Impact of Dissociation and Sensible Heat Release on Pulse Detonation and Gas Turbine Engine Performance

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.

2001-01-01

A thermodynamic cycle analysis of the effect of sensible heat release on the relative performance of pulse detonation and gas turbine engines is presented. Dissociation losses in the PDE (Pulse Detonation Engine) are found to cause a substantial decrease in engine performance parameters.

Dissociation and Recombination Effects on the Performance of Pulse Detonation Engines

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.

2003-01-01

This paper summarizes major theoretical results for pulse detonation engine performance taking into account real gas chemistry, as well as significant performance differences resulting from the presence of ram and compression heating. An unsteady CFD analysis, as well as a thermodynamic cycle analysis, was conducted in order to determine the actual and the ideal performance for an air-breathing pulse detonation engine (PDE) using either a hydrogen-air or ethylene-air mixture over a flight Mach number range from 0 to 4. The results clearly elucidate the competitive regime of PDE application relative to ramjets and gas turbines.

Ignition Study on a Rotary-valved Air-breathing Pulse Detonation Engine

NASA Astrophysics Data System (ADS)

Wu, Yuwen; Han, Qixiang; Shen, Yujia; Zhao, Wei

2017-05-01

In the present study, the ignition effect on detonation initiation was investigated in the air-breathing pulse detonation engine. Two kinds of fuel injection and ignition methods were applied. For one method, fuel and air was pre-mixed outside the PDE and then injected into the detonation tube. The droplet sizes of mixtures were measured. An annular cavity was used as the ignition section. For the other method, fuel-air mixtures were mixed inside the PDE, and a pre-combustor was utilized as the ignition source. At firing frequency of 20 Hz, transition to detonation was obtained. Experimental results indicated that the ignition position and initial flame acceleration had important effects on the deflagration-to-detonation transition.

Thrust Augmentation Measurements Using a Pulse Detonation Engine Ejector

NASA Technical Reports Server (NTRS)

Santoro, Robert J.; Pal, Sibtosh

2005-01-01

Results of an experimental effort on pulse detonation driven ejectors are presented and discussed. The experiments were conducted using a pulse detonation engine (PDE)/ejector setup that was specifically designed for the study and operated at frequencies up to 50 Hz. The results of various experiments designed to probe different aspects of the PDE/ejector setup are reported. The baseline PDE was operated using ethylene (C2H4) as the fuel and an oxygen/nitrogen O2 + N2) mixture at an equivalence ratio of one. The PDE only experiments included propellant mixture characterization using a laser absorption technique, high fidelity thrust measurements using an integrated spring-damper system, and shadowgraph imaging of the detonation/shock wave structure emanating from the tube. The baseline PDE thrust measurement results at each desired frequency agree with experimental and modeling results reported in the literature. These PDE setup results were then used as a basis for quantifying thrust augmentation for various PDE/ejector setups with constant diameter ejector tubes and various ejector lengths, the radius of curvature for the ejector inlets and various detonation tube/ejector tube overlap distances. For the studied experimental matrix, the results showed a maximum thrust augmentation of 106% at an operational frequency of 30 Hz. The thrust augmentation results are complemented by shadowgraph imaging of the flowfield in the ejector tube inlet area and high frequency pressure transducer measurements along the length of the ejector tube.

Fuel Composition and Performance Analysis of Endothermically Heated Fuels for Pulse Detonation Engines

DTIC Science & Technology

2009-03-01

Waste heat from a pulse detonation engine (PDE) was extracted via concentric, counter flow heat exchangers to produce supercritical pyrolytic...mass spectrometry HLPC = High performance liquid chromatography NPT = National pipe thread PAH = Polycyclic aromatic hydrocarbon PDE = Pulse...Precision Liquid Chromatography (HPLC). The resulting “stressed” fuel showed a 29 shift to lower molecular weight compounds, as well as the production

Thrust Augmentation Measurements for a Pulse Detonation Engine Driven Ejector

NASA Technical Reports Server (NTRS)

Pal, S.; Santoro, Robert J.; Shehadeh, R.; Saretto, S.; Lee, S.-Y.

2005-01-01

Thrust augmentation results of an ongoing study of pulse detonation engine driven ejectors are presented and discussed. The experiments were conducted using a pulse detonation engine (PDE) setup with various ejector configurations. The PDE used in these experiments utilizes ethylene (C2H4) as the fuel, and an equi-molar mixture of oxygen and nitrogen as the oxidizer at an equivalence ratio of one. High fidelity thrust measurements were made using an integrated spring damper system. The baseline thrust of the PDE engine was first measured and agrees with experimental and modeling results found in the literature. Thrust augmentation measurements were then made for constant diameter ejectors. The parameter space for the study included ejector length, PDE tube exit to ejector tube inlet overlap distance, and straight versus rounded ejector inlets. The relationship between the thrust augmentation results and various physical phenomena is described. To further understand the flow dynamics, shadow graph images of the exiting shock wave front from the PDE were also made. For the studied parameter space, the results showed a maximum augmentation of 40%. Further increase in augmentation is possible if the geometry of the ejector is tailored, a topic currently studied by numerous groups in the field.

The Feasibility of Applying AC Driven Low-Temperature Plasma for Multi-Cycle Detonation Initiation

NASA Astrophysics Data System (ADS)

Zheng, Dianfeng

2016-11-01

Ignition is a key system in pulse detonation engines (PDE). As advanced ignition methods, nanosecond pulse discharge low-temperature plasma ignition is used in some combustion systems, and continuous alternating current (AC) driven low-temperature plasma using dielectric barrier discharge (DBD) is used for the combustion assistant. However, continuous AC driven plasmas cannot be used for ignition in pulse detonation engines. In this paper, experimental and numerical studies of pneumatic valve PDE using an AC driven low-temperature plasma igniter were described. The pneumatic valve was jointly designed with the low-temperature plasma igniter, and the numerical simulation of the cold-state flow field in the pneumatic valve showed that a complex flow in the discharge area, along with low speed, was beneficial for successful ignition. In the experiments ethylene was used as the fuel and air as oxidizing agent, ignition by an AC driven low-temperature plasma achieved multi-cycle intermittent detonation combustion on a PDE, the working frequency of the PDE reached 15 Hz and the peak pressure of the detonation wave was approximately 2.0 MPa. The experimental verifications of the feasibility in PDE ignition expanded the application field of AC driven low-temperature plasma. supported by National Natural Science Foundation of China (No. 51176001)

Rotating Detonation Engine Operation (Preprint)

DTIC Science & Technology

2012-01-01

MdotH2 = mass flow of hydrogen MdotAir = mass flow of air PCB = Piezoelectric Pressure Sensor PDE = Pulsed Detonation Engine RDE = Rotating ...and unsteady thrust output of PDEs . One of the new designs was the Rotating Detonation Engine (RDE). An RDE operates by exhausting an initial...AFRL-RZ-WP-TP-2012-0003 ROTATING DETONATION ENGINE OPERATION (PREPRINT) James A. Suchocki and Sheng-Tao John Yu The Ohio State

Design and Testing of an H2/O2 Predetonator for a Simulated Rotating Detonation Engine Channel

DTIC Science & Technology

2013-03-01

Diameter PDE Pulse Detonation Engines RDE Rotating Detonation Engine WPAFB Wright Patterson Air Force Base ZND Zeldovich, von Neumann and Doring xv...DESIGN AND TESTING OF AN H2/O2 PREDETONATOR FOR A SIMULATED ROTATING DETONATION ENGINE CHANNEL THESIS Stephen J. Miller, 2Lt, USAF AFIT-ENY-13-M-23...RELEASE; DISTRIBUTION UNLIMITED AFIT-ENY-13-M-23 DESIGN AND TESTING OF AN H2/O2 PREDETONATOR FOR A SIMULATED ROTATING DETONATION ENGINE CHANNEL Stephen

Experimental Study of Propulsion Performance by Single-Pulse Rotating Detonation with Gaseous Fuels-Oxygen Mixtures

NASA Astrophysics Data System (ADS)

Toshimitsu, Kazuhiko; Hara, Kosei; Mikajiri, Shuuto; Takiguchi, Naoki

2016-12-01

A rotating detonation engine (RDE) is one of candidates of aerospace engines for supersonic cruse, which is better for propulsion system than a pulse detonation engine (PDE) from the view of continuous thrust and simple structure. The propulsion performance of a proto-type RDE and a PDE by single pulse explosion with methane-oxygen is investigated. Furthermore, the performance of the RDE with acetylene-oxygen gas mixtures is investigated. Its impulse is estimated through ballistic pendulum method with maximum displacement and damping ratio. The comparison of specific impulses of the mixture gases at atmospheric pressure is shown. The specific impulses of the RDE and the PDE are almost same with methane-oxygen gas. Furthermore, the fuel-base specific impulse of the RDE with acetylene-oxygen gas is about over twice as large as one of methane-oxygen, and its maximum specific impulse is 1100 seconds.

A Hydrocarbon Fuel Flash Vaporization System for a Pulsed Detonation Engine

DTIC Science & Technology

2006-12-01

Experiments were performed in the Air Force Research Laboratory (AFRL) Pulsed Detonation Research Facility at Wright Patterson AFB, Ohio. The PDE ...AFRL-MN-EG-TP-2006-7420 A HYDROCARBON FUEL FLASH VAPORIZATION SYSTEM FOR A PULSED DETONATION ENGINE (PREPRINT) K. Colin Tucker...85,7<&/$66,),&$7,212) E7(/(3+21(180%(5 ,QFOXGHDUHDFRGH A Hydrocarbon Fuel Flash Vaporization System for a Pulsed Detonation Engine K

Performance and environmental impact assessment of pulse detonation based engine systems

NASA Astrophysics Data System (ADS)

Glaser, Aaron J.

Experimental research was performed to investigate the feasibility of using pulse detonation based engine systems for practical aerospace applications. In order to carry out this work a new pulse detonation combustion research facility was developed at the University of Cincinnati. This research covered two broad areas of application interest. The first area is pure PDE applications where the detonation tube is used to generate an impulsive thrust directly. The second focus area is on pulse detonation based hybrid propulsion systems. Within each of these areas various studies were performed to quantify engine performance. Comparisons of the performance between detonation and conventional deflagration based engine cycles were made. Fundamental studies investigating detonation physics and flow dynamics were performed in order to gain physical insight into the observed performance trends. Experimental studies were performed on PDE-driven straight and diverging ejectors to determine the system performance. Ejector performance was quantified by thrust measurements made using a damped thrust stand. The effects of PDE operating parameters and ejector geometric parameters on thrust augmentation were investigated. For all cases tested, the maximum thrust augmentation is found to occur at a downstream ejector placement. The optimum ejector geometry was determined to have an overall length of LEJECT/DEJECT =5.61, including an intermediate-straight section length of LSTRT /DEJECT=2, and diverging exhaust section with 4 deg half-angle. A maximum thrust augmentation of 105% was observed while employing the optimized ejector geometry and operating the PDE at a fill-fraction of 0.6 and a frequency of 10 Hz. When operated at a fill-fraction of 1.0 and a frequency of 30 Hz, the thrust augmentation of the optimized PDE-driven ejector system was observed to be 71%. Static pressure was measured along the interior surface of the ejector, including the inlet and exhaust sections. The diverging ejector pressure distribution shows that the diverging section acts as a subsonic diffuser. To provide a better explanation of the observed performance trends, shadowgraph images of the detonation wave and starting vortex interacting with the ejector inlet were obtained. The acoustic signature of a pulse detonation engine was characterized in both the near-field and far-field regimes. Experimental measurements were performed in an anechoic test facility designed for jet noise testing. Both shock strength and speed were mapped as a function of radial distance and direction from the PDE exhaust plane. It was found that the PDE generated pressure field can be reasonably modeled by a theoretical point-source explosion. The effect of several exit nozzle configurations on the PDE acoustic signature was studies. These included various chevron nozzles, a perforated nozzle, and a set of proprietary noise attenuation mufflers. Experimental studies were carried out to investigate the performance of a hybrid propulsion system integrating an axial flow turbine with multiple pulse detonation combustors. The integrated system consisted of a circular array of six pulse detonation combustor (PDC) tubes exhausting through an axial flow turbine. Turbine component performance was quantified by measuring the amount of power generated by the turbine section. Direct comparisons of specific power output and turbine efficiency between a PDC-driven turbine and a turbine driven by steady-flow combustors were made. It was found that the PDC-driven turbine had comparable performance to that of a steady-burner-driven turbine across the operating map of the turbine.

Rapid detonation initiation by sparks in a short duct: a numerical study

NASA Astrophysics Data System (ADS)

Hu, Z. M.; Dou, H. S.; Khoo, B. C.

2010-06-01

Rapid onset of detonation can efficiently increase the working frequency of a pulse detonation engine (PDE). In the present study, computations of detonation initiation in a duct are conducted to investigate the mechanisms of detonation initiation. The governing equations are the Euler equations and the chemical kinetic model consists of 19 elementary reactions and nine species. Different techniques of initiation have been studied for the purpose of accelerating detonation onset with a relatively weak ignition energy. It is found that detonation ignition induced by means of multiple sparks is applicable to auto-ignition for a PDE. The interaction among shock waves, flame fronts and the strip of pre-compressed fresh (unburned) mixture plays an important role in rapid onset of detonation.

Towards Integrated Pulse Detonation Propulsion and MHD Power

NASA Technical Reports Server (NTRS)

Litchford, Ron J.; Thompson, Bryan R.; Lineberry, John T.

1999-01-01

The interest in pulse detonation engines (PDE) arises primarily from the advantages that accrue from the significant combustion pressure rise that is developed in the detonation process. Conventional rocket engines, for example, must obtain all of their compression from the turbopumps, while the PDE provides additional compression in the combustor. Thus PDE's are expected to achieve higher I(sub sp) than conventional rocket engines and to require smaller turbopumps. The increase in I(sub sp) and the decrease in turbopump capacity must be traded off against each other. Additional advantages include the ability to vary thrust level by adjusting the firing rate rather than throttling the flow through injector elements. The common conclusion derived from these aggregated performance attributes is that PDEs should result in engines which are smaller, lower in cost, and lighter in weight than conventional engines. Unfortunately, the analysis of PDEs is highly complex due to their unsteady operation and non-ideal processes. Although the feasibility of the basic PDE concept has been proven in several experimental and theoretical efforts, the implied performance improvements have yet to be convincingly demonstrated. Also, there are certain developmental issues affecting the practical application of pulse detonation propulsion systems which are yet to be fully resolved. Practical detonation combustion engines, for example, require a repetitive cycle of charge induction, mixing, initiation/propagation of the detonation wave, and expulsion/scavenging of the combustion product gases. Clearly, the performance and power density of such a device depends upon the maximum rate at which this cycle can be successfully implemented. In addition, the electrical energy required for direct detonation initiation can be significant, and a means for direct electrical power production is needed to achieve self-sustained engine operation. This work addresses the technological issues associated with PDEs for integrated aerospace propulsion and MHD power. An effort is made to estimate the energy requirements for direct detonation initiation of potential fuel/oxidizer mixtures and to determine the electrical power requirements. This requirement is evaluated in terms of the possibility for MHD power generation using the combustion detonation wave. Small scale laboratory experiments were conducted using stoichiometric mixtures of acetylene and oxygen with an atomized spray of cesium hydroxide dissolved in alcohol as an ionization seed in the active MHD region. Time resolved thrust and MHD power generation measurements were performed. These results show that PDEs yield higher I(sub sp) levels than a comparable rocket engine and that MHD power generation is viable candidate for achieving self-excited engine operation.

Thrust Measurements for a Pulse Detonation Engine Driven Ejector

NASA Technical Reports Server (NTRS)

Santoro, Robert J.; Pak, Sibtosh; Shehadeh, R.; Saretto, S. R.; Lee, S.-Y.

2005-01-01

Results of an experimental effort on pulse detonation driven ejectors aimed at probing different aspects of PDE ejector processes, are presented and discussed. The PDE was operated using ethylene as the fuel and an equimolar oxygen/nitrogen mixture as the oxidizer at an equivalence ratio of one. The thrust measurements for the PDE alone are in excellent agreement with experimental and modeling results reported in the literature and serve as a Baseline for the ejector studies. These thrust measurements were then used as a basis for quantifying thrust augmentation for various PDE/ejector setups using constant diameter ejector tubes and various detonation tube/ejector tube overlap distances. The results show that for the geometries studied here, a maximum thrust augmentation of 24% is achieved. The thrust augmentation results are complemented by shadowgraph imaging of the flowfield in the ejector tube inlet area and high frequency pressure transducer measurements along the length of the ejector tube.

Oxidation- and Creep-Enhanced Fatigue of Haynes 188 Alloy-Oxide Scale System Under Simulated Pulse Detonation Engine Conditions

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Fox, Dennis S.; Miller, Robert A.

2002-01-01

The development of the pulse detonation engine (PDE) requires robust design of the engine components that are capable of enduring harsh detonation environments. In this study, a high cycle thermal fatigue test rig was developed for evaluating candidate PDE combustor materials using a CO2 laser. The high cycle thermal fatigue behavior of Haynes 188 alloy was investigated under an enhanced pulsed laser test condition of 30 Hz cycle frequency (33 ms pulse period, and 10 ms pulse width including 0.2 ms pulse spike). The temperature swings generated by the laser pulses near the specimen surface were characterized by using one-dimensional finite difference modeling combined with experimental measurements. The temperature swings resulted in significant thermal cyclic stresses in the oxide scale/alloy system, and induced extensive surface cracking. Striations of various sizes were observed at the cracked surfaces and oxide/alloy interfaces under the cyclic stresses. The test results indicated that oxidation and creep-enhanced fatigue at the oxide scale/alloy interface was an important mechanism for the surface crack initiation and propagation under the simulated PDE condition.

Laser High-Cycle Thermal Fatigue of Pulse Detonation Engine Combustor Materials Tested

NASA Technical Reports Server (NTRS)

Zhu, Dong-Ming; Fox, Dennis S.; Miller, Robert A.

2001-01-01

Pulse detonation engines (PDE's) have received increasing attention for future aerospace propulsion applications. Because the PDE is designed for a high-frequency, intermittent detonation combustion process, extremely high gas temperatures and pressures can be realized under the nearly constant-volume combustion environment. The PDE's can potentially achieve higher thermodynamic cycle efficiency and thrust density in comparison to traditional constant-pressure combustion gas turbine engines (ref. 1). However, the development of these engines requires robust design of the engine components that must endure harsh detonation environments. In particular, the detonation combustor chamber, which is designed to sustain and confine the detonation combustion process, will experience high pressure and temperature pulses with very short durations (refs. 2 and 3). Therefore, it is of great importance to evaluate PDE combustor materials and components under simulated engine temperatures and stress conditions in the laboratory. In this study, a high-cycle thermal fatigue test rig was established at the NASA Glenn Research Center using a 1.5-kW CO2 laser. The high-power laser, operating in the pulsed mode, can be controlled at various pulse energy levels and waveform distributions. The enhanced laser pulses can be used to mimic the time-dependent temperature and pressure waves encountered in a pulsed detonation engine. Under the enhanced laser pulse condition, a maximum 7.5-kW peak power with a duration of approximately 0.1 to 0.2 msec (a spike) can be achieved, followed by a plateau region that has about one-fifth of the maximum power level with several milliseconds duration. The laser thermal fatigue rig has also been developed to adopt flat and rotating tubular specimen configurations for the simulated engine tests. More sophisticated laser optic systems can be used to simulate the spatial distributions of the temperature and shock waves in the engine. Pulse laser high-cycle thermal fatigue behavior has been investigated on a flat Haynes 188 alloy specimen, under the test condition of 30-Hz cycle frequency (33-msec pulse period and 10-msec pulse width including a 0.2-msec pulse spike; ref. 4). Temperature distributions were calculated with one-dimensional finite difference models. The calculations show that that the 0.2-msec pulse spike can cause an additional 40 C temperature fluctuation with an interaction depth of 0.08 mm near the specimen surface region. This temperature swing will be superimposed onto the temperature swing of 80 C that is induced by the 10-msec laser pulse near the 0.53-mm-deep surface interaction region.

Design and Evaluation of a Single-Inlet Pulse Detonation Combustor

DTIC Science & Technology

2011-06-01

Kilogram/second m/s Meters/ second N Nitrogen NPS Naval Postgraduate School O Oxygen PDC Pulse Detonation Combustion PDE Pulse Detonation Engine...EVALUATION OF A SINGLE-INLET PULSE DETONATION COMBUSTOR by Danny Soria June 2011 Thesis Advisor: Christopher M. Brophy Second Reader: Garth V...COVERED Master’s Thesis 4. TITLE AND SUBTITLE Design and Evaluation of a Single-Inlet Pulse Detonation Combustor 6. AUTHOR(S) Danny Soria 5

Hybrid Solution-Adaptive Unstructured Cartesian Method for Large-Eddy Simulation of Detonation in Multi-Phase Turbulent Reactive Mixtures

DTIC Science & Technology

2012-03-27

pulse- detonation engines ( PDE ), stage separation, supersonic cav- ity oscillations, hypersonic aerodynamics, detonation induced structural...ADAPTIVE UNSTRUCTURED CARTESIAN METHOD FOR LARGE-EDDY SIMULATION OF DETONATION IN MULTI-PHASE TURBULENT REACTIVE MIXTURES 5b. GRANT NUMBER FA9550...CCL Report TR-2012-03-03 Hybrid Solution-Adaptive Unstructured Cartesian Method for Large-Eddy Simulation of Detonation in Multi-Phase Turbulent

The Experimental Study about the Effect of Operating Conditions on Multi-tube Pulse Detonation Engine Performance

NASA Astrophysics Data System (ADS)

Kim, Jung-Min; Han, Hyung-Seok; Choi, Jeong-Yeol

2018-04-01

This study examines a multi-tube pulse detonation engine (PDE) which has a type of constant volume combustion. We designed and made the multi-tube PDE and then conducted an experiment in various operating frequencies and equivalence ratios. First, experiments with operating frequencies of 40, 80, 120, 160, and 200 Hz resulted in an average thrust and specific impulse 23.14 N and 42.34 s. The next experiment resulted in the equivalence ratio varying from 0.81 to 1.38, which resulted in an average thrust and specific impulse 22.36 N and 40.11 s. The average detonation velocity was 8% lower than that calculated according to C-J theory. The incidence ratios of the detonation wave were stable with the exception of the operating frequency of 200 Hz. However, at 200 Hz, the incidence ratio was less than 50%. We assumed that a low fill fraction occurred for this problem. The thrust of the PDE increased with the operating frequency. However, the thrust increase was at a lower rate than in previous studies, because of a lost thrust output result from the slow response time of the load cell amplifier.

Modeling of Multi-Tube Pulse Detonation Engine Operation

NASA Technical Reports Server (NTRS)

Ebrahimi, Houshang B.; Mohanraj, Rajendran; Merkle, Charles L.

2001-01-01

The present paper explores some preliminary issues concerning the operational characteristics of multiple-tube pulsed detonation engines (PDEs). The study is based on a two-dimensional analysis of the first-pulse operation of two detonation tubes exhausting through a common nozzle. Computations are first performed to assess isolated tube behavior followed by results for multi-tube flow phenomena. The computations are based on an eight-species, finite-rate transient flow-field model. The results serve as an important precursor to understanding appropriate propellant fill procedures and shock wave propagation in multi-tube, multi-dimensional simulations. Differences in behavior between single and multi-tube PDE models are discussed, The influence of multi-tube geometry and the preferred times for injecting the fresh propellant mixture during multi-tube PDE operation are studied.

Applications of Laser Diagnostics

DTIC Science & Technology

2005-03-01

Heat Transfer and Thermal Management of PDE . . . . 39 5.1.2 Application of Optical and Numerical Diagnostic Methods to PDE...in Reno, NV. The paper is included in the Appendix. 5.1.1.16 Heat Transfer and Thermal Management in PDE The unsteady nature of the PDE cycle...January 2003, Reno, NV. 57 “Heat Transfer and Thermal Management in a Pulsed Detonation Engine,” J. Hoke, R. Bradley, and F. Schauer, AIAA Paper No

The Use of Steady and Unsteady Detonation Waves for Propulsion Systems

NASA Technical Reports Server (NTRS)

Adelman, Henry G.; Menees, Gene P.; Cambier, Jean-Luc; Bowles, Jeffrey V.; Cavolowsky, John A. (Technical Monitor)

1995-01-01

Detonation wave enhanced supersonic combustors such as the Oblique Detonation Wave Engine (ODWE) are attractive propulsion concepts for hypersonic flight. These engines utilize detonation waves to enhance fuel-air mixing and combustion. The benefits of wave combustion systems include shorter and lighter engines which require less cooling and generate lower internal drag. These features allow air-breathing operation at higher Mach numbers than the diffusive burning scramjet delaying the need for rocket engine augmentation. A comprehensive vehicle synthesis code has predicted the aerodynamic characteristics and structural size and weight of a typical single-stage-to-orbit vehicle using an ODWE. Other studies have focused on the use of unsteady or pulsed detonation waves. For low speed applications, pulsed detonation engines (PDE) have advantages in low weight and higher efficiency than turbojets. At hypersonic speeds, the pulsed detonations can be used in conjunction with a scramjet type engine to enhance mixing and provide thrust augmentation.

Performance Impact of Deflagration to Detonation Transition Enhancing Obstacles

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Schauer, Frederick; Hopper, David

2012-01-01

A sub-model is developed to account for the drag and heat transfer enhancement resulting from deflagration-to-detonation (DDT) inducing obstacles commonly used in pulse detonation engines (PDE). The sub-model is incorporated as a source term in a time-accurate, quasi-onedimensional, CFD-based PDE simulation. The simulation and sub-model are then validated through comparison with a particular experiment in which limited DDT obstacle parameters were varied. The simulation is then used to examine the relative contributions from drag and heat transfer to the reduced thrust which is observed. It is found that heat transfer is far more significant than aerodynamic drag in this particular experiment.

An Overview of Advanced Concepts for Space Access (Preprint)

DTIC Science & Technology

2008-06-19

One such technology is the pulsed detonation engine ( PDE ). PDEs are conceptually simple devices. Fuel and air are mixed in the closed end of a...to form air detonations that propel the vehicle. Two types of lightcraft engines have been examined using either simple laser-thermal or more complex... detonation waves to propel the vehicle has the advantage of not having to store fuel on-board the vehicle. However as the vehicle ascends, the air

Fuel Composition Analysis of Endothermically Heated JP-8 Fuel for Use in a Pulse Detonation Engine

DTIC Science & Technology

2008-06-01

detonation engine (PDE) was extracted via zeolite catalyst coated concentric tube-counter flow heat exchangers to produce supercritical pyrolytic conditions...gas chromatography flame ionization and thermal conductivity detectors ............................................. 68 Table B.1. Elemental bias... chromatography ...................... 98 Table D.1b. Products found in the liquid sample by gas chromatography (continued) ... 99 Table D.1c

On the deflagration-to-detonation transition (DDT) process with added energetic solid particles for pulse detonation engines (PDE)

NASA Astrophysics Data System (ADS)

Nguyen, V. B.; Li, J.; Chang, P.-H.; Phan, Q. T.; Teo, C. J.; Khoo, B. C.

2018-01-01

In this paper, numerical simulations are performed to study the dynamics of the deflagration-to-detonation transition (DDT) in pulse detonation engines (PDE) using energetic aluminum particles. The DDT process and detonation wave propagation toward the unburnt hydrogen/air mixture containing solid aluminum particles is numerically studied using the Eulerian-Lagrangian approach. A hybrid numerical methodology combined with appropriate sub-models is used to capture the gas dynamic characteristics, particle behavior, combustion characteristics, and two-way solid-particle-gas flow interactions. In our approach, the gas mixture is expressed in the Eulerian frame of reference, while the solid aluminum particles are tracked in the Lagrangian frame of reference. The implemented computer code is validated using published benchmark problems. The obtained results show that the aluminum particles not only shorten the DDT length but also reduce the DDT time. The improvement of DDT is primarily attributed to the heat released from surface chemical reactions on the aluminum particles. The temperatures associated with the DDT process are greater than the case of non-reacting particles added, with an accompanying rise in the pressure. For an appropriate range of particle volume fraction, particularly in this study, the higher volume fraction of the micro-aluminum particles added in the detonation chamber can lead to more heat energy released and more local instabilities in the combustion process (caused by the local high temperature), thereby resulting in a faster DDT process. In essence, the aluminum particles contribute to the DDT process of successfully transitioning to detonation waves for (failure) cases in which the fuel gas mixture can be either too lean or too rich. With a better understanding of the influence of added aluminum particles on the dynamics of the DDT and detonation process, we can apply it to modify the geometry of the detonation chamber (e.g., the length of the detonation tube) accordingly to improve the operational performance of the PDE.

Numerical investigation of combustion phenomena in pulse detonation engine with different fuels

NASA Astrophysics Data System (ADS)

Alam, Noor; Sharma, K. K.; Pandey, K. M.

2018-05-01

The effects of different fuel-air mixture on the cyclic operation of pulse detonation engine (PDE) are numerically investigated. The present simulation is to be consider 1200 mm long straight tube combustor channel and 60 mm internal diameter, and filled with stoichiometric ethane-air and ethylene-air (C2H6-air & C2H4) fuel mixture at atmospheric pressure and temperature of 0.1 MPa and 300 K respectively. The obstacles of blockage ratio (BR) 0.5 and having 60 mm spacing among them are allocated inside the combustor tube. There are realizable k-ɛ turbulence model used to analyze characteristic of combustion flame. The objective of present simulation is to analyze the variation in combustion mechanism for two different fuels with one-step reduced chemical reaction model. The obstacles were creating perturbation inside the PDE tube. Therefore, flame surface area increases and reduces deflagration-to-detonation transition (DDT) run-up length.

Effect of Operating Frequency on PDE Driven Ejector Thrust Performance

NASA Technical Reports Server (NTRS)

Santoro, Robert J.; Pal, Sibtosh; Landry, K.; Shehadeh, R.; Bouvet, N.; Lee, S.-Y.

2005-01-01

Results of an on-going study of pulse detonation engine driven ejectors are presented and discussed. The experiments were conducted using a pulse detonation engine (PDE) designed to operate at frequencies up to 50 Hz. The PDE used in these experiments utilizes an equi-molar mixture of oxygen and nitrogen as the oxidizer, and ethylene (C2H4) as the fuel, with the propellant mixture having an equivalence ratio of one. A line of sight laser absorption technique was used to determine the time needed for proper filling of the tube. Thrust measurements were made using an integrated spring damper system coupled with a linear variable displacement transducer. The baseline thrust of the PDE was first measured at each desired frequency and agrees with experimental and modeling results found in the literature. Thrust augmentation measurements were then made for constant diameter ejectors. The ejectors had varying lengths, and two different inlet geometries were tested for each ejector configuration. The parameter space for the study included PDE operation frequency, ejector length, overlap distance and the radius of curvature for the ejector inlets. For the studied experimental matrix, the results showed a maximum thrust augmentation of 106% at an operational frequency of 30 Hz.

Numerical Analysis of a Rotating Detonation Engine in the Relative Reference Frame

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2014-01-01

A two-dimensional, computational fluid dynamic (CFD) simulation of a semi-idealized rotating detonation engine (RDE) is described. The simulation operates in the detonation frame of reference and utilizes a relatively coarse grid such that only the essential primary flow field structure is captured. This construction yields rapidly converging, steady solutions. Results from the simulation are compared to those from a more complex and refined code, and found to be in reasonable agreement. The performance impacts of several RDE design parameters are then examined. Finally, for a particular RDE configuration, it is found that direct performance comparison can be made with a straight-tube pulse detonation engine (PDE). Results show that they are essentially equivalent.

Parametric Study of High Frequency Pulse Detonation Tubes

NASA Technical Reports Server (NTRS)

Cutler, Anderw D.

2008-01-01

This paper describes development of high frequency pulse detonation tubes similar to a small pulse detonation engine (PDE). A high-speed valve injects a charge of a mixture of fuel and air at rates of up to 1000 Hz into a constant area tube closed at one end. The reactants detonate in the tube and the products exit as a pulsed jet. High frequency pressure transducers are used to monitor the pressure fluctuations in the device and thrust is measured with a balance. The effects of injection frequency, fuel and air flow rates, tube length, and injection location are considered. Both H2 and C2H4 fuels are considered. Optimum (maximum specific thrust) fuel-air compositions and resonant frequencies are identified. Results are compared to PDE calculations. Design rules are postulated and applications to aerodynamic flow control and propulsion are discussed.

The development and testing of pulsed detonation engine ground demonstrators

NASA Astrophysics Data System (ADS)

Panicker, Philip Koshy

2008-10-01

The successful implementation of a PDE running on fuel and air mixtures will require fast-acting fuel-air injection and mixing techniques, detonation initiation techniques such as DDT enhancing devices or a pre-detonator, an effective ignition system that can sustain repeated firing at high rates and a fast and capable, closed-loop control system. The control system requires high-speed transducers for real-time monitoring of the PDE and the detection of the detonation wave speed. It is widely accepted that the detonation properties predicted by C-J detonation relations are fairly accurate in comparison to experimental values. The post-detonation flow properties can also be expressed as a function of wave speed or Mach number. Therefore, the PDE control system can use C-J relations to predict the post-detonation flow properties based on measured initial conditions and compare the values with those obtained from using the wave speed. The controller can then vary the initial conditions within the combustor for the subsequent cycle, by modulating the frequency and duty cycle of the valves, to obtain optimum air and fuel flow rates, as well as modulate the energy and timing of the ignition to achieve the required detonation properties. Five different PDE ground demonstrators were designed, built and tested to study a number of the required sub-systems. This work presents a review of all the systems that were tested, along with suggestions for their improvement. The PDE setups, ranged from a compact PDE with a 19 mm (3/4 in.) i.d., to two 25 mm (1 in.) i.d. setups, to a 101 mm (4 in.) i.d. dual-stage PDE setup with a pre-detonator. Propane-oxygen mixtures were used in the smaller PDEs. In the dual-stage PDE, propane-oxygen was used in the pre-detonator, while propane-air mixtures were used in the main combustor. Both rotary valves and solenoid valve injectors were studied. The rotary valves setups were tested at 10 Hz, while the solenoid valves were tested at up to 30 Hz on a 25 mm i.d. PDE. The dual-stage PDE was run at both 1 Hz and 10 Hz using solenoid valves. The two types of valves have their drawbacks and advantages which are discussed, along with ways to enhance their functionality. Rotary valves with stepper motor drives are recommended to be used for air flow control, while an array of solenoid injectors may be used for liquid or gaseous fuel injection. Various DDT enhancing devices were tested, including Shchelkin spirals (with varying thicknesses, lengths and pitches), grooved sleeves and converging-diverging nozzles. The Shchelkin spirals are found to be the most effective of all, at blockage ratios in the region of 50 to 55%. To improve the durability of Shchelkin spirals, it is recommended that they be grooved into the inside of tubes or inserted as replaceable sleeves. Orifice plates with high blockage ratios, in the region of 50 to 80%, are also recommended due to their simple and rugged design. All these devices along with the PDE combustor will require a strong cooling system to prevent damage from the extreme detonation temperatures. High energy (HE) and low energy (LE) ignition systems were tested and compared along with various designs of igniters and automotive spark plugs. It is concluded that while HE ignition may help unsensitized fuel-air mixtures to achieve detonations faster than LE systems, the former have severe drawbacks. The HE igniters get damaged quickly, and require large and heavy power supplies. While the HE ignition is able to reduce ignition delay in a propane-oxygen pre-detonator, it did not show a significant improvement in bringing about DDT in the main combustor using propane-air mixtures. The compact pre-detonator design with a gradual area change transitioning to a larger combustor is found to be effective for detonation initiation, but the pre-detonator concept is recommended for high-speed applications only, since higher speeds requires more sensitive, easily detonable fuels that have short ignition delays and DDT run-up distances. Dynamic pressure transducers, ion detectors and photo-detectors were compared for the diagnostics of the detonation wave. The ion detector is found to be a safe, cheap and effective choice for obtaining detonation or flame velocities, and better than the optical detector, which is not practical for long-duration PDE operations. The piezoelectric dynamic pressure transducer has problems with heating and requires an effective cooling system to enable it to function in a PDE. Other diagnostics studied include thrust measurement and mass flow rate measurement techniques. Additionally, fuel sensitizing techniques, such as hydrogen blending, along with the DDT devices can ensure that detonations are produced successfully.

Thermal Barrier and Protective Coatings to Improve the Durability of a Combustor Under a Pulse Detonation Engine Environment

NASA Technical Reports Server (NTRS)

Ghosn, Louis J.; Zhu, Dongming

2008-01-01

Pulse detonation engine (PDE) concepts are receiving increasing attention for future aeronautic propulsion applications, due to their potential thermodynamic cycle efficiency and higher thrust to density ratio that lead to the decrease in fuel consumption. But the resulting high gas temperature and pressure fluctuation distributions at high frequency generated with every detonation are viewed to be detrimental to the combustor liner material. Experimental studies on a typical metal combustion material exposed to a laser simulated pulse heating showed extensive surface cracking. Coating of the combustor materials with low thermal conductivity ceramics is shown to protect the metal substrate, reduce the thermal stresses, and hence increase the durability of the PDE combustor liner material. Furthermore, the temperature fluctuation and depth of penetration is observed to decrease with increasing the detonation frequency. A crack propagation rate in the coating is deduced by monitoring the variation of the coating apparent thermal conductivity with time that can be utilized as a health monitoring technique for the coating system under a rapid fluctuating heat flux.

On the Exit Boundary Condition for One-Dimensional Calculations of Pulsed Detonation Engine Performance

NASA Technical Reports Server (NTRS)

Wilson, Jack; Paxson, Daniel E.

2002-01-01

In one-dimensional calculations of pulsed detonation engine (PDE) performance, the exit boundary condition is frequently taken to be a constant static pressure. In reality, for an isolated detonation tube, after the detonation wave arrives at the exit plane, there will be a region of high pressure, which will gradually return to ambient pressure as an almost spherical shock wave expands away from the exit, and weakens. Initially, the flow is supersonic, unaffected by external pressure, but later becomes subsonic. Previous authors have accounted for this situation either by assuming the subsonic pressure decay to be a relaxation phenomenon, or by running a two-dimensional calculation first, including a domain external to the detonation tube, and using the resulting exit pressure temporal distribution as the boundary condition for one-dimensional calculations. These calculations show that the increased pressure does affect the PDE performance. In the present work, a simple model of the exit process is used to estimate the pressure decay time. The planar shock wave emerging from the tube is assumed to transform into a spherical shock wave. The initial strength of the spherical shock wave is determined from comparison with experimental results. Its subsequent propagation, and resulting pressure at the tube exit, is given by a numerical blast wave calculation. The model agrees reasonably well with other, limited, results. Finally, the model was used as the exit boundary condition for a one-dimensional calculation of PDE performance to obtain the thrust wall pressure for a hydrogen-air detonation in tubes of length to diameter ratio (L/D) of 4, and 10, as well as for the original, constant pressure boundary condition. The modified boundary condition had no performance impact for values of L/D > 10, and moderate impact for L/D = 4.

Effect of Detonation through a Turbine Stage

NASA Technical Reports Server (NTRS)

Ellis, Matthew T.

2004-01-01

Pulse detonation engines (PDE) have been investigated as a more efficient means of propulsion due to its constant volume combustion rather than the more often used constant pressure combustion of other propulsion systems. It has been proposed that a hybrid PDE-gas turbine engine would be a feasible means of improving the efficiency of the typical constant pressure combustion gas turbine cycle. In this proposed system, multiple pulse detonation tubes would replace the conventional combustor. Also, some of the compressor stages may be removed due to the pressure rise gained across the detonation wave. The benefits of higher thermal efficiency and reduced compressor size may come at a cost. The first question that arises is the unsteadiness in the flow created by the pulse detonation tubes. A constant pressure combustor has the advantage of supplying a steady and large mass flow rate. The use of the pulse detonation tubes will create an unsteady mass flow which will have currently unknown effects on the turbine located downstream of the combustor. Using multiple pulse detonation tubes will hopefully improve the unsteadiness. The interaction between the turbine and the shock waves exiting the tubes will also have an unknown effect. Noise levels are also a concern with this hybrid system. These unknown effects are being investigated using TURBO, an unsteady turbomachinery flow simulation code developed at Mississippi State University. A baseline case corresponding to a system using a constant pressure combustor with the same mass flow rate achieved with the pulse detonation hybrid system will be investigated first.

CPU and GPU-based Numerical Simulations of Combustion Processes

DTIC Science & Technology

2012-04-27

Distribution unlimited UCLA MAE Research and Technology Review April 27, 2012 Magnetohydrodynamic Augmentation of the Pulse Detonation Rocket Engines...Pulse Detonation Rocket-Induced MHD Ejector (PDRIME) – Energy extract from exhaust flow by MHD generator – Seeded air stream acceleration by MHD...accelerator for thrust enhancement and control • Alternative concept: Magnetic piston – During PDE blowdown process, MHD extracts energy and

Rotary wave-ejector enhanced pulse detonation engine

NASA Astrophysics Data System (ADS)

Nalim, M. R.; Izzy, Z. A.; Akbari, P.

2012-01-01

The use of a non-steady ejector based on wave rotor technology is modeled for pulse detonation engine performance improvement and for compatibility with turbomachinery components in hybrid propulsion systems. The rotary wave ejector device integrates a pulse detonation process with an efficient momentum transfer process in specially shaped channels of a single wave-rotor component. In this paper, a quasi-one-dimensional numerical model is developed to help design the basic geometry and operating parameters of the device. The unsteady combustion and flow processes are simulated and compared with a baseline PDE without ejector enhancement. A preliminary performance assessment is presented for the wave ejector configuration, considering the effect of key geometric parameters, which are selected for high specific impulse. It is shown that the rotary wave ejector concept has significant potential for thrust augmentation relative to a basic pulse detonation engine.

PDE Nozzle Optimization Using a Genetic Algorithm

NASA Technical Reports Server (NTRS)

Billings, Dana; Turner, James E. (Technical Monitor)

2000-01-01

Genetic algorithms, which simulate evolution in natural systems, have been used to find solutions to optimization problems that seem intractable to standard approaches. In this study, the feasibility of using a GA to find an optimum, fixed profile nozzle for a pulse detonation engine (PDE) is demonstrated. The objective was to maximize impulse during the detonation wave passage and blow-down phases of operation. Impulse of each profile variant was obtained by using the CFD code Mozart/2.0 to simulate the transient flow. After 7 generations, the method has identified a nozzle profile that certainly is a candidate for optimum solution. The constraints on the generality of this possible solution remain to be clarified.

Ideal cycle analysis of a regenerative pulse detonation engine for power production

NASA Astrophysics Data System (ADS)

Bellini, Rafaela

Over the last few decades, considerable research has been focused on pulse detonation engines (PDEs) as a promising replacement for existing propulsion systems with potential applications in aircraft ranging from the subsonic to the lower hypersonic regimes. On the other hand, very little attention has been given to applying detonation for electric power production. One method for assessing the performance of a PDE is through thermodynamic cycle analysis. Earlier works have adopted a thermodynamic cycle for the PDE that was based on the assumption that the detonation process could be approximated by a constant volume process, called the Humphrey cycle. The Fickett-Jacob cycle, which uses the one--dimensional Chapman--Jouguet (CJ) theory of detonation, has also been used to model the PDE cycle. However, an ideal PDE cycle must include a detonation based compression and heat release processes with a finite chemical reaction rate that is accounted for in the Zeldovich -- von Neumann -- Doring model of detonation where the shock is considered a discontinuous jump and is followed by a finite exothermic reaction zone. This work presents a thermodynamic cycle analysis for an ideal PDE cycle for power production. A code has been written that takes only one input value, namely the heat of reaction of a fuel-oxidizer mixture, based on which the program computes all the points on the ZND cycle (both p--v and T--s plots), including the von Neumann spike and the CJ point along with all the non-dimensionalized state properties at each point. In addition, the program computes the points on the Humphrey and Brayton cycles for the same input value. Thus, the thermal efficiencies of the various cycles can be calculated and compared. The heat release of combustion is presented in a generic form to make the program usable with a wide variety of fuels and oxidizers and also allows for its use in a system for the real time monitoring and control of a PDE in which the heat of reaction can be obtained as a function of fuel-oxidizer ratio. The Humphrey and ZND cycles are studied in comparison with the Brayton cycle for different fuel-air mixtures such as methane, propane and hydrogen. The validity and limitations of the ZND and Humphrey cycles related to the detonation process are discussed and the criteria for the selection of the best model for the PDE cycle are explained. It is seen that the ZND cycle is a more appropriate representation of the PDE cycle. Next, the thermal and electrical power generation efficiencies for the PDE are compared with those of the deflagration based Brayton cycle. While the Brayton cycle shows an efficiency of 0 at a compressor pressure ratio of 1, the thermal efficiency for the ZND cycle starts out at 42% for hydrogen--air and then climbs to a peak of 66% at a compression ratio of 7 before falling slowly for higher compression ratios. The Brayton cycle efficiency rises above the PDEs for compression ratios above 23. This finding supports the theoretical advantage of PDEs over the gas turbines because PDEs only require a fan or only a few compressor stages, thereby eliminating the need for heavy compressor machinery, making the PDEs less complex and therefore more cost effective than other engines. Lastly, a regeneration study is presented to analyze how the use of exhaust gases can improve the performance of the system. The thermal efficiencies for the regenerative ZND cycle are compared with the efficiencies for the non--regenerative cycle. For a hydrogen--air mixture the thermal efficiency increases from 52%, for a cycle without regeneration, to 78%, for the regenerative cycle. The efficiency is compared with the Carnot efficiency of 84% which is the maximum possible theoretical efficiency of the cycle. When compared to the Brayton cycle thermal efficiencies, the regenerative cycle shows efficiencies that are always higher for the pressure ratio studied of 5 ≤ pic ≤ 25, where pi c the compressor pressure ratio of the cycle. This observation strengthens the idea of using regeneration on PDEs.

Multiple-cycle Simulation of a Pulse Detonation Engine Ejector

NASA Technical Reports Server (NTRS)

Yungster, S.; Perkins, H. D.

2002-01-01

This paper presents the results of a study involving single and multiple-cycle numerical simulations of various PDE-ejector configurations utilizing hydrogen-oxygen mixtures. The objective was to investigate the thrust, impulse and mass flow rate characteristics of these devices. The results indicate that ejector systems can utilize the energy stored in the strong shock wave exiting the detonation tube to augment the impulse obtained from the detonation tube alone. Impulse augmentation ratios of up to 1.9 were achieved. The axial location of the converging-diverging ejectors relative to the end of the detonation tube were shown to affect the performance of the system.

Metallized Gelled Propellants Combustion Experiments in a Pulse Detonation Engine

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan; Jurns, John; Breisacher, Kevin; Kearns, Kim

2006-01-01

A series of combustion tests were performed with metallized gelled JP 8/aluminum fuels in a Pulse Detonation Engine (PDE). Nanoparticles of aluminum were used in the 60 to 100 nanometer diameter. Gellants were also of a nanoparticulate type composed of hydrocarbon alkoxide materials. Using simulated air (a nitrogen-oxygen mixture), the ignition potential of metallized gelled fuels with nanoparticle aluminum was investigated. Ignition of the JP 8/aluminum was possible with less than or equal to a 23-wt% oxygen loading in the simulated air. JP 8 fuel alone was unable to ignite with less than 30 percent oxygen loaded simulated air. The tests were single shot tests of the metallized gelled fuel to demonstrate the capability of the fuel to improve fuel detonability. The tests were conducted at ambient temperatures and with maximal detonation pressures of 1340 psia.

Deflagration-to-detonation transition in gases in tubes with cavities

NASA Astrophysics Data System (ADS)

Smirnov, N. N.; Nikitin, V. F.; Phylippov, Yu. G.

2010-12-01

The existence of a supersonic second combustion mode — detonation — discovered by Mallard and Le Chatelier and by Berthélot and Vieille in 1881 posed the question of mechanisms for transition from one mode to the other. In the period 1959-1969, experiments by Salamandra, Soloukhin, Oppenheim, and their coworkers provided insights into this complex phenomenon. Since then, among all the phenomena related to combustion processes, deflagration-to-detonation transition is, undoubtedly, the most intriguing one. Deflagration-to-detonation transition (DDT) in gases is connected with gas and vapor explosion safety issues. Knowing mechanisms of detonation onset control is of major importance for creating effective mitigation measures addressing two major goals: to prevent DDT in the case of mixture ignition, or to arrest the detonation wave in the case where it has been initiated. A new impetus to the increase in interest in deflagration-to-detonation transition processes was given by the recent development of pulse detonation devices. The probable application of these principles to creation of a new generation of engines put the problem of effectiveness of pulse detonating devices at the top of current research needs. The effectiveness of the pulse detonation cycle turned out to be the key factor characterizing the Pulse Detonation Engine (PDE), whose operation modes were shown to be closely related to periodical onset and degeneration of a detonation wave. Those unsteady-state regimes should be self-sustained to guarantee a reliable operation of devices using the detonation mode of burning fuels as a constitutive part of their working cycle. Thus deflagration-to-detonation transition processes are of major importance for the issue. Minimizing the predetonation length and ensuring stability of the onset of detonation enable one to increase the effectiveness of a PDE. The DDT turned out to be the key factor characterizing the PDE operating cycle. Thus, the problem of DDT control in gaseous fuel-air mixtures became very acute. This paper contains results of theoretical and experimental investigations of DDT processes in combustible gaseous mixtures. In particular, the paper investigates the effect of cavities incorporated in detonation tubes at the onset of detonation in gases. Extensive numerical modeling and simulations allowed studying the features of deflagration-to-detonation transition in gases in tubes incorporating cavities of a wider cross section. The presence of cavities substantially affects the combustion modes being established in the device and their dependence on the governing parameters of the problem. The influence of geometrical characteristics of the confinement and flow turbulization on the onset of detonation and the influence of temperature and fuel concentration in the unburned mixture are discussed. It was demonstrated both experimentally and theoretically that the presence of cavities of wider cross section in the ignition part of the tube promotes DDT and shortens the predetonation length. At the same time, cavities incorporated along the whole length or in the far-end section inhibit detonation and bring about the onset of low-velocity galloping detonation or galloping combustion modes. The presence of cavities in the ignition section turns an increase in the initial mixture temperature into a DDT-promoting factor instead of a DDT-inhibiting factor.

Real Gas Effects on the Performance of Hydrocarbon-fueled Pulse Detonation Engines

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.; Yungster, Shaye

2003-01-01

This paper presents results for a single-pulse detonation tube wherein the effects of high temperature dissociation and the subsequent recombination influence the sensible heat release available for providing propulsive thrust. The study involved the use of ethylene and air at equivalence ratios of 0.7 and 1.0. The real gas effects on the sensible heat release were found to be significantly large so as to have an impact on the thrust, impulse and fuel consumption of a PDE.

Pulse Detonation Engines for High Speed Flight

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.

2002-01-01

Revolutionary concepts in propulsion are required in order to achieve high-speed cruise capability in the atmosphere and for low cost reliable systems for earth to orbit missions. One of the advanced concepts under study is the air-breathing pulse detonation engine. Additional work remains in order to establish the role and performance of a PDE in flight applications, either as a stand-alone device or as part of a combined cycle system. In this paper, we shall offer a few remarks on some of these remaining issues, i.e., combined cycle systems, nozzles and exhaust systems and thrust per unit frontal area limitations. Currently, an intensive experimental and numerical effort is underway in order to quantify the propulsion performance characteristics of this device. In this paper, we shall highlight our recent efforts to elucidate the propulsion potential of pulse detonation engines and their possible application to high-speed or hypersonic systems.

Effects of Fuel Distribution on Detonation Tube Performance

NASA Technical Reports Server (NTRS)

Perkins, Hugh Douglas

2002-01-01

A pulse detonation engine (PDE) uses a series of high frequency intermittent detonation tubes to generate thrust. The process of filling the detonation tube with fuel and air for each cycle may yield non-uniform mixtures. Lack of mixture uniformity is commonly ignored when calculating detonation tube thrust performance. In this study, detonation cycles featuring idealized non-uniform H2/air mixtures were analyzed using the SPARK two-dimensional Navier-Stokes CFD code with 7-step H2/air reaction mechanism. Mixture non-uniformities examined included axial equivalence ratio gradients, transverse equivalence ratio gradients, and partially fueled tubes. Three different average test section equivalence ratios (phi), stoichiometric (phi = 1.00), fuel lean (phi = 0.90), and fuel rich (phi = 1.10), were studied. All mixtures were detonable throughout the detonation tube. It was found that various mixtures representing the same test section equivalence ratio had specific impulses within 1 percent of each other, indicating that good fuel/air mixing is not a prerequisite for optimal detonation tube performance.

Approaches to Cycle Analysis and Performance Metrics

NASA Technical Reports Server (NTRS)

Parson, Daniel E.

2003-01-01

The following notes were prepared as part of an American Institute of Aeronautics and Astronautics (AIAA) sponsored short course entitled Air Breathing Pulse Detonation Engine (PDE) Technology. The course was presented in January of 2003, and again in July of 2004 at two different AIAA meetings. It was taught by seven instructors, each of whom provided information on particular areas of PDE research. These notes cover two areas. The first is titled Approaches to Cycle Analysis and Performance Metrics. Here, the various methods of cycle analysis are introduced. These range from algebraic, thermodynamic equations, to single and multi-dimensional Computational Fluid Dynamic (CFD) solutions. Also discussed are the various means by which performance is measured, and how these are applied in a device which is fundamentally unsteady. The second topic covered is titled PDE Hybrid Applications. Here the concept of coupling a PDE to a conventional turbomachinery based engine is explored. Motivation for such a configuration is provided in the form of potential thermodynamic benefits. This is accompanied by a discussion of challenges to the technology.

Pulsed Ejector Wave Propogation Test Program

NASA Technical Reports Server (NTRS)

Fernandez, Rene; Slater, John W.; Paxson, Daniel E.

2003-01-01

The development of, and initial test data from, a nondetonating Pulse Detonation Engine (PDE) simulator tested in the NASA Glenn 1 x 1 foot Supersonic Wind Tunnel (SWT) is presented in this paper. The concept is a pulsed ejector driven by the simulated exhaust of a PDE. This pro- gram is applicable to a PDE entombed in a ramjet flowpath, i.e., a PDE combined-cycle propulsion system. The ejector primary flow is a pulsed, uiiderexpanded, supersonic nozzle simulating the supersonic waves ema- nating from a PDE, while the ejector secondary flow is the 1 x 1 foot SWT test section operated at subsonic Mach numbers. The objective is not to study the detonation details, but the wave physics including t,he start- ing vortices, the extent of propagation of the wave front, the reflection of the wave from the secondary flowpath walls, and the timing of these events of a pulsed ejector, and correlate these with Computational Fluid Dynamics (CFD) code predictions. Pulsed ejectors have been shown to result in a 3 to 1 improvement in LID (length-to-diameter) and a near 2 to 1 improvement in thrust augmentation over a steady ejector. This program will also explore the extent of upstream interactions between an inlet and large, periodically applied, backpressures to the inlet as would be present due to combustion tube detonations in a PDE. These interactions could result in inlet unstart or buzz for a supersonic mixed compression inlet. The design of the present experiment entailed the use of an 2-t diagram characteristics code to study the nozzle filling and purging timescales as well as a series of CFD analyses conducted using the WIND code. The WIND code is a general purpose CFD code for solution of the Reynolds averaged Navier-Stokes equations and can be applied to both steady state and time-accurate calculations. The first, proof-of-concept, test entry (spring 2001) pressure distributions shown here indicate the simulation concept was successful and therefore the experimental approach is sound.

Wavelength-agile diode-laser sensing strategies for monitoring gas properties in optically harsh flows: application in cesium-seeded pulse detonation

NASA Astrophysics Data System (ADS)

Sanders, Scott Thomas; Mattison, Daniel W.; Ma, Lin; Jeffries, Jay B.; Hanson, Ronald K.

2002-06-01

The rapid, broad wavelength scanning capabilities of advanced diode lasers allow extension of traditional diode-laser absorption techniques to high pressure, transient, and generally hostile environments. Here, we demonstrate this extension by applying a vertical cavity surface-emitting laser (VCSEL) to monitor gas temperature and pressure in a pulse detonation engine (PDE). Using aggressive injection current modulation, the VCSEL is scanned through a 10 cm-1 spectral window at megahertz rates roughly 10 times the scanning range and 1000 times the scanning rate of a conventional diode laser. The VCSEL probes absorption lineshapes of the ~ 852 nm D2 transition of atomic Cs, seeded at ~ 5 ppm into the feedstock gases of a PDE. Using these lineshapes, detonated-gas temperature and pressure histories, spanning 2000 4000 K and 0.5 30 atm, respectively, are recorded with microsecond time response. The increasing availability of wavelength-agile diode lasers should support the development of similar sensors for other harsh flows, using other absorbers such as native H2O.

Examination of Wave Speed in Rotating Detonation Engines Using Simplified Computational Fluid Dynamics

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2018-01-01

A simplified, two-dimensional, computational fluid dynamic (CFD) simulation, with a reactive Euler solver is used to examine possible causes for the low detonation wave propagation speeds that are consistently observed in air breathing rotating detonation engine (RDE) experiments. Intense, small-scale turbulence is proposed as the primary mechanism. While the solver cannot model this turbulence, it can be used to examine the most likely, and profound effect of turbulence. That is a substantial enlargement of the reaction zone, or equivalently, an effective reduction in the chemical reaction rate. It is demonstrated that in the unique flowfield of the RDE, a reduction in reaction rate leads to a reduction in the detonation speed. A subsequent test of reduced reaction rate in a purely one-dimensional pulsed detonation engine (PDE) flowfield yields no reduction in wave speed. The reasons for this are explained. The impact of reduced wave speed on RDE performance is then examined, and found to be minimal. Two other potential mechanisms are briefly examined. These are heat transfer, and reactive mixture non-uniformity. In the context of the simulation used for this study, both mechanisms are shown to have negligible effect on either wave speed or performance.

NOx Emissions from a Rotating Detonation-wave Engine

NASA Astrophysics Data System (ADS)

Kailasanath, Kazhikathra; Schwer, Douglas

2016-11-01

Rotating detonation-wave engines (RDE) are a form of continuous detonation-wave engines. They potentially provide further gains in performance than an intermittent or pulsed detonation-wave engine (PDE). The overall flow field in an idealized RDE, primarily consisting of two concentric cylinders, has been discussed in previous meetings. Because of the high pressures involved and the lack of adequate reaction mechanisms for this regime, previous simulations have typically used simplified chemistry models. However, understanding the exhaust species concentrations in propulsion devices is important for both performance considerations as well as estimating pollutant emissions. Progress towards addressing this need will be discussed in this talk. In this approach, an induction parameter model is used for simulating the detonation but a more detailed finite-chemistry model including NOx chemistry is used in the expansion flow region, where the pressures are lower and the uncertainties in the chemistry model are greatly reduced. Results show that overall radical concentrations in the exhaust flow are substantially lower than from earlier predictions with simplified models. Results to date show that NOx emissions are not a problem for the RDE due to the short residence times and the nature of the flow field. Furthermore, simulations show that the amount of NOx can be further reduced by tailoring the fluid dynamics within the RDE.

Chemical Kinetics in the expansion flow field of a rotating detonation-wave engine

NASA Astrophysics Data System (ADS)

Kailasanath, Kazhikathra; Schwer, Douglas

2014-11-01

Rotating detonation-wave engines (RDE) are a form of continuous detonation-wave engines. They potentially provide further gains in performance than an intermittent or pulsed detonation-wave engine (PDE). The overall flow field in an idealized RDE, primarily consisting of two concentric cylinders, has been discussed in previous meetings. Because of the high pressures involved and the lack of adequate reaction mechanisms for this regime, previous simulations have typically used simplified chemistry models. However, understanding the exhaust species concentrations in propulsion devices is important for both performance considerations as well as estimating pollutant emissions. A key step towards addressing this need will be discussed in this talk. In this approach, an induction parameter model is used for simulating the detonation but a more detailed finite-chemistry model is used in the expansion flow region, where the pressures are lower and the uncertainties in the chemistry model are greatly reduced. Results show that overall radical concentrations in the exhaust flow are substantially lower than from earlier predictions with simplified models. The performance of a baseline hydrogen/air RDE increased from 4940 s to 5000 s with the expansion flow chemistry, due to recombination of radicals and more production of H2O, resulting in additional heat release.

Exhaust Gas Emissions from a Rotating Detonation-wave Engine

NASA Astrophysics Data System (ADS)

Kailasanath, Kazhikathra; Schwer, Douglas

2015-11-01

Rotating detonation-wave engines (RDE) are a form of continuous detonation-wave engines. They potentially provide further gains in performance than an intermittent or pulsed detonation-wave engine (PDE). The overall flow field in an idealized RDE, primarily consisting of two concentric cylinders, has been discussed in previous meetings. Because of the high pressures involved and the lack of adequate reaction mechanisms for this regime, previous simulations have typically used simplified chemistry models. However, understanding the exhaust species concentrations in propulsion devices is important for both performance considerations as well as estimating pollutant emissions. Progress towards addressing this need will be discussed in this talk. In this approach, an induction parameter model is used for simulating the detonation but a more detailed finite-chemistry model including NOx chemistry is used in the expansion flow region, where the pressures are lower and the uncertainties in the chemistry model are greatly reduced. Results show that overall radical concentrations in the exhaust flow are substantially lower than from earlier predictions with simplified models. The performance of a baseline hydrogen/air RDE increased from 4940 s to 5000 s with the expansion flow chemistry, due to recombination of radicals and more production of H2O, resulting in additional heat release. Work sponsored by the Office of Naval Research.

Evaluation of Catalytic and Thermal Cracking in a JP-8 Fueled Pulsed Detonation Engine (Postprint)

DTIC Science & Technology

2007-09-01

this research. Each 0.91-m-long heat exchanger was fabricated with a 50.8-mm-dia, inconel - 625 , Schedule-10 inner tube and a 63.5-mm-dia, inconel -600...detonation tube had an inconel heat exchanger (described later). The PDE cycle consisted of three equally timed phases--fill, fire, and purge, as shown in...prevent phase change. The fuel was pressure fed to the inlet of the fuel heating system (FHS). The FHS consisted of two inconel heat exchangers, a

Effect of Operating Frequency and Fill Time on PDE-Ejector Thrust Performance

NASA Technical Reports Server (NTRS)

Landry, K.; Santoro, Robert J.; Pal, Sibtosh; Shehadeh, R.; Bouvet, N.; Lee, S.-Y.

2005-01-01

Thrust measurements for a pulse detonation engine (PDE)-ejector system were determined for a range of operating frequencies. Various length tubular ejectors were utilized. The results were compared to the measurements of the thrust output of the PDE alone to determine the enhancement provided by each ejector configuration at the specified frequencies. Ethylene was chosen as the fuel, with an equi-molar mixture of nitrogen and oxygen acting as the oxidizer. The propellant was kept at an equivalence ratio of one during all the experiments. The system was operated for frequencies between 20 and 50 Hz. The parameter space of the study included PDE operation frequency, ejector length, overlap percentage, the radius of curvature for the ejector inlets, and duration of the time allowed between cycles. The results of the experiments showed a maximum thrust augmentation of 120% for a PDE-ejector configuration at a frequency of 40Hz with a fill time of 10 ms.

Schlieren Imaging and Pulsed Detonation Engine Testing of Ignition by a Nanosecond Repetitively Pulsed Discharge

DTIC Science & Technology

2016-05-16

in ethylene–air and aviation gasoline (avgas)–air mixtures. Testing of NRP discharges in the glow and corona regimes in PDE engines has been...in further detail in Refs. [17,21–23]. NRP discharges in the pin-to-pin configuration have been shown to operate in three regimes: corona , glow, and...assisted combustion Plasma assisted ignition Aircraft propulsionA nanosecond repetitively pulsed (NRP) discharge in the spark regime has been investigated

Detonation Propulsion - A Navy Perspective

DTIC Science & Technology

2013-07-01

for Detonation of Stoichiometric C2H4/ 02 Pui•DIIIIIdll Elllllbell Pllllllll•a IIIII • Project/Program Components - Single tube multi-cycle PDE ... Detonation (mid stages) • Acoustic Wave Interaction - Rotating Detonation (mid stages) - Spinning Detonation (early stages) 62 1. 2. 3. 4. 5. 6...Session 2 Detonation Propulsion -A Navy Perspective Gabriel Roy Office of Naval Research Global 46 Report Documentation Page Form ApprovedOMB No

Investigation of Thrust Augmentation and Acoustic Performance by Ejectors on PDE

NASA Astrophysics Data System (ADS)

Xu, Gui-yang; Weng, Chun-sheng; Li, Ning; Huang, Xiao-long

2016-04-01

Thrust augmentation and acoustic performance of a Pulse Detonation Engine (PDE) with ejector system is experimentally investigated. For these tests the LEjector/DEjector is varied from 1.18 to 4 and the axial placement of the ejector relative to the PDE exhaust is varied from an x/DPDE of -3 to 3. Results from the tests show that the optimum LEjector/DEjector based on thrust augmentation and Overall Sound Pressure Level (OASPL) is found to be 2.61. The divergent ejector performed the best based on thrust augmentation, while the reduction effect for OASPL and Peak Sound Pressure Level (PSPL) at 60° is most prominent for the convergent ejector. The optimum axial position based on thrust augmentation is determined to be x/DPDE = 2, while, x/DPDE = 0 based on OASPL and PSPL.

Pulse Detonation Propulsion

DTIC Science & Technology

2010-01-01

constant-pressure ( Brayton ) cycle used in gas turbines and ramjets. The advantages of PDE for air- breathing propulsion are simplicity and easy scaling...constant-volume, and detonative combustion cycles will be referred to as Brayton , Humphrey, and PDE cycles. The efficiency of thermodynamic cycles O’ODD...efficiency of Brayton cycle, as 0G HH =′ , i.e., 0==constpχ (3) Constant-volume combustion (point E in Fig. 1) results in temperature K 2647/0E

Simulation of Acoustic Noise Generated by an Airbreathing, Beam-Powered Launch Vehicle

NASA Astrophysics Data System (ADS)

Kennedy, W. C.; Van Laak, P.; Scarton, H. A.; Myrabo, L. N.

2005-04-01

A simple acoustic model is developed for predicting the noise signature vs. power level for advanced laser-propelled lightcraft — capable of single-stage flights into low Earth orbit. This model predicts the noise levels generated by a pulsed detonation engine (PDE) during the initial lift-off and acceleration phase, for two representative `tractor-beam' lightcraft designs: a 1-place `Mercury' vehicle (2.5-m diameter, 900-kg); and a larger 5-place `Apollo' vehicle (5-m diameter, 5555-kg) — both the subject of an earlier study. The use of digital techniques to simulate the expected PDE noise signature is discussed, and three examples of fly-by noise signatures are presented. The reduction, or complete elimination of perceptible noise from such engines, can be accomplished by shifting the pulse frequency into the supra-audible or sub-audible range.

Pressure and Thrust Measurements of a High-Frequency Pulsed Detonation Tube

NASA Technical Reports Server (NTRS)

Nguyen, N.; Cutler, A. D.

2008-01-01

This paper describes measurements of a small-scale, high-frequency pulsed detonation tube. The device utilized a mixture of H2 fuel and air, which was injected into the device at frequencies of up to 1200 Hz. Pulsed detonations were demonstrated in an 8-inch long combustion volume, at about 600 Hz, for the quarter wave mode of resonance. The primary objective of this experiment was to measure the generated thrust. A mean value of thrust was measured up to 6.0 lb, corresponding to H2 flow based specific impulse of 2970 s. This value is comparable to measurements in H2-fueled pulsed detonation engines (PDEs). The injection and detonation frequency for this new experimental case was much higher than typical PDEs, where frequencies are usually less than 100 Hz. The compact size of the device and high frequency of detonation yields a thrust-per-unit-volume of approximately 2.0 pounds per cubic inch, and compares favorably with other experiments, which typically have thrust-per-unit-volume of order 0.01 pound per cubic inch. This much higher volumetric efficiency results in a potentially much more practical device than the typical PDE, for a wide range of potential applications, including high-speed boundary layer separation control, for example in hypersonic engine inlets, and propulsion for small aircraft and missiles.

FY06 NRL DoD High Performance Computing Modernization Program Annual Reports

DTIC Science & Technology

2007-10-31

our simulations yield important new information on the amount and form of the energy that is released by these explosive events. These results...coupled with the ideal-gas equation of state and a one-step Arrhenuis kinetics of energy release. The equations are solved using the explicit...practical applications, including hydrogen safety and pulse -detonation engines (PDE). For example, the results summarizing the effect of obstacle

High Resolution WENO Simulation of 3D Detonation Waves

DTIC Science & Technology

2012-02-27

pocket behind the detonation front was not observed in their results because the rotating transverse detonation completely consumed the unburned gas. Dou...three-dimensional detonations We add source terms (functions of x, y, z and t) to the PDE system so that the following functions are exact solutions to... detonation rotates counter-clockwise, opposite to that in [48]. It can be seen that, the triple lines and transverse waves collide with the walls, and strong

Preliminary Studies of a Pulsed Detonation Rocket Engine

NASA Technical Reports Server (NTRS)

Cambier, Jean-Luc; Adelman, H. G.; Menees, G. P.; Edwards, Thomas A. (Technical Monitor)

1995-01-01

In the new era of space exploration, there is a strong need for more efficient, cheaper and more reliable propulsion devices. With dramatic increase in specific impulse, the overall mass of fuel to be lifted into orbit is decreased, and this leads, in turn, to much lower mass requirements at lift-off, higher payload ratios and lower launch costs. The Pulsed Detonation engine (PDE) has received much attention lately due to its unique combination of simplicity, light-weight and efficiency. Current investigations focus principally on its use as a low speed, airbreathing engine, although other applications have also been proposed. Its use as a rocket propulsion device was first proposed in 1988 by the present authors. The superior efficiency of the Pulsed Detonation Rocket Engine (PDRE) is due to the near constant volume combustion process of a detonation wave. Our preliminary estimates suggest that the PDRE is theoretically capable of achieving specific impulses as high as 720 sec, a dramatic improvement over the current 480 sec of conventional rocket engines, making it competitive with nuclear thermal rockets. In addition to this remarkable efficiency, the PDRE may eliminate the need for high pressure cryogenic turbopumps, a principal source of failures. The heat transfer rates are also much lower, eliminating the need for nozzle cooling. Overall, the engine is more reliable and has a much lower weight. This paper will describe in detail the operation of the PDRE and calculate its performance, through numerical simulations. Engineering issues will be addressed and discussed, and the impact on mission profiles will also be presented. Finally, the performance of the PDRE using in-situ resources, such as CO and O2 from the martian atmosphere, will also be computed.

Heat Transfer Experiments on a Pulse Detonation Driven Combustor

DTIC Science & Technology

2011-03-01

steps that need to take place before such a hybrid is successfully developed. PDEs obtain their increased efficiency by means of detonation , a pressure...combustion in the Brayton cycle. A PDE utilizes detonations , which offer much higher pressures at the site of fuel ignition, generating less...HEAT TRANSFER EXPERIMENTS ON A PULSE DETONATION DRIVEN COMBUSTOR THESIS Nicholas C. Longo, Captain, USAF AFIT/GAE/ENY/11-M18

Numerical Analysis of a Pulse Detonation Cross Flow Heat Load Experiment

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Naples, Andrew .; Hoke, John L.; Schauer, Fred

2011-01-01

A comparison between experimentally measured and numerically simulated, time-averaged, point heat transfer rates in a pulse detonation (PDE) engine is presented. The comparison includes measurements and calculations for heat transfer to a cylinder in crossflow and to the tube wall itself using a novel spool design. Measurements are obtained at several locations and under several operating conditions. The measured and computed results are shown to be in substantial agreement, thereby validating the modeling approach. The model, which is based in computational fluid dynamics (CFD) is then used to interpret the results. A preheating of the incoming fuel charge is predicted, which results in increased volumetric flow and subsequent overfilling. The effect is validated with additional measurements.

Energy Conversion and Combustion Sciences

DTIC Science & Technology

2012-03-08

Rotational /Continuous Detonation • Only Single Initiation needed (Circumvent Initiation/DDT difficulty/loss in PDE ) • 10-100x cycle rate increase • Near...new fuels: 1. Rotational or Continuous Detonation (intense/concentrated combustion); 2. Flameless combustion (distributed combustion process...Steady Exit Flow *CFD Courtesy of NRL Rotational Detonation : (PI: Schauer, AFRL/RZ, working with NRL) Rotational Approach Allows Continuous

ASTP RBCC Activities

NASA Technical Reports Server (NTRS)

Nelson, Karl W.; McArthur, Craig; Leopard, Larry (Technical Monitor)

2000-01-01

This presentation reviews the activities of the Advanced Space Transportation Program (ASTP) in the development of Rocket-Based Combined Cycle (RBCC)technology. The document consist of the presentation slides for a talk scheduled to be given to the World Aviation Congress and Exhibit of SAE. Included in the review is discussion of recent accomplishments in the area of Advanced Reusable technologies (ART), which includes work in flowpath testing, and system studies of the various vehicle/engine combinations including RBCC, Turbine Based Combined Cycle (TBCC) and Pulsed Detonation Engine (PDE). Pictures of the proposed RBCC Flowpaths are included. The next steps in the development process are reviewed.

Studies of Operating Frequency Effects On Ejector-based Thrust Augmentation in a Pulse Detonation Engine

NASA Technical Reports Server (NTRS)

Landry, K.

2005-01-01

Studies were performed in order to characterize the thrust augmentation potential of an ejector in a Pulse Detonation Engine application. A 49-mm diameter tube of 0.914-m length was constructed with one open end and one closed end. Ethylene, oxygen, and nitrogen were introduced into the tube at the closed end through the implementation of a fast mixing injector. The tube was completely filled with a stoichiometric mixture containing a one to one molar ratio of nitrogen to oxygen. Ethylene was selected as the fuel due to its detonation sensitivity and the molar ratio of the oxidizer was chosen for heat transfer purposes. Detonations were initiated in the tube through the use of a spark ignition system. The PDE was operated in a multi-cycle mode at frequencies ranging from 20-Hz to 50-Hz. Baseline thrust measurements with no ejector present were performed while operating the engine at various frequencies and compared to theoretical estimates. The baseline values were observed to agree with the theoretical model at low operating frequencies and proved to be increasingly lower than the predicted values as the operating frequency was increased. The baseline thrust measurements were observed to agree within 15 percent of the model for all operating frequencies. A straight 152-mm diameter ejector was installed and thrust augmentation percentages were measured. The length of the ejector was varied while the overlap percentage (percent of the ejector length which overlapped the tube) was maintained at 25 percent for all tests. In addition, the effect of ejector inlet geometry was investigated by comparing results with a straight inlet to those of a 38-mm inlet diameter. The thrust augmentation of the straight inlet ejector proved to be independent of engine operating frequency, augmenting thrust by 40 percent for the 0.914-m length ejector. In contrast, the rounded lip ejector of the same length seemed to be highly dependent on the engine operating frequency. An optimum operating frequency observed with the rounded inlet occurred at an operating frequency of 30-Hz, resulting in thrust augmentation percentages greater than 100 percent. The effect that the engine operating frequency had on thrust augmentation levels attained with an ejector was characterized and optimum performance parameters were established. Insight into the frequency dependent nature of the ejector performance was pursued. Suggestions for future experiments which are needed to fully understand the means in which thrust augmentation is achieved in a PDE-ejector configuration were noted.

JANNAF 24th Airbreathing Propulsion Subcommittee and 36th Combustion Subcommittee Joint Meeting. Volume 1

NASA Technical Reports Server (NTRS)

Fry, Ronald S. (Editor); Gannaway, Mary T. (Editor)

1999-01-01

Volume 1, the first of three volumes is a compilation of 16 unclassified/unlimited-technical papers presented at the Joint Army-Navy-NASA-Air Force (JANNAF) 24th Airbreathing Propulsion Subcommittee and 36th Combustion Subcommittee held jointly with the 181 Propulsion Systems Hazards Subcommittee. The meeting was held on 18-21 October 1999 at NASA Kennedy Space Center and The DoubleTree Oceanfront Hotel, Cocoa Beach, Florida. Topics covered include overviews of RBCC and PDE hypersonic technology, Hyper-X propulsion ground testing, development of JP-8 for hypersonic vehicle applications, numerical simulation of dual-mode SJ combustion, V&V of M&S computer codes, MHD SJ and Rocket Based Combined Cycle (RBCC) launch vehicle concepts, and Pulse Detonation Engine (PDE) propulsion technology development including fundamental investigations, modeling, aerodynamics, operation and performance.

New detonation concepts for propulsion and power generation

NASA Astrophysics Data System (ADS)

Braun, Eric M.

A series of related analytical and experimental studies are focused on utilizing detonations for emerging propulsion and power generation devices. An understanding of the physical and thermodynamic processes for this unsteady thermodynamic cycle has taken over 100 years to develop. An overview of the thermodynamic processes and development history is provided. Thermodynamic cycle analysis of detonation-based systems has often been studied using surrogate models. A real gas model is used for a thermal efficiency prediction of a detonation wave based on the work and heat specified by process path diagrams and a control volume analysis. A combined first and second law analysis aids in understanding performance trends for different initial conditions. A cycle analysis model for an airbreathing, rotating detonation wave engine (RDE) is presented. The engine consists of a steady inlet system with an isolator which delivers air into an annular combustor. A detonation wave continuously rotates around the combustor with side relief as the flow expands towards the nozzle. Air and fuel enter the combustor when the rarefaction wave pressure behind the detonation front drops to the inlet supply pressure. To create a stable RDE, the inlet pressure is matched in a convergence process with the average combustor pressure by increasing the annulus channel width with respect to the isolator channel. Performance of this engine is considered using several parametric studies. RDEs require a fuel injection system that can cycle beyond the limits of mechanical valves. Fuel injectors composed of an orifice connected to a small plenum cavity were mounted on a detonation tube. These fuel injectors, termed fluidic valves, utilize their geometry and a supply pressure to deliver fuel and contain no moving parts. Their behavior is characterized in order to determine their feasibility for integration with high-frequency RDEs. Parametric studies have been conducted with the type of fuel injected, the orifice diameter, and the plenum cavity pressure. Results indicate that the detonation wave pressure temporarily interrupts the fluidic valve supply, but the wave products can be quickly expelled by the fresh fuel supply to allow for refueling. The interruption time of the valve scales with injection and detonation wave pressure ratios as well as a characteristic time. The feasibility of using a detonation wave as a source for producing power in conjunction with a linear generator is considered. Such a facility can be constructed by placing a piston--spring system at the end of a pulsed detonation engine (PDE). Once the detonation wave reflects off the piston, oscillations of the system drive the linear generator. An experimental facility was developed to explore the interaction of a gaseous detonation wave with the piston. Experimental results were then used to develop a model for the interaction. Governing equations for two engine designs are developed and trends are established to indicate a feasible design space for future development.

Current and Future Critical Issues in Rocket Propulsion Systems

NASA Technical Reports Server (NTRS)

Navaz, Homayun K.; Dix, Jeff C.

1998-01-01

The objective of this research was to tackle several problems that are currently of great importance to NASA. In a liquid rocket engine several complex processes take place that are not thoroughly understood. Droplet evaporation, turbulence, finite rate chemistry, instability, and injection/atomization phenomena are some of the critical issues being encountered in a liquid rocket engine environment. Pulse Detonation Engines (PDE) performance, combustion chamber instability analysis, 60K motor flowfield pattern from hydrocarbon fuel combustion, and 3D flowfield analysis for the Combined Cycle engine were of special interest to NASA. During the summer of 1997, we made an attempt to generate computational results for all of the above problems and shed some light on understanding some of the complex physical phenomena. For this purpose, the Liquid Thrust Chamber Performance (LTCP) code, mainly designed for liquid rocket engine applications, was utilized. The following test cases were considered: (1) Characterization of a detonation wave in a Pulse Detonation Tube; (2) 60K Motor wall temperature studies; (3) Propagation of a pressure pulse in a combustion chamber (under single and two-phase flow conditions); (4) Transonic region flowfield analysis affected by viscous effects; (5) Exploring the viscous differences between a smooth and a corrugated wall; and (6) 3D thrust chamber flowfield analysis of the Combined Cycle engine. It was shown that the LTCP-2D and LTCP-3D codes are capable of solving complex and stiff conservation equations for gaseous and droplet phases in a very robust and efficient manner. These codes can be run on a workstation and personal computers (PC's).

Experimental Investigation of a Multi-Cycle Single-Tube Pulse Detonation Rocket Engine with a Coaxial Rotary Valve

NASA Astrophysics Data System (ADS)

Matsuoka, Ken; Esumi, Motoki; Ikeguchi, Ken Bryan; Kasahara, Jiro; Matsuo, Akiko; Funaki, Ikkoh

We developed a novel coaxial rotary valve for a multi-tube PDE. Since this single valve can supply three different gases (fuel, oxidizer and purge gas) into a combustor, the unification of the valve systems for three different gases is possible by using our newly designed valve. A PDRE system can be simple and lightweight by using this valve, and thus its thrust-weight ratio can be increased. We proposed the design of a multi-tube rotary-valved PDRE system by this rotary valve. Moreover, in preparation for a multi-tube rotary-valved PDRE, we carried out the multi-cycle operation experiment by the single-tube rotary-valved PDRE system. The combustion wave velocity was measured to confirm the operation of the PDRE system. Deflagration-to-detonation transition (DDT) was confirmed and DDT distance decreased under the condition of high operation frequency. In addition, a maximum operation frequency was 159 Hz.

Unsteady Specific Work and Isentropic Efficiency of a Radial Turbine Driven by Pulsed Detonations

DTIC Science & Technology

2012-06-14

iv AFIT/DS/ENY/12-25 Abstract There has been longstanding government and industry interest in pressure-gain combustion for use in Brayton cycle...10 III.A. Unsteady Flow in Conventional Brayton Cycle Turbines ........................10 III.B. Unsteady Flow in Pulsed Detonation Driven...Szpynda and Nalim 2007) 114 Figure 69. Heiser and Pratt comparison of ideal PDE, Humphrey, and Brayton cycles on a temperature-entropy diagram (Heiser

Detonation Jet Engine. Part 2--Construction Features

ERIC Educational Resources Information Center

Bulat, Pavel V.; Volkov, Konstantin N.

2016-01-01

We present the most relevant works on jet engine design that utilize thermodynamic cycle of detonative combustion. Detonation engines of various concepts, pulse detonation, rotational and engine with stationary detonation wave, are reviewed. Main trends in detonation engine development are discussed. The most important works that carried out…

Confined Detonations and Pulse Detonation Engines

DTIC Science & Technology

2003-01-01

chemically reacting flow was described by the 2D Euler equations &q OF(q) +G(q) W (1) 75 CONFINED DETONATIONS AND PULSE DETONATION ENGINES where q = (p...DETONATIONS AND PULSE DETONATION ENGINES 5 CONCLUDING REMARKS Numerical investigations of RR and MR in a supersonic chemically reacting flows have...formalism of hetero- geneous medium mechanics supplemented with an overall chemical reaction was 141 CONFINED DETONATIONS AND PULSE DETONATION ENGINES

Investigation of an Unusually Shallow Earthquake Sequence in Mogul, NV from a Discrimination Perspective

DTIC Science & Technology

2014-08-31

shows that polarity is occasionally flipped between events due to rotation of the focal mechanism. A total of 233,357 cross-correlation times were...model NEIS PDE 2008/04/26 06:40:10.61 39.520 -119.930 1.40 model unknown NSL original catalog 2008/04/26, 06:40:10.6 39.5247 -119.9180 3.08... detonated at Yucca Flat the P-velocity was 1.6 km/s and for nuclear explosions detonated at Pahute Mesa the P-velocity was 2.7 km/s. The S- velocity was

Numerical Investigation of Pre-detonator Geometries for PDE Applications

DTIC Science & Technology

2010-03-01

pattern will be traced that resembles the scales of a fish. The fishscale pattern is a trace of the high pressure transverse waves. Figure 10 shows a...numerically generated smokefoil record that is created by taking a peak pressure histogram of the transient data set. Each of the fishscale -like diamonds

Laboratory Demonstrations for PDE and Metals Combustion at NASA MSFC's Advanced Propulsion Laboratory

NASA Technical Reports Server (NTRS)

2000-01-01

Report provides status reporting on activities under order no. H-30549 for the period December 1 through December 31, 1999. Details the activities of the contract in the coordination of planned conduct of experiments at the MSFC Advanced Propulsion Laboratory in pulse detonation MHD power production and metals combustion.

Propulsion Systems Integration for a `Tractor Beam' Mercury Lightcraft: Liftoff Engine

NASA Astrophysics Data System (ADS)

Myrabo, L. N.

2003-05-01

Described herein is the concept and propulsion systems integration for a revolutionary beam-propelled shuttle called the ``Mercury'' lightcraft - emphasizing the liftoff engine mode. This one-person, ultra-energetic vehicle is designed to ride `tractor beams' into space, transmitted from a future network of satellite solar power stations. The objective is to create a safe, very low cost (e.g., 1000X below chemical rockets) space transportation system for human life, one that is completely `green' and independent of Earth's limited fossil fuel reserves. The lightcraft's airbreathing combined-cycle engine operates in a rotary pulsed detonation mode PDE for lift-offs and landings; at hypersonic speeds it transitions into a magnetohydrodynamic (MHD) slipstream accelerator mode. For the latter, the transatmospheric flight path is momentarily transformed into an extremely long, electromagnetic ``mass-driver'' channel with an effective `fuel' specific impulse in the range of 6000 to 16,000 seconds. These future single-stage-to-orbit, highly-reusuable vehicles will ride ``Highways of Light,'' accelerating at 3 Gs into space, with their throttles just barely beyond `idle' power.

Propulsion and power for 21st century aviation

NASA Astrophysics Data System (ADS)

Sehra, Arun K.; Whitlow, Woodrow

2004-05-01

Air transportation in the new millennium will require revolutionary solutions to meet public demand for improving safety, reliability, environmental compatibility, and affordability. NASA's vision for 21st century aircraft is to develop propulsion systems that are intelligent, highly efficient, virtually inaudible (outside airport boundaries), and have near zero harmful emissions (CO 2 and NO x). This vision includes intelligent engines capable of adapting to changing internal and external conditions to optimally accomplish missions with either minimal or no human intervention. Distributed vectored propulsion will replace current two to four wing mounted and fuselage mounted engine configurations with a large number of small, mini, or micro engines. Other innovative concepts, such as the pulse detonation engine (PDE), which potentially can replace conventional gas turbine engines, also are reviewed. It is envisioned that a hydrogen economy will drive the propulsion system revolution towards the ultimate goal of silent aircrafts with zero harmful emissions. Finally, it is envisioned that electric drive propulsion based on fuel cell power will generate electric power, which in turn will drive propulsors to produce the desired thrust. This paper reviews future propulsion and power concepts that are under development at the National Aeronautics and Space Administration's (NASA) John H. Glenn Research Center at Lewis Field, Cleveland, Ohio, USA.

Build Up and Operation of an Axial Turbine Driven by a Rotary Detonation Engine

DTIC Science & Technology

2012-03-01

RDEs) offer advantages over pulsed detonation engines ( PDEs ) due to a steadier exhaust and fewer total system losses. All previous research on...turbine integration with detonation combustors has focused on utilizing PDEs to drive axial and centrifugal turbines. The objective of this thesis was... detonation engine ............................................. 5 Figure 4. Schematic of the rotating detonation wave structure for an unwrapped view of an

Performance Enhancement of Unsteady Ejectors Investigated Using a Pulsejet Driver

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2003-01-01

Unsteady ejectors are currently under investigation for use in some pulse detonation engine (PDE) propulsion systems. This is due primarily to their potential high performance in comparison to steady ejectors of similar dimensions relative to the source or driver jet. Although some experimental work has been done in the past to study thrust augmentation with unsteady ejectors, there is no proven theory by which optimal design parameters can be selected and an effective ejector constructed for a given pulsed flow. Therefore, an experimental facility was developed at the NASA Glenn Research Center to study the correlation between ejector design and performance, and to get a better understanding of the flow phenomena that result in thrust augmentation. A commercially available pulsejet was used for the unsteady driving jet. This was paired with a basic, yet flexible, ejector design that allowed parametric evaluation of the effects that length, diameter, and inlet radius have on performance.

The Pulse Detonation Rocket Induced MHD Ejector (PDRIME) Concept (Preprint)

DTIC Science & Technology

2008-06-10

flight applications. Thrust augmentation , such as PDE- ejector configurations, can potentially alleviate this problem. Here, we study the potential...flow, to assist in augmentation of the thrust . Ejectors typically transfer energy between streams through shear stress between separate flow streams...and the ejector operates. This is one of several configurations in which the PDRIME concept could be used for thrust augmentation in advanced

Pressure Characteristics of a Diffuser in a Ram RDE Propulsive Device

DTIC Science & Technology

2017-07-21

Continuous detonation Rotating-detonation- engine Ethylene-air Diffuser Pressure feedback Modeling and simulation Office of Naval Research 875 N. Randolph...RDE PROPULSIVE DEVICE INTRODUCTION This report focuses on the diffuser of a ram Rotating Detonation Engine (RDE) device. A ram RDE is a ramjet with...the constant pressure combustion chamber replaced with a Rotating Detonation Engine combustor to accomplish pressure gain combustion. A ram engine

14 CFR 33.47 - Detonation test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Detonation test. 33.47 Section 33.47 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Reciprocating Aircraft Engines § 33.47 Detonation test. Each engine...

14 CFR 33.47 - Detonation test.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Detonation test. 33.47 Section 33.47 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Reciprocating Aircraft Engines § 33.47 Detonation test. Each engine...

14 CFR 33.47 - Detonation test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Detonation test. 33.47 Section 33.47 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Reciprocating Aircraft Engines § 33.47 Detonation test. Each engine...

14 CFR 33.47 - Detonation test.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Detonation test. 33.47 Section 33.47 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Reciprocating Aircraft Engines § 33.47 Detonation test. Each engine...

Detonation Jet Engine. Part 1--Thermodynamic Cycle

ERIC Educational Resources Information Center

Bulat, Pavel V.; Volkov, Konstantin N.

2016-01-01

We present the most relevant works on jet engine design that utilize thermodynamic cycle of detonative combustion. The efficiency advantages of thermodynamic detonative combustion cycle over Humphrey combustion cycle at constant volume and Brayton combustion cycle at constant pressure were demonstrated. An ideal Ficket-Jacobs detonation cycle, and…

Modeling the Effects of Turbulence in Rotating Detonation Engines

NASA Astrophysics Data System (ADS)

Towery, Colin; Smith, Katherine; Hamlington, Peter; van Schoor, Marthinus; TESLa Team; Midé Team

2014-03-01

Propulsion systems based on detonation waves, such as rotating and pulsed detonation engines, have the potential to substantially improve the efficiency and power density of gas turbine engines. Numerous technical challenges remain to be solved in such systems, however, including obtaining more efficient injection and mixing of air and fuels, more reliable detonation initiation, and better understanding of the flow in the ejection nozzle. These challenges can be addressed using numerical simulations. Such simulations are enormously challenging, however, since accurate descriptions of highly unsteady turbulent flow fields are required in the presence of combustion, shock waves, fluid-structure interactions, and other complex physical processes. In this study, we performed high-fidelity three dimensional simulations of a rotating detonation engine and examined turbulent flow effects on the operation, performance, and efficiency of the engine. Along with experimental data, these simulations were used to test the accuracy of commonly-used Reynolds averaged and subgrid-scale turbulence models when applied to detonation engines. The authors gratefully acknowledge the support of the Defense Advanced Research Projects Agency (DARPA).

Innovative Airbreathing Propulsion Concepts for High-speed Applications

NASA Technical Reports Server (NTRS)

Whitlow, Woodrow, Jr.

2002-01-01

The current cost to launch payloads to low earth orbit (LEO) is approximately loo00 U.S. dollars ($) per pound ($22000 per kilogram). This high cost limits our ability to pursue space science and hinders the development of new markets and a productive space enterprise. This enterprise includes NASA's space launch needs and those of industry, universities, the military, and other U.S. government agencies. NASA's Advanced Space Transportation Program (ASTP) proposes a vision of the future where space travel is as routine as in today's commercial air transportation systems. Dramatically lower launch costs will be required to make this vision a reality. In order to provide more affordable access to space, NASA has established new goals in its Aeronautics and Space Transportation plan. These goals target a reduction in the cost of launching payloads to LEO to $lo00 per pound ($2200 per kilogram) by 2007 and to $100' per pound by 2025 while increasing safety by orders of magnitude. Several programs within NASA are addressing innovative propulsion systems that offer potential for reducing launch costs. Various air-breathing propulsion systems currently are being investigated under these programs. The NASA Aerospace Propulsion and Power Base Research and Technology Program supports long-term fundamental research and is managed at GLenn Research Center. Currently funded areas relevant to space transportation include hybrid hyperspeed propulsion (HHP) and pulse detonation engine (PDE) research. The HHP Program currently is addressing rocket-based combined cycle and turbine-based combined cycle systems. The PDE research program has the goal of demonstrating the feasibility of PDE-based hybrid-cycle and combined cycle propulsion systems that meet NASA's aviation and access-to-space goals. The ASTP also is part of the Base Research and Technology Program and is managed at the Marshall Space Flight Center. As technologies developed under the Aerospace Propulsion and Power Base Research and Technology Program mature, they are incorporated into ASTP. One example of this is rocket-based combined cycle systems that are being considered as part of ASTP. The NASA Ultra Efficient Engine Technology (UEET) Program has the goal of developing propulsion system component technology that is relevant to a wide range of vehicle missions. In addition to subsonic and supersonic speed regimes, it includes the hypersonic speed regime. More specifically, component technologies for turbine-based combined cycle engines are being developed as part of UEET.

Accelerating confined premixed flames using a transverse slot jet

NASA Astrophysics Data System (ADS)

Richter, Joseph P.

2011-12-01

An experimental study of the transient interaction of a premixed laminar methane-air flame propagating into a transverse fluidic obstacle is considered. The de agration-to-detonation transition (DDT) mechanism for use in pulse detonation engines (PDE) is the main but not only motivation for this study. When DDT is initiated through the use of solid obstacles, the system incurs a drag penalty and subsequent total pressure losses due to the physical obstacle impeding on the flow. This study utilizes a fluidic obstacle to generate flame acceleration without the subsequent penalties associated with form drag of a solid obstacle. The experimental setup was designed specifically for non-intrusive optical measurement techniques such as schlieren, CH* chemiluminescence and digital particle image velocimetry (DPIV). The channel utilizes a length to width aspect ratio of L/W = 6, and was chosen along with the fuel (CH4) to guarantee the impossibility of excessive overpressures associated with unanticipated detonations. The mixture is ignited in the center of the closed end of the channel, and the flame propagates towards the obstacle located at 3.1H. The medium emitted from the slot-jet orifice is the same methane-air mixture used to fill the channel and is released post ignition to allow an interaction with the laminar propagating flame. A comparison of this transverse fluidic slot jet obstacle is made to four different solid obstacle geometries at various blockage ratios (BR) and at stoichiometric and lean (φ = 0:88) equivalence ratios. The results of this study show that a transverse slot jet is capable of increasing heat release, flame surface area and subsequently flame speed compared to that of any tested solid obstacle with similar maximum flame deflection over an obstacle.

A Three-Dimensional Eulerian Code for Simulation of High-Speed Multimaterial Interactions

DTIC Science & Technology

2011-08-01

PDE -based extension. The extension process is done on only the host cells on a particular processor. After extension the parallel communication is...condensation shocks, explosive debris transport, detonation in heterogeneous media and so on. In these flows complex interactions occur between the...A.22] and ijΩ is the spin tensor. The Jaumann derivative is used to ensure objectivity of the stress tensor with respect to rotation

Analysis of Porous Media as Inlet Concept for Rotating Detonation Engines

NASA Astrophysics Data System (ADS)

Grogan, Kevin; Ihme, Matthias; Department of Mechanical Engineering Team

2016-11-01

Rotating detonation engines combust reactive gas mixtures with a high-speed, annularly-propagating detonation wave, which provides many advantages including a stagnation pressure gain and a compact, lightweight design. However, the optimal design of the inlet to the combustion chamber inlet is a moot topic since improper design can significantly reduce detonability and increase pressure losses. The highly diffusive properties of porous media could make it an ideal material to prevent the flashback of the detonation wave and therefore, allow the inlet gas to be premixed. Motivated by this potential, this work employs simulation to evaluate the application of porous media to the inlet of a rotating detonation engine as a novel means to stabilize a detonation wave while reducing the pressure losses incurred by non-ideal mixing strategies. Department of the Air Force.

Reverse engineering of aircraft wing data using a partial differential equation surface model

NASA Astrophysics Data System (ADS)

Huband, Jacalyn Mann

Reverse engineering is a multi-step process used in industry to determine a production representation of an existing physical object. This representation is in the form of mathematical equations that are compatible with computer-aided design and computer-aided manufacturing (CAD/CAM) equipment. The four basic steps to the reverse engineering process are data acquisition, data separation, surface or curve fitting, and CAD/CAM production. The surface fitting step determines the design representation of the object, and thus is critical to the success or failure of the reverse engineering process. Although surface fitting methods described in the literature are used to model a variety of surfaces, they are not suitable for reversing aircraft wings. In this dissertation, we develop and demonstrate a new strategy for reversing a mathematical representation of an aircraft wing. The basis of our strategy is to take an aircraft design model and determine if an inverse model can be derived. A candidate design model for this research is the partial differential equation (PDE) surface model, proposed by Bloor and Wilson and used in the Rapid Airplane Parameter Input Design (RAPID) tool at the NASA-LaRC Geolab. There are several basic mathematical problems involved in reversing the PDE surface model: (i) deriving a computational approximation of the surface function; (ii) determining a radial parametrization of the wing; (iii) choosing mathematical models or classes of functions for representation of the boundary functions; (iv) fitting the boundary data points by the chosen boundary functions; and (v) simultaneously solving for the axial parameterization and the derivative boundary functions. The study of the techniques to solve the above mathematical problems has culminated in a reverse PDE surface model and two reverse PDE surface algorithms. One reverse PDE surface algorithm recovers engineering design parameters for the RAPID tool from aircraft wing data and the other generates a PDE surface model with spline boundary functions from an arbitrary set of grid points. Our numerical tests show that the reverse PDE surface model and the reverse PDE surface algorithms can be used for the reverse engineering of aircraft wing data.

[Research on diagnosis of gas-liquid detonation exhaust based on double optical path absortion spectroscopy technique].

PubMed

Lü, Xiao-Jing; Li, Ning; Weng, Chun-Sheng

2014-03-01

The effect detection of detonation exhaust can provide measurement data for exploring the formation mechanism of detonation, the promotion of detonation efficiency and the reduction of fuel waste. Based on tunable diode laser absorption spectroscopy technique combined with double optical path cross-correlation algorithm, the article raises the diagnosis method to realize the on-line testing of detonation exhaust velocity, temperature and H2O gas concentration. The double optical path testing system is designed and set up for the valveless pulse detonation engine with the diameter of 80 mm. By scanning H2O absorption lines of 1343nm with a high frequency of 50 kHz, the on-line detection of gas-liquid pulse detonation exhaust is realized. The results show that the optical testing system based on tunable diode laser absorption spectroscopy technique can capture the detailed characteristics of pulse detonation exhaust in the transient process of detonation. The duration of single detonation is 85 ms under laboratory conditions, among which supersonic injection time is 5.7 ms and subsonic injection time is 19.3 ms. The valveless pulse detonation engine used can work under frequency of 11 Hz. The velocity of detonation overflowing the detonation tube is 1,172 m x s(-1), the maximum temperature of detonation exhaust near the nozzle is 2 412 K. There is a transitory platform in the velocity curve as well as the temperature curve. H2O gas concentration changes between 0-7% during detonation under experimental conditions. The research can provide measurement data for the detonation process diagnosis and analysis, which is of significance to advance the detonation mechanism research and promote the research of pulse detonation engine control technology.

Numerical Modeling of Pulse Detonation Rocket Engine Gasdynamics and Performance

NASA Technical Reports Server (NTRS)

Morris, C. I.

2003-01-01

Pulse detonation engines (PDB) have generated considerable research interest in recent years as a chemical propulsion system potentially offering improved performance and reduced complexity compared to conventional gas turbines and rocket engines. The detonative mode of combustion employed by these devices offers a theoretical thermodynamic advantage over the constant-pressure deflagrative combustion mode used in conventional engines. However, the unsteady blowdown process intrinsic to all pulse detonation devices has made realistic estimates of the actual propulsive performance of PDES problematic. The recent review article by Kailasanath highlights some of the progress that has been made in comparing the available experimental measurements with analytical and numerical models.

Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4

DOE PAGES

Cedervall, Peder; Aulabaugh, Ann; Geoghegan, Kieran F.; ...

2015-03-09

Phosphodiesterase 4 (PDE4) is an essential contributor to intracellular signaling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain. Alternative promoters, transcriptional start sites, and mRNA splicing lead to the existence of over 25 variants of PDE4, broadly classified as long, short, and supershort forms. We report the X-ray crystal structure of long form PDE4B containing UCR1, UCR2, and the catalytic domain, crystallized as a dimer in which a disulfide bond cross-linksmore » cysteines engineered into UCR2 and the catalytic domain. Biochemical and mass spectrometric analyses showed that the UCR2-catalytic domain interaction occurs in trans, and established that this interaction regulates the catalytic activity of PDE4. By elucidating the key structural determinants of dimerization, we show that only long forms of PDE4 can be regulated by this mechanism. The results also provide a structural basis for the long-standing observation of high- and low-affinity binding sites for the prototypic inhibitor rolipram.« less

Pulse detonation engines and components thereof

NASA Technical Reports Server (NTRS)

Tangirala, Venkat Eswarlu (Inventor); Rasheed, Adam (Inventor); Vandervort, Christian Lee (Inventor); Dean, Anthony John (Inventor)

2009-01-01

A pulse detonation engine comprises a primary air inlet; a primary air plenum located in fluid communication with the primary air inlet; a secondary air inlet; a secondary air plenum located in fluid communication with the secondary air inlet, wherein the secondary air plenum is substantially isolated from the primary air plenum; a pulse detonation combustor comprising a pulse detonation chamber, wherein the pulse detonation chamber is located downstream of and in fluid communication with the primary air plenum; a coaxial liner surrounding the pulse detonation combustor defining a cooling plenum, wherein the cooling plenum is in fluid communication with the secondary air plenum; an axial turbine assembly located downstream of and in fluid communication with the pulse detonation combustor and the cooling plenum; and a housing encasing the primary air plenum, the secondary air plenum, the pulse detonation combustor, the coaxial liner, and the axial turbine assembly.

A Performance Map for Ideal Air Breathing Pulse Detonation Engines

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2001-01-01

The performance of an ideal, air breathing Pulse Detonation Engine is described in a manner that is useful for application studies (e.g., as a stand-alone, propulsion system, in combined cycles, or in hybrid turbomachinery cycles). It is shown that the Pulse Detonation Engine may be characterized by an averaged total pressure ratio, which is a unique function of the inlet temperature, the fraction of the inlet flow containing a reacting mixture, and the stoichiometry of the mixture. The inlet temperature and stoichiometry (equivalence ratio) may in turn be combined to form a nondimensional heat addition parameter. For each value of this parameter, the average total enthalpy ratio and total pressure ratio across the device are functions of only the reactant fill fraction. Performance over the entire operating envelope can thus be presented on a single plot of total pressure ratio versus total enthalpy ratio for families of the heat addition parameter. Total pressure ratios are derived from thrust calculations obtained from an experimentally validated, reactive Euler code capable of computing complete Pulse Detonation Engine limit cycles. Results are presented which demonstrate the utility of the described method for assessing performance of the Pulse Detonation Engine in several potential applications. Limitations and assumptions of the analysis are discussed. Details of the particular detonative cycle used for the computations are described.

Experimental and numerical investigations on PDE performance augmentation by means of an ejector

NASA Astrophysics Data System (ADS)

Canteins, G.; Franzetti, F.; Zocłońska, E.; Khasainov, B. A.; Zitoun, R.; Desbordes, D.

2006-06-01

To improve the performance of pulse detonation engines, a 48 cm long cylindrical combustion chamber of 5cm internal diameter (i.d.) is fitted with an ejector of constant section. The role of the ejector is (i) to provide partial confinement of the detonation products escaping from the chamber and (ii) to suck in fresh air and then to increase the mass ejected compared to the ejection of burned gases alone. The combustion chamber is fully filled with a stoichiometric ethylene/oxygen mixture at ambient conditions. Three parameters of the ejector are varied: the i.d. D, the length L, and the position d relative to the thrust wall of the combustion chamber. For various configurations, the specific impulse ( I sp) is determined in single shot experiments. The maximum operating frequency ( f max) and the maximum thrust are then deduced. I sp is measured by means of the ballistic pendulum method, and f max is derived from the pressure signal recorded on the combustion chamber thrust wall. The addition of an ejector increases the specific impulse up to 60% in the best configuration tested, from 164s without ejector to 260s with ejector. The specific impulse can be represented by a single curve using suitable dimensionless parameters. The thrust results for the main ejector studied ( D = 80mm) indicate an optimal ( L, d) configuration that provides a 28% thrust gain. For the same ejector, f max remains constant and equal to the frequency obtained without ejector in a large range of ( L, d) values, before decreasing. Two-dimensional unsteady numerical computations agree reasonably with the experiments, slightly overestimating the experimental values. The results indicate that 80% of the I sp gain comes from the action of the expanding detonation products on the annular end surface of the combustion chamber, governed by the tube wall thickness.

Effects of Injection Scheme on Rotating Detonation Engine Operation

NASA Astrophysics Data System (ADS)

Chacon, Fabian; Duvall, James; Gamba, Mirko

2017-11-01

In this work, we experimentally investigate the operation and performance characteristics of a rotating detonation engine (RDE) operated with different fuel injection schemes and operating conditions. In particular, we investigate the detonation and operation characteristics produced with an axial flow injector configuration and semi-impinging injector configurations. These are compared to the characteristics produced with a canonical radial injection system (AFRL injector). Each type produces a different flowfield and mixture distribution, leading to a different detonation initiation, injector dynamic response, and combustor pressure rise. By using a combination of diagnostics, we quantify the pressure loses and gains in the system, the ability to maintain detonation over a range of operating points, and the coupling between the detonation and the air/fuel feed lines. We particularly focus on how this coupling affects both the stability and the performance of the detonation wave. This work is supported by the DOE/UTSR program under project DE-FE0025315.

Determination of Effective Crossover Location and Dimensions for Branched Detonation in a Pulsed Detonation Engine

DTIC Science & Technology

2012-03-22

location is varied from the aft end of the detonation tube to the middle of the detonation tube while the crossover width is varied from 2.5 in to 0.5...the other end where the tube is connected to a source of fuel, oxidizer, and ignition .7 The engine cycle is divided into three equal phases: fill...location and width of the crossover duct for hydrogen, ethylene and an n-alkane. The crossover location is varied from the aft end of the

Relation Between Spark-Ignition Engine Knock, Detonation Waves, and Autoignition as Shown by High-Speed Photography

NASA Technical Reports Server (NTRS)

Miller, Cearcy D

1946-01-01

A critical review of literature bearing on the autoignition and detonation-wave theories of spark-ignition engine knock and on the nature of gas vibrations associated with combustion and knock results in the conclusion that neither the autoignition theory nor the detonation-wave theory is an adequate explanation of spark-ignition engine knock. A knock theory is proposed, combining the autoignition and detonation-wave theories, which introduces the idea that the detonation wave develops in autoignited or after-burning gases, and ascribes comparatively low-pitched heavy knocks to autoignition but high-pitched pinging knocks to detonation waves with the possibility of combinations of the two types of knocks. Analysis of five shots of knocking combustion, taken with the NACA high-speed motion-picture camera at the rate of 40,000 photographs per second reveals propagation speeds ranging from 3250 to more than 5500 feet per second. The range of propagation speeds from 3250 to more than 5500 feet per second is held to be considered with the proposed combined theory but not with either the simple autoignition theory or the simple detonation-wave theory.

Numerical study of chemically reacting viscous flow relevant to pulsed detonation engines

NASA Astrophysics Data System (ADS)

Yi, Tae-Hyeong

2005-11-01

A computational fluid dynamics code for two-dimensional, multi-species, laminar Navier-Stokes equations is developed to simulate a recently proposed engine concept for a pulsed detonation based propulsion system and to investigate the feasibility of the engine of the concept. The governing equations that include transport phenomena such as viscosity, thermal conduction and diffusion are coupled with chemical reactions. The gas is assumed to be thermally perfect and in chemically non-equilibrium. The stiffness due to coupling the fluid dynamics and the chemical kinetics is properly taken care of by using a time-operator splitting method and a variable coefficient ordinary differential equation solver. A second-order Roe scheme with a minmod limiter is explicitly used for space descretization, while a second-order, two-step Runge-Kutta method is used for time descretization. In space integration, a finite volume method and a cell-centered scheme are employed. The first-order derivatives in the equations of transport properties are discretized by a central differencing with Green's theorem. Detailed chemistry is involved in this study. Two chemical reaction mechanisms are extracted from GRI-Mech, which are forty elementary reactions with thirteen species for a hydrogen-air mixture and twenty-seven reactions with eight species for a hydrogen-oxygen mixture. The code is ported to a high-performance parallel machine with Message-Passing Interface. Code validation is performed with chemical kinetic modeling for a stoichiometric hydrogen-air mixture, an one-dimensional detonation tube, a two-dimensional, inviscid flow over a wedge and a viscous flow over a flat plate. Detonation is initiated using a numerically simulated arc-ignition or shock-induced ignition system. Various freestream conditions are utilized to study the propagation of the detonation in the proposed concept of the engine. Investigation of the detonation propagation is performed for a pulsed detonation rocket and a supersonic combustion chamber. For a pulsed detonation rocket case, the detonation tube is embedded in a mixing chamber where an initiator is added to the main detonation chamber. Propagating detonation waves in a supersonic combustion chamber is investigated for one- and two-dimensional cases. The detonation initiated by an arc and a shock wave is studied in the inviscid and viscous flow, respectively. Various features including a detonation-shock interaction, a detonation diffraction, a base flow and a vortex are observed.

Investigation of the effect of the ejector on the performance of the pulse detonation engine nozzle extension

NASA Astrophysics Data System (ADS)

Korobov, A. E.; Golovastov, S. V.

2015-11-01

Influence of an ejector nozzle extension on gas flow at a pulse detonation engine was investigated numerically and experimentally. Detonation formation was organized in stoichiometric hydrogen-oxygen mixture in cylindrical detonation tube. Cylindrical ejector was constructed and mounted at the open end of the tube. Thrust, air consumption and parameters of the detonation were measured in single and multiple regimes of operation. Axisymmetric model was used in numerical investigation. Equations of Navies-Stokes were solved using a finite-difference scheme Roe of second order of accuracy. Initial conditions were estimated on a base of experimental data. Numerical results were validated with experiments data.

A synthetic cGMP-sensitive gene switch providing Viagra(®)-controlled gene expression in mammalian cells and mice.

PubMed

Kim, Taeuk; Folcher, Marc; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

2015-05-01

Cyclic guanosine monophosphate (cGMP) is a universal second messenger that is synthesized from guanosine triphosphate (GTP) by guanylyl cyclases (GCs) and hydrolyzed into guanosine monophosphate (GMP) by phosphodiesterases (PDEs). Small-molecule drugs that induce high cGMP levels in specialized tissues by boosting GC activity or inhibiting PDE activity have become the predominant treatment strategy for a wide range of medical conditions, including congestive heart failure, pulmonary hypertension, atherosclerosis-based claudication and erectile dysfunction. By fusing the cGMP receptor protein (CRP) of Rhodospirillum centenum to the Herpes simplex-derived transactivation domain VP16, we created a novel synthetic mammalian cGMP-sensing transcription factor (GTA) that activates synthetic promoters (PGTA) containing newly identified GTA-specific operator sites in a concentration-dependent manner. In cell lines expressing endogenous natriuretic peptide receptor A (NPR-A) (HeLa), GTA/PGTA-driven transgene expression was induced by B-type natriuretic peptide (BNP; Nesiritide(®)) in a concentration-dependent manner, which activated NPR-A׳s intracellular GC domain and triggered a corresponding cGMP surge. Ectopic expression of NPR-A in NPR-A-negative cell lines (HEK-293T) produced high cGMP levels and mediated maximum GTA/PGTA-driven transgene expression, which was suppressed by co-expression of PDEs (PDE-3A, PDE-5A and PDE-9A) and was re-triggered by the corresponding PDE inhibitor drugs (Pletal(®), Perfan(®), Primacor(®) (PDE-3A), Viagra(®), Levitra(®), Cialis(®) (PDE-5A) and BAY73-6691 (PDE-9A)). Mice implanted with microencapsulated designer cells co-expressing the GTA/PGTA device with NPR-A and PDE-5A showed control of blood SEAP levels through administration of sildenafil (Viagra(®)). Designer cells engineered for PDE inhibitor-modulated transgene expression may provide a cell-based PDE-targeting drug discovery platform and enable drug-adjusted gene- and cell-based therapies. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Detonation wave compression in gas turbines

NASA Technical Reports Server (NTRS)

Wortman, A.

1986-01-01

A study was made of the concept of augmenting the performance of low pressure ratio gas turbines by detonation wave compression of part of the flow. The concept exploits the constant volume heat release of detonation waves to increase the efficiency of the Brayton cycle. In the models studied, a fraction of the compressor output was channeled into detonation ducts where it was processed by transient transverse detonation waves. Gas dynamic studies determined the maximum cycling frequency of detonation ducts, proved that upstream propagation of pressure pulses represented no problems and determined the variations of detonation duct output with time. Mixing and wave compression were used to recombine the combustor and detonation duct flows and a concept for a spiral collector to further smooth the pressure and temperature pulses was presented as an optional component. The best performance was obtained with a single firing of the ducts so that the flow could be re-established before the next detonation was initiated. At the optimum conditions of maximum frequency of the detonation ducts, the gas turbine efficiency was found to be 45 percent while that of a corresponding pressure ratio 5 conventional gas turbine was only 26%. Comparable improvements in specific fuel consumption data were found for gas turbines operating as jet engines, turbofans, and shaft output machines. Direct use of the detonation duct output for jet propulsion proved unsatisfactory. Careful analysis of the models of the fluid flow phenomena led to the conclusion that even more elaborate calculations would not diminish the uncertainties in the analysis of the system. Feasibility of the concept to work as an engine now requires validation in an engineering laboratory experiment.

Research on filling process of fuel and oxidant during detonation based on absorption spectrum technology

NASA Astrophysics Data System (ADS)

Lv, Xiao-Jing; Li, Ning; Weng, Chun-Sheng

2014-12-01

Research on detonation process is of great significance for the control optimization of pulse detonation engine. Based on absorption spectrum technology, the filling process of fresh fuel and oxidant during detonation is researched. As one of the most important products, H2O is selected as the target of detonation diagnosis. Fiber distributed detonation test system is designed to enable the detonation diagnosis under adverse conditions in detonation process. The test system is verified to be reliable. Laser signals at different working frequency (5Hz, 10Hz and 20Hz) are detected. Change of relative laser intensity in one detonation circle is analyzed. The duration of filling process is inferred from the change of laser intensity, which is about 100~110ms. The peak of absorption spectrum is used to present the concentration of H2O during the filling process of fresh fuel and oxidant. Absorption spectrum is calculated, and the change of absorption peak is analyzed. Duration of filling process calculated with absorption peak consisted with the result inferred from the change of relative laser intensity. The pulse detonation engine worked normally and obtained the maximum thrust at 10Hz under experiment conditions. The results are verified through H2O gas concentration monitoring during detonation.

Detonation engine fed by acetylene-oxygen mixture

NASA Astrophysics Data System (ADS)

Smirnov, N. N.; Betelin, V. B.; Nikitin, V. F.; Phylippov, Yu. G.; Koo, Jaye

2014-11-01

The advantages of a constant volume combustion cycle as compared to constant pressure combustion in terms of thermodynamic efficiency has focused the search for advanced propulsion on detonation engines. Detonation of acetylene mixed with oxygen in various proportions is studied using mathematical modeling. Simplified kinetics of acetylene burning includes 11 reactions with 9 components. Deflagration to detonation transition (DDT) is obtained in a cylindrical tube with a section of obstacles modeling a Shchelkin spiral; the DDT takes place in this section for a wide range of initial mixture compositions. A modified ka-omega turbulence model is used to simulate flame acceleration in the Shchelkin spiral section of the system. The results of numerical simulations were compared with experiments, which had been performed in the same size detonation chamber and turbulent spiral ring section, and with theoretical data on the Chapman-Jouguet detonation parameters.

Using CLIPS in the domain of knowledge-based massively parallel programming

NASA Technical Reports Server (NTRS)

Dvorak, Jiri J.

1994-01-01

The Program Development Environment (PDE) is a tool for massively parallel programming of distributed-memory architectures. Adopting a knowledge-based approach, the PDE eliminates the complexity introduced by parallel hardware with distributed memory and offers complete transparency in respect of parallelism exploitation. The knowledge-based part of the PDE is realized in CLIPS. Its principal task is to find an efficient parallel realization of the application specified by the user in a comfortable, abstract, domain-oriented formalism. A large collection of fine-grain parallel algorithmic skeletons, represented as COOL objects in a tree hierarchy, contains the algorithmic knowledge. A hybrid knowledge base with rule modules and procedural parts, encoding expertise about application domain, parallel programming, software engineering, and parallel hardware, enables a high degree of automation in the software development process. In this paper, important aspects of the implementation of the PDE using CLIPS and COOL are shown, including the embedding of CLIPS with C++-based parts of the PDE. The appropriateness of the chosen approach and of the CLIPS language for knowledge-based software engineering are discussed.

Detonation wave augmentation of gas turbines

NASA Technical Reports Server (NTRS)

Wortman, A.

1984-01-01

The results of a feasibility study that examined the effects of using detonation waves to augment the performance of gas turbines are reported. The central ideas were to reduce compressor requirements and to maintain high performance in jet engines. Gasdynamic equations were used to model the flows associated with shock waves generated by the detonation of fuel in detonator tubes. Shock wave attenuation to the level of Mach waves was found possible, thus eliminating interference with the compressor and the necessity of valves and seals. A preliminary parametric study of the performance of a compressor working at a 4:1 ratio in a conceptual design of a detonation wave augmented jet engine in subsonic flight indicated a clear superiority over conventional designs in terms of fuel efficiency and thrust.

Effect of fuel stratification on detonation wave propagation

NASA Astrophysics Data System (ADS)

Masselot, Damien; Fievet, Romain; Raman, Venkat

2016-11-01

Rotating detonation engines (RDEs) form a class of pressure-gain combustion systems of higher efficiency compared to conventional gas turbine engines. One of the key features of the design is the injection system, as reactants need to be continuously provided to the detonation wave to sustain its propagation speed. As inhomogeneities in the reactant mixture can perturb the detonation wave front, premixed fuel jet injectors might seem like the most stable solution. However, this introduces the risk of the detonation wave propagating through the injector, causing catastrophic failure. On the other hand, non-premixed fuel injection will tend to quench the detonation wave near the injectors, reducing the likelihood of such failure. Still, the effects of such non-premixing and flow inhomogeneities ahead of a detonation wave have yet to be fully understood and are the object of this study. A 3D channel filled with O2 diluted in an inert gas with circular H2 injectors is simulated as a detonation wave propagates through the system. The impact of key parameters such as injector spacing, injector size, mixture composition and time variations will be discussed. PhD Candidate.

Impulse generation by detonation tubes

NASA Astrophysics Data System (ADS)

Cooper, Marcia Ann

Impulse generation with gaseous detonation requires conversion of chemical energy into mechanical energy. This conversion process is well understood in rocket engines where the high pressure combustion products expand through a nozzle generating high velocity exhaust gases. The propulsion community is now focusing on advanced concepts that utilize non-traditional forms of combustion like detonation. Such a device is called a pulse detonation engine in which laboratory tests have proven that thrust can be achieved through continuous cyclic operation. Because of poor performance of straight detonation tubes compared to conventional propulsion systems and the success of using nozzles on rocket engines, the effect of nozzles on detonation tubes is being investigated. Although previous studies of detonation tube nozzles have suggested substantial benefits, up to now there has been no systematic investigations over a range of operating conditions and nozzle configurations. As a result, no models predicting the impulse when nozzles are used exist. This lack of data has severely limited the development and evaluation of models and simulations of nozzles on pulse detonation engines. The first experimental investigation measuring impulse by gaseous detonation in plain tubes and tubes with nozzles operating in varying environment pressures is presented. Converging, diverging, and converging-diverging nozzles were tested to determine the effect of divergence angle, nozzle length, and volumetric fill fraction on impulse. The largest increases in specific impulse, 72% at an environment pressure of 100 kPa and 43% at an environment pressure of 1.4 kPa, were measured with the largest diverging nozzle tested that had a 12° half angle and was 0.6 m long. Two regimes of nozzle operation that depend on the environment pressure are responsible for these increases and were first observed from these data. To augment this experimental investigation, all data in the literature regarding partially filled detonation tubes was compiled and analyzed with models investigating concepts of energy conservation and unsteady gas dynamics. A model to predict the specific impulse was developed for partially filled tubes. The role of finite chemical kinetics in detonation products was examined through numerical simulations of the flow in nonsteady expansion waves.

Mid-infrared Laser Absorption Diagnostics for Detonation Studies

NASA Astrophysics Data System (ADS)

Spearrin, R. M.; Goldenstein, C. S.; Jeffries, J. B.; Hanson, R. K.

Detonation-based engines represent a challenging application for diagnostics due to the wide range of thermodynamic conditions involved (T~500-3000 K, P~2-60 atm) and the short time scales of change (~10- 6 to 10- 4 sec) associated with such systems. Non-intrusive laser absorption diagnostics can provide high time-resolution and have been employed extensively in shock tube kinetics experiments (P~1-20 atm), offering high potential for application in detonation environments with modest utilization to date [1-4]. Limiting factors in designing effective tunable laser absorption sensors for detonation engines can be divided into two sets of challenges: high-pressure, high-temperature absorption spectroscopy and harsh thermo-mechanical environments. The present work, conducted in a high-pressure shock tube and operating detonation combustor, addresses both sets of difficulties, with the objective of developing time-resolved, in-situ temperature and concentration sensors for detonation studies.

Role of Air-Breathing Pulse Detonation Engines in High Speed Propulsion

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.; Lee, Jin-Ho; Anderberg, Michael O.

2001-01-01

In this paper, the effect of flight Mach number on the relative performance of pulse detonation engines and gas turbine engines is investigated. The effect of ram and mechanical compression on combustion inlet temperature and the subsequent sensible heat release is determined. Comparison of specific thrust, fuel consumption and impulse for the two engines show the relative benefits over the Mach number range.

The Physical Effects of Detonation in a Closed Cylindrical Chamber

NASA Technical Reports Server (NTRS)

Draper, C S

1935-01-01

Detonation in the internal-combustion engine is studied as a physical process. It is shown that detonation is accompanied by pressure waves within the cylinder charge. Sound theory is applied to the calculation of resonant pressure-wave frequencies. Apparatus is described for direct measurement of pressure-wave frequencies. Frequencies determined from two engines of different cylinder sizes are shown to agree with the values calculated from sound theory. An outline of the theoretically possible modes of vibration in a right circular cylinder with flat ends is included. An appendix by John P. Elting gives a method of calculating pressure in the sound wave following detonation.

Overview of Pulse Detonation Propulsion Technology

DTIC Science & Technology

2001-04-01

PROPULSION TECHNOLOGY M. L. Coleman CHEMICAL PROPULSION INFORMATION AGENCY THE JOHNS HOPKINS UNIVERSITY. WHITING SCHOOL OF ENGINEERING -COLUMBIA...U. 20 R. Santoro, "Advanced Propulsion Research: A Focus of the Penn State Propulsion Engineering Research Center," Chemical Propulsion Information...Detonation Engine ," AIAA 95-3155 (July 1995), U-A. NASA Marshall Space Flight Center Space Transportation Day 2000 Presentation Material, Advance Chemical

Calculated concentrations of any radionuclide deposited on the ground by release from underground nuclear detonations, tests of nuclear rockets, and tests of nuclear ramjet engines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hicks, H.G.

1981-11-01

This report presents calculated gamma radiation exposure rates and ground deposition of related radionuclides resulting from three types of event that deposited detectable radioactivity outside the Nevada Test Site complex, namely, underground nuclear detonations, tests of nuclear rocket engines and tests of nuclear ramjet engines.

[The Diagnostics of Detonation Flow External Field Based on Multispectral Absorption Spectroscopy Technology].

PubMed

Lü, Xiao-jing; Li, Ning; Weng, Chun-sheng

2016-03-01

Compared with traditional sampling-based sensing method, absorption spectroscopy technology is well suitable for detonation flow diagnostics, since it can provide with us fast response, nonintrusive, sensitive solution for situ measurements of multiple flow-field parameters. The temperature and concentration test results are the average values along the laser path with traditional absorption spectroscopy technology, while the boundary of detonation flow external field is unknown and it changes all the time during the detonation engine works, traditional absorption spectroscopy technology is no longer suitable for detonation diagnostics. The trend of line strength with temperature varies with different absorption lines. By increasing the number of absorption lines in the test path, more information of the non-uniform flow field can be obtained. In this paper, based on multispectral absorption technology, the reconstructed model of detonation flow external field distribution was established according to the simulation results of space-time conservation element and solution element method, and a diagnostic method of detonation flow external field was given. The model deviation and calculation error of the least squares method adopted were studied by simulation, and the maximum concentration and temperature calculation error was 20.1% and 3.2%, respectively. Four absorption lines of H2O were chosen and detonation flow was scanned at the same time. The detonation external flow testing system was set up for the valveless gas-liquid continuous pulse detonation engine with the diameter of 80 mm. Through scanning H2O absorption lines with a high frequency of 10 kHz, the on-line detection of detonation external flow was realized by direct absorption method combined with time-division multiplexing technology, and the reconstruction of dynamic temperature distribution was realized as well for the first time, both verifying the feasibility of the test method. The test results show that both of the temperature and H2O concentration rose with the arrival of detonation wave. With the increase of the vertical distance between the detonation tube nozzle and the laser path, the time of temperature and concentration coming to the peak delayed, and the temperature variation trend tended to slow down. At 20 cm from detonation tube nozzle, the maximum temperature hit 1 329 K and the maximum H2O concentration of 0.19 occurred at 4 ms after ignition. The research can provide with us the support for expanding the detonation test field with absorption spectroscopy technology, and can also help to promote the detonation mechanism research and to enhance the level of detonation engine control technology.

Sound vibration signal processing for detection and identification detonation (knock) to optimize performance Otto engine

NASA Astrophysics Data System (ADS)

Sujono, A.; Santoso, B.; Juwana, W. E.

2016-03-01

Problems of detonation (knock) on Otto engine (petrol engine) is completely unresolved problem until now, especially if want to improve the performance. This research did sound vibration signal processing engine with a microphone sensor, for the detection and identification of detonation. A microphone that can be mounted is not attached to the cylinder block, that's high temperature, so that its performance will be more stable, durable and inexpensive. However, the method of analysis is not very easy, because a lot of noise (interference). Therefore the use of new methods of pattern recognition, through filtration, and the regression function normalized envelope. The result is quite good, can achieve a success rate of about 95%.

The Ignition of Two Phase Detonation by a Branching Detonation Tube

NASA Astrophysics Data System (ADS)

Xiong, Cha; Qiu, Hua; Lu, Qinwei

2017-11-01

A branching tube is available to deliver sufficient energy to directly initiate a detonation wave. But sustaining the detonation wave through a branching tube is a challenge. In this study, a preliminary exploration about a branching pulsed detonation engine with a gas-liquid mixture was carried out to evaluate filling conditions on detonation initiation. Two detonation tubes were connected by three different schemes, such as Tail-Tail, Tail-Mid, and Tail-Head. Experimental results showed only end-head connected tubes can be ignited by the branching tube, which is quite different from the results using gas fuels or pre-evaporated liquid fuel. Liquid fuel distribution is crucial for successful detonation traveling through the branching tube.

Characterization of Rotating Detonation Engine Exhaust Through Nozzle Guide Vanes

DTIC Science & Technology

2013-03-21

THROUGH NOZZLE GUIDE VANES THESIS Presented to the Faculty Department of Aeronautics and Astronautics Graduate School of Engineering and Management Air...the first Nozzle Guide Vane (NGV) section from a T63 gas turbine engine to a 6 inch diameter RDE was designed and built for this study. Pressure...CHARACTERIZATION OF ROTATING DETONATION ENGINE EXHAUST THROUGH NOZZLE GUIDE VANES THESIS Nick D. DeBarmore, Second Lieutenant, USAF AFIT/GAE/ENY/13

Alternative Pulse Detonation Engine Ignition System Investigation through Detonation Splitting

DTIC Science & Technology

2002-03-01

on the soccer field and later discovered is a brilliant and dedicated scientist and engineer. He’s been an inspiration and role model, who sees...designing configurations before cutting metal for an experiment reduces research time and cost. Dr. Vish Katta had built an in-house program ( UNICORN

Development and application of theoretical models for Rotating Detonation Engine flowfields

NASA Astrophysics Data System (ADS)

Fievisohn, Robert

As turbine and rocket engine technology matures, performance increases between successive generations of engine development are becoming smaller. One means of accomplishing significant gains in thermodynamic performance and power density is to use detonation-based heat release instead of deflagration. This work is focused on developing and applying theoretical models to aid in the design and understanding of Rotating Detonation Engines (RDEs). In an RDE, a detonation wave travels circumferentially along the bottom of an annular chamber where continuous injection of fresh reactants sustains the detonation wave. RDEs are currently being designed, tested, and studied as a viable option for developing a new generation of turbine and rocket engines that make use of detonation heat release. One of the main challenges in the development of RDEs is to understand the complex flowfield inside the annular chamber. While simplified models are desirable for obtaining timely performance estimates for design analysis, one-dimensional models may not be adequate as they do not provide flow structure information. In this work, a two-dimensional physics-based model is developed, which is capable of modeling the curved oblique shock wave, exit swirl, counter-flow, detonation inclination, and varying pressure along the inflow boundary. This is accomplished by using a combination of shock-expansion theory, Chapman-Jouguet detonation theory, the Method of Characteristics (MOC), and other compressible flow equations to create a shock-fitted numerical algorithm and generate an RDE flowfield. This novel approach provides a numerically efficient model that can provide performance estimates as well as details of the large-scale flow structures in seconds on a personal computer. Results from this model are validated against high-fidelity numerical simulations that may require a high-performance computing framework to provide similar performance estimates. This work provides a designer a new tool to conduct large-scale parametric studies to optimize a design space before conducting computationally-intensive, high-fidelity simulations that may be used to examine additional effects. The work presented in this thesis not only bridges the gap between simple one-dimensional models and high-fidelity full numerical simulations, but it also provides an effective tool for understanding and exploring RDE flow processes.

Investigation on Novel Methods to Increase Specific Thrust in Pulse Detonation Engines via Imploding Detonations

DTIC Science & Technology

2009-12-01

Malliakos. Detonation cell size measurements in high-temperature hydrogen- air-steam mixtures at the bnl high-temperature combustion facility. Technical...Report NUREG/CR-6391, BNL -NUREG-52482, Brookhaven National Laboratory, 1997. [13] W.B. Benedick, R. Knystautas, and J.H.S. Lee. Large-scale

Transatmospheric vehicle research

NASA Technical Reports Server (NTRS)

Adelman, Henry G.; Cambier, Jean-Luc

1990-01-01

Research was conducted into the alternatives to the supersonic combustion ramjet (scramjet) engine for hypersonic flight. A new engine concept, the Oblique Detonation Wave Engine (ODWE) was proposed and explored analytically and experimentally. Codes were developed which can couple the fluid dynamics of supersonic flow with strong shock waves, with the finite rate chemistry necessary to model the detonation process. An additional study was conducted which compared the performance of a hypersonic vehicle powered by a scramjet or an ODWE. Engineering models of the overall performances of the two engines are included. This information was fed into a trajectory program which optimized the flight path to orbit. A third code calculated the vehicle size, weight, and aerodynamic characteristics. The experimental work was carried out in the Ames 20MW arc-jet wind tunnel, focusing on mixing and combustion of fuel injected into a supersonic airstream. Several injector designs were evaluated by sampling the stream behind the injectors and analyzing the mixture with an on-line mass spectrometer. In addition, an attempt was made to create a standing oblique detonation wave in the wind tunnel using hydrogen fuel. It appeared that the conditions in the test chamber were marginal for the generation of oblique detonation waves.

Phosphodiesterases regulate airway smooth muscle function in health and disease.

PubMed

Krymskaya, Vera P; Panettieri, Reynold A

2007-01-01

On the basis of structure, regulation, and kinetic properties, phosphodiesterases (PDEs) represent a superfamily of enzymes divided into 11 subfamilies that catalyze cytosolic levels of 3',5'-cyclic adenosine monophosphate (cAMP) or 3',5'-cyclic guanosine monophosphate (cGMP) to 5'-AMP or 5'-GMP, respectively. PDE4 represents the major PDE expressed in inflammatory cells as well as airway smooth muscle (ASM), and selective PDE4 inhibitors provide a broad spectrum of anti-inflammatory effects such as abrogating cytokine and chemokine release from inflammatory cells and inhibiting inflammatory cell trafficking. Due to cell- and tissue-specific gene expression and regulation, PDEs modulate unique organ-based functions. New tools or compounds that selectively inhibit PDE subfamilies and genetically engineered mice deficient in selective isoforms have greatly enhanced our understanding of PDE function in airway inflammation and resident cell function. This chapter will focus on recent advances in our understanding of the role of PDE in regulating ASM function.

Numerical Simulation of Flow in Fluidic Valves in Rotating Detonation Engines

NASA Astrophysics Data System (ADS)

Gopalakrishnan, Nandini

Rotating detonation engines (RDE) have received considerable research attention in recent times for use in propulsion systems. The cycle frequency of operation of an RDE can be as high as 10,000 Hz. Conventional mechanical valves cannot operate at such high frequencies, leading to the need for propellant injectors or valves with no moving parts. A fluidic valve is such a valve and is the focus of this study. The valve consists of an orifice connected to a constant area plenum cavity which operates at constant pressure. The fluidic valve supplies propellants to the detonation tube through the orifice. Hydrogen - oxygen detonation is studied in a tube with fluidic valves. A detailed 19-step chemical reaction mechanism has been used to model detonation and the flow simulated in ANSYS Fluent. This research aims to determine the location of contact surface in the cavity and the time taken for the contact surface to leave the valve after a shock wave has passed through it. This will help us understand if the steady-state flow in the cavity is comprised of detonation products or fresh propellants.

Effects of Fuel Distribution on Detonation Tube Performance

NASA Technical Reports Server (NTRS)

Perkins, H. Douglas; Sung, Chih-Jen

2003-01-01

A pulse detonation engine uses a series of high frequency intermittent detonation tubes to generate thrust. The process of filling the detonation tube with fuel and air for each cycle may yield non-uniform mixtures. Uniform mixing is commonly assumed when calculating detonation tube thrust performance. In this study, detonation cycles featuring idealized non-uniform Hz/air mixtures were analyzed using a two-dimensional Navier-Stokes computational fluid dynamics code with detailed chemistry. Mixture non-uniformities examined included axial equivalence ratio gradients, transverse equivalence ratio gradients, and partially fueled tubes. Three different average test section equivalence ratios were studied; one stoichiometric, one fuel lean, and one fuel rich. All mixtures were detonable throughout the detonation tube. Various mixtures representing the same average test section equivalence ratio were shown to have specific impulses within 1% of each other, indicating that good fuel/air mixing is not a prerequisite for optimal detonation tube performance under conditions investigated.

The hard start phenomena in hypergolic engines. Volume 5: RCS engine deformation and destruct tests

NASA Technical Reports Server (NTRS)

Miron, Y.; Perlee, H. E.

1974-01-01

Tests were conducted to determine the causes of Apollo Reaction Control (RCS) engine failures. Stainless steel engines constructed for use in the destructive tests are described. The tests conducted during the three phase investigation are discussed. It was determined that the explosive reaction that destroys the RCS engines occurs at the time of engine ignition and is apparently due to either the detonation of the heterogeneous constituents of the rocket engine, consisting primarily of unreacted propellant droplets and vapors, and/or the detonation of explosive materials accumulated on the engine walls from previous pulses. Photographs of the effects of explosions on the simulated RCS engines are provided.

Development of a Gas-Fed Pulse Detonation Research Engine

NASA Technical Reports Server (NTRS)

Litchford, Ron J.; Hutt, John (Technical Monitor)

2001-01-01

In response to the growing need for empirical data on pulse detonation engine performance and operation, NASA Marshall Space Flight Center has developed and placed into operation a low-cost gas-fed pulse detonation research engine. The guiding design strategy was to achieve a simple and flexible research apparatus, which was inexpensive to build and operate. As such, the engine was designed to operate as a heat sink device, and testing was limited to burst-mode operation with run durations of a few seconds. Wherever possible, maximum use was made of standard off-the-shelf industrial or automotive components. The 5-cm diameter primary tube is about 90-cm long and has been outfitted with a multitude of sensor and optical ports. The primary tube is fed by a coaxial injector through an initiator tube, which is inserted directly into the injector head face. Four auxiliary coaxial injectors are also integrated into the injector head assembly. All propellant flow is controlled with industrial solenoid valves. An automotive electronic ignition system was adapted for use, and spark plugs are mounted in both tubes so that a variety of ignition schemes can be examined. A microprocessor-based fiber-optic engine control system was developed to provide precise control over valve and ignition timing. Initial shakedown testing with hydrogen/oxygen mixtures verified the need for Schelkin spirals in both the initiator and primary tubes to ensure rapid development of the detonation wave. Measured pressure wave time-of-flight indicated detonation velocities of 2.4 km/sec and 2.2 km/sec in the initiator and primary tubes, respectively. These values implied a fuel-lean mixture corresponding to an H2 volume fraction near 0.5. The axial distribution for the detonation velocity was found to be essentially constant along the primary tube. Time-resolved thrust profiles were also acquired for both underfilled and overfilled tube conditions. These profiles are consistent with previous time-resolved measurements on single-cycle tubes where the thrust is found to peak as the detonation wave exits the tube, and decay as the tube blows down.

Gaseous detonation initiation via wave implosion

NASA Astrophysics Data System (ADS)

Jackson, Scott Irving

Efficient detonation initiation is a topic of intense interest to designers of pulse detonation engines. This experimental work is the first to detonate propane-air mixtures with an imploding detonation wave and to detonate a gas mixture with a non-reflected, imploding shock. In order to do this, a unique device has been developed that is capable of generating an imploding toroidal detonation wave inside of a tube from a single ignition point without any obstruction to the tube flow path. As part of this study, an initiator that creates a large-aspect-ratio planar detonation wave in gas-phase explosive from a single ignition point has also been developed. The effectiveness of our initiation devices has been evaluated. The minimum energy required by the imploding shock for initiation was determined to scale linearly with the induction zone length, indicating the presence of a planar initiation mode. The imploding toroidal detonation initiator was found to be more effective at detonation initiation than the imploding shock initiator, using a comparable energy input to that of current initiator tubes.

The Attenuation of a Detonation Wave by an Aircraft Engine Axial Turbine Stage

NASA Technical Reports Server (NTRS)

VanZante, Dale; Envia, Edmane; Turner, Mark G.

2007-01-01

A Constant Volume Combustion Cycle Engine concept consisting of a Pulse Detonation Combustor (PDC) followed by a conventional axial turbine was simulated numerically to determine the attenuation and reflection of a notional PDC pulse by the turbine. The multi-stage, time-accurate, turbomachinery solver TURBO was used to perform the calculation. The solution domain consisted of one notional detonation tube coupled to 5 vane passages and 8 rotor passages representing 1/8th of the annulus. The detonation tube was implemented as an initial value problem with the thermodynamic state of the tube contents, when the detonation wave is about to exit, provided by a 1D code. Pressure time history data from the numerical simulation was compared to experimental data from a similar configuration to verify that the simulation is giving reasonable results. Analysis of the pressure data showed a spectrally averaged attenuation of about 15 dB across the turbine stage. An evaluation of turbine performance is also presented.

A Case for Basic Rotating Detonation Engine Research

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2016-01-01

A brief review is provided covering the benefits to air breathing and chemical rocket propulsion found from pressure gain combustion in general, and rotating detonation in particular. Challenges are also identified.

Numerical Study of the Propulsive Performance of the Hollow Rotating Detonation Engine with a Laval Nozzle

NASA Astrophysics Data System (ADS)

Yao, Songbai; Tang, Xinmeng; Wang, Jianping

2017-04-01

The aim of the present paper is to investigate the propulsive performance of the hollow rotating detonation engine (RDE) with a Laval nozzle. Three-dimensional simulations are carried out with a one-step Arrhenius chemistry model. The Laval nozzle is found to improve the propulsive performance of hollow RDE in all respects. The thrust and fuel-based specific impulse are increased up to 12.60 kN and 7484.40 s, respectively, from 6.46 kN and 6720.48 s. Meanwhile, the total mass flow rate increases from 3.63 kg/s to 6.68 kg/s. Overall, the Laval nozzle significantly improves the propulsive performance of the hollow RDE and makes it a promising model among detonation engines.

Design and optimization of a deflagration to detonation transition (ddt) section

NASA Astrophysics Data System (ADS)

Romo, Francisco X.

Throughout the previous century, hydrocarbon-fueled engines have used and optimized the `traditional' combustion process called deflagration (subsonic combustion). An alternative form of combustion, detonation (supersonic combustion), can increase the thermal efficiency of the process by anywhere from 20 - 50%. Even though several authors have studied detonation waves since the 1890's and a plethora of papers and books have been published, it was not until 2008 that the first detonation-powered flight took place. It lasted for 10 seconds at 100 ft. altitude. Achieving detonation presents its own challenges: some fuels are not prone to detonate, severe vibrations caused by the cyclic nature of the engine and its intense noise are some of the key areas that need further research. Also, to directly achieve detonation either a high-energy, bulky, ignition system is required, or the combustion chamber must be fairly long (5 ft. or more in some cases). In the latter method, a subsonic flame front accelerates within the combustion chamber until it reaches supersonic speeds, thus detonation is attained. This is called deflagration-todetonation transition (DDT). Previous papers and experiments have shown that obstacles, such as discs with an orifice, located inside the combustion chamber can shorten the distance required to achieve detonation. This paper describes a hands-on implementation of a DDT device. Different disc geometries inside the chamber alter the wave characteristics at the exit of the tube. Although detonation was reached only when using pure oxygen, testing identified an obstacle configuration for LPG and air mixtures that increased pressure and wave speed significantly when compared to baseline or other obstacle configurations. Mixtures of LPG and air were accelerated to Mach 0.96 in the downstream frame of reference, which would indicate a transition to detonation was close. Reasons for not achieving detonation may include poor fuel and oxidizer mixing, and/or the need for a longer DDT section.

Preliminary Assessment of a Rotary Detonation Engine Concept.

DTIC Science & Technology

1983-09-01

As advances were made in compressors (both axial and centrifugal), it was possible to develop gas turbine engines based on the Brayton cycle rather...induced cycle pressure ratio. In the case of the axial flow compressor, as stages are added to increase the pressure, the blades become progressively...DESIGN OF THE TORQUE TUBE --------- 96 APPENDIX E. EQUIPMENT LISTING- - --------- -- 104 APPENDIX F. DESIGN DRAWINGS FOR ROTARY DETONATION TURBINE

Pulse Detonation Rocket Engine Research at NASA Marshall

NASA Technical Reports Server (NTRS)

Morris, Christopher I.

2003-01-01

Pulse detonation rocket engines (PDREs) offer potential performance improvements over conventional designs, but represent a challenging modeling task. A quasi 1-D, finite-rate chemistry CFD model for a PDRE is described and implemented. A parametric study of the effect of blowdown pressure ratio on the performance of an optimized, fixed PDRE nozzle configuration is reported. The results are compared to a steady-state rocket system using similar modeling assumptions.

Thermal Load Considerations for Detonative Combustion-Based Gas Turbine Engines

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Perkins, H. Douglas

2004-01-01

An analysis was conducted to assess methods for, and performance implications of, cooling the passages (tubes) of a pulse detonation-based combustor conceptually installed in the core of a gas turbine engine typical of regional aircraft. Temperature-limited material stress criteria were developed from common-sense engineering practice, and available material properties. Validated, one-dimensional, numerical simulations were then used to explore a variety of cooling methods and establish whether or not they met the established criteria. Simulation output data from successful schemes were averaged and used in a cycle-deck engine simulation in order to assess the impact of the cooling method on overall performance. Results were compared to both a baseline engine equipped with a constant-pressure combustor and to one equipped with an idealized detonative combustor. Major findings indicate that thermal loads in these devices are large, but potentially manageable. However, the impact on performance can be substantial. Nearly one half of the ideally possible specific fuel consumption (SFC) reduction is lost due to cooling of the tubes. Details of the analysis are described, limitations are presented, and implications are discussed.

Wave combustors for trans-atmospheric vehicles

NASA Technical Reports Server (NTRS)

Menees, Gene P.; Adelman, Henry G.; Cambier, Jean-Luc; Bowles, Jeffrey V.

1989-01-01

The Wave Combustor is an airbreathing hypersonic propulsion system which utilizes shock and detonation waves to enhance fuel-air mixing and combustion in supersonic flow. In this concept, an oblique shock wave in the combustor can act as a flameholder by increasing the pressure and temperature of the air-fuel mixture and thereby decreasing the ignition delay. If the oblique shock is sufficiently strong, then the combustion front and the shock wave can couple into a detonation wave. In this case, combustion occurs almost instantaneously in a thin zone behind the wave front. The result is a shorter, lighter engine compared to the scramjet. This engine, which is called the Oblique Detonation Wave Engine (ODWE), can then be utilized to provide a smaller, lighter vehicle or to provide a higher payload capability for a given vehicle weight. An analysis of the performance of a conceptual trans-atmospheric vehicle powered by an ODWE is given here.

Optical engine initiation: multiple compartment applications

NASA Astrophysics Data System (ADS)

Hunt, Jeffrey H.

2009-05-01

Modern day propulsion systems are used in aerospace applications for different purposes. The aerospace industry typically requires propulsion systems to operate in a rocket mode in order to drive large boost vehicles. The defense industry generally requires propulsion systems to operate in an air-breathing mode in order to drive missiles. A mixed system could use an air-breathing first stage and a rocket-mode upper stage for space access. Thus, propulsion systems can be used for high mass payloads and where the payload is dominated by the fuel/oxidizer mass being used by the propulsion system. The pulse detonation wave engine (PDWE) uses an alternative type of detonation cycle to achieve the same propulsion results. The primary component of the PDWE is the combustion chamber (or detonation tube). The PDWE represents an attractive propulsion source since its engine cycle is thermodynamically closest to that of a constant volume reaction. This characteristic leads to the inference that a maximum of the potential energy of the PDWE is put into thrust and not into flow work. Consequently, the volume must be increased. The technical community has increasingly adopted the alternative choice of increasing total volume by designing the engine to include a set of banks of smaller combustion chambers. This technique increases the complexity of the ignition subsystem because the inter-chamber timing must be considered. Current approaches to igniting the PDWE have involved separate shock or blast wave initiators and chemical additives designed to enhance detonatibility. An optical ignition subsystem generates a series of optical pulses, where the optical pulses ignite the fuel/oxidizer mixture such that the chambers detonate in a desired order. The detonation system also has an optical transport subsystem for transporting the optical pulses from the optical ignition subsystem to the chambers. The use of optical ignition and transport provides a non-toxic, small, lightweight, precisely controlled detonation system.

Mechanism of Gaseous Detonation Propagation Through Reactant Layers Bounded by Inert Gas

NASA Astrophysics Data System (ADS)

Houim, Ryan

2017-11-01

Vapor cloud explosions and rotating detonation engines involve the propagation of gaseous detonations through a layer of reactants that is bounded by inert gas. Mechanistic understanding of how detonations propagate stably or fail in these scenarios is incomplete. Numerical simulations were used to investigate mechanisms of gaseous detonation propagation through reactant layers bounded by inert gas. The reactant layer was a stoichiometric mixture of C2H4/O2 at 1 atm and 300K and is 4 detonation cells in height. Cases where the inert gas temperature was 300, 1500, and 3500 K will be discussed. The detonation failed for the 300 K case and propagated marginally for the 1500 K case. Surprisingly, the detonation propagated stably for the 3500 K case. A shock structure forms that involves a detached shock in the inert gas and a series of oblique shocks in the reactants. A small local explosion is triggered when the Mach stem of a detonation cell interacts with the compressed reactants behind one of these oblique shocks. The resulting pressure wave produces a new Mach stem and a new triple point that leads to a stable detonation. Preliminary results on the influence of a deflagration at the inert/reactant interface on the stability of a layered detonation will be discussed.

Comparison of Numerically Simulated and Experimentally Measured Performance of a Rotating Detonation Engine

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Fotia, Matthew L.; Hoke, John; Schauer, Fred

2015-01-01

A quasi-two-dimensional, computational fluid dynamic (CFD) simulation of a rotating detonation engine (RDE) is described. The simulation operates in the detonation frame of reference and utilizes a relatively coarse grid such that only the essential primary flow field structure is captured. This construction and other simplifications yield rapidly converging, steady solutions. Viscous effects, and heat transfer effects are modeled using source terms. The effects of potential inlet flow reversals are modeled using boundary conditions. Results from the simulation are compared to measured data from an experimental RDE rig with a converging-diverging nozzle added. The comparison is favorable for the two operating points examined. The utility of the code as a performance optimization tool and a diagnostic tool are discussed.

Numerical and Analytical Assessment of a Coupled Rotating Detonation Engine and Turbine Experiment

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Naples, Andrew

2017-01-01

An analysis is presented of an experimental rig comprising a rotating detonation engine (RDE) with bypass ejector flow coupled to a downstream turbine. The analysis used a validated computational fluid dynamics RDE simulation combined with straightforward algebraic mixing equations for the bypass flow. The objectives of the analysis were to supplement and interpret the necessarily sparse measurements from the rig, and to assess the performance of the RDE itself, which was not instrumented in this installation. The analysis is seen to agree reasonably well with available data. It shows that the RDE is operating in an unusual fashion, with subsonic flow throughout the exhaust plane. The detonation event itself is producing a total pressure rise relative to the pre-detonative pressure; however, the length of the device and the substantial flow restriction at the inlet yield an overall pressure loss. This is not surprising since the objective of the rig test was primarily aimed at investigating RDE turbine interactions, and not on performance optimization. Furthermore, the RDE was designed for fundamental detonation studies and not performance. Nevertheless, the analysis indicates that with some small alterations to the design, an RDE with an overall pressure rise is possible.

Numerical and Analytical Assessment of a Coupled Rotating Detonation Engine and Turbine Experiment

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Naples, Andrew

2017-01-01

An analysis is presented of an experimental rig comprising a rotating detonation engine (RDE) with bypass flow coupled to a downstream turbine. The analysis used a validated computational fluid dynamics RDE simulation combined with straightforward algebraic mixing equations for the bypass flow. The objectives of the analysis were to supplement and interpret the necessarily sparse measurements from the rig, and to assess the performance of the RDE itself (which was not instrumented in this installation). The analysis is seen to agree reasonably well with available data. It shows that the RDE is operating in an unusual fashion, with subsonic flow throughout the exhaust plane. The detonation event itself is producing a total pressure rise relative to the pre-detonative pressure; however, the length of the device and the substantial flow restriction at the inlet yield an overall pressure loss. This is not surprising since the objective of the rig test was primarily aimed at investigating RDEturbine interactions, and not on performance optimization. Furthermore, the RDE was designed for fundamental detonation studies and not performance. Nevertheless, the analysis indicates that with some small alterations to the design, an RDE with an overall pressure rise is possible.

Detonation duct gas generator demonstration program

NASA Technical Reports Server (NTRS)

Wortman, Andrew; Brinlee, Gayl A.; Othmer, Peter; Whelan, Michael A.

1991-01-01

The feasibility of the generation of detonation waves moving periodically across high speed channel flow is experimentally demonstrated. Such waves are essential to the concept of compressing requirements and increasing the engine pressure compressor with the objective of reducing conventional compressor requirements and increasing the engine thermodynamic efficiency through isochoric energy addition. By generating transient transverse waves, rather than standing waves, shock wave losses are reduced by an order of magnitude. The ultimate objective is to use such detonation ducts downstream of a low pressure gas turbine compressor to produce a high overall pressure ratio thermodynamic cycle. A 4 foot long, 1 inch x 12 inch cross-section, detonation duct was operated in a blow-down mode using compressed air reservoirs. Liquid or vapor propane was injected through injectors or solenoid valves located in the plenum or the duct itself. Detonation waves were generated when the mixture was ignited by a row of spark plugs in the duct wall. Problems with fuel injection and mixing limited the air speeds to about Mach 0.5, frequencies to below 10 Hz, and measured pressure ratios of about 5 to 6. The feasibility of the gas dynamic compression was demonstrated and the critical problem areas were identified.

Numerical and Analytical Assessment of a Coupled Rotating Detonation Engine and Turbine Experiment

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Naples, Andrew

2017-01-01

An analysis is presented of an experimental rig comprising a rotating detonation engine (RDE) with bypass ejector flow coupled to a downstream turbine. The analysis used a validated computational fluid dynamics RDE simulation combined with straightforward algebraic mixing equations for the bypass flow. The objectives of the analysis were to supplement and interpret the necessarily sparse measurements from the rig, and to assess the performance of the RDE itself, which was not instrumented in this installation. The analysis is seen to agree reasonably well with available data. It shows that the RDE is operating in an unusual fashion, with subsonic flow throughout the exhaust plane. The detonation event itself is producing a total pressure rise relative to the pre-detonative pressure; however, the length of the device and the substantial flow restriction at the inlet yield an overall pressure loss. This is not surprising since the objective of the rig test was primarily aimed at investigating RDE/turbine interactions, and not on performance optimization. Furthermore, the RDE was designed for fundamental detonation studies and not performance. Nevertheless, the analysis indicates that with some small alterations to the design, an RDE with an overall pressure rise is possible.

Use of the KlADH3 promoter for the quantitative production of the murine PDE5A isoforms in the yeast Kluyveromyces lactis.

PubMed

Cardarelli, Silvia; Giorgi, Mauro; Naro, Fabio; Malatesta, Francesco; Biagioni, Stefano; Saliola, Michele

2017-09-22

Phosphodiesterases (PDE) are a superfamily of enzymes that hydrolyse cyclic nucleotides (cAMP/cGMP), signal molecules in transduction pathways regulating crucial aspects of cell life. PDEs regulate the intensity and duration of the cyclic nucleotides signal modulating the downstream biological effect. Due to this critical role associated with the extensive distribution and multiplicity of isozymes, the 11 mammalian families (PDE1 to PDE11) constitute key therapeutic targets. PDE5, one of these cGMP-specific hydrolysing families, is the molecular target of several well known drugs used to treat erectile dysfunction and pulmonary hypertension. Kluyveromyces lactis, one of the few yeasts capable of utilizing lactose, is an attractive host alternative to Saccharomyces cerevisiae for heterologous protein production. Here we established K. lactis as a powerful host for the quantitative production of the murine PDE5 isoforms. Using the promoter of the highly expressed KlADH3 gene, multicopy plasmids were engineered to produce the native and recombinant Mus musculus PDE5 in K. lactis. Yeast cells produced large amounts of the purified A1, A2 and A3 isoforms displaying K m , V max and Sildenafil inhibition values similar to those of the native murine enzymes. PDE5 whose yield was nearly 1 mg/g wet weight biomass for all three isozymes (30 mg/L culture), is well tolerated by K. lactis cells without major growth deficiencies and interferences with the endogenous cAMP/cGMP signal transduction pathways. To our knowledge, this is the first time that the entire PDE5 isozymes family containing both regulatory and catalytic domains has been produced at high levels in a heterologous eukaryotic organism. K. lactis has been shown to be a very promising host platform for large scale production of mammalian PDEs for biochemical and structural studies and for the development of new specific PDE inhibitors for therapeutic applications in many pathologies.

Analytical and experimental investigations of the oblique detonation wave engine concept

NASA Technical Reports Server (NTRS)

Menees, Gene P.; Adelman, Henry G.; Cambier, Jean-Luc

1990-01-01

Wave combustors, which include the oblique detonation wave engine (ODWE), are attractive propulsion concepts for hypersonic flight. These engines utilize oblique shock or detonation waves to rapidly mix, ignite, and combust the air-fuel mixture in thin zones in the combustion chamber. Benefits of these combustion systems include shorter and lighter engines which require less cooling and can provide thrust at higher Mach numbers than conventional scramjets. The wave combustor's ability to operate at lower combustor inlet pressures may allow the vehicle to operate at lower dynamic pressures which could lessen the heating loads on the airframe. The research program at NASA-Ames includes analytical studies of the ODWE combustor using Computational Fluid Dynamics (CFD) codes which fully couple finite rate chemistry with fluid dynamics. In addition, experimental proof-of-concept studies are being performed in an arc heated hypersonic wind tunnel. Several fuel injection design were studied analytically and experimentally. In-stream strut fuel injectors were chosen to provide good mixing with minimal stagnation pressure losses. Measurements of flow field properties behind the oblique wave are compared to analytical predictions.

Analytical and experimental investigations of the oblique detonation wave engine concept

NASA Technical Reports Server (NTRS)

Menees, Gene P.; Adelman, Henry G.; Cambier, Jean-Luc

1991-01-01

Wave combustors, which include the Oblique Detonation Wave Engine (ODWE), are attractive propulsion concepts for hypersonic flight. These engines utilize oblique shock or detonation waves to rapidly mix, ignite, and combust the air-fuel mixture in thin zones in the combustion chamber. Benefits of these combustion systems include shorter and lighter engines which will require less cooling and can provide thrust at higher Mach numbers than conventional scramjets. The wave combustor's ability to operate at lower combustor inlet pressures may allow the vehicle to operate at lower dynamic pressures which could lessen the heating loads on the airframe. The research program at NASA-Ames includes analytical studies of the ODWE combustor using CFD codes which fully couple finite rate chemistry with fluid dynamics. In addition, experimental proof-of-concept studies are being carried out in an arc heated hypersonic wind tunnel. Several fuel injection designs were studied analytically and experimentally. In-stream strut fuel injectors were chosen to provide good mixing with minimal stagnation pressure losses. Measurements of flow field properties behind the oblique wave are compared to analytical predictions.

Characterization and Performance of a Liquid Hydrocarbon-Fueled Pulse Detonation Rocket Engine

DTIC Science & Technology

2001-12-01

head wall pressure (P3) and the two sensors at the end of the tube provided indication of detonation wave passage (Wave1 and Wave2 ). These data...wave speed using the time of passage at Wave1 and Wave2 and the user-defined value of the distance between each sensor (this distance varied slightly...for each tube extension). A detonation velocity of zero was returned for any event in which neither Wave1 or Wave2 sensed a pressure rise of

The effect of diamond burnishing on structure and properties of detonation-gas coatings on gas-turbine engine parts

NASA Astrophysics Data System (ADS)

Boguslaev, V. A.; Yatsenko, V. K.; Yakovlev, V. G.; Stepanova, L. P.; Pukhal'skaya, G. V.

2008-01-01

A diamond burnishing procedure for detonation coatings made from powder alloys PKKhN-15 and VKNA of parts made of steel Kh12NMBFSh is selected and substantiated, which ensures a favorable combination of the surface layer structure and properties.

Combustion and Magnetohydrodynamic Processes in Advanced Pulse Detonation Rocket Engines

NASA Astrophysics Data System (ADS)

Cole, Lord Kahil

A number of promising alternative rocket propulsion concepts have been developed over the past two decades that take advantage of unsteady combustion waves in order to produce thrust. These concepts include the Pulse Detonation Rocket Engine (PDRE), in which repetitive ignition, propagation, and reflection of detonations and shocks can create a high pressure chamber from which gases may be exhausted in a controlled manner. The Pulse Detonation Rocket Induced Magnetohydrodynamic Ejector (PDRIME) is a modification of the basic PDRE concept, developed by Cambier (1998), which has the potential for performance improvements based on magnetohydrodynamic (MHD) thrust augmentation. The PDRIME has the advantage of both low combustion chamber seeding pressure, per the PDRE concept, and efficient energy distribution in the system, per the rocket-induced MHD ejector (RIME) concept of Cole, et al. (1995). In the initial part of this thesis, we explore flow and performance characteristics of different configurations of the PDRIME, assuming quasi-one-dimensional transient flow and global representations of the effects of MHD phenomena on the gas dynamics. By utilizing high-order accurate solvers, we thus are able to investigate the fundamental physical processes associated with the PDRIME and PDRE concepts and identify potentially promising operating regimes. In the second part of this investigation, the detailed coupling of detonations and electric and magnetic fields are explored. First, a one-dimensional spark-ignited detonation with complex reaction kinetics is fully evaluated and the mechanisms for the different instabilities are analyzed. It is found that complex kinetics in addition to sufficient spatial resolution are required to be able to quantify high frequency as well as low frequency detonation instability modes. Armed with this quantitative understanding, we then examine the interaction of a propagating detonation and the applied MHD, both in one-dimensional and two-dimensional transient simulations. The dynamics of the detonation are found to be affected by the application of magnetic and electric fields. We find that the regularity of one-dimensional cesium-seeded detonations can be significantly altered by reasonable applied magnetic fields (Bz ≤ 8T), but that it takes a stronger applied field (Bz > 16T) to significantly alter the cellular structure and detonation velocity of a two-dimensional detonation in the time in which these phenomena were observed. This observation is likely attributed to the additional coupling of the two-dimensional detonation with the transverse waves, which are not captured in the one-dimensional simulations. Future studies involving full ionization kinetics including collisional-radiative processes, will be used to examine these processes in further detail.

Pulse Detonation Rocket MHD Power Experiment

NASA Technical Reports Server (NTRS)

Litchford, Ron J.; Cook, Stephen (Technical Monitor)

2002-01-01

A pulse detonation research engine (MSFC (Marshall Space Flight Center) Model PDRE (Pulse Detonation Rocket Engine) G-2) has been developed for the purpose of examining integrated propulsion and magnetohydrodynamic power generation applications. The engine is based on a rectangular cross-section tube coupled to a converging-diverging nozzle, which is in turn attached to a segmented Faraday channel. As part of the shakedown testing activity, the pressure wave was interrogated along the length of the engine while running on hydrogen/oxygen propellants. Rapid transition to detonation wave propagation was insured through the use of a short Schelkin spiral near the head of the engine. The measured detonation wave velocities were in excess of 2500 m/s in agreement with the theoretical C-J velocity. The engine was first tested in a straight tube configuration without a nozzle, and the time resolved thrust was measured simultaneously with the head-end pressure. Similar measurements were made with the converging-diverging nozzle attached. The time correlation of the thrust and head-end pressure data was found to be excellent. The major purpose of the converging-diverging nozzle was to configure the engine for driving an MHD generator for the direct production of electrical power. Additional tests were therefore necessary in which seed (cesium-hydroxide dissolved in methanol) was directly injected into the engine as a spray. The exhaust plume was then interrogated with a microwave interferometer in an attempt to characterize the plasma conditions, and emission spectroscopy measurements were also acquired. Data reduction efforts indicate that the plasma exhaust is very highly ionized, although there is some uncertainty at this time as to the relative abundance of negative OH ions. The emission spectroscopy data provided some indication of the species in the exhaust as well as a measurement of temperature. A 24-electrode-pair segmented Faraday channel and 0.6 Tesla permanent magnet assembly were then installed on Marshall Space Flight Center's (MSFC's) rectangular channel pulse detonation research engine. Magnetohydrodynamic (MHD) electrical power extraction experiments were carried out for a range of load impedances in which cesium hydroxide seed (dissolved in methanol) was sprayed into the gaseous oxygen/hydrogen propellants. Positive power extraction was obtained, but preliminary analysis of the data indicated that the plasma electrical conductivity is lower than anticipated and the near-electrode voltage drop is not negligible. It is believed that the electrical conductivity is reduced due to a large population of negative OH ions. This occurs because OH has a strong affinity for capturing free electrons. The effect of near-electrode voltage drop is associated with the high surface-to-volume ratio of the channel (1-inch by 1-inch cross-section) where surface effects play a dominant role. As usual for MHD devices, higher performance will require larger scale devices. Overall, the gathered data is extremely valuable from the standpoint of understanding plasma behavior and for developing empirical scaling laws.

Deflagration to Detonation Transition Processes in Pulsed Detonation Engines

DTIC Science & Technology

2002-08-03

which subsequently leads to DDT. The modelling approach taken here is as outlined by Arntzen et al. [9] and features a fractal based eddy-breakup... Arntzen , B.J., Hjertager, B., Lindstedt, R.P., Mercx, W.P.M. and Popat, N. “Investigations to Improve and Assess the Accuracy of Computational Fluid

Numerical Optimisation in Non Reacting Conditions of the Injector Geometry for a Continuous Detonation Wave Rocket Engine

NASA Astrophysics Data System (ADS)

Gaillard, T.; Davidenko, D.; Dupoirieux, F.

2015-06-01

The paper presents the methodology and the results of a numerical study, which is aimed at the investigation and optimisation of different means of fuel and oxidizer injection adapted to rocket engines operating in the rotating detonation mode. As the simulations are achieved at the local scale of a single injection element, only one periodic pattern of the whole geometry can be calculated so that the travelling detonation waves and the associated chemical reactions can not be taken into account. Here, separate injection of fuel and oxidizer is considered because premixed injection is handicapped by the risk of upstream propagation of the detonation wave. Different associations of geometrical periodicity and symmetry are investigated for the injection elements distributed over the injector head. To analyse the injection and mixing processes, a nonreacting 3D flow is simulated using the LES approach. Performance of the studied configurations is analysed using the results on instantaneous and mean flowfields as well as by comparing the mixing efficiency and the total pressure recovery evaluated for different configurations.

Numerical study on the instabilities in H2-air rotating detonation engines

NASA Astrophysics Data System (ADS)

Liu, Yan; Zhou, Weijiang; Yang, Yunjun; Liu, Zhou; Wang, Jianping

2018-04-01

Numerical simulations of rotating detonation engines (RDEs) are performed using two-dimensional Euler equations and a detailed chemistry model of H2-air. Two propagation modes, the one-wave mode and the two-wave mode, are observed in the RDEs. The instabilities of the RDEs are studied and analyzed specifically. A low frequency instability and a high frequency instability are found from the pressure-time trace measured at a fixed location and the average density-time trace of the RDEs. For the low frequency instability, the pressure peak of the pressure-time trace oscillates with a low frequency while the average density is stable. The deviation between the measurement location and the location of the detonation wave results in the low frequency instability. For the high frequency instability, the average density of the RDEs oscillates regularly with a single frequency while the pressure oscillates irregularly with several frequencies. The oscillation of the detonation wave height results in the high frequency instability. Furthermore, the low frequency instability and the high frequency instability both occur in the one-wave and two-wave mode RDEs.

Measurements of gas temperatures at 100 kHz within the annulus of a rotating detonation engine

NASA Astrophysics Data System (ADS)

Rein, Keith D.; Roy, Sukesh; Sanders, Scott T.; Caswell, Andrew W.; Schauer, Frederick R.; Gord, James R.

2017-03-01

Cycle-resolved measurements of H2O temperatures and number densities taken within the detonation channel of a hydrogen—air rotating detonation engine (RDE) at a 100 kHz repetition rate using laser absorption spectroscopy are presented. The laser source used is an MEMS-tunable Vertical-Cavity Surface Emitting laser which scans from 1330 to 1360 nm. Optical access into and out of the RDE is achieved using a dual-core fiber optic. Light is pitched into the RDE through a sapphire window via a single-mode core, retroreflected off the mirror-polished inner radius of the RDE annulus, and collected with the multi-mode fiber core. The resulting absorption spectra are used to determine gas temperatures as a function of time. These measurements allow characterization of the transient-temperature response of the RDE.

Development of Detonation Modeling Capabilities for Rocket Test Facilities: Hydrogen-Oxygen-Nitrogen Mixtures

NASA Technical Reports Server (NTRS)

Allgood, Daniel C.

2016-01-01

The objective of the presented work was to develop validated computational fluid dynamics (CFD) based methodologies for predicting propellant detonations and their associated blast environments. Applications of interest were scenarios relevant to rocket propulsion test and launch facilities. All model development was conducted within the framework of the Loci/CHEM CFD tool due to its reliability and robustness in predicting high-speed combusting flow-fields associated with rocket engines and plumes. During the course of the project, verification and validation studies were completed for hydrogen-fueled detonation phenomena such as shock-induced combustion, confined detonation waves, vapor cloud explosions, and deflagration-to-detonation transition (DDT) processes. The DDT validation cases included predicting flame acceleration mechanisms associated with turbulent flame-jets and flow-obstacles. Excellent comparison between test data and model predictions were observed. The proposed CFD methodology was then successfully applied to model a detonation event that occurred during liquid oxygen/gaseous hydrogen rocket diffuser testing at NASA Stennis Space Center.

Analytical and experimental validation of the Oblique Detonation Wave Engine concept

NASA Technical Reports Server (NTRS)

Adelman, Henry G.; Cambier, Jean-Luc; Menees, Gene P.; Balboni, John A.

1988-01-01

The Oblique Detonation Wave Engine (ODWE) for hypersonic flight has been analytically studied by NASA using the CFD codes which fully couple finite rate chemistry with fluid dynamics. Fuel injector designs investigated included wall and strut injectors, and the in-stream strut injectors were chosen to provide good mixing with minimal stagnation pressure losses. Plans for experimentally validating the ODWE concept in an arc-jet hypersonic wind tunnel are discussed. Measurements of the flow field properties behind the oblique wave will be compared to analytical predictions.

Impact waves and detonation. Part I

NASA Technical Reports Server (NTRS)

Becker, R

1929-01-01

Among the numerous thermodynamic and kinetic problems that have arisen in the application of the gaseous explosive reaction as a source of power in the internal combustion engine, the problem of the mode or way by which the transformation proceeds and the rate at which the heat energy is delivered to the working fluid became very early in the engine's development a problem of prime importance. The work of Becker here given is a notable extension of earlier investigations, because it covers the entire range of the explosive reaction in gases - normal detonation and burning.

First imaging Fourier-transform spectral measurements of detonation in an internal combustion engine

NASA Astrophysics Data System (ADS)

Gross, Kevin C.; Borel, Chris; White, Allen; Sakai, Stephen; DeVasher, Rebecca; Perram, Glen P.

2010-08-01

The Telops Hyper-Cam midwave (InSb 1.5-5.5μm) imaging Fourier-transformspectrometer (IFTS) observed repeated detonations in an ethanol-powered internal combustion (IC) engine. The IC engine is aMegatech Corporation MEG 150 with a 1in. bore, 4in. stroke, and a compression ratio of 3 : 1. The IC combustion cylinder is made from sapphire permitting observation in the visible and infrared. From a distance of 3m, the IFTS imaged the combustion cylinder on a 64×32 pixel array with each pixel covering a 0.1×0.1cm2 area. More than 14,000 interferograms were collected at a rate of 16Hz. The maximum optical path difference of the interferograms was 0.017cm corresponding to an unapodized spectral resolution of 36cm-1. Engine speed was varied between 600-1200RPM to de-correlate the observation time scale from the occurrence of detonations. A method is devised to process the ensemble of interferograms which takes advantage of the DC component so that the time history of the combustion spectrum can be recovered at each pixel location. Preliminary results of this analysis will be presented.

Auto-ignition of hydrazine by engineering materials

NASA Technical Reports Server (NTRS)

Perkins, J. H.; Riehl, W. A.

1978-01-01

Hydrazine, being a monopropellant, can explode and/or detonate in contact with some materials. This has been generally recognized and minimized by testing the compatibility of engineering materials with hydrazine at ambient temperature. Very limited tests have been done at elevated temperatures. To assess the potential hazard of hydrazine leakage into a propulsion compartment (boattail), autoignition characteristics of hydrazine were tested on 18 engineering materials and coatings at temperatures of 120 C to over 330 C. Furthermore, since hydrazine can decompose violently in nitrogen or helium, common purging cannot assure safety. Therefore tests were also made in nitrogen. Detonations occurred on contact with five materials in air. Similar tests in nitrogen did not lead to ignition.

Simplified Analysis of Pulse Detonation Rocket Engine Blowdown Gasdynamics and Performance

NASA Technical Reports Server (NTRS)

Morris, C. I.; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

Pulse detonation rocket engines (PDREs) offer potential performance improvements over conventional designs, but represent a challenging modellng task. A simplified model for an idealized, straight-tube, single-shot PDRE blowdown process and thrust determination is described and implemented. In order to form an assessment of the accuracy of the model, the flowfield time history is compared to experimental data from Stanford University. Parametric Studies of the effect of mixture stoichiometry, initial fill temperature, and blowdown pressure ratio on the performance of a PDRE are performed using the model. PDRE performance is also compared with a conventional steady-state rocket engine over a range of pressure ratios using similar gasdynamic assumptions.

Research on laser detonation pulse circuit with low-power based on super capacitor

NASA Astrophysics Data System (ADS)

Wang, Hao-yu; Hong, Jin; He, Aifeng; Jing, Bo; Cao, Chun-qiang; Ma, Yue; Chu, En-yi; Hu, Ya-dong

2018-03-01

According to the demand of laser initiating device miniaturization and low power consumption of weapon system, research on the low power pulse laser detonation circuit with super capacitor. Established a dynamic model of laser output based on super capacitance storage capacity, discharge voltage and programmable output pulse width. The output performance of the super capacitor under different energy storage capacity and discharge voltage is obtained by simulation. The experimental test system was set up, and the laser diode of low power pulsed laser detonation circuit was tested and the laser output waveform of laser diode in different energy storage capacity and discharge voltage was collected. Experiments show that low power pulse laser detonation based on super capacitor energy storage circuit discharge with high efficiency, good transient performance, for a low power consumption requirement, for laser detonation system and low power consumption and provide reference light miniaturization of engineering practice.

Wave combustors for trans-atmospheric vehicles

NASA Technical Reports Server (NTRS)

Menees, Gene P.; Bowles, Jeffrey V.; Adelman, Henry G.; Cambier, Jean-Luc

1989-01-01

A performance analysis is given of a conceptual transatmospheric vehicle (TAV). The TAV is powered by a an oblique detonation wave engine (ODWE). The ODWE is an airbreathing hypersonic propulsion system which utilizes shock and detonation waves to enhance fuel-air mixing and combustion in supersonic flow. In this wave combustor concept, an oblique shock wave in the combustor can act as a flameholder by increasing the pressure and temperature of the air-fuel mixture, thereby decreasing the ignition delay. If the oblique shock is sufficiently strong, then the combustion front and the shock wave can couple into a detonation wave. In this case, combustion occurs almost instantaneously in a thin zone behind the wave front. The result is a shorter lighter engine compared to the scramjet. The ODWE-powered hypersonic vehicle performance is compared to that of a scramjet-powered vehicle. Among the results outlined, it is found that the ODWE trades a better engine performance above Mach 15 for a lower performance below Mach 15. The overall higher performance of the ODWE results in a 51,000-lb weight savings and a higher payload weight fraction of approximately 12 percent.

Cloning and expression of cDNA for a human low-K sub m , rolipram-sensitive cyclic AMP phosphodiesterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Livi, G.P.; McHale, M.J.; Sathe, G.M.

1990-06-01

The authors have isolated cDNA clones representing cyclic AMP (cAMP)-specific phosphodiesterases (PDEases) from a human monocyte cDNA library. One cDNA clone (hPDE-1) defines a large open reading frame of ca. 2.1 kilobases, predicting a 686-amino-acid, ca. 77-kilodalton protein which contains significant homology to both rat brain and {ital Drosophila} cAMP PDEases, especially within an internal conserved domain of ca. 270 residues. Amino acid sequence divergence exists at the NH{sub 2} terminus and also within a 40- to 100-residue domain near the COOH-terminal end. hPDE-1 hybridizes to a major 4.8-kilobase mRNA transcript from both human monocytes and placenta. The coding regionmore » of hPDE-1 was engineered for expression in COS-1 cells, resulting in the overproduction of cAMP PDEase activity. The hPDE-1 recombinant gene product was identified as a low-{ital K{sub m}} cAMP phosphodiesterase on the basis of several biochemical properties including selective inhibition by the antidepressant drug rolipram. Known inhibitors of other PDEases (cGMP-specific PDEase, cGMP-inhibited PDEase) had little or no effect on the hPDE-1 recombinant gene product.« less

Experimental Study of High-Pressure Rotating Detonation Combustion in Rocket Environments

NASA Astrophysics Data System (ADS)

Stechmann, David Paul

Rotating Detonation Engines (RDEs) represent a promising pressure-gain combustion technology for improving the performance of existing rocket engines. While ample theoretical evidence exists for these benefits in ideal scenarios, additional research is needed to characterize the operational behavior of these devices at high pressure and validate the expected performance gains in practice. To this end, Purdue University developed a high-pressure experimental staged-combustion RDE with a supersonic plug expansion nozzle and conducted four test campaigns using this engine. The first two campaigns employed gaseous hydrogen fuel in conjunction with a liquid oxygen pre-burner. The final two campaigns employed methane and natural gas fuels. Propellant mass flows ranged from 0.47 lbm/s (0.21 Kg/s) to 8.41 lbm/s (3.8 kg/s) while mean chamber pressures ranged from 61 psia (4.1 atm) to 381 psia (25.9 atm). Results from tests conducted with hydrogen were mixed. Detonation briefly appeared at shutdown in some configurations, but the combustor behavior was generally dominated by flame holding instead of detonation. Injector erosion and instrumentation damage were also persistent challenges. Results from tests conducted with natural gas and methane were much more successful. Overall, several different types of detonation wave behavior were observed depending on test configuration and operating conditions. In all configurations, the engine thrust, chamber pressure, wave speed, and wave behavior were characterized for differences in injector orifice area, injection location, chamber width, pre-burner operating temperature, equivalence ratio, mass flow, and throat configuration. General aspects of the plume structure, startup behavior, and dynamic oxidizer manifold response were also characterized. Two configurations were also tested with a transparent combustor to characterize wave height and profile. These observations and measurements provided insight into the effects that high-pressures and rocket propellants have on RDE operating behavior. One of the more intriguing results from the experimental campaigns described above was the simple fact that natural gas and methane behaved so differently from hydrogen despite similar operating pressures, flow rates, and injector geometry. Simplified analysis and modeling of the injector dynamic response, mixing processes, and chemical kinetics provided insight into these differences and the scalability of these processes with pressure. In particular, the chemical kinetic analysis suggests that heat release during the injection and mixing phase can dominate the chamber behavior and prevent stable limit cycle detonation from occurring with certain propellant combinations above certain pressures. These results support the observed differences in engine operating behavior, and they provide insight into potential operability limits of gas-phase RDEs. In addition to the contrast between natural gas and hydrogen, several other important observations were made during the experimental RDE evaluation process. In particular, the installation of a convergent throat appeared to suppress detonation behavior. The number of waves was also invariant with respect to the mass flow and chamber pressure, and a natural transition into limit-cycle detonation modes (i.e. self-excited instabilities) appeared despite using a torch igniter with no initial detonation. Significant manifold interaction and an overall destabilizing effect in the limit-cycle detonation cycle tended to occur at low injector pressure ratios. The relationship between pressure, wave speed, and thrust did not follow the expected correlation and instead displayed a more complex configuration-dependent relationship. While the delivered thrust did not exceed theoretical values for a constant pressure cycle, thrust performance greater than 90% was achieved in configurations with simple injector geometries, simple expansion nozzle geometries and a chamber L* of only 2.75 inches. This suggests that further improvements are possible when heat loss into the wall is considered and improved injector designs are implemented. While heat flux was not measured during any experimental test cases, post-test analysis of the chamber environment using available data suggests that heat flux may be moderately higher in RDEs than in constant pressure combustors operating at the same mean flow conditions. Nevertheless, the computed heat flux was based on limited data and may have been affected by localized conditions near the injector face, so uncertainty remains in this area. Since appreciable uncertainty exists in the theoretical performance benefits relative to the measured experimental values, a detonation engine performance model was developed using modifications to existing zero-dimensional rocket performance relations. This approach made it possible to rapidly characterize the effects of different engine operating parameters on expected performance gains including propellant choice, equivalence ratio, initial propellant temperature, chamber pressure, nozzle configuration, nozzle expansion area, and ambient pressure. While the model was relatively simple, it captured the expected "DC shift" in mean chamber pressure between constant pressure combustors and combustors with steep-fronted non-linear instabilities. (Abstract shortened by ProQuest.).

Quantification of uncertainties for application in detonation simulation

NASA Astrophysics Data System (ADS)

Zheng, Miao; Ma, Zhibo

2016-06-01

Numerical simulation has become an important means in designing detonation systems, and the quantification of its uncertainty is also necessary to reliability certification. As to quantifying the uncertainty, it is the most important to analyze how the uncertainties occur and develop, and how the simulations develop from benchmark models to new models. Based on the practical needs of engineering and the technology of verification & validation, a framework of QU(quantification of uncertainty) is brought forward in the case that simulation is used on detonation system for scientific prediction. An example is offered to describe the general idea of quantification of simulation uncertainties.

Pressure and Thrust Measurements of a High-Frequency Pulsed-Detonation Actuator

NASA Technical Reports Server (NTRS)

Nguyen, Namtran C.; Cutler, Andrew D.

2008-01-01

This paper describes the development of a small-scale, high-frequency pulsed detonation actuator. The device utilized a fuel mixture of H2 and air, which was injected into the device at frequencies of up to 1200 Hz. Pulsed detonations were demonstrated in an 8-inch long combustion volume, at approx.600 Hz, for the lambda/4 mode. The primary objective of this experiment was to measure the generated thrust. A mean value of thrust was measured up to 6.0 lb, corresponding to specific impulse of 2611 s. This value is comparable to other H2-fueled pulsed detonation engines (PDEs) experiments. The injection and detonation frequency for this new experimental case was approx.600 Hz, and was much higher than typical PDEs, where frequencies are usually less than 100 Hz. The compact size of the model and high frequency of detonation yields a thrust-per-unit-volume of approximately 2.0 lb/cu in, and compares favorably with other experiments, which typically have thrust-per-unit-volume values of approximately 0.01 lb/cu in.

Pulse Detonation Rocket Engine Research at NASA Marshall

NASA Technical Reports Server (NTRS)

Morris, Christopher I.

2003-01-01

This viewgraph representation provides an overview of research being conducted on Pulse Detonation Rocket Engines (PDRE) by the Propulsion Research Center (PRC) at the Marshall Space Flight Center. PDREs have a theoretical thermodynamic advantage over Steady-State Rocket Engines (SSREs) although unsteady blowdown processes complicate effective use of this advantage in practice; PRE is engaged in a fundamental study of PDRE gas dynamics to improve understanding of performance issues. Topics covered include: simplified PDRE cycle, comparison of PDRE and SSRE performance, numerical modeling of quasi 1-D rocket flows, time-accurate thrust calculations, finite-rate chemistry effects in nozzles, effect of F-R chemistry on specific impulse, effect of F-R chemistry on exit species mole fractions and PDRE performance optimization studies.

Generalized Pseudo-Reaction Zone Model for Non-Ideal Explosives

NASA Astrophysics Data System (ADS)

Wescott, Bradley

2007-06-01

The pseudo-reaction zone model was proposed to improve engineering scale simulations when using Detonation Shock Dynamics with high explosives that have a slow reaction component. In this work an extension of the pseudo-reaction zone model is developed for non-ideal explosives that propagate well below their steady-planar Chapman-Jouguet velocity. A programmed burn method utilizing Detonation Shock Dynamics and a detonation velocity dependent pseudo-reaction rate has been developed for non-ideal explosives and applied to the explosive mixture of ammonium nitrate and fuel oil (ANFO). The pseudo-reaction rate is calibrated to the experimentally obtained normal detonation velocity---shock curvature relation. The generalized pseudo-reaction zone model proposed here predicts the cylinder expansion to within 1% by accounting for the slow reaction in ANFO.

Fluidically Augmented Nozzles for Pulse Detonation Engine Applications

DTIC Science & Technology

2011-12-01

25 captured the flow soon after the leading shock wave passed through the diverging section of the nozzle. As can be seen, the “pillow” has begun to...35 Figure 25. Initial Detonation Wave Enters the Diverging Section of the Nozzle...charging the combustor with an appropriate fuel/air mixture. This mixture is then ignited, producing a flame that is initially a deflagration wave . A

Numerical Modeling of Pulse Detonation Rocket Engine Gasdynamics and Performance

NASA Technical Reports Server (NTRS)

2003-01-01

This paper presents viewgraphs on the numerical modeling of pulse detonation rocket engines (PDRE), with an emphasis on the Gasdynamics and performance analysis of these engines. The topics include: 1) Performance Analysis of PDREs; 2) Simplified PDRE Cycle; 3) Comparison of PDRE and Steady-State Rocket Engines (SSRE) Performance; 4) Numerical Modeling of Quasi 1-D Rocket Flows; 5) Specific PDRE Geometries Studied; 6) Time-Accurate Thrust Calculations; 7) PDRE Performance (Geometries A B C and D); 8) PDRE Blowdown Gasdynamics (Geom. A B C and D); 9) PDRE Geometry Performance Comparison; 10) PDRE Blowdown Time (Geom. A B C and D); 11) Specific SSRE Geometry Studied; 12) Effect of F-R Chemistry on SSRE Performance; 13) PDRE/SSRE Performance Comparison; 14) PDRE Performance Study; 15) Grid Resolution Study; and 16) Effect of F-R Chemistry on SSRE Exit Species Mole Fractions.

Equation-free and variable free modeling for complex/multiscale systems. Coarse-grained computation in science and engineering using fine-grained models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kevrekidis, Ioannis G.

The work explored the linking of modern developing machine learning techniques (manifold learning and in particular diffusion maps) with traditional PDE modeling/discretization/scientific computation techniques via the equation-free methodology developed by the PI. The result (in addition to several PhD degrees, two of them by CSGF Fellows) was a sequence of strong developments - in part on the algorithmic side, linking data mining with scientific computing, and in part on applications, ranging from PDE discretizations to molecular dynamics and complex network dynamics.

Fast reactions of aluminum and explosive decomposition products in a post-detonation environment

NASA Astrophysics Data System (ADS)

Tappan, Bryce C.; Manner, Virginia W.; Lloyd, Joseph M.; Pemberton, Steven J.

2012-03-01

In order to determine the reaction behavior of Al in RDX or HMX/cast-cured binder formulations shortly after the passage of the detonation, a series of cylinder tests was performed on formulations comprising of varying binder systems and either 3.5 μm spherical Al or LiF (an inert salt with a similar molecular weight and density to Al). In these studies, both detonation velocity and cylinder expansion velocity are measured in order to determine exactly how and when Al contributes to the explosive event, particularly in the presence of oxidizing/energetic binders. The U.S. Army Research, Development and Engineering Laboratory at Picatinny have recently coined the term "combined effects" explosives for materials such as these; as they demonstrate both high metal pushing capability and high blast ability. This study is aimed at developing a fundamental understanding of the reaction of Al with explosives decomposition products, where both the detonation and early post-detonation environment are analyzed. Reaction rates of Al metal are investigated via comparison of predicted performance based on thermoequilibrium calculations. The detonation velocities, wall velocities, and parameters at the CJ plane are some of the parameters that will be discussed.

Controlled Detonation Dynamics in Additively Manufactured High Explosives

NASA Astrophysics Data System (ADS)

Schmalzer, Andrew; Tappan, Bryce; Bowden, Patrick; Manner, Virginia; Clements, Brad; Menikoff, Ralph; Ionita, Axinte; Branch, Brittany; Dattelbaum, Dana; Espy, Michelle; Patterson, Brian; Wu, Ruilian; Mueller, Alexander

2017-06-01

The effect of structure in explosives has long been a subject of interest to explosives engineers and scientists. Through structure, detonation dynamics in explosives can be manipulated, introducing a new level of safety and directed performance into these previously difficult to control materials. New advances in additive manufacturing (AM) allow the deliberate introduction of exact internal structures at dimensions approaching the mesoscale of these energetic materials. We show through simulation and experiment that this structure can be used to control detonation behavior by manipulating complex shockwave interactions. We use high-speed video and shorting mag-wires to determine the detonation velocity in AM generated explosive structures, demonstrating, for the first time, a method of controlling the directional propagation of reactive flow through the controlled introduction of structure within a high explosive. With ongoing improvement in the AM methods available coupled with guidance through modeling and simulations, more complex interactions are being explored. LANL LDRD Office.

Combustion and Magnetohydrodynamic Processes in Advanced Pulse Detonation Rocket Engines

DTIC Science & Technology

2012-10-01

use of high-order numerical methods can also be a powerful tool in the analysis of such complex flows, but we need to understand the interaction of...computational physics, 43(2):357372, 1981. [47] B. Einfeldt. On godunov-type methods for gas dynamics . SIAM Journal on Numerical Analysis , pages 294...dimensional effects with complex reaction kinetics, the simple one-dimensional detonation structure provides a rich spectrum of dynamical features which are

Preliminary engineering report for design of a subscale ejector/diffuser system for high expansion ratio space engine testing

NASA Technical Reports Server (NTRS)

Wojciechowski, C. J.; Kurzius, S. C.; Doktor, M. F.

1984-01-01

The design of a subscale jet engine driven ejector/diffuser system is examined. Analytical results and preliminary design drawings and plans are included. Previously developed performance prediction techniques are verified. A safety analysis is performed to determine the mechanism for detonation suppression.

Explosively generated shock wave processing of metal powders by instrumented detonics

NASA Astrophysics Data System (ADS)

Sharma, A. D.; Sharma, A. K.; Thakur, N.

2013-06-01

The highest pressures generated by dynamic processes resulting either from high velocity impact or by spontaneous release of high energy rate substances in direct contact with a metal find superior applications over normal mechanical means. The special feature of explosive loading to the powder materials over traditional methods is its controlled detonation pressure which directly transmits shock energy to the materials which remain entrapped inside powder resulting into several micro-structural changes and hence improved mechanical properties. superalloy powders have been compacted nearer to the theoretical density by shock wave consolidation. In a single experimental set-up, compaction of metal powder and measurement of detonation velocity have been achieved successfully by using instrumented detonics. The thrust on the work is to obtain uniform, crack-free and fracture-less compacts of superalloys having intact crystalline structure as has been examined from FE-SEM, XRD and mechanical studies. Shock wave processing is an emerging technique and receiving much attention of the materials scientists and engineers owing to its excellent advantages over traditional metallurgical methods due to short processing time, scaleup advantage and controlled detonation pressure.

Science and engineering of nanodiamond particle surfaces for biological applications (Review).

PubMed

Shenderova, Olga A; McGuire, Gary E

2015-09-05

Diamond has outstanding bulk properties such as super hardness, chemical inertness, biocompatibility, luminescence, to name just a few. In the nanoworld, in order to exploit these outstanding bulk properties, the surfaces of nanodiamond (ND) particles must be accordingly engineered for specific applications. Modification of functional groups on the ND's surface and the corresponding electrostatic properties determine their colloidal stability in solvents, formation of photonic crystals, controlled adsorption and release of cargo molecules, conjugation with biomolecules and polymers, and cellular uptake. The optical activity of the luminescent color centers in NDs depends on their proximity to the ND's surface and surface termination. In order to engineer the ND surface, a fundamental understanding of the specific structural features and sp(3)-sp(2) phase transformations on the surface of ND particles is required. In the case of ND particles produced by detonation of carbon containing explosives (detonation ND), it should also be taken into account that its structure depends on the synthesis parameters and subsequent processing. Thus, for development of a strategy of surface modification of detonation ND, it is imperative to know details of its production. In this review, the authors discuss ND particles structure, strategies for surface modification, electrokinetic properties of NDs in suspensions, and conclude with a brief overview of the relevant bioapplications.

Flowfield characterization and model development in detonation tubes

NASA Astrophysics Data System (ADS)

Owens, Zachary Clark

A series of experiments and numerical simulations are performed to advance the understanding of flowfield phenomena and impulse generation in detonation tubes. Experiments employing laser-based velocimetry, high-speed schlieren imaging and pressure measurements are used to construct a dataset against which numerical models can be validated. The numerical modeling culminates in the development of a two-dimensional, multi-species, finite-rate-chemistry, parallel, Navier-Stokes solver. The resulting model is specifically designed to assess unsteady, compressible, reacting flowfields, and its utility for studying multidimensional detonation structure is demonstrated. A reduced, quasi-one-dimensional model with source terms accounting for wall losses is also developed for rapid parametric assessment. Using these experimental and numerical tools, two primary objectives are pursued. The first objective is to gain an understanding of how nozzles affect unsteady, detonation flowfields and how they can be designed to maximize impulse in a detonation based propulsion system called a pulse detonation engine. It is shown that unlike conventional, steady-flow propulsion systems where converging-diverging nozzles generate optimal performance, unsteady detonation tube performance during a single-cycle is maximized using purely diverging nozzles. The second objective is to identify the primary underlying mechanisms that cause velocity and pressure measurements to deviate from idealized theory. An investigation of the influence of non-ideal losses including wall heat transfer, friction and condensation leads to the development of improved models that reconcile long-standing discrepancies between predicted and measured detonation tube performance. It is demonstrated for the first time that wall condensation of water vapor in the combustion products can cause significant deviations from ideal theory.

Compatible Spatial Discretizations for Partial Differential Equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arnold, Douglas, N, ed.

From May 11--15, 2004, the Institute for Mathematics and its Applications held a hot topics workshop on Compatible Spatial Discretizations for Partial Differential Equations. The numerical solution of partial differential equations (PDE) is a fundamental task in science and engineering. The goal of the workshop was to bring together a spectrum of scientists at the forefront of the research in the numerical solution of PDEs to discuss compatible spatial discretizations. We define compatible spatial discretizations as those that inherit or mimic fundamental properties of the PDE such as topology, conservation, symmetries, and positivity structures and maximum principles. A wide varietymore » of discretization methods applied across a wide range of scientific and engineering applications have been designed to or found to inherit or mimic intrinsic spatial structure and reproduce fundamental properties of the solution of the continuous PDE model at the finite dimensional level. A profusion of such methods and concepts relevant to understanding them have been developed and explored: mixed finite element methods, mimetic finite differences, support operator methods, control volume methods, discrete differential forms, Whitney forms, conservative differencing, discrete Hodge operators, discrete Helmholtz decomposition, finite integration techniques, staggered grid and dual grid methods, etc. This workshop seeks to foster communication among the diverse groups of researchers designing, applying, and studying such methods as well as researchers involved in practical solution of large scale problems that may benefit from advancements in such discretizations; to help elucidate the relations between the different methods and concepts; and to generally advance our understanding in the area of compatible spatial discretization methods for PDE. Particular points of emphasis included: + Identification of intrinsic properties of PDE models that are critical for the fidelity of numerical simulations. + Identification and design of compatible spatial discretizations of PDEs, their classification, analysis, and relations. + Relationships between different compatible spatial discretization methods and concepts which have been developed; + Impact of compatible spatial discretizations upon physical fidelity, verification and validation of simulations, especially in large-scale, multiphysics settings. + How solvers address the demands placed upon them by compatible spatial discretizations. This report provides information about the program and abstracts of all the presentations.« less

Evaluation of Straight and Swept Ramp Obstacles on Enhancing Deflagration-to-Detonation Transition in Pulse Detonation Engines

DTIC Science & Technology

2006-12-01

models attempted to bracket the extremes of the conditions of interest. These conditions were Mach 2 and Mach 3 shocks , with initial medium...later, but all traces have been expanded to the area of interest. Pressure readings were primarily used to measure shock speeds, and initially used...results for the clean tube configuration. The characteristics of the initial shock are similar, and are comparable for all configurations tested

Flow Visualization of a Rotating Detonation Engine

DTIC Science & Technology

2016-10-05

2[b]), and a 3-dimensional (3-D) view around the injectors (2[c]). In this study, ethylene and oxygen were used as propellants. These gases were fed...1.0-mm radius; the ethylene injectors had a 0.8-mm radius. A total of 100 sets of injectors were installed at even intervals. The gases were injected...detonation wave, was filled with high-pressure, high-temperature burned gas. This high-pressure burned gas stopped the injection of ethylene and

Impact of an Exhaust Throat on Semi-Idealized Rotating Detonation Engine Performance

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2016-01-01

A computational fluid dynamic (CFD) model of a rotating detonation engine (RDE) is used to examine the impact of an exhaust throat (i.e. a constriction) on performance. The model simulates an RDE which is premixed, adiabatic, inviscid, and which contains an inlet valve that prevents backflow from the high pressure region directly behind the rotating detonation. Performance is assessed in terms of ideal net specific impulse which is computed on the assumption of lossless expansion of the working fluid to the ambient pressure through a notional diverging nozzle section downstream of the throat. Such a semi-idealized analysis, while not real-world, allows the effect of the throat to be examined in isolation from, rather than coupled to (as it actually is) various loss mechanisms. For the single Mach 1.4 flight condition considered, it is found that the addition of a throat can yield a 9.4 percent increase in specific impulse. However, it is also found that when the exit throat restriction gets too small, an unstable type of operation ensues which eventually leads to the detonation failing. This behavior is found to be somewhat mitigated by the addition of an RDE inlet restriction across which there is an aerodynamic loss. Remarkably, this loss is overcome by the benefits of the further exhaust restrictions allowed. The end result is a configuration with a 10.3 percent improvement in ideal net specific thrust.

Impact of an Exhaust Throat on Semi-Idealized Rotating Detonation Engine Performance

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2016-01-01

A computational fluid dynamic (CFD) model of a rotating detonation engine (RDE) is used to examine the impact of an exhaust throat (i.e., a constriction) on performance. The model simulates an RDE which is premixed, adiabatic, inviscid, and which contains an inlet valve that prevents backflow from the high pressure region directly behind the rotating detonation. Performance is assessed in terms of ideal net specific impulse which is computed on the assumption of lossless expansion of the working fluid to the ambient pressure through a notional diverging nozzle section downstream of the throat. Such a semi-idealized analysis, while not real-world, allows the effect of the throat to be examined in isolation from, rather than coupled to (as it actually is) various loss mechanisms. For the single Mach 1.4 flight condition considered, it is found that the addition of a throat can yield a 9.4 percent increase in specific impulse. However, it is also found that when the exit throat restriction gets too small, an unstable type of operation ensues which eventually leads to the detonation failing. This behavior is found to be somewhat mitigated by the addition of an RDE inlet restriction across which there is an aerodynamic loss. Remarkably, this loss is overcome by the benefits of the further exhaust restrictions allowed. The end result is a configuration with a 10.3 percent improvement in ideal net specific thrust.

Mechanism of plasma-assisted ignition for H2 and C1-C5 hydrocarbons

NASA Astrophysics Data System (ADS)

Starikovskiy, Andrey; Aleksandrov, Nikolay

2016-09-01

Nonequilibrium plasma demonstrates ability to control ultra-lean, ultra-fast, low-temperature flames and appears to be an extremely promising technology for a wide range of applications, including aviation GTEs, piston engines, ramjets, scramjets and detonation initiation for pulsed detonation engines. To use nonequilibrium plasma for ignition and combustion in real energetic systems, one must understand the mechanisms of plasma-assisted ignition and combustion and be able to numerically simulate the discharge and combustion processes under various conditions. A new, validated mechanism for high-temperature hydrocarbon plasma assisted combustion was built and allows to qualitatively describe plasma-assisted combustion close and above the self-ignition threshold. The principal mechanisms of plasma-assisted ignition and combustion have been established and validated for a wide range of plasma and gas parameters. These results provide a basis for improving various energy-conversion combustion systems, from automobile to aircraft engines, using nonequilibrium plasma methods.

Generalized Pseudo-Reaction Zone Model for Non-Ideal Explosives

NASA Astrophysics Data System (ADS)

Wescott, B. L.

2007-12-01

The pseudo-reaction zone model was proposed to improve engineering scale simulations with high explosives that have a slow reaction component. In this work an extension of the pseudo-reaction zone model is developed for non-ideal explosives that propagate well below the steady-planar Chapman-Jouguet velocity. A programmed burn method utilizing Detonation Shock Dynamics (DSD) and a detonation velocity dependent pseudo-reaction rate has been developed for non-ideal explosives and applied to the explosive mixture of ammonium nitrate and fuel oil (ANFO). The pseudo-reaction rate is calibrated to the experimentally obtained normal detonation velocity—shock curvature relation. Cylinder test simulations predict the proper expansion to within 1% even though significant reaction occurs as the cylinder expands.

Pulse Detonation Rocket Magnetohydrodynamic Power Experiment

NASA Technical Reports Server (NTRS)

Litchford, R. J.; Jones, J. E.; Dobson, C. C.; Cole, J. W.; Thompson, B. R.; Plemmons, D. H.; Turner, M. W.

2003-01-01

The production of onboard electrical power by pulse detonation engines is problematic in that they generate no shaft power; however, pulse detonation driven magnetohydrodynamic (MHD) power generation represents one intriguing possibility for attaining self-sustained engine operation and generating large quantities of burst power for onboard electrical systems. To examine this possibility further, a simple heat-sink apparatus was developed for experimentally investigating pulse detonation driven MHD generator concepts. The hydrogen oxygen fired driver was a 90 cm long stainless steel tube having a 4.5 cm square internal cross section and a short Schelkin spiral near the head end to promote rapid formation of a detonation wave. The tube was intermittently filled to atmospheric pressure and seeded with a CsOH/methanol prior to ignition by electrical spark. The driver exhausted through an aluminum nozzle having an area contraction ratio of A*/A(sub zeta) = 1/10 and an area expansion ratio of A(sub zeta)/A* = 3.2 (as limited by available magnet bore size). The nozzle exhausted through a 24-electrode segmented Faraday channel (30.5 cm active length), which was inserted into a 0.6 T permanent magnet assembly. Initial experiments verified proper drive operation with and without the nozzle attachment, and head end pressure and time resolved thrust measurements were acquired. The exhaust jet from the nozzle was interrogated using a polychromatic microwave interferometer yielding an electron number density on the order of 10(exp 12)/cm at the generator entrance. In this case, MHD power generation experiments suffered from severe near-electrode voltage drops and low MHD interaction; i.e., low flow velocity, due to an inherent physical constraint on expansion with the available magnet. Increased scaling, improved seeding techniques, higher magnetic fields, and higher expansion ratios are expected to greatly improve performance.

Combustion in a High-Speed Compression-Ignition Engine

NASA Technical Reports Server (NTRS)

Rothrock, A M

1933-01-01

An investigation conducted to determine the factors which control the combustion in a high-speed compression-ignition engine is presented. Indicator cards were taken with the Farnboro indicator and analyzed according to the tangent method devised by Schweitzer. The analysis show that in a quiescent combustion chamber increasing the time lag of auto-ignition increases the maximum rate of combustion. Increasing the maximum rate of combustion increases the tendency for detonation to occur. The results show that by increasing the air temperature during injection the start of combustion can be forced to take place during injection and so prevent detonation from occurring. It is shown that the rate of fuel injection does not in itself control the rate of combustion.

Development of a numerical tool to study the mixing phenomenon occurring during mode one operation of a multi-mode ejector-augmented pulsed detonation rocket engine

NASA Astrophysics Data System (ADS)

Dawson, Joshua

A novel multi-mode implementation of a pulsed detonation engine, put forth by Wilson et al., consists of four modes; each specifically designed to capitalize on flow features unique to the various flow regimes. This design enables the propulsion system to generate thrust through the entire flow regime. The Multi-Mode Ejector-Augmented Pulsed Detonation Rocket Engine operates in mode one during take-off conditions through the acceleration to supersonic speeds. Once the mixing chamber internal flow exceeds supersonic speed, the propulsion system transitions to mode two. While operating in mode two, supersonic air is compressed in the mixing chamber by an upstream propagating detonation wave and then exhausted through the convergent-divergent nozzle. Once the velocity of the air flow within the mixing chamber exceeds the Chapman-Jouguet Mach number, the upstream propagating detonation wave no longer has sufficient energy to propagate upstream and consequently the propulsive system shifts to mode three. As a result of the inability of the detonation wave to propagate upstream, a steady oblique shock system is established just upstream of the convergent-divergent nozzle to initiate combustion. And finally, the propulsion system progresses on to mode four operation, consisting purely of a pulsed detonation rocket for high Mach number flight and use in the upper atmosphere as is needed for orbital insertion. Modes three and four appear to be a fairly significant challenge to implement, while the challenge of implementing modes one and two may prove to be a more practical goal in the near future. A vast number of potential applications exist for a propulsion system that would utilize modes one and two, namely a high Mach number hypersonic cruise vehicle. There is particular interest in the dynamics of mode one operation, which is the subject of this research paper. Several advantages can be obtained by use of this technology. Geometrically the propulsion system is fairly simple and as a result of the rapid combustion process the engine cycle is more efficient compared to its combined cycle counterparts. The flow path geometry consists of an inlet system, followed just downstream by a mixing chamber where an ejector structure is placed within the flow path. Downstream of the ejector structure is a duct leading to a convergent-divergent nozzle. During mode one operation and within the ejector, products from the detonation of a stoichiometric hydrogen/air mixture are exhausted directly into the surrounding secondary air stream. Mixing then occurs between both the primary and secondary flow streams, at which point the air mass containing the high pressure, high temperature reaction products is convected downstream towards the nozzle. The engine cycle is engineered to a specific number of detonations per second, creating the pulsating characteristic of the primary flow. The pulsing nature of the primary flow serves as a momentum augmentation, enhancing the thrust and specific impulse at low speeds. Consequently it is necessary to understand the transient mixing process between the primary and secondary flow streams occurring during mode one operation. Using OPENFOAMRTM, an analytic tool is developed to simulate the dynamics of the turbulent detonation process along with detailed chemistry in order to understand the physics involved with the stream interactions. The computational code has been developed within the framework of OPENFOAMRTM, an open-source alternative to commercial CFD software. A conservative formulation of the Farve averaged Navier-Stokes equations is implemented to facilitate programming and numerical stability. Time discretization is accomplished by using the Crank-Nicolson method, achieving second order convergence in time. Species mass fraction transport equations are implemented and a Seulex ODE solver was used to resolve the system of ordinary differential equations describing the hydrogen-air reaction mechanism detailed in Appendix A. The Seulex ODE solution algorithm is an extrapolation method based on the linearly implicit Euler method with step size control. A second order total variation diminishing method with a modified Sweby flux limiter was used for space discretization. And finally the use of operator splitting (PISO algorithm, and chemical kinetics) is essential due to the significant differences in characteristic time scales evolving simultaneously in turbulent reactive flow. Capturing the turbulent nature of the combustion process was done using the k-o-SST turbulence model, as formulated by Mentor [1]. Mentor's formulation is well suited to resolve the boundary layer while remaining relatively insensitive to freestream conditions, blending the merits of both the k-o and k-epsilon models. Further development of the tool is possible, most notably with the Numerical Propulsion System Simulation application. NPSS allows the user to take advantage of a "zooming" functionality in which high fidelity models of engine components can be integrated into NPSS models, allowing for a more robust propulsion system simulation.

Flowpath Design of a Three-Tube Valve-Less Pulse Detonation Combustor

DTIC Science & Technology

2009-09-01

traditional gas turbine engines since the detonation event produces a lower entropy rise and more available work than a Brayton cycle operating at similar...pressure process ( Brayton cycle), with the result that the combustion process ends at state 3a vice state 3.   6   Figure 3. Pressure – Volume Diagram... Brayton cycle, represented by A1, there is a significantly lower yield when compared to the Humphrey cycle, which envelops area A1+A2. It is

Relation between Spark-Ignition Engine Knock, Detonation Waves, and Autoignition as Shown by High-Speed Photography

DTIC Science & Technology

1946-01-01

unfortunate” fiat this work has not, in the past few years , received more carcf~ll considera- tion. Th~ photographs of %kolik and Voinov wcro taken through a...with the propo8ed combined theory but not with either the simple autoignition theory or the simple detonation- wace theory. INTRODUCTION Knock is one of...countries for about 25 yeara. The past researches on knock have uncovered an immense amount of information, not only concerning the basic nature of knock but

Effects of injection nozzle exit width on rotating detonation engine

NASA Astrophysics Data System (ADS)

Sun, Jian; Zhou, Jin; Liu, Shijie; Lin, Zhiyong; Cai, Jianhua

2017-11-01

A series of numerical simulations of RDE modeling real injection nozzles with different exit widths are performed in this paper. The effects of nozzle exit width on chamber inlet state, plenum flowfield and detonation propagation are analyzed. The results are compared with that using an ideal injection model. Although the ideal injection model is a good approximation method to model RDE inlet, the two-dimensional effects of real nozzles are ignored in the ideal injection model so that some complicated phenomena such as the reflected waves caused by the nozzle walls and the reversed flow into the nozzles can not be modeled accurately. Additionally, the ideal injection model overpredicts the block ratio. In all the cases that stabilize at one-wave mode, the block ratio increases as the nozzle exit width gets smaller. The dual-wave mode case also has a relatively high block ratio. A pressure oscillation in the plenum with the same main frequency with the rotating detonation wave is observed. A parameter σ is applied to describe the non-uniformity in the plenum. σ increases as the nozzle exit width gets larger. Under some condition, the heat release on the interface of fresh premixed gas layer and detonation products can be strong enough to induce a new detonation wave. A spontaneous mode-transition process is observed for the smallest exit width case. Due to the detonation products existing in the premixed gas layer before the detonation wave, the detonation wave will propagate through reactants and products alternately, and therefore its strength will vary with time, especially near the chamber inlet. This tendency gets weaker as the injection nozzle exit width increases.

14 CFR 33.49 - Endurance test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... higher gear ratio under sea level conditions. The condition for operation for the alternate 5 minutes in... suppress detonation. (d) Helicopter engines. To be eligible for use on a helicopter each engine must either... sea level carburetor entrance pressure, if 105 percent of the rated maximum continuous power is not...

14 CFR 33.49 - Endurance test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... higher gear ratio under sea level conditions. The condition for operation for the alternate 5 minutes in... suppress detonation. (d) Helicopter engines. To be eligible for use on a helicopter each engine must either... sea level carburetor entrance pressure, if 105 percent of the rated maximum continuous power is not...

Influence of condensation on heat flux and pressure measurements in a detonation-based short-duration facility

NASA Astrophysics Data System (ADS)

Haase, S.; Olivier, H.

2017-10-01

Detonation-based short-duration facilities provide hot gas with very high stagnation pressures and temperatures. Due to the short testing time, complex and expensive cooling techniques of the facility walls are not needed. Therefore, they are attractive for economical experimental investigations of high-enthalpy flows such as the flow in a rocket engine. However, cold walls can provoke condensation of the hot combustion gas at the walls. This has already been observed in detonation tubes close behind the detonation wave, resulting in a loss of tube performance. A potential influence of condensation at the wall on the experimental results, like wall heat fluxes and static pressures, has not been considered so far. Therefore, in this study the occurrence of condensation and its influence on local heat flux and pressure measurements has been investigated in the nozzle test section of a short-duration rocket-engine simulation facility. This facility provides hot water vapor with stagnation pressures up to 150 bar and stagnation temperatures up to 3800 K. A simple method has been developed to detect liquid water at the wall without direct optical access to the flow. It is shown experimentally and theoretically that condensation has a remarkable influence on local measurement values. The experimental results indicate that for the elimination of these influences the nozzle wall has to be heated to a certain temperature level, which exclusively depends on the local static pressure.

Flame Acceleration and Transition to Detonation in High Speed Turbulent Combustion

DTIC Science & Technology

2016-12-21

gas mixtures and sprays is dif- ficult to overestimate, as it is the main process in all internal-combustion engines used for propulsion and energy...generation. These include piston engines, gas turbines, various types of jet engines, and some rocket engines . On the other hand , preventing high...speed combustion is critical for the safety of any human activities that involve handling of po- t entially explosive gases or volatile liquids . Thus

Identification of the gamma subunit-interacting residues on photoreceptor cGMP phosphodiesterase, PDE6alpha '.

PubMed

Granovsky, A E; Artemyev, N O

2000-12-29

Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the G protein-mediated visual transduction cascade. In the dark, the activity of PDE6 is shut off by the inhibitory gamma subunit (Pgamma). Chimeric proteins between cone PDE6alpha' and cGMP-binding and cGMP-specific PDE (PDE5) have been constructed and expressed in Sf9 cells to study the mechanism of inhibition of PDE6 catalytic activity by Pgamma. Substitution of the segment PDE5-(773-820) by the corresponding PDE6alpha'-(737-784) sequence in the wild-type PDE5 or in a PDE5/PDE6alpha' chimera containing the catalytic domain of PDE5 results in chimeric enzymes capable of inhibitory interaction with Pgamma. The catalytic properties of the chimeric PDEs remained similar to those of PDE5. Ala-scanning mutational analysis of the Pgamma-binding region, PDE6alpha'-(750-760), revealed PDE6alpha' residues essential for the interaction. The M758A mutation markedly impaired and the Q752A mutation moderately impaired the inhibition of chimeric PDE by Pgamma. The analysis of the catalytic properties of mutant PDEs and a model of the PDE6 catalytic domain suggest that residues Met(758) and Gln(752) directly bind Pgamma. A model of the PDE6 catalytic site shows that PDE6alpha'-(750-760) forms a loop at the entrance to the cGMP-binding pocket. Binding of Pgamma to Met(758) would effectively block access of cGMP to the catalytic cavity, providing a structural basis for the mechanism of PDE6 inhibition.

Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs.

PubMed

Zhang, Han-Ting

2009-01-01

Phosphodiesterase-4 (PDE4), one of eleven PDE enzyme families, specifically catalyzes hydrolysis of cyclic AMP (cAMP); it has four subtypes (PDE4A-D) with at least 25 splice variants. PDE4 plays a critical role in the control of intracellular cAMP concentrations. PDE4 inhibitors produce antidepressant actions in both animals and humans via enhancement of cAMP signaling in the brain. However, their clinical utility has been hampered by side effects, in particular nausea and emesis. While there is still a long way to go before PDE4 inhibitors with high therapeutic indices are available for treatment of depressive disorders, important advances have been made in the development of PDE4 inhibitors as antidepressants. First, limited, but significant studies point to PDE4D as the major PDE4 subtype responsible for antidepressant-like effects of PDE4 inhibitors, although the role of PDE4A cannot be excluded. Second, PDE4D may contribute to emesis, the major side effect of PDE4 inhibitors. For this reason, identification of roles of PDE4D splice variants in mediating antidepressant activity is particularly important. Recent studies using small interfering RNAs (siRNAs) have demonstrated the feasibility to identify cellular functions of individual PDE4 variants. Third, mixed inhibitors of PDE4 and PDE7 or PDE4 and serotonin reuptake have been developed and may be potential antidepressants with minimized side effects. Finally, relatively selective inhibitors of one or two PDE4 subtypes have been synthesized using structure- and scaffold-based design. This review also discusses the relationship between PDE4 and antidepressant activity based on structures, brain distributions, and pharmacological properties of PDE4 and its isoforms.

Two Phase Detonation Studies Conducted in 1971

NASA Technical Reports Server (NTRS)

Nicholls, J. A.

1972-01-01

The research covered by this third annual progress report represents a continuation of our efforts devoted to the study of detonation waves in liquid-gas systems. The motivation for the work is associated with liquid propellant rocket motor combustion instability although certainly the studies are also applicable to internal combustion engines, jet propulsion engines, safety aspects of spilled liquid fuel, coal mine explosions, and weaponry. The research has been divided into 5 phases, although all of them are intimately related. For the most part these phases are briefly summarized and the reader is referred to other publications for a more complete treatment. The exception to this is where the material herein represents the only printed information available on the particular facet of the problem. Phase A has been primarily concerned with the breakup and ignition of fuel drops by shock waves. The experimental portion of this study as well as a theoretical treatment of the ignition behavior was completed in the past year. The research is now concentrating on the passage of a shock wave over a burning drop. Phase B has been devoted to the assessment of the approximate energy release pattern in two phase detonations insofar as they affect the significant overpressures observed.

Optimal Area Profiles for Ideal Single Nozzle Air-Breathing Pulse Detonation Engines

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2003-01-01

The effects of cross-sectional area variation on idealized Pulse Detonation Engine performance are examined numerically. A quasi-one-dimensional, reacting, numerical code is used as the kernel of an algorithm that iteratively determines the correct sequencing of inlet air, inlet fuel, detonation initiation, and cycle time to achieve a limit cycle with specified fuel fraction, and volumetric purge fraction. The algorithm is exercised on a tube with a cross sectional area profile containing two degrees of freedom: overall exit-to-inlet area ratio, and the distance along the tube at which continuous transition from inlet to exit area begins. These two parameters are varied over three flight conditions (defined by inlet total temperature, inlet total pressure and ambient static pressure) and the performance is compared to a straight tube. It is shown that compared to straight tubes, increases of 20 to 35 percent in specific impulse and specific thrust are obtained with tubes of relatively modest area change. The iterative algorithm is described, and its limitations are noted and discussed. Optimized results are presented showing performance measurements, wave diagrams, and area profiles. Suggestions for future investigation are also discussed.

Off-Design Analysis of a High Bypass Turbofan Using a Pulsed Detonation Combustor

DTIC Science & Technology

2010-03-01

Engine Off-Design Results.............................................................39 Code Verification and Operating Limit ...38 4.4. Maximum Operating Limit Baseline and Hybrid Engine ......................................... 41 4.5. Throttle...that an isentropic expansion process takes place followed by a heat rejection to close the cycle. The derivation for the solutions for the Chapman

Nitric oxide-induced changes in endothelial expression of phosphodiesterases 2, 3, and 5.

PubMed

Schankin, Christoph J; Kruse, Lars S; Reinisch, Veronika M; Jungmann, Steffen; Kristensen, Julie C; Grau, Stefan; Ferrari, Uta; Sinicina, Inga; Goldbrunner, Roland; Straube, Andreas; Kruuse, Christina

2010-03-01

To investigate nitric oxide (NO)-mediated changes in expression of cyclic nucleotide degrading phosphodiesterases 2A (PDE2A), PDE3B, and PDE5A in human endothelial cells. Nitric oxide induces production of cyclic guanosine monophosphate (cGMP), which along with cyclic adenosine monophosphate (cAMP) is degraded by PDEs. NO donors and selective inhibitors of PDE3 and PDE5 induce migraine-like headache and play a role in endothelial dysfunction during stroke. The current study investigates possible NO modulation of cGMP-related PDEs relevant to headache induction in a cell line containing such PDEs. Real time polymerase chain reaction and Western blots were used to show expression of PDE2A, PDE3B, and PDE5A in a stable cell line of human brain microvascular endothelial cells. Effects of NO on PDE expression were analyzed at specific time intervals after continued DETA NONOate administration. This study shows the expression of PDE2A, PDE3B, and PDE5A mRNA and PDE3B and PDE5A protein in human cerebral endothelial cells. Long-term DETA NONOate administration induced an immediate mRNA up-regulation of PDE5A (1.9-fold, 0.5 hour), an early peak of PDE2A (1.4-fold, 1 and 2 hours) and later up-regulation of both PDE3B (1.6-fold, 4 hours) and PDE2A (1.7-fold, 8 hours and 1.2-fold after 24 hours). Such changes were, however, not translated into significant changes in protein expression indicating few, if any, functional effects. Long-term NO stimulation modulated PDE3 and PDE5 mRNA expression in endothelial cells. However, PDE3 and PDE5 protein levels were unaffected by NO. The presence of PDE3 or PDE5 in endothelial cells indicates that selective inhibitors may have functional effects in such cells. A complex interaction of cGMP and cAMP in response to NO administration may take place if the mRNA translates into active protein. Whether or not this plays a role in the headache mechanisms remains to be investigated.

Detonation Initiation and Evolution in Spray- Fueled Pulsed Detonation Rocket Engines

DTIC Science & Technology

2007-06-28

shock by an nth fluid particle during the induction time is characterized by Z" = Uro ’, where o;,, is the induction time for that particle and o7, is a...12.5 15 z 15 s=20 25. 28 e 10 5 - 0 2.5 5 75 10 12.5 15 z 20 s=3.0, 31, 32 15- I- + E! lo 02.5 T 01251 2 T s 3.3.3.4, 3.5 20 10 F.... 0 25 5 75 10 12.5

Nanotechnology Investigated for Future Gelled and Metallized Gelled Fuels

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan A.

2003-01-01

The objective of this research is to create combustion data for gelled and metallized gelled fuels using unique nanometer-sized gellant particles and/or nanometer-sized aluminum particles. Researchers at the NASA Glenn Research Center are formulating the fuels for both gas turbine and pulsed detonation engines. We intend to demonstrate metallized gelled fuel ignition characteristics for pulse detonation engines with JP/aluminum fuel and for gas turbine engines with gelled JP, propane, and methane fuel. The fuels to be created are revolutionary as they will deliver the highest theoretically maximum performance of gelled and metallized gelled fuels. Past combustion work has used micrometer-sized particles, which have limited the combustion performance of gelled and metallized gelled fuels. The new fuel used nanometer-sized aluminum oxide particles, which reduce the losses due to mismatch in the gas and solid phases in the exhaust. Gelled fuels provide higher density, added safety, reduced fuel slosh, reduced leakage, and increased exhaust velocity. Altogether, these benefits reduce the overall size and mass of the vehicle, increasing its flexibility.

The high-affinity phosphodiesterase PdeH regulates development and aflatoxin biosynthesis in Aspergillus flavus.

PubMed

Yang, Kunlong; Liu, Yinghang; Liang, Linlin; Li, Zhenguo; Qin, Qiuping; Nie, Xinyi; Wang, Shihua

2017-04-01

Cyclic AMP signaling controls a range of physiological processes in response to extracellular stimuli in organisms. Among the signaling cascades, cAMP, as a second messenger, is orchestrated by adenylate cyclase (biosynthesis) and cAMP phosphodiesterases (PDEs) (hydrolysis). In this study, we investigated the function of the high-affinity (PdeH) and low-affinity (PdeL) cAMP phosphodiesterase from the carcinogenic aflatoxin producing fungus Aspergillus flavus, and found that instead of PdeL, inactivation of PdeH exhibited a reduction in conidiation and sclerotia formation. However, the ΔpdeL/ΔpdeH mutant exhibited an enhanced phenotype defects, a similar phenotype defects to wild-type strain treated with exogenous cAMP. The activation of PKA activity was inhibited in the ΔpdeH or ΔpdeL/ΔpdeH mutant, both of whom exhibited increasing AF production. Further analysis by qRT-PCR revealed that pdeH had a high transcriptional level compared to pdeL in wild-type strain, and affected pdeL transcription. Green fluorescent protein tagging at the C-terminus of PDEs showed that PdeH-GFP is broadly compartmentalized in the cytosol, while PdeL-GFP localized mainly to the nucleus. Overall, our results indicated that PdeH plays a major role, but has overlapping function with PdeL, in vegetative growth, development and AF biosynthesis in A. flavus. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Numerical Simulation of Chemical Weapon Detonations

DTIC Science & Technology

1996-08-01

Engineers , is currently involved in the location, removal, and demilitarization of stockpiled and non-stockpiled chemical munitions. To support the...U.S. Army Corps of Engineers , is currently involved in the location, removal, and demilitarization of stockpiled and non-stockpiled chemical munitions...Length 6" As part of the development of a chemical agent confinement structure for use by the Huntsville Corps of Engineers , SwRI performed arena tests on

Energetic Combustion Devices for Aerospace Propulsion and Power

NASA Technical Reports Server (NTRS)

Litchford, Ron J.

2000-01-01

Chemical reactions have long been the mainstay thermal energy source for aerospace propulsion and power. Although it is widely recognized that the intrinsic energy density limitations of chemical bonds place severe constraints on maximum realizable performance, it will likely be several years before systems based on high energy density nuclear fuels can be placed into routine service. In the mean time, efforts to develop high energy density chemicals and advanced combustion devices which can utilize such energetic fuels may yield worthwhile returns in overall system performance and cost. Current efforts in this vein are being carried out at NASA MSFC under the direction of the author in the areas of pulse detonation engine technology development and light metals combustion devices. Pulse detonation engines are touted as a low cost alternative to gas turbine engines and to conventional rocket engines, but actual performance and cost benefits have yet to be convincingly demonstrated. Light metal fueled engines also offer potential benefits in certain niche applications such as aluminum/CO2 fueled engines for endo-atmospheric Martian propulsion. Light metal fueled MHD generators also present promising opportunities with respect to electric power generation for electromagnetic launch assist. This presentation will discuss the applications potential of these concepts with respect to aero ace propulsion and power and will review the current status of the development efforts.

Human PDE4D isoform composition is deregulated in primary prostate cancer and indicative for disease progression and development of distant metastases

PubMed Central

Böttcher, René; Dulla, Kalyan; van Strijp, Dianne; Dits, Natasja; Verhoef, Esther I.; Baillie, George S.; van Leenders, Geert J.L.H.; Houslay, Miles D.; Jenster, Guido; Hoffmann, Ralf

2016-01-01

Phosphodiesterase 4D7 was recently shown to be specifically over-expressed in localized prostate cancer, raising the question as to which regulatory mechanisms are involved and whether other isoforms of this gene family (PDE4D) are affected under the same conditions. We investigated PDE4D isoform composition in prostatic tissues using a total of seven independent expression datasets and also included data on DNA methylation, copy number and AR and ERG binding in PDE4D promoters to gain insight into their effect on PDE4D transcription. We show that expression of PDE4D isoforms is consistently altered in primary human prostate cancer compared to benign tissue, with PDE4D7 being up-regulated while PDE4D5 and PDE4D9 are down-regulated. Disease progression is marked by an overall down-regulation of long PDE4D isoforms, while short isoforms (PDE4D1/2) appear to be relatively unaffected. While these alterations seem to be independent of copy number alterations in the PDE4D locus and driven by AR and ERG binding, we also observed increased DNA methylation in the promoter region of PDE4D5, indicating a long lasting alteration of the isoform composition in prostate cancer tissues. We propose two independent metrics that may serve as diagnostic and prognostic markers for prostate disease: (PDE4D7 - PDE4D5) provides an effective means for distinguishing PCa from normal adjacent prostate, whereas PDE4D1/2 - (PDE4D5 + PDE4D7 + PDE4D9) offers strong prognostic potential to detect aggressive forms of PCa and is associated with metastasis free survival. Overall, our findings highlight the relevance of PDE4D as prostate cancer biomarker and potential drug target. PMID:27683107

Numerical study of rotating detonation engine with an array of injection holes

NASA Astrophysics Data System (ADS)

Yao, S.; Han, X.; Liu, Y.; Wang, J.

2017-05-01

This paper aims to adopt the method of injection via an array of holes in three-dimensional numerical simulations of a rotating detonation engine (RDE). The calculation is based on the Euler equations coupled with a one-step Arrhenius chemistry model. A pre-mixed stoichiometric hydrogen-air mixture is used. The present study uses a more practical fuel injection method in RDE simulations, injection via an array of holes, which is different from the previous conventional simulations where a relatively simple full injection method is usually adopted. The computational results capture some important experimental observations and a transient period after initiation. These phenomena are usually absent in conventional RDE simulations due to the use of an idealistic injection approximation. The results are compared with those obtained from other numerical studies and experiments with RDEs.

Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei

PubMed Central

Rascón, Ana; Soderling, Scott H.; Schaefer, Jonathan B.; Beavo, Joseph A.

2002-01-01

Here we report the cloning, expression, and characterization of a cAMP-specific phosphodiesterase (PDE) from Trypanosoma brucei (TbPDE2B). Using a bioinformatic approach, two different expressed sequence tag clones were identified and used to isolate the complete sequence of two identical PDE genes arranged in tandem. Each gene consists of 2,793 bases that predict a protein of 930 aa with a molecular mass of 103.2 kDa. Two GAF (for cGMP binding and stimulated PDEs, Anabaena adenylyl cyclases, and Escherichia coli FhlA) domains, similar to those contained in many signaling molecules including mammalian PDE2, PDE5, PDE6, PDE10, and PDE11, were located N-terminal to a consensus PDE catalytic domain. The catalytic domain is homologous to the catalytic domain of all 11 mammalian PDEs, the Dictyostelium discoideum RegA, and a probable PDE from Caenorhabditis elegans. It is most similar to the T. brucei PDE2A (89% identity). TbPDE2B has substrate specificity for cAMP with a Km of 2.4 μM. cGMP is not hydrolyzed by TbPDE2B nor does this cyclic nucleotide modulate cAMP PDE activity. The nonselective PDE inhibitors 3-isobutyl-1-methylxanthine, papaverine and pentoxifyline are poor inhibitors of TbPDE2B. Similarly, PDE inhibitors selective for the mammalian PDE families 2, 3, 5, and 6 (erythro-9-[3-(2-hydroxynonyl)]-adenine, enoximone, zaprinast, and sildenafil) were also unable to inhibit this enzyme. However, dipyridamole was a reasonably good inhibitor of this enzyme with an IC50 of 27 μM. cAMP plays key roles in cell growth and differentiation in this parasite, and PDEs are responsible for the hydrolysis of this important second messenger. Therefore, parasite PDEs, including this one, have the potential to be attractive targets for selective drug design. PMID:11930017

Flame Acceleration and Transition to Detonation in High-Speed Turbulent Combustion

DTIC Science & Technology

2016-12-21

Turbulent Combustion 1. Introduction to the Challenge Problem The importance of high-speed t urbulent combustion of gas mixtures and sprays is dif...engines, gas turbines, various types of jet engines, and some rocket engines . On the other hand , preventing high-speed combustion is critical for...the safety of any human activities that involve handling of po- t entially explosive gases or volatile liquids . Thus, the development of more fuel

Theoretical analysis of rotating two phase detonation in a rocket motor

NASA Technical Reports Server (NTRS)

Shen, I.; Adamson, T. C., Jr.

1973-01-01

Tangential mode, non-linear wave motion in a liquid propellant rocket engine is studied, using a two phase detonation wave as the reaction model. Because the detonation wave is followed immediately by expansion waves, due to the side relief in the axial direction, it is a Chapman-Jouguet wave. The strength of this wave, which may be characterized by the pressure ratio across the wave, as well as the wave speed and the local wave Mach number, are related to design parameters such as the contraction ratio, chamber speed of sound, chamber diameter, propellant injection density and velocity, and the specific heat ratio of the burned gases. In addition, the distribution of flow properties along the injector face can be computed. Numerical calculations show favorable comparison with experimental findings. Finally, the effects of drop size are discussed and a simple criterion is found to set the lower limit of validity of this strong wave analysis.

Pharmacophore Based Virtual Screening Approach to Identify Selective PDE4B Inhibitors

PubMed Central

Gaurav, Anand; Gautam, Vertika

2017-01-01

Phosphodiesterase 4 (PDE4) has been established as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B subtype selective inhibitors are known to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. This makes the development of PDE4B subtype selective inhibitors a desirable research goal. To achieve this goal, ligand based pharmacophore modeling approach is employed. Separate pharmacophore hypotheses for PDE4B and PDE4D inhibitors were generated using HypoGen algorithm and 106 PDE4 inhibitors from literature having thiopyrano [3,2-d] Pyrimidines, 2-arylpyrimidines, and triazines skeleton. Suitable training and test sets were created using the molecules as per the guidelines available for HypoGen program. Training set was used for hypothesis development while test set was used for validation purpose. Fisher validation was also used to test the significance of the developed hypothesis. The validated pharmacophore hypotheses for PDE4B and PDE4D inhibitors were used in sequential virtual screening of zinc database of drug like molecules to identify selective PDE4B inhibitors. The hits were screened for their estimated activity and fit value. The top hit was subjected to docking into the active sites of PDE4B and PDE4D to confirm its selectivity for PDE4B. The hits are proposed to be evaluated further using in-vitro assays. PMID:29201082

Existence and Optimality Conditions for Risk-Averse PDE-Constrained Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kouri, Drew Philip; Surowiec, Thomas M.

Uncertainty is ubiquitous in virtually all engineering applications, and, for such problems, it is inadequate to simulate the underlying physics without quantifying the uncertainty in unknown or random inputs, boundary and initial conditions, and modeling assumptions. Here in this paper, we introduce a general framework for analyzing risk-averse optimization problems constrained by partial differential equations (PDEs). In particular, we postulate conditions on the random variable objective function as well as the PDE solution that guarantee existence of minimizers. Furthermore, we derive optimality conditions and apply our results to the control of an environmental contaminant. Lastly, we introduce a new riskmore » measure, called the conditional entropic risk, that fuses desirable properties from both the conditional value-at-risk and the entropic risk measures.« less

Existence and Optimality Conditions for Risk-Averse PDE-Constrained Optimization

DOE PAGES

Kouri, Drew Philip; Surowiec, Thomas M.

2018-06-05

Uncertainty is ubiquitous in virtually all engineering applications, and, for such problems, it is inadequate to simulate the underlying physics without quantifying the uncertainty in unknown or random inputs, boundary and initial conditions, and modeling assumptions. Here in this paper, we introduce a general framework for analyzing risk-averse optimization problems constrained by partial differential equations (PDEs). In particular, we postulate conditions on the random variable objective function as well as the PDE solution that guarantee existence of minimizers. Furthermore, we derive optimality conditions and apply our results to the control of an environmental contaminant. Lastly, we introduce a new riskmore » measure, called the conditional entropic risk, that fuses desirable properties from both the conditional value-at-risk and the entropic risk measures.« less

Partial reconstitution of photoreceptor cGMP phosphodiesterase characteristics in cGMP phosphodiesterase-5.

PubMed

Granovsky, A E; Artemyev, N O

2001-06-15

Photoreceptor cGMP phosphodiesterases (PDE6) are uniquely qualified to serve as effector enzymes in the vertebrate visual transduction cascade. In the dark-adapted photoreceptors, the activity of PDE6 is blocked via tight association with the inhibitory gamma-subunits (Pgamma). The Pgamma block is removed in the light-activated PDE6 by the visual G protein, transducin. Transducin-activated PDE6 exhibits an exceptionally high catalytic rate of cGMP hydrolysis ensuring high signal amplification. To identify the structural determinants for the inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related cyclic GMP-specific, cGMP-binding PDE. PDE5 is insensitive to Pgamma and has a more than 100-fold lower k(cat) for cGMP hydrolysis. Our mutational analysis of chimeric PDE5/PDE6alpha' enzymes revealed that the inhibitory interaction of cone PDE6 catalytic subunits (PDE6alpha') with Pgamma is mediated primarily by three hydrophobic residues at the entry to the catalytic pocket, Met(758), Phe(777), and Phe(781). The maximal catalytic rate of PDE5 was enhanced by at least 10-fold with substitutions of PDE6alpha'-specific glycine residues for the corresponding PDE5 alanine residues, Ala(608) and Ala(612). The Gly residues are adjacent to the highly conserved metal binding motif His-Asn-X-X-His, which is essential for cGMP hydrolysis. Our results suggest that the unique Gly residues allow the PDE6 metal binding site to adopt a more favorable conformation for cGMP hydrolysis.

Phosphodiesterase 4 regulates the migration of B16-F10 melanoma cells.

PubMed

Watanabe, Yoshihiro; Murata, Taku; Shimizu, Kasumi; Morita, Hiroshi; Inui, Madoka; Tagawa, Toshiro

2012-08-01

Phosphodiesterases (PDEs) are important regulators of signal transduction processes. Eleven PDE gene families (PDE1-11) have been identified and several PDE isoforms are selectively expressed in various cell types. PDE4 family members specifically hydrolyze cyclic AMP (cAMP). Four genes (PDE4A-D) are known to encode PDE4 enzymes, with additional diversity generated by the use of alternative mRNA splicing and the use of different promoters. While PDE4 selective inhibitors show therapeutic potential for treating major diseases such as asthma and chronic obstructive pulmonary disease, little is known concerning the role of PDE4 in malignant melanoma. In this study, we examined the role of PDE4 in mouse B16-F10 melanoma cells. In these cells, PDE4 activity was found to be ∼60% of total PDE activity. RT-PCR detected only PDE4B and PDE4D mRNA. Cell growth was inhibited by the cAMP analog, 8-bromo-cAMP, but not by the specific PDE4 inhibitors, rolipram and denbufylline, which increased intracellular cAMP concentrations. Finally, migration of the B16-F10 cells was inhibited by the PDE4 inhibitors and 8-bromo-cAMP, while migration was increased by a protein kinase A (PKA) inhibitor, PKI(14-22), and was not affected by 8-pCPT-2'-O-Me-cAMP, which is an analog of exchange protein activated by cAMP (Epac). The inhibitory effect of rolipram on migration was reversed by PKI(14-22). Based on these results, PDE4 appears to play an important role in the migration of B16-F10 cells, and therefore may be a novel target for the treatment of malignant melanoma.

Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains.

PubMed

Muradov, Khakim G; Granovsky, Alexey E; Schey, Kevin L; Artemyev, Nikolai O

2002-03-26

Retinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vertebrate visual transduction cascade. The activity of PDE6 catalytic subunits is controlled by the Pgamma-subunits. In addition to the inhibition of cGMP hydrolysis at the catalytic sites, Pgamma is known to stimulate a noncatalytic binding of cGMP to the regulatory GAFa-GAFb domains of PDE6. The latter role of Pgamma has been attributed to its polycationic region. To elucidate the structural basis for the regulation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to the polycationic region of Pgamma, Pgamma-21-45, was specifically cross-linked to rod PDE6alphabeta. The site of Pgamma-21-45 cross-linking was localized to Met138Gly139 within the PDE6alpha GAFa domain using mass spectrometric analysis. Chimeras between PDE5 and cone PDE6alpha', containing GAFa and/or GAFb domains of PDE6alpha' have been generated to probe a potential role of the GAFb domains in binding to Pgamma. Analysis of the inhibition of the PDE5/PDE6alpha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with Pgamma. Our results suggest that a direct binding of the polycationic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGMP-binding sites.

Initiation of Gaseous Detonation by Conical Projectiles

NASA Astrophysics Data System (ADS)

Verreault, Jimmy

Initiation and stabilization of detonation by hypersonic conical projectiles launched into combustible gas mixtures is investigated. This phenomenon must be understood for the design and optimization of specific hypersonic propulsion devices, such as the oblique detonation wave engine and the ram accelerator. The criteria for detonation initiation by a projectile is also related to fundamental aspects of detonation research, such as the requirement for direct initiation of a detonation by a blast wave. Experimental results of this problem also offer useful references for validation of numerical and theoretical modeling. Projectiles with cone half angles varying from 15° to 60° were launched into stoichiometric mixtures of hydrogen/oxygen with 70% argon dilution at initial pressures between 10 and 200 kPa. The projectiles were launched from a combustion-driven gas gun at velocities up to 2.2 km/s (corresponding to 133% of the Chapman Jouguet velocity). Pictures of the flowfields generated by the projectiles were taken via Schlieren photography. Five combustion regimes were observed about the projectile ranging from prompt and delayed oblique detonation wave formation, combustion instabilities, a wave splitting, and an inert shock wave. Two types of transition from the prompt oblique detonation wave regime to the inert shock regime were observed. The first (the delayed oblique detonation wave regime) showed an inert shock attached to the tip of the projectile followed by a sharp kink at the onset of an oblique detonation wave; this regime occurred by decreasing the cone angle at high mixture pressures. The second (the combustion instabilities regime) exhibited large density gradients due to combustion ignition and quenching phenomena; this regime occurred by decreasing the mixture pressure at large cone angles. A number of theoretical models were considered to predict critical conditions for the initiation of oblique detonations. The Lee-Vasiljev model agreed qualitatively well with the experimental results for relatively blunt projectiles (cone half-angle larger than 35°) and low mixture pressures (lower than 100 kPa). The trend of the critical Damköhler number calculated along the projectile cone surface was similar to that of the experimental results for slender cones (cone half-angles lower 35°) and high mixture pressures (higher than 100 kPa). Steady 2D simulations of reacting flows over finite wedges using the method of characteristics with a one-step Arrhenius chemical reaction model reproduced the three regimes observed for direct initiation of a detonation: the subcritical, critical and supercritical regimes. It is shown that in order for a 2D wedge to be equivalent to the problem of blast initiation of a detonation (which is the essence of the Lee-Vasiljev model), the Mach number normal to the oblique shock needs to be greater than 50 and the wedge angle has to be smaller than 30°. Simulations of reacting flows over semi-infinite wedges and cones were validated with CFD results. Excellent agreement was reached between the angle of overdriven oblique detonations obtained from the simulations and those from a polar analysis. For wedge or cone angles equal or lower than the minimum angle for which an oblique detonation is attached (according to the polar analysis), a Chapman-Jouguet oblique detonation was initiated. In the conical configuration, the curvature around the cone axis allowed an oblique detonation to be self-sustained at an angle less than without the curvature effect. At larger activation energies, the initiation process of an oblique detonation wave at the tip of a semi-infinite wedge or cone was identified. Unsteady 2D computational simulations were also conducted and showed the cellular structure of an oblique detonation wave. Instabilities in the form of transverse shock waves along the oblique detonation front arise for large activation energies.

Hypersonic Inlet for a Laser Powered Propulsion System

NASA Astrophysics Data System (ADS)

Harrland, Alan; Doolan, Con; Wheatley, Vincent; Froning, Dave

2011-11-01

Propulsion within the lightcraft concept is produced via laser induced detonation of an incoming hypersonic air stream. This process requires suitable engine configurations that offer good performance over all flight speeds and angles of attack to ensure the required thrust is maintained. Stream traced hypersonic inlets have demonstrated the required performance in conventional hydrocarbon fuelled scramjet engines, and has been applied to the laser powered lightcraft vehicle. This paper will outline the current methodology employed in the inlet design, with a particular focus on the performance of the lightcraft inlet at angles of attack. Fully three-dimensional turbulent computational fluid dynamics simulations have been performed on a variety of inlet configurations. The performance of the lightcraft inlets have been evaluated at differing angles of attack. An idealized laser detonation simulation has also been performed to validate that the lightcraft inlet does not unstart during the laser powered propulsion cycle.

Targeted Ablation of the Pde6h Gene in Mice Reveals Cross-species Differences in Cone and Rod Phototransduction Protein Isoform Inventory*

PubMed Central

Brennenstuhl, Christina; Tanimoto, Naoyuki; Burkard, Markus; Wagner, Rebecca; Bolz, Sylvia; Trifunovic, Dragana; Kabagema-Bilan, Clement; Paquet-Durand, Francois; Beck, Susanne C.; Huber, Gesine; Seeliger, Mathias W.; Ruth, Peter; Wissinger, Bernd; Lukowski, Robert

2015-01-01

Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays a key role in the visual transduction cascade in rod and cone photoreceptors. Each type of photoreceptor utilizes discrete catalytic and inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. the degradation of cyclic guanosine-3′,5′-monophosphate at specifically tuned rates and kinetics. Recently, the human PDE6H gene was identified as a novel locus for autosomal recessive (incomplete) color blindness. However, the three different classes of cones were not affected to the same extent. Short wave cone function was more preserved than middle and long wave cone function indicating that some basic regulation of the PDE6 multisubunit enzyme was maintained albeit by a unknown mechanism. To study normal and disease-related functions of cone Pde6h in vivo, we generated Pde6h knock-out (Pde6h−/−) mice. Expression of PDE6H in murine eyes was restricted to both outer segments and synaptic terminals of short and long/middle cone photoreceptors, whereas Pde6h−/− retinae remained PDE6H-negative. Combined in vivo assessment of retinal morphology with histomorphological analyses revealed a normal overall integrity of the retinal organization and an unaltered distribution of the different cone photoreceptor subtypes upon Pde6h ablation. In contrast to human patients, our electroretinographic examinations of Pde6h−/− mice suggest no defects in cone/rod-driven retinal signaling and therefore preserved visual functions. To this end, we were able to demonstrate the presence of rod PDE6G in cones indicating functional substitution of PDE6. The disparities between human and murine phenotypes caused by mutant Pde6h/PDE6H suggest species-to-species differences in the vulnerability of biochemical and neurosensory pathways of the visual signal transduction system. PMID:25739440

Effects of PDE4 Pathway Inhibition in Rat Experimental Stroke

PubMed Central

Yang, Fan; Sumbria, Rachita K.; Xue, Dong; Yu, Chuanhui; He, Dan; Liu, Shuo; Paganini-Hill, Annlia; Fisher, Mark J.

2015-01-01

PURPOSE The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS Rats were subjected to either the ligation or embolic stroke model and treated with rolipram (3mg/kg; i.p.) prior to the ischemic insult. Similarly, the PDE4D knockout rats were subjected to experimental stroke using the embolic model. RESULTS Global inhibition of the PDE4 pathway using rolipram produced infarcts that were 225% (p<0.01) and 138% (p<0.05) of control in the ligation and embolic models, respectively. PDE4D knockout rats subjected to embolic stroke showed no change in infarct size compared to wild-type control. CONCLUSIONS Despite increase in infarct size after global inhibition of the PDE4 pathway with rolipram, specific inhibition of the PDE4D isoform had no effect on experimental stroke. These findings support a role for the PDE4 pathway, independent of the PDE4D isoform, in ischemic stroke pathogenesis. PMID:25224348

Mutation in rod PDE6 linked to congenital stationary night blindness impairs the enzyme inhibition by its gamma-subunit.

PubMed

Muradov, Khakim G; Granovsky, Alexey E; Artemyev, Nikolai O

2003-03-25

Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the vertebrate visual transduction cascade. The activity of rod PDE6 catalytic alpha- and beta-subunits is blocked in the dark by two inhibitory Pgamma-subunits. The inhibition is released upon light-stimulation of photoreceptor cells. Mutation H258N in PDE6beta has been linked to congenital stationary night blindness (CSNB) in a large Danish family (Rambusch pedigree) (Gal, A., Orth, U., Baehr, W., Schwinger, E., and Rosenberg, T. (1994) Nat. Genet. 7, 64-67.) We have analyzed the consequences of this mutation for PDE6 function using a Pgamma-sensitive PDE6alpha'/PDE5 chimera, Chi16. Biochemical analysis of the H257N mutant, an equivalent of PDE6betaH258N, demonstrates that this substitution does not alter the ability of chimeric PDE to dimerize or the enzyme's catalytic properties. The sensitivity of H257N to a competitive inhibitor zaprinast was also unaffected. However, the mutant displayed a significant impairment in the inhibitory interaction with Pgamma, which was apparent from a approximately 20-fold increase in the K(i) value (46 nM) and incomplete maximal inhibition. The inhibitory defect of H257N is not due to perturbation of noncatalytic cGMP binding to the PDE6alpha' GAF domains. The noncatalytic cGMP-binding characteristics of the H257N mutant were similar to those of the parent PDE6alpha'/PDE5 chimera. Since rod PDE6 in the Rambusch CSNB is a catalytic heterodimer of the wild-type PDE6alpha and mutant PDE6beta, Chi16 and H257N were coexpressed, and a heterodimeric PDE, Chi16/H257N, was isolated. It displayed two Pgamma inhibitory sites with the K(i) values of 5 and 57 nM. Our results support the hypothesis that mutation H258N in PDE6beta causes CSNB through incomplete inhibition of PDE6 activity by Pgamma, which leads to desensitization of rod photoreceptors.

AKAP3 Selectively Binds PDE4A Isoforms in Bovine Spermatozoa1

PubMed Central

Bajpai, Malini; Fiedler, Sarah E.; Huang, Zaohua; Vijayaraghavan, Srinivasan; Olson, Gary E.; Livera, Gabriel; Conti, Marco; Carr, Daniel W.

2006-01-01

Cyclic AMP plays an important role in regulating sperm motility and acrosome reaction through activation of cAMP-dependent protein kinase A (PKA). Phosphodiesterases (PDEs) modulate the levels of cyclic nucleotides by catalyzing their degradation. Although PDE inhibitors specific to PDE1 and PDE4 are known to alter sperm motility and capacitation in humans, little is known about the role or subcellular distribution of PDEs in spermatozoa. The localization of PKA is regulated by A-kinase anchoring proteins (AKAPs), which may also control the intracellular distribution of PDE. The present study was undertaken to investigate the role and localization of PDE4 during sperm capacitation. Addition of Rolipram or RS25344, PDE4-specific inhibitors significantly increased the progressive motility of bovine spermatozoa. Immunolocalization techniques detected both PDE4A and AKAP3 (formerly known as AKAP110) in the principal piece of bovine spermatozoa. The PDE4A5 isoform was detected primarily in the Triton X-100-soluble fraction of caudal epididymal spermatozoa. However, in ejaculated spermatozoa it was seen primarily in the SDS-soluble fraction, indicating a shift in PDE4A5 localization into insoluble organelles during sperm capacitation. AKAP3 was detected only in the SDS-soluble fraction of both caudal and ejaculated sperm. Immunoprecipitation experiments using COS cells cotransfected with AKAP3 and either Pde4a5 or Pde4d provide evidence that PDE4A5 but not PDE4D interacts with AKAP3. Pulldown assays using sperm cell lysates confirm this interaction in vitro. These data suggest that AKAP3 binds both PKA and PDE4A and functions as a scaffolding protein in spermatozoa to regulate local cAMP concentrations and modulate sperm functions. PMID:16177223

Estimating the magnitude of near-membrane PDE4 activity in living cells.

PubMed

Xin, Wenkuan; Feinstein, Wei P; Britain, Andrea L; Ochoa, Cristhiaan D; Zhu, Bing; Richter, Wito; Leavesley, Silas J; Rich, Thomas C

2015-09-15

Recent studies have demonstrated that functionally discrete pools of phosphodiesterase (PDE) activity regulate distinct cellular functions. While the importance of localized pools of enzyme activity has become apparent, few studies have estimated enzyme activity within discrete subcellular compartments. Here we present an approach to estimate near-membrane PDE activity. First, total PDE activity is measured using traditional PDE activity assays. Second, known cAMP concentrations are dialyzed into single cells and the spatial spread of cAMP is monitored using cyclic nucleotide-gated channels. Third, mathematical models are used to estimate the spatial distribution of PDE activity within cells. Using this three-tiered approach, we observed two pharmacologically distinct pools of PDE activity, a rolipram-sensitive pool and an 8-methoxymethyl IBMX (8MM-IBMX)-sensitive pool. We observed that the rolipram-sensitive PDE (PDE4) was primarily responsible for cAMP hydrolysis near the plasma membrane. Finally, we observed that PDE4 was capable of blunting cAMP levels near the plasma membrane even when 100 μM cAMP were introduced into the cell via a patch pipette. Two compartment models predict that PDE activity near the plasma membrane, near cyclic nucleotide-gated channels, was significantly lower than total cellular PDE activity and that a slow spatial spread of cAMP allowed PDE activity to effectively hydrolyze near-membrane cAMP. These results imply that cAMP levels near the plasma membrane are distinct from those in other subcellular compartments; PDE activity is not uniform within cells; and localized pools of AC and PDE activities are responsible for controlling cAMP levels within distinct subcellular compartments. Copyright © 2015 the American Physiological Society.

Kaempferia parviflora, a plant used in traditional medicine to enhance sexual performance contains large amounts of low affinity PDE5 inhibitors

PubMed Central

Temkitthawon, Prapapan; Hinds, Thomas R.; Beavo, Joseph A.; Viyoch, Jarupa; Suwanborirux, Khanit; Pongamornkul, Wittaya; Sawasdee, Pattara; Ingkaninan, Kornkanok

2014-01-01

Aim of the study A number of medicinal plants are used in traditional medicine to treat erectile dysfunction. Since cyclic nucleotide PDEs inhibitors underlie several current treatments for this condition, we sought to show whether these plants might contain substantial amounts of PDE5 inhibitors. Materials and methods Forty one plant extracts and eight 7-methoxyflavones from Kaempferia parviflora Wall. ex Baker were screened for PDE5 and PDE6 inhibitory activities using the two-step radioactive assay. The PDE5 and PDE6 were prepared from mice lung and chicken retinas, respectively. All plant extracts were tested at 50 μg/ml whereas the pure compounds were tested at 10 μM. Results From forty one plant extracts tested, four showed the PDE5 inhibitory effect. The chemical constituents isolated from rhizomes of Kaempferia parviflora were further investigated on inhibitory activity against PDE5 and PDE6. The results showed that 7-methoxyflavones from this plant showed inhibition toward both enzymes. The most potent PDE5 inhibitor was 5,7-dimethoxyflavone (IC50 = 10.64 ± 2.09 μM, selectivity on PDE5 over PDE6 = 3.71). Structure activity relationship showed that the methoxyl group at C-5 position of 7-methoxyflavones was necessary for PDE5 inhibition. Conclusions Kaempferia parviflora rhizome extract and its 7-methoxyflavone constituents had moderate inhibitory activity against PDE5. This finding provides an explanation for enhancing sexual performance in the traditional use of Kaempferia parviflora. Moreover, 5,7-dimethoxyflavones should make a useful lead compound to further develop clinically efficacious PDE5 inhibitors. PMID:21884777

Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior.

PubMed

Hansen, Rolf T; Conti, Marco; Zhang, Han-Ting

2014-08-01

Phosphodiesterases (PDEs) are a super family of enzymes responsible for the halting of intracellular cyclic nucleotide signaling and may represent novel therapeutic targets for treatment of cognitive disorders. PDE4 is of considerable interest to cognitive research because it is highly expressed in the brain, particularly in the cognition-related brain regions. Recently, the functional role of PDE4B and PDE4D, two of the four PDE4 subtypes (PDE4A, B, C, and D), in behavior has begun to be identified; however, the role of PDE4A in the regulation of behavior is still unknown. The purpose of this study was to characterize the functional role of PDE4A in behavior. The role of PDE4A in behavior was evaluated through a battery of behavioral tests using PDE4A knockout (KO) mice; urine corticosterone levels were also measured. PDE4A KO mice exhibited improved memory in the step-through-passive-avoidance test. They also displayed anxiogenic-like behavior in elevated-plus maze, holeboard, light-dark transition, and novelty suppressed feeding tests. Consistent with the anxiety profile, PDE4A KO mice had elevated corticosterone levels compared with wild-type controls post-stress. Interestingly, PDE4A KO mice displayed no change in object recognition, Morris water maze, forced swim, tail suspension, and duration of anesthesia induced by co-administration of xylazine and ketamine (suggesting that PDE4A KO may not be emetic). These results suggest that PDE4A may be important in the regulation of emotional memory and anxiety-like behavior, but not emesis. PDE4A could possibly represent a novel therapeutic target in the future for anxiety or disorders affecting memory.

A conformational switch in the inhibitory gamma-subunit of PDE6 upon enzyme activation by transducin.

PubMed

Granovsky, A E; Artemyev, N O

2001-11-06

In response to light, a photoreceptor G protein, transducin, activates cGMP-phosphodiesterase (PDE6) by displacing the inhibitory gamma-subunits (Pgamma) from the enzyme's catalytic sites. Evidence suggests that the activation of PDE6 involves a conformational change of the key inhibitory C-terminal domain of Pgamma. In this study, the C-terminal region of Pgamma, Pgamma-73-85, has been targeted for Ala-scanning mutagenesis to identify the point-to-point interactions between Pgamma and the PDE6 catalytic subunits and to probe the nature of the conformational change. Pgamma mutants were tested for their ability to inhibit PDE6 and a chimeric PDE5-conePDE6 enzyme containing the Pgamma C-terminus-binding site of cone PDE. This analysis has revealed that in addition to previously characterized Ile86 and Ile87, important inhibitory contact residues of Pgamma include Asn74, His75, and Leu78. The patterns of mutant PDE5-conePDE6 enzyme inhibition suggest the interaction between the PgammaAsn74/His75 sequence and Met758 of the cone PDE6alpha' catalytic subunit. This interaction, and the interaction between the PgammaIle86/Ile87 and PDE6alpha'Phe777/Phe781 residues, is most consistent with an alpha-helical structure of the Pgamma C-terminus. The analysis of activation of PDE6 enzymes containing Pgamma mutants with Ala-substituted transducin-contact residues demonstrated the critical role of PgammaLeu76. Accordingly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-alpha with PgammaLeu76. This interaction introduces a bend into the alpha-helical structure of the Pgamma C-terminus, allowing transducin-alpha to further twist the C-terminus thereby uncovering the catalytic pocket of PDE6.

Estimating the magnitude of near-membrane PDE4 activity in living cells

PubMed Central

Xin, Wenkuan; Feinstein, Wei P.; Britain, Andrea L.; Ochoa, Cristhiaan D.; Zhu, Bing; Richter, Wito; Leavesley, Silas J.

2015-01-01

Recent studies have demonstrated that functionally discrete pools of phosphodiesterase (PDE) activity regulate distinct cellular functions. While the importance of localized pools of enzyme activity has become apparent, few studies have estimated enzyme activity within discrete subcellular compartments. Here we present an approach to estimate near-membrane PDE activity. First, total PDE activity is measured using traditional PDE activity assays. Second, known cAMP concentrations are dialyzed into single cells and the spatial spread of cAMP is monitored using cyclic nucleotide-gated channels. Third, mathematical models are used to estimate the spatial distribution of PDE activity within cells. Using this three-tiered approach, we observed two pharmacologically distinct pools of PDE activity, a rolipram-sensitive pool and an 8-methoxymethyl IBMX (8MM-IBMX)-sensitive pool. We observed that the rolipram-sensitive PDE (PDE4) was primarily responsible for cAMP hydrolysis near the plasma membrane. Finally, we observed that PDE4 was capable of blunting cAMP levels near the plasma membrane even when 100 μM cAMP were introduced into the cell via a patch pipette. Two compartment models predict that PDE activity near the plasma membrane, near cyclic nucleotide-gated channels, was significantly lower than total cellular PDE activity and that a slow spatial spread of cAMP allowed PDE activity to effectively hydrolyze near-membrane cAMP. These results imply that cAMP levels near the plasma membrane are distinct from those in other subcellular compartments; PDE activity is not uniform within cells; and localized pools of AC and PDE activities are responsible for controlling cAMP levels within distinct subcellular compartments. PMID:26201952

cAMP-specific PDE4 Phosphodiesterases and AIP in the Pathogenesis of Pituitary Tumors

PubMed Central

Bolger, Graeme B.; Bizzi, Mariana Ferreira; Brant Pinheiro, Sergio Veloso; Trivellin, Giampaolo; Smoot, Lisa; Accavitti, Mary-Ann; Korbonits, Márta; Ribeiro-Oliveira, Antonio

2016-01-01

PDE4 cyclic nucleotide phosphodiesterases regulate cAMP abundance in cells and thereby regulate numerous processes, including cell growth and differentiation. The rat PDE4A5 isoform (human homologue PDE4A4) interacts with the AIP protein (also called XAP2 or ARA-9). Germline mutations in AIP occur in approximately 20% of patients with Familial Isolated Pituitary Adenoma (FIPA) and 20% of childhood-onset simplex somatotroph adenomas. We therefore examined the protein expression of PDE4A4 and the closely-related isoform PDE4A8 in normal human pituitary tissue and in pituitary adenomas. PDE4A4 had low expression in normal pituitary, but was significantly over-expressed in somatotroph, lactotroph, corticotroph and clinically non-functioning gonadotroph adenomas (P<0.0001 for all subtypes). Likewise, PDE4A8 was expressed in normal pituitary and was also significantly over-expressed in the adenoma subtypes (P<0.0001 for all). Among the different adenoma subtypes, corticotroph and lactotroph adenomas were the highest and lowest expressed for PDE4A4, respectively, whereas the opposite was observed for PDE4A8. Naturally occurring oncogenic variants in AIP were shown by a two-hybrid assay to disrupt the ability of AIP to interact with PDE4A5. A reverse-two-hybrid screen identified numerous additional variants in the TPR region of AIP that also disrupted its ability to interact with PDE4A5. The expression of PDE4A4 and PDE4A8 in normal pituitary, their increased expression in adenomatous pituitary cells where AIP is meant to participate, and the disruption of the PDE4A4-AIP interaction by AIP mutants may play a role in pituitary tumorigenesis. PMID:27267386

Optical limiting in suspension of detonation nanodiamonds in engine oil

NASA Astrophysics Data System (ADS)

Mikheev, Konstantin G.; Krivenkov, Roman Yu.; Mogileva, Tatyana N.; Puzyr, Alexey P.; Bondar, Vladimir S.; Bulatov, Denis L.; Mikheev, Gennady M.

2017-07-01

The optical limiting (OL) of detonation nanodiamond (DND) suspensions in engine oil was studied at a temperature range of 20°C to 100°C. Oil suspensions were prepared on the basis of the DNDs with an average nanoparticle cluster size in hydrosols (Daver) of 50 and 110 nm. Raman spectroscopy was used to characterize the samples. The OL investigation was carried out by the z-scan technique. The fundamental (1064 nm) and second (532 nm) harmonic radiations of YAG:Nd3+ laser with passive Q-switching as an excitation source were used. The OL thresholds for both suspensions at 532 and 1064 nm were determined. It is shown that a decrease in the average nanoparticle cluster size as well as an increase of the wavelength of the incident radiation leads to the OL threshold increase. It is established that the OL performance is not influenced by increasing the temperature from 20°C to 100°C. The results obtained show the possibility of using the DNDs suspensions in engine oil as an optical limiter in a wide temperature range.

Quasi-One-Dimensional Modeling of Pulse Detonation Rocket Engines

NASA Technical Reports Server (NTRS)

Morris, Christopher I.

2002-01-01

Pulsed detonation rocket engines (PDREs) have generated considerable research interest in recent years as a chemical propulsion system potentially offering improved performance and reduced complexity compared to conventional rocket engines. The detonative mode of combustion employed by these devices offers a thermodynamic advantage over the constant-pressure deflagrative combustion mode used in conventional rocket engines and gas turbines. However, while this theoretical advantage has spurred a great deal of interest in building PDRE devices, the unsteady blowdown process intrinsic to the PDRE has made realistic estimates of the actual propulsive performance problematic. The recent review article by Kailasanath highlights some of the difficulties in comparing the available experimental measurements with numerical models. In a previous paper by the author, parametric studies of the performance of a single, straight-tube PDRE were reported. A 1-D, unsteady method of characteristics code, employing a constant-gamma assumption behind the detonation front, was developed for that study. Models of this type are computationally inexpensive, and are particularly useful for parametric performance comparisons. For example, a plot showing the specific impulse of various PDRE and steady-state rocket engine (SSRE) configurations as a function of blowdown pressure ratio. The performance curves clearly indicate that a straight-tube PDRE is superior in specific impulse to a SSRE with a sonic nozzle over the entire range of pressure ratios. Note, however, that a straight-tube PDRE in general does not compare favorably to a SSRE fitted with an optimized de Laval supersonic nozzle, particularly at the high pressure ratios typical for boost or in-space rocket applications. However, the calculations also show that if a dynamically optimized, supersonic de Laval nozzle could be could be fitted to a PDRE, then the specific impulse of the device would exceed that of a comparable SSRE. While such a nozzle is a considerable idealization, it is clear that nozzle design and optimization will play a critical role in whether the performance potential of PDREs can be effectively realized in practice. In order to study PDRE nozzle issues with greater accuracy, a quasi-one-dimensional, finite-rate chemistry CFD code has been developed by the author. Comparisons of the code with both the previous MOC model and experimental data from Stanford University are reported. The effect of constant-gamma and finite-rate chemistry assumptions on the flowfield and performance is examined. Parametric studies of the effect of nozzle throat size and expansion ratio, at various blowdown pressure ratios, are reported.

A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood

PubMed Central

Kelly, Michy P.

2017-01-01

The most recently discovered 3′,5′-cyclic nucleotide phosphodiesterase family is the Phosphodiesterase 11 (PDE11) family, which is encoded by a single gene PDE11A. PDE11A is a dual-specific PDE, breaking down both cAMP and cGMP. There are four PDE11A splice variants (PDE11A1–4) with distinct tissue expression profiles and unique N-terminal regulatory regions, suggesting that each isoform could be individually targeted with a small molecule or biologic. PDE11A4 is the PDE11A isoform expressed in brain and is found in the hippocampal formation of humans and rodents. Studies in rodents show that PDE11A4 mRNA expression in brain is, in fact, restricted to the hippocampal formation (CA1, possibly CA2, subiculum, and the adjacently connected amygdalohippocampal area). Within the hippocampal formation of rodents, PDE11A4 protein is expressed in neurons but not astrocytes, with a distribution across nuclear, cytoplasmic, and membrane compartments. This subcellular localization of PDE11A4 is altered in response to social experience in mouse, and in vitro studies show the compartmentalization of PDE11A4 is controlled, at least in part, by homodimerization and N-terminal phosphorylation. PDE11A4 expression dramatically increases in the hippocampus with age in the rodent hippocampus, from early postnatal life to late aging, suggesting PDE11A4 function may evolve across the lifespan. Interestingly, PDE11A4 protein shows a 3–10-fold enrichment in the rodent ventral hippocampal formation (VHIPP; a.k.a. anterior in primates) versus dorsal hippocampal formation (DHIPP). Consistent with this enrichment in VHIPP, studies in knockout mice show that PDE11A regulates the formation of social memories and the stabilization of mood and is a critical mechanism by which social experience feeds back to modify the brain and subsequent social behaviors. PDE11A4 likely controls behavior by regulating hippocampal glutamatergic, oxytocin, and cytokine signaling, as well as protein translation. Given its unique tissue distribution and relatively selective effects on behavior, PDE11A may represent a novel therapeutic target for neuropsychiatric, neurodevelopmental, or age-related disorders. Therapeutically targeting PDE11A4 may be a way to selectively restore aberrant cyclic nucleotide signaling in the hippocampal formation while leaving the rest of the brain and periphery untouched, thus, relieving deficits while avoiding unwanted side effects. PMID:28956334

Innovative Technology Development for Comprehensive Air Quality Characterization from Open Burning

DTIC Science & Technology

2012-04-01

Burning/Open Detonation (OB/OD) has been used as a safe, effective , and economic way to demilitarize munitions for energetic material disposal. Field...target analyte i (lb/lb i in ordnance) ERDC-CERL Engineer Research Development Center, Construction Engineering Research Laboratory GC/FID gas ...chromatograph(y) - flame ionization detector GC/MS gas chromatography/mass spectrometry GPS global positioning system ISO International Organization for

Catecholic amides as potential selective phosphodiesterase 4D inhibitors: Design, synthesis, pharmacological evaluation and structure-activity relationships.

PubMed

Zhou, Zhong-Zhen; Ge, Bing-Chen; Chen, Yu-Fang; Shi, Xiu-Dong; Yang, Xue-Mei; Xu, Jiang-Ping

2015-11-15

In this study, a series of catechol-based amides (8a-n) with different amide linkers linking the catecholic moiety to the terminal phenyl ring was designed and synthesized as potent phosphodiesterase (PDE) 4D inhibitors. The inhibitory activities of these compounds were evaluated against the core catalytic domains of human PDE4 (PDE4CAT), full-length PDE4B1 and PDE4D7 enzymes, and other PDE family members. The results indicated the majority of compounds 8a-n displayed moderate to good inhibitory activities against PDE4CAT. Among these compounds, compound 8 j with a short amide linker (-CONHCH2-) displayed comparable PDE4CAT inhibitory activity (IC50=410 nM) with rolipram. More interestingly, compound 8 g, a potent and selective PDE4D inhibitor (IC50=94 nM), exhibited a 10-fold selectivity over the PDE4B subtypes and an over 1000-fold selectivity against other PDE family members. Docking simulations suggested that 8 g forms three extra H-bonds with the N-H of residue Asn487 and two water molecules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Myocardial Response to Milrinone in Single Right Ventricle Heart Disease.

PubMed

Nakano, Stephanie J; Nelson, Penny; Sucharov, Carmen C; Miyamoto, Shelley D

2016-07-01

Empiric treatment with milrinone, a phosphodiesterase (PDE) 3 inhibitor, has become increasingly common in patients with single ventricle heart disease of right ventricular (RV) morphology (SRV); our objective was to characterize the myocardial response to PDE3 inhibition (PDE3i) in the pediatric population with SRV. Cyclic adenosine monophosphate levels, PDE activity, and phosphorylated phospholamban (PLN) were determined in explanted human ventricular myocardium from nonfailing pediatric donors (n = 10) and pediatric patients transplanted secondary to SRV. Subjects with SRV were further classified by PDE3i treatment (n = 13 with PDE3i and n = 12 without PDE3i). In comparison with nonfailing RV myocardium (n = 8), cyclic adenosine monophosphate levels are lower in patients with SRV treated with PDE3i (n = 12, P = .021). Chronic PDE3i does not alter total PDE or PDE3 activity in SRV myocardium. Compared with nonfailing RV myocardium, SRV myocardium (both with and without PDE3i) demonstrates equivalent phosphorylated PLN at the protein kinase A phosphorylation site. As evidenced by preserved phosphorylated PLN, the molecular adaptation associated with SRV differs significantly from that demonstrated in pediatric heart failure because of dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of heart failure in pediatric patients with SRV, which has direct implications regarding the presumed response to PDE3i treatment in this population. Copyright © 2016 Elsevier Inc. All rights reserved.

Experimental study on incident wave speed and the mechanisms of deflagration-to-detonation transition in a bent geometry

NASA Astrophysics Data System (ADS)

Li, L.; Li, J.; Teo, C. J.; Chang, P. H.; Khoo, B. C.

2018-03-01

The study of deflagration-to-detonation transition (DDT) in bent tubes is important with many potential applications including fuel pipeline and mine tunnel designs for explosion prevention and detonation engines for propulsion. The aim of this study is to exploit low-speed incident shock waves for DDT using an S-shaped geometry and investigate its effectiveness as a DDT enhancement device. Experiments were conducted in a valveless detonation chamber using ethylene-air mixture at room temperature and pressure (303 K, 1 bar). High-speed Schlieren photography was employed to keep track of the wave dynamic evolution. Results showed that waves with velocity as low as 500 m/s can experience a successful DDT process through this S-shaped geometry. To better understand the mechanism, clear images of local explosion processes were captured in either the first curved section or the second curved section depending on the inlet wave velocity, thus proving that this S-shaped tube can act as a two-stage device for DDT. Owing to the curved wall structure, the passing wave was observed to undergo a continuous compression phase which could ignite the local unburnt mixture and finally lead to a local explosion and a detonation transition. Additionally, the phenomenon of shock-vortex interaction near the wave diffraction region was also found to play an important role in the whole process. It was recorded that this interaction could not only result in local head-on reflection of the reflected wave on the wall that could ignite the local mixture, and it could also contribute to the recoupling of the shock-flame complex when a detonation wave is successfully formed in the first curved section.

Role of Ca2+/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophy

PubMed Central

Miller, Clint L.; Oikawa, Masayoshi; Cai, Yujun; Wojtovich, Andrew P.; Nagel, David J.; Xu, Xiangbin; Xu, Haodong; Florio, Vince; Rybalkin, Sergei D.; Beavo, Joseph A.; Chen, Yiu-Fai; Li, Jian-Dong; Blaxall, Burns C.; Abe, Jun-ichi; Yan, Chen

2009-01-01

Rationale Cyclic nucleotide phosphodiesterases (PDE) through the degradation of second messenger cyclic guanosine monophosphate (cGMP) play critical roles in maintaining cardiomyocyte homeostasis. Ca2+/CaM-activated cGMP-hydrolyzing PDE1 family may play a pivotal role in balancing intracellular Ca2+/CaM and cGMP signaling, however its function in cardiomyocytes is unknown. Objective Herein we investigate the role of Ca2+/CaM-stimulated PDE1 in regulating pathological cardiomyocyte hypertrophy in neonatal and adult rat ventricular myocytes (NRVM and ARVM) and in the heart in vivo. Methods and Results Inhibition of PDE1 activity using a PDE1 selective inhibitor IC86340 or downregulation of PDE1A using siRNA prevented phenylephrine (PE) induced pathological myocyte hypertrophy and hypertrophic marker expression in neonatal (NRVM) and adult (ARVM) rat ventricular myocytes. Importantly, administration of the PDE1 inhibitor IC86340 attenuated cardiac hypertrophy induced by chronic ISO infusion in vivo. Both PDE1A and PDE1C mRNA and protein were detected in human hearts, however PDE1A expression was conserved in rodent hearts. Moreover, PDE1A expression was significantly upregulated in vivo in the heart and myocytes from various pathological hypertrophy animal models and in vitro in isolated NRVM and ARVM treated with neurohumoral stimuli such as angiotensin II (Ang II) and ISO. Further, PDE1A plays a critical role in PE-induced reduction of intracellular cGMP and PKG activity, and thereby cardiomyocyte hypertrophy in vitro. Conclusions These results elucidate a novel role for Ca2+/CaM-stimulated PDE1, particularly PDE1A, in regulating pathological cardiomyocyte hypertrophy via a cGMP/PKG-dependent mechanism, thereby demonstrating Ca2+ and cGMP signaling cross-talk during cardiac hypertrophy. PMID:19797176

MYOCARDIAL RESPONSE TO MILRINONE IN SINGLE RIGHT VENTRICLE HEART DISEASE

PubMed Central

Nakano, Stephanie J.; Nelson, Penny; Sucharov, Carmen C.; Miyamoto, Shelley D.

2016-01-01

Objectives Empiric treatment with milrinone, a phosphodiesterase 3 inhibitor (PDE3i), has become increasingly common in patients with single ventricle heart disease of right ventricular morphology (SRV); our objective was to characterize the myocardial response to PDE3i in the pediatric population with SRV. Study design Cyclic adenosine monophosphate (cAMP) levels, phosphodiesterase (PDE) activity, and phospholamban phosphorylation (pPLN) were determined in explanted human ventricular myocardium from nonfailing pediatric donors (n=10) and pediatric patients transplanted secondary to SRV. SRV subjects were further classified by PDE3i treatment (n=13 with PDE3i and n=12 without PDE3i). Results In comparison with nonfailing RV myocardium, cAMP levels are lower in patients with SRV treated with PDE3i (p=0.021). Chronic PDE3i does not alter total PDE or PDE3 activity in SRV myocardium. When compared with nonfailing RV myocardium, SRV myocardium (both with and without PDE3i) demonstrates equivalent pPLN at the protein kinase A phosphorylation site. Conclusions As evidenced by preserved pPLN, the molecular adaptation associated with SRV differs significantly from that demonstrated in pediatric heart failure due to dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of heart failure in pediatric patients with SRV, which has direct implications regarding the presumed response to PDE3i treatment in this population. PMID:27181939

Three-dimensional numerical simulation of a continuously rotating detonation in the annular combustion chamber with a wide gap and separate delivery of fuel and oxidizer

NASA Astrophysics Data System (ADS)

Frolov, S. M.; Dubrovskii, A. V.; Ivanov, V. S.

2016-07-01

The possibility of integrating the Continuous Detonation Chamber (CDC) in a gas turbine engine (GTE) is demonstrated by means of three-dimensional (3D) numerical simulations, i. e., the feasibility of the operation process in the annular combustion chamber with a wide gap and with separate feeding of fuel (hydrogen) and oxidizer (air) is proved computationally. The CDC with an upstream isolator damping pressure disturbances propagating towards the compressor is shown to exhibit a gain in the total pressure of 15% as compared with the same combustion chamber operating in the deflagration mode.

Lectures on combustion theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burstein, S.Z.; Lax, P.D.; Sod, G.A.

1978-09-01

Eleven lectures are presented on mathematical aspects of combustion: fluid dynamics, deflagrations and detonations, chemical kinetics, gas flows, combustion instability, flame spread above solids, spark ignition engines, burning rate of coal particles and hydrocarbon oxidation. Separate abstracts were prepared for three of the lectures. (DLC)

PDE4 as a target for cognition enhancement

PubMed Central

Richter, Wito; Menniti, Frank S.; Zhang, Han-Ting; Conti, Marco

2014-01-01

Introduction The second messengers cAMP and cGMP mediate fundamental aspects of brain function relevant to memory, learning and cognitive functions. Consequently, cyclic nucleotide phosphodiesterases (PDEs), the enzymes that inactivate the cyclic nucleotides, are promising targets for the development of cognition-enhancing drugs. Areas covered PDE4 is the largest of the eleven mammalian PDE families. This review covers the properties and functions of the PDE4 family, highlighting procognitive and memory-enhancing effects associated with their inactivation. Expert opinion PAN-selective PDE4 inhibitors exert a number of memory- and cognition-enhancing effects and have neuroprotective and neuroregenerative properties in preclinical models. The major hurdle for their clinical application is to target inhibitors to specific PDE4 isoforms relevant to particular cognitive disorders to realize the therapeutic potential while avoiding side effects, in particular emesis and nausea. The PDE4 family comprises four genes, PDE4A-D, each expressed as multiple variants. Progress to date stems from characterization of rodent models with selective ablation of individual PDE4 subtypes, revealing that individual subtypes exert unique and non-redundant functions in the brain. Thus, targeting specific PDE4 subtypes, as well as splicing variants or conformational states, represents a promising strategy to separate the therapeutic benefits from the side effects of PAN-PDE4 inhibitors. PMID:23883342

Shock wave physics and detonation physics — a stimulus for the emergence of numerous new branches in science and engineering

NASA Astrophysics Data System (ADS)

Krehl, Peter O. K.

2011-07-01

In the period of the Cold War (1945-1991), Shock Wave Physics and Detonation Physics (SWP&DP) — until the beginning of WWII mostly confined to gas dynamics, high-speed aerodynamics, and military technology (such as aero- and terminal ballistics, armor construction, chemical explosions, supersonic gun, and other firearms developments) — quickly developed into a large interdisciplinary field by its own. This rapid expansion was driven by an enormous financial support and two efficient feedbacks: the Terminal Ballistic Cycleand the Research& Development Cycle. Basic knowledge in SWP&DP, initially gained in the Classic Period(from 1808) and further extended in the Post-Classic Period(from the 1930s to present), is now increasingly used also in other branches of Science and Engineering (S&E). However, also independent S&E branches developed, based upon the fundamentals of SWP&DP, many of those developments will be addressed (see Tab. 2). Thus, shock wave and detonation phenomena are now studied within an enormous range of dimensions, covering microscopic, macroscopic, and cosmic dimensions as well as enormous time spans ranging from nano-/picosecond shock durations (such as produced by ultra-short laser pulses) to shock durations that continue for centuries (such as blast waves emitted from ancient supernova explosions). This paper reviews these developments from a historical perspective.

Homology modeling, docking studies and molecular dynamic simulations using graphical processing unit architecture to probe the type-11 phosphodiesterase catalytic site: a computational approach for the rational design of selective inhibitors.

PubMed

Cichero, Elena; D'Ursi, Pasqualina; Moscatelli, Marco; Bruno, Olga; Orro, Alessandro; Rotolo, Chiara; Milanesi, Luciano; Fossa, Paola

2013-12-01

Phosphodiesterase 11 (PDE11) is the latest isoform of the PDEs family to be identified, acting on both cyclic adenosine monophosphate and cyclic guanosine monophosphate. The initial reports of PDE11 found evidence for PDE11 expression in skeletal muscle, prostate, testis, and salivary glands; however, the tissue distribution of PDE11 still remains a topic of active study and some controversy. Given the sequence similarity between PDE11 and PDE5, several PDE5 inhibitors have been shown to cross-react with PDE11. Accordingly, many non-selective inhibitors, such as IBMX, zaprinast, sildenafil, and dipyridamole, have been documented to inhibit PDE11. Only recently, a series of dihydrothieno[3,2-d]pyrimidin-4(3H)-one derivatives proved to be selective toward the PDE11 isoform. In the absence of experimental data about PDE11 X-ray structures, we found interesting to gain a better understanding of the enzyme-inhibitor interactions using in silico simulations. In this work, we describe a computational approach based on homology modeling, docking, and molecular dynamics simulation to derive a predictive 3D model of PDE11. Using a Graphical Processing Unit architecture, it is possible to perform long simulations, find stable interactions involved in the complex, and finally to suggest guideline for the identification and synthesis of potent and selective inhibitors. © 2013 John Wiley & Sons A/S.

ASTER Images Flooding from Mississippi River Levee Breach

NASA Image and Video Library

2011-05-10

NASA Terra spacecraft shows the resultant flooding of farmland west of the Mississippi 20 miles south of the Mississippi River levee breach. U.S. Army Corps of Engineers detonated explosives at the Birds Point levee near Wyatt, Missouri, on May 2, 2011.

Evaluation of the effect of phosphodiesterase on equine platelet activation and the effect of antigen challenge on platelet phosphodiesterase activity in horses with recurrent airway obstruction.

PubMed

Dunkel, Bettina; Rickards, Karen J; Werling, Dirk; Page, Clive P; Cunningham, Fiona M

2010-05-01

To determine whether expression of equine platelet activation-dependent surface markers is influenced by phospodiesterase (PDE) isoenzyme activity and whether antigen challenge alters platelet PDE activity in horses with recurrent airway obstruction (RAO). 16 horses. 7 healthy horses were used for in vitro experiments, 6 horses with RAO were used for antigen challenge, and 6 healthy horses were used as control animals. Three of the healthy horses had also been used in the in vitro experiments. Effects of PDE inhibition and activation of adenylyl cyclase on CD41/61 and CD62P expression on platelets and platelet-neutrophil aggregate formation in vitro were investigated via flow cytometry. Platelet PDE activity and sensitivity to inhibition of PDE3 and PDE5 isoenzymes were examined in horses with RAO and control horses before and after antigen challenge. Inhibition of PDE or activation of adenylyl cyclase significantly inhibited stimulus-induced expression of CD41/61 and CD62P (by approx 94% and 40%, respectively) and percentage of CD62P positive cells (by approx 30%). Only the PDE3 inhibitor, trequinsin, caused a significant (53%) reduction in platelet-neutrophil aggregate formation. Platelet PDE activity decreased following antigen challenge in RAO-affected horses and control horses. In horses with RAO, a significant increase in sensitivity of platelet PDE to inhibition by the PDE5 inhibitor zaprinast was observed after 5 hours. Results provided further evidence that PDE3 is an important regulator of equine platelet activation and suggested that changes in regulation of platelet PDE5 may contribute to antigen-induced response in horses with RAO.

Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels

PubMed Central

2011-01-01

Eleven phosphodiesterase (PDE) families are known, each having several different isoforms and splice variants. Recent evidence indicates that expression of individual PDE family members is tissue-specific. Little is known concerning detailed PDE component expression in brain microvessels where the blood-brain-barrier and the local cerebral blood flow are thought to be regulated by PDEs. The present study attempted to identify PDE family members that are expressed in brain microvessels. Adult male F344 rats were sacrificed and blocks of the cerebral cortex and infratentorial areas were dissected. Microvessels were isolated using a filtration method, and total RNA was extracted. RNA quality and quantity were determined using an Agilent bioanalyzer. The isolated cortical and infratentorial microvessel total RNA amounts were 2720 ± 750 ng (n = 2) and 250 ± 40 ng (n = 2), respectively. Microarrays with 22 000 transcripts demonstrated that there were 16 PDE transcripts in the PDE superfamily, exhibiting quantifiable density in the microvessels. An additional immunofluorescent study verified that PDE4D (cAMP-specific) and PDE5A (cGMP-specific) were colocalized with RECA-1 (an endothelial marker) in the cerebral cortex using both F344 rats and Sprague–Dawley rats (n = 3–6/strain). In addition, PDE4D and PDE5A were found to be colocalized with alpha-smooth muscle actin which delineates cerebral arteries and arterioles as well as pericytes. In conclusion, a filtration method followed by microarray analyses allows PDE components to be identified in brain microvessels, and confirmed that PDE4D and PDE5A are the primary forms expressed in rat brain microvessels. PMID:22860158

Molecular Theory of Detonation Initiation: Insight from First Principles Modeling of the Decomposition Mechanisms of Organic Nitro Energetic Materials.

PubMed

Tsyshevsky, Roman V; Sharia, Onise; Kuklja, Maija M

2016-02-19

This review presents a concept, which assumes that thermal decomposition processes play a major role in defining the sensitivity of organic energetic materials to detonation initiation. As a science and engineering community we are still far away from having a comprehensive molecular detonation initiation theory in a widely agreed upon form. However, recent advances in experimental and theoretical methods allow for a constructive and rigorous approach to design and test the theory or at least some of its fundamental building blocks. In this review, we analyzed a set of select experimental and theoretical articles, which were augmented by our own first principles modeling and simulations, to reveal new trends in energetic materials and to refine known existing correlations between their structures, properties, and functions. Our consideration is intentionally limited to the processes of thermally stimulated chemical reactions at the earliest stage of decomposition of molecules and materials containing defects.

Molecular Theory of Detonation Initiation: Insight from First Principles Modeling of the Decomposition Mechanisms of Organic Nitro Energetic Materials

DOE PAGES

Tsyshevsky, Roman; Sharia, Onise; Kuklja, Maija

2016-02-19

Our review presents a concept, which assumes that thermal decomposition processes play a major role in defining the sensitivity of organic energetic materials to detonation initiation. As a science and engineering community we are still far away from having a comprehensive molecular detonation initiation theory in a widely agreed upon form. However, recent advances in experimental and theoretical methods allow for a constructive and rigorous approach to design and test the theory or at least some of its fundamental building blocks. In this review, we analyzed a set of select experimental and theoretical articles, which were augmented by our ownmore » first principles modeling and simulations, to reveal new trends in energetic materials and to refine known existing correlations between their structures, properties, and functions. Lastly, our consideration is intentionally limited to the processes of thermally stimulated chemical reactions at the earliest stage of decomposition of molecules and materials containing defects.« less

Axisymmetric Numerical Modeling of Pulse Detonation Rocket Engines

NASA Technical Reports Server (NTRS)

Morris, Christopher I.

2005-01-01

Pulse detonation rocket engines (PDREs) have generated research interest in recent years as a chemical propulsion system potentially offering improved performance and reduced complexity compared to conventional rocket engines. The detonative mode of combustion employed by these devices offers a thermodynamic advantage over the constant-pressure deflagrative combustion mode used in conventional rocket engines and gas turbines. However, while this theoretical advantage has spurred considerable interest in building PDRE devices, the unsteady blowdown process intrinsic to the PDRE has made realistic estimates of the actual propulsive performance problematic. The recent review article by Kailasanath highlights some of the progress that has been made in comparing the available experimental measurements with analytical and numerical models. In recent work by the author, a quasi-one-dimensional, finite rate chemistry CFD model was utilized to study the gasdynamics and performance characteristics of PDREs over a range of blowdown pressure ratios from 1-1000. Models of this type are computationally inexpensive, and enable first-order parametric studies of the effect of several nozzle and extension geometries on PDRE performance over a wide range of conditions. However, the quasi-one-dimensional approach is limited in that it cannot properly capture the multidimensional blast wave and flow expansion downstream of the PDRE, nor can it resolve nozzle flow separation if present. Moreover, the previous work was limited to single-pulse calculations. In this paper, an axisymmetric finite rate chemistry model is described and utilized to study these issues in greater detail. Example Mach number contour plots showing the multidimensional blast wave and nozzle exhaust plume are shown. The performance results are compared with the quasi-one-dimensional results from the previous paper. Both Euler and Navier-Stokes solutions are calculated in order to determine the effect of viscous effects in the nozzle flowfield. Additionally, comparisons of the model results to performance data from CalTech, as well as experimental flowfield measurements from Stanford University, are also reported.

Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction.

PubMed

Li, Longhu; Haider, Husnain Kh; Wang, Linlin; Lu, Gang; Ashraf, Muhammad

2012-05-15

We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction.

Inhibition of calmodulin-dependent phosphodiesterase induces apoptosis in human leukemic cells.

PubMed Central

Jiang, X; Li, J; Paskind, M; Epstein, P M

1996-01-01

Cytosolic extracts from a human lymphoblastoid B-cell line, RPMI-8392, established from a patient with acute lymphocytic leukemia, contain two major forms of cyclic nucleotide phosphodiesterase (PDE): Ca2+-calmodulin dependent PDE (PDE1) and cAMP-specific PDE (PDE4). In contrast, normal quiescent human peripheral blood lymphocytes (HPBL) are devoid of PDE1 activity [Epstein, P. M., Moraski, S., Jr., and Hachisu, R. (1987) Biochem. J. 243, 533-539]. Using reverse transcription-polymerase chain reaction (RT-PCR), we show that the mRNA encoding the 63-kDa form of PDE1 (PDE1B1) is expressed in RPMI-8392 cells, but not in normal, resting HPBL. This mRNA is, however, induced in HPBL following mitogenic stimulation by phytohemagglutinin (PHA). Also using RT-PCR, the full open reading frame for human PDE1B1 cDNA was cloned from RPMI-8392 cells and it encodes a protein of 536 amino acids with 96% identity to bovine, rat, and mouse species. RT-PCR also identifies the presence of PDE1B1 in other human lymphoblastoid and leukemic cell lines of B- (RPMI-1788, Daudi) and T-(MOLT-4, NA, Jurkat) cell origin. Inhibition of PDE1 or PDE4 activity by selective inhibitors induced RPMI-8392 cells, as well as the other cell lines, to undergo apoptosis. Culture of RPMI-8392 cells with an 18-bp phosphorothioate antisense oligodeoxynucleotide, targeted against the translation initiation region of the RPMI-8392 mRNA, led to a specific reduction in the amount of PDE1B1 mRNA after 1 day, and its disappearance after 2 days, and induced apoptosis in these cells in a sequence specific manner. This suggests that PDEs, particularly PDE1B1, because its expression is selective, may be useful targets for inducing the death of leukemic cells. Images Fig. 1 Fig. 3 Fig. 5 Fig. 6 PMID:8855339

Partial differential equation transform — Variational formulation and Fourier analysis

PubMed Central

Wang, Yang; Wei, Guo-Wei; Yang, Siyang

2011-01-01

Nonlinear partial differential equation (PDE) models are established approaches for image/signal processing, data analysis and surface construction. Most previous geometric PDEs are utilized as low-pass filters which give rise to image trend information. In an earlier work, we introduced mode decomposition evolution equations (MoDEEs), which behave like high-pass filters and are able to systematically provide intrinsic mode functions (IMFs) of signals and images. Due to their tunable time-frequency localization and perfect reconstruction, the operation of MoDEEs is called a PDE transform. By appropriate selection of PDE transform parameters, we can tune IMFs into trends, edges, textures, noise etc., which can be further utilized in the secondary processing for various purposes. This work introduces the variational formulation, performs the Fourier analysis, and conducts biomedical and biological applications of the proposed PDE transform. The variational formulation offers an algorithm to incorporate two image functions and two sets of low-pass PDE operators in the total energy functional. Two low-pass PDE operators have different signs, leading to energy disparity, while a coupling term, acting as a relative fidelity of two image functions, is introduced to reduce the disparity of two energy components. We construct variational PDE transforms by using Euler-Lagrange equation and artificial time propagation. Fourier analysis of a simplified PDE transform is presented to shed light on the filter properties of high order PDE transforms. Such an analysis also offers insight on the parameter selection of the PDE transform. The proposed PDE transform algorithm is validated by numerous benchmark tests. In one selected challenging example, we illustrate the ability of PDE transform to separate two adjacent frequencies of sin(x) and sin(1.1x). Such an ability is due to PDE transform’s controllable frequency localization obtained by adjusting the order of PDEs. The frequency selection is achieved either by diffusion coefficients or by propagation time. Finally, we explore a large number of practical applications to further demonstrate the utility of proposed PDE transform. PMID:22207904

Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

PubMed Central

Li, Longhu; Haider, Husnain Kh.; Wang, Linlin; Lu, Gang

2012-01-01

We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction. PMID:22447941

PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

PubMed Central

Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

2016-01-01

Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

A pathophysiological role of PDE3 in allergic airway inflammation

PubMed Central

Beute, Jan; Lukkes, Melanie; Koekoek, Ewout P.; Nastiti, Hedwika; Ganesh, Keerthana; de Bruijn, Marjolein J.W.; Hockman, Steve; van Nimwegen, Menno; Braunstahl, Gert-Jan; Boon, Louis; Lambrecht, Bart N.; Manganiello, Vince C.; Hendriks, Rudi W.

2018-01-01

Phosphodiesterase 3 (PDE3) and PDE4 regulate levels of cyclic AMP, which are critical in various cell types involved in allergic airway inflammation. Although PDE4 inhibition attenuates allergic airway inflammation, reported side effects preclude its application as an antiasthma drug in humans. Case reports showed that enoximone, which is a smooth muscle relaxant that inhibits PDE3, is beneficial and lifesaving in status asthmaticus and is well tolerated. However, clinical observations also showed antiinflammatory effects of PDE3 inhibition. In this study, we investigated the role of PDE3 in a house dust mite–driven (HDM-driven) allergic airway inflammation (AAI) model that is characterized by T helper 2 cell activation, eosinophilia, and reduced mucosal barrier function. Compared with wild-type (WT) littermates, mice with a targeted deletion of the PDE3A or PDE3B gene showed significantly reduced HDM-driven AAI. Therapeutic intervention in WT mice showed that all hallmarks of HDM-driven AAI were abrogated by the PDE3 inhibitors enoximone and milrinone. Importantly, we found that enoximone also reduced the upregulation of the CD11b integrin on mouse and human eosinophils in vitro, which is crucial for their recruitment during allergic inflammation. This study provides evidence for a hitherto unknown antiinflammatory role of PDE3 inhibition in allergic airway inflammation and offers a potentially novel treatment approach. PMID:29367458

Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission.

PubMed

Agis-Torres, Ángel; Recio, Paz; López-Oliva, María Elvira; Martínez, María Pilar; Barahona, María Victoria; Benedito, Sara; Bustamante, Salvador; Jiménez-Cidre, Miguel Ángel; García-Sacristán, Albino; Prieto, Dolores; Fernandes, Vítor S; Hernández, Medardo

2018-03-16

Nitric oxide (NO) and hydrogen sulfide (H 2 S) play a pivotal role in nerve-mediated relaxation of the bladder outflow region. In the bladder neck, a marked phosphodiesterase type 4 (PDE4) expression has also been described and PDE4 inhibitors, as rolipram, produce smooth muscle relaxation. This study investigates the role of PDE4 isoenzyme in bladder neck gaseous inhibitory neurotransmission. We used Western blot and double immunohistochemical staining for the detection of NPP4 (PDE4) and PDE4A and organ baths for isometric force recording to roflumilast and tadalafil, PDE4 and PDE5, respectively, inhibitors in pig and human samples. Endogenous H 2 S production measurement and electrical field stimulation (EFS) were also performed. A rich PDE4 and PDE4A expression was observed mainly limited to nerve fibers of the smooth muscle layer of both species. Moreover, roflumilast produced a much more potent smooth muscle relaxation than that induced by tadalafil. In porcine samples, H 2 S generation was diminished by H 2 S and NO synthase inhibition and augmented by roflumilast. Relaxations elicited by EFS were potentiated by roflumilast. These results suggest that PDE4, mainly PDE4A, is mostly located within nerve fibers of the pig and human bladder neck, where roflumilast produces a powerful smooth muscle relaxation. In pig, the fact that roflumilast increases endogenous H 2 S production and EFS-induced relaxations suggests a modulation of PDE4 on NO- and H 2 S-mediated inhibitory neurotransmission.

A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex

PubMed Central

Horvath, Anelia; Giatzakis, Christoforos; Tsang, Kitman; Greene, Elizabeth; Osorio, Paulo; Boikos, Sosipatros; Libè, Rossella; Patronas, Yianna; Robinson-White, Audrey; Remmers, Elaine; Bertherat, Jerôme; Nesterova, Maria; Stratakis, Constantine A.

2009-01-01

Bilateral adrenocortical hyperplasia (BAH) is the second most common cause of corticotropin-independent Cushing syndrome (CS). Genetic forms of BAH have been associated with complex syndromes such as Carney Complex and McCune Albright syndrome or may present as isolated micronodular adrenocortical disease (iMAD) usually in children and young adults with CS. A genome-wide association study identified inactivating phosphodiesterase (PDE) 11A (PDE11A) sequencing defects as low-penetrance predisposing factors for iMAD and related abnormalities; we also described a mutation (c.914A>C/H305P) in cAMP-specific PDE8B, in a patient with iMAD. In this study we further characterize this mutation; we also found a novel PDE8B isoform, highly expressed in the adrenal gland. This mutation is shown to significantly affect the ability of the protein to degrade cAMP in vitro. Tumor tissues from patients with iMAD and no mutations in the coding PDE8B sequence or any other related genes (PRKAR1A, PDE11A) showed down-regulated PDE8B expression (compared to normal adrenal cortex). Pde8b is detectable in the adrenal gland of newborn mice and is widely expressed in other mouse tissues. We conclude that PDE8B is another PDE gene linked to iMAD; it is a candidate causative gene for other adrenocortical lesions linked to the cAMP-signaling pathway, and possibly for tumors in other tissues. PMID:18431404

Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a.

PubMed

Hufgard, Jillian R; Williams, Michael T; Skelton, Matthew R; Grubisha, Olivera; Ferreira, Filipa M; Sanger, Helen; Wright, Mary E; Reed-Kessler, Tracy M; Rasmussen, Kurt; Duman, Ronald S; Vorhees, Charles V

2017-06-01

Major depressive disorder is a leading cause of suicide and disability. Despite this, current antidepressants provide insufficient efficacy in more than 60% of patients. Most current antidepressants are presynaptic reuptake inhibitors; postsynaptic signal regulation has not received as much attention as potential treatment targets. We examined the effects of disruption of the postsynaptic cyclic nucleotide hydrolyzing enzyme, phosphodiesterase (PDE) 1b, on depressive-like behavior and the effects on PDE1B protein in wild-type (WT) mice following stress. Littermate knockout (KO) and WT mice were tested in locomotor activity, tail suspension (TST), and forced swim tests (FST). FST was also used to compare the effects of two antidepressants, fluoxetine and bupropion, in KO versus WT mice. Messenger RNA (mRNA) expression changes were also determined. WT mice underwent acute or chronic stress and markers of stress and PDE1B expression were examined. Pde1b KO mice exhibited decreased TST and FST immobility. When treated with antidepressants, both WT and KO mice showed decreased FST immobility and the effect was additive in KO mice. Mice lacking Pde1b had increased striatal Pde10a mRNA expression. In WT mice, acute and chronic stress upregulated PDE1B expression while PDE10A expression was downregulated after chronic but not acute stress. PDE1B is a potential therapeutic target for depression treatment because of the antidepressant-like phenotype seen in Pde1b KO mice.

Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.

PubMed Central

Cortijo, J.; Bou, J.; Beleta, J.; Cardelús, I.; Llenas, J.; Morcillo, E.; Gristwood, R. W.

1993-01-01

1. We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDE IV) in the relaxation of human bronchus and guinea-pig trachea in vitro and in guinea-pigs in vivo. 2. Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea-pig preparations in vitro. 3. Two clinically used xanthine non-selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used. 4. The rank order of potency for the four PDE inhibitors in both species was similar. 5. Biochemical studies indicated that PDE IV was the major PDE isoform present in the human bronchial tissue. PDEs I, II and V were also identified. 6. Theophylline and pentoxifylline were, as expected, non-selective inhibitors of the human enzymes, but there was a good correlation between PDE IV inhibitory and bronchorelaxation potencies, suggesting that PDE IV inhibition is important for the clinical bronchodilator activities of the two xanthine compounds. 7. We have confirmed the ability of selective PDE IV inhibitors to cause bronchodilatation in guinea-pigs in vivo. 8. We conclude that our study has provided further evidence that selective PDE IV inhibitors could act as bronchodilators in the clinic. PMID:8383567

Inactivation of Pde8b enhances memory, motor performance, and protects against age-induced motor coordination decay

PubMed Central

Tsai, Li-Chun Lisa; Chan, Guy Chiu-Kai; Nangle, Shannon N.; Shimizu-Albergine, Masami; Jones, Graham; Storm, Daniel R.; Beavo, Joseph A.; Zweifel, Larry S.

2012-01-01

Phosphodiesterases (PDEs) are critical regulatory enzymes in cyclic nucleotide signaling. PDEs have diverse expression patterns within the central nervous system (CNS), show differing affinities for cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), and regulate a vast array of behaviors. Here, we investigated the expression profile of the PDE8 gene family members Pde8a and Pde8b in the mouse brain. We find that Pde8a expression is largely absent in the CNS; by contrast, Pde8b is expressed in select regions of the hippocampus, ventral striatum, and cerebellum. Behavioral analysis of mice with Pde8b gene inactivation (PDE8B KO) demonstrate an enhancement in contextual fear, spatial memory, performance in an appetitive instrumental conditioning task, motor-coordination, and have an attenuation of age-induced motor coordination decline. In addition to improvements observed in select behaviors, we find basal anxiety levels to be increased in PDE8B KO mice. These findings indicate that selective antagonism of PDE8B may be an attractive target for enhancement of cognitive and motor functions; however, possible alterations in affective state will need to be weighed against potential therapeutic value. PMID:22925203

The localization and concentration of the PDE2-encoded high-affinity cAMP phosphodiesterase is regulated by cAMP-dependent protein kinase A in the yeast Saccharomyces cerevisiae.

PubMed

Hu, Yun; Liu, Enkai; Bai, Xiaojia; Zhang, Aili

2010-03-01

The genome of the yeast Saccharomyces cerevisiae encodes two cyclic AMP (cAMP) phosphodiesterases, a low-affinity one, Pde1, and a high-affinity one, Pde2. Pde1 has been ascribed a function for downregulating agonist-induced cAMP accumulation in a protein kinase A (PKA)-governed negative feedback loop, whereas Pde2 controls the basal cAMP level in the cell. Here we show that PKA regulates the localization and protein concentration of Pde2. Pde2 is accumulated in the nucleus in wild-type cells growing on glucose, or in strains with hyperactive PKA. In contrast, in derepressed wild-type cells or cells with attenuated PKA activity, Pde2 is distributed over the nucleus and cytoplasm. We also show evidence indicating that the Pde2 protein level is positively correlated with PKA activity. The increase in the Pde2 protein level in high-PKA strains and in cells growing on glucose was due to its increased half-life. These results suggest that, like its low-affinity counterpart, the high-affinity phosphodiesterase may also play an important role in the PKA-controlled feedback inhibition of intracellular cAMP.

Development and Characterization Testing of an Air Pulsation Valve for a Pulse Detonation Engine Supersonic Parametric Inlet Test Section

NASA Technical Reports Server (NTRS)

Tornabene, Robert

2005-01-01

In pulse detonation engines, the potential exists for gas pulses from the combustor to travel upstream and adversely affect the inlet performance of the engine. In order to determine the effect of these high frequency pulses on the inlet performance, an air pulsation valve was developed to provide air pulses downstream of a supersonic parametric inlet test section. The purpose of this report is to document the design and characterization tests that were performed on a pulsation valve that was tested at the NASA Glenn Research Center 1x1 Supersonic Wind Tunnel (SWT) test facility. The high air flow pulsation valve design philosophy and analyses performed are discussed and characterization test results are presented. The pulsation valve model was devised based on the concept of using a free spinning ball valve driven from a variable speed electric motor to generate air flow pulses at preset frequencies. In order to deliver the proper flow rate, the flow port was contoured to maximize flow rate and minimize pressure drop. To obtain sharp pressure spikes the valve flow port was designed to be as narrow as possible to minimize port dwell time.

Dynamic one-dimensional modeling of secondary settling tanks and system robustness evaluation.

PubMed

Li, Ben; Stenstrom, M K

2014-01-01

One-dimensional secondary settling tank models are widely used in current engineering practice for design and optimization, and usually can be expressed as a nonlinear hyperbolic or nonlinear strongly degenerate parabolic partial differential equation (PDE). Reliable numerical methods are needed to produce approximate solutions that converge to the exact analytical solutions. In this study, we introduced a reliable numerical technique, the Yee-Roe-Davis (YRD) method as the governing PDE solver, and compared its reliability with the prevalent Stenstrom-Vitasovic-Takács (SVT) method by assessing their simulation results at various operating conditions. The YRD method also produced a similar solution to the previously developed Method G and Enquist-Osher method. The YRD and SVT methods were also used for a time-to-failure evaluation, and the results show that the choice of numerical method can greatly impact the solution. Reliable numerical methods, such as the YRD method, are strongly recommended.

Discovery of a novel orally active PDE-4 inhibitor effective in an ovalbumin-induced asthma murine model.

PubMed

Kwak, Hyun Jeong; Nam, Ji Yeon; Song, Jin Sook; No, Zaesung; Yang, Sung Don; Cheon, Hyae Gyeong

2012-06-15

Phosphodiesterase-4 (PDE-4) is responsible for metabolizing adenosine 3',5'-cyclic monophosphate that reduces the activation of a wide range of inflammatory cells including eosinophils. PDE-4 inhibitors are under development for the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease. Herein, we report a novel PDE-4 inhibitor, PDE-423 (3-[1-(3-cyclopropylmethoxy-4-difluoromethoxybenzyl)-1H-pyrazol-3-yl]-benzoic acid), which shows good in vitro and in vivo oral activities. PDE-423 exhibited in vitro IC(50)s of 140 nM and 550 nM in enzyme assay and cell-based assay, respectively. In vivo study using ovalbumin-induced asthmatic mice revealed that PDE-423 reduced methacholine-stimulated airway hyperreactivity in a dose-dependent manner by once daily oral administration (ED(50)=18.3 mg/kg), in parallel with decreased eosinophil peroxidase activity and improved lung histology. In addition, PDE-423 was effective in diminishing lipopolysaccharide-induced neutrophilia in vivo as well as in vitro. Oral administration of PDE-423 (100 mg/kg) had no effect on the duration of xylazine/ketamine-induced anesthesia and did not induce vomiting incidence in ferrets up to the dose of 1000 mg/kg. The present study indicates that a novel PDE-4 inhibitor, PDE-423, has good pharmacological profiles implicating this as a potential candidate for the development of a new anti-asthmatic drug. Copyright © 2012 Elsevier B.V. All rights reserved.

Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing Properties.

PubMed

Dyck, Brian; Branstetter, Bryan; Gharbaoui, Tawfik; Hudson, Andrew R; Breitenbucher, J Guy; Gomez, Laurent; Botrous, Iriny; Marrone, Tami; Barido, Richard; Allerston, Charles K; Cedervall, E Peder; Xu, Rui; Sridhar, Vandana; Barker, Ryan; Aertgeerts, Kathleen; Schmelzer, Kara; Neul, David; Lee, Dong; Massari, Mark Eben; Andersen, Carsten B; Sebring, Kristen; Zhou, Xianbo; Petroski, Robert; Limberis, James; Augustin, Martin; Chun, Lawrence E; Edwards, Thomas E; Peters, Marco; Tabatabaei, Ali

2017-04-27

A series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was discovered. X-ray crystal structures of example compounds from this series in complex with the catalytic domain of PDE1B and PDE10A were determined, allowing optimization of PDE1B potency and PDE selectivity. Reduction of hERG affinity led to greater than a 3000-fold selectivity for PDE1B over hERG. 6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one was identified as an orally bioavailable and brain penetrating PDE1B enzyme inhibitor with potent memory-enhancing effects in a rat model of object recognition memory.

Vibrational and Rotational CARS Measurements of Nitrogen in Afterglow of Streamer Discharge in Atmospheric Pressure Fuel/Air Mixtures

DTIC Science & Technology

2012-01-01

in a variety of different ignition regimes, including pulsed detonation engines ( PDEs ) and automobile engines, with experiments demonstrating TPI to...Vibrational and rotational CARS measurements of nitrogen in afterglow of streamer discharge in atmospheric pressure fuel/air mixtures This article...DATE 2012 2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Vibrational and rotational CARS measurements of

Expression of phosphodiesterase 6 (PDE6) in human breast cancer cells.

PubMed

Dong, Hongli; Claffey, Kevin P; Brocke, Stefan; Epstein, Paul M

2013-01-01

Considerable epidemiological evidence demonstrates a positive association between artificial light at night (LAN) levels and incidence rates of breast cancer, suggesting that exposure to LAN is a risk factor for breast cancer. There is a 30-50% higher risk of breast cancer in the highest LAN exposed countries compared to the lowest LAN countries, and studies showing higher incidence of breast cancer among shift workers exposed to more LAN have led the International Agency for Research on Cancer to classify shift work as a probable human carcinogen. Nevertheless, the means by which light can affect breast cancer is still unknown. In this study we examined established human breast cancer cell lines and patients' primary breast cancer tissues for expression of genetic components of phosphodiesterase 6 (PDE6), a cGMP-specific PDE involved in transduction of the light signal, and previously thought to be selectively expressed in photoreceptors. By microarray analysis we find highly significant expression of mRNA for the PDE6B, PDE6C, and PDE6D genes in both the cell lines and patients' tissues, minimal expression of PDE6A and PDE6G and no expression of PDE6H. Using antibody specific for PDE6β, we find expression of PDE6B protein in a wide range of patients' tissues by immunohistochemistry, and in MCF-7 breast cancer cells by immunofluorescence and Western blot analysis. Considerable expression of key circadian genes, PERIOD 2, CLOCK, TIMELESS, CRYPTOCHROME 1, and CRYPTOCHROME 2 was also seen in all breast cancer cell lines and all patients' breast cancer tissues. These studies indicate that genes for PDE6 and control of circadian rhythm are expressed in human breast cancer cells and tissues and may play a role in transducing the effects of light on breast cancer.

Non-invasive Management Options for Erectile Dysfunction When a Phosphodiesterase Type 5 Inhibitor Fails.

PubMed

Lee, Mary; Sharifi, Roohollah

2018-03-01

Phosphodiesterase type 5 inhibitors (PDE5Is) are the drug of choice for medical management of erectile dysfunction (ED). On-demand PDE5Is have an overall efficacy of 60-70% for ED; 30-35% of patients fail to respond to a PDE5I, and 30-50% of non-responders can be salvaged with detailed counseling on proper use and physician follow-up to ensure that the patient has been prescribed an appropriate and full PDE5I clinical trial. True non-responders may be offered intracavernosal injections of erectogenic drugs, intraurethral alprostadil, or surgical insertion of a penile prosthesis. Such options are not discreet and are associated with more adverse effects than PDE5Is. Thus patients may request additional non-invasive medical management options. This review describes published literature on patients who failed to respond to an on-demand PDE5I regimen and were treated with a non-invasive PDEI-based regimen, including switching from one PDE5I to another; increasing the dose of PDE5I above the labeled dosage range; using two PDE5Is concurrently; using a daily PDE5I regimen; or combining a PDE5I with a testosterone supplement, α-adrenergic antagonist, intraurethral or intracavernosal alprostadil, vacuum erection device, or low-intensity shock wave therapy. The limitations of published clinical trials do not allow for sufficient evidence to recommend one option over another. Therefore, in PDE5I-refractory patients, the choice of a specific next step should be individualized based on the preference of the patient and his sexual partner, the advantages and disadvantages of the various options, the concurrent medical illnesses and medications of the patient, and the patient's response to treatment.

Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-1B (PDE1B) enzyme.

PubMed

Siuciak, J A; McCarthy, S A; Chapin, D S; Reed, T M; Vorhees, C V; Repaske, D R

2007-07-01

PDE1B is a calcium-dependent cyclic nucleotide phosphodiesterase that is highly expressed in the striatum. In order to investigate the physiological role of PDE1B in the central nervous system, PDE1B knockout mice (C57BL/6N background) were assessed in behavioral tests and their brains were assayed for monoamine content. In a variety of well-characterized behavioral tasks, including the elevated plus maze (anxiety-like behavior), forced swim test (depression-like behavior), hot plate (nociception) and two cognition models (passive avoidance and acquisition of conditioned avoidance responding), PDE1B knockout mice performed similarly to wild-type mice. PDE1B knockout mice showed increased baseline exploratory activity when compared to wild-type mice. When challenged with amphetamine (AMPH) and methamphetamine (METH), male and female PDE1B knockout mice showed an exaggerated locomotor response. Male PDE1B knockout mice also showed increased locomotor responses to higher doses of phencyclidine (PCP) and MK-801; however, this effect was not consistently observed in female knockout mice. In the striatum, increased dopamine turnover (DOPAC/DA and HVA/DA ratios) was found in both male and female PDE1B knockout mice. Striatal serotonin (5-HT) levels were also decreased in PDE1B knockout mice, although levels of the metabolite, 5HIAA, were unchanged. The present studies demonstrate increased striatal dopamine turnover in PDE1B knockout mice associated with increased baseline motor activity and an exaggerated locomotor response to dopaminergic stimulants such as methamphetamine and amphetamine. These data further support a role for PDE1B in striatal function.

Geometry of PDE's. IV

NASA Astrophysics Data System (ADS)

Prástaro, Agostino

2008-02-01

Following our previous results on this subject [R.P. Agarwal, A. Prástaro, Geometry of PDE's. III(I): Webs on PDE's and integral bordism groups. The general theory, Adv. Math. Sci. Appl. 17 (2007) 239-266; R.P. Agarwal, A. Prástaro, Geometry of PDE's. III(II): Webs on PDE's and integral bordism groups. Applications to Riemannian geometry PDE's, Adv. Math. Sci. Appl. 17 (2007) 267-285; A. Prástaro, Geometry of PDE's and Mechanics, World Scientific, Singapore, 1996; A. Prástaro, Quantum and integral (co)bordism in partial differential equations, Acta Appl. Math. (5) (3) (1998) 243-302; A. Prástaro, (Co)bordism groups in PDE's, Acta Appl. Math. 59 (2) (1999) 111-201; A. Prástaro, Quantized Partial Differential Equations, World Scientific Publishing Co, Singapore, 2004, 500 pp.; A. Prástaro, Geometry of PDE's. I: Integral bordism groups in PDE's, J. Math. Anal. Appl. 319 (2006) 547-566; A. Prástaro, Geometry of PDE's. II: Variational PDE's and integral bordism groups, J. Math. Anal. Appl. 321 (2006) 930-948; A. Prástaro, Th.M. Rassias, Ulam stability in geometry of PDE's, Nonlinear Funct. Anal. Appl. 8 (2) (2003) 259-278; I. Stakgold, Boundary Value Problems of Mathematical Physics, I, The MacMillan Company, New York, 1967; I. Stakgold, Boundary Value Problems of Mathematical Physics, II, Collier-MacMillan, Canada, Ltd, Toronto, Ontario, 1968], integral bordism groups of the Navier-Stokes equation are calculated for smooth, singular and weak solutions, respectively. Then a characterization of global solutions is made on this ground. Enough conditions to assure existence of global smooth solutions are given and related to nullity of integral characteristic numbers of the boundaries. Stability of global solutions are related to some characteristic numbers of the space-like Cauchy dataE Global solutions of variational problems constrained by (NS) are classified by means of suitable integral bordism groups too.

Co-possession of phosphodiesterase type-5 inhibitors (PDE5-I) with nitrates.

PubMed

Chang, Li-Ling; Ma, Mark; Allmen, Heather von; Henderson, Scott C; Harper, Kristine; Hornbuckle, Kenneth

2010-06-01

Estimate the proportion of phosphodiesterase type-5 inhibitor (PDE5-I) patients who co-possess nitrates and compare the proportion of tadalafil patients dispensed nitrates to a matched control group. Secondarily, examine the percentage of co-possession of PDE5-Is and nitrates where the products were dispensed on the same day or written by the same prescriber. Male patients aged 18+ years filling PDE5-I prescriptions between December 2003 and March 2006 were identified using a U.S. longitudinal prescription database (IMS Health LRx). Similar patients not dispensed a PDE5-I during this period were matched to the tadalafil-dispensed cohort using a propensity score approach. Co-possession, as a proxy for concurrent use, was defined as an overlap in time on therapy for a PDE5-I and nitrate and was compared for the three PDE5-Is and for tadalafil to the matched control group. Among 601,063 tadalafil patients, 3.31% were dispensed a nitrate during the study period, compared to 6.18% in control patients (n = 601,063). When co-possessed prescriptions were defined by overlapping exposure periods, the proportion of PDE5-I patients with co-possessed nitrates ranged from 1.44% (tadalafil) to 1.72% (vardenafil) and 2.13% (sildenafil). Co-possession percentages of PDE5-I prescriptions were 0.83% for tadalafil and 1.07% for sildenafil and vardenafil. The majority (54.29%) of co-possessed PDE5-I and nitrate prescriptions had the nitrate dispensed prior to the PDE5-I prescription identified in the study cohort. Keeping in mind the limitations of observational studies, these results suggest that co-dispensing of nitrates and PDE5-Is is low. Compared to control patients, the proportion of nitrate co-possession was lowest for patients filling tadalafil. Tadalafil patients also had the lowest co-possessed proportion among the three PDE5-I cohorts. While the majority of co-possessed drug pairs were prescribed by different providers, the highest percentage of co-prescribing from the same physician was among cardiologists. These results suggest that physicians adhere to contraindications and are careful about co-prescribing of nitrates with PDE-5Is.

Immunoprecipitation of PDE2 phosphorylated and inactivated by an associated protein kinase.

PubMed

Bentley, J Kelley

2005-01-01

A PDE2A2-associated protein kinase phosphorylates PDE2A2 in vivo and in vitro to inhibit its catalytic activity. Rat brain PDE2A2 may be solubilized using nona (ethylene glycol) mono dodecyl ether (Lubrol 12A9). PDE2A2 exists in a complex with a protein kinase regulating its activity in an adenosine triphosphate-dependent manner. When native or recombinant PDE2 is immunoprecipitated from PC12 cells using an antibody to the amino terminus in a buffer containing Lubrol 12A9, protease inhibitors, and phosphatase inhibitors, a coimmunoprecipitating nerve growth factor-stimulated protein kinase acts to phosphorylate it. PDE2A2 phosphoryla-tion occurs optimally at pH 6.5 in a sodium 2-(4-morpholino)-ethane sulfonate buffer with 5 mM MgCl2 and 1 mM Na3VO4. I describe protocols for producing an antibody to an amino-terminal bacterial fusion protein encoding amino acids 1-251 of PDE2A2 as well as the use of this antibody in immunoprecipitating a PDE2: tyrosine protein-kinase complex from rat brain or PC12 cells.

Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice

PubMed Central

Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Harris, R. Adron

2014-01-01

Some anti-inflammatory medications reduce alcohol consumption in rodent models. Inhibition of phosphodiesterases (PDE) increases cAMP and reduces inflammatory signaling. Rolipram, an inhibitor of PDE4, markedly reduced ethanol intake and preference in mice and reduced ethanol seeking and consumption in alcohol-preferring fawn-hooded rats (Hu et al., 2011; Wen et al., 2012). To determine if these effects were specific for PDE4, we compared nine PDE inhibitors with different subtype selectivity: propentofylline (nonspecific), vinpocetine (PDE1), olprinone, milrinone (PDE3), zaprinast (PDE5), rolipram, mesopram, piclamilast, and CDP840 (PDE4). Alcohol intake was measured in C57BL/6J male mice using 24-h two-bottle choice and two-bottle choice with limited (3-h) access to alcohol. Only the selective PDE4 inhibitors reduced ethanol intake and preference in the 24-h two-bottle choice test. For rolipram, piclamilast, and CDP840, this effect was observed after the first 6 h but not after the next 18 h. Mesopram, however, produced a long-lasting reduction of ethanol intake and preference. In the limited access test, rolipram, piclamilast, and mesopram reduced ethanol consumption and total fluid intake and did not change preference for ethanol, whereas CDP840 reduced both consumption and preference without altering total fluid intake. Our results provide novel evidence for a selective role of PDE4 in regulating ethanol drinking in mice. We suggest that inhibition of PDE4 may be an unexplored target for medication development to reduce excessive alcohol consumption. PMID:24904269

Integrated Pulse Detonation Propulsion and Magnetohydrodynamic Power

NASA Technical Reports Server (NTRS)

Litchford, Ron J.

2001-01-01

The prospects for realizing an integrated pulse detonation propulsion and magnetohydrodynamic (MHD) power system are examined. First, energy requirements for direct detonation initiation of various fuel-oxygen and fuel-air mixtures are deduced from available experimental data and theoretical models. Second, the pumping power requirements for effective chamber scavenging are examined through the introduction of a scavenging ratio parameter and a scavenging efficiency parameter. A series of laboratory experiments were carried out to investigate the basic engineering performance characteristics of a pulse detonation-driven MHD electric power generator. In these experiments, stoichiometric oxy-acetylene mixtures seeded with a cesium hydroxide/methanol spray were detonated at atmospheric pressure in a 1-m-long tube having an i.d. of 2.54 cm. Experiments with a plasma diagnostic channel attached to the end of the tube confirmed the attainment of detonation conditions (p2/p1 approximately 34 and D approximately 2,400 m/sec) and enabled the direct measurement of current density and electrical conductivity (approximately = 6 S/m) behind the detonation wave front, In a second set of experiments, a 30-cm-long continuous electrode Faraday channel, having a height of 2.54 cm and a width of 2 cm, was attached to the end of the tube using an area transition duct. The Faraday channel was inserted in applied magnetic fields of 0.6 and 0.95 T, and the electrodes were connected to an active loading circuit to characterize power extraction dependence on load impedance while also simulating higher effective magnetic induction. The experiments indicated peak power extraction at a load impedance between 5 and 10 Omega. The measured power density was in reasonable agreement with a simple electrodynamic model incorporating a correction for near-electrode potential losses. The time-resolved thrust characteristics of the system were also measured, and it was found that the NM interaction exerted a negligible influence on system thrust and that the measured I(sub sp) of the system (200 see) exceeded that computed for an equivalent nozzleless rocket (120 see).

Integrated Pulse Detonation Propulsion and Magnetohydrodynamic Power

NASA Technical Reports Server (NTRS)

Litchford, R. J.; Lyles, Garry M. (Technical Monitor)

2001-01-01

The prospects for realizing an integrated pulse detonation propulsion and magnetohydrodynamic (MHD) power system are examined. First, energy requirements for direct detonation initiation of various fuel-oxygen and fuel-air mixtures are deduced from available experimental data and theoretical models. Second, the pumping power requirements for effective chamber scavenging are examined through the introduction of a scavenging ratio parameter and a scavenging efficiency parameter. A series of laboratory experiments were carried out to investigate the basic engineering performance characteristics of a pulse detonation-driven MHD electric power generator. In these experiments, stoichiometric oxy-acetylene mixtures seeded with a cesium hydroxide/methanol spray were detonated at atmospheric pressure in a 1-m-long tube having an i.d. of 2.54 cm. Experiments with a plasma diagnostic channel attached to the end of the tube confirmed the attainment of detonation conditions (p(sub 2)/p(sub 1) approx. 34 and D approx. 2,400 m/sec) and enabled the direct measurement of current density and electrical conductivity (=6 S/m) behind the detonation wave front. In a second set of experiments, a 30-cm-long continuous electrode Faraday channel, having a height of 2.54 cm and a width of 2 cm, was attached to the end of the tube using an area transition duct. The Faraday channel was inserted in applied magnetic fields of 0.6 and 0.95 T. and the electrodes were connected to an active loading circuit to characterize power extraction dependence on load impedance while also simulating higher effective magnetic induction. The experiments indicated peak power extraction at a load impedance between 5 and 10 Ohm. The measured power density was in reasonable agreement with a simple electrodynamic model incorporating a correction for near-electrode potential losses. The time-resolved thrust characteristics of the system were also measured, and it was found that the MHD interaction exerted a negligible influence on system thrust and that the measured I(sub sp) of the system (200 sec) exceeded that computed for an equivalent nozzleless rocket (120 sec).

Phosphodiesterase-10A Inverse Changes in Striatopallidal and Striatoentopeduncular Pathways of a Transgenic Mouse Model of DYT1 Dystonia.

PubMed

D'Angelo, Vincenza; Castelli, Valentina; Giorgi, Mauro; Cardarelli, Silvia; Saverioni, Ilaria; Palumbo, Francesca; Bonsi, Paola; Pisani, Antonio; Giampà, Carmela; Sorge, Roberto; Biagioni, Stefano; Fusco, Francesca R; Sancesario, Giuseppe

2017-02-22

We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 receptors and inhibited by D2 receptors preferentially expressed in striatoentopeducuncular/substantia nigra or striatopallidal pathways, respectively. PDE10A was studied in control mice (NT) and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT). Quantitative analysis of PDE10A expression was assessed in different brain areas by rabbit anti-PDE10A antibody immunohistochemistry and Western blotting. PDE10A-dependent cAMP hydrolyzing activity and PDE10A mRNA were also assessed. Striatopallidal neurons were identified by rabbit anti-enkephalin antibody.In NT mice, PDE10A is equally expressed in medium spiny striatal neurons and in their projections to entopeduncular nucleus/substantia nigra and to external globus pallidus. In hMT mice, PDE10A content selectively increases in enkephalin-positive striatal neuronal bodies; moreover, PDE10A expression and activity in hMT mice, compared with NT mice, significantly increase in globus pallidus but decrease in entopeduncular nucleus/substantia nigra. Similar changes of PDE10A occur in hWT mice, but such changes are not always significant. However, PDE10A mRNA expression appears comparable among NT, hWT, and hMT mice.In DYT1 transgenic mice, the inverse changes of PDE10A in striatoentopeduncular and striatopallidal projections might result over time in an imbalance between direct and indirect pathways for properly focusing movement. The decrease of PDE10A in the striatoentopeduncular/nigral projections might lead to increased intensity and duration of D1-stimulated cAMP/cGMP signaling; conversely, the increase of PDE10A in the striatopallidal projections might lead to increased intensity and duration of D2-inhibited cAMP/cGMP signaling. SIGNIFICANCE STATEMENT In DYT1 transgenic mouse model of dystonia, PDE10A, a key enzyme in cAMP and cGMP catabolism, is downregulated in striatal projections to entopeduncular nucleus/substantia nigra, preferentially expressing D1 receptors that stimulate cAMP/cGMP synthesis. Conversely, in DYT1 mice, PDE10A is upregulated in striatal projections to globus pallidus, preferentially expressing D2 receptors that inhibit cAMP/cGMP synthesis. The inverse changes to PDE10A in striatoentopeduncular/substantia nigra and striatopallidal pathways might tightly interact downstream to dopamine receptors, likely resulting over time to increased intensity and duration respectively of D1-stimulated and D2-inhibited cAMP/cGMP signals. Therefore, PDE10A changes in the DYT1 model of dystonia can upset the functional balance of basal ganglia circuits, affecting direct and indirect pathways simultaneously. Copyright © 2017 the authors 0270-6474/17/372113-13$15.00/0.

Investigation of Various Novel Air-Breathing Propulsion Systems

NASA Astrophysics Data System (ADS)

Wilhite, Jarred M.

The current research investigates the operation and performance of various air-breathing propulsion systems, which are capable of utilizing different types of fuel. This study first focuses on a modular RDE configuration, which was mainly studied to determine which conditions yield stable, continuous rotating detonation for an ethylene-air mixture. The performance of this RDE was analyzed by studying various parameters such as mass flow rate, equivalence ratios, wave speed and cell size. For relatively low mass flow rates near stoichiometric conditions, a rotating detonation wave is observed for an ethylene-RDE, but at speeds less than an ideal detonation wave. The current research also involves investigating the newly designed, Twin Oxidizer Injection Capable (TOXIC) RDE. Mixtures of hydrogen and air were utilized for this configuration, resulting in sustained rotating detonation for various mass flow rates and equivalence ratios. A thrust stand was also developed to observe and further measure the performance of the TOXIC RDE. Further analysis was conducted to accurately model and simulate the response of thrust stand during operation of the RDE. Also included in this research are findings and analysis of a propulsion system capable of operating on the Inverse Brayton Cycle. The feasibility of this novel concept was validated in a previous study to be sufficient for small-scale propulsion systems, namely UAV applications. This type of propulsion system consists of a reorganization of traditional gas turbine engine components, which incorporates expansion before compression. This cycle also requires a heat exchanger to reduce the temperature of the flow entering the compressor downstream. While adding a heat exchanger improves the efficiency of the cycle, it also increases the engine weight, resulting in less endurance for the aircraft. Therefore, this study focuses on the selection and development of a new heat exchanger design that is lightweight, and is capable of transferring significant amounts of heat and improving the efficiency and performance of the propulsion system.

Gasdynamic Inlet Isolation in Rotating Detonation Engine

DTIC Science & Technology

2010-12-01

2D Total Variation Diminishing (TVD): Continuous Riemann Solver Minimum Dissipation: LHS & RHS Activate pressure switch : Supersonic Activate...Total Variation Diminishing (TVD) limiter: Continuous Riemann Solver Minimum Dissipation: LHS & RHS Activate pressure switch : Supersonic Activate...Continuous 94 Riemann Solver Minimum Dissipation: LHS & RHS Activate pressure switch : Supersonic Activate pressure gradient switch: Normal

Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A).

PubMed

Hu, Essa; Kunz, Roxanne K; Chen, Ning; Rumfelt, Shannon; Siegmund, Aaron; Andrews, Kristin; Chmait, Samer; Zhao, Sharon; Davis, Carl; Chen, Hang; Lester-Zeiner, Dianna; Ma, Ji; Biorn, Christopher; Shi, Jianxia; Porter, Amy; Treanor, James; Allen, Jennifer R

2013-11-14

Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

Cyclic Nucleotide Phosphodiesterases: important signaling modulators and therapeutic targets

PubMed Central

Ahmad, Faiyaz; Murata, Taku; Simizu, Kasumi; Degerman, Eva; Maurice, Donald; Manganiello, Vincent

2014-01-01

By catalyzing hydrolysis of cAMP and cGMP, cyclic nucleotide phosphodiesterases are critical regulators of their intracellular concentrations and their biological effects. Since these intracellular second messengers control many cellular homeostatic processes, dysregulation of their signals and signaling pathways initiate or modulate pathophysiological pathways related to various disease states, including erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, intermittent claudication, chronic obstructive pulmonary disease, and psoriasis. Alterations in expression of PDEs and PDE-gene mutations (especially mutations in PDE6, PDE8B, PDE11A and PDE4) have been implicated in various diseases and cancer pathologies. PDEs also play important role in formation and function of multi-molecular signaling/regulatory complexes called signalosomes. At specific intracellular locations, individual PDEs, together with pathway-specific signaling molecules, regulators, and effectors, are incorporated into specific signalosomes, where they facilitate and regulate compartmentalization of cyclic nucleotide signaling pathways and specific cellular functions. Currently, only a limited number of PDE inhibitors (PDE3, PDE4, PDE5 inhibitors) are used in clinical practice. Future paths to novel drug discovery include the crystal structure-based design approach, which has resulted in generation of more effective family-selective inhibitors, as well as burgeoning development of strategies to alter compartmentalized cyclic nucleotide signaling pathways by selectively targeting individual PDEs and their signalosome partners. PMID:25056711

Evolution and expression of the phosphodiesterase 6 genes unveils vertebrate novelty to control photosensitivity.

PubMed

Lagman, David; Franzén, Ilkin E; Eggert, Joel; Larhammar, Dan; Abalo, Xesús M

2016-06-13

Phosphodiesterase 6 (PDE6) is a protein complex that hydrolyses cGMP and acts as the effector of the vertebrate phototransduction cascade. The PDE6 holoenzyme consists of catalytic and inhibitory subunits belonging to two unrelated gene families. Rods and cones express distinct genes from both families: PDE6A and PDE6B code for the catalytic and PDE6G the inhibitory subunits in rods while PDE6C codes for the catalytic and PDE6H the inhibitory subunits in cones. We performed phylogenetic and comparative synteny analyses for both gene families in genomes from a broad range of animals. Furthermore, gene expression was investigated in zebrafish. We found that both gene families expanded from one to three members in the two rounds of genome doubling (2R) that occurred at the base of vertebrate evolution. The PDE6 inhibitory subunit gene family appears to be unique to vertebrates and expanded further after the teleost-specific genome doubling (3R). We also describe a new family member that originated in 2R and has been lost in amniotes, which we have named pde6i. Zebrafish has retained two additional copies of the PDE6 inhibitory subunit genes after 3R that are highly conserved, have high amino acid sequence identity, are coexpressed in the same photoreceptor type as their amniote orthologs and, interestingly, show strikingly different daily oscillation in gene expression levels. Together, these data suggest specialisation related to the adaptation to different light intensities during the day-night cycle, most likely maintaining the regulatory function of the PDE inhibitory subunits in the phototransduction cascade.

Recreational Use of Phosphodiesterase 5 Inhibitors and Its Associated Factors among Undergraduate Male Students in an Ethiopian University: A Cross-Sectional Study.

PubMed

Gebreyohannes, Eyob Alemayehu; Bhagavathula, Akshaya Srikanth; Gebresillassie, Begashaw Melaku; Tefera, Yonas Getaye; Belachew, Sewunet Admasu; Erku, Daniel Asfaw

2016-12-01

To assess the prevalence of phosphodiesterase 5 (PDE5) inhibitor use and associated factors among University of Gondar undergraduate students. An institution-based, cross-sectional study, using a survey questionnaire, was conducted from October to December 2015 to assess PDE5 inhibitor use and associated factors among male students at the University of Gondar. A Self-Esteem and Relationship questionnaire (14 items), an International Index of Erectile Function questionnaire (15 items) and a questionnaire on PDE5 inhibitor use (14 items) were included in the survey. Across all respondents (age, 21.9±1.88 years), more than half (55.7%, n=233) had heard about PDE5 inhibitors, but only 23 men (5.5%) reported trying a PDE5 inhibitor drug at least once. Older students were more likely to use PDE5 inhibitors compared to younger students (adjusted odds ratio [AOR], 1.40; 95% confidence interval [CI], 1.109~1.768). Those students who were smokers were 5.15 times more likely to use PDE5 inhibitors as compared to their non-smoking counterparts (AOR, 5.15; 95% CI, 2.096~12.687). In addition, multivariate logistic regression showed that being in a relationship, alcohol use, greater number of cigarettes smoked per day, and more sexual partners were significantly associated with PDE5 inhibitor use. The prevalence of PDE5 inhibitor use among undergraduate students was 5.5%. Cigarette smoking and other substance use, older age, and greater number of sexual partners were significantly associated factors for PDE5 inhibitor use. These findings suggest that restricting access to PDE5 inhibitor drugs is essential to curtailing misuse among university students.

Recreational Use of Phosphodiesterase 5 Inhibitors and Its Associated Factors among Undergraduate Male Students in an Ethiopian University: A Cross-Sectional Study

PubMed Central

Bhagavathula, Akshaya Srikanth; Gebresillassie, Begashaw Melaku; Tefera, Yonas Getaye; Belachew, Sewunet Admasu; Erku, Daniel Asfaw

2016-01-01

Purpose To assess the prevalence of phosphodiesterase 5 (PDE5) inhibitor use and associated factors among University of Gondar undergraduate students. Materials and Methods An institution-based, cross-sectional study, using a survey questionnaire, was conducted from October to December 2015 to assess PDE5 inhibitor use and associated factors among male students at the University of Gondar. A Self-Esteem and Relationship questionnaire (14 items), an International Index of Erectile Function questionnaire (15 items) and a questionnaire on PDE5 inhibitor use (14 items) were included in the survey. Results Across all respondents (age, 21.9±1.88 years), more than half (55.7%, n=233) had heard about PDE5 inhibitors, but only 23 men (5.5%) reported trying a PDE5 inhibitor drug at least once. Older students were more likely to use PDE5 inhibitors compared to younger students (adjusted odds ratio [AOR], 1.40; 95% confidence interval [CI], 1.109~1.768). Those students who were smokers were 5.15 times more likely to use PDE5 inhibitors as compared to their non-smoking counterparts (AOR, 5.15; 95% CI, 2.096~12.687). In addition, multivariate logistic regression showed that being in a relationship, alcohol use, greater number of cigarettes smoked per day, and more sexual partners were significantly associated with PDE5 inhibitor use. Conclusions The prevalence of PDE5 inhibitor use among undergraduate students was 5.5%. Cigarette smoking and other substance use, older age, and greater number of sexual partners were significantly associated factors for PDE5 inhibitor use. These findings suggest that restricting access to PDE5 inhibitor drugs is essential to curtailing misuse among university students. PMID:28053948

The oligomerization state determines regulatory properties and inhibitor sensitivity of type 4 cAMP-specific phosphodiesterases.

PubMed

Richter, Wito; Conti, Marco

2004-07-16

PDE4 splice variants are classified into long and short forms depending on the presence or absence of two unique N-terminal domains termed upstream conserved regions 1 and 2 (UCR1 and -2). We have shown previously that the UCR module mediates dimerization of PDE4 long forms, whereas short forms, which lack UCR1, behave as monomers. In the present study, we demonstrate that dimerization is an essential structural element that determines the regulatory properties and inhibitor sensitivities of PDE4 enzymes. Comparing the properties of the dimeric wild type PDE4D3 with several monomeric mutant PDE4D3 constructs revealed that disruption of dimerization ablates the activation of PDE4 long forms by either protein kinase A phosphorylation or phosphatidic acid binding. Moreover, the analysis of heterodimers consisting of a catalytically active and a catalytically inactive PDE4D3 subunit indicates that protein kinase A phosphorylation of both subunits is essential to fully activate PDE4 enzymes. In addition to affecting enzyme regulation, disruption of dimerization reduces the sensitivity of the enzymes toward the prototypical PDE4 inhibitor rolipram. Parallel binding assays indicated that this shift in rolipram sensitivity is likely mediated by a decrease in the number of inhibitor binding sites in the high affinity rolipram binding state. Thus, although dimerization is not a requirement for high affinity rolipram binding, it functions to stabilize PDE4 long forms in their high affinity rolipram binding conformation. Taken together, our data indicate that dimerization defines the properties of PDE4 enzymes and suggest a common structural and functional organization for all PDEs.

Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background.

PubMed

Siuciak, Judith A; McCarthy, Sheryl A; Chapin, Douglas S; Martin, Ashley N; Harms, John F; Schmidt, Christopher J

2008-02-01

The phenotype of genetically modified animals is strongly influenced by both the genetic background of the animal as well as environmental factors. We have previously reported the behavioral and neurochemical characterization of PDE10A knockout mice maintained on a DBA1LacJ (PDE10A(DBA)) genetic background. The aim of the present studies was to assess the behavioral and neurochemical phenotype of PDE10A knockout mice on an alternative congenic C57BL/6N (PDE10A(C57)) genetic background. Consistent with our previous results, PDE10A(C57) knockout mice showed a decrease in exploratory locomotor activity and a delay in the acquisition of conditioned avoidance responding. Also consistent with previous studies, the elimination of PDE10A did not alter basal levels of striatal cGMP or cAMP or affect behavior in several other well-characterized behavioral assays. PDE10A(C57) knockout mice showed a blunted response to MK-801, although to a lesser degree than previously observed in the PDE10A(DBA) knockout mice, and no differences were observed following a PCP challenge. PDE10A(C57) knockout mice showed a significant change in striatal dopamine turnover, which was accompanied by an enhanced locomotor response to AMPH, These studies demonstrate that while many of the behavioral effects of the PDE10A gene deletion appear to be independent of genetic background, the impact of the deletion on behavior can vary in magnitude. Furthermore, the effects on the dopaminergic system appear to be background-dependent, with significant effects observed only in knockout mice on the C57BL6N genetic background.

Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

PubMed Central

Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

2014-01-01

Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

Distinct phosphodiesterase 5A-containing compartments allow selective regulation of cGMP-dependent signalling in human arterial smooth muscle cells.

PubMed

Wilson, Lindsay S; Guo, Manhong; Umana, M Bibiana; Maurice, Donald H

2017-08-01

Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO · ) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP 3 R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP 3 -mediated release of ER Ca 2+ in human platelets. Herein, we report that PDE5A integrates into an analogous signalosome in human arterial smooth muscle cells (HASMC), wherein it regulates muscarinic agonist-dependent Ca 2+ release and is activated selectively by PKG-dependent phosphorylation. In addition, we report that PDE5A also regulates HASMC functions via events independent of PKG, but rather through actions coordinated by competitive cGMP-mediated inhibition of cAMP hydrolysis by the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A). Indeed, we show that ANP increases both cGMP and cAMP levels in HASMC and promotes phosphorylation of vasodilator-stimulated phospho-protein (VASP) at each the PKG and PKA phospho-acceptor sites. Since selective inhibition of PDE5 decreased DNA synthesis and chemotaxis of HASMC, and that PDE3A knockdown obviated these effects, our findings are consistent with a role for a PDE5A-PDE3A-PKA axis in their regulation. Our findings provide insight into the existence of distinct "pools" of PDE5A in HASMC and support the idea that these discrete compartments regulate distinct cGMP-dependent events. As a corollary, we suggest that it may be possible to target these distinct PDE5A-regulated pools and in so-doing differentially impact selected cGMP-regulated functions in these cells. Copyright © 2017. Published by Elsevier Inc.

Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors

PubMed Central

Cardozo, Suzana Vanessa S.; Carvalho, Vinicius de Frias; Romeiro, Nelilma Correia; Silva, Patrícia Machado Rodrigues e; Martins, Marco Aurélio; Barreiro, Eliezer J.; Lima, Lídia Moreira

2016-01-01

Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k) designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR) was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448) presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral), 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg) also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma. PMID:27695125

A Resonant Pulse Detonation Actuator for High-Speed Boundary Layer Separation Control

NASA Technical Reports Server (NTRS)

Beck, B. T.; Cutler, A. D.; Drummond, J. P.; Jones, S. B.

2004-01-01

A variety of different types of actuators have been previously investigated as flow control devices. Potential applications include the control of boundary layer separation in external flows, as well as jet engine inlet and diffuser flow control. The operating principles for such devices are typically based on either mechanical deflection of control surfaces (which include MEMS flap devices), mass injection (which includes combustion driven jet actuators), or through the use of synthetic jets (diaphragm devices which produce a pulsating jet with no net mass flow). This paper introduces some of the initial flow visualization work related to the development of a relatively new type of combustion-driven jet actuator that has been proposed based on a pulse detonation principle. The device is designed to utilize localized detonation of a premixed fuel (Hydrogen)-air mixture to periodically inject a jet of gas transversely into the primary flow. Initial testing with airflow successfully demonstrated resonant conditions within the range of acoustic frequencies expected for the design. Schlieren visualization of the pulsating air jet structure revealed axially symmetric vortex flow, along with the formation of shocks. Flow visualization of the first successful sustained oscillation condition is also demonstrated for one configuration of the current test section. Future testing will explore in more detail the onset of resonant combustion and the approach to conditions of sustained resonant detonation.

Guide to Using Onionskin Analysis Code (U)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fugate, Michael Lynn; Morzinski, Jerome Arthur

2016-09-15

This document is a guide to using R-code written for the purpose of analyzing onionskin experiments. We expect the user to be very familiar with statistical methods and the R programming language. For more details about onionskin experiments and the statistical methods mentioned in this document see Storlie, Fugate, et al. (2013). Engineers at LANL experiment with detonators and high explosives to assess performance. The experimental unit, called an onionskin, is a hemisphere consisting of a detonator and a booster pellet surrounded by explosive material. When the detonator explodes, a streak camera mounted above the pole of the hemisphere recordsmore » when the shock wave arrives at the surface. The output from the camera is a two-dimensional image that is transformed into a curve that shows the arrival time as a function of polar angle. The statistical challenge is to characterize a baseline population of arrival time curves and to compare the baseline curves to curves from a new, so-called, test series. The hope is that the new test series of curves is statistically similar to the baseline population.« less

Characterizing Laminar Flame Interactions with Turbulent Fluidic Jets and Solid Obstacles for Turbulence Induction

NASA Astrophysics Data System (ADS)

Gerdts, Stephen; Chambers, Jessica; Ahmed, Kareem

2016-11-01

A detonation engine's fundamental design concept focuses on enhancing the Deflagration to Detonation Transition (DDT), the process through which subsonic flames accelerate to form a spontaneous detonation wave. Flame acceleration is driven by turbulent interactions that expand the reaction zone and induce mixing of products and reactants. Turbulence in a duct can be generated using solid obstructions, fluidic obstacles, duct angle changes, and wall skin friction. Solid obstacles have been previously explored and offer repeatable turbulence induction at the cost of pressure losses and additional system weight. Fluidic jet obstacles are a novel technique that provide advantages such as the ability to be throttled, allowing for active control of combustion modes. The scope of the present work is to expand the experimental database of varying parameters such as main flow and jet equivalence ratios, fluidic momentum ratios, and solid obstacle blockage ratios. Schlieren flow visualization and particle image velocimetry (PIV) are employed to investigate turbulent flame dynamics throughout the interaction. Optimum conditions that lead to flame acceleration for both solid and fluidic obstacles will be determined. American Chemical Society.

SURF Model Calibration Strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menikoff, Ralph

2017-03-10

SURF and SURFplus are high explosive reactive burn models for shock initiation and propagation of detonation waves. They are engineering models motivated by the ignition & growth concept of high spots and for SURFplus a second slow reaction for the energy release from carbon clustering. A key feature of the SURF model is that there is a partial decoupling between model parameters and detonation properties. This enables reduced sets of independent parameters to be calibrated sequentially for the initiation and propagation regimes. Here we focus on a methodology for tting the initiation parameters to Pop plot data based on 1-Dmore » simulations to compute a numerical Pop plot. In addition, the strategy for tting the remaining parameters for the propagation regime and failure diameter is discussed.« less

Effect of Fuel-Air Ratio, Inlet Temperature, and Exhaust Pressure on Detonation

NASA Technical Reports Server (NTRS)

Taylor, E S; Leary, W A; Diver, J R

1940-01-01

An accurate determination of the end-gas condition was attempted by applying a refined method of analysis to experimental results. The results are compared with those obtained in Technical Report no. 655. The experimental technique employed afforded excellent control over the engine variables and unusual cyclic reproducibility. This, in conjunction with the new analysis, made possible the determination of the state of the end-gas at any instant to a fair degree of precision. Results showed that for any given maximum pressure the maximum permissible end-gas temperature increased as the fuel-air ratio was increased. The tendency to detonate was slightly reduced by an increase in residual gas content resulting from an increase in exhaust backpressure with inlet pressure constant.

Modeling PBX 9501 overdriven release experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, P.K.

1997-11-01

High Explosives (HE) performs work by the expansion of its detonation products. Along with the propagation of the detonation wave, the equation of state (EOS) of the products determines the HE performance in an engineering system. The authors show the failure of the standard Jones-Wilkins-Lee (JWL) equation of state (EOS) in modeling the overdriven release experiments of PBX 9501. The deficiency can be tracked back to inability of the same EOS in matching the shock pressure and the sound speed on the Hugoniot in the hydrodynamic regime above the Chapman-Jouguet pressure. After adding correction terms to the principal isentrope ofmore » the standard JWL EOS, the authors are able to remedy this shortcoming and the simulation was successful.« less

Phosphodiesterase 4 Inhibitor Therapies for Atopic Dermatitis: Progress and Outlook.

PubMed

Ahluwalia, Jusleen; Udkoff, Jeremy; Waldman, Andrea; Borok, Jenna; Eichenfield, Lawrence F

2017-09-01

Phosphodiesterase 4 (PDE4) is a cyclic AMP degrading enzyme in leukocytes. Several decades ago, increased PDE activity was demonstrated in patients with atopic dermatitis (AD). Currently, several PDE4 inhibitors in both topical and oral formulation have been developed to target the inflammatory cascade of AD. This review shows the pathogenic rationale behind these inhibitors, and discusses multiple PDE4 inhibitors that are under evaluation or in the market. PDE4 inhibitors may be considered as favorable agents in the repertoire of current interventions for AD.

New findings on phosphodiesterases, MoPdeH and MoPdeL, in Magnaporthe oryzae revealed by structural analysis.

PubMed

Yang, Li-Na; Yin, Ziyi; Zhang, Xi; Feng, Wanzhen; Xiao, Yuhan; Zhang, Haifeng; Zheng, Xiaobo; Zhang, Zhengguang

2018-05-01

The cyclic adenosine monophosphate (cAMP) signalling pathway mediates signal communication and sensing during infection-related morphogenesis in eukaryotes. Many studies have implicated cAMP as a critical mediator of appressorium development in the rice blast fungus, Magnaporthe oryzae. The cAMP phosphodiesterases, MoPdeH and MoPdeL, as key regulators of intracellular cAMP levels, play pleiotropic roles in cell wall integrity, cellular morphology, appressorium formation and infectious growth in M. oryzae. Here, we analysed the roles of domains of MoPdeH and MoPdeL separately or in chimeras. The results indicated that the HD and EAL domains of MoPdeH are indispensable for its phosphodiesterase activity and function. Replacement of the MoPdeH HD domain with the L1 and L2 domains of MoPdeL, either singly or together, resulted in decreased cAMP hydrolysis activity of MoPdeH. All of the transformants exhibited phenotypes similar to that of the ΔMopdeH mutant, but also revealed that EAL and L1 play additional roles in conidiation, and that L1 is involved in infectious growth. We further found that the intracellular cAMP level is important for surface signal recognition and hyphal autolysis. The intracellular cAMP level negatively regulates Mps1-MAPK and positively regulates Pmk1-MAPK in the rice blast fungus. Our results provide new information to better understand the cAMP signalling pathway in the development, differentiation and plant infection of the fungus. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

PubMed

Kleiman, Robin J; Chapin, Douglas S; Christoffersen, Curt; Freeman, Jody; Fonseca, Kari R; Geoghegan, Kieran F; Grimwood, Sarah; Guanowsky, Victor; Hajós, Mihály; Harms, John F; Helal, Christopher J; Hoffmann, William E; Kocan, Geralyn P; Majchrzak, Mark J; McGinnis, Dina; McLean, Stafford; Menniti, Frank S; Nelson, Fredrick; Roof, Robin; Schmidt, Anne W; Seymour, Patricia A; Stephenson, Diane T; Tingley, Francis David; Vanase-Frawley, Michelle; Verhoest, Patrick R; Schmidt, Christopher J

2012-05-01

Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

The dangers of sexual enhancement supplements and counterfeit drugs to "treat" erectile dysfunction.

PubMed

Chiang, Jason; Yafi, Faysal A; Dorsey, Philip J; Hellstrom, Wayne J G

2017-02-01

Counterfeit phosphodiesterase-5 inhibitors (PDE-5i) are an increasing problem. Already in widespread use, the market for PDE-5i is steadily growing as the population ages. Counterfeiters are taking advantage of this growing market by developing illicit and counterfeit PDE-5i products. Many factors are contributing to the rapid growth of the illicit market, such as the low risk of prosecution, potentially high financial reward, and ease of distribution via Internet pharmacies. Consumers of illicit PDE-5i often do not realize they are using counterfeit products and placing themselves at an unnecessary health risk. Others seek to bypass the legitimate healthcare system due to either embarrassment of the underlying condition or desire for cheaper alternatives. However, taking illicit PDE-5i may harm consumers directly, as many illicit products contain detrimental contaminants and inaccurate amounts of the active ingredient without the appropriate warnings. Bypassing the legitimate healthcare system also endangers consumers indirectly, as erectile dysfunction (ED) is often associated with other medical comorbidities that patients should be screened for. Furthermore, PDE-5i can have potentially dangerous interactions with other pharmaceuticals that are rarely warned against with counterfeit PDE-5i. This communication reviews the literature regarding counterfeit PDE-5i, and summarizes both the scope and dangers of the illicit PDE-5i market.

A novel thermoregulatory role for PDE10A in mouse and human adipocytes.

PubMed

Hankir, Mohammed K; Kranz, Mathias; Gnad, Thorsten; Weiner, Juliane; Wagner, Sally; Deuther-Conrad, Winnie; Bronisch, Felix; Steinhoff, Karen; Luthardt, Julia; Klöting, Nora; Hesse, Swen; Seibyl, John P; Sabri, Osama; Heiker, John T; Blüher, Matthias; Pfeifer, Alexander; Brust, Peter; Fenske, Wiebke K

2016-07-01

Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the novel radioligand [(18)F]-AQ28A, we found marked levels of PDE10A in interscapular brown adipose tissue (BAT) of mice. Pharmacological inactivation of PDE10A with the highly selective inhibitor MP-10 recruited BAT and potentiated thermogenesis in vivo In diet-induced obese mice, chronic administration of MP-10 caused weight loss associated with increased energy expenditure, browning of white adipose tissue, and improved insulin sensitivity. Analysis of human PET data further revealed marked levels of PDE10A in the supraclavicular region where brown/beige adipocytes are clustered in adults. Finally, the inhibition of PDE10A with MP-10 stimulated thermogenic gene expression in human brown adipocytes and induced browning of human white adipocytes. Collectively, our findings highlight a novel thermoregulatory role for PDE10A in mouse and human adipocytes and promote PDE10A inhibitors as promising candidates for the treatment of obesity and diabetes. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

PDE7B is involved in nandrolone decanoate hydrolysis in liver cytosol and its transcription is up-regulated by androgens in HepG2.

PubMed

Strahm, Emmanuel; Rane, Anders; Ekström, Lena

2014-01-01

Most androgenic drugs are available as esters for a prolonged depot action. However, the enzymes involved in the hydrolysis of the esters have not been identified. There is one study indicating that PDE7B may be involved in the activation of testosterone enanthate. The aims are to identify the cellular compartments where the hydrolysis of testosterone enanthate and nandrolone decanoate occurs, and to investigate the involvement of PDE7B in the activation. We also determined if testosterone and nandrolone affect the expression of the PDE7B gene. The hydrolysis studies were performed in isolated human liver cytosolic and microsomal preparations with and without specific PDE7B inhibitor. The gene expression was studied in human hepatoma cells (HepG2) exposed to testosterone and nandrolone. We show that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate and nandrolone decanoate in liver cytosol. The gene expression of PDE7B was significantly induced 3- and 5- fold after 2 h exposure to 1 μM testosterone enanthate and nandrolone decanoate, respectively. These results show that PDE7B is involved in the activation of esterified nandrolone and testosterone and that the gene expression of PDE7B is induced by supra-physiological concentrations of androgenic drugs.

Identification of cancer cytotoxic modulators of PDE3A by predictive chemogenomics

PubMed Central

de Waal, Luc; Lewis, Timothy A.; Rees, Matthew G.; Tsherniak, Aviad; Wu, Xiaoyun; Choi, Peter S.; Gechijian, Lara; Hartigan, Christina; Faloon, Patrick W.; Hickey, Mark J.; Tolliday, Nicola; Carr, Steven A.; Clemons, Paul A.; Munoz, Benito; Wagner, Bridget K.; Shamji, Alykhan F.; Koehler, Angela N.; Schenone, Monica; Burgin, Alex B.; Schreiber, Stuart L.; Greulich, Heidi; Meyerson, Matthew

2015-01-01

High cancer death rates indicate the need for new anti-cancer therapeutic agents. Approaches to discover new cancer drugs include target-based drug discovery and phenotypic screening. Here, we identified phosphodiesterase 3A modulators as cell-selective cancer cytotoxic compounds by phenotypic compound library screening and target deconvolution by predictive chemogenomics. We found that sensitivity to 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, across 766 cancer cell lines correlates with expression of the phosphodiesterase 3A gene, PDE3A. Like DNMDP, a subset of known PDE3A inhibitors kill selected cancer cells while others do not. Furthermore, PDE3A depletion leads to DNMDP resistance. We demonstrated that DNMDP binding to PDE3A promotes an interaction between PDE3A and Schlafen 12 (SLFN12), suggesting a neomorphic activity. Co-expression of SLFN12 with PDE3A correlates with DNMDP sensitivity, while depletion of SLFN12 results in decreased DNMDP sensitivity. Our results implicate PDE3A modulators as candidate cancer therapeutic agents and demonstrate the power of predictive chemogenomics in small-molecule discovery. PMID:26656089

DISC1, PDE4B, and NDE1 at the centrosome and synapse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradshaw, Nicholas J.; Ogawa, Fumiaki; Antolin-Fontes, Beatriz

Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependantmore » Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.« less

Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD

PubMed Central

Komatsu, Kensei; Lee, Ji-Yun; Miyata, Masanori; Hyang Lim, Jae; Jono, Hirofumi; Koga, Tomoaki; Xu, Haidong; Yan, Chen; Kai, Hirofumi; Li, Jian-Dong

2013-01-01

The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defence response. Here, we show that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. Interestingly, in Cyld-deficient mice, inhibition of PDE4B no longer suppresses inflammation. Moreover, PDE4B negatively regulates CYLD via specific activation of JNK2 but not JNK1. Importantly, ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4. These studies provide insights into how inflammation is tightly regulated via the inhibition of its negative regulator and may also lead to the development of new anti-inflammatory therapeutics that upregulate CYLD expression. PMID:23575688

Identification of a Phosphodiesterase-Inhibiting Fraction from Roasted Coffee (Coffea arabica) through Activity-Guided Fractionation.

PubMed

Röhrig, Teresa; Liesenfeld, David; Richling, Elke

2017-05-17

Recent reports that coffee can significantly inhibit cAMP phosphodiesterases (PDEs) in vitro, as well as in vivo, have described another beneficial effect of coffee consumption. However, the PDE-inhibiting substances remain mostly unknown. We chose activity-guided fractionation and an in vitro test system to identify the coffee components that are responsible for PDE inhibition. This approach indicated that a fraction of melanoidins reveals strong PDE-inhibiting potential (IC 50 = 130 ± 42 μg/mL). These melanoidins were characterized as water-soluble, low-molecular weight melanoidins (<3 kDa) with a nitrogen content of 4.2% and a carbohydrate content lower than those of other melanoidins. Fractions containing known PDE inhibitors such as chlorogenic acids, alkylpyrazines, or trigonelline as well as N-caffeoyl-tryptophan and N-p-coumaroyl-tryptophan did not exert PDE-inhibiting activity. We also observed that the known PDE inhibitor caffeine does not contribute to the PDE-inhibiting effects of coffee.

Engineer: The Professional Bulletin of Army Engineers. Volume 40, September-December 2010

DTIC Science & Technology

2010-12-01

used by the enemy? Do we use sniper screens? What about the entry control point? The whole idea behind a COP is that it’s a secure place close to...more powerful signal, to initiate detonations. U.S. forces countered by using a stronger jamming signal. The C-IED fight escalated and the insurgents...attacked? Information from an existing database helped to locate the enemy and plot his locations on a map by using commer- cial off-the-shelf (COTS

Effect of phosphodiesterase inhibitors in the bladder.

PubMed

Chughtai, Bilal; Ali, Aizaz; Dunphy, Claire; Kaplan, Steven A

2015-01-01

Many aging men will experience lower urinary tract symptoms (LUTS). Phosphodiesterase type 5 (PDE5) inhibitors have shown promise in treating LUTS in these patients. PDE5 inhibitors mediate their effects through several pathways including cAMP, NO/cGMP, K-channel modulated pathways, and the l -cysteine/H 2 S pathway. PDE5 inhibitors exert their effect in muscle cells, nerve fibers, and interstitial cells (ICs). The use of PDE5 inhibitors led to improvement in LUTS. This included urodynamic parameters. PDE5 inhibitors may play a significant role in LUTS due to their effect on the bladder rather than the prostate.

Computer Modeling of a Rotating Detonation Engine in a Rocket Configuration

DTIC Science & Technology

2015-03-01

than the ambient pressure P0, the nozzle was fully supersonic . If the calculated pressure P9 after the normal shock was less than the ambient...18 Gas Properties...66 vii Nomenclature Variable Definition 3∗ Entrance to RDE 4 RDE exit 8 Nozzle 9 Nozzle exit A Area a Speed of

A study of low emissions gas turbine combustions

NASA Technical Reports Server (NTRS)

Adelman, Henry G.

1994-01-01

Analytical studies have been conducted to determine the best methods of reducing NO(x) emissions from proposed civilian supersonic transports. Modifications to the gas turbine engine combustors and the use of additives were both explored. It was found that combustors which operated very fuel rich or lean appear to be able to meet future emissions standards. Ammonia additives were also effective in removing NO(x), but residual ammonia remained a problem. Studies of a novel combustor which reduces emissions and improves performance were initiated. In a related topic, a study was begun on the feasibility of using supersonic aircraft to obtain atmospheric samples. The effects of shock heating and compression on sample integrity were modeled. Certain chemical species, including NO2, HNO3, and ClONO2 were found to undergo changes to their composition after they passed through shock waves at Mach 2. The use of detonation waves to enhance mixing and combustion in supersonic airflows was also investigated. This research is important to the use of airbreathing propulsion to obtain orbital speeds and access to space. Both steady and pulsed detonation waves were shown to improve engine performance.

Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype.

PubMed

Libé, Rossella; Horvath, Anelia; Vezzosi, Delphine; Fratticci, Amato; Coste, Joel; Perlemoine, Karine; Ragazzon, Bruno; Guillaud-Bataille, Marine; Groussin, Lionel; Clauser, Eric; Raffin-Sanson, Marie-Laure; Siegel, Jennifer; Moran, Jason; Drori-Herishanu, Limor; Faucz, Fabio Rueda; Lodish, Maya; Nesterova, Maria; Bertagna, Xavier; Bertherat, Jerome; Stratakis, Constantine A

2011-01-01

Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation of CNC with a great inter-individual variability. Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors. Our objective was to investigate the role of PDE11A as a possible gene modifier of the phenotype in a series of 150 patients with CNC. A higher frequency of PDE11A variants in patients with CNC compared with healthy controls was found (25.3 vs. 6.8%, P < 0.0001). Among CNC patients, those with PPNAD were significantly more frequently carriers of PDE11A variants compared with patients without PPNAD (30.8 vs. 13%, P = 0.025). Furthermore, men with PPNAD were significantly more frequently carriers of PDE11A sequence variants (40.7%) than women with PPNAD (27.3%) (P < 0.001). A higher frequency of PDE11A sequence variants was also found in patients with large-cell calcifying Sertoli cell tumors (LCCSCT) compared with those without LCCSCT (50 vs. 10%, P = 0.0056). PDE11A variants were significantly associated with the copresence of PPNAD and LCCSCT in men: 81 vs. 20%, P < 0.004). The simultaneous inactivation of PRKAR1A and PDE11A by small inhibitory RNA led to an increase in cAMP-regulatory element-mediated transcriptional activity under basal conditions and after stimulation by forskolin. We demonstrate, in a large cohort of CNC patients, a high frequency of PDE11A variants, suggesting that PDE11A is a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation.

Biomolecular surface construction by PDE transform

PubMed Central

Zheng, Qiong; Yang, Siyang; Wei, Guo-Wei

2011-01-01

This work proposes a new framework for the surface generation based on the partial differential equation (PDE) transform. The PDE transform has recently been introduced as a general approach for the mode decomposition of images, signals, and data. It relies on the use of arbitrarily high order PDEs to achieve the time-frequency localization, control the spectral distribution, and regulate the spatial resolution. The present work provides a new variational derivation of high order PDE transforms. The fast Fourier transform is utilized to accomplish the PDE transform so as to avoid stringent stability constraints in solving high order PDEs. As a consequence, the time integration of high order PDEs can be done efficiently with the fast Fourier transform. The present approach is validated with a variety of test examples in two and three-dimensional settings. We explore the impact of the PDE transform parameters, such as the PDE order and propagation time, on the quality of resulting surfaces. Additionally, we utilize a set of 10 proteins to compare the computational efficiency of the present surface generation method and the MSMS approach in Cartesian meshes. Moreover, we analyze the present method by examining some benchmark indicators of biomolecular surface, i.e., surface area, surface enclosed volume, solvation free energy and surface electrostatic potential. A test set of 13 protein molecules is used in the present investigation. The electrostatic analysis is carried out via the Poisson-Boltzmann equation model. To further demonstrate the utility of the present PDE transform based surface method, we solve the Poisson-Nernst-Planck (PNP) equations with a PDE transform surface of a protein. Second order convergence is observed for the electrostatic potential and concentrations. Finally, to test the capability and efficiency of the present PDE transform based surface generation method, we apply it to the construction of an excessively large biomolecule, a virus surface capsid. Virus surface morphologies of different resolutions are attained by adjusting the propagation time. Therefore, the present PDE transform provides a multiresolution analysis in the surface visualization. Extensive numerical experiment and comparison with an established surface model indicate that the present PDE transform is a robust, stable and efficient approach for biomolecular surface generation in Cartesian meshes. PMID:22582140

Powerful relaxation of phosphodiesterase type 4 inhibitor rolipram in the pig and human bladder neck.

PubMed

Ribeiro, Ana S F; Fernandes, Vítor S; Martínez-Sáenz, Ana; Martínez, Pilar; Barahona, María Victoria; Orensanz, Luis M; Blaha, Igor; Serrano-Margüello, Daniel; Bustamante, Salvador; Carballido, Joaquín; García-Sacristán, Albino; Prieto, Dolores; Hernández, Medardo

2014-04-01

Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility. To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck. Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i ) and tension for rolipram in bladder neck samples were used. PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension. PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram> > sildenafil>vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa ) and intermediate (IKCa ) conductance Ca2+ -activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2 S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase. PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]i desensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release. © 2014 International Society for Sexual Medicine.

Phosphodiesterase 5a Inhibition with Adenoviral Short Hairpin RNA Benefits Infarcted Heart Partially through Activation of Akt Signaling Pathway and Reduction of Inflammatory Cytokines.

PubMed

Li, Longhu; Zhao, Dong; Jin, Zhe; Zhang, Jian; Paul, Christian; Wang, Yigang

2015-01-01

Treatment with short hairpin RNA (shRNA) interference therapy targeting phosphodiesterase 5a after myocardial infarction (MI) has been shown to mitigate post-MI heart failure. We investigated the mechanisms that underpin the beneficial effects of PDE5a inhibition through shRNA on post-MI heart failure. An adenoviral vector with an shRNA sequence inserted was adopted for the inhibition of phosphodiesterase 5a (Ad-shPDE5a) in vivo and in vitro. Myocardial infarction (MI) was induced in male C57BL/6J mice by left coronary artery ligation, and immediately after that, the Ad-shPDE5a was injected intramyocardially around the MI region and border areas. Four weeks post-MI, the Ad-shPDE5a-treated mice showed significant mitigation of the left ventricular (LV) dilatation and dysfunction compared to control mice. Infarction size and fibrosis were also significantly reduced in Ad-shPDE5a-treated mice. Additionally, Ad-shPDE5a treatment decreased the MI-induced inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and transforming growth factor-β1, which was confirmed in vitro in Ad-shPDE5a transfected myofibroblasts cultured under oxygen glucose deprivation. Finally, Ad-shPDE5a treatment was found to activate the myocardial Akt signaling pathway in both in vivo and in vitro experiments. These findings indicate that PDE5a inhibition by Ad-shPDE5a via the Akt signal pathway could be of significant value in the design of future therapeutics for post-MI heart failure.

Erectile dysfunction and phosphodiesterase type 5 inhibitor use: associations with sexual activities, function and satisfaction in a population sample of older men.

PubMed

Lee, D M; Nazroo, J; Pendleton, N

2015-07-01

The objective of this study was to examine the association between sexual activities, problems and satisfaction, and ED and PDE5 inhibitor (PDE5i) use. A nationally representative sample of men (n=2612) aged 51-87 years from the English Longitudinal Study of Ageing completed an in-depth Sexual Relationships and Activities Questionnaire. Associations between ED and/or PDE5i use and sexual outcomes were explored using logistic regression models adjusted for age, health and lifestyle factors. PDE5i use in the preceding 3 months was reported by a total of 191 (7%) men, whereas 542 (21%) reported ED but no PDE5i use (untreated ED). Compared with men without ED, PDE5i users were more likely to be sexually active and report more frequent sexual intercourse. Men with untreated ED reported the lowest frequency of sexual activities. Compared with men without ED, both PDE5i users and those with untreated ED were more likely to report being concerned about their level of sexual desire, frequency of sexual activities, erectile function, waking erections and orgasmic experience. PDE5i users were also more concerned about and dissatisfied with their overall sex life than men without ED. This population-based study shows that while PDE5i use is associated with improved sexual functioning, this is not equally reflected in decreased levels of concern and dissatisfaction with their overall sexual health. Clinicians should be aware of this disparity between functional gains and continuing sexual concerns and dissatisfaction, and, where appropriate, offer psychosexual counselling as an adjunct to PDE5i medication.

Multithreaded Model for Dynamic Load Balancing Parallel Adaptive PDE Computations

NASA Technical Reports Server (NTRS)

Chrisochoides, Nikos

1995-01-01

We present a multithreaded model for the dynamic load-balancing of numerical, adaptive computations required for the solution of Partial Differential Equations (PDE's) on multiprocessors. Multithreading is used as a means of exploring concurrency in the processor level in order to tolerate synchronization costs inherent to traditional (non-threaded) parallel adaptive PDE solvers. Our preliminary analysis for parallel, adaptive PDE solvers indicates that multithreading can be used an a mechanism to mask overheads required for the dynamic balancing of processor workloads with computations required for the actual numerical solution of the PDE's. Also, multithreading can simplify the implementation of dynamic load-balancing algorithms, a task that is very difficult for traditional data parallel adaptive PDE computations. Unfortunately, multithreading does not always simplify program complexity, often makes code re-usability not an easy task, and increases software complexity.

Parameter Estimation of Partial Differential Equation Models.

PubMed

Xun, Xiaolei; Cao, Jiguo; Mallick, Bani; Carroll, Raymond J; Maity, Arnab

2013-01-01

Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown, and need to be estimated from the measurements of the dynamic system in the present of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE, and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from LIDAR data.

Prenatal Drug Exposure and Adolescent Cortisol Reactivity: Association with Behavioral Concerns.

PubMed

Buckingham-Howes, Stacy; Mazza, Dayna; Wang, Yan; Granger, Douglas A; Black, Maureen M

2016-09-01

To examine stress reactivity in a sample of adolescents with prenatal drug exposure (PDE) by examining the consequences of PDE on stress-related adrenocortical reactivity, behavioral problems, and drug experimentation during adolescence. Participants (76 PDE, 61 non-drug exposed [NE]; 99% African-American; 50% male; mean age = 14.17 yr, SD = 1.17) provided a urine sample, completed a drug use questionnaire, and provided saliva samples (later assayed for cortisol) before and after a mild laboratory stress task. Caregivers completed the Behavior Assessment System for Children, Second Edition (BASC II) and reported their relationship to the adolescent. The NE group was more likely to exhibit task-related cortisol reactivity compared to the PDE group. Overall behavior problems and drug experimentation were comparable across groups with no differences between PDE and NE groups. In unadjusted mediation analyses, cortisol reactivity mediated the association between PDE and BASC II aggression scores (95% bootstrap confidence interval [CI], 0.04-4.28), externalizing problems scores (95% bootstrap CI, 0.03-4.50), and drug experimentation (95% bootstrap CI, 0.001-0.54). The associations remain with the inclusion of gender as a covariate but not when age is included. Findings support and expand current research in cortisol reactivity and PDE by demonstrating that cortisol reactivity attenuates the association between PDE and behavioral problems (aggression) and drug experimentation. If replicated, PDE may have long-lasting effects on stress-sensitive physiological mechanisms associated with behavioral problems (aggression) and drug experimentation in adolescence.

PDE4 and PDE5 regulate cyclic nucleotide contents and relaxing effects on carbachol-induced contraction in the bovine abomasum.

PubMed

Kaneda, Takeharu; Kido, Yuuki; Tajima, Tsuyoshi; Urakawa, Norimoto; Shimizu, Kazumasa

2015-01-01

The effects of various selective phosphodiesterase (PDE) inhibitors on carbachol (CCh)-induced contraction in the bovine abomasum were investigated. Various selective PDE inhibitors, vinpocetine (type 1), erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, type 2), milrinone (type 3), Ro20-1724 (type 4), vardenafil (type 5), BRL-50481 (type 7) and BAY73-6691 (type 9), inhibited CCh-induced contractions in a concentration-dependent manner. Among the PDE inhibitors, Ro20-1724 and vardenafil induced more relaxation than the other inhibitors based on the data for the IC50 or maximum relaxation. In smooth muscle of the bovine abomasum, we showed the expression of PDE4B, 4C, 4D and 5 by RT-PCR analysis. In the presence of CCh, Ro20-1724 increased the cAMP content, but not the cGMP content. By contrast, vardenafil increased the cGMP content, but not the cAMP content. These results suggest that Ro20-1724-induced relaxation was correlated with cAMP and that vardenafil-induced relaxation was correlated with cGMP in the bovine abomasum. In conclusion, PDE4 and PDE5 are the enzymes involved in regulation of the relaxation associated with cAMP and cGMP, respectively, in the bovine abomasum.

Solving Partial Differential Equations in a data-driven multiprocessor environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaudiot, J.L.; Lin, C.M.; Hosseiniyar, M.

1988-12-31

Partial differential equations can be found in a host of engineering and scientific problems. The emergence of new parallel architectures has spurred research in the definition of parallel PDE solvers. Concurrently, highly programmable systems such as data-how architectures have been proposed for the exploitation of large scale parallelism. The implementation of some Partial Differential Equation solvers (such as the Jacobi method) on a tagged token data-flow graph is demonstrated here. Asynchronous methods (chaotic relaxation) are studied and new scheduling approaches (the Token No-Labeling scheme) are introduced in order to support the implementation of the asychronous methods in a data-driven environment.more » New high-level data-flow language program constructs are introduced in order to handle chaotic operations. Finally, the performance of the program graphs is demonstrated by a deterministic simulation of a message passing data-flow multiprocessor. An analysis of the overhead in the data-flow graphs is undertaken to demonstrate the limits of parallel operations in dataflow PDE program graphs.« less

DNN-state identification of 2D distributed parameter systems

NASA Astrophysics Data System (ADS)

Chairez, I.; Fuentes, R.; Poznyak, A.; Poznyak, T.; Escudero, M.; Viana, L.

2012-02-01

There are many examples in science and engineering which are reduced to a set of partial differential equations (PDEs) through a process of mathematical modelling. Nevertheless there exist many sources of uncertainties around the aforementioned mathematical representation. Moreover, to find exact solutions of those PDEs is not a trivial task especially if the PDE is described in two or more dimensions. It is well known that neural networks can approximate a large set of continuous functions defined on a compact set to an arbitrary accuracy. In this article, a strategy based on the differential neural network (DNN) for the non-parametric identification of a mathematical model described by a class of two-dimensional (2D) PDEs is proposed. The adaptive laws for weights ensure the 'practical stability' of the DNN-trajectories to the parabolic 2D-PDE states. To verify the qualitative behaviour of the suggested methodology, here a non-parametric modelling problem for a distributed parameter plant is analysed.

Preclinical Characterization of the Phosphodiesterase 10A PET Tracer [(11)C]MK-8193.

PubMed

Hostetler, Eric D; Fan, Hong; Joshi, Aniket D; Zeng, Zhizhen; Eng, Waisi; Gantert, Liza; Holahan, Marie; Meng, Xianjun; Miller, Patricia; O'Malley, Stacey; Purcell, Mona; Riffel, Kerry; Salinas, Cristian; Williams, Mangay; Ma, Bennett; Buist, Nicole; Smith, Sean M; Coleman, Paul J; Cox, Christopher D; Flores, Brock A; Raheem, Izzat T; Cook, Jacquelynn J; Evelhoch, Jeffrey L

2016-08-01

A positron emission tomography (PET) tracer for the enzyme phosphodiesterase 10A (PDE10A) is desirable to guide the discovery and development of PDE10A inhibitors as potential therapeutics. The preclinical characterization of the PDE10A PET tracer [(11)C]MK-8193 is described. In vitro binding studies with [(3)H]MK-8193 were conducted in rat, monkey, and human brain tissue. PET studies with [(11)C]MK-8193 were conducted in rats and rhesus monkeys at baseline and following administration of a PDE10A inhibitor. [(3)H]MK-8193 is a high-affinity, selective PDE10A radioligand in rat, monkey, and human brain tissue. In vivo, [(11)C]MK-8193 displays rapid kinetics, low test-retest variability, and a large specific signal that is displaced by a structurally diverse PDE10A inhibitor, enabling the determination of pharmacokinetic/enzyme occupancy relationships. [(11)C]MK-8193 is a useful PET tracer for the preclinical characterization of PDE10A therapeutic candidates in rat and monkey. Further evaluation of [(11)C]MK-8193 in humans is warranted.

Elasticity of crystalline molecular explosives

DOE PAGES

Hooks, Daniel E.; Ramos, Kyle J.; Bolme, C. A.; ...

2015-04-14

Crystalline molecular explosives are key components of engineered explosive formulations. In precision applications a high degree of consistency and predictability is desired under a range of conditions to a variety of stimuli. Prediction of behaviors from mechanical response and failure to detonation initiation and detonation performance of the material is linked to accurate knowledge of the material structure and first stage of deformation: elasticity. The elastic response of pentaerythritol tetranitrate (PETN), cyclotrimethylene trinitramine (RDX), and cyclotetramethylene tetranitramine (HMX), including aspects of material and measurement variability, and computational methods are described in detail. Experimental determinations of elastic tensors are compared, andmore » an evaluation of sources of error is presented. Furthermore, computed elastic constants are also compared for these materials and for triaminotrinitrobenzene (TATB), for which there are no measurements.« less

The History of the Study of Detonation

ERIC Educational Resources Information Center

Bulat, Pavel V.; Volkov, Konstantin N.

2016-01-01

In this article we reviewed the main concepts of detonative combustion. Concepts of slow and fast combustion, of detonation adiabat are introduced. Landmark works on experimental and semi-empirical detonation study are presented. We reviewed Chapman-Jouguet stationary detonation and spin detonation. Various mathematical model of detonation wave…

Building an Efficient Model for Afterburn Energy Release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alves, S; Kuhl, A; Najjar, F

2012-02-03

Many explosives will release additional energy after detonation as the detonation products mix with the ambient environment. This additional energy release, referred to as afterburn, is due to combustion of undetonated fuel with ambient oxygen. While the detonation energy release occurs on a time scale of microseconds, the afterburn energy release occurs on a time scale of milliseconds with a potentially varying energy release rate depending upon the local temperature and pressure. This afterburn energy release is not accounted for in typical equations of state, such as the Jones-Wilkins-Lee (JWL) model, used for modeling the detonation of explosives. Here wemore » construct a straightforward and efficient approach, based on experiments and theory, to account for this additional energy release in a way that is tractable for large finite element fluid-structure problems. Barometric calorimeter experiments have been executed in both nitrogen and air environments to investigate the characteristics of afterburn for C-4 and other materials. These tests, which provide pressure time histories, along with theoretical and analytical solutions provide an engineering basis for modeling afterburn with numerical hydrocodes. It is toward this end that we have constructed a modified JWL equation of state to account for afterburn effects on the response of structures to blast. The modified equation of state includes a two phase afterburn energy release to represent variations in the energy release rate and an afterburn energy cutoff to account for partial reaction of the undetonated fuel.« less

Pharmacologic therapy for erectile dysfunction and its interaction with the cardiovascular system.

PubMed

Ioakeimidis, Nikolaos; Kostis, John B

2014-01-01

Phosphodiesterase (PDE) enzymes are widely distributed throughout the body, having numerous effects and functions. The PDE type 5 (PDE5) inhibitors are widely used to treat erectile dysfunction (ED). Recent, intense preclinical and clinical research with PDE5 inhibitors has shed light on new mechanisms and has revealed a number of pleiotropic effects on the cardiovascular (CV) system. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary arterial hypertension, and both sildenafil and tadalafil are approved for this indication. However, current or future PDE5 inhibitors have the potential of becoming clinically useful in a variety of CV conditions such as heart failure, coronary artery disease, and hypertension. The present review discusses recent findings regarding pharmacologic treatment of ED and its interaction with the CV system and highlights current and future clinical applications beyond ED.

Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design

NASA Astrophysics Data System (ADS)

Howard, Brittany L.; Thompson, Philip E.; Manallack, David T.

2011-08-01

The similarity between Plasmodium falciparum phosphodiesterase enzymes ( PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each model was most similar to human PDE1. Molecular docking was able to model cyclic guanosine monophosphate (cGMP) substrate binding in each case but a docking mode supporting cyclic adenosine monophosphate (cAMP) binding could not be found. Anticipating the potential of PfPDE inhibitors as anti-malarial drugs, a range of reported PDE inhibitors including zaprinast and sildenafil were docked into the model of PfPDEα. The results were consistent with their reported biological activities, and the potential of PDE1/9 inhibitor analogues was also supported by docking.

Expression of three mammalian cDNAs that interfere with RAS function in Saccharomyces cerevisiae.

PubMed Central

Colicelli, J; Nicolette, C; Birchmeier, C; Rodgers, L; Riggs, M; Wigler, M

1991-01-01

Saccharomyces cerevisiae strains expressing the activated RAS2Val19 gene or lacking both cAMP phosphodiesterase genes, PDE1 and PDE2, have impaired growth control and display an acute sensitivity to heat shock. We have isolated two classes of mammalian cDNAs from yeast expression libraries that suppress the heat shock-sensitive phenotype of RAS2Val19 strain. Members of the first class of cDNAs also suppress the heat shock-sensitive phenotype of pde1- pde2- strains and encode cAMP phosphodiesterases. Members of the second class fail to suppress the phenotype of pde1- pde2- strains and therefore are candidate cDNAs encoding proteins that interact with RAS proteins. We report the nucleotide sequence of three members of this class. Two of these cDNAs share considerable sequence similarity, but none are clearly similar to previously isolated genes. Images PMID:1849280

Phosphodiesterase Type 5 Inhibitors, Sport and Doping.

PubMed

Di Luigi, Luigi; Sansone, Massimiliano; Sansone, Andrea; Ceci, Roberta; Duranti, Guglielmo; Borrione, Paolo; Crescioli, Clara; Sgrò, Paolo; Sabatini, Stefania

Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition. This suggests well-controlled research studies to examine the ergogenic effects of PDE5i on performance during activities that simulate real sporting situations are warranted to determine if PDE5i should be included on the prohibited WADA list. In the meantime, there is concern that some otherwise healthy athletes will continue to misuse PDE5i to gain an unfair competitive advantage over their competitors.

Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.

PubMed

Havekes, Robbert; Park, Alan J; Tolentino, Rosa E; Bruinenberg, Vibeke M; Tudor, Jennifer C; Lee, Yool; Hansen, Rolf T; Guercio, Leonardo A; Linton, Edward; Neves-Zaph, Susana R; Meerlo, Peter; Baillie, George S; Houslay, Miles D; Abel, Ted

2016-08-24

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The phosphodiesterase 4 (PDE4) family coordinates the degradation of cAMP, leading to the local attenuation of cAMP-dependent signaling pathways. Sleep deprivation leads to increased hippocampal expression of the PDE4A5 isoform. Here, we explored whether PDE4A5 overexpression mimics behavioral and synaptic plasticity phenotypes associated with sleep deprivation. Viral expression of PDE4A5 in hippocampal neurons impairs long-term potentiation and attenuates the formation of hippocampus-dependent long-term memories. Our findings suggest that PDE4A5 is a molecular constraint on cognitive processes and may contribute to the development of novel therapeutic approaches to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Copyright © 2016 Havekes et al.

cAMP Catalyzing Phosphodiesterases Control Cholinergic Muscular Activity But Their Inhibition Does Not Enhance 5-HT4 Receptor-Mediated Facilitation of Cholinergic Contractions in the Murine Gastrointestinal Tract

PubMed Central

Pauwelyn, Vicky; Lefebvre, Romain A.

2018-01-01

Background: As the signal transduction of 5-HT4 receptors on cholinergic neurons innervating smooth muscle is controlled by phosphodiesterase (PDE) 4 in porcine stomach and colon, and human large intestine, the in vivo gastroprokinetic effects of a 5-HT4 receptor agonist might be enhanced by combination with a selective PDE4 inhibitor. The presence of 5-HT4 receptors on cholinergic neurons towards murine gastrointestinal circular muscle was recently shown. If the control of this receptor pathway by PDE4 is also present in mice, this might be a good model for in vivo testing of the combination therapy. Therefore this study investigates the role of cAMP catalyzing PDEs in smooth muscle cell activity and in the intraneuronal signal transduction of the 5-HT4 receptors in the gastrointestinal tract of C57Bl/6J mice. Methods: In circular smooth muscle strips from murine fundus, jejunum, and colon, submaximal cholinergic contractions were induced by either electrical field stimulation (EFS) or by carbachol (muscarinic receptor agonist). The influence of the PDE inhibitors IBMX (non-selective), vinpocetine (PDE1), EHNA (PDE2), cilostamide (PDE3), and rolipram (PDE4) was tested on these contractions and on the facilitating effect of a submaximal concentration of prucalopride (5-HT4 receptor agonist) on EFS-induced contractions. Results: In the three gastrointestinal regions, IBMX and cilostamide concentration-dependently decreased carbachol- as well as EFS-induced contractions. Some inhibitory effect was also observed with rolipram. In the fundus a non-significant trend for an enhancement of the facilitating effect of prucalopride on EFS-induced contractions was observed with IBMX, but none of the selective PDE inhibitors enhanced the facilitating effect of prucalopride in fundus, jejunum or colon. Conclusion: In analogy with the porcine gastrointestinal tract, in murine fundus, jejunum, and colon circular smooth muscle PDE3 is the main regulator of the cAMP turnover, with some contribution of PDE4. In contrast to the porcine gastrointestinal tract, the in vitro facilitation of electrically induced cholinergic contractions by 5-HT4 receptor stimulation could not be enhanced by specific PDE inhibition. The C57Bl/6J murine model is thus not suitable for in vivo testing of a 5-HT4 receptor agonist combined with a selective PDE4 inhibitor. PMID:29568269

Economic analysis of use of counterfeit drugs: health impairment risk of counterfeit phosphodiesterase type 5 inhibitor taken as an example.

PubMed

Sugita, Minoru; Miyakawa, Michiko

2010-07-01

The size of the market for counterfeit drugs throughout the world is considerable. Many cases of health impairment due to counterfeits have been reported. The market share of counterfeits in drug markets in developed countries is smaller than that in developing countries. However, the size of the market for counterfeits of phosphodiesterase type 5 inhibitors (PDE5Is) used as anti-erectile-dysfunction drugs is not small. The purpose of the present study was to analyze the health impairment risk of taking the counterfeit PDE5Is and the convenience of obtaining the counterfeits in Japan, using an economic methodology in order to work out countermeasures for reducing the health impairment risk. Information was obtained by interviewing employees of pharmaceutical and chemical corporations in Japan. The size of the market for counterfeit PDE5Is in Japan was recently estimated to be about 2.5 times larger than that of genuine PDE5Is. The price of the counterfeits in their market is reported to be nearly equal to that of the genuine PDE5Is. An outbreak of severe hypoglycemia among users of counterfeit PDE5Is containing an antidiabetic drug in Singapore was reported in 2008, and seven patients remained comatose as a result of prolonged neuroglycopenia. Four of them subsequently died, so the health impairment risk due to counterfeit PDE5Is should not be ignored. In order to obtain a genuine PDE5I in Japan, a patient must be examined and have a prescription written at a medical institution, and buy it at a dispensing pharmacy. Focusing on the health impairment risk due to counterfeit PDE5Is and the convenience of obtaining the counterfeits in Japan, we analyzed the effects on the prices and quantities of PDE5Is in the market from demand and supply curves, using an economic methodology. From the analysis, it was shown that the health impairment risk due to the counterfeits is underestimated in the market in Japan. Physicians should warn their patients not to buy counterfeit PDE5Is, and when they write a prescription for purchasing genuine PDE5Is, should inform their patients of the severe health problems that occurred in Singapore. The present economic analysis indicates that the health impairment risk due to counterfeit PDE5Is is underestimated in the market in Japan. Clarification of the underestimation of the severe health impairment risk due to counterfeits is important.

In vivo effects of phosphodiesterase inhibition on basal cyclic guanosine monophosphate levels in the prefrontal cortex, hippocampus and cerebellum of freely moving rats.

PubMed

Marte, Antonella; Pepicelli, Olimpia; Cavallero, Anna; Raiteri, Maurizio; Fedele, Ernesto

2008-11-15

We have characterized the various phosphodiesterases (PDE) that degrade cyclic GMP in the prefrontal cortex, hippocampus, and cerebellum using the microdialysis technique to measure in vivo extracellular cyclic GMP in awake rats. The following PDE blockers were used (100 and 1,000 microM): 8-methoxymethyl-IBMX (8-MM-IBMX), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), milrinone, rolipram, and zaprinast. For solubility reasons, sildenafil was tested only at 100 microM. All drugs were administered locally in the brain regions through the dialysis probe. At 100 microM, 8-MM-IBMX enhanced the cyclic nucleotide extracellular levels in the prefrontal cortex and hippocampus but not in the cerebellum; EHNA and milrinone were active only in the hippocampus; rolipram was devoid of any effect; zaprinast and sildenafil were effective in all three brain areas. At 1 mM, 8-MM-IBMX, milrinone, and zaprinast increased extracellular cyclic GMP in all the brain regions examined, EHNA became active also in the prefrontal cortex and rolipram showed a significant effect only in the cerebellum. This is the first in vivo functional study showing that, in cortex, PDE1, -2, and -5/9 degrade cGMP, with PDE9 probably playing a major role; in hippocampus, PDE5/9 and PDE1 are mainly involved and seem almost equally active, but PDE2 and -3 also contribute; in cerebellum, PDE5/9 are the main cGMP hydrolyzing enzymes, but also PDE1 and -4 significantly operate.

Fuel Injection Strategy for a Next Generation Pulse Detonation Engine

DTIC Science & Technology

2006-06-01

at 45°C CE Approved EMC EMC Directive 89/336/EEC; EN 61326-1 Emissions and Immunity Safety Low Voltage Directive 73/23/EEC; EN 61010 -1...Operating Humidity 0–90% Nonoperating Humidity 0–100% CDRH Class IIIb IEC Class 3B From www.mellesgriot.com 47 SILICON OPTICAL SENSOR Model

Development and Testing of a Rotating Detonation Engine Run on Hydrogen and Air

DTIC Science & Technology

2012-03-22

all gaseous or liquid hydrocarbon fuels mixed with gaseous oxygen or air can be burnt in an annular combustion chamber in the regime of a continuous...constructed for the RDE and securely attached to the concrete . The test stand allowed for direct attachment of the RDE via thru holes in the tabletop. Nuts

Biomolecular surface construction by PDE transform.

PubMed

Zheng, Qiong; Yang, Siyang; Wei, Guo-Wei

2012-03-01

This work proposes a new framework for the surface generation based on the partial differential equation (PDE) transform. The PDE transform has recently been introduced as a general approach for the mode decomposition of images, signals, and data. It relies on the use of arbitrarily high-order PDEs to achieve the time-frequency localization, control the spectral distribution, and regulate the spatial resolution. The present work provides a new variational derivation of high-order PDE transforms. The fast Fourier transform is utilized to accomplish the PDE transform so as to avoid stringent stability constraints in solving high-order PDEs. As a consequence, the time integration of high-order PDEs can be done efficiently with the fast Fourier transform. The present approach is validated with a variety of test examples in two-dimensional and three-dimensional settings. We explore the impact of the PDE transform parameters, such as the PDE order and propagation time, on the quality of resulting surfaces. Additionally, we utilize a set of 10 proteins to compare the computational efficiency of the present surface generation method and a standard approach in Cartesian meshes. Moreover, we analyze the present method by examining some benchmark indicators of biomolecular surface, that is, surface area, surface-enclosed volume, solvation free energy, and surface electrostatic potential. A test set of 13 protein molecules is used in the present investigation. The electrostatic analysis is carried out via the Poisson-Boltzmann equation model. To further demonstrate the utility of the present PDE transform-based surface method, we solve the Poisson-Nernst-Planck equations with a PDE transform surface of a protein. Second-order convergence is observed for the electrostatic potential and concentrations. Finally, to test the capability and efficiency of the present PDE transform-based surface generation method, we apply it to the construction of an excessively large biomolecule, a virus surface capsid. Virus surface morphologies of different resolutions are attained by adjusting the propagation time. Therefore, the present PDE transform provides a multiresolution analysis in the surface visualization. Extensive numerical experiment and comparison with an established surface model indicate that the present PDE transform is a robust, stable, and efficient approach for biomolecular surface generation in Cartesian meshes. Copyright © 2012 John Wiley & Sons, Ltd.

Superoxide from NADPH oxidase upregulates type 5 phosphodiesterase in human vascular smooth muscle cells: inhibition with iloprost and NONOate.

PubMed

Muzaffar, S; Shukla, N; Bond, M; Sala-Newby, G B; Newby, A C; Angelini, G D; Jeremy, J Y

2008-11-01

To determine whether there is an association between vascular NADPH oxidase (NOX), superoxide, the small GTPase Rac(1) and PDE type 5 (PDE5) in human vascular smooth muscle cell (hVSMCs). hVSMCs were incubated with xanthine-xanthine oxidase (X-XO; a superoxide generating system) or the thromboxane A(2) analogue, U46619 (+/-superoxide dismutase (SOD) or apocynin) for 16 h. The expression of PDE5 and NOX-1 was assessed using Western blotting and superoxide measured. The role of Rac(1) in superoxide generation was assessed by overexpressing either the dominant-negative or constitutively active Rac isoforms. The effects of iloprost, DETA-NONOate and the Rho-kinase inhibitor, Y27632, on PDE5 and NOX-1 expression were also studied. Following 16 h incubation, U46619 and X-XO promoted the expression of PDE5 and NOX-1, an effect blocked by SOD or apocynin when co-incubated over the same time course. X-XO and U46619 both promoted the formation of superoxide. Overexpression of dominant-negative Rac(1) or addition of iloprost, DETA-NONOate or Y27632 completely blocked both superoxide release and PDE5 protein expression and activity. These data demonstrate that superoxide derived from NOX upregulates the expression of PDE5 in human VSMCs. As PDE5 hydrolyses cyclic GMP, this effect may blunt the vasculoprotective actions of NO.

Reasons and predictive factors for discontinuation of PDE-5 inhibitors despite successful intercourse in erectile dysfunction patients

PubMed Central

Kim, S-C; Lee, Y-S; Seo, K-K; Jung, G-W; Kim, T-H

2014-01-01

This study was aimed to identify characteristics of ED patients who discontinued PDE5i despite successful intercourse. Data were collected using a questionnaire from 34 urologic clinics regardless of the effect (success or failure) of PDE5i treatment by visiting the clinics (717), e-mail (64) or post (101) for 882 ED patients who had previously taken any kind of PDE5i on demand four or more times. Discontinuation of PDE5i was defined if the patient had never taken PDE5i for the previous 1 year despite successful intercourse. Of the 882 patients, 485 were included in the final analysis. Difference in the socio-demographic, ED- and partner-related data between the continuation and discontinuation group and factors influencing discontinuation of the PDE5i were analyzed. Among 485 respondents (mean age, 53.6), 116 (23.9%) had discontinued PDE5i use despite successful intercourse. Most common reasons for the discontinuation were ‘reluctant medication-dependent intercourse' (31.0%), ‘spontaneous recovery of erectile function without further treatment' (30.2%), and ‘high cost' (26.7%). In multiple logistic regression analysis, independent factors influencing discontinuation of the drug were cause of ED (psychogenic), short duration of ED, low education (⩽ middle school), and religion (Catholic). In partner-related compliance, only partner's religion (Catholic) was a significant factor. PMID:24305610

Comparison of the Pharmacological Profiles of Selective PDE4B and PDE4D Inhibitors in the Central Nervous System

PubMed Central

Zhang, Chong; Xu, Ying; Zhang, Han-Ting; Gurney, Mark E.; O’Donnell, James M.

2017-01-01

Inhibition of cyclic AMP (cAMP)-specific phosphodiesterase 4 (PDE4) has been proposed as a potential treatment for a series of neuropsychological conditions such as depression, anxiety and memory loss. However, the specific involvement of each of the PDE4 subtypes (PDE4A, 4B and 4C) in different categories of behavior has yet to be elucidated. In the present study, we compared the possible pharmacological effects of PDE4B and PDE4D selective inhibitors, A-33 and D159687, in mediating neurological function in mice. Both compounds were equally potent in stimulating cAMP signaling in the mouse hippocampal cell line HT-22 leading to an increase in CREB phosphorylation. In contrast, A-33 and D159687 displayed distinct neuropharmacological effects in mouse behavioral tests. A-33 has an antidepressant-like profile as indicated by reduced immobility time in the forced swim and tail suspension tasks, as well as reduced latency to feed in the novelty suppressed feeding test. D159687, on the other hand, had a procognitive profile as it improved memory in the novel object recognition test but had no antidepressant or anxiolytic benefit. The present data suggests that inhibitors targeting specific subtypes of PDE4 may exhibit differential pharmacological effects and aid a more efficient pharmacotherapy towards neuropsychological conditions. PMID:28054669

Phosphodiesterase type 5 inhibitor abuse: a critical review.

PubMed

Lowe, Gregory; Costabile, Raymond

2011-06-01

Abuse of sildenafil has been reported since its introduction in 1999 and commonly documented in combination with illicit drugs among men and women of all ages. Increased risks of sexually transmissible diseases including HIV have been associated with sildenafil use in men who have sex with men. Recognizing the abuse potential of phosphodiesterase type 5 inhibitors (PDE5), we aim to summarize the current knowledge of this abuse. An investigation of EMBASE, PubMed, the Food and Drug Administration (FDA) website, MedWatch, and search engines was performed to evaluate information regarding sildenafil, tadalafil, and vardenafil abuse. The EMBASE search provided 46 articles fitting the search criteria and evaluation led to 21 separate publications with specific information regarding PDE5 abuse. A PubMed search found 10 additional publications. MedWatch reported 44 separate warnings since 2000, most of which reported contamination of herbal products with active drug components. Few reports of abuse were among the 14,818 reports in the FDA AERS for sildenafil. A search for "internet drug store" revealed 6.4 million hits and of 7000 internet pharmacies identified by the Verified Internet Pharmacy Practice Sites Program (VIPPS) only 4% were in proper compliance. The role internet pharmacies play in counterfeit PDE5 or abuse is not well documented; however based on easy access, direct patient marketing, and low advertised cost it is likely this role is underreported. Currently the best recommendation for providers is to recognize the possibility of abuse and to educate patients on risks of this behavior.

Newer treatments of psoriasis regarding IL-23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors.

PubMed

Wcisło-Dziadecka, Dominika; Zbiciak-Nylec, Martyna; Brzezińska-Wcisło, Ligia; Bebenek, Katarzyna; Kaźmierczak, Agata

2017-11-01

The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23). Phosphodiesterase inhibitors exert an anti-inflammatory action and their most common group is the PDE4 family. PDE4 inhibits cAMP, which reduces the inflammatory response of the pathway of Th helper lymphocytes, Th17, and type 1 interferon which modulates the production of anti-inflammatory cytokines such as IL-10 interleukins. The Janus kinase (JAK) signaling pathway plays an important role in the immunopathogenesis of psoriasis. Tofacitinib suppresses the expression of IL-23, IL-17A, IL-17F, and IL-22 receptors during the stimulation of lymphocytes. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 kinases and the JAK-STAT signaling pathway. This article is a review of the aforementioned drugs as described in the latest available literature. © 2017 Wiley Periodicals, Inc.

Ultralean combustion in general aviation piston engines

NASA Technical Reports Server (NTRS)

Chirivella, J. E.

1979-01-01

The role of ultralean combustion in achieving fuel economy in general aviation piston engines was investigated. The aircraft internal combustion engine was reviewed with regard to general aviation requirements, engine thermodynamics and systems. Factors affecting fuel economy such as those connected with an ideal leanout to near the gasoline lean flammability limit (ultralean operation) were analyzed. A Lycoming T10-541E engine was tested in that program (both in the test cell and in flight). Test results indicate that hydrogen addition is not necessary to operate the engine ultralean. A 17 percent improvement in fuel economy was demonstrated in flight with the Beechcraft Duke B60 by simply leaning the engine at constant cruiser power and adjusting the ignition for best timing. No detonation was encountered, and a 25,000 ft ceiling was available. Engine roughness was shown to be the limiting factor in the leanout.

Development of intra-strain self-cloning procedure for breeding baker's yeast strains.

PubMed

Nakagawa, Youji; Ogihara, Hiroyuki; Mochizuki, Chisato; Yamamura, Hideki; Iimura, Yuzuru; Hayakawa, Masayuki

2017-03-01

Previously reported self-cloning procedures for breeding of industrial yeast strains require DNA from other strains, plasmid DNA, or mutagenesis. Therefore, we aimed to construct a self-cloning baker's yeast strain that exhibits freeze tolerance via an improved self-cloning procedure. We first disrupted the URA3 gene of a prototrophic baker's yeast strain without the use of any marker gene, resulting in a Δura3 homozygous disruptant. Then, the URA3 gene of the parental baker's yeast strain was used as a selection marker to introduce the constitutive TDH3 promoter upstream of the PDE2 gene encoding high-affinity cyclic AMP phosphodiesterase. This self-cloning procedure was performed without using DNA from other Saccharomyces cerevisiae strains, plasmid DNA, or mutagenesis and was therefore designated an intra-strain self-cloning procedure. Using this self-cloning procedure, we succeeded in producing self-cloning baker's yeast strains that harbor the TDH3p-PDE2 gene heterozygously and homozygously, designated TDH3p-PDE2 hetero and TDH3p-PDE2 homo strains, respectively. These self-cloning strains expressed much higher levels of PDE2 mRNA than the parental strain and exhibited higher viability after freeze stress, as well as higher fermentation ability in frozen dough, when compared with the parental strain. The TDH3p-PDE2 homo strain was genetically more stable than the TDH3p-PDE2 hetero strain. These results indicate that both heterozygous and homozygous strains of self-cloning PDE2-overexpressing freeze-tolerant strains of industrial baker's yeast can be prepared using the intra-strain self-cloning procedure, and, from a practical viewpoint, the TDH3p-PDE2 homo strain constructed in this study is preferable to the TDH3p-PDE2 hetero strain for frozen dough baking. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

In permanent atrial fibrillation, PDE3 reduces force responses to 5‐HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias

PubMed Central

Schwarz, Simon; Ravens, Ursula; Knaut, Michael

2016-01-01

Abstract Background and Purpose 5‐HT increases force and L‐type Ca2 + current (ICa,L) and causes arrhythmias through 5‐HT4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5‐HT are blunted, arrhythmias abolished but ICa,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively. Experimental Approach Contractile force, arrhythmic contractions and ICa,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF. Key Results Maximum force responses to 5‐HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5‐HT in peAF and the inotropic potency of 5‐HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5‐HT were not decreased in peAF. Responses of ICa,L to 5‐HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5‐HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF. Conclusions and Implications PDE3, but not PDE4, reduced inotropic responses to 5‐HT in peAF, independently of lusitropy and ICa,L, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5‐HT to induce arrhythmias by inhibition of PDE3 plus PDE4. PMID:27238373

In silico design of novel hERG-neutral sildenafil-like PDE5 inhibitors.

PubMed

Kayık, Gülru; Tüzün, Nurcan Ş; Durdagi, Serdar

2017-10-01

Cyclic nucleotide phosphodiesterase enzymes (PDEs) have functions in regulating the levels of intracellular second messengers, 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), via hydrolysis and decomposing mechanisms in cells. They take essential roles in modulating various cellular activities such as memory and smooth muscle functions. PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction. Patch clamp experiments showed that the IC 50 values of the human ether-à-go-go-related gene (hERG1) potassium (K) ion channel blocking affinity of PDE5 inhibitors sildenafil, vardenafil, and tadalafil as 33, 12, and 100 μM, respectively. hERG1 channel is responsible for the regulation of the action potential of human ventricular myocyte by contributing the rapid component of delayed rectifier K + current (I Kr ) component of the cardiac action potential. In this work, interaction patterns and binding affinity predictions of selected PDE5 inhibitors against the hERG1 channel are studied. It is attempted to develop PDE5 inhibitor analogs with lower binding affinity to hERG1 ion channel while keeping their pharmacological activity against their principal target PDE5 using in silico methods. Based on detailed analyses of docking poses and predicted interaction energies, novel analogs of PDE5 inhibitors with lower predicted binding affinity to hERG1 channels without loosing their principal target activity were proposed. Moreover, molecular dynamics (MD) simulations and post-processing MD analyses (i.e. Molecular Mechanics/Generalized Born Surface Area calculations) were performed. Detailed analysis of molecular simulations helped us to better understand the PDE5 inhibitor-target binding interactions in the atomic level. Results of this study can be useful for designing of novel and safe PDE5 inhibitors with enhanced activity and other tailored properties.

Knocking Combustion Observed in a Spark-Ignition Engine with Simultaneous Direct and Schlieren High-Speed Motion Pictures and Pressure Records

NASA Technical Reports Server (NTRS)

Osterstrom, Gordon E

1948-01-01

Simultaneous direct and Schlieren photographs at 40,000 frames per second and correlated pressure records were taken of knocking combustion in a special spark-ignition engine to ascertain the intensity of certain end-zone reactions previously noted from Schlieren photography alone. A violent propagated homogeneous autoignition, or a similar phenomenon, previously observed, was again observed. The pressure records show autoignition of varying violence before the passage of a probable detonation wave. Extensive autoignition without occurrence of gas vibrations was seen in one explosion.

First-generation phosphodiesterase type 5 inhibitors dropout: a comprehensive review and meta-analysis.

PubMed

Corona, G; Rastrelli, G; Burri, A; Serra, E; Gianfrilli, D; Mannucci, E; Jannini, E A; Maggi, M

2016-11-01

The discontinuation rate with phosphodiesterase type 5 inhibitors (PDE5i) remains very high. The aim of this study was to review and meta-analyze currently available data regarding dropout of the first-generation of PDE5i including sildenafil, vardenafil, and tadalafil. An extensive Medline Embase and Cochrane search was performed including the following words: 'PDE5i', 'discontinuation'. All observational studies reporting the dropout rate of PDE5i and its specific causes without any arbitrary restrictions were included. Out of 103 retrieved articles, 22 were included in the study. Retrieved trials included a total of 162,936 patients with a mean age of 58.8 ± 7.9 years. Prevalence of reported comorbid diabetes and hypertension were 27.7% and 36.9%, respectively. PDE5i were associated with a mean discontinuation rate of 4% per month (almost 50% after one year). This rate was higher in younger subjects and in those reporting a higher prevalence of associated morbidities. Six main reasons of PDE5i dropout were identified in the evaluated trials. Partner-related problems and lack of efficacy represented the most important reasons for PDE5i discontinuation, although no significant difference among factors was detected. In conclusion, despite their high efficacy and easy administration, the discontinuation rate and dissatisfaction with PDE5i are still very high. Our data showed that no single factor plays a major role in PDE5i dropout, suggesting that the discontinuation rate is usually because of a combination of both medical problems and psychosocial and relational factors. © 2016 American Society of Andrology and European Academy of Andrology.

Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia

PubMed Central

Blanchard, Elise; Zlock, Lorna; Lao, Anna; Mika, Delphine; Namkung, Wan; Xie, Moses; Scheitrum, Colleen; Gruenert, Dieter C.; Verkman, Alan S.; Finkbeiner, Walter E.; Conti, Marco; Richter, Wito

2014-01-01

Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that impair its expression and/or chloride channel function. Here, we provide evidence that type 4 cyclic nucleotide phosphodiesterases (PDE4s) are critical regulators of the cAMP/PKA-dependent activation of CFTR in primary human bronchial epithelial cells. In non-CF cells, PDE4 inhibition increased CFTR activity under basal conditions (ΔISC 7.1 μA/cm2) and after isoproterenol stimulation (increased ΔISC from 13.9 to 21.0 μA/cm2) and slowed the return of stimulated CFTR activity to basal levels by >3-fold. In cells homozygous for ΔF508-CFTR, the most common mutation found in CF, PDE4 inhibition alone produced minimal channel activation. However, PDE4 inhibition strongly amplified the effects of CFTR correctors, drugs that increase expression and membrane localization of CFTR, and/or CFTR potentiators, drugs that increase channel gating, to reach ∼25% of the chloride conductance observed in non-CF cells. Biochemical studies indicate that PDE4s are anchored to CFTR and mediate a local regulation of channel function. Taken together, our results implicate PDE4 as an important determinant of CFTR activity in airway epithelia, and support the use of PDE4 inhibitors to potentiate the therapeutic benefits of CFTR correctors and potentiators.—Blanchard, E., Zlock, L., Lao, A., Mika, D., Namkung, W., Xie, M., Scheitrum, C., Gruenert, D.C., Verkman, A.S., Finkbeiner, W.E., Conti, M., Richter, W. Anchored PDE4 regulates chloride conductance in wild type and ΔF508-CFTR human airway epithelia. PMID:24200884

Functional phosphodiesterase 11A mutations may modify the risk of familial and bilateral testicular germ cell tumors

PubMed Central

Horvath, Anelia; Korde, Larissa; Greene, Mark H.; Libe, Rosella; Osorio, Paulo; Faucz, Fabio Rueda; Raffin-Sanson, Marie Laure; Tsang, Kit Man; Drori-Herishanu, Limor; Patronas, Yianna; Remmers, Elaine F; Nikita, Maria-Elena; Moran, Jason; Greene, Joseph; Nesterova, Maria; Merino, Maria; Bertherat, Jerome; Stratakis, Constantine A.

2009-01-01

Inactivating germline mutations in phosphodiesterase 11A (PDE11A) have been implicated in adrenal tumor susceptibility. PDE11A is highly-expressed in endocrine steroidogenic tissues, especially the testis, and mice with inactivated Pde11a exhibit male infertility, a known testicular germ cell tumor (TGCT) risk factor. We sequenced the PDE11A gene-coding region in 95 patients with TGCT from 64 unrelated kindreds. We identified 8 non-synonymous substitutions in 20 patients from 15 families: four (R52T; F258Y; G291R; V820M) were newly-recognized, three (R804H; R867G; M878V) were functional variants previously implicated in adrenal tumor predisposition, and one (Y727C) was a known polymorphism. We compared the frequency of these variants in our patients to unrelated controls that had been screened and found negative for any endocrine diseases: only the two previously-reported variants, R804H and R867G, known to be frequent in general population, were detected in these controls. The frequency of all PDE11A-gene variants (combined) was significantly higher among patients with TGCT (P=0.0002), present in 19% of the families of our cohort. Most variants were detected in the general population, but functional studies showed that all these mutations reduced PDE activity, and that PDE11A protein expression was decreased (or absent) in TGCT samples from carriers. This is the first demonstration of a PDE gene’s involvement in TGCT, although the cAMP signaling pathway has been investigated extensively in other reproductive organs and their diseases. In conclusion, we report that PDE11A-inactivating sequence variants may modify the risk of familial and bilateral TGCT. PMID:19549888

Effects of Alanyl-Glutamine Treatment on the Peritoneal Dialysis Effluent Proteome Reveal Pathomechanism-Associated Molecular Signatures*

PubMed Central

Herzog, Rebecca; Boehm, Michael; Unterwurzacher, Markus; Wagner, Anja; Parapatics, Katja; Májek, Peter; Mueller, André C.; Lichtenauer, Anton; Bennett, Keiryn L.; Alper, Seth L.; Vychytil, Andreas; Aufricht, Christoph; Kratochwill, Klaus

2018-01-01

Peritoneal dialysis (PD) is a modality of renal replacement therapy in which the high volumes of available PD effluent (PDE) represents a rich source of biomarkers for monitoring disease and therapy. Although this information could help guide the management of PD patients, little is known about the potential of PDE to define pathomechanism-associated molecular signatures in PD. We therefore subjected PDE to a high-performance multiplex proteomic analysis after depletion of highly-abundant plasma proteins and enrichment of low-abundance proteins. A combination of label-free and isobaric labeling strategies was applied to PDE samples from PD patients (n = 20) treated in an open-label, randomized, two-period, cross-over clinical trial with standard PD fluid or with a novel PD fluid supplemented with alanyl-glutamine (AlaGln). With this workflow we identified 2506 unique proteins in the PDE proteome, greatly increasing coverage beyond the 171 previously-reported proteins. The proteins identified range from high abundance plasma proteins to low abundance cellular proteins, and are linked to larger numbers of biological processes and pathways, some of which are novel for PDE. Interestingly, proteins linked to membrane remodeling and fibrosis are overrepresented in PDE compared with plasma, whereas the proteins underrepresented in PDE suggest decreases in host defense, immune-competence and response to stress. Treatment with AlaGln-supplemented PD fluid is associated with reduced activity of membrane injury-associated mechanisms and with restoration of biological processes involved in stress responses and host defense. Our study represents the first application of the PDE proteome in a randomized controlled prospective clinical trial of PD. This novel proteomic workflow allowed detection of low abundance biomarkers to define pathomechanism-associated molecular signatures in PD and their alterations by a novel therapeutic intervention. PMID:29208752

Precursor detonation wave development in ANFO due to aluminum confinement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, Scott I; Klyanda, Charles B; Short, Mark

2010-01-01

Detonations in explosive mixtures of ammonium-nitrate-fuel-oil (ANFO) confined by aluminum allow for transport of detonation energy ahead of the detonation front due to the aluminum sound speed exceeding the detonation velocity. The net effect of this energy transport on the detonation is unclear. It could enhance the detonation by precompressing the explosive near the wall. Alternatively, it could decrease the explosive performance by crushing porosity required for initiation by shock compression or destroying confinement ahead of the detonation. At present, these phenomena are not well understood. But with slowly detonating, non-ideal high explosive (NIHE) systems becoming increasing prevalent, proper understandingmore » and prediction of the performance of these metal-confined NIHE systems is desirable. Experiments are discussed that measured the effect of this ANFO detonation energy transported upstream of the front by a 76-mm-inner-diameter aluminum confining tube. Detonation velocity, detonation-front shape, and aluminum response are recorded as a function of confiner wall thickness and length. Detonation shape profiles display little curvature near the confining surface, which is attributed to energy transported upstream modifying the flow. Average detonation velocities were seen to increase with increasing confiner thickness, while wavefront curvature decreased due to the stiffer, subsonic confinement. Significant radial sidewall tube motion was observed immediately ahead of the detonation. Axial motion was also detected, which interfered with the front shape measurements in some cases. It was concluded that the confiner was able to transport energy ahead of the detonation and that this transport has a definite effect on the detonation by modifying its characteristic shape.« less

Physics and chemistry of plasma-assisted combustion.

PubMed

Starikovskiy, Andrey

2015-08-13

There are several mechanisms that affect a gas when using discharge plasma to initiate combustion or to stabilize a flame. There are two thermal mechanisms-the homogeneous and inhomogeneous heating of the gas due to 'hot' atom thermalization and vibrational and electronic energy relaxation. The homogeneous heating causes the acceleration of the chemical reactions. The inhomogeneous heating generates flow perturbations, which promote increased turbulence and mixing. Non-thermal mechanisms include the ionic wind effect (the momentum transfer from an electric field to the gas due to the space charge), ion and electron drift (which can lead to additional fluxes of active radicals in the gradient flows in the electric field) and the excitation, dissociation and ionization of the gas by e-impact, which leads to non-equilibrium radical production and changes the kinetic mechanisms of ignition and combustion. These mechanisms, either together or separately, can provide additional combustion control which is necessary for ultra-lean flames, high-speed flows, cold low-pressure conditions of high-altitude gas turbine engine relight, detonation initiation in pulsed detonation engines and distributed ignition control in homogeneous charge-compression ignition engines, among others. Despite the lack of knowledge in mechanism details, non-equilibrium plasma demonstrates great potential for controlling ultra-lean, ultra-fast, low-temperature flames and is extremely promising technology for a very wide range of applications. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Discovery of a Phosphodiesterase 9A Inhibitor as a Potential Hypoglycemic Agent

PubMed Central

2015-01-01

Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer’s disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs. The HepG2 cell-based assay shows that 3r inhibits the mRNA expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase. These activities of 3r, together with the reasonable pharmacokinetic properties and no acute toxicity at 1200 mg/kg dosage, suggest its potential as a hypoglycemic agent. The crystal structure of PDE9-3r reveals significantly different conformation and hydrogen bonding pattern of 3r from those of previously published 28s. Both 3r and 28s form a hydrogen bond with Tyr424, a unique PDE9 residue (except for PDE8), but 3r shows an additional hydrogen bond with Ala452. This structure information might be useful for design of PDE9 inhibitors. PMID:25432025

Multiscale Modeling of Angiogenesis and Predictive Capacity

NASA Astrophysics Data System (ADS)

Pillay, Samara; Byrne, Helen; Maini, Philip

Tumors induce the growth of new blood vessels from existing vasculature through angiogenesis. Using an agent-based approach, we model the behavior of individual endothelial cells during angiogenesis. We incorporate crowding effects through volume exclusion, motility of cells through biased random walks, and include birth and death-like processes. We use the transition probabilities associated with the discrete model and a discrete conservation equation for cell occupancy to determine collective cell behavior, in terms of partial differential equations (PDEs). We derive three PDE models incorporating single, multi-species and no volume exclusion. By fitting the parameters in our PDE models and other well-established continuum models to agent-based simulations during a specific time period, and then comparing the outputs from the PDE models and agent-based model at later times, we aim to determine how well the PDE models predict the future behavior of the agent-based model. We also determine whether predictions differ across PDE models and the significance of those differences. This may impact drug development strategies based on PDE models.

A short review on structure and role of cyclic-3',5'-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool.

PubMed

Eskandari, Nahid; Mirmosayyeb, Omid; Bordbari, Gazaleh; Bastan, Reza; Yousefi, Zahra; Andalib, Alireza

2015-01-01

Cyclic nucleotide phosphodiesterases (PDEs) are known as a super-family of enzymes which catalyze the metabolism of the intracellular cyclic nucleotides, cyclic-3',5'-adenosine monophosphate (cAMP), and cyclic-3',5'-guanosine monophosphate that are expressed in a variety of cell types that can exert various functions based on their cells distribution. The PDE4 family has been the focus of vast research efforts over recent years because this family is considered as a prime target for therapeutic intervention in a number of inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, and it should be used and researched by pharmacists. This is because the major isoform of PDE that regulates inflammatory cell activity is the cAMP-specific PDE, PDE4. This review discusses the relationship between PDE4 and its inhibitor drugs based on structures, cells distribution, and pharmacological properties of PDE4 which can be informative for all pharmacy specialists.

Superoxide from NADPH oxidase upregulates type 5 phosphodiesterase in human vascular smooth muscle cells: inhibition with iloprost and NONOate

PubMed Central

Muzaffar, S; Shukla, N; Bond, M; Sala-Newby, G B; Newby, A C; Angelini, G D; Jeremy, J Y

2008-01-01

Background and purpose: To determine whether there is an association between vascular NADPH oxidase (NOX), superoxide, the small GTPase Rac1 and PDE type 5 (PDE5) in human vascular smooth muscle cell (hVSMCs). Experimental approach: hVSMCs were incubated with xanthine–xanthine oxidase (X-XO; a superoxide generating system) or the thromboxane A2 analogue, U46619 (±superoxide dismutase (SOD) or apocynin) for 16 h. The expression of PDE5 and NOX-1 was assessed using Western blotting and superoxide measured. The role of Rac1 in superoxide generation was assessed by overexpressing either the dominant-negative or constitutively active Rac isoforms. The effects of iloprost, DETA-NONOate and the Rho-kinase inhibitor, Y27632, on PDE5 and NOX-1 expression were also studied. Key results: Following 16 h incubation, U46619 and X-XO promoted the expression of PDE5 and NOX-1, an effect blocked by SOD or apocynin when co-incubated over the same time course. X-XO and U46619 both promoted the formation of superoxide. Overexpression of dominant-negative Rac1 or addition of iloprost, DETA-NONOate or Y27632 completely blocked both superoxide release and PDE5 protein expression and activity. Conclusions and implications: These data demonstrate that superoxide derived from NOX upregulates the expression of PDE5 in human VSMCs. As PDE5 hydrolyses cyclic GMP, this effect may blunt the vasculoprotective actions of NO. PMID:18660830

An insight into the pharmacophores of phosphodiesterase-5 inhibitors from synthetic and crystal structural studies

PubMed Central

Chen, Gong; Wang, Huanchen; Robinson, Howard; Cai, Jiwen; Wan, Yiqian; Ke, Hengming

2008-01-01

Selective inhibitors of cyclic nucleotide phosphodiesterase-5 (PDE5) have been used as drugs for treatment of male erectile dysfunction and pulmonary hypertension. An insight into the pharmacophores of PDE5 inhibitors is essential for development of second generation of PDE5 inhibitors, but has not been completely illustrated. Here we report the synthesis of a new class of the sildenafil derivatives and a crystal structure of the PDE5 catalytic domain in complex with 5-(2-ethoxy-5-(sulfamoyl)-3-thienyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d] pyrimidin-7-one (12). Inhibitor 12 induces conformational change of the H-loop (residues 660–683), which is different from any of the known PDE5 structures. The pyrazolopyrimidinone groups of 12 and sildenafil are well superimposed, but their sulfonamide groups show a positional difference of as much as 1.5 Å. The structure-activity analysis suggests that a small hydrophobic pocket and the H-loop of PDE5 are important for the inhibitor affinity, in addition to two common elements for binding of almost all the PDE inhibitors: the stack against the phenylalanine and the hydrogen bond with the invariant glutamine. However, the PDE5-12 structure does not provide a full explanation to affinity changes of the inhibitors. Thus alternatives such as conformational change of the M-loop are open and further structural study is required. PMID:18346713

PDE and cognitive processing: beyond the memory domain.

PubMed

Heckman, P R A; Blokland, A; Ramaekers, J; Prickaerts, J

2015-03-01

Phosphodiesterase inhibitors (PDE-Is) enhance cAMP and/or cGMP signaling via reducing the degradation of these cyclic nucleotides. Both cAMP and cGMP signaling are essential for a variety of cellular functions and exert their effects both pre- and post-synaptically. Either of these second messengers relays and amplifies incoming signals at receptors on the cell surface making them important elements in signal transduction cascades and essential in cellular signaling in a variety of cell functions including neurotransmitter release and neuroprotection. Consequently, these processes can be influenced by PDE-Is as they increase cAMP and/or cGMP concentrations. PDE-Is have been considered as possible therapeutic agents to treat impaired memory function linked to several brain disorders, including depression, schizophrenia and Alzheimer's disease (AD). This review will, however, focus on the possible role of phosphodiesterases (PDEs) in cognitive decline beyond the memory domain. Here we will discuss the involvement of PDEs on three related domains: attention, information filtering (sensory- and sensorimotor gating) and response inhibition (drug-induced hyperlocomotion). Currently, these are emerging cognitive domains in the field of PDE research. Here we discuss experimental studies and the potential beneficial effects of PDE-I drugs on these cognitive domains, as effects of PDE-Is on these domains could potentially influence effects on memory performance. Overall, PDE4 seems to be the most promising target for all domains discussed in this review. Copyright © 2014 Elsevier Inc. All rights reserved.

Dialysate bacterial endotoxin as a prognostic indicator of peritoneal dialysis related peritonitis.

PubMed

Szeto, Cheuk-Chun; Lai, Ka-Bik; Chow, Kai-Ming; Kwan, Bonnie Ching-Ha; Law, Man-Ching; Pang, Wing-Fai; Ma, Terry King-Wing; Leung, Chi-Bon; Li, Philip Kam-Tao

2016-12-01

Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count. © 2016 Asian Pacific Society of Nephrology.

The effect of changes in compression ratio upon engine performance

NASA Technical Reports Server (NTRS)

Sparrow, Stanwood W

1925-01-01

This report is based upon engine tests made at the Bureau of Standards during 1920, 1921, 1922, and 1923. The majority of these tests were of aviation engines and were made in the Altitude Laboratory. For a small portion of the work a single cylinder experimental engine was used. This, however, was operated only at sea-level pressures. The report shows that an increase in break horsepower and a decrease in the pounds of fuel used per brake horsepower hour usually results from an increase in compression ratio. This holds true at least up to the highest ratio investigated, 14 to 1, provided there is no serious preignition or detonation at any ratio. To avoid preignition and detonation when employing high-compression ratios, it is often necessary to use some fuel other than gasoline. It has been found that the consumption of some of these fuels in pounds per brake horsepower hour is so much greater than the consumption of gasoline that it offsets the decrease derived from the use of the high-compression ratio. The changes in indicated thermal efficiency with changes in compression ratio are in close agreement with what would be anticipated from a consideration of the air cycle efficiencies at the various ratios. In so far as these tests are concerned there is no evidence that a change in compression ratio produces an appreciable, consistent change in friction horsepower, volumetric efficiency, or in the range of fuel-air ratios over which the engine can operate. The ratio between the heat loss to the jacket water and the heat converted into brake horsepower or indicated horsepower decreases with increase in compression ratio. (author)

A Fractional PDE Approach to Turbulent Mixing; Part II: Numerical Simulation

NASA Astrophysics Data System (ADS)

Samiee, Mehdi; Zayernouri, Mohsen

2016-11-01

We propose a generalizing fractional order transport model of advection-diffusion kind with fractional time- and space-derivatives, governing the evolution of passive scalar turbulence. This approach allows one to incorporate the nonlocal and memory effects in the underlying anomalous diffusion i.e., sub-to-standard diffusion to model the trapping of particles inside the eddied, and super-diffusion associated with the sudden jumps of particles from one coherent region to another. For this nonlocal model, we develop a high order numerical (spectral) method in addition to a fast solver, examined in the context of some canonical problems. PhD student, Department of Mechanical Engineering, & Department Computational Mathematics, Science, and Engineering.

Performance and operational improvements made to the Waukesha AT27-GL engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinbold, E.O.

1996-12-31

This paper presents the results of combustion and engine performance studies performed on the AT27GL lean burn engine. One study was to evaluate the effect of the pre-combustion chamber cup geometry on engine performance under several operating conditions including: Air-Fuel Ratio (AFR), ignition timing, and engine load. The study examined several combustion parameters; including IMEP, coefficient of variation of IMEP, heat release rates, and maximum combustion pressures. The study also examined engine thermal efficiency, and brake specific emissions of Oxides of Nitrogen, Carbon Monoxide, and Total Hydrocarbons (gaseous). Studies were also performed on different spark plug designs, comparing firing voltages,more » and electrode temperatures while operating under conditions of varying AFR, and ignition timing. In addition an Air-Fuel-Ratio controller was recently tested and released on the engine. The controller was tested under conditions of varying fuel quality, along with a detonation control system.« less

Photoaffinity labelling of cyclic GMP-inhibited phosphodiesterase (PDE III) in human and rat platelets and rat tissues: effects of phosphodiesterase inhibitors.

PubMed

Tang, K M; Jang, E K; Haslam, R J

1994-06-15

Ultraviolet irradiation of human platelet cytosol in the presence of 32P-labelled cyclic GMP (cGMP) can specifically label 110, 80, 55, 49 and 38 kDa proteins; the 110 kDa species is the subunit of cGMP-inhibited phosphodiesterase (PDE III) and the 80 kDa species that of cGMP-dependent protein kinase (Tang et al., 1993, Biochem. J. 294, 329). We have now shown that although photolabelling of platelet PDE III was inhibited by unlabelled cGMP, 8-bromo-cGMP and cyclic AMP (cAMP), it was not affected by phosphorothioate analogues of these cyclic nucleotides. Specific concentration-dependent inhibitions of the photolabelling of PDE III were observed with the following PDE inhibitors: trequinsin (IC50 = 13 +/- 2 nM), lixazinone (IC50 = 22 +/- 4 nM), milrinone (IC50 = 56 +/- 12 nM), cilostamide (IC50 = 70 +/- 9 nM), siguazodan (IC50 = 117 +/- 29 nM) and 3-isobutyl 1-methylxanthine (IBMX) (IC50 = 3950 +/- 22 nM). Thus, measurements of the inhibitory effects of compounds on the photolabelling of platelet PDE III provide a simple quantitative means of investigating their actions at a molecular level that avoids the need to purify the enzyme. Photolabelling of rat platelet lysate or rat heart homogenate by [32P]cGMP showed that the 110 kDa PDE III present in human material was replaced by a 115 kDa protein, labelling of which was also blocked by PDE III inhibitors. Heart and other rat tissues contained much less of this putative 115 kDa PDE III than rat platelets. In contrast, the 80 kDa protein was labelled much less in platelets than in many other rat tissue homogenates (e.g., heart, aorta, uterus and lung). Thus, comparison of the relative amounts of specific photolabelled proteins in different cells may provide an indication of different patterns of cyclic nucleotide action. We compared the abilities of phosphodiesterase inhibitors to block the photolabelling of PDE III in human platelet cytosol and to increase the iloprost-stimulated accumulation of cAMP in intact platelets. Whereas trequinsin (EC50 = 19 +/- 3 nM), lixazinone (EC50 = 122 +/- 8 nM), milrinone (EC50 = 5320 +/- 970 nM) and siguazodan (EC50 = 18880 +/- 3110 nM) all increased platelet cAMP to the same maximum extent, cilostamide and IBMX increased cAMP further, indicating that they inhibited a PDE isozyme in addition to PDE III.

Characterization of Residues from the Detonation of Insensitive Munitions

DTIC Science & Technology

Unfortunately, many energetic compounds are toxic or harmful to the environment and human health. The US Army Cold Regions Research and Engineering...Laboratory and Defence Research and Development Canada Valcartier have developed methods through SERDP and ESTCP programs that enable the reproducible...reproducible method for energetics residues characterization research . SERDP Project ER-2219 is focused on three areas: determining mass DEPOSITION and

Rotating Detonation Engine Research at NRL

DTIC Science & Technology

2013-07-01

Bykovskii, Wolanski, Falempin, Hayashi, Schauer, Yi, Wang, Brophy, Wu, Clafin, Smith, Tsuboi, Frolov, et al.) Recant RDE Studies at NRL Flow-field...Symposium) Injection/inflow effects (JPC 2011~044; ASM 2012-0617, ASM 2013-1178) the expansion region change RDE performance. Can this model be...Efficient Complex Configuration Simulation Capability 158 BASELINE SOLUTION • Basetine configUration Stoichiometric hydrogen-air RDE of Wolanski

Experimental study of a valveless pulse detonation rocket engine using nontoxic hypergolic propellants

NASA Astrophysics Data System (ADS)

Kan, Brandon K.

A pulsed detonation rocket engine concept was explored through the use of hypergolic propellants in a fuel-centered pintle injector combustor. The combustor design yielded a simple open ended chamber with a pintle type injection element and pressure instrumentation. High-frequency pressure measurements from the first test series showed the presence of large pressure oscillations in excess of 2000 psia at frequencies between 400-600 hz during operation. High-speed video confirmed the high-frequency pulsed behavior and large amounts of after burning. Damaged hardware and instrumentation failure limited the amount of data gathered in the first test series, but the experiments met original test objectives of producing large over-pressures in an open chamber. A second test series proceeded by replacing hardware and instrumentation, and new data showed that pulsed events produced under expanded exhaust prior to pulsing, peak pressures around 8000 psi, and operating frequencies between 400-800 hz. Later hot-fires produced no pulsed behavior despite undamaged hardware. The research succeeded in producing pulsed combustion behavior using hypergolic fuels in a pintle injector setup and provided insights into design concepts that would assist future injector designs and experimental test setups.

PDE1 Encodes a P-Type ATPase Involved in Appressorium-Mediated Plant Infection by the Rice Blast Fungus Magnaporthe grisea

PubMed Central

Balhadère, Pascale V.; Talbot, Nicholas J.

2001-01-01

Plant infection by the rice blast fungus Magnaporthe grisea is brought about by the action of specialized infection cells called appressoria. These infection cells generate enormous turgor pressure, which is translated into an invasive force that allows a narrow penetration hypha to breach the plant cuticle. The Magnaporthe pde1 mutant was identified previously by restriction enzyme–mediated DNA integration mutagenesis and is impaired in its ability to elaborate penetration hyphae. Here we report that the pde1 mutation is the result of an insertion into the promoter of a P-type ATPase-encoding gene. Targeted gene disruption confirmed the role of PDE1 in penetration hypha development and pathogenicity but highlighted potential differences in PDE1 regulation in different Magnaporthe strains. The predicted PDE1 gene product was most similar to members of the aminophospholipid translocase group of P-type ATPases and was shown to be a functional homolog of the yeast ATPase gene ATC8. Spatial expression studies showed that PDE1 is expressed in germinating conidia and developing appressoria. These findings implicate the action of aminophospholipid translocases in the development of penetration hyphae and the proliferation of the fungus beyond colonization of the first epidermal cell. PMID:11549759

UCR1C is a novel activator of phosphodiesterase 4 (PDE4) long isoforms and attenuates cardiomyocyte hypertrophy.

PubMed

Wang, Li; Burmeister, Brian T; Johnson, Keven R; Baillie, George S; Karginov, Andrei V; Skidgel, Randal A; O'Bryan, John P; Carnegie, Graeme K

2015-05-01

Hypertrophy increases the risk of heart failure and arrhythmia. Prevention or reversal of the maladaptive hypertrophic phenotype has thus been proposed to treat heart failure. Chronic β-adrenergic receptor (β-AR) stimulation induces cardiomyocyte hypertrophy by elevating 3',5'-cyclic adenosine monophosphate (cAMP) levels and activating downstream effectors such protein kinase A (PKA). Conversely, hydrolysis of cAMP by phosphodiesterases (PDEs) spatiotemporally restricts cAMP signaling. Here, we demonstrate that PDE4, but not PDE3, is critical in regulating cardiomyocyte hypertrophy, and may represent a potential target for preventing maladaptive hypertrophy. We identify a sequence within the upstream conserved region 1 of PDE4D, termed UCR1C, as a novel activator of PDE4 long isoforms. UCR1C activates PDE4 in complex with A-kinase anchoring protein (AKAP)-Lbc resulting in decreased PKA signaling facilitated by AKAP-Lbc. Expression of UCR1C in cardiomyocytes inhibits hypertrophy in response to chronic β-AR stimulation. This effect is partially due to inhibition of nuclear PKA activity, which decreases phosphorylation of the transcription factor cAMP response element-binding protein (CREB). In conclusion, PDE4 activation by UCR1C attenuates cardiomyocyte hypertrophy by specifically inhibiting nuclear PKA activity. Published by Elsevier Inc.

PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

PubMed Central

Molenaar, Peter; Christ, Torsten; Hussain, Rizwan I; Engel, Andreas; Berk, Emanuel; Gillette, Katherine T; Chen, Lu; Galindo-Tovar, Alejandro; Krobert, Kurt A; Ravens, Ursula; Levy, Finn Olav; Kaumann, Alberto J

2013-01-01

Background and Purpose PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3–1 μM) or PDE4 inhibitor rolipram (1–10 μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental Approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1 adrenoceptors (β2 adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2 adrenoceptors (β1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key Results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (-)-adrenaline (0.78 ± 0.12 log units) than (-)-noradrenaline (0.47 ± 0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and Implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1 and β2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of catecholamines in failing human ventricle. Linked Article This article is commented on by Eschenhagen, pp 524–527 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12168 PMID:23489141

CHBPR: Decreased cGMP level contributes to increased contraction in arteries from hypertensive rats: role of PDE1

PubMed Central

Giachini, Fernanda R.; Lima, Victor V.; Carneiro, Fernando S.; Tostes, Rita C.; Webb, R. Clinton

2011-01-01

Recent evidence suggests that angiotensin II (Ang II) upregulates phosphodiesterase (PDE)-1A expression. We hypothesized that Ang II augmented PDE1 activation, decreasing the bioavailability of cyclic cyclic guanosine 3', 5'-monophosphate (cGMP), contributing to increased vascular contractility. Male Sprague-Dawley rats received mini-osmotic pumps with Ang II (60 ng.min−1) or saline for 14 days. PE-induced contractions were increased in aorta (Emax168±8 vs. 136±4%) and small-mesenteric arteries [(SMA), Emax170±6 vs. 143±3%] from Ang II infused rats compared to control. PDE1 inhibition with vinpocetine (10µM) reduced PE-induced contraction in aortas from Ang II rats (Emax94±12%) but not in control (154±7%). Vinpocetine decreased the sensitivity to PE in SMA from Ang II rats compared to vehicle (pD2 5.1±0.1 vs. 5.9±0.06), but not in control (6.0±0.03 vs. 6.1±0.04). Sildenafil (10µM), a PDE5 inhibitor reduced PE-induced maximal contraction similarly in Ang II and control rats. Arteries were contracted with PE (1µM) and concentration-dependent relaxation to vinpocetine and sildenafil was evaluated. Aortas from Ang II rats displayed increased relaxation to vinpocetine compared to control (Emax82±12 vs. 44±5%). SMA from Ang II rats showed greater sensitivity during vinpocetine-induced relaxation, compared to control (pD2 6.1±0.3 vs. 5.3±0.1). No differences in sildenafil-induced relaxation were observed. PDE1A and PDE1C expressions in aorta and PDE1A expression in SMA were increased in Ang II rats. cGMP production, which is decreased in arteries from Ang II rats, was restored after PDE1 blockade. We conclude that PDE1 activation reduces cGMP bioavailability in arteries from ANG II, contributing to increased contractile responsiveness. PMID:21282562

Measurements of observables during detonator function

NASA Astrophysics Data System (ADS)

Smilowitz, Laura; Henson, Bryan; Remelius, Dennis

Thermal explosion and detonation are two phenomena which can both occur as the response of explosives to thermal or mechanical insults. Thermal explosion is typically considered in the safety envelope and detonation is considered in the performance regime of explosive behavior. However, the two regimes are tied together by a phenomenon called deflagration to detonation transition (DDT). In this talk, I will discuss experiments on commercial detonators aimed at understanding the mechanism for energy release during detonator function. Diagnostic development towards measuring temperature, pressure, and density during the extreme conditions and time scales of detonation will be discussed. Our current ability to perform table-top dynamic radiography on functioning detonators will be described. Dynamic measurements of temperature, pressure, and density will be shown and discussion of the function of a detonator will be given in terms of our current understanding of deflagration, detonation, and the transition between the two.

Fuels for high-compression engines

NASA Technical Reports Server (NTRS)

Sparrow, Stanwood W

1926-01-01

From theoretical considerations one would expect an increase in power and thermal efficiency to result from increasing the compression ratio of an internal combustion engine. In reality it is upon the expansion ratio that the power and thermal efficiency depend, but since in conventional engines this is equal to the compression ratio, it is generally understood that a change in one ratio is accompanied by an equal change in the other. Tests over a wide range of compression ratios (extending to ratios as high as 14.1) have shown that ordinarily an increase in power and thermal efficiency is obtained as expected provided serious detonation or preignition does not result from the increase in ratio.

Cyanidin-3-glucoside suppresses B[a]PDE-induced cyclooxygenase-2 expression by directly inhibiting Fyn kinase activity.

PubMed

Lim, Tae-Gyu; Kwon, Jung Yeon; Kim, Jiyoung; Song, Nu Ry; Lee, Kyung Mi; Heo, Yong-Seok; Lee, Hyong Joo; Lee, Ki Won

2011-07-15

Benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE) is a well-known carcinogen that is associated with skin cancer. Abnormal expression of cyclooxygenase-2 (COX-2) is an important mediator in inflammation and tumor promotion. We investigated the inhibitory effect of cyanidin-3-glucoside (C3G), an anthocyanin present in fruits, on B[a]PDE-induced COX-2 expression in mouse epidermal JB6 P+ cells. Pretreatment with C3G resulted in the reduction of B[a]PDE-induced expression of COX-2 and COX-2 promoter activity. The activation of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) induced by B[a]PDE was also attenuated by C3G. C3G attenuated the B[a]PDE-induced phosphorylation of MEK, MKK4, Akt, and mitogen-activated protein kinases (MAPKs), but no effect on the phosphorylation of the upstream MAPK regulator Fyn. However, kinase assays demonstrated that C3G suppressed Fyn kinase activity and C3G directly binds Fyn kinase noncompetitively with ATP. By using PP2, a pharmacological inhibitor for SFKs, we showed that Fyn kinase regulates B[a]PDE-induced COX-2 expression by activating MAPKs, AP-1 and NF-κB. These results suggest that C3G suppresses B[a]PDE-induced COX-2 expression mainly by blocking the activation of the Fyn signaling pathway, which may contribute to its chemopreventive potential. Copyright © 2011 Elsevier Inc. All rights reserved.

Regulation of Phosphodiesterase 3 in the Pulmonary Arteries During the Perinatal Period in Sheep

PubMed Central

Chen, Bernadette; Lakshminrusimha, Satyan; Czech, Lyubov; Groh, Beezly S.; Gugino, Sylvia F.; Russell, James A.; Farrow, Kathryn N.; Steinhorn, Robin H.

2009-01-01

The role of cAMP in the pulmonary vasculature during the transition from intrauterine to extrauterine life is poorly understood. We hypothesized that cAMP levels are regulated by alterations in phosphodiesterase 3 (PDE3), which hydrolyzes cAMP. PDE3 protein expression and hydrolytic activity were increased in resistance pulmonary arteries (PA) from spontaneously breathing one-day-old (1dSB) lambs relative to equivalent-gestation fetuses. This was accompanied by a decrease in steady-state cAMP. Ventilation with 21% O2 and 100% O2 for 24h disrupted the normal transition, whereas ventilation with 100% O2+inhaled NO (iNO) for 24h restored both PDE3 activity and cAMP to 1dSB levels. Consistent with these findings, relaxation to milrinone, a PDE3 inhibitor, was greater in PA isolated from 1dSB and 100% O2+iNO lambs, relative to fetal, 21% O2, and 100% O2 lambs. In conclusion, PDE3 expression and activity in PA dramatically increase after birth, with a concomitant decrease in steady-state cAMP. Ventilation with either 21% O2 or 100% O2 blunts this PDE3 increase, whereas iNO restores PDE3 activity to levels equivalent to 1dSB lambs. The vasodilatory effects of milrinone were most pronounced in vessels from lambs with the highest PDE3 activity, i.e. 1dSB and 100% O2+iNO lambs. Thus, milrinone may be most beneficial when used in conjunction with iNO. PMID:19707176

Inhibition of Cyclic Adenosine Monophosphate-Specific Phosphodiesterase by Various Food Plant-Derived Phytotherapeutic Agents

PubMed Central

Pacjuk, Olga; Hernández-Huguet, Silvia; Körner, Johanna; Scherer, Katharina; Richling, Elke

2017-01-01

Background: Phosphodiesterases (PDEs) play a major role in the regulation of cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-mediated pathways. Their inhibitors exhibit anti-inflammatory, vasodilatory and antithrombotic effects. Therefore, consumption of foods with PDE-inhibiting potential may possess beneficial influence on the risk of cardiovascular diseases. Methods: Four plant extracts (Arbutus unedo, Camellia sinensis, Cynara scolymus, Zingiber officinale) with promising ingredient profiles and physiological effects were tested for their ability to inhibit cAMP-specific PDE in vitro in a radioactive assay. Results: Strawberry tree fruit (Arbutus unedo) and tea (Camellia sinensis) extracts did not inhibit PDE markedly. Alternatively, artichoke (Cynara scolymus) extract had a significant inhibitory influence on PDE activity (IC50 = 0.9 ± 0.1 mg/mL) as well as its flavone luteolin (IC50 = 41 ± 10 μM) and 3,4-dicaffeoylquinic acid (IC50 > 1.0 mM). Additionally, the ginger (Zingiber officinale) extract and one of its constituents, [6]-gingerol, significantly inhibited PDE (IC50 = 1.7 ± 0.2 mg/mL and IC50 > 1.7 mM, respectively). Crude fractionation of ginger extract showed that substances responsible for PDE inhibition were in the lipoid fraction (IC50 = 455 ± 19 μg/mL). Conclusions: A PDE-inhibitory effect was shown for artichoke and ginger extract. Whether PDE inhibition in vivo can be achieved through ingestion of artichoke or ginger extracts leading to physiological effects concerning cardiovascular health should be addressed in future research. PMID:29113064

PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer.

PubMed

Das, Anindita; Durrant, David; Salloum, Fadi N; Xi, Lei; Kukreja, Rakesh C

2015-03-01

The phosphodiesterase 5 (PDE5) inhibitors, including sildenafil (Viagra™), vardenafil (Levitra™), and tadalafil (Cialis™) have been developed for treatment of erectile dysfunction. Moreover, sildenafil and tadalafil are used for the management of pulmonary arterial hypertension in patients. Since our first report showing the cardioprotective effect of sildenafil in 2002, there has been tremendous growth of preclinical and clinical studies on the use of PDE5 inhibitors for cardiovascular diseases and cancer. Numerous animal studies have demonstrated that PDE5 inhibitors have powerful protective effect against myocardial ischemia/reperfusion (I/R) injury, doxorubicin cardiotoxicity, ischemic and diabetic cardiomyopathy, cardiac hypertrophy, Duchenne muscular dystrophy and the improvement of stem cell efficacy for myocardial repair. Mechanistically, PDE5 inhibitors protect the heart against I/R injury through increased expression of nitric oxide synthases, activation of protein kinase G (PKG), PKG-dependent hydrogen sulfide generation, and phosphorylation of glycogen synthase kinase-3β - a master switch immediately proximal to mitochondrial permeability transition pore and the end effector of cardioprotection. In addition, PDE5 inhibitors enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs, including doxorubicin. Many clinical trials with PDE5 inhibitors have focused on the potential cardiovascular and anti-cancer benefits. Despite mixed results of these clinical trials, there is a continuing strong interest by basic scientists and clinical investigators in exploring their new clinical uses. It is our hope that future new mechanistic investigations and carefully designed clinical trials would help in reaping additional benefits of PDE5 inhibitors for cardiovascular disease and cancer in patients. Copyright © 2014 Elsevier Inc. All rights reserved.

The safety of phosphodiesterase type 5 inhibitors for erectile dysfunction.

PubMed

Ventimiglia, Eugenio; Capogrosso, Paolo; Montorsi, Francesco; Salonia, Andrea

2016-01-01

Phosphodiesterase type 5 inhibitors (PDE5Is) are the leading drugs for the treatment of erectile dysfunction (ED), being recommended as a first line treatment by both the European and US urological guidelines. PDE5Is are highly effective as compared to placebo, well tolerated and have a very low, though not negligible, rate of severe treatment-related adverse events. This paper reviews the safety profile of currently available PDE5Is, comparing them in a broad spectrum ED population and outlining a number of real-life aspects of importance in the real-life everyday clinical setting. Guidelines unanimously agree in considering PDE5Is as first line treatments for ED when well-tolerated and not contraindicated. Despite the fact that no high-grade evidence comparing the efficacy and the safety for PDE5Is is currently available, published data seem to suggest that there are no major differences in their safety profiles. Moreover, although oral PDE5Is were shown to cause more AEs than placebo, they were generally mild and well tolerated.

A substrate selectivity and inhibitor design lesson from the PDE10-cAMP crystal structure: a computational study.

PubMed

Lau, Justin Kai-Chi; Li, Xiao-Bo; Cheng, Yuen-Kit

2010-04-22

Phosphodiesterases (PDEs) catalyze the hydrolysis of second messengers cAMP and cGMP in regulating many important cellular signals and have been recognized as important drug targets. Experimentally, a range of specificity/selectivity toward cAMP and cGMP is well-known for the individual PDE families. The study reported here reveals that PDEs might also exhibit selectivity toward conformations of the endogenous substrates cAMP and cGMP. Molecular dynamics simulations and free energy study have been applied to study the binding of the cAMP torsional conformers about the glycosyl bond in PDE10A2. The computational results elucidated that PDE10A2 is energetically more favorable in complex with the syn cAMP conformer (as reported in the crystal structure) and the binding of anti cAMP to PDE10A2 would lead to either a nonreactive configuration or significant perturbation on the catalytic pocket of the enzyme. This experimentally inaccessible information provides important molecular insights for the development of effective PDE10 ligands.

East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease.

PubMed

Sharma, Manju; Levenson, Corey; Browning, John C; Becker, Emily M; Clements, Ian; Castella, Paul; Cox, Michael E

2018-01-01

Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity in vitro . In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation, and pro-inflammatory cytokines/chemokine production. These results suggest that EISO anti-inflammatory activity is mediated through suppressing PDE activity, thus facilitating cAMP-regulated inhibition of NF-κB and indicate EISO as an attractive natural therapeutic for chronic and acute inflammatory disorders.

Inhibitors of cyclic nucleotide phosphodiesterase 3 and 5 as therapeutic agents in heart failure.

PubMed

Stehlik, Josef; Movsesian, Matthew A

2006-07-01

Cyclic nucleotide phosphodiesterases (PDE) 3 and 5 regulate cAMP and cGMP signalling in cardiac and smooth muscle myocytes. Important advances in the understanding of the roles of these enzymes have recently been made. PDE3 inhibitors have inotropic and vasodilatory properties, and although they acutely improve haemodynamics in patients with heart failure, they do not improve long-term morbidity and mortality. Although combination therapy with beta-adrenergic receptor antagonists or selective inhibition of specific PDE3 isoforms might result in a more favourable long-term outcome, more clinical data are needed to test this proposition. The role of PDE5 inhibitors in the treatment of cardiac disease is evolving. PDE5 inhibitors cause pulmonary and systemic vasodilation. How these drugs will compare with other vasodilators in terms of long-term outcomes in patients with heart failure is unknown. Recent studies also suggest that PDE5 inhibitors may have antihypertropic effects, exerted through increased myocardial cGMP signalling, that could be of additional benefit in patients with heart failure.

East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease

PubMed Central

Sharma, Manju; Levenson, Corey; Browning, John C.; Becker, Emily M.; Clements, Ian; Castella, Paul; Cox, Michael E.

2018-01-01

Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity in vitro. In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation, and pro-inflammatory cytokines/chemokine production. These results suggest that EISO anti-inflammatory activity is mediated through suppressing PDE activity, thus facilitating cAMP-regulated inhibition of NF-κB and indicate EISO as an attractive natural therapeutic for chronic and acute inflammatory disorders. PMID:29593534

Topical otic drugs in a multi-purpose manufacturing facility: a guide on determination and application of permitted daily exposure (PDE).

PubMed

Wiesner, Lisa; Prause, Maarten; Lovsin Barle, Ester

2018-03-01

Due to newly introduced EU GMP (Good Manufacturing Practice) guideline for Medicinal Products for Human and Veterinary use, product specific permitted daily exposure (PDE) for toxicological evaluation in multi-purpose facilities are required within a documented process for risk assessment. European Medicines Agency (EMA) guidance on setting PDE limits so far focused on systemic administration routes such as intravenous (IV), oral or inhalation. This article provides guidance on setting PDE values for risk management purposes in multi-purpose facilities for active pharmaceutical ingredients (APIs) applied as topical otic drugs to the outer ear canal. The therewith determined PDE otic, is used for the calculation of maximum safe carry-over (MSC) in manufacturing scenarios where a topical otic product is manufactured followed by another topical otic product.

Rip3 knockdown rescues photoreceptor cell death in blind pde6c zebrafish.

PubMed

Viringipurampeer, I A; Shan, X; Gregory-Evans, K; Zhang, J P; Mohammadi, Z; Gregory-Evans, C Y

2014-05-01

Achromatopsia is a progressive autosomal recessive retinal disease characterized by early loss of cone photoreceptors and later rod photoreceptor loss. In most cases, mutations have been identified in CNGA3, CNGB3, GNAT2, PDE6C or PDE6H genes. Owing to this genetic heterogeneity, mutation-independent therapeutic schemes aimed at preventing cone cell death are very attractive treatment strategies. In pde6c(w59) mutant zebrafish, cone photoreceptors expressed high levels of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3) kinases, key regulators of necroptotic cell death. In contrast, rod photoreceptor cells were alternatively immunopositive for caspase-3 indicating activation of caspase-dependent apoptosis in these cells. Morpholino gene knockdown of rip3 in pde6c(w59) embryos rescued the dying cone photoreceptors by inhibiting the formation of reactive oxygen species and by inhibiting second-order neuron remodelling in the inner retina. In rip3 morphant larvae, visual function was restored in the cones by upregulation of the rod phosphodiesterase genes (pde6a and pde6b), compensating for the lack of cone pde6c suggesting that cones are able to adapt to their local environment. Furthermore, we demonstrated through pharmacological inhibition of RIP1 and RIP3 activity that cone cell death was also delayed. Collectively, these results demonstrate that the underlying mechanism of cone cell death in the pde6c(w59) mutant retina is through necroptosis, whereas rod photoreceptor bystander death occurs through a caspase-dependent mechanism. This suggests that targeting the RIP kinase signalling pathway could be an effective therapeutic intervention in retinal degeneration patients. As bystander cell death is an important feature of many retinal diseases, combinatorial approaches targeting different cell death pathways may evolve as an important general principle in treatment.

Nebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum and penile arteries from diabetic patients by enhancing the NO/cGMP pathway.

PubMed

Martínez-Salamanca, Juan I; La Fuente, José M; Cardoso, José; Fernández, Argentina; Cuevas, Pedro; Wright, Harold M; Angulo, Javier

2014-05-01

The efficacy of oral pharmacotherapy for erectile dysfunction (ED) (i.e., type 5 phosphodiesterase[PDE5] inhibitors) is significantly reduced in diabetic patients. Nebivolol is a selective β1-blocker used for treatinghy pertension that has been shown to increase the efficacy of sildenafil to reverse ED in diabetic rats. To evaluate the effects of nebivolol on the efficacy of the PDE5 inhibitors, sildenafil, tadalafil, and vardenafil to relax human corpus cavernosum (HCC) and vasodilate human penile resistance arteries (HPRA) from diabetic patients with ED (DMED). The influence of nebivolol on the capacity of these three PDE5 inhibitors to stimulate cyclic guanosine monophosphate (cGMP) production in HCC was also evaluated. HCC and HPRA were obtained from organ donors without ED (NEND; n = 18) or patients with diabetes undergoing penile prosthesis implantation (DMED; n = 19). Relaxations of HCC strips and HPRA to sildenafil,tadalafil, and vardenafil were evaluated in organ chambers and wire myographs. cGMP content in HCC was determined by ether extraction and quantification by ELISA. Effects of nebivolol on PDE5 inhibitor-induced relaxation of HCC, vasodilation ofHPRA and cGMP accumulation in HCC. Treatment with nebivolol (1 μM) significantly potentiated sildenafil-, tadalafil- and vardenafil-induced relaxations of HCC and vasodilations of HPRA from both NEND and DMED. Enhancement of relaxant capacity by nebivolol resulted in reversion of the impairment of PDE5 inhibition-induced responses in DMED and it was accompanied by enhancing the ability of PDE5 inhibitors to increase cGMP in HCC restoring reduced cGMP levelsin HCC from DMED. Nebivolol potentiated the capacity of PDE5 inhibitors to relax vascular structures of erectile tissue from diabetic patients by enhancing the nitric oxide (NO)/cGMP pathway in these tissues. These effects suggest a potential therapeutic utility of nebivolol as an adjunct to PDE5 inhibitors for the treatment of ED associated with diabetes.

Characterization of particulate cyclic nucleotide phosphodiesterases from bovine brain: Purification of a distinct cGMP-stimulated isoenzyme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murashima, Seiko; Tanaka, Takayuki; Hockman, S.

1990-06-05

In the absence of detergent, {approx}80-85% of the total cGMP-stimulated phosphodiesterase (PDE) activity in bovine brain was associated with washed particulate fractions; {approx}85-90% of the calmodulin-sensitive PDE was soluble. Particulate cGMP-stimulated PDE was higher in cerebral cortical gray matter than in other regions. Homogenization of the brain particulate fraction in 1% Lubrol increased cGMP-stimulated activity {approx}100% and calmodulin-stimulated {approx}400-500%. Although 1% Lubrol readily solubilized these PDE activities, {approx}75% of the cAMP PDE activity (0.5 {mu}M ({sup 3}H)cAMP) that was not affected by cGMP was not solubilized. This cAMP PDE activity was very sensitive to inhibition by Rolipram but not cilostamide.more » Thus, three different PDE types, i.e., cGMP stimulated, calmodulin sensitive, and Rolipram inhibited, are associated in different ways with crude bovine brain particulate fractions. The brain enzyme exhibited a slightly greater subunit M{sub r} than did soluble forms from calf liver or bovine brain, as evidenced by protein staining or immunoblotting after polyacrylamide gel electrophoresis under denaturing conditions. Incubation of brain particulate and liver soluble cGMP-stimulated PDEs with V{sub 8} protease produced several peptides of similar size, as well as at least two distinct fragments of {approx}27 kDa from the brain and {approx}23 kDa from the liver enzyme. After photolabeling in the presence of ({sup 32}P)cGMP and digestion with V{sub 8} protease, ({sup 32}P)cGMP in each PDE was predominantly recovered with a peptide of {approx}14 kDa. All of these observations are consistent with the existence of at least two discrete forms (isoenzymes) of cGMP-stimulated PDE.« less

Does educational status affect a patient's behavior toward erectile dysfunction?

PubMed

Salonia, Andrea; Abdollah, Firas; Gallina, Andrea; Pellucchi, Federico; Castillejos Molina, Ricardo Alonso; Maccagnano, Carmen; Rocchini, Lorenzo; Zanni, Giuseppe; Rigatti, Patrizio; Montorsi, Francesco

2008-08-01

Educational status has been investigated rarely as a potential factor affecting the behavior of patients with new onset erectile dysfunction (ED) toward seeking first medical help and subsequent compliance with prescribed phosphodiesterase type 5 inhibitor (PDE5) therapy. To test whether the educational status of patients with new onset ED and naïve to PDE5 therapy may have a significant impact on the delay before seeking first medical help (DSH) and compliance with the suggested PDE5. Assessing DSH and compliance with PDE5 in new onset ED patients according to their educational status by means of detailed logistic regression analyses. Data from 302 consecutive patients with new onset ED and naïve to PDE5s were comprehensively analyzed. Patients were segregated according to their educational status into low (elementary and/or secondary school education) and high (high school and/or university degrees) educational levels. Complete data were available for 231 assessable patients. Univariate (UVA) and multivariate (MVA) logistic regression analyses addressed the association between educational status and DSH after adjusting for age, relationship status, and Sexual Health Inventory for Men score. Likewise, UVA and MVA were performed to test the association between educational status and patient compliance with PDE5 at the 9-month median follow-up. Median DSH was 24 months (range 1-350; mean 38.1 +/- 42.8). The lower the educational status, the shorter the DSH (P = 0.03). In contrast, a significantly (P < 0.0001) greater proportion of patients with a higher educational status showed compliance with the suggested PDE5 at the 9-month follow-up. Overall, educational status was not an independent predictor of either DSH or patient compliance with PDE5 therapy. After adjusting for other variables, our findings suggest that in new onset ED patients, educational status does not independently affect the DSH and patient compliance with PDE5 therapy.

A boundary PDE feedback control approach for the stabilization of mortgage price dynamics

NASA Astrophysics Data System (ADS)

Rigatos, G.; Siano, P.; Sarno, D.

2017-11-01

Several transactions taking place in financial markets are dependent on the pricing of mortgages (loans for the purchase of residences, land or farms). In this article, a method for stabilization of mortgage price dynamics is developed. It is considered that mortgage prices follow a PDE model which is equivalent to a multi-asset Black-Scholes PDE. Actually it is a diffusion process evolving in a 2D assets space, where the first asset is the house price and the second asset is the interest rate. By applying semi-discretization and a finite differences scheme this multi-asset PDE is transformed into a state-space model consisting of ordinary nonlinear differential equations. For the local subsystems, into which the mortgage PDE is decomposed, it becomes possible to apply boundary-based feedback control. The controller design proceeds by showing that the state-space model of the mortgage price PDE stands for a differentially flat system. Next, for each subsystem which is related to a nonlinear ODE, a virtual control input is computed, that can invert the subsystem's dynamics and can eliminate the subsystem's tracking error. From the last row of the state-space description, the control input (boundary condition) that is actually applied to the multi-factor mortgage price PDE system is found. This control input contains recursively all virtual control inputs which were computed for the individual ODE subsystems associated with the previous rows of the state-space equation. Thus, by tracing the rows of the state-space model backwards, at each iteration of the control algorithm, one can finally obtain the control input that should be applied to the mortgage price PDE system so as to assure that all its state variables will converge to the desirable setpoints. By showing the feasibility of such a control method it is also proven that through selected modification of the PDE boundary conditions the price of the mortgage can be made to converge and stabilize at specific reference values.

The novel functions of cGMP-specific phosphodiesterase 5 and its inhibitors in carcinoma cells and pulmonary/cardiovascular vessels.

PubMed

Zhu, Bing; Strada, Samuel J

2007-01-01

PDE5 is a key enzyme involved in the regulation of cGMP-specific signaling pathways in normal physiological processes such as smooth muscle contraction and relaxation. For this reason, inhibition of the enzyme can alter those pathophysiological conditions associated with a lowering cGMP level in tissues. For example, selective PDE5 inhibitors, such as sildenafil (Viagra, Pfizer), tadalafil (Cialis, Lilly-ICOS), and vardenafil (Levitra, Bayer), have been successfully used to treat the condition of human erectile dysfunction. More recently, the involvement of this enzyme has been proposed to influence antiproliferation and proapoptotic mechanism in multiple carcinomas. The data supporting this idea is based on increases in PDE5 activities in many carcinomas and the ability of PDE5 inhibitors such as exisulind and its analogs related to anticancer activities. Inhibition of PDE5 that results in sustained increases in [cGMP](i) are required to modify the process of apoptosis and mitotic arrest in those carcinoma cells with enhanced PDE5 expressions. Increases in PDE5 are also involved in contributing to the pathological changes in the pulmonary system resulting in hyper-proliferative remodeling of both smooth muscle and endothelium in models of pulmonary hypertension. For this reason, the use of PDE5 inhibitors in the treatment of human pulmonary hypertension has met with some success. The differences that we have previously noted in PDE isoenzymes in pulmonary arterial and microvascular endothelial cells may provide a more selective cellular strategy for use of such inhibitor. Additional studies on structure biology of these enzymes should lead to the development of agents with better cellular specificity than currently available drugs. Considering the enormous progress that has been made in the last few years, the future looks promising for agents affecting this enzyme and related systems.

[A study of PDE6B gene mutation and phenotype in Chinese cases with retinitis pigmentosa].

PubMed

Cui, Yun; Zhao, Kan-xing; Wang, Li; Wang, Qing; Zhang, Wei; Chen, Wei-ying; Wang, Li-ming

2003-01-01

To identify the mutation spectrum of phosphodiesterase beta subunit (PDE6B) gene, the incidence in Chinese patients with retinitis pigmentosa (RP) and their clinical phenotypic characteristics. Screening of mutations within PDE6B gene was performed using polymerase chain reaction-heteroduplex-single strand conformation polymorphism (PCR-SSCP) and DNA sequence in 35 autosomal recessive (AR) RP and 55 sporadic RP cases. The phenotypes of the patients with the gene mutation were examined and analyzed. Novel complex heterozygous variants of PDE6B gene in a sporadic case, a T to C transversion in codon 323 resulting in the substitution of Gly by Ser and 2 base pairs (bp: G and T) insert between the 27th-28th bp upstream of the 5'-end of exon 10 were both present in a same isolate RP. But they are not found in 100 unrelated healthy individuals. Ocular findings showed diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi, optic atrophy and vessel attenuation. Multi-focal ERG indicated that the rod function was more severely deteriorated. A mutation was found in a case with RP in a ARRP family, a G to A transversion at 19th base upstream 5'-end of exon 11 (within intron 10) of PDE6B gene. A sporadic RP carried a sequence variant of PDE6B gene, a G to C transition, at the 15th base adjacent to the 3'-end of exon l8. In another isolate case with RP was found 2 bp (GT) insert between 31st and 32nd base upstream 5'-end of exon 4 (in intron 3) of PDE6B gene. There are novel complex heterozygous mutations of PDE6B gene responsible for a sporadic RP patient in China. This gene mutation associated with rod deterioration and RP. Several DNA variants were found in introns of PDE6B gene in national population.

Tidal double detonation: a new mechanism for the thermonuclear explosion of a white dwarf induced by a tidal disruption event

NASA Astrophysics Data System (ADS)

Tanikawa, Ataru

2018-03-01

We suggest tidal double detonation as a new mechanism for the thermonuclear explosion of a white dwarf (WD) induced by a tidal disruption event (TDE). Tidal detonation is also a WD explosion induced by a TDE. In this case, helium (He) and carbon-oxygen (CO) detonation waves incinerate He WDs and CO WDs, respectively. On the other hand, for tidal double detonation, He detonation is first excited in the He shell of a CO WD, which then drives CO detonation in the CO core. We name this mechanism after the double detonation scenario in the context of type Ia supernovae. In this paper, by performing numerical simulations for CO WDs of mass 0.60 M⊙ with and without a He shell, we show that tidal double detonation occurs in the shallower encounter of a CO WD with an intermediate-mass black hole (IMBH) compared to simple tidal detonation. We expect tidal double detonation will increase the possibility of the occurrence of WD TDEs, which can help us to understand IMBHs.

Detonation properties of 1,1-diamino-2,2-dinitroethene (DADNE).

PubMed

Trzciński, Waldemar A; Cudziło, Stanisław; Chyłek, Zbigniew; Szymańczyk, Leszek

2008-09-15

1,1-Diamino-2,2-dinitroethene (DADNE, FOX-7) is an explosive of current interest. In our work, an advanced study of detonation characteristics of this explosive was performed. DADNE was prepared and recrystallized on a laboratory scale. Some sensitivity and detonation properties of DADNE were determined. The detonation performance was established by measurements of the detonation wave velocity, detonation pressure and calorimetric heat of explosion as well as the accelerating ability. The JWL (Jones-Wilkins-Lee) isentrope and the constant-gamma isentrope for the detonation products of DADNE were also found.

State and prospects of solid propellant rocket development

NASA Astrophysics Data System (ADS)

Kukushkin, V. Kh.

1992-07-01

An overview is presented of aspects of solid-propellant rocket engine (SPRE) development with individual treatment given to sustainer and spacecraft SPRE technologies. The paper focuses on low-modulus fuels of composite solid propellant, requirements for adhesion stability, and enhancement of the power characteristics of solid propellants. R&D activities are described that relate to the use of SPREs with extending nozzles and to the design of ultradimensional nozzles for upper-stage engines. Other developments for the SPREs include engines with separate loading and pasty fuel applications, and progress is reported in the direction of detonation SPREs. The SPREs using pasty propellants provide good control over thrust characteristics and fuel qualities. A device is incorporated that assures fuel burning in the combustion region and reliable ignition during restarting of these engines.

Planckian Information (Ip): A New Measure of Order in Atoms, Enzymes, Cells, Brains, Human Societies, and the Cosmos

NASA Astrophysics Data System (ADS)

Ji, Sungchul

A new mathematical formula referred to as the Planckian distribution equation (PDE) has been found to fit long-tailed histograms generated in various fields of studies, ranging from atomic physics to single-molecule enzymology, cell biology, brain neurobiology, glottometrics, econophysics, and to cosmology. PDE can be derived from a Gaussian-like equation (GLE) by non-linearly transforming its variable, x, while keeping the y coordinate constant. Assuming that GLE represents a random distribution (due to its symmetry), it is possible to define a binary logarithm of the ratio between the areas under the curves of PDE and GLE as a measure of the non-randomness (or order) underlying the biophysicochemical processes generating long-tailed histograms that fit PDE. This new function has been named the Planckian information, IP, which (i) may be a new measure of order that can be applied widely to both natural and human sciences and (ii) can serve as the opposite of the Boltzmann-Gibbs entropy, S, which is a measure of disorder. The possible rationales for the universality of PDE may include (i) the universality of the wave-particle duality embedded in PDE, (ii) the selection of subsets of random processes (thereby breaking the symmetry of GLE) as the basic mechanism of generating order, organization, and function, and (iii) the quantity-quality complementarity as the connection between PDE and Peircean semiotics.

Development of a Scintillation Proximity Assay (SPA) Based, High Throughput Screening Feasible Method for the Identification of PDE12 Activity Modulators.

PubMed

Mang, Samuel; Bucher, Hannes; Nickolaus, Peter

2016-01-01

The scintillation proximity assay (SPA) technology has been widely used to establish high throughput screens (HTS) for a range of targets in the pharmaceutical industry. PDE12 (aka. 2'- phosphodiesterase) has been published to participate in the degradation of oligoadenylates that are involved in the establishment of an antiviral state via the activation of ribonuclease L (RNAse-L). Degradation of oligoadenylates by PDE12 terminates these antiviral activities, leading to decreased resistance of cells for a variety of viral pathogens. Therefore inhibitors of PDE12 are discussed as antiviral therapy. Here we describe the use of the yttrium silicate SPA bead technology to assess inhibitory activity of compounds against PDE12 in a homogeneous, robust HTS feasible assay using tritiated adenosine-P-adenylate ([3H]ApA) as substrate. We found that the used [3H]ApA educt, was not able to bind to SPA beads, whereas the product [3H]AMP, as known before, was able to bind to SPA beads. This enables the measurement of PDE12 activity on [3H]ApA as a substrate using a wallac microbeta counter. This method describes a robust and high throughput capable format in terms of specificity, commonly used compound solvents, ease of detection and assay matrices. The method could facilitate the search for PDE12 inhibitors as antiviral compounds.

Identification of New Signaling Components in the Sensory Epithelium of Human Saccule

PubMed Central

Degerman, Eva; Rauch, Uwe; Göransson, Olga; Lindberg, Sven; Hultgårdh, Anna; Magnusson, Måns

2011-01-01

Objective: To locate components and target proteins of relevance for the cAMP and cGMP signaling networks including cAMP and cGMP phosphodiesterases (PDEs), salt-inducible kinases (SIKs), subunits of Na+, K+-ATPases, and aquaporins (AQPs) in the human saccule. Methods: The human saccule was dissected out during the removal of vestibular schwannoma via the translabyrinthine approach and immediately fixed. Immunohistochemistry was performed using PDE, SIK, Na+, K+-ATPase, and AQP antibodies. Results: PDEs selective for cAMP (PDE4A, PDE4D, and PDE8A) and cGMP (PDE9A) as well a dual specificity PDE (PDE10A) were detected in the sensory epithelium of the saccule. Furthermore, AQP2, 4, and 9, SIK1 and the α-1 subunit of the Na+, K+-ATPase were detected. Conclusion: cAMP and cGMP are important regulators of ion and water homeostasis in the inner ear. The identification of PDEs and SIK1 in the vestibular system offers new treatment targets for endolymphatic hydrops. Exactly how the PDEs are connected to SIK1 and the SIK1 substrate Na+, K+-ATPase and to AQPs 2, 4, 9 remains to be elucidated. The dissection of the signaling networks utilizing these components and evaluating their roles will add new basic knowledge regarding inner ear physiology. PMID:21886636

Synthesis of Fluorine-Containing Phosphodiesterase 10A (PDE10A) Inhibitors and the In Vivo Evaluation of F-18 Labeled PDE10A PET Tracers in Rodent and Nonhuman Primate

PubMed Central

Li, Junfeng; Zhang, Xiang; Jin, Hongjun; Fan, Jinda; Flores, Hubert; Perlmutter, Joel S.; Tu, Zhude

2015-01-01

A series of fluorine-containing PDE10A inhibitors were designed and synthesized to improve the metabolic stability of [11C]MP-10. Twenty of the 22 new analogues had high potency and selectivity for PDE10A: 18a–j, 19d–j, 20a–b, and 21b had IC50 values <5 nM for PDE10A. Seven F-18 labeled compounds [18F]18a–e, [18F]18g, and [18F]20a were radiosynthesized by 18F-introduction onto the quinoline rather than the pyrazole moiety of the MP-10 pharmacophore and performed in vivo evaluation. Biodistribution studies in rats showed ~2-fold higher activity in the PDE10A-enriched striatum than nontarget brain regions; this ratio increased from 5 to 30 min postinjection, particularly for [18F]18a–d and [18F]20a. Micro-PET studies of [18F]18d and [18F]20a in nonhuman primates provided clear visualization of striatum with suitable equilibrium kinetics and favorable metabolic stability. These results suggest this strategy may identify a 18F-labeled PET tracer for quantifying the levels of PDE10A in patients with CNS disorders including Huntington’s disease and schizophrenia. PMID:26430878

Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance.

PubMed

Nawrocki, Andrea R; Rodriguez, Carlos G; Toolan, Dawn M; Price, Olga; Henry, Melanie; Forrest, Gail; Szeto, Daphne; Keohane, Carol Ann; Pan, Yie; Smith, Karen M; Raheem, Izzat T; Cox, Christopher D; Hwa, Joyce; Renger, John J; Smith, Sean M

2014-01-01

Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric intake and energy homeostasis. PDE10A-deficient mice are resistant to diet-induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight gain is due to hypophagia after mice are fed a highly palatable diet rich in fats and sugar but not a standard diet. PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body weight loss, and reduced adiposity at doses that produced antipsychotic efficacy in behavioral models. We show that PDE10A inhibition increased whole-body energy expenditure in DIO mice fed a Western-style diet, achieving weight loss and reducing adiposity beyond the extent seen with food restriction alone. Therefore, chronic THPP-6 treatment conferred improved insulin sensitivity and reversed hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a novel antipsychotic target that may have additional metabolic benefits over current medications for schizophrenia by suppressing food intake, alleviating weight gain, and reducing the risk for the development of diabetes.

The rational search for PDE10A inhibitors from Sophora flavescens roots using pharmacophore‑ and docking‑based virtual screening.

PubMed

Fan, Han-Tian; Guo, Jun-Fang; Zhang, Yu-Xin; Gu, Yu-Xi; Ning, Zhong-Qi; Qiao, Yan-Jiang; Wang, Xing

2018-01-01

Phosphodiesterase 10A (PDE10A) has been confirmed to be an important target for the treatment of central nervous system (CNS) disorders. The purpose of the present study was to identify PDE10A inhibitors from herbs used in traditional Chinese medicine. Pharmacophore and molecular docking techniques were used to virtually screen the chemical molecule database of Sophora flavescens, a well‑known Chinese herb that has been used for improving mental health and regulating the CNS. The pharmacophore model generated recognized the common functional groups of known PDE10A inhibitors. In addition, molecular docking was used to calculate the binding affinity of ligand‑PDE10A interactions and to investigate the possible binding pattern. Virtual screening based on the pharmacophore model and molecular docking was performed to identify potential PDE10A inhibitors from S. flavescens. The results demonstrated that nine hits from S. flavescens were potential PDE10A inhibitors, and their biological activity was further validated using literature mining. A total of two compounds were reported to inhibit cyclic adenosine monophosphate phosphodiesterase, and one protected against glutamate‑induced oxidative stress in the CNS. The remaining six compounds require further bioactivity validation. The results of the present study demonstrated that this method was a time‑ and cost‑saving strategy for the identification of bioactive compounds from traditional Chinese medicine.

A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma

PubMed Central

Suhasini, Avvaru N.; Lin, An-Ping; Bhatnagar, Harshita; Kim, Sang-Woo; Moritz, August W.; Aguiar, Ricardo C. T.

2015-01-01

Angiogenesis associates with poor outcome in diffuse large B-cell lymphoma (DLBCL), but the contribution of the lymphoma cells to this process remains unclear. Addressing this knowledge gap may uncover unsuspecting proangiogenic signaling nodes and highlight alternative antiangiogenic therapies. Here we identify the second messenger cyclic-AMP (cAMP) and the enzyme that terminates its activity, phosphodiesterase 4B (PDE4B), as regulators of B-cell lymphoma angiogenesis. We first show that cAMP, in a PDE4B-dependent manner, suppresses PI3K/AKT signals to down-modulate VEGF secretion and vessel formation in vitro. Next, we create a novel mouse model that combines the lymphomagenic Myc transgene with germline deletion of Pde4b. We show that lymphomas developing in a Pde4b-null background display significantly lower microvessel density in association with lower VEGF levels and PI3K/AKT activity. We recapitulate these observations by treating lymphoma-bearing mice with the FDA-approved PDE4 inhibitor Roflumilast. Lastly, we show that primary human DLBCLs with high PDE4B expression display significantly higher microvessel density. Here, we defined an unsuspected signaling circuitry in which the cAMP generated in lymphoma cells downmodulates PI3K/AKT and VEGF secretion to negatively influence vessel development in the microenvironment. These data identify PDE4 as an actionable antiangiogenic target in DLBCL. PMID:26503641

New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment.

PubMed

Brullo, Chiara; Ricciarelli, Roberta; Prickaerts, Jos; Arancio, Ottavio; Massa, Matteo; Rotolo, Chiara; Romussi, Alessia; Rebosio, Claudia; Marengo, Barbara; Pronzato, Maria Adelaide; van Hagen, Britt T J; van Goethem, Nick P; D'Ursi, Pasqualina; Orro, Alessandro; Milanesi, Luciano; Guariento, Sara; Cichero, Elena; Fossa, Paola; Fedele, Ernesto; Bruno, Olga

2016-11-29

Phosphodiesterase type 4D (PDE4D) has been indicated as a promising target for treating neurodegenerative pathologies such as Alzheimer's Disease (AD). By preventing cAMP hydrolysis, PDE4 inhibitors (PDE4Is) increase the cAMP response element-binding protein (CREB) phosphorylation, synaptic plasticity and long-term memory formation. Pharmacological and behavioral studies on our hit GEBR-7b demonstrated that selective PDE4DIs could improve memory without causing emesis and sedation. The hit development led to new molecule series, herein reported, characterized by a catechol structure bonded to five member heterocycles. Molecular modeling studies highlighted the pivotal role of a polar alkyl chain in conferring selective enzyme interaction. Compound 8a showed PDE4D3 selective inhibition and was able to increase intracellular cAMP levels in neuronal cells, as well as in the hippocampus of freely moving rats. Furthermore, 8a was able to readily cross the blood-brain barrier and enhanced memory performance in mice without causing any emetic-like behavior. These data support the view that PDE4D is an adequate molecular target to restore memory deficits in different neuropathologies, including AD, and also indicate compound 8a as a promising candidate for further preclinical development. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

High-Speed Photography of Detonation Propagation in Dynamically Precompressed Liquid Explosives

NASA Astrophysics Data System (ADS)

Petel, O. E.; Higgins, A. J.; Yoshinaka, A. C.; Zhang, F.

2007-12-01

The propagation of detonation in shock-compressed nitromethane was observed with a high-speed framing camera. The test explosive, nitromethane, was compressed by a reverberating shock wave to pressures as high as 10 GPa prior to being detonated by a secondary detonation event. The pressure and density in the test explosive prior to detonation were determined using two methods: manganin stress gauge measurements and LS-DYNA simulations. The velocity of the detonation front was determined from consecutive frames and correlated to the density of the reverberating shock-compressed explosive prior to detonation. Observing detonation propagation under these non-ambient conditions provides data which can be useful in the validation of equation of state models.

Detonation control

DOEpatents

Mace, Jonathan L.; Seitz, Gerald J.; Bronisz, Lawrence E.

2016-10-25

Detonation control modules and detonation control circuits are provided herein. A trigger input signal can cause a detonation control module to trigger a detonator. A detonation control module can include a timing circuit, a light-producing diode such as a laser diode, an optically triggered diode, and a high-voltage capacitor. The trigger input signal can activate the timing circuit. The timing circuit can control activation of the light-producing diode. Activation of the light-producing diode illuminates and activates the optically triggered diode. The optically triggered diode can be coupled between the high-voltage capacitor and the detonator. Activation of the optically triggered diode causes a power pulse to be released from the high-voltage capacitor that triggers the detonator.

Hard Fighting: Israel in Lebanon and Gaza

DTIC Science & Technology

2011-01-01

mines . Hezbollah itself also proved an unexpectedly formidable adversary. During the years leading up to the Second Lebanon War, Hezbollah forces...hitting Hamas positions and detonating mines and IEDs. IDF engineers used armored D-9 bulldozers to clear paths through the remaining IEDs. Armored...discipline; cellular structure; small formations (squads) • Weapons: small arms; RPGs; mortars; short- range rockets; IEDs/ mines • Command and control

Pressure Distribution and Performance Impacts of Aerospike Nozzles on Rotating Detonation Engines

DTIC Science & Technology

2017-06-01

design methodology at both on- and off-design conditions anticipated throughout the combustion cycle. Steady-state, non -reacting computational fluid...operation. Therefore, the nozzle contour was designed using a traditional, steady-state design methodology at both on- and off-design conditions...anticipated throughout the combustion cycle. Steady-state, non -reacting computational fluid dynamics (CFD) simulations were performed on various nozzle

Using Kokkos for Performant Cross-Platform Acceleration of Liquid Rocket Simulations

DTIC Science & Technology

2017-05-08

NUMBER (Include area code) 08 May 2017 Briefing Charts 05 April 2017 - 08 May 2017 Using Kokkos for Performant Cross-Platform Acceleration of Liquid ...ERC Incorporated RQRC AFRL-West Using Kokkos for Performant Cross-Platform Acceleration of Liquid Rocket Simulations 2DISTRIBUTION A: Approved for... Liquid Rocket Combustion Simulation SPACE simulation of rotating detonation engine (courtesy of Dr. Christopher Lietz) 3DISTRIBUTION A: Approved

On the Interface of Probabilistic and PDE Methods in a Multifactor Term Structure Theory

ERIC Educational Resources Information Center

Mamon, Rogemar S.

2004-01-01

Within the general framework of a multifactor term structure model, the fundamental partial differential equation (PDE) satisfied by a default-free zero-coupon bond price is derived via a martingale-oriented approach. Using this PDE, a result characterizing a model belonging to an exponential affine class is established using only a system of…

Experimental study on transmission of an overdriven detonation wave from propane/oxygen to propane/air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J.; Lai, W.H.; Chung, K.

2008-08-15

Two sets of experiments were performed to achieve a strong overdriven state in a weaker mixture by propagating an overdriven detonation wave via a deflagration-to-detonation transition (DDT) process. First, preliminary experiments with a propane/oxygen mixture were used to evaluate the attenuation of the overdriven detonation wave in the DDT process. Next, experiments were performed wherein a propane/oxygen mixture was separated from a propane/air mixture by a thin diaphragm to observe the transmission of an overdriven detonation wave. Based on the characteristic relations, a simple wave intersection model was used to calculate the state of the transmitted detonation wave. The resultsmore » showed that a rarefaction effect must be included to ensure that there is no overestimate of the post-transmission wave properties when the incident detonation wave is overdriven. The strength of the incident overdriven detonation wave plays an important role in the wave transmission process. The experimental results showed that a transmitted overdriven detonation wave occurs instantaneously with a strong incident overdriven detonation wave. The near-CJ state of the incident wave leads to a transmitted shock wave, and then the transition to the overdriven detonation wave occurs downstream. The attenuation process for the overdriven detonation wave decaying to a near-CJ state occurs in all tests. After the attenuation process, an unstable detonation wave was observed in most tests. This may be attributed to the increase in the cell width in the attenuation process that exceeds the detonability cell width limit. (author)« less

PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes.

PubMed

Yu, Hea Min; Chung, Hyo Kyun; Kim, Koon Soon; Lee, Jae Min; Hong, Jun Hwa; Park, Kang Seo

2017-11-04

Adipocytes are involved in many metabolic disorders. It was recently reported that phosphodiesterase type 5 (PDE5) is expressed in human adipose tissue. In addition, PDE5 inhibitors have been shown to improve insulin sensitivity in humans. However, the mechanism underlying the role of PDE5 inhibitors as an insulin sensitizer remains largely unknown. The present study was undertaken to investigate the role of the PDE5 inhibitor udenafil in insulin signaling in adipocytes and whether this is mediated through the regulation of mitochondrial function. To study the mechanism underlying the insulin sensitizing action of PDE5 inhibitors, we evaluated quantitative changes in protein or mRNA levels of mitochondrial oxidative phosphorylation (OxPhos) complex, oxygen consumption rate (OCR), and fatty acid oxidation with varying udenafil concentrations in 3T3-L1 cells. Our cell study suggested that udenafil enhanced the insulin signaling pathway in 3T3-L1 cells. Following udenafil treatment, basal mitochondrial OCR, maximal OxPhos capacity, and OxPhos gene expression significantly increased. Finally, we examined whether udenafil can affect the fatty acid oxidation process. Treatment of 3T3-L1 cells with udenafil (10 and 20 μM) significantly increased fatty acid oxidation rate in a dose-dependent manner. In addition, the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) significantly increased. We demonstrated that the PDE5 inhibitor udenafil enhances insulin sensitivity by improving mitochondrial function in 3T3-L1 cells. This might be the mechanism underlying the PDE5 inhibitor-enhanced insulin signaling in adipocytes. This also suggests that udenafil may provide benefit in the treatment of type 2 diabetes and other related cardiovascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

The multinational Men's Attitudes to Life Events and Sexuality (MALES) Study Phase II: understanding PDE5 inhibitor treatment seeking patterns, among men with erectile dysfunction.

PubMed

Fisher, William A; Rosen, Raymond C; Eardley, Ian; Niederberger, Craig; Nadel, Andrea; Kaufman, Joel; Sand, Michael

2004-09-01

The aim of Phase II of the Men's Attitudes to Life Events and Sexuality (MALES) Study is to explore PDE5 inhibitor treatment seeking among men with erectile dysfunction (ED). Phase II of the MALES study involved 2,912 men, aged 20-75 years, from 8 countries (U.S., U.K., Germany, France, Italy, Spain, Mexico, and Brazil), who reported ED. Participants were recruited from the MALES Phase I sample [1] and via booster methods (e.g., physician referral, street interception), and completed self-report questionnaires concerning the characteristics of their ED, their efforts to seek PDE5 inhibitor treatment for their sexual dysfunction, and attitudinal and referent influences that potentially affect treatment-seeking. Statistical analyses focus on identification of correlates of PDE5 inhibitor treatment seeking. PDE5 inhibitor utilization is strongly associated with ED sufferers' assessment of the severity of their sexual dysfunction, with their belief that medication for ED is dangerous, and with their perceptions of whether physicians, other professionals, and spouses or family members are supportive of their seeking treatment. ED sufferers who evaluate their sexual dysfunction as severe, who believe that medication for ED is not dangerous, and who perceive support for treatment seeking from referent others, are more likely to utilize PDE5 inhibitor treatment. Findings indicate that perceived ED severity, beliefs about ED medication, and referent influences are strongly correlated with utilization of PDE5 inhibitor therapy. These findings aid our understanding of factors that may incline men with ED to seek-or to avoid-PDE5 inhibitor therapy for their sexual dysfunction, and provide a basis for clinical and educational interventions to assist men with ED to seek appropriate treatment.

Phosphodiesterase (PDE5) inhibition assay for rapid detection of erectile dysfunction drugs and analogs in sexual enhancement products.

PubMed

Santillo, Michael F; Mapa, Mapa S T

2018-02-28

Products marketed as dietary supplements for sexual enhancement are frequently adulterated with phosphodiesterase-5 (PDE5) inhibitors, which are erectile dysfunction drugs or their analogs that can cause adverse health effects. Due to widespread adulteration, a rapid screening assay was developed to detect PDE5 inhibitors in adulterated products. The assay employs fluorescence detection and is based on measuring inhibition of PDE5 activity, the pharmacological mechanism shared among the adulterants. Initially, the assay reaction scheme was established and characterized, followed by analysis of 9 representative PDE5 inhibitors (IC 50 , 0.4-4.0 ng mL -1 ), demonstrating sensitive detection in matrix-free solutions. Next, dietary supplements serving as matrix blanks (n = 25) were analyzed to determine matrix interference and establish a threshold value; there were no false positives. Finally, matrix blanks were spiked with 9 individual PDE5 inhibitors, along with several mixtures. All 9 adulterants were successfully detected (≤ 5 % false negative rate; n = 20) at a concentration of 1.00 mg g -1 , which is over 5 times lower than concentrations commonly encountered in adulterated products. A major distinction of the PDE5 inhibition assay is the ability to detect adulterants without prior knowledge of their chemical structures, demonstrating a broad-based detection capability that can address a continuously evolving threat of new adulterants. The PDE5 inhibition assay can analyze over 40 samples simultaneously within 15 minutes and involves a single incubation step and simple data analysis, all of which are advantageous for combating the widespread adulteration of sex-enhancement products. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Selective Effects of PDE10A Inhibitors on Striatopallidal Neurons Require Phosphatase Inhibition by DARPP-321,2,3

PubMed Central

Polito, Marina; Guiot, Elvire; Gangarossa, Giuseppe; Longueville, Sophie; Doulazmi, Mohamed; Valjent, Emmanuel; Hervé, Denis; Girault, Jean-Antoine

2015-01-01

Abstract Type 10A phosphodiesterase (PDE10A) is highly expressed in the striatum, in striatonigral and striatopallidal medium-sized spiny neurons (MSNs), which express D1 and D2 dopamine receptors, respectively. PDE10A inhibitors have pharmacological and behavioral effects suggesting an antipsychotic profile, but the cellular bases of these effects are unclear. We analyzed the effects of PDE10A inhibition in vivo by immunohistochemistry, and imaged cAMP, cAMP-dependent protein kinase A (PKA), and cGMP signals with biosensors in mouse brain slices. PDE10A inhibition in mouse striatal slices produced a steady-state increase in intracellular cAMP concentration in D1 and D2 MSNs, demonstrating that PDE10A regulates basal cAMP levels. Surprisingly, the PKA-dependent AKAR3 phosphorylation signal was strong in D2 MSNs, whereas D1 MSNs remained unresponsive. This effect was also observed in adult mice in vivo since PDE10A inhibition increased phospho-histone H3 immunoreactivity selectively in D2 MSNs in the dorsomedial striatum. The PKA-dependent effects in D2 MSNs were prevented in brain slices and in vivo by mutation of the PKA-regulated phosphorylation site of 32 kDa dopamine- and cAMP-regulated phosphoprotein (DARPP-32), which is required for protein phosphatase-1 inhibition. These data highlight differences in the integration of the cAMP signal in D1 and D2 MSNs, resulting from stronger inhibition of protein phosphatase-1 by DARPP-32 in D2 MSNs than in D1 MSNs. This study shows that PDE10A inhibitors share with antipsychotic medications the property of activating preferentially PKA-dependent signaling in D2 MSNs. PMID:26465004

Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells.

PubMed

Baburski, Aleksandar Z; Sokanovic, Srdjan J; Andric, Silvana A; Kostic, Tatjana S

2017-05-01

The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation. Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of genes involved in cAMP production (increased circadian pattern of Adcy7, Adcy9, Adcy10 and decreased Adcy3); cAMP degradation (increased Pde4a, decreased Pde8b, canceled rhythm of Pde4d, completely reversed circadian pattern of Pde7b and Pde8a); and circadian expression of protein kinase A subunits (Prkac/PRKAC and Prkar2a). Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP circadian oscillations in Leydig cells. In addition, the expression of cGMP-dependent kinase, Prkg1/PRKG1 is up-regulated. It seems that aging potentiate cGMP- and reduce cAMP-signaling in Leydig cells. Since both signaling pathways affect testosterone production and clockwork in the cells, further insights into these signaling pathways will help to unravel disorders linked to the circadian timing system, aging and reproduction.

Targeting the Dopamine 1 Receptor or its Downstream Signalling by Inhibiting Phosphodiesterase-1 Improves Cognitive Performance.

PubMed

Pekcec, Anton; Schülert, Niklas; Stierstorfer, Birgit; Deiana, Serena; Dorner-Ciossek, Cornelia; Rosenbrock, Holger

2018-05-03

Insufficient prefrontal dopamine 1 (D1) receptor signalling has been linked to cognitive dysfunction in several psychiatric conditions. Because the phosphodiesterase-1 (PDE1) isoform B (PDE1B) is postulated to regulate D1 receptor-dependent signal transduction, this study intended to elucidate the role of PDE1 for cognitive processes reliant on D1 receptor function. Cognitive performance of the D1 receptor agonist, SKF38393, was studied in the T-maze continuous alternation task and the 5-Choice Serial Reaction Time Task. D1 receptor/ PDE1B double-immunohistochemistry was performed using human and rat prefrontal brain sections. Pharmacological activity of the PDE1 inhibitor, ITI-214, was assessed by measuring the increase of cAMP/ cGMP in prefrontal brain tissue and its effect on working memory performance. Mechanistic studies on modulation of prefrontal neuronal transmission by SKF38393 and ITI-214 were performed using extracellular recordings in brain slices. SKF38393 improved working memory and attentional performance in rodents. D1 receptor/ PDE1B co-expression was verified in both, human and rat prefrontal brain sections. The pharmacological activity of ITI-214 on its target was demonstrated by increased prefrontal cAMP/ cGMP upon administration. In addition, ITI-214 improved working memory performance. SKF38393 and ITI-214 facilitated neuronal transmission in prefrontal brain slices. We hypothesise that PDE1 inhibition may improve working memory performance by increasing prefrontal synaptic transmission and/or postsynaptic D1 receptor signalling, by modulating prefrontal downstream second messenger levels. These data may therefore support the use of PDE1 inhibitors as a potential approach for the treatment of cognitive dysfunction. This article is protected by copyright. All rights reserved.

Genome-wide Association Analysis Identifies PDE4D as an Asthma-Susceptibility Gene

PubMed Central

Himes, Blanca E.; Hunninghake, Gary M.; Baurley, James W.; Rafaels, Nicholas M.; Sleiman, Patrick; Strachan, David P.; Wilk, Jemma B.; Willis-Owen, Saffron A.G.; Klanderman, Barbara; Lasky-Su, Jessica; Lazarus, Ross; Murphy, Amy J.; Soto-Quiros, Manuel E.; Avila, Lydiana; Beaty, Terri; Mathias, Rasika A.; Ruczinski, Ingo; Barnes, Kathleen C.; Celedón, Juan C.; Cookson, William O.C.; Gauderman, W. James; Gilliland, Frank D.; Hakonarson, Hakon; Lange, Christoph; Moffatt, Miriam F.; O'Connor, George T.; Raby, Benjamin A.; Silverman, Edwin K.; Weiss, Scott T.

2009-01-01

Asthma, a chronic airway disease with known heritability, affects more than 300 million people around the world. A genome-wide association (GWA) study of asthma with 359 cases from the Childhood Asthma Management Program (CAMP) and 846 genetically matched controls from the Illumina ICONdb public resource was performed. The strongest region of association seen was on chromosome 5q12 in PDE4D. The phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) gene (PDE4D) is a regulator of airway smooth-muscle contractility, and PDE4 inhibitors have been developed as medications for asthma. Allelic p values for top SNPs in this region were 4.3 × 10−07 for rs1588265 and 9.7 × 10−07 for rs1544791. Replications were investigated in ten independent populations with different ethnicities, study designs, and definitions of asthma. In seven white and Hispanic replication populations, two PDE4D SNPs had significant results with p values less than 0.05, and five had results in the same direction as the original population but had p values greater than 0.05. Combined p values for 18,891 white and Hispanic individuals (4,342 cases) in our replication populations were 4.1 × 10−04 for rs1588265 and 9.2 × 10−04 for rs1544791. In three black replication populations, which had different linkage disequilibrium patterns than the other populations, original findings were not replicated. Further study of PDE4D variants might lead to improved understanding of the role of PDE4D in asthma pathophysiology and the efficacy of PDE4 inhibitor medications. PMID:19426955

Pinus densiflora extract protects human skin fibroblasts against UVB-induced photoaging by inhibiting the expression of MMPs and increasing type I procollagen expression.

PubMed

Jung, Hoe-Yune; Shin, Jae-Cheon; Park, Seon-Min; Kim, Na-Ri; Kwak, Wonjung; Choi, Bo-Hwa

2014-01-01

Exposure to ultraviolet (UV) light can cause skin photoaging, which is associated with upregulation of matrix metalloproteinases (MMPs) and downregulation of collagen synthesis. It has been reported that MMPs, especially MMP-1, MMP-3 and MMP-9, decrease the elasticity of the dermis by degrading collagen. In this study, we assessed the effects of Pinus densiflora extract (PDE) on photoaging and investigated its mechanism of action in human skin fibroblast (Hs68) cells after UVB exposure using real-time polymerase chain reaction, Western blot analysis, and enzymatic activity assays. PDE exhibited an antioxidant activity and inhibited elastase activities in vitro. We also found that PDE inhibited UVB-induced cytotoxicity, MMP-1 production and expression of MMP-1, -3 and -9 mRNA in Hs68 cells. In addition, PDE decreased UVB-induced MMP-2 activity and MMP-2 mRNA expression. Moreover, PDE prevented the decrease of type I procollagen mediated by exposure to UVB irradiation, an effect that is linked to the upregulation and downregulation of Smad3 and Smad7, respectively. Another effect of UV irradiation is to stimulate activator protein 1 (AP-1) activity via overexpression of c-Jun/c-Fos, which, in turn, upregulates MMP-1, -3, and -9. In this study, we found that PDE suppressed UV-induced c-Jun and c-Fos mRNA expression. Taken together, these results demonstrate that PDE regulates UVB-induced expression of MMPs and type I procollagen synthesis by inhibiting AP-1 activity and restoring impaired Smad signaling, suggesting that PDE may be useful as an effective anti-photoaging agent.

β2-Agonist Induced cAMP Is Decreased in Asthmatic Airway Smooth Muscle Due to Increased PDE4D

PubMed Central

Trian, Thomas; Burgess, Janette K.; Niimi, Kyoko; Moir, Lyn M.; Ge, Qi; Berger, Patrick; Liggett, Stephen B.; Black, Judith L.; Oliver, Brian G.

2011-01-01

Background and Objective Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. Objective To characterize the potential defect in β-agonist induced cAMP in ASM derived from asthmatic in comparison to non-asthmatic subjects and to investigate its mechanism. Methods We examined β2-adrenergic (β2AR) receptor expression and basal β-agonist and forskolin (direct activator of adenylyl cyclase) stimulated cAMP production in asthmatic cultured ASM (n = 15) and non-asthmatic ASM (n = 22). Based on these results, PDE activity, PDE4D expression and cell proliferation were determined. Results In the presence of IBMX, a pan PDE inhibitor, asthmatic ASM had ∼50% lower cAMP production in response to isoproterenol, albuterol, formoterol, and forskolin compared to non-asthmatic ASM. However when PDE4 was specifically inhibited, cAMP production by the agonists and forskolin was normalized in asthmatic ASM. We then measured the amount and activity of PDE4, and found ∼2-fold greater expression and activity in asthmatic ASM compared to non-asthmatic ASM. Furthermore, inhibition of PDE4 reduced asthmatic ASM proliferation but not that of non-asthmatic ASM. Conclusion Decreased β-agonist induced cAMP in ASM from asthmatics results from enhanced degradation due to increased PDE4D expression. Clinical manifestations of this dysregulation would be suboptimal β-agonist-mediated bronchodilation and possibly reduced control over increasing ASM mass. These phenotypes appear to be “hard-wired” into ASM from asthmatics, as they do not require an inflammatory environment in culture to be observed. PMID:21611147

Detonability of H/sub 2/-air-diluent mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tieszen, S.R.; Sherman, M.P.; Benedick, W.B.

1987-06-01

This report describes the Heated Detonation Tube (HDT). Detonation cell width and velocity results are presented for H/sub 2/-air mixtures, undiluted and diluted with CO/sub 2/ and H/sub 2/O for a range of H/sub 2/ concentration, initial temperature and pressure. The results show that the addition of either CO/sub 2/ or H/sub 2/O significantly increases the detonation cell width and hence reduces the detonability of the mixture. The results also show that the detonation cell width is reduced (detonability is increased) for increased initial temperature and/or pressure.

Characterization of Detonator Performance as a Function of Porosity via the Hayes Effect via Rogowski Coil

NASA Astrophysics Data System (ADS)

Nakamoto, Teagan; Parrack, Kristina; Smith, Dalton; Trujillo, Chris; Wilde, Zak; Gibson, John; Lodes, Rylie; Malcolm, Hayden

2017-06-01

Researchers experimented with a novel diagnostic to study the effects of porosity on detonator performance. The new diagnostic takes advantage of the detonation electric effect observed by Hayes (1966). Detonation-produced electrical charges induce a current in the detonator wire that may be detected by use of a Rogowski coil developed and tailored for the purpose. Data collected by the Rogowski coil were then used to characterize detonations. Researchers tested PETN charges of various porosity levels (as characterized by measured particle size and surface area) to study the effect of porosity on detonation characteristics. This novel method was compared with and verified by the well-established technique of using PVDF gauges for detonator response characterization.

High-Speed Photography of Detonation Propagation in Dynamically Precompressed Liquid Explosives

NASA Astrophysics Data System (ADS)

Petel, Oren; Higgins, Andrew; Yoshinaka, Akio; Zhang, Fan

2007-06-01

The propagation of detonation in shock compressed nitromethane was observed with a high speed framing camera. The test explosive, nitromethane, was compressed by a reverberating shock wave to pressures on the order of 10 GPa prior to being detonated by a secondary detonation event. The pressure and density in the test explosive prior to detonation was determined using two methods: manganin strain gauge measurements and LS-DYNA simulations. The velocity of the detonation front was determined from consecutive frames and correlated to the density of the explosive post-reverberating shock wave and prior to being detonated. Observing detonation propagation under these non-ambient conditions provides data which can be useful in the validation of equation of state models.

The ignition of carbon detonations via converging shock waves in white dwarfs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Ken J.; Bildsten, Lars, E-mail: kenshen@astro.berkeley.edu, E-mail: bildsten@kitp.ucsb.edu

2014-04-10

The progenitor channel responsible for the majority of Type Ia supernovae is still uncertain. One emergent scenario involves the detonation of a He-rich layer surrounding a C/O white dwarf, which sends a shock wave into the core. The quasi-spherical shock wave converges and strengthens at an off-center location, forming a second, C-burning, detonation that disrupts the whole star. In this paper, we examine this second detonation of the double detonation scenario using a combination of analytic and numeric techniques. We perform a spatially resolved study of the imploding shock wave and outgoing detonation and calculate the critical imploding shock strengthsmore » needed to achieve a core C detonation. We find that He detonations in recent two-dimensional simulations yield converging shock waves that are strong enough to ignite C detonations in high-mass C/O cores, with the caveat that a truly robust answer requires multi-dimensional detonation initiation calculations. We also find that convergence-driven detonations in low-mass C/O cores and in O/Ne cores are harder to achieve and are perhaps unrealized in standard binary evolution.« less

How Schools and Students Respond to School Improvement Programs: The Case of Brazil's PDE

ERIC Educational Resources Information Center

Carnoy, Martin; Gove, Amber K.; Loeb, Susanna; Marshall, Jeffrey H.; Socias, Miguel

2008-01-01

This study uses rich empirical data from Brazil to assess how a government program (PDE) that decentralizes school management decisions changes what goes on in schools and how these changes affect student outcomes. It appears that the PDE resulted in some improvements in management and learning materials, but little change in other areas including…

N Termini of apPDE4 Isoforms Are Responsible for Targeting the Isoforms to Different Cellular Membranes

ERIC Educational Resources Information Center

Jang, Deok-Jin; Park, Soo-Won; Lee, Jin-A; Lee, Changhoon; Chae, Yeon-Su; Park, Hyungju; Kim, Min-Jeong; Choi, Sun-Lim; Lee, Nuribalhae; Kim, Hyoung; Kaang, Bong-Kiun

2010-01-01

Phosphodiesterases (PDEs) are known to play a key role in the compartmentalization of cAMP signaling; however, the molecular mechanisms underlying intracellular localization of different PDE isoforms are not understood. In this study, we have found that each of the supershort, short, and long forms of apPDE4 showed distinct localization in the…

Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility.

PubMed

Rzasa, Robert M; Frohn, Michael J; Andrews, Kristin L; Chmait, Samer; Chen, Ning; Clarine, Jeffrey G; Davis, Carl; Eastwood, Heather A; Horne, Daniel B; Hu, Essa; Jones, Adrie D; Kaller, Matthew R; Kunz, Roxanne K; Miller, Silke; Monenschein, Holger; Nguyen, Thomas; Pickrell, Alexander J; Porter, Amy; Reichelt, Andreas; Zhao, Xiaoning; Treanor, James J S; Allen, Jennifer R

2014-12-01

We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum.

Bivariate spline solution of time dependent nonlinear PDE for a population density over irregular domains.

PubMed

Gutierrez, Juan B; Lai, Ming-Jun; Slavov, George

2015-12-01

We study a time dependent partial differential equation (PDE) which arises from classic models in ecology involving logistic growth with Allee effect by introducing a discrete weak solution. Existence, uniqueness and stability of the discrete weak solutions are discussed. We use bivariate splines to approximate the discrete weak solution of the nonlinear PDE. A computational algorithm is designed to solve this PDE. A convergence analysis of the algorithm is presented. We present some simulations of population development over some irregular domains. Finally, we discuss applications in epidemiology and other ecological problems. Copyright © 2015 Elsevier Inc. All rights reserved.

An odor interaction model of binary odorant mixtures by a partial differential equation method.

PubMed

Yan, Luchun; Liu, Jiemin; Wang, Guihua; Wu, Chuandong

2014-07-09

A novel odor interaction model was proposed for binary mixtures of benzene and substituted benzenes by a partial differential equation (PDE) method. Based on the measurement method (tangent-intercept method) of partial molar volume, original parameters of corresponding formulas were reasonably displaced by perceptual measures. By these substitutions, it was possible to relate a mixture's odor intensity to the individual odorant's relative odor activity value (OAV). Several binary mixtures of benzene and substituted benzenes were respectively tested to establish the PDE models. The obtained results showed that the PDE model provided an easily interpretable method relating individual components to their joint odor intensity. Besides, both predictive performance and feasibility of the PDE model were proved well through a series of odor intensity matching tests. If combining the PDE model with portable gas detectors or on-line monitoring systems, olfactory evaluation of odor intensity will be achieved by instruments instead of odor assessors. Many disadvantages (e.g., expense on a fixed number of odor assessors) also will be successfully avoided. Thus, the PDE model is predicted to be helpful to the monitoring and management of odor pollutions.

Phosphodiesterase 4 inhibitors.

PubMed

Zebda, Rema; Paller, Amy S

2018-03-01

Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US Food and Drug Administration-approved for children older than 2 years and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety. Copyright © 2017. Published by Elsevier Inc.

Beneficial long term effect of a phosphodiesterase-5-inhibitor in cirrhotic portal hypertension: A case report with 8 years follow-up.

PubMed

Deibert, Peter; Lazaro, Adhara; Stankovic, Zoran; Schaffner, Denise; Rössle, Martin; Kreisel, Wolfgang

2018-01-21

Non-selective beta-blockers are the mainstay of medical therapy for portal hypertension in liver cirrhosis. Inhibitors of phosphodiesterase-5 (PDE-5-inhibitors) reduce portal pressure in the acute setting by > 10% which may suggest a long-term beneficial effect. Currently, there is no available data on long-term treatment of portal hypertension with PDE-5-inhibitors. This case of a patient with liver cirrhosis secondary to autoimmune liver disease with episodes of bleeding from esophageal varices is the first documented case in which a treatment with a PDE-5-inhibitor for eight years was monitored. In the acute setting, the PDE-5-inhibitor Vardenafil lowered portal pressure by 13%. The portal blood flow increased by 28% based on Doppler sonography and by 16% using MRI technique. As maintenance medication the PDE-5-inhibitor Tadalafil was used for eight consecutive years with comparable effects on portal pressure and portal blood flow. There were no recurrence of bleeding and no formation of new varices. Influencing the NO-pathway by the use of PDE-5 inhibitors may have long-term beneficial effects in compensated cirrhosis.

Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function.

PubMed

Lukyanenko, Yevgeniya O; Younes, Antoine; Lyashkov, Alexey E; Tarasov, Kirill V; Riordon, Daniel R; Lee, Joonho; Sirenko, Syevda G; Kobrinsky, Evgeny; Ziman, Bruce; Tarasova, Yelena S; Juhaszova, Magdalena; Sollott, Steven J; Graham, David R; Lakatta, Edward G

2016-09-01

Constitutive Ca(2+)/calmodulin (CaM)-activation of adenylyl cyclases (ACs) types 1 and 8 in sinoatrial nodal cells (SANC) generates cAMP within lipid-raft-rich microdomains to initiate cAMP-protein kinase A (PKA) signaling, that regulates basal state rhythmic action potential firing of these cells. Mounting evidence in other cell types points to a balance between Ca(2+)-activated counteracting enzymes, ACs and phosphodiesterases (PDEs) within these cells. We hypothesized that the expression and activity of Ca(2+)/CaM-activated PDE Type 1A is higher in SANC than in other cardiac cell types. We found that PDE1A protein expression was 5-fold higher in sinoatrial nodal tissue than in left ventricle, and its mRNA expression was 12-fold greater in the corresponding isolated cells. PDE1 activity (nimodipine-sensitive) accounted for 39% of the total PDE activity in SANC lysates, compared to only 4% in left ventricular cardiomyocytes (LVC). Additionally, total PDE activity in SANC lysates was lowest (10%) in lipid-raft-rich and highest (76%) in lipid-raft-poor fractions (equilibrium sedimentation on a sucrose density gradient). In intact cells PDE1A immunolabeling was not localized to the cell surface membrane (structured illumination microscopy imaging), but located approximately within about 150nm inside of immunolabeling of hyperpolarization-activated cyclic nucleotide-gated potassium channels (HCN4), which reside within lipid-raft-rich microenvironments. In permeabilized SANC, in which surface membrane ion channels are not functional, nimodipine increased spontaneous SR Ca(2+) cycling. PDE1A mRNA silencing in HL-1 cells increased the spontaneous beating rate, reduced the cAMP, and increased cGMP levels in response to IBMX, a broad spectrum PDE inhibitor (detected via fluorescence resonance energy transfer microscopy). We conclude that signaling via cAMP generated by Ca(2+)/CaM-activated AC in SANC lipid raft domains is limited by cAMP degradation by Ca(2+)/CaM-activated PDE1A in non-lipid raft domains. This suggests that local gradients of [Ca(2+)]-CaM or different AC and PDE1A affinity regulate both cAMP production and its degradation, and this balance determines the intensity of Ca(2+)-AC-cAMP-PKA signaling that drives SANC pacemaker function. Copyright © 2016. Published by Elsevier Ltd.

A Computational Examination of Detonation Physics and Blast Chemistry

DTIC Science & Technology

2011-08-01

State 5 3 Detonation and Shock Hugoniots for TNT using the JWL Equation of State 6 4 Detonation and Shock Hugoniots for HMX using the JWL ...Equation of State 6 5 Detonation and Shock Hugoniots for Composition C-4 using the JWL Equation of State 7 6 Detonation and Shock...Hugoniots for PBX-9502 using the JWL Equation of State 7 7 Detonation and Shock Hugoniots for PETN using the JWL Equation of State 8 8

A Computational Examination of Detonation Physics and Blast Chemistry

DTIC Science & Technology

2011-08-01

Equation of State 5 3 Detonation and Shock Hugoniots for TNT using the JWL Equation of State 6 4 Detonation and Shock Hugoniots for HMX using the... JWL Equation of State 6 5 Detonation and Shock Hugoniots for Composition C-4 using the JWL Equation of State 7 6 Detonation and...Shock Hugoniots for PBX-9502 using the JWL Equation of State 7 7 Detonation and Shock Hugoniots for PETN using the JWL Equation of State 8

The dependence of Ammonium-Nitrate Fuel-Oil (ANFO) detonation on confinement

DOE PAGES

Jackson, Scott I.

2016-11-17

As detonation is a coupled fluid-chemical process, flow divergence inside the detonation reaction zone can strongly influence detonation velocity and energy release. Such divergence is responsible for the diameter-effect and failure-diameter phenomena in condensed-phase explosives and particularly dominant in detonation of nonideal explosives such as Ammonium Nitrate and Fuel Oil (ANFO). In this study, the effect of reaction zone flow divergence on ANFO detonation was explored through variation of the inert confinement and explosive diameter in the rate-stick geometry with cylinder expansion experiments. New tests are discussed and compared to prior experiments. Presented results include the detonation velocity as amore » function of diameter and confinement, reaction zone times, detonation product isentropes and energies, as well as sonic surface pressures and velocities. Product energy densities and isentropes were found to increase with detonation velocity, indicating more complete chemical reaction with increased detonation velocity. In addition, detonation reaction zone times were found to scale with the acoustic transit time of the confiner wall and used to show that the ANFO diameter effect scaled with the reaction zone time for a particle along the flow centerline, regardless of the confinement. Such a result indicates that the ANFO reaction mechanisms are sufficiently slow that the centerline fluid expansion timescale is a limiting factor controlling detonation velocity and energy release.« less

Ignition and growth reactive flow modeling of recent HMX/TATB detonation experiments

NASA Astrophysics Data System (ADS)

Tarver, Craig M.

2017-01-01

Two experimental studies in which faster HMX detonation waves produced oblique detonation waves in adjoining slower detonating TATB charges were modeled using the Ignition and Growth (I&G) reactive flow detonation model parameters for PBX 9501 (95% HMX / 2.5% Estane / 2.5% BDNPA/F) and PBX 9502 (95% TATB / 5% Kel-F binder). Matignon et al. used X1 explosive (96% HMX / 4% binder) to drive an oblique detonation wave into an attached charge of T2 explosive (97% TATB / 3% binder). The flow angles were measured in the T2 shock initiation region and in steady T2 detonation. Anderson et al. used detonating PBX 9501 slabs of various thicknesses ranging from 0.56 mm to 2.5 mm to create oblique detonation waves in 8 mm thick slabs of PBX 9502. Several diagnostics were employed to: photograph the waves; measure detonation velocities and flow angles; and determine the output of the PBX 9501 slabs, the PBX 9502 slabs, and the "initiation regions" using LiF windows and PDV probes.

US/UK second level panel discussions on the health and value of: Ageing and lifetime predictions (u)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castro, Richard G

2011-01-18

Many healthy physics, engineering, and materials exchanges are being accomplished in ageing and lifetime prediction that directly supports US and UK Stockpile Management Programs. Lifetime assessment studies of silicon foams under compression - Joint AWE/LANLlLLNL study of compression set in stress cushions completed. Provides phenomenological prediction out to 50 years. Polymer volatile out-gassing studies - New exchange on the out-gassing of Ethylene Vinyl Acetate (EVA) using isotopic {sup 13}C labeling studies to interrogate mechanistic processes. Infra-red (IR) gas cell analytical capabilities developed by AWE will be used to monitor polymer out-gassing profiles. Pu Strength ageing Experiments and Constitutive Modeling -more » In recently compared modeling strategies for ageing effects on Pu yield strength at high strain rates, a US/UK consensus was reached on the general principle that the ageing effect is additive and not multiplicative. The fundamental mechanisms for age-strengthening in Pu remains unknown. Pu Surface and Interface Reactions - (1) US/UK secondment resulted in developing a metal-metal oxide model for radiation damaged studies consistent with a Modified Embedded Atom Method (MEAM) potential; and (2) Joint US/UK collaboration to study the role of impurities in hydride initiation. Detonator Ageing (wide range of activities) - (1) Long-term ageing study with field trials at Pantex incorporating materials from LANL, LLNL, SNL and AWE; (2) Characterization of PETN growth to detonation process; (3) Detonator performance modeling; and (4) Performance fault tree analysis. Benefits are a unified approach to lifetime prediction that Includes: materials characterization and the development of ageing models through improved understanding of the relationship between materials properties, ageing properties and detonator performance.« less

Molecular modeling study of binding to the catalytic site of PDE4 enzymes by a novel class of inhibitors

NASA Astrophysics Data System (ADS)

Lawrenz, Morgan E.; Salter, E. A.; Wierzbicki, Andrzej; Thompson, W. J.

Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of enzymes that hydrolyze the second messengers adenosine and guanosine 3',5'-cyclic monophosphate (cAMP and cGMP) to their noncyclic nucleotides (5'-AMP and 5'-GMP). Selective inhibitors of all 11 gene families of PDEs are being sought based on the different biochemical properties of the different isoforms, including their substrate specificities. The PDE4 gene family consists of cAMP-specific isoforms; selective PDE4 inhibitors such as rolipram have been developed, and related agents are used clinically as anti-inflammatory agents for asthma and COPD. The known crystal structures of PDE4 bound with rolipram and IBMX have allowed us to define plausible binding orientations for a novel class of benzylpyridazinone-based PDE4 inhibitors represented by EMD 94360 and EMD 95832 that are structurally distinct from rolipram. Molecular mechanics modeling with autodocking is used to explore energetically favorable binding orientations within the PDE4 catalytic site. We present two putative orientations for EMD 94360/95832 inhibitor binding. Our estimated interaction energies for rolipram, IBMX, EMD 94360, and EMD 95832 are consistent with the experimental data for their IC50 values. Key binding residues and interactions in these orientations are identified and compared with known binding motifs proposed for rolipram. The experimentally observed improved strength of inhibition exhibited by this novel class of PDE4 inhibitors is explained by the molecular modeling reported here.

Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes.

PubMed

Kim, Hyoung-June; Lee, Eunyoung; Lee, Moonyoung; Ahn, Sungjin; Kim, Jungmin; Liu, Jingjing; Jin, Sun Hee; Ha, Jaehyoun; Bae, Il Hong; Lee, Tae Ryong; Noh, Minsoo

2018-01-01

Benzophenone-3 (BP-3), which is extensively used in organic sunscreen, has phototoxic potential in human skin. Phosphodiesterase 4B (PDE4B) has a well-established role in inflammatory responses in immune cells. Currently, it is unknown if PDE4B is associated with BP-3-induced phototoxicity in normal human keratinocytes (NHKs). We found that BP-3 significantly increased PDE4B expression in ultraviolet B (UVB)-irradiated NHKs. Notably, BP-8, a sunscreen agent that shares the 2-hydroxy-4-methoxyphenyl methanone moiety with BP-3, also upregulated PDE4B expression in NHKs. Upon UVB irradiation, BP-3 upregulated the expression of pro-inflammatory factors, such as prostaglandin endoperoxide synthase 2, tumor necrosis factor α, interleukin 8, and S100A7, and downregulated the level of cornified envelope associated proteins, which are important in the development of the epidermal permeability barrier. The additive effects of UVB-activated BP-3 on the expression of both pro-inflammatory mediators and cornified envelope associated proteins were antagonized by treatment with the PDE4 inhibitor rolipram. The BP-3 and UVB co-stimulation-induced PDE4B upregulation and its association with the upregulation of pro-inflammatory mediators and the downregulation of epidermal differentiation markers were confirmed in a reconstituted three dimensional human epidermis model. Therefore, PDE4B has a role in the mechanism of BP-3-induced phototoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Alcohol Exposure Disrupts Visual Cortex Plasticity in Mice

PubMed Central

Lantz, Crystal L.; Wang, Weili; Medina, Alexandre E.

2012-01-01

There is growing evidence that deficits in neuronal plasticity underlie the cognitive problems seen in fetal alcohol spectrum disorders (FASD). However, the mechanisms behind these deficits are not clear. Here we test the effects of early alcohol exposure on ocular dominance plasticity (ODP) in mice and the reversibility of these effects by phosphodiesterase (PDE) inhibitors. Mouse pups were exposed to 5 g/kg of 25% ethanol i.p. on postnatal days (P) 5, 7 and 9. This type of alcohol exposure mimics binge drinking during the third trimester equivalent of human gestation. To assess ocular dominance plasticity animals were monocularly deprived at P21 for 10 days, and tested using optical imaging of intrinsic signals. During the period of monocular deprivation animals were treated with vinpocetine (20mg/kg; PDE1 inhibitor), rolipram (1.25 mg/Kg; PDE4 inhibitor), vardenafil (3 mg/Kg; PDE5 inhibitor) or vehicle solution. Monocular deprivation resulted in the expected shift in ocular dominance of the binocular zone in saline controls but not in the ethanol group. While vinpocetine successfully restored ODP in the ethanol group, rolipram and vardenafil did not. However, when rolipram and vardenafil were given simultaneously ODP was restored. PDE4 and PDE5 are specific to cAMP and cGMP respectively, while PDE1 acts on both of these nucleotides. Our findings suggest that the combined activation of the cAMP and cGMP cascades may be a good approach to improve neuronal plasticity in FASD models. PMID:22617459

Identification, characterization and subcellular localization of TcPDE1, a novel cAMP-specific phosphodiesterase from Trypanosoma cruzi.

PubMed Central

D'Angelo, Maximiliano A; Sanguineti, Santiago; Reece, Jeffrey M; Birnbaumer, Lutz; Torres, Héctor N; Flawiá, Mirtha M

2004-01-01

Compartmentalization of cAMP phosphodiesterases plays a key role in the regulation of cAMP signalling in mammals. In the present paper, we report the characterization and subcellular localization of TcPDE1, the first cAMP-specific phosphodiesterase to be identified from Trypanosoma cruzi. TcPDE1 is part of a small gene family and encodes a 929-amino-acid protein that can complement a heat-shock-sensitive yeast mutant deficient in phospho-diesterase genes. Recombinant TcPDE1 strongly associates with membranes and cannot be released with NaCl or sodium cholate, suggesting that it is an integral membrane protein. This enzyme is specific for cAMP and its activity is not affected by cGMP, Ca2+, calmodulin or fenotiazinic inhibitors. TcPDE1 is sensitive to the phosphodiesterase inhibitor dipyridamole but is resistant to 3-isobutyl-1-methylxanthine, theophylline, rolipram and zaprinast. Papaverine, erythro-9-(2-hydroxy-3-nonyl)-adenine hydrochloride, and vinpocetine are poor inhibitors of this enzyme. Confocal laser scanning of T. cruzi epimastigotes showed that TcPDE1 is associated with the plasma membrane and concentrated in the flagellum of the parasite. The association of TcPDE1 with this organelle was confirmed by subcellular fractionation and cell-disruption treatments. The localization of this enzyme is a unique feature that distinguishes it from all the trypanosomatid phosphodiesterases described so far and indicates that compartmentalization of cAMP phosphodiesterases could also be important in these parasites. PMID:14556647

Predicting propagation limits of laser-supported detonation by Hugoniot analysis

NASA Astrophysics Data System (ADS)

Shimamura, Kohei; Ofosu, Joseph A.; Komurasaki, Kimiya; Koizumi, Hiroyuki

2015-01-01

Termination conditions of a laser-supported detonation (LSD) wave were investigated using control volume analysis with a Shimada-Hugoniot curve and a Rayleigh line. Because the geometric configurations strongly affect the termination condition, a rectangular tube was used to create the quasi-one-dimensional configuration. The LSD wave propagation velocity and the pressure behind LSD were measured. Results reveal that the detonation states during detonation and at the propagation limit are overdriven detonation and Chapman-Jouguet detonation, respectively. The termination condition is the minimum velocity criterion for the possible detonation solution. Results were verified using pressure measurements of the stagnation pressure behind the LSD wave.

Diminishing detonator effectiveness through electromagnetic effects

DOEpatents

Schill, Jr, Robert A.

2016-09-20

An inductively coupled transmission line with distributed electromotive force source and an alternative coupling model based on empirical data and theory were developed to initiate bridge wire melt for a detonator with an open and a short circuit detonator load. In the latter technique, the model was developed to exploit incomplete knowledge of the open circuited detonator using tendencies common to all of the open circuit loads examined. Military, commercial, and improvised detonators were examined and modeled. Nichrome, copper, platinum, and tungsten are the detonator specific bridge wire materials studied. The improvised detonators were made typically made with tungsten wire and copper (.about.40 AWG wire strands) wire.

Researches on Preliminary Chemical Reactions in Spark-Ignition Engines

NASA Technical Reports Server (NTRS)

Muehlner, E.

1943-01-01

Chemical reactions can demonstrably occur in a fuel-air mixture compressed in the working cylinder of an Otto-cycle (spark ignition) internal-combustion engine even before the charge is ignited by the flame proceeding from the sparking plug. These are the so-called "prelinminary reactions" ("pre-flame" combustion or oxidation), and an exact knowledge of their characteristic development is of great importance for a correct appreciation of the phenomena of engine-knock (detonation), and consequently for its avoidance. Such reactions can be studied either in a working engine cylinder or in a combustion bomb. The first method necessitates a complicated experimental technique, while the second has the disadvantage of enabling only a single reaction to be studied at one time. Consequently, a new series of experiments was inaugurated, conducted in a motored (externally-driven) experimental engine of mixture-compression type, without ignition, the resulting preliminary reactions being detectable and measurable thermometrically.

High Explosive Detonation-Confiner Interactions

NASA Astrophysics Data System (ADS)

Short, Mark; Quirk, James J.

2018-01-01

The primary purpose of a detonation in a high explosive (HE) is to provide the energy to drive a surrounding confiner, typically for mining or munitions applications. The details of the interaction between an HE detonation and its confinement are essential to achieving the objectives of the explosive device. For the high pressures induced by detonation loading, both the solid HE and confiner materials will flow. The structure and speed of a propagating detonation, and ultimately the pressures generated in the reaction zone to drive the confiner, depend on the induced flow both within the confiner and along the HE-confiner material interface. The detonation-confiner interactions are heavily influenced by the material properties and, in some cases, the thickness of the confiner. This review discusses the use of oblique shock polar analysis as a means of characterizing the possible range of detonation-confiner interactions. Computations that reveal the fluid mechanics of HE detonation-confiner interactions for finite reaction-zone length detonations are discussed and compared with the polar analysis. This includes cases of supersonic confiner flow; subsonic, shock-driven confiner flow; subsonic, but shockless confiner flow; and sonic flow at the intersection of the detonation shock and confiner material interface. We also summarize recent developments, including the effects of geometry and porous material confinement, on detonation-confiner interactions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, Scott I.

As detonation is a coupled fluid-chemical process, flow divergence inside the detonation reaction zone can strongly influence detonation velocity and energy release. Such divergence is responsible for the diameter-effect and failure-diameter phenomena in condensed-phase explosives and particularly dominant in detonation of nonideal explosives such as Ammonium Nitrate and Fuel Oil (ANFO). In this study, the effect of reaction zone flow divergence on ANFO detonation was explored through variation of the inert confinement and explosive diameter in the rate-stick geometry with cylinder expansion experiments. New tests are discussed and compared to prior experiments. Presented results include the detonation velocity as amore » function of diameter and confinement, reaction zone times, detonation product isentropes and energies, as well as sonic surface pressures and velocities. Product energy densities and isentropes were found to increase with detonation velocity, indicating more complete chemical reaction with increased detonation velocity. In addition, detonation reaction zone times were found to scale with the acoustic transit time of the confiner wall and used to show that the ANFO diameter effect scaled with the reaction zone time for a particle along the flow centerline, regardless of the confinement. Such a result indicates that the ANFO reaction mechanisms are sufficiently slow that the centerline fluid expansion timescale is a limiting factor controlling detonation velocity and energy release.« less

Numerical modeling of divergent detonation wave

NASA Astrophysics Data System (ADS)

Li, Zhiwei; Liu, Bangdi

1987-11-01

The indefinite nature of divergent detonations under the assumption of instantaneous stable detonation is described. In the numerical modeling method for divergent detonation, the artificial cohesiveness was improved and the Cochran reaction rate and the JWL equations of state were used to describe the ignition process of the explosion. Several typical divergent detonation problems were computed obtaining rather satisfying results.

Fuels and Lubrication Researcher at the Aircraft Engine Research Laboratory

NASA Image and Video Library

1943-08-21

A researcher at the National Advisory Committee for Aeronautics (NACA) Aircraft Engine Research Laboratory studies the fuel ignition process. Improved fuels and lubrication was an area of particular emphasis at the laboratory during World War II. The military sought to use existing types of piston engines in order to get large numbers of aircraft into the air as quickly as possible. To accomplish its goals, however, the military needed to increase the performance of these engines without having to wait for new models or extensive redesigns. The Aircraft Engine Research Laboratory was called on to lead this effort. The use of superchargers successfully enhanced engine performance, but the resulting heat increased engine knock [fuel detonation] and structural wear. These effects could be offset with improved cooling, lubrication, and fuel mixtures. The NACA researchers in the Fuels and Lubrication Division concentrated on new synthetic fuels, higher octane fuels, and fuel-injection systems. The laboratory studied 16 different types of fuel blends during the war, including extensive investigations of triptane and xylidine.

Role of selective cyclic GMP phosphodiesterase inhibition in the myorelaxant actions of M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine.

PubMed Central

Souness, J. E.; Brazdil, R.; Diocee, B. K.; Jordan, R.

1989-01-01

1. The mechanism by which M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine (MIMAX), which have been described as selective cyclic GMP phosphodiesterase (PDE) inhibitors, relax rat aorta was investigated. 2. Three cyclic nucleotide PDEs were identified in the soluble fraction of rat aorta; a Ca2+-insensitive form exhibiting substrate selectivity for cyclic GMP (cGMP PDE), a Ca2+/calmodulin-stimulated form which also preferentially hydrolyzed cyclic GMP (Ca2+ PDE), and a form demonstrating substrate selectivity for cyclic AMP (cAMP PDE). 3. M&B 22,948 and MIMAX inhibited cGMP PDE (Ki = 0.16 microM and 0.43 microM, respectively) and Ca2+ PDE (Ki = 9.9 microM and 0.55 microM, respectively), but exhibited weak activity against cAMP PDE (Ki = 249 microM and 42 microM, respectively). MY-5445 selectivity inhibited cGMP PDE (Ki = 1.3 microM) and vinpocetine selectively inhibited Ca2+ PDE (Ki = 14 microM). 4. M&B 22,948 and MIMAX induced dose-dependent increases in the accumulation of cyclic GMP, but not cyclic AMP, in rat aorta pieces. These effects were greatly reduced by endothelial denudation and by methylene blue (5 microM) which blocks the actions of endothelium-derived relaxant factor. MY-5445 and vinpocetine had no effect on rat aorta cyclic GMP or cyclic AMP accumulation. 5. All four compounds caused dose-related relaxation of 5-hydroxytryptamine (10 microM) contracted, endothelium-intact rat aorta, the effects of M&B 22,948 and MIMAX being greatly reduced by methylene blue (5 microM). Methylene blue also caused 10 fold and 100 fold rightward shifts in the dose-response curves of MY-5445 and vinpocetine, respectively. 6. The results are consistent with the smooth muscle relaxant actions of M&B 22,948 and MIMAX, but not vinpocetine and MY-5445, being mediated through a mechanism involving inhibition of cyclic GMP hydrolysis. PMID:2480168

Spatially localized phosphorous metabolism of skeletal muscle in Duchenne muscular dystrophy patients: 24-month follow-up.

PubMed

Hooijmans, M T; Doorenweerd, N; Baligand, C; Verschuuren, J J G M; Ronen, I; Niks, E H; Webb, A G; Kan, H E

2017-01-01

To assess the changes in phosphodiester (PDE)-levels, detected by 31P magnetic resonance spectroscopy (MRS), over 24-months to determine the potential of PDE as marker for muscle tissue changes in Duchenne Muscular Dystrophy (DMD) patients. Spatially resolved phosphorous datasets were acquired in the right lower leg of 18 DMD patients (range: 5-15.4 years) and 12 age-matched healthy controls (range: 5-14 years) at three time-points (baseline, 12-months, and 24-months) using a 7T MR-System (Philips Achieva). 3-point Dixon images were acquired at 3T (Philips Ingenia) to determine muscle fat fraction. Analyses were done for six muscles that represent different stages of muscle wasting. Differences between groups and time-points were assessed with non-parametric tests with correction for multiple comparisons. Coefficient of variance (CV) were determined for PDE in four healthy adult volunteers in high and low signal-to-noise ratio (SNR) datasets. PDE-levels were significantly higher (two-fold) in DMD patients compared to controls in all analyzed muscles at almost every time point and did not change over the study period. Fat fraction was significantly elevated in all muscles at all time points compared to healthy controls, and increased significantly over time, except in the tibialis posterior muscle. The mean within subject CV for PDE-levels was 4.3% in datasets with high SNR (>10:1) and 5.7% in datasets with low SNR. The stable two-fold increase in PDE-levels found in DMD patients in muscles with different levels of muscle wasting over 2-year time, including DMD patients as young as 5.5 years-old, suggests that PDE-levels may increase very rapidly early in the disease process and remain elevated thereafter. The low CV values in high and low SNR datasets show that PDE-levels can be accurately and reproducibly quantified in all conditions. Our data confirms the great potential of PDE as a marker for muscle tissue changes in DMD patients.

Spatially localized phosphorous metabolism of skeletal muscle in Duchenne muscular dystrophy patients: 24–month follow-up

PubMed Central

Doorenweerd, N.; Baligand, C.; Verschuuren, J. J. G. M.; Ronen, I.; Niks, E. H.; Webb, A. G.; Kan, H. E.

2017-01-01

Objectives To assess the changes in phosphodiester (PDE)-levels, detected by 31P magnetic resonance spectroscopy (MRS), over 24-months to determine the potential of PDE as marker for muscle tissue changes in Duchenne Muscular Dystrophy (DMD) patients. Methods Spatially resolved phosphorous datasets were acquired in the right lower leg of 18 DMD patients (range: 5–15.4 years) and 12 age-matched healthy controls (range: 5–14 years) at three time-points (baseline, 12-months, and 24-months) using a 7T MR-System (Philips Achieva). 3-point Dixon images were acquired at 3T (Philips Ingenia) to determine muscle fat fraction. Analyses were done for six muscles that represent different stages of muscle wasting. Differences between groups and time-points were assessed with non-parametric tests with correction for multiple comparisons. Coefficient of variance (CV) were determined for PDE in four healthy adult volunteers in high and low signal-to-noise ratio (SNR) datasets. Results PDE-levels were significantly higher (two-fold) in DMD patients compared to controls in all analyzed muscles at almost every time point and did not change over the study period. Fat fraction was significantly elevated in all muscles at all time points compared to healthy controls, and increased significantly over time, except in the tibialis posterior muscle. The mean within subject CV for PDE-levels was 4.3% in datasets with high SNR (>10:1) and 5.7% in datasets with low SNR. Discussion and conclusion The stable two-fold increase in PDE-levels found in DMD patients in muscles with different levels of muscle wasting over 2-year time, including DMD patients as young as 5.5 years-old, suggests that PDE-levels may increase very rapidly early in the disease process and remain elevated thereafter. The low CV values in high and low SNR datasets show that PDE-levels can be accurately and reproducibly quantified in all conditions. Our data confirms the great potential of PDE as a marker for muscle tissue changes in DMD patients. PMID:28763477

The Association Between Phosphodiesterase Type 5 Inhibitor Use and Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

PubMed

Liu, Bing; Zhu, Linxin; Zhong, Jingxiang; Zeng, Guohua; Deng, Tuo

2018-06-05

Phosphodiesterase type 5 inhibitors (PDE5-Is) are first-line drugs for erectile dysfunction. Non-arteritic anterior ischemic optic neuropathy (NAION) has been linked with PDE5-I use. However, no meta-analysis or conclusive review has explored the association between NAION and PDE5-I use. To investigate the association between PDE5-I use and risk of NAION. A comprehensive literature search was conducted using online databases in October 2017 to obtain studies researching the association between PDE5-I application and occurrence of NAION. Summarized unadjusted risk ratios (RRs) with 95% CIs were calculated for the strength of this association. This study was conducted in accordance to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and registered in PROSPERO under number CRD42017080865. The strength of association between PDE5-I use and risk of NAION was assessed through pooled unadjusted RRs and 95% CIs. 5 original articles with 6 clinical observations were included in the meta-analysis. No significant higher risk of NAION was observed after the use of PDE5-Is within a 1-month period (RR = 1.16, 95% CI = 0.98-1.39, P = .09). Subgroup analyses indicated 2 PDE5-Is were significantly related to NAION (tadalafil: RR = 2.14, 95% CI = 1.20-3.84, P = .01; sildenafil: RR = 2.25, 95% CI = 1.29-3.94, P = .004). Although we found no association between NAION and PDE5-I use, our results should be interpreted cautiously because we included only observational studies and could not control for potential confounders. Because NAION is a rare ocular disease and difficult to diagnose, this association should be confirmed in prospective comparative studies with larger samples and more rigorous designs. Liu B, Zhu L, Zhong J, et al. The Association Between Phosphodiesterase Type 5 Inhibitor Use and Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis. Sex Med 2018;X:XXX-XXX. Copyright © 2018. Published by Elsevier Inc.

Detonator Performance Characterization Using Multi-Frame Laser Schlieren Imaging

NASA Astrophysics Data System (ADS)

Clarke, S. A.; Landon, C. D.; Murphy, M. J.; Martinez, M. E.; Mason, T. A.; Thomas, K. A.

2009-12-01

Several experiments that are part of a phased plan to understand the evolution of detonation in a detonator from initiation shock through run to detonation to full detonation to transition to booster and booster detonation will be presented. High speed laser schlieren movies have been used to study several explosive initiation events, such as exploding bridgewires (EBW), exploding foil initiators (EFI) (or slappers), direct optical initiation (DOI), and electrostatic discharge (ESD). Additionally, a series of tests have been performed on "cut-back" detonators with varying initial pressing (IP) heights. We have also used this diagnostic to visualize a range of EBW, EFI, and DOI full-up detonators. Future applications to other explosive events such as boosters and IHE booster evaluation will be discussed. The EPIC hydrodynamic code has been used to analyze the shock fronts from the schlieren images to reverse calculate likely boundary or initial conditions to determine the temporal-spatial pressure profile across the output face of the detonator. LA-UR-05099

Using Schlieren Visualization to Track Detonator Performance

NASA Astrophysics Data System (ADS)

Clarke, S. A.; Bolme, C. A.; Murphy, M. J.; Landon, C. D.; Mason, T. A.; Adrian, R. J.; Akinci, A. A.; Martinez, M. E.; Thomas, K. A.

2007-12-01

Several experiments will be presented that are part of a phased plan to understand the evolution of detonation in a detonator from initiation shock through run to detonation, to full detonation, to transition, to booster and booster detonation. High-speed multiframe schlieren imagery has been used to study several explosive initiation events, such as exploding bridgewires (EBWs), exploding foil initiators (EFIs or "slappers"), direct optical initiation (DOI), and electrostatic discharge. Additionally, a series of tests has been performed on "cut-back" detonators with varying initial pressing heights. We have also used this diagnostic to visualize a range of EBW, EFI, and DOI full-up detonators. Future applications to other explosive events, such as boosters and insensitive high explosives booster evaluation, will be discussed. The EPIC finite element code has been used to analyze the shock fronts from the schlieren images to solve iteratively for consistent boundary or initial conditions to determine the temporal-spatial pressure profile across the output face of the detonator.

Using Schlieren Visualization to Track Detonator Performance

NASA Astrophysics Data System (ADS)

Clarke, Steven; Thomas, Keith; Martinez, Michael; Akinci, Adrian; Murphy, Michael; Adrian, Ronald

2007-06-01

Several experiments that are part of a phased plan to understand the evolution of detonation in a detonator from initiation shock through run to detonation to full detonation to transition to booster and booster detonation will be presented. High Speed Laser Schlieren Movies have been used to study several explosive initiation events, such as exploding bridgewires (EBW), Exploding Foil Initiators (EFI) (or slappers), Direct Optical Initiation (DOI), and ElectroStatic Discharge (ESD). Additionally, a series of tests have been performed on ``cut-back'' detonators with varying initial pressing (IP) heights. We have also used this diagnostic to visualize a range of EBW, EFI, and DOI full-up detonators. Future applications to other explosive events such as boosters and IHE booster evaluation will be discussed. EPIC Hydrodynamic code has been used to analyze the shock fronts from the Schlieren images to reverse calculate likely boundary or initial conditions to determine the temporal-spatial pressure profile across the output face of the detonator. LA-UR-07-1229

Advanced Stimulated Scattering Measurements in Supercritical Fluids

DTIC Science & Technology

2006-09-01

supercritical fluid measurement techniques. Ajay Agrawal, optical diagnostics. Mel Roquemore, turbine engines. Fred Schauer, pulse detonation propulsion...Lett. 87, 233902 (2001). 11. R. W. Gammon, H. L. Swinney, and H. Z. Cummins, "Brillouin scattering in carbon dioxide in the critical region," Phys. Rev...Stimulated Scattering Measurements in Supercritical F49620-03-C-0015 Fluids 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) 5d

Magnetohydrodynamic Augmentation of Pulse Detonation Rocket Engines (Preprint)

DTIC Science & Technology

2010-09-28

augmentation of the thrust . Ejectors typically transfer energy between streams through shear stress between separate flow streams, where a portion of the...the opportunity to extract energy and apply it to a separate stream where the net thrust can be increased. With MHD augmentation , such as in the Pulse...with the PDRIME for separate or additional thrust augmentation . Results show potential performance gains under many flight and operating conditions

Fragment-Based Discovery of Pyrimido[1,2-b]indazole PDE10A Inhibitors.

PubMed

Chino, Ayaka; Seo, Ryushi; Amano, Yasushi; Namatame, Ichiji; Hamaguchi, Wataru; Honbou, Kazuya; Mihara, Takuma; Yamazaki, Mayako; Tomishima, Masaki; Masuda, Naoyuki

2018-01-01

In this study, we report the identification of potent pyrimidoindazoles as phosphodiesterase10A (PDE10A) inhibitors by using the method of fragment-based drug discovery (FBDD). The pyrazolopyridine derivative 2 was found to be a fragment hit compound which could occupy a part of the binding site of PDE10A enzyme by using the method of the X-ray co-crystal structure analysis. On the basis of the crystal structure of compound 2 and PDE10A protein, a number of compounds were synthesized and evaluated, by means of structure-activity relationship (SAR) studies, which culminated in the discovery of a novel pyrimidoindazole derivative 13 having good physicochemical properties.

Second-order oriented partial-differential equations for denoising in electronic-speckle-pattern interferometry fringes.

PubMed

Tang, Chen; Han, Lin; Ren, Hongwei; Zhou, Dongjian; Chang, Yiming; Wang, Xiaohang; Cui, Xiaolong

2008-10-01

We derive the second-order oriented partial-differential equations (PDEs) for denoising in electronic-speckle-pattern interferometry fringe patterns from two points of view. The first is based on variational methods, and the second is based on controlling diffusion direction. Our oriented PDE models make the diffusion along only the fringe orientation. The main advantage of our filtering method, based on oriented PDE models, is that it is very easy to implement compared with the published filtering methods along the fringe orientation. We demonstrate the performance of our oriented PDE models via application to two computer-simulated and experimentally obtained speckle fringes and compare with related PDE models.

Effect of Aluminium Confinement on ANFO Detonation

NASA Astrophysics Data System (ADS)

Short, Mark; Jackson, Scott; Kiyanda, Charles; Shinas, Mike; Hare, Steve; Briggs, Matt

2013-06-01

Detonations in confined non-ideal high explosives often have velocities below the confiner sound speed. The effect on detonation propagation of the resulting subsonic flow in the confiner (such as confiner stress waves traveling ahead of the main detonation front or upstream wall deflection into the HE) has yet to be fully understood. Previous work by Sharpe and Bdzil (J. Eng. Math, 2006) has shown that for subsonic confiner flow, there is no limiting thickness for which the detonation dynamics are uninfluenced by further increases in wall thickness. The critical parameters influencing detonation behavior are the wall thickness relative to the HE reaction zone size, and the difference in the detonation velocity and confiner sound speed. Additional possible outcomes of subsonic flow are that for increasing thickness, the confiner is increasingly deflected into the HE upstream of the detonation, and that for sufficiently thick confiners, the detonation speed could be driven up to the sound speed in the confiner. We report here on a further series of experiments in which a mixture of ammonium nitrate and fuel oil (ANFO) is detonated in aluminum confiners with varying HE charge diameter and confiner thickness, and compare the results with the outcomes suggested by Sharpe and Bdzil.

On the propagation mechanism of a detonation wave in a round tube with orifice plates

NASA Astrophysics Data System (ADS)

Ciccarelli, G.; Cross, M.

2016-09-01

This study deals with the investigation of the detonation propagation mechanism in a circular tube with orifice plates. Experiments were performed with hydrogen air in a 10-cm-inner-diameter tube with the second half of the tube filled with equally spaced orifice plates. A self-sustained Chapman-Jouguet (CJ) detonation wave was initiated in the smooth first half of the tube and transmitted into the orifice-plate-laden second half of the tube. The details of the propagation were obtained using the soot-foil technique. Two types of foils were used between obstacles, a wall-foil placed on the tube wall, and a flat-foil (sooted on both sides) placed horizontally across the diameter of the tube. When placed after the first orifice plate, the flat foil shows symmetric detonation wave diffraction and failure, while the wall foil shows re-initiation via multiple local hot spots created when the decoupled shock wave interacts with the tube wall. At the end of the tube, where the detonation propagated at an average velocity much lower than the theoretical CJ value, the detonation propagation is much more asymmetric with only a few hot spots on the tube wall leading to local detonation initiation. Consecutive foils also show that the detonation structure changes after each obstacle interaction. For a mixture near the detonation propagation limit, detonation re-initiation occurs at a single wall hot spot producing a patch of small detonation cells. The local overdriven detonation wave is short lived, but is sufficient to keep the global explosion front propagating. Results associated with the effect of orifice plate blockage and spacing on the detonation propagation mechanism are also presented.

Design of integrated laser initiator

NASA Astrophysics Data System (ADS)

Cao, Chunqiang; He, Aifeng; Jing, Bo; Ma, Yue

2018-03-01

This paper analyzes the design principle of integrated laser detonator, introduces the design method of integrated laser Detonators. Based on the integrated laser detonator, structure, laser energy -exchange device, circuit design and the energetic material properties and the charge parameters, developed a high level of integration Antistatic ability Small size of the integrated laser prototype Detonator. The laser detonator prototype antistatic ability of 25 kV. The research of this paper can solve the key design of laser detonator miniaturization and integration of weapons and equipment, satisfy the electromagnetic safety and micro weapons development of explosive demand.

Continuous spin detonation of poorly detonable fuel-air mixtures in annular combustors

NASA Astrophysics Data System (ADS)

Bykovskii, F. A.; Zhdan, S. A.

2017-09-01

This paper reports on the results of experimental investigations of continuous spin detonation of three fuel-air mixtures (syngas-air, CH4/H2-air, and kerosene/H2-air in a flow-type annular cylindrical combustor 503 mm in diameter. The limits of existence of continuous detonation in terms of the specific flow rates of the mixtures (minimum values) are determined. It is found that all gas mixtures, including the least detonable methane-air mixture, with addition of hydrogen can be burned in the continuous spin detonation regime.

Rational rates of uniform decay for strong solutions to a fluid-structure PDE system

NASA Astrophysics Data System (ADS)

Avalos, George; Bucci, Francesca

2015-06-01

In this work we investigate the uniform stability properties of solutions to a well-established partial differential equation (PDE) model for a fluid-structure interaction. The PDE system under consideration comprises a Stokes flow which evolves within a three-dimensional cavity; moreover, a Kirchhoff plate equation is invoked to describe the displacements along a (fixed) portion - say, Ω - of the cavity wall. Contact between the respective fluid and structure dynamics occurs on the boundary interface Ω. The main result in the paper is as follows: the solutions to the composite PDE system, corresponding to smooth initial data, decay at the rate of O (1 / t). Our method of proof hinges upon the appropriate invocation of a relatively recent resolvent criterion for polynomial decays of C0-semigroups. While the characterization provided by said criterion originates in the context of operator theory and functional analysis, the work entailed here is wholly within the realm of PDE.

Discovery of Phosphodiesterase 10A (PDE10A) PET Tracer AMG 580 to Support Clinical Studies.

PubMed

Hu, Essa; Chen, Ning; Kunz, Roxanne K; Hwang, Dah-Ren; Michelsen, Klaus; Davis, Carl; Ma, Ji; Shi, Jianxia; Lester-Zeiner, Dianna; Hungate, Randall; Treanor, James; Chen, Hang; Allen, Jennifer R

2016-07-14

We report the discovery of PDE10A PET tracer AMG 580 developed to support proof of concept studies with PDE10A inhibitors in the clinic. To find a tracer with higher binding potential (BPND) in NHP than our previously reported tracer 1, we implemented a surface plasmon resonance assay to measure the binding off-rate to identify candidates with slower washout rate in vivo. Five candidates (2-6) from two structurally distinct scaffolds were identified that possessed both the in vitro characteristics that would favor central penetration and the structural features necessary for PET isotope radiolabeling. Two cinnolines (2, 3) and one keto-benzimidazole (5) exhibited PDE10A target specificity and brain uptake comparable to or better than 1 in the in vivo LC-MS/MS kinetics distribution study in SD rats. In NHP PET imaging study, [(18)F]-5 produced a significantly improved BPND of 3.1 and was nominated as PDE10A PET tracer clinical candidate for further studies.

Phosphodiesterase inhibitors in clinical urology.

PubMed

Ückert, Stefan; Kuczyk, Markus A; Oelke, Matthias

2013-05-01

To date, benign diseases of the male and female lower urinary and genital tract, such as erectile dysfunction, bladder overactivity, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and symptoms of female sexual dysfunction (including arousal and orgasmic disorders), can be therapeutically approached by influencing the function of the smooth musculature of the respective tissues. The use of isoenzyme-selective phosphodiesterase (PDE) inhibitors is considered a great opportunity to treat various diseases of the human urogenital tract. PDE inhibitors, in particular the PDE5 (cyclic GMP PDE) inhibitors avanafil, lodenafil, sildenafil, tadalafil, udenafil and vardenafil, are regarded as efficacious, having a fast onset of drug action and an improved effect-to-adverse event ratio, combining a high response rate with the advantage of an on-demand intake. The purpose of this review is to summarize recent as well as potential future indications, namely, erectile dysfunction, Peyronie's disease, overactive bladder, urinary stone disease, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and premature ejaculation, for the use of PDE inhibitors in clinical urology.

Discovery of novel PDE9 inhibitors capable of inhibiting Aβ aggregation as potential candidates for the treatment of Alzheimer's disease.

PubMed

Su, Tao; Zhang, Tianhua; Xie, Shishun; Yan, Jun; Wu, Yinuo; Li, Xingshu; Huang, Ling; Luo, Hai-Bin

2016-02-25

Recently, phosphodiesterase-9 (PDE9) inhibitors and biometal-chelators have received much attention as potential therapeutics for the treatment of Alzheimer's disease (AD). Here, we designed, synthesized, and evaluated a novel series of PDE9 inhibitors with the ability to chelate metal ions. The bioassay results showed that most of these molecules strongly inhibited PDE9 activity. Compound 16 showed an IC50 of 34 nM against PDE9 and more than 55-fold selectivity against other PDEs. In addition, this compound displayed remarkable metal-chelating capacity and a considerable ability to halt copper redox cycling. Notably, in comparison to the reference compound clioquinol, it inhibited metal-induced Aβ(1-42) aggregation more effectively and promoted greater disassembly of the highly structured Aβ fibrils generated through Cu(2+)-induced Aβ aggregation. These activities of 16, together with its favorable blood-brain barrier permeability, suggest that 16 may be a promising compound for treatment of AD.

Structure-Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel PDE10 Inhibitors with Antioxidant Activities

NASA Astrophysics Data System (ADS)

Li, Jinxuan; Chen, Jing-Yi; Deng, Ya-Lin; Zhou, Qian; Wu, Yinuo; Wu, Deyan; Luo, Hai-Bin

2018-05-01

Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized. Nine out of thirteen designed compounds showed good PDE10 inhibition at the concentration of 1.0 μM. Among these compounds, eight exhibited moderate to excellent antioxidant activity with ORAC (oxygen radical absorbance capacity) value above 1.0. Molecular docking was performed for better understanding of the binding patterns of these compounds with PDE10. Compound 11e, which showed remarkable inhibitory activity against PDE10 and antioxidant activity may serve as a lead for the further modification.

Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds.

PubMed

Prosdocimi, Tommaso; Mollica, Luca; Donini, Stefano; Semrau, Marta S; Lucarelli, Anna Paola; Aiolfi, Egidio; Cavalli, Andrea; Storici, Paola; Alfei, Silvana; Brullo, Chiara; Bruno, Olga; Parisini, Emilio

2018-05-01

Selected members of the large rolipram-related GEBR family of type 4 phosphodiesterase (PDE4) inhibitors have been shown to facilitate long-term potentiation and to improve memory functions without causing emetic-like behavior in rodents. Despite their micromolar-range binding affinities and their promising pharmacological and toxicological profiles, few if any structure-activity relationship studies have been performed to elucidate the molecular bases of their action. Here, we report the crystal structure of a number of GEBR library compounds in complex with the catalytic domain of PDE4D as well as their inhibitory profiles for both the long PDE4D3 isoform and the catalytic domain alone. Furthermore, we assessed the stability of the observed ligand conformations in the context of the intact enzyme using molecular dynamics simulations. The longer and more flexible ligands appear to be capable of forming contacts with the regulatory portion of the enzyme, thus possibly allowing some degree of selectivity between the different PDE4 isoforms.

Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.

PubMed

Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

2015-09-15

Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors.

A morphological investigation of soot produced by the detonation of munitions.

PubMed

Pantea, Dana; Brochu, Sylvie; Thiboutot, Sonia; Ampleman, Guy; Scholz, Günter

2006-10-01

The morphology of three different detonation soot samples along with other common soot materials such as carbon black, diesel soot and chimney soot was studied by elemental and proximate analysis, X-ray diffraction and electron microscopy. The goal of this study was to better define the morphology of the detonation soot in order to better assess the interactions of this type of soot with explosive residues. The detonation soot samples were obtained by the detonation of artillery 155mm projectiles filled with either pure TNT (2,4,6-trinitrotoluene) or composition B, a military explosive based on a mixture of TNT and RDX (trimethylentrinitramine). The carbon content of the soot samples varied considerably depending on the feedstock composition. Detonation soot contains less carbon and more nitrogen than the other carbonaceous samples studied, due to the molecular structure of the energetic materials detonated such as TNT and RDX. The ash concentration was higher for detonation soot samples due to the high metal content coming from the projectiles shell and to the soil contamination which occurred during the detonation. By X-ray diffraction, diamond and graphite were found to be the major crystalline carbon forms in the detonation soot. Two electron microscopy techniques were used in this study to visualise the primary particles and to try to explain the formation mechanism of detonation soot samples.

Treatment of psoriasis with crisaborole.

PubMed

Lee, Erica B; Lebwohl, Mark G; Wu, Jashin J

2018-06-08

Crisaborole, a topical phosphodiesterase-4 (PDE4) inhibitor, is effective in patients with atopic dermatitis. As systemic PDE4 inhibition has also been used with success in psoriasis, clinical trials are underway to determine the utility of topical PDE4 inhibitors in these patients. However, there is no current literature documenting use of crisaborole for psoriasis. Here, we present two cases in which patients with psoriasis were treated successfully with crisaborole.

Rutin inhibits B[a]PDE-induced cyclooxygenase-2 expression by targeting EGFR kinase activity.

PubMed

Choi, Seunghwan; Lim, Tae-Gyu; Hwang, Mun Kyung; Kim, Yoon-A; Kim, Jiyoung; Kang, Nam Joo; Jang, Tae Su; Park, Jun-Seong; Yeom, Myeong Hun; Lee, Ki Won

2013-11-15

Rutin is a well-known flavonoid that exists in various natural sources. Accumulative studies have represented the biological effects of rutin, such as anti-oxidative and anti-inflammatory effects. However, the underlying mechanisms of rutin and its direct targets are not understood. We investigated whether rutin reduced B[a]PDE-induced-COX-2 expression. The transactivation of AP-1 and NF-κB were inhibited by rutin. Rutin also attenuated B[a]PDE-induced Raf/MEK/ERK and Akt activation, but had no effect on the phosphorylation of EGFR. An in vitro kinase assay revealed rutin suppressed EGFR kinase activity. We also confirmed direct binding between rutin and EGFR, and found that the binding was regressed by ATP. The EGFR inhibitor also inhibited the B[a]PDE-induced MEK/ERK and Akt signaling pathways and subsequently, suppressed COX-2 expression and promoter activity, in addition to suppressing the transactivation of AP-1 and NF-κB. In EGFR(-/-)mouse embryonic fibroblast cells, B[a]PDE-induced COX-2 expression was also diminished. Collectively, rutin inhibits B[a]PDE-induced COX-2 expression by suppressing the Raf/MEK/ERK and Akt signaling pathways. EGFR appeared to be the direct target of rutin. Copyright © 2013 Elsevier Inc. All rights reserved.

Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study.

PubMed

French, Dustin D; Margo, Curtis E

2010-02-01

The purpose of this study was to determine if there is an increased risk of central serous chorioretinopathy (CSC) associated with prescription exposure to phosphodiesterase-5 (PDE-5) inhibitors. A case-control study linking 2 National Veterans Health Administration databases (clinical and pharmacy) for fiscal years 2004 to 2005. The likelihood of past exposure to PDE-5 inhibitors among newly diagnosed patients with CSC, identified through International Classification of Diseases, 9th Edition, Clinical Modification codes, was compared with 2 age-matched control groups after excluding subjects with risk factors for CSC. Among 577 men, aged 59 years and younger with newly diagnosed CSC during the study year, 111 were prescribed a PDE-5 inhibitor (19.2%). The proportions of age-matched controls prescribed a PDE-5 inhibitor in the 2 groups were 18.5% and 21.5%. The odds ratio of exposure was 1.05 (95% confidence limit: 0.74-1.22) and 0.87 (95% confidence limit: 0.68-1.12). Patients with CSC had no increase in prescription exposure to PDE-5 inhibitors than did age-matched control subjects. Although the findings in this study do not support an association between CSC and PDE-5 inhibitors, postmarketing surveillance methods for drug-related side effects have acknowledged limitations.

New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is).

PubMed

Ribaudo, Giovanni; Pagano, Mario Angelo; Bova, Sergio; Zagotto, Giuseppe

2016-01-01

Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED). In addition to this, sildenafil and tadalafil, have also been approved for the treatment of pulmonary arterial hypertension. Due to its expression and localization in many tissues, PDE5 and its regulation has been reported to be involved in several other diseases. We aim to provide an updated overview of the emerging therapeutic applications of PDE5-Is besides ED, taking into account the latest ongoing research reports. We searched online databases (Pubmed, Reaxys, Scopus) to lay the bases for an accurate, quality criteria-based literature update. We focused our attention on most recent research reports, in particular when supported by pre-clinical and clinical data. The regulation of PDE5 may influence pathological conditions such as, among the others, heart failure, cystic fibrosis, cancer, CNS-related diseases, diabetes and dysfunctions affecting male urinary/reproductive system. Sildenafil, vardenafil, tadalafil and the other chemical entities considered PDE5-Is showed overall positive results and significant improvements in the studied disease, thus some discordant results, in particular when comparing pre-clinical and clinical data, have to be pointed out, suggesting that further insights are needed especially to assess the exact molecular pathway underlying.

Sildenafil Can Affect Innate and Adaptive Immune System in Both Experimental Animals and Patients

PubMed Central

Boguska, Agnieszka

2017-01-01

Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects. Sildenafil influences angiogenesis, platelet activation, proliferation of regulatory T cells, and production of proinflammatory cytokines and autoantibodies. Sildenafil action in humans and animals appears to be different. Surprisingly, it also acts differently in males and females organisms. Although the immunomodulatory effects of PDE5 inhibitors appear to be promising, none of them reached the point of being tested in clinical trials. Data on the influence of selective PDE5-Is on the human immune system are limited. The main objective of this review is to discuss the immunomodulatory effects of sildenafil in both patients and experimental animals. This is the first review of the current state of knowledge about the effects of sildenafil on the immune system. PMID:28316997

Effect of phoshpodiesterase 4 (PDE4) inhibibtors on eotaxin expression in humen bronchial epithelial cells.

PubMed

Paplinska, M; Chazan, R; Grubek-Jaworska, H

2011-06-01

The increasing number of eosinophils into bronchoaelvolar space is observed during noninfectious inflammatory lung diseases. Eotaxins (eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26) are the strongest chemotactic agents for eosinophils. Inhibitors of phosphodiesterase 4 (PDE4), the enzyme decomposing cAMP, are anti-inflammatory agents which act through cAMP elevation and inhibit numerous steps of allergic inflammation. The effect of PDE4 inhibitors on eotaxin expression is not known in details. The aim of our study was to evaluate the influence of PDE4 inhibitors: rolipram and RO-20-1724 on expression of eotaxins in bronchial epithelial cell line BEAS-2B. Cells were preincubated with PDE4 inhibitors or dexamethasone for 1 hour and then stimulated with IL-4 or IL-13 alone or in combination with TNF-α. After 48 hours eotaxin protein level was measured by ELISA and mRNA level by real time PCR. PDE4 inhibitors decreased CCL11 and CCL26 expression only in cultures co-stimulated with TNF-α. In cultures stimulated with IL-4 and TNF-α rolipram and RO-20-1724 diminished CCL11 mRNA expression by 34 and 37%, respectively, and CCL26 by 43 and 47%. In cultures stimulated with IL-13 and TNF-α rolipram and RO-20-1724 decreased expression of both eotaxins by about 50%. These results were confirmed at the protein level. The effect of PDE4 inhibitors on eotaxin expression in BEAS-2B cells, in our experimental conditions, depends on TNF-α contribution.

Ab Initio QM/MM Study Shows a Highly Dissociated SN2 Hydrolysis Mechanism for the cGMP-Specific Phosphodiesterase-5.

PubMed

Li, Zhe; Wu, Yinuo; Feng, Ling-Jun; Wu, Ruibo; Luo, Hai-Bin

2014-12-09

Phosphodiesterases (PDEs) are the sole enzymes hydrolyzing the important second messengers cGMP and cAMP and have been identified as therapeutic targets for several diseases. The most successful examples are PDE5 inhibitors (i.e., sildenafil and tadalafil), which have been approved for the treatment of male erectile dysfunction and pulmonary hypertension. However, the side effects mostly due to nonselective inhibition toward other PDE isoforms, set back the clinical usage of PDE5 inhibitors. Until now, the exact catalytic mechanism of the substrate cGMP by PDE5 is still unclear. Herein, the first computational study on the catalytic hydrolysis mechanism of cGMP for PDE5 (catalytic domain) is performed by employing the state-of-the-art ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations. Our simulations show a SN2 type reaction procedure via a highly dissociated transition state with a reaction barrier of 8.88 kcal/mol, which is quite different from the previously suggested hydrolysis mechanism of cAMP for PDE4. Furthermore, the subsequent ligand exchange and the release of the product GMP have also been investigated by binding energy analysis and MD simulations. It is deduced that ligand exchange would be the rate-determining step of the whole reaction, which is consistent with many previous experimental results. The obtained mechanistic insights should be valuable for not only the rational design of more specific inhibitors toward PDE5 but also understanding the general hydrolysis mechanism of cGMP-specific PDEs.

The limit of photoreceptor sensitivity: molecular mechanisms of dark noise in retinal cones.

PubMed

Holcman, David; Korenbrot, Juan I

2005-06-01

Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise). To understand the mechanisms that limit light sensitivity, we characterized the molecular origin of dark noise in intact, isolated bass single cones. Dark noise is caused by continuous fluctuations in the cytoplasmic concentrations of both cGMP and Ca(2+) that arise from the activity in darkness of both guanylate cyclase (GC), the enzyme that synthesizes cGMP, and phosphodiesterase (PDE), the enzyme that hydrolyzes it. In cones loaded with high concentration Ca(2+) buffering agents, we demonstrate that variation in cGMP levels arise from fluctuations in the mean PDE enzymatic activity. The rates of PDE activation and inactivation determine the quantitative characteristics of the dark noise power density spectrum. We developed a mathematical model based on the dynamics of PDE activity that accurately predicts this power spectrum. Analysis of the experimental data with the theoretical model allows us to determine the rates of PDE activation and deactivation in the intact photoreceptor. In fish cones, the mean lifetime of active PDE at room temperature is approximately 55 ms. In nonmammalian rods, in contrast, active PDE lifetime is approximately 555 ms. This remarkable difference helps explain why cones are noisier than rods and why cone photocurrents are smaller in peak amplitude and faster in time course than those in rods. Both these features make cones less light sensitive than rods.

Preservation of nitric oxide-induced relaxation of porcine coronary artery: roles of the dimers of soluble guanylyl cyclase, phosphodiesterase type 5, and cGMP-dependent protein kinase.

PubMed

Liu, Juan; Chen, Zhengju; Ye, Liping; Liu, Huixia; Dou, Dou; Liu, Limei; Yu, Xiaoxing; Gao, Yuansheng

2014-10-01

Soluble guanylyl cyclase (sGC), phosphodiesterase type 5 (PDE5), and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (PKG) are all dimeric. The present study was to determine the role of their dimeric status in nitric oxide-induced vasodilatation. In isolated porcine coronary arteries, after 20 h incubation with serum-free medium, serum-containing medium, or phosphate-buffered saline solution, the protein levels of the dimers of sGC, PDE5, and PKG were diminished while the monomer levels remained unchanged, associated with reduced cGMP elevation in response to DETA NONOate and decreased PDE5 activity; the activity of PKG was not significantly altered. DETA NONOate caused a greater relaxation in arteries incubated for 20 vs. 2 h. The relaxant response was largely abolished by 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, an sGC inhibitor. Zaprinast, a PDE5 inhibitor, had no effect on relaxation caused by DETA NONOate of arteries incubated for 20 h but augmented the response incubated for 2 h. A greater relaxation to 8-bromo-guanosine 3'5'-cyclic monophosphate occurred in arteries incubated for 20 than for 2 h. The protein level of the dimers but not monomers of PDE5 was reduced by dithiothreitol and unaffected by hydrogen peroxide, accompanied with decreased PDE5 activity and reduced response to DETA NONOate. These results demonstrate that the dimeric but not monomeric status of sGC and PDE5 of coronary arteries are closely related to their activities. The preserved vasodilator response after 20 h incubation may result in part from a synchronous reduction of the dimer levels of sGC and PDE5 as well as an augmented response to cGMP.

Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes

PubMed Central

Hackett, Geoffrey; Jones, Peter W; Strange, Richard C; Ramachandran, Sudarshan

2017-01-01

AIM To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men. METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I/untreated and PDE5I/treated; and (3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality (logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age (OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated (OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated (OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated (OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln (mortality) was plotted against age. The probability of mortality and 95%CI (from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5I and TRT reduce mortality in diabetes. PDE5I, alone and with the other treatments significantly alter age related mortality in diabetic men. PMID:28344753