a simple MOSFET (metal oxide semiconductor field-effect transistor) switching circuit]. A simple 2D machined mechanical binary latch has been developed to complement the capabilities of SMA wire

  15. Functional Properties of a Newly Identified C-terminal Splice Variant of Cav1.3 L-type Ca2+ Channels*

    PubMed Central

    Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E.; Sinnegger-Brauns, Martina J.; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

    2011-01-01

    An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Cav1.3 L-type Ca2+ channels (Cav1.3L) is a major determinant of their voltage- and Ca2+-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Cav1.342A channels that activate at a more negative voltage range and exhibit more pronounced Ca2+-dependent inactivation. Here we describe the discovery of a novel short splice variant (Cav1.343S) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Cav1.342A, still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Cav1.343S also activated at more negative voltages like Cav1.342A but Ca2+-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Cav1.3L. The presence of the proximal C terminus in Cav1.343S channels preserved their modulation by distal C terminus-containing Cav1.3- and Cav1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca2+ influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Cav1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca2+ channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca2+ accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca2+-induced neurodegenerative processes. PMID:21998310

  16. Down-regulation of CaV1.2 channels during hypertension: how fewer CaV1.2 channels allow more Ca2+ into hypertensive arterial smooth muscle

    PubMed Central

    Tajada, Sendoa; Cidad, Pilar; Colinas, Olaia; Santana, L Fernando; López-López, José R; Pérez-García, M Teresa

    2013-01-01

    Hypertension is a clinical syndrome characterized by increased arterial tone. Although the mechanisms are varied, the generally accepted view is that increased CaV1.2 channel function is a common feature of this pathological condition. Here, we investigated the mechanisms underlying vascular dysfunction in a mouse model of genetic hypertension. Contrary to expectation, we found that whole-cell CaV1.2 currents (ICa) were lower in hypertensive (BPH line) than normotensive (BPN line) myocytes. However, local CaV1.2 sparklet activity was higher in BPH cells, suggesting that the relatively low ICa in these cells was produced by a few hyperactive CaV1.2 channels. Furthermore, our data suggest that while the lower expression of the pore-forming α1c subunit of CaV1.2 currents underlies the lower ICa in BPH myocytes, the increased sparklet activity was due to a different composition in the auxiliary subunits of the CaV1.2 complexes. ICa currents in BPN cells were produced by channels composed of α1c/α2δ/β3 subunits, while in BPH myocytes currents were probably generated by the opening of channels formed by α1c/α2δ/β2 subunits. In addition, Ca2+ sparks evoked large conductance, Ca2+-activated K+ (BK) currents of lower magnitude in BPH than in BPN myocytes, because BK channels were less sensitive to Ca2+. Our data are consistent with a model in which a decrease in the global number of CaV1.2 currents coexist with the existence of a subpopulation of highly active channels that dominate the resting Ca2+ influx. The decrease in BK channel activity makes the hyperpolarizing brake ineffective and leads BPH myocytes to a more contracted resting state. PMID:24167226

  17. Optimal Control and Coordination of Connected and Automated Vehicles at Urban Traffic Intersections

    SciTech Connect

    Zhang, Yue J.; Malikopoulos, Andreas; Cassandras, Christos G.

    2016-01-01

    We address the problem of coordinating online a continuous flow of connected and automated vehicles (CAVs) crossing two adjacent intersections in an urban area. We present a decentralized optimal control framework whose solution yields for each vehicle the optimal acceleration/deceleration at any time in the sense of minimizing fuel consumption. The solu- tion, when it exists, allows the vehicles to cross the intersections without the use of traffic lights, without creating congestion on the connecting road, and under the hard safety constraint of collision avoidance. The effectiveness of the proposed solution is validated through simulation considering two intersections located in downtown Boston, and it is shown that coordination of CAVs can reduce significantly both fuel consumption and travel time.

  18. Evaluation of aero-optical distortion effects in PIV

    NASA Astrophysics Data System (ADS)

    Elsinga, G. E.; Oudheusden, B. W.; Scarano, F.

    2005-08-01

    Aero-optical distortion effects on the accuracy of particle image velocimetry (PIV) are investigated. When the illuminated particles are observed through a medium that is optically inhomogeneous due to flow compressibility, the resulting particle image pattern is subjected to deformation and blur. In relation to PIV two forms of error can be identified: position error and velocity error. In this paper a model is presented that describes these errors and particle image blur in relation to the refractive index field of the flow. In the case of 2D flows the model equations can be simplified and, furthermore, the background oriented schlieren technique (BOS) can be applied as a means to assess and correct for the optical error in PIV. The model describing the optical distortion is validated by both computer simulation and real experiments of 2D flows. Two flow features are considered: one with optical distortion normal to the velocity (shear layer) and one with optical distortion in the direction of the flow (expansion fan). Both simulation and experiments demonstrate that the major source for the velocity error is the second derivative of the refractive index in the direction of the velocity vector. The aero-optical distortion effect is less critical for shearing interfaces in comparison with compression/expansion fronts, the most critical case being represented by shock waves. Based on the results from the simulated experiments, it is concluded that for the 2D flow case the BOS method allows a measurement of the mean velocity error in PIV and can reduce it to a large extent.

  19. Aero-acoustics of Drag Generating Swirling Exhaust Flows

    NASA Technical Reports Server (NTRS)

    Shah, P. N.; Mobed, D.; Spakovszky, Z. S.; Brooks, T. F.; Humphreys, W. M. Jr.

    2007-01-01

    Aircraft on approach in high-drag and high-lift configuration create unsteady flow structures which inherently generate noise. For devices such as flaps, spoilers and the undercarriage there is a strong correlation between overall noise and drag such that, in the quest for quieter aircraft, one challenge is to generate drag at low noise levels. This paper presents a rigorous aero-acoustic assessment of a novel drag concept. The idea is that a swirling exhaust flow can yield a steady, and thus relatively quiet, streamwise vortex which is supported by a radial pressure gradient responsible for pressure drag. Flows with swirl are naturally limited by instabilities such as vortex breakdown. The paper presents a first aero-acoustic assessment of ram pressure driven swirling exhaust flows and their associated instabilities. The technical approach combines an in-depth aerodynamic analysis, plausibility arguments to qualitatively describe the nature of acoustic sources, and detailed, quantitative acoustic measurements using a medium aperture directional microphone array in combination with a previously established Deconvolution Approach for Mapping of Acoustic Sources (DAMAS). A model scale engine nacelle with stationary swirl vanes was designed and tested in the NASA Langley Quiet Flow Facility at a full-scale approach Mach number of 0.17. The analysis shows that the acoustic signature is comprised of quadrupole-type turbulent mixing noise of the swirling core flow and scattering noise from vane boundary layers and turbulent eddies of the burst vortex structure near sharp edges. The exposed edges are the nacelle and pylon trailing edge and the centerbody supporting the vanes. For the highest stable swirl angle setting a nacelle area based drag coefficient of 0.8 was achieved with a full-scale Overall Sound Pressure Level (OASPL) of about 40dBA at the ICAO approach certification point.

  20. Correcting the aero-optical aberration of the supersonic mixing layer with adaptive optics: concept validation.

    PubMed

    Gao, Qiong; Jiang, Zongfu; Yi, Shihe; Xie, Wenke; Liao, Tianhe

    2012-06-10

    We describe an adaptive optics (AO) system for correcting the aero-optical aberration of the supersonic mixing layer and test its performance with numerical simulations. The AO system is based on the measurement of distributed Strehl ratios and the stochastic parallel gradient descent (SPGD) algorithm. The aero-optical aberration is computed by the direct numerical simulation of a two-dimensional supersonic mixing layer. When the SPGD algorithm is applied directly, the AO cannot give effective corrections. This paper suggests two strategies to improve the performance of the SPGD algorithm for use in aero-optics. The first one is using an iteration process keeping finite memory, and the second is based on the frozen hypothesis. With these modifications, the performance of AO is improved and the aero-optical aberration can be corrected to some noticeable extent. The possibility of experimental implementation is also discussed. PMID:22695671

  1. A Frame-Shift Mutation in CAV1 Is Associated with a Severe Neonatal Progeroid and Lipodystrophy Syndrome.

    PubMed

    Schrauwen, Isabelle; Szelinger, Szabolcs; Siniard, Ashley L; Kurdoglu, Ahmet; Corneveaux, Jason J; Malenica, Ivana; Richholt, Ryan; Van Camp, Guy; De Both, Matt; Swaminathan, Shanker; Turk, Mari; Ramsey, Keri; Craig, David W; Narayanan, Vinodh; Huentelman, Matthew J

    2015-01-01

    A 3-year-old female patient presenting with an unknown syndrome of a neonatal progeroid appearance, lipodystrophy, pulmonary hypertension, cutis marmorata, feeding disorder and failure to thrive was investigated by whole-genome sequencing. This revealed a de novo, heterozygous, frame-shift mutation in the Caveolin1 gene (CAV1) (p.Phe160X). Mutations in CAV1, encoding the main component of the caveolae in plasma membranes, cause Berardinelli-Seip congenital lipodystrophy type 3 (BSCL). Although BSCL is recessive, heterozygous carriers either show a reduced phenotype of partial lipodystrophy, pulmonary hypertension, or no phenotype. To investigate the pathogenic mechanisms underlying this syndrome in more depth, we performed next generation RNA sequencing of peripheral blood, which showed several dysregulated pathways in the patient that might be related to the phenotypic progeroid features (apoptosis, DNA repair/replication, mitochondrial). Secondly, we found a significant down-regulation of known Cav1 interaction partners, verifying the dysfunction of CAV1. Other known progeroid genes and lipodystrophy genes were also dysregulated. Next, western blotting of lysates of cultured fibroblasts showed that the patient shows a significantly decreased expression of wild-type CAV1 protein, demonstrating a loss-of-function mutation, though her phenotype is more severe that other heterozygotes with similar mutations. This phenotypic variety could be explained by differences in genetic background. Indications for this are supported by additional rare variants we found in AGPAT2 and LPIN1 lipodystrophy genes. CAV1, AGPAT2 and LPIN1 all play an important role in triacylglycerol (TAG) biosynthesis in adipose tissue, and the defective function in different parts of this pathway, though not all to the same extend, could contribute to a more severe lipoatrophic phenotype in this patient. In conclusion, we report, for the first time, an association of CAV1 dysfunction with a syndrome

  2. Redundancy of Cav2.1 channel accessory subunits in transmitter release at the mouse neuromuscular junction.

    PubMed

    Kaja, Simon; Todorov, Boyan; van de Ven, Rob C G; Ferrari, Michel D; Frants, Rune R; van den Maagdenberg, Arn M J M; Plomp, Jaap J

    2007-04-27

    Ca(v)2.1 (P/Q-type) channels possess a voltage-sensitive pore-forming alpha(1) subunit that can associate with the accessory subunits alpha(2)delta, beta and gamma. The primary role of Ca(v)2.1 channels is to mediate transmitter release from nerve terminals both in the central and peripheral nervous system. Whole-cell voltage-clamp studies in in vitro expression systems have indicated that accessory channel subunits can have diverse modulatory effects on membrane expression and biophysical properties of Ca(v)2.1 channels. However, there is only limited knowledge on whether similar modulation also occurs in the specific presynaptic environment in vivo and, hence, whether accessory subunits influence neurotransmitter release. Ducky, lethargic and stargazer are mutant mice that lack functional alpha(2)delta-2, beta(4) and gamma(2) accessory Ca(v) channel subunits, respectively. The neuromuscular junction (NMJ) is a peripheral synapse, where transmitter release is governed exclusively by Ca(v)2.1 channels, and which can be characterized electrophysiologically with relative experimental ease. In order to investigate a possible synaptic influence of accessory subunits in detail, we electrophysiologically measured acetylcholine (ACh) release at NMJs of these three mutants. Surprisingly, we did not find any changes compared to wild-type littermates, other than a small reduction (25%) of evoked ACh release at ducky NMJs. This effect is most likely due to the approximately 40% reduced synapse size, associated with the reduced size of ducky mice, rather than resulting directly from reduced Ca(v)2.1 channel function due to alpha(2)delta-2 absence. We conclude that alpha(2)delta-2, beta(4), and gamma(2) accessory subunits are redundant for the transmitter release-mediating function of presynaptic Ca(v)2.1 channels at the mouse NMJ.

  3. CFD-based aero-optical analysis of flow fields over two-dimensional cavities with active flow control

    NASA Astrophysics Data System (ADS)

    Tan, Yan

    Prediction and control of optical wave front distortions and aberrations in a high energy laser beam due to interaction with an unsteady highly non-uniform flow field is of great importance in the development of directed energy weapon systems for Unmanned Air Vehicles (UAV). The unsteady shear layer over the weapons bay cavity is the primary cause of this distortion of the optical wave front. The large scale vortical structure of the shear layer over the cavity can be significantly reduced by employing an active flow control technique combined with passive flow control. This dissertation explores various active and passive control methods to suppress the cavity oscillations and thereby improve the aero-optics of cavity flow. In active flow control technique, a steady or a pulsed jet is applied at the sharp leading edge of cavities of different aspect ratios L/D (=2, 4, 15), where L and D are the width and the depth of a cavity respectively. In the passive flow control approach, the sharp leading or trailing edge of the cavity is modified into a round edge of different radii. Both of these active and passive flow control approaches are studied independently and in combination. Numerical simulations are performed, with and without active flow control for subsonic free stream flow past two-dimensional sharp and round leading or trailing edge cavities using Unsteady Reynolds-Averaged Navier-Stokes (URANS) equations with a two-equation Shear Stress Transport (SST) turbulence model or a hybrid SST/Large Eddy Simulation (LES) model. Aero-optical analysis is developed and applied to all the simulation cases. Index of refraction and Optical Path Difference (OPD) are compared for flow fields without and with active flow control. Root-Mean-Square (RMS) value of OPD is calculated and compared with the experimental data, where available. The effect of steady and pulsed blowing on buffet loading on the downstream face of the cavity is also computed. Using the numerical

  4. Aero-Thermal Calibration of the NASA Glenn Icing Research Tunnel (2012 Tests)

    NASA Technical Reports Server (NTRS)

    Pastor-Barsi, Christine; Allen, Arrington E.

    2013-01-01

    A full aero-thermal calibration of the NASA Glenn Icing Research Tunnel (IRT) was completed in 2012 following the major modifications to the facility that included replacement of the refrigeration plant and heat exchanger. The calibration test provided data used to fully document the aero-thermal flow quality in the IRT test section and to construct calibration curves for the operation of the IRT.

  5. An integrated aerodynamic/propulsion study for generic aero-space planes based on waverider concepts

    NASA Technical Reports Server (NTRS)

    Rasmussen, M. L.; Emanuel, George

    1989-01-01

    The design of a unified aero-space plane based on waverider technology is analyzed. The overall aerodynamic design and performance of an aero-space plane are discussed in terms of the forebody, scramjet, and afterbody. Other subjects considered in the study are combustion/nozzle optimization, the idealized tip-to-tail waverider model, and the two-dimensional minimum length nozzle. Charts and graphs are provided to show the results of the preliminary investigations.

  6. Dynamic finite element model validation of an assembled aero-engine casing

    NASA Astrophysics Data System (ADS)

    Huang, Zi; Zang, Chaoping; Jiang, Yuying; Wang, Xiaowei

    2016-09-01

    Structural dynamic model updating and validation of an aero-engine casing is critical to the design and development of an aircraft engine. It helps to identify the dynamic characteristics and reduce the response of the aero-engine. The modelling and parameter identification of joint are extremely difficult and important in structural dynamic analysis of the assembled aero-engine casing. In this paper, dynamic model validation technique was applied to update and validate the finite element model of an assembled aero-engine casing. First, modal test of individual casings and the assembled casing was performed by using the traditional acceleration sensors and a hammer. The modal frequencies and mode shapes were obtained by modal analysis tools. Second, the Inverse Eigen-sensitivity Method was used to correct frequency errors and MAC values of correlated mode pairs in the individual components to obtain validated models. Last, the bolt joints of two aero-engine casings were modelled by thin layer of shell elements. The material parameters or element properties of the thin-layer contact elements were updated to obtain reliable connection parameters. The results show that the errors of natural frequencies between the validated FE model of an assembled aero-engine casing and test data are within 7%, and the MAC values of main modes are above 70%, which can verify the feasibility and effectiveness of this approach.

  7. Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

    NASA Technical Reports Server (NTRS)

    Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

    2008-01-01

    Under the NASA Fundamental Aeronautics Program, the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero-Propulso-Servo-Elastic model and for propulsion efficiency studies.

  8. Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

    NASA Technical Reports Server (NTRS)

    Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

    2010-01-01

    Under the NASA Fundamental Aeronautics Program the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero-Propulso-Servo-Elastic model and for propulsion efficiency studies.

  9. Phoneutria nigriventer omega-phonetoxin IIA blocks the Cav2 family of calcium channels and interacts with omega-conotoxin-binding sites.

    PubMed

    Dos Santos, Raquel Gouvea; Van Renterghem, Catherine; Martin-Moutot, Nicole; Mansuelle, Pascal; Cordeiro, Marta N; Diniz, Carlos Ribeiro; Mori, Yasuo; De Lima, Maria Elena; Seagar, Michael

    2002-04-19

    omega-Phonetoxin IIA (omegaPtxIIA), a peptide from spider venom (Phoneutria nigriventer), inhibits high threshold voltage-dependent calcium currents in neurons. To define its pharmacological specificity, we have used patch-clamp methods in cell lines expressing recombinant Ca(v)2.1, Ca(v)2.2, and Ca(v)2.3 channels (P/Q-, N-, and R-type currents, respectively). Calcium currents generated by Ca(v)2.1 and Ca(v)2.2 were blocked almost irreversibly by 3 nm omegaPtxIIA, whereas Ca(v)2.3 showed partial and readily reversible inhibition. Binding assays with mono[(125)I]iodo-omegaPtxIIA indicated that membranes expressing recombinant Ca(v)2.1 or Ca(v)2.2 channels showed a single class of sites with similar affinity (K(D) approximately 50 pm), whereas low affinity interactions were detectable with Ca(v)2.3. Kinetic, saturation, and displacement assays demonstrated that rat brain synaptosomes displayed multiple classes of binding sites for (125)I-omegaPtxIIA. High affinity binding of (125)I-omegaPtxIIA was totally displaced by omegaPtxIIA (K(i) = 100 pm), but only partially by omega-conotoxin GVIA (25% inhibition) and omega-conotoxin MVIIC (50% inhibition at 0.3 microm). (125)I-omegaPtxIIA thus defines a unique high affinity binding site that is predominantly associated with Ca(v)2.1 or Ca(v)2.2 channels.

  10. Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice.

    PubMed

    Han, Jung Woo; Lee, Young Ho; Yoen, Su-In; Abramowitz, Joel; Birnbaumer, Lutz; Lee, Min Goo; Kim, Joo Young

    2016-10-01

    Sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) reprograms cardiovascular cell fate, leading to cellular hypertrophy via Ca(2+)-calmodulin/calcineurin (Cn)/NFAT activation. Accumulating evidence suggests that transient receptor potential canonical (Trpc) channels play important roles in the development of pathologic cardiac hypertrophy. Here, we demonstrated that Trpc3 mediates pathologic cardiac hypertrophy in neurohumoral elevation via direct regulation of CaV1.2 expressions. Elevated PE (phenylephrine) was maintained in mice by continuous infusion using an osmotic pump. Wild-type (WT) mice, but not Trpc3 (-/-) showed a sudden decrease in blood pressure (BP) or death following elevation of BP under conditions of elevated PE. Trpc3 (-/-) mesenteric artery showed decreased PE-stimulated vasoconstriction. Analysis of morphology, function, and pathologic marker expression revealed that PE elevation caused pathologic cardiac hypertrophy in WT mice, which was prevented by deletion of Trpc3. Interestingly, protection by Trpc3 deletion seemed to be a result of reduced cardiac CaV1.2 expressions. Basal and PE induced increased expression of protein and mRNA of CaV1.2 was decreased in Trpc3 (-/-) heart. Accordingly, altered expression of CaV1.2 was observed by knockdown or stimulation of Trpc3 in cardiomyocytes. These findings suggest that Trpc3 is a mediator of pathologic cardiac hypertrophy not only through mediating part of the Ca(2+) influx, but also through control of CaV1.2 expressions.

  11. Molecular and biophysical basis of glutamate and trace metal modulation of voltage-gated Cav2.3 calcium channels

    PubMed Central

    Vitko, Iuliia; Lazarenko, Roman M.; Orestes, Peihan; Todorovic, Slobodan M.

    2012-01-01

    Here, we describe a new mechanism by which glutamate (Glu) and trace metals reciprocally modulate activity of the Cav2.3 channel by profoundly shifting its voltage-dependent gating. We show that zinc and copper, at physiologically relevant concentrations, occupy an extracellular binding site on the surface of Cav2.3 and hold the threshold for activation of these channels in a depolarized voltage range. Abolishing this binding by chelation or the substitution of key amino acid residues in IS1–IS2 (H111) and IS2–IS3 (H179 and H183) loops potentiates Cav2.3 by shifting the voltage dependence of activation toward more negative membrane potentials. We demonstrate that copper regulates the voltage dependence of Cav2.3 by affecting gating charge movements. Thus, in the presence of copper, gating charges transition into the “ON” position slower, delaying activation and reducing the voltage sensitivity of the channel. Overall, our results suggest a new mechanism by which Glu and trace metals transiently modulate voltage-dependent gating of Cav2.3, potentially affecting synaptic transmission and plasticity in the brain. PMID:22371363

  12. Lipid Modulation of Calcium Flux through CaV2.3 Regulates Acrosome Exocytosis and Fertilization

    PubMed Central

    Cohen, Roy; Buttke, Danielle E.; Asano, Atsushi; Mukai, Chinatsu; Nelson, Jacquelyn L.; Ren, Dongjun; Miller, Richard; Cohen-Kutner, Moshe; Atlas, Daphne; Travis, Alexander J.

    2014-01-01

    Summary Membrane lipid regulation of cell function is poorly understood. In early development, sterol efflux and the ganglioside GM1 regulate sperm acrosome exocytosis (AE) and fertilization competence through unknown mechanisms. Here, we show that sterol efflux and focal enrichment of GM1 trigger Ca2+ influx necessary for AE through CaV2.3, whose activity has been highly controversial in sperm. Sperm lacking CaV2.3’s pore-forming α1E subunit showed altered Ca2+ responses, reduced AE, and a strong sub-fertility phenotype. Surprisingly, AE depended on spatio-temporal information encoded by flux through CaV2.3—not merely the presence/ amplitude of Ca2+ waves. Using both studies in sperm and voltage clamp of Xenopus oocytes, we define a molecular mechanism for GM1/CaV2.3 regulatory interaction, requiring GM1’s lipid and sugar components and CaV2.3’s α1E and α2δ subunits. Our results provide mechanistic understanding of membrane lipid regulation of Ca2+ flux and therefore Ca2+-dependent cellular and developmental processes such as exocytosis and fertilization. PMID:24525187

  13. Cav1.3 (CACNA1D) L‐type Ca2+ channel dysfunction in CNS disorders

    PubMed Central

    Striessnig, Jörg

    2016-01-01

    Abstract Cav1.3 belongs to the family of voltage‐gated L‐type Ca2+ channels and is encoded by the CACNA1D gene. Cav1.3 channels are not only essential for cardiac pacemaking, hearing and hormone secretion but are also expressed postsynaptically in neurons, where they shape neuronal firing and plasticity. Recent findings provide evidence that human mutations in the CACNA1D gene can confer risk for the development of neuropsychiatric disease and perhaps also epilepsy. Loss of Cav1.3 function, as shown in knock‐out mouse models and by human mutations, does not result in neuropsychiatric or neurological disease symptoms, whereas their acute selective pharmacological activation results in a depressive‐like behaviour in mice. Therefore it is likely that CACNA1D mutations enhancing activity may be disease relevant also in humans. Indeed, whole exome sequencing studies, originally prompted to identify mutations in primary aldosteronism, revealed de novo CACNA1D missense mutations permitting enhanced Ca2+ signalling through Cav1.3. Remarkably, apart from primary aldosteronism, heterozygous carriers of these mutations also showed seizures and neurological abnormalities. Different missense mutations with very similar gain‐of‐function properties were recently reported in patients with autism spectrum disorders (ASD). These data strongly suggest that CACNA1D mutations enhancing Cav1.3 activity confer a strong risk for – or even cause – CNS disorders, such as ASD. PMID:26842699

  14. The L-Type voltage-gated calcium channel Cav1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice.

    PubMed

    McKinney, Brandon C; Murphy, Geoffrey G

    2006-01-01

    Using pharmacological techniques, it has been demonstrated that both consolidation and extinction of Pavlovian fear conditioning are dependent to some extent upon L-type voltage-gated calcium channels (LVGCCs). Although these studies have successfully implicated LVGCCs in Pavlovian fear conditioning, they do not provide information about the specific LVGCC isoform involved. Both of the major LVGCC subtypes found in the brain (Cav1.2 and Cav1.3) are targets of the pharmacological manipulations used in earlier work. In this study, we used mice in which the gene for the pore-forming subunit (alpha1D) Cav1.3 was deleted (Cav1.3 knockout mice) to elucidate its contribution to consolidation and extinction of conditioned fear. We find that Cav1.3 knockout mice exhibit significant impairments in consolidation of contextual fear conditioning. However, once sufficiently overtrained, the Cav1.3 knockout mice exhibit rates of extinction that are identical to that observed in wild-type mice. We also find that Cav1.3 knockout mice perform as well as wild-type mice on the hidden platform version of the Morris water maze, suggesting that the consolidation deficit in conditioned fear observed in the Cav1.3 knockout mice is not likely the result of an inability to encode the context, but may reflect an inability to make the association between the context and the unconditioned stimulus.

  15. Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II

    PubMed Central

    Jenkins, Meagan A.; Christel, Carl J.; Jiao, Yuxia; Abiria, Sunday; Kim, Kristin Y.; Usachev, Yuriy M.; Obermair, Gerald J.; Colbran, Roger J.; Lee, Amy

    2010-01-01

    Cav1 (L-type) channels and calmodulin-dependent protein kinase II (CaMKII) are key regulators of Ca2+ signaling in neurons. CaMKII directly potentiates the activity of Cav1.2 and Cav1.3 channels, but the underlying molecular mechanisms are incompletely understood. Here, we report that the CaMKII-associated protein, densin, is required for Ca2+-dependent facilitation of Cav1.3 channels. While neither CaMKII nor densin independently affect Cav1.3 properties in transfected HEK293T cells, the two together augment Cav1.3 Ca2+ currents during repetitive, but not sustained, depolarizing stimuli. Facilitation requires Ca2+, CaMKII activation and its association with densin, as well as densin binding to the Cav1.3 α1 subunit C-terminal domain. Cav1.3 channels and densin are targeted to dendritic spines in neurons and form a complex with CaMKII in the brain. Our results demonstrate a novel mechanism for Ca2+-dependent facilitation that may intensify postsynaptic Ca2+ signals during high-frequency stimulation. PMID:20392935

  16. Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy.

    PubMed

    Shi, Yin; Tan, Shi-Hao; Ng, Shukie; Zhou, Jing; Yang, Na-Di; Koo, Gi-Bang; McMahon, Kerrie-Ann; Parton, Robert G; Hill, Michelle M; Del Pozo, Miguel A; Kim, You-Sun; Shen, Han-Ming

    2015-01-01

    CAV1 (caveolin 1, caveolae protein, 22kDa) is well known as a principal scaffolding protein of caveolae, a specialized plasma membrane structure. Relatively, the caveolae-independent function of CAV1 is less studied. Autophagy is a process known to involve various membrane structures, including autophagosomes, lysosomes, and autolysosomes for degradation of intracellular proteins and organelles. Currently, the function of CAV1 in autophagy remains largely elusive. In this study, we demonstrate for the first time that CAV1 deficiency promotes both basal and inducible autophagy. Interestingly, the promoting effect was found mainly in the late stage of autophagy via enhancing lysosomal function and autophagosome-lysosome fusion. Notably, the regulatory function of CAV1 in lysosome and autophagy was found to be caveolae-independent, and acts through lipid rafts. Furthermore, the elevated autophagy level induced by CAV1 deficiency serves as a cell survival mechanism under starvation. Importantly, downregulation of CAV1 and enhanced autophagy level were observed in human breast cancer cells and tissues. Taken together, our data reveal a novel function of CAV1 and lipid rafts in breast cancer development via modulation of lysosomal function and autophagy.

  17. Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy

    PubMed Central

    Shi, Yin; Tan, Shi-Hao; Ng, Shukie; Zhou, Jing; Yang, Na-Di; Koo, Gi-Bang; McMahon, Kerrie-Ann; Parton, Robert G; Hill, Michelle M; del Pozo, Miguel A; Kim, You-Sun; Shen, Han-Ming

    2015-01-01

    CAV1 (caveolin 1, caveolae protein, 22kDa) is well known as a principal scaffolding protein of caveolae, a specialized plasma membrane structure. Relatively, the caveolae-independent function of CAV1 is less studied. Autophagy is a process known to involve various membrane structures, including autophagosomes, lysosomes, and autolysosomes for degradation of intracellular proteins and organelles. Currently, the function of CAV1 in autophagy remains largely elusive. In this study, we demonstrate for the first time that CAV1 deficiency promotes both basal and inducible autophagy. Interestingly, the promoting effect was found mainly in the late stage of autophagy via enhancing lysosomal function and autophagosome-lysosome fusion. Notably, the regulatory function of CAV1 in lysosome and autophagy was found to be caveolae-independent, and acts through lipid rafts. Furthermore, the elevated autophagy level induced by CAV1 deficiency serves as a cell survival mechanism under starvation. Importantly, downregulation of CAV1 and enhanced autophagy level were observed in human breast cancer cells and tissues. Taken together, our data reveal a novel function of CAV1 and lipid rafts in breast cancer development via modulation of lysosomal function and autophagy. PMID:25945613

  18. Alternative splicing in the C-terminus of CaV2.2 controls expression and gating of N-type calcium channels

    PubMed Central

    Castiglioni, Andrew J; Raingo, Jesica; Lipscombe, Diane

    2006-01-01

    N-type CaV2.2 calcium channels localize to presynaptic nerve terminals of nociceptors where they control neurotransmitter release. Nociceptive neurons express a unique set of ion channels and receptors important for optimizing their role in transmission of noxious stimuli. Included among these is a structurally and functionally distinct N-type calcium channel splice isoform, CaV2.2e[37a], expressed in a subset of nociceptors and with limited expression in other parts of the nervous system. CaV2.2[e37a] arises from the mutually exclusive replacement of e37a for e37b in the C-terminus of CaV2.2 mRNA. N-type current densities in nociceptors that express a combination of CaV2.2e[37a] and CaV2.2e[37b] mRNAs are significantly larger compared to cells that express only CaV2.2e[37b]. Here we show that e37a supports increased expression of functional N-type channels and an increase in channel open time as compared to CaV2.2 channels that contain e37b. To understand how e37a affects N-type currents we compared macroscopic and single-channel ionic currents as well as gating currents in tsA201 cells expressing CaV2.2e[37a] and CaV2.2e[37b]. When activated, CaV2.2e[37a] channels remain open for longer and are expressed at higher density than CaV2.2e[37b] channels. These unique features of the CaV2.2e[37a] isoform combine to augment substantially the amount of calcium that enters cells in response to action potentials. Our studies of the e37a/e37b splice site reveal a multifunctional domain in the C-terminus of CaV2.2 that regulates the overall activity of N-type calcium channels in nociceptors. PMID:16857708

  19. Dynamic performance of an aero-assist spacecraft - AFE

    NASA Technical Reports Server (NTRS)

    Chang, Ho-Pen; French, Raymond A.

    1992-01-01

    Dynamic performance of the Aero-assist Flight Experiment (AFE) spacecraft was investigated using a high-fidelity 6-DOF simulation model. Baseline guidance logic, control logic, and a strapdown navigation system to be used on the AFE spacecraft are also modeled in the 6-DOF simulation. During the AFE mission, uncertainties in the environment and the spacecraft are described by an error space which includes both correlated and uncorrelated error sources. The principal error sources modeled in this study include navigation errors, initial state vector errors, atmospheric variations, aerodynamic uncertainties, center-of-gravity off-sets, and weight uncertainties. The impact of the perturbations on the spacecraft performance is investigated using Monte Carlo repetitive statistical techniques. During the Solid Rocket Motor (SRM) deorbit phase, a target flight path angle of -4.76 deg at entry interface (EI) offers very high probability of avoiding SRM casing skip-out from the atmosphere. Generally speaking, the baseline designs of the guidance, navigation, and control systems satisfy most of the science and mission requirements.

  20. Multidisciplinary Design Optimization on Conceptual Design of Aero-engine

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao-bo; Wang, Zhan-xue; Zhou, Li; Liu, Zeng-wen

    2016-06-01

    In order to obtain better integrated performance of aero-engine during the conceptual design stage, multiple disciplines such as aerodynamics, structure, weight, and aircraft mission are required. Unfortunately, the couplings between these disciplines make it difficult to model or solve by conventional method. MDO (Multidisciplinary Design Optimization) methodology which can well deal with couplings of disciplines is considered to solve this coupled problem. Approximation method, optimization method, coordination method, and modeling method for MDO framework are deeply analyzed. For obtaining the more efficient MDO framework, an improved CSSO (Concurrent Subspace Optimization) strategy which is based on DOE (Design Of Experiment) and RSM (Response Surface Model) methods is proposed in this paper; and an improved DE (Differential Evolution) algorithm is recommended to solve the system-level and discipline-level optimization problems in MDO framework. The improved CSSO strategy and DE algorithm are evaluated by utilizing the numerical test problem. The result shows that the efficiency of improved methods proposed by this paper is significantly increased. The coupled problem of VCE (Variable Cycle Engine) conceptual design is solved by utilizing improved CSSO strategy, and the design parameter given by improved CSSO strategy is better than the original one. The integrated performance of VCE is significantly improved.

  1. High-order parabolic beam approximation for aero-optics

    SciTech Connect

    White, Michael D.

    2010-08-01

    The parabolic beam equations are solved using high-order compact differences for the Laplacians and Runge-Kutta integration along the beam path. The solution method is verified by comparison to analytical solutions for apertured beams and both constant and complex index of refraction. An adaptive 4th-order Runge-Kutta using an embedded 2nd-order method is presented that has demonstrated itself to be very robust. For apertured beams, the results show that the method fails to capture near aperture effects due to a violation of the paraxial approximation in that region. Initial results indicate that the problem appears to be correctable by successive approximations. A preliminary assessment of the effect of turbulent scales is undertaken using high-order Lagrangian interpolation. The results show that while high fidelity methods are necessary to accurately capture the large scale flow structure, the method may not require the same level of fidelity in sampling the density for the index of refraction. The solution is used to calculate a phase difference that is directly compared with that commonly calculated via the optical path difference. Propagation through a supersonic boundary layer shows that for longer wavelengths, the traditional method to calculate the optical path is less accurate than for shorter wavelengths. While unlikely to supplant more traditional methods for most aero-optics applications, the current method can be used to give a quantitative assessment of the other methods as well as being amenable to the addition of more physics.

  2. Commercial Modular Aero-Propulsion System Simulation 40k

    NASA Technical Reports Server (NTRS)

    Guo, Ten-Huei; Lavelle, Thomas; Litt, Jonathan; Csank, Jeffrey; May, Ryan

    2011-01-01

    The Commercial Modular Aero-Propulsion System Simulation 40k (CMAPSS40k) software package is a nonlinear dynamic simulation of a 40,000-pound (approximately equals 178-kN) thrust class commercial turbofan engine, written in the MATLAB/Simulink environment. The model has been tuned to capture the behavior of flight test data, and is capable of running at any point in the flight envelope [up to 40,000 ft (approximately equals 12,200 m) and Mach 0.8]. In addition to the open-loop engine, the simulation includes a controller whose architecture is representative of that found in industry. C-MAPSS40k fills the need for an easy-to-use, realistic, transient simulation of a medium-size commercial turbofan engine with a representative controller. It is a detailed component level model (CLM) written in the industry-standard graphical MATLAB/Simulink environment to allow for easy modification and portability. At the time of this reporting, no other such model exists in the public domain.

  3. Aberrant Splicing Promotes Proteasomal Degradation of L-type CaV1.2 Calcium Channels by Competitive Binding for CaVβ Subunits in Cardiac Hypertrophy

    PubMed Central

    Hu, Zhenyu; Wang, Jiong-Wei; Yu, Dejie; Soon, Jia Lin; de Kleijn, Dominique P. V.; Foo, Roger; Liao, Ping; Colecraft, Henry M.; Soong, Tuck Wah

    2016-01-01

    Decreased expression and activity of CaV1.2 calcium channels has been reported in pressure overload-induced cardiac hypertrophy and heart failure. However, the underlying mechanisms remain unknown. Here we identified in rodents a splice variant of CaV1.2 channel, named CaV1.2e21+22, that contained the pair of mutually exclusive exons 21 and 22. This variant was highly expressed in neonatal hearts. The abundance of this variant was gradually increased by 12.5-folds within 14 days of transverse aortic banding that induced cardiac hypertrophy in adult mouse hearts and was also elevated in left ventricles from patients with dilated cardiomyopathy. Although this variant did not conduct Ca2+ ions, it reduced the cell-surface expression of wild-type CaV1.2 channels and consequently decreased the whole-cell Ca2+ influx via the CaV1.2 channels. In addition, the CaV1.2e21+22 variant interacted with CaVβ subunits significantly more than wild-type CaV1.2 channels, and competition of CaVβ subunits by CaV1.2e21+22 consequently enhanced ubiquitination and subsequent proteasomal degradation of the wild-type CaV1.2 channels. Our findings show that the resurgence of a specific neonatal splice variant of CaV1.2 channels in adult heart under stress may contribute to heart failure. PMID:27731386

  4. Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Ca(v)3.3 channels.

    PubMed

    Joksovic, Pavle M; Brimelow, Barbara C; Murbartián, Janet; Perez-Reyes, Edward; Todorovic, Slobodan M

    2005-01-01

    Reticular thalamocortical neurons express a slowly inactivating T-type Ca(2+) current that is quite similar to that recorded from recombinant Ca(v)3.3b (alpha1Ib) channels. These neurons also express abundant Ca(v)3.3 mRNA, suggesting that it underlies the native current. Here, we test this hypothesis by comparing the anesthetic sensitivities of recombinant Ca(v)3.3b channels stably expressed in HEK 293 cells to native T channels in reticular thalamic neurons (nRT) from brain slices of young rats. Barbiturates completely blocked both Ca(v)3.3 and nRT currents, with pentobarbital being about twice more potent in blocking Ca(v)3.3 currents. Isoflurane had about the same potency in blocking Ca(v)3.3 and nRT currents, but enflurane, etomidate, propofol, and ethanol exhibited 2-4 fold higher potency in blocking nRT vs Ca(v)3.3 currents. Nitrous oxide (N(2)O; laughing gas) blocked completely nRT currents with IC(50) of 20%, but did not significantly affect Ca(v)3.3 currents at four-fold higher concentrations. In addition, we observed that in lower concentration, N(2)O reversibly increased nRT but not Ca(v)3.3 currents. In conclusion, contrasting anesthetic sensitivities of Ca(v)3.3 and nRT T-type Ca(2+) channels strongly suggest that different molecular structures of Ca(2+) channels give rise to slowly inactivating T-type Ca(2+) currents. Furthermore, effects of volatile anesthetics and ethanol on slowly inactivating T-type Ca(2+) channel variants may contribute to the clinical effects of these agents. PMID:15644869

  5. Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness.

    PubMed

    Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R

    2015-06-23

    In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca(2+) channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states.

  6. CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

    PubMed

    Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

    2010-05-01

    Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

  7. Optimal guidance of aero-assisted transfer vehicles based on matched asymptotic expansions

    NASA Astrophysics Data System (ADS)

    Calise, A. J.; Melamed, N.

    This paper addresses a number of issues related to the matched asymptotic expansions analysis of skip trajectories, or any class of problems that give rise to inner layers that are not associated directly with satisfying boundary conditions. The procedure for matching inner and outer solutions, and using the composite solution to satisfy boundary conditions is rigorously followed in developing a complete algebraic solution to the problem of inclination change with minimum energy loss. Repeated solution of these algebraic equations along the trajectory, treating each current state as an initial state, constitute a feedback guidance algorithm.

  8. Taking advantage of surface proximity effects with aero-marine vehicles

    NASA Astrophysics Data System (ADS)

    Trillo, Robert L.

    A comprehensive account is given of the operational characteristics and limiting operational conditions of 'wing-in-ground' surface effect marine aircraft. It is emphasized that operation must be restricted to the calmest of river and lake waters, not merely for the sake of safety margin enhancement but for the maximization of air cushion effect efficiency, and its consequent economic benefits. Quietness of operation in these environments is also essential, strongly recommending reliance on shrouded propellers as the primary means of propulsion.

  9. Spatial-temporal-covariance-based modeling, analysis, and simulation of aero-optics wavefront aberrations.

    PubMed

    Vogel, Curtis R; Tyler, Glenn A; Wittich, Donald J

    2014-07-01

    We introduce a framework for modeling, analysis, and simulation of aero-optics wavefront aberrations that is based on spatial-temporal covariance matrices extracted from wavefront sensor measurements. Within this framework, we present a quasi-homogeneous structure function to analyze nonhomogeneous, mildly anisotropic spatial random processes, and we use this structure function to show that phase aberrations arising in aero-optics are, for an important range of operating parameters, locally Kolmogorov. This strongly suggests that the d5/3 power law for adaptive optics (AO) deformable mirror fitting error, where d denotes actuator separation, holds for certain important aero-optics scenarios. This framework also allows us to compute bounds on AO servo lag error and predictive control error. In addition, it provides us with the means to accurately simulate AO systems for the mitigation of aero-effects, and it may provide insight into underlying physical processes associated with turbulent flow. The techniques introduced here are demonstrated using data obtained from the Airborne Aero-Optics Laboratory.

  10. Aero-Thermal Calibration of the NASA Glenn Icing Research Tunnel (2012 Test)

    NASA Technical Reports Server (NTRS)

    Pastor-Barsi, Christine M.; Arrington, E. Allen; VanZante, Judith Foss

    2012-01-01

    A major modification of the refrigeration plant and heat exchanger at the NASA Glenn Icing Research Tunnel (IRT) occurred in autumn of 2011. It is standard practice at NASA Glenn to perform a full aero-thermal calibration of the test section of a wind tunnel facility upon completion of major modifications. This paper will discuss the tools and techniques used to complete an aero-thermal calibration of the IRT and the results that were acquired. The goal of this test entry was to complete a flow quality survey and aero-thermal calibration measurements in the test section of the IRT. Test hardware that was used includes the 2D Resistive Temperature Detector (RTD) array, 9-ft pressure survey rake, hot wire survey rake, and the quick check survey rake. This test hardware provides a map of the velocity, Mach number, total and static pressure, total temperature, flow angle and turbulence intensity. The data acquired were then reduced to examine pressure, temperature, velocity, flow angle, and turbulence intensity. Reduced data has been evaluated to assess how the facility meets flow quality goals. No icing conditions were tested as part of the aero-thermal calibration. However, the effects of the spray bar air injections on the flow quality and aero-thermal calibration measurements were examined as part of this calibration.

  11. Observation and analysis of aero-optic effects on the ORCA laser communication system

    NASA Astrophysics Data System (ADS)

    Wayne, David T.; Phillips, Ronald L.; Andrews, Larry C.; Leclerc, Troy; Sauer, Paul

    2011-06-01

    In this paper we show evidence of aero-optic effects on the measured beacon beam as the gimbal angle of a nosemounted turret changes from 0 to 90 degrees and greater with respect to the line of flight. Data from the beacon beam was collected with a new technology 3-aperture scintillometer over a 82km to 104km air-to-ground downlink during field testing of the ORCA system in Nevada in May 2009. In this paper we present data analysis on the impact of an aero-optic boundary layer on a laser link between an aircraft and a ground-based stationary node. Particularly we look at the impact of an aero-optic boundary layer on the mean, variance, scintillation, probability density function (PDF), power spectral density (PSD), and fading of the received irradiance. We find that the most compelling argument for the presence of strong aero-optic effects comes from calculating the PSD of the received beacon intensity. We also find the cumulative effect of the aero-optic boundary layer differs depending on the transmitted beam parameters, i.e. collimated or divergent.

  12. Spatial-temporal-covariance-based modeling, analysis, and simulation of aero-optics wavefront aberrations.

    PubMed

    Vogel, Curtis R; Tyler, Glenn A; Wittich, Donald J

    2014-07-01

    We introduce a framework for modeling, analysis, and simulation of aero-optics wavefront aberrations that is based on spatial-temporal covariance matrices extracted from wavefront sensor measurements. Within this framework, we present a quasi-homogeneous structure function to analyze nonhomogeneous, mildly anisotropic spatial random processes, and we use this structure function to show that phase aberrations arising in aero-optics are, for an important range of operating parameters, locally Kolmogorov. This strongly suggests that the d5/3 power law for adaptive optics (AO) deformable mirror fitting error, where d denotes actuator separation, holds for certain important aero-optics scenarios. This framework also allows us to compute bounds on AO servo lag error and predictive control error. In addition, it provides us with the means to accurately simulate AO systems for the mitigation of aero-effects, and it may provide insight into underlying physical processes associated with turbulent flow. The techniques introduced here are demonstrated using data obtained from the Airborne Aero-Optics Laboratory. PMID:25121456

  13. Fault Diagnosis of Demountable Disk-Drum Aero-Engine Rotor Using Customized Multiwavelet Method.

    PubMed

    Chen, Jinglong; Wang, Yu; He, Zhengjia; Wang, Xiaodong

    2015-10-23

    The demountable disk-drum aero-engine rotor is an important piece of equipment that greatly impacts the safe operation of aircraft. However, assembly looseness or crack fault has led to several unscheduled breakdowns and serious accidents. Thus, condition monitoring and fault diagnosis technique are required for identifying abnormal conditions. Customized ensemble multiwavelet method for aero-engine rotor condition identification, using measured vibration data, is developed in this paper. First, customized multiwavelet basis function with strong adaptivity is constructed via symmetric multiwavelet lifting scheme. Then vibration signal is processed by customized ensemble multiwavelet transform. Next, normalized information entropy of multiwavelet decomposition coefficients is computed to directly reflect and evaluate the condition. The proposed approach is first applied to fault detection of an experimental aero-engine rotor. Finally, the proposed approach is used in an engineering application, where it successfully identified the crack fault of a demountable disk-drum aero-engine rotor. The results show that the proposed method possesses excellent performance in fault detection of aero-engine rotor. Moreover, the robustness of the multiwavelet method against noise is also tested and verified by simulation and field experiments.

  14. Fault Diagnosis of Demountable Disk-Drum Aero-Engine Rotor Using Customized Multiwavelet Method

    PubMed Central

    Chen, Jinglong; Wang, Yu; He, Zhengjia; Wang, Xiaodong

    2015-01-01

    The demountable disk-drum aero-engine rotor is an important piece of equipment that greatly impacts the safe operation of aircraft. However, assembly looseness or crack fault has led to several unscheduled breakdowns and serious accidents. Thus, condition monitoring and fault diagnosis technique are required for identifying abnormal conditions. Customized ensemble multiwavelet method for aero-engine rotor condition identification, using measured vibration data, is developed in this paper. First, customized multiwavelet basis function with strong adaptivity is constructed via symmetric multiwavelet lifting scheme. Then vibration signal is processed by customized ensemble multiwavelet transform. Next, normalized information entropy of multiwavelet decomposition coefficients is computed to directly reflect and evaluate the condition. The proposed approach is first applied to fault detection of an experimental aero-engine rotor. Finally, the proposed approach is used in an engineering application, where it successfully identified the crack fault of a demountable disk-drum aero-engine rotor. The results show that the proposed method possesses excellent performance in fault detection of aero-engine rotor. Moreover, the robustness of the multiwavelet method against noise is also tested and verified by simulation and field experiments. PMID:26512668

  15. Fault Diagnosis of Demountable Disk-Drum Aero-Engine Rotor Using Customized Multiwavelet Method.

    PubMed

    Chen, Jinglong; Wang, Yu; He, Zhengjia; Wang, Xiaodong

    2015-01-01

    The demountable disk-drum aero-engine rotor is an important piece of equipment that greatly impacts the safe operation of aircraft. However, assembly looseness or crack fault has led to several unscheduled breakdowns and serious accidents. Thus, condition monitoring and fault diagnosis technique are required for identifying abnormal conditions. Customized ensemble multiwavelet method for aero-engine rotor condition identification, using measured vibration data, is developed in this paper. First, customized multiwavelet basis function with strong adaptivity is constructed via symmetric multiwavelet lifting scheme. Then vibration signal is processed by customized ensemble multiwavelet transform. Next, normalized information entropy of multiwavelet decomposition coefficients is computed to directly reflect and evaluate the condition. The proposed approach is first applied to fault detection of an experimental aero-engine rotor. Finally, the proposed approach is used in an engineering application, where it successfully identified the crack fault of a demountable disk-drum aero-engine rotor. The results show that the proposed method possesses excellent performance in fault detection of aero-engine rotor. Moreover, the robustness of the multiwavelet method against noise is also tested and verified by simulation and field experiments. PMID:26512668

  16. Fueling the National Aero-Space Plane with slush hydrogen

    NASA Technical Reports Server (NTRS)

    Hannum, Ned P.; Berkopec, Frank D.

    1989-01-01

    The National Aerospace Plane is a horizontal take off and landing, single stage-to-orbit vehicle using hydrogen as the fuel. The first flights are planned for the mid 1990s. The high heating value, cooling capacity, and combustion properties make hydrogen the fuel of choice, but the low density results in a large vehicle. Both the fuel cooling capacity and density are increased with the use of slush hydrogen and result in significant reductions in size of the vehicle. A national program to advance this technology and to find engineering solutions to the many design issues is now underway.

  17. The use of C(av) rather than AUC in safety assessment.

    PubMed

    Smith, D A; Morgan, P; Vogel, W M; Walker, D K

    2010-06-01

    Toxicokinetic data have traditionally been presented as maximum observed plasma concentrations (C(max)) and area under the concentration time curve (AUC) values. These values have been used to compare exposures across studies and species to provide valuable interpretation of drug safety data. Increasingly, questions are asked of toxicology studies to more accurately describe the concentration effect relationships in terms of compound affinity for target and off-target receptors. C(max) values can immediately be referenced to known pharmacological activities, particularly when the extent of plasma protein binding is taken into account. This provides a measure of the more pharmacologically relevant free drug exposure. AUC values on the other hand contain the component of time, which means that direct comparison to pharmacological activity values are not immediately possible. Conversion of AUC to average plasma concentration (C(av)) provides a simple and convenient means to allow such a comparison without losing any information imparted by AUC values. In this paper, the benefit and advantage of applying C(av) values is illustrated using examples taken from the literature.

  18. The use of C(av) rather than AUC in safety assessment.

    PubMed

    Smith, D A; Morgan, P; Vogel, W M; Walker, D K

    2010-06-01

    Toxicokinetic data have traditionally been presented as maximum observed plasma concentrations (C(max)) and area under the concentration time curve (AUC) values. These values have been used to compare exposures across studies and species to provide valuable interpretation of drug safety data. Increasingly, questions are asked of toxicology studies to more accurately describe the concentration effect relationships in terms of compound affinity for target and off-target receptors. C(max) values can immediately be referenced to known pharmacological activities, particularly when the extent of plasma protein binding is taken into account. This provides a measure of the more pharmacologically relevant free drug exposure. AUC values on the other hand contain the component of time, which means that direct comparison to pharmacological activity values are not immediately possible. Conversion of AUC to average plasma concentration (C(av)) provides a simple and convenient means to allow such a comparison without losing any information imparted by AUC values. In this paper, the benefit and advantage of applying C(av) values is illustrated using examples taken from the literature. PMID:20074607

  19. [Gene cloning and sequencing of chicken anemia virus(CAV) isolated from Harbin].

    PubMed

    He, Chengqing; Ding, Naizheng; Li, Jingpeng; Li, Yunlong

    2002-08-01

    A Chicken anemia virus has been isolated from a chicken flock in Harbin of China. The genome of the ivrus was cloned through polymerase chain reaction(PCR) and sequence of the genome was analyzed. The cycle genome is made of 2298 base pairs including three overlapping open reading frames(vp1, vp2, vp3) and a regulative region. Comparing sequence of the genome through BLAST in GenBank, this sequence exhibits 96.9% identity with other genome of CA Vs and least. Multiple alignment of this genome of this virus, 26p4, strain isolated in Germany, strain isolated in Malaysia and Cux-1 found that this sequence exhibits 98.2% (42/2298), 98.2% (42/2298), 96.9% (72/2298) and 97.5% (60/2319) identify with them, respectively. A new CAV strain was isolated and it has better identify with CAV isolated in Europe countries than is Asia country Malaysia. Multiple alignment of VP1, VP2, VP3 of 26p4, strain isolated in Germany, strain isolated in Malaysia, Cux-1 and strain isolated in Harbin of China found the VP2 the most conservative.

  20. Orbital transfer vehicle - An overview

    NASA Astrophysics Data System (ADS)

    Caluori, V. A.; Saxton, D. R.

    1981-05-01

    A summary is given of the concept definition phase of NASA's Orbital Transfer Vehicle (OTV) program. The mission requirements are threefold: (1) the ability to deliver payloads well beyond the capability of any current system at low acceleration levels, (2) the extension of the cost effectiveness from reusability and operational flexibility provided by the Shuttle at LEO to the geosynchronous altitude, and (3) the provision of the round trip capability needed to service and maintain this expanded and more valuable resource at GEO. The initial Shuttle-matched, reusable OTV is shown to be cost effective with low development cost, relatively short development period and high projected reliability. The performance enhancement provided by aero-assist is discussed, which will enable the difficult round trip to be flown in a single Shuttle launch. Two methods of reducing vehicle velocity are available: (1) aeromaneuvering, which uses vehicle lift to climb or descend and thereby correct for density variations, and (2) aerobraking which varies vehicle drag directly to correct for density.

  1. 75 FR 43101 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will... fuel heater was due to chafing with an oil cooling system hose. PIAGGIO AERO INDUSTIRES (PAI) issued... system hose. Piaggio Aero Industries (PAI) issued Service Bulletin (SB) 80- 0175, which was applicable...

  2. AeroMACS C-Band Interference Modeling and Simulation Results

    NASA Technical Reports Server (NTRS)

    Wilson, Jeffrey

    2010-01-01

    A new C-band (5091-5150 MHz) airport communications system designated as Aeronautical Mobile Airport Communications System (AeroMACS) is being planned under the Federal Aviation Administration s NextGen program. It is necessary to establish practical limits on AeroMACS transmission power from airports so that the threshold of interference into the Mobile Satellite Service (Globalstar) feeder uplinks is not exceeded. To help provide guidelines for these limits, interference models have been created with the commercial software Visualyse Professional. In this presentation, simulation results were shown for the aggregate interference power at low earth orbit from AeroMACS transmitters at each of up to 757 airports in the United States, Canada, Mexico, and the surrounding area. Both omni-directional and sectoral antenna configurations were modeled. Effects of antenna height, beamwidth, and tilt were presented.

  3. Frequency-domain Model Matching PID Controller Design for Aero-engine

    NASA Astrophysics Data System (ADS)

    Liu, Nan; Huang, Jinquan; Lu, Feng

    2014-12-01

    The nonlinear model of aero-engine was linearized at multiple operation points by using frequency response method. The validation results indicate high accuracy of static and dynamic characteristics of the linear models. The improved PID tuning method of frequency-domain model matching was proposed with the system stability condition considered. The proposed method was applied to the design of PID controller of the high pressure rotor speed control in the flight envelope, and the control effects were evaluated by the nonlinear model. Simulation results show that the system had quick dynamic response with zero overshoot and zero steadystate error. Furthermore, a PID-fuzzy switching control scheme for aero-engine was designed, and the fuzzy switching system stability was proved. Simulations were studied to validate the applicability of the multiple PIDs fuzzy switching controller for aero-engine with wide range dynamics.

  4. Whole exome sequencing identifies de novo heterozygous CAV1 mutations associated with a novel neonatal onset lipodystrophy syndrome.

    PubMed

    Garg, Abhimanyu; Kircher, Martin; Del Campo, Miguel; Amato, R Stephen; Agarwal, Anil K

    2015-08-01

    Despite remarkable progress in identifying causal genes for many types of genetic lipodystrophies in the last decade, the molecular basis of many extremely rare lipodystrophy patients with distinctive phenotypes remains unclear. We conducted whole exome sequencing of the parents and probands from six pedigrees with neonatal onset of generalized loss of subcutaneous fat with additional distinctive phenotypic features and report de novo heterozygous null mutations, c.424C>T (p.Q142*) and c.479_480delTT (p.F160*), in CAV1 in a 7-year-old male and a 3-year-old female of European origin, respectively. Both the patients had generalized fat loss, thin mottled skin and progeroid features at birth. The male patient had cataracts requiring extraction at age 30 months and the female patient had pulmonary arterial hypertension. Dermal fibroblasts of the female patient revealed negligible CAV1 immunofluorescence staining compared to control but there were no differences in the number and morphology of caveolae upon electron microscopy examination. Based upon the similarities in the clinical features of these two patients, previous reports of CAV1 mutations in patients with lipodystrophies and pulmonary hypertension, and similar features seen in CAV1 null mice, we conclude that these variants are the most likely cause of one subtype of neonatal onset generalized lipodystrophy syndrome.

  5. Pathophysiological implication of CaV3.1 T-type Ca2+ channels in trigeminal neuropathic pain

    PubMed Central

    Choi, Soonwook; Yu, Eunah; Hwang, Eunjin; Llinás, Rodolfo R.

    2016-01-01

    A crucial pathophysiological issue concerning central neuropathic pain is the modification of sensory processing by abnormally increased low-frequency brain rhythms. Here we explore the molecular mechanisms responsible for such abnormal rhythmicity and its relation to neuropathic pain syndrome. Toward this aim, we investigated the behavioral and electrophysiological consequences of trigeminal neuropathic pain following infraorbital nerve ligations in CaV3.1 T-type Ca2+ channel knockout and wild-type mice. CaV3.1 knockout mice had decreased mechanical hypersensitivity and reduced low-frequency rhythms in the primary somatosensory cortex and related thalamic nuclei than wild-type mice. Lateral inhibition of gamma rhythm in primary somatosensory cortex layer 4, reflecting intact sensory contrast, was present in knockout mice but severely impaired in wild-type mice. Moreover, cross-frequency coupling between low-frequency and gamma rhythms, which may serve in sensory processing, was pronounced in wild-type mice but not in CaV3.1 knockout mice. Our results suggest that the presence of CaV3.1 channels is a key element in the pathophysiology of trigeminal neuropathic pain. PMID:26858455

  6. Graded Ca2+/calmodulin-dependent coupling of voltage-gated CaV1.2 channels

    PubMed Central

    Dixon, Rose E; Moreno, Claudia M; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Navedo, Manuel F; Santana, Luis F

    2015-01-01

    In the heart, reliable activation of Ca2+ release from the sarcoplasmic reticulum during the plateau of the ventricular action potential requires synchronous opening of multiple CaV1.2 channels. Yet the mechanisms that coordinate this simultaneous opening during every heartbeat are unclear. Here, we demonstrate that CaV1.2 channels form clusters that undergo dynamic, reciprocal, allosteric interactions. This ‘functional coupling’ facilitates Ca2+ influx by increasing activation of adjoined channels and occurs through C-terminal-to-C-terminal interactions. These interactions are initiated by binding of incoming Ca2+ to calmodulin (CaM) and proceed through Ca2+/CaM binding to the CaV1.2 pre-IQ domain. Coupling fades as [Ca2+]i decreases, but persists longer than the current that evoked it, providing evidence for ‘molecular memory’. Our findings suggest a model for CaV1.2 channel gating and Ca2+-influx amplification that unifies diverse observations about Ca2+ signaling in the heart, and challenges the long-held view that voltage-gated channels open and close independently. DOI: http://dx.doi.org/10.7554/eLife.05608.001 PMID:25714924

  7. On Proper Selection of Multihop Relays for Future Enhancement of AeroMACS Networks

    NASA Technical Reports Server (NTRS)

    Kamali, Behnam; Kerczewski, Robert J.; Apaza, Rafael D.

    2015-01-01

    As the Aeronautical Mobile Airport Communications System (AeroMACS) has evolved from a technology concept to a deployed communications network over major US airports, it is now time to contemplate whether the existing capacity of AeroMACS is sufficient to meet the demands set forth by all fixed and mobile applications over the airport surface given the AeroMACS constraints regarding bandwidth and transmit power. The underlying idea in this article is to present IEEE 802.16j-based WiMAX as a technology that can address future capacity enhancements and therefore is most feasible for AeroMACS applications. The principal argument in favor IEEE 802.16j technology is the flexible and cost effective extension of radio coverage that is afforded by relay fortified networks, with virtually no increase in the power requirements and virtually no rise in interference levels to co-allocated applications. The IEEE 802.16j-based multihop relay systems are briefly described. The focus is on key features of this technology, frame structure, and its architecture. Next, AeroMACS is described as a WiMAX-based wireless network. The two major relay modes supported by IEEE 802.16j amendment, i.e., transparent and non-transparent are described. The benefits of employing multihop relays are listed. Some key challenges related to incorporating relays into AeroMACS networks are discussed. The selection of relay type in a broadband wireless network affects a number of network parameters such as latency, signal overhead, PHY (Scalable Physical Layer) and MAC (Media Access Layer) layer protocols, consequently it can alter key network quantities of throughput and QoS (Quality of Service).

  8. Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene Groups

    PubMed Central

    Licursi, Valerio; Brito, Catarina; La Torre, Mattia; Alves, Paula M.; Simao, Daniel; Mottini, Carla; Salinas, Sara; Negri, Rodolfo; Tagliafico, Enrico; Kremer, Eric J.; Saggio, Isabella

    2015-01-01

    Brain gene transfer using viral vectors will likely become a therapeutic option for several disorders. Helper-dependent (HD) canine adenovirus type 2 vectors (CAV-2) are well suited for this goal. These vectors are poorly immunogenic, efficiently transduce neurons, are retrogradely transported to afferent structures in the brain and lead to long-term transgene expression. CAV-2 vectors are being exploited to unravel behavior, cognition, neural networks, axonal transport and therapy for orphan diseases. With the goal of better understanding and characterizing HD-CAV-2 for brain therapy, we analyzed the transcriptomic modulation induced by HD-CAV-2 in human differentiated neurospheres derived from midbrain progenitors. This 3D model system mimics several aspects of the dynamic nature of human brain. We found that differentiated neurospheres are readily transduced by HD-CAV-2 and that transduction generates two main transcriptional responses: a DNA damage response and alteration of centromeric and microtubule probes. Future investigations on the biochemistry of processes highlighted by probe modulations will help defining the implication of HD-CAV-2 and CAR receptor binding in enchaining these functional pathways. We suggest here that the modulation of DNA damage genes is related to viral DNA, while the alteration of centromeric and microtubule probes is possibly enchained by the interaction of the HD-CAV-2 fibre with CAR. PMID:26207738

  9. Large Ca2+-dependent facilitation of CaV2.1 channels revealed by Ca2+ photo-uncaging

    PubMed Central

    Lee, Shin-Rong; Adams, Paul J; Yue, David T

    2015-01-01

    Key points CaV2.1 channels constitute a dominant Ca2+ entry pathway into brain neurons, triggering downstream Ca2+-dependent processes such as neurotransmitter release. CaV2.1 is itself modulated by Ca2+, resulting in activity-dependent enhancement of channel opening termed Ca2+-dependent facilitation (CDF). Real-time Ca2+ imaging and Ca2+ uncaging here reveal that CDF turns out to be strikingly faster, more Ca2+ sensitive, and larger than anticipated on previous grounds. Robust resolution of the quantitative profile of CDF enables deduction of a realistic biophysical model for this process. These results suggest that CaV2.1 CDF would figure most prominently in short-term synaptic plasticity and cerebellar Purkinje cell rhythmicity. Abstract CaV2.1 (P-type) voltage-gated Ca2+ channels constitute a major source of neuronal Ca2+ current, strongly influencing rhythmicity and triggering neurotransmitter release throughout the central nervous system. Fitting with such stature among Ca2+ entry pathways, CaV2.1 is itself feedback regulated by intracellular Ca2+, acting through calmodulin to facilitate channel opening. The precise neurophysiological role of this calcium-dependent facilitation (CDF) remains uncertain, however, in large measure because the very magnitude, Ca2+ dependence and kinetics of CDF have resisted quantification by conventional means. Here, we utilize the photo-uncaging of Ca2+ with CaV2.1 channels fluxing Li+ currents, so that voltage-dependent activation of channel gating is no longer conflated with Ca2+ entry, and CDF is then driven solely by light-induced increases in Ca2+. By using this strategy, we now find that CDF can be unexpectedly large, enhancing currents by as much as twofold at physiological voltages. CDF is steeply Ca2+ dependent, with a Hill coefficient of approximately two, a half-maximal effect reached by nearly 500 nm Ca2+, and Ca2+ on/off kinetics in the order of milliseconds to tens of milliseconds. These properties were

  10. Aero-Thermal Calibration of the NASA Glenn Icing Research Tunnel (2004 and 2005 Tests)

    NASA Technical Reports Server (NTRS)

    Arrington, E. Allen; Pastor, Christine M.; Gonsalez, Jose C.; Curry, Monroe R., III

    2010-01-01

    A full aero-thermal calibration of the NASA Glenn Icing Research Tunnel was completed in 2004 following the replacement of the inlet guide vanes upstream of the tunnel drive system and improvement to the facility total temperature instrumentation. This calibration test provided data used to fully document the aero-thermal flow quality in the IRT test section and to construct calibration curves for the operation of the IRT. The 2004 test was also the first to use the 2-D RTD array, an improved total temperature calibration measurement platform.

  11. Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

    PubMed

    Mallmann, Robert Theodor; Elgueta, Claudio; Sleman, Faten; Castonguay, Jan; Wilmes, Thomas; van den Maagdenberg, Arn; Klugbauer, Norbert

    2013-01-01

    Voltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V)2.1 mouse models. Global Ca(V)2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V)2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V)2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V)2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V)2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V)2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V)2.1 in the adult murine forebrain.

  12. MiR-103 inhibits osteoblast proliferation mainly through suppressing Cav1.2 expression in simulated microgravity.

    PubMed

    Sun, Zhongyang; Cao, Xinsheng; Hu, Zebing; Zhang, Lianchang; Wang, Han; Zhou, Hua; Li, Dongtao; Zhang, Shu; Xie, Manjiang

    2015-07-01

    Emerging evidence indicates that microRNAs (miRNAs) play important roles in modulating osteoblast function and bone formation. However, the influence of miRNA on osteoblast proliferation and the possible mechanisms underlying remain to be defined. In this study, we aimed to investigate whether miR-103 regulates osteoblast proliferation under simulated microgravity condition through regulating Cav1.2, the primary subunit of L-type voltage sensitive calcium channels (LTCCs). We first investigated the effect of simulated microgravity on osteoblast proliferation and the outcomes clearly demonstrated that the mechanical unloading inhibits MC3T3-E1 osteoblast-like cell proliferation. Using quantitative Real-Time PCR (qRT-PCR), we provided data showing that miR-103 was up-regulated in response to simulated microgravity. In addition, we observed that up-regulation of miR-103 inhibited and down-regulation of miR-103 promoted osteoblast proliferation under simulated microgravity condition. Furthermore, knocking-down or over-expressing miR-103, respectively, up- or down-regulated the level of Cav1.2 expression and LTCC currents, suggesting that miR-103 acts as an endogenous attenuator of Cav1.2 in osteoblasts under simulated microgravity condition. More importantly, we showed that the effect of miR-103 on osteoblast proliferation was diminished in simulated microgravity, when co-transfecting miR-103 mimic or inhibitor with Cav1.2 siRNA. Taken together, our data suggest that miR-103 inhibits osteoblast proliferation mainly through suppression of Cav1.2 expression under simulated microgravity condition. This work may provide a novel mechanism of microgravity-induced detrimental effects on osteoblast proliferation, identifying miR-103 as a novel possible therapeutic target in bone remodeling disorders in this mechanical unloading.

  13. Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels.

    PubMed

    Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E; Sinnegger-Brauns, Martina J; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

    2011-12-01

    An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Ca(v)1.3 L-type Ca(2+) channels (Ca(v)1.3(L)) is a major determinant of their voltage- and Ca(2+)-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Ca(v)1.3(42A) channels that activate at a more negative voltage range and exhibit more pronounced Ca(2+)-dependent inactivation. Here we describe the discovery of a novel short splice variant (Ca(v)1.3(43S)) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Ca(v)1.3(42A), still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Ca(v)1.3(43S) also activated at more negative voltages like Ca(v)1.3(42A) but Ca(2+)-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Ca(v)1.3(L). The presence of the proximal C terminus in Ca(v)1.3(43S) channels preserved their modulation by distal C terminus-containing Ca(v)1.3- and Ca(v)1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca(2+) influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Ca(v)1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca(2+) channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca(2+) accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca(2+)-induced neurodegenerative processes.

  14. A Mission Concept: Re-Entry Hopper-Aero-Space-Craft System on-Mars (REARM-Mars)

    NASA Technical Reports Server (NTRS)

    Davoodi, Faranak

    2013-01-01

    Future missions to Mars that would need a sophisticated lander, hopper, or rover could benefit from the REARM Architecture. The mission concept REARM Architecture is designed to provide unprecedented capabilities for future Mars exploration missions, including human exploration and possible sample-return missions, as a reusable lander, ascend/descend vehicle, refuelable hopper, multiple-location sample-return collector, laboratory, and a cargo system for assets and humans. These could all be possible by adding just a single customized Re-Entry-Hopper-Aero-Space-Craft System, called REARM-spacecraft, and a docking station at the Martian orbit, called REARM-dock. REARM could dramatically decrease the time and the expense required to launch new exploratory missions on Mars by making them less dependent on Earth and by reusing the assets already designed, built, and sent to Mars. REARM would introduce a new class of Mars exploration missions, which could explore much larger expanses of Mars in a much faster fashion and with much more sophisticated lab instruments. The proposed REARM architecture consists of the following subsystems: REARM-dock, REARM-spacecraft, sky-crane, secure-attached-compartment, sample-return container, agile rover, scalable orbital lab, and on-the-road robotic handymen.

  15. Benefits to the Simulation Training Community of a New ANSI Standard for the Exchange of Aero Simulation Models

    NASA Technical Reports Server (NTRS)

    Hildreth, Bruce L.; Jackson, E. Bruce

    2009-01-01

    The American Institute of Aeronautics Astronautics (AIAA) Modeling and Simulation Technical Committee is in final preparation of a new standard for the exchange of flight dynamics models. The standard will become an ANSI standard and is under consideration for submission to ISO for acceptance by the international community. The standard has some a spects that should provide benefits to the simulation training community. Use of the new standard by the training simulation community will reduce development, maintenance and technical refresh investment on each device. Furthermore, it will significantly lower the cost of performing model updates to improve fidelity or expand the envelope of the training device. Higher flight fidelity should result in better transfer of training, a direct benefit to the pilots under instruction. Costs of adopting the standard are minimal and should be paid back within the cost of the first use for that training device. The standard achie ves these advantages by making it easier to update the aerodynamic model. It provides a standard format for the model in a custom eXtensible Markup Language (XML) grammar, the Dynamic Aerospace Vehicle Exchange Markup Language (DAVE-ML). It employs an existing XML grammar, MathML, to describe the aerodynamic model in an input data file, eliminating the requirement for actual software compilation. The major components of the aero model become simply an input data file, and updates are simply new XML input files. It includes naming and axis system conventions to further simplify the exchange of information.

  16. Global dust model intercomparison in AeroCom phase I

    SciTech Connect

    Huneeus, N.; Schulz, M.; Balkanski, Y.; Griesfeller, J.; Prospero, J.; Kinne, S.; Bauer, S.; Boucher, O.; Chin, M.; Dentener, F.; Diehl, T.; Easter, R.; Fillmore, D.; Ghan, S.; Ginoux, P.; Grini, A.; Horowitz, L.; Koch, D.; Krol, M. C.; Landing, W.; Liu, X.; Mahowald, N.; Miller, R.; Morcrette, J. -J.; Myhre, G.; Penner, J.; Perlwitz, J.; Stier, P.; Takemura, T.; Zender, C. S.

    2011-08-01

    This study presents the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project. Each model is compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth (AOD) and dust deposition. Additional comparisons to Angström exponent (AE), coarse mode AOD and dust surface concentrations are included to extend the assessment of model performance and to identify common biases present in models. These data comprise a benchmark dataset that is proposed for model inspection and future dust model development. There are large differences among the global models that simulate the dust cycle and its impact on climate. In general, models simulate the climatology of vertically integrated parameters (AOD and AE) within a factor of two whereas the total deposition and surface concentration are reproduced within a factor of 10. In addition, smaller mean normalized bias and root mean square errors are obtained for the climatology of AOD and AE than for total deposition and surface concentration. Characteristics of the datasets used and their uncertainties may influence these differences. Large uncertainties still exist with respect to the deposition fluxes in the southern oceans. Further measurements and model studies are necessary to assess the general model performance to reproduce dust deposition in ocean regions sensible to iron contributions. Models overestimate the wet deposition in regions dominated by dry deposition. They generally simulate more realistic surface concentration at stations downwind of the main sources than at remote ones. Most models simulate the gradient in AOD and AE between the different dusty regions. However the seasonality and magnitude of both variables is better simulated at African stations than Middle East ones. The models simulate the offshore transport of West Africa throughout the year but they

  17. Spectrum of Cav1.4 dysfunction in congenital stationary night blindness type 2☆

    PubMed Central

    Burtscher, Verena; Schicker, Klaus; Novikova, Elena; Pöhn, Birgit; Stockner, Thomas; Kugler, Christof; Singh, Anamika; Zeitz, Christina; Lancelot, Marie-Elise; Audo, Isabelle; Leroy, Bart Peter; Freissmuth, Michael; Herzig, Stefan; Matthes, Jan; Koschak, Alexandra

    2014-01-01

    Defective retinal synaptic transmission in patients affected with congenital stationary night blindness type 2 (CSNB2) can result from different dysfunction phenotypes in Cav1.4 L-type calcium channels. Here we investigated two prototypical Cav1.4 variants from either end of the functional spectrum. Using whole-cell and single-channel patch-clamp techniques, we provide analysis of the biophysical characteristics of the point mutation L860P and the C-terminal truncating mutation R1827X. L860P showed a typical loss-of-function phenotype attributed to a reduced number of functional channels expressed at the plasma membrane as implied by gating current and non-stationary noise analyses. This phenotype can be rationalized, because the inserted proline is predicted to break an amphipatic helix close to the transmembrane segment IIIS1 and thus to reduce channel stability and promote misfolding. In fact, L860P was subject to an increased turnover. In contrast, R1827X displayed an apparent gain-of-function phenotype, i.e., due to a hyperpolarizing shift of the IV-curve and increased single-channel activity. However, truncation also resulted in the loss of functional C-terminal modulation and thus unmasked calcium-dependent inactivation. Thus R1827X failed to support continuous calcium influx. Current inactivation curtails the dynamic range of photoreceptors (e.g., when adapting to variation in illumination). Taken together, the analysis of two representative mutations that occur in CSNB2 patients revealed fundamental differences in the underlying defect. These may explain subtle variations in the clinical manifestation and must be taken into account, if channel function is to be restored by pharmacochaperones or related approaches. PMID:24796500

  18. Ascent Heating Thermal Analysis on the Spacecraft Adaptor (SA) Fairings and the Interface with the Crew Launch Vehicle (CLV)

    NASA Technical Reports Server (NTRS)

    Wang, Xiao-Yen; Yuko, James; Motil, Brian

    2009-01-01

    When the crew exploration vehicle (CEV) is launched, the spacecraft adaptor (SA) fairings that cover the CEV service module (SM) are exposed to aero heating. Thermal analysis is performed to compute the fairing temperatures and to investigate whether the temperatures are within the material limits for nominal ascent aero heating case. Heating rates from Thermal Environment (TE) 3 aero heating analysis computed by engineers at Marshall Space Flight Center (MSFC) are used in the thermal analysis. Both MSC Patran 2007r1b/Pthermal and C&R Thermal Desktop 5.1/Sinda models are built to validate each other. The numerical results are also compared with those reported by Lockheed Martin (LM) and show a reasonably good agreement.

  19. 77 FR 35888 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... 12866, (2) Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034... PIAGGIO AERO INDUSTRIES S.p.A Model P-180 airplanes, serial numbers (S/Ns) 1002 and 1004 through 1223... flap external screwjacks installed during production. (g) Credit for Actions Accomplished in...

  20. 78 FR 22168 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... published in the Federal Register on January 9, 2013 (78 FR 1776). That NPRM proposed to require the... ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will not.... SUMMARY: We are adopting a new airworthiness directive (AD) for certain International Aero Engines AG...

  1. Application of Multihop Relay for Performance Enhancement of AeroMACS Networks

    NASA Technical Reports Server (NTRS)

    Kamali, Behnam; Wilson, Jeffrey D.; Kerczewski, Robert J.

    2012-01-01

    A new transmission technology, based on IEEE 802.16-2009 (WiMAX), is currently being developed for airport surface communications. A C-band spectrum allocation at 5091 to 5150 MHz has been created by International Telecommunications Union (ITU) to carry this application. The proposed technology, known as AeroMACS, will be used to support fixed and mobile ground to ground applications and services. This article proposes and demonstrates that IEEE 802.16j-amendment-based WiMAX is most feasible for AeroMACS applications. This amendment introduces multihop relay as an optional deployment that may be used to provide additional coverage and/or enhance the capacity of the network. Particular airport surface radio coverage situations for which IEEE 802.16-2009-WiMAX provides resolutions that are inefficient, costly, or excessively power consuming are discussed. In all these cases, it is argued that 16j technology offers a much better alternative. A major concern about deployment of AeroMACS is interference to co-allocated applications such as the Mobile Satellite Service (MSS) feeder link. Our initial simulation results suggest that no additional interference to MSS feeder link is caused by deployment of IEEE 802.16j-based AeroMACS.

  2. Numerical analysis of the aero-optic effects induced by the turbulence field surrounding hypersonic aircrafts

    NASA Astrophysics Data System (ADS)

    Yang, Wenxia; Cai, Chao; Ding, Mingyue; Zhou, Chengping; Guo, Xiaoxing

    2007-11-01

    The goal of this paper is to numerically simulate and analyze the aero-optic effects caused by the hyper-speed turbulence fields surrounding the aircraft under different flight conditions, and to characterize them with the associated optical transfer functions. First, analysis and computation of the aero-optic effects under different flight conditions have been addressed, where the parameters characterizing the hyper-speed turbulence field were obtained by solving its N-S equations via CFD methods. The infrared ray trajectories passing through the flow field with a non-homogeneous distribution of the refraction indices were acquired using the gradient index ray-tracing method, and the transfer function to represent the aero-optic effects was derived considering the principles of Fourier optics. The simulation results showed that the aero-optic transfer function is characterized as a low-pass filter of nonlinearly varying phases, which results the blurring and shifting of the objects in the acquired images.

  3. Finite element model for aero-elastically tailored residential wind turbine blade design

    NASA Astrophysics Data System (ADS)

    Robinson, Eric Alan

    Advances in passive wind turbine control systems have allowed wind turbines to achieve higher efficiencies and operate in wider inflow conditions than ever before. Within recent years, the adoption of aero-elastically tailored (bend-twist coupled) composite blades have been a pursued strategy. Unfortunately, for this strategy to be applied, traditional means of modeling, designing and manufacturing are no longer adequate. New parameters regarding non-linearities in deflections, stiffness, and aerodynamic loadings must now be implemented. To aid in the development of passive wind turbine system design, a finite element based aero-elastic program capable of computationally predicting blade deflection and twist under loading was constructed. The program was built around the idea of iteratively solving a blade composite structure to reach a maximum aero-elastic twist configuration under elevated wind speeds. Adopting a pre-existing blade geometry, from a pitch controlled small scale (3.5kW) turbine design, the program was tested to discover the geometry bend-twist coupling potential. This research would be a contributing factor in designing a passive pitch control replacement system for the turbine. A study of various model loading configurations was first performed to insure model validity. Then, a final model was used to analyze composite layups for selected spar configurations. Results characterize the aero-elastic twist properties for the selected configurations.

  4. Application of Multihop Relay for Performance Enhancement of AeroMACS Networks

    NASA Technical Reports Server (NTRS)

    Kamali, Behnam; Wilson, Jeffrey D.; Kerczewski, Robert J.

    2012-01-01

    A new transmission technology, based on IEEE 802.16-2009 (WiMAX), is currently being developed for airport surface communications. A C-band spectrum allocation at 5091-5150 MHz has been created by ITU to carry this application. The proposed technology, known as AeroMACS, will be used to support fixed and mobile ground to ground applications and services. This article proposes and demonstrates that IEEE 802.16j-amendment-based WiMAX is most feasible for AeroMACS applications. This amendment introduces multihop relay as an optional deployment that may be used to provide additional coverage and/or enhance the capacity of the network. Particular airport surface radio coverage situations for which IEEE 802.16-2009-WiMAX provides resolutions that are inefficient, costly, or excessively power consuming are discussed. In all these cases, it is argued that 16j technology offers a much better alternative. A major concern about deployment of AeroMACS is interference to co-allocated applications such as the Mobile Satellite Service (MSS) feeder link. Our initial simulation results suggest that no additional interference to MSS feeder link is caused by deployment of IEEE 802.16j-based AeroMACS.

  5. Swept Blade Aero-Elastic Model for a Small Wind Turbine (Presentation)

    SciTech Connect

    Damiani, R.; Lee, S.; Larwood, S.

    2014-07-01

    A preprocessor for analyzing preswept wind turbines using the in-house aero-elastic tool coupled with a multibody dynamic simulator was developed. A baseline 10-kW small wind turbine with straight blades and various configurations that featured bend-torsion coupling via blade-tip sweep were investigated to study their impact on ultimate loads and fatigue damage equivalent loads.

  6. OC3 -- Benchmark Exercise of Aero-Elastic Offshore Wind Turbine Codes: Preprint

    SciTech Connect

    Passon, P.; Kuhn, M.; Butterfield, S.; Jonkman, J.; Camp, T.; Larsen, T. J.

    2007-08-01

    This paper introduces the work content and status of the first international investigation and verification of aero-elastic codes for offshore wind turbines as performed by the "Offshore Code Comparison Collaboration" (OC3) within the "IEA Wind Annex XXIII -- Subtask 2".

  7. AERO: A Decision Support Tool for Wind Erosion Assessment in Rangelands and Croplands

    NASA Astrophysics Data System (ADS)

    Galloza, M.; Webb, N.; Herrick, J.

    2015-12-01

    Wind erosion is a key driver of global land degradation, with on- and off-site impacts on agricultural production, air quality, ecosystem services and climate. Measuring rates of wind erosion and dust emission across land use and land cover types is important for quantifying the impacts and identifying and testing practical management options. This process can be assisted by the application of predictive models, which can be a powerful tool for land management agencies. The Aeolian EROsion (AERO) model, a wind erosion and dust emission model interface provides access by non-expert land managers to a sophisticated wind erosion decision-support tool. AERO incorporates land surface processes and sediment transport equations from existing wind erosion models and was designed for application with available national long-term monitoring datasets (e.g. USDI BLM Assessment, Inventory and Monitoring, USDA NRCS Natural Resources Inventory) and monitoring protocols. Ongoing AERO model calibration and validation are supported by geographically diverse data on wind erosion rates and land surface conditions collected by the new National Wind Erosion Research Network. Here we present the new AERO interface, describe parameterization of the underpinning wind erosion model, and provide a summary of the model applications across agricultural lands and rangelands in the United States.

  8. Simultaneous measurement of aero-optical distortion and turbulent structure in a heated boundary layer

    NASA Astrophysics Data System (ADS)

    Saxton-Fox, Theresa; McKeon, Beverley; Smith, Adam; Gordeyev, Stanislav

    2014-11-01

    This study examines the relationship between turbulent structures and the aero-optical distortion of a laser beam passing through a turbulent boundary layer. Previous studies by Smith et al. (AIAA, 2014--2491) have found a bulk convection velocity of 0 . 8U∞ for aero-optical distortion in turbulent boundary layers, motivating a comparison of the distortion with the outer boundary layer. In this study, a turbulent boundary layer is developed over a flat plate with a moderately-heated section of length 25 δ . Density variation in the thermal boundary layer leads to aero-optical distortion, which is measured with a Malley probe (Smith et al., AIAA, 2013--3133). Simultaneously, 2D PIV measurements are recorded in a wall-normal, streamwise plane centered on the Malley probe location. Experiments are run at Reθ = 2100 and at a Mach number of 0.03, with the heated wall 10 to 20°C above the free stream temperature. Correlations and conditional averages are carried out between Malley probe distortion angles and flow features in the PIV vector fields. Aero-optical distortion in this study will be compared to distortion in higher Mach number flows studied by Gordeyev et al. (J. Fluid Mech., 2014), with the aim of extending conclusions into compressible flows. This research is made possible by the Department of Defense through the National Defense & Engineering Graduate Fellowship (NDSEG) Program and by the Air Force Office of Scientific Research Grant # FA9550-12-1-0060.

  9. 76 FR 60396 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... 12866; 2. Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034... Industries S.p.A. Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT... (AD) for certain Piaggio Aero Industries S.p.A. Model P-180 airplanes. This proposed AD results...

  10. 78 FR 69600 - Airworthiness Directives; Piaggio Aero Industries S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will not affect intrastate aviation in Alaska... Industries S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT... (AD) for certain Piaggio Aero Industries S.p.A. Model P-180 airplanes. This proposed AD results...

  11. Efficacy of predictive wavefront control for compensating aero-optical aberrations

    NASA Astrophysics Data System (ADS)

    Goorskey, David J.; Schmidt, Jason; Whiteley, Matthew R.

    2013-07-01

    Imaging and laser beam propagation from airborne platforms are degraded by dynamic aberrations due to air flow around the aircraft, aero-mechanical distortions and jitter, and free atmospheric turbulence. For certain applications, like dim-object imaging, free-space optical communications, and laser weapons, adaptive optics (AO) is necessary to compensate for the aberrations in real time. Aero-optical flow is a particularly interesting source of aberrations whose flowing structures can be exploited by adaptive and predictive AO controllers, thereby realizing significant performance gains. We analyze dynamic aero-optical wavefronts to determine the pointing angles at which predictive wavefront control is more effective than conventional, fixed-gain, linear-filter control. It was found that properties of the spatial decompositions and temporal statistics of the wavefronts are directly traceable to specific features in the air flow. Furthermore, the aero-optical wavefront aberrations at the side- and aft-looking angles were the most severe, but they also benefited the most from predictive AO.

  12. FJ44 Turbofan Engine Test at NASA Glenn Research Center's Aero-Acoustic Propulsion Laboratory

    NASA Technical Reports Server (NTRS)

    Lauer, Joel T.; McAllister, Joseph; Loew, Raymond A.; Sutliff, Daniel L.; Harley, Thomas C.

    2009-01-01

    A Williams International FJ44-3A 3000-lb thrust class turbofan engine was tested in the NASA Glenn Research Center s Aero-Acoustic Propulsion Laboratory. This report presents the test set-up and documents the test conditions. Farfield directivity, in-duct unsteady pressures, duct mode data, and phased-array data were taken and are reported separately.

  13. Dependence of AeroMACS Interference on Airport Radiation Pattern Characteristics

    NASA Technical Reports Server (NTRS)

    Wilson, Jeffrey D.

    2012-01-01

    AeroMACS (Aeronautical Mobile Airport Communications System), which is based upon the IEEE 802.16e mobile wireless standard, is expected to be implemented in the 5091 to 5150 MHz frequency band. As this band is also occupied by Mobile Satellite Service (MSS) feeder uplinks, AeroMACS must be designed to avoid interference with this incumbent service. The aspects of AeroMACS operation that present potential interference are under analysis in order to enable the definition of standards that assure that such interference will be avoided. In this study, the cumulative interference power distribution at low earth orbit from AeroMACS transmitters at the 497 major airports in the contiguous United States was simulated with the Visualyse Professional software. The dependence of the interference power on the number of antenna beams per airport, gain patterns, and beam direction orientations was simulated. As a function of these parameters, the simulation results are presented in terms of the limitations on transmitter power required to maintain the cumulative interference power under the established threshold.

  14. Dependence of AeroMACS Interference on Airport Radiation Pattern Characteristics

    NASA Technical Reports Server (NTRS)

    Wilson, Jeffrey D.

    2012-01-01

    AeroMACS (Aeronautical Mobile Airport Communications System), which is based upon the IEEE 802.16e mobile wireless standard, is expected to be implemented in the 5091-5150 MHz frequency band. As this band is also occupied by Mobile Satellite Service (MSS) feeder uplinks, AeroMACS must be designed to avoid interference with this incumbent service. The aspects of AeroMACS operation that present potential interference are under analysis in order to enable the definition of standards that assure that such interference will be avoided. In this study, the cumulative interference power distribution at low earth orbit from AeroMACS transmitters at the 497 major airports in the contiguous United States was simulated with the Visualyse Professional software. The dependence of the interference power on the number of antenna beams per airport, gain patterns, and beam direction orientations was simulated. As a function of these parameters, the simulation results are presented in terms of the limitations on transmitter power required to maintain the cumulative interference power under the established threshold.

  15. Computational methods to compute wavefront error due to aero-optic effects

    NASA Astrophysics Data System (ADS)

    Genberg, Victor; Michels, Gregory; Doyle, Keith; Bury, Mark; Sebastian, Thomas

    2013-09-01

    Aero-optic effects can have deleterious effects on high performance airborne optical sensors that must view through turbulent flow fields created by the aerodynamic effects of windows and domes. Evaluating aero-optic effects early in the program during the design stages allows mitigation strategies and optical system design trades to be performed to optimize system performance. This necessitates a computationally efficient means to evaluate the impact of aero-optic effects such that the resulting dynamic pointing errors and wavefront distortions due to the spatially and temporally varying flow field can be minimized or corrected. To this end, an aero-optic analysis capability was developed within the commercial software SigFit that couples CFD results with optical design tools. SigFit reads the CFD generated density profile using the CGNS file format. OPD maps are then created by converting the three-dimensional density field into an index of refraction field and then integrating along specified paths to compute OPD errors across the optical field. The OPD maps may be evaluated directly against system requirements or imported into commercial optical design software including Zemax® and Code V® for a more detailed assessment of the impact on optical performance from which design trades may be performed.

  16. Optimization of the genomic DNA extraction method of silverleaf nightshade/ (Solanum elaeagnifolium /Cav.), an invasive plant in the cultivated areas within the Mediterranean region

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The geographical origin of an invasive in the cultivated area within the Mediterranean region, silverleaf nightshade, Solanum elaeagnifolium Cav, (Solanaceae) should be identified through the analysis of genetic similarities between native and introduced populations using microsatellite markers. Bef...

  17. Characterization of a Synaptic Vesicle Binding Motif on the Distal CaV2.2 Channel C-terminal.

    PubMed

    Gardezi, Sabiha R; Nath, Arup R; Li, Qi; Stanley, Elise F

    2016-01-01

    Neurotransmitter is released from synaptic vesicles (SVs) that are gated to fuse with the presynaptic membrane by calcium ions that enter through voltage-gated calcium channels (CaVs). There is compelling evidence that SVs associate closely with the CaVs but the molecular linking mechanisms remain poorly understood. Using a cell-free, synaptic vesicle-pull-down assay method (SV-PD) we have recently demonstrated that SVs can bind both to the intact CaV2.2 channel and also to a fusion protein comprising the distal third, C3 segment, of its long C-terminal. This site was localized to a 49 amino acid region just proximal to the C-terminal tip. To further restrict the SV binding site we generated five, 10 amino acid mimetic blocking peptides spanning this region. Of these, HQARRVPNGY effectively inhibited SV-PD and also inhibited SV recycling when cryoloaded into chick brain nerve terminals (synaptosomes). Further, SV-PD was markedly reduced using a C3 fusion protein that lacked the HQARRVPNGY sequence, C3HQless. We zeroed in on the SV binding motif within HQARRVPNGY by means of a palette of mutant blocking peptides. To our surprise, peptides that lacked the highly conserved VPNGY sequence still blocked SV-PD. However, substitution of the HQ and RR amino acids markedly reduced block. Of these, the RR pair was essential but not sufficient as the full block was not observed without H suggesting a CaV2.2 SV binding motif of HxxRR. Interestingly, CaV2.1, the other primary presynaptic calcium channel, exhibits a similar motif, RHxRR, that likely serves the same function. Bioinformatic analysis showed that variations of this binding motif, +(+) xRR (where + is a positively charged aa H or R), are conserved from lung-fish to man. Further studies will be necessary to identify the C terminal motif binding partner on the SV itself and to determine the role of this molecular interaction in synaptic transmission. We hypothesize that the distal C-terminal participates in the capture

  18. Characterization of a Synaptic Vesicle Binding Motif on the Distal CaV2.2 Channel C-terminal

    PubMed Central

    Gardezi, Sabiha R.; Nath, Arup R.; Li, Qi; Stanley, Elise F.

    2016-01-01

    Neurotransmitter is released from synaptic vesicles (SVs) that are gated to fuse with the presynaptic membrane by calcium ions that enter through voltage-gated calcium channels (CaVs). There is compelling evidence that SVs associate closely with the CaVs but the molecular linking mechanisms remain poorly understood. Using a cell-free, synaptic vesicle-pull-down assay method (SV-PD) we have recently demonstrated that SVs can bind both to the intact CaV2.2 channel and also to a fusion protein comprising the distal third, C3 segment, of its long C-terminal. This site was localized to a 49 amino acid region just proximal to the C-terminal tip. To further restrict the SV binding site we generated five, 10 amino acid mimetic blocking peptides spanning this region. Of these, HQARRVPNGY effectively inhibited SV-PD and also inhibited SV recycling when cryoloaded into chick brain nerve terminals (synaptosomes). Further, SV-PD was markedly reduced using a C3 fusion protein that lacked the HQARRVPNGY sequence, C3HQless. We zeroed in on the SV binding motif within HQARRVPNGY by means of a palette of mutant blocking peptides. To our surprise, peptides that lacked the highly conserved VPNGY sequence still blocked SV-PD. However, substitution of the HQ and RR amino acids markedly reduced block. Of these, the RR pair was essential but not sufficient as the full block was not observed without H suggesting a CaV2.2 SV binding motif of HxxRR. Interestingly, CaV2.1, the other primary presynaptic calcium channel, exhibits a similar motif, RHxRR, that likely serves the same function. Bioinformatic analysis showed that variations of this binding motif, +(+) xRR (where + is a positively charged aa H or R), are conserved from lung-fish to man. Further studies will be necessary to identify the C terminal motif binding partner on the SV itself and to determine the role of this molecular interaction in synaptic transmission. We hypothesize that the distal C-terminal participates in the capture

  19. The Best Disease-Linked Cl Channel hBest1 Regulates Cav1 (L-type) Ca2+ Channels Via SH3-binding Domains

    PubMed Central

    Yu, Kuai; Xiao, Qinghuan; Cui, Guiying; Lee, Amy; Hartzell, H. Criss

    2008-01-01

    Mutations in the bestrophin-1 (Best1) gene are linked to several kinds of macular degeneration in both humans and dogs. Although bestrophins have been shown clearly to be Cl− ion channels, it is controversial whether Cl− channel dysfunction can explain the diseases. It has been suggested that bestrophins are multi-functional proteins: they may regulate voltage-gated Ca2+ channels in addition to functioning as Cl− channels. Here we show that hBest1 differentially modulates Cav1.3 (L-type) voltage-gated Ca2+ channels through association with the Cavβ subunit. In transfected HEK-293 cells, hBest1 inhibited Cav1.3. Inhibition of Cav1.3 was not observed in the absence of the β subunit. Also, the hBest1 C-terminus binds to Cavβ subunits, suggesting that the effect of hBest1 was mediated by the Cavβ subunit. The region of hBest1 responsible for the effect was localized to a region (amino acids 330 − 370) in the cytoplasmic C-terminus that contains a predicted SH3-binding domain that is not present in other bestrophin subtypes. Mutation of Pro330 and Pro334 abolished the effects of hBest1 on Cav1.3. The effect was specific to hBest1: it was not observed with mBest1, -2, or -3. Wild type hBest1 and the disease-causing mutants R92S, G299R, and D312N inhibited Cav currents the same amount, whereas the A146K and G222E mutants were less effective. We propose that hBest1 regulates Cav channels by interacting with the Cavβ subunit and altering channel availability. Our findings reveal a novel function of bestrophin in regulation of Cav channels and suggest a possible mechanism for the role of hBest1 in macular degeneration. PMID:18509027

  20. Endogenous and exogenous hydrogen sulfide facilitates T-type calcium channel currents in Cav3.2-expressing HEK293 cells.

    PubMed

    Sekiguchi, Fumiko; Miyamoto, Yosuke; Kanaoka, Daiki; Ide, Hiroki; Yoshida, Shigeru; Ohkubo, Tsuyako; Kawabata, Atsufumi

    2014-02-28

    Hydrogen sulfide (H2S), a gasotransmitter, is formed from l-cysteine by multiple enzymes including cystathionine-γ-lyase (CSE). We have shown that an H2S donor, NaHS, causes hyperalgesia in rodents, an effect inhibited by knockdown of Cav3.2 T-type Ca(2+) channels (T-channels), and that NaHS facilitates T-channel-dependent currents (T-currents) in NG108-15 cells that naturally express Cav3.2. In the present study, we asked if endogenous and exogenous H2S participates in regulation of the channel functions in Cav3.2-transfected HEK293 (Cav3.2-HEK293) cells. dl-Propargylglycine (PPG), a CSE inhibitor, significantly decreased T-currents in Cav3.2-HEK293 cells, but not in NG108-15 cells. NaHS at 1.5mM did not affect T-currents in Cav3.2-HEK293 cells, but enhanced T-currents in NG108-15 cells. In the presence of PPG, NaHS at 1.5mM, but not 0.1-0.3mM, increased T-currents in Cav3.2-HEK293 cells. Similarly, Na2S, another H2S donor, at 0.1-0.3mM significantly increased T-currents in the presence, but not absence, of PPG in Cav3.2-HEK293 cells. Expression of CSE was detected at protein and mRNA levels in HEK293 cells. Intraplantar administration of Na2S, like NaHS, caused mechanical hyperalgesia, an effect blocked by NNC 55-0396, a T-channel inhibitor. The in vivo potency of Na2S was higher than NaHS. These results suggest that the function of Cav3.2 T-channels is tonically enhanced by endogenous H2S synthesized by CSE in Cav3.2-HEK293 cells, and that exogenous H2S is capable of enhancing Cav3.2 function when endogenous H2S production by CSE is inhibited. In addition, Na2S is considered a more potent H2S donor than NaHS in vitro as well as in vivo.

  1. Isolation, synthesis and characterization of ω-TRTX-Cc1a, a novel tarantula venom peptide that selectively targets L-type Cav channels.

    PubMed

    Klint, Julie K; Berecki, Géza; Durek, Thomas; Mobli, Mehdi; Knapp, Oliver; King, Glenn F; Adams, David J; Alewood, Paul F; Rash, Lachlan D

    2014-05-15

    Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba(2+) currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC50) values of 825nM and 2.24μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV channels but did not affect low voltage-activated T-type CaV channels. Cc1a exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1-E5) or C-terminus (ΔW35-V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type CaV channels.

  2. Gain-of-function nature of Cav1.4 L-type calcium channels alters firing properties of mouse retinal ganglion cells

    PubMed Central

    Knoflach, Dagmar; Schicker, Klaus; Glösmann, Martin; Koschak, Alexandra

    2015-01-01

    Proper function of Cav1.4 L-type calcium channels is crucial for neurotransmitter release in the retina. Our understanding about how different levels of Cav1.4 channel activity affect retinal function is still limited. In the gain-of-function mouse model Cav1.4-IT we expected a reduction in the photoreceptor dynamic range but still transmission toward retinal ganglion cells. A fraction of Cav1.4-IT ganglion cells responded to light stimulation in multielectrode array recordings from whole-mounted retinas, but showed a significantly delayed response onset. Another significant number of cells showed higher activity in darkness. In addition to structural remodeling observed at the first retinal synapse of Cav1.4-IT mice the functional data suggested a loss of contrast enhancement, a fundamental feature of our visual system. In fact, Cav1.4-IT mouse retinas showed a decline in spatial response and changes in their contrast sensitivity profile. Photoreceptor degeneration was obvious from the nodular structure of cone axons and enlarged pedicles which partly moved toward the outer nuclear layer. Loss of photoreceptors was also expressed as reduced expression of proteins involved in chemical and electrical transmission, as such metabotropic glutamate receptor mGluR6 and the gap junction protein Connexin 36. Such gross changes in retinal structure and function could also explain the diminished visual performance of CSNB2 patients. The expression pattern of the plasma-membrane calcium ATPase 1 which participates in the maintenance of the intracellular calcium homeostasis in photoreceptors was changed in Cav1.4-IT mice. This might be part of a protection mechanism against increased calcium influx, as this is suggested for Cav1.4-IT channels. PMID:26274509

  3. Isolation, synthesis and characterization of ω-TRTX-Cc1a, a novel tarantula venom peptide that selectively targets L-type Cav channels.

    PubMed

    Klint, Julie K; Berecki, Géza; Durek, Thomas; Mobli, Mehdi; Knapp, Oliver; King, Glenn F; Adams, David J; Alewood, Paul F; Rash, Lachlan D

    2014-05-15

    Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba(2+) currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC50) values of 825nM and 2.24μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV channels but did not affect low voltage-activated T-type CaV channels. Cc1a exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1-E5) or C-terminus (ΔW35-V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type CaV channels. PMID:24561180

  4. Understanding Aero-Fractures using optics and acoustics

    NASA Astrophysics Data System (ADS)

    Turkaya, Semih; Toussaint, Renaud; Kvalheim Eriksen, Fredrik; Zecevic, Megan; Daniel, Guillaume; Grude Flekkøy, Eirik; Jørgen Måløy, Knut

    2016-04-01

    exponent p value around 0.5. An analytical model of overpressure diffusion predicting p = 0.5 and two other free parameters of the Omori Law (prefactor and origin time) is developed. The spatial density of the seismic events, and the time of end of formation of the channels can also be predicted using this developed model. Using direct simulations of acoustic emissions due to the air vibration in opening fractal cavities, the evolution in the power spectrum is investigated. 1. Turkaya S, Toussaint R, Eriksen FK, Zecevic M, Daniel G, Flekkøy EG, Måløy KJ. "Bridging aero-fracture evolution with the characteristics of the acoustic emissions in a porous medium." Front. Phys.3:70. 2015 doi: 10.3389/fphy.2015.00070

  5. Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle CaV1.1 calcium channel splice variants

    PubMed Central

    Tuluc, Petronel; Flucher, Bernhard E.

    2014-01-01

    Voltage-gated calcium channels are multi-subunit protein complexes that specifically allow calcium ions to enter the cell in response to membrane depolarization. But, for many years it seemed that the skeletal muscle calcium channel CaV1.1 is the exception. The classical splice variant CaV1.1a activates slowly, has a very small current amplitude and poor voltage sensitivity. In fact adult muscle fibers work perfectly well even in the absence of calcium influx. Recently a new splice variant of the skeletal muscle calcium channel CaV1.1e has been characterized. The lack of the 19 amino acid exon 29 in this splice variant results in a rapidly activating calcium channel with high current amplitude and good voltage sensitivity. CaV1.1e is the dominant channel in embryonic muscle, where the expression of this high calcium-conducting CaV1.1 isoform readily explains developmental processes depending on L-type calcium currents. Moreover, the availability of these two structurally similar but functionally distinct channel variants facilitates the analysis of the molecular mechanisms underlying the unique current properties of the classical CaV1.1a channel. PMID:22057633

  6. T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants

    PubMed Central

    Gangarossa, Giuseppe; Laffray, Sophie; Bourinet, Emmanuel; Valjent, Emmanuel

    2014-01-01

    The fine-tuning of neuronal excitability relies on a tight control of Ca2+ homeostasis. The low voltage-activated (LVA) T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here, we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse. Using a wide range of behavioral assays we show that genetic ablation of the cacna1h gene results in an anxiety-like phenotype, whereas novelty-induced locomotor activity is unaffected. Deletion of the T-type channel Cav3.2 also triggers impairment of hippocampus-dependent recognition memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and cocaine are dramatically reduced in T-type Cav3.2 deficient mice. In addition, the administration of the T-type blocker TTA-A2 prevented the expression of locomotor sensitization observed in wildtype mice. In conclusion, our data reveal that physiological activity of this specific Ca2+ channel is required for affective and cognitive behaviors. Moreover, our work highlights the interest of T-type channel blockers as therapeutic strategies to reverse drug-associated alterations. PMID:24672455

  7. A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant.

    PubMed

    Dahimene, Shehrazade; Page, Karen M; Nieto-Rostro, Manuela; Pratt, Wendy S; D'Arco, Marianna; Dolphin, Annette C

    2016-09-01

    Episodic ataxia 2 (EA2) is an autosomal dominant disorder caused by mutations in the gene CACNA1A that encodes the pore-forming CaV2.1 calcium channel subunit. The majority of EA2 mutations reported so far are nonsense or deletion/insertion mutations predicted to form truncated proteins. Heterologous expression of wild-type CaV2.1, together with truncated constructs that mimic EA2 mutants, significantly suppressed wild-type calcium channel function, indicating that the truncated protein produces a dominant-negative effect (Jouvenceau et al., 2001; Page et al., 2004). A similar finding has been shown for CaV2.2 (Raghib et al., 2001). We show here that a highly conserved sequence in the cytoplasmic N-terminus is involved in this process, for both CaV2.1 and CaV2.2 channels. Additionally, we were able to interfere with the suppressive effect of an EA2 construct by mutating key N-terminal residues within it. We postulate that the N-terminus of the truncated channel plays an essential part in its interaction with the full-length CaV2.1, which prevents the correct folding of the wild-type channel. In agreement with this, we were able to disrupt the interaction between EA2 and the full length channel by co-expressing a free N-terminal peptide. PMID:27260834

  8. A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant.

    PubMed

    Dahimene, Shehrazade; Page, Karen M; Nieto-Rostro, Manuela; Pratt, Wendy S; D'Arco, Marianna; Dolphin, Annette C

    2016-09-01

    Episodic ataxia 2 (EA2) is an autosomal dominant disorder caused by mutations in the gene CACNA1A that encodes the pore-forming CaV2.1 calcium channel subunit. The majority of EA2 mutations reported so far are nonsense or deletion/insertion mutations predicted to form truncated proteins. Heterologous expression of wild-type CaV2.1, together with truncated constructs that mimic EA2 mutants, significantly suppressed wild-type calcium channel function, indicating that the truncated protein produces a dominant-negative effect (Jouvenceau et al., 2001; Page et al., 2004). A similar finding has been shown for CaV2.2 (Raghib et al., 2001). We show here that a highly conserved sequence in the cytoplasmic N-terminus is involved in this process, for both CaV2.1 and CaV2.2 channels. Additionally, we were able to interfere with the suppressive effect of an EA2 construct by mutating key N-terminal residues within it. We postulate that the N-terminus of the truncated channel plays an essential part in its interaction with the full-length CaV2.1, which prevents the correct folding of the wild-type channel. In agreement with this, we were able to disrupt the interaction between EA2 and the full length channel by co-expressing a free N-terminal peptide.

  9. Results of investigations conducted in the LaRC 8-foot transonic pressure tunnel using the 0.010-scale 72-OTS model of the space shuttle integrated vehicle (IA93), volume 2

    NASA Technical Reports Server (NTRS)

    Nichols, M. E.

    1976-01-01

    Test procedures, history, and plotted coefficient data are presented for an aero-loads investigation on the updated configuration-5 space shuttle launch vehicle at Mach numbers from 0.600 to 1.205. Six-component vehicle forces and moments, base and sting-cavity pressures, elevon hinge moments, wing-root bending and torsion moments, and normal shear force data were obtained. Full simulation of updated vehicle protuberances and attach hardware was employed.

  10. Curcumin inhibits ACTH- and angiotensin II-stimulated cortisol secretion and Ca(v)3.2 current.

    PubMed

    Enyeart, Judith A; Liu, Haiyan; Enyeart, John J

    2009-08-01

    Adrenocorticotropic hormone and angiotensin II stimulate cortisol secretion from bovine adrenal zona fasciculata cells by the activation of adenylate cyclase and phospholipase C-coupled receptors. Curcumin (1- 20 muM), a compound found in the spice turmeric, inhibited cortisol secretion stimulated by ACTH, AngII, and 8CPT-cAMP. Curcumin also suppressed ACTH-stimulated increases in mRNAs coding for steroid acute regulatory protein and CYP11a1 steroid hydroxylase. In whole cell patch clamp recordings from AZF cells, curcumin at slightly higher concentrations also inhibited Ca(v)3.2 current. These results identify curcumin as an effective inhibitor of ACTH- and AngII-stimulated cortisol secretion. The inhibition of Ca(v)3.2 current by curcumin may contribute to its suppression of secretion.

  11. Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC

    PubMed Central

    Jeon, Daejong; Kim, Sangwoo; Chetana, Mattu; Jo, Daewoong; Ruley, H Earl; Lin, Shih-Yao; Rabah, Dania; Kinet, Jean-Pierre; Shin, Hee-Sup

    2010-01-01

    Fear can be acquired vicariously through social observation of others suffering from aversive stimuli. We found that mice (observers) developed freezing behavior by observing other mice (demonstrators) receive repetitive foot shocks. Observers had higher fear responses when demonstrators were socially related to themselves, such as siblings or mating partners. Inactivation of anterior cingulate cortex (ACC) and parafascicular or mediodorsal thalamic nuclei, which comprise the medial pain system representing pain affection, substantially impaired this observational fear learning, whereas inactivation of sensory thalamic nuclei had no effect. The ACC neuronal activities were increased and synchronized with those of the lateral amygdala at theta rhythm frequency during this learning. Furthermore, an ACC-limited deletion of Cav1.2 Ca2+ channels in mice impaired observational fear learning and reduced behavioral pain responses. These results demonstrate the functional involvement of the affective pain system and Cav1.2 channels of the ACC in observational social fear. PMID:20190743

  12. Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC.

    PubMed

    Jeon, Daejong; Kim, Sangwoo; Chetana, Mattu; Jo, Daewoong; Ruley, H Earl; Lin, Shih-Yao; Rabah, Dania; Kinet, Jean-Pierre; Shin, Hee-Sup

    2010-04-01

    Fear can be acquired vicariously through social observation of others suffering from aversive stimuli. We found that mice (observers) developed freezing behavior by observing other mice (demonstrators) receive repetitive foot shocks. Observers had higher fear responses when demonstrators were socially related to themselves, such as siblings or mating partners. Inactivation of anterior cingulate cortex (ACC) and parafascicular or mediodorsal thalamic nuclei, which comprise the medial pain system representing pain affection, substantially impaired this observational fear learning, whereas inactivation of sensory thalamic nuclei had no effect. The ACC neuronal activities were increased and synchronized with those of the lateral amygdala at theta rhythm frequency during this learning. Furthermore, an ACC-limited deletion of Ca(v)1.2 Ca(2+) channels in mice impaired observational fear learning and reduced behavioral pain responses. These results demonstrate the functional involvement of the affective pain system and Ca(v)1.2 channels of the ACC in observational social fear.

  13. RGS12 interacts with the SNARE-binding region of the Cav2.2 calcium channel.

    PubMed

    Richman, Ryan W; Strock, Jesse; Hains, Melinda D; Cabanilla, Nory Jun; Lau, King-Kei; Siderovski, David P; Diversé-Pierluissi, María

    2005-01-14

    Activation of GABAB receptors in chick dorsal root ganglion (DRG) neurons inhibits the Cav2.2 calcium channel in both a voltage-dependent and voltage-independent manner. The voltage-independent inhibition requires activation of a tyrosine kinase that phosphorylates the alpha1 subunit of the channel and thereby recruits RGS12, a member of the "regulator of G protein signaling" (RGS) proteins. Here we report that RGS12 binds to the SNARE-binding or "synprint" region (amino acids 726-985) in loop II-III of the calcium channel alpha1 subunit. A recombinant protein encompassing the N-terminal PTB domain of RGS12 binds to the synprint region in protein overlay and surface plasmon resonance binding assays; this interaction is dependent on tyrosine phosphorylation and yet is within a sequence that differs from the canonical NPXY motif targeted by other PTB domains. In electrophysiological experiments, microinjection of DRG neurons with synprint-derived peptides containing the tyrosine residue Tyr-804 altered the rate of desensitization of neurotransmitter-mediated inhibition of the Cav2.2 calcium channel, whereas peptides centered about a second tyrosine residue, Tyr-815, were without effect. RGS12 from a DRG neuron lysate was precipitated using synprint peptides containing phosphorylated Tyr-804. The high degree of conservation of Tyr-804 in the SNARE-binding region of Cav2.1 and Cav2.2 calcium channels suggests that this region, in addition to the binding of SNARE proteins, is also important for determining the time course of the modulation of calcium current via tyrosine phosphorylation.

  14. Complex regulation of voltage-dependent activation and inactivation properties of retinal voltage-gated Cav1.4 L-type Ca2+ channels by Ca2+-binding protein 4 (CaBP4).

    PubMed

    Shaltiel, Lior; Paparizos, Christos; Fenske, Stefanie; Hassan, Sami; Gruner, Christian; Rötzer, Katrin; Biel, Martin; Wahl-Schott, Christian A

    2012-10-19

    Cav1.4 L-type Ca(2+) channels are crucial for synaptic transmission in retinal photoreceptors and bipolar neurons. Recent studies suggest that the activity of this channel is regulated by the Ca(2+)-binding protein 4 (CaBP4). In the present study, we explored this issue by examining functional effects of CaBP4 on heterologously expressed Cav1.4. We show that CaBP4 dramatically increases Cav1.4 channel availability. This effect crucially depends on the presence of the C-terminal ICDI (inhibitor of Ca(2+)-dependent inactivation) domain of Cav1.4 and is absent in a Cav1.4 mutant lacking the ICDI. Using FRET experiments, we demonstrate that CaBP4 interacts with the IQ motif of Cav1.4 and that it interferes with the binding of the ICDI domain. Based on these findings, we suggest that CaBP4 increases Cav1.4 channel availability by relieving the inhibitory effects of the ICDI domain on voltage-dependent Cav1.4 channel gating. We also functionally characterized two CaBP4 mutants that are associated with a congenital variant of human night blindness and other closely related nonstationary retinal diseases. Although both mutants interact with Cav1.4 channels, the functional effects of CaBP4 mutants are only partially preserved, leading to a reduction of Cav1.4 channel availability and loss of function. In conclusion, our study sheds new light on the functional interaction between CaBP4 and Cav1.4. Moreover, it provides insights into the mechanism by which CaBP4 mutants lead to loss of Cav1.4 function and to retinal disease. PMID:22936811

  15. β-Adrenergic–regulated phosphorylation of the skeletal muscle CaV1.1 channel in the fight-or-flight response

    PubMed Central

    Emrick, Michelle A.; Sadilek, Martin; Konoki, Keiichi; Catterall, William A.

    2010-01-01

    CaV1 channels initiate excitation–contraction coupling in skeletal and cardiac muscle. During the fight-or-flight response, epinephrine released by the adrenal medulla and norepinephrine released from sympathetic nerves increase muscle contractility by activation of the β-adrenergic receptor/cAMP-dependent protein kinase pathway and up-regulation of CaV1 channels in skeletal and cardiac muscle. Although the physiological mechanism of this pathway is well defined, the molecular mechanism and the sites of protein phosphorylation required for CaV1 channel regulation are unknown. To identify the regulatory sites of phosphorylation under physiologically relevant conditions, CaV1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac CaV1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that CaV1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas CaV1.1-T1579 is a substrate for casein kinase 2. Treatment of rabbits with isoproterenol to activate β-adrenergic receptors increased phosphorylation of S1575 in skeletal muscle CaV1.1 channels in vivo, and treatment with propranolol to inhibit β-adrenergic receptors reduced phosphorylation. As S1575 and T1579 in CaV1.1 channels and their homologs in CaV1.2 channels are located at a key regulatory interface between the distal and proximal C-terminal domains, it is likely that phosphorylation of these sites in skeletal and cardiac muscle is directly involved in calcium channel regulation in response to the sympathetic nervous system in the fight-or-flight response. PMID:20937870

  16. Beta-adrenergic-regulated phosphorylation of the skeletal muscle Ca(V)1.1 channel in the fight-or-flight response.

    PubMed

    Emrick, Michelle A; Sadilek, Martin; Konoki, Keiichi; Catterall, William A

    2010-10-26

    Ca(V)1 channels initiate excitation-contraction coupling in skeletal and cardiac muscle. During the fight-or-flight response, epinephrine released by the adrenal medulla and norepinephrine released from sympathetic nerves increase muscle contractility by activation of the β-adrenergic receptor/cAMP-dependent protein kinase pathway and up-regulation of Ca(V)1 channels in skeletal and cardiac muscle. Although the physiological mechanism of this pathway is well defined, the molecular mechanism and the sites of protein phosphorylation required for Ca(V)1 channel regulation are unknown. To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2. Treatment of rabbits with isoproterenol to activate β-adrenergic receptors increased phosphorylation of S1575 in skeletal muscle Ca(V)1.1 channels in vivo, and treatment with propranolol to inhibit β-adrenergic receptors reduced phosphorylation. As S1575 and T1579 in Ca(V)1.1 channels and their homologs in Ca(V)1.2 channels are located at a key regulatory interface between the distal and proximal C-terminal domains, it is likely that phosphorylation of these sites in skeletal and cardiac muscle is directly involved in calcium channel regulation in response to the sympathetic nervous system in the fight-or-flight response.

  17. Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory Hyperalgesia in Mouse Dorsal Root Ganglion Neurons

    PubMed Central

    Shibata, Yasuhiro; Kumamoto, Natsuko; Shimada, Shoichi; Ugawa, Shinya

    2015-01-01

    The Cav3.2 isoform of the T-type calcium channel is expressed in primary sensory neurons of the dorsal root ganglion (DRG), and these channels contribute to nociceptive and neuropathic pain in rats. However, there are conflicting reports on the roles of these channels in pain processing in rats and mice. In addition, the function of T-type channels in persistent inflammatory hyperalgesia is poorly understood. We performed behavioral and comprehensive histochemical analyses to characterize Cav3.2-expressing DRG neurons and examined the regulation of T-type channels in DRGs from C57BL/6 mice with carrageenan-induced inflammatory hyperalgesia. We show that approximately 20% of mouse DRG neurons express Cav3.2 mRNA and protein. The size of the majority of Cav3.2-positive DRG neurons (69 ± 8%) ranged from 300 to 700 μm2 in cross-sectional area and 20 to 30 μm in estimated diameter. These channels co-localized with either neurofilament-H (NF-H) or peripherin. The peripherin-positive cells also overlapped with neurons that were positive for isolectin B4 (IB4) and calcitonin gene-related peptide (CGRP) but were distinct from transient receptor potential vanilloid 1 (TRPV1)-positive neurons during normal mouse states. In mice with carrageenan-induced inflammatory hyperalgesia, Cav3.2 channels, but not Cav3.1 or Cav3.3 channels, were upregulated in ipsilateral DRG neurons during the sub-acute phase. The increased Cav3.2 expression partially resulted from an increased number of Cav3.2-immunoreactive neurons; this increase in number was particularly significant for TRPV1-positive neurons. Finally, preceding and periodic intraplantar treatment with the T-type calcium channel blockers mibefradil and NNC 55-0396 markedly reduced and reversed mechanical hyperalgesia during the acute and sub-acute phases, respectively, in mice. These data suggest that Cav3.2 T-type channels participate in the development of inflammatory hyperalgesia, and this channel might play an even greater

  18. Current Progress of a Finite Element Computational Fluid Dynamics Prediction of Flutter for the AeroStructures Test Wing

    NASA Technical Reports Server (NTRS)

    Arena, Andrew S., Jr.

    2002-01-01

    This progress report focuses on the use of the STructural Analysis RoutineS suite program, SOLIDS, input for the AeroStructures Test Wing. The AeroStructures Test Wing project as a whole is described. The use of the SOLIDS code to find the mode shapes of a structure is discussed. The frequencies, and the structural dynamics to which they relate are examined. The results of the CFD predictions are compared to experimental data from a Ground Vibration Test.

  19. Expression patterns of T-type Cav3.2 channel and insulin-like growth factor-1 receptor in dorsal root ganglion neurons of mice after sciatic nerve axotomy.

    PubMed

    Lin, Si-Fang; Yu, Xiao-Lu; Liu, Xiao-Ya; Wang, Bing; Li, Cheng-Hui; Sun, Yan-Gang; Liu, Xing-Jun

    2016-10-19

    Substantial evidence indicates that T-type Cav3.2 channel and insulin-like growth factor-1 (IGF-1) contribute to pain hypersensitivity within primary sensory nerves. A recent study suggested that activation of IGF-1 receptor (IGF-1R) could increase Cav3.2 channel currents and further contribute to inflammatory pain sensitivity. However, the expression patterns of Cav3.2 and IGF-1R and their colocalization in dorsal root ganglion (DRG) in chronic neuropathic pain condition remain unknown. In this study, we explored expression patterns of Cav3.2, IGF-1R and their colocalization, and whether phenotypic switch occurs in a subpopulation of Cav3.2 or IGF-1R neurons in mouse DRGs after sciatic nerve axotomy with immunofluorescence, real-time reverse transcription-PCR, and western blot assays. We found that expressions of Cav3.2 and IGF-1R, and their colocalization were not increased in DRGs of mice following axotomy. In addition, Cav3.2 or IGF-1R subpopulation neurons did not acquire significant switch in expression phenotype after sciatic nerve axotomy. Our findings argue for an upregulation of Cav3.2 and IGF-1R expression in lumbar DRGs post-sciatic nerve axotomy and provided an insight for understanding the functions of peripheral afferent Cav3.2 channel and IGF-1/IGF-1R signaling in chronic neuropathic pain. PMID:27571431

  20. Computational Aero-acoustics As a Tool For Turbo-machinery Noise Reduction

    NASA Technical Reports Server (NTRS)

    Dyson, Rodger W.

    2003-01-01

    This talk will provide an overview of the field of computational aero-acoustics and its use in fan noise prediction. After a brief history of computational fluid dynamics, some of the recent developments in computational aero-acoustics will be explored. Computational issues concerning sound wave production, propagation, and reflection in practical turbo-machinery applications will be discussed including: (a) High order/High Resolution Numerical Techniques. (b) High Resolution Boundary Conditions. [c] MIMD Parallel Computing. [d] Form of Governing Equations Useful for Simulations. In addition, the basic design of our Broadband Analysis Stator Simulator (BASS) code and its application to a 2 D rotor wake-stator interaction will be shown. An example of the noise produced by the wakes from a rotor impinging upon a stator cascade will be shown.

  1. Global Mobile Satellite Service Interference Analysis for the AeroMACS

    NASA Technical Reports Server (NTRS)

    Wilson, Jeffrey D.; Apaza, Rafael D..; Hall, Ward; Phillips, Brent

    2013-01-01

    The AeroMACS (Aeronautical Mobile Airport Communications System), which is based on the IEEE 802.16-2009 mobile wireless standard, is envisioned as the wireless network which will cover all areas of airport surfaces for next generation air transportation. It is expected to be implemented in the 5091-5150 MHz frequency band which is also occupied by mobile satellite service uplinks. Thus the AeroMACS must be designed to avoid interference with this incumbent service. Simulations using Visualyse software were performed utilizing a global database of 6207 airports. Variations in base station and subscriber antenna distribution and gain pattern were examined. Based on these simulations, recommendations for global airport base station and subscriber antenna power transmission limitations are provided.

  2. Large Wind Turbine Rotor Design using an Aero-Elastic / Free-Wake Panel Coupling Code

    NASA Astrophysics Data System (ADS)

    Sessarego, Matias; Ramos-García, Néstor; Shen, Wen Zhong; Nørkær Sørensen, Jens

    2016-09-01

    Despite the advances in computing resources in the recent years, the majority of large wind-turbine rotor design problems still rely on aero-elastic codes that use blade element momentum (BEM) approaches to model the rotor aerodynamics. The present work describes an approach to wind-turbine rotor design by incorporating a higher-fidelity free-wake panel aero-elastic coupling code called MIRAS-FLEX. The optimization procedure includes a series of design load cases and a simple structural design code. Due to the heavy MIRAS-FLEX computations, a surrogate-modeling approach is applied to mitigate the overall computational cost of the optimization. Improvements in cost of energy, annual energy production, maximum flap-wise root bending moment, and blade mass were obtained for the NREL 5MW baseline wind turbine.

  3. Altered short-term synaptic plasticity and reduced muscle strength in mice with impaired regulation of presynaptic CaV2.1 Ca2+ channels.

    PubMed

    Nanou, Evanthia; Yan, Jin; Whitehead, Nicholas P; Kim, Min Jeong; Froehner, Stanley C; Scheuer, Todd; Catterall, William A

    2016-01-26

    Facilitation and inactivation of P/Q-type calcium (Ca(2+)) currents through the regulation of voltage-gated Ca(2+) (CaV) 2.1 channels by Ca(2+) sensor (CaS) proteins contributes to the facilitation and rapid depression of synaptic transmission in cultured neurons that transiently express CaV2.1 channels. To examine the modulation of endogenous CaV2.1 channels by CaS proteins in native synapses, we introduced a mutation (IM-AA) into the CaS protein-binding site in the C-terminal domain of CaV2.1 channels in mice, and tested synaptic facilitation and depression in neuromuscular junction synapses that use exclusively CaV2.1 channels for Ca(2+) entry that triggers synaptic transmission. Even though basal synaptic transmission was unaltered in the neuromuscular synapses in IM-AA mice, we found reduced short-term facilitation in response to paired stimuli at short interstimulus intervals in IM-AA synapses. In response to trains of action potentials, we found increased facilitation at lower frequencies (10-30 Hz) in IM-AA synapses accompanied by slowed synaptic depression, whereas synaptic facilitation was reduced at high stimulus frequencies (50-100 Hz) that would induce strong muscle contraction. As a consequence of altered regulation of CaV2.1 channels, the hindlimb tibialis anterior muscle in IM-AA mice exhibited reduced peak force in response to 50 Hz stimulation and increased muscle fatigue. The IM-AA mice also had impaired motor control, exercise capacity, and grip strength. Taken together, our results indicate that regulation of CaV2.1 channels by CaS proteins is essential for normal synaptic plasticity at the neuromuscular junction and for muscle strength, endurance, and motor coordination in mice in vivo.

  4. Agronomical and chemical characterisation of Thymbra capitata (L.) Cav. biotypes from Sicily, Italy.

    PubMed

    Tuttolomondo, Teresa; Dugo, Giacomo; Leto, Claudio; Cicero, Nicola; Tropea, Alessia; Virga, Giuseppe; Leone, Raffaele; Licata, Mario; La Bella, Salvatore

    2015-01-01

    In this study, the agronomical and chemical characterisation of 13 Sicilian biotypes of Thymbra capitata (L.) Cav., grown under the same agricultural and environmental condition, are reported. The main morpho-productive parameters and quali-quantitative profile of essential oils (EOs) were determined. The EOs were analysed by gas chromatography-flame ionisation detector and gas chromatography-mass spectrometry. Hierarchical cluster analysis and principal component analysis statistical methods were used to group biotypes according to the EOs chemical composition. The EO yield ranged between 4.6 and 8.1 (v/w). A total of 38 EO compounds have been identified. The compounds mostly represented were α-pinene, myrcene, α-terpinene, p-cymene, γ-terpinene, borneol, carvacrol and β-caryophyllene. In all biotypes, the carvacrol (67.4-79.5%) was the main compound, confirming that T. capitata is a carvacrol chemotype. The results showed that all Sicilian Thymbra biotypes have a good adaptation to the climatic conditions of the test environment.

  5. A comparative study of mucilage and pulp polysaccharides from tamarillo fruit (Solanum betaceum Cav.).

    PubMed

    do Nascimento, Georgia Erdmann; Iacomini, Marcello; Cordeiro, Lucimara M C

    2016-07-01

    A comparative study of mucilage (locular tissue) and pulp polysaccharides from ripe tamarillo fruits (Solanum betaceum Cav.) was carried out. After aqueous and alkaline extractions and various purification steps (freeze-thaw and α-amylase - EC 3.2.1.1 treatments, Fehling precipitation and ultrafiltration through 50 kDa cut-off membrane), the obtained fractions from mucilage were analyzed by sugar composition, HPSEC, and NMR spectroscopy analyses. The results showed that the mucilage of tamarillo contains a highly methoxylated homogalacturonans mixed with type I arabinogalactans, a linear (1 → 5)-linked α-L-arabinan, and a linear (1 → 4)-β-D-xylan. A comparison with polysaccharides extracted from the pulp revealed that differences were observed in the yield and in the ratio of extracted polysaccharides. Moreover, structural differences between pulp and mucilage polysaccharides were also observed, such as in the length of side chains of the pectins, and in the degree of branching of the xylans. PMID:27163609

  6. Chemical constituents and biological activities of Galinsoga parviflora cav. (Asteraceae) from Egypt.

    PubMed

    Mostafa, Islam; Abd El-Aziz, Ehsan; Hafez, Samia; El-Shazly, Assem

    2013-01-01

    The phytochemical investigation of an aqueous ethanolic extract of Galinsoga parviflora Cav. (Asteraceae) resulted in the isolation and identification of eleven compounds namely: triacontanol, phytol, beta-sitosterol, stigmasterol, 7-hydroxy-beta-sitosterol, 7-hydroxystigmasterol, beta-sitosterol-3-O-beta-D-glucoside, 3,4-dimethoxycinnamic acid, protocatechuic acid, fumaric acid, and uracil. Furthermore, 48 volatile constituents were identified in the hydrodistilled oil of the aerial parts. The ethanolic extract at a content of 400 mg/kg body weight (BW) exerted 87% reduction in the alanine aminotransferase enzyme level in cirrhotic rats compared with the standard silymarin (150 mg/kg BW) and also exerted a reduction in the blood glucose level equivalent to that of glibenclamide (5 mg/kg BW) in diabetic rats. The ethanolic extract, light petroleum and ethyl acetate fractions exhibited substantial antimicrobial activity against Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Aspergillus niger, and Candida albicans. The ethyl acetate fraction showed strong antioxidant activity at a concentration of 150 mg/mL as compared with 0.1 M ascorbic acid. The cytotoxic effect against the MCF-7 cell line was found to be weak. PMID:24066513

  7. Agronomical and chemical characterisation of Thymbra capitata (L.) Cav. biotypes from Sicily, Italy.

    PubMed

    Tuttolomondo, Teresa; Dugo, Giacomo; Leto, Claudio; Cicero, Nicola; Tropea, Alessia; Virga, Giuseppe; Leone, Raffaele; Licata, Mario; La Bella, Salvatore

    2015-01-01

    In this study, the agronomical and chemical characterisation of 13 Sicilian biotypes of Thymbra capitata (L.) Cav., grown under the same agricultural and environmental condition, are reported. The main morpho-productive parameters and quali-quantitative profile of essential oils (EOs) were determined. The EOs were analysed by gas chromatography-flame ionisation detector and gas chromatography-mass spectrometry. Hierarchical cluster analysis and principal component analysis statistical methods were used to group biotypes according to the EOs chemical composition. The EO yield ranged between 4.6 and 8.1 (v/w). A total of 38 EO compounds have been identified. The compounds mostly represented were α-pinene, myrcene, α-terpinene, p-cymene, γ-terpinene, borneol, carvacrol and β-caryophyllene. In all biotypes, the carvacrol (67.4-79.5%) was the main compound, confirming that T. capitata is a carvacrol chemotype. The results showed that all Sicilian Thymbra biotypes have a good adaptation to the climatic conditions of the test environment. PMID:25600887

  8. Calmodulin kinase II is involved in voltage-dependent facilitation of the L-type Cav1.2 calcium channel: Identification of the phosphorylation sites.

    PubMed

    Lee, Tae-Seong; Karl, Rosi; Moosmang, Sven; Lenhardt, Peter; Klugbauer, Norbert; Hofmann, Franz; Kleppisch, Thomas; Welling, Andrea

    2006-09-01

    Calcium-dependent facilitation of L-type calcium channels has been reported to depend on the function of calmodulin kinase II. In contrast, the mechanism for voltage-dependent facilitation is not clear. In HEK 293 cells expressing Ca(v)1.2, Ca(v)beta2a, and calmodulin kinase II, the calcium current measured at +30 mV was facilitated up to 1.5-fold by a 200-ms-long prepulse to +160 mV. This voltage-dependent facilitation was prevented by the calmodulin kinase II inhibitors KN93 and the autocamtide-2-related peptide. In cells expressing the Ca(v)1.2 mutation I1649E, a residue critical for the binding of Ca2+-bound calmodulin, facilitation was also abolished. Calmodulin kinase II was coimmunoprecipitated with the Ca(v)1.2 channel from murine heart and HEK 293 cells expressing Ca(v)1.2 and calmodulinkinase II. The precipitated Ca(v)1.2 channel was phosphorylated in the presence of calmodulin and Ca2+. Fifteen putative calmodulin kinase II phosphorylation sites were identified mostly in the carboxyl-terminal tail of Ca(v)1.2. Neither truncation at amino acid 1728 nor changing the II-III loop serines 808 and 888 to alanines affected facilitation of the calcium current. In contrast, facilitation was decreased by the single mutations S1512A and S1570A and abolished by the double mutation S1512A/S1570A. These serines flank the carboxyl-terminal EF-hand motif. Immunoprecipitation of calmodulin kinase II with the Ca(v)1.2 channel was not affected by the mutation S1512A/S1570A. The phosphorylation of the Ca(v)1.2 protein was strongly decreased in the S1512A/S1570A double mutant. These results suggest that voltage-dependent facilitation of the Ca(v)1.2 channel depends on the phosphorylation of Ser1512/Ser1570 by calmodulin kinase II. PMID:16820363

  9. Modulation of Voltage- and Ca2+-dependent Gating of CaV1.3 L-type Calcium Channels by Alternative Splicing of a C-terminal Regulatory Domain*

    PubMed Central

    Singh, Anamika; Gebhart, Mathias; Fritsch, Reinhard; Sinnegger-Brauns, Martina J.; Poggiani, Chiara; Hoda, Jean-Charles; Engel, Jutta; Romanin, Christoph; Striessnig, Jörg; Koschak, Alexandra

    2008-01-01

    Low voltage activation of CaV1.3 L-type Ca2+ channels controls excitability in sensory cells and central neurons as well as sinoatrial node pacemaking. CaV1.3-mediated pacemaking determines neuronal vulnerability of dopaminergic striatal neurons affected in Parkinson disease. We have previously found that in CaV1.4 L-type Ca2+ channels, activation, voltage, and calcium-dependent inactivation are controlled by an intrinsic distal C-terminal modulator. Because alternative splicing in the CaV1.3 α1 subunit C terminus gives rise to a long (CaV1.342) and a short form (CaV1.342A), we investigated if a C-terminal modulatory mechanism also controls CaV1.3 gating. The biophysical properties of both splice variants were compared after heterologous expression together with β3 and α2δ1 subunits in HEK-293 cells. Activation of calcium current through CaV1.342A channels was more pronounced at negative voltages, and inactivation was faster because of enhanced calcium-dependent inactivation. By investigating several CaV1.3 channel truncations, we restricted the modulator activity to the last 116 amino acids of the C terminus. The resulting CaV1.3ΔC116 channels showed gating properties similar to CaV1.342A that were reverted by co-expression of the corresponding C-terminal peptide C116. Fluorescence resonance energy transfer experiments confirmed an intramolecular protein interaction in the C terminus of CaV1.3 channels that also modulates calmodulin binding. These experiments revealed a novel mechanism of channel modulation enabling cells to tightly control CaV1.3 channel activity by alternative splicing. The absence of the C-terminal modulator in short splice forms facilitates CaV1.3 channel activation at lower voltages expected to favor CaV1.3 activity at threshold voltages as required for modulation of neuronal firing behavior and sinoatrial node pacemaking. PMID:18482979

  10. Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation

    PubMed Central

    Zhang, Ping-xia; Cheng, Jijun; Zou, Siying; D’Souza, Anthony D.; Koff, Jonathan L.; Lu, Jun; Lee, Patty J.; Krause, Diane S.; Egan, Marie E.; Bruscia, Emanuela M.

    2015-01-01

    In Cystic Fibrosis (CF) patients, hyper-inflammation is a key factor in lung destruction and disease morbidity. We have previously demonstrated that macrophages drive the lung hyper-inflammatory response to LPS in CF mice, due to reduced levels of the scaffold protein CAV1 with subsequent uncontrolled TLR4 signaling. Here we show that reduced CAV1 and, consequently, increased TLR4 signaling, in human and murine CF macrophages and murine CF lungs, is caused by high microRNA-199a-5p levels, which are PI3K/AKT-dependent. Down-regulation of microRNA-199a-5p or increased AKT signaling restores CAV1 expression and reduces hyper-inflammation in CF macrophages. Importantly, the FDA approved drug celecoxib reestablishes the AKT/miR-199a-5p/CAV1 axis in CF macrophages, and ameliorates lung hyper-inflammation in Cftr-deficient mice. Thus, we identify the AKT/miR-199a-5p/CAV1 pathway as a regulator of innate immunity, which is dysfunctional in CF macrophages contributing to lung hyper-inflammation. Importantly, this pathway is targeted by celecoxib. PMID:25665524

  11. Investigation of biological activity of polar extracts isolated from Phlomis crinita Cav ssp. mauritanica Munby.

    PubMed

    Limem-Ben Amor, Ilef; Skandrani, Ines; Boubaker, Jihed; Ben Sghaïer, Mohamed; Neffati, Aicha; Bhouri, Wissem; Bouhlel, Ines; Chouchane, Nabil; Kilani, Soumaya; Guedon, Emmanuel; Ghoul, Mohamed; Ghedira, Kamel; Chekir-Ghedira, Leila

    2009-01-01

    The lyophilized infusion, the methanol, the ethyl acetate, and the total oligomer flavonoid (TOF)-enriched extracts prepared from the dried leaves of Phlomis crinita Cav. ssp. mauritanica Munby were investigated for the contents of flavonoids, tannins, coumarines and steroids. Antibacterial activity was investigated toward five bacterial strains. An inhibitory effect was observed against Staphyllococcus aureus and Enterococcus feacalis, and the minimal inhibitory concentrations ranged from 2.5 to 5 mg/mL of extract. The tested extracts exhibit an important free radical scavenging activity toward the 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical; with IC(50) values of 30.5, 6, 32, and 31.5 microg/mL, respectively, in the presence of lyophilized infusion, the TOF, the methanol, and the ethyl acetate extracts. Genotoxic and antigenotoxic properties of the different extracts were studied by using the SOS chromotest with Escherichia coli PQ37. The lyophilized infusion and TOF extracts obtained from P. crinita ssp. mauritanica showed no genotoxicity, whereas methanol and ethyl acetate extracts are considered as marginally genotoxic. On the other hand, we showed that each extract inhibited the mutagenicity induced by aflatoxin B1 (AFB1) (10 microg/assay) and nifuroxazide (NF) (10 microg/assay). The ethyl acetate extract showed the strongest level of protection toward the genotoxicity induced by both directly and indirectly genotoxic NF and AFB1. These tests proved that the lyophilized infusion possesses an antiradical activity likewise, it showed no genotoxic effect; that is why we choose this extract to assess its antiulcerogenic activity by using an ethanol-induced ulcerogenesis model in the rat. This test demonstrates that 300 mg/kg of a P. crinita ssp. mauritanica lyophilized infusion was more effective than the reference compound, cimetidine. PMID:19514937

  12. Electrophysiological characterization of activation state-dependent Ca(v)2 channel antagonist TROX-1 in spinal nerve injured rats.

    PubMed

    Patel, R; Rutten, K; Valdor, M; Schiene, K; Wigge, S; Schunk, S; Damann, N; Christoph, T; Dickenson, A H

    2015-06-25

    Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury. PMID:25839150

  13. Hydrogen sulfide-induced itch requires activation of Cav3.2 T-type calcium channel in mice

    PubMed Central

    Wang, Xue-Long; Tian, Bin; Huang, Ya; Peng, Xiao-Yan; Chen, Li-Hua; Li, Jun-Cheng; Liu, Tong

    2015-01-01

    The contributions of gasotransmitters to itch sensation are largely unknown. In this study, we aimed to investigate the roles of hydrogen sulfide (H2S), a ubiquitous gasotransmitter, in itch signaling. We found that intradermal injection of H2S donors NaHS or Na2S, but not GYY4137 (a slow-releasing H2S donor), dose-dependently induced scratching behavior in a μ-opioid receptor-dependent and histamine-independent manner in mice. Interestingly, NaHS induced itch via unique mechanisms that involved capsaicin-insensitive A-fibers, but not TRPV1-expressing C-fibers that are traditionally considered for mediating itch, revealed by depletion of TRPV1-expressing C-fibers by systemic resiniferatoxin treatment. Moreover, local application of capsaizapine (TRPV1 blocker) or HC-030031 (TRPA1 blocker) had no effects on NaHS-evoked scratching. Strikingly, pharmacological blockade and silencing of Cav3.2 T-type calcium channel by mibefradil, ascorbic acid, zinc chloride or Cav3.2 siRNA dramatically decreased NaHS-evoked scratching. NaHS induced robust alloknesis (touch-evoked itch), which was inhibited by T-type calcium channels blocker mibefradil. Compound 48/80-induced itch was enhanced by an endogenous precursor of H2S (L-cysteine) but attenuated by inhibitors of H2S-producing enzymes cystathionine γ-lyase and cystathionine β-synthase. These results indicated that H2S, as a novel nonhistaminergic itch mediator, may activates Cav3.2 T-type calcium channel, probably located at A-fibers, to induce scratching and alloknesis in mice. PMID:26602811

  14. Hydrogen sulfide-induced itch requires activation of Cav3.2 T-type calcium channel in mice.

    PubMed

    Wang, Xue-Long; Tian, Bin; Huang, Ya; Peng, Xiao-Yan; Chen, Li-Hua; Li, Jun-Cheng; Liu, Tong

    2015-01-01

    The contributions of gasotransmitters to itch sensation are largely unknown. In this study, we aimed to investigate the roles of hydrogen sulfide (H2S), a ubiquitous gasotransmitter, in itch signaling. We found that intradermal injection of H2S donors NaHS or Na2S, but not GYY4137 (a slow-releasing H2S donor), dose-dependently induced scratching behavior in a μ-opioid receptor-dependent and histamine-independent manner in mice. Interestingly, NaHS induced itch via unique mechanisms that involved capsaicin-insensitive A-fibers, but not TRPV1-expressing C-fibers that are traditionally considered for mediating itch, revealed by depletion of TRPV1-expressing C-fibers by systemic resiniferatoxin treatment. Moreover, local application of capsaizapine (TRPV1 blocker) or HC-030031 (TRPA1 blocker) had no effects on NaHS-evoked scratching. Strikingly, pharmacological blockade and silencing of Cav3.2 T-type calcium channel by mibefradil, ascorbic acid, zinc chloride or Cav3.2 siRNA dramatically decreased NaHS-evoked scratching. NaHS induced robust alloknesis (touch-evoked itch), which was inhibited by T-type calcium channels blocker mibefradil. Compound 48/80-induced itch was enhanced by an endogenous precursor of H2S (L-cysteine) but attenuated by inhibitors of H2S-producing enzymes cystathionine γ-lyase and cystathionine β-synthase. These results indicated that H2S, as a novel nonhistaminergic itch mediator, may activates Cav3.2 T-type calcium channel, probably located at A-fibers, to induce scratching and alloknesis in mice. PMID:26602811

  15. Cav1.2 splice variant with exon 9* is critical for regulation of cerebral artery diameter

    PubMed Central

    Nystoriak, Matthew A.; Murakami, Kentaro; Penar, Paul L.

    2009-01-01

    L-type voltage-dependent Ca2+ channels (VDCCs) are essential for numerous processes in the cardiovascular and nervous systems. Alternative splicing modulates proteomic composition of Cav1.2 to generate functional variation between channel isoforms. Here, we describe expression and function of Cav1.2 channels containing alternatively spliced exon 9* in cerebral artery myocytes. RT-PCR showed expression of Cav1.2 splice variants both containing (α1C9/9*/10) and lacking (α1C9/10) exon 9* in intact rabbit and human cerebral arteries. With the use of laser capture microdissection and RT-PCR, expression of mRNA for both α1C9/9*/10 and α1C9/10 was demonstrated in isolated cerebral artery myocytes. Quantitative real-time PCR revealed significantly greater α1C9/9*/10 expression relative to α1C9/10 in intact rabbit cerebral arteries compared with cardiac tissue and cerebral cortex. To demonstrate a functional role for α1C9/9*/10, smooth muscle of intact cerebral arteries was treated with antisense oligonucleotides targeting α1C9/9*/10 (α1C9/9*/10-AS) or exon 9 (α1C-AS), expressed in all Cav1.2 splice variants, by reversible permeabilization and organ cultured for 1–4 days. Treatment with α1C9/9*/10-AS reduced maximal constriction induced by elevated extracellular K+ ([K+]o) by ∼75% compared with α1C9/9*/10-sense-treated arteries. Maximal constriction in response to the Ca2+ ionophore ionomycin and [K+]o EC50 values were not altered by antisense treatment. Decreases in maximal [K+]o-induced constriction were similar between α1C9/9*/10-AS and α1C-AS groups (22.7 ± 9% and 25.6 ± 4% constriction, respectively). We conclude that although cerebral artery myocytes express both α1C9/9*/10 and α1C9/10 VDCC splice variants, α1C9/9*/10 is functionally dominant in the control of cerebral artery diameter. PMID:19717733

  16. Inhibitory and excitatory axon terminals share a common nano-architecture of their Cav2.1 (P/Q-type) Ca(2+) channels.

    PubMed

    Althof, Daniel; Baehrens, David; Watanabe, Masahiko; Suzuki, Noboru; Fakler, Bernd; Kulik, Ákos

    2015-01-01

    Tuning of the time course and strength of inhibitory and excitatory neurotransmitter release is fundamental for the precise operation of cortical network activity and is controlled by Ca(2+) influx into presynaptic terminals through the high voltage-activated P/Q-type Ca(2+) (Cav2.1) channels. Proper channel-mediated Ca(2+)-signaling critically depends on the topographical arrangement of the channels in the presynaptic membrane. Here, we used high-resolution SDS-digested freeze-fracture replica immunoelectron microscopy together with automatized computational analysis of Cav2.1 immunogold labeling to determine the precise subcellular organization of Cav2.1 channels in both inhibitory and excitatory terminals. Immunoparticles labeling the pore-forming α1 subunit of Cav2.1 channels were enriched over the active zone of the boutons with the number of channels (3-62) correlated with the area of the synaptic membrane. Detailed analysis showed that Cav2.1 channels are non-uniformly distributed over the presynaptic membrane specialization where they are arranged in clusters of an average five channels per cluster covering a mean area with a diameter of about 70 nm. Importantly, clustered arrangement and cluster properties did not show any significant difference between GABAergic and glutamatergic terminals. Our data demonstrate a common nano-architecture of Cav2.1 channels in inhibitory and excitatory boutons in stratum radiatum of the hippocampal CA1 area suggesting that the cluster arrangement is crucial for the precise release of transmitters from the axonal boutons. PMID:26321916

  17. Alternative splicing generates a smaller assortment of CaV2.1 transcripts in cerebellar Purkinje cells than in the cerebellum.

    PubMed

    Kanumilli, Srinivasan; Tringham, Elizabeth W; Payne, C Elizabeth; Dupere, Jonathan R B; Venkateswarlu, Kanamarlapudi; Usowicz, Maria M

    2006-01-12

    P/Q-type calcium channels control many calcium-driven functions in the brain. The CACNA1A gene encoding the pore-forming CaV2.1 (alpha1A) subunit of P/Q-type channels undergoes alternative splicing at multiple loci. This results in channel variants with different phenotypes. However, the combinatorial patterns of alternative splice events at two or more loci, and hence the diversity of CaV2.1 transcripts, are incompletely defined for specific brain regions and types of brain neurons. Using RT-PCR and splice variant-specific primers, we have identified multiple CaV2.1 transcript variants defined by different pairs of splice events in the cerebellum of adult rat. We have uncovered new splice variations between exons 28 and 34 (some of which predict a premature stop codon) and a new variation in exon 47 (which predicts a novel extended COOH-terminus). Single cell RT-PCR reveals that each individual cerebellar Purkinje neuron also expresses multiple alternative CaV2.1 transcripts, but the assortment is smaller than in the cerebellum. Two of these variants encode different extended COOH-termini which are not the same as those previously reported in Purkinje cells of the mouse. Our patch-clamp recordings show that calcium channel currents in the soma and dendrites of Purkinje cells are largely inhibited by a concentration of omega-agatoxin IVA selective for P-type over Q-type channels, suggesting that the different transcripts may form phenotypic variants of P-type calcium channels in Purkinje cells. These results expand the known diversity of CaV2.1 transcripts in cerebellar Purkinje cells, and propose the selective expression of distinct assortments of CaV2.1 transcripts in different brain neurons and species.

  18. Acute effects of pregabalin on the function and cellular distribution of Ca(V)2.1 in HEK293t cells.

    PubMed

    Weissmann, Carina; Di Guilmi, Mariano N; Urbano, Francisco J; Uchitel, Osvaldo D

    2013-01-01

    We established a cell model to study the acute effects of pregabalin (PGB), a drug widely used in epilepsy and neuropathic pain, on voltage gated Ca(V)2.1 (P/Q-type) calcium channels function and distribution at the membrane level. HEK293t cells were transfected with plasmids coding for all subunits of the Ca(V)2.1 channel. We used a α1 fused to an eGFP tag to follow its distribution in time and at different experimental conditions. The expressed channel was functional as shown by the presence of barium-mediated, calcium currents of transfected cells measured by 'whole-cell voltage-clamp' recordings, showing a maximum current peak in the I-V curve at +20 mV. The GFP fluorescent signal was confined to the periphery of the cells. Incubation with 500 μM PGB, that binds α2δ subunits, for 30 min induced changes in localization of the fluorescent subunits as measured by fluorescent time lapse microscopy. These changes correlated with a reversible reduction of barium currents through Ca(V)2.1 calcium channels under the same conditions. However, no changes in the cellular distribution of the subunits were visualized for cells either expressing another membrane associated protein or after exposure of the Ca(V)2.1 channels to isoleucine, another α2δ ligand. Together these results show strong evidence for an acute effect of PGB on Ca(V)2.1 calcium channels' currents and distribution and suggest that internalization of Ca(V)2.1 channels might be a mechanism of PGB action. PMID:23063705

  19. Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca(2+) channels.

    PubMed

    Garau, Gianpiero; Magotti, Paola; Heine, Martin; Korotchenko, Svetlana; Lievens, Patricia Marie-Jeanne; Berezin, Vladimir; Dityatev, Alexander

    2015-12-01

    Our previous studies revealed that L-type voltage-dependent Ca(2+) channels (Cav1.2 L-VDCCs) are modulated by the neural extracellular matrix backbone, polyanionic glycan hyaluronic acid. Here we used isothermal titration calorimetry and screened a set of peptides derived from the extracellular domains of Cav1.2α1 to identify putative binding sites between the channel and hyaluronic acid or another class of polyanionic glycans, such as heparin/heparan sulfates. None of the tested peptides showed detectable interaction with hyaluronic acid, but two peptides derived from the first pore-forming domain of Cav1.2α1 subunit bound to heparin. At 25 °C the binding of the peptide P7 (MGKMHKTCYN) was at ~50 μM, and that of the peptide P8 (GHGRQCQNGTVCKPGWDGPKHG) was at ~21 μM. The Cav1.2α1 first pore forming segment that contained both peptides maintained a high affinity for heparin (~23 μM), integrating their enthalpic and entropic binding contributions. Interaction between heparin and recombinant as well as native full-length neuronal Cav1.2α1 channels was confirmed using the heparin-agarose pull down assay. Whole cell patch clamp recordings in HEK293 cells transfected with neuronal Cav1.2 channels revealed that enzymatic digestion of highly sulfated heparan sulfates with heparinase 1 affects neither voltage-dependence of channel activation nor the level of steady state inactivation, but did speed up channel inactivation. Treatment of hippocampal cultures with heparinase 1 reduced the firing rate and led to appearance of long-lasting bursts in the same manner as treatment with the inhibitor of L-VDCC diltiazem. Thus, heparan sulfate proteoglycans may bind to and regulate L-VDCC inactivation and network activity.

  20. Electric vehicles

    SciTech Connect

    Not Available

    1990-03-01

    Quiet, clean, and efficient, electric vehicles (EVs) may someday become a practical mode of transportation for the general public. Electric vehicles can provide many advantages for the nation's environment and energy supply because they run on electricity, which can be produced from many sources of energy such as coal, natural gas, uranium, and hydropower. These vehicles offer fuel versatility to the transportation sector, which depends almost solely on oil for its energy needs. Electric vehicles are any mode of transportation operated by a motor that receives electricity from a battery or fuel cell. EVs come in all shapes and sizes and may be used for different tasks. Some EVs are small and simple, such as golf carts and electric wheel chairs. Others are larger and more complex, such as automobile and vans. Some EVs, such as fork lifts, are used in industries. In this fact sheet, we will discuss mostly automobiles and vans. There are also variations on electric vehicles, such as hybrid vehicles and solar-powered vehicles. Hybrid vehicles use electricity as their primary source of energy, however, they also use a backup source of energy, such as gasoline, methanol or ethanol. Solar-powered vehicles are electric vehicles that use photovoltaic cells (cells that convert solar energy to electricity) rather than utility-supplied electricity to recharge the batteries. This paper discusses these concepts.

  1. ATP hydrolysis is critically required for function of CaV1.3 channels in cochlear inner hair cells via fueling Ca2+ clearance.

    PubMed

    Weiler, Simon; Krinner, Stefanie; Wong, Aaron B; Moser, Tobias; Pangršič, Tina

    2014-05-14

    Sound encoding is mediated by Ca(2+) influx-evoked release of glutamate at the ribbon synapse of inner hair cells. Here we studied the role of ATP in this process focusing on Ca(2+) current through CaV1.3 channels and Ca(2+) homeostasis in mouse inner hair cells. Patch-clamp recordings and Ca(2+) imaging demonstrate that hydrolyzable ATP is essential to maintain synaptic Ca(2+) influx in inner hair cells via fueling Ca(2+)-ATPases to avoid an increase in cytosolic [Ca(2+)] and subsequent Ca(2+)/calmodulin-dependent inactivation of CaV1.3 channels.

  2. Advanced technologies for rocket single-stage-to-orbit vehicles

    NASA Astrophysics Data System (ADS)

    Wilhite, Alan W.; Bush, Lance B.; Cruz, Christopher I.; Lepsch, Roger A.; Morris, W. Douglas; Stanley, Douglas O.; Wurster, Kathryn E.

    1991-01-01

    A single-stage-to-orbit vertical takeoff/horizontal landing rocket vehicle was studied to determine the benefits of advanced technology. Advanced technologies that were included in the study were variable mixture ratio oxygen/hydrogen rocket engines and materials, structures, and subsystem technologies currently being developed in the National Aero-Space Plane Program. The application of advanced technology results in an 85 percent reduction in vehicle dry weight. With advanced materials, an external thermal protection system, like the Space Shuttle tiles, was not required. Compared to an all-airbreathing horizontal takeoff/horizontal landing vehicle using the same advanced technologies and mission requirements, the rocket vehicle is lighter in dry weight and has fewer subsystems. To increase reliability and safety, operational features were included in the rocket vehicle-robust subsystems, 5 percent additional margin, no slush hydrogen, fail-operational with an engine out, and a crew escape module. The resulting vehicle grew in dry weight and was still lower in dry weight than the airbreathing vehicle.

  3. Development and Validation of a New Blade Element Momentum Skewed-Wake Model within AeroDyn: Preprint

    SciTech Connect

    Ning, S. A.; Hayman, G.; Damiani, R.; Jonkman, J.

    2014-12-01

    Blade element momentum methods, though conceptually simple, are highly useful for analyzing wind turbines aerodynamics and are widely used in many design and analysis applications. A new version of AeroDyn is being developed to take advantage of new robust solution methodologies, conform to a new modularization framework for National Renewable Energy Laboratory's FAST, utilize advanced skewed-wake analysis methods, fix limitations with previous implementations, and to enable modeling of highly flexible and nonstraight blades. This paper reviews blade element momentum theory and several of the options available for analyzing skewed inflow. AeroDyn implementation details are described for the benefit of users and developers. These new options are compared to solutions from the previous version of AeroDyn and to experimental data. Finally, recommendations are given on how one might select from the various available solution approaches.

  4. The spectral analysis of an aero-engine assembly incorporating a squeeze-film damper

    NASA Technical Reports Server (NTRS)

    Holmes, R.; Dede, M. M.

    1989-01-01

    Aero-engine structures have very low inherent damping and so artificial damping is often introduced by pumping oil into annular gaps between the casings and the outer races of some or all of the rolling-element bearings supporting the rotors. The thin oil films so formed are called squeeze film dampers and they can be beneficial in reducing rotor vibration due to unbalance and keeping to reasonable limits the forces transmitted to the engine casing. However, squeeze-film dampers are notoriously non-linear and as a result can introduce into the assembly such phenomena as subharmonic oscillations, jumps and combination frequencies. The purpose of the research is to investigate such phenomena both theoretically and experimentally on a test facility reproducing the essential features of a medium-size aero engine. The forerunner of this work was published. It was concerned with the examination of a squeeze-film damper in series with housing flexibility when supporting a rotor. The structure represented to a limited extent the essentials of the projected Rolls Royce RB401 engine. That research demonstrated the ability to calculate the oil-film forces arising from the squeeze film from known motions of the bearing components and showed that the dynamics of a shaft fitted with a squeeze film bearing can be predicted reasonably accurately. An aero-engine will normally have at least two shafts and so in addition to the excitation forces which are synchronous with the rotation of one shaft, there will also be forces at other frequencies from other shafts operating on the squeeze-film damper. Theoretical and experimental work to consider severe loading of squeeze-film dampers and to include these additional effects are examined.

  5. AeroCom INSITU Project: Comparing modeled and measured aerosol optical properties

    NASA Astrophysics Data System (ADS)

    Andrews, Elisabeth; Schmeisser, Lauren; Schulz, Michael; Fiebig, Markus; Ogren, John; Bian, Huisheng; Chin, Mian; Easter, Richard; Ghan, Steve; Kokkola, Harri; Laakso, Anton; Myhre, Gunnar; Randles, Cynthia; da Silva, Arlindo; Stier, Phillip; Skeie, Ragnehild; Takemura, Toshihiko; van Noije, Twan; Zhang, Kai

    2016-04-01

    AeroCom, an open international collaboration of scientists seeking to improve global aerosol models, recently initiated a project comparing model output to in-situ, surface-based measurements of aerosol optical properties. The model/measurement comparison project, called INSITU, aims to evaluate the performance of a suite of AeroCom aerosol models with site-specific observational data in order to inform iterative improvements to model aerosol modules. Surface in-situ data has the unique property of being traceable to physical standards, which is an asset in accomplishing the overall goal of bettering the accuracy of aerosols processes and the predicative capability of global climate models. Here we compare dry, in-situ aerosol scattering and absorption data from ~75 surface, in-situ sites from various global aerosol networks (including NOAA, EUSAAR/ACTRIS and GAW) with a simulated optical properties from a suite of models participating in the AeroCom project. We report how well models reproduce aerosol climatologies for a variety of time scales, aerosol characteristics and behaviors (e.g., aerosol persistence and the systematic relationships between aerosol optical properties), and aerosol trends. Though INSITU is a multi-year endeavor, preliminary phases of the analysis suggest substantial model biases in absorption and scattering coefficients compared to surface measurements, though the sign and magnitude of the bias varies with location. Spatial patterns in the biases highlight model weaknesses, e.g., the inability of models to properly simulate aerosol characteristics at sites with complex topography. Additionally, differences in modeled and measured systematic variability of aerosol optical properties suggest that some models are not accurately capturing specific aerosol behaviors, for example, the tendency of in-situ single scattering albedo to decrease with decreasing aerosol extinction coefficient. The endgoal of the INSITU project is to identify specific

  6. An integrated analytical aeropropulsive/aeroelastic model for the dynamic analysis of hypersonic vehicles

    NASA Technical Reports Server (NTRS)

    Chavez, Frank R.; Schmidt, David K.

    1992-01-01

    The development of an approach to the determination of the dynamic characteristics of hypersonic vehicles which is intentionally generic and basic is given. The approach involves a 2D hypersonic aerodynamic analysis utilizing Newtonian theory, coupled with a 1D aero/thermoanalysis of the flow in a scramjet-type propulsion system. In addition, the airframe is considered to be elastic, and the structural dynamics are characterized in terms of a simple lumped-mass model of the invacuo vibration modes. The vibration modes are coupled to the rigid-body modes through the aero/propulsive forces acting on the structure. The control effectors considered on a generic study configuration include aerodynamic pitch-control surfaces, as well as engine fuel flow and diffuser area ratio. The study configuration is shown to be highly statically unstable in pitch, and to exhibit strong airframe/engine/elastic coupling in the aeroelastic and attitude dynamics, as well as the engine responses.

  7. Radiative forcing of the direct aerosol effect from AeroCom Phase II simulations

    SciTech Connect

    Myhre, G.; Samset, B. H.; Schulz, M.; Balkanski, Y.; Bauer, S.; Berntsen, T. K.; Bian, H.; Bellouin, N.; Chin, M.; Diehl, T.; Easter, R. C.; Feichter, J.; Ghan, S. J.; Hauglustaine, D.; Iversen, T.; Kinne, S.; Kirkevåg, A.; Lamarque, J. -F.; Lin, G.; Liu, X.; Lund, M. T.; Luo, G.; Ma, X.; van Noije, T.; Penner, J. E.; Rasch, P. J.; Ruiz, A.; Seland, Ø.; Skeie, R. B.; Stier, P.; Takemura, T.; Tsigaridis, K.; Wang, P.; Wang, Z.; Xu, L.; Yu, H.; Yu, F.; Yoon, J. -H.; Zhang, K.; Zhang, H.; Zhou, C.

    2013-01-01

    We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 16 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 16 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has a range from -0.58 to -0.02 Wm-2, with a mean of -0.27 Wm-2 for the 16 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information from the other AeroCom models reduces the range and slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of -0.35 Wm-2. Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study. We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results.

  8. The Brief Introduction of Different Laser Diagnostics Methods Used in Aero-Engine Combustion Research

    NASA Astrophysics Data System (ADS)

    Xing, Fei; Song, Ge; Ruan, Can; Zhao, Jian; Yang, Yongjun

    2016-06-01

    Combustion test diagnose has always been one of the most important technologies for the development of aerospace engineering. Laser diagnostics techniques developed quickly in the past several years. They are used to measure the parameters of the combustion flow field such as velocity, temperature, components concentration with high space and time resolution and brought no disturbance. Planar Laser-Induced Fluorescence, Coherent Anti-Stokes Raman Scattering, Tunable Diode Laser Absorption Spectroscopy and Raman Scattering were introduced systemically in this paper. After analysis their own advantages and disadvantages, it is believed that Raman Scattering system is more suitable for research activities on aero-engine combustion systems.

  9. Applications of aero-acoustics to wind turbine noise prediction and control

    NASA Astrophysics Data System (ADS)

    Lowson, Martin V.

    1993-01-01

    Wind turbine noise generation mechanisms are essentially equivalent to the aero-acoustic mechanisms of other rotors, which have been studied in depth for many years. Basic sources for the wind turbine noise radiation process are defined, and their significance assessed. From the analysis, areas of potential improvement in wind turbine noise prediction are defined. Suggestions are made for approaches to wind turbine noise control which separate the noise problems at cut-in from those at rated power. Some of these offer the possibility of noise reduction without unfavourable effects on performance.

  10. AeroPropulsoServoElasticity: Dynamic Modeling of the Variable Cycle Propulsion System

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2012-01-01

    This presentation was made at the 2012 Fundamental Aeronautics Program Technical Conference and it covers research work for the Dynamic Modeling of the Variable cycle Propulsion System that was done under the Supersonics Project, in the area of AeroPropulsoServoElasticity. The presentation covers the objective for the propulsion system dynamic modeling work, followed by the work that has been done so far to model the variable Cycle Engine, modeling of the inlet, the nozzle, the modeling that has been done to model the affects of flow distortion, and finally presenting some concluding remarks and future plans.

  11. Structured grid generation using a CAD solid model for an aero-gas turbine combustion system

    SciTech Connect

    Eccles, N.C.; Manners, A.P.

    1996-12-31

    An aero-gas turbine combustion system was used to demonstrate the problems of creating a single block structured grid suitable for CFD predictions from a designer`s parametric solid model. The solid model had to be filtered of sub-grid detail and computational fluid volumes generated from the solid model of the metal. Alternative methods of transferring the geometry from the CAD package to the grid generator were considered. The type and method of grid generation was found to influence all stages in manipulating the geometry.

  12. Optical key distribution based on aero-optical effect of boundary layer flow

    NASA Astrophysics Data System (ADS)

    Wu, Xu; Wu, Kenan; Liu, Chao

    2014-07-01

    An optical key distribution method based on aero-optical effect of boundary layer flow is proposed. The technique exploits the underlying dynamics of the turbulence boundary layer to generate secret key for both communication parties. Corresponding computer simulation and experiments are carried out. The bit error rate of key distribution is 0.05% and 0.22% in the simulation and the experiment, respectively. Further test also shows that the proposed key generation technique is valid to work with optical encryption technique.

  13. Cadmium tolerance and accumulation of Althaea rosea Cav. and its potential as a hyperaccumulator under chemical enhancement.

    PubMed

    Liu, Jia Nv; Zhou, Qi Xing; Wang, Song; Sun, Ting

    2009-02-01

    The role of ornamental plants has drawn much attention as the urban pollution levels exacerbate. Althaea rosea Cav. had showed its strong tolerance and accumulation ability of Cd in our previous work, thus, the effects of ethylenediamine triacetic acid (EDTA), ethylenegluatarotriacetic acid (EGTA) and sodium dodecyl sulfate (SDS) on its Cd phytoremediation capacity were further investigated in this work. It reconfirmed that the species had strong tolerance and accumulation ability of Cd. Particularly, the species can be regarded as a potential Cd-hyperaccumulator through applying chemical agents. However, different chelators and surfactants had great differences in affecting hyperaccumulating characteristics of the species. EGTA and SDS could not only increase the dry biomass of the plants, but also promote Cd accumulation in shoots and roots. On the contrary, EDTA was toxic to the species by restraining the growth of plants, although it could promote Cd accumulation in shoots and roots of the plants to a certain extent. Thus, EGTA and SDS were effective in enhancing phytoremediation with Althaea rosea Cav. for Cd contaminated soils, while EDTA is ineffective in this regard. PMID:18259884

  14. A rare schizophrenia risk variant of CACNA1I disrupts CaV3.3 channel activity

    PubMed Central

    Andrade, A.; Hope, J.; Allen, A.; Yorgan, V.; Lipscombe, D.; Pan, J. Q.

    2016-01-01

    CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 α1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, of hCaV3.3 were identified in individuals with schizophrenia. Here we show that R1346H, but not T797M, is associated with lower hCaV3.3 protein levels, reduced glycosylation, and lower membrane surface levels of hCaV3.3 when expressed in human cell lines compared to wild-type. Consistent with our biochemical analyses, whole-cell hCaV3.3 currents in cells expressing the R1346H variant were ~50% of those in cells expressing WT hCaV3.3, and neither R1346H nor T797M altered channel biophysical properties. Employing the NEURON simulation environment, we found that reducing hCaV3.3 current densities by 22% or more eliminates rebound bursting in model thalamic reticular nucleus (TRN) neurons. Our analyses suggest that a single copy of Chr22: 39665939G > A CACNA1I has the capacity to disrupt CaV3.3 channel-dependent functions, including rebound bursting in TRN neurons, with potential implications for schizophrenia pathophysiology. PMID:27756899

  15. Cadmium tolerance and accumulation of Althaea rosea Cav. and its potential as a hyperaccumulator under chemical enhancement.

    PubMed

    Liu, Jia Nv; Zhou, Qi Xing; Wang, Song; Sun, Ting

    2009-02-01

    The role of ornamental plants has drawn much attention as the urban pollution levels exacerbate. Althaea rosea Cav. had showed its strong tolerance and accumulation ability of Cd in our previous work, thus, the effects of ethylenediamine triacetic acid (EDTA), ethylenegluatarotriacetic acid (EGTA) and sodium dodecyl sulfate (SDS) on its Cd phytoremediation capacity were further investigated in this work. It reconfirmed that the species had strong tolerance and accumulation ability of Cd. Particularly, the species can be regarded as a potential Cd-hyperaccumulator through applying chemical agents. However, different chelators and surfactants had great differences in affecting hyperaccumulating characteristics of the species. EGTA and SDS could not only increase the dry biomass of the plants, but also promote Cd accumulation in shoots and roots. On the contrary, EDTA was toxic to the species by restraining the growth of plants, although it could promote Cd accumulation in shoots and roots of the plants to a certain extent. Thus, EGTA and SDS were effective in enhancing phytoremediation with Althaea rosea Cav. for Cd contaminated soils, while EDTA is ineffective in this regard.

  16. Cavβ2 transcription start site variants modulate calcium handling in newborn rat cardiomyocytes.

    PubMed

    Moreno, Cristian; Hermosilla, Tamara; Morales, Danna; Encina, Matías; Torres-Díaz, Leandro; Díaz, Pablo; Sarmiento, Daniela; Simon, Felipe; Varela, Diego

    2015-12-01

    In the heart, the main pathway for calcium influx is mediated by L-type calcium channels, a multi-subunit complex composed of the pore-forming subunit CaV1.2 and the auxiliary subunits CaVα2δ1 and CaVβ2. To date, five distinct CaVβ2 transcriptional start site (TSS) variants (CaVβ2a-e) varying only in the composition and length of the N-terminal domain have been described, each of them granting distinct biophysical properties to the L-type current. However, the physiological role of these variants in Ca(2+) handling in the native tissue has not been explored. Our results show that four of these variants are present in neonatal rat cardiomyocytes. The contribution of those CaVβ2 TSS variants on endogenous L-type current and Ca(2+) handling was explored by adenoviral-mediated overexpression of each CaVβ2 variant in cultured newborn rat cardiomyocytes. As expected, all CaVβ2 TSS variants increased L-type current density and produced distinctive changes on L-type calcium channel (LTCC) current activation and inactivation kinetics. The characteristics of the induced calcium transients were dependent on the TSS variant overexpressed. Moreover, the amplitude of the calcium transients varied depending on the subunit involved, being higher in cardiomyocytes transduced with CaVβ2a and smaller in CaVβ2d. Interestingly, the contribution of Ca(2+) influx and Ca(2+) release on total calcium transients, as well as the sarcoplasmic calcium content, was found to be TSS-variant-dependent. Remarkably, determination of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) messenger RNA (mRNA) abundance and cell size change indicates that CaVβ2 TSS variants modulate the cardiomyocyte hypertrophic state. In summary, we demonstrate that expression of individual CaVβ2 TSS variants regulates calcium handling in cardiomyocytes and, consequently, has significant repercussion in the development of hypertrophy.

  17. Cavβ2 transcription start site variants modulate calcium handling in newborn rat cardiomyocytes.

    PubMed

    Moreno, Cristian; Hermosilla, Tamara; Morales, Danna; Encina, Matías; Torres-Díaz, Leandro; Díaz, Pablo; Sarmiento, Daniela; Simon, Felipe; Varela, Diego

    2015-12-01

    In the heart, the main pathway for calcium influx is mediated by L-type calcium channels, a multi-subunit complex composed of the pore-forming subunit CaV1.2 and the auxiliary subunits CaVα2δ1 and CaVβ2. To date, five distinct CaVβ2 transcriptional start site (TSS) variants (CaVβ2a-e) varying only in the composition and length of the N-terminal domain have been described, each of them granting distinct biophysical properties to the L-type current. However, the physiological role of these variants in Ca(2+) handling in the native tissue has not been explored. Our results show that four of these variants are present in neonatal rat cardiomyocytes. The contribution of those CaVβ2 TSS variants on endogenous L-type current and Ca(2+) handling was explored by adenoviral-mediated overexpression of each CaVβ2 variant in cultured newborn rat cardiomyocytes. As expected, all CaVβ2 TSS variants increased L-type current density and produced distinctive changes on L-type calcium channel (LTCC) current activation and inactivation kinetics. The characteristics of the induced calcium transients were dependent on the TSS variant overexpressed. Moreover, the amplitude of the calcium transients varied depending on the subunit involved, being higher in cardiomyocytes transduced with CaVβ2a and smaller in CaVβ2d. Interestingly, the contribution of Ca(2+) influx and Ca(2+) release on total calcium transients, as well as the sarcoplasmic calcium content, was found to be TSS-variant-dependent. Remarkably, determination of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) messenger RNA (mRNA) abundance and cell size change indicates that CaVβ2 TSS variants modulate the cardiomyocyte hypertrophic state. In summary, we demonstrate that expression of individual CaVβ2 TSS variants regulates calcium handling in cardiomyocytes and, consequently, has significant repercussion in the development of hypertrophy. PMID:26265381

  18. Aero Spacelines B377PG Pregnant Guppy on ramp in preparation for flight tests and pilot evaluation

    NASA Technical Reports Server (NTRS)

    1962-01-01

    The Aero Spacelines B377PG Pregnant Guppy was flown by Aero Spacelines pilots to Dryden for tests and evaluation by pilots Joe Vensel and Stan Butchart in October 1962. The outsized cargo aircraft incorporated the wings, engines, lower fuselage and tail from a Boeing 377 Stratocruiser with a huge upper fuselage more than 20 feet in diameter. The modified aircraft was built to transport outsized cargo for NASA's Apollo program, primarily to carry portions of the Saturn V rockets from the manufacturer to Cape Canaveral. Later versions of the aircraft, including the Super Guppy and the Super Guppy Turbine, are still in use.

  19. Descent vehicles

    NASA Technical Reports Server (NTRS)

    Popov, Y. I.

    1985-01-01

    The creation of descent vehicles marked a new stage in the development of cosmonautics, involving the beginning of manned space flight and substantial progress in space research on the distant bodies of the Solar System. This booklet describes these vehicles and their structures, systems, and purposes. It is intended for the general public interested in modern problems of space technology.

  20. Resveratrol Ameliorates High Glucose and High-Fat/Sucrose Diet-Induced Vascular Hyperpermeability Involving Cav-1/eNOS Regulation

    PubMed Central

    Peng, Xiao lin; Qu, Wei; Wang, Lin zhi; Huang, Bin qing; Ying, Chen jiang; Sun, Xiu fa; Hao, Li ping

    2014-01-01

    Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation. PMID:25419974

  1. Stantonia pallida (Ashmead)(Hymenoptera: Braconidae) reared from Neomusotima conspurcatalis Warren (Lepidoptera: Crambidae), a classical biological control agent of Lygodium microphyllum (Cav.)R.Br.(Polypodiales: Lygodiaceae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stantonia pallida (Ashmead) sensu Braet and Quicke (2004) and an undetermined species of Cotesia are reported from Neomusotima conspurcatalis Warren, a classical biological control agent of Lygodium microphyllum (Cav.) R. Br. in Florida. They are the first reported parasitoids of N. conspurcatalis. ...

  2. Cav3-type α1T calcium channels mediate transient calcium currents that regulate repetitive firing in Drosophila antennal lobe PNs

    PubMed Central

    Iniguez, Jorge; Schutte, Soleil S.

    2013-01-01

    Projection neurons (PNs), located in the antennal lobe region of the insect brain, play a key role in processing olfactory information. To explore how activity is regulated at the level of single PNs within this central circuit we have recorded from these neurons in adult Drosophila melanogaster brains. Our previous study demonstrated that PNs express voltage-gated calcium currents with a transient and sustained component. We found that the sustained component is mediated by cac gene-encoded Cav2-type channels involved in regulating action potential-independent release of neurotransmitter at excitatory cholinergic synapses. The function of the transient calcium current and the gene encoding the underlying channels, however, were unknown. Here we report that the transient current blocked by prepulse inactivation is sensitive to amiloride, a vertebrate Cav3-type channel blocker. In addition PN-specific RNAi knockdown of α1T, the Drosophila Cav3-type gene, caused a dramatic reduction in the transient current without altering the sustained component. These data demonstrate that the α1T gene encodes voltage-gated calcium channels underlying the amiloride-sensitive transient current. Alterations in evoked firing and spontaneous burst firing in the α1T knockdowns demonstrate that the Cav3-type calcium channels are important in regulating excitability in adult PNs. PMID:23864373

  3. ZC88, a novel N-type calcium channel blocker from 4-amino-piperidine derivatives state-dependent inhibits Cav2.2 calcium channels.

    PubMed

    Zhang, Shuzhuo; Yang, Lujia; Zhang, Kang; Liu, Xiaoyan; Dai, Weiwei; Zhang, Cheng; Yong, Zheng; Li, Jin; Zheng, Jianquan

    2015-04-24

    Small molecular inhibitors of Cav2.2 have been reported for the treatment of neuropathic pain; however, low selectivity and side effects limit their further development. In our study, a series of new compounds were designed and synthesized by optimizing the 4-amino-piperidine template. The results show that ZC88 inhibits transiently expressed Cav2.2 in state-dependent manner in oocytes with an IC50 of 0.45 ± 0.09 μM. The steady-state inactivation relationship curve is shifted to more negative potentials for the calcium channels, suggesting that ZC88 blocks inactivated state of the channel. ZC88 does not present any remarkable effects on voltage-gated P/Q-type calcium channel currents, l-type calcium channel currents, potassium channel and sodium channel currents. Taken together, these in vitro data suggest that ZC88 is a voltage-dependent, subtype-selective Cav2.2 channel inhibitor and can achieve an improved therapeutic window over the relatively state-independent Cav2.2-selective inhibitor, which may have potential to be developed into a novel analgesic agent. PMID:25681549

  4. Combined anti-ages and antioxidant activities of different solvent extracts of Solanum elaeagnifolium Cav (Solanacea) fruits during ripening and related to their phytochemical compositions

    PubMed Central

    Houda, Mejri; Derbré, Séverine; Jedy, Ahmed; Tlili, Nizar; Legault, Jean; Richomme, Pascal; Limam, Ferid; Saidani-Tounsi, Moufida

    2014-01-01

    Oxidative stress and advanced glycation end products (AGEs) are known as key factors for the development of diabetic complications such as retinopathy, cataract as well as atherosclerosis and neurodegenerative diseases, including Alzheimer’s diseases. In this context, natural products have been previously identified as promising sources for antioxidant and anti-glycation compounds. The current study focuses on the evaluation of antioxidant and glycation inhibitory activities of different solvent extracts of Solanum elaeagnifolium Cav (Solanaceae) fruits at different ripening stages. The results showed that antioxidant and anti-AGEs activities were significantly influenced by solvents polarities and ripening stages of S. elaeagnifolium Cav. With one exception, methanolic extract of overripe S. elaeagnifolium Cav fruit showed important protective effects against cellular oxidative stress. The aqueous extract showed the highest ABTS+ scavenging ability. Principal component analysis showed that total phenolic and flavonoid contents correlated well with observed antioxidants and anti-glycation activities. These results bring attention to the possible use of S. elaeagnifolium Cav as a valuable source of bioactive compounds exhibiting antioxidant effects and potentially alleviating diabetic complications. PMID:26417319

  5. ZC88, a novel N-type calcium channel blocker from 4-amino-piperidine derivatives state-dependent inhibits Cav2.2 calcium channels.

    PubMed

    Zhang, Shuzhuo; Yang, Lujia; Zhang, Kang; Liu, Xiaoyan; Dai, Weiwei; Zhang, Cheng; Yong, Zheng; Li, Jin; Zheng, Jianquan

    2015-04-24

    Small molecular inhibitors of Cav2.2 have been reported for the treatment of neuropathic pain; however, low selectivity and side effects limit their further development. In our study, a series of new compounds were designed and synthesized by optimizing the 4-amino-piperidine template. The results show that ZC88 inhibits transiently expressed Cav2.2 in state-dependent manner in oocytes with an IC50 of 0.45 ± 0.09 μM. The steady-state inactivation relationship curve is shifted to more negative potentials for the calcium channels, suggesting that ZC88 blocks inactivated state of the channel. ZC88 does not present any remarkable effects on voltage-gated P/Q-type calcium channel currents, l-type calcium channel currents, potassium channel and sodium channel currents. Taken together, these in vitro data suggest that ZC88 is a voltage-dependent, subtype-selective Cav2.2 channel inhibitor and can achieve an improved therapeutic window over the relatively state-independent Cav2.2-selective inhibitor, which may have potential to be developed into a novel analgesic agent.

  6. An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca2+-dependent regulation

    PubMed Central

    Limpitikul, Worawan B.; Dick, Ivy E.; Ben-Johny, Manu; Yue, David T.

    2016-01-01

    CaV1.3 channels are a major class of L-type Ca2+ channels which contribute to the rhythmicity of the heart and brain. In the brain, these channels are vital for excitation-transcription coupling, synaptic plasticity, and neuronal firing. Moreover, disruption of CaV1.3 function has been associated with several neurological disorders. Here, we focus on the de novo missense mutation A760G which has been linked to autism spectrum disorder (ASD). To explore the role of this mutation in ASD pathogenesis, we examined the effects of A760G on CaV1.3 channel gating and regulation. Introduction of the mutation severely diminished the Ca2+-dependent inactivation (CDI) of CaV1.3 channels, an important feedback system required for Ca2+ homeostasis. This reduction in CDI was observed in two major channel splice variants, though to different extents. Using an allosteric model of channel gating, we found that the underlying mechanism of CDI reduction is likely due to enhanced channel opening within the Ca2+-inactivated mode. Remarkably, the A760G mutation also caused an opposite increase in voltage-dependent inactivation (VDI), resulting in a multifaceted mechanism underlying ASD. When combined, these regulatory deficits appear to increase the intracellular Ca2+ concentration, thus potentially disrupting neuronal development and synapse formation, ultimately leading to ASD. PMID:27255217

  7. Applicability of the aero-optic linking equation to a highly coherent, transitional shear layer.

    PubMed

    Hugo, R J; Jumper, E J

    2000-08-20

    We investigate the validity of applying a simplified (under the assumptions of isotropic and homogeneous turbulence) aero-optic linking equation to a flow field that is known to consist of anisotropic and nonhomogeneous turbulence. The investigation is performed in the near-nozzle region of a heated two-dimensional jet, and the study makes use of a conditional-sampling experiment to acquire a spatiotemporal temperature field database for the heated-jet flow field. After compensating for the bandwidth limitations of constant-current wire temperature measurements, the temperature field database is applied to the computation of optical degradation through both direct and indirect methods, relying on the aero-optic linking equation. The simplified version of the linking equation was found to provide good agreement with direct calculations, provided that the length scale of the density fluctuations was interpreted as being the integral scale, with the limits of integration being the first two zero crossings of the covariance coefficient function. PMID:18350028

  8. Dynamics of fine particles and photo-oxidants in the Eastern Mediterranean (SUB-AERO)

    NASA Astrophysics Data System (ADS)

    Lazaridis, M.; Eleftheriadis, K.; Smolik, J.; Colbeck, I.; Kallos, G.; Drossinos, Y.; Zdimal, V.; Vecera, Z.; Mihalopoulos, N.; Mikuska, P.; Bryant, C.; Housiadas, C.; Spyridaki, A.; Astitha, Marina; Havranek, V.

    As part of the European project SUB-AERO, comprehensive aerosol and gaseous pollutant measurement campaigns were performed at the Finokalia station (July 2000 and January 2001) on the island of Crete (Greece) in combination with boat measurements in the eastern part of the Mediterranean area. The measurements were performed with the participation of nine European research institutions. The objective of the measurement campaigns was to evaluate and assess the spatial and temporal variability of photochemical pollutants and fine particles. The current overview paper presents the framework and main results of the measurements and modelling studies performed during the project. Extensive measurements of gaseous and atmospheric-aerosol physical, chemical and optical characteristics were performed during the measurement campaigns in conjunction with detailed chemical analyses of the aerosol species. Along with the experimental work mesoscale modelling, using a combination of the UAM-AERO air quality model together with the RAMS prognostic meteorological model, was used to reveal the dynamics of particulate matter and photo-oxidants. Furthermore, regional chemistry transport models were applied to determine the background and initial conditions for the mesoscale modelling.

  9. A Rapid Method to Achieve Aero-Engine Blade Form Detection

    PubMed Central

    Sun, Bin; Li, Bing

    2015-01-01

    This paper proposes a rapid method to detect aero-engine blade form, according to the characteristics of an aero-engine blade surface. This method first deduces an inclination error model in free-form surface measurements based on the non-contact laser triangulation principle. Then a four-coordinate measuring system was independently developed, a special fixture was designed according to the blade shape features, and a fast measurement of the blade features path was planned. Finally, by using the inclination error model for correction of acquired data, the measurement error that was caused by tilt form is compensated. As a result the measurement accuracy of the Laser Displacement Sensor was less than 10 μm. After the experimental verification, this method makes full use of optical non-contact measurement fast speed, high precision and wide measuring range of features. Using a standard gauge block as a measurement reference, the coordinate system conversion data is simple and practical. It not only improves the measurement accuracy of the blade surface, but also its measurement efficiency. Therefore, this method increases the value of the measurement of complex surfaces. PMID:26039420

  10. Implications of the homogeneous turbulence assumption on the aero-optic linking equation

    NASA Astrophysics Data System (ADS)

    Hugo, Ronald J.; Jumper, Eric J.

    1995-09-01

    This paper investigates the validity of applying the simplified (under the assumptions of isotropic and homogeneous turbulence) aero-optic linking equation to a flowfield that is known to consist of anisotropic and nonhomogeneous turbulence. The investigation is performed in the near nozzle-region of a heated two-dimensional jet, and the study makes use of a conditional sampling experiment to acquire a spatio-temporal temperature field data base for the heated jet flowfield. After compensating for the bandwidth limitations of constant-current-wire temperature measurements, the temperature field data base is applied to the computation of optical degradation through both direct methods and indirect methods relying on the aero-optic linking equation. The simplified version of the linking equation was found to provide very good agreement with direct calculations provided that the length scale of the density fluctuations was interpreted as being the integral scale, with the limits of the integration being the two first zero crossings of the covariance coefficient function.

  11. Applicability of the Aero-Optic Linking Equation to a Highly Coherent, Transitional Shear Layer

    NASA Astrophysics Data System (ADS)

    Hugo, Ronald J.; Jumper, Eric J.

    2000-08-01

    We investigate the validity of applying a simplified (under the assumptions of isotropic and homogeneous turbulence) aero-optic linking equation to a flow field that is known to consist of anisotropic and nonhomogeneous turbulence. The investigation is performed in the near-nozzle region of a heated two-dimensional jet, and the study makes use of a conditional-sampling experiment to acquire a spatiotemporal temperature field database for the heated-jet flow field. After compensating for the bandwidth limitations of constant-current wire temperature measurements, the temperature field database is applied to the computation of optical degradation through both direct and indirect methods, relying on the aero-optic linking equation. The simplified version of the linking equation was found to provide good agreement with direct calculations, provided that the length scale of the density fluctuations was interpreted as being the integral scale, with the limits of integration being the first two zero crossings of the covariance coefficient function.

  12. Aero-Propulsion Technology (APT) Task V Low Noise ADP Engine Definition Study

    NASA Technical Reports Server (NTRS)

    Holcombe, V.

    2003-01-01

    A study was conducted to identify and evaluate noise reduction technologies for advanced ducted prop propulsion systems that would allow increased capacity operation and result in an economically competitive commercial transport. The study investigated the aero/acoustic/structural advancements in fan and nacelle technology required to match or exceed the fuel burned and economic benefits of a constrained diameter large Advanced Ducted Propeller (ADP) compared to an unconstrained ADP propulsion system with a noise goal of 5 to 10 EPNDB reduction relative to FAR 36 Stage 3 at each of the three measuring stations namely, takeoff (cutback), approach and sideline. A second generation ADP was selected to operate within the maximum nacelle diameter constrain of 160 deg to allow installation under the wing. The impact of fan and nacelle technologies of the second generation ADP on fuel burn and direct operating costs for a typical 3000 nm mission was evaluated through use of a large, twin engine commercial airplane simulation model. The major emphasis of this study focused on fan blade aero/acoustic and structural technology evaluations and advanced nacelle designs. Results of this study have identified the testing required to verify the interactive performance of these components, along with noise characteristics, by wind tunnel testing utilizing and advanced interaction rig.

  13. Wind tunnel validation of AeroDyn within LIFES50+ project: imposed Surge and Pitch tests

    NASA Astrophysics Data System (ADS)

    Bayati, I.; Belloli, M.; Bernini, L.; Zasso, A.

    2016-09-01

    This paper presents the first set of results of the steady and unsteady wind tunnel tests, performed at Politecnico di Milano wind tunnel, on a 1/75 rigid scale model of the DTU 10 MW wind turbine, within the LIFES50+ project. The aim of these tests is the validation of the open source code AeroDyn developed at NREL. Numerical and experimental steady results are compared in terms of thrust and torque coefficients, showing good agreement, as well as for unsteady measurements gathered with a 2 degree-of-freedom test rig, capable of imposing the displacements at the base of the model, and providing the surge and pitch motion of the floating offshore wind turbine (FOWT) scale model. The measurements of the unsteady test configuration are compared with AeroDyn/Dynin module results, implementing the generalized dynamic wake (GDW) model. Numerical and experimental comparison showed similar behaviours in terms of non linear hysteresis, however some discrepancies are herein reported and need further data analysis and interpretations about the aerodynamic integral quantities, with a special attention to the physics of the unsteady phenomenon.

  14. Heat pipes for wing leading edges of hypersonic vehicles

    NASA Technical Reports Server (NTRS)

    Boman, B. L.; Citrin, K. M.; Garner, E. C.; Stone, J. E.

    1990-01-01

    Wing leading edge heat pipes were conceptually designed for three types of vehicle: an entry research vehicle, aero-space plane, and advanced shuttle. A full scale, internally instrumented sodium/Hastelloy X heat pipe was successfully designed and fabricated for the advanced shuttle application. The 69.4 inch long heat pipe reduces peak leading edge temperatures from 3500 F to 1800 F. It is internally instrumented with thermocouples and pressure transducers to measure sodium vapor qualities. Large thermal gradients and consequently large thermal stresses, which have the potential of limiting heat pipe life, were predicted to occur during startup. A test stand and test plan were developed for subsequent testing of this heat pipe. Heat pipe manufacturing technology was advanced during this program, including the development of an innovative technique for wick installation.

  15. Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis.

    PubMed

    Terada, Yuka; Fujimura, Mayuko; Nishimura, Sachiyo; Tsubota, Maho; Sekiguchi, Fumiko; Kawabata, Atsufumi

    2015-02-01

    Hydrogen sulfide (H(2)S), formed by multiple enzymes, including cystathionine-γ-lyase (CSE), targets Ca(v)3.2 T-type Ca(2+) channels (T channels) and transient receptor potential ankyrin-1 (TRPA1), facilitating somatic pain. Pancreatitis-related pain also appears to involve activation of T channels by H(2)S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca(v)3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T-channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H(2)S donor. In the mice with cerulein-induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55-0396 (NNC), a selective T-channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca(v)3.2 selectively among three T-channel isoforms; and knockdown of Ca(v)3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein-induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca(v)3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein-induced pancreatitis. The data indicate that TRPA1 and Ca(v)3.2 mediate the exogenous H(2)S-induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca(v)3.2 targeted by H(2)S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling.

  16. Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis.

    PubMed

    Terada, Yuka; Fujimura, Mayuko; Nishimura, Sachiyo; Tsubota, Maho; Sekiguchi, Fumiko; Kawabata, Atsufumi

    2015-02-01

    Hydrogen sulfide (H(2)S), formed by multiple enzymes, including cystathionine-γ-lyase (CSE), targets Ca(v)3.2 T-type Ca(2+) channels (T channels) and transient receptor potential ankyrin-1 (TRPA1), facilitating somatic pain. Pancreatitis-related pain also appears to involve activation of T channels by H(2)S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca(v)3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T-channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H(2)S donor. In the mice with cerulein-induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55-0396 (NNC), a selective T-channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca(v)3.2 selectively among three T-channel isoforms; and knockdown of Ca(v)3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein-induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca(v)3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein-induced pancreatitis. The data indicate that TRPA1 and Ca(v)3.2 mediate the exogenous H(2)S-induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca(v)3.2 targeted by H(2)S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling. PMID:25267397

  17. Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice.

    PubMed

    Vecchia, Dania; Tottene, Angelita; van den Maagdenberg, Arn M J M; Pietrobon, Daniela

    2014-09-01

    Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. In FHM1 knockin mice, excitatory neurotransmission at cortical pyramidal cell synapses is enhanced, but inhibitory neurotransmission at connected pairs of fast-spiking (FS) interneurons and pyramidal cells is unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying the unaltered GABA release at cortical FS interneuron synapses remains unknown. Here, we show that the FHM1 R192Q mutation does not affect inhibitory transmission at autapses of cortical FS and other types of multipolar interneurons in microculture from R192Q knockin mice, and investigate the underlying mechanism. Lowering the extracellular [Ca(2+)] did not reveal gain-of-function of evoked transmission neither in control nor after prolongation of the action potential (AP) with tetraethylammonium, indicating unaltered AP-evoked presynaptic calcium influx at inhibitory autapses in FHM1 KI mice. Neither saturation of the presynaptic calcium sensor nor short duration of the AP can explain the unaltered inhibitory transmission in the mutant mice. Recordings of the P/Q-type calcium current in multipolar interneurons in microculture revealed that the current density and the gating properties of the CaV2.1 channels expressed in these interneurons are barely affected by the FHM1 mutation, in contrast with the enhanced current density and left-shifted activation gating of mutant CaV2.1 channels in cortical pyramidal cells. Our findings suggest that expression of specific CaV2.1 channels differentially sensitive to modulation by FHM1 mutations in inhibitory and excitatory cortical neurons underlies the gain-of-function of excitatory but unaltered inhibitory synaptic transmission and the likely consequent dysregulation of the cortical excitatory-inhibitory balance in FHM1. PMID:24907493

  18. Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to short-term synaptic plasticity in hippocampal neurons.

    PubMed

    Nanou, Evanthia; Sullivan, Jane M; Scheuer, Todd; Catterall, William A

    2016-01-26

    Short-term synaptic plasticity is induced by calcium (Ca(2+)) accumulating in presynaptic nerve terminals during repetitive action potentials. Regulation of voltage-gated CaV2.1 Ca(2+) channels by Ca(2+) sensor proteins induces facilitation of Ca(2+) currents and synaptic facilitation in cultured neurons expressing exogenous CaV2.1 channels. However, it is unknown whether this mechanism contributes to facilitation in native synapses. We introduced the IM-AA mutation into the IQ-like motif (IM) of the Ca(2+) sensor binding site. This mutation does not alter voltage dependence or kinetics of CaV2.1 currents, or frequency or amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs); however, synaptic facilitation is completely blocked in excitatory glutamatergic synapses in hippocampal autaptic cultures. In acutely prepared hippocampal slices, frequency and amplitude of mEPSCs and amplitudes of evoked EPSCs are unaltered. In contrast, short-term synaptic facilitation in response to paired stimuli is reduced by ∼ 50%. In the presence of EGTA-AM to prevent global increases in free Ca(2+), the IM-AA mutation completely blocks short-term synaptic facilitation, indicating that synaptic facilitation by brief, local increases in Ca(2+) is dependent upon regulation of CaV2.1 channels by Ca(2+) sensor proteins. In response to trains of action potentials, synaptic facilitation is reduced in IM-AA synapses in initial stimuli, consistent with results of paired-pulse experiments; however, synaptic depression is also delayed, resulting in sustained increases in amplitudes of later EPSCs during trains of 10 stimuli at 10-20 Hz. Evidently, regulation of CaV2.1 channels by CaS proteins is required for normal short-term plasticity and normal encoding of information in native hippocampal synapses.

  19. Free radical signalling underlies inhibition of CaV3.2 T-type calcium channels by nitrous oxide in the pain pathway.

    PubMed

    Orestes, Peihan; Bojadzic, Damir; Lee, Jeonghan; Leach, Emily; Salajegheh, Reza; Digruccio, Michael R; Nelson, Michael T; Todorovic, Slobodan M

    2011-01-01

    Nitrous oxide (N2O, laughing gas) has been used as an anaesthetic and analgesic for almost two centuries, but its cellular targets remain unclear. Here, we present a molecular mechanism of nitrous oxide's selective inhibition of CaV3.2 low-voltage-activated (T-type) calcium channels in pain pathways. Using site-directed mutagenesis and metal chelators such as diethylenetriamine pentaacetic acid and deferoxamine, we reveal that a unique histidine at position 191 of CaV3.2 participates in a critical metal binding site, which may in turn interact with N2O to produce reactive oxygen species (ROS). These free radicals are then likely to oxidize H191 of CaV3.2 in a localized metal-catalysed oxidation reaction. Evidence of hydrogen peroxide and free radical intermediates is given in that N2O inhibition of CaV3.2 channels is attenuated when H2O2 is neutralized by catalase. We also use the adrenochrome test as an indicator of ROS in vitro in the presence of N2O and iron. Ensuing in vivo studies indicate that mice lacking CaV3.2 channels display decreased analgesia to N2O in response to formalin-induced inflammatory pain. Furthermore, a superoxide dismutase and catalase mimetic, EUK-134, diminished pain responses to formalin in wild-type mice, but EUK-134 and N2O analgesia were not additive. This suggests that reduced ROS levels led to decreased inflammation, but without the presence of ROS, N2O was not able to provide additional analgesia. These findings reveal a novel mechanism of interaction between N2O and ion channels, furthering our understanding of this widely used analgesic in pain processing. PMID:21059758

  20. Free radical signalling underlies inhibition of CaV3.2 T-type calcium channels by nitrous oxide in the pain pathway

    PubMed Central

    Orestes, Peihan; Bojadzic, Damir; Lee, JeongHan; Leach, Emily; Salajegheh, Reza; DiGruccio, Michael R; Nelson, Michael T; Todorovic, Slobodan M

    2011-01-01

    Nitrous oxide (N2O, laughing gas) has been used as an anaesthetic and analgesic for almost two centuries, but its cellular targets remain unclear. Here, we present a molecular mechanism of nitrous oxide's selective inhibition of CaV3.2 low-voltage-activated (T-type) calcium channels in pain pathways. Using site-directed mutagenesis and metal chelators such as diethylenetriamine pentaacetic acid and deferoxamine, we reveal that a unique histidine at position 191 of CaV3.2 participates in a critical metal binding site, which may in turn interact with N2O to produce reactive oxygen species (ROS). These free radicals are then likely to oxidize H191 of CaV3.2 in a localized metal-catalysed oxidation reaction. Evidence of hydrogen peroxide and free radical intermediates is given in that N2O inhibition of CaV3.2 channels is attenuated when H2O2 is neutralized by catalase. We also use the adrenochrome test as an indicator of ROS in vitro in the presence of N2O and iron. Ensuing in vivo studies indicate that mice lacking CaV3.2 channels display decreased analgesia to N2O in response to formalin-induced inflammatory pain. Furthermore, a superoxide dismutase and catalase mimetic, EUK-134, diminished pain responses to formalin in wild-type mice, but EUK-134 and N2O analgesia were not additive. This suggests that reduced ROS levels led to decreased inflammation, but without the presence of ROS, N2O was not able to provide additional analgesia. These findings reveal a novel mechanism of interaction between N2O and ion channels, furthering our understanding of this widely used analgesic in pain processing. PMID:21059758

  1. Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population

    PubMed Central

    Chen, Shanshan; Wang, Chuchu; Wang, Xiaojing; Xu, Chengqi; Wu, Manman; Wang, Pengxia; Tu, Xin; Wang, Qing K

    2015-01-01

    Background Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies. Methods and Results Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF (Padj=4.77×10−5), and the finding was replicated in 2 other independent populations with 709 cases and 2175 controls, 463 cases and 644 controls, and the combined population with a total of 2113 cases and 3381 controls (Padj=2.20×10−9; odds ratio [OR]=1.34 for major allele G). Meta-analysis, together with data from previous reports in Chinese and Japanese populations, also showed a significant association between rs3807989 and AF (P=3.40×10−4; OR=1.24 for allele G). We also found that rs3807989 showed a significant association with lone AF in 3 independent populations and in the combined population (Padj=3.85×10−8; OR=1.43 for major allele G). Conclusions The data in this study revealed a significant association between rs3807989 and AF in the Chinese Han population. Together with the findings that caveolin-1 interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF across different ethnic populations. This study is the first to show a significant association between rs3807989 and lone AF. PMID:25953654

  2. Aero Spacelines B377SG Super Guppy on Ramp Loading the X-24B and HL-10 Lifting Bodies.

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The Aero Spacelines B377SG Super Guppy was at Dryden in May, 1976, to ferry the X-24 and HL-10 lifting bodies from the Center to the Air Force Museum at Wright-Patterson Air Force Base, Ohio. The oversized cargo aircraft is a further modification of the B377PG Pregnant Guppy, which was built to transport outsized cargo for NASA's Apollo program, primarily to carry portions of the Saturn V rockets from the manufacturer to Cape Canaveral. The original Guppy modification incorporated the wings, engines, lower fuselage and tail from a Boeing 377 Stratocruiser with a huge upper fuselage more than 20 feet in diameter. The Super Guppy further expanded the fuselage added a taller vertical tail for better lateral stability. A later version, the Super Guppy Turbine, is still in occasional use by NASA to transport oversize structures. The X-24 was one of a group of lifting bodies flown by the NASA Flight Research Center (now Dryden Flight Research Center), Edwards, California, in a joint program with the U.S. Air Force at Edwards Air Force Base from 1963 to 1975. The lifting bodies were used to demonstrate the ability of pilots to maneuver and safely land wingless vehicles designed to fly back to Earth from space and be landed like an airplane at a predetermined site. Lifting bodies' aerodynamic lift, essential to flight in the atmosphere, was obtained from their shape. The addition of fins and control surfaces allowed the pilots to stabilize and control the vehicles and regulate their flight paths. Built by Martin Aircraft Company, Maryland, for the U.S. Air Force, the X-24A was a bulbous vehicle shaped like a teardrop with three vertical fins at the rear for directional control. It weighed 6,270 pounds, was 24.5 feet long and 11.5 feet wide (measuring just the fuselage, not the distance between the tips of the outboard fins). Its first unpowered glide flight was on April 17, 1969, with Air Force Maj. Jerauld Gentry at the controls. Gentry also piloted its first powered

  3. Aero Spacelines B377SG Super Guppy on Ramp Loading the X-24B and HL-10 Lifting Bodies.

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The Aero Spacelines B377SG Super Guppy was at Dryden in May, 1976, to ferry the X-24 and HL-10 lifting bodies from the Center to the Air Force Museum at Wright-Patterson Air Force Base, Ohio. The oversized cargo aircraft is a further modification of the B377PG Pregnant Guppy, which was built to transport outsized cargo for NASA's Apollo program, primarily to carry portions of the Saturn V rockets from the manufacturer to Cape Canaveral. The original Guppy modification incorporated the wings, engines, lower fuselage and tail from a Boeing 377 Stratocruiser with a huge upper fuselage more than 20 feet in diameter. The Super Guppy further expanded the fuselage added a taller vertical tail for better lateral stability. A later version, the Super Guppy Turbine, is still in occasional use by NASA to transport oversize structures. The X-24 was one of a group of lifting bodies flown by the NASA Flight Research Center (now Dryden Flight Research Center), Edwards, California, in a joint program with the U.S. Air Force at Edwards Air Force Base from 1963 to 1975. The lifting bodies were used to demonstrate the ability of pilots to maneuver and safely land wingless vehicles designed to fly back to Earth from space and be landed like an airplane at a predetermined site. Lifting bodies' aerodynamic lift, essential to flight in the atmosphere, was obtained from their shape. The addition of fins and control surfaces allowed the pilots to stabilize and control the vehicles and regulate their flight paths. Built by Martin Aircraft Company, Maryland, for the U.S. Air Force, the X-24A was a bulbous vehicle shaped like a teardrop with three vertical fins at the rear for directional control. It weighed 6,270 pounds, was 24.5 feet long and 11.5 feet wide (measuring just the fuselage, not the distance between the tips of the outboard fins). Its first unpowered glide flight was on April 17, 1969, with Air Force Maj. Jerauld Gentry at the controls. Gentry also piloted its first powered

  4. 76 FR 72235 - Abviva, Inc., ACTIS Global Ventures, Inc., aeroTelesis, Inc., Amwest Insurance Group, Inc., and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-22

    ... COMMISSION Abviva, Inc., ACTIS Global Ventures, Inc., aeroTelesis, Inc., Amwest Insurance Group, Inc., and... information concerning the securities of ACTIS Global Ventures, Inc. because it has not filed any periodic... securities of the above-listed companies. Therefore, it is ordered, pursuant to Section 12(k) of...

  5. A dynamic prescribed vortex wake model for the FAST/AeroDyn wind energy conversion simulation code

    NASA Astrophysics Data System (ADS)

    Currin, Hugh D.

    2007-12-01

    A Dynamic Prescribed Vortex Wake model for analysis of horizontal axis wind turbines has been developed. This model extends the HAWTDAWG steady state prescribed wake code to dynamic flows. This extension assumes wake vortices follow prescription functions valid at the time each vortex is generated. This allows modeling of dynamic wake effects known to exist. This assumption is supported through analysis and comparison to UAE Phase VI test data. The new Dynamic Prescribed Vortex Wake model is built into AeroDyn as a third aerodynamic model and uses the FAST structural dynamic model. It implements the wind models and dynamic stall model in AeroDyn. FAST structural degrees of freedom are implemented. Comparisons are made to UAE Phase VI wind tunnel data, and to the other two AeroDyn models, Blade Element Momentum and Generalized Dynamic Wake. Both steady, to verify the base model, and dynamic, to validate the extension to dynamic flow, conditions are considered. Both axial and yawed flow are analyzed. Dynamic UAE test data analyzed include rapid pitch, Sequence Q, and yaw release, Sequence E. The Dynamic Prescribed Wake model compares favorably to test data and to other AeroDyn models. Small rapid dynamic response is noted in each model and the test data. The new Dynamic Prescribed Vortex Wake model shows promise. Release of the code for experimental use and further validation is recommended.

  6. Robotic vehicle

    DOEpatents

    Box, W.D.

    1997-02-11

    A robotic vehicle is described for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendable appendages, each of which is radially extendable relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendable members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle. 20 figs.

  7. Robotic vehicle

    DOEpatents

    Box, W.D.

    1998-08-11

    A robotic vehicle is described for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendible appendages, each of which is radially extendible relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendible members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle. 20 figs.

  8. Robotic vehicle

    SciTech Connect

    Box, W. Donald

    1998-01-01

    A robotic vehicle for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendable appendages, each of which is radially extendable relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendable members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle.

  9. Robotic vehicle

    SciTech Connect

    Box, W. Donald

    1997-01-01

    A robotic vehicle for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendable appendages, each of which is radially extendable relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendable members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle.

  10. Rhizosphere effect and salinity competing to shape microbial communities in Phragmites australis (Cav.) Trin. ex-Steud.

    PubMed

    Borruso, Luigimaria; Bacci, Giovanni; Mengoni, Alessio; De Philippis, Roberto; Brusetti, Lorenzo

    2014-10-01

    Rhizobacterial communities associated with Phragmites australis (Cav.) Trin. ex Steud. in a hypersaline pond close to Wuliangsuhai Lake (Inner Mongolia - China) were investigated and compared with the microbial communities in bulk sediments of the same pond. Microbiological analyses have been done by automated ribosomal intergenic spacer analysis (ARISA) and partial 16S rRNA gene 454 pyrosequencing. Although community richness was higher in the rhizosphere samples than in bulk sediments, the salinity seemed to be the major factor shaping the structure of the microbial communities. Halanaerobiales was the most abundant taxon found in all the different samples and Desulfosalsimonas was observed to be present more in the rhizosphere rather than in bulk sediment.

  11. Spatial variability of methane emissions in a Phragmites australis (Cav.) Trin. Ex Steud. dominated restored coastal brackish fen

    NASA Astrophysics Data System (ADS)

    Koch, Stefan; Jurasinski, Gerald; Glatzel, Stephan

    2013-04-01

    Methane is a major greenhouse gas that significantly contributes to global warming with a global warming potential 25 times higher than carbon dioxide over a 100 year time horizon. Recently, closed chamber measurements of methane are replaced by ecosystem based Eddy Covariance measurements where possible. However estimates of emission factors for single vegetation units still need chamber based measurements. The resulting emission factors may be influenced by the arrangement of measurement spots in the ecosystem. Here, we analyze the spatial variability of annual emissions estimates based on dynamic closed chamber measurements in pure and mixed stands of Phragmites australis (Cav.) Trin. ex Steud. in a restored coastal brackish fen. Annual methane emissions per measurement location vary largely between 76.54 and 1332 kg ha-1 a-1 CH4 but they do not differ significantly between pure and mixed stands of Phragmites australis. Mantel tests show no correlation of distances between spots and the variation in methane emissions (p

  12. GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat cerebellar granule neurons

    PubMed Central

    Lu, Jun-Mei; Wang, Chang-Ying; Hu, Changlong; Fang, Yan-Jia; Mei, Yan-Ai

    2016-01-01

    GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K+ currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca2+ concentration ([Ca2+]i) in response to membrane depolarization, as determined by Ca2+ imaging. Whole-cell current recordings indicated that GDF-15 increased the inward Ca2+ current (ICa) without altering steady-state activation of Ca2+ channels. Treatment with nifedipine, an inhibitor of L-type Ca2+ channels, abrogated GDF-15-induced increases in [Ca2+]i and ICa. The GDF-15-induced increase in ICa was mediated via up-regulation of the Cav1.3 α subunit, which was attenuated by inhibiting Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by pharmacological inhibition of Src-mediated TβRII phosphorylation. Given that Cav1.3 is not only a channel for Ca2+ influx, but also a transcriptional regulator, our data confirm that GDF-15 induces protein expression via TβRII and activation of a non-Smad pathway, and provide novel insight into the mechanism of GDF-15 function in neurons. PMID:27114559

  13. Contribution of Ion Channels in Calcium Signaling Regulating Phagocytosis: MaxiK, Cav1.3 and Bestrophin-1.

    PubMed

    Strauß, Olaf; Reichhart, Nadine; Gomez, Nestor Mas; Müller, Claudia

    2016-01-01

    Mutations in the BEST1 gene lead to a variety of retinal degenerations including Best's vitelliforme macular degeneration. The BEST1 gene product, bestrophin-1, is expressed in the retinal pigment epithelium (RPE). It is likely that mutant bestrophin-1 impairs functions of the RPE which support photoreceptor function and will thus lead to retinal degeneration. However, the RPE function which is influenced by bestrophin-1 is so far not identified. Previously we showed that bestrophin-1 interacts with L-type Ca²⁺ channels of the CaV1.3 subtype and that the endogenously expressed bestrophin-1 is required for intracellular Ca²⁺ regulation. A hallmark of Best's disease is the fast lipofuscin accumulation occurring already at young ages. Therefore, we addressed the hypothesis that bestrophin-1 might influence phagocytosis of photoreceptor outer segments (POS) by the RPE. Here, siRNA knock-down of bestrophin-1 expression as well as inhibition of L-type Ca²⁺ channel activity modulated the POS phagocytosis in vitro. In vivo CaV1.3 expression appeared to be diurnal regulated with a higher expression rate in the afternoon. Compared to wild-type littermates, Ca V 1.3 (-/-) mice showed a shift in the circadian POS phagocytosis with an increased activity in the afternoon. Thus we suggest that mutant bestrophin-1 leads to an impaired regulation of the POS phagocytosis by the RPE which would explain the fast lipofuscin accumulation in Best patients.

  14. Radiative Forcing of the Direct Aerosol Effect from AeroCom Phase II Simulations

    NASA Technical Reports Server (NTRS)

    Myhre, G.; Samset, B. H.; Schulz, M.; Balkanski, Y.; Bauer, S.; Berntsen, T. K.; Bian, H.; Bellouin, N.; Chin, M.; Diehl, T.; Easter, R. C.; Feichter, J.; Ghan, S. J.; Hauglustaine, D.; Iversen, T.; Kinne, S.; Kirkevag, A.; Lamarque, J.-F.; Lin, G.; Liu, X.; Lund, M. T.; Luo, G.; Ma, X.; vanNoije, T.; Penner, J. E.; Rasch, P. J.; Ruiz, A.; Seland, O.; Skeie, R. B.; Stier, P.; Takemura, T.; Tsigaridis, K.; Wang, P.; Wang, Z.; Xu, L.; Yu, H.; Yu, F.; Yoon, J. -H.; Zhang, K.; Zhang, H.; Zhou, C.

    2013-01-01

    We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 16 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 16 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has a range from -0.58 to -0.02 W m(sup-2), with a mean of -0.27 W m(sup-2 for the 16 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of -0.35 W m(sup-2). Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study.We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results

  15. A comparison of measured and inferred temperatures from AEROS-B. [of earth atmosphere

    NASA Technical Reports Server (NTRS)

    Chandra, S.; Spencer, N. W.; Krankowsky, D.; Laemmerzahl, P.

    1976-01-01

    The neutral composition and the temperature data obtained from the AEROS-B Neutral Atmosphere Temperature Experiment (NATE) and the Neutral and Ion Mass Spectrometer (NIMS) are compared, and the general validity of inferring gas temperatures from N2 and Ar density profiles is examined by comparing them with the in situ measured values of the neutral kinetic temperature (NATE). At times serious discrepancies are noted between the inferred and the measured temperature. This is particularly evident during periods of increased magnetic activity when the normally observed latitudinal variations are apparently modulated by waves propagating from the polar region to low latitudes. Under these conditions the N2 and Ar densities and temperature oscillations are usually out of phase, and the temperatures inferred from N2 and Ar at a given point become meaningless.

  16. User's manual for UCAP: Unified Counter-Rotation Aero-Acoustics Program

    NASA Technical Reports Server (NTRS)

    Culver, E. M.; Mccolgan, C. J.

    1993-01-01

    This is the user's manual for the Unified Counter-rotation Aeroacoustics Program (UCAP), the counter-rotation derivative of the UAAP (Unified Aero-Acoustic Program). The purpose of this program is to predict steady and unsteady air loading on the blades and the noise produced by a counter-rotation Prop-Fan. The aerodynamic method is based on linear potential theory with corrections for nonlinearity associated with axial flux induction, vortex lift on the blades, and rotor-to-rotor interference. The theory for acoustics and the theory for individual blade loading and wakes are derived in Unified Aeroacoustics Analysis for High Speed Turboprop Aerodynamics and Noise, Volume 1 (NASA CR-4329). This user's manual also includes a brief explanation of the theory used for the modelling of counter-rotation.

  17. A Modular Aero-Propulsion System Simulation of a Large Commercial Aircraft Engine

    NASA Technical Reports Server (NTRS)

    DeCastro, Jonathan A.; Litt, Jonathan S.; Frederick, Dean K.

    2008-01-01

    A simulation of a commercial engine has been developed in a graphical environment to meet the increasing need across the controls and health management community for a common research and development platform. This paper describes the Commercial Modular Aero Propulsion System Simulation (C-MAPSS), which is representative of a 90,000-lb thrust class two spool, high bypass ratio commercial turbofan engine. A control law resembling the state-of-the-art on board modern aircraft engines is included, consisting of a fan-speed control loop supplemented by relevant engine limit protection regulator loops. The objective of this paper is to provide a top-down overview of the complete engine simulation package.

  18. Ultrasonic evaluation of residual stresses in aero engine materials using bulk and Rayleigh surface waves

    NASA Astrophysics Data System (ADS)

    Hubel, Sebastian; Dillhöfer, Alexander; Rieder, Hans; Spies, Martin; Bamberg, Joachim; Götz, Joshua; Hessert, Roland; Preikszas, Christina

    2014-02-01

    The evaluation of residual stresses using ultrasound can be a very complex issue, because different material properties may effect the propagation of ultrasonic waves. Nevertheless, in the manufacturing of modern aero engines it is essential to benefit from the full potential of the employed materials. In this context, it is indispensable to test whether ultrasonic stress measurement is applicable for the highly developed nickel- and titanium-based alloys. This contribution contains basic investigations on the achievable measurement effect in samples made of Inconel IN718 and the Titanium alloy Ti 6-2-4-6. Furthermore, we give an overview over the principles of ultrasonic stress measurement using bulk and Rayleigh waves and present first results which are discussed with respect to texture effects and future work.

  19. Aero-acoustic performance comparison of core engine noise suppressors on NASA quiet engine C

    NASA Technical Reports Server (NTRS)

    Bloomer, H. E.; Schaefer, J. W.

    1977-01-01

    The relative aero-acoustic effectiveness of two core engine suppressors, a contractor-designed suppressor delivered with the Quiet Engine, and a NASA-designed suppressor was evaluated. The NASA suppressor was tested with and without a splitter making a total of three configurations being reported in addition to the baseline hardwall case. The aerodynamic results are presented in terms of tailpipe pressure loss, corrected net thrust, and corrected specific fuel consumption as functions of engine power setting. The acoustic results are divided into duct and far-field acoustic data. The NASA-designed core suppressor did the better job of suppressing aft end noise, but the splitter associated with it caused a significant engine performance penality. The NASA core suppressor without the spltter suppressed most of the core noise without any engine performance penalty.

  20. An AeroCom assessment of black carbon in Arctic snow and sea ice

    SciTech Connect

    Jiao, C.; Flanner, M. G.; Balkanski, Y.; Bauer, S. E.; Bellouin, N.; Berntsen, T. K.; Bian, H.; Carslaw, K. S.; Chin, M.; De Luca, N.; Diehl, T.; Ghan, S. J.; Iversen, T.; Kirkevåg, A.; Koch, D.; Liu, X.; Mann, G. W.; Penner, J. E.; Pitari, G.; Schulz, M.; Seland, Ø.; Skeie, R. B.; Steenrod, S. D.; Stier, P.; Takemura, T.; Tsigaridis, K.; van Noije, T.; Yun, Y.; Zhang, K.

    2014-01-01

    Though many global aerosols models prognose surface deposition, only a few models have been used to directly simulate the radiative effect from black carbon (BC) deposition to snow and sea ice. In this paper, we apply aerosol deposition fields from 25 models contributing to two phases of the Aerosol Comparisons between Observations and Models (AeroCom) project to simulate and evaluate within-snow BC concentrations and radiative effect in the Arctic. We accomplish this by driving the offline land and sea ice components of the Community Earth System Model with different deposition fields and meteorological conditions from 2004 to 2009, during which an extensive field campaign of BC measurements in Arctic snow occurred. We find that models generally underestimate BC concentrations in snow in northern Russia and Norway, while overestimating BC amounts elsewhere in the Arctic. Although simulated BC distributions in snow are poorly correlated with measurements, mean values are reasonable. The multi-model mean (range) bias in BC concentrations, sampled over the same grid cells, snow depths, and months of measurements, are -4.4 (-13.2 to +10.7) ng g-1 for an earlier phase of AeroCom models (phase I), and +4.1 (-13.0 to +21.4) ng g-1 for a more recent phase of AeroCom models (phase II), compared to the observational mean of 19.2 ng g-1. Factors determining model BC concentrations in Arctic snow include Arctic BC emissions, transport of extra-Arctic aerosols, precipitation, deposition efficiency of aerosols within the Arctic, and meltwater removal of particles in snow. Sensitivity studies show that the model–measurement evaluation is only weakly affected by meltwater scavenging efficiency because most measurements were conducted in non-melting snow. The Arctic (60–90° N) atmospheric residence time for BC in phase II models ranges from 3.7 to 23.2 days, implying large inter-model variation in local BC deposition efficiency. Combined with

  1. An AeroCom Assessment of Black Carbon in Arctic Snow and Sea Ice

    NASA Technical Reports Server (NTRS)

    Jiao, C.; Flanner, M. G.; Balkanski, Y.; Bauer, S. E.; Bellouin, N.; Bernsten, T. K.; Bian, H.; Carslaw, K. S.; Chin, M.; DeLuca, N.; Diehl, T.; Ghan, S. J.; Iversen, T.; Kirkevag, A.; Koch, D.; Liu, X.; Mann, G. W.; Penner, J. E.; Pitari, G.; Schulz, M.; Seland, O; Skeie, R. B.; Steenrod, S. D.; Stier, P.; Tkemura, T.

    2014-01-01

    Though many global aerosols models prognose surface deposition, only a few models have been used to directly simulate the radiative effect from black carbon (BC) deposition to snow and sea ice. Here, we apply aerosol deposition fields from 25 models contributing to two phases of the Aerosol Comparisons between Observations and Models (AeroCom) project to simulate and evaluate within-snow BC concentrations and radiative effect in the Arctic. We accomplish this by driving the offline land and sea ice components of the Community Earth System Model with different deposition fields and meteorological conditions from 2004 to 2009, during which an extensive field campaign of BC measurements in Arctic snow occurred. We find that models generally underestimate BC concentrations in snow in northern Russia and Norway, while overestimating BC amounts elsewhere in the Arctic. Although simulated BC distributions in snow are poorly correlated with measurements, mean values are reasonable. The multi-model mean (range) bias in BC concentrations, sampled over the same grid cells, snow depths, and months of measurements, are -4.4 (-13.2 to +10.7) ng/g for an earlier phase of AeroCom models (phase I), and +4.1 (-13.0 to +21.4) ng/g for a more recent phase of AeroCom models (phase II), compared to the observational mean of 19.2 ng/g. Factors determining model BC concentrations in Arctic snow include Arctic BC emissions, transport of extra-Arctic aerosols, precipitation, deposition efficiency of aerosols within the Arctic, and meltwater removal of particles in snow. Sensitivity studies show that the model-measurement evaluation is only weakly affected by meltwater scavenging efficiency because most measurements were conducted in non-melting snow. The Arctic (60-90degN) atmospheric residence time for BC in phase II models ranges from 3.7 to 23.2 days, implying large inter-model variation in local BC deposition efficiency. Combined with the fact that most Arctic BC deposition originates

  2. A Summary of the Slush Hydrogen Technology Program for the National Aero-Space Plane

    NASA Technical Reports Server (NTRS)

    Mcnelis, Nancy B.; Hardy, Terry L.; Whalen, Margaret V.; Kudlac, Maureen T.; Moran, Matthew E.; Tomsik, Thomas M.; Haberbusch, Mark S.

    1995-01-01

    Slush hydrogen, a mixture of solid and liquid hydrogen, offers advantages of higher density (16 percent) and higher heat capacity (18 percent) than normal boiling point hydrogen. The combination of increased density and heat capacity of slush hydrogen provided a potential to decrease the gross takeoff weight of the National Aero-Space Plane (NASP) and therefore slush hydrogen was selected as the propellant. However, no large-scale data was available on the production, transfer and tank pressure control characteristics required to use slush hydrogen as a fuel. Extensive testing has been performed at the NASA Lewis Research Center K-Site and Small Scale Hydrogen Test Facility between 1990 and the present to provide a database for the use of slush hydrogen. This paper summarizes the results of this testing.

  3. Unified Multi-speed analysis (UMA) for the condition monitoring of aero-engines

    NASA Astrophysics Data System (ADS)

    Nembhard, Adrian D.; Sinha, Jyoti K.

    2015-12-01

    For rotating machinery in which speeds and dynamics constantly change, performing vibration-based condition monitoring can be challenging. Thus, an effort is made here to develop a Unified Multi-speed fault diagnosis technique that can exploit useful vibration information available at various speeds from a rotating machine in a single analysis. Commonly applied indicators are computed from data collected from a rig at different speeds for a baseline case and different faults. Four separate analyses are performed: single speed at a single bearing, integrated features from multiple speeds at a single bearing, single speed for integrated features from multiple bearings and the proposed Unified Multi-speed analysis. The Unified Multi-speed approach produces the most conspicuous separation and isolation among the conditions tested. Observations made here suggest integration of more dynamic features available at different speeds improves the learning process of the tool which could prove useful for aero-engine condition monitoring.

  4. Autonomous vehicles

    SciTech Connect

    Meyrowitz, A.L.; Blidberg, D.R.; Michelson, R.C. |

    1996-08-01

    There are various kinds of autonomous vehicles (AV`s) which can operate with varying levels of autonomy. This paper is concerned with underwater, ground, and aerial vehicles operating in a fully autonomous (nonteleoperated) mode. Further, this paper deals with AV`s as a special kind of device, rather than full-scale manned vehicles operating unmanned. The distinction is one in which the AV is likely to be designed for autonomous operation rather than being adapted for it as would be the case for manned vehicles. The authors provide a survey of the technological progress that has been made in AV`s, the current research issues and approaches that are continuing that progress, and the applications which motivate this work. It should be noted that issues of control are pervasive regardless of the kind of AV being considered, but that there are special considerations in the design and operation of AV`s depending on whether the focus is on vehicles underwater, on the ground, or in the air. The authors have separated the discussion into sections treating each of these categories.

  5. Aero-Structural Optimization of HSCT Configurations in Transonic and Supersonic Flow

    NASA Technical Reports Server (NTRS)

    Alonso, Juan J.

    1999-01-01

    This document outlines the progress made under NASA Cooperative Research Agreement NCC2- 5226 for the period 10/01/97-09/30/98. The work statement originally proposed was meant to extend over the period of two complete years of which only one was funded. Consequently, only a portion of the goals were achieved. Similar work will continue in our group under different sponsorship and will be available in the form of conference and journal publications. The following sections summarize the technical accomplishments obtained during the last year. Details of these accomplishments can be found in the accompanying paper that was presented at the AIAA 37th Aerospace Sciences and Exhibit Meeting which was held in Reno, NV in January of this year. The original proposal outlined a research program meant to lay down the foundation for the development of high-fidelity, fully-coupled aerodynamic/structural optimization methods applicable to a variety of aerospace applications including the design optimization of High Speed Civil Transport (HSCT) configurations. The necessary research and development work was divided into two main efforts which addressed the necessities of the long term goal. Initially, our experience in the simulation of unsteady aeroelastic flows was directly applied to existing aerodynamic optimization techniques in order to provide insight into the effects of aeroelastic deformations on the performance of aircraft which have been designed based on purely aerodynamic cost functions. The intention was to follow up this work with a detailed investigation into the basic research work that has to be completed for the development of an optimization framework which efficiently allows the truly coupled design of aero-structural systems. This follow-up effort was not funded. The outcome of our efforts during the past year was the development of a coupled aero-structural analysis and design environment that was applied to the design of a complete aircraft configuration.

  6. Ka-band MMIC array system for ACTS aeronautical terminal experiment (Aero-X)

    NASA Technical Reports Server (NTRS)

    Raquet, Charles A.; Zakrajsek, Robert J.; Lee, Richard Q.; Andro, Monty; Turtle, John P.

    1995-01-01

    During the summer of 1994, the Advanced Communication Technology Satellite (ACTS) Aeronautical Terminal Experiment (Aero-X) was successfully completed by the NASA Lewis Research Center (LeRC) and the Jet Propulsion Laboratory (JPL). 4.8 and 9.6 Kbps duplex voice links were established between the LeRC Learjet and the ACTS Link Evaluation Terminal (LET) in Cleveland, Ohio, via the ACTS. The antenna system used in this demonstration was developed by LeRC and featured LeRC and US Air Force experimental arrays using GaAs MMIC devices at each radiating element for electronic beam steering and distributed power amplification. The antenna system consisted of three arrays mounted inside the LeRC Learjet, pointing out through the windows. An open loop tracking controller developed by LeRC used information from the aircraft position and attitude sensors to automatically steer the arrays toward ACTS during flight JPL ACTS Mobile Terminal (AMT) system hardware was used as transceivers both on the aircraft and at the LET. The single 32 element MMIC transmit array developed by NASA/LeRC and Texas Instruments has an EIRP of 23.4 dBW at boresight. The two 20 GHz MMIC receive arrays were developed in a cooperative effort with the USAF Rome Laboratory/Electronic System Center, taking advantage of existing USAF array development contracts with Boeing and Martin Marietta. The Boeing array has 23 elements and a G/T of 16/6 db/degK at boresight. The Martin Marietta array has 16 elements and a G/T of 16.1 db/degK at boresight. The three proof-of-concept arrays, the array control system and their integration and operation in the Learjet for Aero-X are described.

  7. Integrated line-of-sight Modeling of the Airborne Aero-Optics Laboratory

    NASA Astrophysics Data System (ADS)

    Griffin, S.; Blackburn, J.; Thordahl, J.; Wittich, D.; Gordeyev, S.; Jumper, E.

    2013-09-01

    The Airborne Aero-Optics Laboratory (AAOL) is a recently completed research effort to measure the effects of turbulent flow on the wavefront of a laser projected from an airplane in flight. The flight-test system consists of two Cessna Citation Bravo aircraft flying in formation at a distance of approximately 50 m. One aircraft projects a laser beam to the other aircraft which receives the beam using an inertially stabilized turret with a high bandwidth track loop. In addition to its benefit in providing a means for understanding and correcting optical wavefront distortion due to turbulence, AAOL also provides an ideal platform for predicting line-of-sight jitter and comparing it to measured results. AAOL has the essential elements of an airborne optical beam control system and is subject to relevant aero-loading, but operates at low power and provides a relatively inexpensive platform for collecting flight data. This paper presents the integrated AAOL line-of-sight model for prediction of optical jitter due to flight disturbances. To accomplish this, a dynamic simulation model was derived from a finite element model of the system, optical sensitivities and control loops for calculation of closed loop, line-of-sight jitter. Disturbance inputs include measured in-flight base loading and pressure loading on the turret generated from an unsteady computational fluid dynamics model. The influence of model uncertainty was also addressed by considering two separate models. The first model was based on the initial hardware design before hardware assembly. The second model was updated based on modal tests performed on the assembled flight hardware. Frequency-varying model uncertainty factors for both models required to accurately predict the measured flight data were calculated. Predicted results with and without model uncertainty factors will be compared with measured flight data from AAOL.

  8. Future orbital transfer vehicle technology study. Volume 2: Technical report

    NASA Technical Reports Server (NTRS)

    Davis, E. E.

    1982-01-01

    Missions for future orbit transfer vehicles (1995-2010) are identified and the technology, operations and vehicle concepts that satisfy the transportation requirements are defined. Comparison of reusable space and ground based LO2/LH2 OTV's was made. Both vehicles used advanced space engines and aero assist capability. The SB OTV provided advantages in life cycle cost, performance and potential for improvement. Comparison of an all LO2/LH2 OTV fleet with a fleet of LO2/LH2 OTVs and electric OTV's was also made. The normal growth technology electric OTV used silicon cells with heavy shielding and argon ion thrusters. This provided a 23% advantage in total transportation cost. The impact of accelerated technology was considered in terms of improvements in performance and cost effectiveness. The accelerated technology electric vehicle used GaAs cells and annealing but did not result in the mixed fleet being any cheaper than an all LO2/LH2 OTV fleet. It is concluded that reusable LO2/LH2 OTV's can serve all general purpose cargo roles between LEO and GEO for the forseeable future. The most significant technology for the second generation vehicle would be space debris protection, on-orbit propellant storage and transfer and on-orbit maintenance capability.

  9. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia.

    PubMed

    Makarenko, Vladislav V; Ahmmed, Gias U; Peng, Ying-Jie; Khan, Shakil A; Nanduri, Jayasri; Kumar, Ganesh K; Fox, Aaron P; Prabhakar, Nanduri R

    2016-01-01

    Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca(2+)]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca(2+)]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca(2+)]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca(2+) channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca(2+)]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca(2+) currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca(2+) influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane.

  10. Splice-variant changes of the CaV3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development

    PubMed Central

    David, Laurence S; Garcia, Esperanza; Cain, Stuart M; Thau, Elana M; Tyson, John R

    2010-01-01

    Low voltage-activated T-type calcium (Ca) channels contribute to the normal development of the heart and are also implicated in pathophysiological states such as cardiac hypertrophy. Functionally distinct T-type Ca channel isoforms can be generated by alternative splicing from each of three different T-type genes (CaV3.1, CaV3.2, CaV3.3), although it remains to be described whether specific splice variants are associated with developmental states and pathological conditions. We aimed to identify and functionally characterize CaV3.2 T-type Ca channel alternatively spliced variants from newborn animals and to compare with adult normotensive and spontaneously hypertensive rats (SHR). DNA sequence analysis of full-length CaV3.2 cDNA generated from newborn heart tissue identified ten major regions of alternative splicing, the more common variants of which were analyzed by quantitative real-time PCR (qRT-PCR) and also subject to functional examination by whole-cell patch clamp. The main findings are that: (1) cardiac CaV3.2 T-type Ca channels are subject to considerable alternative splicing, (2) there is preferential expression of CaV3.2(−25) splice variant channels in newborn rat heart with a developmental shift in adult heart that results in approximately equal levels of expression of both (+25) and (−25) exon variants, (3) in the adult stage of hypertensive rats there is both an increase in overall CaV3.2 expression and a shift towards expression of CaV3.2(+25) containing channels as the predominant form and (4) alternative splicing confers a variant-specific voltage-dependent facilitation of CaV3.2 channels. We conclude that CaV3.2 alternative splicing generates significant T-type Ca channel structural and functional diversity with potential implications relevant to cardiac developmental and pathophysiological states. PMID:20699644

  11. Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice

    PubMed Central

    Poetschke, Christina; Dragicevic, Elena; Duda, Johanna; Benkert, Julia; Dougalis, Antonios; DeZio, Roberta; Snutch, Terrance P.; Striessnig, Joerg; Liss, Birgit

    2015-01-01

    The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson’s disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca2+ burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary for SN DA pacemaker-activity at either age, but rather contributed to their pacemaker-precision. Moreover, juvenile Cav1.3 KO but not WT mice displayed adult wildtype-like, sensitised inhibitory dopamine-D2-autoreceptor (D2-AR) responses that depended upon both, interaction of the neuronal calcium sensor NCS-1 with D2-ARs, and on voltage-gated T-type calcium channel (TTCC) activity. This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age-dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L-type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age- and calcium-dependent activity-control of SN DA neurons and its pharmacological modulation. PMID:26381090

  12. Chronic fluoxetine administration increases expression of the L-channel gene Cav1.2 in astrocytes from the brain of treated mice and in culture and augments K(+)-induced increase in [Ca(2+)]i.

    PubMed

    Du, Ting; Liang, Chunguang; Li, Baoman; Hertz, Leif; Peng, Liang

    2014-03-01

    We have recently shown that freshly isolated astrocytes from the mouse brain express mRNA for the L-channel gene Cav1.3 to at least the same degree (per mg mRNA) as corresponding neurons. The amount of extracellular Ca(2+) actually entering cultured astrocytes by its opening is modest, but due to secondary Ca(2+)-mediated stimulation of the ryanodine receptor (RyR) the increase in free cytosolic Ca(2+) [Ca(2+)]i is substantial. The other Cav1 subtype expressed in brain is Cav1.2, which is even expressed in higher density. Although the different primers used for the two genes preclude exact quantitative comparison, the present study suggests that this is also the case in the freshly isolated astrocytes and neurons, which express equal Cav1.2 densities. Again, most of the increase in [Ca(2+)]i occurred by RyR activity. In contrast to Cav1.3 the expression of Cav1.2 was greatly increased (doubled) after two weeks of treatment with fluoxetine hydrochloride (10mg/kg). Accordingly [Ca(2+)]i in cultured astrocytes exposed to the addition of 10-60mM KCl increased substantially in cultured astrocytes treated chronically with fluoxetine with the lag time until the effect was observed depending upon the fluoxetine concentration. This effect was inhibited by nifedipine or siRNA against Cav1.2. The increase in K(+)-induced rise in [Ca(2+)]i after fluoxetine treatment is directly opposite to a decrease in [Ca(2+)]i after treatment with any of the anti-bipolar drugs lithium, carbamazepine or valproic acid, due to reduced capacitative Ca(2+) influx. We have previously shown a similar effect after fluoxetine treatment, but it becomes overridden by the Cav1.2 up-regulation. PMID:24513410

  13. Ca2+ Binding/Permeation via Calcium Channel, CaV1.1, Regulates the Intracellular Distribution of the Fatty Acid Transport Protein, CD36, and Fatty Acid Metabolism.

    PubMed

    Georgiou, Dimitra K; Dagnino-Acosta, Adan; Lee, Chang Seok; Griffin, Deric M; Wang, Hui; Lagor, William R; Pautler, Robia G; Dirksen, Robert T; Hamilton, Susan L

    2015-09-25

    Ca(2+) permeation and/or binding to the skeletal muscle L-type Ca(2+) channel (CaV1.1) facilitates activation of Ca(2+)/calmodulin kinase type II (CaMKII) and Ca(2+) store refilling to reduce muscle fatigue and atrophy (Lee, C. S., Dagnino-Acosta, A., Yarotskyy, V., Hanna, A., Lyfenko, A., Knoblauch, M., Georgiou, D. K., Poché, R. A., Swank, M. W., Long, C., Ismailov, I. I., Lanner, J., Tran, T., Dong, K., Rodney, G. G., Dickinson, M. E., Beeton, C., Zhang, P., Dirksen, R. T., and Hamilton, S. L. (2015) Skelet. Muscle 5, 4). Mice with a mutation (E1014K) in the Cacna1s (α1 subunit of CaV1.1) gene that abolishes Ca(2+) binding within the CaV1.1 pore gain more body weight and fat on a chow diet than control mice, without changes in food intake or activity, suggesting that CaV1.1-mediated CaMKII activation impacts muscle energy expenditure. We delineate a pathway (Cav1.1→ CaMKII→ NOS) in normal skeletal muscle that regulates the intracellular distribution of the fatty acid transport protein, CD36, altering fatty acid metabolism. The consequences of blocking this pathway are decreased mitochondrial β-oxidation and decreased energy expenditure. This study delineates a previously uncharacterized CaV1.1-mediated pathway that regulates energy utilization in skeletal muscle.

  14. Ca2+ Binding/Permeation via Calcium Channel, CaV1.1, Regulates the Intracellular Distribution of the Fatty Acid Transport Protein, CD36, and Fatty Acid Metabolism*

    PubMed Central

    Georgiou, Dimitra K.; Dagnino-Acosta, Adan; Lee, Chang Seok; Griffin, Deric M.; Wang, Hui; Lagor, William R.; Pautler, Robia G.; Dirksen, Robert T.; Hamilton, Susan L.

    2015-01-01

    Ca2+ permeation and/or binding to the skeletal muscle L-type Ca2+ channel (CaV1.1) facilitates activation of Ca2+/calmodulin kinase type II (CaMKII) and Ca2+ store refilling to reduce muscle fatigue and atrophy (Lee, C. S., Dagnino-Acosta, A., Yarotskyy, V., Hanna, A., Lyfenko, A., Knoblauch, M., Georgiou, D. K., Poché, R. A., Swank, M. W., Long, C., Ismailov, I. I., Lanner, J., Tran, T., Dong, K., Rodney, G. G., Dickinson, M. E., Beeton, C., Zhang, P., Dirksen, R. T., and Hamilton, S. L. (2015) Skelet. Muscle 5, 4). Mice with a mutation (E1014K) in the Cacna1s (α1 subunit of CaV1.1) gene that abolishes Ca2+ binding within the CaV1.1 pore gain more body weight and fat on a chow diet than control mice, without changes in food intake or activity, suggesting that CaV1.1-mediated CaMKII activation impacts muscle energy expenditure. We delineate a pathway (Cav1.1→ CaMKII→ NOS) in normal skeletal muscle that regulates the intracellular distribution of the fatty acid transport protein, CD36, altering fatty acid metabolism. The consequences of blocking this pathway are decreased mitochondrial β-oxidation and decreased energy expenditure. This study delineates a previously uncharacterized CaV1.1-mediated pathway that regulates energy utilization in skeletal muscle. PMID:26245899

  15. C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 2: Test Bed Performance Evaluation and Final AeroMACS Recommendations

    NASA Technical Reports Server (NTRS)

    Hall, Edward; Magner, James

    2011-01-01

    This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II (this document) describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

  16. C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 1: Concepts of Use, Initial System Requirements, Architecture, and AeroMACS Design Considerations

    NASA Technical Reports Server (NTRS)

    Hall, Edward; Isaacs, James; Henriksen, Steve; Zelkin, Natalie

    2011-01-01

    This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I (this document) is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

  17. CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Cav3.2 T-type calcium channel activity and reticular thalamic neuron firing.

    PubMed

    Rzhepetskyy, Yuriy; Lazniewska, Joanna; Blesneac, Iulia; Pamphlett, Roger; Weiss, Norbert

    2016-11-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. In a recent study by Steinberg and colleagues, 2 recessive missense mutations were identified in the Cav3.2 T-type calcium channel gene (CACNA1H), in a family with an affected proband (early onset, long duration ALS) and 2 unaffected parents. We have introduced and functionally characterized these mutations using transiently expressed human Cav3.2 channels in tsA-201 cells. Both of these mutations produced mild but significant changes on T-type channel activity that are consistent with a loss of channel function. Computer modeling in thalamic reticular neurons suggested that these mutations result in decreased neuronal excitability of thalamic structures. Taken together, these findings implicate CACNA1H as a susceptibility gene in amyotrophic lateral sclerosis.

  18. Robotic vehicle

    DOEpatents

    Box, W.D.

    1996-03-12

    A robotic vehicle is described for travel through an enclosed or partially enclosed conduit or pipe including vertical and/or horizontal conduit or pipe. The robotic vehicle comprises forward and rear housings each provided with a surface engaging mechanism for selectively engaging the walls of the conduit through which the vehicle is travelling, whereby the housings are selectively held in a stationary position within the conduit. The vehicle also includes at least three selectively extendable members, each of which defines a cavity therein. The forward end portion of each extendable member is secured to the forward housing and the rear end portion of each housing is secured to the rear housing. Each of the extendable members is independently extendable from a retracted position to an extended position upon the injection of a gas under pressure into the cavity of the extendable member such that the distance between the forward housing and the rear housing can be selectively increased. Further, each of the extendable members is independently retractable from the extended position to the retracted position upon the application of a vacuum to the cavity of the extendable member such that the distance between the forward housing and the rear housing can be selectively decreased. 14 figs.

  19. Robotic vehicle

    DOEpatents

    Box, W.D.

    1994-03-15

    A robotic vehicle is described for travel through an enclosed or partially enclosed conduit or pipe including vertical and/or horizontal conduit or pipe. The robotic vehicle comprises forward and rear housings each provided with a surface engaging mechanism for selectively engaging the walls of the conduit through which the vehicle is travelling, whereby the housings are selectively held in a stationary position within the conduit. The vehicle also includes at least three selectively extendable members, each of which defines a cavity therein. The forward end portion of each extendable member is secured to the forward housing and the rear end portion of each housing is secured to the rear housing. Each of the extendable members is independently extendable from a retracted position to an extended position upon the injection of a gas under pressure into the cavity of the extendable member such that the distance between the forward housing and the rear housing can be selectively increased. Further, each of the extendable members is independently retractable from the extended position to the retracted position upon the application of a vacuum to the cavity of the extendable member such that the distance between the forward housing and the rear housing can be selectively decreased. 11 figures.

  20. Robotic vehicle

    DOEpatents

    Box, W. Donald

    1996-01-01

    A robotic vehicle (10) for travel through an enclosed or partially enclosed conduit or pipe including vertical and/or horizontal conduit or pipe. The robotic vehicle (10) comprises forward and rear housings (32 and 12) each provided with a surface engaging mechanism for selectively engaging the walls of the conduit through which the vehicle is travelling, whereby the housings (32 and 12) are selectively held in a stationary position within the conduit. The vehicle (10) also includes at least three selectively extendable members (46), each of which defines a cavity (56) therein. The forward end portion (50) of each extendable member (46) is secured to the forward housing (32) and the rear end portion (48) of each housing is secured to the rear housing (12). Each of the extendable members (46) is independently extendable from a retracted position to an extended position upon the injection of a gas under pressure into the cavity (56) of the extendable member such that the distance between the forward housing (32 ) and the rear housing (12) can be selectively increased. Further, each of the extendable members (46) is independently retractable from the extended position to the retracted position upon the application of a vacuum to the cavity (56) of the extendable member (46) such that the distance between the forward housing (32) and the rear housing (12) can be selectively decreased.

  1. Robotic vehicle

    DOEpatents

    Box, W. Donald

    1994-01-01

    A robotic vehicle (10) for travel through an enclosed or partially enclosed conduit or pipe including vertical and/or horizontal conduit or pipe. The robotic vehicle (10) comprises forward and rear housings (32 and 12) each provided with a surface engaging mechanism for selectively engaging the walls of the conduit through which the vehicle is travelling, whereby the housings (32 and 12) are selectively held in a stationary position within the conduit. The vehicle (10) also includes at least three selectively extendable members (46), each of which defines a cavity (56) therein. The forward end portion (50) of each extendable member (46) is secured to the forward housing (32) and the rear end portion (48) of each housing is secured to the rear housing (12). Each of the extendable members (46) is independently extendable from a retracted position to an extended position upon the injection of a gas under pressure into the cavity (56) of the extendable member such that the distance between the forward housing (32 ) and the rear housing (12) can be selectively increased. Further, each of the extendable members (46) is independently retractable from the extended position to the retracted position upon the application of a vacuum to the cavity (56) of the extendable member (46) such that the distance between the forward housing (32) and the rear housing (12) can be selectively decreased.

  2. “Slow” Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA)

    PubMed Central

    Zhu, Lei; McDavid, Sarah; Currie, Kevin P. M.

    2015-01-01

    CaV2.2 (N-type) voltage-gated calcium channels (Ca2+ channels) play key roles in neurons and neuroendocrine cells including the control of cellular excitability, neurotransmitter / hormone secretion, and gene expression. Calcium entry is precisely controlled by channel gating properties including multiple forms of inactivation. “Fast” voltage-dependent inactivation is relatively well-characterized and occurs over the tens-to- hundreds of milliseconds timeframe. Superimposed on this is the molecularly distinct, but poorly understood process of “slow” voltage-dependent inactivation, which develops / recovers over seconds-to-minutes. Protein kinases can modulate “slow” inactivation of sodium channels, but little is known about if/how second messengers control “slow” inactivation of Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed in HEK293 cells and native CaV2 channels endogenously expressed in adrenal chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA) dramatically prolonged recovery from “slow” inactivation, but an inactive control (4α-PMA) had no effect. This effect of PMA was prevented by calphostin C, which targets the C1-domain on PKC, but only partially reduced by inhibitors that target the catalytic domain of PKC. The subtype of the channel β-subunit altered the kinetics of inactivation but not the magnitude of slowing produced by PMA. Intracellular GDP-β-S reduced the effect of PMA suggesting a role for G proteins in modulating “slow” inactivation. We postulate that the kinetics of recovery from “slow” inactivation could provide a molecular memory of recent cellular activity and help control CaV2 channel availability, electrical excitability, and neurotransmission in the seconds-to-minutes timeframe. PMID:26222492

  3. Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1, and enhances skeletal muscle force in aging sedentary mice.

    PubMed

    Zhang, Tan; Pereyra, Andrea S; Wang, Zhong-Min; Birbrair, Alexander; Reisz, Julie A; Files, Daniel Clark; Purcell, Lina; Feng, Xin; Messi, Maria L; Feng, Hanzhong; Chalovich, Joseph; Jin, Jian-Ping; Furdui, Cristina; Delbono, Osvaldo

    2016-06-01

    Loss of strength in human and animal models of aging can be partially attributed to a well-recognized decrease in muscle mass; however, starting at middle-age, the normalized force (force/muscle cross-sectional area) in the knee extensors and single muscle fibers declines in a curvilinear manner. Strength is lost faster than muscle mass and is a more consistent risk factor for disability and death. Reduced expression of the voltage sensor Ca(2+) channel α1 subunit (Cav1.1) with aging leads to excitation-contraction uncoupling, which accounts for a significant fraction of the decrease in skeletal muscle function. We recently reported that in addition to its classical cytoplasmic location, fast skeletal muscle troponin T3 (TnT3) is fragmented in aging mice, and both full-length TnT3 (FL-TnT3) and its carboxyl-terminal (CT-TnT3) fragment shuttle to the nucleus. Here, we demonstrate that it regulates transcription of Cacna1s, the gene encoding Cav1.1. Knocking down TnT3 in vivo downregulated Cav1.1. TnT3 downregulation or overexpression decreased or increased, respectively, Cacna1s promoter activity, and the effect was ablated by truncating the TnT3 nuclear localization sequence. Further, we mapped the Cacna1s promoter region and established the consensus sequence for TnT3 binding to Cacna1s promoter. Systemic administration of BDA-410, a specific calpain inhibitor, prevented TnT3 fragmentation, and Cacna1s and Cav1.1 downregulation and improved muscle force generation in sedentary old mice.

  4. Ca(v)3.2 channel is a molecular substrate for inhibition of T-type calcium currents in rat sensory neurons by nitrous oxide.

    PubMed

    Todorovic, S M; Jevtovic-Todorovic, V; Mennerick, S; Perez-Reyes, E; Zorumski, C F

    2001-09-01

    Although nitrous oxide (N(2)O; laughing gas) remains widely used as an anesthetic and analgesic in clinical practice, its cellular mechanisms of action remain inadequately understood. In this report, we examined the effects of N(2)O on voltage-gated Ca(2+) channels in acutely dissociated small sensory neurons of adult rat. At subanesthetic concentrations, N(2)O blocks low-voltage-activated, T-type Ca(2+) currents (T currents), but not high-voltage-activated (HVA) currents. This blockade of T currents was concentration dependent, with an IC(50) value of 45 +/- 13%, maximal block of 38 +/- 12%, and Hill coefficient of 2.6 +/- 1.0. No desensitization of the response or change in current kinetics was observed during N(2)O application. The magnitude of T current blockade by N(2)O does not seem to reflect any use- or voltage-dependent properties. In addition, T current blockade was not altered when intracellular GTP was replaced with guanosine 5'-(gamma-thio)triphosphate or guanosine 5'-0-(2-thiodiphosphate) suggesting a lack of involvement of G-proteins in the inhibition. N(2)O selectively blocked currents arising from the Ca(v)3.2 but not Ca(v)3.1 recombinant channels stably expressed in human embryonic kidney (HEK) cells in a concentration-dependent manner with an apparent affinity and potency similar to native dorsal root ganglion currents. Analogously, the block of Ca(v)3.2 T currents exhibited little voltage- or use-dependence. These data indicate that N(2)O selectively blocks T-type but not HVA Ca(2+) currents in small sensory neurons and Ca(v)3.2 currents in HEK cells at subanesthetic concentrations. Blockade of T currents may contribute to the anesthetic and/or analgesic effects of N(2)O. PMID:11502893

  5. Persistent increases in Ca(2+) influx through Cav1.2 shortens action potential and causes Ca(2+) overload-induced afterdepolarizations and arrhythmias.

    PubMed

    Zhang, Xiaoying; Ai, Xiaojie; Nakayama, Hiroyuki; Chen, Biyi; Harris, David M; Tang, Mingxin; Xie, Yuping; Szeto, Christopher; Li, Yingxin; Li, Ying; Zhang, Hongyu; Eckhart, Andrea D; Koch, Walter J; Molkentin, Jeffery D; Chen, Xiongwen

    2016-01-01

    Persistent elevation of Ca(2+) influx due to prolongation of the action potential (AP), chronic activation of the β-adrenergic system and molecular remodeling occurs in stressed and diseased hearts. Increases in Ca(2+) influx are usually linked to prolonged myocyte action potentials and arrhythmias. However, the contribution of chronic enhancement of Cav1.2 activity on cardiac electrical remodeling and arrhythmogenicity has not been completely defined and is the subject of this study. Chronically increased Cav1.2 activity was produced with a cardiac specific, inducible double transgenic (DTG) mouse system overexpressing the β2a subunit of Cav (Cavβ2a). DTG myocytes had increased L-type Ca(2+) current (ICa-L), myocyte shortening, and Ca(2+) transients. DTG mice had enhanced cardiac performance, but died suddenly and prematurely. Telemetric electrocardiograms revealed shortened QT intervals in DTG mice. The action potential duration (APD) was shortened in DTG myocytes due to significant increases of potassium currents and channel abundance. However, shortened AP in DTG myocytes did not fully limit excess Ca(2+) influx and increased the peak and tail ICa-L. Enhanced ICa promoted sarcoplasmic reticulum (SR) Ca(2+) overload, diastolic Ca(2+) sparks and waves, and increased NCX activity, causing increased occurrence of early and delayed afterdepolarizations (EADs and DADs) that may contribute to premature ventricular beats and ventricular tachycardia. AV blocks that could be related to fibrosis of the AV node were also observed. Our study suggests that increasing ICa-L does not necessarily result in AP prolongation but causes SR Ca(2+) overload and fibrosis of AV node and myocardium to induce cellular arrhythmogenicity, arrhythmias, and conduction abnormalities.

  6. Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel.

    PubMed

    Sun, Yu; Xu, Jianjun; Minobe, Etsuko; Shimoara, Shoken; Hao, Liying; Kameyama, Masaki

    2015-07-01

    Although it has been well documented that redox can modulate Cav1.2 channel activity, the underlying mechanisms are not fully understood. In our study, we examined the effects of redox on Cav1.2 channel activity and on CaM interaction with the Cav1.2 α1 subunit. Dithiothreitol (DTT, 1 mM) in the cell-attached mode decreased, while hydrogen peroxide (H2O2, 1 mM) increased channel activity to 72 and 303%, respectively. The effects of redox were maintained in the inside-out mode where channel activity was induced by CaM + ATP: DTT (1 mM) decreased, while H2O2 (1 mM) increased the channel activity. These results were mimicked by the thioredoxin and oxidized glutathione system. To test whether the redox state might determine channel activity by affecting the CaM interaction with the channel, we examined the effects of DTT and H2O2 on CaM binding to the N- and C-terminal fragments of the channel. We found that DTT concentration-dependently inhibited CaM binding to the C-terminus (IC50 37 μM), but H2O2 had no effect. Neither DTT nor H2O2 had an effect on CaM interaction with the N-terminus. These results suggest that redox-mediated regulation of the Cav1.2 channel is governed, at least partially, by modulation of the CaM interaction with the channel.

  7. Systems analysis and technology development for the NASA Orbit Transfer Vehicle

    NASA Technical Reports Server (NTRS)

    Roberts, B. B.

    1985-01-01

    The benefits derived from aerobraking technology development for the Orbit Transfer Vehicle (OTV) are analyzed. The relative advantages of several other candidate OTV technologies are evaluated, and a relative ranking on the basis of performance considerations is presented. It is shown that aerobraking technologies can provide significant cost reductions for delivery of payloads to geosynchronous orbit, and that new and unique design concepts for OTVs must be pursued in order to realize the promised cost benefits. The goal for an aerobraked vehicle is an upper limit of 20 percent of the vehicle devoted to aero systems. Practical OTV configurations based on a concept of integrated structural design that can achieve this goal are suggested. A concept for a flight experiment to acquire the data needed to advance the discussed aeroassist technologies is proposed.

  8. An Innovative Structural Mode Selection Methodology: Application for the X-33 Launch Vehicle Finite Element Model

    NASA Technical Reports Server (NTRS)

    Hidalgo, Homero, Jr.

    2000-01-01

    An innovative methodology for determining structural target mode selection and mode selection based on a specific criterion is presented. An effective approach to single out modes which interact with specific locations on a structure has been developed for the X-33 Launch Vehicle Finite Element Model (FEM). We presented Root-Sum-Square (RSS) displacement method computes resultant modal displacement for each mode at selected degrees of freedom (DOF) and sorts to locate modes with highest values. This method was used to determine modes, which most influenced specific locations/points on the X-33 flight vehicle such as avionics control components, aero-surface control actuators, propellant valve and engine points for use in flight control stability analysis and for flight POGO stability analysis. Additionally, the modal RSS method allows for primary or global target vehicle modes to also be identified in an accurate and efficient manner.

  9. CONSIDERATIONS ON ANATOMY AND PHYSIOLOGY OF LYMPH VESSELS OF UPPER AERO DIGESTIVE ORGANS AND CERVICAL SATELLITE LYMPH NODE GROUP.

    PubMed

    Ciupilan, Corina; Stan, C I

    2016-01-01

    The almost constant local regional development of the cancers of upper aero digestive organs requires the same special attention to cervical lymph node metastases, as well as to the primary neoplastic burning point. The surgical therapy alone or associated has a mutilating, damaging character, resulting in loss of an organ and function, most of the times with social implications, involving physical distortions with aesthetic consequences, which make the reintegration of the individual into society questionable. The problem of cervical lymph node metastases is vast and complex, reason why we approached several anatomical and physiological aspects of lymph vessels of the aero digestive organs. Among the available elements during treatment, the headquarters of the tumour, its histologic degree, and its infiltrative nature, each of them significantly influences the possibility of developing metastases.

  10. CONSIDERATIONS ON ANATOMY AND PHYSIOLOGY OF LYMPH VESSELS OF UPPER AERO DIGESTIVE ORGANS AND CERVICAL SATELLITE LYMPH NODE GROUP.

    PubMed

    Ciupilan, Corina; Stan, C I

    2016-01-01

    The almost constant local regional development of the cancers of upper aero digestive organs requires the same special attention to cervical lymph node metastases, as well as to the primary neoplastic burning point. The surgical therapy alone or associated has a mutilating, damaging character, resulting in loss of an organ and function, most of the times with social implications, involving physical distortions with aesthetic consequences, which make the reintegration of the individual into society questionable. The problem of cervical lymph node metastases is vast and complex, reason why we approached several anatomical and physiological aspects of lymph vessels of the aero digestive organs. Among the available elements during treatment, the headquarters of the tumour, its histologic degree, and its infiltrative nature, each of them significantly influences the possibility of developing metastases. PMID:27483727

  11. Cross-Correlations and Structures of Aero-Engine Gas Path System Based on DCCA Coefficient and Rooted Tree

    NASA Astrophysics Data System (ADS)

    Dong, Keqiang; Fan, Jie; Gao, You

    2015-12-01

    Identifying the mutual interaction is a crucial problem that facilitates the understanding of emerging structures in complex system. We here focus on aero-engine dynamic as an example of complex system. By applying the detrended cross-correlation analysis (DCCA) coefficient method to aero-engine gas path system, we find that the low-spool rotor speed (N1) and high-spool rotor speed (N2) fluctuation series exhibit cross-correlation characteristic. Further, we employ detrended cross-correlation coefficient matrix and rooted tree to investigate the mutual interactions of other gas path variables. The results can infer that the exhaust gas temperature (EGT), N1, N2, fuel flow (WF) and engine pressure ratio (EPR) are main gas path parameters.

  12. β-Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-κB Signaling Pathway.

    PubMed

    Zhu, Xiangzhan; Zhang, Yanting; Li, Qinghua; Yang, Lu; Zhang, Nannan; Ma, Shanshan; Zhang, Kun; Song, Jishi; Guan, Fangxia

    2016-03-01

    β-carotene, a type of terpenoid, has many metabolic and physiological functions. In particular, β-carotene has an antitumor effect. However, the efficacy of β-carotene against esophageal squamous cell carcinoma (ESCC) remains unclear. In our study, β-carotene inhibited the growth of ESCC cells and downregulated expression of the Caveolin-1 (Cav-1) protein. Cav-1 protein was expressed only in ESCC cells, not in Het-1A cells. Moreover, β-carotene triggered apoptosis, induced cell cycle G0⁄G1 phase arrest, and inhibited cell migration. To explore the mechanism involved in these processes, we further examined the effect of β-carotene on the Cav-1-mediated AKT/NF-κB pathway. The results showed that the level of AKT and NF-κB phosphorylation was dramatically inhibited, which led to an increase in the Bax/Bcl-2 ratio. Correspondingly, the activity of Caspase-3 was also enhanced. These data suggest that β-carotene has an antiproliferative role in ESCC cells and may be a promising chemotherapeutic agent for use against ESCC cells. PMID:26733226

  13. CaV3.2 T-type channels mediate Ca²⁺ entry during oocyte maturation and following fertilization.

    PubMed

    Bernhardt, Miranda L; Zhang, Yingpei; Erxleben, Christian F; Padilla-Banks, Elizabeth; McDonough, Caitlin E; Miao, Yi-Liang; Armstrong, David L; Williams, Carmen J

    2015-12-01

    Initiation of mouse embryonic development depends upon a series of fertilization-induced rises in intracellular Ca(2+). Complete egg activation requires influx of extracellular Ca(2+); however, the channels that mediate this influx remain unknown. Here, we tested whether the α1 subunit of the T-type channel CaV3.2, encoded by Cacna1h, mediates Ca(2+) entry into oocytes. We show that mouse eggs express a robust voltage-activated Ca(2+) current that is completely absent in Cacna1h(-/-) eggs. Cacna1h(-/-) females have reduced litter sizes, and careful analysis of Ca(2+) oscillation patterns in Cacna1h(-/-) eggs following in vitro fertilization (IVF) revealed reductions in first transient length and oscillation persistence. Total and endoplasmic reticulum (ER) Ca(2+) stores were also reduced in Cacna1h(-/-) eggs. Pharmacological inhibition of CaV3.2 in wild-type CF-1 strain eggs using mibefradil or pimozide reduced Ca(2+) store accumulation during oocyte maturation and reduced Ca(2+) oscillation persistence, frequency and number following IVF. Overall, these data show that CaV3.2 T-type channels have prev8iously unrecognized roles in supporting the meiotic-maturation-associated increase in ER Ca(2+) stores and mediating Ca(2+) influx required for the activation of development.

  14. Transcriptional repression of Caveolin-1 (CAV1) gene expression by GATA-6 in bladder smooth muscle hypertrophy in mice and human beings.

    PubMed

    Boopathi, Ettickan; Gomes, Cristiano Mendes; Goldfarb, Robert; John, Mary; Srinivasan, Vittala Gopal; Alanzi, Jaber; Malkowicz, S Bruce; Kathuria, Hasmeena; Zderic, Stephen A; Wein, Alan J; Chacko, Samuel

    2011-05-01

    Hypertrophy occurs in urinary bladder wall smooth muscle (BSM) in men with partial bladder outlet obstruction (PBOO) caused by benign prostatic hyperplasia (BPH) and in animal models of PBOO. Hypertrophied BSM from the rabbit model exhibits down-regulation of caveolin-1, a structural and functional protein of caveolae that function as signaling platforms to mediate interaction between receptor proteins and adaptor and effector molecules to regulate signal generation, amplification, and diversification. Caveolin-1 expression is diminished in PBOO-induced BSM hypertrophy in mice and in men with BPH. The proximal promoter of the human and mouse caveolin-1 (CAV1) gene was characterized, and it was observed that the transcription factor GATA-6 binds this promoter, causing reduced expression of caveolin-1. Furthermore, caveolin-1 expression levels inversely correlate with the abundance of GATA-6 in BSM hypertrophy in mice and human beings. Silencing of GATA6 gene expression up-regulates caveolin-1 expression, whereas overexpression of GATA-6 protein sustains the transcriptional repression of caveolin-1 in bladder smooth muscle cells. Together, these data suggest that GATA-6 acts as a transcriptional repressor of CAV1 gene expression in PBOO-induced BSM hypertrophy in men and mice. GATA-6-induced transcriptional repression represents a new regulatory mechanism of CAV1 gene expression in pathologic BSM, and may serve as a target for new therapy for BPH-induced bladder dysfunction in aging men.

  15. Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

    PubMed

    Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

    2014-04-01

    Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

  16. The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials.

    PubMed

    Savalli, Nicoletta; Pantazis, Antonios; Sigg, Daniel; Weiss, James N; Neely, Alan; Olcese, Riccardo

    2016-08-01

    Excitation-evoked calcium influx across cellular membranes is strictly controlled by voltage-gated calcium channels (CaV), which possess four distinct voltage-sensing domains (VSDs) that direct the opening of a central pore. The energetic interactions between the VSDs and the pore are critical for tuning the channel's voltage dependence. The accessory α2δ-1 subunit is known to facilitate CaV1.2 voltage-dependent activation, but the underlying mechanism is unknown. In this study, using voltage clamp fluorometry, we track the activation of the four individual VSDs in a human L-type CaV1.2 channel consisting of α1C and β3 subunits. We find that, without α2δ-1, the channel complex displays a right-shifted voltage dependence such that currents mainly develop at nonphysiological membrane potentials because of very weak VSD-pore interactions. The presence of α2δ-1 facilitates channel activation by increasing the voltage sensitivity (i.e., the effective charge) of VSDs I-III. Moreover, the α2δ-1 subunit also makes VSDs I-III more efficient at opening the channel by increasing the coupling energy between VSDs II and III and the pore, thus allowing Ca influx within the range of physiological membrane potentials. PMID:27481713

  17. Body mass scaling of frontal area in competitive cyclists not using aero-handlebars.

    PubMed

    Heil, Daniel P

    2002-10-01

    This study was designed to evaluate the scaling relationship between body mass ( m(b)) and projected frontal area ( A(P)) in competitive male cyclists using traditional drop-style handlebars. A group of 21 male cyclists [mean (SD) m(b) 74.4 (7.2) kg, height 1.82 (0.06) m, age 23.6 (5.1) years] had A(P) determined from photographs taken while seated on their own racing bicycles in four body positions: (1) stem position; (2) brake hoods position; (3) drops position; (4) traditional aero-position. For each position, A(P) for the body of the cyclist (Body A(P)), as well as the cyclist and his bicycle (Total A(P)), were determined. Body A(P) was significantly smaller than Total A(P) in all four positions by a nearly constant bicycle A(P) of 0.117-0.124 m(2). Using multiple log-linear regression analysis procedures, prediction equations were developed for both Body A(P) and Total A(P) (dependent variables) using a cluster of binary-coded variables to indicate body position and m(b) as independent variables ( n=88 observations). The regression analysis revealed that Body A(P) scaled with m(b) to the +0.720 power [95% confidence interval (CI): 0.585-0.855], which did not differ significantly from the +0.762 exponent reported previously for Body A(P) whilst using aero-handlebars. In contrast, Total A(P) scaled with m(b) to the +0.594 power (95% CI: 0.468-0.720) which was significantly lower than +0.762 exponent reported previously. The lower exponent for Total A(P) is explained by the nearly constant contribution of the bicycle A(P) to Total A(P) (mean bicycle A(P)=0.122 m(2)). These data help to explain the determinants of A(P) and aerodynamic drag in competitive male cyclists who use the traditional body postures.

  18. Adaptive-optic approach to mitigating aero-optic disturbances for a forced shear layer

    NASA Astrophysics Data System (ADS)

    Nightingale, Alice M.

    Non-uniform, variable-density fields, resulting from compressibility effects in turbulent flows, are the source of aero-optical distortions which cause significant reductions in optical system performance. As a laser beam transverses through an optically active medium, containing index-of-refraction variations, several optical phenomena occur including beam wander, image distortion, and beam defocus. When encountering a variation in the index field, light waves refract causing an otherwise planar wavefront of a laser beam to become aberrated, contributing to the adverse effects mentioned above. Adaptive-Optics (AO) is a technique used to correct for such spatially and temporally varying aberrations on an optical beam by applying a conjugate waveform correction prior to the beams transmission through the flow. Conventional AO systems are bandwidth limited by real-time processing issues and wavefront sensor limitations. Therefore, an alternative to the conventional AO approach has been proposed, developed and evaluated with the goal of overcoming such bandwidth limitations. The alternative AO system, presented throughout this document, consists of two main features; feed-forward flow control and a phase-locked-loop AO control strategy. Initially irregular, unpredictable large-scale structures within a shear layer are regularized using flow control. Subsequently, the resulting optical wavefront, and corresponding optical signal, emerging from the regularized flow becomes more periodic and predictable effectively reducing the bandwidth necessary to make real-time corrections. A phase-lock-loop controller is then used to perform real-time corrections. Wavefront corrections are estimated based upon the regularized flow, while two small aperture laser beams provide a non-intrusive means of acquiring amplitude and phase error measurements. The phase-lock-loop controller uses these signals as feedback to synchronize the deformable mirror's waveform to that of the shear

  19. Control of turbulent flow over an articulating turret for reduction of adverse aero-optic effects

    NASA Astrophysics Data System (ADS)

    Wallace, Ryan

    2011-12-01

    Force Research Laboratory wind tunnel at Wright-Patterson Air Force Base. Direct measurements of the aero-optic effects were taken via a Malley probe at a fixed pitch angle with and without suction control at a Mach number 0.3, and a corresponding Reynolds number of 2,000,000. Reduction of the aero-optic effects in this test demonstrated that suction control is a practical control input to reduce the near field wavefront abberations due to the turbulent flow over the aperture.

  20. Developmental pathway from leaves to galls induced by a sap-feeding insect on Schinus polygamus (Cav.) Cabrera (Anacardiaceae).

    PubMed

    Dias, Graciela G; Ferreira, Bruno G; Moreira, Gilson R P; Isaias, Rosy M S

    2013-03-01

    Galling sap-feeding insects are presumed to cause only minor changes in host plant tissues, because they usually do not require development of nutritive tissues for their own use. This premise was examined through comparison of the histometry, cytometry and anatomical development of non-galled leaves and galls of Calophya duvauae (Scott) (Hemiptera: Calophyidae) on Schinus polygamus (Cav.) Cabrera (Anacardiaceae). Cell fates changed from non-galled leaves to galls during the course of tissue differentiation. C. duvauae caused changes in dermal, ground, and vascular systems of the leaves of S. polygamus. Its feeding activity induced the homogenization of the parenchyma, and the neoformation of vascular bundles and trichomes. The histometric and cytometric data revealed compensatory effects of hyperplasia and cell hypertrophy in the epidermis, with hyperplasia predominating in the adaxial epidermis. There was a balance between these processes in the other tissues. Thus, we found major differences between the developmental pathways of non-galled leaves and galls. These changes were associated with phenotypic alterations related to shelter and appropriate microenvironmental conditions for the gall inducer. The nondifferentiation of a typical nutritive tissue in this case was compared to other non-phylogenetically related arthropod gall systems, and is suggested to result from convergence associated with the piercing feeding apparatus of the corresponding gall-inducer.

  1. Phosphorylation Sites in the Hook Domain of CaVβ Subunits Differentially Modulate CaV1.2 Channel Function

    PubMed Central

    Brunet, Sylvain; Emrick, Michelle A.; Sadilek, Martin; Scheuer, Todd; Catterall, William A.

    2015-01-01

    Regulation of L-type calcium current is critical for the development, function, and regulation of many cell types. CaV1.2 channels that conduct L-type calcium currents are regulated by many protein kinases, but the sites of action of these kinases remain unknown in most cases. We combined mass spectrometry (LC-MS/MS) and whole-cell patch clamp techniques in order to identify sites of phosphorylation of CaVβ subunits in vivo and test the impact of mutations of those sites on CaV1.2 channel function in vitro. Using the CaV1.1 channel purified from rabbit skeletal muscle as a substrate for phosphoproteomic analysis, we found that Ser193 and Thr205 in the HOOK domain of CaVβ1a subunits were both phosphorylated in vivo. Ser193 is located in a potential consensus sequence for casein kinase II, but it was not phosphorylated in vitro by that kinase. In contrast, Thr205 is located in a consensus sequence for cAMP-dependent phosphorylation, and it was robustly phosphorylated in vitro by PKA. These two sites are conserved in multiple CaVβ subunit isoforms, including the principal CaVβ subunit of cardiac CaV1.2 channels, CaVβ2b. In order to assess potential modulatory effects of phosphorylation at these sites separately from effects of phosphorylation of the α11.2 subunit, we inserted phosphomimetic or phosphoinhibitory mutations in CaVβ2b and analyzed their effects on CaV1.2 channel function in transfected nonmuscle cells. The phosphomimetic mutation CaVβ2bS152E decreased peak channel currents and shifted the voltage dependence of both activation and inactivation to more positive membrane potentials. The phosphoinhibitory mutation CaVβ2bS152A had opposite effects. There were no differences in peak CaV1.2 currents or voltage dependence between the phosphomimetic mutation CaVβ2bT164D and the phosphoinhibitory mutation CaVβ2bT164A. However, calcium-dependent inactivation was significantly increased for the phosphomimetic mutation CaVβ2bT164D. This effect was subunit

  2. PREFACE: 3rd International Conference on Geological, Geographical, Aerospace and Earth Science 2015 (AeroEarth 2015)

    NASA Astrophysics Data System (ADS)

    Gaol, F. L.

    2016-02-01

    The 3rd International Conferences on Geological, Geographical, Aerospaces and Earth Sciences 2015 (AeroEarth 2015), was held at The DoubleTree Hilton, Jakarta, Indonesia during 26 - 27 September 2015. The 1st AeoroEarth was held succefully in Jakarta in 2013. The success continued to The 2nd AeroEarth 2014 that was held in Kuta Bali, Indonesia. The publications were published by EES IOP in http://iopscience.iop.org/1755-1315/19/1 and http://iopscience.iop.org/1755-1315/23/1 respectively. The AeroEarth 2015 conference aims to bring together researchers, engineers and scientists from around the world. Through research and development, Earth's scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. The theme of AeroEarth 2015 is ''Earth and Aerospace Sciences : Challenges and Opportunities'' Earth provides resources and the exact conditions to make life possible. However, with the advent of technology and industrialization, the Earth's resources are being pushed to the brink of depletion. Non-sustainable industrial practices are not only endangering the supply of the Earth's natural resources, but are also putting burden on life itself by bringing about pollution and climate change. A major role of earth science scholars is to examine the delicate balance between the Earth's resources and the growing demands of industrialization. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting Conference Program as well as the invited and plenary speakers. This year, we received 78 papers and after rigorous review, 18 papers were accepted. The participants

  3. Advances in SiC/SiC Composites for Aero-Propulsion

    NASA Technical Reports Server (NTRS)

    DiCarlo, James A.

    2013-01-01

    In the last decade, considerable progress has been made in the development and application of ceramic matrix composites consisting of silicon carbide (SiC) based matrices reinforced by small-diameter continuous-length SiC-based fibers. For example, these SiC/SiC composites are now in the early stages of implementation into hot-section components of civil aero-propulsion gas turbine engines, where in comparison to current metallic components they offer multiple advantages due to their lighter weight and higher temperature structural capability. For current production-ready SiC/SiC, this temperature capability for long time structural applications is 1250 degC, which is better than 1100 degC for the best metallic superalloys. Foreseeing that even higher structural reliability and temperature capability would continue to increase the advantages of SiC/SiC composites, progress in recent years has also been made at NASA toward improving the properties of SiC/SiC composites by optimizing the various constituent materials and geometries within composite microstructures. The primary objective of this chapter is to detail this latter progress, both fundamentally and practically, with particular emphasis on recent advancements in the materials and processes for the fiber, fiber coating, fiber architecture, and matrix, and in the design methods for incorporating these constituents into SiC/SiC microstructures with improved thermo-structural performance.

  4. Near-field sound radiation of fan tones from an installed turbofan aero-engine.

    PubMed

    McAlpine, Alan; Gaffney, James; Kingan, Michael J

    2015-09-01

    The development of a distributed source model to predict fan tone noise levels of an installed turbofan aero-engine is reported. The key objective is to examine a canonical problem: how to predict the pressure field due to a distributed source located near an infinite, rigid cylinder. This canonical problem is a simple representation of an installed turbofan, where the distributed source is based on the pressure pattern generated by a spinning duct mode, and the rigid cylinder represents an aircraft fuselage. The radiation of fan tones can be modelled in terms of spinning modes. In this analysis, based on duct modes, theoretical expressions for the near-field acoustic pressures on the cylinder, or at the same locations without the cylinder, have been formulated. Simulations of the near-field acoustic pressures are compared against measurements obtained from a fan rig test. Also, the installation effect is quantified by calculating the difference in the sound pressure levels with and without the adjacent cylindrical fuselage. Results are shown for the blade passing frequency fan tone radiated at a supersonic fan operating condition. PMID:26428770

  5. DSMC aero-thermo-dynamic analysis of a sample-return capsule

    NASA Astrophysics Data System (ADS)

    Zuppardi, Gennaro; Savino, Raffaele; Boffa, Chiara; Carandente, Valerio

    2012-11-01

    A rarefied aero-thermo-dynamic analysis of a sample Earth Return Capsule during the high energy, high altitude re-entry path from an exploration mission is presented. The altitude interval 70-120 km is considered, where the capsule experiences different flow fields. In fact, the flow regime ranges from continuum low density to near free molecular flow and, even though the free stream velocity is almost constant (13 km/s) in the whole altitude interval, the Mach number changes from 44 to 32 and the Reynolds number, based on the capsule diameter, ranges from 4.92×104 to 9. The computations have been carried out using two direct simulation Monte Carlo codes: DS2V to compute local quantities such as heat flux, thermal and aerodynamic loads at zero angle of attack and DS3V to compute global aerodynamic coefficients in the range of the angle of attack 0-60 deg; The results verified that in this altitude interval the heat flux and the thermal load reasonably satisfy specific requirements for the thermal protection system and that the capsule is longitudinally stable up to an angle of attack of about 40 deg..

  6. Uncertainty of measurement for large product verification: evaluation of large aero gas turbine engine datums

    NASA Astrophysics Data System (ADS)

    Muelaner, J. E.; Wang, Z.; Keogh, P. S.; Brownell, J.; Fisher, D.

    2016-11-01

    Understanding the uncertainty of dimensional measurements for large products such as aircraft, spacecraft and wind turbines is fundamental to improving efficiency in these products. Much work has been done to ascertain the uncertainty associated with the main types of instruments used, based on laser tracking and photogrammetry, and the propagation of this uncertainty through networked measurements. Unfortunately this is not sufficient to understand the combined uncertainty of industrial measurements, which include secondary tooling and datum structures used to locate the coordinate frame. This paper presents for the first time a complete evaluation of the uncertainty of large scale industrial measurement processes. Generic analysis and design rules are proven through uncertainty evaluation and optimization for the measurement of a large aero gas turbine engine. This shows how the instrument uncertainty can be considered to be negligible. Before optimization the dominant source of uncertainty was the tooling design, after optimization the dominant source was thermal expansion of the engine; meaning that no further improvement can be made without measurement in a temperature controlled environment. These results will have a significant impact on the ability of aircraft and wind turbines to improve efficiency and therefore reduce carbon emissions, as well as the improved reliability of these products.

  7. [Aero-transport of a MDR-TB affected patient with bio-containment systems].

    PubMed

    Lastilla, M; Bisetti, R; Autore, A; Aragonese, F; Di Stefano, M; Sarlo, O

    2007-01-01

    The Italian Air Force medical service, in order to attend to its duty, has to deal with the search, rescue and aero-medical evacuation of the wounded and sick. Due to the increase of air transportation, the likelihood of contracting disease, such as haemorrhagic fevers has risen and it is necessary to know how to treat a patient abroad suffering from severe infectious disease without running any risk either for the medical personnel or for the air crew. The military sanitary service of the Air Force has been preparing for this purpose through a meticulous preparation in Italy and in the USA in order to satisfy these need and through the use of stretchers specifically designed to transport highly contagious patients: Aircraft Transit Isolators (ATIs) and Stretcher Transit Isolators (STIs). These particular medical tools are provided by filter HEPA and they are completely insulated in a PVC envelope. The former (ATI) is used to transport the patient by airplane, the latter is used for road travel. Last January 24th the first real mission was performed transporting a severe TBC-MDR (case) from Alghero to Milan. All went well and the patient left the hospital of Sondalo two months later. PMID:17598993

  8. KC-135 aero-optical turbulent boundary layer/shear layer experiment revisited

    NASA Technical Reports Server (NTRS)

    Craig, J.; Allen, C.

    1987-01-01

    The aero-optical effects associated with propagating a laser beam through both an aircraft turbulent boundary layer and artificially generated shear layers are examined. The data present comparisons from observed optical performance with those inferred from aerodynamic measurements of unsteady density and correlation lengths within the same random flow fields. Using optical instrumentation with tens of microsecond temporal resolution through a finite aperture, optical performance degradation was determined and contrasted with the infinite aperture time averaged aerodynamic measurement. In addition, the optical data were artificially clipped to compare to theoretical scaling calculations. Optical instrumentation consisted of a custom Q switched Nd:Yag double pulsed laser, and a holographic camera which recorded the random flow field in a double pass, double pulse mode. Aerodynamic parameters were measured using hot film anemometer probes and a five hole pressure probe. Each technique is described with its associated theoretical basis for comparison. The effects of finite aperture and spatial and temporal frequencies of the random flow are considered.

  9. An AeroCom Initial Assessment - Optical Properties in Aerosol Component Modules of Global Models

    SciTech Connect

    Kinne, Stefan; Schulz, M.; Textor, C.; Guibert, S.; Balkanski, Y.; Bauer, S.; Berntsen, T.; Berglen, T.; Boucher, Olivier; Chin, M.; Collins, W.; Dentener, F.; Diehl, T.; Easter, Richard C.; Feichter, H.; Fillmore, D.; Ghan, Steven J.; Ginoux, P.; Gong, S.; Grini, A.; Hendricks, J.; Herzog, M.; Horrowitz, L.; Isaksen, I.; Iversen, T.; Kirkevag, A.; Kloster, S.; Koch, D.; Kristjansson, J. E.; Krol, M.; Lauer, A.; Lamarque, J. F.; Lesins, G.; Liu, Xiaohong; Lohmann, U.; Montanaro, V.; Myhre, G.; Penner, Joyce E.; Pitari, G.; Reddy, S.; Seland, O.; Stier, P.; Takemura, T.; Tie, X.

    2006-05-29

    The AeroCom exercise diagnoses multi-component aerosol modules in global modeling. In an initial assessment global fields for mass and for mid-visible aerosol optical thickness (aot) were compared among aerosol component modules of 21 different global models. There is general agreement among models for the annual global mean of component combined aot. At 0.12 to 0.14, simulated aot values are at the lower end of global averages suggested by remote sensing from ground (AERONET ca 0.14) and space (MODIS-MISR composite ca 0.16). More detailed comparisons, however, reveal that larger differences in regional distribution and significant differences in compositional mixture have remained. Of particular concern is the large model diversity for contributions by dust and carbon, because it leads to significant uncertainty in aerosol absorption (aab). Since not only aot but also aab influence the aerosol impact on the radiative energy-balance, aerosol (direct) forcing uncertainty in modeling is larger than differences in aot might suggest. New diagnostic approaches are proposed to trace model differences in terms of aerosol processing and transport: These include the prescription of common input (e.g. amount, size and injection of aerosol component emissions) and the use of observational capabilities from ground (e.g. measurements networks) and space (e.g. correlations between retrieved aerosol and cloud properties).

  10. User's Guide for the Commercial Modular Aero-Propulsion System Simulation (C-MAPSS): Version 2

    NASA Technical Reports Server (NTRS)

    Liu, Yuan; Frederick, Dean K.; DeCastro, Jonathan A.; Litt, Jonathan S.; Chan, William W.

    2012-01-01

    This report is a Users Guide for version 2 of the NASA-developed Commercial Modular Aero-Propulsion System Simulation (C-MAPSS) software, which is a transient simulation of a large commercial turbofan engine (up to 90,000-lb thrust) with a realistic engine control system. The software supports easy access to health, control, and engine parameters through a graphical user interface (GUI). C-MAPSS v.2 has some enhancements over the original, including three actuators rather than one, the addition of actuator and sensor dynamics, and an improved controller, while retaining or improving on the convenience and user-friendliness of the original. C-MAPSS v.2 provides the user with a graphical turbofan engine simulation environment in which advanced algorithms can be implemented and tested. C-MAPSS can run user-specified transient simulations, and it can generate state-space linear models of the nonlinear engine model at an operating point. The code has a number of GUI screens that allow point-and-click operation, and have editable fields for user-specified input. The software includes an atmospheric model which allows simulation of engine operation at altitudes from sea level to 40,000 ft, Mach numbers from 0 to 0.90, and ambient temperatures from -60 to 103 F. The package also includes a power-management system that allows the engine to be operated over a wide range of thrust levels throughout the full range of flight conditions.

  11. Nonlocal sparse model with adaptive structural clustering for feature extraction of aero-engine bearings

    NASA Astrophysics Data System (ADS)

    Zhang, Han; Chen, Xuefeng; Du, Zhaohui; Li, Xiang; Yan, Ruqiang

    2016-04-01

    Fault information of aero-engine bearings presents two particular phenomena, i.e., waveform distortion and impulsive feature frequency band dispersion, which leads to a challenging problem for current techniques of bearing fault diagnosis. Moreover, although many progresses of sparse representation theory have been made in feature extraction of fault information, the theory also confronts inevitable performance degradation due to the fact that relatively weak fault information has not sufficiently prominent and sparse representations. Therefore, a novel nonlocal sparse model (coined NLSM) and its algorithm framework has been proposed in this paper, which goes beyond simple sparsity by introducing more intrinsic structures of feature information. This work adequately exploits the underlying prior information that feature information exhibits nonlocal self-similarity through clustering similar signal fragments and stacking them together into groups. Within this framework, the prior information is transformed into a regularization term and a sparse optimization problem, which could be solved through block coordinate descent method (BCD), is formulated. Additionally, the adaptive structural clustering sparse dictionary learning technique, which utilizes k-Nearest-Neighbor (kNN) clustering and principal component analysis (PCA) learning, is adopted to further enable sufficient sparsity of feature information. Moreover, the selection rule of regularization parameter and computational complexity are described in detail. The performance of the proposed framework is evaluated through numerical experiment and its superiority with respect to the state-of-the-art method in the field is demonstrated through the vibration signals of experimental rig of aircraft engine bearings.

  12. Rotary-Wing Relevant Compressor Aero Research and Technology Development Activities at Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Welch, Gerard E.; Hathaway, Michael D.; Skoch, Gary J.; Snyder, Christopher A.

    2012-01-01

    Technical challenges of compressors for future rotorcraft engines are driven by engine-level and component-level requirements. Cycle analyses are used to highlight the engine-level challenges for 3000, 7500, and 12000 SHP-class engines, which include retention of performance and stability margin at low corrected flows, and matching compressor type, axial-flow or centrifugal, to the low corrected flows and high temperatures in the aft stages. At the component level: power-to-weight and efficiency requirements impel designs with lower inherent aerodynamic stability margin; and, optimum engine overall pressure ratios lead to small blade heights and the associated challenges of scale, particularly increased clearance-to-span ratios. The technical challenges associated with the aerodynamics of low corrected flows and stability management impel the compressor aero research and development efforts reviewed herein. These activities include development of simple models for clearance sensitivities to improve cycle calculations, full-annulus, unsteady Navier-Stokes simulations used to elucidate stall, its inception, and the physics of stall control by discrete tip-injection, development of an actuator-duct-based model for rapid simulation of nonaxisymmetric flow fields (e.g., due inlet circumferential distortion), advanced centrifugal compressor stage development and experimentation, and application of stall control in a T700 engine.

  13. North Slope, Alaska: A case study of Sedimentary AeroMagnetics (SAM)

    SciTech Connect

    McConnell, T.J.

    1995-12-31

    Sedimentary AeroMagnetics (SAM) is the application of very high resolution aeromagnetic data to the exploration for hydrocarbons in the sedimentary section of a basin. Basically SAM provides very high spatial resolution of very low amplitude (<1 nT) anomalies originating from structures within the weakly magnetic sedimentary column. These sedimentary anomalies are superimposed upon the conventional high amplitude magnetic anomalies created by the crystalline basement. These low intensity anomalies generated from within the sediments are related to changes in the magnetic composition of the rocks. This can occur when rocks of differing magnetic susceptibilities are juxtaposed across a fault, or at a stratigraphic truncation. Fluid flow along faults, or at a stratigraphic truncation. Fluid flow along faults and fracture zones can also produce magnetization effects which can allow direct delineament of the fault or fracture zone. Stratigraphic units of weakly magnetic shale and sandstone also create subtle plateau effects in the magnetic amplitude maps. SAM data is a result of combining improvements in aeromagnetic data acquisition technology with new ideas on the design of the survey parameters. SAM surveys are generally flown at 200 - 800 meter line spacing with a terrain clearance of 60 - 150 meters. Data processing techniques are used which preserve the broad band frequency spectrum of the acquired data thereby allowing interpretation of the separate and distinct anomaly sources of the sedimentary column and of the crystalline basement.

  14. LES prediction and analysis of the aero-optical environment around a 3-D turret

    NASA Astrophysics Data System (ADS)

    Mathews, Edwin; Wang, Kan; Wang, Meng; Jumper, Eric

    2015-11-01

    Using wall-modeled large-eddy simulation, a Mach 0.4 flow over a hemisphere-on-cylinder turret at the experimental Reynolds number of ReD = 2 . 3 ×106 is simulated to study the aero-optical distortions caused by turbulent density fluctuations. The optical distortions are calculated at over 250 viewing angles during the simulation to thoroughly investigate the optical environment around the turret. Flow field and optical results show good comparisons with experimental measurements. A large database of three-dimensional velocity and density fields is generated for study of the connection between global flow dynamics and local optical distortions. Proper orthogonal decomposition and dynamic mode decomposition are applied to both the distorted wavefronts and the flow-field database. A method of reconstructing the optical wavefronts from the density field modes is investigated. Relations between prominent flow features and wavefront components including tip/tilt and higher-order effects will be discussed. Supported by HEL-JTO through AFOSR Grant FA9550-13-1-0001.

  15. [Aero-transport of a MDR-TB affected patient with bio-containment systems].

    PubMed

    Lastilla, M; Bisetti, R; Autore, A; Aragonese, F; Di Stefano, M; Sarlo, O

    2007-01-01

    The Italian Air Force medical service, in order to attend to its duty, has to deal with the search, rescue and aero-medical evacuation of the wounded and sick. Due to the increase of air transportation, the likelihood of contracting disease, such as haemorrhagic fevers has risen and it is necessary to know how to treat a patient abroad suffering from severe infectious disease without running any risk either for the medical personnel or for the air crew. The military sanitary service of the Air Force has been preparing for this purpose through a meticulous preparation in Italy and in the USA in order to satisfy these need and through the use of stretchers specifically designed to transport highly contagious patients: Aircraft Transit Isolators (ATIs) and Stretcher Transit Isolators (STIs). These particular medical tools are provided by filter HEPA and they are completely insulated in a PVC envelope. The former (ATI) is used to transport the patient by airplane, the latter is used for road travel. Last January 24th the first real mission was performed transporting a severe TBC-MDR (case) from Alghero to Milan. All went well and the patient left the hospital of Sondalo two months later.

  16. Vehicle barrier

    DOEpatents

    Hirsh, Robert A.

    1991-01-01

    A vehicle security barrier which can be conveniently placed across a gate opening as well as readily removed from the gate opening to allow for easy passage. The security barrier includes a barrier gate in the form of a cable/gate member in combination with laterally attached pipe sections fixed by way of the cable to the gate member and lateral, security fixed vertical pipe posts. The security barrier of the present invention provides for the use of cable restraints across gate openings to provide necessary security while at the same time allowing for quick opening and closing of the gate areas without compromising security.

  17. Survey of Aerothermodynamics Facilities Useful for the Design of Hypersonic Vehicles Using Air-Breathing Propulsion

    NASA Technical Reports Server (NTRS)

    Arnold, James O.; Deiwert, G. S.

    1997-01-01

    The dream of producing an air-breathing, hydrogen fueled, hypervelocity aircraft has been before the aerospace community for decades. However, such a craft has not yet been realized, even in an experimental form. Despite the simplicity and beauty of the concept, many formidable problems must be overcome to make this dream a reality. This paper summarizes the aero/aerothermodynamic issues that must be addressed to make the dream a reality and discusses how aerothermodynamics facilities and their modem companion, real-gas computational fluid dynamics (CFD), can help solve the problems blocking the way to realizing the dream. The approach of the paper is first to outline the concept of an air-breathing hypersonic vehicle and then discuss the nose-to-tail aerothermodynamics issues and special aerodynamic problems that arise with such a craft. Then the utility of aerothermodynamic facilities and companion CFD analysis is illustrated by reviewing results from recent United States publications wherein these problems have been addressed. Papers selected for the discussion have k e n chosen such that the review will serve to survey important U.S. aero/aerothermodynamic real gas and conventional wind tunnel facilities that are useful in the study of hypersonic, hydrogen propelled hypervelocity vehicles.

  18. Composting Phragmites australis Cav. plant material and compost effects on soil and tomato (Lycopersicon esculentum Mill.) growth.

    PubMed

    Toumpeli, Anna; Pavlatou-Ve, Athina K; Kostopoulou, Sofia K; Mamolos, Andreas P; Siomos, Anastasios S; Kalburtji, Kiriaki L

    2013-10-15

    Composting organic residues is a friendly to the environment alternative to producing fertilizer. This research was carried out to study the process of composting Phragmites australis Cav. plant material alone or with animal manure on a pilot-scale, to evaluate firstly the quality of the composts produced and secondly, using a pot experiment, the effects of their application on soil physicochemical characteristics and tomato plants development. For the compost production a randomized complete block design was used with five treatments (five compost types) and four replications. For the pot experiment, a completely randomized design was used with 17 treatments (plain soil, soil with synthetic fertilizer and the application of five compost types, at three rates each) and five replications. Compost N increased with composting time, while C/N ratio decreased significantly and by the end it ranged from 43.3 for CM to 22.6 for CY. Compost pH became almost neutral, ranging from 6.73 for CY to 7.21 for CM3Y3AM4 by the end. Compost combinations CY7AM3 and CM7AM3 had a more positive influence on the soil physicochemical characteristics than the others. Soil N, P, Ca and Mg concentrations and the reduction of clay dispersion were the highest when CM7AM3 compost was added. The macro-aggregate stability was the highest for CY7AM3, which also sustained plant growth. The latter compost combination improved most of the soil physicochemical characteristics and plant growth especially, when the application rate was 4% (w/w), which equals to 156 Mg ha(-1). PMID:23747375

  19. Composting Phragmites australis Cav. plant material and compost effects on soil and tomato (Lycopersicon esculentum Mill.) growth.

    PubMed

    Toumpeli, Anna; Pavlatou-Ve, Athina K; Kostopoulou, Sofia K; Mamolos, Andreas P; Siomos, Anastasios S; Kalburtji, Kiriaki L

    2013-10-15

    Composting organic residues is a friendly to the environment alternative to producing fertilizer. This research was carried out to study the process of composting Phragmites australis Cav. plant material alone or with animal manure on a pilot-scale, to evaluate firstly the quality of the composts produced and secondly, using a pot experiment, the effects of their application on soil physicochemical characteristics and tomato plants development. For the compost production a randomized complete block design was used with five treatments (five compost types) and four replications. For the pot experiment, a completely randomized design was used with 17 treatments (plain soil, soil with synthetic fertilizer and the application of five compost types, at three rates each) and five replications. Compost N increased with composting time, while C/N ratio decreased significantly and by the end it ranged from 43.3 for CM to 22.6 for CY. Compost pH became almost neutral, ranging from 6.73 for CY to 7.21 for CM3Y3AM4 by the end. Compost combinations CY7AM3 and CM7AM3 had a more positive influence on the soil physicochemical characteristics than the others. Soil N, P, Ca and Mg concentrations and the reduction of clay dispersion were the highest when CM7AM3 compost was added. The macro-aggregate stability was the highest for CY7AM3, which also sustained plant growth. The latter compost combination improved most of the soil physicochemical characteristics and plant growth especially, when the application rate was 4% (w/w), which equals to 156 Mg ha(-1).

  20. Forestry Vehicle

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Power Pack II provides an economical means of moving a power source into remote roadless forest areas. It was developed by Prof. Miles and his associates, working in cooperation with the University of California's Department of Forestry. The team combined its own design of an all-terrain vehicle with a suspension system based on the NASA load equalization technology. Result is an intermediate-sized unit which carries a power source and the powered tools to perform a variety of forest management tasks which cannot be done economically with current equipment. Power Pack II can traverse very rough terrain and climb a 60 degree slope; any one of the wheels can move easily over an obstacle larger than itself. Work is being done on a more advanced Power Pack III.

  1. Analysis and Quantification of the Diversities of Aerosol Life Cycles within AeroCom

    SciTech Connect

    Textor, C.; Schulz, M.; Guibert, S.; Kinne, Stefan; Balkanski, Y.; Bauer, S.; Berntsen, T.; Berglen, T.; Boucher, Olivier; Chin, M.; Dentener, F.; Diehl, T.; Easter, Richard C.; Feichter, H.; Fillmore, D.; Ghan, Steven J.; Ginoux, P.; Gong, S.; Grini, A.; Hendricks, J.; Horrowitz, L.; Huang, P.; Isaksen, I.; Iversen, T.; Kloster, S.; Koch, D.; Kirkevag, A.; Kristjansson, J. E.; Krol, M.; Lauer, A.; Lamarque, J. F.; Liu, Xiaohong; Montanaro, V.; Myhre, G.; Penner, Joyce E.; Pitari, G.; Reddy, S.; Seland, O.; Stier, P.; Takemura, T.; Tie, X.

    2006-05-29

    Simulation results of global aerosol models have been assembled in the framework of the AeroCom intercomparison exercise. In this paper, we analyze the life cycles of dust, sea salt, sulfate, black carbon and particulate organic matter as simulated by sixteen global aerosol models. The diversities among the models for the sources and sinks, burdens, particle sizes, water uptakes, and spatial dispersals have been established. The AeroCom all-models-average emissions are dominated by the mass of sea salt (SS), followed by dust (DU), sulfate (SO4), particulate organic matter (POM), and finally black carbon (BC). Interactive parameterizations of the emissions and contrasting particles sizes of SS and DU lead generally to higher diversities of these species, and for total aerosol, which they dominate in mass. The lower diversity of the emissions of the fine aerosols, BC, POM, and SO4, is due to the use of similar emission inventories, and does therefore not necessarily indicate a better understanding of their sources. The diversity of SO4-sources is mainly caused by the disagreement on depositional loss of precursor gases and on chemical production. The diversities of the emissions are passed on to the burdens, but the latter are also strongly affected by the model-specific treatments of transport and aerosol processes. The burdens of dry mass decrease along DU, SS, SO4, POM, and BC. The all-models-average residence time was the shortest for sea salt with about half a day, followed by SO4 and DU with four days, and POM and BC with six and seven days, respectively. The wet deposition rate is controlled by the solubility and increases from DU, BC, POM to SO4 and SS. It is the dominant sink for SO4, BC, and POM, and contributes about one third to the total removal rate coefficients of SS and DU species. For SS and DU we find high diversities for the removal rate coefficients and deposition pathways. Models do neither agree on the split between wet and dry deposition, nor

  2. Presynaptic CaV2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held

    PubMed Central

    Inchauspe, Carlota González; Urbano, Francisco J.; Di Guilmi, Mariano N.; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Forsythe, Ian D.

    2012-01-01

    CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type 1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harboring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the medial nucleus of the trapezoid body (MNTB). Although synaptic transmission seems unaffected by low-frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+ concentrations (<1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared with wild type (WT), meaning significant differences in the nonlinear calcium dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+ channels) via Cav2.1-triggered exocytosis, R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short-term depression of EPSCs that recovered significantly faster in R192Q KI mice than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles. PMID:22956801

  3. Laser Fine-Adjustment Thruster For Space Vehicles

    SciTech Connect

    Rezunkov, Yu. A.; Egorov, M. S.; Repina, E. V.; Safronov, A. L.; Rebrov, S. G.

    2010-05-06

    To the present time, a few laser propulsion engine devices have been developed by using dominant mechanisms of laser propulsion. Generally these mechanisms are laser ablation, laser breakdown of gases, and laser detonation waves that are induced due to extraction of the internal energy of polymer propellants. In the paper, we consider the Aero-Space Laser Propulsion Engine (ASLPE) developed earlier, in which all of these mechanisms are realized via interaction of laser radiation with polymers both in continuous wave (CW) and in repetitively pulsed modes of laser operation. The ASLPE is considered to be exploited as a unit of a laser propulsion device being arranged onboard space vehicles moving around the Earth or in interplanetary missions and intended to correct the vehicles orbits. To produce a thrust, a power of the solar pumped lasers designed to the present time is considered in the paper. The problem of increasing the efficiency of the laser propulsion device is analyzed as applied to space missions of vehicles by optimizing the laser propulsion propellant composition.

  4. ESA Intermediate Experimental Vehicle. Independent Aerothermodynamic Characterization And Aerodatabase Development

    NASA Astrophysics Data System (ADS)

    Rufolo, Giuseppe C.; Di Benedetto, Sara; Walpot, Louis; Roncioni, Pietro; Marini, Marco

    2011-05-01

    In the frame of the Intermediate eXperimental Vehicle (IXV) project, the European Space Agency (ESA) is coordinating a series of technical assistance activities aimed at verifying and supporting the IXV industrial design and development process. The technical assistance is operated with the support of the Italian Space Agency (ASI), by means of the Italian Aerospace Research Center (CIRA), and the European Space Research and Technology Centre (ESTEC) under the super visioning and coordination of ESA IXV team. One of the purposes of the activity is to develop an independent capability for the assessment and verification of the industrial results with respect to the aerothermodynamic characterization of the IXV vehicle. To this aim CIRA is developing and independent AeroThermodynamics DataBase (ATDB), intended as a tool generating in output the time histories of local quantities (heat flux, pressure, skin friction) for each point of the IXV vehicle and for each trajectory (in a pre-defined envelope), together with an uncertainties model. The reference Computational Fluid Dynamics (CFD) solutions needed for the development of the tool have been provided by ESA-ESTEC (with the CFD code LORE) and CIRA (with the CFD code H3NS).

  5. Aeronautical-Satellite-Assisted Process Being Developed for Information Exchange Through Network Technologies (Aero-SAPIENT)

    NASA Technical Reports Server (NTRS)

    Zernic, Michael J.

    2001-01-01

    Communications technologies are being developed to address safety issues during aviation travel. Some of these technologies enable the aircraft to be in constant bidirectional communications with necessary systems, people, and other aircraft that are not currently in place today. Networking technologies, wireless datalinks, and advanced avionics techniques are areas of particular importance that the NASA Glenn Research Center has contributed. Glenn, in conjunction with the NASA Ames Research Center, NASA Dryden Flight Research Center, and NASA Langley Research Center, is investigating methods and applications that would utilize these communications technologies. In mid-June 2000, the flight readiness of the network and communications technologies were demonstrated via a simulated aircraft. A van simulating an aircraft was equipped with advanced phased-array antennas (Advanced Communications/Air Traffic Management (AC/ATM) Advanced Air Transportation Technologies (AATT) project) that used commercial Ku-band satellite communications to connect Glenn, Dryden, and Ames in a combined system ground test. This test simulated air-ground bidirectional transport of real-time digital audio, text, and video data via a hybrid network configuration that demonstrated the flight readiness of the network and communications technologies. Specifically, a Controller Pilot Data Link Communications application was used with other applications to demonstrate a multiprotocol capability via Internet-protocol encapsulated ATN (Aeronautical Telecommunications Network) data packets. The significance of this combined ground test is its contribution to the Aero Information Technology Base Program Level I milestone (Software Technology investment area) of a real-time data link for the National Airspace System. The objective of this milestone was to address multiprotocol technology applicable for real-time data links between aircraft, a satellite, and the ground as well as the ability to

  6. A Neural Network Aero Design System for Advanced Turbo-Engines

    NASA Technical Reports Server (NTRS)

    Sanz, Jose M.

    1999-01-01

    An inverse design method calculates the blade shape that produces a prescribed input pressure distribution. By controlling this input pressure distribution the aerodynamic design objectives can easily be met. Because of the intrinsic relationship between pressure distribution and airfoil physical properties, a Neural Network can be trained to choose the optimal pressure distribution that would meet a set of physical requirements. Neural network systems have been attempted in the context of direct design methods. From properties ascribed to a set of blades the neural network is trained to infer the properties of an 'interpolated' blade shape. The problem is that, especially in transonic regimes where we deal with intrinsically non linear and ill posed problems, small perturbations of the blade shape can produce very large variations of the flow parameters. It is very unlikely that, under these circumstances, a neural network will be able to find the proper solution. The unique situation in the present method is that the neural network can be trained to extract the required input pressure distribution from a database of pressure distributions while the inverse method will still compute the exact blade shape that corresponds to this 'interpolated' input pressure distribution. In other words, the interpolation process is transferred to a smoother problem, namely, finding what pressure distribution would produce the required flow conditions and, once this is done, the inverse method will compute the exact solution for this problem. The use of neural network is, in this context, highly related to the use of proper optimization techniques. The optimization is used essentially as an automation procedure to force the input pressure distributions to achieve the required aero and structural design parameters. A multilayered feed forward network with back-propagation is used to train the system for pattern association and classification.

  7. Mixing Process in Ejector Nozzles Studied at Lewis' Aero-Acoustic Propulsion Laboratory

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The NASA Lewis Research Center has been studying mixing processes in ejector nozzles for its High Speed Research (HSR) Program. This work is directed at finding ways to minimize the noise of a future supersonic airliner. Much of the noise such an airplane would generate would come from the nozzle, where a hot, high-speed jet exits the engine. Several different nozzle configurations were used to produce nozzle systems with different acoustical and aerodynamic characteristics. The acoustical properties were measured by an array of microphones in an anechoic chamber, and the aerodynamics were measured by traditional pressure and temperature instruments as well as by Laser Doppler Velocimetry (LDV), a technique for visualizing the airflow pattern without disturbing it. These measurements were put together and compared for different configurations to examine the relationships between mixing and noise generation. The mixer-ejector nozzle with the installed flow-visualization windows (foreground), the optical equipment and the supporting structure for the Laser Doppler Velocimetry flow visualization (midfield), and the sound-absorbing wedges used to create an anechoic environment for acoustic testing (background) is shown. The High Speed Research Program is a NASA-funded effort, in cooperation with the U.S. aerospace industry, to develop enabling technologies for a future supersonic airliner. One of the technological barriers being addressed is noise generated during near-airport operation. The mixer-ejector nozzle concept is being examined as a way to reduce jet noise while maintaining thrust. Ambient air is mixed with the high-velocity engine exhaust to reduce the jet velocity and hence the noise generated by the jet. The model was designed and built by Pratt & Whitney under NASA contract. The test, completed in June 1995, was conducted in Lewis' Aero-Acoustic Propulsion Laboratory.

  8. Fungal aero-decontamination efficacy of mobile air-treatment systems.

    PubMed

    Fréalle, Emilie; Lestrez, Christophe; Skierlak, Tiphaine; Melboucy, Djallil; Guery, Benoît; Durand-Joly, Isabelle; Delhaes, Laurence; Loukili, Noureddine

    2011-11-01

    Immunosuppressed patients are at high risk of acquiring airborne fungal infections, mainly caused by Aspergillus species. Although HEPA filters are recommended to prevent environmental exposure, mobile air-treatment units can be an alternative. However, many different models of mobile units are available but there are few data on their fungal aero-decontamination efficacy and usefulness in the prevention of Aspergillus infections. Thus, we developed a challenge test, based on the aerosolization of 10(6) Aspergillus niger conidia, in order to compare the particle and fungal decontamination efficacy of the following four mobile air-treatment systems; Plasmair T2006, Mobil'Air 1200 (MA1200), Mobil'Air 600 (MA600) combined with Compact AirPur Mobile C250 (C250), and the prototype unit Compact AirPur Mobile 1800 (C1800). The use of all these air-treatment systems was able to significantly decrease the concentration of particles or fungal viable conidia. ISO7 was the maximum particle class reached within 20 min with the Plasmair T2006 and MA1200, 1 h by the combined MA600/C250, and 1 h and 30 min with the C1800. After 2 h, fungal counts were significantly lower with Plasmair T2006, MA1200 and the combined MA600/C250 (2.2 ± 1.9 to 5.0 ± 3.7 CFU/m(3)) than achieved with the C1800 (23.8 ± 12.8 CFU/m(3); P ≤ 6.0E-3). All the air-treatment systems were able to decrease aerial particle and fungal counts, but their efficacy was variable, depending on the units' air-treatment modalities and rates of air volume that was processed. This comparative study could be helpful in making an informed choice of mobile units, and in improving the prevention of air-transmitted fungal infections in non-protected areas.

  9. Traversing Microphone Track Installed in NASA Lewis' Aero-Acoustic Propulsion Laboratory Dome

    NASA Technical Reports Server (NTRS)

    Bauman, Steven W.; Perusek, Gail P.

    1999-01-01

    The Aero-Acoustic Propulsion Laboratory is an acoustically treated, 65-ft-tall dome located at the NASA Lewis Research Center. Inside this laboratory is the Nozzle Acoustic Test Rig (NATR), which is used in support of Advanced Subsonics Technology (AST) and High Speed Research (HSR) to test engine exhaust nozzles for thrust and acoustic performance under simulated takeoff conditions. Acoustic measurements had been gathered by a far-field array of microphones located along the dome wall and 10-ft above the floor. Recently, it became desirable to collect acoustic data for engine certifications (as specified by the Federal Aviation Administration (FAA)) that would simulate the noise of an aircraft taking off as heard from an offset ground location. Since nozzles for the High-Speed Civil Transport have straight sides that cause their noise signature to vary radially, an additional plane of acoustic measurement was required. Desired was an arched array of 24 microphones, equally spaced from the nozzle and each other, in a 25 off-vertical plane. The various research requirements made this a challenging task. The microphones needed to be aimed at the nozzle accurately and held firmly in place during testing, but it was also essential that they be easily and routinely lowered to the floor for calibration and servicing. Once serviced, the microphones would have to be returned to their previous location near the ceiling. In addition, there could be no structure could between the microphones and the nozzle, and any structure near the microphones would have to be designed to minimize noise reflections. After many concepts were considered, a single arched truss structure was selected that would be permanently affixed to the dome ceiling and to one end of the dome floor.

  10. Novel Framework for Reduced Order Modeling of Aero-engine Components

    NASA Astrophysics Data System (ADS)

    Safi, Ali

    The present study focuses on the popular dynamic reduction methods used in design of complex assemblies (millions of Degrees of Freedom) where numerous iterations are involved to achieve the final design. Aerospace manufacturers such as Rolls Royce and Pratt & Whitney are actively seeking techniques that reduce computational time while maintaining accuracy of the models. This involves modal analysis of components with complex geometries to determine the dynamic behavior due to non-linearity and complicated loading conditions. In such a case the sub-structuring and dynamic reduction techniques prove to be an efficient tool to reduce design cycle time. The components whose designs are finalized can be dynamically reduced to mass and stiffness matrices at the boundary nodes in the assembly. These matrices conserve the dynamics of the component in the assembly, and thus avoid repeated calculations during the analysis runs for design modification of other components. This thesis presents a novel framework in terms of modeling and meshing of any complex structure, in this case an aero-engine casing. In this study the affect of meshing techniques on the run time are highlighted. The modal analysis is carried out using an extremely fine mesh to ensure all minor details in the structure are captured correctly in the Finite Element (FE) model. This is used as the reference model, to compare against the results of the reduced model. The study also shows the conditions/criteria under which dynamic reduction can be implemented effectively, proving the accuracy of Criag-Bampton (C.B.) method and limitations of Static Condensation. The study highlights the longer runtime needed to produce the reduced matrices of components compared to the overall runtime of the complete unreduced model. Although once the components are reduced, the assembly run is significantly. Hence the decision to use Component Mode Synthesis (CMS) is to be taken judiciously considering the number of

  11. Trichoderma matsushimae and T. aeroaquaticum: two aero-aquatic species with Pseudaegerita-like propagules.

    PubMed

    Yamaguchi, Kaoru; Tsurumi, Yasuhisa; Suzuki, Rieko; Chuaseeharonnachai, Charuwan; Sri-Indrasutdhi, Veera; Boonyuen, Nattawut; Okane, Izumi; Suzuki, Ken-ichiro; Nakagiri, Akira

    2012-01-01

    Four isolates tentatively identified as Pseudaegerita matsushimae on the basis of the morphology of bulbil-like propagules were collected from substrates submerged in water in Thailand and Japan. In culture studies the two Thai isolates were found to produce phialoconidia on conidiogenous cells and phialoconidiophores whose morphology was similar to that of Trichoderma. Phylogenetic analysis based on D1/D2 regions of LSU rDNA sequences showed that the four isolates were nested in Hypocrea/Trichoderma (Hypocreales) while P. corticalis, the type species of Pseudaegerita, belongs to Hyaloscypha (Helotiales). Preliminary analysis by ISTH Web tools based on 5.8S-ITS rDNA and phylogenetic analysis based on rpb2 and tef1-int4 genes showed that the isolates have specific sequences of Trichoderma (anchors 1-5) and belong to the Hamatum clade but they grouped apart from any known species of Trichoderma. The sequences of the tef1-int4 gene, which were amplified from the authentic specimen of P. matsushimae (IMI 266915), also showed that it belongs to the Hamatum clade closely clustering with T. yunnanense but separate from our four isolates. The morphology of P. matsushimae (IMI 266915), especially the sizes of phialides and phialoconidia, were different from T. yunnanense. Thus, we conclude that IMI 266915 and our isolates are to be assigned to two different species in the Hamatum clade of Trichoderma, although both species have similar morphology of bulbils and phialoconidia. Morphology and molecular data revealed that P. matsushimae should be assigned to the genus Trichoderma as T. matsushimae and the Thai and Japanese isolates are placed in T. aeroaquaticum sp. nov. This finding supports the interpretation that aero-aquatic fungi have evolved from terrestrial fungi. We assume that these fungi probably were derived from typically soil-inhabiting species of Trichoderma; an adaptation to aquatic environments is shown by formation of bulbil-like propagules floating on water.

  12. Dynamics of aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Schmidt, David K.

    1991-01-01

    Papers on the following subjects are presented: (1) multivariable flight control synthesis and literal robustness analysis for an aeroelastic vehicles; (2) numerical and literal aeroelastic-vehicle-model reduction for feedback control synthesis; and (3) dynamics of aerospace vehicles.

  13. Host Model Uncertainties in Aerosol Radiative Forcing Estimates: Results from the AeroCom Prescribed Intercomparison Study

    SciTech Connect

    Stier, Phillip; Schutgens, Nick A.; Bellouin, N.; Bian, Huisheng; Boucher, Olivier; Chin, Mian; Ghan, Steven J.; Huneeus, N.; Kinne, Stefan; Lin, G.; Ma, Xiaoyan; Myhre, G.; Penner, J. E.; Randles, Cynthia; Samset, B. H.; Schulz, M.; Takemura, T.; Yu, Fangqun; Yu, Hongbin; Zhou, Cheng

    2013-03-20

    Simulated multi-model "diversity" in aerosol direct radiative forcing estimates is often perceived as mea- sure of aerosol uncertainty. However, current models used for aerosol radiative forcing calculations vary considerably in model components relevant for forcing calculations and the associated "host-model uncertainties" are generally convoluted with the actual aerosol uncertainty. In this AeroCom Prescribed intercomparison study we systematically isolate and quantify host model uncertainties on aerosol forcing experiments through prescription of identical aerosol radiative properties in nine participating models. Even with prescribed aerosol radiative properties,simulated clear-sky and all-sky aerosol radiative forcings show significant diversity. For a purely scattering case with globally constant optical depth of 0.2, the global-mean all-sky top-of-atmosphere radiative forcing is -4.51 Wm-2 and the inter-model standard deviation is 0.70 Wm-2, corresponding to a relative standard deviation of 15%. For a case with partially absorbing aerosol with an aerosol optical depth of 0.2 and single scattering albedo of 0.8, the forcing changes to 1.26 Wm-2, and the standard deviation increases to 1.21 W-2, corresponding to a significant relative standard deviation of 96%. However, the top-of-atmosphere forcing variability owing to absorption is low, with relative standard deviations of 9% clear-sky and 12% all-sky. Scaling the forcing standard deviation for a purely scattering case to match the sulfate radiative in the AeroCom Direct Effect experiment, demonstrates that host model uncertain- ties could explain about half of the overall sulfate forcing diversity of 0.13 Wm-2 in the AeroCom Direct Radiative Effect experiment. Host model errors in aerosol radiative forcing are largest in regions of uncertain host model components, such as stratocumulus cloud decks or areas with poorly constrained.

  14. AeroCom INSITU Project: Comparison of Aerosol Optical Properties from In-situ Surface Measurements and Model Simulations

    NASA Astrophysics Data System (ADS)

    Schmeisser, L.; Andrews, E.; Schulz, M.; Fiebig, M.; Zhang, K.; Randles, C. A.; Myhre, G.; Chin, M.; Stier, P.; Takemura, T.; Krol, M. C.; Bian, H.; Skeie, R. B.; da Silva, A. M., Jr.; Kokkola, H.; Laakso, A.; Ghan, S.; Easter, R. C.

    2015-12-01

    AeroCom, an open international collaboration of scientists seeking to improve global aerosol models, recently initiated a project comparing model output to in-situ, surface-based measurements of aerosol optical properties. The model/measurement comparison project, called INSITU, aims to evaluate the performance of a suite of AeroCom aerosol models with site-specific observational data in order to inform iterative improvements to model aerosol modules. Surface in-situ data have the unique property of being traceable to physical standards, which is a big asset in accomplishing the overarching goal of bettering the accuracy of aerosol processes and predicative capability of global climate models. The INSITU project looks at how well models reproduce aerosol climatologies on a variety of time scales, aerosol characteristics and behaviors (e.g., aerosol persistence and the systematic relationships between aerosol optical properties), and aerosol trends. Though INSITU is a multi-year endeavor, preliminary phases of the analysis, using GOCART and other models participating in this AeroCom project, show substantial model biases in absorption and scattering coefficients compared to surface measurements, though the sign and magnitude of the bias varies with location and optical property. Spatial patterns in the biases highlight model weaknesses, e.g., the inability of models to properly simulate aerosol characteristics at sites with complex topography (see Figure 1). Additionally, differences in modeled and measured systematic variability of aerosol optical properties suggest that some models are not accurately capturing specific aerosol co-dependencies, for example, the tendency of in-situ surface single scattering albedo to decrease with decreasing aerosol extinction coefficient. This study elucidates specific problems with current aerosol models and suggests additional model runs and perturbations that could further evaluate the discrepancies between measured and modeled

  15. N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1+/- mice.

    PubMed

    Duan, J-H; Hodgdon, K E; Hingtgen, C M; Nicol, G D

    2014-06-13

    Major aspects of neuronal function are regulated by Ca(2+) including neurotransmitter release, excitability, developmental plasticity, and gene expression. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1+/-) exhibited both greater excitability and evoked release of neuropeptides compared to wildtype mice. Furthermore, augmented voltage-dependent sodium currents but not potassium currents contribute to the enhanced excitability. To determine the mechanisms giving rise to the enhanced release of substance P and calcitonin gene-related peptide in the Nf1+/- sensory neurons, the potential differences in the total voltage-dependent calcium current (ICa) as well as the contributions of individual Ca(2+) channel subtypes were assessed. Whole-cell patch-clamp recordings from small-diameter capsaicin-sensitive sensory neurons demonstrated that the average peak ICa densities were not different between the two genotypes. However, by using selective blockers of channel subtypes, the current density of N-type (Cav2.2) ICa was significantly larger in Nf1+/- neurons compared to wildtype neurons. In contrast, there were no significant differences in L-, P/Q- and R-type currents between the two genotypes. Quantitative real-time polymerase chain reaction measurements made from the isolated but intact dorsal root ganglia indicated that N-type (Cav2.2) and P/Q-type (Cav2.1) Ca(2+) channels exhibited the highest mRNA expression levels although there were no significant differences in the levels of mRNA expression between the genotypes. These results suggest that the augmented N-type (Cav2.2) ICa observed in the Nf1+/- sensory neurons does not result from genomic differences but may reflect post-translational or some other non-genomic modifications. Thus, our results demonstrate that sensory neurons from Nf1+/- mice, exhibit increased N-type ICa and likely account for the increased release of substance P and

  16. γ-Aminobutyric acid type B (GABAB) receptor expression is needed for inhibition of N-type (Cav2.2) calcium channels by analgesic α-conotoxins.

    PubMed

    Cuny, Hartmut; de Faoite, Andrew; Huynh, Thuan G; Yasuda, Takahiro; Berecki, Géza; Adams, David J

    2012-07-01

    α-Conotoxins Vc1.1 and RgIA are small peptides isolated from the venom of marine cone snails. They have effective anti-nociceptive actions in rat models of neuropathic pain. Pharmacological studies in rodent dorsal root ganglion (DRG) show their analgesic effect is mediated by inhibition of N-type (Ca(v)2.2) calcium channels via a pathway involving γ-aminobutyric acid type B (GABA(B)) receptor. However, there is no direct demonstration that functional GABA(B) receptors are needed for inhibition of the Ca(v)2.2 channel by analgesic α-conotoxins. This study examined the effect of the GABA(B) agonist baclofen and α-conotoxins Vc1.1 and RgIA on calcium channel currents after transient knockdown of the GABA(B) receptor using RNA interference. Isolated rat DRG neurons were transfected with small interfering RNAs (siRNA) targeting GABA(B) subunits R1 and R2. Efficient knockdown of GABA(B) receptor expression at mRNA and protein levels was confirmed by quantitative real time PCR (qRT-PCR) and immunocytochemical analysis, respectively. Whole-cell patch clamp recordings conducted 2-4 days after transfection showed that inhibition of N-type calcium channels in response to baclofen, Vc1.1 and RgIA was significantly reduced in GABA(B) receptor knockdown DRG neurons. In contrast, neurons transfected with a scrambled nontargeting siRNA were indistinguishable from untransfected neurons. In the HEK 293 cell heterologous expression system, Vc1.1 and RgIA inhibition of Ca(v)2.2 channels needed functional expression of both human GABA(B) receptor subunits. Together, these results confirm that GABA(B) receptors must be activated for the modulation of N-type (Ca(v)2.2) calcium channels by analgesic α-conotoxins Vc1.1 and RgIA.

  17. Exome Sequencing of Phenotypic Extremes Identifies CAV2 and TMC6 as Interacting Modifiers of Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis

    PubMed Central

    Emond, Mary J.; Louie, Tin; Emerson, Julia; Chong, Jessica X.; Mathias, Rasika A.; Knowles, Michael R.; Rieder, Mark J.; Tabor, Holly K.; Nickerson, Debbie A.; Barnes, Kathleen C.; GO, Lung; Gibson, Ronald L.; Bamshad, Michael J.

    2015-01-01

    Discovery of rare or low frequency variants in exome or genome data that are associated with complex traits often will require use of very large sample sizes to achieve adequate statistical power. For a fixed sample size, sequencing of individuals sampled from the tails of a phenotype distribution (i.e., extreme phenotypes design) maximizes power and this approach was recently validated empirically with the discovery of variants in DCTN4 that influence the natural history of P. aeruginosa airway infection in persons with cystic fibrosis (CF; MIM219700). The increasing availability of large exome/genome sequence datasets that serve as proxies for population-based controls affords the opportunity to test an alternative, potentially more powerful and generalizable strategy, in which the frequency of rare variants in a single extreme phenotypic group is compared to a control group (i.e., extreme phenotype vs. control population design). As proof-of-principle, we applied this approach to search for variants associated with risk for age-of-onset of chronic P. aeruginosa airway infection among individuals with CF and identified variants in CAV2 and TMC6 that were significantly associated with group status. These results were validated using a large, prospective, longitudinal CF cohort and confirmed a significant association of a variant in CAV2 with increased age-of-onset of P. aeruginosa airway infection (hazard ratio = 0.48, 95% CI=[0.32, 0.88]) and variants in TMC6 with diminished age-of-onset of P. aeruginosa airway infection (HR = 5.4, 95% CI=[2.2, 13.5]) A strong interaction between CAV2 and TMC6 variants was observed (HR=12.1, 95% CI=[3.8, 39]) for children with the deleterious TMC6 variant and without the CAV2 protective variant. Neither gene showed a significant association using an extreme phenotypes design, and conditions for which the power of an extreme phenotype vs. control population design was greater than that for the extreme phenotypes design were

  18. Small wind turbine performance evaluation using field test data and a coupled aero-electro-mechanical model

    NASA Astrophysics Data System (ADS)

    Wallace, Brian D.

    A series of field tests and theoretical analyses were performed on various wind turbine rotor designs at two Penn State residential-scale wind-electric facilities. This work involved the prediction and experimental measurement of the electrical and aerodynamic performance of three wind turbines; a 3 kW rated Whisper 175, 2.4 kW rated Skystream 3.7, and the Penn State designed Carolus wind turbine. Both the Skystream and Whisper 175 wind turbines are OEM blades which were originally installed at the facilities. The Carolus rotor is a carbon-fiber composite 2-bladed machine, designed and assembled at Penn State, with the intent of replacing the Whisper 175 rotor at the off-grid system. Rotor aerodynamic performance is modeled using WT_Perf, a National Renewable Energy Laboratory developed Blade Element Momentum theory based performance prediction code. Steady-state power curves are predicted by coupling experimentally determined electrical characteristics with the aerodynamic performance of the rotor simulated with WT_Perf. A dynamometer test stand is used to establish the electromechanical efficiencies of the wind-electric system generator. Through the coupling of WT_Perf and dynamometer test results, an aero-electro-mechanical analysis procedure is developed and provides accurate predictions of wind system performance. The analysis of three different wind turbines gives a comprehensive assessment of the capability of the field test facilities and the accuracy of aero-electro-mechanical analysis procedures. Results from this study show that the Carolus and Whisper 175 rotors are running at higher tip-speed ratios than are optimum for power production. The aero-electro-mechanical analysis predicted the high operating tip-speed ratios of the rotors and was accurate at predicting output power for the systems. It is shown that the wind turbines operate at high tip-speeds because of a miss-match between the aerodynamic drive torque and the operating torque of the wind

  19. PREFACE: The 2nd International Conference on Geological, Geographical, Aerospace and Earth Sciences 2014 (AeroEarth 2014)

    NASA Astrophysics Data System (ADS)

    Lumban Gaol, Ford; Soewito, Benfano

    2015-01-01

    The 2nd International Conference on Geological, Geographical, Aerospace and Earth Sciences 2014 (AeroEarth 2014), was held at Discovery Kartika Plaza Hotel, Kuta, Bali, Indonesia during 11 - 12 October 2014. The AeroEarth 2014 conference aims to bring together researchers and engineers from around the world. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. Earth provides resources and the exact conditions to make life possible. However, with the advent of technology and industrialization, the Earth's resources are being pushed to the brink of depletion. Non-sustainable industrial practices are not only endangering the supply of the Earth's natural resources, but are also putting burden on life itself by bringing about pollution and climate change. A major role of earth science scholars is to examine the delicate balance between the Earth's resources and the growing demands of industrialization. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting Conference Program as well as the invited and plenary speakers. This year, we received 98 papers and after rigorous review, 17 papers were accepted. The participants come from eight countries. There are four Parallel Sessions and two invited Speakers. It is an honour to present this volume of IOP Conference Series: Earth and Environmental Science (EES) and we deeply thank the authors for their enthusiastic and high-grade contributions. Finally, we would like to thank the conference chairmen, the members of the steering committee, the organizing committee

  20. A new method for the estimation of high temperature radiant heat emittance by means of aero-acoustic levitation

    NASA Astrophysics Data System (ADS)

    Greffrath, Fabian; Prieler, Robert; Telle, Rainer

    2014-11-01

    A new method for the experimental estimation of radiant heat emittance at high temperatures has been developed which involves aero-acoustic levitation of samples, laser heating and contactless temperature measurement. Radiant heat emittance values are determined from the time dependent development of the sample temperature which requires analysis of both the radiant and convective heat transfer towards the surroundings by means of fluid dynamics calculations. First results for the emittance of a corundum sample obtained with this method are presented in this article and found in good agreement with literature values.

  1. The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination.

    PubMed

    Page, Karen M; Rothwell, Simon W; Dolphin, Annette C

    2016-09-23

    CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598-9611). Here we show that, in the absence of CaVβ subunits, a construct consisting of the I-II loop of CaV2.2 was directly ubiquitinated and degraded by the proteasome system. Ubiquitination could be prevented by mutation of all 12 lysine residues in the I-II loop to arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop was insufficient to target it to the plasma membrane in the absence of CaVβ subunits even when proteasomal degradation was inhibited with MG132 or ubiquitination was prevented by the lysine-to-arginine mutations. In the presence of CaVβ subunit, the palmitoylated CaV2.2 I-II loop was protected from degradation, although oligoubiquitination could still occur, and was efficiently trafficked to the plasma membrane. We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaVβ subunit. PMID:27489103

  2. Effects of AP39, a novel triphenylphosphonium derivatised anethole dithiolethione hydrogen sulfide donor, on rat haemodynamic parameters and chloride and calcium Cav3 and RyR2 channels.

    PubMed

    Tomasova, Lenka; Pavlovicova, Michaela; Malekova, Lubica; Misak, Anton; Kristek, Frantisek; Grman, Marian; Cacanyiova, Sona; Tomasek, Milan; Tomaskova, Zuzana; Perry, Alexis; Wood, Mark E; Lacinova, Lubica; Ondrias, Karol; Whiteman, Matthew

    2015-04-30

    H2S donor molecules have the potential to be viable therapeutic agents. The aim of this current study was (i) to investigate the effects of a novel triphenylphosphonium derivatised dithiolethione (AP39), in the presence and absence of reduced nitric oxide bioavailability and (ii) to determine the effects of AP39 on myocardial membrane channels; CaV3, RyR2 and Cl(-). Normotensive, L-NAME- or phenylephrine-treated rats were administered Na2S, AP39 or control compounds (AP219 and ADT-OH) (0.25-1 µmol kg(-1)i.v.) and haemodynamic parameters measured. The involvement of membrane channels T-type Ca(2+) channels CaV3.1, CaV3.2 and CaV3.3 as well as Ca(2+) ryanodine (RyR2) and Cl(-) single channels derived from rat heart sarcoplasmic reticulum were also investigated. In anaesthetised Wistar rats, AP39 (0.25-1 µmol kg(-1) i.v) transiently decreased blood pressure, heart rate and pulse wave velocity, whereas AP219 and ADT-OH and Na2S had no significant effect. In L-NAME treated rats, AP39 significantly lowered systolic blood pressure for a prolonged period, decreased heart rate and arterial stiffness. In electrophysiological studies, AP39 significantly inhibited Ca(2+) current through all three CaV3 channels. AP39 decreased RyR2 channels activity and increased conductance and mean open time of Cl(-) channels. This study suggests that AP39 may offer a novel therapeutic opportunity in conditions whereby (•)NO and H2S bioavailability are deficient such as hypertension, and that CaV3, RyR2 and Cl(-) cardiac membrane channels might be involved in its biological actions.

  3. Luminal glucose does not enhance active intestinal calcium absorption in mice: evidence against a role for Ca(v)1.3 as a mediator of calcium uptake during absorption.

    PubMed

    Reyes-Fernandez, Perla C; Fleet, James C

    2015-11-01

    Intestinal Ca absorption occurs through a 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-regulated transcellular pathway, especially when habitual dietary Ca intake is low. Recently the L-type voltage-gated Ca channel, Cav1.3, was proposed to mediate active, transcellular Ca absorption in response to membrane depolarization caused by elevated luminal glucose levels after a meal. We tested the hypothesis that high luminal glucose could reveal a role for Cav1.3 in active intestinal Ca absorption in mice. Nine-week-old male C57BL/6 J mice were fed AIN93G diets containing either low (0.125%) or high (1%) Ca for 1 week, and Ca absorption was examined by an oral gavage method using a 45Ca-transport buffer containing 25 mmol/L of glucose or fructose. Transient receptor potential vanilloid 6 (TRPV6), calbindin D9k (CaBPD9k), and Cav1.3 messenger RNA (mRNA) levels were measured in the duodenum, jejunum, and ileum. TRPV6 and CaBPD9k expressions were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs, whereas Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low-Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (P = .003), serum 1,25(OH)2D3 (P < .001), and Ca absorption efficiency by 2-fold with the fructose buffer. However, the glucose buffer used to favor Cav1.3 activation did not increase Ca absorption efficiency (P = .6) regardless of the dietary Ca intake level. Collectively, our results show that glucose did not enhance Ca absorption and they do not support a critical role for Cav1.3 in either basal or vitamin D-regulated intestinal Ca absorption in vivo.

  4. The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination*

    PubMed Central

    Page, Karen M.; Rothwell, Simon W.; Dolphin, Annette C.

    2016-01-01

    CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598–9611). Here we show that, in the absence of CaVβ subunits, a construct consisting of the I-II loop of CaV2.2 was directly ubiquitinated and degraded by the proteasome system. Ubiquitination could be prevented by mutation of all 12 lysine residues in the I-II loop to arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop was insufficient to target it to the plasma membrane in the absence of CaVβ subunits even when proteasomal degradation was inhibited with MG132 or ubiquitination was prevented by the lysine-to-arginine mutations. In the presence of CaVβ subunit, the palmitoylated CaV2.2 I-II loop was protected from degradation, although oligoubiquitination could still occur, and was efficiently trafficked to the plasma membrane. We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaVβ subunit. PMID:27489103

  5. July 2004 Working Group Meeting on Heavy Vehicle Aerodynamic Drag: Presentation, Summary of Comments, and Conclusions

    SciTech Connect

    McCallen, R; Salari, K; Ortega, J; Castellucci, P; Eastwood, C; DeChant, L; Hassan, B; Browand, F; Arcas, D; Ross, J; Heineck, J; Storms, B; Walker, S; Leonard, A; Roy, C; Whitfield, D; Pointer, D; Sofu, T; Englar, R; Funk, R

    2004-08-17

    A Working Group Meeting on Heavy Vehicle Aerodynamic Drag was held in Portland, Oregon on July 1, 2004. The purpose of the meeting was to provide a summary of achievements, discuss pressing issues, present a general overview of future plans, and to provide a forum for dialogue with the Department of Energy (DOE) and industry representatives. The meeting was held in Portland, because the DOE Aero Team participated in an exclusive session on Heavy Truck Vehicle Aerodynamic Drag at the 34th AIAA Fluid Dynamics Conference and Exhibit in Portland on the morning of July 1st, just preceding our Working Group meeting. Even though the paper session was on the last day of the Conference, the Team presented to a full room of interested attendees.

  6. FY 2004 Annual Report: DOE Project on Heavy Vehicle Aerodynamic Drag

    SciTech Connect

    McCallen, R C; Salari, K; Ortega, J; Castellucci, P; Eastwood, C; Whittaker, K; DeChant, L J; Roy, C J; Payne, J L; Hassan, B; Pointer, W D; Browand, F; Hammache, M; Hsu, T; Ross, J; Satran, D; Heineck, J T; Walker, S; Yaste, D; Englar, R; Leonard, A; Rubel, M; Chatelain, P

    2004-11-18

    The objective of this report is: (1) Provide guidance to industry in the reduction of aerodynamic drag of heavy truck vehicles; and (2) Establish a database of experimental, computational, and conceptual design information, and demonstrate potential of new drag-reduction devices. The approaches used were: (1) Develop and demonstrate the ability to simulate and analyze aerodynamic flow around heavy truck vehicles using existing and advanced computational fluid dynamics (CFD) tools; (2) Through an extensive experimental effort, generate an experimental data base for code validation; (3) Using experimental data base, validate computations; (4) Provide industry with design guidance and insight into flow phenomena from experiments and computations; and (5) Investigate aero devices (e.g., base flaps, tractor-trailer gap stabilizer, underbody skirts and wedges, blowing and acoustic devices), provide industry with conceptual designs of drag reducing devices, and demonstrate the full-scale fuel economy potential of these devices.

  7. Modeling C-Band Co-Channel Interference From AeroMACS Omni-Directional Antennas to Mobile Satellite Service Feeder Uplinks

    NASA Technical Reports Server (NTRS)

    Wilson, Jeffrey D.

    2011-01-01

    A new C-band (5091 to 5150 MHz) airport communications system designated as Aeronautical Mobile Airport Communications System (AeroMACS) is being planned under the Federal Aviation Administration s NextGen program. An interference analysis software program, Visualyse Professional (Transfinite Systems Ltd), is being utilized to provide guidelines on limitations for AeroMACS transmitters to avoid interference with other systems. A scenario consisting of a single omni-directional transmitting antenna at each of the major contiguous United States airports is modeled and the steps required to build the model are reported. The results are shown to agree very well with a previous study.

  8. Design, manufacturing and characterization of aero-elastically scaled wind turbine blades for testing active and passive load alleviation techniques within a ABL wind tunnel

    NASA Astrophysics Data System (ADS)

    Campagnolo, Filippo; Bottasso, Carlo L.; Bettini, Paolo

    2014-06-01

    In the research described in this paper, a scaled wind turbine model featuring individual pitch control (IPC) capabilities, and equipped with aero-elastically scaled blades featuring passive load reduction capabilities (bend-twist coupling, BTC), was constructed to investigate, by means of wind tunnel testing, the load alleviation potential of BTC and its synergy with active load reduction techniques. The paper mainly focus on the design of the aero-elastic blades and their dynamic and static structural characterization. The experimental results highlight that manufactured blades show desired bend-twist coupling behavior and are a first milestone toward their testing in the wind tunnel.

  9. A Single Amino Acid Deletion (ΔF1502) in the S6 Segment of CaV2.1 Domain III Associated with Congenital Ataxia Increases Channel Activity and Promotes Ca2+ Influx

    PubMed Central

    Drechsel, Oliver; Rahman, Rubayte; Marcé-Grau, Anna; Prieto, Marta; Ossowski, Stephan; Macaya, Alfons; Fernández-Fernández, José M.

    2015-01-01

    Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, result in heterogeneous human neurological disorders, including familial and sporadic hemiplegic migraine along with episodic and progressive forms of ataxia. Hemiplegic Migraine (HM) mutations induce gain-of-channel function, mainly by shifting channel activation to lower voltages, whereas ataxia mutations mostly produce loss-of-channel function. However, some HM-linked gain-of-function mutations are also associated to congenital ataxia and/or cerebellar atrophy, including the deletion of a highly conserved phenylalanine located at the S6 pore region of α1A domain III (ΔF1502). Functional studies of ΔF1502 CaV2.1 channels, expressed in Xenopus oocytes, using the non-physiological Ba2+ as the charge carrier have only revealed discrete alterations in channel function of unclear pathophysiological relevance. Here, we report a second case of congenital ataxia linked to the ΔF1502 α1A mutation, detected by whole-exome sequencing, and analyze its functional consequences on CaV2.1 human channels heterologously expressed in mammalian tsA-201 HEK cells, using the physiological permeant ion Ca2+. ΔF1502 strongly decreases the voltage threshold for channel activation (by ~ 21 mV), allowing significantly higher Ca2+ current densities in a range of depolarized voltages with physiological relevance in neurons, even though maximal Ca2+ current density through ΔF1502 CaV2.1 channels is 60% lower than through wild-type channels. ΔF1502 accelerates activation kinetics and slows deactivation kinetics of CaV2.1 within a wide range of voltage depolarization. ΔF1502 also slowed CaV2.1 inactivation kinetic and shifted the inactivation curve to hyperpolarized potentials (by ~ 28 mV). ΔF1502 effects on CaV2.1 activation and deactivation properties seem to be of high physiological relevance. Thus, ΔF1502 strongly promotes Ca2+ influx in response to either single or trains of action

  10. A Single Amino Acid Deletion (ΔF1502) in the S6 Segment of CaV2.1 Domain III Associated with Congenital Ataxia Increases Channel Activity and Promotes Ca2+ Influx.

    PubMed

    Bahamonde, Maria Isabel; Serra, Selma Angèlica; Drechsel, Oliver; Rahman, Rubayte; Marcé-Grau, Anna; Prieto, Marta; Ossowski, Stephan; Macaya, Alfons; Fernández-Fernández, José M

    2015-01-01

    Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, result in heterogeneous human neurological disorders, including familial and sporadic hemiplegic migraine along with episodic and progressive forms of ataxia. Hemiplegic Migraine (HM) mutations induce gain-of-channel function, mainly by shifting channel activation to lower voltages, whereas ataxia mutations mostly produce loss-of-channel function. However, some HM-linked gain-of-function mutations are also associated to congenital ataxia and/or cerebellar atrophy, including the deletion of a highly conserved phenylalanine located at the S6 pore region of α1A domain III (ΔF1502). Functional studies of ΔF1502 CaV2.1 channels, expressed in Xenopus oocytes, using the non-physiological Ba2+ as the charge carrier have only revealed discrete alterations in channel function of unclear pathophysiological relevance. Here, we report a second case of congenital ataxia linked to the ΔF1502 α1A mutation, detected by whole-exome sequencing, and analyze its functional consequences on CaV2.1 human channels heterologously expressed in mammalian tsA-201 HEK cells, using the physiological permeant ion Ca2+. ΔF1502 strongly decreases the voltage threshold for channel activation (by ~ 21 mV), allowing significantly higher Ca2+ current densities in a range of depolarized voltages with physiological relevance in neurons, even though maximal Ca2+ current density through ΔF1502 CaV2.1 channels is 60% lower than through wild-type channels. ΔF1502 accelerates activation kinetics and slows deactivation kinetics of CaV2.1 within a wide range of voltage depolarization. ΔF1502 also slowed CaV2.1 inactivation kinetic and shifted the inactivation curve to hyperpolarized potentials (by ~ 28 mV). ΔF1502 effects on CaV2.1 activation and deactivation properties seem to be of high physiological relevance. Thus, ΔF1502 strongly promotes Ca2+ influx in response to either single or trains of action

  11. A Single Amino Acid Deletion (ΔF1502) in the S6 Segment of CaV2.1 Domain III Associated with Congenital Ataxia Increases Channel Activity and Promotes Ca2+ Influx.

    PubMed

    Bahamonde, Maria Isabel; Serra, Selma Angèlica; Drechsel, Oliver; Rahman, Rubayte; Marcé-Grau, Anna; Prieto, Marta; Ossowski, Stephan; Macaya, Alfons; Fernández-Fernández, José M

    2015-01-01

    Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, result in heterogeneous human neurological disorders, including familial and sporadic hemiplegic migraine along with episodic and progressive forms of ataxia. Hemiplegic Migraine (HM) mutations induce gain-of-channel function, mainly by shifting channel activation to lower voltages, whereas ataxia mutations mostly produce loss-of-channel function. However, some HM-linked gain-of-function mutations are also associated to congenital ataxia and/or cerebellar atrophy, including the deletion of a highly conserved phenylalanine located at the S6 pore region of α1A domain III (ΔF1502). Functional studies of ΔF1502 CaV2.1 channels, expressed in Xenopus oocytes, using the non-physiological Ba2+ as the charge carrier have only revealed discrete alterations in channel function of unclear pathophysiological relevance. Here, we report a second case of congenital ataxia linked to the ΔF1502 α1A mutation, detected by whole-exome sequencing, and analyze its functional consequences on CaV2.1 human channels heterologously expressed in mammalian tsA-201 HEK cells, using the physiological permeant ion Ca2+. ΔF1502 strongly decreases the voltage threshold for channel activation (by ~ 21 mV), allowing significantly higher Ca2+ current densities in a range of depolarized voltages with physiological relevance in neurons, even though maximal Ca2+ current density through ΔF1502 CaV2.1 channels is 60% lower than through wild-type channels. ΔF1502 accelerates activation kinetics and slows deactivation kinetics of CaV2.1 within a wide range of voltage depolarization. ΔF1502 also slowed CaV2.1 inactivation kinetic and shifted the inactivation curve to hyperpolarized potentials (by ~ 28 mV). ΔF1502 effects on CaV2.1 activation and deactivation properties seem to be of high physiological relevance. Thus, ΔF1502 strongly promotes Ca2+ influx in response to either single or trains of action

  12. Vehicle/engine integration. [orbit transfer vehicles

    NASA Technical Reports Server (NTRS)

    Cooper, L. P.; Vinopal, T. J.; Florence, D. E.; Michel, R. W.; Brown, J. R.; Bergeron, R. P.; Weldon, V. A.

    1984-01-01

    VEHICLE/ENGINE Integration Issues are explored for orbit transfer vehicles (OTV's). The impact of space basing and aeroassist on VEHICLE/ENGINE integration is discussed. The AOTV structure and thermal protection subsystem weights were scaled as the vehicle length and surface was changed. It is concluded that for increased allowable payload lengths in a ground-based system, lower length-to-diameter (L/D) is as important as higher mixture ration (MR) in the range of mid L/D ATOV's. Scenario validity, geometry constraints, throttle levels, reliability, and servicing are discussed in the context of engine design and engine/vehicle integration.

  13. The AERO system: a 3D-like approach for recording gene expression patterns in the whole mouse embryo.

    PubMed

    Shimizu, Hirohito; Kubo, Atsushi; Uchibe, Kenta; Hashimoto, Megumi; Yokoyama, Shigetoshi; Takada, Shuji; Mitsuoka, Kazuhiko; Asahara, Hiroshi

    2013-01-01

    We have recently constructed a web-based database of gene expression in the mouse whole embryo, EMBRYS (http://embrys.jp/embrys/html/MainMenu.html). To allow examination of gene expression patterns to the fullest extent possible, this database provides both photo images and annotation data. However, since embryos develop via an intricate process of morphogenesis, it would be of great value to track embryonic gene expression from a three dimensional perspective. In fact, several methods have been developed to achieve this goal, but highly laborious procedures and specific operational skills are generally required. We utilized a novel microscopic technique that enables the easy capture of rotational, 3D-like images of the whole embryo. In this method, a rotary head equipped with two mirrors that are designed to obtain an image tilted at 45 degrees to the microscope stage captures serial images at 2-degree intervals. By a simple operation, 180 images are automatically collected. These 2D images obtained at multiple angles are then used to reconstruct 3D-like images, termed AERO images. By means of this system, over 800 AERO images of 191 gene expression patterns were captured. These images can be easily rotated on the computer screen using the EMBRYS database so that researchers can view an entire embryo by a virtual viewing on a computer screen in an unbiased or non-predetermined manner. The advantages afforded by this approach make it especially useful for generating data viewed in public databases. PMID:24146773

  14. AeroVironment Technician Marshall MacCready carefully lays a panel of solar cells into place on a wi

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Technician Marshall MacCready carefully lays a panel of solar cells into place on a wing section of the Helios Prototype flying wing at AeroVironment's Design Development Center in Simi Valley, California. More than 1,800 panels containing some 64,000 bi-facial cells, fabricated by SunPower, Inc., of Sunnyvale, California, have been installed on the solar-powered aircraft to provide electricity to its 14 motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights above 50,000 feet altitude 2003 with the aid of a regenerative fuel cell-based energy storage system now being developed.

  15. Effective L/D: A Theoretical Approach to the Measurement of Aero-Structural Efficiency in Aircraft Design

    NASA Technical Reports Server (NTRS)

    Guynn, Mark D.

    2015-01-01

    There are many trade-offs in aircraft design that ultimately impact the overall performance and characteristics of the final design. One well recognized and well understood trade-off is that of wing weight and aerodynamic efficiency. Higher aerodynamic efficiency can be obtained by increasing wing span, usually at the expense of higher wing weight. The proper balance of these two competing factors depends on the objectives of the design. For example, aerodynamic efficiency is preeminent for sailplanes and long slender wings result. Although the wing weight-drag trade is universally recognized, aerodynamic efficiency and structural efficiency are not usually considered in combination. This paper discusses the concept of "aero-structural efficiency," which combines weight and drag characteristics. A metric to quantify aero-structural efficiency, termed effective L/D, is then derived and tested with various scenarios. Effective L/D is found to be a practical and robust means to simultaneously characterize aerodynamic and structural efficiency in the context of aircraft design. The primary value of the effective L/D metric is as a means to better communicate the combined system level impacts of drag and structural weight.

  16. An engineer at AeroVironment's Design Development Center inspects a set of silicon solar cells for p

    NASA Technical Reports Server (NTRS)

    2000-01-01

    An engineer at AeroVironment's Design Development Center in Simi Valley, California, closely inspects a set of silicon solar cells for potential defects. The cells, fabricated by SunPower, Inc., of Sunnyvale, California, are among 64,000 solar cells which have been installed on the Helios Prototype solar-powered aircraft to provide power to its 14 electric motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights in 2003 with the aid of a regenerative fuel cell-based energy storage system now in development.

  17. Experimental analysis of the aero-acoustic coupling in a plane impinging jet on a slotted plate

    NASA Astrophysics Data System (ADS)

    Assoum, Hassan H.; El Hassan, Mouhammad; Abed-Meraïm, Kamel; Martinuzzi, Robert; Sakout, Anas

    2013-08-01

    Impinging jets are encountered in many industrial applications and suppression of the noise generated by these jets is of great fundamental and practical interest. The vortex dynamics and the interaction between the vortical structures and the impinging wall should be understood in order to control the aero-acoustic coupling between shear layer oscillation and the acoustic modes (self-sustained tones). In this study, a plane jet issuing from a rectangular nozzle and impinging on a plate is considered for Re = 3900. The sound pressure, the vibration of the impinged plate and the spatial velocity field are obtained simultaneously using a microphone, an accelerometer and the time-resolved particle image velocimetry technique, respectively. Spectra and cross-correlations are used to educe the role of different vortical structures leading to the aero-acoustic coupling. The results show the evolution of the correlation between acoustic and transverse velocity fields in the longitudinal direction. A pre-whitening technique is used to investigate the coupling between the acoustic and the velocity signals. This method shows that the correlation between the two signals has a centred peak that is not directly related to the passage of the dominant Kelvin-Helmholtz vortices.

  18. Age-related downregulation of the CaV3.1 T-type calcium channel as a mediator of amyloid beta production

    PubMed Central

    Rice, Rachel A.; Berchtold, Nicole C.; Cotman, Carl W.; Green, Kim N.

    2014-01-01

    Alzheimer's is a crippling neurodegenerative disease that largely affects aged individuals. Decades of research have highlighted age-related changes in calcium homeostasis that occur before and throughout the duration of the disease, and the contributions of such dysregulation to Alzheimer's disease pathogenesis. We report an age-related decrease in expression of the CaV3.1 T-type calcium channel at the level of messenger RNA and protein in both humans and mice that is exacerbated with the presence of Alzheimer's disease. Downregulating T-type calcium channels in N2a cells and the 3xTg-AD mouse model of Alzheimer's disease, by way of pharmacologic inhibition with NNC-55-0396, results in a rapid increase in amyloid beta production via reductions in non-amyloidogenic processing, whereas genetic over-expression of the channel in human embryonic kidney cells expressing amyloid precursor protein produces complementary effects. The age-related decline in CaV3.1 expression may therefore contribute to a pro-amyloidogenic environment in the aging brain and represents a novel opportunity to intervene in the course of Alzheimer's disease pathogenesis. PMID:24268883

  19. Soma size and Cav1.3 channel expression in vulnerable and resistant motoneuron populations of the SOD1G93A mouse model of ALS

    PubMed Central

    Shoenfeld, Liza; Westenbroek, Ruth E.; Fisher, Erika; Quinlan, Katharina A.; Tysseling, Vicki M.; Powers, Randall K.; Heckman, Charles J.; Binder, Marc D.

    2014-01-01

    Abstract Although the loss of motoneurons is an undisputed feature of amyotrophic lateral sclerosis (ALS) in man and in its animal models (SOD1 mutant mice), how the disease affects the size and excitability of motoneurons prior to their degeneration is not well understood. This study was designed to test the hypothesis that motoneurons in mutant SOD1G93A mice exhibit an enlargement of soma size (i.e., cross‐sectional area) and an increase in Cav1.3 channel expression at postnatal day 30, well before the manifestation of physiological symptoms that typically occur at p90 (Chiu et al. 1995). We made measurements of spinal and hypoglossal motoneurons vulnerable to degeneration, as well as motoneurons in the oculomotor nucleus that are resistant to degeneration. Overall, we found that the somata of motoneurons in male SOD1G93A mutants were larger than those in wild‐type transgenic males. When females were included in the two groups, significance was lost. Expression levels of the Cav1.3 channels were not differentiated by genotype, sex, or any interaction of the two. These results raise the intriguing possibility of an interaction between male sex steroid hormones and the SOD1 mutation in the etiopathogenesis of ALS. PMID:25107988

  20. Age-related downregulation of the CaV3.1 T-type calcium channel as a mediator of amyloid beta production.

    PubMed

    Rice, Rachel A; Berchtold, Nicole C; Cotman, Carl W; Green, Kim N

    2014-05-01

    Alzheimer's is a crippling neurodegenerative disease that largely affects aged individuals. Decades of research have highlighted age-related changes in calcium homeostasis that occur before and throughout the duration of the disease, and the contributions of such dysregulation to Alzheimer's disease pathogenesis. We report an age-related decrease in expression of the CaV3.1 T-type calcium channel at the level of messenger RNA and protein in both humans and mice that is exacerbated with the presence of Alzheimer's disease. Downregulating T-type calcium channels in N2a cells and the 3xTg-AD mouse model of Alzheimer's disease, by way of pharmacologic inhibition with NNC-55-0396, results in a rapid increase in amyloid beta production via reductions in non-amyloidogenic processing, whereas genetic overexpression of the channel in human embryonic kidney cells expressing amyloid precursor protein produces complementary effects. The age-related decline in CaV3.1 expression may therefore contribute to a pro-amyloidogenic environment in the aging brain and represents a novel opportunity to intervene in the course of Alzheimer's disease pathogenesis.

  1. Gβ₂ mimics activation kinetic slowing of CaV2.2 channels by noradrenaline in rat sympathetic neurons.

    PubMed

    Hernández-Castellanos, Juan M; Vivas, Oscar; Garduño, Julieta; De la Cruz, Lizbeth; Arenas, Isabel; Elías-Viñas, David; Mackie, Ken; García, David E

    2014-02-28

    Several neurotransmitters and hormones acting through G protein-coupled receptors elicit a voltage-dependent regulation of CaV2.2 channels, having profound effects on cell function and the organism. It has been hypothesized that protein-protein interactions define specificity in signal transduction. Yet it is unknown how the molecular interactions in an intracellular signaling cascade determine the specificity of the voltage-dependent regulation induced by a specific neurotransmitter. It has been suspected that specific effector regions on the Gβ subunits of the G proteins are responsible for voltage-dependent regulation. The present study examines whether a neurotransmitter's specificity can be revealed by simple ion-current kinetic analysis likely resulting from interactions between Gβ subunits and the channel-molecule. Noradrenaline is a neurotransmitter that induces voltage-dependent regulation. By using biochemical and patch-clamp methods in rat sympathetic neurons we examined calcium current modulation induced by each of the five Gβ subunits and found that Gβ2 mimics activation kinetic slowing of CaV2.2 channels by noradrenaline. Furthermore, overexpression of the Gβ2 isoform reproduces the effect of noradrenaline in the willing-reluctant model. These results advance our understanding on the mechanisms by which signals conveying from a variety of membrane receptors are able to display precise homeostatic responses. PMID:24513289

  2. A Conus regularis Conotoxin with a Novel Eight-Cysteine Framework Inhibits CaV2.2 Channels and Displays an Anti-Nociceptive Activity

    PubMed Central

    Bernáldez, Johanna; Román-González, Sergio A.; Martínez, Oscar; Jiménez, Samanta; Vivas, Oscar; Arenas, Isabel; Corzo, Gerardo; Arreguín, Roberto; García, David E.; Possani, Lourival D.; Licea, Alexei

    2013-01-01

    A novel peptide, RsXXIVA, was isolated from the venom duct of Conus regularis, a worm-hunting species collected in the Sea of Cortez, México. Its primary structure was determined by mass spectrometry and confirmed by automated Edman degradation. This conotoxin contains 40 amino acids and exhibits a novel arrangement of eight cysteine residues (C-C-C-C-CC-CC). Surprisingly, two loops of the novel peptide are highly identical to the amino acids sequence of ω-MVIIA. The total length and disulfide pairing of both peptides are quite different, although the two most important residues for the described function of ω-MVIIA (Lys2 and Tyr13) are also present in the peptide reported here. Electrophysiological analysis using superior cervical ganglion (SCG) neurons indicates that RsXXIVA inhibits CaV2.2 channel current in a dose-dependent manner with an EC50 of 2.8 μM, whose effect is partially reversed after washing. Furthermore, RsXXIVA was tested in hot-plate assays to measure the potential anti-nociceptive effect to an acute thermal stimulus, showing an analgesic effect in acute thermal pain at 30 and 45 min post-injection. Also, the toxin shows an anti-nociceptive effect in a formalin chronic pain test. However, the low affinity for CaV2.2 suggests that the primary target of the peptide could be different from that of ω-MVIIA. PMID:23567319

  3. A microchip filter device incorporating slit arrays and 3-D flow for detection of circulating tumor cells using CAV1-EpCAM conjugated microbeads.

    PubMed

    Kim, Yeon Jeong; Koo, Gi-Bang; Lee, June-Young; Moon, Hui-Sung; Kim, Dong-Gun; Lee, Da-Gyum; Lee, Ju-Yeon; Oh, Jin Ho; Park, Jong-Myeon; Kim, Minseok S; Woo, Hyun Goo; Kim, Seung-Il; Kang, Pilsung; Choi, Wonshik; Sim, Tae Seok; Park, Woong-Yang; Lee, Jeong-Gun; Kim, You-Sun

    2014-08-01

    Circulating tumor cells (CTCs) are rare cells and the presence of these cells may indicate a poor prognosis and a high potential for metastasis. Despite highly promising clinical applications, CTCs have not been investigated thoroughly, due to many technical limitations faced in their isolation and identification. Current CTC detection techniques mostly take the epithelial marker epithelial cell adhesion molecule (EpCAM), however, accumulating evidence suggests that CTCs show heterogeneous EpCAM expression due to the epithelial-to-mesenchymal transition (EMT). In this study, we report that a microchip filter device incorporating slit arrays and 3-dimensional flow that can separate heterogeneous population of cells with marker for CTCs. To select target we cultured breast cancer cells under prolonged mammosphere culture conditions which induced EMT phenotype. Under these conditions, cells show upregulation of caveolin1 (CAV1) but down-regulation of EpCAM expression. The proposed device which contains CAV1-EpCAM conjugated bead has several tens of times increased throughput. More importantly, this platform enables the enhanced capture yield from metastatic breast cancer patients and obtained cells that expressed various EMT markers. Further understanding of these EMT-related phenotypes will lead to improved detection techniques and may provide an opportunity to develop therapeutic strategies for effective treatment and prevention of cancer metastasis.

  4. The exogenous particles of heavy metals and/or radionuclide interaction with cellular organelles in Phragmites australis (Cav.) Steudel leaf

    NASA Astrophysics Data System (ADS)

    Corneanu, Gabriel; Corneanu, Mihaela; Craciun, Constantin; Tripon, Septimiu

    2013-04-01

    Phragmites australis (Cav.) Steudel (reed), is a phytoremediatory species, meet in the swampy areas, being a hypperaccumulator for chromium (Calheiros et al., 2008; Ait Ali et al., 2004, a/o). In nature there are cytotypes with a different somatic chromosome number (6x - 16x), with a good adaptation at various environmental conditions. Weis and Weis (2004) consider that reed is an invasive species, sequester more metals than some native species and recommended to use it, in wetlands, for phytoremediation and marsh restoration. Researches performed by Hakmaoui et al. (2007) regarding the ultrastructural effect of cadmium and cooper on reed, evidenced the presence of the ferritin aggregates in the chloroplast stroma, as well as some reversible modifications in chloroplast. In this paper, the ultrastructural features of the leaf in three Phragmites australis genotypes, from the Middle Jiu river valley (Gorj county, Romania), were analyzed: Control (Ţânţăreni village); a population from neighbourhood of TEPP-Turceni; and other population developed at the basis a sterile waste dump of 40 years-old (near Cocoreni village). The heavy metal and radionuclide content of the soil was different in the three sites, with the lowest values in Control and the highest values for many heavy metals (Zn, Mn, Ni, Co, Cd) and radionuclide's (U-238, Ra-226, Pb-210, Bi-214, Pb-214, U-235, Ac-228, Pb-212, Cs-137) on the sterile waste dump. The analysis of the ultrastructural features of the leaf in mature plants revealed some differences between the three Phragmites australis genotypes. The ultrastructural investigations underlined the adaptation of this species against the stress factors (heavy metals and radionuclides). The exogenous particles penetrated the foliar tissue through the epidermis and stomata, being spread in the cells, at the plasmodesmata level, through endoplasmic reticulum, and through the vascular system. The exogenous particles were present on the endoplasmic

  5. Electric and hybrid vehicles

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Report characterizes state-of-the-art electric and hybrid (combined electric and heat engine) vehicles. Performance data for representative number of these vehicles were obtained from track and dynamometer tests. User experience information was obtained from fleet operators and individual owners of electric vehicles. Data on performance and physical characteristics of large number of vehicles were obtained from manufacturers and available literature.

  6. New Acoustic Arena Qualified at NASA Glenn's Aero-Acoustic Propulsion Laboratory

    NASA Technical Reports Server (NTRS)

    Wnuk, Stephen P.

    2004-01-01

    A new acoustic arena has been qualified in the Aero-Acoustic Propulsion Laboratory (AAPL) at the NASA Glenn Research Center. This arena is outfitted specifically for conducting fan noise research with the Advanced Noise Control Fan (ANCF) test rig. It features moveable walls with large acoustic wedges (2 by 2 by 1 ft) that create an acoustic environment usable at frequencies as low as 250 Hz. The arena currently uses two dedicated microphone arrays to acquire fan inlet and exhaust far-field acoustic data. It was used successfully in fiscal year 2003 to complete three ANCF tests. It also allowed Glenn to improve the operational efficiency of the four test rigs at AAPL and provided greater flexibility to schedule testing. There were a number of technical challenges to overcome in bringing the new arena to fruition. The foremost challenge was conflicting acoustic requirements of four different rigs. It was simply impossible to construct a static arena anywhere in the facility without intolerably compromising the acoustic test environment of at least one of the test rigs. This problem was overcome by making the wall sections of the new arena movable. Thus, the arena can be reconfigured to meet the operational requirements of any particular rig under test. Other design challenges that were encountered and overcome included structural loads of the large wedges, personnel access requirements, equipment maintenance requirements, and typical time and budget constraints. The new acoustic arena improves operations at the AAPL facility in several significant ways. First, it improves productivity by allowing multiple rigs to operate simultaneously. Second, it improves research data quality by providing a unique test area within the facility that is optimal for conducting fan noise research. Lastly, it reduces labor and equipment costs by eliminating the periodic need to transport the ANCF into and out of the primary AAPL acoustic arena. The investment to design, fabricate, and

  7. Trajectory-Based Loads for the Ares I-X Test Flight Vehicle

    NASA Technical Reports Server (NTRS)

    Vause, Roland F.; Starr, Brett R.

    2011-01-01

    In trajectory-based loads, the structural engineer treats each point on the trajectory as a load case. Distributed aero, inertial, and propulsion forces are developed for the structural model which are equivalent to the integrated values of the trajectory model. Free-body diagrams are then used to solve for the internal forces, or loads, that keep the applied aero, inertial, and propulsion forces in dynamic equilibrium. There are several advantages to using trajectory-based loads. First, consistency is maintained between the integrated equilibrium equations of the trajectory analysis and the distributed equilibrium equations of the structural analysis. Second, the structural loads equations are tied to the uncertainty model for the trajectory systems analysis model. Atmosphere, aero, propulsion, mass property, and controls uncertainty models all feed into the dispersions that are generated for the trajectory systems analysis model. Changes in any of these input models will affect structural loads response. The trajectory systems model manages these inputs as well as the output from the structural model over thousands of dispersed cases. Large structural models with hundreds of thousands of degrees of freedom would execute too slowly to be an efficient part of several thousand system analyses. Trajectory-based loads provide a means for the structures discipline to be included in the integrated systems analysis. Successful applications of trajectory-based loads methods for the Ares I-X vehicle are covered in this paper. Preliminary design loads were based on 2000 trajectories using Monte Carlo dispersions. Range safety loads were tied to 8423 malfunction turn trajectories. In addition, active control system loads were based on 2000 preflight trajectories using Monte Carlo dispersions.

  8. The AeroCom evaluation and intercomparison of organic aerosol in global models

    DOE PAGES

    Tsigaridis, K.; Daskalakis, N.; Kanakidou, M.; Adams, P. J.; Artaxo, P.; Bahadur, R.; Balkanski, Y.; Bauer, S. E.; Bellouin, N.; Benedetti, A.; et al

    2014-10-15

    This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemicalmore » and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models. The median global primary OA (POA) source strength is 56 Tg a–1 (range 34–144 Tg a−1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a–1 (range 13–121 Tg a−1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a–1 (range 16–121 Tg a−1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a–1; range 13–20 Tg a–1, with one model at 37 Tg a−1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6–2.0 Tg and 4 between 2.0 and 3.8 Tg), with a median OA lifetime of 5.4 days (range 3.8–9.6 days

  9. A multi-scale model for geared transmission aero-thermodynamics

    NASA Astrophysics Data System (ADS)

    McIntyre, Sean M.

    A multi-scale, multi-physics computational tool for the simulation of high-per- formance gearbox aero-thermodynamics was developed and applied to equilibrium and pathological loss-of-lubrication performance simulation. The physical processes at play in these systems include multiphase compressible ow of the air and lubricant within the gearbox, meshing kinematics and tribology, as well as heat transfer by conduction, and free and forced convection. These physics are coupled across their representative space and time scales in the computational framework developed in this dissertation. These scales span eight orders of magnitude, from the thermal response of the full gearbox O(100 m; 10 2 s), through effects at the tooth passage time scale O(10-2 m; 10-4 s), down to tribological effects on the meshing gear teeth O(10-6 m; 10-6 s). Direct numerical simulation of these coupled physics and scales is intractable. Accordingly, a scale-segregated simulation strategy was developed by partitioning and treating the contributing physical mechanisms as sub-problems, each with associated space and time scales, and appropriate coupling mechanisms. These are: (1) the long time scale thermal response of the system, (2) the multiphase (air, droplets, and film) aerodynamic flow and convective heat transfer within the gearbox, (3) the high-frequency, time-periodic thermal effects of gear tooth heating while in mesh and its subsequent cooling through the rest of rotation, (4) meshing effects including tribology and contact mechanics. The overarching goal of this dissertation was to develop software and analysis procedures for gearbox loss-of-lubrication performance. To accommodate these four physical effects and their coupling, each is treated in the CFD code as a sub problem. These physics modules are coupled algorithmically. Specifically, the high- frequency conduction analysis derives its local heat transfer coefficient and near-wall air temperature boundary conditions from a quasi

  10. The AeroCom evaluation and intercomparison of organic aerosol in global models

    NASA Astrophysics Data System (ADS)

    Tsigaridis, K.; Daskalakis, N.; Kanakidou, M.; Adams, P. J.; Artaxo, P.; Bahadur, R.; Balkanski, Y.; Bauer, S. E.; Bellouin, N.; Benedetti, A.; Bergman, T.; Berntsen, T. K.; Beukes, J. P.; Bian, H.; Carslaw, K. S.; Chin, M.; Curci, G.; Diehl, T.; Easter, R. C.; Ghan, S. J.; Gong, S. L.; Hodzic, A.; Hoyle, C. R.; Iversen, T.; Jathar, S.; Jimenez, J. L.; Kaiser, J. W.; Kirkevåg, A.; Koch, D.; Kokkola, H.; Lee, Y. H.; Lin, G.; Liu, X.; Luo, G.; Ma, X.; Mann, G. W.; Mihalopoulos, N.; Morcrette, J.-J.; Müller, J.-F.; Myhre, G.; Myriokefalitakis, S.; Ng, N. L.; O'Donnell, D.; Penner, J. E.; Pozzoli, L.; Pringle, K. J.; Russell, L. M.; Schulz, M.; Sciare, J.; Seland, Ø.; Shindell, D. T.; Sillman, S.; Skeie, R. B.; Spracklen, D.; Stavrakou, T.; Steenrod, S. D.; Takemura, T.; Tiitta, P.; Tilmes, S.; Tost, H.; van Noije, T.; van Zyl, P. G.; von Salzen, K.; Yu, F.; Wang, Z.; Wang, Z.; Zaveri, R. A.; Zhang, H.; Zhang, K.; Zhang, Q.; Zhang, X.

    2014-10-01

    This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models. The median global primary OA (POA) source strength is 56 Tg a-1 (range 34-144 Tg a-1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a-1 (range 13-121 Tg a-1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a-1 (range 16-121 Tg a-1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a-1; range 13-20 Tg a-1, with one model at 37 Tg a-1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6-2.0 Tg and 4 between 2.0 and 3.8 Tg), with a median OA lifetime of 5.4 days (range 3.8-9.6 days). In models that reported both OA and

  11. The AeroCom evaluation and intercomparison of organic aerosol in global models

    SciTech Connect

    Tsigaridis, K.; Daskalakis, N.; Kanakidou, M.; Adams, P. J.; Artaxo, P.; Bahadur, R.; Balkanski, Y.; Bauer, S. E.; Bellouin, N.; Benedetti, A.; Bergman, T.; Berntsen, T. K.; Beukes, J. P.; Bian, H.; Carslaw, K. S.; Chin, M.; Curci, G.; Diehl, T.; Easter, R. C.; Ghan, S. J.; Gong, S. L.; Hodzic, A.; Hoyle, C. R.; Iversen, T.; Jathar, S.; Jimenez, J. L.; Kaiser, J. W.; Kirkevåg, A.; Koch, D.; Kokkola, H.; Lee, Y. H.; Lin, G.; Liu, X.; Luo, G.; Ma, X.; Mann, G. W.; Mihalopoulos, N.; Morcrette, J. -J.; Müller, J. -F.; Myhre, G.; Myriokefalitakis, S.; Ng, N. L.; O'Donnell, D.; Penner, J. E.; Pozzoli, L.; Pringle, K. J.; Russell, L. M.; Schulz, M.; Sciare, J.; Seland, Ø.; Shindell, D. T.; Sillman, S.; Skeie, R. B.; Spracklen, D.; Stavrakou, T.; Steenrod, S. D.; Takemura, T.; Tiitta, P.; Tilmes, S.; Tost, H.; van Noije, T.; van Zyl, P. G.; von Salzen, K.; Yu, F.; Wang, Z.; Wang, Z.; Zaveri, R. A.; Zhang, H.; Zhang, K.; Zhang, Q.; Zhang, X.

    2014-10-15

    This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models.

    The median global primary OA (POA) source strength is 56 Tg a–1 (range 34–144 Tg a−1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a–1 (range 13–121 Tg a−1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a–1 (range 16–121 Tg a−1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a–1; range 13–20 Tg a–1, with one model at 37 Tg a−1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0

  12. The AeroCom evaluation and intercomparison of organic aerosol in global models

    NASA Astrophysics Data System (ADS)

    Tsigaridis, K.; Daskalakis, N.; Kanakidou, M.; Adams, P. J.; Artaxo, P.; Bahadur, R.; Balkanski, Y.; Bauer, S. E.; Bellouin, N.; Benedetti, A.; Bergman, T.; Berntsen, T. K.; Beukes, J. P.; Bian, H.; Carslaw, K. S.; Chin, M.; Curci, G.; Diehl, T.; Easter, R. C.; Ghan, S. J.; Gong, S. L.; Hodzic, A.; Hoyle, C. R.; Iversen, T.; Jathar, S.; Jimenez, J. L.; Kaiser, J. W.; Kirkevåg, A.; Koch, D.; Kokkola, H.; Lee, Y. H.; Lin, G.; Liu, X.; Luo, G.; Ma, X.; Mann, G. W.; Mihalopoulos, N.; Morcrette, J.-J.; Müller, J.-F.; Myhre, G.; Myriokefalitakis, S.; Ng, S.; O'Donnell, D.; Penner, J. E.; Pozzoli, L.; Pringle, K. J.; Russell, L. M.; Schulz, M.; Sciare, J.; Seland, Ø.; Shindell, D. T.; Sillman, S.; Skeie, R. B.; Spracklen, D.; Stavrakou, T.; Steenrod, S. D.; Takemura, T.; Tiitta, P.; Tilmes, S.; Tost, H.; van Noije, T.; van Zyl, P. G.; von Salzen, K.; Yu, F.; Wang, Z.; Wang, Z.; Zaveri, R. A.; Zhang, H.; Zhang, K.; Zhang, Q.; Zhang, X.

    2014-03-01

    This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry/transport and general circulation models have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over an order of magnitude exists in the modeled vertical distribution of OA that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing and is important for model evaluation against OA and OC observations, it is resolved only by few global models. The median global primary OA (POA) source strength is 56 Tg a-1 (range 34-144 Tg a-1) and the median secondary OA source strength (natural and anthropogenic) is 19 Tg a-1 (range 13-121 Tg a-1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a-1 (range 16-121 Tg a-1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a-1; range 13-20 Tg a-1, with one model at 37 Tg a-1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6-2.0 Tg and 4 between 2.4-3.8 Tg) with a median OA lifetime of 5.4 days (range 3.8-9.6 days). In models that reported both OA and sulfate burdens, the median value of

  13. Evaluation of the aero-optical properties of the SOFIA cavity by means of computional fluid dynamics and a super fast diagnostic camera

    NASA Astrophysics Data System (ADS)

    Engfer, Christian; Pfüller, Enrico; Wiedemann, Manuel; Wolf, Jürgen; Lutz, Thorsten; Krämer, Ewald; Röser, Hans-Peter

    2012-09-01

    The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a 2.5 m reflecting telescope housed in an open cavity on board of a Boeing 747SP. During observations, the cavity is exposed to transonic flow conditions. The oncoming boundary layer evolves into a free shear layer being responsible for optical aberrations and for aerodynamic and aeroacoustic disturbances within the cavity. While the aero-acoustical excitation of an airborne telescope can be minimized by using passive flow control devices, the aero-optical properties of the flow are difficult to improve. Hence it is important to know how much the image seen through the SOFIA telescope is perturbed by so called seeing effects. Prior to the SOFIA science fights Computational Fluid Dynamics (CFD) simulations using URANS and DES methods were carried out to determine the flow field within and above the cavity and hence in the optical path in order to provide an assessment of the aero-optical properties under baseline conditions. In addition and for validation purposes, out of focus images have been taken during flight with a Super Fast Diagnostic Camera (SFDC). Depending on the binning factor and the sub-array size, the SFDC is able to take and to read out images at very high frame rates. The paper explains the numerical approach based on CFD to evaluate the aero-optical properties of SOFIA. The CFD data is then compared to the high speed images taken by the SFDC during flight.

  14. Control Relevant Modeling and Design of Scramjet-Powered Hypersonic Vehicles

    NASA Astrophysics Data System (ADS)

    Dickeson, Jeffrey James

    This report provides an overview of scramjet-powered hypersonic vehicle modeling and control challenges. Such vehicles are characterized by unstable non-minimum phase dynamics with significant coupling and low thrust margins. Recent trends in hypersonic vehicle research are summarized. To illustrate control relevant design issues and tradeoffs, a generic nonlinear 3DOF longitudinal dynamics model capturing aero-elastic-propulsive interactions for wedge-shaped vehicle is used. Limitations of the model are discussed and numerous modifications have been made to address control relevant needs. Two different baseline configurations are examined over a two-stage to orbit ascent trajectory. The report highlights how vehicle level-flight static (trim) and dynamic properties change over the trajectory. Thermal choking constraints are imposed on control system design as a direct consequence of having a finite FER margin. The implication of this state-dependent nonlinear FER margin constraint, the right half plane (RHP) zero, and lightly damped flexible modes, on control system bandwidth (BW) and FPA tracking has been discussed. A control methodology has been proposed that addresses the above dynamics while providing some robustness to modeling uncertainty. Vehicle closure (the ability to fly a trajectory segment subject to constraints) is provided through a proposed vehicle design methodology. The design method attempts to use open loop metrics whenever possible to design the vehicle. The design method is applied to a vehicle/control law closed loop nonlinear simulation for validation. The 3DOF longitudinal modeling results are validated against a newly released NASA 6DOF code.

  15. Initial impacts and field validation of host range for Boreioglycaspis melaleucae Moore (Hemiptera: Psyllidae),a biological control agent of the invasive tree Melaleuca quinquenervia (Cav.) Blake (Myrtales: Myrtaceae: Leptosp

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Invasion of south Florida wetlands by the Australian paperbark tree (“melaleuca”), Melaleuca quinquenervia (Cav.) S.T. Blake (melaleuca) has caused adverse economic and environmental impacts. The tree’s biological attributes along with favorable ambient biophysical conditions combine to complicate ...

  16. Advanced Technology Vehicle Testing

    SciTech Connect

    James Francfort

    2003-11-01

    The light-duty vehicle transportation sector in the United States depends heavily on imported petroleum as a transportation fuel. The Department of Energy’s Advanced Vehicle Testing Activity (AVTA) is testing advanced technology vehicles to help reduce this dependency, which would contribute to the economic stability and homeland security of the United States. These advanced technology test vehicles include internal combustion engine vehicles operating on 100% hydrogen (H2) and H2CNG (compressed natural gas) blended fuels, hybrid electric vehicles, neighborhood electric vehicles, urban electric vehicles, and electric ground support vehicles. The AVTA tests and evaluates these vehicles with closed track and dynamometer testing methods (baseline performance testing) and accelerated reliability testing methods (accumulating lifecycle vehicle miles and operational knowledge within 1 to 1.5 years), and in normal fleet environments. The Arizona Public Service Alternative Fuel Pilot Plant and H2-fueled vehicles are demonstrating the feasibility of using H2 as a transportation fuel. Hybrid, neighborhood, and urban electric test vehicles are demonstrating successful applications of electric drive vehicles in various fleet missions. The AVTA is also developing electric ground support equipment (GSE) test procedures, and GSE testing will start during the fall of 2003. All of these activities are intended to support U.S. energy independence. The Idaho National Engineering and Environmental Laboratory manages these activities for the AVTA.

  17. Future orbital transfer vehicle technology study. Volume 1: Executive summary

    NASA Technical Reports Server (NTRS)

    Davis, E. E.

    1982-01-01

    Reusable space and ground based LO2/LH2 OTV's, both advanced space engines and aero assist capability were compared. The SB OTV provided advantages in life cycle cost, performance and potential for improvement. An all LO2/LH2 OTV fleet was also compared with a fleet of LO2/.H2 OTV's and electric OTV's. The normal growth technology electric OTV used silicon cells with heavy shielding and argon ion thrusters. In this case, the LO2/LH2 OTV fleet provided a 23% advantage in total transportation cost. An accelerated technology LF2/LH2 OTV provided improvements in performance relative to LO2/.H2 OTV but has higher DDT&E cost which negated its cost effectiveness. The accelerated technology electric vehicle used GaAs cells and annealing but still did not result in the mixed fleet being any cheaper than an all LO2/LH2 OTV fleet. It is concluded that reusable LO2/LH2 OTV's can serve all general purpose cargo roles between LEO and GEO for the forseeable future. The most significant technology for the second generation vehicle would be space debris protection, on orbit propellant storage and transfer and on orbit maintenance capability.

  18. Optimal diving maneuver strategy considering guidance accuracy for hypersonic vehicle

    NASA Astrophysics Data System (ADS)

    Zhu, Jianwen; Liu, Luhua; Tang, Guojian; Bao, Weimin

    2014-11-01

    An optimal maneuver strategy considering terminal guidance accuracy for hypersonic vehicle in dive phase is investigated in this paper. First, it derives the complete three-dimensional nonlinear coupled motion equation without any approximations based on diving relative motion relationship directly, and converts it into linear decoupled state space equation with the same relative degree by feedback linearization. Second, the diving guidance law is designed based on the decoupled equation to meet the terminal impact point and falling angle constraints. In order to further improve the interception capability, it constructs maneuver control model through adding maneuver control item to the guidance law. Then, an integrated performance index consisting of maximum line-of-sight angle rate and minimum energy consumption is designed, and optimal control is employed to obtain optimal maneuver strategy when the encounter time is determined and undetermined, respectively. Furthermore, the performance index and suboptimal strategy are reconstructed to deal with the control capability constraint and the serous influence on terminal guidance accuracy caused by maneuvering flight. Finally, the approach is tested using the Common Aero Vehicle-H model. Simulation results demonstrate that the proposed strategy can achieve high precision guidance and effective maneuver at the same time, and the indices are also optimized.

  19. Lockheed Martin approach to a Reusable Launch Vehicle (RLV)

    NASA Astrophysics Data System (ADS)

    Elvin, John D.

    1996-03-01

    This paper discusses Lockheed Martin's perspective on the development of a cost effective Reusable Launch Vehicle (RLV). Critical to a successful Single Stage To Orbit (SSTO) program are; an economic development plan sensitive to fiscal constraints; a vehicle concept satisfying present and future US launch needs; and an operations concept commensurate with a market driven program. Participation in the economic plan by government, industry, and the commercial sector is a key element of integrating our development plan and funding profile. The RLV baseline concept design, development evolution and several critical trade studies illustrate the superior performance achieved by our innovative approach to the problem of SSTO. Findings from initial aerodynamic and aerothermodynamic wind tunnel tests and trajectory analyses on this concept confirm the superior characteristics of the lifting body shape combined with the Linear Aerospike rocket engine. This Aero Ballistic Rocket (ABR) concept captures the essence of The Skunk Works approach to SSTO RLV technology integration and system engineering. These programmatic and concept development topics chronicle the key elements to implementing an innovative market driven next generation RLV.

  20. Caveolin-1 Facilitates the Direct Coupling between Large Conductance Ca2+-activated K+ (BKCa) and Cav1.2 Ca2+ Channels and Their Clustering to Regulate Membrane Excitability in Vascular Myocytes*

    PubMed Central

    Suzuki, Yoshiaki; Yamamura, Hisao; Ohya, Susumu; Imaizumi, Yuji

    2013-01-01

    L-type voltage-dependent Ca2+ channels (LVDCC) and large conductance Ca2+-activated K+ channels (BKCa) are the major factors defining membrane excitability in vascular smooth muscle cells (VSMCs). The Ca2+ release from sarcoplasmic reticulum through ryanodine receptor significantly contributes to BKCa activation in VSMCs. In this study direct coupling between LVDCC (Cav1.2) and BKCa and the role of caveoline-1 on their interaction in mouse mesenteric artery SMCs were examined. The direct activation of BKCa by Ca2+ influx through coupling LVDCC was demonstrated by patch clamp recordings in freshly isolated VSMCs. Using total internal reflection fluorescence microscopy, it was found that a large part of yellow fluorescent protein-tagged BKCa co-localized with the cyan fluorescent protein-tagged Cav1.2 expressed in the plasma membrane of primary cultured mouse VSMCs and that the two molecules often exhibited FRET. It is notable that each BKα subunit of a tetramer in BKCa can directly interact with Cav1.2 and promotes Cav1.2 cluster in the molecular complex. Furthermore, caveolin-1 deficiency in knock-out (KO) mice significantly reduced not only the direct coupling between BKCa and Cav1.2 but also the functional coupling between BKCa and ryanodine receptor in VSMCs. The measurement of single cell shortening by 40 mm K+ revealed enhanced contractility in VSMCs from KO mice than wild type. Taken together, caveolin-1 facilitates the accumulation/clustering of BKCa-LVDCC complex in caveolae, which effectively regulates spatiotemporal Ca2+ dynamics including the negative feedback, to control the arterial excitability and contractility. PMID:24202214

  1. System safety activities supporting an aero-space plane ground support technology

    NASA Technical Reports Server (NTRS)

    Mattern, Steven F.

    1992-01-01

    An overview is presented of the specific system safety activities required to support the ground support technology program associated with the design of an aerospace plane. Safe zones must be assessed to ensure that explosive safety requirements are attained to protect the vehicle, personnel, and support and operational facilities. Attention is given to the specific and unique design requirements connected with the utilization of cryogenic fuels as they apply to the design and development of an aerospace plane.

  2. Pressure and heat transfer investigation of a modified NASP baseline configuration at M = 6. [National Aero-Space Plane

    NASA Technical Reports Server (NTRS)

    Reubush, David E.; Omar, M. Emmett

    1989-01-01

    A cooperative NASA Langley-Boeing investigation was conducted in the Langley eight-Foot High Temperature Tunnel to obtain hypersonic pressure and heat transfer data. In this investigation a large scale (1/20), modified version of the National Aero-Space Plane configuration known as the 'Government Baseline' was tested at a nominal Mach number of 6; at two Reynolds numbers (0.6 and 1.6 million per foot); and at angles of attack from about 0 to 15 deg. There were several purposes for the investigation: to provide a windward and leeward pressure and heat transfer data base for a realistic configuration for verification of computational methods, to provide these data for a large-scale model, and to provide these data for true temperature conditions because of concern about data from low temperature tunnels.

  3. In flight demonstration of mass property identification and jet plume interaction on the AeroAssist Flight Experiment

    NASA Technical Reports Server (NTRS)

    Bergmann, Edward V.; Blanchard, R. C.

    1989-01-01

    Algorithms have been developed for in-flight demonstration of spacecraft mass, center of mass, and inertia matrix which autonomously measure mass properties as they change in-flight due to consumable expenditures, payload deployment/retrieval, and docking. The testing of these algorithms can be conducted by means of a mass-properties estimator, which is a second-order nonlinear filter resembling an extended Kalman filter. The AeroAssist Flight Experiment, which will demonstrate the use of the earth's atmosphere to assist orbital changes, will carry the Rarefied-flow Aerodynamic Measurement Experiment (RAME); data taken by RAME will be used by the mass-properties estimator to ascertain spacecraft mass properties, and estimates from this filter will be compared to predicted values of the mass properties to validate the estimator.

  4. High-Temperature Oxidation Behavior of Two Nickel-Based Superalloys Produced by Metal Injection Molding for Aero Engine Applications

    NASA Astrophysics Data System (ADS)

    Albert, Benedikt; Völkl, Rainer; Glatzel, Uwe

    2014-09-01

    For different high-temperature applications like aero engines or turbochargers, metal injection molding (MIM) of superalloys is an interesting processing alternative. For operation at high temperatures, oxidation behavior of superalloys produced by MIM needs to match the standard of cast or forged material. The oxidation behavior of nickel-based superalloys Inconel 713 and MAR-M247 in the temperature interval from 1073 K to 1373 K (800 °C to 1100 °C) is investigated and compared to cast material. Weight gain is measured discontinuously at different oxidation temperatures and times. Analysis of oxidized samples is done via SEM and EDX-measurements. MIM samples exhibit homogeneous oxide layers with a thickness up to 4 µm. After processing by MIM, Inconel 713 exhibits lower weight gain and thinner oxide layers than MAR-M247.

  5. Identification of aero-acoustic scattering matrices from large eddy simulation: Application to whistling orifices in duct

    NASA Astrophysics Data System (ADS)

    Lacombe, R.; Föller, S.; Jasor, G.; Polifke, W.; Aurégan, Y.; Moussou, P.

    2013-09-01

    The identification of the aero-acoustic scattering matrix of an orifice in a duct is achieved by computational fluid dynamics. The methodology first consists in performing a large eddy simulation of a turbulent compressible flow, with superimposed broadband acoustic excitations. After extracting time series of acoustic data with a specific filter, system identification techniques are applied. They allow us to determine the components of the acoustic scattering matrix of the orifice. Following the same procedure, a previous paper determines the scattering features of a sudden area expansion. In the present paper, the focus is on whistling orifices. The whistling ability of the tested orifice is evaluated by deriving the acoustic power balance from the scattering matrix. Comparisons with experiments at two different Mach numbers show a good agreement. The potential whistling frequency range is well predicted in terms of frequency and amplitude.

  6. In vitro antioxidant, lipoxygenase and xanthine oxidase inhibitory activities of fractions from Cienfuegosia digitata Cav., Sida alba L. and Sida acuta Burn f. (Malvaceae).

    PubMed

    Konaté, K; Souza, A; Coulibaly, A Y; Meda, N T R; Kiendrebeogo, M; Lamien-Meda, A; Millogo-Rasolodimby, J; Lamidi, M; Nacoulma, O G

    2010-11-15

    In this study polyphenol content, antioxidant activity, lipoxygenase (LOX) and Xanthine Oxidase (XO) inhibitory effects of n-hexane, dichloromethane, ethyl acetate and n-butanol fractions of aqueous acetone extracts from S. alba L., S. acuta Burn f and Cienfuegosia digitata Cav. were investigated. The total phenolics, flavonoids, flavonols and total tannins were determined by spectrophotometric methods using Folin-ciocalteu, AlCl3 reagents and tannic acid, respectively. The antioxidant potential was evaluated using three methods: inhibition of free radical 2,2-diphenyl-1-picrylhydramzyl (DPPH), ABTS radical cation decolorization assay and Iron (III) to iron (II) reduction activity (FRAP). For enzymatic activity, lipoxygenase and xanthine oxidase inhibitory activities were used. This study shows a relationship between polyphenol contents, antioxidant and enzymatic activities. Present results showed that ethyl acetate and dichloromethane fractions elicit the highest polyphenol content, antioxidant and enzymatic activities.

  7. Parasuicide and drug self-poisoning: analysis of the epidemiological and clinical variables of the patients admitted to the Poisoning Treatment Centre (CAV), Niguarda General Hospital, Milan

    PubMed Central

    2005-01-01

    Epidemiological knowledge of parasuicides and drug self-poisoning is still limited by a lack of data. A number of preliminary studies, which require further analysis, evidenced that parasuicidal acts occur more often among females, that the peak rate is generally recorded between the ages of 15 and 34 years and psychotropic medications seems to be the most frequently used. The aim of this study was to describe the demographic and clinical variables of a sample of subjects admitted to the Posisoning Treatment Centre (CAV), Niguarda General Hospital, Milan, following drug self-poisoning. Furthermore, this study is aimed to identify the risk factors associated to parasuicidal gestures, with special care for the used drugs, the presence of psychiatric or organic disorders, alcoholism and drug addiction. The study included the 201 patients attending the CAV in 1999 and 2000 who satisfied the criteria of self-poisoning attempts: 106 cases in 1999 and 95 in 2000. The sample had a prevalence of females (64%). The peak rates of parasuicides from drug self-poisoning were reached between 21 and 30 years among the females, and 31 and 40 years among the males. 81.6% of the patients used one or more psychoactive drugs, the most frequent being the benzodiazepines (58.7%), classic neuroleptics (16.9%) and new-generation antidepressants (SSRIs, SNRIs, NARIs) (12.9%). The prevalence of mood disorders was higher among females (64% vs 42%), whereas schizophrenia was more frequently diagnosed in males (22% vs 10%). 61% (33%) had a history of previous attempted suicides. The presence of clinically relevant organic diseases was observed in 24.9% of the sample. PMID:15967050

  8. Cytoplasmic location of α1A voltage-gated calcium channel C-terminal fragment (Cav2.1-CTF) aggregate is sufficient to cause cell death.

    PubMed

    Takahashi, Makoto; Obayashi, Masato; Ishiguro, Taro; Sato, Nozomu; Niimi, Yusuke; Ozaki, Kokoro; Mogushi, Kaoru; Mahmut, Yasen; Tanaka, Hiroshi; Tsuruta, Fuminori; Dolmetsch, Ricardo; Yamada, Mitsunori; Takahashi, Hitoshi; Kato, Takeo; Mori, Osamu; Eishi, Yoshinobu; Mizusawa, Hidehiro; Ishikawa, Kinya

    2013-01-01

    The human α1A voltage-dependent calcium channel (Cav2.1) is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C)-tail contains a small poly-glutamine (Q) tract, whose length is normally 4∼19 Q, but when expanded up to 20∼33Q, the tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6). A recent study has shown that a 75-kDa C-terminal fragment (CTF) containing the polyQ tract remains soluble in normal brains, but becomes insoluble mainly in the cytoplasm with additional localization to the nuclei of human SCA6 Purkinje cells. However, the mechanism by which the CTF aggregation leads to neurodegeneration is completely elusive, particularly whether the CTF exerts more toxicity in the nucleus or in the cytoplasm. We tagged recombinant (r)CTF with either nuclear-localization or nuclear-export signal, created doxycyclin-inducible rat pheochromocytoma (PC12) cell lines, and found that the CTF is more toxic in the cytoplasm than in the nucleus, the observations being more obvious with Q28 (disease range) than with Q13 (normal-length). Surprisingly, the CTF aggregates co-localized both with cAMP response element-binding protein (CREB) and phosphorylated-CREB (p-CREB) in the cytoplasm, and Western blot analysis showed that the quantity of CREB and p-CREB were both decreased in the nucleus when the rCTF formed aggregates in the cytoplasm. In human brains, polyQ aggregates also co-localized with CREB in the cytoplasm of SCA6 Purkinje cells, but not in other conditions. Collectively, the cytoplasmic Cav2.1-CTF aggregates are sufficient to cause cell death, and one of the pathogenic mechanisms may be abnormal CREB trafficking in the cytoplasm and reduced CREB and p-CREB levels in the nuclei. PMID:23505410

  9. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia.

    PubMed

    Coutelier, Marie; Blesneac, Iulia; Monteil, Arnaud; Monin, Marie-Lorraine; Ando, Kunie; Mundwiller, Emeline; Brusco, Alfredo; Le Ber, Isabelle; Anheim, Mathieu; Castrioto, Anna; Duyckaerts, Charles; Brice, Alexis; Durr, Alexandra; Lory, Philippe; Stevanin, Giovanni

    2015-11-01

    Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs. PMID:26456284

  10. Fine Tuning of CaV1.3 Ca2+ Channel Properties in Adult Inner Hair Cells Positioned in the Most Sensitive Region of the Gerbil Cochlea

    PubMed Central

    Zampini, Valeria; Johnson, Stuart L.; Franz, Christoph; Knipper, Marlies; Holley, Matthew C.; Magistretti, Jacopo; Russo, Giancarlo; Marcotti, Walter; Masetto, Sergio

    2014-01-01

    Hearing relies on faithful signal transmission by cochlear inner hair cells (IHCs) onto auditory fibres over a wide frequency and intensity range. Exocytosis at IHC ribbon synapses is triggered by Ca2+ inflow through CaV1.3 (L-type) Ca2+ channels. We investigated the macroscopic (whole-cell) and elementary (cell-attached) properties of Ca2+ currents in IHCs positioned at the middle turn (frequency ∼2 kHz) of the adult gerbil cochlea, which is their most sensitive hearing region. Using near physiological recordings conditions (body temperature and a Na+ based extracellular solution), we found that the macroscopic Ca2+ current activates and deactivates very rapidly (time constant below 1 ms) and inactivates slowly and only partially. Single-channel recordings showed an elementary conductance of 15 pS, a sub-ms latency to first opening, and a very low steady-state open probability (Po: 0.024 in response to 500-ms depolarizing steps at ∼−18 mV). The value of Po was significantly larger (0.06) in the first 40 ms of membrane depolarization, which corresponds to the time when most Ca2+ channel openings occurred clustered in bursts (mean burst duration: 19 ms). Both the Po and the mean burst duration were smaller than those previously reported in high-frequency basal IHCs. Finally, we found that middle turn IHCs are likely to express about 4 times more Ca2+ channels per ribbon than basal cells. We propose that middle-turn IHCs finely-tune CaV1.3 Ca2+ channel gating in order to provide reliable information upon timing and intensity of lower-frequency sounds. PMID:25409445

  11. Cytoplasmic Location of α1A Voltage-Gated Calcium Channel C-Terminal Fragment (Cav2.1-CTF) Aggregate Is Sufficient to Cause Cell Death

    PubMed Central

    Takahashi, Makoto; Obayashi, Masato; Ishiguro, Taro; Sato, Nozomu; Niimi, Yusuke; Ozaki, Kokoro; Mogushi, Kaoru; Mahmut, Yasen; Tanaka, Hiroshi; Tsuruta, Fuminori; Dolmetsch, Ricardo; Yamada, Mitsunori; Takahashi, Hitoshi; Kato, Takeo; Mori, Osamu; Eishi, Yoshinobu; Mizusawa, Hidehiro; Ishikawa, Kinya

    2013-01-01

    The human α1A voltage-dependent calcium channel (Cav2.1) is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C)-tail contains a small poly-glutamine (Q) tract, whose length is normally 4∼19 Q, but when expanded up to 20∼33Q, the tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6). A recent study has shown that a 75-kDa C-terminal fragment (CTF) containing the polyQ tract remains soluble in normal brains, but becomes insoluble mainly in the cytoplasm with additional localization to the nuclei of human SCA6 Purkinje cells. However, the mechanism by which the CTF aggregation leads to neurodegeneration is completely elusive, particularly whether the CTF exerts more toxicity in the nucleus or in the cytoplasm. We tagged recombinant (r)CTF with either nuclear-localization or nuclear-export signal, created doxycyclin-inducible rat pheochromocytoma (PC12) cell lines, and found that the CTF is more toxic in the cytoplasm than in the nucleus, the observations being more obvious with Q28 (disease range) than with Q13 (normal-length). Surprisingly, the CTF aggregates co-localized both with cAMP response element-binding protein (CREB) and phosphorylated-CREB (p-CREB) in the cytoplasm, and Western blot analysis showed that the quantity of CREB and p-CREB were both decreased in the nucleus when the rCTF formed aggregates in the cytoplasm. In human brains, polyQ aggregates also co-localized with CREB in the cytoplasm of SCA6 Purkinje cells, but not in other conditions. Collectively, the cytoplasmic Cav2.1-CTF aggregates are sufficient to cause cell death, and one of the pathogenic mechanisms may be abnormal CREB trafficking in the cytoplasm and reduced CREB and p-CREB levels in the nuclei. PMID:23505410

  12. (S)-Lacosamide Binding to Collapsin Response Mediator Protein 2 (CRMP2) Regulates CaV2.2 Activity by Subverting Its Phosphorylation by Cdk5.

    PubMed

    Moutal, Aubin; François-Moutal, Liberty; Perez-Miller, Samantha; Cottier, Karissa; Chew, Lindsey Anne; Yeon, Seul Ki; Dai, Jixun; Park, Ki Duk; Khanna, May; Khanna, Rajesh

    2016-04-01

    The neuronal circuit remodels during development as well as in human neuropathologies such as epilepsy. Neurite outgrowth is an obligatory step in these events. We recently reported that alterations in the phosphorylation state of an axon specification/guidance protein, the collapsin response mediator protein 2 (CRMP2), play a major role in the activity-dependent regulation of neurite outgrowth. We also identified (S)-LCM, an inactive stereoisomer of the clinically used antiepileptic drug (R)-LCM (Vimpat®), as a novel tool for preferentially targeting CRMP2-mediated neurite outgrowth. Here, we investigated the mechanism by which (S)-LCM affects CRMP2 phosphorylation by two key kinases, cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3β (GSK-3β). (S)-LCM application to embryonic cortical neurons resulted in reduced levels of Cdk5- and GSK-3β-phosphorylated CRMP2. Mechanistically, (S)-LCM increased CRMP2 binding to both Cdk5- and GSK-3β without affecting binding of CRMP2 to its canonical partner tubulin. Saturation transfer difference nuclear magnetic resonance (STD NMR) and differential scanning fluorimetry (DSF) experiments demonstrated direct binding of (S)-LCM to CRMP2. Using an in vitro luminescent kinase assay, we observed that (S)-LCM specifically inhibited Cdk5-mediated phosphorylation of CRMP2. Cross-linking experiments and analytical ultracentrifugation showed no effect of (S)-LCM on the oligomerization state of CRMP2. The increased association between Cdk5-phosphorylated CRMP2 and CaV2.2 was reduced by (S)-LCM in vitro and in vivo. This reduction translated into a decrease of calcium influx via CaV2.2 in (S)-LCM-treated neurons compared to controls. (S)-LCM, to our knowledge, is the first molecule described to directly inhibit CRMP2 phosphorylation and may be useful for delineating CRMP2-facilitated functions.

  13. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia

    PubMed Central

    Coutelier, Marie; Blesneac, Iulia; Monteil, Arnaud; Monin, Marie-Lorraine; Ando, Kunie; Mundwiller, Emeline; Brusco, Alfredo; Le Ber, Isabelle; Anheim, Mathieu; Castrioto, Anna; Duyckaerts, Charles; Brice, Alexis; Durr, Alexandra; Lory, Philippe; Stevanin, Giovanni

    2015-01-01

    Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs. PMID:26456284

  14. Automotive vehicle sensors

    SciTech Connect

    Sheen, S.H.; Raptis, A.C.; Moscynski, M.J.

    1995-09-01

    This report is an introduction to the field of automotive vehicle sensors. It contains a prototype data base for companies working in automotive vehicle sensors, as well as a prototype data base for automotive vehicle sensors. A market analysis is also included.

  15. Electric Vehicle Technician

    ERIC Educational Resources Information Center

    Moore, Pam

    2011-01-01

    With President Obama's goal to have one million electric vehicles (EV) on the road by 2015, the electric vehicle technician should have a promising and busy future. "The job force in the car industry is ramping up for a revitalized green car industry," according to Greencareersguide.com. An electric vehicle technician will safely troubleshoot and…

  16. Energy 101: Electric Vehicles

    SciTech Connect

    2012-01-01

    This edition of Energy 101 highlights the benefits of electric vehicles, including improved fuel efficiency, reduced emissions, and lower maintenance costs. For more information on electric vehicles from the Office of Energy Efficiency and Renewable Energy, visit the Vehicle Technologies Program website: http://www1.eere.energy.gov/vehiclesandfuels/

  17. Electric vehicles: Driving range

    NASA Astrophysics Data System (ADS)

    Kempton, Willett

    2016-09-01

    For uptake of electric vehicles to increase, consumers' driving-range needs must be fulfilled. Analysis of the driving patterns of personal vehicles in the US now shows that today's electric vehicles can meet all travel needs on almost 90% of days from a single overnight charge.

  18. MRV - Modular Robotic Vehicle

    NASA Technical Reports Server (NTRS)

    Ridley, Justin; Bluethmann, Bill

    2015-01-01

    The Modular Robotic Vehicle, or MRV, completed in 2013, was developed at the Johnson Space Center in order to advance technologies which have applications for future vehicles both in space and on Earth. With seating for two people, MRV is a fully electric vehicle modeled as a "city car", suited for busy urban environments.

  19. Solar space vehicle

    SciTech Connect

    Lee, R.E.

    1982-10-19

    This invention relates to space vehicle where solar energy is used to generate steam, which in turn, propels the vehicle in space. A copper boiler is provided and a novel solar radiation condensing means is used to focus the sunlight on said boiler. Steam generated in said boiler is exhausted to the environment to provide a thrust for the vehicle.

  20. Energy 101: Electric Vehicles

    ScienceCinema

    None

    2016-07-12

    This edition of Energy 101 highlights the benefits of electric vehicles, including improved fuel efficiency, reduced emissions, and lower maintenance costs. For more information on electric vehicles from the Office of Energy Efficiency and Renewable Energy, visit the Vehicle Technologies Program website: http://www1.eere.energy.gov/vehiclesandfuels/

  1. Marine vehicle ride quality

    NASA Technical Reports Server (NTRS)

    Gornstein, R. J.; Shultz, W. M.; Stair, L. D.

    1972-01-01

    The effects of marine vehicle design on passenger exposure to vibration and discomfort are discussed. The ride quality of advanced marine vehicles is examined. as a basis for marine vehicle selection in modern water transport systems. The physiological effects of rough water on passengers are identified as requiring investigation in order to determine the acceptable limits.

  2. Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis.

    PubMed

    Das, Sambuddha; Nath, Sayantan; Bhowmik, Aditi; Ghosh, Sankar Kumar; Choudhury, Yashmin

    2016-01-01

    Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mortality around the world. DNA repair genes play a vital role in preventing carcinogenesis by maintaining genomic integrity. Polymorphisms in the nucleotide sequence of DNA repair genes are often reported to be associated with an increased risk for different cancers. The OGG1 gene encodes the enzyme 8-oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA. Several studies report that the OGG1 Ser326Cys polymorphism increases the risk for cancers of the upper aero-digestive and gastrointestinal tract. However, other studies provide evidence that such an association does not exist. A meta-analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the upper aero-digestive and gastrointestinal tract was therefore undertaken in order to resolve this ambiguity. Seventeen studies were recruited for this meta-analysis after screening 58 articles with a total of 5533 cases and 6834 controls for which the odds ratio with 95 % confidence interval was calculated. Begg's funnel test and Egger's test were performed for calculating publication bias. Our study reveals an association between OGG1 Ser326Cys polymorphism and cancer susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs CC; odds ratio, OR 1.22; 95 % CI 1.05-1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09-1.70; GG vs CC; OR 1.46; 95 % CI 1.12-1.92). Subgroup analysis based on cancer types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism to the risk for upper aero-digestive and gastrointestinal tract cancers among both the Asian and the Caucasian populations. No risk was however observed for smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys polymorphism may be associated with the increased risk for aero-digestive tract and gastro-intestinal cancers in both Asian and Caucasian populations. PMID:27026921

  3. Cooperative robotic sentry vehicles

    NASA Astrophysics Data System (ADS)

    Feddema, John T.; Lewis, Christopher L.; Klarer, Paul; Eisler, G. R.; Caprihan, Rahul

    1999-08-01

    As part of a project for the Defense Advanced Research Projects Agency, Sandia National Laboratories' Intelligent Systems and Robotics Center is developing and testing the feasibility of a cooperative team of robotic sentry vehicles to guard a perimeter and to perform a surround task. This paper describes on-going activities in the development of these robotic sentry vehicles. To date, we have developed a robotic perimeter detection system which consists of eight 'Roving All Terrain Lunar Explorer Rovers' (RATLER), a laptop-based base-station, and several Miniature Intrusion Detection Sensors (MIDS). A radio frequency receiver on each of the RATLER vehicles alerts the sentry vehicles of alarms from the hidden MIDS. When an alarm is received, each vehicle decides whether it should investigate the alarm based on the proximity of itself and the other vehicles to the alarm. As one vehicle attends an alarm, the other vehicles adjust their position around the perimeter to better prepare for another alarm. For the surround task, both potential field and A* search path planners have been added to the base-station and vehicles. At the base-station, the operator specifies goal and exclusion regions on a GIS map. The path planner generates vehicles paths that are previewed by the operator. Once the operator has validated the path, the appropriate information is downloaded t the vehicles. For the potential field path planner, the polygons and line segments that represent the obstacles and goals are downloaded to the vehicles, instead of the simulated paths. On board the vehicles, the same potential field path planner generates the path except that it uses the true location of itself and the nearest neighboring vehicle. For the A* path planner, the actual path is downloaded to the vehicles because of limited on-board computational power.

  4. Energy efficient passenger vehicle

    SciTech Connect

    Dessert, R.

    1983-02-22

    An energy efficient passenger carrying vehicle for road use. The vehicle basically comprises a long, narrow body carrying two passengers in a back-to-back relationship. The vehicle is basically a battery powered electric vehicle that can be charged by all free energy sources; namely, the sun, the wind, human muscles and momentum. The vehicle comprises four modules, namely body, solar, and two power modules. An electric power module is located within each end of the body module. This module includes electric motors driving the vehicle supporting wheels and rechargeable batteries to power the motors. Pedals, similar to those on a bicycle, located at each power module, drive generators to help recharge the batteries during operation of the vehicle, or directly help drive the vehicle wheels. A solar module comprising a large electricity generating solar cell panel covers most of the vehicle roof to aid in charging the batteries. Means are provided to tilt the solar cell panel toward the sun about a longitudinal axis. A unique flexible duct below the solar panel serves to cool the cells and, if desired, heat the passenger compartment. Further energy savings are obtained by canting the rear wheels while steering with the front wheels, so that the vehicle moves down the road at a crab angle which provides a sail effect when wind is from the vehicle beam or aft of the beam. Regenerative braking means can be used when slowing down, on a long down grade, when sailing speed is greater than required, or any other time when vehicle momentum is greater than necessary for vehicle operation, to use the excess forward momentum to drive generators to charge the batteries. Thus, a single battery charge will be conserved and vehicle operation will be assisted in a manner giving maximum vehicle range and speed.

  5. Results of investigations conducted in the LaRC 4-foot unitary plan wind tunnel leg no. 1 using the 0.010-scale 72-OTS model of the space shuttle integrated vehicle (IA94A)

    NASA Technical Reports Server (NTRS)

    Nichols, M. E.

    1976-01-01

    Aero-loads investigations were conducted on the updated configuration-5 space shuttle launch vehicle at Mach numbers 2.50, 3.50, and 4.50. Six-component vehicle forces and moments, base and sting-cavity pressures, elevon hinge moments, wing-root bending and torsion moments, and normal shear force data were obtained. Full simulation of updated vehicle protuberances and attach hardware was employed. Various elevon deflection angles were tested, with two different forward orbiter-to-external-tank attach-strut configurations. The entire vehicle model 72-OTS was supported by means of a balance mounted in the orbiter through its base and suspended from an appropriate sting for the specific tunnel.

  6. VEHICLE FOR SLAVE ROBOT

    DOEpatents

    Goertz, R.C.; Lindberg, J.F.

    1962-01-30

    A reeling device is designed for an electrical cable supplying power to the slave slde of a remote control manipulator mounted on a movable vehicle. As the vehicle carries the slave side about in a closed room, the device reels the cable in and out to maintain a variable length of the cable between the vehicle and a cable inlet in the wall of the room. The device also handles a fixed length of cable between the slave side and the vehicle, in spite of angular movement of the slave side with respect to the vehicle. (AEC)

  7. Vehicle capture system

    NASA Astrophysics Data System (ADS)

    Tacke, Kenneth L.

    1998-12-01

    Primex Aerospace Company, under contract with the U.S. Army Armament Research Development & Engineering Center (ARDEC), has developed a portable vehicle capture system for use at vehicle checkpoints. Currently when a vehicle does not stop at a checkpoint, there are three possible reactions: let the vehicle go unchallenged, pursue the vehicle or stop the vehicle with lethal force. This system provides a non-lethal alternative that will stop and contain the vehicle. The system is completely portable with the heaviest component weighing less than 120 pounds. It can be installed with no external electrical power or permanent anchors required. In its standby mode, the system does not impede normal traffic, but on command erects a barrier in less than 1.5 seconds. System tests have been conducted using 5,100 and 8.400 pound vehicles, traveling at speeds up to 45 mph. The system is designed to minimize vehicle damage and occupant injury, typically resulting in deceleration forces of less than 2.5 gs on the vehicle. According to the drivers involved in tests at 45 mph, the stopping forces feel similar to a panic stop with the vehicle brakes locked. The system is completely reusable and be rapidly reset.

  8. Experience with Aero- and Fluid-Dynamic Testing for Engineering and CFD Validation

    NASA Technical Reports Server (NTRS)

    Ross, James C.

    2016-01-01

    Ever since computations have been used to simulate aerodynamics the need to ensure that the computations adequately represent real life has followed. Many experiments have been performed specifically for validation and as computational methods have improved, so have the validation experiments. Validation is also a moving target because computational methods improve requiring validation for the new aspect of flow physics that the computations aim to capture. Concurrently, new measurement techniques are being developed that can help capture more detailed flow features pressure sensitive paint (PSP) and particle image velocimetry (PIV) come to mind. This paper will present various wind-tunnel tests the author has been involved with and how they were used for validation of various kinds of CFD. A particular focus is the application of advanced measurement techniques to flow fields (and geometries) that had proven to be difficult to predict computationally. Many of these difficult flow problems arose from engineering and development problems that needed to be solved for a particular vehicle or research program. In some cases the experiments required to solve the engineering problems were refined to provide valuable CFD validation data in addition to the primary engineering data. All of these experiments have provided physical insight and validation data for a wide range of aerodynamic and acoustic phenomena for vehicles ranging from tractor-trailers to crewed spacecraft.

  9. Energy efficient passenger vehicle

    SciTech Connect

    Dessert, R.

    1980-01-01

    An energy efficient passenger carrying vehicle for road use comprised of a long, narrow body carrying two passengers in a back-to-back relationship is described. The vehicle is basically a battery powered electric vehicle that can be charged by all free energy sources; namely, the sun, the wind, human muscles and momentum. The vehicle comprises four modules: body, solar, and two power modules. An electric power module is located within each end of the body module. This module includes electric motors driving the vehicle supporting wheels and rechargeable batteries to power the motors. Pedals, similar to those on a bicycle, located at each power module, drive generators to help recharge the batteries during operation of the vehicle, or directly help drive the vehicle wheels. A solar module comprising a large electricity generating solar cell panel covers most of the vehicle roof to aid in charging the batteries. Means are provided to tilt the solar cell panel toward the sun about a longitudinal axis. A unique flexible duct below the solar panel serves to cool the cells and, if desired, heat the passenger compartment. Further energy savings are obtained by canting the rear wheels while steering with the front wheels, so that the vehicle moves down the road at a crab angle which provides a sail effect when wind is from the vehicle beam or aft of the beam. Regenerative braking means can be used when slowing down, on a long down grade, when sailing speed is greater than required, or any other time when vehicle momentum is greater than necessary for vehicle operation, to use the excess forward momentum to drive generators to charge the batteries. Thus, a single battery charge will be conserved and vehicle operation will be assisted in a manner giving maximum vehicle range and speed.

  10. Aerosol single-scattering albedo over the global oceans: Comparing PARASOL retrievals with AERONET, OMI, and AeroCom models estimates

    SciTech Connect

    Lacagnina, Carlo; Hasekamp, Otto P.; Bian, Huisheng; Curci, Gabriele; Myhre, Gunnar; van Noije, Twan; Schulz, Michael; Skeie, Ragnhild B.; Takemura, Toshihiko; Zhang, Kai

    2015-09-27

    The aerosol Single Scattering Albedo (SSA) over the global oceans is evaluated based on polarimetric measurements by the PARASOL satellite. The retrieved values for SSA and Aerosol Optical Depth (AOD) agree well with the ground-based measurements of the AErosol RObotic NETwork (AERONET). The global coverage provided by the PARASOL observations represents a unique opportunity to evaluate SSA and AOD simulated by atmospheric transport model runs, as performed in the AeroCom framework. The SSA estimate provided by the AeroCom models is generally higher than the SSA retrieved from both PARASOL and AERONET. On the other hand, the mean simulated AOD is about right or slightly underestimated compared with observations. An overestimate of the SSA by the models would suggest that these simulate an overly strong aerosol radiative cooling at top-of-atmosphere (TOA) and underestimate it at surface. This implies that aerosols have a potential stronger impact within the atmosphere than currently simulated.

  11. A study of the cleft region using synoptic ionospheric plasma data obtained by the polar orbiting satellites Aeros-B and Isis-2

    NASA Technical Reports Server (NTRS)

    Kist, R.; Klumpar, D.

    1980-01-01

    The concentrations of O(+) and NO(+) in the dayside high-latitude cleft region of the ionosphere are investigated based on synoptic particle and plasma measurements obtained by the polar orbiting Aeros-B and Isis-2 satellites. At a time when the orbital planes of the satellites are almost at right angles to each other, three maxima in ion temperature are observed, with two of them accompanied by an increased electron temperature and electron density irregularities, and the density of the molecular ions NO(+) and O2(+) is found to increase at the expense of O(+) density. Results are discussed in terms of a theory relating perpendicular electric fields to oxygen atom reaction rates. Systematic analysis of the Aeros data base reveals 14 additional instances of O(+) to NO(+) conversion, with a large variety of forms and structures reflecting the complex structure and dynamics of the high-latitude dayside ionosphere.

  12. Development Of Metallic Thermal Protection System For The Expert Re-Entry Vehicle: Design Verification

    NASA Astrophysics Data System (ADS)

    Fatemi, Javad

    2011-05-01

    The thermal protection system of the EXPERT re-entry vehicle is subjected to accelerations, vibrations, acoustic and shock loads during launch and aero-heating loads and aerodynamic forces during re-entry. To fully understand the structural and thermomechanical performances of the TPS, heat transfer analysis, thermal stress analysis, and thermal buckling analysis must be performed. This requires complex three-dimensional thermal and structural models of the entire TPS including the insulation and sensors. Finite element (FE) methods are employed to assess the thermal and structural response of the TPS to the mechanical and aerothermal loads. The FE analyses results are used for the design verification and design improvement of the EXPERT thermal protection system.

  13. Development of methodologies for the estimation of thermal properties associated with aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Scott, Elaine P.

    1993-01-01

    Thermal stress analyses are an important aspect in the development of aerospace vehicles such as the National Aero-Space Plane (NASP) and the High-Speed Civil Transport (HSCT) at NASA-LaRC. These analyses require knowledge of the temperature within the structures which consequently necessitates the need for thermal property data. The initial goal of this research effort was to develop a methodology for the estimation of thermal properties of aerospace structural materials at room temperature and to develop a procedure to optimize the estimation process. The estimation procedure was implemented utilizing a general purpose finite element code. In addition, an optimization procedure was developed and implemented to determine critical experimental parameters to optimize the estimation procedure. Finally, preliminary experiments were conducted at the Aircraft Structures Branch (ASB) laboratory.

  14. 75 FR 71373 - Airworthiness Directives; International Aero Engines V2500-A1, V2522-A5, V2524-A5, V2525-D5...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-23

    ..., 2000 (65 FR 19477-78). Examining the AD Docket You may examine the AD docket on the Internet at http... ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3... Aero Engines (IAE) V2500-A1, V2522-A5, V2524-A5, V2525-D5, V2527-A5, V2527E-A5, V2527M-A5,...

  15. Aero-acoustic experimental verification of optimum configuration of variable-pitch fans for 40 x 80 foot subsonic wind tunnel

    NASA Technical Reports Server (NTRS)

    Lown, H.

    1977-01-01

    The aerodynamic and acoustic performance of two drive fan configurations (low-speed and high-speed variable pitch design) for a 40 x 80 foot wind tunnel were monitored. A 1/7-scale model was utilized. The necessary aero-acoustic data reduction computer program logic was supplied. Test results were evaluated, and the optimum configuration to be employed in the 40 foot full scale fan was recommended.

  16. Evaluation of the aerosol vertical distribution in global aerosol models through comparison against CALIOP measurements: AeroCom phase II results

    NASA Astrophysics Data System (ADS)

    Koffi, Brigitte; Schulz, Michael; Bréon, François-Marie; Dentener, Frank; Steensen, Birthe Marie; Griesfeller, Jan; Winker, David; Balkanski, Yves; Bauer, Susanne E.; Bellouin, Nicolas; Berntsen, Terje; Bian, Huisheng; Chin, Mian; Diehl, Thomas; Easter, Richard; Ghan, Steven; Hauglustaine, Didier A.; Iversen, Trond; Kirkevâg, Alf; Liu, Xiaohong; Lohmann, Ulrike; Myhre, Gunnar; Rasch, Phil; Seland, Åyvind; Skeie, Ragnhild B.; Steenrod, Stephen D.; Stier, Philip; Tackett, Jason; Takemura, Toshihiko; Tsigaridis, Kostas; Vuolo, Maria Raffaella; Yoon, Jinho; Zhang, Kai

    2016-06-01

    The ability of 11 models in simulating the aerosol vertical distribution from regional to global scales, as part of the second phase of the AeroCom model intercomparison initiative (AeroCom II), is assessed and compared to results of the first phase. The evaluation is performed using a global monthly gridded data set of aerosol extinction profiles built for this purpose from the CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) Layer Product 3.01. Results over 12 subcontinental regions show that five models improved, whereas three degraded in reproducing the interregional variability in Zα0-6 km, the mean extinction height diagnostic, as computed from the CALIOP aerosol profiles over the 0-6 km altitude range for each studied region and season. While the models' performance remains highly variable, the simulation of the timing of the Zα0-6 km peak season has also improved for all but two models from AeroCom Phase I to Phase II. The biases in Zα0-6 km are smaller in all regions except Central Atlantic, East Asia, and North and South Africa. Most of the models now underestimate Zα0-6 km over land, notably in the dust and biomass burning regions in Asia and Africa. At global scale, the AeroCom II models better reproduce the Zα0-6 km latitudinal variability over ocean than over land. Hypotheses for the performance and evolution of the individual models and for the intermodel diversity are discussed. We also provide an analysis of the CALIOP limitations and uncertainties contributing to the differences between the simulations and observations.

  17. Determination of the mutual coherence function and determination of the point-spread function in a transversely and longitudinally inhomogeneous aero-optic turbulence layer.

    PubMed

    Monteiro, A; Jarem, J

    1993-01-10

    The mutual coherence function (MCF) of strong-fluctuation theory as a result of optical energy passing through a transversely and longitudinally inhomogeneous aero-optic turbulent layer is studied. Solutions for the MCF equation are determined by decomposing the MCF solution into coherent and incoherent parts and by solving separately the equations that result from this decomposition. The MCF equations for an arbitrary three-dimensional inhomogeneous layer are presented. A simplified version of these equations for the case in which the turbulence inhomogeneity is longitudinally inhomogeneous and is transversely inhomogeneous in one dimension is also presented. A numerical method for solving the parabolic MCF equations by the Lax-Wendroff explicit finite-difference algorithm is given, and numerical examples of the MCF solution for three different inhomogeneous aero-optic layers are discussed. Equations to relate the point-spread function, the optical transfer function, and image formation to the MCF of an inhomogeneous aero-optic turbulence layer are derived. An approximate MCF Fourier integral solution is presented and compared with the exact finite-difference solution. A formula to estimate the validity of the approximate integral solution is given. PMID:20802679

  18. Simulating Global AeroMACS Airport Ground Station Antenna Power Transmission Limits to Avoid Interference With Mobile Satellite Service Feeder Uplinks

    NASA Technical Reports Server (NTRS)

    Wilson, Jeffrey D.

    2013-01-01

    The Aeronautical Mobile Airport Communications System (AeroMACS), which is based upon the IEEE 802.16e mobile wireless standard, is expected to be implemented in the 5091 to 5150 MHz frequency band. As this band is also occupied by Mobile Satellite Service feeder uplinks, AeroMACS must be designed to avoid interference with this incumbent service. The aspects of AeroMACS operation that present potential interference are under analysis in order to enable the definition of standards that assure that such interference will be avoided. In this study, the cumulative interference power distribution at low Earth orbit from transmitters at global airports was simulated with the Visualyse Professional software. The dependence of the interference power on antenna distribution, gain patterns, duty cycle, and antenna tilt was simulated. As a function of these parameters, the simulation results are presented in terms of the limitations on transmitter power from global airports required to maintain the cumulative interference power under the established threshold.

  19. A Honeycomb-Structured Ti-6Al-4V Oil-Gas Separation Rotor Additively Manufactured by Selective Electron Beam Melting for Aero-engine Applications

    NASA Astrophysics Data System (ADS)

    Tang, H. P.; Wang, Q. B.; Yang, G. Y.; Gu, J.; Liu, N.; Jia, L.; Qian, M.

    2016-03-01

    Oil -gas separation is a key process in an aero-engine lubrication system. This study reports an innovative development in oil -gas separation. A honeycomb-structured rotor with hexagonal cone-shaped pore channels has been designed, additively manufactured from Ti-6Al-4V using selective electron beam melting (SEBM) and assessed for oil -gas separation for aero-engine application. The Ti-6Al-4V honeycomb structure showed a high compressive strength of 110 MPa compared to less than 20 MPa for metal foam structures. The oil -gas separation efficiency of the honeycomb-structured separation rotor achieved 99.8% at the rotation speed of 6000 rpm with much lower ventilation resistance (17.3 kPa) than that of the separator rotor constructed using a Ni-Cr alloy foam structure (23.5 kPa). The honeycomb-structured Ti-6Al-4V separator rotor produced by SEBM provides a promising solution to more efficient oil -gas separation in the aero-engine lubrication system.

  20. Asp residues of the Glu-Glu-Asp-Asp pore filter contribute to ion permeation and selectivity of the Ca(v)3.2 T-type channel.

    PubMed

    Park, Hyun-Jee; Park, So-Jung; Ahn, Eun-Joo; Lee, So-Young; Seo, Haengsoo; Lee, Jung-Ha

    2013-09-01

    Voltage-activated Ca2+ channels are membrane protein machinery performing selective permeation of external calcium ions. The main Ca2+ selective filters of all high-voltage-activated Ca2+ channel isoforms are commonly composed of four Glu residues (EEEE), while those of low-voltage-activated T-type Ca2+ channel isoforms are made up of two Glu and two Asp residues (EEDD). We here investigate how the Asp residues at the pore loops of domains III and IV affect biophysical properties of the Ca(v)3.2 channel. Electrophysiological characterization of the pore mutant channels in which the pore Asp residue(s) were replaced with Glu, showed that both Asp residues critically control the biophysical properties of Ca(v)3.2, including relative permeability between Ba2+ and Ca2+, anomalous mole fraction effect (AMFE), voltage dependency of channel activation, Cd2+ blocking sensitivity, and pH effects, in distinctive ways.