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Sample records for aero vehicles cavs

  1. Common Aero Vehicle Autonomous Reentry Trajectory Optimization Satisfying Waypoint and No-Fly Zone Constraints

    DTIC Science & Technology

    2007-09-01

    used to converge to the optimal solution. This numerical approach is applied to the Common Aero Vehicle (CAV) as the test platform for the full three...6 EAGLE Evolved Acceleration Guidance Logic for Entry . . . . . . 10 POSTII Program To Optimize Simulated Trajectories II...11 LQR linear quadratic regulator . . . . . . . . . . . . . . . . . . 12 MILP Mixed- Integer Linear Programming

  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. 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.

  4. Common aero vehicle autonomous reentry trajectory optimization satisfying waypoint and no-fly zone constraints

    NASA Astrophysics Data System (ADS)

    Jorris, Timothy R.

    2007-12-01

    To support the Air Force's Global Reach concept, a Common Aero Vehicle is being designed to support the Global Strike mission. "Waypoints" are specified for reconnaissance or multiple payload deployments and "no-fly zones" are specified for geopolitical restrictions or threat avoidance. Due to time critical targets and multiple scenario analysis, an autonomous solution is preferred over a time-intensive, manually iterative one. Thus, a real-time or near real-time autonomous trajectory optimization technique is presented to minimize the flight time, satisfy terminal and intermediate constraints, and remain within the specified vehicle heating and control limitations. This research uses the Hypersonic Cruise Vehicle (HCV) as a simplified two-dimensional platform to compare multiple solution techniques. The solution techniques include a unique geometric approach developed herein, a derived analytical dynamic optimization technique, and a rapidly emerging collocation numerical approach. This up-and-coming numerical technique is a direct solution method involving discretization then dualization, with pseudospectral methods and nonlinear programming used to converge to the optimal solution. This numerical approach is applied to the Common Aero Vehicle (CAV) as the test platform for the full three-dimensional reentry trajectory optimization problem. The culmination of this research is the verification of the optimality of this proposed numerical technique, as shown for both the two-dimensional and three-dimensional models. Additionally, user implementation strategies are presented to improve accuracy and enhance solution convergence. Thus, the contributions of this research are the geometric approach, the user implementation strategies, and the determination and verification of a numerical solution technique for the optimal reentry trajectory problem that minimizes time to target while satisfying vehicle dynamics and control limitation, and heating, waypoint, and no

  5. Adaptive guidance for an aero-assisted boost vehicle

    NASA Technical Reports Server (NTRS)

    Pamadi, Bandu N.; Taylor, Lawrence W., Jr.; Price, Douglas B.

    1988-01-01

    An adaptive guidance system incorporating dynamic pressure constraint is studied for a single stage to low earth orbit (LEO) aero-assist booster with thrust gimbal angle as the control variable. To derive an adaptive guidance law, cubic spline functions are used to represent the ascent profile. The booster flight to LEO is divided into initial and terminal phases. In the initial phase, the ascent profile is continuously updated to maximize the performance of the boost vehicle enroute. A linear feedback control is used in the terminal phase to guide the aero-assisted booster onto the desired LEO. The computer simulation of the vehicle dynamics considers a rotating spherical earth, inverse square (Newtonian) gravity field and an exponential model for the earth's atmospheric density. This adaptive guidance algorithm is capable of handling large deviations in both atmospheric conditions and modeling uncertainties, while ensuring maximum booster performance.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. A guidance-motivated sensitivity analysis of an aero-assisted boost vehicle

    NASA Technical Reports Server (NTRS)

    Taylor, L. W.; Gracey, C.; Armstrong, C. D.

    1986-01-01

    A simple model of an aero-assisted booster is used to examine the contributions of propulsion system type, aerodynamic lift and flight trajectory to the efficiency with which payloads can be placed into low earth orbit. The higher propulsive efficiency of ramjet and scramjet propulsion has the potential of increasing the payload mass ratio significantly. The contributions of turbojet propulsion and aerodynamic lift are less significant. The additional complexity involved in using aerodynamic propulsion and lift requires dealing with a more comprehensive set of design variables than for rocket boosters. The approach taken is to derive a set of sensitivity functions which relate booster performance to the design variables. The problems of optimum mixing of aerodynamic lift with thrust and determining the optimal boost trajectory is treated. The potential payload capacity of a horizontal take-off air-breathing boost vehicle is examined. The optimization problem which considers propulsive efficiency, aerodynamic configuration, and control and guidance issues is discussed.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Benchmarking of the state-of-the-art in nondestructive testing/evaluation for applicability in the Composite Armored Vehicle (CAV) Advanced Technology Demonstrator (ATD) program, phase 1

    NASA Astrophysics Data System (ADS)

    Carriveau, Gary W.

    1993-11-01

    This technology assessment report is the result of compilation, review, and assessment of information and data concerning the development and use of NDE/T as applied to advanced composites that may be used in the CAV (Composite Armored Vehicle) ATD (Advanced Technology Demonstrator) Program. This information has been gained from both published literature and as well as work in progress. It includes the results of a detailed bibliographic search using all the data bases held within the Defense Technical Information Center, supplemented wherever possible by other data bases. In addition, direct contacts and academic, industrial, and government research and development centers and applications laboratories were made. Discussions and recommendations contained in this report focus on the current state-of-the-art of composite NDE/T technologies and their capabilities and limitations for both the classical post process and real-time in-process inspection techniques. Furthermore, this effort includes an assessment of future developments and research trends including a projected time line.

  19. 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.

  20. Aero-optics analysis

    NASA Astrophysics Data System (ADS)

    Russell, Lynn D.

    1991-01-01

    The U.S. Army Strategic Defense Command (USASDC) has several ongoing and planned programs that utilize optical sensors aboard missiles traveling at hypersonic velocities in the atmosphere. Central to the missile homing problem are aero-optical effects upon a missile-borne sensor/seeker which looks through both an electromagnetic window and the flow field about the vehicle. Aspects of the problem include modeling and simulation of the flow field on incident radiation from a target, and finally, predicting the resultant image imperfections and error in apparent object position as perceived by the sensor.

  1. 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.

  2. 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.

  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. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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...

  10. [New aero-allergens].

    PubMed

    De Blay, F; Bessot, J C; Pauli, G

    1996-01-01

    As the number of proteins recognized as causing allergic respiratory diseases increases, new aero allergens have appeared in the animal and vegetable realms, both in home and professional environments. Lepidoglyphus destructor and Blomia tropicalis, two mites found in storage areas, are particularly important in agricultural areas and in homes. Over the last ten years, the frequency of reactions to cockroaches has also increased in several countries. The allergenicity of non-biting insects is a frequent cause of allergy in certain countries including Japan. Chironomides cause respiratory diseases in professional and outdoor environments. The important role of Alternaria, a mold, in producing severe asthma has also been demonstrated. The pathophysiology of pollen-induced asthma has been shown to result from pollen allergens carried by particles less than 5 microns in diameter. Cyprus and ash tree pollen also cause an increasing number of pollinoses and flowers can cause rhinitis and asthma. Respiratory allergy to Ficus benjamina inaugurated a new type of allergies caused airborne allergens from non-pollinating plants. Allergy to latex raises a particular problem for health care workers. The immunochemical structures of the major and minor airborne allergens are now better known and the homologous structures of different allergens largely explains certain cross-reactions. In the future, recombinant allergens will probably be used to better understand the role of allergens in inducing and maintaining the allergic reaction and should help in our approach to diagnosis and therapy.

  11. 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.

  12. 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

  13. A coupled-adjoint method for high-fidelity aero-structural optimization

    NASA Astrophysics Data System (ADS)

    Martins, Joaquim Rafael Rost A.

    A new integrated aero-structural design method for aerospace vehicles is presented. The approach combines an aero-structural analysis solver, a coupled aero-structural adjoint solver, a geometry engine, and an efficient gradient-based optimization algorithm. The aero-structural solver ensures accurate solutions by using high-fidelity models for the aerodynamics, structures, and coupling procedure. The coupled aero-structural adjoint solver is used to calculate the sensitivities of aerodynamic and structural cost functions with respect to both aerodynamic shape and structural variables. The aero-structural adjoint sensitivities are compared with those given by the complex-step derivative approximation and finite differences. The proposed method is shown to be both accurate and efficient, exhibiting a significant cost advantage when the gradient of a small number of functions with respect to a large number of design variables is needed. The optimization of a supersonic business jet configuration demonstrates the usefulness and importance of computing aero-structural sensitivities using the coupled-adjoint method.

  14. 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.

  15. 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.

  16. Nonlinear feedback guidance law for aero-assisted orbit transfer maneuvers

    NASA Technical Reports Server (NTRS)

    Menon, P. K. A.

    1992-01-01

    Aero-assisted orbit transfer vehicles have the potential for significantly reducing the fuel requirements in certain classes of orbit transfer operations. Development of a nonlinear feedback guidance law for performing aero-assisted maneuvers that accomplish simultaneous change of all the orbital elements with least vehicle acceleration magnitude is discussed. The analysis is based on a sixth order nonlinear point-mass vehicle model with lift, bank angle, thrust and drag modulation as the control variables. The guidance law uses detailed vehicle aerodynamic and the atmosphere models in the feedback loop. Higher-order gravitational harmonics, planetary atmosphere rotation and ambient winds are included in the formulation. Due to modest computational requirements, the guidance law is implementable on-board an orbit transfer vehicle. The guidance performance is illustrated for three sets of boundary conditions.

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

    SciTech Connect

    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 reduce both fuel consumption and travel time.

  18. Are Cav1.3 pacemaker channels in chromaffin cells?

    PubMed Central

    Striessnig, Joerg

    2011-01-01

    Mouse and rat chromaffin cells (MCCs, RCCs) fire spontaneously at rest and their activity is mainly supported by the two L-type Ca2+ channels expressed in these cells (Cav1.2 and Cav1.3). Using Cav1.3−/− KO MCCs we have shown that Cav1.3 possess all the prerequisites for carrying subthreshold currents that sustain low frequency cell firing near resting (0.5 to 2 Hz at −50 mV):1 low-threshold and steep voltage dependence of activation, slow and incomplete inactivation during pulses of several hundreds of milliseconds. Cav1.2 contributes also to pacemaking MCCs and possibly even Na+ channels may participate in the firing of a small percentage of cells. We now show that at potentials near resting (−50 mV), Cav1.3 carries equal amounts of Ca2+ current to Cav1.2 but activates at 9 mV more negative potentials. MCCs express only TTX-sensitive Nav1 channels that activate at 24 mV more positive potentials than Cav1.3 and are fully inactivating. Their blockade prevents the firing only in a small percentage of cells (13%). This suggests that the order of importance with regard to pacemaking MCCs is: Cav1.3, Cav1.2 and Nav1. The above conclusions, however, rely on the proper use of DHPs, whose blocking potency is strongly holding potential dependent. We also show that small increases of KCl concentration steadily depolarize the MCCs causing abnormally increased firing frequencies, lowered and broadened AP waveforms and an increased facility of switching “non-firing” into “firing” cells that may lead to erroneous conclusions about the role of Cav1.3 and Cav1.2 as pacemaker channels in MCCs.2 PMID:21406973

  19. 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

  20. 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.

  1. 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.

  2. Energy Impact of Different Penetrations of Connected and Automated Vehicles: A Preliminary Assessment

    SciTech Connect

    Rios-Torres, Jackeline; Malikopoulos, Andreas

    2016-01-01

    Previous research reported in the literature has shown the benefits of traffic coordination to alleviate congestion, and reduce fuel consumption and emissions. However, there are still many remaining challenges that need to be addressed before a massive deployment of fully automated vehicles. This paper aims to investigate the energy impacts of different penetration rates of connected and automated vehicles (CAVs) and their interaction with human-driven vehicles. We develop a simulation framework for mixed traffic (CAVs interacting with human-driven vehicles) in merging roadways and analyze the energy impact of different penetration rates of CAVs on the energy consumption. The Gipps car following model is used along with heuristic controls to represent the driver decisions in a merging roadways traffic scenario. Using different penetration rates of CAVs, the simulation results indicated that for low penetration rates, the fuel consumption benefits are significant but the total travel time increases. The benefits in travel time are noticeable for higher penetration rates of CAVs.

  3. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA.

    PubMed

    Wiggs, Janey L; Kang, Jae Hee; Yaspan, Brian L; Mirel, Daniel B; Laurie, Cathy; Crenshaw, Andrew; Brodeur, Wendy; Gogarten, Stephanie; Olson, Lana M; Abdrabou, Wael; DelBono, Elizabeth; Loomis, Stephanie; Haines, Jonathan L; Pasquale, Louis R

    2011-12-01

    Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women.

  4. 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.

  5. Derivation of Aero-Induced Fluctuating Pressure Environments for Ares I-X

    NASA Technical Reports Server (NTRS)

    Yang, Michael Y.; Wilby, John F.

    2008-01-01

    A description is given of the external aero-inducted fluctuating pressure model which was fit and anchored to wind tunnel data from the past 40 years. This model is based upon the assumption that the flow around a vehicle can be divided into discrete flow zones with independent fluctuating pressure properties. The model is then used to derive fluctuating pressure environments during ascent for the Ares I-X test vehicle. A sensitivity study of the structural response to the spatial correlation of the fluctuating pressures is also performed.

  6. 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

  7. Hypersonic Force Application and Launch Technology Demonstration

    DTIC Science & Technology

    2004-09-14

    region Regardless of anti-access threats In a single or multi-theater environment Distribution: Gov & Gov Contractors, ITAR Restricted 4 SMALL SATELLITE...demand Distribution: Gov & Gov Contractors, ITAR Restricted Objective: CAV Technology Demonstration Flight Test Description of CAV: Lifting aeroshell...Common Aero Vehicle (CAV) Distribution: Gov & Gov Contractors, ITAR Restricted 7 HYPERSONIC TECHNOLOGY EVOLUTION Building Block Tech Development and

  8. 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.

  9. Genetic, Cellular, and Functional Evidence for Ca2+ Inflow through Cav1.2 and Cav1.3 Channels in Murine Spiral Ganglion Neurons

    PubMed Central

    Lv, Ping; Kim, Hyo Jeong; Lee, Jeong-Han; Sihn, Choong-Ryoul; Fathabad Gharaie, Somayeh; Mousavi-Nik, Atefeh; Wang, Wenying; Wang, Hong-Gang; Gratton, Michael Anne; Doyle, Karen J.; Zhang, Xiao-Dong; Chiamvimonvat, Nipavan

    2014-01-01

    Spiral ganglion neurons (SGNs) of the eighth nerve serve as the bridge between hair cells and the cochlear nucleus. Hair cells use Cav1.3 as the primary channel for Ca2+ inflow to mediate transmitter release. In contrast, SGNs are equipped with multiple Ca2+ channels to mediate Ca2+-dependent functions. We examined directly the role of Cav1.3 channels in SGNs using Cav1.3-deficient mice (Cav1.3−/−). We revealed a surprising finding that SGNs functionally express the cardiac-specific Cav1.2, as well as neuronal Cav1.3 channels. We show that evoked action potentials recorded from SGNs show a significant decrease in the frequency of firing in Cav1.3−/− mice compared with wild-type (Cav1.3+/+) littermates. Although Cav1.3 is the designated L-type channel in neurons, whole-cell currents recorded in isolated SGNs from Cav1.3−/− mice showed a surprising remnant current with sensitivity toward the dihydropyridine (DHP) agonist and antagonist, and a depolarization shift in the voltage-dependent activation compared with that in the Cav1.3+/+ mice. Indeed, direct measurement of the elementary properties of Ca2+ channels, in Cav1.3+/+ neurons, confirmed the existence of two DHP-sensitive single-channel currents, with distinct open probabilities and conductances. We demonstrate that the DHP-sensitive current in Cav1.3−/− mice is derived from Cav1.2 channel activity, providing for the first time, to our knowledge, functional data for the expression of Cav1.2 currents in neurons. Finally, using shRNA gene knockdown methodology, and histological analyses of SGNs from Cav1.2+/− and Cav1.3+/− mice, we were able to establish the differential roles of Cav1.2 and Cav1.3 in SGNs. PMID:24849370

  10. Cav1.2, but not Cav1.3, L-type calcium channel subtype mediates nicotine-induced conditioned place preference in miceo.

    PubMed

    Liu, Yudan; Harding, Meghan; Dore, Jules; Chen, Xihua

    2017-04-03

    Nicotine use is one of the most common forms of drug addiction. Although L-type calcium channels (LTCCs) are involved in nicotine addiction, the contribution of the two primary LTCC subtypes (Cav1.2 and 1.3) is unknown. This study aims to determine the contribution of these two LTCC subtypes to nicotine-induced conditioned place preference (CPP) responses by using transgenic mouse models that do not express Cav1.3 (Cav1.3(-/-)) or contain a mutation in the dihydropyridine (DHP) site of the Cav1.2 (Cav1.2DHP(-/-)). We found a hyperbolic dose dependent nicotine (0.1-1mg/kg; 0.5mg/kg optimum) effect on place preference in wild type (WT) mice, that could be prevented by the DHP LTCC blocker nifedipine pretreatment. Similarly, Cav1.3(-/-) mice showed nicotine-induced place preference which was antagonized by nifedipine. In contrast, nifedipine pretreatment of Cav1.2DHP(-/-) mice had no effect on nicotine-induced CPP responses, suggesting an involvement of Cav1.2 subtype in the nicotine-induced CPP response. Nifedipine alone failed to produce either conditioned place aversion or CPP in WT mice. These results collectively indicate Cav1.2, but not Cav1.3 LTCC subtype regulates, at least in part, the reinforcing effects of nicotine use.

  11. 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.

  12. 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.

  13. 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.

  14. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA

    PubMed Central

    Wiggs, Janey L.; Hee Kang, Jae; Yaspan, Brian L.; Mirel, Daniel B.; Laurie, Cathy; Crenshaw, Andrew; Brodeur, Wendy; Gogarten, Stephanie; Olson, Lana M.; Abdrabou, Wael; DelBono, Elizabeth; Loomis, Stephanie; Haines, Jonathan L.; Pasquale, Louis R.

    2011-01-01

    Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women. PMID:21873608

  15. 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

  16. 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!

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Estimated Bounds and Important Factors for Fuel Use and Consumer Costs of Connected and Automated Vehicles

    SciTech Connect

    Stephens, T. S.; Gonder, Jeff; Chen, Yuche; Lin, Z.; Liu, C.; Gohlke, D.

    2016-11-01

    This report details a study of the potential effects of connected and automated vehicle (CAV) technologies on vehicle miles traveled (VMT), vehicle fuel efficiency, and consumer costs. Related analyses focused on a range of light-duty CAV technologies in conventional powertrain vehicles -- from partial automation to full automation, with and without ridesharing -- compared to today's base-case scenario. Analysis results revealed widely disparate upper- and lower-bound estimates for fuel use and VMT, ranging from a tripling of fuel use to decreasing light-duty fuel use to below 40% of today's level. This wide range reflects uncertainties in the ways that CAV technologies can influence vehicle efficiency and use through changes in vehicle designs, driving habits, and travel behavior. The report further identifies the most significant potential impacting factors, the largest areas of uncertainty, and where further research is particularly needed.

  2. 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

  3. Aero-thermal modeling framework for TMT

    NASA Astrophysics Data System (ADS)

    Vogiatzis, Konstantinos

    2011-09-01

    The Performance Error Budget of the Thirty Meter Telescope (TMT) suggests that nearly one third of the total image degradation is due to aero-thermal disturbances (mirror and dome seeing, dynamic wind loading and thermal deformations of the optics, telescope structure and enclosure). An update of the current status of aero-thermal modeling and Computational Fluid-Solid Dynamics (CFSD) simulations for TMT is presented. A fast three-dimensional transient conduction-convection-radiation bulk-air-volume model has also been developed for the enclosure and selected telescope components in order to track the temperature variations of the surfaces, structure and interstitial air over a period of three years using measured environmental conditions. It is used for Observatory Heat Budget analysis and also provides estimates of thermal boundary conditions required by the CFD/FEA models and guidance to the design. Detailed transient CFSD conjugate heat transfer simulations of the mirror support assemblies determine the direction of heat flow from important heat sources and provide guidance to the design. Finally, improved CFD modeling is used to calculate wind forces and temperature fields. Wind loading simulations are demonstrated through TMT aperture deflector forcing. Temperature fields are transformed into refractive index ones and the resulting Optical Path Differences (OPDs) are fed into an updated thermal seeing model to estimate seeing performance metrics. Keck II simulations are the demonstrator for the latter type of modeling.

  4. Genomic Variant in CAV1 Increases Susceptibility to Coronary Artery Disease and Myocardial Infarction

    PubMed Central

    Zhang, Rongfeng; Wang, Fan; Xu, Chaoping; Huang, Yufeng; Li, Sisi; Yin, Dan; Xiong, Xin; Li, Xiuchun; Chen, Qiuyun; Tu, Xin; Yang, Yanzong; Xia, Yonglong; Xu, Chengqi; Wang, Qing K.

    2016-01-01

    Background The CAV1 gene encodes caveolin-1 expressed in cell types relevant to atherosclerosis. Cav-1-null mice showed a protective effect on atherosclerosis under the ApoE−/− background. However, it is unknown whether CAV1 is linked to CAD and MI in humans. In this study we analyzed a tagSNP for CAV1 in intron 2, rs3807989, for potential association with CAD. Methods and Results We performed case-control association studies in three independent Chinese Han populations from GeneID, including 1,249 CAD cases and 841 controls in Population I, 1,260 cases and 833 controls in Population II and 790 cases and 1,212 controls in Population III (a total of 3,299 cases and 2,886 controls). We identified significant association between rs3807989 and CAD in three independent populations and in the combined population (Padj=2.18×10−5, OR=1.19 for minor allele A). We also detected significant association between rs3807989 and MI (Padj=5.43×10−5, OR=1.23 for allele A). Allele A of SNP rs3807989 was also associated with a decreased level of LDL cholesterol. Although rs3807989 is a tagSNP for both CAV1 and nearby CAV2, allele A of SNP rs3807989 was associated with an increased expression level of CAV1 (both mRNA and protein), but not CAV2. Conclusions The data in this study demonstrated that rs3807989 at the CAV1/CAV2 locus was associated with significant risk of CAD and MI by increasing expression CAV1 (but not CAV2). Thus, CAV1 becomes a strong candidate susceptibility gene for CAD/MI in humans. PMID:26775120

  5. Antimitogenic effect of Larrea divaricata Cav.: participation in arachidonate metabolism.

    PubMed

    Anesini, C; Genaro, A; Cremaschi, G; Sterin Borda, L; Borda, E

    1999-02-01

    Aqueous extracts of the leaves of Larrea divaricata Cav. exert antimitogenic effects on tumor cells (BW 5147 murine immature T-lymphoma) and normal, stimulated lymphocytes. The effective concentration was four times smaller in the case of tumor cells than in the case of normal, stimulated lymphocytes. Inhibitor studies of arachidonate pathway suggest that the proliferative effect of the extract is due to the activation of lipoxygenase metabolism, while the inhibitory action could be a direct effect.

  6. 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.

  7. Proceedings of the Non-Linear Aero Prediction Requirements Workshop

    NASA Technical Reports Server (NTRS)

    Logan, Michael J. (Editor)

    1994-01-01

    The purpose of the Non-Linear Aero Prediction Requirements Workshop, held at NASA Langley Research Center on 8-9 Dec. 1993, was to identify and articulate requirements for non-linear aero prediction capabilities during conceptual/preliminary design. The attendees included engineers from industry, government, and academia in a variety of aerospace disciplines, such as advanced design, aerodynamic performance analysis, aero methods development, flight controls, and experimental and theoretical aerodynamics. Presentations by industry and government organizations were followed by panel discussions. This report contains copies of the presentations and the results of the panel discussions.

  8. BIN1 is Reduced and Cav1.2 Trafficking is Impaired in Human Failing Cardiomyocytes

    PubMed Central

    Hong, Ting-Ting; Smyth, James W.; Chu, Kevin Y.; Vogan, Jacob M.; Fong, Tina S.; Jensen, Brian C.; Fang, Kun; Halushka, Marc K.; Russell, Stuart D.; Colecraft, Henry; Hoopes, Charles W.; Ocorr, Karen; Chi, Neil C.; Shaw, Robin M.

    2011-01-01

    Background Heart failure is a growing epidemic and a typical aspect of heart failure pathophysiology is altered calcium transients. Normal cardiac calcium transients are initiated by Cav1.2 channels at cardiac T-tubules. BIN1 is a membrane scaffolding protein that causes Cav1.2 to traffic to T-tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in heart failure are not known. Objective To study BIN1 expression and its effect on Cav1.2 trafficking in failing hearts. Methods Intact myocardium and freshly isolated cardiomyocytes from non-failing and end-stage failing human hearts were used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface expression dependence on BIN1, patch clamp recordings were performed of Cav1.2 current in cell lines with and without trafficking competent BIN1. Also, in adult mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after shRNA mediated knockdown of BIN1. For a functional readout in intact heart, calcium transients and cardiac contractility were analyzed in a zebrafish model with morpholino mediated knockdown of BIN1. Results BIN1 expression is significantly decreased in failing cardiomyocytes at both mRNA (30% down) and protein (36% down) levels. Peripheral Cav1.2 is reduced 42% by imaging and biochemical T-tubule fraction of Cav1.2 is reduced 68%. Total calcium current is reduced 41% in a cell line expressing non-trafficking BIN1 mutant. In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in calcium transients and severe ventricular contractile dysfunction. Conclusions The data indicate that BIN1 is significantly reduced in human heart failure, and this reduction impairs Cav1.2 trafficking, calcium transients, and contractility. PMID:22138472

  9. 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.

  10. MEMS and mil/aero: technology push and market pull

    NASA Astrophysics Data System (ADS)

    Clifford, Thomas H.

    2001-04-01

    MEMS offers attractive solutions to high-density fluidics, inertial, optical, switching and other demanding military/aerospace (mil/aero) challenges. However, full acceptance must confront the realities of production-scale producibility, verifiability, testability, survivability, as well as long-term reliability. Data on these `..ilities' are crucial, and are central in funding and deployment decisions. Similarly, mil/aero users must highlight specific missions, environmental exposures, and procurement issues, as well as the quirks of its designers. These issues are particularly challenging in MEMS, because of the laws of physics and business economics, as well as the risks of deploying leading-edge technology into no-fail applications. This paper highlights mil/aero requirements, and suggests reliability/qualification protocols, to guide development effort and to reassure mil/aero users that MEMS labs are mindful of the necessary realities.

  11. 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

  12. 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.

  13. CaV1.1: The atypical prototypical voltage-gated Ca2+ channel

    PubMed Central

    Bannister, Roger A.; Beam, Kurt G.

    2012-01-01

    CaV1.1 is the prototype for the other nine known CaV channel isoforms, yet it has functional properties that make it truly atypical of this group. Specifically, CaV1.1 is expressed solely in skeletal muscle where it serves multiple purposes; it is the voltage sensor for excitation-contraction (EC) coupling and it is an L-type Ca2+ channel which contributes to a form of activity-dependent Ca2+ entry that has been termed Excitation-Coupled Ca2+ Entry (ECCE). The ability of CaV1.1 to serve as voltage-sensor for EC coupling appears to be unique amongst CaV channels, whereas the physiological role of its more conventional function as a Ca2+ channel has been a matter of uncertainty for nearly 50 years. In this chapter, we discuss how CaV1.1 supports EC coupling, the possible relevance of Ca2+ entry through CaV1.1 and how alterations of CaV1.1 function can have pathophysiological consequences. PMID:22982493

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy.

    PubMed

    Li, Yan; Tatsui, Claudio Esteves; Rhines, Laurence D; North, Robert Y; Harrison, Daniel S; Cassidy, Ryan M; Johansson, Caj A; Kosturakis, Alyssa K; Edwards, Denaya D; Zhang, Hongmei; Dougherty, Patrick M

    2017-03-01

    Here, it is shown that paclitaxel-induced neuropathy is associated with the development of spontaneous activity (SA) and hyperexcitability in dorsal root ganglion (DRG) neurons that is paralleled by increased expression of low-voltage-activated calcium channels (T-type; Cav3.2). The percentage of DRG neurons showing SA and the overall mean rate of SA were significantly higher at day 7 in rats receiving paclitaxel treatment than in rats receiving vehicle. Cav3.2 expression was increased in L4-L6 DRG and spinal cord segments in paclitaxel-treated rats, localized to small calcitonin gene-related peptide and isolectin B4 expressing DRG neurons and to glial fibrillary acidic protein-positive spinal cord cells. Cav3.2 expression was also co-localized with toll-like receptor 4 (TLR4) in both the DRG and the dorsal horn. T-type current amplitudes and density were increased at day 7 after paclitaxel treatment. Perfusion of the TLR4 agonist lipopolysaccharide directly activated DRG neurons, whereas this was prevented by pretreatment with the specific T-type calcium channel inhibitor ML218 hydrochloride. Paclitaxel-induced behavioral hypersensitivity to mechanical stimuli in rats was prevented but not reversed by spinal administration of ML218 hydrochloride or intravenous injection of the TLR4 antagonist TAK242. Paclitaxel induced inward current and action potential discharges in cultured human DRG neurons, and this was blocked by ML218 hydrochloride pretreatment. Furthermore, ML218 hydrochloride decreased firing frequency in human DRG, where spontaneous action potentials were present. In summary, Cav3.2 in concert with TLR4 in DRG neurons appears to contribute to paclitaxel-induced neuropathy.

  20. 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.

  1. 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.

  2. 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

  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.

  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. 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.

  6. 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.

  7. Vortex-Based Aero- and Hydrodynamic Estimation

    NASA Astrophysics Data System (ADS)

    Hemati, Maziar Sam

    Flow control strategies often require knowledge of unmeasurable quantities, thus presenting a need to reconstruct flow states from measurable ones. In this thesis, the modeling, simulation, and estimator design aspects of flow reconstruction are considered. First, a vortex-based aero- and hydrodynamic estimation paradigm is developed to design a wake sensing algorithm for aircraft formation flight missions. The method assimilates wing distributed pressure measurements with a vortex-based wake model to better predict the state of the flow. The study compares Kalman-type algorithms with particle filtering algorithms, demonstrating that the vortex nonlinearities require particle filters to yield adequate performance. Furthermore, the observability structure of the wake is shown to have a negative impact on filter performance regardless of the algorithm applied. It is demonstrated that relative motions can alleviate the filter divergence issues associated with this observability structure. In addition to estimator development, the dissertation addresses the need for an efficient unsteady multi-body aerodynamics testbed for estimator and controller validation studies. A pure vortex particle implementation of a vortex panel-particle method is developed to satisfy this need. The numerical method is demonstrated on the impulsive startup of a flat plate as well as the impulsive startup of a multi-wing formation. It is clear, from these validation studies, that the method is able to accommodate the unsteady wake effects that arise in formation flight missions. Lastly, successful vortex-based estimation is highly dependent on the reliability of the low-order vortex model used in representing the flow of interest. The present treatise establishes a systematic framework for vortex model improvement, grounded in optimal control theory and the calculus of variations. By minimizing model predicted errors with respect to empirical data, the shortcomings of the baseline vortex model

  8. Molecular epidemiology of chicken anemia virus (CAV) in southeastern Chinese live birds markets.

    PubMed

    Ducatez, M F; Chen, H; Guan, Y; Muller, C P

    2008-03-01

    Between January 2004 and December 2005, cloacal swabs from essentially healthy chickens and silky chickens from live birds markets in Guangdong and Hunan provinces in southeastern China were screened for chicken anemia virus (CAV) by polymerase chain reaction. Phylogenetic analysis of the major structural protein VP1 sequences showed no clear genotype cluster and no correlation with the geographic origin of CAV strains. Virus evolution at the amino acid level was very slow, which corresponds to a strong negative selection of the VP1 gene in China and worldwide. A high proportion (87%) of birds was CAV positive, suggesting that many farms in the region were infected. Further investigations are necessary to evaluate the economic losses caused by CAV and the cost-benefit of vaccination.

  9. Classification of ASASSN-17dj (AT2017cav) with the Liverpool Telescope

    NASA Astrophysics Data System (ADS)

    Bersier, David

    2017-03-01

    We obtained a spectrum of the candidate supernova ASASSN-17dj/AT 2017cav (ATEL #10155) with the SPRAT spectrograph mounted on the robotic 2m Liverpool Telescope at the Roque de los Muchachos observatory (La Palma).

  10. 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 ...

  11. 76 FR 77108 - Airworthiness Directives; International Aero Engines Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ... Engines Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for International Aero Engines (IAE) V2500-A1... engines. This AD was prompted by three reports of high- pressure turbine (HPT) case burn-through...

  12. 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.

  13. Human native Cav1 channels in chromaffin cells: contribution to exocytosis and firing of spontaneous action potentials.

    PubMed

    Hernández-Vivanco, Alicia; Sanz-Lázaro, Sara; Jiménez-Pompa, Amanda; García-Magro, Nuria; Carmona-Hidalgo, Beatriz; Pérez-Alvarez, Alberto; Caba-González, Jose Carlos; Tabernero, Angel; Alonso Y Gregorio, Sergio; Passas, Juan; Blázquez, Jesús; González-Enguita, Carmen; de Castro-Guerín, Cristina; Albillos, Almudena

    2017-02-05

    The present study was performed to evaluate the Cav1 channel subtypes expressed in human chromaffin cells and the role that these channels play in exocytosis and cell excitability. Here we show that human chromaffin cells obtained from organ donors express Cav1.2 and Cav1.3 subtypes using molecular and pharmacological techniques. Immunocytochemical data demonstrated the presence of Cav1.2 and Cav1.3 subtypes, but not Cav1.1 or Cav1.4. Electrophysiological experiments were conducted to investigate the contribution of Cav1 channels to the exocytotic process and cell excitability. Cav1 channels contribute to the exocytosis of secretory vesicles, evidenced by the block of 3μM nifedipine (36.5±2%) of membrane capacitance increment elicited by 200ms depolarizing pulses. These channels show a minor contribution to the initiation of spontaneous action potential firing, as shown by the 2.5 pA of current at the threshold potential (-34mV), which elicits 10.4mV of potential increment. In addition, we found that only 8% of human chromaffin cells exhibit spontaneous action potentials. These data offer novel information regarding human chromaffin cells and the role of human native Cav1 channels in exocytosis and cell excitability.

  14. CaV3.2 Channels and the Induction of Negative Feedback in Cerebral Arteries

    PubMed Central

    Harraz, Osama F.; Abd El-Rahman, Rasha R.; Bigdely-Shamloo, Kamran; Wilson, Sean M.; Brett, Suzanne E.; Romero, Monica; Gonzales, Albert L.; Earley, Scott; Vigmond, Edward J.; Nygren, Anders; Menon, Bijoy K.; Mufti, Rania E.; Watson, Tim; Starreveld, Yves; Furstenhaupt, Tobias; Muellerleile, Philip R.; Kurjiaka, David T.; Kyle, Barry D.; Braun, Andrew P.; Welsh, Donald G.

    2015-01-01

    Rationale T-type (CaV3.1/CaV3.2) Ca2+ channels are expressed in rat cerebral arterial smooth muscle. Although present, their functional significance remains uncertain with findings pointing to a variety of roles. Objective This study tested whether CaV3.2 channels mediate a negative feedback response by triggering Ca2+ sparks, discrete events that initiate arterial hyperpolarization by activating large-conductance Ca2+-activated K+ channels. Methods and Results Micromolar Ni2+, an agent that selectively blocks CaV3.2 but not CaV1.2/CaV3.1, was first shown to depolarize/constrict pressurized rat cerebral arteries; no effect was observed in CaV3.2−/− arteries. Structural analysis using 3-dimensional tomography, immunolabeling, and a proximity ligation assay next revealed the existence of microdomains in cerebral arterial smooth muscle which comprised sarcoplasmic reticulum and caveolae. Within these discrete structures, CaV3.2 and ryanodine receptor resided in close apposition to one another. Computational modeling revealed that Ca2+ influx through CaV3.2 could repetitively activate ryanodine receptor, inducing discrete Ca2+-induced Ca2+ release events in a voltage-dependent manner. In keeping with theoretical observations, rapid Ca2+ imaging and perforated patch clamp electrophysiology demonstrated that Ni2+ suppressed Ca2+ sparks and consequently spontaneous transient outward K+ currents, large-conductance Ca2+-activated K+ channel mediated events. Additional functional work on pressurized arteries noted that paxilline, a large-conductance Ca2+-activated K+ channel inhibitor, elicited arterial constriction equivalent, and not additive, to Ni2+. Key experiments on human cerebral arteries indicate that CaV3.2 is present and drives a comparable response to moderate constriction. Conclusions These findings indicate for the first time that CaV3.2 channels localize to discrete microdomains and drive ryanodine receptor–mediated Ca2+ sparks, enabling large

  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. 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

  17. 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.

  18. 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.

  19. 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.

  20. Technology requirements and readiness for very large vehicles

    NASA Technical Reports Server (NTRS)

    Conner, D. W.

    1979-01-01

    Common concerns of very large vehicles in the areas of economics, transportation system interfaces and operational problems were reviewed regarding their influence on vehicle configurations and technology. Fifty-four technology requirements were identified which are judged to be unique, or particularly critical, to very large vehicles. The requirements were about equally divided among the four general areas of aero/hydrodynamics, propulsion and acoustics, structures, and vehicle systems and operations. The state of technology readiness was judged to be poor to fair for slightly more than one half of the requirements. In the classic disciplinary areas, the state of technology readiness appears to be more advanced than for vehicle systems and operations.

  1. 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

  2. CaV channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics.

    PubMed

    Buchanan, Paul J; McCloskey, Karen D

    2016-10-01

    The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (CaV) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the CaV channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. CaV channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several CaV channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of CaV channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that CaV canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of CaV channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.

  3. 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.

  4. Fatigue crack monitoring in aero-engines: simulation and experiments

    NASA Astrophysics Data System (ADS)

    Gelman, Leonid M.; Petrunin, Ivan V.; Thompson, Chris

    2004-03-01

    A new genetic approach to fatigue crack monitoring in aero-engine blades is presented. The approach consists of simultaneously using two diagnostic features: the real and imaginary parts of the Fourier transform of vibroacoustical signals. This approach is more fundamental than traditional approaches based on the power spectral density, phase spectrum and Hartley transform; each of these approaches is a special case of the proposed approach. Numerical examples are given based on the processing of signals generated using a nonlinear model of tested blades. The generated signals are the forced vibroacoustical oscillations of cracked and un-cracked blades. The numerical examples show that crack detection ismore effective when using the new approach than when u sing the power spectral density approach. The presented experimental results using un-cracked and cracked turbuine blades from an aero-engine are matched with numerical results. The proposed approach offers an effectiveness improvement over the traditional approach based on power spectral density.

  5. 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.

  6. Current Challenges for HTCMC Aero-Propulsion Components

    NASA Technical Reports Server (NTRS)

    DiCarlo, James A.; Bansal, Narottam P.

    2007-01-01

    In comparison to the best metallic materials, HTCMC aero-propulsion engine components offer the opportunity of reduced weight and higher temperature operation, with corresponding improvements in engine cooling requirements, emissions, thrust, and specific fuel consumption. Although much progress has been made in the development of advanced HTCMC constituent materials and processes, major challenges still remain for their implementation into these components. The objectives of this presentation are to briefly review (1) potential HTCMC aero-propulsion components and their generic material performance requirements, (2) recent progress at NASA and elsewhere concerning advanced constituents and processes for meeting these requirements, (3) key HTCMC component implementation challenges that are currently being encountered, and (4) on-going activities within the new NASA Fundamental Aeronautics Program that are addressing these challenges.

  7. Integrated Aero-Propulsion CFD Methodology for the Hyper-X Flight Experiment

    NASA Technical Reports Server (NTRS)

    Cockrell, Charles E., Jr.; Engelund, Walter C.; Bittner, Robert D.; Dilley, Arthur D.; Jentink, Tom N.; Frendi, Abdelkader

    2000-01-01

    Computational fluid dynamics (CFD) tools have been used extensively in the analysis and development of the X-43A Hyper-X Research Vehicle (HXRV). A significant element of this analysis is the prediction of integrated vehicle aero-propulsive performance, which includes an integration of aerodynamic and propulsion flow fields. This paper describes analysis tools used and the methodology for obtaining pre-flight predictions of longitudinal performance increments. The use of higher-fidelity methods to examine flow-field characteristics and scramjet flowpath component performance is also discussed. Limited comparisons with available ground test data are shown to illustrate the approach used to calibrate methods and assess solution accuracy. Inviscid calculations to evaluate lateral-directional stability characteristics are discussed. The methodology behind 3D tip-to-tail calculations is described and the impact of 3D exhaust plume expansion in the afterbody region is illustrated. Finally, future technology development needs in the area of hypersonic propulsion-airframe integration analysis are discussed.

  8. 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'.

  9. Exploring the dominant role of Cav1 channels in signalling to the nucleus

    PubMed Central

    Ma, Huan; Cohen, Samuel; Li, Boxing; Tsien, Richard W.

    2012-01-01

    Calcium is important in controlling nuclear gene expression through the activation of multiple signal-transduction pathways in neurons. Compared with other voltage-gated calcium channels, CaV1 channels demonstrate a considerable advantage in signalling to the nucleus. In this review, we summarize the recent progress in elucidating the mechanisms involved. CaV1 channels, already advantaged in their responsiveness to depolarization, trigger communication with the nucleus by attracting colocalized clusters of activated CaMKII (Ca2+/calmodulin-dependent protein kinase II). CaV2 channels lack this ability, but must work at a distance of >1 μm from the CaV1-CaMKII co-clusters, which hampers their relative efficiency for a given rise in bulk [Ca2+]i (intracellular [Ca2+]). Moreover, Ca2+ influx from CaV2 channels is preferentially buffered by the ER (endoplasmic reticulum) and mitochondria, further attenuating their effectiveness in signalling to the nucleus. PMID:23088728

  10. Low Voltage Activation of KCa1.1 Current by Cav3-KCa1.1 Complexes

    PubMed Central

    Rehak, Renata; Bartoletti, Theodore M.; Engbers, Jordan D. T.; Berecki, Geza; Turner, Ray W.; Zamponi, Gerald W.

    2013-01-01

    Calcium-activated potassium channels of the KCa1.1 class are known to regulate repolarization of action potential discharge through a molecular association with high voltage-activated calcium channels. The current study examined the potential for low voltage-activated Cav3 (T-type) calcium channels to interact with KCa1.1 when expressed in tsA-201 cells and in rat medial vestibular neurons (MVN) in vitro. Expression of the channel α-subunits alone in tsA-201 cells was sufficient to enable Cav3 activation of KCa1.1 current. Cav3 calcium influx induced a 50 mV negative shift in KCa1.1 voltage for activation, an interaction that was blocked by Cav3 or KCa1.1 channel blockers, or high internal EGTA. Cav3 and KCa1.1 channels coimmunoprecipitated from lysates of either tsA-201 cells or rat brain, with Cav3 channels associating with the transmembrane S0 segment of the KCa1.1 N-terminus. KCa1.1 channel activation was closely aligned with Cav3 calcium conductance in that KCa1.1 current shared the same low voltage dependence of Cav3 activation, and was blocked by voltage-dependent inactivation of Cav3 channels or by coexpressing a non calcium-conducting Cav3 channel pore mutant. The Cav3-KCa1.1 interaction was found to function highly effectively in a subset of MVN neurons by activating near –50 mV to contribute to spike repolarization and gain of firing. Modelling data indicate that multiple neighboring Cav3-KCa1.1 complexes must act cooperatively to raise calcium to sufficiently high levels to permit KCa1.1 activation. Together the results identify a novel Cav3-KCa1.1 signaling complex where Cav3-mediated calcium entry enables KCa1.1 activation over a wide range of membrane potentials according to the unique voltage profile of Cav3 calcium channels, greatly extending the roles for KCa1.1 potassium channels in controlling membrane excitability. PMID:23626738

  11. Distinct roles for Cav2.1–2.3 in activity-dependent synaptic dynamics

    PubMed Central

    Ricoy, Ulises M.

    2014-01-01

    Synaptic transmission throughout most of the CNS is steeply dependent on presynaptic calcium influx through the voltage-gated calcium channels Cav2.1–Cav2.3. In addition to triggering exocytosis, this calcium influx also recruits short-term synaptic plasticity. During the complex patterns of presynaptic activity that occur in vivo, several forms of plasticity combine to generate a synaptic output that is dynamic, in which the size of a given excitatory postsynaptic potential (EPSP) in response to a given spike depends on the short-term history of presynaptic activity. It remains unclear whether the different Cav2 channels play distinct roles in defining these synaptic dynamics and, if so, under what conditions different Cav2 family members most effectively determine synaptic output. We examined these questions by measuring the effects of calcium channel-selective toxins on synaptic transmission at the Schaffer collateral synapse in hippocampal slices from adult mice in response to both low-frequency stimulation and complex stimulus trains derived from in vivo recordings. Blockade of Cav2.1 had a greater inhibitory effect on synaptic transmission during low-frequency components of the stimulus train than on synaptic transmission during high-frequency components of the train, indicating that Cav2.1 had a greater fractional contribution to synaptic transmission at low frequencies than at high frequencies. Relative to Cav2.1, Cav2.2 had a disproportionately reduced contribution to synaptic transmission at frequencies >20 Hz, while Cav2.3 had a disproportionately increased contribution to synaptic transmission at frequencies >1 Hz. These activity-dependent effects of different Cav2 family members shape the filtering characteristics of GABAB receptor-mediated presynaptic inhibition. Thus different Cav2 channels vary in their coupling to synaptic transmission over different frequency ranges, with consequences for the frequency tuning of both synaptic dynamics and

  12. Pharmacognostic standardization of stems of Thespesia lampas (Cav.) Dalz & Gibs

    PubMed Central

    Chumbhale, DS; Upasani, CD

    2012-01-01

    Objective To establish the standardization parameters for complete pharmacognostic evaluation of stems of Thespesia lampas (T. lampas) (Cav.) Dalz & Gibs (Malvaceae), an important plant in the Indian system of medicine. Methods Morphological, microscopical, physico-chemical evaluations, florescence analysis of T. lampas stems were investigated and preliminary phytochemical analysis, GC-MS analysis and HPTLC fingerprinting were carried out for qualitative phytochemical evaluation of various extracts of stems of T. lampas. Results Chemo-microscopy revealed the presence of lignin, starch grains and calcium oxalate crystals. Physico-chemical evaluation used to determine numerical standards showed a result with total ash (9.03 ± 0.05) % w/w, acid insoluble ash (1.50 ± 0.01) % w/w, water soluble ash (2.51 ± 0.02) % w/w, sulphated ash (7.50 ± 0.01) % w/w, ethanol soluble extractive (0.24 ± 0.02) % w/w, water soluble extractive (0.08 ± 0.01) % w/w, moisture content (6.03 ± 0.05) % w/w and total crude fibre content of stem powder (47.36 ± 0.32) % w/w. Behavior characteristics of the stem powder showed presence of steroids, starch, alkaloid, flavonoids and proteins. Preliminary phytochemical analysis revealed presence of glycosides, phenolic compounds, tannins, steroids, saponins, flavonoids, carbohydrates and proteins. GC-MS analysis showed the presence of fatty acids such as dodecanoic acid, tetradecanoic acid, n-hexadecanoic acid, 9-tetradecenal and HPTLC fingerprinting revealed the presence of β-sitosterol and quercetin in stems of T. lampas. Conclusions The pharmacognostic standardization of T. lampas is useful towards establishing standards for quality, purity and sample identification. PMID:23569930

  13. Densin-180 controls the trafficking and signaling of L-type voltage-gated Cav1.2 Ca(2+) channels at excitatory synapses.

    PubMed

    Wang, Shiyi; Stanika, Ruslan I; Wang, Xiaohan; Hagen, Jussara; Kennedy, Mary B; Obermair, Gerald J; Colbran, Roger J; Lee, Amy

    2017-03-31

    Voltage-gated Cav1.2 and Cav1.3 (L-type) Ca(2+) channels regulate neuronal excitability, synaptic plasticity, and learning and memory. Densin-180 (densin) is an excitatory synaptic protein that promotes Ca(2+)-dependent facilitation of voltage-gated Cav1.3 Ca(2+) channels in transfected cells. Mice lacking densin (densin KO) exhibit defects in synaptic plasticity, spatial memory, and increased anxiety-related behaviors --phenotypes that more closely match those in mice lacking Cav1.2 than Cav1.3. Thus, we investigated the functional impact of densin on Cav1.2. We report that densin is an essential regulator of Cav1.2 in neurons, but has distinct modulatory effects compared to its regulation of Cav1.3. Densin binds to the N-terminal domain of Cav1.2 but not Cav1.3, and increases Cav1.2 currents in transfected cells and in neurons. In transfected cells, densin accelerates the forward trafficking of Cav1.2 channels without affecting their endocytosis. Consistent with a role for densin in increasing the number of postsynaptic Cav1.2 channels, overexpression of densin increases the clustering of Cav1.2 in dendrites of hippocampal neurons in culture. Compared to wild-type mice, the cell-surface levels of Cav1.2 in the brain as well as Cav1.2 current density and signaling to the nucleus are reduced in neurons from densin KO mice. We conclude that densin is an essential regulator of neuronal Cav1 channels and ensures efficient Cav1.2 Ca(2+) signaling at excitatory synapses.SIGNIFICANCE STATEMENTThe number and localization of voltage-gated Cav Ca(2+) channels are crucial determinants of neuronal excitability and synaptic transmission. We report that a protein that is highly enriched at excitatory synapses in the brain, densin-180, enhances the cell-surface trafficking and postsynaptic localization of Cav1.2 L-type Ca(2+) channels in neurons. This interaction promotes coupling of Cav1.2 channels to activity-dependent gene transcription. Our results reveal a mechanism that

  14. The CAV program for numerical evaluation of laminar natural convection heat transfer in vertical rectangular cavities

    NASA Astrophysics Data System (ADS)

    Novak, Milos H.; Nowak, Edwin S.

    1993-12-01

    To analyze the laminar natural convection heat transfer and fluid flow distribution in vertical rectangular cavities with or without inner partitions, the personal computer finite difference program entitled CAV is used. The CAV program was tested successfully for slender cavities with aspect ratios as high as R = H/ L = 90 and for the Grashof numbers, based on the cavity height, up to GrH = 3 x10 9. To make the CAV program useful for a number of applications, various types of boundary conditions can also be imposed on the program calculations. Presented are program applications dealing with the 2-D numerical analysis of natural convection heat transfer in very slender window cavities with and without small inner partitions and recommendations are made for window design.

  15. Cav1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells

    PubMed Central

    Vandael, David H.F.; Marcantoni, Andrea; Carbone, Emilio

    2015-01-01

    Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuron-like” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress. PMID:25966692

  16. [Effect of overexpression of CAV1 mediated by lentivirus on proliferation and apoptosis of HL-60 cells].

    PubMed

    Ma, Wei; Wang, Di-Di; Wang, Zhao; Zhu, Gui-Ming; Zhang, Peng-Xia

    2013-08-01

    This study was purposed to explore the effect of lentivirus-mediated CAV1 overexpression on proliferation and apoptosis in HL-60 cells. Recombinant lentiviral expression vector pcDNA-EF1-CAV1 was constructed, and cotransfected the 293TN cells with a mixture of pPACK packaging plasmids. Then collecting virus suspension infects the HL-60 cells, which make CAV1 gene stable transfection and high expression in the cells. The CAV1 protein expression status in HL-60 cells transfected was evaluated through Western blot method. Proliferative activity and apoptosis of HL-60 cells before and after transfection were detected by CCK-8 method and flow cytometry, respectively. The results showed that the PCR-positive clone screening and results of nucleotide sequencing confirmed that the CAV1 gene inserted into the expression vector pcDNA-EF1-GFP correctly, recombinant lentiviral particles Lv-CAV1 transfected HL-60 cells successfully and with transfection rate up to 90%. The result of Western blot showed that CAV1 protein expression in HL-60 cells significantly increased at 48 hours after transfection. CCK-8 result indicated that cell proliferation activity increased at 48 h after transfection (P < 0.05), flow cytometry testing results displayed that apoptosis rate of HL-60 cells obviously decreased after transfection (P < 0.01). It is concluded that the overexpression of CAV1 in HL-60 cells can inhibit cell proliferation activity and promote cell apoptosis.

  17. CaV3.1 is a tremor rhythm pacemaker in the inferior olive

    PubMed Central

    Park, Young-Gyun; Park, Hye-Yeon; Lee, C. Justin; Choi, Soonwook; Jo, Seonmi; Choi, Hansol; Kim, Yang-Hann; Shin, Hee-Sup; Llinas, Rodolfo R.; Kim, Daesoo

    2010-01-01

    The rhythmic motor pathway activation by pacemaker neurons or circuits in the brain has been proposed as the mechanism for the timing of motor coordination, and the abnormal potentiation of this mechanism may lead to a pathological tremor. Here, we show that the potentiation of CaV3.1 T-type Ca2+ channels in the inferior olive contributes to the onset of the tremor in a pharmacological model of essential tremor. After administration of harmaline, 4- to 10-Hz synchronous neuronal activities arose from the IO and then propagated to cerebellar motor circuits in wild-type mice, but those rhythmic activities were absent in mice lacking CaV3.1 gene. Intracellular recordings in brain-stem slices revealed that the CaV3.1-deficient inferior olive neurons lacked the subthreshold oscillation of membrane potentials and failed to trigger 4- to 10-Hz rhythmic burst discharges in the presence of harmaline. In addition, the selective knockdown of CaV3.1 gene in the inferior olive by shRNA efficiently suppressed the harmaline-induced tremor in wild-type mice. A mathematical model constructed based on data obtained from patch-clamping experiments indicated that harmaline could efficiently potentiate CaV3.1 channels by changing voltage-dependent responsiveness in the hyperpolarizing direction. Thus, CaV3.1 is a molecular pacemaker substrate for intrinsic neuronal oscillations of inferior olive neurons, and the potentiation of this mechanism can be considered as a pathological cause of essential tremor. PMID:20498062

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Calcium CaV1 channel subtype mRNA expression in Parkinson's disease examined by in situ hybridization.

    PubMed

    Hurley, Michael J; Gentleman, Steve M; Dexter, David T

    2015-03-01

    The factors which make some neurons vulnerable to neurodegeneration in Parkinson's disease while others remain resistant are not fully understood. Studies in animal models of Parkinson's disease suggest that preferential use of CaV1.3 subtypes by neurons may contribute to the neurodegenerative process by increasing mitochondrial oxidant stress. This study quantified the level of mRNA for the CaV1 subtypes found in the brain by in situ hybridization using CaV1 subtype-specific [(35)S]-radiolabelled oligonucleotide probes. In normal brain, the greatest amount of messenger RNA (mRNA) for each CaV1 subtype was found in the midbrain (substantia nigra), with a moderate level in the pons (locus coeruleus) and lower quantities in cerebral cortex (cingulate and primary motor). In Parkinson's disease, the level of CaV1 subtype mRNA was maintained in the midbrain and pons, despite cell loss in these areas. In cingulate cortex, CaV1.2 and CaV1.3 mRNA increased in cases with late-stage Parkinson's disease. In primary motor cortex, the level of CaV1.2 mRNA increased in late-stage Parkinson's disease. The level of CaV1.3 mRNA increased in primary motor cortex of cases with early-stage Parkinson's disease and normalized to near the control level in cases from late-stage Parkinson's disease. The finding of elevated CaV1 subtype expression in cortical brain regions supports the view that disturbed calcium homeostasis is a feature of Parkinson's disease throughout brain and not only a compensatory consequence to the neurodegenerative process in areas of cell loss.

  3. Replication of chicken anemia virus (CAV) requires apoptin and is complemented by VP3 of human torque teno virus (TTV).

    PubMed

    Prasetyo, Afiono Agung; Kamahora, Toshio; Kuroishi, Ayumu; Murakami, Kyoko; Hino, Shigeo

    2009-03-01

    To test requirement for apoptin in the replication of chicken anemia virus (CAV), an apoptin-knockout clone, pCAV/Ap(-), was constructed. DNA replication was completely abolished in cells transfected with replicative form of CAV/Ap(-). A reverse mutant competent in apoptin production regained the full level of DNA replication. DNA replication and virus-like particle (VLP) production of CAV/Ap(-) was fully complemented by supplementation of the wild-type apoptin. The virus yield of a point mutant, CAV/ApT(108)I, was 1/40 that of the wild type, even though its DNA replication level was full. The infectious titer of CAV was fully complemented by supplementing apoptin. Progeny virus was free from reverse mutation for T(108)I. To localize the domain within apoptin molecule inevitable for CAV replication, apoptin-mutant expressing plasmids, pAp1, pAp2, pAp3, and pAp4, were constructed by deleting amino acids 10-36, 31-59, 59-88 and 80-112, respectively. While Ap1 and Ap2 were preferentially localized in nuclei, Ap3 and Ap4 were mainly present in cytoplasm. Although complementation capacity of Ap3 and Ap4 was 1/10 of the wild type, neither of them completely lost its activity. VP3 of TTV did fully complement the DNA replication and VLP of CAV/Ap(-). These data suggest that apoptin is inevitable not only for DNA replication but also VLP of CAV. The common feature of apoptin and TTV-VP3 presented another evidence for close relatedness of CAV and TTV.

  4. 78 FR 32363 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA), Department... propose to rescind an airworthiness directive (AD) for PIAGGIO AERO INDUSTRIES S.p.A. Model P-180...-140, 1200 New Jersey Avenue SE., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday...

  5. 77 FR 35888 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for PIAGGIO AERO INDUSTRIES S.p.A. Model P-180 airplanes. This...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For...

  6. 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...

  7. 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...

  8. 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...

  9. Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.

    PubMed

    Findeisen, Felix; Campiglio, Marta; Jo, Hyunil; Abderemane-Ali, Fayal; Rumpf, Christine H; Pope, Lianne; Rossen, Nathan D; Flucher, Bernhard E; DeGrado, William F; Minor, Daniel L

    2017-03-17

    For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein-protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (CaV) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (CaVβ). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:CaVβ interactions and reduce the entropic penalty associated with AID binding to CaVβ. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the CaVα1:CaVβ interaction that modulate CaV function in an CaVβ isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein-protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based CaV modulator design.

  10. Exhaust System Experiments at NASA's AeroAcoustic Propulsion Lab

    NASA Technical Reports Server (NTRS)

    Bridges, James

    2011-01-01

    This presentation gives an overview of the planned testing in the AeroAcoustic Propulsion Lab (AAPL) in the coming 15 months. It was stressed in the presentation that these are plans that are subject to change due to changes in funding and/or programmatic direction. The first chart shows a simplified schedule of test entries with funding sponsor and dates for each. In subsequent charts are pages devoted to the Objectives and Issues with each test entry, along with a graphic intended to represent the test activity. The chart for each test entry also indicates sponsorship of the activity, and a contact person.!

  11. 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.

  12. Unsteady fluid and optical simulation of transonic aero-windows

    NASA Technical Reports Server (NTRS)

    Atwood, Christopher A.

    1993-01-01

    The time-varying fluid and optical fields of several cavity configurations have been computed on overset mesh systems using the Reynolds-averaged Navier-Stokes equations and geometric optics. Comparisons between numerical results and Airborne Optical Adjunct (AOA) flight data are made in two-dimensions for a quieted cavity geometry with two lip-blowing rates. In three-dimensions, two proposed aero-window locations for the Stratospheric Observatory For Infrared Astronomy (SOFIA) are discussed. The simulations indicate that convection of large shear layer structures across the aperture cause the blur circle diameter to be three times the diffraction-limited diameter in the near-infrared band.

  13. Fatigue Life Analysis of Turbine Disks Based on Load Spectra of Aero-engines

    NASA Astrophysics Data System (ADS)

    Li, Yan-Feng; Lv, Zhiqiang; Cai, Wei; Zhu, Shun-Peng; Huang, Hong-Zhong

    2016-04-01

    Load spectra of aero-engines reflect the process of operating aircrafts as well as the changes of parameters of aircrafts. According to flight hours and speed cycle numbers of the aero-engines, the relationship between load spectra and the fatigue life of main components of the aero-engines is obtained. Based on distribution function and a generalized stress-strength interference model, the cumulative fatigue damage of aero-engines is then calculated. After applying the analysis of load spectra and the cumulative fatigue damage theory, the fatigue life of the first-stage turbine disks of the aero-engines is evaluated by using the S-N curve and Miner's rule in this paper.

  14. 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.

  15. 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

  16. CAV1 siRNA Reduces Membrane Estrogen Receptor-α Levels and Attenuates Sexual Receptivity

    PubMed Central

    Christensen, Amy

    2012-01-01

    Although classic estrogen receptors (ER) have been proposed to mediate estradiol signaling, it has been relatively recently that mechanisms of trafficking these receptors have been elucidated. ERα is palmitoylated and associates with caveolin proteins to be targeted to the cell membrane. Caveolins are scaffold proteins that not only traffic ERα to the membrane but also are involved in establishing metabotropic glutamate receptor interactions that are necessary for activating G protein signaling. To demonstrate the role of caveolin proteins in regulating an estradiol-dependent behavior, sexual receptivity, we used small interfering RNA to knock down caveolin-1 (CAV1) expression in the arcuate nucleus of the hypothalamus. In CAV1 knockdown rats, membrane, but not intracellular levels of ERα, were significantly reduced. As expected, estrogenic stimulation of the arcuate nucleus of the hypothalamus to medial preoptic nucleus projection was abrogated in CAV1 knockdown rats, indicating that the membrane-initiated activation of this circuit was compromised. Moreover, estradiol-induced lordosis behavior that is dependent on activation of μ-opioid receptors in the medial preoptic nucleus was also significantly reduced. Thus, CAV1-mediated ERα trafficking to the cell membrane is required for estradiol activation of circuits underlying female sexual receptivity. PMID:22669893

  17. 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...

  18. 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...

  19. Involvement of the Cav3.2 T-type calcium channel in thalamic neuron discharge patterns

    PubMed Central

    2011-01-01

    Background Mice that have defects in their low-threshold T-type calcium channel (T-channel) genes show altered pain behaviors. The changes in the ratio of nociceptive neurons and the burst firing property of reticular thalamic (RT) and ventroposterior (VP) neurons in Cav3.2 knockout (KO) mice were studied to test the involvement of thalamic T-channel and burst firing activity in pain function. Results Under pentobarbital or urethane anesthesia, the patterns of tonic and burst firings were recorded in functionally characterized RT and VPL neurons of Cav3.2 KO mice. Many RT neurons were nociceptive (64% under pentobarbital anesthesia and 50% under urethane anesthesia). Compared to their wild-type (WT) controls, fewer nociceptive RT neurons were found in Cav3.2 KO mice. Both nociceptive and tactile RT neurons showed fewer bursts in Cav3.2 KO mice. Within a burst, RT neurons of Cav3.2 KO mice had a lower spike frequency and less-prominent accelerando-decelerando change. In contrast, VP neurons of Cav3.2 KO mice showed a higher ratio of bursts and a higher discharge rate within a burst than those of the WT control. In addition, the long-lasting tonic firing episodes in RT neurons of the Cav3.2 KO had less stereotypic regularity than their counterparts in WT mice. Conclusions RT might be important in nociception of the mouse. In addition, we showed an important role of Cav3.2 subtype of T-channel in RT burst firing pattern. The decreased occurrence and slowing of the bursts in RT neurons might cause the increased VP bursts. These changes would be factors contributing to alternation of pain behavior in the Cav3.2 KO mice. PMID:21639922

  20. Caldendrin, a neuron-specific modulator of Cav/1.2 (L-type) Ca2+ channels.

    PubMed

    Tippens, Alyssa L; Lee, Amy

    2007-03-16

    EF-hand Ca2+-binding proteins such as calmodulin and CaBP1 have emerged as important regulatory subunits of voltage-gated Ca2+ channels. Here, we show that caldendrin, a variant of CaBP1 enriched in the brain, interacts with and distinctly modulates Cav1.2 (L-type) voltage-gated Ca2+ channels relative to other Ca2+-binding proteins. Caldendrin binds to the C-terminal IQ-domain of the pore-forming alpha1-subunit of Cav1.2 (alpha(1)1.2) and competitively displaces calmodulin and CaBP1 from this site. Compared with CaBP1, caldendrin causes a more modest suppression of Ca2+-dependent inactivation of Cav1.2 through a different subset of molecular determinants. Caldendrin does not bind to the N-terminal domain of alpha11.2, a site that is critical for functional interactions of the channel with CaBP1. Deletion of the N-terminal domain inhibits CaBP1, but spares caldendrin modulation of Cav1.2 inactivation. In contrast, mutations of the IQ-domain abolish physical and functional interactions of caldendrin and Cav1.2, but do not prevent channel modulation by CaBP1. Using antibodies specific for caldendrin and Cav1.2, we show that caldendrin coimmunoprecipitates with Cav1.2 from the brain and colocalizes with Cav1.2 in somatodendritic puncta of cortical neurons in culture. Our findings reveal functional diversity within related Ca2+-binding proteins, which may enhance the specificity of Ca2+ signaling by Cav1.2 channels in different cellular contexts.

  1. Contribution of electromechanical coupling between KV and CaV1.2 channels to coronary dysfunction in obesity

    PubMed Central

    Berwick, Zachary C.; Dick, Gregory M.; O’Leary, Heather A.; Bender, Shawn B.; Goodwill, Adam G.; Moberly, Steven P.; Owen, Meredith Kohr; Miller, Steven J.; Obukhov, Alexander G.

    2013-01-01

    Previous investigations indicate that diminished functional expression of voltage-dependent K+ (KV) channels impairs control of coronary blood flow in obesity/metabolic syndrome. The goal of this investigation was to test the hypothesis that KV channels are electromechanically coupled to CaV1.2 channels and that coronary microvascular dysfunction in obesity is related to subsequent increases in CaV1.2 channel activity. Initial studies revealed that inhibition of KV channels with 4-aminopyridine (4AP, 0.3 mM) increased intracellular [Ca2+], contracted isolated coronary arterioles and decreased coronary reactive hyperemia. These effects were reversed by blockade of CaV1.2 channels. Further studies in chronically instrumented Ossabaw swine showed that inhibition of CaV1.2 channels with nifedipine (10 μg/kg, iv) had no effect on coronary blood flow at rest or during exercise in lean swine. However, inhibition of CaV1.2 channels significantly increased coronary blood flow, conductance, and the balance between coronary flow and metabolism in obese swine (P < 0.05). These changes were associated with a ~50 % increase in inward CaV1.2 current and elevations in expression of the pore-forming subunit (α1c) of CaV1.2 channels in coronary smooth muscle cells from obese swine. Taken together, these findings indicate that electromechanical coupling between KV and CaV1.2 channels is involved in the regulation of coronary vasomotor tone and that increases in CaV1.2 channel activity contribute to coronary microvascular dysfunction in the setting of obesity. PMID:23856709

  2. 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.

  3. 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.

  4. Spectral Behavior of Weakly Compressible Aero-Optical Distortions

    NASA Astrophysics Data System (ADS)

    Mathews, Edwin; Wang, Kan; Wang, Meng; Jumper, Eric

    2016-11-01

    In classical theories of optical distortions by atmospheric turbulence, an appropriate and key assumption is that index-of-refraction variations are dominated by fluctuations in temperature and the effects of turbulent pressure fluctuations are negligible. This assumption is, however, not generally valid for aero-optical distortions caused by turbulent flow over an optical aperture, where both temperature and pressures fluctuations may contribute significantly to the index-of-refraction fluctuations. A general expression for weak fluctuations in refractive index is derived using the ideal gas law and Gladstone-Dale relation and applied to describe the spectral behavior of aero-optical distortions. Large-eddy simulations of weakly compressible, temporally evolving shear layers are then used to verify the theoretical results. Computational results support theoretical findings and confirm that if the log slope of the 1-D density spectrum in the inertial range is -mρ , the optical phase distortion spectral slope is given by - (mρ + 1) . The value of mρ is then shown to be dependent on the ratio of shear-layer free-stream densities and bounded by the spectral slopes of temperature and pressure fluctuations. Supported by HEL-JTO through AFOSR Grant FA9550-13-1-0001 and Blue Waters Graduate Fellowship Program.

  5. 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

  6. 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

  7. C-Terminal Modulatory Domain Controls Coupling of Voltage-Sensing to Pore Opening in Cav1.3 L-type Ca2+ Channels

    PubMed Central

    Lieb, Andreas; Ortner, Nadine; Striessnig, Jörg

    2014-01-01

    Activity of voltage-gated Cav1.3 L-type Ca2+ channels is required for proper hearing as well as sinoatrial node and brain function. This critically depends on their negative activation voltage range, which is further fine-tuned by alternative splicing. Shorter variants miss a C-terminal regulatory domain (CTM), which allows them to activate at even more negative potentials than C-terminally long-splice variants. It is at present unclear whether this is due to an increased voltage sensitivity of the Cav1.3 voltage-sensing domain, or an enhanced coupling of voltage-sensor conformational changes to the subsequent opening of the activation gate. We studied the voltage-dependence of voltage-sensor charge movement (QON-V) and of current activation (ICa-V) of the long (Cav1.3L) and a short Cav1.3 splice variant (Cav1.342A) expressed in tsA-201 cells using whole cell patch-clamp. Charge movement (QON) of Cav1.3L displayed a much steeper voltage-dependence and a more negative half-maximal activation voltage than Cav1.2 and Cav3.1. However, a significantly higher fraction of the total charge had to move for activation of Cav1.3 half-maximal conductance (Cav1.3: 68%; Cav1.2: 52%; Cav3.1: 22%). This indicated a weaker coupling of Cav1.3 voltage-sensor charge movement to pore opening. However, the coupling efficiency was strengthened in the absence of the CTM in Cav1.342A, thereby shifting ICa-V by 7.2 mV to potentials that were more negative without changing QON-V. We independently show that the presence of intracellular organic cations (such as n-methyl-D-glucamine) induces a pronounced negative shift of QON-V and a more negative activation of ICa-V of all three channels. These findings illustrate that the voltage sensors of Cav1.3 channels respond more sensitively to depolarization than those of Cav1.2 or Cav3.1. Weak coupling of voltage sensing to pore opening is enhanced in the absence of the CTM, allowing short Cav1.342A splice variants to activate at lower voltages

  8. Ammonium Increases TRPC1 Expression Via Cav-1/PTEN/AKT/GSK3β Pathway.

    PubMed

    Wang, Wei; Gu, Li; Verkhratsky, Alexei; Peng, Liang

    2017-03-01

    Hyperammonemia occurring following acute liver failure is the primary cause of hepatic encephalopathy. In the brain, ammonium is catabolised by glutamine synthetase expressed exclusively in astroglia; ammonium overload impairs astroglial homeostatic systems. Previously, we had reported that chronic treatment with 3 mM ammonia increased expression of transient receptor potential canonic 1 (TRPC1) channels and Ca(2+) release from intracellular Ca(2+) stores (Liang et al. in Neurochem Res 39:2127-2135, 2014). Glycogen synthase kinase 3β (GSK-3β) has a key role in several astroglial signalling pathways and is known to be affected in various CNS diseases. We have studied the involvement of Cav-1/PTEN/AKT/GSK-3β signalling system in regulation of TRPC1 gene expression by ammonium. Effects of chronic (1-5 days) treatment with ammonium chloride (ammonium), at pathologically relevant concentrations of 1-5 mM were investigated on primary cultures of mouse cerebral astrocytes. We quantified expression of caveolin-1 (Cav-1), membrane content of phosphatase and tensin homologue (PTEN), phosphorylation of AKT and GSK-3β, and expression of TRPC1 channels. Ammonium significantly increased expression of Cav-1 mRNA and protein, mRNA of TRPC1 as well as membrane content of PTEN; conversely phosphorylation of AKT and GSK-3β were significantly decreased. These changes were abolished following astrocytes treatment with siRNA specific to Cav-1, indicating the involvement of Cav-1/PTEN/PI3K/AKT pathway. Similar results were found in the brains of adult mice subjected to intraperitoneal injection of urease (a model for hyperammoniemia) for 1-5 days. In transgenic mice tagged with an astrocyte-specific or neurone-specific markers (used for fluorescence-activated cell sorting of astrocytes vs. neurones) and treated with intraperitoneal injections of urease for 3 days, the Cav-1 gene mRNA expression was up-regulated in astrocytes, but not in neurones. The up-regulation of TRPC1 gene

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. The Modular Aero-Propulsion System Simulation (MAPSS) Users' Guide

    NASA Technical Reports Server (NTRS)

    Parker, Khary I.; Melcher, Kevin J.

    2004-01-01

    The Modular Aero-Propulsion System Simulation is a flexible turbofan engine simulation environment that provides the user a platform to develop advanced control algorithms. It is capable of testing the performance of control designs on a validated and verified generic engine model. In addition, it is able to generate state-space linear models of the engine model to aid in controller design. The engine model used in MAPSS is a generic high-pressure ratio, dual-spool, lowbypass, military-type, variable cycle turbofan engine with a digital controller. MAPSS is controlled by a graphical user interface (GUI) and this guide explains how to use it to take advantage of the capabilities of MAPSS.

  14. 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.

  15. 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

  16. A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons.

    PubMed

    Bravo-Martínez, Jorge; Arenas, Isabel; Vivas, Oscar; Rebolledo-Antúnez, Santiago; Vázquez-García, Mario; Larrazolo, Arturo; García, David E

    2012-10-01

    No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(V)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(V)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca(V)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(V)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

  17. 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

  18. 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.

  19. 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

  20. Technical Note: Simulation of detailed aerosol chemistry on the global scale using MECCA-AERO

    NASA Astrophysics Data System (ADS)

    Kerkweg, A.; Sander, R.; Tost, H.; Jöckel, P.; Lelieveld, J.

    2007-06-01

    We present the MESSy submodel MECCA-AERO, which simulates both aerosol and gas phase chemistry within one comprehensive mechanism. Including the aerosol phase into the chemistry mechanism increases the stiffness of the resulting set of differential equations. The numerical aspects of the approach followed in MECCA-AERO are presented. MECCA-AERO requires input of an aerosol dynamical/microphysical model to provide the aerosol size and particle number information of the modes/bins for which the chemistry is explicitly calculated. Additional precautions are required to avoid the double counting of processes, especially for sulphate in the aerosol dynamical and the chemistry model. This coupling is explained in detail. To illustrate the capabilities of the new aerosol submodel, examples for species usually treated in aerosol dynamical models are shown. The aerosol chemistry as provided by MECCA-AERO is very sumptuous and not readily applicable for long-term simulations, though it provides a reference to evaluate simplified approaches.

  1. Technical Note: simulation of detailed aerosol chemistry on the global scale using MECCA-AERO

    NASA Astrophysics Data System (ADS)

    Kerkweg, A.; Sander, R.; Tost, H.; Jöckel, P.; Lelieveld, J.

    2007-03-01

    We present the MESSy submodel MECCA-AERO, which simulates both aerosol and gas phase chemistry with the same mechanism. Including the aerosol phase into the chemistry mechanism increases the stiffness of the resulting set of differential equations. The numerical aspects of the approach followed in MECCA-AERO are presented. MECCA-AERO requires input of an aerosol dynamical/microphysical model to provide the aerosol size and particle number information of the modes/bins for which the chemistry is explicitly calculated. Additional precautions are required to avoid the double counting of processes, especially for sulphate in the aerosol dynamical and the chemistry model. This coupling is explained in detail. To illustrate the capabilities of the new aerosol submodel, examples for species usually treated in aerosol dynamical models are shown. The aerosol chemistry as provided by MECCA-AERO is very sumptuous and not readily applicable for long-term simulations, though it provides a reference to evaluate simplified approaches.

  2. [Flight nurses' comprehension about their role in the multiprofesional team of aero-medical transport].

    PubMed

    Scuissiato, Dayane Reinhardt; Boffi, Letícia Valois; da Rocha, Roseline da Rocha; Montezeli, Juliana Helena; Bordin, Michelle Taverna; Peres, Aida Maris

    2012-01-01

    This is a descriptive qualitative research which aimed at identifying the flight nurses' comprehension by about their role in the aero-medical multiprofesional team. A semi-structured interview was carried out with eight flight nurses from Curitiba-PR, from June to August 2009. The speeches were analyzed by the content analysis, from which three categories emerged. The first describes the responsibilities of the flight nurses as managers of the aero-medical mission, planning for before, during and after the transport, what includes the aircraft check-list and knowledge of the patient's case. The second category deals with aspects of these professionals as care providers to the aero-transferred patient. The third describes communication and team-work as fundamental requirements for flight nurses. It was concluded that the nurse in aero-medical team mixes management and caring in his/her professional practice by the use of specific competences.

  3. c-Src/Cav1-dependent activation of the EGFR by Dsg2

    PubMed Central

    Roberts, Brett J.; Cooper, Felicia; Brennan-Crispi, Donna M.; Deguchi, Takahiro; Peltonen, Sirkku; James K., Wahl; Mahoney, M? G.

    2016-01-01

    The desmosomal cadherin, desmoglein 2 (Dsg2), is deregulated in a variety of human cancers including those of the skin. When ectopically expressed in the epidermis of transgenic mice, Dsg2 activates multiple mitogenic signaling pathways and increases susceptibility to tumorigenesis. However, the molecular mechanism responsible for Dsg2-mediated cellular signaling is poorly understood. Here we show overexpression as well as co-localization of Dsg2 and EGFR in cutaneous SCCs in vivo. Using HaCaT keratinocytes, knockdown of Dsg2 decreases EGFR expression and abrogates the activation of EGFR, c-Src and Stat3, but not Erk1/2 or Akt, in response to EGF ligand stimulation. To determine whether Dsg2 mediates signaling through lipid microdomains, sucrose density fractionation illustrated that Dsg2 is recruited to and displaces Cav1, EGFR and c-Src from light density lipid raft fractions. STED imaging confirmed that the presence of Dsg2 disperses Cav1 from the cell-cell borders. Perturbation of lipid rafts with the cholesterol-chelating agent MβCD also shifts Cav1, c-Src and EGFR out of the rafts and activates signaling pathways. Functionally, overexpression of Dsg2 in human SCC A431 cells enhances EGFR activation and increases cell proliferation and migration through a c-Src and EGFR dependent manner. In summary, our data suggest that Dsg2 stimulates cell growth and migration by positively regulating EGFR level and signaling through a c-Src and Cav1-dependent mechanism using lipid rafts as signal modulatory platforms. PMID:26918609

  4. 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

  5. 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.

  6. The surge of flavonoids as novel, fine regulators of cardiovascular Cav channels.

    PubMed

    Fusi, Fabio; Spiga, Ottavia; Trezza, Alfonso; Sgaragli, Giampietro; Saponara, Simona

    2017-02-05

    Ion channels underlie a wide variety of physiological processes that involve rapid changes in cell dynamics, such as cardiac and vascular smooth muscle contraction. Overexpression or dysfunction of these membrane proteins are the basis of many cardiovascular diseases that represent the leading cause of morbidity and mortality for human beings. In the last few years, flavonoids, widely distributed in the plant kingdom, have attracted the interest of many laboratories as an emerging class of fine ion, in particular Cav, channels modulators. Pieces of in vitro evidence for direct as well as indirect effects exerted by various flavonoids on ion channel currents are now accumulating in the scientific literature. This activity may be responsible, at least in part, for the beneficial and protective effects of dietary flavonoids toward cardiovascular diseases highlighted in several epidemiological studies. Here we examine numerous studies aimed at analysing this feature of flavonoids, focusing on the mechanisms that promote their sometimes controversial activities at cardiovascular Cav channels. New methodological approaches, such as molecular modelling and docking to Cav1.2 channel α1c subunit, used to elucidate flavonoids intrinsic mechanism of action, are introduced. Moreover, flavonoid-membrane interaction, bioavailability, and antioxidant activity are taken into account and discussed.

  7. 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.

  8. Genetic Tracing of Cav3.2 T-Type Calcium Channel Expression in the Peripheral Nervous System

    PubMed Central

    Bernal Sierra, Yinth A.; Haseleu, Julia; Kozlenkov, Alexey; Bégay, Valérie; Lewin, Gary R.

    2017-01-01

    Characterizing the distinct functions of the T-type ion channel subunits Cav3.1, 3.2 or 3.3 has proven difficult due to their highly conserved amino-acid sequences and the lack of pharmacological blockers specific for each subunit. To precisely determine the expression pattern of the Cav3.2 channel in the nervous system we generated two knock-in mouse strains that express EGFP or Cre recombinase under the control of the Cav3.2 gene promoter. We show that in the brains of these animals, the Cav3.2 channel is predominantly expressed in the dentate gyrus of the hippocampus. In the peripheral nervous system, the activation of the promoter starts at E9.5 in neural crest cells that will give rise to dorsal root ganglia (DRG) neurons, but not sympathetic neurons. As development progresses the number of DRG cells expressing the Cav3.2 channel reaches around 7% of the DRG at E16.5, and remains constant until E18.5. Characterization of sensory neuron subpopulations at E18.5 showed that EGFP+ cells are a heterogeneous population consisting mainly of TrkB+ and TrkC+ cells, while only a small percentage of DRG cells were TrkA+. Genetic tracing of the sensory nerve end-organ innervation of the skin showed that the activity of the Cav3.2 channel promoter in sensory progenitors marks many mechanoreceptor and nociceptor endings, but spares slowly adapting mechanoreceptors with endings associated with Merkel cells. Our genetic analysis reveals for the first time that progenitors that express the Cav3.2 T-type calcium channel, defines a sensory specific lineage that populates a large proportion of the DRG. Using our Cav3.2-Cre mice together with AAV viruses containing a conditional fluorescent reporter (tdTomato) we could also show that Cre expression is largely restricted to two functionally distinct sensory neuron types in the adult ganglia. Cav3.2 positive neurons innervating the skin were found to only form lanceolate endings on hair follicles and are probably identical to D

  9. Isoflurane, But Not the Nonimmobilizers F6 and F8, Inhibits Rat Spinal Cord Motor Neuron CaV1 Calcium Currents

    PubMed Central

    Recio-Pinto, Esperanza; Montoya-Gacharna, Jose V.; Xu, Fang; Blanck, Thomas J.J.

    2015-01-01

    Background Volatile anesthetics decrease Ca2+ entry through voltage-dependent Ca2+ channels. Ca2+ influences neurotransmitter release and neuronal excitability. Because volatile anesthetics act specifically on the spinal cord to produce immobility, we examined the effect of isoflurane and the nonimmobilizers F6 (1, 2- dichlorohexafluorocyclobutane) and F8 (2, 3- dichlorooctafluorobutane) on CaV1 and CaV2 Ca2+ channels in spinal cord motor neurons and dorsal root ganglion neurons. Methods Using patch clamping, we compared the effects of isoflurane with those of F6 and F8 on CaV1 and CaV2 channels in isolated, cultured adult rat spinal cord motor neurons and on CaV1 and CaV2 channels in adult rat dorsal root ganglion sensory neurons. Results In spinal cord motor neurons, isoflurane, but not F6 or F8, inhibited currents through CaV1 channels. Isoflurane and at least one of the nonimmobilizers inhibited currents through CaV1 and CaV2 channels in dorsal root ganglion neurons and Cav2 in spinal cord motor neurons Conclusion The findings that isoflurane, but not nonimmobilizers, inhibited CaV1 Ca2+ channels in spinal cord motor neurons are consistent with the notion that spinal cord motor neurons might mediate isoflurane-induced immobility. Additional studies are required to examine whether inhibition of CaV1 calcium currents in spinal cord motor neurons are sufficient, or whether actions on other channels/proteins also contribute to isoflurane-induced immobility. PMID:26702867

  10. The voltage-dependent L-type Ca2+ (CaV1.2) channel C-terminus fragment is a bi-modal vasodilator.

    PubMed

    Bannister, John P; Leo, Marie Dennis; Narayanan, Damodaran; Jangsangthong, Wanchana; Nair, Anitha; Evanson, Kirk W; Pachuau, Judith; Gabrick, Kyle S; Boop, Frederick A; Jaggar, Jonathan H

    2013-06-15

    Voltage-dependent L-type Ca(2+) channels (CaV1.2) are the primary Ca(2+) entry pathway in vascular smooth muscle cells (myocytes). CaV1.2 channels control systemic blood pressure and organ blood flow and are pathologically altered in vascular diseases, which modifies vessel contractility. The CaV1.2 distal C-terminus is susceptible to proteolytic cleavage, which yields a truncated CaV1.2 subunit and a cleaved C-terminal fragment (CCt). Previous studies in cardiac myocytes and neurons have identified CCt as both a transcription factor and CaV1.2 channel inhibitor, with different signalling mechanisms proposed to underlie some of these effects. CCt existence and physiological functions in arterial myocytes are unclear, but important to study given the functional significance of CaV1.2 channels. Here, we show that CCt exists in myocytes of both rat and human resistance-size cerebral arteries, where it locates to both the nucleus and plasma membrane. Recombinant CCt expression in arterial myocytes inhibited CaV1.2 transcription and reduced CaV1.2 protein. CCt induced a depolarizing shift in the voltage dependence of both CaV1.2 current activation and inactivation, and reduced non-inactivating current in myocytes. Recombinant truncated CCt lacking a putative nuclear localization sequence (92CCt) did not locate to the nucleus and had no effect on arterial CaV1.2 transcription or protein. However, 92CCt shifted the voltage dependence of CaV1.2 activation and inactivation similarly to CCt. CCt and 92CCt both inhibited pressure- and depolarization-induced vasoconstriction, although CCt was a far more effective vasodilator. These data demonstrate that endogenous CCt exists and reduces both CaV1.2 channel expression and voltage sensitivity in arterial myocytes. Thus, CCt is a bi-modal vasodilator.

  11. Voltage-dependent regulation of CaV2.2 channels by Gq-coupled receptor is facilitated by membrane-localized β subunit.

    PubMed

    Keum, Dongil; Baek, Christina; Kim, Dong-Il; Kweon, Hae-Jin; Suh, Byung-Chang

    2014-10-01

    G protein-coupled receptors (GPCRs) signal through molecular messengers, such as Gβγ, Ca(2+), and phosphatidylinositol 4,5-bisphosphate (PIP2), to modulate N-type voltage-gated Ca(2+) (CaV2.2) channels, playing a crucial role in regulating synaptic transmission. However, the cellular pathways through which GqPCRs inhibit CaV2.2 channel current are not completely understood. Here, we report that the location of CaV β subunits is key to determining the voltage dependence of CaV2.2 channel modulation by GqPCRs. Application of the muscarinic agonist oxotremorine-M to tsA-201 cells expressing M1 receptors, together with CaV N-type α1B, α2δ1, and membrane-localized β2a subunits, shifted the current-voltage relationship for CaV2.2 activation 5 mV to the right and slowed current activation. Muscarinic suppression of CaV2.2 activity was relieved by strong depolarizing prepulses. Moreover, when the C terminus of β-adrenergic receptor kinase (which binds Gβγ) was coexpressed with N-type channels, inhibition of CaV2.2 current after M1 receptor activation was markedly reduced and delayed, whereas the delay between PIP2 hydrolysis and inhibition of CaV2.2 current was decreased. When the Gβγ-insensitive CaV2.2 α1C-1B chimera was expressed, voltage-dependent inhibition of calcium current was virtually abolished, suggesting that M1 receptors act through Gβγ to inhibit CaV2.2 channels bearing membrane-localized CaV β2a subunits. Expression of cytosolic β subunits such as β2b and β3, as well as the palmitoylation-negative mutant β2a(C3,4S), reduced the voltage dependence of M1 muscarinic inhibition of CaV2.2 channels, whereas it increased inhibition mediated by PIP2 depletion. Together, our results indicate that, with membrane-localized CaV β subunits, CaV2.2 channels are subject to Gβγ-mediated voltage-dependent inhibition, whereas cytosol-localized β subunits confer more effective PIP2-mediated voltage-independent regulation. Thus, the voltage dependence of

  12. Inter-channel scaffolding of presynaptic CaV2.2 via the C terminal PDZ ligand domain.

    PubMed

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

    2013-05-15

    Calcium entry through CaV2.2 calcium channels clustered at the active zone (AZ) of the presynaptic nerve terminal gates synaptic vesicle (SV) fusion and the discharge of neurotransmitters, but the mechanism of channel scaffolding remains poorly understood. Recent studies have implicated the binding of a PDZ ligand domain (PDZ-LD) at the tip of the channel C terminal to a partner PDZ domain on RIM1/2, a synaptic vesicle-associated protein. To explore CaV2.2 scaffolding, we created intracellular region fusion proteins and used these to test for binding by 'fishing' for native CaV2.2 channels from cell lysates. Fusion proteins mimicking the distal half of the channel C terminal (C3strep) reliably captured CaV2.2 from whole brain crude membrane or purified synaptosome membrane lysates, whereas channel I-II loop or the distal half of the II-III loop proteins were negative. This capture could be replicated in a non-synaptic environment using CaV2.2 expressed in a cell line. The distal tip PDZ-LD, DDWC-COOH, was confirmed as the critical binding site by block of pull-down with mimetic peptides. Pull-down experiments using brain crude membrane lysates confirmed that RIM1/2 can bind to the DDWC PDZ-LD. However, robust CaV2.2 capture was observed from synaptosome membrane or in the cell line expression system with little or no RIM1/2 co-capture. Thus, we conclude that CaV2.2 channels can scaffold to each other via an interaction that involves the PDZ-LD by an inter-channel linkage bridged by an unknown protein.

  13. AeroCOM Biomass Burning Emissions Experiment-Overview

    NASA Astrophysics Data System (ADS)

    Petrenko, M. M.; Chin, M.; Kahn, R. A.; Val Martin, M.

    2014-12-01

    Biomass burning (BB) is one of the major sources of optically and chemically potent carbonaceous aerosols, gaseous aerosol precursors, and volatile organic compounds. It is, therefore, important to represent these emissions as accurately as possible in the global and regional models. To correctly simulate BB emissions from a fire, the model needs two key inputs: emission source strength for the fire and the emission injection height. Based on pilot studies of injection height by M. Val Martin et al. (2010, 2012), and of source strength by M. Petrenko et al. (2012), we proposed an AeroCom-coordinated multi-model BB experiment. The core objectives of the experiment are: To inter-compare and quantify the accuracy and diversity of the AeroCom model simulated BB AOD using a common emissions inventory. To propose a region-by-region emission correction scheme based on the comparisons of model output with satellite snapshots of smoke-plume optical depth from the MODIS and MISR instruments. This will allow us to bring the widely used GFED v3 emissions inventory to the levels needed to improve model-observation comparisons. To test smoke injection height-emission intensity relationships used in global models against MISR multi-angle smoke-plume-height retrievals. With the first stage of the BB experiment focused on the source strength, this talk will provide an update on development and testing the method of using satellite-measured aerosol optical depth snapshots to constrain BB aerosol emissions in the global models. The global datasets of fire-and-smoke events, observed by MISR and MODIS during 2006, 2007 and 2008, to be used for model-satellite comparisons, will also be described. These events were selected according to a number of criteria to be suitable for model-observation comparison at the scales of global model resolution. In addition, we will showcase preliminary results of model inter-comparisons within the BB experiment, outline plans for future output analysis

  14. Integrated Aero-Servo-Thermo-Propulso-Elasticity (ASTPE) for Hypersonic Scramjet Vehicle Design/Analysis

    DTIC Science & Technology

    2009-12-04

    experience in the last decade also indicates that large discrepancies exist between measured data ( wind - tunnel model) and flight data. This is so because the... wind - tunnel data. The coefficients of out-of-phase forces with varying Mach numbers for a pitching 10° cone and a 20° cone about the apex are...Aerodynamic Method for Design of Analysis Shock Expansion (CD) Hypersonic/ Euler & Viscous Aerodynamic Methods CFD(A) - CFD - Inlet Design - Yes

  15. Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model

    PubMed Central

    Giotis, Efstathios S.; Rothwell, Lisa; Scott, Alistair; Hu, Tuanjun; Talbot, Richard; Todd, Daniel; Burt, David W.; Glass, Elizabeth J.; Kaiser, Pete

    2015-01-01

    Chicken Anaemia Virus (CAV) is an economically important virus that targets lymphoid and erythroblastoid progenitor cells leading to immunosuppression. This study aimed to investigate the interplay between viral infection and the host’s immune response to better understand the pathways that lead to CAV-induced immunosuppression. To mimic vertical transmission of CAV in the absence of maternally-derived antibody, day-old chicks were infected and their responses measured at various time-points post-infection by qRT-PCR and gene expression microarrays. The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR. The global gene expression profiles of mock-infected (control) and CAV-infected chickens at 14 dpi were also compared using a chicken immune-related 5K microarray. Although in the thymus there was evidence of induction of an innate immune response following CAV infection, this was limited in magnitude. There was little evidence of a Th1 adaptive immune response in any lymphoid tissue, as would normally be expected in response to viral infection. Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow. From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis. Expression levels of a number of adaptor proteins, such as src-like adaptor protein (SLA), a negative regulator of T-cell receptor signalling and the transcription factor Special AT-rich Binding Protein 1 (SATB1), were significantly down-regulated by CAV infection, suggesting potential roles for these genes as regulators of viral infection or cell defence

  16. 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.

  17. 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.

  18. 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.

  19. On the precision of aero-thermal simulations for TMT

    NASA Astrophysics Data System (ADS)

    Vogiatzis, Konstantinos; Thompson, Hugh

    2016-08-01

    Environmental effects on the Image Quality (IQ) of the Thirty Meter Telescope (TMT) are estimated by aero-thermal numerical simulations. These simulations utilize Computational Fluid Dynamics (CFD) to estimate, among others, thermal (dome and mirror) seeing as well as wind jitter and blur. As the design matures, guidance obtained from these numerical experiments can influence significant cost-performance trade-offs and even component survivability. The stochastic nature of environmental conditions results in the generation of a large computational solution matrix in order to statistically predict Observatory Performance. Moreover, the relative contribution of selected key subcomponents to IQ increases the parameter space and thus computational cost, while dictating a reduced prediction error bar. The current study presents the strategy followed to minimize prediction time and computational resources, the subsequent physical and numerical limitations and finally the approach to mitigate the issues experienced. In particular, the paper describes a mesh-independence study, the effect of interpolation of CFD results on the TMT IQ metric, and an analysis of the sensitivity of IQ to certain important heat sources and geometric features.

  20. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy.

    PubMed

    Wang, Guangfu; Bochorishvili, Genrieta; Chen, Yucai; Salvati, Kathryn A; Zhang, Peng; Dubel, Steve J; Perez-Reyes, Edward; Snutch, Terrance P; Stornetta, Ruth L; Deisseroth, Karl; Erisir, Alev; Todorovic, Slobodan M; Luo, Jian-Hong; Kapur, Jaideep; Beenhakker, Mark P; Zhu, J Julius

    2015-07-15

    CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. We discovered that CaV3.2 channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated transmission at rat central synapses. Interestingly, functional CaV3.2 channels primarily incorporate into synapses, replace existing CaV3.2 channels, and can induce local calcium influx to control NMDA transmission strength in an activity-dependent manner. Moreover, human childhood absence epilepsy (CAE)-linked hCaV3.2(C456S) mutant channels have a higher channel open probability, induce more calcium influx, and enhance glutamatergic transmission. Remarkably, cortical expression of hCaV3.2(C456S) channels in rats induces 2- to 4-Hz spike and wave discharges and absence-like epilepsy characteristic of CAE patients, which can be suppressed by AMPA-R and NMDA-R antagonists but not T-type calcium channel antagonists. These results reveal an unexpected role of CaV3.2 channels in regulating NMDA-R-mediated transmission and a novel epileptogenic mechanism for human CAE.

  1. 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

  2. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy

    PubMed Central

    Wang, Guangfu; Bochorishvili, Genrieta; Chen, Yucai; Salvati, Kathryn A.; Zhang, Peng; Dubel, Steve J.; Perez-Reyes, Edward; Snutch, Terrance P.; Stornetta, Ruth L.; Deisseroth, Karl; Erisir, Alev; Todorovic, Slobodan M.; Luo, Jian-Hong; Kapur, Jaideep; Beenhakker, Mark P.; Zhu, J. Julius

    2015-01-01

    CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. We discovered that CaV3.2 channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated transmission at rat central synapses. Interestingly, functional CaV3.2 channels primarily incorporate into synapses, replace existing CaV3.2 channels, and can induce local calcium influx to control NMDA transmission strength in an activity-dependent manner. Moreover, human childhood absence epilepsy (CAE)-linked hCaV3.2(C456S) mutant channels have a higher channel open probability, induce more calcium influx, and enhance glutamatergic transmission. Remarkably, cortical expression of hCaV3.2(C456S) channels in rats induces 2- to 4-Hz spike and wave discharges and absence-like epilepsy characteristic of CAE patients, which can be suppressed by AMPA-R and NMDA-R antagonists but not T-type calcium channel antagonists. These results reveal an unexpected role of CaV3.2 channels in regulating NMDA-R-mediated transmission and a novel epileptogenic mechanism for human CAE. PMID:26220996

  3. Low-Voltage-Activated CaV3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles.

    PubMed

    Wang, Huiyun; Zhang, Xuexin; Xue, Li; Xing, Juan; Jouvin, Marie-Hélène; Putney, James W; Anderson, Matthew P; Trebak, Mohamed; Kinet, Jean-Pierre

    2016-04-19

    Activation of T cells is mediated by the engagement of T cell receptors (TCRs) followed by calcium entry via store-operated calcium channels. Here we have shown an additional route for calcium entry into T cells-through the low-voltage-activated T-type CaV3.1 calcium channel. CaV3.1 mediated a substantial current at resting membrane potentials, and its deficiency had no effect on TCR-initiated calcium entry. Mice deficient for CaV3.1 were resistant to the induction of experimental autoimmune encephalomyelitis and had reduced productions of the granulocyte-macrophage colony-stimulating factor (GM-CSF) by central nervous system (CNS)-infiltrating T helper 1 (Th1) and Th17 cells. CaV3.1 deficiency led to decreased secretion of GM-CSF from in vitro polarized Th1 and Th17 cells. Nuclear translocation of the nuclear factor of activated T cell (NFAT) was also reduced in CaV3.1-deficient T cells. These data provide evidence for T-type channels in immune cells and their potential role in shaping the autoimmune response.

  4. 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

  5. Characterization of the substituted N-triazole oxindole TROX-1, a small-molecule, state-dependent inhibitor of Ca(V)2 calcium channels.

    PubMed

    Swensen, Andrew M; Herrington, James; Bugianesi, Randal M; Dai, Ge; Haedo, Rodolfo J; Ratliff, Kevin S; Smith, McHardy M; Warren, Vivien A; Arneric, Stephen P; Eduljee, Cyrus; Parker, David; Snutch, Terrance P; Hoyt, Scott B; London, Clare; Duffy, Joseph L; Kaczorowski, Gregory J; McManus, Owen B

    2012-03-01

    Biological, genetic, and clinical evidence provide validation for N-type calcium channels (Ca(V)2.2) as therapeutic targets for chronic pain. A state-dependent Ca(V)2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl Ca(V)2.2 inhibitor used clinically. Supporting this notion, we recently reported that in preclinical models, the state-dependent Ca(V)2 inhibitor (3R)-5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one (TROX-1) has an improved therapeutic window compared with ziconotide. Here we characterize TROX-1 inhibition of Cav2.2 channels in more detail. When channels are biased toward open/inactivated states by depolarizing the membrane potential under voltage-clamp electrophysiology, TROX-1 inhibits Ca(V)2.2 channels with an IC(50) of 0.11 μM. The voltage dependence of Ca(V)2.2 inhibition was examined using automated electrophysiology. TROX-1 IC(50) values were 4.2, 0.90, and 0.36 μM at -110, -90, and -70 mV, respectively. TROX-1 displayed use-dependent inhibition of Ca(V)2.2 with a 10-fold IC(50) separation between first (27 μM) and last (2.7 μM) pulses in a train. In a fluorescence-based calcium influx assay, TROX-1 inhibited Ca(V)2.2 channels with an IC(50) of 9.5 μM under hyperpolarized conditions and 0.69 μM under depolarized conditions. Finally, TROX-1 potency was examined across the Ca(V)2 subfamily. Depolarized IC(50) values were 0.29, 0.19, and 0.28 μM by manual electrophysiology using matched conditions and 1.8, 0.69, and 1.1 μM by calcium influx for Ca(V)2.1, Ca(V)2.2, and Ca(V)2.3, respectively. Together, these in vitro data support the idea that a state-dependent, non-subtype-selective Ca(V)2 channel inhibitor can achieve an improved therapeutic window over the relatively state-independent Ca(V)2.2-selective inhibitor ziconotide in preclinical models of chronic pain.

  6. Adenosine triphosphate regulates the activity of guinea pig Cav1.2 channel by direct binding to the channel in a dose-dependent manner.

    PubMed

    Feng, Rui; Xu, Jianjun; Minobe, Etsuko; Kameyama, Asako; Yang, Lei; Yu, Lifeng; Hao, Liying; Kameyama, Masaki

    2014-05-01

    The present study is to investigate the mechanism by which ATP regulates Cav1.2 channel activity. Ventricular tissue was obtained from adult guinea pig hearts using collagenase. Ca(2+) channel activity was monitored using the patch-clamp technique. Proteins were purified using wheat germ agglutinin-Sepharose, and the concentration was determined using the Coomassie brilliant blue technique. ATP binding to the Cav1.2 channel was examined using the photoaffinity method. EDA-ATP-biotin maintains Ca(2+) channel activity in inside-out membrane patches. ATP directly bound to the Cav1.2 channel in a dose-dependent manner, and at least two molecules of ATP bound to one molecule of the Cav1.2 channel. Low levels of calmodulin (CaM) increased ATP binding to the Cav1.2 channel, but higher levels of CaM decreased ATP binding to the Cav1.2 channel. In addition, Ca(2+) was another regulator for ATP binding to the Cav1.2 channel. Furthermore, ATP bound to GST-fusion peptides of NH2-terminal region (amino acids 6-140) and proximal COOH-terminal region (amino acids 1,509-1,789) of the main subunit (α1C) of the Cav1.2 channel. Our data suggest that ATP might regulate Cav1.2 channel activity by directly binding to the Cav1.2 channel in a dose-dependent manner. In addition, the ATP-binding effect to the Cav1.2 channel was both CaM- and Ca(2+) dependent.

  7. Pharmacoresistant Cav 2·3 (E-type/R-type) voltage-gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction.

    PubMed

    Galetin, Thomas; Tevoufouet, Etienne E; Sandmeyer, Jakob; Matthes, Jan; Nguemo, Filomain; Hescheler, Jürgen; Weiergräber, Marco; Schneider, Toni

    2013-07-01

    Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contraction coupling. Whereas L-type (Cav 1·2, Cav 1·3) and T-type (Cav 3·1, Cav 3·2) channels are widely accepted for their functional relevance in the heart, the role of Cav 2·3 Ca(2+) channels expressing R-type currents remains to be elucidated. We have investigated heart rate dynamics in control and Cav 2·3-deficient mice using implantable electrocardiogram radiotelemetry and pharmacological injection experiments. Autonomic block revealed that the intrinsic heart rate does not differ between both genotypes. Systemic administration of isoproterenol resulted in a significant reduction in interbeat interval in both genotypes. It remained unaffected after administering propranolol in Cav 2·3(-|-) mice. Heart rate from isolated hearts as well as atrioventricular conduction for both genotypes differed significantly. Additionally, we identified and analysed the developmental expression of two splice variants, i.e. Cav 2·3c and Cav 2·3e. Using patch clamp technology, R-type currents could be detected in isolated prenatal cardiomyocytes and be related to R-type Ca(2+) channels. Our results indicate that on the systemic level, the pharmacologically inducible heart rate range and heart rate reserve are impaired in Cav 2·3 (-|-) mice. In addition, experiments on Langendorff perfused hearts elucidate differences in basic properties between both genotypes. Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation.

  8. CaV3.2 KO mice have altered retinal waves but normal direction selectivity.

    PubMed

    Hamby, Aaron M; Rosa, Juliana M; Hsu, Ching-Hsiu; Feller, Marla B

    2015-01-01

    Early in development, before the onset of vision, the retina establishes direction-selective responses. During this time period, the retina spontaneously generates bursts of action potentials that propagate across its extent. The precise spatial and temporal properties of these "retinal waves" have been implicated in the formation of retinal projections to the brain. However, their role in the development of direction selective circuits within the retina has not yet been determined. We addressed this issue by combining multielectrode array and cell-attached recordings to examine mice that lack the CaV3.2 subunit of T-type Ca2+ channels (CaV3.2 KO) because these mice exhibit disrupted waves during the period that direction selective circuits are established. We found that the spontaneous activity of these mice displays wave-associated bursts of action potentials that are altered from that of control mice: the frequency of these bursts is significantly decreased and the firing rate within each burst is reduced. Moreover, the projection patterns of the retina demonstrate decreased eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN). However, after eye-opening, the direction selective responses of CaV3.2 KO direction selective ganglion cells (DSGCs) are indistinguishable from those of wild-type DSGCs. Our data indicate that although the temporal properties of the action potential bursts associated with retinal waves are important for activity-dependent refining of retinal projections to central targets, they are not critical for establishing direction selectivity in the retina.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Salvileucalin B, a novel diterpenoid with an unprecedented rearranged neoclerodane skeleton from Salvia leucantha Cav.

    PubMed

    Aoyagi, Yutaka; Yamazaki, Akira; Nakatsugawa, Chihiro; Fukaya, Haruhiko; Takeya, Koichi; Kawauchi, Susumu; Izumi, Hiroshi

    2008-10-16

    Salvileucalin B (2), having an unprecedented rearranged neoclerodane skeleton, was isolated from the aerial parts of Salvia leucantha Cav. (Labiatae) along with salvileucalin A (1). The absolute structures were elucidated by spectroscopic analysis, X-ray crystallographic analysis, and vibrational circular dichroism. Compound 2 represents a novel neoclerodane, characterized by a tricyclo[3.2.1.0 (2,7)]octane substructure incorporating the exocyclic C-20 methylene of 1. This molecule exerted cytotoxic activity against A549 and HT-29 cells with IC50 values of 5.23 and 1.88 microg/mL, respectively.

  14. Vehicle Rustproofing,

    DTIC Science & Technology

    1982-03-01

    Corrosion Areas - G.M.) 11. Vehicle Rustproofing Guide for Vehicle Maintenance Managers 12. Chart - Vehicle Buy Program FY 83-87 13. Vehicle ...on the Vehicle Buy Program. k. The impact of a total fleet rustproofing policy on industry. I. Potential problems in Quality Control and Warranty...FY83-87, the Air Force intends to buy $2.5 billion worth of vehicles (Atch 12); thus, a total fleet treatment program for that period could cost as

  15. PIP₂ hydrolysis is responsible for voltage independent inhibition of CaV2.2 channels in sympathetic neurons.

    PubMed

    Vivas, Oscar; Castro, Hector; Arenas, Isabel; Elías-Viñas, David; García, David E

    2013-03-08

    GPCRs regulate Ca(V)2.2 channels through both voltage dependent and independent inhibition pathways. The aim of the present work was to assess the phosphatidylinositol-4,5-bisphosphate (PIP2) as the molecule underlying the voltage independent inhibition of Ca(V)2.2 channels in SCG neurons. We used a double pulse protocol to study the voltage independent inhibition and changed the PIP(2) concentration by means of blocking the enzyme PLC, filling the cell with a PIP(2) analogue and preventing the PIP(2) resynthesis with wortmannin. We found that voltage independent inhibition requires the activation of PLC and can be hampered by internal dialysis of exogenous PIP(2). In addition, the recovery from voltage independent inhibition is blocked by inhibition of the enzymes involved in the resynthesis of PIP(2). These results support that the hydrolysis of PIP(2) is responsible for the voltage independent inhibition of Ca(V)2.2 channels.

  16. Numerical Validation of a Near-Field Fugitive Dust Model for Vehicles Moving on Unpaved Surfaces

    DTIC Science & Technology

    2013-02-05

    eld dust emission and tranport technology is also discussed. 15. SUBJECT TERMS Fugitive Dust Emission, Computational Fluid Dynamics, Multiphase...the near field of moving vehicles. The weakness of the current near-field dust emission and tranport technology is also discussed. key word: Fugitive...USA Email: xltong@cavs.msstate.edu Phone number: 001-662-3253048 Fax number: 001-662-3257692 E. A. Luke Department of Computer Science, Mississippi

  17. Crystal structure of the CaV2 IQ domain in complex with Ca2+/calmodulin: high-resolution mechanistic implications for channel regulation by Ca2+.

    PubMed

    Mori, Masayuki X; Vander Kooi, Craig W; Leahy, Daniel J; Yue, David T

    2008-04-01

    Calmodulin (CaM) regulation of Ca(2+) channels is central to Ca(2+) signaling. Ca(V)1 versus Ca(V)2 classes of these channels exhibit divergent forms of regulation, potentially relating to customized CaM/IQ interactions among different channels. Here we report the crystal structures for the Ca(2+)/CaM IQ domains of both Ca(V)2.1 and Ca(V)2.3 channels. These highly similar structures emphasize that major CaM contacts with the IQ domain extend well upstream of traditional consensus residues. Surprisingly, upstream mutations strongly diminished Ca(V)2.1 regulation, whereas downstream perturbations had limited effects. Furthermore, our Ca(V)2 structures closely resemble published Ca(2+)/CaM-Ca(V)1.2 IQ structures, arguing against Ca(V)1/2 regulatory differences based solely on contrasting CaM/IQ conformations. Instead, alanine scanning of the Ca(V)2.1 IQ domain, combined with structure-based molecular simulation of corresponding CaM/IQ binding energy perturbations, suggests that the C lobe of CaM partially dislodges from the IQ element during channel regulation, allowing exposed IQ residues to trigger regulation via isoform-specific interactions with alternative channel regions.

  18. 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.

  19. A potent and selective indole N-type calcium channel (Ca(v)2.2) blocker for the treatment of pain.

    PubMed

    Tyagarajan, Sriram; Chakravarty, Prasun K; Park, Min; Zhou, Bishan; Herrington, James B; Ratliff, Kevin; Bugianesi, Randall M; Williams, Brande; Haedo, Rodolfo J; Swensen, Andrew M; Warren, Vivien A; Smith, McHardy; Garcia, Maria; Kaczorowski, Gregory J; McManus, Owen B; Lyons, Kathryn A; Li, Xiaohua; Madeira, Maria; Karanam, Bindhu; Green, Mitchell; Forrest, Michael J; Abbadie, Catherine; McGowan, Erin; Mistry, Shruti; Jochnowitz, Nina; Duffy, Joseph L

    2011-01-15

    N-type calcium channels (Ca(v)2.2) have been shown to play a critical role in pain. A series of low molecular weight 2-aryl indoles were identified as potent Ca(v)2.2 blockers with good in vitro and in vivo potency.

  20. Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception

    PubMed Central

    Bourinet, Emmanuel; Alloui, Abdelkrim; Monteil, Arnaud; Barrère, Christian; Couette, Brigitte; Poirot, Olivier; Pages, Anne; McRory, John; Snutch, Terrance P; Eschalier, Alain; Nargeot, Joël

    2005-01-01

    Analgesic therapies are still limited and sometimes poorly effective, therefore finding new targets for the development of innovative drugs is urgently needed. In order to validate the potential utility of blocking T-type calcium channels to reduce nociception, we explored the effects of intrathecally administered oligodeoxynucleotide antisenses, specific to the recently identified T-type calcium channel family (CaV3.1, CaV3.2, and CaV3.3), on reactions to noxious stimuli in healthy and mononeuropathic rats. Our results demonstrate that the antisense targeting CaV3.2 induced a knockdown of the CaV3.2 mRNA and protein expression as well as a large reduction of ‘CaV3.2-like' T-type currents in nociceptive dorsal root ganglion neurons. Concomitantly, the antisense treatment resulted in major antinociceptive, anti-hyperalgesic, and anti-allodynic effects, suggesting that CaV3.2 plays a major pronociceptive role in acute and chronic pain states. Taken together, the results provide direct evidence linking CaV3.2 T-type channels to pain perception and suggest that CaV3.2 may offer a specific molecular target for the treatment of pain. PMID:15616581

  1. Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice.

    PubMed

    Wang, Kang; Kelley, Melissa H; Wu, Wendy W; Adelman, John P; Maylie, James

    2015-01-01

    SK2- and KV4.2-containing K+ channels modulate evoked synaptic potentials in CA1 pyramidal neurons. Each is coupled to a distinct Ca2+ source that provides Ca2+-dependent feedback regulation to limit AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated postsynaptic depolarization. SK2-containing channels are activated by Ca2+ entry through NMDARs, whereas KV4.2-containing channel availability is increased by Ca2+ entry through SNX-482 (SNX) sensitive CaV2.3 R-type Ca2+ channels. Recent studies have challenged the functional coupling between NMDARs and SK2-containing channels, suggesting that synaptic SK2-containing channels are instead activated by Ca2+ entry through R-type Ca2+ channels. Furthermore, SNX has been implicated to have off target affects, which would challenge the proposed coupling between R-type Ca2+ channels and KV4.2-containing K+ channels. To reconcile these conflicting results, we evaluated the effect of SK channel blocker apamin and R-type Ca2+ channel blocker SNX on evoked excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal neurons from CaV2.3 null mice. The results show that in the absence of CaV2.3 channels, apamin application still boosted EPSPs. The boosting effect of CaV2.3 channel blockers on EPSPs observed in neurons from wild type mice was not observed in neurons from CaV2.3 null mice. These data are consistent with a model in which SK2-containing channels are functionally coupled to NMDARs and KV4.2-containing channels to CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of CA1 pyramidal neurons.

  2. Accelerating the Design of Space Vehicles

    NASA Technical Reports Server (NTRS)

    Laufenberg, Larry (Editor)

    2003-01-01

    One of NASA's key goals is to increase the safety and reduce the cost of space transportation. Thus, a key element of NASA's new Integrated Space Transportation Plan is to develop new propulsion, structures, and operations for future generations of reusable launch vehicles (RLVs). As part of this effort to develop the next RLV, the ClCT Program's Computing, Networking, and Information Systems (CNIS) Project is developing and demonstrating collaborative software technologies that use the collective power of the NASA Grid to accelerate spacecraft design. One of these technologies, called AeroDB, automates the execution and monitoring of computational fluid dynamics (CFD) parameter studies on the NASA Grid. About the NASA Grid The NASA Grid, or Information Power Grid,. is being developed to leverage the distributed resources of NASA's many computers. instruments, simulators, and data storage systems. The goal is to use these combined resources to sdve difficult NASA challenges, such as iimulating the entire flight of a space vehicle from ascent to descent.To realize the vision of the NASA Grid, the CNIS Project is developing the software framework and protocols for building domain-specific environments and interfaces, new Grid services based on emerging industry standards, and advanced networking and computing testbeds to support new Grid-based applications such as AeroDB.

  3. Developmental expression of Ca(v)1.3 (alpha1d) calcium channels in the mouse inner ear.

    PubMed

    Hafidi, A; Dulon, D

    2004-06-21

    Voltage-gated calcium channels are important for neurotransmission at the level of inner hair cells (IHCs) and outer hair cells (OHCs). These channels open when mechanical stimulation depolarises the hair cell membrane and the resulting calcium influx triggers neurotransmitter release. Voltage-gated calcium channels expressed in hair cells are known to be of the L-type with a predominance of the Ca(v)1.3 subunit. The present study describes the developmental expression of the Ca(v)1.3 protein in the cochlea and the vestibular system using immunohistochemical technique. In the adult organ of Corti (OC), Ca(v)1.3 was localized in both sensory and non-sensory cells with a more intense expression in IHCs and Deiters cells when compared to OHCs. In both hair cell types, immunoreactivity was observed in the apical pole, basolateral membrane and at the basal pole (synaptic zone). Similar results were obtained in the vestibular organs. During development, Ca(v)1.3 immunoreactivity was observed in the cochlea as early as embryonic day 15, with expression increasing at birth. At these early stages of cochlear development, Ca(v)1.3 was expressed in all cell types surrounding the scala media. In the OC, the labeling was observed in IHCs, OHCs and supporting cells. The Ca(v)1.3 expression reached an adult-like pattern by the end of the second postnatal week. The present findings suggested that, in addition to their implication in hair cells synaptic transmission, Ca(v)1.3 calcium channels also play an important role in vesicle recycling and transport, as suggested by their extrasynaptic location at the apical pole of the hair cells. The Ca(v)1.3 channels in Deiters cells could participate in active calcium-induced changes in micromechanics of these supporting cells. An early expression during development suggested that these calcium channels are in addition important in the development of the cochlear and vestibular sensory epithelium.

  4. SFC Optimization for Aero Engine Based on Hybrid GA-SQP Method

    NASA Astrophysics Data System (ADS)

    Li, Jie; Fan, Ding; Sreeram, Victor

    2013-12-01

    This study focuses on on-line specific fuel consumption (SFC) optimization of aero engines. For solving this optimization problem, a nonlinear pneumatic and thermodynamics model of the aero engine is built and a hybrid optimization technique which is formed by combining the genetic algorithm (GA) and the sequential quadratic programming (SQP) is presented. The ability of standard GA and standard SQP in solving this type of problem is investigated. It has been found that, although the SQP is fast, very little SFC reductions can be obtained. The GA is able to solve the problem well but a lot of computational time is needed. The presented hybrid GA-SQP gives a good SFC optimization effect and saves 76.6% computational time when compared to the standard GA. It has been shown that the hybrid GA-SQP is a more effective and higher real-time method for SFC on-line optimization of the aero engine.

  5. 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.

  6. 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.

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

    PubMed Central

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

    2015-01-01

    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 Ca2+ 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. PMID:26056284

  9. Regulation of Ca(V)2 calcium channels by G protein coupled receptors.

    PubMed

    Zamponi, Gerald W; Currie, Kevin P M

    2013-07-01

    Voltage gated calcium channels (Ca²⁺ channels) are key mediators of depolarization induced calcium influx into excitable cells, and thereby play pivotal roles in a wide array of physiological responses. This review focuses on the inhibition of Ca(V)2 (N- and P/Q-type) Ca²⁺-channels by G protein coupled receptors (GPCRs), which exerts important autocrine/paracrine control over synaptic transmission and neuroendocrine secretion. Voltage-dependent inhibition is the most widespread mechanism, and involves direct binding of the G protein βγ dimer (Gβγ) to the α1 subunit of Ca(V)2 channels. GPCRs can also recruit several other distinct mechanisms including phosphorylation, lipid signaling pathways, and channel trafficking that result in voltage-independent inhibition. Current knowledge of Gβγ-mediated inhibition is reviewed, including the molecular interactions involved, determinants of voltage-dependence, and crosstalk with other cell signaling pathways. A summary of recent developments in understanding the voltage-independent mechanisms prominent in sympathetic and sensory neurons is also included. This article is part of a Special Issue entitled: Calcium channels.

  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. 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.

  12. 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.

  13. Performance analysis of rocket-ramjet propelled SSTO-vehicles

    NASA Astrophysics Data System (ADS)

    Schoettle, U. M.

    1985-10-01

    Winged single-stage-to-orbit (SSTO) vehicles designed for vertical or horizontal takeoff and horizontal landing with both rocket and rocket-ramjet propulsion concepts are analyzed and their performance and costs are compared. For this purpose, LOX/LH2 rocket baseline vehicles with payload and mission requirements similar to the Space Shuttle system are modified to accommodate hydrogen-fueled ramjet engines. The use of the airbreathing engines results in a substantial decrease in propellant consumption but is heavily penalized by the added weights of the ramjet engine and structural reinforcements to resist higher aero-thermodynamic loads. The results suggest that for vehicles of the same gross lift-off weight the total system costs of the airbreathing vehicles are 19 percent higher compared to rocket systems; however, due to increased payload capabilities, the specific transportation costs are lower.

  14. A comparison of modeled and measured energy use in hybrid electric vehicles

    NASA Astrophysics Data System (ADS)

    Cuddy, Matthew

    1995-01-01

    CarSim 2.5.4, written by AeroVironment, Inc. of Monrovia, California and SIMPLEV 3.0, written by Idaho National Engineering Laboratory were used to simulate two series-configured hybrid electric vehicles that competed in the 1994 Hybrid Electric Vehicle Challenge. Vehicle speed and battery energy use were measured over a 0.2-km maximum effort acceleration and a 58-km range event. The simulations' predictions are compared to each other and to measured data. A rough uncertainty analysis of the validation is presented. The programs agree with each other to within 5% and with the measured energy data within the uncertainty of the experiment.

  15. Whole Exome Sequencing Identifies De Novo Heterozygous CAV1 Mutations Associated with a Novel Neonatal Onset Lipodystrophy Syndrome

    PubMed Central

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

    2016-01-01

    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. PMID:25898808

  16. 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

  17. Adiponectin at Physiologically Relevant Concentrations Enhances the Vasorelaxative Effect of Acetylcholine via Cav-1/AdipoR-1 Signaling

    PubMed Central

    Du, Yunhui; Li, Rui; Lau, Wayne Bigond; Zhao, Jianli; Lopez, Bernard; Christopher, Theodore A.; Ma, Xin-Liang; Wang, Yajing

    2016-01-01

    Clinical studies have identified hypoadiponectinemia as an independent hypertension risk factor. It is known that adiponectin (APN) can directly cause vasodilation, but the doses required exceed physiologic levels several fold. In the current study, we determine the effect of physiologically relevant APN concentrations upon vascular tone, and investigate the mechanism(s) responsible. Physiologic APN concentrations alone induced no significant vasorelaxation. Interestingly, pretreatment of wild type mouse aortae with physiologic APN levels significantly enhanced acetylcholine (ACh)-induced vasorelaxation (P<0.01), an endothelium-dependent and nitric oxide (NO)-mediated process. Knockout of adiponectin receptor 1 (AdipoR1) or caveolin-1 (Cav-1, a cell signaling facilitating molecule), but not adiponectin receptor 2 (AdipoR2) abolished APN-enhanced ACh-induced vasorelaxation. Immunoblot assay revealed APN promoted the AdipoR1/Cav1 signaling complex in human endothelial cells. Treatment of HUVECs with physiologic APN concentrations caused significant eNOS phosphorylation and nitric oxide (NO) production (P<0.01), an effect abolished in knockdown of either AdipoR1 or Cav-1. Taken together, these data demonstrate for the first time physiologic APN levels enhance the vasorelaxative response to ACh by inducing NO production through AdipoR1/Cav-1 mediated signaling. In physiologic conditions, APN plays an important function of maintaining vascular tone. PMID:27023866

  18. 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.

  19. 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

  20. Association of eNOS and Cav-1 gene polymorphisms with susceptibility risk of large artery atherosclerotic stroke

    PubMed Central

    Shyu, Hann-Yeh; Chen, Ming-Hua; Hsieh, Yi-Hsien; Shieh, Jia-Ching; Yen, Ling-Rong; Wang, Hsiao-Wei; Cheng, Chun-Wen

    2017-01-01

    Endothelial nitric oxide synthase (eNOS) is localized in caveole and has important effects on caveolar coordination through its interaction with caveolin-1 (Cav-1), which supports normal functioning of vascular endothelial cells. However, the relationship between genotypic polymorphisms of e-NOS and Cav-1 genes and ischemic stroke (IS) remains lesser reported. This hospital-based case-control study aimed to determine the genetic polymorphisms of the eNOS (Glu298Asp) and Cav-1 (G14713A and T29107A) genes in association with susceptibility risk in patients who had suffered from a large artery atherosclerotic (LAA) stroke. Genotyping determination for these variant alleles was performed using the TaqMan assay. The distributions of observed allelic and genotypic frequencies for the polymorphisms were in Hardy-Weinberg equilibrium in healthy controls. The risk for an LAA stroke in the Asp298 variant was 1.72 (95% CI = 1.09–2.75) versus Glu298 of the eNOS. In the GA/AA (rs3807987) variant, it was 1.79 (95% CI = 1.16–2.74) versus GG and in TA/AA (rs7804372) was 1.61 (95% CI = 1.06–2.43) versus TT of the Cav-1, respectively. A tendency toward an increased LAA stroke risk was significant in carriers with the eNOS Glu298Asp variant in conjunction with the G14713 A and T29107A polymorphisms of the Cav-1 (aOR = 2.03, P-trend = 0.002). A synergistic effect between eNOS and Cav-1 polymorphisms on IS risk elevation was significantly influenced by alcohol drinking, heavy cigarette smoking (P-trend<0.01), and hypercholesterolemia (P-trend < 0.001). In conclusion, genotypic polymorphisms of the eNOS Glu298Asp and Cav-1 14713A/29107A polymorphisms are associated with the elevated risk of LAA stroke among Han Chinese in Taiwan. PMID:28346478

  1. 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

  2. Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage

    PubMed Central

    Lin, Shin-Shiou; Tzeng, Bing-Hsiean; Lee, Kuan-Rong; Smith, Richard J. H.; Campbell, Kevin P.; Chen, Chien-Chang

    2014-01-01

    Intracellular Ca2+ transient is crucial in initiating the differentiation of mesenchymal cells into chondrocytes, but whether voltage-gated Ca2+ channels are involved remains uncertain. Here, we show that the T-type voltage-gated Ca2+ channel Cav3.2 is essential for tracheal chondrogenesis. Mice lacking this channel (Cav3.2−/−) show congenital tracheal stenosis because of incomplete formation of cartilaginous tracheal support. Conversely, Cav3.2 overexpression in ATDC5 cells enhances chondrogenesis, which could be blunted by both blocking T-type Ca2+ channels and inhibiting calcineurin and suggests that Cav3.2 is responsible for Ca2+ influx during chondrogenesis. Finally, the expression of sex determination region of Y chromosome (SRY)-related high-mobility group-Box gene 9 (Sox9), one of the earliest markers of committed chondrogenic cells, is reduced in Cav3.2−/− tracheas. Mechanistically, Ca2+ influx via Cav3.2 activates the calcineurin/nuclear factor of the activated T-cell (NFAT) signaling pathway, and a previously unidentified NFAT binding site is identified within the mouse Sox9 promoter using a luciferase reporter assay and gel shift and ChIP studies. Our findings define a previously unidentified mechanism that Ca2+ influx via the Cav3.2 T-type Ca2+ channel regulates Sox9 expression through the calcineurin/NFAT signaling pathway during tracheal chondrogenesis. PMID:24778262

  3. 77 FR 30371 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-23

    ... Engines AG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are superseding an existing airworthiness directive (AD) for all International Aero Engines AG (IAE) V2500-A1, V2525-D5 and V2528-D5 turbofan engines, and certain serial numbers (S/Ns) of IAE...

  4. 78 FR 22168 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... Engines AG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain International Aero Engines AG (IAE), V2525-D5 and V2528-D5 turbofan engines, with a certain No. 4 bearing internal scavenge tube and...

  5. 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.

  6. 78 FR 69600 - Airworthiness Directives; Piaggio Aero Industries S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... 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 from... p.m., Monday through Friday, except Federal holidays. For service information identified in...

  7. 75 FR 5690 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A. Model P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... INDUSTRIES S.p.A. Model P- 180 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The AD docket contains the NPRM...: 2010-03-04 PIAGGIO AERO INDUSTRIES S.p.A.: Amendment 39-16187; Docket No. FAA-2009-1081;...

  8. 76 FR 27872 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... INDUSTRIES S.p.A Model P- 180 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ] ACTION: Final... known U.S. owners and operators of PIAGGIO AERO INDUSTRIES S.p.A (Piaggio) Model PIAGGIO P-180 airplanes... fuselage on a number of Piaggio Model P.180 aeroplanes, which resulted in jamming of the flight...

  9. 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.

  10. 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.

  11. 78 FR 56589 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-13

    ... INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT... INDUSTRIES S.p.A Model P-180 airplanes. This AD results from mandatory continuing airworthiness information...., Washington, DC 20590. For service information identified in this AD, contact Piaggio Aero Industries...

  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. 78 FR 1776 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... Engines AG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... Aero Engines AG (IAE), V2525-D5 and V2528-D5 turbofan engines, with a certain number (No.) 4 bearing... prompted by a report of an engine under-cowl fire and commanded in-flight shutdown. This proposed AD...

  14. 76 FR 82202 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ... Engines AG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... International Aero Engines AG (IAE) V2500-A1, V2525-D5 and V2528-D5 turbofan engines, and certain serial numbers... engines. The existing AD currently requires initial and repetitive on-wing ultrasonic inspections...

  15. 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".

  16. 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.

  17. 48 CFR 1852.235-70 - Center for AeroSpace Information.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... avail itself of the services provided by the NASA Center for AeroSpace Information (CASI) (http://www.sti.nasa.gov) for the conduct of research or research and development required under this contract. CASI provides a variety of services and products as a NASA repository and database of...

  18. 48 CFR 1852.235-70 - Center for AeroSpace Information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... avail itself of the services provided by the NASA Center for AeroSpace Information (CASI) (http://www.sti.nasa.gov) for the conduct of research or research and development required under this contract. CASI provides a variety of services and products as a NASA repository and database of...

  19. 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.

  20. 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.

  1. A Coupled-Adjoint Method for High-Fidelity Aero-Structural Optimization

    DTIC Science & Technology

    2002-10-01

    geometry engine, and an efficient gradient-based optimization algorithm. The aero-structural solver ensures accurate solutions by using high-fidelity...22 2.3.1 Geometry Engine and Database . . . . . . . . . . . . . . . . . . . . . 23 2.3.2 Displacement Transfer...86 5-6 Airfoil geometry at the root. . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 5-7 Airfoil geometry at mid semi-span

  2. 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.

  3. 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.

  4. 77 FR 67764 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-14

    ... Aero Industries S.p.A. Model P-180 airplanes. That AD currently requires replacement of any firewall... only affects those firewall shutoff valves referenced in the referenced service information. We are... determination of whether any firewall shutoff or crossfeed valve with a serial number in a certain range...

  5. Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells.

    PubMed

    Tirado, Oscar M; Mateo-Lozano, Silvia; Villar, Joaquín; Dettin, Luis E; Llort, Anna; Gallego, Soledad; Ban, Jozef; Kovar, Heinrich; Notario, Vicente

    2006-10-15

    Tumors of the Ewing's sarcoma family (ESFT), such as Ewing's sarcoma (EWS) and primitive neuroectodermal tumors (PNET), are highly aggressive malignancies predominantly affecting children and young adults. ESFT express chimeric transcription factors encoded by hybrid genes fusing the EWS gene with several ETS genes, most commonly FLI-1. EWS/FLI-1 proteins are responsible for the malignant phenotype of ESFT, but only few of their transcriptional targets are known. Using antisense and short hairpin RNA-mediated gene expression knockdown, array analyses, chromatin immunoprecipitation methods, and reexpression studies, we show that caveolin-1 (CAV1) is a new direct target of EWS/FLI-1 that is overexpressed in ESFT cell lines and tumor specimens and is necessary for ESFT tumorigenesis. CAV1 knockdown led to up-regulation of Snail and the concomitant loss of E-cadherin expression. Consistently, loss of CAV1 expression inhibited the anchorage-independent growth of EWS cells and markedly reduced the growth of EWS cell-derived tumors in nude mice xenografts, indicating that CAV1 promotes the malignant phenotype in EWS carcinogenesis. Reexpression of CAV1 or E-cadherin in CAV1 knockdown EWS cells rescued the oncogenic phenotype of the original EWS cells, showing that the CAV1/Snail/E-cadherin pathway plays a central role in the expression of the oncogenic transformation functions of EWS/FLI-1. Overall, these data identify CAV1 as a key determinant of the tumorigenicity of ESFT and imply that targeting CAV1 may allow the development of new molecular therapeutic strategies for ESFT patients.

  6. Turret optimization using passive flow control to minimize aero-optic effects

    NASA Astrophysics Data System (ADS)

    Crahan, Grady C.

    Over the past several decades, optical systems have begun to be deployed regularly on aircraft that fly at compressible flow speeds. During this time, these optical systems have also moved towards shorter operating wavelengths that can deliver a higher peak irradiance in the focused spot on a distant target, and the assumption is that future systems will use even shorter-wavelength lasers. As this trend towards short-wavelength systems continues, the need to take into account the effect of flow-induced, or "aero-optic," aberrations that occur in the vicinity of the parent aircraft has become progressively more important. The conventional method for mounting an optical system is to place it in a hemispherical turret; however, from an aero-optic standpoint, there are two problems with this mounting arrangement. First, shocks begin to form on the surface of a sphere (or hemisphere) at a critical Mach number of only around 0.55. Furthermore, a shear layer is produced due to flow separation on the aft side of the sphere; both of these flows, shocks and separated shear layers, involve strong index-of-refraction variations in the flow that would severely aberrate the outgoing beam. One approach to the problem would be to employ adaptive-optic (AO) methods in which the conjugate of the aberration is applied to the outgoing beam before it transmits through the aero-optic flow; however, state-of-the-art AO systems are generally unable to match the high temporal frequencies associated with aero-optic flows. As such, there is a need for innovative mounting strategies for optical systems that avoid or mitigate the formation of optically-aberrating flows in the first place. This dissertation outlines an investigation into aerodynamic shaping of turrets to mitigate the aero-optic aberrations produced by shock waves and shear layers. Specifically, a computational and experimental investigation into the "virtual duct" concept, which is a passive flow-control approach to mitigating

  7. AeroStat: NASA Giovanni Tool for Statistical Intercomparison of Aerosols

    NASA Astrophysics Data System (ADS)

    Wei, J. C.; Petrenko, M.; Leptoukh, G. G.; Lynnes, C.; Da Silva, D.; Hegde, M.; Ichoku, C. M.

    2011-12-01

    Giovanni is a NASA's interactive online visualization and analysis tool for exploring very large global Earth science datasets. One of the new Giovanni analytical and statistical tools is called AeroStat, and it is designed to perform the direct statistical intercomparison of global aerosol parameters. Currently, we incorporate the MAPSS (A Multi-sensor Aerosol Products Sampling System) data that provides spatio-temporal statistics for multiple spatial spaceborne Level 2 aerosol products (MODIS Terra, MODIS Aqua, MISR, POLDER, OMI and CALIOP) sampled over AERONET ground stations. The dataset period, 1997-2011 (up to date), is long enough to encompass a number of scientifically challenging cases of long-term global aerosol validation from multi-sensors. AeroStat allows users to easily visualize and analyze in details the statistical properties of such cases, including data collected from multiple sensors and quality assurance (QA) properties of these data. One of the goals of AeroStat is to also provide a collaborative research environment, where aerosol scientists can share pertinent research workflow information, including data cases of interest, algorithms, best practices, and known errors, with the broader science community and enable other users of the system to easily reproduce and independently verify their results. Furthermore, AeroStat provides an easy access to the data provenance (data lineage) and quality information, which allows for a convenient tracing of scientific results back to their original input data, thus further ensuring the reliability of these results. Case studies will be presented to show the described functionality and capabilities of AeroStat, and possible directions of the future development.

  8. Proceedings of the RAND Project AIR FORCE Workshop on Transatmospheric Vehicles

    DTIC Science & Technology

    1997-01-01

    a design problem associated with using the materials in a multi-functioning capacity. Titanium aluminides are "advanced" metallic compounds...Space Technology, June 17,1996, p. 29. National Aero-Space Plane Materials and Structures Augmentation Program, Titanium Aluminides /Advanced...counterforce capability. Similarly, if a TAV could quickly deliver such weapons against terrestrial targets such as armored vehicles, it could serve

  9. Redetermination of metarossite, CaV5+ 2O6·2H2O

    PubMed Central

    Kobsch, Anaïs; Downs, Robert T.; Domanik, Kenneth J.

    2016-01-01

    The crystal structure of metarossite, ideally CaV2O6·2H2O [chemical name: calcium divanadium(V) hexa­oxide dihydrate], was first determined using precession photographs, with fixed isotropic displacement parameters and without locating the positions of the H atoms, leading to a reliability factor R = 0.11 [Kelsey & Barnes (1960 ▸). Can. Mineral. 6, 448–466]. This communication reports a structure redetermination of this mineral on the basis of single-crystal X-ray diffraction data of a natural sample from the Blue Cap mine, San Juan County, Utah, USA (R1 = 0.036). Our study not only confirms the structural topology reported in the previous study, but also makes possible the refinement of all non-H atoms with anisotropic displacement parameters and all H atoms located. The metarossite structure is characterized by chains of edge-sharing [CaO8] polyhedra parallel to [100] that are themselves connected by chains of alternating [VO5] trigonal bipyramids parallel to [010]. The two H2O mol­ecules are bonded to Ca. Analysis of the displacement parameters show that the [VO5] chains librate around [010]. In addition, we measured the Raman spectrum of metarossite and compared it with IR and Raman data previously reported. Moreover, heating of metarossite led to a loss of water, which results in a transformation to the brannerite-type structure, CaV2O6, implying a possible dehydration pathway for the compounds M 2+V2O6·xH2O, with M = Cu, Cd, Mg or Mn, and x = 2 or 4. PMID:27920917

  10. 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

  11. 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...

  12. 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.

  13. 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.

  14. Aero-Optical Wavefront Propagation and Refractive Fluid Interfaces in Large-Reynolds-Number Compressible Turbulent Flows

    DTIC Science & Technology

    2005-12-31

    are utilized with the eikonal equation of geometrical optics to propagate computationally the optical wavefronts in the near field. As long as the...aero- optical interactions. In terms of the refractive index field n and the optical path length (OPL), the eikonal equation is: |∇ (OPL)| = n , (9) (e.g...Final Report to the Air Force Office of Scientific Research AFOSR Grant FA9550-04-1-0386, Period: 06-01-2004 to 12-31-2005 Aero- Optical Wavefront

  15. Rab27a GTPase modulates L-type Ca2+ channel function via interaction with the II-III linker of CaV1.3 subunit.

    PubMed

    Reichhart, Nadine; Markowski, Magdalena; Ishiyama, Shimpei; Wagner, Andrea; Crespo-Garcia, Sergio; Schorb, Talitha; Ramalho, José S; Milenkovic, Vladimir M; Föckler, Renate; Seabra, Miguel C; Strauß, Olaf

    2015-11-01

    In a variety of cells, secretory processes require the activation of both Rab27a and L-type channels of the Ca(V)1.3 subtype. In the retinal pigment epithelium (RPE), Rab27a and Ca(V)1.3 channels regulate growth-factor secretion towards its basolateral side. Analysis of murine retina sections revealed a co-localization of both Rab27a and Ca(V)1.3 at the basolateral membrane of the RPE. Heterologously expressed Ca(V)1.3/β3/α2δ1 channels showed negatively shifted voltage-dependence and decreased current density of about 70% when co-expressed with Rab27a. However, co-localization analysis using α(5)β(1) integrin as a membrane marker revealed that Rab27a co-expression reduced the surface expression of Ca(V)1.3 only about 10%. Physical binding of heterologously expressed Rab27a with Ca(V)1.3 channels was shown by co-localization in immunocytochemistry as well as co-immunoprecipitation which was abolished after deletion of a MyRIP-homologous amino acid sequence at the II-III linker of the Ca(V)1.3 subunit. Rab27a over-expression in ARPE-19 cells positively shifted the voltage dependence, decreased current density of endogenous Ca(V)1.3 channels and reduced VEGF-A secretion. We show the first evidence of a direct functional modulation of an ion channel by Rab27a suggesting a new mechanism of Rab and ion channel interaction in the control of VEGF-A secretion in the RPE.

  16. 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

  17. CACNA1B (Cav2.2) Overexpression and Its Association with Clinicopathologic Characteristics and Unfavorable Prognosis in Non-Small Cell Lung Cancer

    PubMed Central

    Zhou, Xiaoyu; Wang, Wei; Zhang, Shu; Wang, Xudong; Tang, Zhiyuan; Gu, Jun; Li, Jun

    2017-01-01

    CACNA1B (Cav2.2) encodes an N-type voltage-gated calcium channel (VGCC) ubiquitously expressed in brain and peripheral nervous system that is important for regulating neuropathic pain. Because intracellular calcium concentration is a key player in cell proliferation and apoptosis, VGCCs are implicated in tumorigenesis. Recent studies have identified CACNA1B (Cav2.2) being overexpressed in prostate and breast cancer tissues when compared to adjacent normal tissues; however, its role in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we determined the mRNA and protein expression of CACNA1B (Cav2.2) in NSCLC tumorous and adjacent nontumorous tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC), respectively. CACNA1B (Cav2.2) protein expressions in tumorous tissues were correlated with NSCLC patients' clinical characteristics and overall survival. CACNA1B (Cav2.2) mRNA and protein expression levels were higher in NSCLC tumorous tissues than in nontumorous tissues. High CACNA1B (Cav2.2) protein expression was associated with higher TNM stages, and CACNA1B (Cav2.2) protein expression is an independent prognostic marker in NSCLC. Based on our results, we conclude that CACNA1B (Cav2.2) plays a role in NSCLC development and progression. Elucidating the underlying mechanism may help design novel treatment by specifically targeting the calcium regulation pathway for NSCLC, a devastating disease with increasing incidence and mortality in China. PMID:28127114

  18. Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells.

    PubMed

    Ávila-Medina, Javier; Calderón-Sánchez, Eva; González-Rodríguez, Patricia; Monje-Quiroga, Francisco; Rosado, Juan Antonio; Castellano, Antonio; Ordóñez, Antonio; Smani, Tarik

    2016-09-30

    Voltage-dependent CaV1.2 L-type Ca(2+) channels (LTCC) are the main route for calcium entry in vascular smooth muscle cells (VSMC). Several studies have also determined the relevant role of store-operated Ca(2+) channels (SOCC) in vascular tone regulation. Nevertheless, the role of Orai1- and TRPC1-dependent SOCC in vascular tone regulation and their possible interaction with CaV1.2 are still unknown. The current study sought to characterize the co-activation of SOCC and LTCC upon stimulation by agonists, and to determine the possible crosstalk between Orai1, TRPC1, and CaV1.2. Aorta rings and isolated VSMC obtained from wild type or smooth muscle-selective conditional CaV1.2 knock-out (CaV1.2(KO)) mice were used to study vascular contractility, intracellular Ca(2+) mobilization, and distribution of ion channels. We found that serotonin (5-HT) or store depletion with thapsigargin (TG) enhanced intracellular free Ca(2+) concentration ([Ca(2+)]i) and stimulated aorta contraction. These responses were sensitive to LTCC and SOCC inhibitors. Also, 5-HT- and TG-induced responses were significantly attenuated in CaV1.2(KO) mice. Furthermore, hyperpolarization induced with cromakalim or valinomycin significantly reduced both 5-HT and TG responses, whereas these responses were enhanced with LTCC agonist Bay-K-8644. Interestingly, in situ proximity ligation assay revealed that CaV1.2 interacts with Orai1 and TRPC1 in untreated VSMC. These interactions enhanced significantly after stimulation of cells with 5-HT and TG. Therefore, these data indicate for the first time a functional interaction between Orai1, TRPC1, and CaV1.2 channels in VSMC, confirming that upon agonist stimulation, vessel contraction involves Ca(2+) entry due to co-activation of Orai1- and TRPC1-dependent SOCC and LTCC.

  19. Impaired Long-term Potentiation and Enhanced Neuronal Excitability in the Amygdala of CaV1.3 Knockout Mice

    PubMed Central

    McKinney, Brandon C.; Sze, Wilson; Lee, Benjamin; Murphy, Geoffrey G.

    2009-01-01

    Previously, we demonstrated that mice in which the gene for the L-type voltage-gated calcium channel CaV1.3 is deleted (CaV1.3 knockout mice) exhibit an impaired ability to consolidate contextually-conditioned fear. Given that this form of Pavlovian fear conditioning is critically dependent on the basolateral complex of the amygdala (BLA), we were interested in the mechanisms by which CaV1.3 contributes to BLA neurophysiology. In the present study, we used in vitro amygdala slices prepared from CaV1.3 knockout mice and wild-type littermates to explore the role of CaV1.3 in long-term potentiation (LTP) and intrinsic neuronal excitability in the BLA. We found that LTP in the lateral nucleus (LA) of the BLA, induced by high-frequency stimulation of the external capsule, was significantly reduced in CaV1.3 knockout mice. Additionally, we found that BLA principal neurons from CaV1.3 knockout mice were hyperexcitable, exhibiting significant increases in firing rates and decreased interspike intervals in response to prolonged somatic depolarization. This aberrant increase in neuronal excitability appears to be at least in part due to a concomitant reduction in the slow component of the post-burst afterhyperpolarization. Together, these results demonstrate altered neuronal function in the BLA of CaV1.3 knockout mice which may account for the impaired ability of these mice to consolidate contextually-conditioned fear. PMID:19595780

  20. Cholinergic control of firing pattern and neurotransmission in rat neostriatal projection neurons: role of CaV2.1 and CaV2.2 Ca2+ channels.

    PubMed

    Perez-Rosello, Tamara; Figueroa, Alejandra; Salgado, Humberto; Vilchis, Carmen; Tecuapetla, Fatuel; Guzman, Jaime N; Galarraga, Elvira; Bargas, Jose

    2005-05-01

    Besides a reduction of L-type Ca2+-currents (Ca(V)1), muscarine and the peptidic M1-selective agonist, MT-1, reduced currents through Ca(V)2.1 (P/Q) and Ca(V)2.2 (N) Ca2+ channel types. This modulation was strongly blocked by the peptide MT-7, a specific muscarinic M1-type receptor antagonist but not significantly reduced by the peptide MT-3, a specific muscarinic M4-type receptor antagonist. Accordingly, MT-7, but not MT-3, blocked a muscarinic reduction of the afterhyperpolarizing potential (AHP) and decreased the GABAergic inhibitory postsynaptic currents (IPSCs) produced by axon collaterals that interconnect spiny neurons. Both these functions are known to be dependent on P/Q and N types Ca2+ channels. The action on the AHP had an important effect in increasing firing frequency. The action on the IPSCs was shown to be caused presynaptically as it coursed with an increase in the paired-pulse ratio. These results show: first, that muscarinic M1-type receptor activation is the main cholinergic mechanism that modulates Ca2+ entry through voltage-dependent Ca2+ channels in spiny neurons. Second, this muscarinic modulation produces a postsynaptic facilitation of discharge together with a presynaptic inhibition of the GABAergic control mediated by axon collaterals. Together, both effects would tend to recruit more spiny neurons for the same task.

  1. Limited Efficacy of α-Conopeptides, Vc1.1 and RgIA, To Inhibit Sensory Neuron CaV Current1,2,3

    PubMed Central

    Wright, Andrew B.; Norimatsu, Yohei; McIntosh, J. Michael; Elmslie, Keith S.

    2015-01-01

    Abstract Chronic pain is very difficult to treat. Thus, novel analgesics are a critical area of research. Strong preclinical evidence supports the analgesic effects of α-conopeptides, Vc1.1 and RgIA, which block α9α10 nicotinic acetylcholine receptors (nAChRs). However, the analgesic mechanism is controversial. Some evidence supports the block of α9α10 nAChRs as an analgesic mechanism, while other evidence supports the inhibition of N-type CaV (CaV2.2) current via activation of GABAB receptors. Here, we reassess the effect of Vc1.1 and RgIA on CaV current in rat sensory neurons. Unlike the previous findings, we found highly variable effects among individual sensory neurons, but on average only minimal inhibition induced by Vc1.1, and no significant effect on the current by RgIA. We also investigated the potential involvement of GABAB receptors in the Vc1.1-induced inhibition, and found no correlation between the size of CaV current inhibition induced by baclofen (GABAB agonist) versus that induced by Vc1.1. Thus, GABAB receptors are unlikely to mediate the Vc1.1-induced CaV current inhibition. Based on the present findings, CaV current inhibition in dorsal root ganglia is unlikely to be the predominant mechanism by which either Vc1.1 or RgIA induce analgesia. PMID:26078999

  2. 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

  3. Regulation of Postsynaptic Stability by the L-type Calcium Channel CaV1.3 and its Interaction with PDZ Proteins

    PubMed Central

    Stanika, Ruslan I.; Flucher, Bernhard E.; Obermair, Gerald J.

    2015-01-01

    Alterations in dendritic spine morphology and postsynaptic structure are a hallmark of neurological disorders. Particularly spine pruning of striatal medium spiny neurons and aberrant rewiring of corticostriatal synapses have been associated with the pathology of Parkinson’s disease and L-DOPA induced dyskinesia, respectively. Owing to its low activation threshold the neuronal L-type calcium channel CaV1.3 is particularly critical in the control of neuronal excitability and thus in the calcium-dependent regulation of neuronal functions. CaV1.3 channels are located in dendritic spines and contain a C-terminal class 1 PDZ domain-binding sequence. Until today the postsynaptic PDZ domain proteins shank, densin-180, and erbin have been shown to interact with CaV1.3 channels and to modulate their current properties. Interestingly experimental evidence suggests an involvement of all three PDZ proteins as well as CaV1.3 itself in regulating dendritic and postsynaptic morphology. Here we briefly review the importance of CaV1.3 and its proposed interactions with PDZ proteins for the stability of dendritic spines. With a special focus on the pathology associated with Parkinson’s disease, we discuss the hypothesis that CaV1.3 L-type calcium channels may be critical modulators of dendritic spine stability. PMID:25966696

  4. 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

  5. Electric vehicles

    NASA Astrophysics Data System (ADS)

    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. These concepts are discussed.

  6. 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.

  7. 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.

  8. Studies on dynamic characteristics of the joint in the aero-engine rotor system

    NASA Astrophysics Data System (ADS)

    Shuguo, Liu; Yanhong, Ma; Dayi, Zhang; Jie, Hong

    2012-05-01

    The joint as a major part of the aero-engine rotating shafts directly influences its rotordynamics and state stability. This paper studies the dynamic effects of structure parameters and the external load on the stiffness and contact state of the rotor joints with nonlinear finite-element method and experiments. And a sensitivity analysis of critical speeds and vibration modes with respect to typical parameters (stiffness of the spline joints) is performed with finite difference methods, through two approaches, i.e. relative sensitivity analysis and absolute sensitivity analysis. The study results show that the stiffness and contact state of joints vary with external loads and geometry structures, and affect the rotor system operating. It is advisable to consider the influence of the position, structural parameter and external load of the rotor joints on aero-engine structure dynamics design.

  9. 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.

  10. Grain Selection during Directional Solidification of Aero-Engine Turbine Blades

    NASA Astrophysics Data System (ADS)

    Dong, Hongbiao

    2008-09-01

    The operating temperature of turbine blades in aero-engine engines has been demanded to increase for saving energy and increasing thrust. Turbine blades are made of nickel-base superalloys. Superalloys are a class of materials specifically developed for high temperature applications, particularly in the case of gas turbines for aero engines as well as land based power generation. Grain structure governs prolonged high temperature strength; this has formed the impetus both for alloy development as well as grain morphology, i.e. equiaxed—directional—single crystal solidification. In this paper, the evolution of grain structure and the control of crystal orientation in gas turbine blades are presented. The conditions leading to the solidification of columnar grain and single crystal blades are analysed, and techniques for producing columnar grain and single crystal blades in industry are reported.

  11. Study on aero-optical effect of a hypersonic missile infrared image guide

    NASA Astrophysics Data System (ADS)

    Han, Wei; Zhao, Yuejin; Hu, Xinqi

    2009-11-01

    When a hypersonic missile with a side mounted IR seeker is launched in the atmosphere, a serious aero-optical effect is formed and affects the quality of the detector's imaging. And in the course of the missile flight time,aero-optical effects changes over time, which makes real-time, accurate correction of optical distortion becomes very difficult. Therefore, it is necessary to study the relationship between the optical distortion and time.In this paper, Fluent,a computational fluid dynamics(CFD) internet applications is used to make researches on effect of optical transmission of the flow field outside the IR window. And a thermal finite element analysis (FEA) of an IR window is used to study the aerodynamic heat effect.

  12. Research on Aero-Thermodynamic Distortion Induced Structural Dynamic Response of Multi-Stage Compressor Blading.

    DTIC Science & Technology

    1983-06-01

    aerodynamic forced responses of gas turbine engine blading have been generated by a wide variety of aero- themodynamic distortion sources. These...To then relate the wake generated velocity profiles with the surface dynamic pressures on the instrumented vanes, the rotor exit velo- city triangles...quantities will be determined. As previously noted the cross hot-wire probe will be posi- tioned at mid rotor-stator axial spacing. To relate the

  13. Aero-/hydro-elastic stability of flexible panels: Prediction and control using localised spring support

    NASA Astrophysics Data System (ADS)

    Tan, B. H.; Lucey, A. D.; Howell, R. M.

    2013-12-01

    We study the effect of adding localised stiffness, via a spring support, on the stability of flexible panels subjected to axial uniform incompressible flow. Applications are considered that range from the hydro-elasticity of hull panels of high-speed ships to the aero-elasticity of glass panels in the curtain walls of high-rise buildings in very strong winds. A two-dimensional linear analysis is conducted using a hybrid of theoretical and computational methods that calculates the system eigen-states but can also be used to capture the transient behaviour that precedes these. We show that localised stiffening is a very effective means to increase the divergence-onset flow speed in both hydro- and aero-elastic applications. It is most effective when located at the mid-chord of the panel and there exists an optimum value of added stiffness beyond which further increases to the divergence-onset flow speed do not occur. For aero-elastic applications, localised stiffening can be used to replace the more destructive flutter instability that follows divergence at higher flow speeds by an extended range of divergence. The difference in eigen-solution morphology between aero- and hydro-elastic applications is highlighted, showing that for the former coalescence of two non-oscillatory divergence modes is the mechanism for flutter onset. This variation in solution morphology is mapped out in terms of a non-dimensional mass ratio. Finally, we present a short discussion of the applicability of the stabilisation strategy in a full three-dimensional system.

  14. Analysis of MMIC arrays for use in the ACTS Aero Experiment

    NASA Technical Reports Server (NTRS)

    Zimmerman, M.; Lee, R.; Rho, E.; Zaman, Z.

    1993-01-01

    The Aero Experiment is designed to demonstrate communication from an aircraft to an Earth terminal via the ACTS. This paper describes the link budget and antenna requirements for a 4.8 kbps full-duplex voice link at Ka-Band frequencies. Three arrays, one transmit array developed by TI and two receive arrays developed by GE and Boeing, were analyzed. The predicted performance characteristics of these arrays are presented and discussed in the paper.

  15. Whole-Field Measurements of Turbulent Flow for the Study of Aero-optical Effects

    DTIC Science & Technology

    2007-11-02

    Aerooptical phenomena associated with the propagation of optical beams and imaging through turbulent index-of-refraction fields have been investigated...Using simultaneous imaging of optical -beam distortion and the turbulent index-or-refraction field, we have documented near-field behavior, following...of TECHNOLOGY Pasadena, California 91125 Whole-field measurements of turbulent flow for the study of aero- optical effects Paul E. Dimotakis Air

  16. Results of a WINGDES2/AERO2S Flap Optimization for the TCA

    NASA Technical Reports Server (NTRS)

    Yaros, Steven F.

    1999-01-01

    The codes WINGDES2 and AERO2S were easy to obtain, and technical help was readily available. The codes have a long, well-documented history of successful optimizations of various aircraft configurations. The codes were easy to use, although specification of input data was time-consuming. The Run times were short, allowing the many runs necessary for the Suction Parameter matrix to be accomplished within a day or two. The results of the optimization appear to be reasonable.

  17. LES/RANS Modeling of Aero-Optical Effects in a Supersonic Cavity Flow

    DTIC Science & Technology

    2016-06-13

    which focused on simulations of the effects of heat release due to lasing chemistry on shock-train formation within chemical oxygen iodine lasers...complete some of the work proposed under the original statement of work. 2.0 INTRODUCTION Externally-mounted optical systems (e.g. an aircraft... systems , it is important to be able to predict and model these aero-optical effects. Figure 1. Schematic of cavity flow with optical reflector at

  18. Active Flutter Suppression Using Cooperative, High Frequency, Dynamic-Resonant Aero-Effectors

    DTIC Science & Technology

    2006-12-13

    Final 06/15/03-09/14/06 4. TITLE AND SUBTITLE Sa . CONTRACT NUMBER Active Flutter Suppression Using Cooperative, High Frequency, Dynamic Resonant Aero...maneuvering performance. Conventional active vibration control and flutter suppression systems are servo -hydraulic. Conventional servo -hydraulic...technology is burdened by a set of undesirable characteristics that effectively restrict their use to large aircraft. The servo -hydraulic based systems have

  19. Integrated Line-of-Sight Modeling of the Airborne Aero-Optics Laboratory

    DTIC Science & Technology

    2013-09-01

    compensator. The PID coefficients were adjusted to match the measured behavior. The measured and tuned results are shown in Fig. 6. Measured Tuned ...strain energy in the bond between them. As with the measured data, this mode is destabilized in the tuned model as shown in Figure 6 with the PID ...uncertainty with model tuning based on available experimental measurements was examined for one flight condition. 2. INTRODUCTION The Airborne Aero

  20. Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation.

    PubMed

    Ondacova, Katarina; Karmazinova, Maria; Lazniewska, Joanna; Weiss, Norbert; Lacinova, Lubica

    2016-01-01

    Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. However, the role of N-glycans in the conducting function of T-type channels remains elusive. In the present study, we used human Cav3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. Patch-clamp recordings of gating currents revealed that N-glycans attached to hCav3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. Our data suggest that modulation of N-linked glycosylation of hCav3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states.

  1. CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis.

    PubMed

    Uchitel, Osvaldo D; Inchauspe, Carlota González; Urbano, Francisco J; Di Guilmi, Mariano N

    2012-01-01

    Studies on the genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ion channels have given crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological disorders. In this review we focus on the role of mutated CaV2.1 (i.e., P/Q-type) voltage-activated Ca2+ channels, and on the ultimate consequences that mutations causing familial hemiplegic migraine type-1 (FHM1) have in neurotransmitter release. Transgenic mice harboring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used as models to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are a powerful tool to explore presynaptic regulation associated with expression of CaV2.1 channels. Mutated CaV2.1 channels activate at more hyperpolarizing potentials and lead to a gain-of-function in synaptic transmission. This gain-of-function might underlie alterations in the excitatory/ inhibitory balance of synaptic transmission, favoring a persistent state of hyperexcitability in cortical neurons that would increase the susceptibility for cortical spreading depression (CSD), a mechanism believed to initiate the attacks of migraine with aura.

  2. STAC3 stably interacts through its C1 domain with CaV1.1 in skeletal muscle triads

    PubMed Central

    Campiglio, Marta; Flucher, Bernhard E.

    2017-01-01

    The adaptor protein STAC3 is essential for skeletal muscle excitation-contraction (EC) coupling and a mutation in the STAC3 gene has been linked to a severe muscle disease, Native American myopathy (NAM). However the function of STAC3, its interaction partner, and the mode of interaction within the EC-coupling complex remained elusive. Here we demonstrate that STAC3 forms a stable interaction with the voltage-sensor of EC-coupling, CaV1.1, and that this interaction depends on a hitherto unidentified protein-protein binding pocket in the C1 domain of STAC3. While the NAM mutation does not affect the stability of the STAC3-CaV1.1 interaction, mutation of two crucial residues in the C1 binding pocket increases the turnover of STAC3 in skeletal muscle triads. Thus, the C1 domain of STAC3 is responsible for its stable incorporation into the CaV1.1 complex, whereas the SH3 domain containing the NAM mutation site may be involved in low-affinity functional interactions in EC-coupling. PMID:28112192

  3. Vehicle Characteristics

    DTIC Science & Technology

    2008-02-14

    Dimensions. Pertinent physical dimensions are determined using standard mensurative instrumentation such as steel tape measures, plumb bobs...vehicles use ITOP 2-2- 801(1)5. 4.2.3 Center of Gravity (CG). Determine the center of gravity of the test vehicle in accordance with TOP 2-2...8006. For tracked vehicles use ITOP 2-2-800(1)7. 4.2.4 Ground Pressure. Determine ground pressure in accordance with TOP 2-2-801. For tracked

  4. Launch vehicle

    NASA Astrophysics Data System (ADS)

    Rutledge, William S.

    1994-06-01

    Concentrated efforts by NASA and the DOD to begin development of a new large launch vehicle have been under way for over a decade. Options include the National Launch System, Advanced Launch System, a heavy lift vehicle, a Shuttle-derived vehicle, a Titan-derived vehicle, Single stage To Orbit, NASP and Spacelifter, to name a few. All initially promised low operations costs achieved at development costs in the $5 billion - $10 billion range. However, none has obtained approval for development, primarily because it became apparent that these cost goals could not realistically be met.

  5. Characterization of Surface Treated Aero Engine Alloys by Rayleigh Wave Velocity Dispersion

    NASA Astrophysics Data System (ADS)

    Köhler, B.; Barth, M.; Schubert, F.; Bamberg, J.; Baron, H.-U.

    2010-02-01

    In aero engines mechanically high stressed components made of high-strength alloys like IN718 and Ti6Al4V are usually surface treated by shot-peening. Other methods, e.g. laser-peening, deep rolling and low plasticity burnishing are also available. All methods introduce compres-sive residual stress desired for minimize sensitivity to fatigue or stress corrosion failure mechanisms, resulting in improved performance and increased lifetime of components. Beside that, also cold work is introduced in an amount varying from method to method. To determine the remaining life time of critical aero engine components like compressor and turbine discs, a quantitative non-destructive determination of compressive stresses is required. The opportunity to estimate residual stress in surface treated aero engine alloys by SAW phase velocity measurements has been re-examined. For that original engine relevant material IN718 has been used. Contrary to other publications a significant effect of the surface treatment to the sound velocity was observed which disappeared after thermal treatment. Also preliminary measurements of the acousto-elastic coefficient fit into this picture.

  6. Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes.

    PubMed

    Furukawa, Taiji; Nukada, Toshihide; Namiki, Yoshiko; Miyashita, Yoriko; Hatsuno, Kento; Ueno, Yasunari; Yamakawa, Takeshi; Isshiki, Takaaki

    2009-06-24

    1,4-dihydropyridine (DHP) Ca(2+) antagonists have recently been shown to block T-type Ca(2+) channels, which may render favorable actions on cardiovascular systems. However, this evaluation remains to be done systematically for each T-type Ca(2+) channel subtype except for the Ca(v)3.1 (alpha(1G)) subtype. To address this issue at the molecular level, blocking effects of 14 kinds of DHPs (amlodipine, aranidipine, azelnidipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nitrendipine), which are clinically used for treatments of hypertension, on 3 subtypes of T-type Ca(2+) channels [Ca(v)3.2 (alpha(1H)), Ca(v)3.3 (alpha(1I)), and Ca(v)3.1 (alpha(1G))] were investigated in the Xenopus oocyte expression system using the two-microelectrode voltage-clamp technique. These 3 kinds (alpha(1H), alpha(1I) and alpha(1G)) of T-type channels were blocked by amlodipine, manidipine and nicardipine. On the other hand, azelnidipine, barnidipine, benidipine and efonidipine significantly blocked alpha(1H) and alpha(1G), but not alpha(1I) channels, while nilvadipine and nimodipine apparently blocked alpha(1H) and alpha(1I), but not alpha(1G) channels. Moreover, aranidipine blocked only alpha(1H) channels. By contrast, cilnidipine, felodipine, nifedipine and nitrendipine had little effects on these subtypes of T-type channels. The result indicates that the blockade of T-type Ca(2+) channels by derivatives of DHP Ca(2+) antagonist was selective for the channel subtype. Therefore, these selectivities of DHPs in blocking T-type Ca(2+) channel subtypes would provide useful pharmacological and clinical information on the mode of action of the drugs including side-effects and adverse effects.

  7. 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.

  8. 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

  9. Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes

    PubMed Central

    Nystoriak, Matthew A.; Nieves-Cintrón, Madeline; Patriarchi, Tommaso; Buonarati, Olivia R.; Prada, Maria Paz; Morotti, Stefano; Grandi, Eleonora; Fernandes, Julia Dos Santos; Forbush, Katherine; Hofmann, Franz; Sasse, Kent C.; Scott, John D.; Ward, Sean M.; Hell, Johannes W.; Navedo, Manuel F.

    2017-01-01

    Hypercontractility of arterial myocytes and enhanced vascular tone during diabetes are, in part, attributed to the effects of increased glucose (hyperglycemia) on L-type CaV1.2 channels. In murine arterial myocytes, kinase-dependent mechanisms mediate the increase in CaV1.2 activity in response to increased extracellular glucose. We identified a subpopulation of the CaV1.2 channel pore-forming subunit (α1C) within nanometer proximity of protein kinase A (PKA) at the sarcolemma of murine and human arterial myocytes. This arrangement depended upon scaffolding of PKA by an A-kinase anchoring protein 150 (AKAP150) in mice. Glucose-mediated increases in CaV1.2 channel activity were associated with PKA activity, leading to α1C phosphorylation at Ser1928. Compared to arteries from low-fat diet (LFD)–fed mice and nondiabetic patients, arteries from high-fat diet (HFD)–fed mice and from diabetic patients had increased Ser1928 phosphorylation and CaV1.2 activity. Arterial myocytes and arteries from mice lacking AKAP150 or expressing mutant AKAP150 unable to bind PKA did not exhibit increased Ser1928 phosphorylation and CaV1.2 current density in response to increased glucose or to HFD. Consistent with a functional role for Ser1928 phosphorylation, arterial myocytes and arteries from knockin mice expressing a CaV1.2 with Ser1928 mutated to alanine (S1928A) lacked glucose-mediated increases in CaV1.2 activity and vasoconstriction. Furthermore, the HFD-induced increases in CaV1.2 current density and myogenic tone were prevented in S1928A knockin mice. These findings reveal an essential role for α1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes. PMID:28119464

  10. Role of extracellular Ca2+ in gating of CaV1.2 channels

    PubMed Central

    Babich, Olga; Isaev, Dmytro; Shirokov, Roman

    2005-01-01

    We examined changes in ionic and gating currents in CaV1.2 channels when extracellular Ca2+ was reduced from 10 mm to 0.1 μm. Saturating gating currents decreased by two-thirds (KD≈ 40 μm) and ionic currents increased 5-fold (KD≈ 0.5 μm) due to increasing Na+ conductance. A biphasic time dependence for the activation of ionic currents was observed at low [Ca2+], which appeared to reflect the rapid activation of channels that were not blocked by Ca2+ and a slower reversal of Ca2+ blockade of the remaining channels. Removal of Ca2+ following inactivation of Ca2+ currents showed that Na+ currents were not affected by Ca2+-dependent inactivation. Ca2+-dependent inactivation also induced a negative shift of the reversal potential for ionic currents suggesting that inactivation alters channel selectivity. Our findings suggest that activation of Ca2+ conductance and Ca2+-dependent inactivation depend on extracellular Ca2+ and are linked to changes in selectivity. PMID:15845581

  11. Extension of CAVS coarse-grained model to phospholipid membranes: The importance of electrostatics.

    PubMed

    Shen, Hujun; Deng, Mingsen; Zhang, Yachao

    2017-05-15

    It is evident from experiment that electrostatic potential (or dipole potential) is positive inside PC or PE lipid bilayers in the absence of ions. MARTINI coarse-grained (CG) model, which has been widely used in simulating physical properties of lipid bilayers, fails to reproduce the positive value for the dipole potential in the membrane interior. Although the total dipole potential can be correctly described by the BMW/MARTINI model, the contribution from the ester dipoles, playing a nontrivial role in the electrostatic potential across lipid membranes, is neglected by this hybrid approach. In the ELBA CG model, the role of the ester dipoles is considered, but it is overweighed because various atomistic models have consistently shown that water is actually the leading contributor of dipole potential. Here, we present a CG approach by combining the BMW-like water model (namely CAVS model) with the ELBA-like lipid model proposed in this work. Our CG model was designed not only to correctly reproduce the positive values for the dipole potential inside PC and PE lipid bilayers but also to properly balance the individual contributions from the ester dipoles and water, surmounting the limitations of current CG models in the calculations of dipole potential. © 2017 Wiley Periodicals, Inc.

  12. Chemical composition and antifungal activity of the essential oils of Lavandula pedunculata (Miller) Cav.

    PubMed

    Zuzarte, Monica; Gonçalves, Maria J; Cavaleiro, Carlos; Dinis, Augusto M; Canhoto, Jorge M; Salgueiro, Lígia R

    2009-08-01

    The chemical composition and antifungal activity of the essential oils of Lavandula pedunculata (Miller) Cav., harvested in North and Central Portugal, were investigated. The essential oils were isolated by hydrodistillation and analyzed by GC and GC/MS. The minimal-inhibitory concentration (MIC) and the minimal-lethal concentration (MLC) of the essential oils and of their major constituents were used to evaluate the antifungal activity against different strains of fungi involved in candidosis, dematophytosis, and aspergillosis. The oils were characterized by a high percentage of oxygenated monoterpenes, the main compounds being 1,8-cineole (2.4-55.5%), fenchone (1.3-59.7%), and camphor (3.6-48.0%). Statistical analysis differentiated the essential oils into two main types, one characterized by the predominance of fenchone and the other one by the predominance of 1,8-cineole. Within the 1,8-cineole chemotype, two subgroups were well-defined taking into account the percentages of camphor. A significant antifungal activity of the oils was found against dermatophyte strains. The essential oil with the highest content of camphor was the most active with MIC and MLC values ranging from 0.32-0.64 microl/ml.

  13. Vehicle systems

    NASA Technical Reports Server (NTRS)

    Bales, Tom; Modlin, Tom; Suddreth, Jack; Wheeler, Tom; Tenney, Darrel R.; Bayless, Ernest O.; Lisagor, W. Barry; Bolstad, Donald A.; Croop, Harold; Dyer, J.

    1993-01-01

    Perspectives of the subpanel on expendable launch vehicle structures and cryotanks are: (1) new materials which provide the primary weight savings effect on vehicle mass/size; (2) today's investment; (3) typically 10-20 years to mature and fully characterize new materials.

  14. 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.

  15. Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain.

    PubMed

    Huang, Chia-Yi; Chu, Dachen; Hwang, Wei-Chao; Tsaur, Meei-Ling

    2012-11-01

    Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K⁺ channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca²⁺ channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca²⁺ -dependent electrical activity of pioneer axons and play important roles during axon pathfinding.

  16. PKA and phosphatases attached to the Ca(V)1.2 channel regulate channel activity in cell-free patches.

    PubMed

    Xu, Jianjun; Yu, Lifeng; Minobe, Etsuko; Lu, Liting; Lei, Ming; Kameyama, Masaki

    2016-01-15

    Calmodulin (CaM) + ATP can reprime voltage-gated L-type Ca(2+) channels (Ca(V)1.2) in inside-out patches for activation, but this effect decreases time dependently. This suggests that the Ca(V)1.2 channel activity is regulated by additional cytoplasmic factors. To test this hypothesis, we examined the role of cAMP-dependent protein kinase A (PKA) and protein phosphatases in the regulation of Ca(V)1.2 channel activity in the inside-out mode in guinea pig ventricular myocytes. Ca(V)1.2 channel activity quickly disappeared after the patch was excised from the cell and recovered to only 9% of that in the cell-attached mode on application of CaM + ATP at 10 min after the inside out. However, immediate exposure of the excised patch to the catalytic subunit of PKA + ATP or the nonspecific phosphatase inhibitor okadaic acid significantly increased the Ca(V)1.2 channel activity recovery by CaM + ATP (114 and 96%, respectively) at 10 min. Interestingly, incubation of the excised patches with cAMP + ATP also increased CaM/ATP-induced Ca(V)1.2 channel activity recovery (108%), and this effect was blocked by the nonspecific protein kinase inhibitor K252a. The channel activity in the inside-out mode was not maintained by either catalytic subunit of PKA or cAMP + ATP in the absence of CaM, but was stably maintained in the presence of CaM for more than 40 min. These results suggest that PKA and phosphatase(s) attached on or near the Ca(V)1.2 channel regulate the basal channel activity, presumably through modulation of the dynamic CaM interaction with the channel.

  17. Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

    PubMed Central

    Wormuth, Carola; Lundt, Andreas; Henseler, Christina; Müller, Ralf; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

    2016-01-01

    Background: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca2+ channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Cav2.1 P/Q-type and Cav3.2 T-type Ca2+ channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2.3 R-type Ca2+ channel which exhibits an intriguing role in ictogenesis and seizure propagation. Cav2.3 R-type voltage gated Ca2+ channels (VGCC) emerged to be important factors in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and cellular epileptiform activity, e.g. in CA1 neurons. They also serve as potential target for various antiepileptic drugs, such as lamotrigine and topiramate. Objective: This review provides a summary of structure, function and pharmacology of VGCCs and their fundamental role in cellular Ca2+ homeostasis. We elaborate the unique modulatory properties of Cav2.3 R-type Ca2+ channels and point to recent findings in the proictogenic and proneuroapoptotic role of Cav2.3 R-type VGCCs in generalized convulsive tonic–clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity. Conclusion: Development of novel Cav2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders. PMID:27843503

  18. Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels.

    PubMed

    Zhou, Hong; Kim, Seong-Ah; Kirk, Elizabeth A; Tippens, Alyssa L; Sun, Hong; Haeseleer, Françoise; Lee, Amy

    2004-05-12

    Ca2+-binding protein-1 (CaBP1) is a Ca2+-binding protein that is closely related to calmodulin (CaM) and localized in somatodendritic regions of principal neurons throughout the brain, but how CaBP1 participates in postsynaptic Ca2+ signaling is not known. Here, we describe a novel role for CaBP1 in the regulation of Ca2+ influx through Ca(v)1.2 (L-type) Ca2+ channels. CaBP1 interacts directly with the alpha1 subunit of Ca(v)1.2 at sites that also bind CaM. CaBP1 binding to one of these sites, the IQ domain, is Ca2+ dependent and competitive with CaM binding. The physiological significance of this interaction is supported by the association of Ca(v)1.2 and CaBP1 in postsynaptic density fractions purified from rat brain. Moreover, in double-label immunofluorescence experiments, CaBP1 and Ca(v)1.2 colocalize in numerous cell bodies and dendrites of neurons, particularly in pyramidal cells in the CA3 region of the hippocampus and in the dorsal cortex. In electrophysiological recordings of cells transfected with Ca(v)1.2, CaBP1 greatly prolonged Ca2+ currents, prevented Ca2+-dependent inactivation, and caused Ca2+-dependent facilitation of currents evoked by step depolarizations and repetitive stimuli. These effects contrast with those of CaM, which promoted strong Ca2+-dependent inactivation of Ca(v)1.2 with these same voltage protocols. Our findings reveal how Ca2+-binding proteins, such as CaM and CaBP1, differentially adjust Ca2+ influx through Ca(v)1.2 channels, which may specify diverse modes of Ca2+ signaling in neurons.

  19. Space vehicle

    NASA Technical Reports Server (NTRS)

    Vonpragenau, G. L. (Inventor)

    1975-01-01

    A space vehicle having an improved ascent configuration for use in traveling in space is presented. Components of the vehicle are: (1) a winged orbiter having an elongater fuselage and rearwardly directed main engines fixed to the fuselage; (2) an elongated tank assembly of an improved configuration disposed forwardly of the fuselage and connected with the main engines of the vehicle for supplying liquid propellants; and (3) a booster stage comprising a pair of integrated solid rocket boosters connected with the orbiter immediately beneath the fuselage and extended in substantial parallelism.

  20. Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells.

    PubMed

    Fukami, Kazuki; Sekiguchi, Fumiko; Yasukawa, Miku; Asano, Erina; Kasamatsu, Ryuji; Ueda, Mai; Yoshida, Shigeru; Kawabata, Atsufumi

    2015-10-01

    Neuroendocrine-differentiated prostate cancer cells may contribute to androgen-independent proliferation of surrounding cells through Ca(2+)-dependent secretion of mitogenic factors. Human prostate cancer LNCaP cells, when neuroendocrine-differentiated, overexpress Cav3.2 T-type Ca(2+) channels that contribute to Ca(2+)-dependent secretion. Given evidence for the acceleration of Cav3.2 activity by hydrogen sulfide (H2S), we examined the roles of the H2S/Cav3.2 pathway and then analyzed the molecular mechanisms of the Cav3.2 overexpression in neuroendocrine-differentiated LNCaP cells. LNCaP cells were differentiated by dibutyryl cyclic AMP. Protein levels and T-type Ca(2+) channel-dependent currents (T-currents) were measured by immunoblotting and whole-cell pacth-clamp technique, respectively. Spontaneous release of prostatic acid phosphatase (PAP) was monitored to evaluate secretory function. The differentiated LNCaP cells exhibited neurite outgrowth, androgen-independent proliferation and upregulation of mitogenic factors, and also showed elevation of Cav3.2 expression or T-currents. Expression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS), H2S-forming enzymes, and spontaneous secretion of PAP increased following the differentiation. The augmented T-currents were enhanced by H2S donors and suppressed by inhibitors of CSE, but not CBS. The PAP secretion was reduced by inhibition of CSE or T-type Ca(2+) channels. During differentiation, Egr-1 and REST, positive and negative transcriptional regulators for Cav3.2, were upregulated and downregulated, respectively, and Egr-1 knockdown prevented the Cav3.2 overexpression. Our data suggest that, in neuroendocrine-differentiated LNCaP cells, H2S formed by the upregulated CSE promotes the activity of the upregulated Cav3.2, leading to the elevated secretory functions. The overexpression of Cav3.2 appears to involve upregulation of Egr-1 and downregulation of REST.

  1. GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta

    PubMed Central

    Wang, Di; Yang, Ruirui; Sang, Hui; Han, Linlin; Zhu, Yuexia; Lu, Yanyan; Tan, Yeke; Shang, Zhanping

    2017-01-01

    Objective To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta. Methods We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR. Results In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (p<0.05) and CON groups (p<0.05). In GDMM placenta group, there was a significant negative correlation observed between neonatal birth weight (NBW) and protein expression levels of Cav-1, p-ACC(Ser79) and p-AMPKα(Thr172) (p<0.05), while positive relationship with ACC and GLUT1 protein levels. Besides, in GDMM group placental mRNA levels, NBW had a positive correlation with GLUT1 (p<0.05), while negative with Cav-1, AMPKα and ACC expression (p<0.05). Cav-1 protein expression was positively associated with p-AMPK and p-ACC (p<0.05), and negatively associated with GLUT1 (p<0.05). Interestingly, p-AMPK protein expression was closely related to p-ACC (p<0.05), but not with GLUT1. Conclusion GDM-induced macrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and

  2. A Novel CaV1.2 N Terminus Expressed in Smooth Muscle Cells of Resistance Size Arteries Modifies Channel Regulation by Auxiliary Subunits*S

    PubMed Central

    Cheng, Xiaoyang; Liu, Jianxi; Asuncion-Chin, Maria; Blaskova, Eva; Bannister, John P.; Dopico, Alejandro M.; Jaggar, Jonathan H.

    2008-01-01

    Voltage-dependent L-type Ca2+ (CaV1.2) channels are the principal Ca2+ entry pathway in arterial myocytes. CaV1.2 channels regulate multiple vascular functions and are implicated in the pathogenesis of human disease, including hypertension. However, the molecular identity of CaV1.2 channels expressed in myocytes of myogenic arteries that regulate vascular pressure and blood flow is unknown. Here, we cloned CaV1.2 subunits from resistance size cerebral arteries and demonstrate that myocytes contain a novel, cysteine rich N terminus that is derived from exon 1 (termed “exon 1c”), which is located within CACNA1C, the CaV1.2 gene. Quantitative PCR revealed that exon 1c was predominant in arterial myocytes, but rare in cardiac myocytes, where exon 1a prevailed. When co-expressed with α2δ subunits, CaV1.2 channels containing the novel exon 1c-derived N terminus exhibited: 1) smaller whole cell current density, 2) more negative voltages of half activation (V1/2,act) and half-inactivation (V1/2,inact), and 3) reduced plasma membrane insertion, when compared with channels containing exon 1b. β1b and β2a subunits caused negative shifts in the V1/2,act and V1/2,inact of exon 1b-containing CaV1.2α1/α2δ currents that were larger than those in exon 1c-containing CaV1.2α1/α2δ currents. In contrast, β3 similarly shifted V1/2,act and V1/2,inact of currents generated by exon 1b- and exon 1c-containing channels. β subunits isoform-dependent differences in current inactivation rates were also detected between N-terminal variants. Data indicate that through novel alternative splicing at exon 1, the CaV1.2 N terminus modifies regulation by auxiliary subunits. The novel exon 1c should generate distinct voltage-dependent Ca2+ entry in arterial myocytes, resulting in tissue-specific Ca2+ signaling. PMID:17699517

  3. Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons

    PubMed Central

    Qian, Hai; Patriarchi, Tommaso; Price, Jennifer L.; Matt, Lucas; Lee, Boram; Nieves-Cintrón, Madeline; Buonarati, Olivia R.; Chowdhury, Dhrubajyoti; Nanou, Evanthia; Nystoriak, Matthew A.; Catterall, William A.; Poomvanicha, Montatip; Hofmann, Franz; Navedo, Manuel F.; Hell, Johannes W.

    2017-01-01

    The L-type Ca2+ channel Cav1.2 controls multiple functions throughout the body including heart rate and neuronal excitability. It is a key mediator of fight-or-flight stress responses triggered by a signaling pathway involving β-adrenergic receptors (βARs), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). PKA readily phosphorylates Ser1928 in Cav1.2 in vitro and in vivo, including in rodents and humans. However, S1928A knock-in (KI) mice have normal PKA-mediated L-type channel regulation in the heart, indicating that Ser1928 is not required for regulation of cardiac Cav1.2 by PKA in this tissue. We report that augmentation of L-type currents by PKA in neurons was absent in S1928A KI mice. Furthermore, S1928A KI mice failed to induce long-term potentiation in response to prolonged theta-tetanus (PTT-LTP), a form of synaptic plasticity that requires Cav1.2 and enhancement of its activity by the β2-adrenergic receptor (β2AR)–cAMP–PKA cascade. Thus, there is an unexpected dichotomy in the control of Cav1.2 by PKA in cardiomyocytes and hippocampal neurons. PMID:28119465

  4. Gating charges per channel of Ca(V)2.2 channels are modified by G protein activation in rat sympathetic neurons.

    PubMed

    Rebolledo-Antúnez, Santiago; Farías, José M; Arenas, Isabel; García, David E

    2009-06-01

    It has been suggested that voltage-dependent G protein modulation of Ca(V)2.2 channels is carried out at closed states of the channel. Our purpose was to estimate the number of gating charges of Ca(V)2.2 channel in control and G protein-modulated conditions. By using a Cole-Moore protocol we observed a significant delay in Ca(V)2.2 channel activation according to a transit of the channel through a series of closed states before channel opening. If G protein voltage-dependent modulation were carried out at these closed states, then we would have expected a greater Cole-Moore lag in the presence of a neurotransmitter. This prediction was confirmed for noradrenaline, while no change was observed in the presence of angiotensin II, a voltage-insensitive G protein modulator. We used the limiting slope method for calculation of the gating charge per channel. Effective charge z was 6.32+/-0.65 for Ca(V)2.2 channels in unregulated conditions, while GTPgammaS reduced elementary charge by approximately 4 e(0). Accordingly, increased concentration of noradrenaline induced a gradual decrease on z, indicating that this decrement was due to a G protein voltage-sensitive modulation. This paper shows for the first time a significant and reversible decrease in charge transfer of Ca(V)2.2 channels under G protein modulation, which might depend on the activated G protein inhibitory pathway.

  5. Molecular simulations study of novel 1,4-dihydropyridines derivatives with a high selectivity for Cav3.1 calcium channel

    PubMed Central

    Liu, Xiaoguang; Yu, Hui; Zhao, Xi; Huang, Xu-Ri

    2015-01-01

    1,4-Dihydropyridines (DHPs) have been developed to treat hypertension, angina, and nerve system disease. They are thought to mainly target the L-type calcium channels, but low selectivity prompts them to block Cav1.2 and Cav3.1 channels simultaneously. Recently, some novel DHPs with different hydrophobic groups have been synthesized and among them M12 has a higher selectivity for Cav3.1. However, the structural information about Cav3.1-DHPs complexes is not available in the experiment. Thus, we combined homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations to quantitatively elucidate the inhibition mechanism of DHPs. The calculated results indicate that our model is in excellent agreement with experimental results. On the basis of conformational analysis, we identify the main interactions between DHPs and calcium channels and further elaborate on the different selectivity of ligands from the micro perspective. In conjunction with energy distribution, we propose that the binding sites of Cav3.1-DHPs is characterized by several interspersed hydrophobic amino acid residues on the IIIS6 and IVS6 segments. We also speculate the favorable function groups on prospective DHPs. Besides, our model provides important information for further mutagenesis experiments. PMID:26256672

  6. Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation

    PubMed Central

    Findeisen, Felix; Minor, Daniel L.

    2010-01-01

    Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (CaVs) with unusual properties. CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit CaV1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF-hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the CaV1.2 IQ domain at a site that overlaps with the Ca2+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates CaVs. PMID:21134641

  7. Amyloid Precursor Protein Regulates Cav1.2 L-type Calcium Channel Levels and Function to Influence GABAergic Short-term Plasticity

    PubMed Central

    Yang, Li; Wang, Zilai; Wang, Baiping; Justice, Nicholas J.; Zheng, Hui

    2010-01-01

    Amyloid precursor protein (APP) has been strongly implicated in the pathogenesis of Alzheimer’s disease (AD). Although impaired synaptic function is believed to be an early and causative event in AD, how APP physiologically regulates synaptic properties remains poorly understood. Here, we report a critical role for APP in the regulation of L-type calcium channels (LTCC) in GABAergic inhibitory neurons in striatum and hippocampus. APP deletion in mice leads to an increase in the levels of Cav1.2, the pore-forming subunit of LTCCs, and subsequent increases in GABAergic calcium currents (ICa 2+) that can be reversed by re-introduction of APP. Upregulated levels of Cav1.2 result in reduced GABAergic paired-pulse inhibition (PPI) and increased GABAergic post-tetanic potentiation (PTP) in both striatal and hippocampal neurons, indicating that APP modulates synaptic properties of GABAergic neurons by regulating Cav1.2. Furthermore, APP physically interacts with Cav1.2, suggesting a mechanism in which loss of APP leads to an inappropriate accumulation and aberrant activity of Cav1.2. These results provide a direct link between APP and calcium signaling and might help explain how altered APP regulation leads to changes in synaptic function that occur with AD. PMID:20016080

  8. Molecular simulations study of novel 1,4-dihydropyridines derivatives with a high selectivity for Cav3.1 calcium channel.

    PubMed

    Liu, Xiaoguang; Yu, Hui; Zhao, Xi; Huang, Xu-Ri

    2015-11-01

    1,4-Dihydropyridines (DHPs) have been developed to treat hypertension, angina, and nerve system disease. They are thought to mainly target the L-type calcium channels, but low selectivity prompts them to block Cav1.2 and Cav3.1 channels simultaneously. Recently, some novel DHPs with different hydrophobic groups have been synthesized and among them M12 has a higher selectivity for Cav3.1. However, the structural information about Cav3.1-DHPs complexes is not available in the experiment. Thus, we combined homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations to quantitatively elucidate the inhibition mechanism of DHPs. The calculated results indicate that our model is in excellent agreement with experimental results. On the basis of conformational analysis, we identify the main interactions between DHPs and calcium channels and further elaborate on the different selectivity of ligands from the micro perspective. In conjunction with energy distribution, we propose that the binding sites of Cav3.1-DHPs is characterized by several interspersed hydrophobic amino acid residues on the IIIS6 and IVS6 segments. We also speculate the favorable function groups on prospective DHPs. Besides, our model provides important information for further mutagenesis experiments.

  9. 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.

  10. 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.

  11. Robotic vehicle

    DOEpatents

    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.

  12. Robotic vehicle

    DOEpatents

    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.

  13. 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.

  14. Antidepressant-like effect of Tagetes lucida Cav. extract in rats: involvement of the serotonergic system.

    PubMed

    Gabriela, Guadarrama-Cruz; Javier, Alarcón-Aguilar Francisco; Elisa, Vega-Avila; Gonzalo, Vázquez-Palacios; Herlinda, Bonilla-Jaime

    2012-01-01

    It has been demonstrated that the decoction of the aerial parts of Tagetes lucida Cav. produces an antidepressant effect during the forced swimming test (FST) in rats. The aim of this study was to evaluate the effect of different organic extracts and one aqueous extract of the aerial parts of T. lucida on the FST. In addition, the possible involvement of the serotonergic system in the antidepressant-like effect of T. lucida in the FST was evaluated, as was its potential toxicological effect. The different extracts of T. lucida (methanol, hexane, dichloromethane and aqueous, 10 and 50 mg/kg), as well as fluoxetine (FLX, 5 mg/kg), were administered per os (p.o.) to rats for 14 days. All animals were subjected to the FST. Only the aqueous extract of T. lucida at a dose of 50 mg/kg significantly reduced immobility behavior and increased swimming in the FST, similar to FLX. Later, the aqueous extract of T. lucida (50mg/kg) was administered for 1, 7 and 14 days. An antidepressant effect was observed after 7 days of treatment. To evaluate the participation of the serotoninergic system, the animals were pretreated with PCPA, an inhibitor of serotonin synthesis (100 mg/kg/day for 4 consecutive days). The animals were treated with the aqueous extract of T. lucida (50 mg/kg) and FLX (5 mg/kg) 24 h after the final injection and were then subjected to the FST. Pretreatment with PCPA inhibited the antidepressant effect of both T. lucida and FLX. Finally, T. lucida was administered p.o. and intraperitoneal route to evaluate its acute toxicological effect. The aqueous extract of T. lucida, administered p.o., did not produce lethality or any significant changes in behavior. In conclusion, the aqueous extract of T. lucida manifested an antidepressant-like effect in the FST mediated by the serotonergic system, with no adverse effects when administered p.o.

  15. 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.

  16. 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.

  17. Dynamical mechanism in aero-engine gas path system using minimum spanning tree and detrended cross-correlation analysis

    NASA Astrophysics Data System (ADS)

    Dong, Keqiang; Zhang, Hong; Gao, You

    2017-01-01

    Identifying the mutual interaction in aero-engine gas path system is a crucial problem that facilitates the understanding of emerging structures in complex system. By employing the multiscale multifractal detrended cross-correlation analysis method to aero-engine gas path system, the cross-correlation characteristics between gas path system parameters are established. Further, we apply multiscale multifractal detrended cross-correlation distance matrix and minimum spanning tree to investigate the mutual interactions of gas path variables. The results can infer that the low-spool rotor speed (N1) and engine pressure ratio (EPR) are main gas path parameters. The application of proposed method contributes to promote our understanding of the internal mechanisms and structures of aero-engine dynamics.

  18. 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.

  19. 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

  20. Electrophysiological characterization of activation state-dependent Cav2 channel antagonist TROX-1 in spinal nerve injured rats

    PubMed Central

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

    2015-01-01

    Prialt, a synthetic version of Cav2.2 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 Cav2.1, 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 Cav2.2 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

  1. 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.

  2. Mechanisms of inhibition of CaV3.1 T-type calcium current by aliphatic alcohols

    PubMed Central

    Eckle, Veit-Simon; Todorovic, Slobodan M

    2010-01-01

    Many aliphatic alcohols modulate activity of various ion channels involved in sensory processing and also exhibit anesthetic capacity in vivo. Although the interaction of one such compound, 1-octanol (octanol) with different T-type calcium channels (T-channels) has been described, the mechanisms of current modulation and its functional significance are not well studied. Using patch-clamp technique, we investigated the mechanisms of inhibition of T-currents by a series of aliphatic alcohols in recombinant human CaV3.1 (α1G) T-channel isoform expressed in human embryonic kidney (HEK) 293 cells and thalamocortical (TC) relay neurons in brain slices of young rats. Octanol, 1-heptanol (heptanol) and 1-hexanol (hexanol) inhibited the recombinant CaV3.1 currents in concentration-dependent manner yielding IC50 values of 362 µM, 1063 µM and 3167 µM, respectively. Octanol similarly inhibited native thalamic CaV3.1 T-currents with an IC50 of 287 µM and diminished burst firing without significant effect on passive membrane properties of these neurons. Inhibitory effect of octanol on T-currents in both native and recombinant cells was accompanied with accelerated macroscopic inactivation kinetics and hyperpolarizing shift in the steady-state inactivation curve. Additionally, octanol induced a depolarizing shift in steady-state activation curves of T-current in TC neurons. Surprisingly, the recovery from fast inactivation at hyperpolarized membrane potentials was accelerated by octanol up three-fold in native but not recombinant channels. Given the importance of thalamocortical pathways in providing sleep, arousal, and anesthetic states, modulation of thalamic T-currents may at least contribute to the pharmacological effects of aliphatic alcohols. PMID:20363234

  3. 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

  4. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

    2013-02-01

    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.

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

    NASA Astrophysics Data System (ADS)

    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.; Luo, G.; Ma, X.; Penner, J. E.; Rasch, P. J.; Seland, Ø.; Skeie, R. B.; Stier, P.; Takemura, T.; Tsigaridis, K.; Wang, Z.; Xu, L.; Yu, H.; Yu, F.; Yoon, J.-H.; Zhang, K.; Zhang, H.; Zhou, C.

    2012-08-01

    We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 15 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 15 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-2, with a mean of -0.30 W m-2 for the 15 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 -0.39 W m-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.

  7. A Preliminary to War: The 1st Aero Squadron and the Mexican Punitive Expedition of 1916

    DTIC Science & Technology

    2003-01-01

    ordered a reconnaissance along the Mexican Northwestern railroad south toward Cumbre Pass in the Sierra Madre mountains. Dodd and Foulois flew this...Casas Grandes and Galeana Valleys ranged between 6,000 and 7,000 feet, and that Cumbre Pass lay at about 9,000 feet. All of these altitudes were higher...of the Cumbre Pass tunnel, but could go no farther. For two hours, 25 The 1st Aero Squadron in Mexico; probably following a mission by Signal Corps No

  8. Performance Analysis of the AeroTP Transport Protocol for Highly-Dynamic Airborne Telemetry Networks

    DTIC Science & Technology

    2011-06-03

    Acknowledgment Options.” RFC 2018 (Proposed Standard ), Oct. 1996. [11] “The ns- 3 network simulator.” http://www.nsnam.org, July 2009. [12] M. AL-Enazi, S. A. Gogi...AFFTC-PA- 11146 Performance Analysis of the AeroTP Transport Protocol for Highly-Dynamic Airborne Telemetry Networks James P.G. Sterbenz...Kamakshi Sirisha Pathapati, Truc Anh N. Nguyen, Justin P. Rohrer AIR FORCE FLIGHT TEST CENTER EDWARDS AFB, CA JUNE 3 , 2011 A F F T C

  9. 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.

  10. 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.

  11. Suppression of peripheral pain by blockade of Cav2.2 channels in nociceptors induces RANKL and impairs recovery from inflammatory arthritis

    PubMed Central

    Baddack, Uta; Frahm, Silke; Antolin-Fontes, Beatriz; Grobe, Jenny; Lipp, Martin; Müller, Gerd; Ibañez-Tallon, Ines

    2015-01-01

    Objective A hallmark of rheumatoid arthritis (RA) is the chronic pain that accompanies the inflammation and joint deformation. Patients with RA rate pain relief with highest priority, however, few studies have addressed the efficacy and safety of therapies directed specifically towards pain pathways. The conotoxin MVIIA (Prialt/Ziconotide) is used in humans to alleviate persistent pain syndromes because it specifically blocks the CaV2.2 voltage-gated calcium channel, which mediates the release of neurotransmitters and proinflammatory mediators from peripheral nociceptor nerve terminals. The purpose of this study was to investigate whether block of CaV2.2 can suppress arthritic pain, and to examine the progression of induced arthritis during persistent CaV2.2 blockade. Methods Transgenic mice (Tg-MVIIA) expressing a membrane-tethered form of the ω-conotoxin MVIIA, under the control of a nociceptor-specific gene, were employed. These mice were subjected to unilateral induction of joint inflammation using the Antigen- and Collagen-Induced Arthritis (ACIA) model. Results We observed that CaV2.2-blockade mediated by t-MVIIA effectively suppressed arthritis-induced pain; however, in contrast to their wild-type littermates, which ultimately regained use of their injured joint as inflammation subsides, Tg-MVIIA mice showed continued inflammation with an up-regulation of the osteoclast activator RANKL and concomitant joint and bone destruction. Conclusion Altogether, our results indicate that alleviation of peripheral pain by blockade of CaV2.2- mediated calcium influx and signaling in nociceptor sensory neurons, impairs recovery from induced arthritis and point to the potentially devastating effects of using CaV2.2 channel blockers as analgesics during inflammation. PMID:25733371

  12. Inhibitory gene expression of the Cav3.1 T-type calcium channel to improve neuronal injury induced by lidocaine hydrochloride.

    PubMed

    Wen, Xianjie; Xu, Shiyuan; Zhang, Qingguo; Li, Xiaohong; Liang, Hua; Yang, Chenxiang; Wang, Hanbing; Liu, Hongzhen

    2016-03-15

    Cav3.1 is a low-voltage-activated (LVA) calcium channel that plays a key role in regulating intracellular calcium ion levels. In this study, we observed the effects of lidocaine hydrochloride on the pshRNA-CACNA1G-SH-SY5Y cells that silenced Cav3.1 mRNA by RNA interference, and investigated the roles of p38 MAPK in these effects. We constructed the pNC-puro-CACNA1G-SH-SY5Y cells and pshRNA-CACNA1G -SH-SY5Y cells by the RNA interference. All the cells were cultured with or without 10mM lidocaine hydrochloride for 24 h. The cell morphology, cell viability, Cav3.1 and p38 protein expression, cell apoptosis rate and intracellular calcium ion concentration were detected. We found that all cells treated with 10mM lidocaine hydrochloride for 24 h showed cellular rounding, axonal regression, and cellular floating. Compared with the cells in SH-SY5Y+Lido group and NC+Lido group, those in the RNAi+Lido group showed similar changes, but of smaller magnitude. Additionally, following lidocaine hydrochloride all cells displayed increased Cav3.1 and p38 MAPK protein, apoptosis rate, and intracellular calcium ion levels; however,these changes in the RNAi+Lido group were less pronounced than in the SH-SY5Y+Lido and NC+Lido groups. The cell viability decreased following lidocaine hydrochloride treatment, but viability of the cells in the RNAi+Lido group was higher than in the SH-SY5Y+Lido and NC+Lido groups. The results showed that Cav3.1 may be involved in neuronal injury induced by lidocaine hydrochloride and that p38 MAPK phosphorylation was reduced upon Cav3.1 gene silencing.

  13. Rem, a member of the RGK GTPases, inhibits recombinant CaV1.2 channels using multiple mechanisms that require distinct conformations of the GTPase.

    PubMed

    Yang, Tingting; Xu, Xianghua; Kernan, Timothy; Wu, Vincent; Colecraft, Henry M

    2010-05-15

    Rad/Rem/Gem/Kir (RGK) GTPases potently inhibit Ca(V)1 and Ca(V)2 (Ca(V)1-2) channels, a paradigm of ion channel regulation by monomeric G-proteins with significant physiological ramifications and potential biotechnology applications. The mechanism(s) underlying how RGK proteins inhibit I(Ca) is unknown, and it is unclear how key structural and regulatory properties of these GTPases (such as the role of GTP binding to the nucleotide binding domain (NBD), and the C-terminus which contains a membrane-targeting motif) feature in this effect. Here, we show that Rem inhibits Ca(V)1.2 channels by three independent mechanisms that rely on distinct configurations of the GTPase: (1) a reduction in surface density of channels is accomplished by enhancing dynamin-dependent endocytosis, (2) a diminution of channel open probability (P(o)) that occurs without impacting on voltage sensor movement, and (3) an immobilization of Ca(V) channel voltage sensors. The presence of both the Rem NBD and C-terminus (whether membrane-targeted or not) in one molecule is sufficient to reconstitute all three mechanisms. However, membrane localization of the NBD by a generic membrane-targeting module reconstitutes only the decreased P(o) function (mechanism 2). A point mutation that prevents GTP binding to the NBD selectively eliminates the capacity to immobilize voltage sensors (mechanism 3). The results reveal an uncommon multiplicity in the mechanisms Rem uses to inhibit I(Ca), predict new physiological dimensions of the RGK GTPase-Ca(V) channel crosstalk, and suggest original approaches for developing novel Ca(V) channel blockers.

  14. Ultrastructural evidence for pre- and postsynaptic localization of Cav1.2 L-type Ca2+ channels in the rat hippocampus.

    PubMed

    Tippens, Alyssa L; Pare, Jean-Francois; Langwieser, Nicole; Moosmang, Sven; Milner, Teresa A; Smith, Yoland; Lee, Amy

    2008-02-01

    In the hippocampal formation, Ca(v)1.2 (L-type) voltage-gated Ca(2+) channels mediate Ca(2+) signals that can trigger long-term alterations in synaptic efficacy underlying learning and memory. Immunocytochemical studies indicate that Ca(v)1.2 channels are localized mainly in the soma and proximal dendrites of hippocampal pyramidal neurons, but electrophysiological data suggest a broader distribution of these channels. To define the subcellular substrates underlying Ca(v)1.2 Ca(2+) signals, we analyzed the localization of Ca(v)1.2 in the hippocampal formation by using antibodies against the pore-forming alpha(1)-subunit of Ca(v)1.2 (alpha(1)1.2). By light microscopy, alpha(1)1.2-like immunoreactivity (alpha(1)1.2-IR) was detected in pyramidal cell soma and dendritic fields of areas CA1-CA3 and in granule cell soma and fibers in the dentate gyrus. At the electron microscopic level, alpha(1)1.2-IR was localized in dendrites, but also in axons, axon terminals, and glial processes in all hippocampal subfields. Plasmalemmal immunogold particles representing alpha(1)1.2-IR were more significant for small- than large-caliber dendrites and were largely associated with extrasynaptic regions in dendritic spines and axon terminals. These findings provide the first detailed ultrastructural analysis of Ca(v)1.2 localization in the brain and support functionally diverse roles of these channels in the hippocampal formation.

  15. 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.

  16. Dynamic similarity design method for an aero-engine dualrotor test rig

    NASA Astrophysics Data System (ADS)

    Miao, H.; Zang, C.; Friswell, M. I.

    2016-09-01

    This paper presents a dynamic similarity design method to design a scale dynamic similarity model (DSM) for a dual-rotor test rig of an aero-engine. Such a test rig is usually used to investigate the major dynamic characteristics of the full-size model (FSM) and to reduce the testing cost and time for experiments on practical aero engine structures. Firstly, the dynamic equivalent model (DEM) of a dual-rotor system is modelled based on its FSM using parametric modelling, and the first 10 frequencies and mode shapes of the DEM are updated to agree with the FSM by modifying the geometrical shapes of the DEM. Then, the scaling laws for the relative parameters (such as geometry sizes of the rotors, stiffness of the supports, inherent properties) between the DEM and its scale DSM were derived from their equations of motion, and the scaling factors of the above-mentioned parameters are determined by the theory of dimensional analyses. After that, the corresponding parameters of the scale DSM of the dual-rotor test rig can be determined by using the scaling factors. In addition, the scale DSM is further updated by considering the coupling effect between the disks and shafts. Finally, critical speed and unbalance response analysis of the FSM and the updated scale DSM are performed to validate the proposed method.

  17. 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.

  18. Physics and Measurement of Aero-Optical Effects: Past and Present

    NASA Astrophysics Data System (ADS)

    Jumper, Eric J.; Gordeyev, Stanislav

    2017-01-01

    The field of aero-optics is devoted to the study of the effects of turbulent flow fields on laser beams projected from airborne laser systems. This article reviews the early and present periods of research in aero-optics. Both periods generated impressive amounts of research activity; however, the types and amount of data differ greatly in accuracy, quality, and type owing to the development of new types of instrumentation available to collect and analyze the aberrated wave fronts of otherwise collimated laser beams projected through turbulent compressible flow fields of the type that form over beam directors. This review traces the activities and developments associated with both periods but particularly focuses on the development of modern high-bandwidth wave-front sensors used in the present research period. We describe how these modern wave-front data are collected and analyzed and the fluid mechanic information that can be gleaned from them; the use of these data in the fundamental study of turbulence is emphasized.

  19. A rapid method to achieve aero-engine blade form detection.

    PubMed

    Sun, Bin; Li, Bing

    2015-06-01

    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.

  20. 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

  1. 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.

  2. Digital holographic interferometry for characterizing deformable mirrors in aero-optics

    NASA Astrophysics Data System (ADS)

    Trolinger, James D.; Hess, Cecil F.; Razavi, Payam; Furlong, Cosme

    2016-08-01

    Measuring and understanding the transient behavior of a surface with high spatial and temporal resolution are required in many areas of science. This paper describes the development and application of a high-speed, high-dynamic range, digital holographic interferometer for high-speed surface contouring with fractional wavelength precision and high-spatial resolution. The specific application under investigation here is to characterize deformable mirrors (DM) employed in aero-optics. The developed instrument was shown capable of contouring a deformable mirror with extremely high-resolution at frequencies exceeding 40 kHz. We demonstrated two different procedures for characterizing the mechanical response of a surface to a wide variety of input forces, one that employs a high-speed digital camera and a second that employs a low-speed, low-cost digital camera. The latter is achieved by cycling the DM actuators with a step input, producing a transient that typically lasts up to a millisecond before reaching equilibrium. Recordings are made at increasing times after the DM initiation from zero to equilibrium to analyze the transient. Because the wave functions are stored and reconstructable, they can be compared with each other to produce contours including absolute, difference, and velocity. High-speed digital cameras recorded the wave functions during a single transient at rates exceeding 40 kHz. We concluded that either method is fully capable of characterizing a typical DM to the extent required by aero-optical engineers.

  3. 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.

  4. Spheroid formation of human thyroid cancer cells under simulated microgravity: a possible role of CTGF and CAV1

    PubMed Central

    2014-01-01

    Background Multicellular tumor spheroids (MCTS) formed scaffold-free under microgravity are of high interest for research and medicine. Their formation mechanism can be studied in space in real microgravity or on Earth using ground-based facilities (GBF), which simulate microgravity. On Earth, these experiments are more cost-efficient and easily performable. However, each GBF might exert device-specific and altered superimposingly gravity-dependent effects on the cells. Results FTC-133 human thyroid cancer cells were cultivated on a 2D clinostat (CN) and a random positioning machine (RPM) and compared with corresponding 1 g control cells. Harvested cell samples were investigated by microscopy, quantitative realtime-PCR and Multi-Analyte Profiling. Spheroid formation and growth occurred during 72 h of cultivation on both devices. Cytokine secretion and gene activation patterns frequently altered in different ways, when the cells were cultured either on the RPM or the CN. A decreased expression of CAV1 and CTGF in MCTS compared to adherent cells was observed after cultivation on both machines. Conclusion The development of MCTS proceeds similarly on the RPM and the CN resembling the situation observed under real microgravity conditions, while no MCTS formation was observed at 1 g under identical experimental conditions. Simultaneously, changes in the regulation of CTGF and CAV1 appeared in a comparable manner on both machines. A relationship between these molecules and MCTS formation is discussed. PMID:24885050

  5. CAV_KO: a Simple 1-D Langrangian Hydrocode for MS EXCEL™ with Automatic Generation of X-T Diagrams

    NASA Astrophysics Data System (ADS)

    Tsembelis, K.; Ramsden, B.; Proud, W. G.; Borg, J.

    2007-12-01

    Hydrocodes are widely used to predict or simulate highly dynamic and transient events such as blast and impact. Codes such as GRIM, CTH or AUTODYN are well developed and involve complex numerical methods and in many cases require a large computing infrastructure. In this paper we present a simple 1-D Langrangian hydrocode developed at the University of Cambridge, called CAV_KO written in Visual Basic. The motivation being to produce a code which, while being relatively simple, is useful for both experimental planning and teaching. The code has been adapted from the original KO code written in FORTRAN by J. Borg, which, in turn, is based on the algorithm developed by Wilkins [1]. The developed GUI within MS Excel™ and the automatic generation of x-t diagrams allow CAV_KO to be a useful tool for quick calculations of plate impact events and teaching purposes. The VB code is licensed under the GNU General Public License and a MS Excel™ spreadsheet containing the code can be downloaded from www.shockphysics.com together with a copy of the user guide.

  6. 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

  7. New 5-unsubstituted dihydropyridines with improved CaV1.3 selectivity as potential neuroprotective agents against ischemic injury.

    PubMed

    Tenti, Giammarco; Parada, Esther; León, Rafael; Egea, Javier; Martínez-Revelles, Sonia; Briones, Ana María; Sridharan, Vellaisamy; López, Manuela G; Ramos, María Teresa; Menéndez, J Carlos

    2014-05-22

    C5-unsubstituted-C6-aryl-1,4-dihydropyridines were prepared by a CAN-catalyzed multicomponent reaction from chalcones, β-dicarbonyl compounds, and ammonium acetate. These compounds were able to block Ca(2+) entry after a depolarizing stimulus and showed an improved Cav1.3/Cav1.2 selectivity in comparison with nifedipine. Furthermore, they were able to protect neuroblastoma cells against Ca(2+) overload and oxidative stress models. Their selectivity ratio makes them highly interesting for the treatment of neurological disorders where Ca(2+) dyshomeostasis and high levels of oxidative stress have been demonstrated. Furthermore, their low potency toward the cardiovascular channel subtype makes them safer by reducing their probable side effects, in comparison to classical 1,4-dihydropyridines. Some compounds afforded good protective profile in a postincubation model that simulates the real clinical situation of ictus patients, offering a therapeutic window of opportunity of great interest for patient recovery after a brain ischemic episode. Good activities were also found in acute ischemia/reperfusion models of oxygen and glucose deprivation.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 75 FR 22512 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Industries S.p.A. Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of....regulations.gov ; or in person at the Docket Management Facility between 9 a.m. and 5 p.m., Monday through... 2. The FAA amends Sec. 39.13 by adding the following new AD: 2010-09-09 Piaggio Aero Industries...

  15. 75 FR 67639 - Airworthiness Directives; Piaggio Aero Industries S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-03

    ... Industries S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... Airplane Flight Manual, stating that the towing bar P/N 01-1227-0000 or similar ferromagnetic masses are... maintenance requirements and/or airworthiness limitations developed by Piaggio Aero Industries S.p.A....

  16. 76 FR 7694 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-11

    ... INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... Docket Management Facility between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The..., etc. for PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 airplanes. As published, the...

  17. 76 FR 10224 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... this AD, contact Piaggio Aero Industries S.p.A., Via Cibrario, 4-16154 Genoa, Italy; phone: +39 010... that the towing bar P/N 01-1227-0000 or similar ferromagnetic masses are prohibited to be carried...

  18. 76 FR 36980 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ...-013-AD; Amendment 39-16697; AD 2011-09-51] RIN 2120-AA64 Airworthiness Directives; PIAGGIO AERO...: Final rule; correction. ] SUMMARY: The FAA is correcting an airworthiness directive (AD) that published in the Federal Register. That AD applies to the products listed above. The AD number in the...

  19. Green Vehicle Guide

    MedlinePlus

    ... United States Environmental Protection Agency Search Search Green Vehicle Guide Share Facebook Twitter Google+ Pinterest Contact Us ... your needs. Search for a SmartWay Vehicle Green Vehicle Guide ​What is a green vehicle? Alternative fuels ...

  20. 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

  1. An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation.

    PubMed

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

    2016-06-03

    CaV1.3 channels are a major class of L-type Ca(2+) 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 Ca(2+)-dependent inactivation (CDI) of CaV1.3 channels, an important feedback system required for Ca(2+) 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 Ca(2+)-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 Ca(2+) concentration, thus potentially disrupting neuronal development and synapse formation, ultimately leading to ASD.

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

    PubMed

    Iniguez, Jorge; Schutte, Soleil S; O'Dowd, Diane K

    2013-10-01

    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.

  3. Voltage-independent inhibition of Ca(V)2.2 channels is delimited to a specific region of the membrane potential in rat SCG neurons.

    PubMed

    Vivas, Oscar; Arenas, Isabel; García, David E

    2012-06-01

    Neurotransmitters and hormones regulate Ca(V)2.2 channels through a voltage-independent pathway which is not well understood. It has been suggested that this voltage-independent inhibition is constant at all membrane voltages. However, changes in the percent of voltage-independent inhibition of Ca(V)2.2 have not been tested within a physiological voltage range. Here, we used a double-pulse protocol to isolate the voltage-independent inhibition of Ca(V)2.2 channels induced by noradrenaline in rat superior cervical ganglion neurons. To assess changes in the percent of the voltage-independent inhibition, the activation voltage of the channels was tested between -40 and +40 mV. We found that the percent of voltage-independent inhibition induced by noradrenaline changed with the activation voltage used. In addition, voltage-independent inhibition induced by oxo-M, a muscarinic agonist, exhibited the same dependence on activation voltage, which supports that this pattern is not exclusive for adrenergic activation. Our results suggested that voltage-independent inhibition of Ca(V)2.2 channels depends on the activation voltage of the channel in a physiological voltage range. This may have relevant implications in the understanding of the mechanism involved in voltage-independent inhibition.

  4. 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

  5. Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation.

    PubMed

    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.

  6. Binding mechanisms of 1,4-dihydropyridine derivatives to L-type calcium channel Cav1.2: a molecular modeling study.

    PubMed

    Xu, Lei; Li, Dan; Tao, Li; Yang, Yanling; Li, Youyong; Hou, Tingjun

    2016-02-01

    L-type Ca(2+) channels (LTCCs), the heteromultimeric proteins, are associated with electrical signaling and provide the key link between electrical signals and non-electrical processes. 1,4-Dihydropyridine (DHP) derivatives are a major class of blockers for LTCCs, and have experienced widespread use in the treatment of cardiovascular diseases. However, the precise knowledge of the binding mechanism of these ligands to LTCCs at the atomic level has remained unknown because of the unavailability of the crystal structures of LTCCs. In this study, homology modeling, molecular docking, molecular dynamics (MD) simulations, free energy calculations and decomposition were employed to explore the structural requirement of the binding of DHP derivatives to human Cav1.2, a member of LTCCs. The binding conformations of the DHPs in the active site of Cav1.2 were predicted, and the rank of the binding free energies of Cav1.2/DHPs is generally consistent with the experimental data. The structural analysis shows that most studied ligands fit into a hydrophobic pocket formed by Phe1129, Ile1173, Phe1176, Met1177 and Met1509, and form aryl-aryl interaction with Phe1129 or Tyr1508. The consistency between the predictions and experimental data suggest that the developed model is reliable and can be used as a valuable platform for the structure-based design of new potent ligands of Cav1.2.

  7. Experimental investigation on aero-optical aberration of shock wave/boundary layer interactions

    NASA Astrophysics Data System (ADS)

    Ding, Haolin; Yi, Shihe; Fu, Jia; He, Lin

    2016-10-01

    After streaming through the flow field which including the expansion, shock wave, boundary, etc., the optical wave would be distorted by fluctuations in the density field. Interactions between laminar/turbulent boundary layer and shock wave contain large number complex flow structures, which offer a condition for studying the influences that different flow structures of the complex flow field have on the aero-optical aberrations. Interactions between laminar/turbulent boundary layer and shock wave are investigated in a Mach 3.0 supersonic wind tunnel, based on nanoparticle-tracer planar laser scattering (NPLS) system. Boundary layer separation/attachment, induced suppression waves, induced shock wave, expansion fan and boundary layer are presented by NPLS images. Its spatial resolution is 44.15 μm/pixel. Time resolution is 6ns. Based on the NPLS images, the density fields with high spatial-temporal resolution are obtained by the flow image calibration, and then the optical path difference (OPD) fluctuations of the original 532nm planar wavefront are calculated using Ray-tracing theory. According to the different flow structures in the flow field, four parts are selected, (1) Y=692 600pixel; (2) Y=600 400pixel; (3) Y=400 268pixel; (4) Y=268 0pixel. The aerooptical effects of different flow structures are quantitatively analyzed, the results indicate that: the compressive waves such as incident shock wave, induced shock wave, etc. rise the density, and then uplift the OPD curve, but this kind of shock are fixed in space position and intensity, the aero-optics induced by it can be regarded as constant; The induced shock waves are induced by the coherent structure of large size vortex in the interaction between turbulent boundary layer, its unsteady characteristic decides the induced waves unsteady characteristic; The space position and intensity of the induced shock wave are fixed in the interaction between turbulent boundary layer; The boundary layer aero-optics are

  8. 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

  9. Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis

    PubMed Central

    Rahman, W.; Patel, R.; Dickenson, A.H.

    2015-01-01

    Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. TROX-1 is an orally available, use dependent and state-selective Cav2 antagonist, exerting its analgesic effect primarily via Cav2.2 blockade, with an improved therapeutic window compared with ziconitide. Using a rat model of monosodium iodoacetate (MIA), 2 mg, induced OA we used in vivo electrophysiology to assess the effects of spinal or systemic administration of TROX-1 on the evoked activity of wide dynamic range spinal dorsal horn neurons in response to electrical, natural mechanical (dynamic brush and von Frey 2, 8, 26 and 6 g) and thermal (40, 45 and 45 °C) stimuli applied to the peripheral receptive field. MIA injection into the knee joint resulted in mechanical hypersensitivity of the ipsilateral hind paw and weight-bearing asymmetry. Spinal administration of TROX-1 (0.1 and 1 μg/50 μl) produced a significant dose-related inhibition of dynamic brush, mechanical (von Frey filament (vF) 8, 26 and 60 g) and noxious thermal-(45 and 48 °C) evoked neuronal responses in MIA rats only. Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60 g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased

  10. 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.

  11. Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

    PubMed

    Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

    2016-06-01

    Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms

  12. 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

  13. Demonstration of Binding of Neuronal Calcium Sensor-1 to the Cav2.1 P/Q-Type Calcium Channel

    PubMed Central

    2014-01-01

    In neurons, entry of extracellular calcium (Ca2+) into synaptic terminals through Cav2.1 (P/Q-type) Ca2+ channels is the driving force for exocytosis of neurotransmitter-containing synaptic vesicles. This class of Ca2+ channel is, therefore, pivotal during normal neurotransmission in higher organisms. In response to channel opening and Ca2+ influx, specific Ca2+-binding proteins associate with cytoplasmic regulatory domains of the P/Q channel to modulate subsequent channel opening. Channel modulation in this way influences synaptic plasticity with consequences for higher-level processes such as learning and memory acquisition. The ubiquitous Ca2+-sensing protein calmodulin (CaM) regulates the activity of all types of mammalian voltage-gated Ca2+ channels, including the P/Q class, by direct binding to specific regulatory motifs. More recently, experimental evidence has highlighted a role for additional Ca2+-binding proteins, particularly of the CaBP and NCS families in the regulation of P/Q channels. NCS-1 is a protein found from yeast to humans and that regulates a diverse number of cellular functions. Physiological and genetic evidence indicates that NCS-1 regulates P/Q channel activity, including calcium-dependent facilitation, although a direct physical association between the proteins has yet to be demonstrated. In this study, we aimed to determine if there is a direct interaction between NCS-1 and the C-terminal cytoplasmic tail of the Cav2.1 α-subunit. Using distinct but complementary approaches, including in vitro binding of bacterially expressed recombinant proteins, fluorescence spectrophotometry, isothermal titration calorimetry, nuclear magnetic resonance, and expression of fluorescently tagged proteins in mammalian cells, we show direct binding and demonstrate that CaM can compete for it. We speculate about how NCS-1/Cav2.1 association might add to the complexity of calcium channel regulation mediated by other known calcium-sensing proteins and how

  14. Upregulation of Voltage-Gated Calcium Channel Cav1.3 in Bovine Somatotropes Treated with Ghrelin

    PubMed Central

    Salinas Zarate, V. M.; Magdaleno Méndez, A.; Domínguez Mancera, B.; Rodríguez Andrade, A.; Barrientos Morales, M.; Cervantes Acosta, P.; Hernández Beltrán, A.; Romero Salas, D.; Flores Hernández, J. L. V.; Monjaraz Guzmán, E.; Félix Grijalva, D. R.

    2013-01-01

    Activation of the growth hormone (GH) secretagogue receptor (GHS-R) by synthetic GH releasing peptides (GHRP) or its endogenous ligand (Ghrelin) stimulates GH release. Though much is known about the signal transduction underlying short-term regulation, there is far less information on the mechanisms that produce long-term effects. In the current report, using an enzyme-linked immunosorbent assay for GH detection and whole-cell patch-clamp recordings, we assessed the long-term actions of such regulatory factors on voltage-activated Ca2+ currents in bovine somatotropes (BS) separated on a Percoll gradient and detected by immunohistochemistry. After 24 h of treatment with Ghrelin (10 nM) or GHRP-6 (100 nM) enhanced BS secretory activity; GH secretion stimulated by GHS through the activation of GHS-R because treatment with the antagonist of GHS-R (D-Lys3-GHRP-6, 10 μM) blocked the GH secretion, and the effect was dose and time dependent (24, 48, and 72 h). GH secretion stimulated by GHRP-6 was abolished by nifedipine (0.5 μM), a blocker of L-type HVA Ca2+ channels, and KN-62 (10 μM), an inhibitor of Ca2+/CaM-KII. After 72 h in culture, all recorded BS exhibited two main Ca2+ currents: a low voltage-activated (LVA; T-type) and a high voltage-activated (HVA; mostly dihydropyridine-sensitive L-type) current. Interestingly, HVA and LVA channels were differentially upregulated by Ghrelin. Chronic treatment with the GHS induced a significant selective increase on the Ba2+ current through HVA Ca2+ channels, and caused only a small increase of currents through LVA channels. The stimulatory effect on HVA current density was accompanied by an augment in maximal conductance with no apparent changes in the kinetics and the voltage dependence of the Ca2+ currents, suggesting an increase in the number of functional channels in the cell membrane. Lastly, in consistency with the functional data, quantitative real-time RT-PCR revealed transcripts encoding for the Cav

  15. Vehicle Controller

    NASA Technical Reports Server (NTRS)

    1985-01-01

    UNISTICK is an airplane-like joystick being developed by Johnson Engineering under NASA and VA sponsorship. It allows a driver to control a vehicle with one hand, and is based upon technology developed for the Apollo Lunar Landings of the 1970's. It allows severely handicapped drivers to operate an automobile or van easily. The system is expected to be in production by March 1986.

  16. The Calmodulin-Binding, Short Linear Motif, NSCaTE Is Conserved in L-Type Channel Ancestors of Vertebrate Cav1.2 and Cav1.3 Channels

    PubMed Central

    Taiakina, Valentina; Boone, Adrienne N.; Fux, Julia; Senatore, Adriano; Weber-Adrian, Danielle

    2013-01-01

    NSCaTE is a short linear motif of (xWxxx(I or L)xxxx), composed of residues with a high helix-forming propensity within a mostly disordered N-terminus that is conserved in L-type calcium channels from protostome invertebrates to humans. NSCaTE is an optional, lower affinity and calcium-sensitive binding site for calmodulin (CaM) which competes for CaM binding with a more ancient, C-terminal IQ domain on L-type channels. CaM bound to N- and C- terminal tails serve as dual detectors to changing intracellular Ca2+ concentrations, promoting calcium-dependent inactivation of L-type calcium channels. NSCaTE is absent in some arthropod species, and is also lacking in vertebrate L-type isoforms, Cav1.1 and Cav1.4 channels. The pervasiveness of a methionine just downstream from NSCaTE suggests that L-type channels could generate alternative N-termini lacking NSCaTE through the choice of translational start sites. Long N-terminus with an NSCaTE motif in L-type calcium channel homolog LCav1 from pond snail Lymnaea stagnalis has a faster calcium-dependent inactivation than a shortened N-termini lacking NSCaTE. NSCaTE effects are present in low concentrations of internal buffer (0.5 mM EGTA), but disappears in high buffer conditions (10 mM EGTA). Snail and mammalian NSCaTE have an alpha-helical propensity upon binding Ca2+-CaM and can saturate both CaM N-terminal and C-terminal domains in the absence of a competing IQ motif. NSCaTE evolved in ancestors of the first animals with internal organs for promoting a more rapid, calcium-sensitive inactivation of L-type channels. PMID:23626724

  17. Neurochemical characterization of the striatum and the nucleus accumbens in L-type Ca(v)1.3 channels knockout mice.

    PubMed

    Sagala, Ferry S P; Harnack, Daniel; Bobrov, Evgeny; Sohr, Reinhard; Gertler, Christoph; James Surmeier, D; Kupsch, Andreas

    2012-02-01

    L-type Ca(v)1.3 channels control the autonomous pacemaking of the substantia nigra (SN) dopamine (DA) neurons, which maintains the sustained release of DA in the striatum, its target structure. The persistent engagement of L-type channels during pacemaking might lead to increased vulnerability to environmental stressors or degenerative processes, providing a mechanism for the development of Parkinson's disease (PD). Interestingly, L-type channels are not necessary for pacemaking, opening the possible use of calcium channel antagonists as neuroprotective agents for PD without disturbing normal DA function. In this study we aimed to evaluate the consequences of Ca(v)1.3 channels deletion at the neurochemical level. For this purpose, tissue concentrations of DA and their respective metabolites were measured using high performance liquid chromatography (HPLC) in the striatum and the nucleus accumbens (NAcc) of mice lacking the gene for the Ca(v)1.3 channel subunit (CACNA1D) and compared to those in wild-type mice. Striatal DA level did not differ between the two groups. In contrast, the level of serotonin, glutamate, GABA, and taurine were increased by more than 50% in the striatum of Ca(v)1.3 null mice. Neurotransmitters levels in the NAcc did not differ between the different groups. In conclusion, our results neurochemically corroborate the robustness of the nigrostriatal DA neurons in the absence of Ca(v)1.3 channels, but suggest that complete deletion of this channel affected a variety of other transmitter systems.

  18. miR-29a Promotes Lipid Droplet and Triglyceride Formation in HCV Infection by Inducing Expression of SREBP-1c and CAV1

    PubMed Central

    Mahdy, Mennatallah Mamdouh; El-Ekiaby, Nada Magdy; Hashish, Rana Mahmoud; Salah, Radwa Ayman; Hanafi, Rasha Sayed; El-Said Azzazy, Hassan Mohamed; Abdelaziz, Ahmed Ihab

    2016-01-01

    Abstract Aims: To examine the regulation of SREBP-1c and CAV1 by microRNA-29a (miR-29a) in cells infected with hepatitis C virus (HCV) in an attempt to control HCV-induced non-alcoholic fatty liver disease. Methods: In order to examine the manipulation of SREBP-1c and CAV1 by miR-29a, oleic acid (OA)-treated JFH-I-infected Huh-7 cells were used. OA was added 24 h post-transfection and gene expression was investigated by qRT-PCR at 48 h post treatment. The functional impact of the observed alteration in SREBP-1c and CAV1 expression was analyzed by examining lipid droplet (LD) and triglyceride (TG) content at 72 h post-OA treatment using light microscopy and spectrophotometry, respectively. Viral load was quantified by qRT-PCR at 72 h post-transfection. Results: OA treatment induced the expression of miR-29a and SREBP-1c, as compared to untreated cells. Forced miR-29a expression led to a significant up-regulation of SREBP-1c as well as CAV1 compared to mock untransfected cells. Ectopic expression of miR-29a resulted in a marked increase in LDs and their respective TGs, while miR-29a antagomirs decreased both the LD and TG content compared to mock untransfected cells. Moreover, forcing the expression of miR-29a in JFH-1 HCV-infected Huh-7 cells resulted in 53% reduction in viral titers compared to mock untransfected Huh-7 cells. Conclusion: Inducing miR-29a expression significantly induces SREBP-1c and CAV1 expression, thereby increasing LDs as well as their respective TGs. Nonetheless, forcing the expression of miR-29a resulted in reduction of HCV RNA levels in Huh-7 cells. PMID:28097097

  19. Functional, electrophysiological and molecular docking analysis of the modulation of Cav1.2 channels in rat vascular myocytes by murrayafoline A

    PubMed Central

    Saponara, S; Durante, M; Spiga, O; Mugnai, P; Sgaragli, G; Huong, TT; Khanh, PN; Son, NT; Cuong, NM

    2016-01-01

    Background and Purpose The carbazole alkaloid murrayafoline A (MuA) enhances contractility and the Ca2+ currents carried by the Cav1.2 channels [ICa1.2] of rat cardiomyocytes. As only few drugs stimulate ICa1.2, this study was designed to analyse the effects of MuA on vascular Cav1.2 channels. Experimental Approach Vascular activity was assessed on rat aorta rings mounted in organ baths. Cav1.2 Ba2+ current [IBa1.2] was recorded in single rat aorta and tail artery myocytes by the patch‐clamp technique. Docking at a 3D model of the rat, α1c central pore subunit of the Cav1.2 channel was simulated in silico. Key Results In rat aorta rings MuA, at concentrations ≤14.2 μM, increased 30 mM K+‐induced tone and shifted the concentration‐response curve to K+ to the left. Conversely, at concentrations >14.2 μM, it relaxed high K+ depolarized rings and antagonized Bay K 8644‐induced contraction. In single myocytes, MuA stimulated IBa1.2 in a concentration‐dependent, bell‐shaped manner; stimulation was stable, incompletely reversible upon drug washout and accompanied by a leftward shift of the voltage‐dependent activation curve. MuA docked at the α1C subunit central pore differently from nifedipine and Bay K 8644, although apparently interacting with the same amino acids of the pocket. Neither Bay K 8644‐induced stimulation nor nifedipine‐induced block of IBa1.2 was modified by MuA. Conclusions and Implications Murrayafoline A is a naturally occurring vasoactive agent able to modulate Cav1.2 channels and dock at the α1C subunit central pore in a manner that differed from that of dihydropyridines. © 2015 The British Pharmacological Society PMID:26493241

  20. Hermes vehicle

    NASA Astrophysics Data System (ADS)

    Cretenet, J.-C.

    1984-10-01

    Projected mission profiles and computational models of the Hermes winged manned reentry vehicle are discussed. Launched into a low orbit with a crew of at most four by the Ariane 5 vehicle, Hermes will serve transportation, crew relief, safety, and freight carriage functions. It will have a nominal 300-500 km circular or 600-900 km heliosynchronous orbit, weigh from 13,500-16,700 kg, and return in hypersonic glide to a wheeled landing. The vehicle dimensions will be 15-18 m length, 6 m height at the tail fin, and a 10 m span. The L/D ratio will be 1.5-1.6, thereby furnishing a cross range of 2500 km. Hermes will have a Shuttle-type fuselage, carbon-carbon nose, and insulation on the extrados designed to keep the structure at 175 C or lower. The avionics will have 3-4 levels of redundance, each mission phase-dependent. Power will be supplied by three fuel cells and a bank of four Ag-Zn batteries. Hardware development is scheduled to begin in 1988.

  1. 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

  2. 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.

  3. 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.

  4. Numerical Study of a Fuel Centrifugal Pump with Variable Impeller Width for Aero-engines

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Guan, Huasheng; Ye, Zhifeng

    2015-12-01

    As typical pump with large flow rate and high reliability, centrifugal pumps in fuel system of aero-engines mostly regulate flow rate by flow bypass, which leads to low efficiency and large fuel temperature rise especially at low flow rate. An innovative fuel centrifugal pump with variable impeller width is a more effective way to regulate flow rate than flow bypass. To find external characteristics of the centrifugal pump with variable impeller width proposed in this paper, flow domain within the pump is simulated numerically and some primary performance parameters and their correlation are analyzed. Results show that flow rate of the pump can be regulated by variable impeller width and that efficiency for this scheme is higher than that for flow bypass. The higher outlet static pressure the pump runs at, the wider range of flow rates can be obtained with stronger nonlinear relationship between flow rate and impeller width.

  5. 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.

  6. 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.

  7. 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

  8. 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 purpose of the experimental program reported herein was to evaluate and compare the relative aero-acoustic effectiveness of two core engine suppressors, a contractor-designed suppressor delivered with the Quiet Engine, and a NASA-designed suppressor, designed and built subsequently. 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 penalty. The NASA core suppressor without the splitter suppressed most of the core noise without any engine performance penalty.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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. 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

  15. Cooperative activation of the T-type CaV3.2 channel: interaction between Domains II and III.

    PubMed

    Demers-Giroux, Pierre-Olivier; Bourdin, Benoîte; Sauvé, Rémy; Parent, Lucie

    2013-10-11

    T-type CaV3 channels are important mediators of Ca(2+) entry near the resting membrane potential. Little is known about the molecular mechanisms responsible for channel activation. Homology models based upon the high-resolution structure of bacterial NaV channels predict interaction between the S4-S5 helix of Domain II (IIS4-S5) and the distal S6 pore region of Domain II (IIS6) and Domain III (IIIS6). Functional intra- and inter-domain interactions were investigated with a double mutant cycle analysis. Activation gating and channel kinetics were measured for 47 single mutants and 20 pairs of mutants. Significant coupling energies (ΔΔG(interact) ≥ 1.5 kcal mol(-1)) were measured for 4 specific pairs of mutants introduced between IIS4-S5 and IIS6 and between IIS4-S5 and IIIS6. In agreement with the computer based models, Thr-911 in IIS4-S5 was functionally coupled with Ile-1013 in IIS6 during channel activation. The interaction energy was, however, found to be stronger between Val-907 in IIS4-S5 and Ile-1013 in IIS6. In addition Val-907 was significantly coupled with Asn-1548 in IIIS6 but not with Asn-1853 in IVS6. Altogether, our results demonstrate that the S4-S5 and S6 helices from adjacent domains are energetically coupled during the activation of a low voltage-gated T-type CaV3 channel.

  16. Redox mechanism of S-nitrosothiol modulation of neuronal CaV3.2 T-type calcium channels.

    PubMed

    Lee, Jeonghan; Nelson, Michael T; Rose, Kirstin E; Todorovic, Slobodan M

    2013-10-01

    T-type calcium channels in the dorsal root ganglia (DRG) have a central function in tuning neuronal excitability and are implicated in sensory processing including pain. Previous studies have implicated redox agents in control of T-channel activity; however, the mechanisms involved are not completely understood. Here, we recorded T-type calcium currents from acutely dissociated DRG neurons from young rats and investigated the mechanisms of CaV3.2 T-type channel modulation by S-nitrosothiols (SNOs). We found that extracellular application of S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl-penicillamine rapidly reduced T-type current amplitudes. GSNO did not affect voltage dependence of steady-state inactivation and macroscopic current kinetics of T-type channels. The effects of GSNO were abolished by pretreatment of the cells with N-ethylmaleimide, an irreversible alkylating agent, but not by pretreatment with 1H-(1,2,4) oxadiazolo (4,3-a) quinoxalin-1-one, a specific soluble guanylyl cyclase inhibitor, suggesting a potential effect of GSNO on putative extracellular thiol residues on T-type channels. Expression of wild-type CaV3.2 channels or a quadruple Cys-Ala mutant in human embryonic kidney cells revealed that Cys residues in repeats I and II on the extracellular face of the channel were required for channel inhibition by GSNO. We propose that SNO-related molecules in vivo may lead to alterations of T-type channel-dependent neuronal excitability in sensory neurons and in the central nervous system in both physiological and pathological conditions such as neuronal ischemia/hypoxia.

  17. Differential sensitivities of CaV1.2 IIS5-S6 mutants to 1,4-dihydropyridine analogs.

    PubMed

    Hui, Kwokyin; Kwok, Trevor C Y; Kostelecki, Wojciech; Leen, Jessica; Roy, Peter John; Feng, Zhong-Ping

    2009-01-14

    1,4-Dihydropyridines (DHPs), L-type calcium channel (Ca(V)1) blockers, are known to interact with Ca(V)1.2 subunits through their binding site located at IIIS5-S6 and IVS6 regions. We recently identified two domain II residues (S666 and A752) critical for nifedipine blockade (Kwok et al., 2008). In this study, we examined the blockade effects of two DHP analogues, nemadipine and nicardipine, on wildtype, M1161A (in IIIS6), S666V (in IIS5) and A752T (in IIS6) mutants of the rat alpha(1C) subunit transiently expressed with beta(2a) and alpha(2)delta in cultured tsA201 cells. We found that the IC(50) ratio of the mutants to the wildtype channel was similar in S666V and M1161A mutants for both drugs, but in A752T it was lower for nemadipine than nicardipine (P<0.05). At saturating drug concentrations, not all the current was completely blocked in the mutants. The residual current recorded in 100 microM nemadipine was approximately 10% of the total current for the A752T channel, which was significantly higher than that in 100 microM nicardipine (approximately 2%). In wildtype, S666V and M1161A, there was no significant difference in residual current between nemadipine and nicardipine, although it was greater in S666V (approximately 15%) and M1161A approximately 30%) as compared to the wildtype channel (<5%). Taken together, our findings suggest that the domain II residues alter the DHP effect in a structure-specific manner and may be involved in a pathway downstream of DHP binding.

  18. 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.

  19. 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.

  20. 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.

  1. The Role of Guidance, Navigation, and Control in Hypersonic Vehicle Multidisciplinary Design and Optimization

    NASA Technical Reports Server (NTRS)

    Ouzts, Peter J.; Soloway, Donald I.; Moerder, Daniel D.; Wolpert, David H.; Benavides, Jose Victor

    2009-01-01

    Airbreathing hypersonic systems offer distinct performance advantages over rocket-based systems for space access vehicles. However, these performance advantages are dependent upon advances in current state-of-the-art technologies in many areas such as ram/scramjet propulsion integration, high temperature materials, aero-elastic structures, thermal protection systems, transition to hypersonics and hypersonic control elements within the framework of complex physics and new design methods. The complex interactions between elements of an airbreathing hypersonic vehicle represent a new paradigm in vehicle design to achieve the optimal performance necessary to meet space access mission objectives. In the past, guidance, navigation, and control (GNC) analysis often follows completion of the vehicle conceptual design process. Individual component groups design subsystems which are then integrated into a vehicle configuration. GNC is presented the task of developing control approaches to meet vehicle performance objectives given that configuration. This approach may be sufficient for vehicles where significant performance margins exist. However, for higher performance vehicles engaging the GNC discipline too late in the design cycle has been costly. For example, the X-29 experimental flight vehicle was built as a technology demonstrator. One of the many technologies to be demonstrated was the use of light-weight material composites for structural components. The use of light-weight materials increased the flexibility of the X- 29 beyond that of conventional metal alloy constructed aircraft. This effect was not considered when the vehicle control system was designed and built. The impact of this is that the control system did not have enough control authority to compensate for the effects of the first fundamental structural mode of the vehicle. As a result, the resulting pitch rate response of the vehicle was below specification and no post-design changes could recover the

  2. 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.

  3. Luminal Glucose Does Not Enhance Active Intestinal Calcium Absorption in mice: Evidence Against a Role for Cav1.3 as a Mediator of Calcium Uptake During Absorption

    PubMed Central

    Reyes-Fernandez, Perla C.; Fleet, James C.

    2015-01-01

    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 following 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/6J 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 mRNA levels were measured in the duodenum, jejunum and ileum. TRPV6 and CaBPD9k expression were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs while Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (p=0.003), serum 1,25(OH)2D3 (p<0.001) 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=0.6) 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. PMID:26403486

  4. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia

    PubMed Central

    Makarenko, Vladislav V.; Ahmmed, Gias U.; Peng, Ying-Jie; Khan, Shakil A.; Nanduri, Jayasri; Kumar, Ganesh K.; Fox, Aaron P.

    2015-01-01

    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 ([Ca2+]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 [Ca2+]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 [Ca2+]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 Ca2+ 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 [Ca2+]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca2+ 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 Ca2+ influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane. PMID:26561606

  5. 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.

  6. National Emissions Report (1978): National Emissions Data Systems (NEDS) of the Aerometric and Emissions Reporting System (AEROS). Annual report

    SciTech Connect

    Not Available

    1980-12-01

    The National Emissions Report summarizes annual cumulative estimates of source emissions of five criteria pollutants: particulates, sulfur oxides, nitrogen oxides, hydrocarbons, and carbon monoxide. Source emissions data are reported to the U. S. Environmental Protection Agency under provisions of Section 110 of the Clean Air Act, as amended 1977, and EPA Regulations, Title 40, Code of Federal Regulations, Part 51.321. Summary data are presented for the nation as a whole, for individual states, and for Air Quality Control Regions and individual interstate portions thereof. The data compilations result from the operations of the National Emissions Data System (NEDS), which functions as a component of the comprehensive EPA air information system--the Aerometric and Emissions Reporting System (AEROS). AEROS is managed by the National Air Data Branch, Monitoring and Data Analysis Division, Office of Air Quality Planning and Standards, U. S. Environmental Protection Agency at Research Triangle Park, North Carolina 27711.

  7. National emissions report (1979): National Emissions Data Systems (NEDS) of the Aerometric and Emissions Reporting System (AEROS). Annual report

    SciTech Connect

    Not Available

    1981-08-01

    The National Emissions Report summarizes annual cumulative estimates of source emissions of five criteria pollutants: particulates, sulfur oxides, nitrogen oxides, hydrocarbons, and carbon monoxide. Source emissions data are reported to the U. S. Environmental Protection Agency under provisions of Section 110 of the Clean Air Act, as amended 1977, and EPA Regulations, Title 40, Code of Federal Regulations, Part 51.321. Summary data are presented for the nation as a whole, for individual states, and for Air Quality Control Regions and individual interstate portions thereof. The data compilations result from the operations of the National Emissions Data System (NEDS), which functions as a component of the comprehensive EPA air information system--the Aerometric and Emissions Reporting System (AEROS). AEROS is managed by the National Air Data Branch, Monitoring and Data Analysis Division, Office of Air Quality Planning and Standards, U. S. Environmental Protection Agency at Research Triangle Park, North Carolina 27711.

  8. National emissions report, 1985: National Emissions Data Systems (NEDS) of the Aerometric and Emissions Reporting System (AEROS). Final report

    SciTech Connect

    Not Available

    1988-09-01

    The National Emissions Report summarizes annual cumulative estimates of source emissions of five criteria pollutants: particulates, sulfur oxides, nitrogen oxides, volatile organic compounds, and carbon monoxide. Source emissions data are reported to the U.S. Environmental Protection Agency under provisions of Section 110 of the Clean Air Act, as amended 1977, and EPA regulations, Title 40, Code of Federal Regulations, Part 51.321. Summary data are presented for the Nation as a whole, for individual States, and for Air Quality Control Regions and for individual interstate portions thereof. The data compilations result from the operations of the National Emissions Data System (NED), which functions as a component of the comprehensive EPA air information system--the Aerometric and Emissions Reporting System (AEROS). AEROS is managed by the National Air Data Branch, Emissions Standard Division, Office of Air Quality Planning and Standards, U.S. Environmental Protection Agency, at Research Triangle Park, North Carolina.

  9. National Emissions Report, 1983: national emissions data systems (neds) of the Aerometric and Emissions Reporting System (AEROS). Final report

    SciTech Connect

    Not Available

    1985-12-01

    The National Emissions Report summarizes annual cumulative estimates of source emissions of five criteria pollutants: particulates, sulfur oxides, nitrogen oxides, volatile organic compounds, and carbon monoxide. Source emissions data are reported to the U.S. Environmental Protection Agency under provisions of Section 110 of the Clean Air Act, as amended 1977, and EPA Regulations, Title 40, Code of Federal Regulations, Part 51.321. Summary data are presented for the Nation as a whole, for individual States, and for Air Quality Control Regions and for individual interstate portions thereof. The data compilations result from the operations of the National Emissions Data System (NEDS), which functions as a component of the comprehensive EPA air information system--the Aerometric and Emissions Reporting System (AEROS). AEROS is managed by the National Air Data Branch, Monitoring and Data Analysis Division, Office of Air Quality Planning and Standards, U.S. Environmental Protection Agency at Research Triangle Park, North Carolina 27711.

  10. Splice-variant changes of the Ca(V)3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development.

    PubMed

    David, Laurence S; Garcia, Esperanza; Cain, Stuart M; Thau, Elana; Tyson, John R; Snutch, Terrance P

    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 (Ca(V)3.1, Ca(V)3.2,Ca(V)3.3), 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 Ca(V)3.2 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 Ca(V)3.2 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 Ca(V)3.2 T-type Ca channels are subject to considerable alternative splicing, (2) there is preferential expression of Ca(V)3.2(-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 a both an increase in overall Ca(V)3.2 expression and a shift towards expression of Ca(V)3.2(+25) containing channels as the predominant form, and (4) alternative splicing confers a variant-specific voltage-dependent facilitation of Ca(V)3.2 channels. We conclude that Ca(V)3.2 alternative splicing generates significant T-type Ca channel structural and functional diversity with potential implications relevant to cardiac developmental and pathophysiological states.

  11. Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution

    PubMed Central

    LV, XINTONG; GUO, FENG; XU, XIAOXUE; CHEN, ZAIXING; SUN, XUEFEI; MIN, DONGYU; CAO, YONGGANG; SHI, XIANBAO; WANG, LEI; CHEN, TIANBAO; SHAW, CHRIS; GAO, HUILING; HAO, LIYING; CAI, JIQUN

    2015-01-01

    Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence-like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+-free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p-CaMKII; Thr-286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p-CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p-CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co-localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg2+-free solution. PMID:26299765

  12. 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.

  13. Vehicle suspension

    SciTech Connect

    Mikina, S.J.

    1986-08-05

    This patent describes a vehicle consisting of sprung and unsprung masses, the combination of struts and support springs for the weight of the sprung mass, an axis defined by pivots between sprung and unsprung masses, with a front pivot approximately midway between the wheels and near the vertical and horizontal planes through the front axles, with a rear pivot lying in an axis through the front pivot and in a plane through the center-of-gravity of the sprung mass, with the plane parallel to the centrifugal force vector through the center-of-gravity of the sprung mass, and with the rear pivot positioned approximately midway between the rear wheels, means for transmitting the centrifugal force component on the front pivot to the front wheels and ground, and means for transmitting the centrifugal force component on the rear pivot to the rear wheels and ground.

  14. Launch vehicles

    NASA Astrophysics Data System (ADS)

    Moss, J. B.

    The basic principles which determine launcher design and hence constrain the spacecraft payload are determined. Some key features of the principal launcher alternatives in Europe and the U.S., namely, the unmanned, expendable Ariane and the manned, substantially reusable, Space Shuttle, are outlined. The equations of motion of the rocket are specialized to the vertical plane, parallel and normal to the flight direction, and to the motion of the center of mass and the pitch rotation. A typical Ariane 2 flight profile for transfer into GTO is illustrated. Some representative mission requirements for spacecraft launches are reviewed. Launch vehicle burnout velocities for spacecraft emplacement are given. Geostationary orbit emplacement, orbital mission performance, and configuration interactions are discussed.

  15. Numerical prediction of the spatial and temporal characteristics of the aero-optical disturbance produced by a helicopter in hover

    NASA Astrophysics Data System (ADS)

    Kelly, Ryan T.

    Aero-optical disturbances produced from turbulent compressible flow-fields can seriously degrade the performance of an optical signal. At compressible flight speeds these disturbances stem from the density variations present in turbulent boundary layers and free shear layers; however helicopters typically operate at incompressible speeds, which nearly eliminates the aberrating effect of these flows. For helicopter platforms the sources of aberration originate from the high subsonic flow-field near the rotor blade tips in the form of rotor-tip vortices and from the high temperatures of the engine effluence. During hover the shed rotor-tip vortices and engine effluence convect with the rotor wake encircling the airframe and subsequently a helicopter mounted optical system. The aero-optical effects of the wake beneath a hovering helicopter were analyzed using a combination of Unsteady RANS (URANS) and Large-Eddy Simulations (LES). The spatial and temporal characteristics of the numerical optical wavefronts were compared to full-scale aero-optic experimental measurements. The results indicate that the turbulence of the rotor-tip vortices contributes to the higher order aberrations measured experimentally and that the thermal exhaust plumes effectively limit the optical field-of-regard to forward- and side-looking beam directions. This information along with the computed optical aberrations of the wake can be used to guide the development of adaptive-optic systems or other beam-control approaches.

  16. Integrated approach for stress based lifing of aero gas turbine blades

    NASA Astrophysics Data System (ADS)

    Abu, Abdullahi Obonyegba

    In order to analyse the turbine blade life, the damage due to the combined thermal and mechanical loads should be adequately accounted for. This is more challenging when detailed component geometry is limited. Therefore, a compromise between the level of geometric detail and the complexity of the lifing method to be implemented would be necessary. This research focuses on how the life assessment of aero engine turbine blades can be done, considering the balance between available design inputs and adequate level of fidelity. Accordingly, the thesis contributes to developing a generic turbine blade lifing method that is based on the engine thermodynamic cycle; as well as integrating critical design/technological factors and operational parameters that influence the aero engine blade life. To this end, thermo-mechanical fatigue was identified as the critical damage phenomenon driving the life of the turbine blade.. The developed approach integrates software tools and numerical models created using the minimum design information typically available at the early design stages. Using finite element analysis of an idealised blade geometry, the approach captures relevant impacts of thermal gradients and thermal stresses that contribute to the thermo-mechanical fatigue damage on the gas turbine blade. The blade life is evaluated using the Neu/Sehitoglu thermo-mechanical fatigue model that considers damage accumulation due to fatigue, oxidation, and creep. The leading edge is examined as a critical part of the blade to estimate the damage severity for different design factors and operational parameters. The outputs of the research can be used to better understand how the environment and the operating conditions of the aircraft affect the blade life consumption and therefore what is the impact on the maintenance cost and the availability of the propulsion system. This research also finds that the environmental (oxidation) effect drives the blade life and the blade coolant

  17. Aero-Optical Turbulent Boundary Layer/Shear Layer Experiment On The KC-135 Aircraft Revisited

    NASA Astrophysics Data System (ADS)

    Craig, James E.; Allen, C.

    1985-06-01

    This paper examines the aero-optical effects associated with propagating a laser beam through both an aircraft turbulent boundary layer and artificially generated shear layers. The data present comparisons of observed optical performances with those inferred from aerodynamic measurements of unsteady density and correlation lengths within the same random flow fields. Using optical instrumentation with tens of microseconds 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 that recorded the random flow field in a double-pass, double-pulse mode. Aero-dynamic parameters were measured using hot film anemometer probes and a five-hole pressure probe. Each technique is described with its associated theo-retical basis for comparison. The effects of finite aperture and spatial and temporal frequencies of the random flow are considered. The results presented represent five flights flown at altitudes from 1.8 km to 10.7 km and at Mach numbers from 0.32 to 0.79. Single-pass phase deviations for the boundary layer were from 0.06 to 0.17 waves (at X = 0.53 ;Am) with piston and tilt components removed. Measured phase deviations for the artificially induced shear flows were from 0.10 to 0.279 waves (at X = 0.53 /um) with piston and tilt components removed. However, when low order aberrations through coma were removed, the remaining deviations were only 0.09 to 0.18 waves. This resulted in a 33 to 250% increase in the Strehl ratio at the 14 cm optical aperture. It was further shown that the low order aberrations corresponded to the longer wavelengths in the random flow, and these waves propagated with a longer characteristic time than the higher order

  18. 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.

  19. Voltage control of Ca²⁺ permeation through N-type calcium (Ca(V)2.2) channels.

    PubMed

    Buraei, Zafir; Liang, Haoya; Elmslie, Keith S

    2014-09-01

    Voltage-gated calcium (Ca(V)) channels deliver Ca(2+) to trigger cellular functions ranging from cardiac muscle contraction to neurotransmitter release. The mechanism by which these channels select for Ca(2+) over other cations is thought to involve multiple Ca(2+)-binding sites within the pore. Although the Ca(2+) affinity and cation preference of these sites have been extensively investigated, the effect of voltage on these sites has not received the same attention. We used a neuronal preparation enriched for N-type calcium (Ca(V)2.2) channels to investigate the effect of voltage on Ca(2+) flux. We found that the EC50 for Ca(2+) permeation increases from 13 mM at 0 mV to 240 mM at 60 mV, indicating that, during permeation, Ca(2+) ions sense the electric field. These data were nicely reproduced using a three-binding-site step model. Using roscovitine to slow Ca(V)2.2 channel deactivation, we extended these measurements to voltages <0 mV. Permeation was minimally affected at these hyperpolarized voltages, as was predicted by the model. As an independent test of voltage effects on permeation, we examined the Ca(2+)-Ba(2+) anomalous mole fraction (MF) effect, which was both concentration and voltage dependent. However, the Ca(2+)-Ba(2+) anomalous MF data could not be reproduced unless we added a fourth site to our model. Thus, Ca(2+) permeation through Ca(V)2.2 channels may require at least four Ca(2+)-binding sites. Finally, our results suggest that the high affinity of Ca(2+) for the channel helps to enhance Ca(2+) influx at depolarized voltages relative to other ions (e.g., Ba(2+) or Na(+)), whereas the absence of voltage effects at negative potentials prevents Ca(2+) from becoming a channel blocker. Both effects are needed to maximize Ca(2+) influx over the voltages spanned by action potentials.

  20. Biophysical characterization of the honeybee DSC1 orthologue reveals a novel voltage-dependent Ca2+ channel subfamily: CaV4

    PubMed Central

    Gosselin-Badaroudine, Pascal; Moreau, Adrien; Simard, Louis; Cens, Thierry; Rousset, Matthieu; Collet, Claude; Charnet, Pierre

    2016-01-01

    Bilaterian voltage-gated Na+ channels (NaV) evolved from voltage-gated Ca2+ channels (CaV). The Drosophila melanogaster Na+ channel 1 (DSC1), which features a D-E-E-A selectivity filter sequence that is intermediate between CaV and NaV channels, is evidence of this evolution. Phylogenetic analysis has classified DSC1 as a Ca2+-permeable Na+ channel belonging to the NaV2 family because of its sequence similarity with NaV channels. This is despite insect NaV2 channels (DSC1 and its orthologue in Blatella germanica, BSC1) being more permeable to Ca2+ than Na+. In this study, we report the cloning and molecular characterization of the honeybee (Apis mellifera) DSC1 orthologue. We reveal several sequence variations caused by alternative splicing, RNA editing, and genomic variations. Using the Xenopus oocyte heterologous expression system and the two-microelectrode voltage-clamp technique, we find that the channel exhibits slow activation and inactivation kinetics, insensitivity to tetrodotoxin, and block by Cd2+ and Zn2+. These characteristics are reminiscent of CaV channels. We also show a strong selectivity for Ca2+ and Ba2+ ions, marginal permeability to Li+, and impermeability to Mg2+ and Na+ ions. Based on current ion channel nomenclature, the D-E-E-A selectivity filter, and the properties we have uncovered, we propose that DSC1 homologues should be classified as CaV4 rather than NaV2. Indeed, channels that contain the D-E-E-A selectivity sequence are likely to feature the same properties as the honeybee’s channel, namely slow activation and inactivation kinetics and strong selectivity for Ca2+ ions. PMID:27432995

  1. Conditional Knockout of Cav2.1 Disrupts the Accuracy of Spatial Recognition of CA1 Place Cells and Spatial/Contextual Recognition Behavior

    PubMed Central

    Jung, Dahee; Hwang, Yu J.; Ryu, Hoon; Kano, Masanobu; Sakimura, Kenji; Cho, Jeiwon

    2016-01-01

    Hippocampal pyramidal neurons play an essential role in processing spatial information as implicated with its place-dependent firing. Although, previous slice physiology studies have reported that voltage gated calcium channels contribute to spike shapes and corresponding firing rate in the hippocampus, the roles of P/Q type calcium channels (Cav2.1) underlying neural activity in behaving mice have not been well-investigated. To determine physiological and behavioral roles of Cav2.1, we conducted place cell recordings in CA1 and hippocampus dependent learning/memory tasks using mice lacking Cav2.1 in hippocampal pyramidal neurons under CamK2α-Cre recombinase expression. Results suggested that impairments shown in behavioral tasks requiring spatial and contextual information processing were statistically significant while general neurological behaviors did not differ between groups. In particular, deficits were more profound in recognition than in acquisition. Furthermore, place cell recordings also revealed that the ability to recollect spatial representation on re-visit in the conditional knockout was also altered in terms of the cue recognition while the capability of a place cell to encode a place was intact compared to the control group. Interestingly, CA1 pyramidal neurons of conditional knockout mice showed reduced burst frequency as well as abnormal temporal patterns of burst spiking. These results provide potential evidence that Cav2.1 in hippocampal pyramidal cells modulates temporal integration of bursts, which, in turn, might influence the recognition of place field and consequently disrupt spatial recognition ability. PMID:27857685

  2. Biophysical characterization of the honeybee DSC1 orthologue reveals a novel voltage-dependent Ca2+ channel subfamily: CaV4.

    PubMed

    Gosselin-Badaroudine, Pascal; Moreau, Adrien; Simard, Louis; Cens, Thierry; Rousset, Matthieu; Collet, Claude; Charnet, Pierre; Chahine, Mohamed

    2016-08-01

    Bilaterian voltage-gated Na(+) channels (NaV) evolved from voltage-gated Ca(2+) channels (CaV). The Drosophila melanogaster Na(+) channel 1 (DSC1), which features a D-E-E-A selectivity filter sequence that is intermediate between CaV and NaV channels, is evidence of this evolution. Phylogenetic analysis has classified DSC1 as a Ca(2+)-permeable Na(+) channel belonging to the NaV2 family because of its sequence similarity with NaV channels. This is despite insect NaV2 channels (DSC1 and its orthologue in Blatella germanica, BSC1) being more permeable to Ca(2+) than Na(+) In this study, we report the cloning and molecular characterization of the honeybee (Apis mellifera) DSC1 orthologue. We reveal several sequence variations caused by alternative splicing, RNA editing, and genomic variations. Using the Xenopus oocyte heterologous expression system and the two-microelectrode voltage-clamp technique, we find that the channel exhibits slow activation and inactivation kinetics, insensitivity to tetrodotoxin, and block by Cd(2+) and Zn(2+) These characteristics are reminiscent of CaV channels. We also show a strong selectivity for Ca(2+) and Ba(2+) ions, marginal permeability to Li(+), and impermeability to Mg(2+) and Na(+) ions. Based on current ion channel nomenclature, the D-E-E-A selectivity filter, and the properties we have uncovered, we propose that DSC1 homologues should be classified as CaV4 rather than NaV2. Indeed, channels that contain the D-E-E-A selectivity sequence are likely to feature the same properties as the honeybee's channel, namely slow activation and inactivation kinetics and strong selectivity for Ca(2+) ions.

  3. Low-threshold exocytosis induced by cAMP-recruited CaV3.2 (alpha1H) channels in rat chromaffin cells.

    PubMed

    Giancippoli, A; Novara, M; de Luca, A; Baldelli, P; Marcantoni, A; Carbone, E; Carabelli, V

    2006-03-01

    We have studied the functional role of CaV3 channels in triggering fast exocytosis in rat chromaffin cells (RCCs). CaV3 T-type channels were selectively recruited by chronic exposures to cAMP (3 days) via an exchange protein directly activated by cAMP (Epac)-mediated pathway. Here we show that cAMP-treated cells had increased secretory responses, which could be evoked even at very low depolarizations (-50, -40 mV). Potentiation of exocytosis in cAMP-treated cells did not occur in the presence of 50 microM Ni2+, which selectively blocks T-type currents in RCCs. This suggests that the "low-threshold exocytosis" induced by cAMP is due to increased Ca2+ influx through cAMP-recruited T-type channels, rather than to an enhanced secretion downstream of Ca2+ entry, as previously reported for short-term cAMP treatments (20 min). Newly recruited T-type channels increase the fast secretory response at low voltages without altering the size of the immediately releasable pool. They also preserve the Ca2+ dependence of exocytosis, the initial speed of vesicle depletion, and the mean quantal size of single secretory events. All this indicates that cAMP-recruited CaV3 channels enhance the secretory activity of RCCs at low voltages by coupling to the secretory apparatus with a Ca2+ efficacy similar to that of already existing high-threshold Ca2+ channels. Finally, using RT-PCRs we found that the fast inactivating low-threshold Ca2+ current component recruited by cAMP is selectively associated to the alpha1H (CaV3.2) channel isoform.

  4. Molecular determinants of inactivation within the I-II linker of alpha1E (CaV2.3) calcium channels.

    PubMed Central

    Berrou, L; Bernatchez, G; Parent, L

    2001-01-01

    Voltage-dependent inactivation of CaV2.3 channels was investigated using point mutations in the beta-subunit-binding site (AID) of the I-II linker. The quintuple mutant alpha1E N381K + R384L + A385D + D388T + K389Q (NRADK-KLDTQ) inactivated like the wild-type alpha1E. In contrast, mutations of alpha1E at position R378 (position 5 of AID) into negatively charged residues Glu (E) or Asp (D) significantly slowed inactivation kinetics and shifted the voltage dependence of inactivation to more positive voltages. When co-injected with beta3, R378E inactivated with tau(inact) = 538 +/- 54 ms (n = 14) as compared with 74 +/- 4 ms (n = 21) for alpha1E (p < 0.001) with a mid-potential of inactivation E(0.5) = -44 +/- 2 mV (n = 10) for R378E as compared with E(0.5) = -64 +/- 3 mV (n = 9) for alpha1E. A series of mutations at position R378 suggest that positively charged residues could promote voltage-dependent inactivation. R378K behaved like the wild-type alpha1E whereas R378Q displayed intermediate inactivation kinetics. The reverse mutation E462R in the L-type alpha1C (CaV1.2) produced channels with inactivation properties comparable to alpha1E R378E. Hence, position 5 of the AID motif in the I-II linker could play a significant role in the inactivation of Ca(V)1.2 and CaV2.3 channels. PMID:11159396

  5. 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

  6. Fluctuation of ROS regulates proliferation and mediates inhibition of migration by reducing the interaction between DLC1 and CAV-1 in breast cancer cells.

    PubMed

    Yang, Bingwu; Zhu, Wenzhen; Zheng, Zhaodi; Chai, Rongfei; Ji, Shuhua; Ren, Guanghui; Liu, Tingting; Liu, Zhaojun; Song, Taiyu; Li, Fenglin; Liu, Shan; Li, Guorong

    2017-01-27

    The aim of our present study was to elucidate the effects of up-regulation and down-regulation of intracellular reactive oxygen species (ROS) level on proliferation, migration, and related molecular mechanism. Breast cancer cells were treated by catalase or H2O2. MTT, colony formation assay, and Hoechst/PI staining were used to evaluate proliferation and apoptosis. The level of intracellular ROS was measured by dichlorodihydrofluorescein diacetate probes. The ability of migration was detected by wound healing. Western blotting and coimmunoprecipitation (co-IP) were used to determine the expression of DLC1 and CAV-1 and their interaction. Our data indicated that up-regulation of intracellular ROS induced by H2O2 significantly inhibited proliferation and induced apoptosis accompanying G1 cell cycle arrest and elevated expression of p53. For cell migration, either up-regulation or down-regulation of ROS induced migration inhibition with reduction of interaction between DLC1 and CAV-1. Our results suggested that up-regulation of intracellular ROS inhibited proliferation by promoting expression of p53 and induced G1 cycle arrest and apoptosis. Fluctuation of ROS inhibited migration through reducing the interaction between DLC1 and CAV-1.

  7. The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials

    PubMed Central

    Pantazis, Antonios; Sigg, Daniel; Weiss, James N.; Neely, Alan

    2016-01-01

    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

  8. Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of CaV1.1 calcium channel

    PubMed Central

    Tang, Zhen Zhi; Yarotskyy, Viktor; Wei, Lan; Sobczak, Krzysztof; Nakamori, Masayuki; Eichinger, Katy; Moxley, Richard T.; Dirksen, Robert T.; Thornton, Charles A.

    2012-01-01

    Myotonic dystrophy type 1 and type 2 (DM1 and DM2) are genetic diseases in which mutant transcripts containing expanded CUG or CCUG repeats cause cellular dysfunction by altering the processing or metabolism of specific mRNAs and miRNAs. The toxic effects of mutant RNA are mediated partly through effects on proteins that regulate alternative splicing. Here we show that alternative splicing of exon 29 (E29) of CaV1.1, a calcium channel that controls skeletal muscle excitation–contraction coupling, is markedly repressed in DM1 and DM2. The extent of E29 skipping correlated with severity of weakness in tibialis anterior muscle of DM1 patients. Two splicing factors previously implicated in DM1, MBNL1 and CUGBP1, participated in the regulation of E29 splicing. In muscle fibers of wild-type mice, the CaV1.1 channel conductance and voltage sensitivity were increased by splice-shifting oligonucleotides that induce E29 skipping. In contrast to human DM1, expression of CUG-expanded RNA caused only a modest increase in E29 skipping in mice. However, forced skipping of E29 in these mice, to levels approaching those observed in human DM1, aggravated the muscle pathology as evidenced by increased central nucleation. Together, these results indicate that DM-associated splicing defects alter CaV1.1 function, with potential for exacerbation of myopathy. PMID:22140091

  9. Regulation of neuronal high-voltage activated Ca(V)2 Ca(2+) channels by the small GTPase RhoA.

    PubMed

    Rousset, Matthieu; Cens, Thierry; Menard, Claudine; Bowerman, Melissa; Bellis, Michel; Brusés, Juan; Raoul, Cedric; Scamps, Frédérique; Charnet, Pierre

    2015-10-01

    High-Voltage-Activated (HVA) Ca(2+) channels are known regulators of synapse formation and transmission and play fundamental roles in neuronal pathophysiology. Small GTPases of Rho and RGK families, via their action on both cytoskeleton and Ca(2+) channels are key molecules for these processes. While the effects of RGK GTPases on neuronal HVA Ca(2+) channels have been widely studied, the effects of RhoA on the HVA channels remains however elusive. Using heterologous expression in Xenopus laevis oocytes, we show that RhoA activity reduces Ba(2+) currents through CaV2.1, CaV2.2 and CaV2.3 Ca(2+) channels independently of CaVβ subunit. This inhibition occurs independently of RGKs activity and without modification of biophysical properties and global level of expression of the channel subunit. Instead, we observed a marked decrease in the number of active channels at the plasma membrane. Pharmacological and expression studies suggest that channel expression at the plasma membrane is impaired via a ROCK-sensitive pathway. Expression of constitutively active RhoA in primary culture of spinal motoneurons also drastically reduced HVA Ca(2+) current amplitude. Altogether our data revealed that HVA Ca(2+) channels regulation by RhoA might govern synaptic transmission during development and potentially contribute to pathophysiological processes when axon regeneration and growth cone kinetics are impaired.

  10. 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.

  11. 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.

  12. Beneficial effects of bumetanide in a CaV1.1-R528H mouse model of hypokalaemic periodic paralysis.

    PubMed

    Wu, Fenfen; Mi, Wentao; Cannon, Stephen C

    2013-12-01

    Transient attacks of weakness in hypokalaemic periodic paralysis are caused by reduced fibre excitability from paradoxical depolarization of the resting potential in low potassium. Mutations of calcium channel and sodium channel genes have been identified as the underlying molecular defects that cause instability of the resting potential. Despite these scientific advances, therapeutic options remain limited. In a mouse model of hypokalaemic periodic paralysis from a sodium channel mutation (NaV1.4-R669H), we recently showed that inhibition of chloride influx with bumetanide reduced the susceptibility to attacks of weakness, in vitro. The R528H mutation in the calcium channel gene (CACNA1S encoding CaV1.1) is the most common cause of hypokalaemic periodic paralysis. We developed a CaV1.1-R528H knock-in mouse model of hypokalaemic periodic paralysis and show herein that bumetanide protects against both muscle weakness from low K+ challenge in vitro and loss of muscle excitability in vivo from a glucose plus insulin infusion. This work demonstrates the critical role of the chloride gradient in modulating the susceptibility to ictal weakness and establishes bumetanide as a potential therapy for hypokalaemic periodic paralysis arising from either NaV1.4 or CaV1.1 mutations.

  13. 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.

  14. 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.

  15. Laser Fine-Adjustment Thruster For Space Vehicles

    NASA Astrophysics Data System (ADS)

    Rezunkov, Yu. A.; Egorov, M. S.; Rebrov, S. G.; Repina, E. V.; Safronov, A. L.

    2010-05-01

    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.

  16. 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).

  17. [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.

  18. User's Guide for the Commercial Modular Aero-Propulsion System Simulation (C-MAPSS)

    NASA Technical Reports Server (NTRS)

    Frederick, Dean K.; DeCastro, Jonathan A.; Litt, Jonathan S.

    2007-01-01

    This report is a Users Guide for 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 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.

  19. 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.

  20. 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..

  1. KC-135 aero-optical turbulent boundary layer/shear layer experiment revisited

    NASA Astrophysics Data System (ADS)

    Craig, J.; Allen, C.

    1987-05-01

    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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Distinct Components of Retrograde Ca(V)1.1-RyR1 Coupling Revealed by a Lethal Mutation in RyR1.

    PubMed

    Bannister, Roger A; Sheridan, David C; Beam, Kurt G

    2016-02-23

    The molecular basis for excitation-contraction coupling in skeletal muscle is generally thought to involve conformational coupling between the L-type voltage-gated Ca(2+) channel (CaV1.1) and the type 1 ryanodine receptor (RyR1). This coupling is bidirectional; in addition to the orthograde signal from CaV1.1 to RyR1 that triggers Ca(2+) release from the sarcoplasmic reticulum, retrograde signaling from RyR1 to CaV1.1 results in increased amplitude and slowed activation kinetics of macroscopic L-type Ca(2+) current. Orthograde coupling was previously shown to be ablated by a glycine for glutamate substitution at RyR1 position 4242. In this study, we investigated whether the RyR1-E4242G mutation affects retrograde coupling. L-type current in myotubes homozygous for RyR1-E4242G was substantially reduced in amplitude (∼80%) relative to that observed in myotubes from normal control (wild-type and/or heterozygous) myotubes. Analysis of intramembrane gating charge movements and ionic tail current amplitudes indicated that the reduction in current amplitude during step depolarizations was a consequence of both decreased CaV1.1 membrane expression (∼50%) and reduced channel Po (∼55%). In contrast, activation kinetics of the L-type current in RyR1-E4242G myotubes resembled those of normal myotubes, unlike dyspedic (RyR1 null) myotubes in which the L-type currents have markedly accelerated activation kinetics. Exogenous expression of wild-type RyR1 partially restored L-type current density. From these observations, we conclude that mutating residue E4242 affects RyR1 structures critical for retrograde communication with CaV1.1. Moreover, we propose that retrograde coupling has two distinct and separable components that are dependent on different structural elements of RyR1.

  10. First-principles investigation of exchange interactions in quasi-one-dimensional antiferromagnet CaV2O4

    NASA Astrophysics Data System (ADS)

    Pchelkina, Z. V.; Solovyev, I. V.

    2015-01-01

    The effects of orbital degrees of freedom on the exchange interactions in a quasi-one-dimensional spin-1 antiferromagnet CaV2O4 are systematically studied. For this purpose a realistic low-energy electron model with the parameters derived from the first-principles calculations is constructed in the Wannier basis for the t2g bands. The exchange interactions are calculated using both the theory of infinitesimal spin rotations near the mean-field ground state and the superexchange model, which provide a consistent description. The obtained behaviour of exchange interactions differs substantially from the previously proposed phenomenological picture based on magnetic measurements and structural considerations, namely: (i) despite the quasi-one-dimensional character of the crystal structure, consisting of the zigzag chains of the edge-sharing VO6 octahedra, the electronic structure is essentially three-dimensional, that leads to finite interactions between the chains; (ii) the exchange interactions along the legs of the chains appear to dominate; and (iii) there is a substantial difference in exchange interactions in two crystallographically inequivalent chains. The combination of these three factors successfully reproduces the behaviour of experimental magnetic susceptibility.

  11. Perinatal and Postnatal Expression of Cav1.3 α1D Ca2+ Channel in the Rat Heart

    PubMed Central

    Qu, Yongxia; Karnabi, Eddy; Ramadan, Omar; Yue, Yuankun; Chahine, Mohamed; Boutjdir, Mohamed

    2011-01-01

    The novel Cav1.3 (α1D) L-type Ca2+ channel plays a significant role in sino-atrial, atrioventricular nodes function and in atrial fibrillation. However, the characterization of α1D Ca2+ channel during heart development is very limited. We used real-time RT-PCR, Western blotting and indirect immunostaining to characterize the developmental expression and localization of α1D Ca2+ channel in rat hearts. Both protein and mRNA levels of α1D Ca2+ channel decreased postnatally. Two forms of α1D Ca2+ channel protein (250 kD and 190 kD) were observed, with the full length (250kD) channel protein being predominant in the prenatal stages. Both Western blots and confocal imaging demonstrated that α1D Ca2+ channel protein was expressed in both atria and ventricles at fetal and neonatal stages but was absent in the adult ventricles. Interestingly, α1D Ca2+ channel was also found at the nucleus/perinucleus of immature, but not adult atrial cells. Furthermore, the nuclear staining was reproduced in adult atrial cell line, HL-1 cells, which possess immature properties. The data are first to show that α1D Ca2+ channel has unique age-dependent expression profile and subcellular localization in the heart, suggesting a developmental stage dependent specific function. PMID:21378599

  12. Cav1.4 IT mouse as model for vision impairment in human congenital stationary night blindness type 2.

    PubMed

    Knoflach, Dagmar; Kerov, Vasily; Sartori, Simone B; Obermair, Gerald J; Schmuckermair, Claudia; Liu, Xiaoni; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Baker, Sheila A; Glösmann, Martin; Schicker, Klaus; Seeliger, Mathias; Lee, Amy; Koschak, Alexandra

    2013-01-01

    Mutations in the CACNA1F gene encoding the Cav1.4 Ca (2+) channel are associated with X-linked congenital stationary night blindness type 2 (CSNB2). Despite the increasing knowledge about the functional behavior of mutated channels in heterologous systems, the pathophysiological mechanisms that result in vision impairment remain to be elucidated. This work provides a thorough functional characterization of the novel IT mouse line that harbors the gain-of-function mutation I745T reported in a New Zealand CSNB2 family. (1) Electroretinographic recordings in IT mice permitted a direct comparison with human data. Our data supported the hypothesis that a hyperpolarizing shift in the voltage-dependence of channel activation-as seen in the IT gain-of-function mutant (2)-may reduce the dynamic range of photoreceptor activity. Morphologically, the retinal outer nuclear layer in adult IT mutants was reduced in size and cone outer segments appeared shorter. The organization of the outer plexiform layer was disrupted, and synaptic structures of photoreceptors had a variable, partly immature, appearance. The associated visual deficiency was substantiated in behavioral paradigms. The IT mouse line serves as a specific model for the functional phenotype of human CSNB2 patients with gain-of-function mutations and may help to further understand the dysfunction in CSNB.

  13. KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling

    PubMed Central

    Schou, Kenneth B.; Mogensen, Johanne B.; Morthorst, Stine K.; Nielsen, Brian S.; Aleliunaite, Aiste; Serra-Marques, Andrea; Fürstenberg, Nicoline; Saunier, Sophie; Bizet, Albane A.; Veland, Iben R.; Akhmanova, Anna; Christensen, Søren T.; Pedersen, Lotte B.

    2017-01-01

    Ciliary membrane composition is controlled by transition zone (TZ) proteins such as RPGRIP1, RPGRIPL and NPHP4, which are vital for balanced coordination of diverse signalling systems like the Sonic hedgehog (Shh) pathway. Activation of this pathway involves Shh-induced ciliary accumulation of Smoothened (SMO), which is disrupted by disease-causing mutations in TZ components. Here we identify kinesin-3 motor protein KIF13B as a novel member of the RPGRIP1N-C2 domain-containing protein family and show that KIF13B regulates TZ membrane composition and ciliary SMO accumulation. KIF13B is upregulated during ciliogenesis and is recruited to the ciliary base by NPHP4, which binds to two distinct sites in the KIF13B tail region, including an RPGRIP1N-C2 domain. KIF13B and NPHP4 are both essential for establishment of a CAV1 membrane microdomain at the TZ, which in turn is required for Shh-induced ciliary SMO accumulation. Thus KIF13B is a novel regulator of ciliary TZ configuration, membrane composition and Shh signalling. PMID:28134340

  14. Cav1.4 IT mouse as model for vision impairment in human congenital stationary night blindness type 2

    PubMed Central

    Knoflach, Dagmar; Kerov, Vasily; Sartori, Simone B; Obermair, Gerald J; Schmuckermair, Claudia; Liu, Xiaoni; Sothilingam, Vithiyanjali; Garrido, Marina Garcia; Baker, Sheila A; Glösmann, Martin; Schicker, Klaus; Seeliger, Mathias; Lee, Amy; Koschak, Alexandra

    2013-01-01

    Mutations in the CACNA1F gene encoding the Cav1.4 Ca2+ channel are associated with X-linked congenital stationary night blindness type 2 (CSNB2). Despite the increasing knowledge about the functional behavior of mutated channels in heterologous systems, the pathophysiological mechanisms that result in vision impairment remain to be elucidated. This work provides a thorough functional characterization of the novel IT mouse line that harbors the gain-of-function mutation I745T reported in a New Zealand CSNB2 family.1 Electroretinographic recordings in IT mice permitted a direct comparison with human data. Our data supported the hypothesis that a hyperpolarizing shift in the voltage-dependence of channel activation—as seen in the IT gain-of-function mutant2—may reduce the dynamic range of photoreceptor activity. Morphologically, the retinal outer nuclear layer in adult IT mutants was reduced in size and cone outer segments appeared shorter. The organization of the outer plexiform layer was disrupted, and synaptic structures of photoreceptors had a variable, partly immature, appearance. The associated visual deficiency was substantiated in behavioral paradigms. The IT mouse line serves as a specific model for the functional phenotype of human CSNB2 patients with gain-of-function mutations and may help to further understand the dysfunction in CSNB. PMID:24051672

  15. Techno-functional properties and in vitro bile acid-binding capacities of tamarillo (Solanum betaceum Cav.) hydrocolloids.

    PubMed

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

    2016-04-01

    Hydrocolloids were extracted from seed mucilage and the pulp fractions from red tamarillo (Solanum betaceum Cav.) mesocarp, and characterisation of their techno-functional properties and in vitro bile acid-binding capacities was performed. The seed mucilage hydrocolloids that were extracted, using either 1% citric acid (THC) or water (THW), had a good foaming capacity (32-36%), whereas the pulp hydrocolloids that were extracted, using 72% ethanol (THE) or 20mM HEPES buffer (THH), had no foaming capacity. The pulp hydrocolloid, however, possessed high oil-holding and water-holding capacities in the range of 3.3-3.6 g oil/g dry sample and 25-27 g water/g dry sample, respectively. This enabled the pulp hydrocolloid to entrap more bile acids (35-38% at a hydrocolloid concentration of 2%) in its gelatinous network in comparison to commercial oat fibre and other hydrocolloids studied. The exceptional emulsifying properties (80-96%) of both hydrocolloids suggest their potential applications as food emulsifiers and bile acid binders.

  16. 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.

  17. 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.

  18. 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

  19. Immunohistological demonstration of CaV3.2 T-type voltage-gated calcium channel expression in soma of dorsal root ganglion neurons and peripheral axons of rat and mouse

    PubMed Central

    Rose, Kirstin E.; Lunardi, Nadia; Boscolo, Annalisa; Dong, Xinzhong; Erisir, Alev; Jevtovic-Todorovic, Vesna; Todorovic, Slobodan M.

    2013-01-01

    Previous behavioural studies have revealed that CaV3.2 T-type calcium channels support peripheral nociceptive transmission and electrophysiological studies have established the presence of T-currents in putative nociceptive sensory neurons of dorsal root ganglion (DRG). To date, however, the localization pattern of this key nociceptive channel in the soma and peripheral axons of these cells has not been demonstrated due to lack of isoform-selective anti-CaV3.2 antibodies. In the present study a new polyclonal CaV3.2 antibody is used to localize CaV3.2 expression in rodent DRG neurons using different staining techniques including confocal and electron microscopy. Confocal microscopy of both acutely dissociated cells and short-term cultures demonstrated strong immunofluorescence of anti-CaV3.2 antibody that was largely confined to smaller diameter DRG neurons where it co-localized with established immuno-markers of unmyelinated nociceptors, such as, CGRP, IB4 and peripherin. In contrast, a smaller proportion of these CaV3.2-labeled DRG cells also co-expressed NF-200, a marker of myelinated sensory neurons. In the rat sciatic nerve preparation, confocal microscopy demonstrated anti-CaV3.2 immunofluorescence which was co-localized with both peripherin and NF-200. Further, electron microscopy revealed immuno-gold labelling of CaV3.2 preferentially in association with un-myelinated sensory fibres from mouse sciatic nerve. Finally, we demonstrated the expression of CaV3.2 channels in peripheral nerve endings of mouse hindpaw skin as shown by co-localisation with Mrgpd-GFP-positive fibres. The CaV3.2 expression within the soma and peripheral axons of nociceptive sensory neurons further demonstrates the importance of this channel in peripheral pain transmission. PMID:23867767

  20. Three-dimensional robust diving guidance for hypersonic vehicle

    NASA Astrophysics Data System (ADS)

    Zhu, Jianwen; Liu, Luhua; Tang, Guojian; Bao, Weimin

    2016-01-01

    A novel three-dimensional robust guidance law based on H∞ filter and H∞ control is proposed to meet the constraints of the impact accuracy and the flight direction under process disturbances for the dive phase of hypersonic vehicle. Complete three-dimensional coupling relative motion equations are established and decoupled into linear ones by feedback linearization to simplify the design process of the further guidance law. Based on the linearized equations, H∞ filter is introduced to eliminate the measurement noises of line-of-sight angles and estimate the angular rates. Furthermore, H∞ robust control is well employed to design guidance law, and the filtered information is used to generate guidance commands to meet the guidance goal accurately and robustly. The simulation results of CAV-H indicate that the proposed three-dimensional equations can describe the coupling character more clearly than the traditional decoupling guidance, and the proposed guidance strategy can guide the vehicle to satisfy different multiple constraints with high accuracy and robustness.

  1. The Hypersonic Revolution. Volume 2. From Scramjet to the National Aero-Space Plane

    DTIC Science & Technology

    1995-08-01

    for thermal protection on the pods during high-crossrange missions. NASA did not implement this recommendation. 2 7 Ultimately, a "C-9" coating was... protection . The design of future vehicles should include the requirement that the vehicle not be sensitive to moisture , salt air, or rain impingement...Its structure would employ advanced materials and a simplified thermal protection system, and its avionics would be hardened against nuclear blast

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Calibration of aero-structural reduced order models using full-field experimental measurements

    NASA Astrophysics Data System (ADS)

    Perez, R.; Bartram, G.; Beberniss, T.; Wiebe, R.; Spottswood, S. M.

    2017-03-01

    The structural response of hypersonic aircraft panels is a multi-disciplinary problem, where the nonlinear structural dynamics, aerodynamics, and heat transfer models are coupled. A clear understanding of the impact of high-speed flow effects on the structural response, and the potential influence of the structure on the local environment, is needed in order to prevent the design of overly-conservative structures, a common problem in past hypersonic programs. The current work investigates these challenges from a structures perspective. To this end, the first part of this investigation looks at the modeling of the response of a rectangular panel to an external heating source (thermo-structural coupling) where the temperature effect on the structure is obtained from forward looking infrared (FLIR) measurements and the displacement via 3D-digital image correlation (DIC). The second part of the study uses data from a previous series of wind-tunnel experiments, performed to investigate the response of a compliant panel to the effects of high-speed flow, to train a pressure surrogate model. In this case, the panel aero-loading is obtained from fast-response pressure sensitive paint (PSP) measurements, both directly and from the pressure surrogate model. The result of this investigation is the use of full-field experimental measurements to update the structural model and train a computational efficient model of the loading environment. The use of reduced order models, informed by these full-field physical measurements, is a significant step toward the development of accurate simulation models of complex structures that are computationally tractable.

  7. Numerical Prediction of Flow and Heat Transfer on lubricant Supplying and Scavenging Flow Path of an Aero-Engine Lubrication System

    NASA Astrophysics Data System (ADS)

    Huang, S. Q.; Liu, Z. X.; Lv, Y. G.; Zhang, L. F.; Xu, T.

    This paper presents a numerical model of internal flows on lubricant supplying and scavenging flow path of an aero-engine lubrication system. The numerical model was built in the General Analysis Software of Aero-engine Lubrication System (GASLS), developed by Northwestern Polytechnical University. The lubricant flow flux, pressure and temperature distribution at steady state were calculated. GASLS is a general purpose computer program employed a ID steady state network algorithm for analyzing flowrates, pressures and temperatures in a complex flow network. All kinds of aero-engine lubrication systems can be divided into finite correlative typical elements and nodes from which the calculation network is developed in GASLS. Special emphasis is put on how to use combinational elements which is a type of typical elements to replace some complex components such as bearing compartments, accessory drive gearboxes or heat exchangers. This method can reduce network complexity and improve calculation efficiency. The computational results show good agreement with experimental data.

  8. 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.

  9. 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

  10. A method for the assessment of operational severity for a high pressure turbine blade of an aero-engine

    NASA Astrophysics Data System (ADS)

    Haslam, Anthony; Abu, Abdullahi; Laskaridis, Panagiotis

    2015-12-01

    This paper provides a tool for the estimation of the operational severity of a high pressure turbine blade of an aero engine. A multidisciplinary approach using aircraft/ engine performance models which provide inputs to a thermo-mechanical fatigue damage model is presented. In the analysis, account is taken of blade size, blade metal temperature distribution, relevant heat transfer coefficients and mechanical and thermal stresses. The leading edge of the blade is selected as the critical part in the estimation of damage severity for different design and operational parameters. The study also suggests a method for production of operational severity data for the prediction of maintenance intervals.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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).

  17. 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.

  18. The design of hypersonic waveriders for aero-assisted interplanetary trajectories

    NASA Astrophysics Data System (ADS)

    Lewis, Mark J.; McRonald, Angus D.

    1991-01-01

    The aerodynamic performance of a vehicle designed to execute an aerogravity assisted maneuver, which combines a gravitational turn with a low-drag atmosphere pass, is examined. The advantage of the aerogravity assisted maneuver, as opposed to a more traditional gravity-assist trajectory, is that, through the use of a controlled atmospheric flight, nearly any deflection angle around a gravitating body can be realized. This holds the promise of providing extremely large values of Delta V. The success of such a maneuver depends on being able to design a vehicle which can execute sustained atmospheric flight at Mach numbers in the range of 50 - 100 with minimal drag losses. Some simple modeling is used to demonstrate design rules for the design of such vehicles, and to estimate the deterioration of their performance during the flight. Two sample aerogravity-assisted maneuvers are detailed, including a close solar approach requiring modest Delta V, and a sprint mission to Pluto.

  19. Gain of Function in FHM-1 Cav2.1 Knock-In Mice Is Related to the Shape of the Action Potential

    PubMed Central

    Inchauspe, Carlota González; Urbano, Francisco J.; Di Guilmi, Mariano N.; Forsythe, Ian D.; Ferrari, Michel D.; van den Maagdenberg, Arn M.J.M.

    2010-01-01

    Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca2+ channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI CaV2.1 Ca2+ channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents (IpCa) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. CaV2.1 Ca2+ channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca2+ currents (ICa) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when ICawas evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca2+ currents evoked at the presynaptic terminals (IpCa)of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine. PMID:20484531

  20. 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

  1. Cav2-type calcium channels encoded by cac regulate AP-independent neurotransmitter release at cholinergic synapses in adult Drosophila brain.

    PubMed

    Gu, Huaiyu; Jiang, Shaojuan Amy; Campusano, Jorge M; Iniguez, Jorge; Su, Hailing; Hoang, Andy An; Lavian, Monica; Sun, Xicui; O'Dowd, Diane K

    2009-01-01

    Voltage-gated calcium channels containing alpha1 subunits encoded by Ca(v)2 family genes are critical in regulating release of neurotransmitter at chemical synapses. In Drosophila, cac is the only Ca(v)2-type gene. Cacophony (CAC) channels are localized in motor neuron terminals where they have been shown to mediate evoked, but not AP-independent, release of glutamate at the larval neuromuscular junction (NMJ). Cultured embryonic neurons also express CAC channels, but there is no information about the properties of CAC-mediated currents in adult brain nor how these channels regulate transmission in central neural circuits where fast excitatory synaptic transmission is predominantly cholinergic. Here we report that wild-type neurons cultured from late stage pupal brains and antennal lobe projection neurons (PNs) examined in adult brains, express calcium currents with two components: a slow-inactivating current sensitive to the spider toxin Plectreurys toxin II (PLTXII) and a fast-inactivating PLTXII-resistant component. CAC channels are the major contributors to the slow-inactivating PLTXII-sensitive current based on selective reduction of this component in hypomorphic cac mutants (NT27 and TS3). Another characteristic of cac mutant neurons both in culture and in whole brain recordings is a reduced cholinergic miniature excitatory postsynaptic current frequency that is mimicked in wild-type neurons by acute application of PLTXII. These data demonstrate that cac encoded Ca(v)2-type calcium channels regulate action potential (AP)-independent release of neurotransmitter at excitatory cholinergic synapses in the adult brain, a function not predicted from studies at the larval NMJ.

  2. The National Aero-Space Plane, the guidance and control engineer's dream or nightmare?

    NASA Astrophysics Data System (ADS)

    Sanchez, Felix

    Major technical challenges associated with the National Aerospace Plane (NASP) Program are discussed, including the ones viewed from a controls perspective. Design and engineering challenges encountered in the propulsion system, the structural material selection, and the computational fluid dynamic mechanisms to predict Mach 8+ regimes, are briefly discussed. Emphasis is put on those significant challenges in the guidance and control fields relating to vehicle management systems, integrated propulsion/flight control, optimal vehicle trajectory control, and challenges in the associated fields on instrumentation and information systems. An insight into the complexity of the problem is provided, and the importance of guidance and control in future NASP achievements is highlighted.

  3. 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

  4. Familial hemiplegic migraine type-1 mutated cav2.1 calcium channels alter inhibitory and excitatory synaptic transmission in the lateral superior olive of mice.

    PubMed

    Inchauspe, Carlota González; Pilati, Nadia; Di Guilmi, Mariano N; Urbano, Francisco J; Ferrari, Michel D; van den Maagdenberg, Arn M J M; Forsythe, Ian D; Uchitel, Osvaldo D

    2015-01-01

    CaV2.1 Ca(2+) channels play a key role in triggering neurotransmitter release and mediating synaptic transmission. Familial hemiplegic migraine type-1 (FHM-1) is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca(2+) channels. We used knock-in (KI) transgenic mice harbouring the pathogenic FHM-1 mutation R192Q to study inhibitory and excitatory neurotransmission in the principle neurons of the lateral superior olive (LSO) in the auditory brainstem. We tested if the R192Q FHM-1 mutation differentially affects excitatory and inhibitory synaptic transmission, disturbing the normal balance between excitation and inhibition in this nucleus. Whole cell patch-clamp was used to measure neurotransmitter elicited excitatory (EPSCs) and inhibitory (IPSCs) postsynaptic currents in wild-type (WT) and R192Q KI mice. Our results showed that the FHM-1 mutation in CaV2.1 channels has multiple effects. Evoked EPSC amplitudes were smaller whereas evoked and miniature IPSC amplitudes were larger in R192Q KI compared to WT mice. In addition, in R192Q KI mice, the release probability was enhanced compared to WT, at both inhibitory (0.53 ± 0.02 vs. 0.44 ± 0.01, P = 2.10(-5), Student's t-test) and excitatory synapses (0.60 ± 0.03 vs. 0.45 ± 0.02, P = 4 10(-6), Student's t-test). Vesicle pool size was diminished in R192Q KI mice compared to WT mice (68 ± 6 vs 91 ± 7, P = 0.008, inhibitory; 104 ± 13 vs 335 ± 30, P = 10(-6), excitatory, Student's t-test). R192Q KI mice present enhanced short-term plasticity. Repetitive stimulation of the afferent axons caused short-term depression (STD) of E/IPSCs that recovered significantly faster in R192Q KI mice compared to WT. This supports the hypothesis of a gain-of-function of the CaV2.1 channels in R192Q KI mice, which alters the balance of excitatory/inhibitory inputs and could also have implications in the altered cortical excitability responsible for FHM

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. A 2μm-pump laser-based DIRCM system and aero-optics in the mid-IR

    NASA Astrophysics Data System (ADS)

    Renz, Günther; Bohn, Willy

    2007-10-01

    The improvement of the security of platforms (aircrafts) with countermeasure techniques in the mid-IR especially in the take-off or landing phase is nowadays more stringent due to upcoming threats. We report on the development of a Tm:YLF-fiber laser (1.908 μm) pumped Ho:YAG (2.09 µm) high energy laser system with pulse energies up to 100 mJ at pulse lengths close to 20 ns and repetition rates of 100 Hz. A high quality laser beam leaving a platform through a variable-index-of-refraction airflow will experience wave-front aberrations and consequently lose its ability to be perfectly focused in the far field. Two main causes of laser beam degradations are issued in this investigation. First, there is the degradation immediately around the fuselage, referred to aero-optic problems and second the atmospheric propagation influence via air turbulence. The aero-optic influence on the laser beam degradation will be investigated in a laboratory experimental approach with a mid-IR laser beam traversing a transonic free air stream relevant to a real air flow around a fuselage. The propagation characteristics of a laser beam passing turbulent air will be numerically simulated with a multiple phase-screen method and a Fourier propagation technique. Different turbulence degrees relevant to propagation directions especially behind aircrafts will be considered.

  13. Soot volume fraction measurements in aero-engine exhausts using extinction-calibrated backward laser-induced incandescence

    NASA Astrophysics Data System (ADS)

    Delhay, J.; Desgroux, P.; Therssen, E.; Bladh, H.; Bengtsson, P.-E.; Hönen, H.; Black, J. D.; Vallet, I.

    2009-06-01

    Control and reduction of soot particle emissions from aeronautic turbines requires a monitoring system suitable for quantification of these emissions. Currently, such emissions are estimated using the technique of smoke number. This is an extractive method, which is not sensitive enough for the low emission levels of modern gas turbines. Within a recent European project, AEROTEST, part of the project aimed at investigating an alternative soot monitoring technique, laser-induced incandescence (LII) as an in-situ optical diagnostic for quantification of soot emissions. For aero-engine applications, especially those involving large-scale turbines, it is necessary