Unsteady Ejector Performance: an Experimental Investigation Using a Pulsejet Driver

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Wilson, Jack; Dougherty, Kevin T.

2002-01-01

An experimental investigation is described in which thrust augmentation and mass entrainment were measured for a variety of simple cylindrical ejectors driven by a gasoline-fueled pulsejet. The ejectors were of varying length, diameter, and inlet radius. Measurements were also taken to determine the effect on performance of the distance between pulsejet exit and ejector inlet. Limited tests were also conducted to determine the effect of driver cross-sectional shape. Optimal values were found for all three ejector parameters with respect to thrust augmentation. This was not the case with mass entrainment, which increased monotonically with ejector diameter. Thus, it was found that thrust augmentation is not necessarily directly related to mass entrainment, as is often supposed for ejectors. Peak thrust augmentation values of 1.8 were obtained. Peak mass entrainment values of 30 times the driver mass flow were also observed. Details of the experimental setup and results are presented. Preliminary analysis of the results indicates that the enhanced performance obtained with an unsteady jet (primary source) over comparably sized ejectors driven with steady jets is due primarily to the structure of the starting vortex-type flow associated with the former.

Design and experimental investigation of an ejector in an air-conditioning and refrigeration system

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

AL-Khalidy, N.; Zayonia, A.

1995-12-31

This paper discusses the conservation of energy in a refrigerant ejector refrigerating machine using heat driven from the concentrator collectors. The working refrigerant was R-113. The design of an ejector operating in an air-conditioning and refrigerating system with a low thermal source (70 C to 100 C) is presented. The influence of three major parameters--boiler, condenser, and evaporator temperature--on ejector efficiency is discussed. Experimental results show that the condenser temperature is the major influence at a low evaporator temperature. The maximum ejector efficiency was 31%.

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

Parametric Study of Pulse-Combustor-Driven Ejectors at High-Pressure

NASA Technical Reports Server (NTRS)

Yungster, Shaye; Paxson, Daniel E.; Perkins, Hugh D.

2015-01-01

Pulse-combustor configurations developed in recent studies have demonstrated performance levels at high-pressure operating conditions comparable to those observed at atmospheric conditions. However, problems related to the way fuel was being distributed within the pulse combustor were still limiting performance. In the first part of this study, new configurations are investigated computationally aimed at improving the fuel distribution and performance of the pulse-combustor. Subsequent sections investigate the performance of various pulse-combustor driven ejector configurations operating at highpressure conditions, focusing on the effects of fuel equivalence ratio and ejector throat area. The goal is to design pulse-combustor-ejector configurations that maximize pressure gain while achieving a thermal environment acceptable to a turbine, and at the same time maintain acceptable levels of NOx emissions and flow non-uniformities. The computations presented here have demonstrated pressure gains of up to 2.8%.

Parametric Study of Pulse-Combustor-Driven Ejectors at High-Pressure

NASA Technical Reports Server (NTRS)

Yungster, Shaye; Paxson, Daniel E.; Perkins, Hugh D.

2015-01-01

Pulse-combustor configurations developed in recent studies have demonstrated performance levels at high-pressure operating conditions comparable to those observed at atmospheric conditions. However, problems related to the way fuel was being distributed within the pulse combustor were still limiting performance. In the first part of this study, new configurations are investigated computationally aimed at improving the fuel distribution and performance of the pulse-combustor. Subsequent sections investigate the performance of various pulse-combustor driven ejector configurations operating at high pressure conditions, focusing on the effects of fuel equivalence ratio and ejector throat area. The goal is to design pulse-combustor-ejector configurations that maximize pressure gain while achieving a thermal environment acceptable to a turbine, and at the same time maintain acceptable levels of NO(x) emissions and flow non-uniformities. The computations presented here have demonstrated pressure gains of up to 2.8.

Performance Assessment of a Large Scale Pulsejet- Driven Ejector System

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Litke, Paul J.; Schauer, Frederick R.; Bradley, Royce P.; Hoke, John L.

2006-01-01

Unsteady thrust augmentation was measured on a large scale driver/ejector system. A 72 in. long, 6.5 in. diameter, 100 lb(sub f) pulsejet was tested with a series of straight, cylindrical ejectors of varying length, and diameter. A tapered ejector configuration of varying length was also tested. The objectives of the testing were to determine the dimensions of the ejectors which maximize thrust augmentation, and to compare the dimensions and augmentation levels so obtained with those of other, similarly maximized, but smaller scale systems on which much of the recent unsteady ejector thrust augmentation studies have been performed. An augmentation level of 1.71 was achieved with the cylindrical ejector configuration and 1.81 with the tapered ejector configuration. These levels are consistent with, but slightly lower than the highest levels achieved with the smaller systems. The ejector diameter yielding maximum augmentation was 2.46 times the diameter of the pulsejet. This ratio closely matches those of the small scale experiments. For the straight ejector, the length yielding maximum augmentation was 10 times the diameter of the pulsejet. This was also nearly the same as the small scale experiments. Testing procedures are described, as are the parametric variations in ejector geometry. Results are discussed in terms of their implications for general scaling of pulsed thrust ejector systems

An Experimental Investigation of Unsteady Thrust Augmentation Using a Speaker-Driven Jet

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Wernet, Mark P.; John, Wentworth T.

2004-01-01

An experimental investigation is described in which a simple speaker-driven jet was used as a pulsed thrust source (driver) for an ejector configuration. The objectives of the investigation were twofold: first, to add to the experimental body of evidence showing that an unsteady thrust source, combined with a properly sized ejector generally yields higher thrust augmentation values than a similarly sized, steady driver of equivalent thrust. Second, to identify characteristics of the unsteady driver that may be useful for sizing ejectors, and predicting what thrust augmentation values may be achieved. The speaker-driven jet provided a convenient source for the investigation because it is entirely unsteady (having no mean component) and because relevant parameters such as frequency, time-averaged thrust, and diameter are easily variable. The experimental setup will be described, as will the various measurements made. These include both thrust and Digital Particle Imaging Velocimetry of the driver. It will be shown that thrust augmentation values as high as 1.8 were obtained, that the diameter of the best ejector scaled with the dimensions of the emitted vortex, and that the so-called Formation Number serves as a useful dimensionless number by which to characterize the jet and predict performance.

Investigation of the gas-jet ejector in KamAZ trucks

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

Shkret, L.Y.; Berezea, A.I.; Lobkov, A.N.

1984-03-01

This article considers the possibility of using gas-jet vacuum pumps in tank trucks for transporting liquids (water) at drilling sites. The discharge system of the KamAZ trucks can be reliably sealed by an engine brake, an important prerequisite of reliable operation of a gas-jet ejector that is switched on when the tank is being filled. The ejector consists of a housing, a Laval nozzle, a front wall with cylindrical neck, a tin-plate diffuser, an air supply pipe, and a flange for attaching the ejector to the flange of the exhaust muffler of the truck. The gas-jet ejectors are driven bymore » the exhaust gas (EG) of the trucks. The dependences of the EG flow rate, fuel expenditure, EG temperature ahead of the ejector, and the rotational frequency of the engine crankshaft on the diameter at different EG pressures. It is recommended that gas-jet ejectors be used on series produced tank trucks instead of rotary vacuum pumps with mechanical drive.« less

A new thermally driven refrigeration system with environmental benefits

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

Garris, C.A. Jr.; Hong, W.J.; Mavriplis, C.

1998-07-01

The pressure-exchange ejector offers the possibility of attaining a breakthrough in the level of performance of ejectors by means of utilizing non-dissipative non-steady flow mechanisms. Yet, the device retains much of the mechanical simplicity of conventional steady-flow ejectors. If such a substantial improvement in performance is demonstrated, its application to ejector refrigeration will be very important. Such a development would provide significant benefits for the environment in terms of both CFC usage reduction and greenhouse gas reduction. The current paper will discuss in detail the concept of pressure-exchange ejector refrigeration, compare it with existing technologies, and discuss the potential impactmore » that might be derived if certain levels of ejector performance can be achieved. Since the limiting issue on the system performance is in the fluid dynamics of non-steady flow induction, research issues and recent progress will be discussed.« less

Jet Engines as High-Capacity Vacuum Pumps

NASA Technical Reports Server (NTRS)

Wojciechowski, C. J.

1983-01-01

Large diffuser operations envelope and long run times possible. Jet engine driven ejector/diffuser system combines two turbojet engines and variable-area-ratio ejector in two stages. Applications in such industrial proesses as handling corrosive fumes, evaporation of milk and fruit juices, petroleum distillation, and dehydration of blood plasma and penicillin.

Experimental Investigation of Unsteady Thrust Augmentation Using a Speaker-Driven Jet

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Wernet, Mark P.; John, Wentworth T.

2007-01-01

An experimental investigation is described in which a simple speaker-driven jet was used as a pulsed thrust source (driver) for an ejector configuration. The objectives of the investigation were twofold. The first was to expand the experimental body of evidence showing that an unsteady thrust source, combined with a properly sized ejector generally yields higher thrust augmentation values than a similarly sized, steady driver of equivalent thrust. The second objective was to identify characteristics of the unsteady driver that may be useful for sizing ejectors, and for predicting the thrust augmentation levels that may be achieved. The speaker-driven jet provided a convenient source for the investigation because it is entirely unsteady (i.e., it has no mean velocity component) and because relevant parameters such as frequency, time-averaged thrust, and diameter are easily variable. The experimental setup will be described, as will the two main measurements techniques employed. These are thrust and digital particle imaging velocimetry of the driver. It will be shown that thrust augmentation values as high as 1.8 were obtained, that the diameter of the best ejector scaled with the dimensions of the emitted vortex, and that the so-called formation time serves as a useful dimensionless parameter by which to characterize the jet and predict performance.

Theoretical and experimental investigation of turbulent mixing on ejector configuration and performance in a solar-driven organic-vapor ejector cycle chiller

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

Kucha, E.I.

1984-01-01

A general method was developed to calculate two dimensional (axisymmetric) mixing of a compressible jet in a variable cross-sectional area mixing channel of the ejector. The analysis considers mixing of the primary and secondary fluids at constant pressure and incorporates finite difference approximations to the conservation equations. The flow model is based on the mixing length approximations. A detailed study and modeling of the flow phenomenon determines the best (optimum) mixing channel geometry of the ejector. The detailed ejector performance characteristics are predicted by incorporating the flow model into a solar-powered ejector cycle cooling system computer model. Freon-11 is usedmore » as both the primary and secondary fluids. Performance evaluation of the cooling system is examined for its coefficient of performance (COP) under a variety of operating conditions. A study is also conducted on a modified ejector cycle in which a secondary pump is introduced at the exit of the evaporator. Results show a significant improvement in the overall performance over that of the conventional ejector cycle (without a secondary pump). Comparison between one and two-dimensional analyses indicates that the two-dimensional ejector fluid flow analysis predicts a better overall system performance. This is true for both the conventional and modified ejector cycles.« less

A combined power and ejector refrigeration cycle for low temperature heat sources

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

Zheng, B.; Weng, Y.W.

A combined power and ejector refrigeration cycle for low temperature heat sources is under investigation in this paper. The proposed cycle combines the organic Rankine cycle and the ejector refrigeration cycle. The ejector is driven by the exhausts from the turbine to produce power and refrigeration simultaneously. A simulation was carried out to analyze the cycle performance using R245fa as the working fluid. A thermal efficiency of 34.1%, an effective efficiency of 18.7% and an exergy efficiency of 56.8% can be obtained at a generating temperature of 395 K, a condensing temperature of 298 K and an evaporating temperature ofmore » 280 K. Simulation results show that the proposed cycle has a big potential to produce refrigeration and most exergy losses take place in the ejector. (author)« less

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.

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)

Pulse Detonation Engine Test Bed Developed

NASA Technical Reports Server (NTRS)

Breisacher, Kevin J.

2002-01-01

A detonation is a supersonic combustion wave. A Pulse Detonation Engine (PDE) repetitively creates a series of detonation waves to take advantage of rapid burning and high peak pressures to efficiently produce thrust. NASA Glenn Research Center's Combustion Branch has developed a PDE test bed that can reproduce the operating conditions that might be encountered in an actual engine. It allows the rapid and cost-efficient evaluation of the technical issues and technologies associated with these engines. The test bed is modular in design. It consists of various length sections of both 2- and 2.6- in. internal-diameter combustor tubes. These tubes can be bolted together to create a variety of combustor configurations. A series of bosses allow instrumentation to be inserted on the tubes. Dynamic pressure sensors and heat flux gauges have been used to characterize the performance of the test bed. The PDE test bed is designed to utilize an existing calorimeter (for heat load measurement) and windowed (for optical access) combustor sections. It uses hydrogen as the fuel, and oxygen and nitrogen are mixed to simulate air. An electronic controller is used to open the hydrogen and air valves (or a continuous flow of air is used) and to fire the spark at the appropriate times. Scheduled tests on the test bed include an evaluation of the pumping ability of the train of detonation waves for use in an ejector and an evaluation of the pollutants formed in a PDE combustor. Glenn's Combustion Branch uses the National Combustor Code (NCC) to perform numerical analyses of PDE's as well as to evaluate alternative detonative combustion devices. Pulse Detonation Engine testbed.

The Effect of Pulse Length and Ejector Radius on Unsteady Ejector Performance

NASA Technical Reports Server (NTRS)

Wilson, Jack

2005-01-01

The thrust augmentation of a set of ejectors driven by a shrouded Hartmann-Sprenger tube has been measured at four different frequencies. Each frequency corresponded to a different length to diameter ratio of the pulse of air leaving the driver shroud. Two of the frequencies had length to diameter ratios below the formation number, and two above. The formation number is the value of length to diameter ratio below which the pulse converts to a vortex ring only, and above which the pulse becomes a vortex ring plus a trailing jet. A three level, three parameter Box-Behnken statistical design of experiment scheme was performed at each frequency, measuring the thrust augmentation generated by the appropriate ejectors from the set. The three parameters were ejector length, radius, and inlet radius. The results showed that there is an optimum ejector radius and length at each frequency. Using a polynomial fit to the data, the results were interpolated to different ejector radii and pulse length to diameter ratios. This showed that a peak in thrust augmentation occurs when the pulse length to diameter ratio equals the formation number, and that the optimum ejector radius is 0.87 times the sum of the vortex ring radius and the core radius.

Credit WCT. Photographic copy of photograph, view north across "neutralization ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit WCT. Photographic copy of photograph, view north across "neutralization pond" at Test Stand "D," showing complete Dd station with new Y-Stage and Z-Stage steam-driven ejectors, and "Hyprox" steam generator which powered ejectors. (JPL negative no. 384-3356-B, 20 November 1962) - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Credit BG. Looking northwest at the Dd stand complex. To ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit BG. Looking northwest at the Dd stand complex. To the left is the Test Stand "D" tower with steam-driven ejectors and interstage condenser visible along with steam lines. The steam accumulator appears in the left foreground (sphere); steam lines emerging from the top conduct steam to the Dv, Dd, and Dy stand ejectors. The T-shaped vertical pipes atop the accumulator are burst-disk type safety valves. The ejector ends of the Dd and Dy trains are visible to the right. Tracks permitted each train to expand and contract with temperature or equipment changes - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Pumping Performance or RBCC Engine under Sea Level Static Condition

NASA Astrophysics Data System (ADS)

Kouchi, Toshinori; Tomioka, Sadatake; Kanda, Takeshi

Numerical simulations were conducted to predict the ejector pumping performance of a rocket-ramjet combined-cycle engine under a take-off condition. The numerical simulations revealed that the suction airflow was chocked at the exit of the engine throat when the ejector rocket was driven by cold N2 gas at the chamber pressure of 3MPa. When the ejector-driving gas was changed from cold N2 gas to hot combustion gas, the suction performance decreased remarkably. Mach contours in the engine revealed that the rocket plume constricted when the driving gas was the hot combustion gas. The change of the area of the stream tube area seemed to induce the pressure rise in the duct and decreasing in the pumping performance.

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.

Ejector gas cooling. Phase 1. Final report, 1 April 1987-30 April 1988

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

MacCracken, C.D.; Silvetti, B.M.; Hrbek, R.

1988-11-01

Closed-circuit ejector cooling systems have never in the past achieved acceptable operating efficiencies in their vapor-compression cycle using standard refrigerants. Despite their long history, relative simplicity, quietness, rugged design, low maintenance and low cost, they could not compete with electric-motor-driven compressors. Phase I is an assessment of two immiscible fluids in an ejector cooling system with different latent heat capacity and molecular weights intended to require less heat in the boiler producing the propellant and taking more heat out in the evaporator cooling fluid. Actual tests corrected to standard conditions and neglecting thermal losses showed 0.5 closed-cycle thermal COP (excludingmore » stack losses), higher than ever previously achieved but below original expectations. Computer programs developed indicate higher COP values are attainable along with competitive first costs.« less

Starting Vortex Identified as Key to Unsteady Ejector Performance

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2004-01-01

Unsteady ejectors are currently under investigation for use in some pulse-detonation-engine-based propulsion systems. Experimental measurements made in the past, and recently at the NASA Glenn Research Center, have demonstrated that thrust augmentation can be enhanced considerably when the driver is unsteady. In ejector systems, thrust augmentation is defined as = T(sup Total)/T(sup j), where T(sup Total) is the total thrust of the combined ejector and driving jet and T(sup j) is the thrust due to the driving jet alone. There are three images in this figure, one for each of the named thrust sources. The images are color contours of measured instantaneous vorticity. Each image is an ensemble average of at least 150 phase-locked measurements. The flow is from right to left, and the shape and location of each driver is shown on the far right of each image. The emitted vortex is a clearly defined "doughnut" of highly vortical (spinning) flow. In these planar images, the vortex appears as two distorted circles, one above, and one below the axis of symmetry. Because they are spinning in the opposite direction, the two circles have vorticity of opposite sign and thus are different colors. There is also a rectangle shown in each image. Its width represents the ejector diameter that was found experimentally to yield the highest thrust augmentation. It is apparent that the optimal ejector diameter is that which just "captures" the vortex: that is, the diameter bounding the outermost edge of the vortex structure. The exact mechanism behind the enhanced performance is unclear; however, it is believed to be related to the powerful vortex emitted with each pulse of the unsteady driver. As such, particle imaging velocimetry (PIV) measurements were obtained for three unsteady drivers: a pulsejet, a resonance tube, and a speaker-driven jet. All the drivers were tested with ejectors, and all exhibited performance enhancement over similarly sized steady drivers. The characteristic starting vortices of each driver are shown in these images. The images are color contours of measured instantaneous vorticity. Each image is an ensemble average of at least 150 phase-locked measurements. The flow is from right to left. The shape and location of each driver is shown on the far right of each image. The rectangle shown in each image represents the ejector diameter that was found experimentally to yield the highest thrust augmentation. It is apparent that the optimal ejector diameter is that which just "captures" the vortex: that is, the diameter bounding the outermost edge of the vortex structure. Although not shown, it was observed that the emitted vortex spread as it traveled downstream. The spreading rate for the pulsejet is shown as the dashed lines in the top image. A tapered ejector was fabricated that matched this shape. When tested, the ejector demonstrated superior performance to all those previously tested at Glenn (which were essentially of straight, cylindrical form), achieving a remarkable thrust augmentation of 2. The measured thrust augmentation is shown as a function of ejector length. Also shown are the thrust augmentation values achieved with the straight, cylindrical ejectors of varying diameters. Here, thrust augmentation is plotted as a function of ejector length for several families of ejector diameters. It can be seen that large thrust augmentation values are indeed obtained and that they are sensitive to both ejector length and diameter, particularly the latter. Five curves are shown. Four correspond to straight ejector diameters of 2.2, 3.0, 4.0, and 6.0 in. The fifth curve corresponds to the tapered ejector contoured to bound the emitted vortex. For each curve, there are several data points corresponding to different lengths. The largest value of thrust augmentation is 2.0 for the tapered ejector and 1.81 for the straight ejectors. Regardless of their diameters, all the ejectors trend toward peak performance at a particular leng. That the cross-sectional dimensions of optimal ejectors scaled precisely with the vortex dimensions on three separate pulsed thrust sources demonstrates that the action of the vortex is responsible for the enhanced ejector performance. The result also suggests that, in the absence of a complete understanding of the entrainment and augmentation mechanisms, methods of characterizing starting vortices may be useful for correlating and predicting unsteady ejector performance.

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

Investigation of Sustained Detonation Devices: the Pulse Detonation Engine-Crossover System and the Rotating Detonation Engine System

NASA Astrophysics Data System (ADS)

Driscoll, Robert B.

An experimental study is conducted on a Pulse Detonation Engine-Crossover System to investigate the feasibility of repeated, shock-initiated combustion and characterize the initiation performance. A PDE-crossover system can decrease deflagration-to-detonation transition length while employing a single spark source to initiate a multi-PDE system. Visualization of a transferred shock wave propagating through a clear channel reveals a complex shock train behind the leading shock. Shock wave Mach number and decay rate remains constant for varying crossover tube geometries and operational frequencies. A temperature gradient forms within the crossover tube due to forward flow of high temperature ionized gas into the crossover tube from the driver PDE and backward flow of ionized gas into the crossover tube from the driven PDE, which can cause intermittent auto-ignition of the driver PDE. Initiation performance in the driven PDE is strongly dependent on initial driven PDE skin temperature in the shock wave reflection region. An array of detonation tubes connected with crossover tubes is developed using optimized parameters and successful operation utilizing shock-initiated combustion through shock wave reflection is achieved and sustained. Finally, an air-breathing, PDE-Crossover System is developed to characterize the feasibility of shock-initiated combustion within an air-breathing pulse detonation engine. The initiation effectiveness of shock-initiated combustion is compared to spark discharge and detonation injection through a pre-detonator. In all cases, shock-initiated combustion produces improved initiation performance over spark discharge and comparable detonation transition run-up lengths relative to pre-detonator initiation. A computational study characterizes the mixing processes and injection flow field within a rotating detonation engine. Injection parameters including reactant flow rate, reactant injection area, placement of the fuel injection, and fuel injection distribution are varied to assess the impact on mixing. Decreasing reactant injection areas improves fuel penetration into the cross-flowing air stream, enhances turbulent diffusion of the fuel within the annulus, and increases local equivalence ratio and fluid mixedness. Staggering fuel injection holes produces a decrease in mixing when compared to collinear fuel injection. Finally, emulating nozzle integration by increasing annulus back-pressure increases local equivalence ratio in the injection region due to increased convection residence time.

Vacuum generation in pneumatic artificial heart drives with a specially designed ejector system.

PubMed

Schima, H; Huber, L; Spitaler, F

1990-06-01

To improve the filling characteristics of pneumatically driven membrane artificial hearts (AHs), a vacuum is applied during diastole. This paper describes an ejector system for AH-drivers based on the Venturi effect, which was designed for this purpose. It provides vacuums of more than -40 mmHg at flow rates up to 50 l/min requiring a supplying primary gas pressure of less than 150 kPa (1140 mmHg). Under normal working conditions, the necessary supply flow was less than 5l/min. The device is small, cheap, quiet and fail-safe, and has been evaluated successfully in experimental and clinical use.

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

Machinist's Mate 1 and C: Rate Training Manual.

ERIC Educational Resources Information Center

Naval Training Command, Pensacola, FL.

The rate training manual covers the duties required to efficiently operate and maintain ship propulsion machinery and associated equipment and to maintain applicable records and reports. Chapters cover: turbines; reduction gears; steam-driven generators; heat exchangers and air ejectors; pumps; piping and valves; distilling plants; refrigeration…

Novel PDE4 Inhibitors Derived from Chinese Medicine Forsythia

PubMed Central

Coon, Tiffany A.; McKelvey, Alison C.; Weathington, Nate M.; Birru, Rahel L.; Lear, Travis; Leikauf, George D.; Chen, Bill B.

2014-01-01

Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects. Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields. Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms. Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell. Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation. Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response. PMID:25549252

Performance tests of a two phase ejector

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

Harrell, G.S.; Kornhauser, A.A.

1995-12-31

The ejector expansion refrigeration cycle is a modified vapor compression cycle in which a two phase ejector is used to recover a portion of the work otherwise lost in the expansion valve. The ejector improves cycle performance by increasing compressor inlet pressure and by lowering the quality of liquid entering the evaporator. Theoretically, a cooling COP improvement of approximately 23% is achievable for a typical refrigerating cycle and an ideal ejector. If the ejector performed as well as typical single phase ejectors an improvement of 12% could be achieved. Previous tests have demonstrated a smaller 3.7% improvement; the difference ismore » in the poor performance of the two phase ejector. The purpose of this research is to understand the operating characteristics of the two phase ejector and to devise design improvements. A two phase ejector test rig has been constructed and tested. Preliminary data show performance superior to previously tested two phase ejectors, but still inferior to single phase ejectors. Ejector performance corresponds to refrigeration cycle COP improvements ranging from 3.9% to 7.6%.« less

2. Credit BG. Looking west at east facade of Steam ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Credit BG. Looking west at east facade of Steam Generator Plant, Building 4280/E-81; steam generators have been removed as part of dismantling program for Test Stand 'D.' Metal cylindrical objects to left of door were roof vents. The steam-driven ejector system for Dv Cell is clearly visible on the east side of Test Stand 'D' tower. The X-stage ejector is vertically installed at the bottom left of the tower, Y-stage is horizontally positioned close to the tower top, and the Z- and Z-1 stages are attached to the top of the interstage condenser. Light-colored piping is thermally insulated steam line. - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Steam Generator Plant, Edwards Air Force Base, Boron, Kern County, CA

Credit BG. View looking northeast down from the tower onto ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit BG. View looking northeast down from the tower onto the two horizontal test stations at Test Stand "D." Station Dy is at the far left (Dy vacuum cell out of view), with in-line exhaust gas cooling sections and steam-driven "air ejector" (or evacuator) discharging engine exhausts to the east. The Dd cell is visible at the lower left, and the Dd exhaust train has the same functions as at Dy. The spherical tank is an electrically heated "accumulator" which supplies steam to the ejectors at Dv, Dd, and Dy stations. Other large piping delivered cooling water to the horizontal train cooling sections. The horizontal duct at the "Y" branch in the Dd train connects the Dd ejector to the Dv and Cv vacuum duct system (a blank can be bolted into this duct to isolate the Dd system). The shed roof for the Dpond test station appears at bottom center of this image. The open steel frame to the lower left of the image supports a hoist and crane for installing or removing test engines from the Dd test cell - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Driven exercise in the absence of binge eating: Implications for purging disorder.

PubMed

Lydecker, Janet A; Shea, Megan; Grilo, Carlos M

2018-02-01

Purging disorder (PD) is characterized by recurrent purging without objectively large binge-eating episodes. PD has received relatively little attention, and questions remain about the clinical significance of "purging" by exercise that is driven or compulsive (i.e., as extreme compensatory or weight-control behavior). The little available research suggests that individuals who use exercise as a compensatory behavior might have less eating-disorder psychopathology than those who purge by vomiting or laxatives, but those studies have had smaller sample sizes, defined PD using low-frequency thresholds, and defined exercise without weight-compensatory or driven elements. Participants (N = 2,017) completed a web-based survey with established measures of eating-disorder psychopathology, depression, and physical activity. Participants were categorized (regular compensatory driven exercise, PD-E, n = 297; regular compensatory vomiting/laxatives, PD-VL, n = 59; broadly defined anorexia nervosa, AN, n = 20; and no eating-disordered behaviors, NED, n = 1,658) and compared. PD-E, PD-VL, and AN had higher eating-disorder psychopathology and physical activity than NED but did not significantly differ from each other on most domains. PD-VL and AN had higher depression than PD-E, which was higher than NED. Findings suggest that among participants with regularly compensatory behaviors without binge eating, those who use exercise alone have similar levels of associated eating-disorder psychopathology as those who use vomiting/laxatives, although they have lower depression levels and overall frequency of purging. Findings provide further support for the clinical significance of PD. Clinicians and researchers should recognize the severity of driven exercise as a compensatory behavior, and the need for further epidemiological and treatment research. © 2017 Wiley Periodicals, Inc.

Development of dry coal feeders

NASA Technical Reports Server (NTRS)

Bonin, J. H.; Cantey, D. E.; Daniel, A. D., Jr.; Meyer, J. W.

1977-01-01

Design and fabrication of equipment of feed coal into pressurized environments were investigated. Concepts were selected based on feeder system performance and economic projections. These systems include: two approaches using rotating components, a gas or steam driven ejector, and a modified standpipe feeder concept. Results of development testing of critical components, design procedures, and performance prediction techniques are reviewed.

Parametric Investigation of Thrust Augmentation by Ejectors on a Pulsed Detonation Tube

NASA Technical Reports Server (NTRS)

Wilson, Jack; Sgondea, Alexandru; Paxson, Daniel E.; Rosenthal, Bruce N.

2006-01-01

A parametric investigation has been made of thrust augmentation of a 1 in. diameter pulsed detonation tube by ejectors. A set of ejectors was used which permitted variation of the ejector length, diameter, and nose radius, according to a statistical design of experiment scheme. The maximum augmentation ratios for each ejector were fitted using a polynomial response surface, from which the optimum ratios of ejector diameter to detonation tube diameter, and ejector length and nose radius to ejector diameter, were found. Thrust augmentation ratios above a factor of 2 were measured. In these tests, the pulsed detonation device was run on approximately stoichiometric air-hydrogen mixtures, at a frequency of 20 Hz. Later measurements at a frequency of 40 Hz gave lower values of thrust augmentation. Measurements of thrust augmentation as a function of ejector entrance to detonation tube exit distance showed two maxima, one with the ejector entrance upstream, and one downstream, of the detonation tube exit. A thrust augmentation of 2.5 was observed using a tapered ejector.

Unsteady Ejector Performance: An Experimental Investigation Using a Resonance Tube Driver

NASA Technical Reports Server (NTRS)

Wilson, Jack; Paxson, Daniel E.

2002-01-01

A statistically designed experiment to characterize thrust augmentation for unsteady ejectors has been conducted at the NASA Glenn Research Center. The variable parameters included ejector diameter, length, and nose radius. The pulsed jet driving the ejectors was produced by a shrouded resonance (or Hartmann-Sprenger) tube. In contrast to steady ejectors, an optimum ejector diameter was found, which coincided with the diameter of the vortex ring created at the pulsed jet exit. Measurements of ejector exit velocity using a hot-wire permitted evaluation of the mass augmentation ratio, which was found to correlate to thrust augmentation following a formula derived for steady ejectors.

A new methodology for sizing and performance predictions of a rotary wing ejector

NASA Astrophysics Data System (ADS)

Moodie, Alex Montfort

The application of an ejector nozzle integrated with a reaction drive rotor configuration for a vertical takeoff and landing rotorcraft is considered in this research. The ejector nozzle is a device that imparts energy from a high speed airflow source to a lower speed secondary airflow inside a duct. The overall nozzle exhaust mass flow rate is increased through fluid entrainment, while the exhaust gas velocity is simultaneously decreased. The exhaust gas velocity is strongly correlated to the jet noise produced by the nozzle, making the ejector a good candidate for propulsion system noise reduction. Ejector nozzles are mechanically simple in that there are no moving parts. However, coupled fluid dynamic processes are involved, complicating analysis and design. Geometric definitions of the ejector nozzle are determined through a reduced fidelity, multi-disciplinary, representation of the rotary wing ejector. The resulting rotary wing ejector geometric sizing procedure relates standard vehicle and rotor design parameters to the ejector. Additionally, a rotary wing ejector performance procedure is developed to compare this rotor configuration to a conventional rotor. Performance characteristics and aerodynamic effects of the rotor and ejector nozzle are analytically studied. Ejector nozzle performance, in terms of exit velocities, is compared to the primary reaction drive nozzle; giving an indication of the potential for noise reduction. Computational fluid dynamics are paramount in predicting the aerodynamic effects of the ejector nozzle located at the rotor blade tip. Two-dimensional, steady-state, Reynolds-averaged Navier-Stokes (RANS) models are implemented for sectional lift and drag predictions required for the rotor aerodynamic model associated with both the rotary wing ejector sizing and performance procedures. A three-dimensional, unsteady, RANS simulation of the rotary wing ejector is performed to study the aerodynamic interactions between the ejector nozzle and rotor. Overall performance comparisons are made between the two- and three-dimensional models of the rotary wing ejector, and a similar conventional rotor.

Application of thrusting ejectors to tactical aircraft having vertical lift and short-field capability

NASA Technical Reports Server (NTRS)

Koenig, D. G.; Stoll, F.; Aoyagi, K.

1981-01-01

The status of ejector development in terms of application to V/STOL aircraft is reported in three categories: aircraft systems and ejector concepts; ejector performance including prediction techniques and experimental data base available; and, integration of the ejector with complete aircraft configurations. Available prediction techniques are reviewed and performance of three ejector designs with vertical lift capability is summarized. Applications of the 'fuselage' and 'short diffuser' ejectors to fighter aircraft are related to current and planned research programs. Recommendations are listed for effort needed to evaluate installed performance.

Steam jet ejectors for the process industries. [Glossary included

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

Power, R.B.

1994-01-01

Steam jet ejectors were for many years the workhorse of the chemical process industries for producing vacuum. With increasing emphasis on stricter pollution control, their use was curtailed. There are still many applications, however, such as those with large capacity requirements, where ejectors are the only equipment that can produce sufficient vacuum. Chapter 1 is a short overview on how to use the text. Chapter 2 discusses what an ejector is and how it works. How ejector stages work is reviewed in Chapter 3. Engineering calculations for ejector stages is thoroughly discussed in Chapter 4. In Chapter 5, contact andmore » surface condensers are reviewed, and calculation procedures are presented. The various types of pressure control are discussed in Chapter 6. Chapter 7 is an excellent review of installation of ejector vacuum systems. The final chapter of Part 2 (Chapters 3--8) thoroughly covers all aspects of operation, testing, troubleshooting and maintenance. Part 3, consisting of two chapters, is devoted to specifying and purchasing steam jet ejectors. Part 4 on other ejector applications and upgrading ejector usage also consists of two chapters. Chapter 11 reviews steam-jet refrigeration, steam-jet and gas-jet compressors, liquid jet eductors, desuperheaters, special design situations, and designing one's own systems. Upgrading of existing ejector procedures and hardware is reviewed in Chapter 12. The 12 appendixes cover: physical properties of common fluids; handy vacuum engineering data and rules of thumb; SI unit conversions; sizing air and steam metering orifices for testing; drill sizes; ejector operating costs and design optimization; forms for ejector calculations, tests, and inspections; instructions for preparing ejector specifications; test kit contents list; ejector manufacturers and suppliers of referenced hardware and information; and failure modes and symptoms.« less

13. Coal ejectors mounted on aft bulkhead of coal bunker. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. Coal ejectors mounted on aft bulkhead of coal bunker. Ejectors were used to flush overboard live coals and clinkers from firebed (pipe for carrying coals overboard has been removed from ejector in foreground). Coal doors from bunker appear beside ejector in foreground). Coal doors from bunker appear beside ejectors at deck; note firing shovels in background against hull. - Steamboat TICONDEROGA, Shelburne Museum Route 7, Shelburne, Chittenden County, VT

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.

Parallel Work of CO2 Ejectors Installed in a Multi-Ejector Module of Refrigeration System

NASA Astrophysics Data System (ADS)

Bodys, Jakub; Palacz, Michal; Haida, Michal; Smolka, Jacek; Nowak, Andrzej J.; Banasiak, Krzysztof; Hafner, Armin

2016-09-01

A performance analysis on of fixed ejectors installed in a multi-ejector module in a CO2 refrigeration system is presented in this study. The serial and the parallel work of four fixed-geometry units that compose the multi-ejector pack was carried out. The executed numerical simulations were performed with the use of validated Homogeneous Equilibrium Model (HEM). The computational tool ejectorPL for typical transcritical parameters at the motive nozzle were used in all the tests. A wide range of the operating conditions for supermarket applications in three different European climate zones were taken into consideration. The obtained results present the high and stable performance of all the ejectors in the multi-ejector pack.

Aeroacoustic Characteristics of a Rectangular Multi-Element Supersonic Jet Mixer-Ejector Nozzle

NASA Technical Reports Server (NTRS)

Raman, Ganesh; Taghavi, Ray

1996-01-01

This paper provides a unique, detailed evaluation of the acoustics and aerodynamics of a rectangular multi-element supersonic jet mixer-ejector noise suppressor. The performance of such mixer-ejectors is important in aircraft engine application for noise suppression and thrust augmentation. In contrast to most prior experimental studies on ejectors that reported either aerodynamic or acoustic data, our work documents both types of data. We present information on the mixing, pumping, ejector wall pressure distribution, thrust augmentation and noise suppression characteristics of four simple, multi-element, jet mixer-ejector configurations. The four configurations included the effect of ejector area ratio (AR = ejector area/primary jet area) and the effect of non-parallel ejector walls. We also studied in detail the configuration that produced the best noise suppression characteristics. Our results show that ejector configurations that produced the maximum maximum pumping (entrained flow per secondary inlet area) also exhibited the lowest wall pressures in the inlet region, and the maximum thrust augmentation. When cases having the same total mass flow were compared, we found that noise suppression trends corresponded with those for pumping. Surprisingly, the mixing (quantified by the peak Mach number, and flow uniformity) at the ejector exit exhibited no relationship to the noise suppression at moderate primary jet fully expanded Mach numbers (Mj is less than 1.4). However, the noise suppression dependence on the mixing was apparent at higher Mj. The above observations are justified by noting that the mixing at the ejector exit is ot a strong factor in determining the radiated noise when noise produced internal to the ejector dominates the noise field outside the ejector.

Subsonic Performance of Ejector Systems

NASA Astrophysics Data System (ADS)

Weil, Samuel

Combined cycle engines combining scramjets with turbo jets or rockets can provide efficient hypersonic flight. Ejectors have the potential to increase the thrust and efficiency of combined cycle engines near static conditions. A computer code was developed to support the design of a small-scale, turbine-based combined cycle demonstrator with an ejector, built around a commercially available turbojet engine. This code was used to analyze the performance of an ejector system built around a micro-turbojet. With the use of a simple ejector, net thrust increases as large as 20% over the base engine were predicted. Additionally the specific fuel consumption was lowered by 10%. Increasing the secondary to primary area ratio of the ejector lead to significant improvements in static thrust, specific fuel consumption (SFC), and propulsive efficiency. Further ejector performance improvements can be achieved by using a diffuser. Ejector performance drops off rapidly with increasing Mach number. The ejector has lower thrust and higher SFC than the turbojet core at Mach numbers above 0.2. When the nozzle chokes a significant drop in ejector performance is seen. When a diffuser is used, higher Mach numbers lead to choking in the mixer and a shock in the nozzle causing a significant decrease in ejector performance. Evaluation of different turbo jets shows that ejector performance depends significantly on the properties of the turbojet. Static thrust and SFC improvements can be achieved with increasing ejector area for all engines, but size of increase and change in performance at higher Mach numbers depend heavily on the turbojet. The use of an ejector in a turbine based combined cycle configuration also increases performance at static conditions with a thrust increase of 5% and SFC decrease of 5% for the tested configuration.

A geometric level set model for ultrasounds analysis

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

Sarti, A.; Malladi, R.

We propose a partial differential equation (PDE) for filtering and segmentation of echocardiographic images based on a geometric-driven scheme. The method allows edge-preserving image smoothing and a semi-automatic segmentation of the heart chambers, that regularizes the shapes and improves edge fidelity especially in presence of distinct gaps in the edge map as is common in ultrasound imagery. A numerical scheme for solving the proposed PDE is borrowed from level set methods. Results on human in vivo acquired 2D, 2D+time,3D, 3D+time echocardiographic images are shown.

Self-focused acoustic ejectors for viscous liquids.

PubMed

Hon, S F; Kwok, K W; Li, H L; Ng, H Y

2010-06-01

Self-focused acoustic ejectors using the Fresnel zone plate (FZP) have been developed for ejecting viscous liquids, without nozzle, in the drop-on-demand mode. The FZP is composed of a lead zirconate titanate piezoelectric plate patterned with a series of annular electrodes, with the unelectroded region of the plate removed. Our results show that the acoustic waves are effectively self-focused by constructive interference in glycerin (with a viscosity of 1400 mPa s), giving small focal points with a high pressure. Due to the high attenuation, the wave pressure decreases significantly with the distance from the FZP. Nevertheless, the pressure at the focal points 2.5 and 6.5 mm from the FZP is high enough to eject glycerin droplets in the drop-on-demand mode. Driven by a simple wave train comprising a series of sinusoidal voltages with an amplitude of 35 V, a frequency of 4.28 MHz, and a duration of 2 ms, the ejector can eject fine glycerin droplets with a diameter of 0.4 mm at a repetition frequency of 120 Hz in a downward direction. Droplets of other viscous liquids, such as the prepolymer of an epoxy with a viscosity of 2000 mPa s, can also be ejected in the drop-on-demand mode under similar conditions.

Parametric Investigation of Thrust Augmentation by Ejectors on a Pulsed Detonation Tube

NASA Technical Reports Server (NTRS)

Wilson, Jack; Sgondea, Alexandru; Paxson, Daniel E.; Rosenthal, Bruce N.

2005-01-01

A parametric investigation has been made of thrust augmentation of a 1 inch diameter pulsed detonation tube by ejectors. A set of ejectors was used which permitted variation of the ejector length, diameter, and nose radius, according to a statistical design of experiment scheme. The maximum augmentations for each ejector were fitted using a polynomial response surface, from which the optimum ejector diameters, and nose radius, were found. Thrust augmentations above a factor of 2 were measured. In these tests, the pulsed detonation device was run on approximately stoichiometric air-hydrogen mixtures, at a frequency of 20 Hz. Later measurements at a frequency of 40 Hz gave lower values of thrust augmentation. Measurements of thrust augmentation as a function of ejector entrance to detonation tube exit distance showed two maxima, one with the ejector entrance upstream, and one downstream, of the detonation tube exit. A thrust augmentation of 2.5 was observed using a tapered ejector.

DTNSRDC Library Subject Thesaurus.

DTIC Science & Technology

1980-03-01

COLLISIONS BISTATIC SONAR BT SONAR BIRDS BT VERTEBRATES BITES AND STINGS NT CHICKENS BT WOUNDS AND INJURIES DUCKS GEESE BITUMENS GULLS ST ORGANIC...NT DECAPODA EL SALVADOR GUATEMALA CEPSTRUM TECHNIQUE HONDURAS MEXICO CERAMIC BODIES NICARAGUA RT BODIES PANAMA CERAMIC BONDING CENTRAL EUROPE BT...EJECTORS E EJECTORS(ORDNANCE) EGG ALBUMIN BT ALBUMINS EJECTORS(DRONANCE) BT EJECTORS EGG FO0 YOUNG NT BOMB EJECTORS USE EGGS( CHICKEN ) AND COO

Recent developments in ejector technology in the Air Force: An overview

NASA Technical Reports Server (NTRS)

Nagaraja, K. S.

1979-01-01

Basic and applied studies in thrust augmentation conducted at the Aerospace Research Laboratory at Wright-Patterson AFB which led to an effective configuration of the jet flap diffuser ejector, are reviewed. A method for compressible ejector flow analysis, developed in support of the preliminary design of an ejector thrust aircraft, is discussed and applied to single- and two-stage ejectors.

Design of an air ejector for boundary-layer bleed of an acoustically treated turbofan engine inlet during ground testing

NASA Technical Reports Server (NTRS)

Stakolich, E. G.

1978-01-01

An air ejector was designed and built to remove the boundary-layer air from the inlet a turbofan engine during an acoustic ground test program. This report describes; (1) how the ejector was sized; (2) how the ejector performed; and (3) the performance of a scale model ejector built and tested to verify the design. With proper acoustic insulation, the ejector was effective in reducing boundary layer thickness in the inlet of the turbofan engine while obtaining the desired acoustic test conditions.

Analysis of a domestic refrigerator cycle with an ejector

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

Tomasek, M.L.; Radermacher, R.

1995-08-01

In this paper, an improved cooling cycle for a conventional domestic refrigerator-freezer utilizing an ejector for vapor precompression is analyzed using an idealized model Its energy efficiency is compared to that of the conventional refrigerator-freezer system. Emphasis is placed on off-design conditions. The ejector-enhanced refrigeration cycle consists of two evaporators that operate at different pressure and temperature levels. The ejector combines the vapor flows exiting the two evaporators into one at an intermediate pressure level The ejector cycle gives an increase of up to 12.4% in the coefficient of performance (COP) compared to that of a standard refrigerator-freezer refrigeration cycle.more » The analysis includes calculations on the optimum throat diameters of the ejector. The investigation on the off-design performance of the ejector cycle shows little dependency of energy consumption on constant ejector throat diameters.« less

Internal performance characteristics of vectored axisymmetric ejector nozzles

NASA Technical Reports Server (NTRS)

Lamb, Milton

1993-01-01

A series of vectoring axisymmetric ejector nozzles were designed and experimentally tested for internal performance and pumping characteristics at NASA-Langley Research Center. These ejector nozzles used convergent-divergent nozzles as the primary nozzles. The model geometric variables investigated were primary nozzle throat area, primary nozzle expansion ratio, effective ejector expansion ratio (ratio of shroud exit area to primary nozzle throat area), ratio of minimum ejector area to primary nozzle throat area, ratio of ejector upper slot height to lower slot height (measured on the vertical centerline), and thrust vector angle. The primary nozzle pressure ratio was varied from 2.0 to 10.0 depending upon primary nozzle throat area. The corrected ejector-to-primary nozzle weight-flow ratio was varied from 0 (no secondary flow) to approximately 0.21 (21 percent of primary weight-flow rate) depending on ejector nozzle configuration. In addition to the internal performance and pumping characteristics, static pressures were obtained on the shroud walls.

Efficiency Enhancement of Chiller and Heat Pump Using Natural Working Fluids with Two-phase Flow Ejector

NASA Astrophysics Data System (ADS)

Yoshikawa, Choiku; Hattori, Kazuhiro; Jeong, Jongsoo; Saito, Kiyoshi; Kawai, Sunao

An ejector can transform the expansion energy of the driving flow into the pressure build-up energy of the suction flow. Therefore, by utilizing the ejector instead of the expansion valve for the vapor compression cycle, the performance of the cycle can be greatly improved. Until now, the performance of the vapor compression cycle with the ejector has not been examined sufficiently. Therefore, this paper constructs the simulation model of the vapor compression cycle with the ejector and investigates the performance of that cycle by the simulation. Working fluids are ammonia and CO2. As a result, in case of the ejector efficiency 90%, COP of the vapor compression cycle using ammonia with the ejector is 5% higher than that of the conventional cycle and COP using CO2 with the ejector is 22% higher than that of the conventional cycle.

Internal-Performance Evaluation of Two Fixed-Divergent-Shroud Ejectors

NASA Technical Reports Server (NTRS)

Mihaloew, James R.

1960-01-01

Ejectors designed for use in a Mach 2.2 aircraft were evaluated over a range of representative primary pressure ratios and ejector corrected weight-flow ratios. Basic thrust and pumping characteristics are discussed in terms of an assumed engine operating schedule to illustrate the variation of performance with Mach number. The two designs differed about 16 percent in the shroud longitudinal spacing ratio. For corrected ejector weight-flow ratios up to 0.10, the performance of the fixed-shroud ejector designs is comparable with that of a similar continuously variable ejector except at conditions corresponding to acceleration with afterburning from Mach 0.4 to 1.2. In this region, the ejector thrust ratio decreased to a minimum of 0.96.

Viscid/inviscid interaction analysis of thrust augmenting ejectors

NASA Technical Reports Server (NTRS)

Bevilacqua, P. M.; Dejoode, A. D.

1979-01-01

A method was developed for calculating the static performance of thrust augmenting ejectors by matching a viscous solution for the flow through the ejector to an inviscid solution for the flow outside the ejector. A two dimensional analysis utilizing a turbulence kinetic energy model is used to calculate the rate of entrainment by the jets. Vortex panel methods are then used with the requirement that the ejector shroud must be a streamline of the flow induced by the jets to determine the strength of circulation generated around the shroud. In effect, the ejector shroud is considered to be flying in the velocity field of the jets. The solution is converged by iterating between the rate of entrainment and the strength of the circulation. This approach offers the advantage of including external influences on the flow through the ejector. Comparisons with data are presented for an ejector having a single central nozzle and Coanda jet on the walls. The accuracy of the matched solution is found to be especially sensitive to the jet flap effect of the flow just downstream of the ejector exit.

Vapor Jet Ejector Used to Generate Free Waste Heat Driven Cooling in Military Environmental Cooling Units

DTIC Science & Technology

2012-07-01

vap erant vapor is or by a J-tub essure side of using similar pressure incre ump in order o the diesel-e per heat excha recovered at to the exhaus...top of the a tering the com at exchanger. g of the conve id flow. A nit essure pulsati tor where the ed in the cool erature level. ger where wa

Ejector device for direct injection fuel jet

DOEpatents

Upatnieks, Ansis [Livermore, CA

2006-05-30

Disclosed is a device for increasing entrainment and mixing in an air/fuel zone of a direct fuel injection system. The device comprises an ejector nozzle in the form of an inverted funnel whose central axis is aligned along the central axis of a fuel injector jet and whose narrow end is placed just above the jet outlet. It is found that effective ejector performance is achieved when the ejector geometry is adjusted such that it comprises a funnel whose interior surface diverges about 7.degree. to about 9.degree. away from the funnel central axis, wherein the funnel inlet diameter is about 2 to about 3 times the diameter of the injected fuel plume as the fuel plume reaches the ejector inlet, and wherein the funnel length equal to about 1 to about 4 times the ejector inlet diameter. Moreover, the ejector is most effectively disposed at a separation distance away from the fuel jet equal to about 1 to about 2 time the ejector inlet diameter.

Internal-external flow integration for a thin ejector-flapped wing section

NASA Technical Reports Server (NTRS)

Woolard, H. W.

1979-01-01

Thin airfoil theories of an ejector flapped wing section are reviewed. The global matching of the external airfoil flow with the ejector internal flow and the overall ejector flapped wing section aerodynamic performance are examined. Mathematical models of the external and internal flows are presented. The delineation of the suction flow coefficient characteristics are discussed. The idealized lift performance of an ejector flapped wing relative to a jet augmented flapped wing are compared.

Fluid channeling system

NASA Technical Reports Server (NTRS)

Davis, Donald Y. (Inventor); Hitch, Bradley D. (Inventor)

1994-01-01

A fluid channeling system includes a fluid ejector, a heat exchanger, and a fluid pump disposed in series flow communication The ejector includes a primary inlet for receiving a primary fluid, and a secondary inlet for receiving a secondary fluid which is mixed with the primary fluid and discharged therefrom as ejector discharge. Heat is removed from the ejector discharge in the heat exchanger, and the heat exchanger discharge is compressed in the fluid pump and channeled to the ejector secondary inlet as the secondary fluid In an exemplary embodiment, the temperature of the primary fluid is greater than the maximum operating temperature of a fluid motor powering the fluid pump using a portion of the ejector discharge, with the secondary fluid being mixed with the primary fluid so that the ejector discharge temperature is equal to about the maximum operating temperature of the fluid motor.

Entrainment and thrust augmentation in pulsatile ejector flows

NASA Technical Reports Server (NTRS)

Sarohia, V.; Bernal, L.; Bui, T.

1981-01-01

This study comprised direct thrust measurements, flow visualization by use of a spark shadowgraph technique, and mean and fluctuating velocity measurements with a pitot tube and linearized constant temperature hot-wire anemometry respectively. A gain in thrust of as much as 10 to 15% was observed for the pulsatile ejector flow as compared to the steady flow configuration. From the velocity profile measurements, it is concluded that this enhanced augmentation for pulsatile flow as compared to a nonpulsatile one was accomplished by a corresponding increased entrainment by the primary jet flow. It is also concluded that the augmentation and total entrainment by a constant area ejector critically depends upon the inlet geometry of the ejector. Experiments were performed to evaluate the influence of primary jet to ejector area ratio, ejector length, and presence of a diffuser on pulsatile ejector performance.

A cold ejector for closed-cycle helium refrigerators

NASA Technical Reports Server (NTRS)

Johnson, D. L.; Daggett, D. L.

1987-01-01

The test results are presented of an initial cold helium ejector design that can be installed on a closed cycle refrigerator to provide refrigeration at temperatures below 4.2 K. The ejector, test apparatus, instrumentation, and test results are described. Tests were conducted both at room temperature and at cryogenic temperatures to provide operational experience with the ejector as well as for future use in the subsequent design of an ejector that will provide refrigeration at temperatures below 3 K.

Design and test of a prototype scale ejector wing

NASA Technical Reports Server (NTRS)

Mefferd, L. A.; Alden, R. E.; Bevilacqua, P. M.

1979-01-01

A two dimensional momentum integral analysis was used to examine the effect of changing inlet area ratio, diffuser area ratio, and the ratio of ejector length to width. A relatively wide range of these parameters was considered. It was found that for constant inlet area ratio the augmentation increases with the ejector length, and for constant length: width ratio the augmentation increases with inlet area ratio. Scale model tests were used to verify these trends and to examine th effect of aspect ratio. On the basis of these results, an ejector configuration was selected for fabrication and testing at a scale representative of an ejector wing aircraft. The test ejector was powered by a Pratt-Whitney F401 engine developing approximately 12,000 pounds of thrust. The results of preliminary tests indicate that the ejector develops a thrust augmentation ratio better than 1.65.

Experiments on high speed ejectors

NASA Technical Reports Server (NTRS)

Wu, J. J.

1986-01-01

Experimental studies were conducted to investigate the flow and the performance of thrust augmenting ejectors for flight Mach numbers in the range of 0.5 to 0.8, primary air stagnation pressures up to 107 psig (738 kPa), and primary air stagnation temperatures up to 1250 F (677 C). The experiment verified the existence of the second solution ejector flow, where the flow after complete mixing is supersonic. Thrust augmentation in excess of 1.2 was demonstrated for both hot and cold primary jets. The experimental ejector performed better than the corresponding theoretical optimal first solution ejector, where the mixed flow is subsonic. Further studies are required to realize the full potential of the second solution ejector. The research program was started by the Flight Dynamics Research Corporation (FDRC) to investigate the characteristic of a high speed ejector which augments thrust of a jet at high flight speeds.

An experimental investigation of two-dimensional thrust augmenting ejectors, part 2

NASA Technical Reports Server (NTRS)

Bernal, L.; Sarohia, V.

1984-01-01

The flow-field within a two-dimensional thrust augmenting ejector has been documented experimentally. Results are presented on the mean velocity field and the turbulent correlations by Laser Doppler Velocimeter, surface pressure distribution, surface temperature distribution, and thrust performance for two shroud geometries. The maximum primary nozzle pressure ratio tested was 3.0. The tests were conducted at primary nozzle temperature ratios of 1.0, 1.8 and 2.7. Two ejector characteristic lengths have been identified based on the dynamics of the ejector flow field, i.e., a minimum length L sub m below which no significant mixing occurs, and a critical length L sub c associated with the development of U'V' correlation in the ejector. These characteristic lengths divide the ejector flow field into three distinctive regions: the entrance region where there is no direct interaction between the primary flow and the ejector shroud; the interaction region where there is an increased momentum of induced flow near the shroud surface; and a pipe flow region characterized by an increased skin friction where x is the distance downstream from the ejector inlet. The effect of the coflowing induced flow has been shown to produce inside the ejector a centerline velocity that has increased over the free-jet data.

Pulsed Ejector Thrust Amplification Tested and Modeled

NASA Technical Reports Server (NTRS)

Wilson, Jack

2004-01-01

There is currently much interest in pulsed detonation engines for aeronautical propulsion. This, in turn, has sparked renewed interest in pulsed ejectors to increase the thrust of such engines, since previous, though limited, research had indicated that pulsed ejectors could double the thrust in a short device. An experiment has been run at the NASA Glenn Research Center, using a shrouded Hartmann-Sprenger tube as a source of pulsed flow, to measure the thrust augmentation of a statistically designed set of ejectors. A Hartmann- Sprenger tube directs the flow from a supersonic nozzle (Mach 2 in the present experiment) into a closed tube. Under appropriate conditions, an oscillation is set up in which the jet flow alternately fills the tube and then spills around flow emerging from the tube. The tube length determines the frequency of oscillation. By shrouding the tube, the flow was directed out of the shroud as an axial stream. The set of ejectors comprised three different ejector lengths, three ejector diameters, and three nose radii. The thrust of the jet alone, and then of the jet plus ejector, was measured using a thrust plate. The arrangement is shown in this photograph. Thrust augmentation is defined as the thrust of the jet with an ejector divided by the thrust of the jet alone. The experiments exhibited an optimum ejector diameter and length for maximizing the thrust augmentation, but little dependence on nose radius. Different frequencies were produced by changing the length of the Hartmann-Sprenger tube, and the experiment was run at a total of four frequencies. Additional measurements showed that the major feature of the pulsed jet was a starting vortex ring. The size of the vortex ring depended on the frequency, as did the optimum ejector diameter.

Ejectors of power plants turbine units efficiency and reliability increasing

NASA Astrophysics Data System (ADS)

Aronson, K. E.; Ryabchikov, A. Yu.; Kuptsov, V. K.; Murmanskii, I. B.; Brodov, Yu. M.; Zhelonkin, N. V.; Khaet, S. I.

2017-11-01

The functioning of steam turbines condensation systems influence on the efficiency and reliability of a power plant a lot. At the same time, the condensation system operating is provided by basic ejectors, which maintain the vacuum level in the condenser. Development of methods of efficiency and reliability increasing for ejector functioning is an actual problem of up-to-date power engineering. In the paper there is presented statistical analysis of ejector breakdowns, revealed during repairing processes, the influence of such damages on the steam turbine operating reliability. It is determined, that 3% of steam turbine equipment breakdowns are the ejector breakdowns. At the same time, about 7% of turbine breakdowns are caused by different ejector malfunctions. Developed and approved design solutions, which can increase the ejector functioning indexes, are presented. Intercoolers are designed in separated cases, so the air-steam mixture can’t move from the high-pressure zones to the low-pressure zones and the maintainability of the apparatuses is increased. By U-type tubes application, the thermal expansion effect of intercooler tubes is compensated and the heat-transfer area is increased. By the applied nozzle fixing construction, it is possible to change the distance between a nozzle and a mixing chamber (nozzle exit position) for operating performance optimization. In operating conditions there are provided experimental researches of more than 30 serial ejectors and also high-efficient 3-staged ejector EPO-3-80, designed by authors. The measurement scheme of the designed ejector includes 21 indicator. The results of experimental tests with different nozzle exit positions of the ejector EPO-3-80 stream devices are presented. The pressure of primary stream (water steam) is optimized. Experimental data are well-approved by the calculation results.

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

A model for prediction of STOVL ejector dynamics

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1989-01-01

A semi-empirical control-volume approach to ejector modeling for transient performance prediction is presented. This new approach is motivated by the need for a predictive real-time ejector sub-system simulation for Short Take-Off Verticle Landing (STOVL) integrated flight and propulsion controls design applications. Emphasis is placed on discussion of the approximate characterization of the mixing process central to thrust augmenting ejector operation. The proposed ejector model suggests transient flow predictions are possible with a model based on steady-flow data. A practical test case is presented to illustrate model calibration.

An experimental study of a three-dimensional thrust augmenting ejector using laser Doppler velocimetry

NASA Technical Reports Server (NTRS)

Storms, Bruce Lowell

1989-01-01

Flow field measurements were obtained in a three-dimensional thrust augmenting ejector using laser Doppler velocimetry and hot wire anemometry. The primary nozzle, segmented into twelve slots of aspect ratio 3.0, was tested at a pressure ratio of 1.15. Results are presented on the mean velocity, turbulence intensity, and Reynolds stress progressions in the mixing chamber of the constant area ejector. The segmented nozzle was found to produce streamwise vortices that may increase the mixing efficiency of the ejector flow field. Compared to free jet results, the jet development is reduced by the presence of the ejector walls. The resulting thrust augmentation ratio of this ejector was also calculated to be 1.34.

Highly Variable Cycle Exhaust Model Test (HVC10)

NASA Technical Reports Server (NTRS)

Henderson, Brenda; Wernet, Mark; Podboy, Gary; Bozak, Rick

2010-01-01

Results from acoustic and flow-field studies using the Highly Variable Cycle Exhaust (HVC) model were presented. The model consisted of a lobed mixer on the core stream, an elliptic nozzle on the fan stream, and an ejector. For baseline comparisons, the fan nozzle was replaced with a round nozzle and the ejector doors were removed from the model. Acoustic studies showed far-field noise levels were higher for the HVC model with the ejector than for the baseline configuration. Results from Particle Image Velocimetry (PIV) studies indicated that large flow separation regions occurred along the ejector doors, thus restricting flow through the ejector. Phased array measurements showed noise sources located near the ejector doors for operating conditions where tones were present in the acoustic spectra.

Credit BG. View looking northeast at southwestern side of Test ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit BG. View looking northeast at southwestern side of Test Stand "D" complex. Test Stand "D" workshop (Building 4222/E-23) is at left; shed to its immediate right is an entrance to underground tunnel system which interconnects all test stands. To the right of Test Stand "D" tower are four Clayton water-tube flash boilers once used in the Steam Generator Plant 4280/E-81 to power the vacuum ejector system at "D" and "C" stands. A corner of 4280/E-81 appears behind the boilers. Boilers were removed as part of stand dismantling program. The Dv (vertical vacuum) Test Cell is located in the Test Stand "D" tower, behind the sunscreen on the west side. The top of the tower contains a hoist for lifting or lowering rocket engines into the Dv Cell. Other equipment mounted in the tower is part of the steam-driven vacuum ejector system - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

The Nozzle Acoustic Test Rig: an Acoustic and Aerodynamic Free-jet Facility

NASA Technical Reports Server (NTRS)

Castner, Raymond S.

1994-01-01

The nozzle acoustic test rig (NATR) was built at NASA Lewis Research Center to support the High Speed Research Program. The facility is capable of measuring the acoustic and aerodynamic performance of aircraft engine nozzle concepts. Trade-off studies are conducted to compare performance and noise during simulated low-speed flight and takeoff. Located inside an acoustically treated dome with a 62-ft radius, the NATR is a free-jet that has a 53-in. diameter and is driven by an air ejector. This ejector is operated with 125 lb/s of compressed air, at 125 psig, to achieve 375 lb/s at Mach 0.3. Acoustic and aerodynamic data are collected from test nozzles mounted in the free-jet flow. The dome serves to protect the surrounding community from high noise levels generated by the nozzles, and to provide an anechoic environment for acoustic measurements. Information presented in this report summarizes free-jet performance, fluid support systems, and data acquisition capabilities of the NATR.

Investigation of an ejector heat pump by analytical methods

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

Hsu, C.T.

1984-07-01

Using existing theories of ejector design, the optimum geometry of a high-efficiency ejector - including mixing section cross-sectional area, mass flow entrainment rate, ejector efficiency, and overall COP - for a heat pump cycle was determined. A parametric study was performed to evaluate the COP values for different operating conditions. A sensitivity study determined th effects of nozzle efficiency and diffuser efficiency on the overall ejector heat pump COP. The off-design study estimated the COP for an ejector heat pump operating at off-design conditions. Refrigerants 11, 113, and 114 are three of the halocarbons which best satisfy the criteria formore » an ejector heat pump system. The estimated COPs were 0.3 for the cooling mode and 1.3 for the heating mode at standard operating conditions: a boiler temperature of 93.3/sup 0/C (200/sup 0/F), a condenser temperature of 43.3/sup 0/C (110/sup 0/F), and an evaporator temperature of 10/sup 0/C (50/sup 0/F). Based on the same operating conditions, an optimum ejector geometry was estimated for each of the refrigerants R-11 and R-113. Since the COP values for heating obtained in this analysis are greater than unity, the performance of an ejector heat pump operating in the heating mode should be competitive with that of oil- or gas-fired furnaces or electrical resistance heaters.« less

Development of acoustically lined ejector technology for multitube jet noise suppressor nozzles by model and engine tests over a wide range of jet pressure ratios and temperatures

NASA Technical Reports Server (NTRS)

Atvars, J.; Paynter, G. C.; Walker, D. Q.; Wintermeyer, C. F.

1974-01-01

An experimental program comprising model nozzle and full-scale engine tests was undertaken to acquire parametric data for acoustically lined ejectors applied to primary jet noise suppression. Ejector lining design technology and acoustical scaling of lined ejector configurations were the major objectives. Ground static tests were run with a J-75 turbojet engine fitted with a 37-tube, area ratio 3.3 suppressor nozzle and two lengths of ejector shroud (L/D = 1 and 2). Seven ejector lining configurations were tested over the engine pressure ratio range of 1.40 to 2.40 with corresponding jet velocities between 305 and 610 M/sec. One-fourth scale model nozzles were tested over a pressure ratio range of 1.40 to 4.0 with jet total temperatures between ambient and 1088 K. Scaling of multielement nozzle ejector configurations was also studied using a single element of the nozzle array with identical ejector lengths and lining materials. Acoustic far field and near field data together with nozzle thrust performance and jet aerodynamic flow profiles are presented.

Characteristics of Five Ejector Configurations at Free-Stream Mach Numbers from 0 to 2.0

NASA Technical Reports Server (NTRS)

Klann, John L.; Huff, Ronald G.

1959-01-01

Thrust, air-handling, and base-pressure characteristics of five ejector configurations were investigated in the Lewis 8-by 6-foot wind tunnel at free-stream Mach numbers from 0 to 2.0 over ranges of primary-jet pressure ratio up to 24 and corrected secondary weight-flow ratio up to 13 percent. The ejector-shroud geometries varied from convergent to divergent. Base pressure ratio and ejector performance were interrelated by means of an exit-momentum parameter. Correlations, to at least a first approximation, with base pressure ratio, of both internal-ejector-flow separation and external-flow separation over the model boattail were shown. Furthermore, it was shown that magnitudes and exact trends in base pressure ratio depended largely, and in a complicated fashion, on ejector geometry and amount of secondary flow. External-stream effects on ejector jet thrust were determined for a typical schedule of jet-engine pressure ratios. With the exception of the ejector having the largest (1.81) shroud-exit-to primary-diameter ratio, there were no stream effects at Mach numbers from 1.5 to 2.0 and variations from quiescent-air thrust data were less than 2.5 percent at the subsonic speed investigated.

Internal performance characteristics of thrust-vectored axisymmetric ejector nozzles

NASA Technical Reports Server (NTRS)

Lamb, Milton

1995-01-01

A series of thrust-vectored axisymmetric ejector nozzles were designed and experimentally tested for internal performance and pumping characteristics at the Langley research center. This study indicated that discontinuities in the performance occurred at low primary nozzle pressure ratios and that these discontinuities were mitigated by decreasing expansion area ratio. The addition of secondary flow increased the performance of the nozzles. The mid-to-high range of secondary flow provided the most overall improvements, and the greatest improvements were seen for the largest ejector area ratio. Thrust vectoring the ejector nozzles caused a reduction in performance and discharge coefficient. With or without secondary flow, the vectored ejector nozzles produced thrust vector angles that were equivalent to or greater than the geometric turning angle. With or without secondary flow, spacing ratio (ejector passage symmetry) had little effect on performance (gross thrust ratio), discharge coefficient, or thrust vector angle. For the unvectored ejectors, a small amount of secondary flow was sufficient to reduce the pressure levels on the shroud to provide cooling, but for the vectored ejector nozzles, a larger amount of secondary air was required to reduce the pressure levels to provide cooling.

A computational study of thrust augmenting ejectors based on a viscous-inviscid approach

NASA Technical Reports Server (NTRS)

Lund, Thomas S.; Tavella, Domingo A.; Roberts, Leonard

1987-01-01

A viscous-inviscid interaction technique is advocated as both an efficient and accurate means of predicting the performance of two-dimensional thrust augmenting ejectors. The flow field is subdivided into a viscous region that contains the turbulent jet and an inviscid region that contains the ambient fluid drawn into the device. The inviscid region is computed with a higher-order panel method, while an integral method is used for the description of the viscous part. The strong viscous-inviscid interaction present within the ejector is simulated in an iterative process where the two regions influence each other en route to a converged solution. The model is applied to a variety of parametric and optimization studies involving ejectors having either one or two primary jets. The effects of nozzle placement, inlet and diffuser shape, free stream speed, and ejector length are investigated. The inlet shape for single jet ejectors is optimized for various free stream speeds and Reynolds numbers. Optimal nozzle tilt and location are identified for various dual-ejector configurations.

Aerodynamic and acoustic performance of ejectors for engine-under-the-wing concepts

NASA Technical Reports Server (NTRS)

Vonglahn, U.; Goodykoontz, J. H.; Groesbeck, D.

1974-01-01

Subsonic thrust augmentation, exhaust plume velocity contours and acoustic characteristics of a small-scale, 6-tube mixer nozzle with ejector were obtained with and without a wing. Thrust augmentation up to 30 percent was achieved. Aerodynamic results showed that at a given location, greater downstream velocities are obtained with an ejector than with the baseline nozzle. Ejectors reduce high frequency noise; however, low frequency noise amplification also occurs. Acoustic reflections off the wing increase the noise level to a ground observer. With an ejector, the acoustic benefits of forward velocity may be significantly reduced compared with the baseline nozzle.

Improvements to the ejector expansion refrigeration cycle

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

Menegay, P.; Kornhauser, A.A.

1996-12-31

The ejector expansion refrigeration cycle (EERC) is a variant of the standard vapor compression cycle in which an ejector is used to recover part of the work that would otherwise be lost in the expansion valve. In initial testing EERC performance was poor, mainly due to thermodynamic non-equilibrium conditions in the ejector motive nozzle. Modifications were made to correct this problem, and significant performance improvements were found.

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

1. EXTERIOR CONTEXT VIEW OF BUILDING 620, THE SEWAGE EJECTOR, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. EXTERIOR CONTEXT VIEW OF BUILDING 620, THE SEWAGE EJECTOR, LOOKING NORTHEAST. - Mill Valley Air Force Station, Sewage Ejector, East Ridgecrest Boulevard, Mount Tamalpais, Mill Valley, Marin County, CA

Focused Experimental and Analytical Studies of the RBCC Rocket-Ejector

NASA Technical Reports Server (NTRS)

Lehman, M.; Pal, S.; Schwes, D.; Chen, J. D.; Santoro, R. J.

1999-01-01

The rocket-ejector mode of a Rocket Based Combined Cycle Engine (RBCC) was studied through a joint experimental/analytical approach. A two-dimensional variable geometry rocket-ejector system with enhanced optical access was designed and fabricated for experimentation. The rocket-ejector system utilizes a single two-dimensional gaseous oxygen/gaseous hydrogen rocket as the ejector. To gain a systematic understanding of the rocket ejector's internal fluid mechanic/combustion phenomena, experiments were conducted with both direct-connect and sea-level static configurations for a range of rocket operating conditions Overall system performance was obtained through Global measurements of wall static pressure profiles, heat flux profiles and engine thrust, whereas detailed mixing and combustion information was obtained through Raman spectroscopy measurements of major species (gaseous oxygen, hydrogen. nitrogen and water vapor). These experimental efforts were complemented by Computational Fluid Dynamic (CFD) flowfield analyses.

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

Hybrid Vapor Compression Ejector Cycle: Presentation to IAPG Mechanical Working Group

DTIC Science & Technology

2011-08-01

Compression Ejector Cycle: Presentation to IAPG Mechanical Working Group Parmesh Verma and Tom Radcliff, United Technologies Research Center UNCLASSIFIED... Ejector Cycle Presentation to IAPG Mechanical Working Group 5a. CONTRACT NUMBER W909MY-10-C-0005 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...hybrid vapor compression ejector heat pump cycle developed under an American Recovery and Reinvestment Act funded contract is provided. 15. SUBJECT

Credit WCT. Photographic copy of photograph, view east showing the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit WCT. Photographic copy of photograph, view east showing the Y-stage ejector nozzle as the Y-stage ejector is being installed in the Dd ejector train in 1962. In the distance can be seen the western end of the Z-stage ejector. (JPL negative no. 384-3345-A, 8 November 1962) - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Energetics of Vortex Ring Formation.

DTIC Science & Technology

1983-11-01

Sorohia, V., "An Experimental Investigation of Thrust Augmenting Ejector Flows", Proceedings of the Ejector Workshop for Aerospace Applications, AFWAL-TR...induction thrust augmentrs, su’h comparing thr mass and energy content of fully formed as the ejector , the migration of finite sized eddie, laminar vortex...Intermittent Jet to a Secondary Fluid in an Ejector Type Thrust Augmentor", Hiller Aircraft Company, Interim Report ARD-305, June 1962. 3. Bernal, L. and

Comparison of the initial development of shear layers in two-dimensional and axisymmetric ejector configurations

NASA Technical Reports Server (NTRS)

Dufflocq, M.; Benjamin, M. A.; Roan, V. P.

1993-01-01

A two-phase experimental investigation designed to study the development of shear layers in axisymmetric and two-dimensional single-nozzle ejectors has been completed. In this study, combinations of similar and dissimilar gases were used as the supersonic primary and subsonic secondary. Test cases included combinations of air/air, argon/air and helium/air as the supersonic primary and subsonic secondary, respectively. Similar flow conditions were studied for each ejector configuration. Mixing of the gases occurred in a constant-area tube, where the inlet pressure was maintained at 34.5 kPa. The cases studied resulted in convective Mach numbers that range between 0.06 and 1.9. The data gathered shows differences between the initial shear-layer development for the two ejector geometries, and also between the different test cases studied for each ejector configuration. The measured growth rates for the axisymmetric ejector are more than twice those measured for the two-dimensional ejector. However, in both cases the results show that compressibility has a reducing effect on the growth rate. Further, in the region immediately after the inlet to the mixing tube, compressibility seems to affect the ejector shear layers in a manner similar to that of two-stream two-dimensional mixing layers.

Ultra-high-throughput microarray generation and liquid dispensing using multiple disposable piezoelectric ejectors.

PubMed

Hsieh, Huangpin Ben; Fitch, John; White, Dave; Torres, Frank; Roy, Joy; Matusiak, Robert; Krivacic, Bob; Kowalski, Bob; Bruce, Richard; Elrod, Scott

2004-03-01

The authors have constructed an array of 12 piezoelectric ejectors for printing biological materials. A single-ejector footprint is 8 mm in diameter, standing 4 mm high with 2 reservoirs totaling 76 micro L. These ejectors have been tested by dispensing various fluids in several environmental conditions. Reliable drop ejection can be expected in both humidity-controlled and ambient environments over extended periods of time and in hot and cold room temperatures. In a prototype system, 12 ejectors are arranged in a rack, together with an X - Y stage, to allow printing any pattern desired. Printed arrays of features are created with a biological solution containing bovine serum albumin conjugated oligonucleotides, dye, and salty buffer. This ejector system is designed for the ultra-high-throughput generation of arrays on a variety of surfaces. These single or racked ejectors could be used as long-term storage vessels for materials such as small molecules, nucleic acids, proteins, or cell libraries, which would allow for efficient preprogrammed selection of individual clones and greatly reduce the chance of cross-contamination and loss due to transfer. A new generation of design ideas includes plastic injection molded ejectors that are inexpensive and disposable and handheld personal pipettes for liquid transfer in the nanoliter regime.

Preliminary dynamic tests of a flight-type ejector

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1992-01-01

A thrust augmenting ejector was tested to provide experimental data to assist in the assessment of theoretical models to predict duct and ejector fluid-dynamic characteristics. Eleven full-scale thrust augmenting ejector tests were conducted in which a rapid increase in the ejector nozzle pressure ratio was effected through a unique facility, bypass/burst-disk subsystem. The present work examines two cases representative of the test performance window. In the first case, the primary nozzle pressure ration (NPR) increased 36 percent from one unchoked (NPR = 1.29) primary flow condition to another (NPR = 1.75) over a 0.15 second interval. The second case involves choked primary flow conditions, where a 17 percent increase in primary nozzle flowrate (from NPR = 2.35 to NPR = 2.77) occurred over approximately 0.1 seconds. Although the real-time signal measurements support qualitative remarks on ejector performance, extracting quantitative ejector dynamic response was impeded by excessive aerodynamic noise and thrust stand dynamic (resonance) characteristics. It does appear, however, that a quasi-steady performance assumption is valid for this model with primary nozzle pressure increased on the order of 50 lb(sub f)/s. Transient signal treatment of the present dataset is discussed and initial interpretations of the results are compared with theoretical predictions for a similar Short Takeoff and Vertical Landing (STOVL) ejector model.

Achieving an adequate minute volume through a 2 mm transtracheal catheter in simulated upper airway obstruction using a modified industrial ejector.

PubMed

Hamaekers, A E W; Götz, T; Borg, P A J; Enk, D

2010-03-01

Needle cricothyrotomy and subsequent transtracheal jet ventilation (TTJV) is one of the last options to restore oxygenation while managing an airway emergency. However, in cases of complete upper airway obstruction, conventional TTJV is ineffective and dangerous. We transformed a small, industrial ejector into a simple, manual ventilator providing expiratory ventilation assistance (EVA). An ejector pump was modified to allow both insufflation of oxygen and jet-assisted expiration through an attached 75 mm long transtracheal catheter (TTC) with an inner diameter (ID) of 2 mm by alternately occluding and releasing the gas outlet of the ejector pump. In a lung simulator, the modified ejector pump was tested at different compliances and resistances. Inspiration and expiration times were measured and achievable minute volumes (MVs) were calculated to determine the effect of EVA. The modified ejector pump shortened the expiration time and an MV up to 6.6 litre min(-1) could be achieved through a 2 mm ID TTC in a simulated obstructed airway. The principle of ejector-based EVA seems promising and deserves further evaluation.

Steam ejector as an industrial heat pump

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

Arnold, H.G.; Huntley, W.R.; Perez-Blanco, H.

1982-01-01

The steam ejector is analyzed for use in industrial heat recovery applications and compared to mechanical compressor heat pumps. An estimated ejector performance was analyzed using methods based on conservation of mass, momentum, and energy; using steam properties to account for continuity; and using appropriate efficiencies for the nozzle and diffuse performance within the ejector. A potential heat pump application at a paper plant in which waste water was available in a hot well downstream of the paper machine was used to describe use of the stream ejector. Both mechanical compression and jet ejector heat pumps were evaluated for recompressionmore » of flashed steam from the hot well. It is noted that another possible application of vapor recompression heat pumps is the recovery of waste heat from large facilities such as the gaseous diffusion plants. The economics of recovering waste heat in similar applications is analyzed. (MCW)« less

Experiment/Analytical Characterization of the RBCC Rocket-Ejector Mode

NASA Technical Reports Server (NTRS)

Ruf, J. H.; Lehman, M.; Pal, S.; Santoro, R. J.; West, J.; Turner, James E. (Technical Monitor)

2000-01-01

Experimental and complementary CFD results from the study of the rocket-ejector mode of a Rocket Based Combined Cycle (RBCC) engine are presented and discussed. The experiments involved systematic flowfield measurements in a two-dimensional, variable geometry rocket-ejector system. The rocket-ejector system utilizes a single two-dimensional, gaseous oxygen/gaseous hydrogen rocket as the ejector. To gain a thorough understanding of the rocket-ejector's internal fluid mechanic/combustion phenomena, experiments were conducted with both direct-connect and sea-level static configurations for a range of rocket operating conditions. Overall system performance was obtained through global measurements of wall static pressure profiles, heat flux profiles and engine thrust, whereas detailed mixing and combustion information was obtained through Raman spectroscopy measurements of major species (oxygen, hydrogen, nitrogen and water vapor). The experimental results for both the direct-connect and sea-level static configurations are compared with CFD predictions of the flowfield.

Preliminary dynamic tests of a flight-type ejector

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1992-01-01

A thrust augmenting ejector was tested to provide experimental data to assist in the assessment of theoretical models to predict duct and ejector fluid-dynamic characteristics. Eleven full-scale thrust augmenting ejector tests were conducted in which a rapid increase in the ejector nozzle pressure ratio was effected through a unique bypass/burst-disk subsystem. The present work examines two cases representative of the test performance window. In the first case, the primary nozzle pressure ration (NPR) increased 36 percent from one unchoked (NPR = 1.29) primary flow condition to another (NPR = 1.75) over a 0.15 second interval. The second case involves choked primary flow conditions, where a 17 percent increase in primary nozzle flowrate (from NPR = 2.35 to NPR = 2.77) occurred over approximately 0.1 seconds. Transient signal treatment of the present dataset is discussed and initial interpretations of the results are compared with theoretical predictions for a similar STOVL ejector model.

Acoustic, Flow Related, and Performance Related Experimental Results for Generation 1.5 High Speed Civil Transport (HSCT) 2-Dimensional Exhaust Nozzles

NASA Technical Reports Server (NTRS)

Salikuddin, M.; Wisler, S.; Majjigi, R.

2004-01-01

The principle objectives of the current program were to experimentally investigate the repeatability of acoustic and aerodynamic characteristics of 2D-CD mixer-ejector nozzles and the effects on the acoustic and aerodynamic characteristics of 2D mixer-ejectors due to (1) the configurational variations, which include mixers with aligned CD chutes, aligned convergent chutes, and staggered CD chutes and aerodynamic cycle variables, (2) treatment variations by using different treatment materials, treating the ejector with varying area, location, and treatment thickness for a mixer-ejector configuration, and (3) secondary inlet shape (i.e., a more realistic inlet) and the blockage across the inlet (a possible fin-like structure needed for installation purpose) by modifying one of the inlet of a mixer-ejector configuration. The objectives also included the measurement dynamic pressures internal to the ejector for a few selected configuration to examine the internal noise characteristics.

Credit BG. View west of Test Stand "D" complex, with ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit BG. View west of Test Stand "D" complex, with ends of Dd (left) and Dy (right) station ejectors in view. Steam piping from accumulator (sphere) to ejectors is apparent; long horizontal loops in the pipes permit expansion and contraction without special joints. The small platform straddling the Dd ejector (near the accumulator) was originally constructed for a "Hyprox" steam generator which supplied steam to the Dd ejector before the accumulator and Dy stand were built. Note ejectors on top of interstage condenser in Test Stand "D" tower. Metal shed in far right background is for storage - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Augmenting ejector endwall effects. [V/STOL aircraft

NASA Technical Reports Server (NTRS)

Porter, J. L.; Squyers, R. A.

1979-01-01

Rectangular inlet ejectors which had multiple hypermixing nozzles for their primary jets were investigated for the effects of endwall blowing on thrust augmentation performance. The ejector configurations tested had both straight wall and active boundary layer control type diffusers. Endwall flows were energized and controlled by simple blowing jets suitably located in the ejector. Both the endwall and boundary layer control diffuser blowing rates were varied to determine optimum performance. High area ratio diffusers with insufficient endwall blowing showed endwall separation and rapid degradation of thrust performance. Optimized values of diffuser boundary layer control and endwall nozzle blowing rates in an ejector augmenter were shown to achieve high levels of augmentation performance for maximum compactness.

Internal Performance Evaluation of a Two Position Divergent Shroud Ejector

NASA Technical Reports Server (NTRS)

Mihaloew, James R.; Stofan, Andrew J.

1960-01-01

A two-position divergent shroud ejector was investigated in an unheated quiescent-air facility over a range of operational variables applicable to a Mach 2.5 aircraft. The performance data are shown in terms of hypothetical engine operating conditions to illustrate variations of performance with Mach number. The overall thrust performance was reasonably good, with ejector thrust ratios ranging from 0.97 to 0.98 for all conditions except that corresponding to acceleration with afterburning through the transonic flight Mach number region from 0.9 to 1.1, where the ejector thrust ratio decreased to as low as 0.945 for an ejector corrected weight-flow ratio of 0.105.

Parametric analysis of diffuser requirements for high expansion ratio space engine

NASA Technical Reports Server (NTRS)

Wojciechowski, C. J.; Anderson, P. G.

1981-01-01

A supersonic diffuser ejector design computer program was developed. Using empirically modified one dimensional flow methods the diffuser ejector geometry is specified by the code. The design code results for calculations up to the end of the diffuser second throat were verified. Diffuser requirements for sea level testing of high expansion ratio space engines were defined. The feasibility of an ejector system using two commonly available turbojet engines feeding two variable area ratio ejectors was demonstrated.

Preliminary Internal Performance Data for a Variable-Ejector Assembly on the XJ79-GE-1 Turbojet Engine. II; Afterburning Configurations

NASA Technical Reports Server (NTRS)

Bloomer, Harry E.; Groesbeck, Donald E.

1957-01-01

Internal performance of an XJ79-GE-1 variable ejector was experimentally determined with the primary nozzle in two representative after-burning positions. Jet-thrust and air-handling data were obtained in quiescent air for 4 selected ejector configurations over a wide range of secondary to primary airflow ratios and primary-nozzle pressure ratios. The experimental ejector data are presented in both graphical and tabulated form.

Parametric Studies of the Ejector Process within a Turbine-Based Combined-Cycle Propulsion System

NASA Technical Reports Server (NTRS)

Georgiadis, Nicholas J.; Walker, James F.; Trefny, Charles J.

1999-01-01

Performance characteristics of the ejector process within a turbine-based combined-cycle (TBCC) propulsion system are investigated using the NPARC Navier-Stokes code. The TBCC concept integrates a turbine engine with a ramjet into a single propulsion system that may efficiently operate from takeoff to high Mach number cruise. At the operating point considered, corresponding to a flight Mach number of 2.0, an ejector serves to mix flow from the ramjet duct with flow from the turbine engine. The combined flow then passes through a diffuser where it is mixed with hydrogen fuel and burned. Three sets of fully turbulent Navier-Stokes calculations are compared with predictions from a cycle code developed specifically for the TBCC propulsion system. A baseline ejector system is investigated first. The Navier-Stokes calculations indicate that the flow leaving the ejector is not completely mixed, which may adversely affect the overall system performance. Two additional sets of calculations are presented; one set that investigated a longer ejector region (to enhance mixing) and a second set which also utilized the longer ejector but replaced the no-slip surfaces of the ejector with slip (inviscid) walls in order to resolve discrepancies with the cycle code. The three sets of Navier-Stokes calculations and the TBCC cycle code predictions are compared to determine the validity of each of the modeling approaches.

Solar-powered compression-enhanced ejector air conditioner

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

Sokolov, M.; Hershgal, D.

1993-09-01

This article is an extension of an earlier investigation into the possibility of adaptation of the ejector refrigeration cycle to solar air-conditioning. In a previous work the ejector cycle has been proven a viable option only for a limited number of cases. These include systems with combined (heating, cooling, and hot water supply) loads where means for obtaining low condensing temperature are available. The purpose of this work is to extend the applicability of such systems by enhancing their efficiency and thereby improving their economical attractiveness. This is done by introducing the compression enhanced ejector system in which mechanical (rathermore » than thermal) energy is used to boost the pressure of the secondary stream into the ejector, Such a boost improves the performance of the whole system. Similar to the conventional ejector, the compression-enhanced ejector system utilizes practically the same hardware for solar heating during the winter and for solar cooling during the summer. Thus, it is capable of providing a year-round space air-conditioning. Optimization of the best combination in which the solar and refrigeration systems combine through the vapor generator working temperature is also presented.« less

Focused RBCC Experiments: Two-Rocket Configuration Experiments and Hydrocarbon/Oxygen Rocket Ejector Experiments

NASA Technical Reports Server (NTRS)

Santoro, Robert J.; Pal, Sibtosh

2003-01-01

This addendum report documents the results of two additional efforts for the Rocket Based Combined Cycle (RBCC) rocket-ejector mode research work carried out at the Penn State Propulsion Engineering Research Center in support of NASA s technology development efforts for enabling 3 d generation Reusable Launch Vehicles (RLV). The tasks reported here build on an earlier NASA MSFC funded research program on rocket ejector investigations. The first task investigated the improvements of a gaseous hydrogen/oxygen twin thruster RBCC rocket ejector system over a single rocket system. The second task investigated the performance of a hydrocarbon (liquid JP-7)/gaseous oxygen single thruster rocket-ejector system. To gain a systematic understanding of the rocket-ejector s internal fluid mechanic/combustion phenomena, experiments were conducted with both direct-connect and sea-level static diffusion and afterburning (DAB) configurations for a range of rocket operating conditions. For all experimental conditions, overall system performance was obtained through global measurements of wall static pressure profiles, heat flux profiles and engine thrust. Detailed mixing and combustion information was obtained through Raman spectroscopy measurements of major species (gaseous oxygen, hydrogen, nitrogen and water vapor) for the gaseous hydrogen/oxygen rocket ejector experiments.

Study of an engine flow diverter system for a large scale ejector powered aircraft model

NASA Technical Reports Server (NTRS)

Springer, R. J.; Langley, B.; Plant, T.; Hunter, L.; Brock, O.

1981-01-01

Requirements were established for a conceptual design study to analyze and design an engine flow diverter system and to include accommodations for an ejector system in an existing 3/4 scale fighter model equipped with YJ-79 engines. Model constraints were identified and cost-effective limited modification was proposed to accept the ejectors, ducting and flow diverter valves. Complete system performance was calculated and a versatile computer program capable of analyzing any ejector system was developed.

Some tests on small-scale rectangular throat ejector. [thrust augmentation for V/STOL aircraft

NASA Technical Reports Server (NTRS)

Dean, W. N., Jr.; Franke, M. E.

1979-01-01

A small scale rectangular throat ejector with plane slot nozzles and a fixed throat area was tested to determine the effects of diffuser sidewall length, diffuser area ratio, and sidewall nozzle position on thrust and mass augmentation. The thrust augmentation ratio varied from approximately 0.9 to 1.1. Although the ejector did not have good thrust augmentation performance, the effects of the parameters studied are believed to indicate probable trends in thrust augmenting ejectors.

Design and Testing of Scaled Ejector-Diffusers for Jet Engine Test Facility Applications.

DTIC Science & Technology

1983-09-01

the test cell such that the exhaust will be vented into an augmenting tube which acts as an ejector -diffuser assembly. 11 The kinetic energy of the...OF STANDARDS-1963-A ..’I -Dy , - 77 *4********* Z 7.77- NAVAL POSTGRADUATE SCHOOL Monterey, California W I THESIS DESIGN AND TESTING OF SCALED EJECTOR ...PERIOD COVERED Design and Testing of Scaled Ejector - "flglfeerls Thesis~ Diffusers for Jet Engine Test Facility Spebr18 S. PERFORMING ORG. REPORT

Meso-scale controlled motion for a microfluidic drop ejector.

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

Galambos, Paul C.; Givler, Richard C.; Pohl, Kenneth Roy

2004-12-01

The objective of this LDRD was to develop a uniquely capable, novel droplet solution based manufacturing system built around a new MEMS drop ejector. The development all the working subsystems required was completed, leaving the integration of these subsystems into a working prototype still left to accomplish. This LDRD report will focus on the three main subsystems: (1) MEMS drop ejector--the MEMS ''sideshooter'' effectively ejected 0.25 pl drops at 10 m/s, (2) packaging--a compact ejector package based on a modified EMDIP (Electro-Microfluidic Dual In-line Package--SAND2002-1941) was fabricated, and (3) a vision/stage system allowing precise ejector package positioning in 3 dimensionsmore » above a target was developed.« less

Fluid-acoustic interactions in a low area ratio supersonic jet ejector

NASA Technical Reports Server (NTRS)

Krothapalli, Anjaneyulu; Ross, Christopher; Yamomoto, K.; Joshi, M. C.

1994-01-01

An experimental investigation carried out to determine aerodynamic and acoustic characteristics of a low area ratio rectangular jet ejector is reported. A supersonic primary jet issuing from a rectangular convergent-divergent nozzle of aspect ratio 4, into a rectangular duct of area ratio 3, was used. Improved performance was found when the ejector screech tone is most intense and appears to match the most unstable Strouhal number of the free rectangular jet. When the primary jet was operating at over and ideally expanded conditions, significant noise reduction was obtained with the ejector as compared to a corresponding free jet. Application of particle image velocimetry to high speed ejector flows was demonstrated through the measurement of instantaneous two dimensional velocity fields.

Nonsteady-Flow Thrust Augmenting Ejectors

NASA Technical Reports Server (NTRS)

Foa, J. V.

1979-01-01

Ejector augmenters in which the transfer of mechanical energy from the primary to the secondary flow takes place through the work of interface pressure forces are investigated. Nonsteady flow processes are analyzed from the standpoint of energy transfer efficiency and a comparison of a rotary jet augmenter to an ejector is presented.

Interface concerns of ejector integration in V/STOL aircraft

NASA Technical Reports Server (NTRS)

Lowry, R. B.

1979-01-01

A number of areas which have in the past contributed to weight, complexity, and thrust losses in the ejector-powered V/STOL vehicle were identified. Most of these interfaces taken singly do not represent a severe compromise to the vehicle; however, the bottom line is that the sum of compromises and the subsequent effects on performance, flight operations and maintenance have rendered the ejector V/STOL aircraft unattractive. In addition to some of the unique ejector/aircraft integration problems, the vehicle by virtue of having a V/STOL capability, is compromised in other areas. To be successful and acceptable, the advantages must outweight the disadvantages and simplicity with minimum penalties must be the rule. It is concluded that more emphasis must be placed on the ejector/aircraft interface for the concept to be successful.

Internal Performance of Several Divergent-Shroud Ejector Nozzles with High Divergence Angles

NASA Technical Reports Server (NTRS)

Trout, Arthur M.; Papell, S. Stephen; Povolny, John H.

1957-01-01

Nine divergent-shroud ejector configurations were investigated to determine the effect of shroud divergence angle on ejector internal performance. Unheated dry air was used for both the primary and secondary flows. The decrease in the design-point thrust coefficient with increasing flow divergence angle (angle measured from primary exit to shroud exit) followed very closely a simple relation involving the cosine of the angle. This indicates that design-point thrust performance for divergent-shroud ejectors can be predicted with reasonable accuracy within the range investigated. The decrease in design-point thrust coefficient due to increasing the flow divergence engle from 120deg to 30deg (half-singles) was approximately 6 percent. Ejector air-handling characteristics and the primary-nozzle flow coefficient were not significantly affected by change in shroud divergence angle.

Thrust Augmentation with Mixer/Ejector Systems

NASA Technical Reports Server (NTRS)

Presz, Walter M., Jr.; Reynolds, Gary; Hunter, Craig

2002-01-01

Older commercial aircraft often exceed FAA (Federal Aviation Administration) sideline noise regulations. The major problem is the jet noise associated with the high exhaust velocities of the low bypass ratio engines on such aircraft. Mixer/ejector exhaust systems can provide a simple means of reducing the jet noise on these aircraft by mixing cool ambient air with the high velocity engine gases before they are exhausted to ambient. This paper presents new information on thrust performance predictions, and thrust augmentation capabilities of mixer/ejectors. Results are presented from the recent development program of the patented Alternating Lobe Mixer Ejector Concept (ALMEC) suppressor system for the Gulfstream GII, GIIB and GIII aircraft. Mixer/ejector performance procedures are presented which include classical control volume analyses, compound compressible flow theory, lobed nozzle loss correlations and state of the art computational fluid dynamic predictions. The mixer/ejector thrust predictions are compared to subscale wind tunnel test model data and actual aircraft flight test measurements. The results demonstrate that a properly designed mixer/ejector noise suppressor can increase effective engine bypass ratio and generate large thrust gains at takeoff conditions with little or no thrust loss at cruise conditions. The cruise performance obtained for such noise suppressor systems is shown to be a strong function of installation effects on the aircraft.

Steam ejector-condenser: stage I of a differential vacuum pumping station

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

Hanson, C.L.; Alger, T.W.

1981-04-01

A steam ejector-condenser unit was built and tested to produce a 10 Torr (13.3 x 10/sup 2/Pa) vacuum with a 2 cm aperture to the atmosphere. This unit is the first stage of a differential vacuum pumping station that will be used with the Experimental Test Accelerator. The accelerator's electron beam will pass through a series of openings from a high vacuum (5 x 10/sup -6/ Torr) to the atmosphere. The differential system consists of four vacuum pumping units separated by 2 cm-diam apertures. Superheated steam is injected near the final beamline orifice to reduce the quantity of atmospheric airmore » flowing into the steam ejector--condenser unit. The steam ejector in the condenser vessel is open at its center to permit passage of the accelerator beam. Five nozzles mounted in a conical array produce the ejector vacuum of 10 Torr. The ejector exhausts into the condenser and forms a barrier to air flow into the lower pressure region. This feature permits high volume cold trapping and cryopumping of water vapor in the remaining lower-pressure stages. Tests have proven that the steam ejector--condenser is a reliable operating unit and suitable for long-term, steady-state accelerator operation.« less

Focused Rocket-Ejector RBCC Experiments

NASA Technical Reports Server (NTRS)

Santoro, Robert J.; Pal, Sibtosh

2003-01-01

This document reports the results of additional efforts for the Rocket Based Combined Cycle (RBCC) rocket-ejector mode research work carried out at the Perm State Propulsion Engineering Research Center in support of NASA s technology development efforts for enabling 3rd generation Reusable Launch Vehicles (RLV). The two tasks conducted under this program build on earlier NASA MSFC funded research program on rocket ejector investigations. The first task continued a systematic investigation of the improvements provided by a gaseous hydrogen (GHz)/oxygen (GO2) twin thruster RBCC rocket ejector system over a single rocket system. In a similar vein, the second task continued investigations into the performance of a hydrocarbon (liquid JP-7)/gaseous oxygen single thruster rocket-ejector system. To gain a systematic understanding of the rocket-ejector s internal fluid mechanic/combustion phenomena, experiments were conducted with both direct-connect and sea-level static diffusion and afterburning (DAB) configurations for a range of rocket operating conditions. For all experimental conditions, overall system performance was obtained through global measurements of wall static pressure profiles, heat flux profiles and engine thrust. For the GH2/GO2 propellant rocket ejector experiments, high frequency measurements of the pressure field within the system were also made to understand the unsteady behavior of the flowfield.

Performance characteristics of low global warming potential R134a alternative refrigerants in ejector-expansion refrigeration system

NASA Astrophysics Data System (ADS)

Mishra, Shubham; Sarkar, Jahar

2016-12-01

Performance assessment of ejector-expansion vapor compression refrigeration system with eco-friendly R134a alternative refrigerants (R152a, R1234yf, R600a, R600, R290, R161, R32, and propylene) is presented for air-conditioning application. Ejector has been modeled by considering experimental data based correlations of component efficiencies to take care of all irreversibilities. Ejector area ratio has been optimized based on maximum coefficient of performance (COP) for typical air-conditioner operating temperatures. Selected refrigerants have been compared based on area ratio, pressure lift ratio, entrainment ratio, COP, COP improvement and volumetric cooling capacity. Effects of normal boiling point and critical point on the performances have been studied as well. Using ejector as an expansion device, maximum improvement in COP is noted in R1234yf (10.1%), which reduces the COP deviation with R134a (4.5% less in basic cycle and 2.5% less in ejector cycle). Hence, R1234yf seems to be best alternative for ejector expansion system due to its mild flammability and comparable volumetric capacity and cooling COP. refrigerant R161 is superior to R134a in terms of both COP and volumetric cooling capacity, although may be restricted for low capacity application due to its flammability.

Rocket-Induced Magnetohydrodynamic Ejector: A Single-Stage-to-Orbit Advanced Propulsion Concept

NASA Technical Reports Server (NTRS)

Cole, John; Campbell, Jonathan; Robertson, Anthony

1995-01-01

During the atmospheric boost phase of a rocket trajectory, magnetohydrodynamic (MHD) principles can be utilized to augment the thrust by several hundred percent without the input of additional energy. The concept is an MHD implementation of a thermodynamic ejector. Some ejector history is described and some test data showing the impressive thrust augmentation capabilities of thermodynamic ejectors are provided. A momentum and energy balance is used to derive the equations to predict the MHD ejector performance. Results of these equations are compared with the test data and then applied to a specific performance example. The rocket-induced MHD ejector (RIME) engine is described and a status of the technology and availability of the engine components is provided. A top level vehicle sizing analysis is performed by scaling existing MHD designs to the required flight vehicle levels. The vehicle can achieve orbit using conservative technology. Modest improvements are suggested using recently developed technologies, such as superconducting magnets, which can improve predicted performance well beyond those expected for current single-stage-to-orbit (SSTO) designs.

Internal Mixing Studied for GE/ARL Ejector Nozzle

NASA Technical Reports Server (NTRS)

Zaman, Khairul

2005-01-01

To achieve jet noise reduction goals for the High Speed Civil Transport aircraft, researchers have been investigating the mixer-ejector nozzle concept. For this concept, a primary nozzle with multiple chutes is surrounded by an ejector. The ejector mixes low-momentum ambient air with the hot engine exhaust to reduce the jet velocity and, hence, the jet noise. It is desirable to mix the two streams as fast as possible in order to minimize the length and weight of the ejector. An earlier model of the mixer-ejector nozzle was tested extensively in the Aerodynamic Research Laboratory (ARL) of GE Aircraft Engines at Cincinnati, Ohio. While testing was continuing with later generations of the nozzle, the earlier model was brought to the NASA Lewis Research Center for relatively fundamental measurements. Goals of the Lewis study were to obtain details of the flow field to aid computational fluid dynamics (CFD) efforts and obtain a better understanding of the flow mechanisms, as well as to experiment with mixing enhancement devices, such as tabs. The measurements were made in an open jet facility for cold (unheated) flow without a surrounding coflowing stream.

An experimental investigation of ejector performance based upon different refrigerants

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

Chen, S.L.; Yen, J.Y.; Huang, M.C.

1998-12-31

This article experimentally compares the characteristics of different refrigerants as the working fluid in an ejector cooling system. The study covers common refrigerants including R-113, R-114, R-142b, and R-718. The critical choking conditions against the variation of condenser back pressure, the evaporator pressure, and the generator pressure are determined for each refrigerant. The results are compiled into a convenient performance curve and COP chart. These results can serve as an important reference for future design of ejector cooling systems. Finally, this paper presents a comparison of the performances of different refrigerants in an ejector cooling system.

Thrust and pumping characteristics of cylindrical ejectors using afterburning turbojet gas generator

NASA Technical Reports Server (NTRS)

Samanich, N. E.; Huntley, S. C.

1969-01-01

Static tests of cylindrical ejectors having ejector to primary diameter ratios from 1.1 to 1.6 and ejector length to primary nozzle diameter ratios from 0.9 to 2.1 are reported. Power setting of the J85-13 turbojet engine was varied from part power to maximum afterburning. Corrected secondary weight flow ratio was varied from 0.02 to 0.08 over a range of exhaust nozzle pressure ratios from 2.0 to 9.0. Secondary flow temperature rise and pressure drop characteristics through the nacelle secondary flow passage were also obtained.

An overview of current Navy programs to develop thrust augmenting ejectors

NASA Technical Reports Server (NTRS)

Green, K. A.

1979-01-01

The primary objective of Navy sponsored research in thrust augmentation is the development of an improved augmenter for V/STOL application. In support of this goal, a data base is being established to provide an accurate prediction capability for use in ejector design. A general technology development of ejectors and associated effects presently is split into the more specific areas of lift and control, since thrust augmenting ejectors may be suitable for both. Research areas examined include advanced diffuser and end wall design; advanced primary nozzles; analytic studies; augmenting reaction controls; and nozzle design.

THRSTER: A THRee-STream Ejector Ramjet Analysis and Design Tool

NASA Technical Reports Server (NTRS)

Chue, R. S.; Sabean, J.; Tyll, J.; Bakos, R. J.

2000-01-01

An engineering tool for analyzing ejectors in rocket based combined cycle (RBCC) engines has been developed. A key technology for multi-cycle RBCC propulsion systems is the ejector which functions as the compression stage of the ejector ramjet cycle. The THRee STream Ejector Ramjet analysis tool was developed to analyze the complex aerothermodynamic and combustion processes that occur in this device. The formulated model consists of three quasi-one-dimensional streams, one each for the ejector primary flow, the secondary flow, and the mixed region. The model space marches through the mixer, combustor, and nozzle to evaluate the solution along the engine. In its present form, the model is intended for an analysis mode in which the diffusion rates of the primary and secondary into the mixed stream are stipulated. The model offers the ability to analyze the highly two-dimensional ejector flowfield while still benefits from the simplicity and speed of an engineering tool. To validate the developed code, wall static pressure measurements from the Penn-State and NASA-ART RBCC experiments were used to compare with the results generated by the code. The calculated solutions were generally found to have satisfactory agreement with the pressure measurements along the engines, although further modeling effort may be required when a strong shock train is formed at the rocket exhaust. The range of parameters in which the code would generate valid results are presented and discussed.

THRSTER: A Three-Stream Ejector Ramjet Analysis and Design Tool

NASA Technical Reports Server (NTRS)

Chue, R. S.; Sabean, J.; Tyll, J.; Bakos, R. J.; Komar, D. R. (Technical Monitor)

2000-01-01

An engineering tool for analyzing ejectors in rocket based combined cycle (RBCC) engines has been developed. A key technology for multi-cycle RBCC propulsion systems is the ejector which functions as the compression stage of the ejector ramjet cycle. The THRee STream Ejector Ramjet analysis tool was developed to analyze the complex aerothermodynamic and combustion processes that occur in this device. The formulated model consists of three quasi-one-dimensional streams, one each for the ejector primary flow, the secondary flow, and the mixed region. The model space marches through the mixer, combustor, and nozzle to evaluate the solution along the engine. In its present form, the model is intended for an analysis mode in which the diffusion rates of the primary and secondary into the mixed stream are stipulated. The model offers the ability to analyze the highly two-dimensional ejector flowfield while still benefits from the simplicity and speed of an engineering tool. To validate the developed code, wall static pressure measurements from the Penn-State and NASA-ART RBCC experiments were used to compare with the results generated by the code. The calculated solutions were generally found to have satisfactory agreement with the pressure measurements along the engines, although further modeling effort may be required when a strong shock train is formed at the rocket exhaust. The range of parameters in which the code would generate valid results are presented and discussed.

A Numerical and Experimental Study of Ejector Internal Flow Structure and Geometry Modification for Maximized Performance

NASA Astrophysics Data System (ADS)

Falsafioon, Mehdi; Aidoun, Zine; Poirier, Michel

2017-12-01

A wide range of industrial refrigeration systems are good candidates to benefit from the cooling and refrigeration potential of supersonic ejectors. These are thermally activated and can use waste heat recovery from industrial processes where it is abundantly generated and rejected to the environment. In other circumstances low cost heat from biomass or solar energy may also be used in order to produce a cooling effect. Ejector performance is however typically modest and needs to be maximized in order to take full advantage of the simplicity and low cost of the technology. In the present work, the behavior of ejectors with different nozzle exit positions has been investigated using a prototype as well as a CFD model. The prototype was used in order to measure the performance advantages of refrigerant (R-134a) flowing inside the ejector. For the CFD model, it is assumed that the ejectors are axi-symmetric along x-axis, thus the generated model is in 2D. The preliminary CFD results are validated with experimental data over a wide range of conditions and are in good accordance in terms of entrainment and compression ratios. Next, the flow patterns of four different topologies are studied in order to discuss the optimum geometry in term of ejector entrainment improvement. Finally, The numerical simulations were used to find an optimum value corresponding to maximized entrainment ratio for fixed operating conditions.

The surface roughness effect on the performance of supersonic ejectors

NASA Astrophysics Data System (ADS)

Brezgin, D. V.; Aronson, K. E.; Mazzelli, F.; Milazzo, A.

2017-07-01

The paper presents the numerical simulation results of the surface roughness influence on gas-dynamic processes inside flow parts of a supersonic ejector. These simulations are performed using two commercial CFD solvers (Star- CCM+ and Fluent). The results are compared to each other and verified by a full-scale experiment in terms of global flow parameters (the entrainment ratio: the ratio between secondary to primary mass flow rate - ER hereafter) and local flow parameters distribution (the static pressure distribution along the mixing chamber and diffuser walls). A detailed comparative study of the employed methods and approaches in both CFD packages is carried out in order to estimate the roughness effect on the logarithmic law velocity distribution inside the boundary layer. Influence of the surface roughness is compared with the influence of the backpressure (static pressure at the ejector outlet). It has been found out that increasing either the ejector backpressure or the surface roughness height, the shock position displaces upstream. Moreover, the numerical simulation results of an ejector with rough walls in the both CFD solvers are well quantitatively agreed with each other in terms of the mean ER and well qualitatively agree in terms of the local flow parameters distribution. It is found out that in the case of exceeding the "critical roughness height" for the given boundary conditions and ejector's geometry, the ejector switches to the "off-design" mode and its performance decreases considerably.

Ejector/liquid ring pump provides <0. 30 mm Hg vacuum for polymerization vessel

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

Lockwood, A.; Gaines, A.

1982-03-01

Firestone Fibers and Textiles Company, a division of Firestone Tire and Rubber Company, manufactures tire and industrial yarns of polyester and nylon-6. Nylon-6 molding and extrusion resins are also produced at the plant in Hopewell, Virginia. The process for making polyester requires an extremely low vacuum on the polymerization reactor. A consistent polymerization vessel vacuum of 0.3 mm Hg is needed, but the existing vacuum source, a five-stage steam jet ejector, could only provide a 0.5 mm Hg level. Two options were considered when the company decided to replace the original system with a system designed for 0.15 mm Hgmore » with a non-condensible gas load of 10.8 lb/hr. A new five-stage jet ejector system to meet these requirements would use 1395 lb/hr of 100 psig steam. The other option was a hybrid vacuum source composed of a three-stage steam ejector system and a liquid ring vacuum pump that is more energy efficient than ejectors for low vacuum applications. The hybrid system was selected because the three-stage jet ejector would use only 1240 lb/hr of 100 psig steam. The liquid ring vacuum pump would increase the material and installation cost of the system by about $4000, but the savings in steam consumption would pay back the added cost in less than two years. The jet ejector/liquid ring vacuum pump system has provided both the capacity and the extremely low vacuum needed for the polyester polymerization vessel, after making a small modification. The hybrid vacuum source is reliable, requires only routine maintenance, and will contiue to save substantial amounts of steam each year compared to the five-stage steam jet ejector.« less

Aerodynamic performance investigation of advanced mechanical suppressor and ejector nozzle concepts for jet noise reduction

NASA Technical Reports Server (NTRS)

Wagenknecht, C. D.; Bediako, E. D.

1985-01-01

Advanced Supersonic Transport jet noise may be reduced to Federal Air Regulation limits if recommended refinements to a recently developed ejector shroud exhaust system are successfully carried out. A two-part program consisting of a design study and a subscale model wind tunnel test effort conducted to define an acoustically treated ejector shroud exhaust system for supersonic transport application is described. Coannular, 20-chute, and ejector shroud exhaust systems were evaluated. Program results were used in a mission analysis study to determine aircraft takeoff gross weight to perform a nominal design mission, under Federal Aviation Regulation (1969), Part 36, Stage 3 noise constraints. Mission trade study results confirmed that the ejector shroud was the best of the three exhaust systems studied with a significant takeoff gross weight advantage over the 20-chute suppressor nozzle which was the second best.

Stacked Buoyant Payload Launcher

DTIC Science & Technology

2013-05-14

unit, the signal ejector , or through the escape hatch lockout trunk. Each of these deployment methods has disadvantages. [0005] Torpedo tubes are... ejector tube can accommodate payloads approximately three inches in diameter. Thus, payload size is extremely limited. The escape hatch lockout trunk...signal ejector tube. Additionally, the system 10 can launch multiple payloads during one launch sequence, or can provide multiple launches at

The wide-range ejector flowmeter: calibrated gas evacuation comprising both high and low gas flows.

PubMed

Waaben, J; Brinkløv, M M; Jørgensen, S

1984-11-01

The wide-range ejector flowmeter is an active scavenging system applying calibrated gas removal directly to the anaesthetic circuit. The evacuation rate can be adjusted on the flowmeter under visual control using the calibration scale ranging from 200 ml X min-1 to 151 X min-1. The accuracy of the calibration was tested on three ejector flowmeters at 12 different presettings. The percentage deviation from presetting varied from + 18 to - 19.4 per cent. The ejector flowmeter enables the provision of consistent and accurately calibrated extraction of waste gases and is applicable within a wide range of fresh gas flows.

Recent development of a jet-diffuser ejector

NASA Technical Reports Server (NTRS)

Alperin, M.; Wu, J. J.

1980-01-01

The paper considers thrust augmenting ejectors in which the processes of mixing and diffusion are partly carried out downstream of the ejector solid surfaces. A jet sheet surrounding the periphery of a widely diverging diffuser prevents separation and forms a gaseous, curved surface to provide effective diffuser ratio and additional length for mixing of primary and induced flows. Three-dimensional potential flow methods achieved a large reduction in the length of the associated solid surface; primary nozzle design further reduced the volume required by the jet-diffuser ejectors, resulting in thrust augmentation in excess of two, and an overall length of about 2 1/2 times the throat width.

Does using an ejector chair affect muscle activation patterns in rheumatoid arthritic patients? A preliminary investigation.

PubMed

Munro, B J; Steele, J R

2000-02-01

The present study examined knee and arm extensor muscle activation patterns displayed by 12 elderly female rheumatoid arthritic patients (mean age = 65.5 +/- 8.6 yr) rising from an instrumented Eser ejector chair under four conditions: high seat (540 mm), low seat (450 mm), with and without ejector assistance. Electromyographic (EMG) signals were sampled (1000 Hz) for vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF) and triceps brachii (TB) using a Noraxon Telemyo System (bandwidth 0-340 Hz). Muscle onset, offset and peak activity relative to loss of seat contact (SS), and integrated EMG, were calculated for each muscle burst before SS. A high seat significantly (p < or = 005) decreased VL and TB intensity but did not change muscle activation patterns compared with rising from a low seat. Ejector assistance significantly increased VM and RF burst duration and RF intensity but had no effect on vastii muscle intensity. It was concluded that concerns pertaining to muscle disuse when rising with ejector assistance were unfounded in the present study. However, further research is required to investigate the effects of habitual use of a mechanical ejector device on muscle activation patterns.

Wall roughness effect on gas dynamics in supersonic ejector

NASA Astrophysics Data System (ADS)

Aronson, K. E.; Brezgin, D. V.

2016-10-01

The paper presents the numerical simulations results in order to figure out the influence of the wall surface roughness on gas-dynamic processes inside the supersonic ejector. For these purposes two commercial CFD-solvers (Star-CCM+ and Fluent) were used. A detailed comparative study of the built-in tools and approaches in both CFD-packages for evaluation of surface roughness effects on the logarithmic law velocity distribution inside the boundary layer is carried out. Influence of ejector surface roughness is compared with the influence of the backpressure. It is found out that either increasing the backpressure behind the ejector or increasing the surface roughness height, the appearance section of a pressure shock is displaced upstream (closer to the primary nozzle). The numerical simulations results of the ejector with rough walls in both CFD-solvers are well quantitative agreed between each other in terms of the mass flow rates and are well qualitative consistent in terms of the local flow parameters distribution. It is found out that in case of exceeding the "critical roughness height" for the given geometry and boundary conditions, the ejector switches to the "off-design" mode and its performance is significantly reduced.

Pratt & Whitney 2D Model in LeRC 9 ft x 15 ft Acoustics

NASA Technical Reports Server (NTRS)

Bridges, James; Marino, Jodilyn

1999-01-01

The theory of mixer-ejectors for noise suppression is illustrated in this cartoon. Since jet noise SPL scales as velocity to the eighth power and diameter squared, increasing the jet diameter while lowering its velocity and keeping thrust constant decreases the noise. However, in supersonic craft, the drag penalty for increasing diameter at supersonic cruise makes this option very expensive. One would like to have a large engine during takeoff which could be shrunk during cruise. The retractable ejector is such an expandable engine. If the mixer flow can be expanded to the size of the ejector exit, the noise generated downstream of the ejector will be much less than the small diameter mixer nozzle alone. Of course, this also requires that the noise created in expanding the flow to fill the ejector be absorbed by a liner in the ejector walls so that none of this noise is heard. Since this mixing of internal hot gas and external cold air must take place in as short a distance as possible, the mixer must be very effective and therefore probably much noisier than a simple nozzle.

Generation 1.5 High Speed Civil Transport (HSCT) Exhaust Nozzle Program

NASA Technical Reports Server (NTRS)

Thayer, E. B.; Gamble, E. J.; Guthrie, A. R.; Kehret, D. F.; Barber, T. J.; Hendricks, G. J.; Nagaraja, K. S.; Minardi, J. E.

2004-01-01

The objective of this program was to conduct an experimental and analytical evaluation of low noise exhaust nozzles suitable for future High-Speed Civil Transport (HSCT) aircraft. The experimental portion of the program involved parametric subscale performance model tests of mixer/ejector nozzles in the takeoff mode, and high-speed tests of mixer/ejectors converted to two-dimensional convergent-divergent (2-D/C-D), plug, and single expansion ramp nozzles (SERN) in the cruise mode. Mixer/ejector results show measured static thrust coefficients at secondary flow entrainment levels of 70 percent of primary flow. Results of the high-speed performance tests showed that relatively long, straight-wall, C-D nozzles could meet supersonic cruise thrust coefficient goal of 0.982; but the plug, ramp, and shorter C-D nozzles required isentropic contours to reach the same level of performance. The computational fluid dynamic (CFD) study accurately predicted mixer/ejector pressure distributions and shock locations. Heat transfer studies showed that a combination of insulation and convective cooling was more effective than film cooling for nonafterburning, low-noise nozzles. The thrust augmentation study indicated potential benefits for use of ejector nozzles in the subsonic cruise mode if the ejector inlet contains a sonic throat plane.

A Reduced Ejector Equation,

DTIC Science & Technology

Ejectors , * Thrust augmentation , * Thrust augmentor nozzles, *Mathematical models, Equations, Supersonic characteristics, Inlets, Exits, Aerodynamics, Vertical takeoff aircraft, Short takeoff aircraft, Workshops

Functioning efficiency of intermediate coolers of multistage steam-jet ejectors of steam turbines

NASA Astrophysics Data System (ADS)

Aronson, K. E.; Ryabchikov, A. Yu.; Brodov, Yu. M.; Zhelonkin, N. V.; Murmanskii, I. B.

2017-03-01

Designs of various types of intermediate coolers of multistage ejectors are analyzed and thermal effectiveness and gas-dynamic resistance of coolers are estimated. Data on quantity of steam condensed from steam-air mixture in stage I of an ejector cooler was obtained on the basis of experimental results. It is established that the amount of steam condensed in the cooler constitutes 0.6-0.7 and is almost independent of operating steam pressure (and, consequently, of steam flow) and air amount in steam-air mixture. It is suggested to estimate the amount of condensed steam in a cooler of stage I based on comparison of computed and experimental characteristics of stage II. Computation taking this hypothesis for main types of mass produced multistage ejectors into account shows that 0.60-0.85 of steam amount should be condensed in stage I of the cooler. For ejectors with "pipe-in-pipe" type coolers (EPO-3-200) and helical coolers (EO-30), amount of condensed steam may reach 0.93-0.98. Estimation of gas-dynamic resistance of coolers shows that resistance from steam side in coolers with built-in and remote pipe bundle constitutes 100-300 Pa. Gas-dynamic resistance of "pipein- pipe" and helical type coolers is significantly higher (3-6 times) compared with pipe bundle. However, performance by "dry" (atmospheric) air is higher for ejectors with relatively high gas-dynamic resistance of coolers than those with low resistance at approximately equal operating flow values of ejectors.

Effect of Geometric Parameters on the Performance of Second Throat Annular Steam Ejectors

DTIC Science & Technology

1991-07-01

Cell Pressure versus Rake Average Exit Pitot Pressure . . . . . . . . . . . 42 15. Baseline Wall Pressure Profiles...diffuser exit plane pitot pressure rake . 2.5.2 Alternate Configurations Six alternate ejector diffuser configurations were tested. A summary of...along the walls of the diffusers to help characterize the flow. The ejector diffuser exit pitot pressure was measured with a 6-probe pitot pressure rake

On the rational design of compressible flow ejectors

NASA Technical Reports Server (NTRS)

Ortwerth, P. J.

1979-01-01

A fluid mechanics review of chemical laser ejectors is presented. The characteristics of ejectors with single and multiple driver nozzles are discussed. Methods to compute an optimized performance map in which secondary Mach number and performance are computed versus mass ratio, to compute the flow distortion at each optimized condition, and to determine the thrust area for the design point to match diffuser impedence are examined.

Peptide synthesis on glass substrate using acoustic droplet ejector.

PubMed

Youngki Choe; Shih-Jui Chen; Eun Sok Kim

2014-03-01

This paper describes the synthesis of a 9-mers-long peptide ladder structure of glycine on a modified glass surface using a nanoliter droplet ejector. To synthesize peptide on a glass substrate, SPOT peptide synthesis protocol was followed with a nozzleless acoustic droplet ejector being used to eject about 300 droplets of preactivated amino acid solution to dispense 60 nL of the solution per mer. The coupling efficiency of each mer was measured with FITC fluorescent tag to be 96%, resulting in net 70% efficiency for the whole 9-mer-long peptide of glycine. Usage of a nanoliter droplet ejector for SPOT peptide synthesis increases the density of protein array on a chip.

A Multidisciplinary Approach to Mixer-Ejector Analysis and Design

NASA Technical Reports Server (NTRS)

Hendricks, Eric, S.; Seidel, Jonathan, A.

2012-01-01

The design of an engine for a civil supersonic aircraft presents a difficult multidisciplinary problem to propulsion system engineers. There are numerous competing requirements for the engine, such as to be efficient during cruise while yet quiet enough at takeoff to meet airport noise regulations. The use of mixer-ejector nozzles presents one possible solution to this challenge. However, designing a mixer-ejector which will successfully address both of these concerns is a difficult proposition. Presented in this paper is an integrated multidisciplinary approach to the analysis and design of these systems. A process that uses several low-fidelity tools to evaluate both the performance and acoustics of mixer-ejectors nozzles is described. This process is further expanded to include system-level modeling of engines and aircraft to determine the effects on mission performance and noise near airports. The overall process is developed in the OpenMDAO framework currently being developed by NASA. From the developed process, sample results are given for a notional mixer-ejector design, thereby demonstrating the capabilities of the method.

Effect of Afterbody-Ejector Configurations on the Performance at Transonic Speeds of a Pylon-Supported Nacelle Model having a Hot-Jet Exhaust

NASA Technical Reports Server (NTRS)

Swihart, John M.; Mercer, Charles E.; Norton, Harry T., Jr.

1959-01-01

An investigation of several afterbody-ejector configurations on a pylon-supported nacelle model has been completed in the Langley 16-foot transonic tunnel at Mach numbers from 0.80 to 1.05. The propulsive performance of two nacelle afterbodies with low boattailing and long ejector spacing was compared with a configuration corresponding to a turbojet-engine installation having a highly boattailed afterbody with a short ejector. The jet exhaust was simulated with a hydrogen peroxide turbojet simulator. The angle of attack was maintained at 0 deg, and the average Reynolds number based on body length was 20 x 10(exp 6). The results of the investigation indicated that the configuration with a conical afterbody with smooth transition to a 15 deg boattail angle had large beneficial jet effects on afterbody pressure-drag coefficient and had the best thrust-minus-drag performance of the afterbody-ejector configurations investigated.

Simulated flight acoustic investigation of treated ejector effectiveness on advanced mechanical suppresors for high velocity jet noise reduction

NASA Technical Reports Server (NTRS)

Brausch, J. F.; Motsinger, R. E.; Hoerst, D. J.

1986-01-01

Ten scale-model nozzles were tested in an anechoic free-jet facility to evaluate the acoustic characteristics of a mechanically suppressed inverted-velocity-profile coannular nozzle with an accoustically treated ejector system. The nozzle system used was developed from aerodynamic flow lines evolved in a previous contract, defined to incorporate the restraints imposed by the aerodynamic performance requirements of an Advanced Supersonic Technology/Variable Cycle Engine system through all its mission phases. Accoustic data of 188 test points were obtained, 87 under static and 101 under simulated flight conditions. The tests investigated variables of hardwall ejector application to a coannular nozzle with 20-chute outer annular suppressor, ejector axial positioning, treatment application to ejector and plug surfaces, and treatment design. Laser velocimeter, shadowgraph photograph, aerodynamic static pressure, and temperature measurement were acquired on select models to yield diagnositc information regarding the flow field and aerodynamic performance characteristics of the nozzles.

A comparison of homogeneous equilibrium and relaxation model for CO2 expansion inside the two-phase ejector

NASA Astrophysics Data System (ADS)

Palacz, M.; Haida, M.; Smolka, J.; Nowak, A. J.; Hafner, A.

2016-09-01

In this study, the comparison of the accuracy of the homogeneous equilibrium model (HEM) and homogeneous relaxation model (HRM) is presented. Both models were applied to simulate the CO2 expansion inside the two-phase ejectors. Moreover, the mentioned models were implemented in the robust and efficient computational tool ejectorPL. That tool guarantees the fully automated computational process and the repeatable computations for the various ejector shapes and operating conditions. The simulated motive nozzle mass flow rates were compared to the experimentally measured mass flow rates. That comparison was made for both, HEM and HRM. The results showed the unsatisfying fidelity of the HEM for the operating regimes far from the carbon dioxide critical point. On the other hand, the HRM accuracy for such conditions was slightly higher. The approach presented in this paper, showed the limitation of applicability of both two-phase models for the expansion phenomena inside the ejectors.

Numerical prediction of 3-D ejector flows

NASA Technical Reports Server (NTRS)

Roberts, D. W.; Paynter, G. C.

1979-01-01

The use of parametric flow analysis, rather than parametric scale testing, to support the design of an ejector system offers a number of potential advantages. The application of available 3-D flow analyses to the design ejectors can be subdivided into several key elements. These are numerics, turbulence modeling, data handling and display, and testing in support of analysis development. Experimental and predicted jet exhaust for the Boeing 727 aircraft are examined.

Conceptual design, evaluation and research identification for Remote Augmented Propulsive Lift Systems (RALS) with ejectors for VTOL aircraft

NASA Technical Reports Server (NTRS)

Willis, W. S.; Konarski, M.; Sutherland, M. V.

1982-01-01

Ejector concepts for use with a remote augmented lift system (RALS) exhaust nozzle were studied. A number of concepts were considered and three were selected as having the greatest promise of providing the desired aircraft and exhaust gas cooling and lift enhancement. A scale model test program is recommended to explore the effects of the more important parameters on ejector performance.

Experimental and Numerical Study on Supersonic Ejectors Working with R-1234ze(E)

NASA Astrophysics Data System (ADS)

Kracik, Jan; Dvorak, Vaclav; Nguyen Van, Vu; Smierciew, Kamil

2018-06-01

These days, much effort is being put into lowering the consumption of electric energy and involving renewable energy sources. Many engineers and designers are trying to develop environment-friendly technologies worldwide. It is related to incorporating appropriate devices into such technologies. The object of this paper is to investigate these devices in connection with refrigeration systems. Ejectors can be considered such as these devices. The primary interest of this paper is to investigate the suitability of a numerical model for an ejector, which is incorporated into a refrigeration system. In the present paper, there have been investigated seven different test runs of working of the ejector with a working fluid R-1234ze(E). Some of the investigated cases seem to have a good agreement and there are no significant discrepancies between them, however, there are also cases that do not correspond to the experimental data at all. The ejector has been investigated in both on-design and off-design working modes. A comparison between the experimental and numerical data (CFD) performed by Ansys Fluent software is presented and discussed for both an ideal and a real gas model. In addition, an enhanced analytical model has been introduced for all runs of the ejector.

Noise measurements from an ejector suppressor nozzle in the NASA Lewis 9- by 15-foot low speed wind tunnel

NASA Technical Reports Server (NTRS)

Krejsa, Eugene A.; Cooper, Beth A.; Hall, David G.; Khavaran, Abbas

1990-01-01

Acoustic results are presented of a cooperative nozzle test program between NASA and Pratt and Whitney, conducted in the NASA-Lewis 9 x 15 ft Anechoic Wind Tunnel. The nozzle tested was the P and W Hypermix Nozzle concept, a 2-D lobed mixer nozzle followed by a short ejector section made to promote rapid mixing of the induced ejector nozzle flow. Acoustic and aerodynamic measurements were made to determine the amount of ejector pumping, degree of mixing, and noise reduction achieved. A series of tests were run to verify the acoustic quality of this tunnel. The results indicated that the tunnel test section is reasonably anechoic but that background noise can limit the amount of suppression observed from suppressor nozzles. Also, a possible internal noise was observed in the air supply system. The P and W ejector suppressor nozzle demonstrated the potential of this concept to significantly reduce jet noise. Significant reduction in low frequency noise was achieved by increasing the peak jet noise frequency. This was accomplished by breaking the jet into segments with smaller dimensions than those of the baseline nozzle. Variations in ejector parameters had little effect on the noise for the geometries and the range of temperatures and pressure ratios tested.

Ejector-turbine studies and experimental data. Final report, August 1, 1979-October 31, 1982

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

Minardi, J.E.; Lawson, M.O.; Krolak, R.V.

1982-11-01

An innovative low-power Rankine turbine concept is described which promises competitive efficiencies, low cost, significant reduction in rpm, low maintenance, and long-life operation over similarly rated turbines. The cycle uses a highly efficient two-fluid ejector which greatly lowers the turbine inlet pressure and temperature. The two-fluid ejector cycle is shown by theoretical studies to be capable of transferring energy at efficiencies in excess of 90% from a high-power flux fluid medium to a low-power flux fluid medium. The volume flow of the thermodynamic fluid can be augmented by as much as one-hundred fold. For very low-power turbine applications this couldmore » result in far-more-favorable turbine sizes and rpm. One major application for this type turbine is the heating and cooling with heat pumps. The concept permits engine cycles that cover an extremely broad range of peak temperatures, including those corresponding to stoichiometric combustion of hydrocarbon fuels, waste heat sources, and solar. Actual test data indicated ejector efficiencies as high as 85%. A two-fluid, ejector turbine was designed and tested. The turbine achieved 94% of design power. Additional data indicated that the ejector attached to the turbine operated on the supersonic branch.« less

Performance of an Axisymmetric Rocket Based Combined Cycle Engine During Rocket Only Operation Using Linear Regression Analysis

NASA Technical Reports Server (NTRS)

Smith, Timothy D.; Steffen, Christopher J., Jr.; Yungster, Shaye; Keller, Dennis J.

1998-01-01

The all rocket mode of operation is shown to be a critical factor in the overall performance of a rocket based combined cycle (RBCC) vehicle. An axisymmetric RBCC engine was used to determine specific impulse efficiency values based upon both full flow and gas generator configurations. Design of experiments methodology was used to construct a test matrix and multiple linear regression analysis was used to build parametric models. The main parameters investigated in this study were: rocket chamber pressure, rocket exit area ratio, injected secondary flow, mixer-ejector inlet area, mixer-ejector area ratio, and mixer-ejector length-to-inlet diameter ratio. A perfect gas computational fluid dynamics analysis, using both the Spalart-Allmaras and k-omega turbulence models, was performed with the NPARC code to obtain values of vacuum specific impulse. Results from the multiple linear regression analysis showed that for both the full flow and gas generator configurations increasing mixer-ejector area ratio and rocket area ratio increase performance, while increasing mixer-ejector inlet area ratio and mixer-ejector length-to-diameter ratio decrease performance. Increasing injected secondary flow increased performance for the gas generator analysis, but was not statistically significant for the full flow analysis. Chamber pressure was found to be not statistically significant.

Liquid sampling system

DOEpatents

Larson, L.L.

1984-09-17

A conduit extends from a reservoir through a sampling station and back to the reservoir in a closed loop. A jet ejector in the conduit establishes suction for withdrawing liquid from the reservoir. The conduit has a self-healing septum therein upstream of the jet ejector for receiving one end of a double-ended cannula, the other end of which is received in a serum bottle for sample collection. Gas is introduced into the conduit at a gas bleed between the sample collection bottle and the reservoir. The jet ejector evacuates gas from the conduit and the bottle and aspirates a column of liquid from the reservoir at a high rate. When the withdrawn liquid reaches the jet ejector the rate of flow therethrough reduces substantially and the gas bleed increases the pressure in the conduit for driving liquid into the sample bottle, the gas bleed forming a column of gas behind the withdrawn liquid column and interrupting the withdrawal of liquid from the reservoir. In the case of hazardous and toxic liquids, the sample bottle and the jet ejector may be isolated from the reservoir and may be further isolated from a control station containing remote manipulation means for the sample bottle and control valves for the jet ejector and gas bleed. 5 figs.

Liquid sampling system

DOEpatents

Larson, Loren L.

1987-01-01

A conduit extends from a reservoir through a sampling station and back to the reservoir in a closed loop. A jet ejector in the conduit establishes suction for withdrawing liquid from the reservoir. The conduit has a self-healing septum therein upstream of the jet ejector for receiving one end of a double-ended cannula, the other end of which is received in a serum bottle for sample collection. Gas is introduced into the conduit at a gas bleed between the sample collection bottle and the reservoir. The jet ejector evacuates gas from the conduit and the bottle and aspirates a column of liquid from the reservoir at a high rate. When the withdrawn liquid reaches the jet ejector the rate of flow therethrough reduces substantially and the gas bleed increases the pressure in the conduit for driving liquid into the sample bottle, the gas bleed forming a column of gas behind the withdrawn liquid column and interrupting the withdrawal of liquid from the reservoir. In the case of hazardous and toxic liquids, the sample bottle and the jet ejector may be isolated from the reservoir and may be further isolated from a control station containing remote manipulation means for the sample bottle and control valves for the jet ejector and gas bleed.

A kinematic and kinetic analysis of the sit-to-stand transfer using an ejector chair: implications for elderly rheumatoid arthritic patients.

PubMed

Munro, B J; Steele, J R; Bashford, G M; Ryan, M; Britten, N

1998-03-01

Twelve elderly female rheumatoid arthritis patients (mean age = 65.5 +/- 8.6 yr) were assessed rising from an instrumented Eser Ejector chair under four conditions: high seat (540 mm), low seat (450 mm), with and without the ejector mechanism operating. Sagittal plane motion, ground reaction forces, and vertical chair arm rest forces were recorded during each trial with the signals synchronised at initial subject head movement. When rising from a high seat, subjects displayed significantly (p < 0.05) greater time to seat off; greater trunk, knee and ankle angles at seat off; increased ankle angular displacement; decreased knee angular displacement; and decreased total net and normalised arm rest forces compared to rising from a low seat. When rising using the ejector mechanism, time to seat off and trunk and knee angle at seat off significantly increased, whereas trunk and knee angular displacement, and total net and normalised arm rest forces significantly decreased compared to rising unassisted. Regardless of seat height or ejector mechanism use, there were no significant differences in the peak, or time to peak horizontal velocity of the subjects' total body centre of mass, or net knee and ankle moments. It was concluded that increased seat height and use of the ejector mechanism facilitated sit-to-stand transfers performed by elderly female rheumatoid arthritic patients. However, using the ejector chair may be preferred by these patients compared to merely raising seat height because it does not necessitate the use of a footstool, a possible obstacle contributing to falls.

Analysis of experimental characteristics of multistage steam-jet electors of steam turbines

NASA Astrophysics Data System (ADS)

Aronson, K. E.; Ryabchikov, A. Yu.; Brodov, Yu. M.; Brezgin, D. V.; Zhelonkin, N. V.; Murmanskii, I. B.

2017-02-01

A series of questions for specification of physical gas dynamics model in flow range of steam-jet unit and ejector computation methodology, as well as functioning peculiarities of intercoolers, was formulated based on analysis of experimental characteristics of multistage team-jet steam turbines. It was established that coefficient defining position of critical cross-section of injected flow depends on characteristics of the "sound tube" zone. Speed of injected flow within this tube may exceed that of sound, and pressure jumps in work-steam decrease at the same time. Characteristics of the "sound tube" define optimal axial sizes of the ejector. According to measurement results, the part of steam condensing in the first-stage coolant constitutes 70-80% of steam amount supplied into coolant and is almost independent of air content in steam. Coolant efficiency depends on steam pressure defined by operation of steam-jet unit of ejector of the next stage after coolant of steam-jet stage, temperature, and condensing water flow. As a rule, steam entering content of steam-air mixture supplied to coolant is overheated with respect to saturation temperature of steam in the mixture. This should be taken into account during coolant computation. Long-term operation causes changes in roughness of walls of the ejector's mixing chamber. The influence of change of wall roughness on ejector characteristic is similar to the influence of reverse pressure of the steam-jet stage. Until some roughness value, injection coefficient of the ejector stage operating in superlimiting regime hardly changed. After reaching critical roughness, the ejector switches to prelimiting operating regime.

Effect of Installation of Mixer/Ejector Nozzles on the Core Flow Exhaust of High-Bypass-Ratio Turbofan Engines

NASA Technical Reports Server (NTRS)

Harrington, Douglas E.

1998-01-01

The aerospace industry is currently investigating the effect of installing mixer/ejector nozzles on the core flow exhaust of high-bypass-ratio turbofan engines. This effort includes both full-scale engine tests at sea level conditions and subscale tests in static test facilities. Subscale model tests are to be conducted prior to full-scale testing. With this approach, model results can be analyzed and compared with analytical predications. Problem areas can then be identified and design changes made and verified in subscale prior to committing to any final design configurations for engine ground tests. One of the subscale model test programs for the integrated mixer/ejector development was a joint test conducted by the NASA Lewis Research Center and Pratt & Whitney Aircraft. This test was conducted to study various mixer/ejector nozzle configurations installed on the core flow exhaust of advanced, high-bypass-ratio turbofan engines for subsonic, commercial applications. The mixer/ejector concept involves the introduction of largescale, low-loss, streamwise vortices that entrain large amounts of secondary air and rapidly mix it with the primary stream. This results in increased ejector pumping relative to conventional ejectors and in more complete mixing within the ejector shroud. The latter improves thrust performance through the efficient energy exchange between the primary and secondary streams. This experimental program was completed in April 1997 in Lewis' CE-22 static test facility. Variables tested included the nozzle area ratio (A9/A8), which ranged from 1.6 to 3.0. This ratio was varied by increasing or decreasing the nozzle throat area, A8. Primary nozzles tested included both lobed mixers and conical primaries. These configurations were tested with and without an outer shroud, and the shroud position was varied by inserting spacers in it. In addition, data were acquired with and without secondary flow.

Combined Numerical/Analytical Perturbation Solutions of the Navier-Stokes Equations for Aerodynamic (Ejector Nozzle) Flows

NASA Technical Reports Server (NTRS)

DeChant, Lawrence J.

1997-01-01

In spite of the rapid advances in both scalar and parallel computational tools, the large number and breadth of variables involved in aerodynamic systems make the use of parabolized or even boundary layer fluid flow models impractical for both preliminary design and inverse design problems. Given this restriction, we have concluded that reduced or approximate models are an important family of tools for design purposes. This study of a combined perturbation/numerical modeling methodology with an application to ejector-mixer nozzles (shown schematically in the following figure) is nearing completion. The work is being funded by a grant from the NASA Lewis Research Center to Texas A&M University. These ejector-mixer nozzle models are designed to be of use to the High Speed Civil Transport Program and may be adopted by both NASA and industry. A computer code incorporating the ejector-mixer models is under development. This code, the Differential Reduced Ejector/Mixer Analysis (DREA), can be run fast enough to be used as a subroutine or to be called by a design optimization routine. Simplified conservation equations--x-momentum, energy, and mass conservation--are used to define the model. Unlike other preliminary design models, DREA requires minimal empirical input and includes vortical mixing and a fully compressible formulation among other features. DREA is being validated by comparing it with results obtained from open literature and proprietary industry data. Preliminary results for a subsonic ejector and a supersonic ejector are shown. In addition, dedicated experiments have been performed at Texas A&M. These experiments use a hydraulic/gas flow analog to provide information about the inviscid mixing interface structure. Final validation and documentation of this work is expected by May of 1997. However, preliminary versions of DREA can be expected in early 1997. In summary, DREA provides a sufficiently detailed and realistic ejector-mixer nozzle model at a computational cost compatible with preliminary design applications.

Impacts of Venturi Turbulent Mixing on the Size Distributions of Sodium Chloride and Dioctyl-Phthalate Aerosols

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

Cheng, M-D.

2000-08-23

Internal combustion engines are a major source of airborne particulate matter (PM). The size of the engine PM is in the sub-micrometer range. The number of engine particles per unit volume is high, normally in the range of 10{sup 12} to 10{sup 14}. To measure the size distribution of the engine particles dilution of an aerosol sample is required. A diluter utilizing a venturi ejector mixing technique is commercially available and tested. The purpose of this investigation was to determine if turbulence created by the ejector in the mini-dilutor changes the size of particles passing through it. The results ofmore » the NaCl aerosol experiments show no discernible difference in the geometric mean diameter and geometric standard deviation of particles passing through the ejector. Similar results were found for the DOP particles. The ratio of the total number concentrations before and after the ejector indicates that a dilution ratio of approximately 20 applies equally for DOP and NaCl particles. This indicates the dilution capability of the ejector is not affected by the particle composition. The statistical analysis results of the first and second moments of a distribution indicate that the ejector may not change the major parameters (e.g., the geometric mean diameter and geometric standard deviation) characterizing the size distributions of NaCl and DOP particles. However, when the skewness was examined, it indicates that the ejector modifies the particle size distribution significantly. The ejector could change the skewness of the distribution in an unpredictable and inconsistent manner. Furthermore, when the variability of particle counts in individual size ranges as a result of the ejector is examined, one finds that the variability is greater for DOP particles in the size range of 40-150 nm than for NaCl particles in the size range of 30 to 350 nm. The numbers or particle counts in this size region are high enough that the Poisson counting errors are small (<10%) compared with the tail regions. This result shows that the ejector device could have a higher bin-to-bin counting uncertainty for ''soft'' particles such as DOP than for a solid dry particle like NaCl. The results suggest that it may be difficult to precisely characterize the size distribution of particles ejected from the mini-dilution system if the particle is not solid.« less

A modified homogeneous relaxation model for CO2 two-phase flow in vapour ejector

NASA Astrophysics Data System (ADS)

Haida, M.; Palacz, M.; Smolka, J.; Nowak, A. J.; Hafner, A.; Banasiak, K.

2016-09-01

In this study, the homogenous relaxation model (HRM) for CO2 flow in a two-phase ejector was modified in order to increase the accuracy of the numerical simulations The two- phase flow model was implemented on the effective computational tool called ejectorPL for fully automated and systematic computations of various ejector shapes and operating conditions. The modification of the HRM was performed by a change of the relaxation time and the constants included in the relaxation time equation based on the experimental result under the operating conditions typical for the supermarket refrigeration system. The modified HRM was compared to the HEM results, which were performed based on the comparison of motive nozzle and suction nozzle mass flow rates.

Exhaust Nozzles for Supersonic Flight with Turbojet Engines

NASA Technical Reports Server (NTRS)

Shillito, Thomas B.; Hearth, Donald P.; Cortright, Edgar M.

1956-01-01

Good internal performance over a wide range of flight conditions can be obtained with either a plug nozzle or a variable ejector nozzle that can provide a divergent shroud at high pressure ratios. For both the ejector and the plug nozzle, external flow can sometimes cause serious drag losses and, for some plug-nozzle installations, external flow can cause serious internal performance losses. Plug-nozzle cooling and design of the secondary-air-flow systems for ejectors were also considered .

Effects of Multiple Nozzles on Asymmetric Ejector Performance

NASA Technical Reports Server (NTRS)

Lineberry, D.; Landrum, B.

2005-01-01

This paper presents a comparison of a single nozzle and a dual nozzle strut based ejector. The results are focused on the fluid properties in the ejector duct. The research focused on choking mechanisms, mass flow entrainment, and mixing duct pressure distributions. The two ejectors were tests at equivalent primary mass flow rates. This corresponds to chamber pressures ranging from 100 psi to 900 psi in the single nozzle strut and 50 psi to 450 psi in the dual nozzle strut. Secondary flow was drawn from the lab at atmospheric pressure, and was not controlled. The secondary flow was found to choke at a value of 2.3 lb/s for a primary mass flow rate at approximately 2.1 lb/s for both ejectors. This choke was believed to be a mass addition choke rather than a traditional aerodynamic choke. The mixing duct pressure distribution exhibited two distinct trends at "low pressure" trend and at "high pressure" trend. For the low pressure trend, the mixing length for the ejectors remained fixed around 20 inches, regardless of the chamber pressure. For the higher pressure trend, the mixing length was considerably longer and increased with increasing chamber pressure. At high chamber pressures (high mass flow rates), a supersonic core flow was present at the exit of the duct. For these cases, the two streams did not have time to mix by the end of the duct.

Ejector Noise Suppression with Auxiliary Jet Injection

NASA Technical Reports Server (NTRS)

Berman, Charles H.; Andersen, Otto P., Jr.

1997-01-01

An experimental program to reduce aircraft jet turbulence noise investigated the interaction of small auxiliary jets with a larger main jet. Significant reductions in the far field jet noise were obtained over a range of auxiliary jet pressures and flow rates when used in conjunction with an acoustically lined ejector. While the concept is similar to that of conventional ejector suppressors that use mechanical mixing devices, the present approach should improve thrust and lead to lower weight and less complex noise suppression systems since no hardware needs to be located in the main jet flow. A variety of auxiliary jet and ejector configurations and operating conditions were studied. The best conditions tested produced peak to peak noise reductions ranging from 11 to 16 dB, depending on measurement angle, for auxiliary jet mass flows that were 6.6% of the main jet flow with ejectors that were 8 times the main jet diameter in length. Much larger reductions in noise were found at the original peak frequencies of the unsuppressed jet over a range of far field measurement angles.

The effects of the secondary fluid temperature on the energy transfer in an unsteady ejector with a radial-flow diffuser

NASA Astrophysics Data System (ADS)

Ababneh, Amer Khalil; Jawarneh, Ali M.; Tlilan, Hitham M.; Ababneh, Mohammad K.

2009-11-01

Unsteady ejectors are devices whereby energy is exchanged between directly interacting fluids. Unlike steady ejectors, the mechanism responsible for the energy transfer is reversible in nature and thus higher efficiencies are perceivable. A potential application for PEE is for enhancement in output power per weight as in turbochargers. The unsteady ejector when used as a turbocharger the device is expected to perform under wide range of ambient temperatures. Therefore, it is important to investigate the effects of the temperature of the induced ambient air on the energy transfer. The radial-flow ejector, which usually leads to higher-pressure ratios with fewer stages, was selected for the investigation. The flow field is investigated at two Mach numbers 2.5 and 3.0 utilizing rectangular short-length supersonic nozzles for accelerating the primary fluid. Fundamental to the enhancement of these devices performance relies on the management of the flow field in such a way to minimize entropy production. The numerical analyses were conducted utilizing a package of computational fluid dynamics.

System Regulates the Water Contents of Fuel-Cell Streams

NASA Technical Reports Server (NTRS)

Vasquez, Arturo; Lazaroff, Scott

2005-01-01

An assembly of devices provides for both humidification of the reactant gas streams of a fuel cell and removal of the product water (the water generated by operation of the fuel cell). The assembly includes externally-sensing forward-pressure regulators that supply reactant gases (fuel and oxygen) at variable pressures to ejector reactant pumps. The ejector supply pressures depend on the consumption flows. The ejectors develop differential pressures approximately proportional to the consumption flow rates at constant system pressure and with constant flow restriction between the mixer-outlet and suction ports of the ejectors. For removal of product water from the circulating oxygen stream, the assembly includes a water/gas separator that contains hydrophobic and hydrophilic membranes. The water separator imposes an approximately constant flow restriction, regardless of the quality of the two-phase flow that enters it from the fuel cell. The gas leaving the water separator is nearly 100 percent humid. This gas is returned to the inlet of the fuel cell along with a quantity of dry incoming oxygen, via the oxygen ejector, thereby providing some humidification.

Lobed Mixer Optimization for Advanced Ejector Geometries

NASA Technical Reports Server (NTRS)

Waitz, Ian A.

1996-01-01

The overall objectives are: 1) to pursue analytical, computational, and experimental studies that enhance basic understanding of forced mixing phenomena relevant to supersonic jet noise reduction, and 2) to integrate this enhanced understanding (analytical, computational, and empirical) into a design-oriented model of a mixer-ejector noise suppression system. The work is focused on ejector geometries and flow conditions typical of those being investigated in the NASA High Speed Research Program (HSRP). The research will be carried out in collaboration with the NASA HSRP Nozzle Integrated Technology Development (ITD) Team, and will both contribute to, and benefit from, the results of other HSRP research. The noise suppressor system model that is being developed under this grant is distinct from analytical tools developed by industry because it directly links details of lobe geometry to mixer-ejector performance. In addition, the model provides a 'technology road map to define gaps in the current understanding of various phenomena related to mixer-ejector design and to help prioritize research areas. This report describes research completed in the past year, as well as work proposed for the following year.

Thermodynamic Analysis of a Mixed Refrigerant Ejector Refrigeration Cycle Operating with Two Vapor-liquid Separators

NASA Astrophysics Data System (ADS)

Tan, Yingying; Chen, Youming; Wang, Lin

2018-06-01

A mixed refrigerant ejector refrigeration cycle operating with two-stage vapor-liquid separators (MRERC2) is proposed to obtain refrigeration temperature at -40°C. The thermodynamic investigations on performance of MRERC2 using zeotropic mixture refrigerant R23/R134a are performed, and the comparisons of cycle performance between MRERC2 and MRERC1 (MRERC with one-stage vapor-liquid separator) are conducted. The results show that MRERC2 can achieve refrigeration temperature varying between -23.9°C and -42.0°C when ejector pressure ratio ranges from 1.6 to 2.3 at the generation temperature of 57.3-84.9°C. The parametric analysis indicates that increasing condensing temperature decreases coefficient of performance ( COP) of MRERC2, and increasing ejector pressure ratio and mass fraction of the low boiling point component in the mixed refrigerant can improve COP of MRERC2. The MRERC2 shows its potential in utilizing low grade thermal energy as driving power to obtain low refrigeration temperature for the ejector refrigeration cycle.

A Simple Model of Pulsed Ejector Thrust Augmentation

NASA Technical Reports Server (NTRS)

Wilson, Jack; Deloof, Richard L. (Technical Monitor)

2003-01-01

A simple model of thrust augmentation from a pulsed source is described. In the model it is assumed that the flow into the ejector is quasi-steady, and can be calculated using potential flow techniques. The velocity of the flow is related to the speed of the starting vortex ring formed by the jet. The vortex ring properties are obtained from the slug model, knowing the jet diameter, speed and slug length. The model, when combined with experimental results, predicts an optimum ejector radius for thrust augmentation. Data on pulsed ejector performance for comparison with the model was obtained using a shrouded Hartmann-Sprenger tube as the pulsed jet source. A statistical experiment, in which ejector length, diameter, and nose radius were independent parameters, was performed at four different frequencies. These frequencies corresponded to four different slug length to diameter ratios, two below cut-off, and two above. Comparison of the model with the experimental data showed reasonable agreement. Maximum pulsed thrust augmentation is shown to occur for a pulsed source with slug length to diameter ratio equal to the cut-off value.

Transient Ejector Analysis (TEA) code user's guide

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1993-01-01

A FORTRAN computer program for the semi analytic prediction of unsteady thrust augmenting ejector performance has been developed, based on a theoretical analysis for ejectors. That analysis blends classic self-similar turbulent jet descriptions with control-volume mixing region elements. Division of the ejector into an inlet, diffuser, and mixing region allowed flexibility in the modeling of the physics for each region. In particular, the inlet and diffuser analyses are simplified by a quasi-steady-analysis, justified by the assumption that pressure is the forcing function in those regions. Only the mixing region is assumed to be dominated by viscous effects. The present work provides an overview of the code structure, a description of the required input and output data file formats, and the results for a test case. Since there are limitations to the code for applications outside the bounds of the test case, the user should consider TEA as a research code (not as a production code), designed specifically as an implementation of the proposed ejector theory. Program error flags are discussed, and some diagnostic routines are presented.

3-D zebrafish embryo image filtering by nonlinear partial differential equations.

PubMed

Rizzi, Barbara; Campana, Matteo; Zanella, Cecilia; Melani, Camilo; Cunderlik, Robert; Krivá, Zuzana; Bourgine, Paul; Mikula, Karol; Peyriéras, Nadine; Sarti, Alessandro

2007-01-01

We discuss application of nonlinear PDE based methods to filtering of 3-D confocal images of embryogenesis. We focus on the mean curvature driven and the regularized Perona-Malik equations, where standard as well as newly suggested edge detectors are used. After presenting the related mathematical models, the practical results are given and discussed by visual inspection and quantitatively using the mean Hausdorff distance.

Ejector subassembly for dual wall air drilling

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

Kolle, J.J.

1996-09-01

The dry drilling system developed for the Yucca Mountain Site Characterization Project incorporates a surface vacuum system to prevent drilling air and cuttings from contaminating the borehole wall during coring operations. As the drilling depth increases, however there is a potential for borehole contamination because of the limited volume of air which can be removed by the vacuum system. A feasibility analysis has shown that an ejector subassembly mounted in the drill string above the core barrel could significantly enhance the depth capacity of the dry drilling system. The ejector subassembly would use a portion of the air supplied tomore » the core bit to maintain a vacuum on the hole bottom. The results of a design study including performance testing of laboratory scale ejector simulator are presented here.« less

The ejector flowmeter as air/oxygen mixing device. An apparatus providing gas mixtures with adjustable oxygen content for high-flow humidification systems.

PubMed

Christensen, K N; Waaben, J; Jørgensen, S

1980-04-01

The ejector flowmeter is constructed for continuous removal of excess gas from anaesthetic circuits. This instrument can be used as an air/oxygen mixing device for high-flow humidification systems in wards where compressed air is not available. Pure oxygen is used as driving gas through the ejector. A nomogram has been constructed to show the relationship between oxygen driving pressure, inlet of air to the flowmeter, FIO2 and total outflow.

Credit WCT. Photographic copy of photograph, view east southeast across ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit WCT. Photographic copy of photograph, view east southeast across Dd station ejectors showing detail of "Hyprox" steam generator. Note that steam generator is placed above Z-stage ejector; an insulated pipe running between the Dd train rails supplies steam to the Y-Stage ejector. Note emergency eyewash stand at extreme right of view. (JPL negative no. 384-3376, 3 December 1962) - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Performance of solar refrigerant ejector refrigerating machine

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

Al-Khalidy, N.A.H.

1997-12-31

In this work a detailed analysis for the ideal, theoretical, and experimental performance of a solar refrigerant ejector refrigerating machine is presented. A comparison of five refrigerants to select a desirable one for the system is made. The theoretical analysis showed that refrigerant R-113 is more suitable for use in the system. The influence of the boiler, condenser, and evaporator temperatures on system performance is investigated experimentally in a refrigerant ejector refrigerating machine using R-113 as a working refrigerant.

SST Technology Follow-On Program - Phase 2. Noise Suppressor/Nozzle Development. Volume 5. Advanced Suppressor Concepts and Full Scale Tests

DTIC Science & Technology

1975-03-01

Approved for U.S. Government only. This docu- ment is exempted from public availability be- cause of restrictions imposed by the Export Con- trol Act...Transmittal of this document outside the U.S. Government must have prior approval of the Supersonic Transport Office. 20 Security Classif (of this...linings may be determined by comparing nozzle/ejector radiated noise power levels between the unlined (hardwall) ejector case and the lined ejector

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.

Control-Volume Analysis Of Thrust-Augmenting Ejectors

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1990-01-01

New method of analysis of transient flow in thrust-augmenting ejector based on control-volume formulation of governing equations. Considered as potential elements of propulsion subsystems of short-takeoff/vertical-landing airplanes.

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.

Apparatus and method for suppressing sound in a gas turbine engine powerplant

NASA Technical Reports Server (NTRS)

Wynosky, Thomas A. (Inventor); Mischke, Robert J. (Inventor)

1992-01-01

A method and apparatus for suppressing jet noise in a gas turbine engine powerplant 10 is disclosed. Various construction details are developed for providing sound suppression at sea level take-off operative conditions and not providing sound suppression at cruise operative conditions. In one embodiment, the powerplant 10 has a lobed mixer 152 between a primary flowpath 44 and a second flowpath 46, a diffusion region downstream of the lobed mixer region (first mixing region 76), and a deployable ejector/mixer 176 in the diffusion region which forms a second mixing region 78 having a diffusion flowpath 72 downstream of the ejector/mixer and sound absorbing structure 18 bounding the flowpath throughout the diffusion region. The method includes deploying the ejector/mixer 176 at take-off and stowing the ejector/mixer at cruise.

Thermodynamic analysis of a new dual evaporator CO2 transcritical refrigeration cycle

NASA Astrophysics Data System (ADS)

Abdellaoui, Ezzaalouni Yathreb; Kairouani, Lakdar Kairouani

2017-03-01

In this work, a new dual-evaporator CO2 transcritical refrigeration cycle with two ejectors is proposed. In this new system, we proposed to recover the lost energy of condensation coming off the gas cooler and operate the refrigeration cycle ejector free and enhance the system performance and obtain dual-temperature refrigeration simultaneously. The effects of some key parameters on the thermodynamic performance of the modified cycle are theoretically investigated based on energetic and exergetic analysis. The simulation results for the modified cycle indicate more effective system performance improvement than the single ejector in the CO2 vapor compression cycle using ejector as an expander ranging up to 46%. The exergetic analysis for this system is made. The performance characteristics of the proposed cycle show its promise in dual-evaporator refrigeration system.

Use of an approximate similarity principle for the thermal scaling of a full-scale thrust augmenting ejector

NASA Technical Reports Server (NTRS)

Barankiewicz, Wendy S.; Perusek, Gail P.; Ibrahim, Mounir B.

1992-01-01

Full temperature ejector model simulations are expensive, and difficult to implement experimentally. If an approximate similarity principle could be established, properly chosen performance parameters should be similar for both hot and cold flow tests if the initial Mach number and total pressures of the flow field are held constant. Existing ejector data is used to explore the utility of one particular similarity principle; the Munk and Prim similarity principle for isentropic flows. Static performance test data for a full-scale thrust augmenting ejector are analyzed for primary flow temperatures up to 1560 R. At different primary temperatures, exit pressure contours are compared for similarity. A nondimensional flow parameter is then used to eliminate primary nozzle temperature dependence and verify similarity between the hot and cold flow experiments.

Use of an approximate similarity principle for the thermal scaling of a full-scale thrust augmenting ejector

NASA Technical Reports Server (NTRS)

Barankiewicz, Wendy; Perusek, Gail P.; Ibrahim, Mounir

1992-01-01

Full temperature ejector model simulations are expensive, and difficult to implement experimentally. If an approximate similarity principle could be established, properly chosen performance parameters should be similar for both hot and cold flow tests if the initial Mach number and total pressures of the flow field are held constant. Existing ejector data is used to explore the utility of one particular similarity principle; the Munk and Prim similarity principle for isentropic flows. Static performance test data for a full-scale thrust augmenting ejector are analyzed for primary flow temperatures up to 1560 R. At different primary temperatures, exit pressure contours are compared for similarity. A nondimensional flow paramenter is then used to eliminate primary nozzle temperature dependence and verify similarity between the hot and cold flow experiments.

Transition aerodynamics for 20-percent-scale VTOL unmanned aerial vehicle

NASA Technical Reports Server (NTRS)

Kjerstad, Kevin J.; Paulson, John W., Jr.

1993-01-01

An investigation was conducted in the Langley 14- by 22-Foot Subsonic Tunnel to establish a transition data base for an unmanned aerial vehicle utilizing a powered-lift ejector system and to evaluate alterations to the ejector system for improved vehicle performance. The model used in this investigation was a 20-percent-scale, blended-body, arrow-wing configuration with integrated twin rectangular ejectors. The test was conducted from hover through transition conditions with variations in angle of attack, angle of sideslip, free-stream dynamic pressure, nozzle pressure ratio, and model ground height. Force and moment data along with extensive surface pressure data were obtained. A laser velocimeter technique for measuring inlet flow velocities was demonstrated at a single flow condition, and also a low order panel method was successfully used to numerically simulate the ejector inlet flow.

The future is today: emerging drugs for the treatment of erectile dysfunction

PubMed Central

Albersen, Maarten; Shindel, Alan; Mwamukonda, Kuwong; Lue, Tom

2011-01-01

Erectile Dysfunction (ED) is the most common male sexual dysfunction presented for treatment, and the most thoroughly studied sexual dysfunction in men. In the late 20th century, important discoveries were made regarding both the physiologic processes of penile erection and the pathophysiology of ED. These discoveries led to the commercial introduction of the phosphodiesterase type 5 inhibitors (PDE5I), a class of medications which now accounts for the largest segment of the ED market. While these drugs are highly efficacious for many men, a relatively large subset of ED patients who do not respond to PDE5I has been identified. Recognition of this subset of the ED population and the ageing of the population has driven researchers to investigate novel treatment targets for ED. Increased research efforts have resulted in the development of several orally available compounds that combine high efficacy with low rates of adverse events. In this review we report on various compounds that regulate penile erection both centrally (Clavulanic acid, Dopamine and Melanocortin receptor agonists) and peripherally (novel PDE5I, soluble and particulate Guanylil Cyclase activators, Rho-kinase inhibitors and Maxi-K channel openers), and discuss the preclinical and clinical evidence supporting the development of these emerging drugs for ED. PMID:20415601

CFD study of ejector flow behavior in a blast furnace gas galvanizing plant

NASA Astrophysics Data System (ADS)

Besagni, Giorgio; Mereu, Riccardo; Inzoli, Fabio

2015-02-01

In recent years, there has been a growing interest toward Blast Furnace Gas (BFG) as a low-grade energy source for industrial furnaces. This paper considers the revamping of a galvanic plant furnace converted to BFG from natural gas. In the design of the new system, the ejector on the exhaust line is a critical component. This paper studies the flow behavior of the ejector using a Computational Fluid Dynamics (CFD) analysis. The CFD model is based on a 3D representation of the ejector, using air and exhaust gases as working fluids. This paper is divided in three parts. In the first part, the galvanic plant used as case study is presented and discussed, in the second part the CFD approach is outlined, and in the third part the CFD approach is validated using experimental data and the numerical results are presented and discussed. Different Reynolds-Averaged Navier-Stokes (RANS) turbulence models ( k-ω SST and k-ɛ Realizable) are evaluated in terms of convergence capability and accuracy in predicting the pressure drop along the ejector. Suggestions for future optimization of the system are also provided.

An Experiment on the Near Flow Field of the GE/ARL Mixer Ejector Nozzle

NASA Technical Reports Server (NTRS)

Zaman, K. B. M. Q.

2004-01-01

This report is a documentation of the results on flowfield surveys for the GE/ARL mixer-ejector nozzle carried out in an open jet facility at NASA Glenn Research Center. The results reported are for cold (unheated) flow without any surrounding co-flowing stream. Distributions of streamwise vorticity as well as turbulent stresses, obtained by hot-wire anemometry, are presented for a low subsonic condition. Pitot probe survey results are presented for nozzle pressure ratios up to 3.5. Flowfields both inside and outside of the ejector are considered. Inside the ejector, the mean velocity distribution exhibits a cellular pattern on the cross sectional plane, originating from the flow through the primary and secondary chutes. With increasing downstream distance an interchange of low velocity regions with adjacent high velocity regions takes place due to the action of the streamwise vortices. At the ejector exit, the velocity distribution is nonuniform at low and high pressure ratios but reasonably uniform at intermediate pressure ratios. The effects of two chevron configurations and a tab configuration on the evolution of the downstream jet are also studied. Compared to the baseline case, minor but noticeable effects are observed on the flowfield.

A novel solar bi-ejector refrigeration system and the performance of the added injector with different structures and operation parameters

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

Wang, Fei; Shen, Shengqiang

2009-12-15

A novel solar bi-ejector refrigeration system was investigated, whose difference compared to the traditional system is that the circulation pump is replaced by a thermal injector. The new system works more stably and needs less maintenance work than the old one, and the whole system can more fully utilize the solar energy. The mathematical models for calculating the performance of the injector and the whole solar refrigeration system were established. The pressure rise performance of injector under different structure and operation parameters and the performance of solar bi-ejector refrigeration system were studied with R123. The results show that the dischargedmore » pressure of injector is affected by structure dimensions of injector and operation conditions. With increasing generation temperature, the entrainment ratio of ejector becomes better while that of injector becomes worse and the overall thermal efficiency of the solar bi-ejector refrigeration system first increases and then decreases with an optimum value of 0.132 at generation temperature of 105 C, condensation temperature of 35 C and evaporation temperature of 10 C. (author)« less

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.

GRC-2010-C-00635

NASA Image and Video Library

2006-02-15

New testing is underway in the Aero-Acoustic Propulsion Laboratory (AAPL) at NASA's Glenn Research Center. The research focuses on a model called the Highly Variable Cycle Exhaust System -- a 0.17 scale model of an exhaust system that will operate at subsonic, transonic and supersonic exhaust speeds in a future supersonic business jet. The model features ejector doors used at different angles. Researchers are investigating the impact of these ejectors on the resulting acoustic radiation. Here, Steven Sedensky, a mechanical engineer with Jacobs Sverdrup, takes measurements of the ejector door positions.

Experimental study of cleaning aircraft GTE fuel injectors using a vortex ejector

NASA Astrophysics Data System (ADS)

Evdokimov, O. A.; Piralishvili, Sh A.; Veretennikov, S. V.; Elkes, A. A.

2017-11-01

The main ways of cleaning the fuel injectors and the circuits of jet and vortex ejectors used for pumping gas, liquid and two-phase media, as well as for evacuation of enclosed spaces are analyzed. The possibility of organizing the process of pumping the liquid out of the fuel injection manifold secondary circuit using a vortex ejector is shown experimentally. The regimes of manifold evacuation at various inlet liquid pressure values are studied. The technology of carbon cleaning fuel injectors using a washing liquid at various working process parameters is tested.

Experimental investigation of an ejector-powered free-jet facility

NASA Technical Reports Server (NTRS)

Long, Mary JO

1992-01-01

NASA Lewis Research Center's (LeRC) newly developed Nozzle Acoustic Test Rig (NATR) is a large free-jet test facility powered by an ejector system. In order to assess the pumping performance of this ejector concept and determine its sensitivity to various design parameters, a 1/5-scale model of the NATR was built and tested prior to the operation of the actual facility. This paper discusses the results of the 1/5-scale model tests and compares them with the findings from the full-scale tests.

Probabilistic density function method for nonlinear dynamical systems driven by colored noise

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

Barajas-Solano, David A.; Tartakovsky, Alexandre M.

2016-05-01

We present a probability density function (PDF) method for a system of nonlinear stochastic ordinary differential equations driven by colored noise. The method provides an integro-differential equation for the temporal evolution of the joint PDF of the system's state, which we close by means of a modified Large-Eddy-Diffusivity-type closure. Additionally, we introduce the generalized local linearization (LL) approximation for deriving a computable PDF equation in the form of the second-order partial differential equation (PDE). We demonstrate the proposed closure and localization accurately describe the dynamics of the PDF in phase space for systems driven by noise with arbitrary auto-correlation time.more » We apply the proposed PDF method to the analysis of a set of Kramers equations driven by exponentially auto-correlated Gaussian colored noise to study the dynamics and stability of a power grid.« less

Operating and hydrodynamic characteristics of a reversed flow jet loop bioreactor (RFJLB) with ejector.

PubMed

Wagh, Sameer M; Koranne, Kishore V; Sonolikar, Ram L

2012-04-01

The hydrodynamic characteristics of RFJLB was studied with superficial liquid velocity (Ul), nozzle diameter (Dn) and nozzle height (Hn) in the range of 0.0293-0.094m/s, 17.4-22.0mm and 50-400mm, respectively. For Dn=17.4mm, Hn=50 and 200mm, with ejector mode and regular operating procedure i.e. simultaneous entry of gas with increasing liquid velocity, had limitation of not establishing the circulation loop. To overcome this limitation a modified operating procedure i.e. entry of gas after established liquid circulation loop is proposed. Also the comparison of gas holdups with ejector and injector mode proves the effectiveness of ejector mode and can eliminate the supply of compressed gas. Thus proper choice of Dn, Hn and also the operating procedure becomes necessary. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vacuum chamber with a supersonic flow aerodynamic window

DOEpatents

Hanson, Clark L.

1982-01-01

A supersonic flow aerodynamic window, whereby a steam ejector situated in a primary chamber at vacuum exhausts superheated steam toward an orifice to a region of higher pressure, creating a barrier to the gas in the region of higher pressure which attempts to enter through the orifice. In a mixing chamber outside and in fluid communication with the primary chamber, superheated steam and gas are combined into a mixture which then enters the primary chamber through the orifice. At the point of impact of the ejector/superheated steam and the incoming gas/superheated steam mixture, a barrier is created to the gas attempting to enter the ejector chamber. This barrier, coupled with suitable vacuum pumping means and cooling means, serves to keep the steam ejector and primary chamber at a negative pressure, even though the primary chamber has an orifice to a region of higher pressure.

Enhancing the efficiency of a three-lobe roots blower by means of by-passing gas to the working cavity through an ejector adaptor

NASA Astrophysics Data System (ADS)

Vizgalov, S. V.; Volkov, M. V.; Chekushkin, G. N.; Khisameev, I. G.

2017-08-01

A positive displacement Roots blower with two- or three-lobe straight-tooth or twisted rotors demonstrates high performance with small specific dimensions and is used to boost internal combustion engines, aerate tanks of treatment facilities, is employed in air and gas transport systems in the food, petrochemical and metallurgical industry. It is common knowledge that several solutions have been implemented in Roots blower designs with straight-tooth with three-lobe or more-lobes rotors. It is more practical to bypass a portion of the compressed gas to the working cavity of the blower through an ejector. The purpose of developing a mathematical model for a blower working in conjunction with an ejector adapter and the further research is to determine the efficiency of this scheme un-der different discharge pressure conditions and different ejector active flow temperatures (the gas cooling effect before the nozzle).

Vacuum chamber with a supersonic-flow aerodynamic window

DOEpatents

Hanson, C.L.

1980-10-14

A supersonic flow aerodynamic window is disclosed whereby a steam ejector situated in a primary chamber at vacuum exhausts superheated steam toward an orifice to a region of higher pressure, creating a barrier to the gas in the region of higher pressure which attempts to enter through the orifice. In a mixing chamber outside and in fluid communication with the primary chamber, superheated steam and gas are combined into a mixture which then enters the primary chamber through the orifice. At the point of impact of the ejector/superheated steam and the incoming gas/superheated steam mixture, a barrier is created to the gas attempting to enter the ejector chamber. This barrier, coupled with suitable vacuum pumping means and cooling means, serves to keep the steam ejector and primary chamber at a negative pressure, even though the primary chamber has an orifice to a region of higher pressure.

Rocket Ejector Studies for Application to RBCC Engines: An Integrated Experimental/CFD Approach

NASA Technical Reports Server (NTRS)

Pal, S.; Merkle, C. L.; Anderson, W. E.; Santoro, R. J.

1997-01-01

Recent interest in low cost, reliable access to space has generated increased interest in advanced technology approaches to space transportation systems. A key to the success of such programs lies in the development of advanced propulsion systems capable of achieving the performance and operations goals required for the next generation of space vehicles. One extremely promising approach involves the combination of rocket and air- breathing engines into a rocket-based combined-cycle engine (RBCC). A key element of that engine is the rocket ejector which is utilized in the zero to Mach two operating regime. Studies of RBCC engine concepts are not new and studies dating back thirty years are well documented in the literature. However, studies focused on the rocket ejector mode of the RBCC cycle are lacking. The present investigation utilizes an integrated experimental and computation fluid dynamics (CFD) approach to examine critical rocket ejector performance issues. In particular, the development of a predictive methodology capable of performance prediction is a key objective in order to analyze thermal choking and its control, primary/secondary pressure matching considerations, and effects of nozzle expansion ratio. To achieve this objective, the present study emphasizes obtaining new data using advanced optical diagnostics such as Raman spectroscopy and CFD techniques to investigate mixing in the rocket ejector mode. A new research facility for the study of the rocket ejector mode is described along with the diagnostic approaches to be used. The CFD modeling approach is also described along with preliminary CFD predictions obtained to date.

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

46 CFR 56.50-95 - Overboard discharges and shell connections.

Code of Federal Regulations, 2014 CFR

2014-10-01

... securing both the cover and the valve when the chute is not in use. When ash-ejectors or similar expelling... ash ejector discharge shall be not less than Schedule 80. (h) Where deck drains, soil lines, and...

46 CFR 56.50-95 - Overboard discharges and shell connections.

Code of Federal Regulations, 2013 CFR

2013-10-01

... securing both the cover and the valve when the chute is not in use. When ash-ejectors or similar expelling... ash ejector discharge shall be not less than Schedule 80. (h) Where deck drains, soil lines, and...

46 CFR 56.50-95 - Overboard discharges and shell connections.

Code of Federal Regulations, 2012 CFR

2012-10-01

... securing both the cover and the valve when the chute is not in use. When ash-ejectors or similar expelling... ash ejector discharge shall be not less than Schedule 80. (h) Where deck drains, soil lines, and...

Application Focused Schlieren to Nozzle Ejector Flowfields

NASA Technical Reports Server (NTRS)

Mitchell, L. Kerry; Ponton, Michael K.; Seiner, John M.; Manning, James C.; Jansen, Bernard J.; Lagen, Nicholas T.

1999-01-01

The motivation of the testing was to reduce noise generated by eddy Mach wave emission via enhanced mixing in the jet plume. This was to be accomplished through the use of an ejector shroud, which would bring in cooler ambient fluid to mix with the hotter jet flow. In addition, the contour of the mixer, with its chutes and lobes, would accentuate the merging of the outer and inner flows. The objective of the focused schlieren work was to characterize the mixing performance inside of the ejector. Using flow visualization allowed this to be accomplished in a non-intrusive manner.

Credit WCT. Photographic copy of photograph, view of Test Stand ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit WCT. Photographic copy of photograph, view of Test Stand "D" from the south with tower ejector system in operation during a 1972 engine test. Note steam evolving from Z-stage ejectors atop the interstage condenser in the tower. Note also the "Hyprox" steam generator straddling the Dd ejector train to the right. The new Dy horizontal train has not been erected as of this date. In the distance is Test Stand "E." (JPL negative no. 384-9766-AC, 28 November 1972) - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

A control-volume method for analysis of unsteady thrust augmenting ejector flows

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1988-01-01

A method for predicting transient thrust augmenting ejector characteristics is presented. The analysis blends classic self-similar turbulent jet descriptions with a control volume mixing region discretization to solicit transient effects in a new way. Division of the ejector into an inlet, diffuser, and mixing region corresponds with the assumption of viscous-dominated phenomenon in the latter. Inlet and diffuser analyses are simplified by a quasi-steady analysis, justified by the assumptions that pressure is the forcing function in those regions. Details of the theoretical foundation, the solution algorithm, and sample calculations are given.

Low-Cost Flow Visualization for a Supersonic Ejector

NASA Technical Reports Server (NTRS)

Olden, George W.; Lineberry, David M.; Linn, Christopher A. B.; Landrum, Brian D.; Hawk, Clark W.

2005-01-01

Shadowgraph techniques were applied to the cold flow ejector facility at the Propulsion Research Center at the University of Alabama in Huntsville. The setup for the experiments was relatively simple and was accomplished at very little cost. Series of shadowgraph images were taken of both dual nozzle and single nozzle strut based ejectors operating over a range of chamber pressures. The density gradient patterns in the shadowgraphs were compared to pressure data measured along the top and side walls of the mixing duct. The shadowgraph images showed the presence of barrel shocks emanating from the nozzles which at low pressures terminated in Mach disks and at higher pressures extended beyond the barrel shape and reflected off the walls of the duct. Based on pressure data from previous testing, reflected shocks were expected on the walls of the duct. The shadowgraph images confirmed the locations of these reflected shocks on the top wall of the duct. The shadowgraph images also showed the structure change which correlated to a change in pitch of the ejector noise, and corresponded to a change in trend of the duct wall pressure ratio distributions. The images produced from the setup provided insight into the complex flow behavior inside the ejector duct. In addition, the techniques were a valuable tool as an educational device for students.

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

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.

12. Sewage Ejector Pumps, view to the southwest. These pumps ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. Sewage Ejector Pumps, view to the southwest. These pumps are connected to sewage treatment tanks. - Washington Water Power Clark Fork River Cabinet Gorge Hydroelectric Development, Powerhouse, North Bank of Clark Fork River at Cabinet Gorge, Cabinet, Bonner County, ID

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.

Hydrocarbon fluid, ejector refrigeration system

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

Kowalski, G.J.; Foster, A.R.

1993-08-31

A refrigeration system is described comprising: a vapor ejector cycle including a working fluid having a property such that entropy of the working fluid when in a saturated vapor state decreases as pressure decreases, the vapor ejector cycle comprising: a condenser located on a common fluid flow path; a diverter located downstream from the condenser for diverting the working fluid into a primary fluid flow path and a secondary fluid flow path parallel to the primary fluid flow path; an evaporator located on the secondary fluid flow path; an expansion device located on the secondary fluid flow path upstream ofmore » the evaporator; a boiler located on the primary fluid flow path parallel to the evaporator for boiling the working fluid, the boiler comprising an axially extending core region having a substantially constant cross sectional area and a porous capillary region surrounding the core region, the core region extending a length sufficient to produce a near sonic velocity saturated vapor; and an ejector having an outlet in fluid communication with the inlet of the condenser and an inlet in fluid communication with the outlet of the evaporator and the outlet of the boiler and in which the flows of the working fluid from the evaporator and the boiler are mixed and the pressure of the working fluid is increased to at least the pressure of the condenser, the ejector inlet, located downstream from the axially extending core region, including a primary nozzle located sufficiently close to the outlet of the boiler to minimize a pressure drop between the boiler and the primary nozzle, the primary nozzle of the ejector including a converging section having an included angle and length preselected to receive the working fluid from the boiler as a near sonic velocity saturated vapor.« less

Results of Aero/Acoustic Tests and Analytical Studies of a Two-Dimensional Eight-Lobe Mixer-Ejector Exhaust Nozzle at Takeoff Conditions

NASA Technical Reports Server (NTRS)

Harrington, Douglas (Technical Monitor); Schweiger, P.; Stern, A.; Gamble, E.; Barber, T.; Chiappetta, L.; LaBarre, R.; Salikuddin, M.; Shin, H.; Majjigi, R.

2005-01-01

Hot flow aero-acoustic tests were conducted with Pratt & Whitney's High-Speed Civil Transport (HSCT) Mixer-Ejector Exhaust Nozzles by General Electric Aircraft Engines (GEAE) in the GEAE Anechoic Freejet Noise Facility (Cell 41) located in Evendale, Ohio. The tests evaluated the impact of various geometric and design parameters on the noise generated by a two-dimensional (2-D) shrouded, 8-lobed, mixer-ejector exhaust nozzle. The shrouded mixer-ejector provides noise suppression by mixing relatively low energy ambient air with the hot, high-speed primary exhaust jet. Additional attenuation was obtained by lining the shroud internal walls with acoustic panels, which absorb acoustic energy generated during the mixing process. Two mixer designs were investigated, the high mixing "vortical" and aligned flow "axial", along with variations in the shroud internal mixing area ratios and shroud length. The shrouds were tested as hardwall or lined with acoustic panels packed with a bulk absorber. A total of 21 model configurations at 1:11.47 scale were tested. The models were tested over a range of primary nozzle pressure ratios and primary exhaust temperatures representative of typical HSCT aero thermodynamic cycles. Static as well as flight simulated data were acquired during testing. A round convergent unshrouded nozzle was tested to provide an acoustic baseline for comparison to the test configurations. Comparisons were made to previous test results obtained with this hardware at NASA Glenn's 9- by 15-foot low-speed wind tunnel (LSWT). Laser velocimetry was used to investigate external as well as ejector internal velocity profiles for comparison to computational predictions. Ejector interior wall static pressure data were also obtained. A significant reduction in exhaust system noise was demonstrated with the 2-D shrouded nozzle designs.

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

A novel high-temperature ejector-topping power cycle

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

Freedman, B.Z.; Lior, N.

1994-01-01

A novel, patented topping power cycle is described that takes its energy from a very high-temperature heat source and in which the temperature of the heat sink is still high enough to operate another, conventional power cycle. The top temperatures heat source is used to evaporate a low saturation pressure liquid, which serves as the driving fluid for compressing the secondary fluid in an ejector. Due to the inherently simple construction of ejectors, they are well suited for operation at temperatures higher than those that can be used with gas turbines. The gases exiting from the ejector transfer heat tomore » the lower temperature cycle, and are separated by condensing the primary fluid. The secondary gas is then used to drive a turbine. For a system using sodium as the primary fluid and helium as the secondary fluid, and using a bottoming Rankine steam cycle, the overall thermal efficiency can be at least 11 percent better than that of conventional steam Rankine cycles.« less

Statistical Approaches to Type Determination of the Ejector Marks on Cartridge Cases.

PubMed

Warren, Eric M; Sheets, H David

2018-03-01

While type determination on bullets has been performed for over a century, type determination on cartridge cases is often overlooked. Presented here is an example of type determination of ejector marks on cartridge cases from Glock and Smith & Wesson Sigma series pistols using Naïve Bayes and Random Forest classification methods. The shapes of ejector marks were captured from images of test-fired cartridge cases and subjected to multivariate analysis. Naïve Bayes and Random Forest methods were used to assign the ejector shapes to the correct class of firearm with success rates as high as 98%. This method is easily implemented with equipment already available in crime laboratories and can serve as an investigative lead in the form of a list of firearms that could have fired the evidence. Paired with the FBI's General Rifling Characteristics (GRC) database, this could be an invaluable resource for firearm evidence at crime scenes. © 2017 American Academy of Forensic Sciences.

Jet Noise Reduction Potential from Emerging Variable Cycle Technologies

NASA Technical Reports Server (NTRS)

Henderson, Brenda; Bridges, James; Wernet, Mark

2012-01-01

Acoustic and flow-field experiments were conducted on exhaust concepts for the next generation supersonic, commercial aircraft. The concepts were developed by Lockheed Martin (LM), Rolls-Royce Liberty Works (RRLW), and General Electric Global Research (GEGR) as part of an N+2 (next generation forward) aircraft system study initiated by the Supersonics Project in NASA s Fundamental Aeronautics Program. The experiments were conducted in the Aero-Acoustic Propulsion Laboratory at the NASA Glenn Research Center. The exhaust concepts utilized ejectors, inverted velocity profiles, and fluidic shields. One of the ejector concepts was found to produce stagnant flow within the ejector and the other ejector concept produced discrete-frequency tones that degraded the acoustic performance of the model. The concept incorporating an inverted velocity profile and fluid shield produced overall-sound-pressure-level reductions of 6 dB relative to a single stream nozzle at the peak jet noise angle for some nozzle pressure ratios. Flow separations in the nozzle degraded the acoustic performance of the inverted velocity profile model at low nozzle pressure ratios.

Jet Noise Reduction Potential From Emerging Variable Cycle Technologies

NASA Technical Reports Server (NTRS)

2012-01-01

Acoustic and flow-field experiments were conducted on exhaust concepts for the next generation supersonic, commercial aircraft. The concepts were developed by Lockheed Martin (LM), Rolls-Royce Liberty Works (RRLW), and General Electric Global Research (GEGR) as part of an N+2 (next generation forward) aircraft system study initiated by the Supersonics Project in NASA s Fundamental Aeronautics Program. The experiments were conducted in the Aero-Acoustic Propulsion Laboratory at the NASA Glenn Research Center. The exhaust concepts utilized ejectors, inverted velocity profiles, and fluidic shields. One of the ejector concepts was found to produce stagnant flow within the ejector and the other ejector concept produced discrete-frequency tones that degraded the acoustic performance of the model. The concept incorporating an inverted velocity profile and fluid shield produced overall-sound-pressure-level reductions of 6 dB relative to a single stream nozzle at the peak jet noise angle for some nozzle pressure ratios. Flow separations in the nozzle degraded the acoustic performance of the inverted velocity profile model at low nozzle pressure ratios.

A three-dimensional turbulent compressible flow model for ejector and fluted mixers

NASA Technical Reports Server (NTRS)

Rushmore, W. L.; Zelazny, S. W.

1978-01-01

A three dimensional finite element computer code was developed to analyze ejector and axisymmetric fluted mixer systems whose flow fields are not significantly influenced by streamwise diffusion effects. A two equation turbulence model was used to make comparisons between theory and data for various flow fields which are components of the ejector system, i.e., (1) turbulent boundary layer in a duct; (2) rectangular nozzle (free jet); (3) axisymmetric nozzle (free jet); (4) hypermixing nozzle (free jet); and (5) plane wall jet. Likewise, comparisons of the code with analytical results and/or other numerical solutions were made for components of the axisymmetric fluted mixer system. These included: (1) developing pipe flow; (2) developing flow in an annular pipe; (3) developing flow in an axisymmetric pipe with conical center body and no fluting and (4) developing fluted pipe flow. Finally, two demonstration cases are presented which show the code's ability to analyze both the ejector and axisymmetric fluted mixers.

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.

Nitrous oxide as a tracer gas in the ASHRAE 110-1995 Standard.

PubMed

Burke, Martin; Wong, Larry; Gonzales, Ben A; Knutson, Gerhard

2014-01-01

ANSI/ASHRAE Standard 110 provides a quantitative method for testing the performance of laboratory fume hoods. Through release of a known quantity (4.0 Lpm) of a tracer gas, and subsequent monitoring of the tracer gas concentration in the "breathing zone" of a mannequin positioned in front of the hood, this method allows for evaluation of laboratory hood performance. Standard 110 specifies sulfur hexafluoride (SF6) as the tracer gas; however, suitable alternatives are allowed. Through three series of performance tests, this analysis serves to investigate the use of nitrous oxide (N2O) as an alternate tracer gas for hood performance testing. Single gas tests were performed according to ASHRAE Standard 110-1995 with each tracer gas individually. These tests showed identical results using an acceptance criterion of AU 0.1 with the sash half open, nominal 18 inches (0.46m) high, and the face velocity at a nominal 60 fpm (0.3 m/s). Most data collected in these single gas tests, for both tracer gases, were below the minimum detection limit, thus two dual gas tests were developed for simultaneous sampling of both tracer gases. Dual gas dual ejector tests were performed with both tracer gases released simultaneously through two ejectors, and the concentration measured with two detectors using a common sampling probe. Dual gas single ejector tests were performed with both tracer gases released though a single ejector, and the concentration measured in the same manner as the dual gas dual ejector tests. The dual gas dual ejector tests showed excellent correlation, with R typically greater than 0.9. Variance was observed in the resulting regression line for each hood, likely due to non-symmetry between the two challenges caused by variables beyond the control of the investigators. Dual gas single ejector tests resulted in exceptional correlation, with R>0.99 typically for the consolidated data, with a slope of 1.0. These data indicate equivalent results for ASHRAE 110 performance testing using either SF6 or N2O, indicating N2O as an applicable alternate tracer gas.

Pressure Regulator With Internal Ejector Circulation Pump, Flow and Pressure Measurement Porting, and Fuel Cell System Integration Options

NASA Technical Reports Server (NTRS)

Vasquez, Arturo

2011-01-01

An advanced reactant pressure regulator with an internal ejector reactant circulation pump has been developed to support NASA's future fuel cell power systems needs. These needs include reliable and safe operation in variable-gravity environments, and for exploration activities with both manned and un manned vehicles. This product was developed for use in Proton Exchange Membrane Fuel Cell (PEMFC) power plant reactant circulation systems, but the design could also be applied to other fuel cell system types, (e.g., solid-oxide or alkaline) or for other gas pressure regulation and circulation needs. The regulator design includes porting for measurement of flow and pressure at key points in the system, and also includes several fuel cell system integration options. NASA has recognized ejectors as a viable alternative to mechanical pumps for use in spacecraft fuel cell power systems. The ejector motive force is provided by a variable, high-pressure supply gas that travels through the ejector s jet nozzle, whereby the pressure energy of the fluid stream is converted to kinetic energy in the gas jet. The ejector can produce circulation-to-consumption-flow ratios that are relatively high (2-3 times), and this phenomenon can potentially (with proper consideration of the remainder of the fuel cell system s design) be used to provide completely for reactant pre-humidification and product water removal in a fuel cell system. Specifically, a custom pressure regulator has been developed that includes: (1) an ejector reactant circulation pump (with interchangeable jet nozzles and mixer sections, gas-tight sliding and static seals in required locations, and internal fluid porting for pressure-sensing at the regulator's control elements) and (2) internal fluid porting to allow for flow rate and system pressure measurements. The fluid porting also allows for inclusion of purge, relief, and vacuum-breaker check valves on the regulator assembly. In addition, this regulator could also be used with NASA's advanced nonflow-through fuel cell power systems by simply incorporating a jet nozzle with an appropriate nozzle diameter.

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

A User's Guide for the Differential Reduced Ejector/Mixer Analysis "DREA" Program. 1.0

NASA Technical Reports Server (NTRS)

DeChant, Lawrence J.; Nadell, Shari-Beth

1999-01-01

A system of analytical and numerical two-dimensional mixer/ejector nozzle models that require minimal empirical input has been developed and programmed for use in conceptual and preliminary design. This report contains a user's guide describing the operation of the computer code, DREA (Differential Reduced Ejector/mixer Analysis), that contains these mathematical models. This program is currently being adopted by the Propulsion Systems Analysis Office at the NASA Glenn Research Center. A brief summary of the DREA method is provided, followed by detailed descriptions of the program input and output files. Sample cases demonstrating the application of the program are presented.

A modeling technique for STOVL ejector and volume dynamics

NASA Technical Reports Server (NTRS)

Drummond, C. K.; Barankiewicz, W. S.

1990-01-01

New models for thrust augmenting ejector performance prediction and feeder duct dynamic analysis are presented and applied to a proposed Short Take Off and Vertical Landing (STOVL) aircraft configuration. Central to the analysis is the nontraditional treatment of the time-dependent volume integrals in the otherwise conventional control-volume approach. In the case of the thrust augmenting ejector, the analysis required a new relationship for transfer of kinetic energy from the primary flow to the secondary flow. Extraction of the required empirical corrections from current steady-state experimental data is discussed; a possible approach for modeling insight through Computational Fluid Dynamics (CFD) is presented.

Static performance tests of a flight-type STOVL ejector

NASA Technical Reports Server (NTRS)

Barankiewicz, Wendy S.

1991-01-01

The design and development of thrust augmenting STOVL ejectors has typically been based on experimental iteration (i.e., trial and error). Static performance tests of a full scale vertical lift ejector were performed at primary flow temperatures up to 1560 R (1100 F). Flow visualization (smoke generators and yarn tufts) were used to view the inlet air flow, especially around the primary nozzle and end plates. Performance calculations are presented for ambient temperatures close to 480 R (20 F) and 535 R (75 F) which simulate seasonal aircraft operating conditions. Resulting thrust augmentation ratios are presented as functions of nozzle pressure ratio and temperature.

Air ejector augmented compressed air energy storage system

DOEpatents

Ahrens, F.W.; Kartsounes, G.T.

Energy is stored in slack demand periods by charging a plurality of underground reservoirs with air to the same peak storage pressure, during peak demand periods throttling the air from one storage reservoir into a gas turbine system at a constant inlet pressure until the air presure in the reservoir falls to said constant inlet pressure, thereupon permitting air in a second reservoir to flow into said gas turbine system while drawing air from the first reservoir through a variable geometry air ejector and adjusting said variable geometry air ejector, said air flow being essentially at the constant inlet pressure of the gas turbine system.

Air ejector augmented compressed air energy storage system

DOEpatents

Ahrens, Frederick W.; Kartsounes, George T.

1980-01-01

Energy is stored in slack demand periods by charging a plurality of underground reservoirs with air to the same peak storage pressure, during peak demand periods throttling the air from one storage reservoir into a gas turbine system at a constant inlet pressure until the air pressure in the reservoir falls to said constant inlet pressure, thereupon permitting air in a second reservoir to flow into said gas turbine system while drawing air from the first reservoir through a variable geometry air ejector and adjusting said variable geometry air ejector, said air flow being essentially at the constant inlet pressure of the gas turbine system.

A design study of a reaction control system for a V/STOL fighter/attack aircraft

NASA Technical Reports Server (NTRS)

Beard, B. B.; Foley, W. H.

1983-01-01

Attention is given to a short takeoff vertical landing (STOVL) aircraft reaction control system (RCS) design study. The STOVL fighter/attack aircraft employs an existing turbofan engine, and its hover requirement places a premium on weight reduction, which eliminates prospective nonairbreathing RCSs. A simple engine compressor bleed RCS degrades overall performance to an unacceptable degree, and the supersonic requirement precludes the large volume alternatives of thermal or ejector thrust augmentation systems as well as the ducting of engine exhaust gases and the use of a dedicated turbojet. The only system which addressed performance criteria without requiring major engine modifications was a dedicated load compressor driven by an auxilliary power unit.

The 1D Richards' equation in two layered soils: a Filippov approach to treat discontinuities

NASA Astrophysics Data System (ADS)

Berardi, Marco; Difonzo, Fabio; Vurro, Michele; Lopez, Luciano

2018-05-01

The infiltration process into the soil is generally modeled by the Richards' partial differential equation (PDE). In this paper a new approach for modeling the infiltration process through the interface of two different soils is proposed, where the interface is seen as a discontinuity surface defined by suitable state variables. Thus, the original 1D Richards' PDE, enriched by a particular choice of the boundary conditions, is first approximated by means of a time semidiscretization, that is by means of the transversal method of lines (TMOL). In such a way a sequence of discontinuous initial value problems, described by a sequence of second order differential systems in the space variable, is derived. Then, Filippov theory on discontinuous dynamical systems may be applied in order to study the relevant dynamics of the problem. The numerical integration of the semidiscretized differential system will be performed by using a one-step method, which employs an event driven procedure to locate the discontinuity surface and to adequately change the vector field.

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

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.

Transient flow thrust prediction for an ejector propulsion concept

NASA Technical Reports Server (NTRS)

Drummond, Colin K.

1989-01-01

A method for predicting transient thrust augmenting ejector characteristics is introduced. The analysis blends classic self-similar turbulent jet descriptions with a mixing region control volume analysis to predict transient effects in a new way. Details of the theoretical foundation, the solution algorithm, and sample calculations are given.

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

Computational Analyses in Support of Sub-scale Diffuser Testing for the A-3 Facility. Part 1; Steady Predictions

NASA Technical Reports Server (NTRS)

Allgood, Daniel C.; Graham, Jason S.; Ahuja, Vineet; Hosangadi, Ashvin

2008-01-01

Simulation technology can play an important role in rocket engine test facility design and development by assessing risks, providing analysis of dynamic pressure and thermal loads, identifying failure modes and predicting anomalous behavior of critical systems. Advanced numerical tools assume greater significance in supporting testing and design of high altitude testing facilities and plume induced testing environments of high thrust engines because of the greater inter-dependence and synergy in the functioning of the different sub-systems. This is especially true for facilities such as the proposed A-3 facility at NASA SSC because of a challenging operating envelope linked to variable throttle conditions at relatively low chamber pressures. Facility designs in this case will require a complex network of diffuser ducts, steam ejector trains, fast operating valves, cooling water systems and flow diverters that need to be characterized for steady state performance. In this paper, we will demonstrate with the use of CFD analyses s advanced capability to evaluate supersonic diffuser and steam ejector performance in a sub-scale A-3 facility at NASA Stennis Space Center (SSC) where extensive testing was performed. Furthermore, the focus in this paper relates to modeling of critical sub-systems and components used in facilities such as the A-3 facility. The work here will address deficiencies in empirical models and current CFD analyses that are used for design of supersonic diffusers/turning vanes/ejectors as well as analyses for confined plumes and venting processes. The primary areas that will be addressed are: (1) supersonic diffuser performance including analyses of thermal loads (2) accurate shock capturing in the diffuser duct; (3) effect of turning duct on the performance of the facility (4) prediction of mass flow rates and performance classification for steam ejectors (5) comparisons with test data from sub-scale diffuser testing and assessment of confidence levels in CFD based flowpath modeling of the facility. The analyses tools used here expand on the multi-element unstructured CFD which has been tailored and validated for impingement dynamics of dry plumes, complex valve/feed systems, and high pressure propellant delivery systems used in engine and component test stands at NASA SSC. The analyses performed in the evaluation of the sub-scale diffuser facility explored several important factors that influence modeling and understanding of facility operation such as (a) importance of modeling the facility with Real Gas approximation, (b) approximating the cluster of steam ejector nozzles as a single annular nozzle, (c) existence of mixed subsonic/supersonic flow downstream of the turning duct, and (d) inadequacy of two-equation turbulence models in predicting the correct pressurization in the turning duct and expansion of the second stage steam ejectors. The procedure used for modeling the facility was as follows: (i) The engine, test cell and first stage ejectors were simulated with an axisymmetric approximation (ii) the turning duct, second stage ejectors and the piping downstream of the second stage ejectors were analyzed with a three-dimensional simulation utilizing a half-plane symmetry approximation. The solution i.e. primitive variables such as pressure, velocity components, temperature and turbulence quantities were passed from the first computational domain and specified as a supersonic boundary condition for the second simulation. (iii) The third domain comprised of the exit diffuser and the region in the vicinity of the facility (primary included to get the correct shock structure at the exit of the facility and entrainment characteristics). The first set of simulations comprising the engine, test cell and first stage ejectors was carried out both as a turbulent real gas calculation as well as a turbulent perfect gas calculation. A comparison for the two cases (Real Turbulent and Perfect gas turbulent) of the Ma Number distribution and temperature distributions are shown in Figures 1 and 2 respectively. The Mach Number distribution shows small yet distinct differences between the two cases such as locations of shocks/shock reflections and a slightly different impingement point on the wall of the diffuser from the expansion at the exit of the nozzle. Similarly the temperature distribution indicates different flow recirculation patterns in the test cell. Both cases capture all the essential flow phenomena such as the shock-boundary layer interaction, plume expansion, expansion of the first stage ejectors, mixing between the engine plume and the first stage ejector flow and pressurization due to the first stage ejectors. The final paper will discuss thermal loads on the walls of the diffuser and cooling mechanisms investigated.

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.

Approximate similarity principle for a full-scale STOVL ejector

NASA Astrophysics Data System (ADS)

Barankiewicz, Wendy S.; Perusek, Gail P.; Ibrahim, Mounir B.

1994-03-01

Full-scale ejector experiments are expensive and difficult to implement at engine exhaust temperatures. For this reason the utility of using similarity principles, in particular the Munk and prim principle for isentropic flow, was explored. Static performance test data for a full-scale thrust augmenting ejector were analyzed for primary flow temperature up to 1560 R. At different primary temperatures, exit pressure contours were compared for similarity. A nondimensional flow parameter is then used to eliminate primary nozzle temperature dependence and verify similarity between the hot and cold flow experiments. Under the assumption that an appropriate similarity principle can be established, properly chosen performance parameters were found to be similar for both flow and cold flow model tests.

A lifting surface theory for thrust augmenting ejectors

NASA Technical Reports Server (NTRS)

Bevilaqua, P. M.

1977-01-01

The circulation theory of airfoil lift has been applied to calculate the performance of thrust augmenting ejectors. The ejector shroud is considered to be 'flying' in the secondary velocity field induced by the entrainment of the primary jet, so that the augmenting thrust is viewed as analogous to the lift on an airfoil. Vortex lattice methods are utilized to compute the thrust augmentation from the force on the flaps. The augmentation is shown to be a function of the length and shape of the flaps, as well as their position and orientation. Predictions of this new theory are compared with the results of classical methods of calculating the augmentation by integration of the stream thrust.

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

R744 ejector technology future perspectives

NASA Astrophysics Data System (ADS)

Hafner, Armin; Banasiak, Krzysztof

2016-09-01

Carbon Dioxide, CO2 (R744) was one of the first commonly applied working fluids in the infancy of refrigeration more than 100 years ago. In contrast to ammonia it mainly disappeared after the first generation of synthetic refrigerants have been introduced to the market after 1930. One reason was that the transition from low-rpm belt driven compressors towards the direct electrical motor driven compressors (50-60 Hz) was not performed for CO2 compressors before the revival introduced by Gustav Lorentzen in the 90is of last century. Since 1988 an enormous R & D effort has been made to further develop CO2 refrigeration technology in spite of the opposition from the chemical industry. Today CO2 refrigeration and heat pumping technologies are accepted as viable and sustainable alternatives for several applications like commercial refrigeration, transport refrigeration, vehicle air conditioning & heat pumping, domestic hot water heat pumps and industrial applications. For some applications, the current threshold to introduce R744 technology can be overcome when the system design takes into account the advantage of the thermo dynamical- and fluid properties of CO2. I.e. the system is designed for transcritical operation with all it pros and cons and takes into consideration how to minimize the losses, and to apply the normally lost expansion work. Shortcut-designs, i.e. drop in solutions, just replacing the H(C)FC refrigeration unit with an CO2 systems adapted for higher system pressures will not result in energy efficient products. CO2 systems do offer the advantage of enabling flooded evaporators supported with adapted ejector technology. These units offer high system performances at low temperature differences and show low temperature air mal-distributions across evaporators. This work gives an overview for the development possibilities for several applications during the next years. Resulting in a further market share increase of CO2 refrigeration and heat pump systems, as energy efficient alternatives to current systems not applying natural working fluids.

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.

An engine trade study for a supersonic STOVL fighter-attack aircraft, volume 1

NASA Technical Reports Server (NTRS)

Beard, B. B.; Foley, W. H.

1982-01-01

The best main engine for an advanced STOVL aircraft flight demonstrator was studied. The STOVL aircraft uses ejectors powered by engine bypass flow together with vectored core exhaust to achieve vertical thrust capability. Bypass flow and core flow are exhausted through separate nozzles during wingborne flight. Six near term turbofan engines were examined for suitability for this aircraft concept. Fan pressure ratio, thrust split between bypass and core flow, and total thrust level were used to compare engines. One of the six candidate engines was selected for the flight demonstrator configuration. Propulsion related to this aircraft concept was studied. A preliminary candidate for the aircraft reaction control system for hover attitude control was selected. A mathematical model of transfer of bypass thrust from ejectors to aft directed nozzle during the transition to wingborne flight was developed. An equation to predict ejector secondary air flow rate and ram drag is derived. Additional topics discussed include: nozzle area control, ejector to engine inlet reingestion, bypass/core thrust split variation, and gyroscopic behavior during hover.

An Ejector Air Intake Design Method for a Novel Rocket-Based Combined-Cycle Rocket Nozzle

NASA Astrophysics Data System (ADS)

Waung, Timothy S.

Rocket-based combined-cycle (RBCC) vehicles have the potential to reduce launch costs through the use of several different air breathing engine cycles, which reduce fuel consumption. The rocket-ejector cycle, in which air is entrained into an ejector section by the rocket exhaust, is used at flight speeds below Mach 2. This thesis develops a design method for an air intake geometry around a novel RBCC rocket nozzle design for the rocket-ejector engine cycle. This design method consists of a geometry creation step in which a three-dimensional intake geometry is generated, and a simple flow analysis step which predicts the air intake mass flow rate. The air intake geometry is created using the rocket nozzle geometry and eight primary input parameters. The input parameters are selected to give the user significant control over the air intake shape. The flow analysis step uses an inviscid panel method and an integral boundary layer method to estimate the air mass flow rate through the intake geometry. Intake mass flow rate is used as a performance metric since it directly affects the amount of thrust a rocket-ejector can produce. The design method results for the air intake operating at several different points along the subsonic portion of the Ariane 4 flight profile are found to under predict mass flow rate by up to 8.6% when compared to three-dimensional computational fluid dynamics simulations for the same air intake.

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

Experimental/Analytical Characterization of the RBCC Rocket-Ejector Mode

NASA Technical Reports Server (NTRS)

Ruf, J. H.; Lehman, M.; Pal, S.; Santoro, R. J.

2000-01-01

The experimental/analytical research work described here addresses the rocket-ejector mode (Mach 0-2 operational range) of the RBCC engine. The experimental phase of the program includes studying the mixing and combustion characteristics of the rocket-ejector system utilizing state-of-the-art diagnostic techniques. A two-dimensional variable geometry rocket-ejector system with enhanced optical access was utilized as the experimental platform. The goals of the experimental phase of the research being conducted at Penn State are to: (a) systematically increase the range of rocket-ejector understanding over a wide range of flow/geometry parameters and (b) provide a comprehensive data base for evaluating and anchoring CFD codes. Concurrent with the experimental activities, a CFD code benchmarking effort at Marshall Space Flight Center is also being used to further investigate the RBCC rocket-ejector mode. Experiments involving the single rocket based optically-accessible rocket-ejector system have been conducted for Diffusion and Afterburning (DAB) as well as Simultaneous Mixing and Combustion configurations. For the DAB configuration, air is introduced (direct-connect) or ejected (sea-level static) into a constant area mixer section with a centrally located gaseous oxygen (GO2)/gaseous hydrogen (GH2) rocket combustor. The downstream flowpath for this configuration includes a diffuser, an afterburner and a final converging nozzle. For the SMC configuration, the rocket is centrally located in a slightly divergent duct. For all tested configurations, global measurements of the axial pressure and heat transfer profiles as well as the overall engine thrust were made. Detailed measurements include major species concentration (H2 O2 N2 and H2O) profiles at various mixer locations made using Raman spectroscopy. Complementary CFD calculations of the flowfield at the experimental conditions also provide additional information on the physics of the problem. These calculations are being conducted at Marshall Space Flight Center to benchmark the FDNS code for RBCC engine operations for such configurations. The primary fluid physics of interests are the mixing and interaction of the rocket plume and secondary flow, subsequent combustion of the fuel rich rocket exhaust with the secondary flow and combustion of the injected afterburner flow. The CFD results are compared to static pressure along the RBCC duct walls, Raman Spectroscopy specie distribution data at several axial locations, net engine thrust and entrained air for the SLS cases. The CFD results compare reasonably well with the experimental results.

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

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.

Cotton roll isolation versus Vac-Ejector isolation.

PubMed

Wood, A J; Saravia, M E; Farrington, F H

1989-01-01

A visible-light-cured, white pit-and-fissure sealant was applied to 523 teeth in school children using either cotton rolls or a VacEjector for isolation. After a minimum of six months, the patients were recalled and the retention of the sealants was evaluated. No significant difference in sealant retention was found between the two isolation methods.

Credit WCT. Photographic copy of photograph, view west into Dd ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit WCT. Photographic copy of photograph, view west into Dd or Dy ejector, showing steam nozzles which drive the ejector to evacuate the test cell to which it is connected. (JPL negative no. 344-2516-B, 29 August 1977) - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Computer program for calculating the flow field of supersonic ejector nozzles

NASA Technical Reports Server (NTRS)

Anderson, B. H.

1974-01-01

An analytical procedure for computing the performance of supersonic ejector nozzles is presented. This procedure includes real sonic line effects and an interaction analysis for the mixing process between the two streams. The procedure is programmed in FORTRAN 4 and has operated successfully on IBM 7094, IBM 360, CDC 6600, and Univac 1108.

Refrigerant pressurization system with a two-phase condensing ejector

DOEpatents

Bergander, Mark [Madison, CT

2009-07-14

A refrigerant pressurization system including an ejector having a first conduit for flowing a liquid refrigerant therethrough and a nozzle for accelerating a vapor refrigerant therethrough. The first conduit is positioned such that the liquid refrigerant is discharged from the first conduit into the nozzle. The ejector includes a mixing chamber for condensing the vapor refrigerant. The mixing chamber comprises at least a portion of the nozzle and transitions into a second conduit having a substantially constant cross sectional area. The condensation of the vapor refrigerant in the mixing chamber causes the refrigerant mixture in at least a portion of the mixing chamber to be at a pressure greater than that of the refrigerant entering the nozzle and greater than that entering the first conduit.

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.

Piston-Driven Fluid Ejectors In Silicon Mems

DOEpatents

Galambos, Paul C.; Benavides, Gilbert L.; Jokiel, Jr., Bernhard; Jakubczak II, Jerome F.

2005-05-03

A surface-micromachined fluid-ejection apparatus is disclosed which utilizes a piston to provide for the ejection of jets or drops of a fluid (e.g. for ink-jet printing). The piston, which is located at least partially inside a fluid reservoir, is moveable into a cylindrical fluid-ejection chamber connected to the reservoir by a microelectromechanical (MEM) actuator which is located outside the reservoir. In this way, the reservoir and fluid-ejection chamber can be maintained as electric-field-free regions thereby allowing the apparatus to be used with fluids that are electrically conductive or which may react or break down in the presence of a high electric field. The MEM actuator can comprise either an electrostatic actuator or a thermal actuator.

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.

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.

Combined cold compressor/ejector helium refrigerator

DOEpatents

Brown, D.P.

1984-06-05

A refrigeration apparatus having an ejector operatively connected with a cold compressor to form a two-stage pumping system. This pumping system is used to lower the pressure, and thereby the temperature of a bath of boiling refrigerant (helium). The apparatus as thus arranged and operated has substantially improved operating efficiency when compared to other processes or arrangements for achieving a similar low pressure.

Combined cold compressor/ejector helium refrigerator

DOEpatents

Brown, Donald P.

1985-01-01

A refrigeration apparatus having an ejector operatively connected with a cold compressor to form a two-stage pumping system. This pumping system is used to lower the pressure, and thereby the temperature of a bath of boiling refrigerant (helium). The apparatus as thus arranged and operated has substantially improved operating efficiency when compared to other processes or arrangements for achieving a similar low pressure.

The ejector-loop fermenter: Description and performance of the apparatus.

PubMed

Moresi, M; Bartolo Gianturco, G; Sebastiani, E

1983-12-01

A novel fermentation unit, the ejector-loop fermenter (ELF), consisting of an outer-loop tower fermenter, a centrifugal pump, a plate-heat exchanger, and a gas-liquid ejector, was designed and constructed. Aeration was achieved by continuously recirculating the fermentation medium through two different nozzle devices instead of using the traditional expensive air compressor. By carrying out a whey fermentation with Kluyveromyces fragilis as the test organism, either in the ELF or in conventional stirred fermenter, it was possible to confirm that the high sheat streses and mixing shock occurring in the ejector nozzle and diffuser sections did not affect microbial growth. Within the range of experimental power consumption per unit volume (-0.1-5 kW/m(3)), the oxygen transfer capability of the ELF per unit power input was found to vary from 1 to 2.5 kg O(2) kW(-1)h(-1). Moreover, it is shown that there is suficient room for improvement in the performance of the ELF unit by care fully designing the aeration device. In fact, at constant volumetric oxygen transfer coefficient, the power consumpotion per unit volume in a 4-mm nozzle was found to be about 40% less than that in a 6-mm nozzle.

A CFD Study of Turbojet and Single-Throat Ramjet Ejector Interaction

NASA Technical Reports Server (NTRS)

Chang, Ing; Hunter, Louis

1996-01-01

Supersonic ejector-diffuse systems have application in driving an advanced airbreathing propulsion system, consisting of turbojet engines acting as the primary and a single throat ramjet acting as the secondary. The turbojet engines are integrated into the single throat ramjet to minimize variable geometry and eliminate redundant propulsion components. The result is a simple, lightweight system that is operable from takeoff to high Mach numbers. At this high Mach number (approximately Mach 3.0), the turbojets are turned off and the high speed ramjet/scramjet take over and drive the vehicle to Mach 6.0. The turbojet-ejector-ramjet system consists of nonafterburning turbojet engines with ducting canted at 20 degrees to supply supersonic flow (downstream of CD nozzle) to the horizontal ramjet duct at a supply total pressure and temperature. Two conditions were modelled by a 2-D full Navier Stokes code at Mach 2.0. The code modelled the Fabri choke as well as the non-Fabri non critical case, using a computational throat to supply the back pressure. The results, which primarily predict the secondary mass flow rate and the mixed conditions at the ejector exit were in reasonable agreement with the 1-D cycle code (TBCC).

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

Computational Analyses in Support of Sub-scale Diffuser Testing for the A-3 Facility. Part 1; Steady Predictions

NASA Technical Reports Server (NTRS)

Allgood, Daniel C.; Graham, Jason S.; Ahuja, Vineet; Hosangadi, Ashvin

2010-01-01

Simulation technology can play an important role in rocket engine test facility design and development by assessing risks, providing analysis of dynamic pressure and thermal loads, identifying failure modes and predicting anomalous behavior of critical systems. Advanced numerical tools assume greater significance in supporting testing and design of high altitude testing facilities and plume induced testing environments of high thrust engines because of the greater inter-dependence and synergy in the functioning of the different sub-systems. This is especially true for facilities such as the proposed A-3 facility at NASA SSC because of a challenging operating envelope linked to variable throttle conditions at relatively low chamber pressures. Facility designs in this case will require a complex network of diffuser ducts, steam ejector trains, fast operating valves, cooling water systems and flow diverters that need to be characterized for steady state performance. In this paper, we will demonstrate with the use of CFD analyses s advanced capability to evaluate supersonic diffuser and steam ejector performance in a sub-scale A-3 facility at NASA Stennis Space Center (SSC) where extensive testing was performed. Furthermore, the focus in this paper relates to modeling of critical sub-systems and components used in facilities such as the A-3 facility. The work here will address deficiencies in empirical models and current CFD analyses that are used for design of supersonic diffusers/turning vanes/ejectors as well as analyses for confined plumes and venting processes. The primary areas that will be addressed are: (1) supersonic diffuser performance including analyses of thermal loads (2) accurate shock capturing in the diffuser duct; (3) effect of turning duct on the performance of the facility (4) prediction of mass flow rates and performance classification for steam ejectors (5) comparisons with test data from sub-scale diffuser testing and assessment of confidence levels in CFD based flowpath modeling of the facility. The analyses tools used here expand on the multi-element unstructured CFD which has been tailored and validated for impingement dynamics of dry plumes, complex valve/feed systems, and high pressure propellant delivery systems used in engine and component test stands at NASA SSC. The analyses performed in the evaluation of the sub-scale diffuser facility explored several important factors that influence modeling and understanding of facility operation such as (a) importance of modeling the facility with Real Gas approximation, (b) approximating the cluster of steam ejector nozzles as a single annular nozzle, (c) existence of mixed subsonic/supersonic flow downstream of the turning duct, and (d) inadequacy of two-equation turbulence models in predicting the correct pressurization in the turning duct and expansion of the second stage steam ejectors. The procedure used for modeling the facility was as follows: (i) The engine, test cell and first stage ejectors were simulated with an axisymmetric approximation (ii) the turning duct, second stage ejectors and the piping downstream of the second stage ejectors were analyzed with a three-dimensional simulation utilizing a half-plane symmetry approximation. The solution i.e. primitive variables such as pressure, velocity components, temperature and turbulence quantities were passed from the first computational domain and specified as a supersonic boundary condition for the second simulation. (iii) The third domain comprised of the exit diffuser and the region in the vicinity of the facility (primary included to get the correct shock structure at the exit of the facility and entrainment characteristics). The first set of simulations comprising the engine, test cell and first stage ejectors was carried out both as a turbulent real gas calculation as well as a turbulent perfect gas calculation. A comparison for the two cases (Real Turbulent and Perfect gas turbulent) of the Ma Number distribution and temperature distributions are shown in Figures 1 and 2 respectively.

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.

Wet atmospheric generation apparatus

NASA Technical Reports Server (NTRS)

Hamner, Richard M. (Inventor); Allen, Janice K. (Inventor)

1990-01-01

The invention described relates to an apparatus for providing a selectively humidified gas to a camera canister containing cameras and film used in space. A source of pressurized gas (leak test gas or motive gas) is selected by a valve, regulated to a desired pressure by a regulator, and routed through an ejector (venturi device). A regulated source of water vapor in the form of steam from a heated reservoir is coupled to a low pressure region of the ejector which mixes with high velocity gas flow through the ejector. This mixture is sampled by a dew point sensor to obtain dew point thereof (ratio of water vapor to gas) and the apparatus adjusted by varying gas pressure or water vapor to provide a mixture at a connector having selected humidity content.

Cold-flow acoustic evaluation of a small scale, divergent, lobed nozzle for supersonic jet noise suppression

NASA Technical Reports Server (NTRS)

Huff, R. G.; Groesbeck, D. E.

1975-01-01

A supersonic jet noise suppressor was tested with cold flow for acoustic and thrust characteristics at nozzle- to atmospheric-pressure ratios of 1.5 to 4.0. Jet noise suppression and spectral characteristics of the divergent, lobed, suppressor (DLS) nozzle with and without an ejector are presented. Suppression was obtained at nozzle pressure ratios of 2.5 to 4.0. The largest, maximum-lobe, sound pressure level suppression with a hard-wall ejector was 14.6 decibels at a nozzle pressure ratio of 3.5. The thrust loss was 2 percent. In general, low-frequency jet noise was suppressed, leaving higher frequencies essentially unchanged. Without the ejector the nozzle showed a thrust loss of 11 percent together with slightly poorer noise suppression.

Current and emerging topical therapies for atopic dermatitis.

PubMed

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

The pathogenesis of atopic dermatitis (AD) involves epidermal barrier dysfunction and T helper cell type 2 (T h 2) lymphocyte-driven inflammation. Cytokines, such as interleukin 4 (IL-4) and IL-13, are important in this reaction. They stimulate B cells to produce immunoglobulin E, causing atopic disease. This process has been well characterized, and new therapies for AD, such as phosphodiesterase 4 (PDE-4) inhibitors, T h 2-expressed chemoattractant receptor-homologous molecule antagonists, and Janus kinase inhibitors, work by antagonizing this cellular pathway. Recently, there have been many advances in treatment strategies and novel therapies for AD. This review summarizes the clinical evidence supporting the use of current and emerging topical treatments for AD, as well as their safety and efficacy profiles. Crisaborole, a novel PDE-4 inhibitor, is of particular note because phase III clinical trials were recently completed, as summarized here. It is prudent for dermatologists to be current with updates in the field because therapies are constantly changing. In addition to the academic interest, this results in improvement of patient care and advancement of the field. Copyright © 2017 Elsevier Inc. All rights reserved.

Notes on the ExactPack Implementation of the DSD Rate Stick Solver

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

Kaul, Ann

It has been shown above that the discretization scheme implemented in the ExactPack solver for the DSD Rate Stick equation is consistent with the Rate Stick PDE. In addition, a stability analysis has provided a CFL condition for a stable time step. Together, consistency and stability imply convergence of the scheme, which is expected to be close to first-order in time and second-order in space. It is understood that the nonlinearity of the underlying PDE will affect this rate somewhat. In the solver I implemented in ExactPack, I used the one-sided boundary condition described above at the outer boundary. Inmore » addition, I used 80% of the time step calculated in the stability analysis above. By making these two changes, I was able to implement a solver that calculates the solution without any arbitrary limits placed on the values of the curvature at the boundary. Thus, the calculation is driven directly by the conditions at the boundary as formulated in the DSD theory. The chosen scheme is completely coherent and defensible from a mathematical standpoint.« less

Computational Analyses in Support of Sub-scale Diffuser Testing for the A-3 Facility. Part 2; Unsteady Analyses and Risk Assessment

NASA Technical Reports Server (NTRS)

Ahuja, Vineet; Hosangadi, Ashvin; Allgood, Daniel

2008-01-01

Simulation technology can play an important role in rocket engine test facility design and development by assessing risks, providing analysis of dynamic pressure and thermal loads, identifying failure modes and predicting anomalous behavior of critical systems. This is especially true for facilities such as the proposed A-3 facility at NASA SSC because of a challenging operating envelope linked to variable throttle conditions at relatively low chamber pressures. Design Support of the feasibility of operating conditions and procedures is critical in such cases due to the possibility of startup/shutdown transients, moving shock structures, unsteady shock-boundary layer interactions and engine and diffuser unstart modes that can result in catastrophic failure. Analyses of such systems is difficult due to resolution requirements needed to accurately capture moving shock structures, shock-boundary layer interactions, two-phase flow regimes and engine unstart modes. In a companion paper, we will demonstrate with the use of CFD, steady analyses advanced capability to evaluate supersonic diffuser and steam ejector performance in the sub-scale A-3 facility. In this paper we will address transient issues with the operation of the facility especially at startup and shutdown, and assess risks related to afterburning due to the interaction of a fuel rich plume with oxygen that is a by-product of the steam ejectors. The primary areas that will be addressed in this paper are: (1) analyses of unstart modes due to flow transients especially during startup/ignition, (2) engine safety during the shutdown process (3) interaction of steam ejectors with the primary plume i.e. flow transients as well as probability of afterburning. In this abstract we discuss unsteady analyses of the engine shutdown process. However, the final paper will include analyses of a staged startup, drawdown of the engine test cell pressure, and risk assessment of potential afterburning in the facility. Unsteady simulations have been carried out to study the engine shutdown process in the facility and understand the physics behind the interactions between the steam ejectors, the test cell and the supersonic diffuser. As a first approximation, to understand the dominant unsteady mechanisms in the engine test cell and the supersonic diffuser, the turning duct in the facility was removed. As the engine loses power a rarefaction wave travels downstream that disrupts the shock cell structure in the supersonic diffuser. Flow from the test cell is seen to expand into the supersonic diffuser section and re-pressurizes the area around the nozzle along with a upstream traveling compression wave that emanates from near the first stage ejectors. Flow from the first stage ejector expands to the center of the duct and a new shock train is formed between the first and second stage ejectors. Both stage ejectors keep the facility pressurized and prevent any large amplitude pressure fluctuations from affecting the engine nozzle. The resultant pressure loads the nozzle experiences in the shutdown process are small.

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.

Modeling and simulation of high dimensional stochastic multiscale PDE systems at the exascale

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

Zabaras, Nicolas J.

2016-11-08

Predictive Modeling of multiscale and Multiphysics systems requires accurate data driven characterization of the input uncertainties, and understanding of how they propagate across scales and alter the final solution. This project develops a rigorous mathematical framework and scalable uncertainty quantification algorithms to efficiently construct realistic low dimensional input models, and surrogate low complexity systems for the analysis, design, and control of physical systems represented by multiscale stochastic PDEs. The work can be applied to many areas including physical and biological processes, from climate modeling to systems biology.

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

Development of a Liner Design Methodology and Relevant Results of Acoustic Suppression in the Farfield for Mixer-Ejector Nozzles

NASA Technical Reports Server (NTRS)

Salikuddin, M.

2006-01-01

We have developed a process to predict noise field interior to the ejector and in the farfield for any liner design for a mixer-ejector of arbitrary scale factor. However, a number of assumptions, not verified for the current application, utilized in this process, introduce uncertainties in the final result, especially, on a quantitative basis. The normal impedance model for bulk with perforated facesheet is based on homogeneous foam materials of low resistivity. The impact of flow conditions for HSCT application as well as the impact of perforated facesheet on predicted impedance is not properly accounted. Based on the measured normal impedance for deeper bulk samples (i.e., 2.0 in.) the predicted reactance is much higher compared to the data at frequencies above 2 kHz for T-foam and 200 ppi SiC. The resistance is under predicted at lower frequencies (below 4 kHz) for these samples. Thus, the use of such predicted data in acoustic suppression is likely to introduce inaccuracies. It should be noted that the impedance prediction methods developed recently under liner technology program are not utilized in the studies described in this report due to the program closeout. Acoustic suppression prediction is based on the uniform flow and temperature conditions in a two-sided treated constant area rectangular duct. In addition, assumptions of equal energy per mode noise field and interaction of all frequencies with the treated surface for the entire ejector length may not be accurate. While, the use of acoustic transfer factor minimizes the inaccuracies associated with the prediction for a known test case, the assumption of the same factor for other liner designs and with different linear scale factor ejectors seems to be very optimistic. As illustrated in appendix D that the predicted noise suppression for LSM-1 is lower compared to the measured data is an indication of the above argument. However, the process seems to be more reliable when used for the same scale models for different liner designs as demonstrated for Gen. 1 mixer-ejectors.

Dependence of charge transfer phenomena during solid-air two-phase flow on particle disperser

NASA Astrophysics Data System (ADS)

Tanoue, Ken-ichiro; Suedomi, Yuuki; Honda, Hirotaka; Furutani, Satoshi; Nishimura, Tatsuo; Masuda, Hiroaki

2012-12-01

An experimental investigation of the tribo-electrification of particles has been conducted during solid-air two-phase turbulent flow. The current induced in a metal plate by the impact of polymethylmethacrylate (PMMA) particles in a high-speed air flow was measured for two different plate materials. The results indicated that the contact potential difference between the particles and a stainless steel plate was positive, while for a nickel plate it was negative. These results agreed with theoretical contact charge transfer even if not only the particle size but also the kind of metal plate was changed. The specific charge of the PMMA particles during solid-air two-phase flow using an ejector, a stainless steel branch pipe, and a stainless steel straight pipe was measured using a Faraday cage. Although the charge was negative in the ejector, the particles had a positive specific charge at the outlet of the branch pipe, and this positive charge increased in the straight pipe. The charge decay along the flow direction could be reproduced by the charging and relaxation theory. However, the proportional coefficients in the theory changed with the particle size and air velocity. Therefore, an unexpected charge transfer occurred between the ejector and the branch pipe, which could not be explained solely by the contact potential difference. In the ejector, an electrical current in air might have been produced by self-discharge of particles with excess charge between the nickel diffuser in the ejector and the stainless steel nozzle or the stainless steel pipe due to a reversal in the contact potential difference between the PMMA and the stainless steel. The sign of the current depended on the particle size, possibly because the position where the particles impacted depended on their size. When dual coaxial glass pipes were used as a particle disperser, the specific charge of the PMMA particles became more positive along the particle flow direction due to the contact potential difference between the PMMA and the stainless steel. Furthermore, the current in air using the dual coaxial glass pipes was less than that using the ejector.

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

Ejector Enhanced Pulsejet Based Pressure Gain Combustors: An Old Idea With a New Twist

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Dougherty, Kevin T.

2005-01-01

An experimental investigation of pressure-gain combustion for gas turbine application is described. The test article consists of an off-the-shelf valved pulsejet, and an optimized ejector, both housed within a shroud. The combination forms an effective can combustor across which there is a modest total pressure rise rather than the usual loss found in conventional combustors. Although the concept of using a pulsejet to affect semi-constant volume (i.e., pressure-gain) combustion is not new, that of combining it with a well designed ejector to efficiently mix the bypass flow is. The result is a device which to date has demonstrated an overall pressure rise of approximately 3.5 percent at an overall temperature ratio commensurate with modern gas turbines. This pressure ratio is substantially higher than what has been previously reported in pulsejet-based combustion experiments. Flow non-uniformities in the downstream portion of the device are also shown to be substantially reduced compared to those within the pulsejet itself. The standard deviation of total pressure fluctuations, measured just downstream of the ejector was only 5.0 percent of the mean. This smoothing aspect of the device is critical to turbomachinery applications since turbine performance is, in general, negatively affected by flow non-uniformities and unsteadiness. The experimental rig will be described and details of the performance measurements will be presented. Analyses showing the thermodynamic benefits from this level of pressure-gain performance in a gas turbine will also be assessed for several engine types. Issues regarding practical development of such a device are discussed, as are potential emissions reductions resulting from the rich burning nature of the pulsejet and the rapid mixing (quenching) associated with unsteady ejectors.

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.

Optimal coupling and feasibility of a solar-powered year-round ejector air conditioner

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

Sokolov, M.; Hershgal, D.

1993-06-01

An ejector refrigeration system that uses a conventional refrigerant (R-114) is introduced as a possible mechanism for providing solar-based air-conditioning. Optimal coupling conditions between the collectors' energy output and energy requirements of the cooling system, are investigated. Operation at such optimal conditions assures maximized overall efficiency. Procedures leading to the evaluation of the performance of a real system are disclosed. Design curves for such a system with R-114 as refrigerant are provided. A multi-ejectors arrangement that provides an efficient adjustment for variations of ambient conditions, is described. Year-round air-conditioning is facilitated by rerouting the refrigerant flow through a heating modemore » of the system. Calculations are carried out for illustrative configurations in which relatively low condensing temperature (water reservoirs, cooling towers, or moderate climate) can be maintained.« less

A 1/10 Scale Model Test of a Fixed Chute Mixer-Ejector Nozzle in Unsuppressed Model. Part 1; Test Overview

NASA Technical Reports Server (NTRS)

Wolter, John D.

2007-01-01

This paper discusses a test of a nozzle concept for a high-speed commercial aircraft. While a great deal of effort has been expended to und erstand the noise-suppressed, take-off performance of mixer-ejector n ozzles, little has been done to assess their performance in unsuppressed mode at other flight conditions. To address this, a 1/10th scale m odel mixer-ejector nozzle in unsuppressed mode was tested at conditio ns representing transonic acceleration, supersonic cruise, subsonic cruise, and approach. Various configurations were tested to understand the effects of acoustic liners and several geometric parameters, such as throat area, expansion ratio, and nozzle length on nozzle performance. Thrust, flow, and internal pressures were measured. A statistica l model of the peak thrust coefficient results is presented and discussed.

Acoustic and Aerothermal Performance Test of the Axisymmetric Coannular Ejector Nozzle. Volume 2; Acoustic Performance

NASA Technical Reports Server (NTRS)

Herkes, William

2000-01-01

Acoustic and propulsion performance testing of a model-scale Axisymmetric Coannular Ejector nozzle was conducted in the Boeing Low-speed Aeroacoustic Facility. This nozzle is a plug nozzle with an ejector design to provide aspiration of about 20% of the engine flow. A variety of mixing enhancers were designed to promote mixing of the engine and the aspirated flows. These included delta tabs, tone-injection rods, and wheeler ramps. This report addresses the acoustic aspects of the testing. The spectral characteristics of the various configurations of the nozzle are examined on a model-scale basis. This includes indentifying particular noise sources contributing to the spectra and the data are projected to full-scale flyover conditions to evaluate the effectiveness of the nozzle, and of the various mixing enhancers, on reducing the Effective Perceived Noise Levels.

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.

Theoretical and Experimental Analysis of the Constant-Area, Supersonic- Supersonic Ejector

DTIC Science & Technology

1976-10-01

4.3-1 Optimum Chemical Laser System Data, Case No. 1 ....... .... 85 (a) Minn;wum ... ..* ............ 85 ( b ) Minimum P60/P 2...Optimum Chemical Laser System Data, Case No. 2 .... ....... 89 (a) Minimum Wp/Ws .... .. . . . . . . . . . . . . 89 ( b ) Minimum P6 0 /P2...6 Photograph- of the Ejector Model Components .......... ... 48 (a) Front View cf the Secondary Stagnation Chamber * * , 48 ( b ) Rear View of the

Ejector-Enhanced, Pulsed, Pressure-Gain Combustor

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.; Dougherty, Kevin T.

2009-01-01

An experimental combination of an off-the-shelf valved pulsejet combustor and an aerodynamically optimized ejector has shown promise as a prototype of improved combustors for gas turbine engines. Despite their name, the constant pressure combustors heretofore used in gas turbine engines exhibit typical pressure losses ranging from 4 to 8 percent of the total pressures delivered by upstream compressors. In contrast, the present ejector-enhanced pulsejet combustor exhibits a pressure rise of about 3.5 percent at overall enthalpy and temperature ratios compatible with those of modern turbomachines. The modest pressure rise translates to a comparable increase in overall engine efficiency and, consequently, a comparable decrease in specific fuel consumption. The ejector-enhanced pulsejet combustor may also offer potential for reducing the emission of harmful exhaust compounds by making it practical to employ a low-loss rich-burn/quench/lean-burn sequence. Like all prior concepts for pressure-gain combustion, the present concept involves an approximation of constant-volume combustion, which is inherently unsteady (in this case, more specifically, cyclic). The consequent unsteadiness in combustor exit flow is generally regarded as detrimental to the performance of downstream turbomachinery. Among other adverse effects, this unsteadiness tends to detract from the thermodynamic benefits of pressure gain. Therefore, it is desirable in any intermittent combustion process to minimize unsteadiness in the exhaust path.

Credit WCT. Photographic copy of photograph, view looking northeast down ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit WCT. Photographic copy of photograph, view looking northeast down onto new Dd test station from Test Stand "D" tower. Hatch of Dd test cell is open, and a test engine sits on a dolly nearby awaiting mounting. Note the water-cooled diffuser on the east end of the test chamber; this was soon replaced with a new diffuser and a steam-driven ejector for simulated high-altitude tests. A closed circuit television camera is mounted on the west end of the test cell. At the lower left of the view are fuel and oxidizer run tanks which supply propellants for test runs. (JPL negative no. 384-2650-A, 8 February 1961) - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

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.

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.

Detonation Propagation Through Ducts in a Pulsed Detonation Engine

DTIC Science & Technology

2011-03-01

PDE head. This convention is used based on the fill and purge flow directions, not the detonation direction. Figure 21. Adapter used to rotate ...presented for the development of a continuously operating pulsed detonation engine ( PDE ). A PDE without a high energy ignition system or a... detonation wave. Propagation is left to right in the bottom tube. ..... 19  Figure 15. Research PDE head

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.

Store Separation Simulation of the Penguin Missile from Helicopters

DTIC Science & Technology

2006-05-01

Fin Sections – Parent Aircraft Aerodynamic Modeling • Fuselage • Wing and Pylon – Flight Simulation Features • Eqns. Of Motion • Ejectors , Thrust ...model – Lanyard model – Models for ejectors , thrust , mass, etc… – Helicopter rotor wake model – Penguin wing deployment dynamics – Penguin wing roll...umbilical, wing roll tabs, time dependent thrust and mass properties, and the incorporation of a realistic autopilot. The modeling of the unique

Design Rules and Issues with Respect to Rocket Based Combined Cycles

DTIC Science & Technology

2010-09-01

cause thrust augmentation due to the ejector effects, which in turn, can reduce the requirement for the rocket engine output. In the speed regime with...should produce sufficient thrust to takeoff and to overcome the drag at transonic regime. When embedded into a flow pass, the rocket exhaust can...between the ejector -jet operation and ramjet operation, between the ramjet operations at various flight conditions, and between the ramjet operation and

Electro-Microfluidic Packaging

NASA Astrophysics Data System (ADS)

Benavides, G. L.; Galambos, P. C.

2002-06-01

There are many examples of electro-microfluidic products that require cost effective packaging solutions. Industry has responded to a demand for products such as drop ejectors, chemical sensors, and biological sensors. Drop ejectors have consumer applications such as ink jet printing and scientific applications such as patterning self-assembled monolayers or ejecting picoliters of expensive analytes/reagents for chemical analysis. Drop ejectors can be used to perform chemical analysis, combinatorial chemistry, drug manufacture, drug discovery, drug delivery, and DNA sequencing. Chemical and biological micro-sensors can sniff the ambient environment for traces of dangerous materials such as explosives, toxins, or pathogens. Other biological sensors can be used to improve world health by providing timely diagnostics and applying corrective measures to the human body. Electro-microfluidic packaging can easily represent over fifty percent of the product cost and, as with Integrated Circuits (IC), the industry should evolve to standard packaging solutions. Standard packaging schemes will minimize cost and bring products to market sooner.

Gen 2.0 Mixer/Ejector Nozzle Test at LSAF June 1995 to July 1996

NASA Technical Reports Server (NTRS)

Arney, L. D.; Sandquist, D. L.; Forsyth, D. W.; Lidstone, G. L.; Long-Davis, Mary Jo (Technical Monitor)

2005-01-01

Testing of the HSCT Generation 2.0 nozzle model hardware was conducted at the Boeing Low Speed Aeroacoustic Facility, LSAF. Concurrent measurements of noise and thrust were made at critical takeoff design conditions for a variety of mixer/ejector model hardware. Design variables such as suppressor area ratio, mixer area ratio, liner type and thickness, ejector length, lobe penetration, and mixer chute shape were tested. Parallel testing was conducted at G.E.'s Cell 41 acoustic free jet facility to augment the LSAF test. The results from the Gen 2.0 testing are being used to help shape the current nozzle baseline configuration and guide the efforts in the upcoming Generation 2.5 and 3.0 nozzle tests. The Gen 2.0 results have been included in the total airplane system studies conducted at MDC and Boeing to provide updated noise and thrust performance estimates.

FDNS CFD Code Benchmark for RBCC Ejector Mode Operation

NASA Technical Reports Server (NTRS)

Holt, James B.; Ruf, Joe

1999-01-01

Computational Fluid Dynamics (CFD) analysis results are compared with benchmark quality test data from the Propulsion Engineering Research Center's (PERC) Rocket Based Combined Cycle (RBCC) experiments to verify fluid dynamic code and application procedures. RBCC engine flowpath development will rely on CFD applications to capture the multi-dimensional fluid dynamic interactions and to quantify their effect on the RBCC system performance. Therefore, the accuracy of these CFD codes must be determined through detailed comparisons with test data. The PERC experiments build upon the well-known 1968 rocket-ejector experiments of Odegaard and Stroup by employing advanced optical and laser based diagnostics to evaluate mixing and secondary combustion. The Finite Difference Navier Stokes (FDNS) code was used to model the fluid dynamics of the PERC RBCC ejector mode configuration. Analyses were performed for both Diffusion and Afterburning (DAB) and Simultaneous Mixing and Combustion (SMC) test conditions. Results from both the 2D and the 3D models are presented.

Flight investigation of an underwing nacelle installation of an auxiliary-inlet ejector nozzle with a clamshell flow diverter from Mach 0.6 to 1.3

NASA Technical Reports Server (NTRS)

Head, V. L.

1972-01-01

A nozzle installation of general interest is a podded engine mounted near the aft lower surface of the wing. The effect of this installation on the performance of an auxiliary-inlet ejector nozzle with a clamshell flow diverter was investigated over a Mach number range of 0.6 to 1.3 by using a modified F-106B aircraft. The clamshell flow diverter was tested in a 17 deg position with double-hinged synchronized floating doors. The ejector nozzle trailing-edge flaps were simulated in the closed position with a rigid structure which provided a boattail angle of 10 deg. Primary nozzle area was varied as exhaust gas temperature was varied between 975 and 1561 K. With the nozzle in a subsonic cruise position, the nozzle gross thrust coefficient was 0.918 at a flight Mach number of 0.9.

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

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.

Electrosonic ejector microarray for drug and gene delivery.

PubMed

Zarnitsyn, Vladimir G; Meacham, J Mark; Varady, Mark J; Hao, Chunhai; Degertekin, F Levent; Fedorov, Andrei G

2008-04-01

We report on development and experimental characterization of a novel cell manipulation device-the electrosonic ejector microarray-which establishes a pathway for drug and/or gene delivery with control of biophysical action on the length scale of an individual cell. The device comprises a piezoelectric transducer for ultrasound wave generation, a reservoir for storing the sample mixture and a set of acoustic horn structures that form a nozzle array for focused application of mechanical energy. The nozzles are micromachined in silicon or plastic using simple and economical batch fabrication processes. When the device is driven at a particular resonant frequency of the acoustic horn structures, the sample mixture of cells and desired transfection agents/molecules suspended in culture medium is ejected from orifices located at the nozzle tips. During sample ejection, focused mechanical forces (pressure and shear) are generated on a microsecond time scale (dictated by nozzle size/geometry and ejection velocity) resulting in identical "active" microenvironments for each ejected cell. This process enables a number of cellular bioeffects, from uptake of small molecules and gene delivery/transfection to cell lysis. Specifically, we demonstrate successful calcein uptake and transfection of DNA plasmid encoding green fluorescent protein (GFP) into human malignant glioma cells (cell line LN443) using electrosonic microarrays with 36, 45 and 50 mum diameter nozzle orifices and operating at ultrasound frequencies between 0.91 and 0.98 MHz. Our results suggest that efficacy and the extent of bioeffects are mainly controlled by nozzle orifice size and the localized intensity of the applied acoustic field.

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.

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.

A Preliminary Investigation of Exhaust-Gas Ejectors for Ground Cooling

DTIC Science & Technology

1942-07-01

of teste of ejectore with regard to jet- thrust augmentation . The testa were conducted, for the most; part, with emall- scale models actuated by...their thrust - augmentation , characteristics . D i In view of the lack of experimental data directly applicable to the problem, an invsetigation wae...J e t Propulsion w i t h Special Reference t o Thrust Augmentors. NACA TN No. 442, 1933. 3. Lee, John G.: Progress Report on Augmented J e t

Numerical Evaluation of an Ejector-Enhanced Resonant Pulse Combustor with a Poppet Inlet Valve and a Converging Exhaust Nozzle

NASA Technical Reports Server (NTRS)

Yungster, Shaye; Paxson, Daniel E.; Perkins, Hugh D.

2016-01-01

A computational investigation of a pressure-gain combustor system for gas turbine applications is presented. The system consists of a valved pulse combustor and an ejector, housed within a shroud. The study focuses on two enhancements to previous models, related to the valve and ejector components. First, a new poppet inlet valve system is investigated, replacing the previously used reed valve configuration. Secondly, a new computational approach to approximating the effects of choked turbine inlet guide vanes present immediately downstream of the Ejector-Enhanced Resonant Pulse Combustor (EERPC) is investigated. Instead of specifying a back pressure at the EERPC exit boundary (as was done in previous studies) the new model adds a converging-diverging (CD) nozzle at the exit of the EERPC. The throat area of the CD nozzle can be adjusted to obtain the desired back pressure level and total mass flow rate. The results presented indicate that the new poppet valve configuration performs nearly as well as the original reed valve system, and that the addition of the CD nozzle is an effective method to approximate the exit boundary effects of a turbine present downstream of the EERPC. Furthermore, it is shown that the more acoustically reflective boundary imposed by a nozzle as compared to a constant pressure surface does not significantly affect operation or performance.

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.

Bounding the electrostatic free energies associated with linear continuum models of molecular solvation.

PubMed

Bardhan, Jaydeep P; Knepley, Matthew G; Anitescu, Mihai

2009-03-14

The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

Bounding the electrostatic free energies associated with linear continuum models of molecular solvation

NASA Astrophysics Data System (ADS)

Bardhan, Jaydeep P.; Knepley, Matthew G.; Anitescu, Mihai

2009-03-01

The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

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

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

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.

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.

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

Practical problems relating to the hovercraft application of marine gas turbines

NASA Astrophysics Data System (ADS)

Jin-Zhang, Z.

Design specifications of the marine gas turbine in a hovercraft application are discussed, in addition to the requirements for load distribution of the turbine power in this application. The effective load of the gas turbine is found to be about 57 percent higher than that of the air-cooled diesel engine, and a comparison between the two engines indicates that the effective load of the diesel-driven boat becomes advantageous only when the endurance is more than 26 hours. A multistage filter for air-water separation could reduce the salt content to less than 0.01 ppm where the pressure loss is less than 100 mm water head, and a low profile-resistance ejector without a mixing section could be developed to reduce the engine room pressure to the 45-50 C range.

Halon Replacement Program for Aviation, Aircraft Engine Nacelle Application Phase II - Operational Comparison of Selected Extinguishants

DTIC Science & Technology

1997-05-01

Control Butterfly Hi-Pressure High Flow Control Butterfly Ejector Primary Clycol Control Valve Scrubber Fan Pressure Control Butterfly 8" Venturi ...the scrubber . 20 ■ SCRUBBER FAN BLOWER INLET VALVE VP-2 VP-3 VP-4 VP-5 VP-6 VP-7 VP-8 VP-9 VP-10 SV-1 SV-2 DESCRIPTION Atmospheric...Blower Bypass Butterfly 24" Venturi Control Butterfly 24" Test Section Exit Butterfly Ejector 10’ Secondary Inlet-Butterfly Hi-pressure Low Flow

Oxygen-iodine ejector laser with a centrifugal bubbling singlet-oxygen generator

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

Zagidullin, M V; Nikolaev, V D; Svistun, M I

2005-10-31

It is shown that if a supersonic oxygen-iodine ejector laser is fed by singlet oxygen from a centrifugal bubbling generator operating at a centrifugal acceleration of {approx}400g, the laser output power achieves a value 1264 W at a chemical efficiency of 24.6% for an alkaline hydrogen peroxide flow rate of 208 cm{sup 3}s{sup -1} and a specific chlorine load of 1.34 mmol s{sup -1} per square centimetre of the bubble layer. (lasers)

Exhaust system for use with a turbine and method of assembling same

DOEpatents

Dalsania, Prakash Bavanjibhai; Sadhu, Antanu

2015-08-18

An exhaust system for use with a steam turbine is provided. An exhaust hood includes an input and an output, the input receiving fluid from the steam turbine. The exhaust hood includes a first side wall that extends between the input and the output. The first side wall includes an aperture. An ejector is coupled to the exhaust hood. The ejector includes inlets and an outlet. At least one of the inlets receives fluid from the exhaust hood via the aperture.

The ejector flowmeter: an evaluation of its accuracy.

PubMed

Waaben, J; Thomsen, A

1978-01-01

The accuracy of five ejector flowmeters was assessed using three different gases and four flow-rates. A soap-bubble flowmeter was used for the calibaration. Significant variations were found between individual flowmeters and between different gas mixtures. No variation was found between the four different flowrates, indicating that the calibration is linear. The mean calibration factor was 84.8% +/- 4.1 (100% O2:87.4 +/- 3.4, 50% N2O/O2: 84.2 +/- 2.8, and 100% N2O: 83.0 +/- 4.6).

Remote mass spectrometric sampling of electrospray- and desorption electrospray-generated ions using an air ejector.

PubMed

Dixon, R Brent; Bereman, Michael S; Muddiman, David C; Hawkridge, Adam M

2007-10-01

A commercial air ejector was coupled to an electrospray ionization linear ion trap mass spectrometer (LTQ) to transport remotely generated ions from both electrospray (ESI) and desorption electrospray ionization (DESI) sources. We demonstrate the remote analysis of a series of analyte ions that range from small molecules and polymers to polypeptides using the AE-LTQ interface. The details of the ESI-AE-LTQ and DESI-AE-LTQ experimental configurations are described and preliminary mass spectrometric data are presented.

Remote Mass Spectrometric Sampling of Electrospray- and Desorption Electrospray-Generated Ions Using an Air Ejector

PubMed Central

Dixon, R. Brent; Bereman, Michael S.; Muddiman, David C.; Hawkridge, Adam M.

2007-01-01

A commercial air ejector was coupled to an electrospray ionization linear ion trap mass spectrometer (LTQ) to transport remotely generated ions from both electrospray (ESI) and desorption electrospray ionization (DESI) sources. We demonstrate the remote analysis of a series of analyte ions that range from small molecules and polymers to polypeptides using the AE-LTQ interface. The details of the ESI-AE-LTQ and DESI-AE-LTQ experimental configurations are described and preliminary mass spectrometric data is presented. PMID:17716909

A-3 Test Stand construction moves forward

NASA Image and Video Library

2010-07-13

Work on the A-3 Test Stand at Stennis Space Center took a step forward in July with delivery of the first-stage steam ejector July 13. Stennis employees are shown preparing the ejector to be lifted into place on the test stand. When activated in 2012, the A-3 Test Stand will allow operators to test rocket engines at simulated altitudes of 100,000 feet, a critical feature for next-generation engines that will take humans beyond low-Earth orbit once more.

Diffuser/ejector system for a very high vacuum environment

NASA Technical Reports Server (NTRS)

Riggs, K. E.; Wojciechowski, C. J. (Inventor)

1984-01-01

Turbo jet engines are used to furnish the necessary high temperature, high volume, medium pressure gas to provide a high vacuum test environment at comparatively low cost for space engines at sea level. Moreover, the invention provides a unique way by use of the variable area ratio ejectors with a pair of meshing cones are used. The outer cone is arranged to translate fore and aft, and the inner cone is interchangeable with other cones having varying angles of taper.

Thermal energy recycling fuel cell arrangement

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

Hanrahan, Paul R.

An example fuel cell arrangement includes a fuel cell stack configured to receive a supply fluid and to provide an exhaust fluid that has more thermal energy than the supply fluid. The arrangement also includes an ejector and a heat exchanger. The ejector is configured to direct at least some of the exhaust fluid into the supply fluid. The heat exchanger is configured to increase thermal energy in the supply fluid using at least some of the exhaust fluid that was not directed into the supply fluid.

Operationally efficient propulsion system study (OEPSS) data book. Volume 10; Air Augmented Rocket Afterburning

NASA Technical Reports Server (NTRS)

Farhangi, Shahram; Trent, Donnie (Editor)

1992-01-01

A study was directed towards assessing viability and effectiveness of an air augmented ejector/rocket. Successful thrust augmentation could potentially reduce a multi-stage vehicle to a single stage-to-orbit vehicle (SSTO) and, thereby, eliminate the associated ground support facility infrastructure and ground processing required by the eliminated stage. The results of this preliminary study indicate that an air augmented ejector/rocket propulsion system is viable. However, uncertainties resulting from simplified approach and assumptions must be resolved by further investigations.

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

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.

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.

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.

Initiation of small-satellite formations via satellite ejector

NASA Astrophysics Data System (ADS)

McMullen, Matthew G

Small satellites can be constructed at a fraction of the cost of a full-size satellite. One full-size satellite can be replaced with a multitude of small satellites, offering expanded area coverage through formation flight. However, the shortcoming to the smaller size is usually a lack of thrusting capabilities. Furthermore, current designs for small satellite deployment mechanisms are only capable of love deployment velocities (on the order of meters per second). Motivated to address this shortcoming, a conceived satellite ejector would offer a significant orbit change by ejecting the satellite at higher deployment velocities (125-200 m/s). Focusing on the applications of the ejector, it is sought to bridge the gap in prior research by offering a method to initiate formation flight. As a precursor to the initiation, the desired orbit properties to initiate the formation are specified in terms of spacing and velocity change vector. From this, a systematic method is developed to find the relationship among velocity change vector, the desired orbit's orientation, and the spacing required to initiate the formation.

Multiplexed operation of a micromachined ultrasonic droplet ejector array.

PubMed

Forbes, Thomas P; Degertekin, F Levent; Fedorov, Andrei G

2007-10-01

A dual-sample ultrasonic droplet ejector array is developed for use as a soft-ionization ion source for multiplexed mass spectrometry (MS). Such a multiplexed ion source aims to reduce MS analysis time for multiple analyte streams, as well as allow for the synchronized ejection of the sample(s) and an internal standard for quantitative results and mass calibration. Multiplexing is achieved at the device level by division of the fluid reservoir and separating the active electrodes of the piezoelectric transducer for isolated application of ultrasonic wave energy to each domain. The transducer is mechanically shaped to further reduce the acoustical crosstalk between the domains. Device design is performed using finite-element analysis simulations and supported by experimental characterization. Isolated ejection of approximately 5 microm diameter water droplets from individual domains in the micromachined droplet ejector array at around 1 MHz frequency is demonstrated by experiments. The proof-of-concept demonstration using a dual-sample device also shows potential for multiplexing with larger numbers of analytes.

Quadrant CFD Analysis of a Mixer-Ejector Nozzle for HSCT Applications

NASA Technical Reports Server (NTRS)

Yoder, Dennis A.; Georgiadis, Nicholas J.; Wolter, John D.

2005-01-01

This study investigates the sidewall effect on flow within the mixing duct downstream of a lobed mixer-ejector nozzle. Simulations which model only one half-chute width of the ejector array are compared with those which model one complete quadrant of the nozzle geometry and with available experimental data. These solutions demonstrate the applicability of the half-chute technique to model the flowfield far away from the sidewall and the necessity of a full-quadrant simulation to predict the formation of a low-energy flow region near the sidewall. The quadrant solutions are further examined to determine the cause of this low-energy region, which reduces the amount of mixing and lowers the thrust of the nozzle. Grid resolution and different grid topologies are also examined. Finally, an assessment of the half-chute and quadrant approaches is made to determine the ability of these simulations to provide qualitative and/or quantitative predictions for this type of complex flowfield.

Multiplexed operation of a micromachined ultrasonic droplet ejector array

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

Forbes, Thomas P.; Degertekin, F. Levent; Fedorov, Andrei G.

2007-10-15

A dual-sample ultrasonic droplet ejector array is developed for use as a soft-ionization ion source for multiplexed mass spectrometry (MS). Such a multiplexed ion source aims to reduce MS analysis time for multiple analyte streams, as well as allow for the synchronized ejection of the sample(s) and an internal standard for quantitative results and mass calibration. Multiplexing is achieved at the device level by division of the fluid reservoir and separating the active electrodes of the piezoelectric transducer for isolated application of ultrasonic wave energy to each domain. The transducer is mechanically shaped to further reduce the acoustical crosstalk betweenmore » the domains. Device design is performed using finite-element analysis simulations and supported by experimental characterization. Isolated ejection of {approx}5 {mu}m diameter water droplets from individual domains in the micromachined droplet ejector array at around 1 MHz frequency is demonstrated by experiments. The proof-of-concept demonstration using a dual-sample device also shows potential for multiplexing with larger numbers of analytes.« less

FDNS CFD Code Benchmark for RBCC Ejector Mode Operation: Continuing Toward Dual Rocket Effects

NASA Technical Reports Server (NTRS)

West, Jeff; Ruf, Joseph H.; Turner, James E. (Technical Monitor)

2000-01-01

Computational Fluid Dynamics (CFD) analysis results are compared with benchmark quality test data from the Propulsion Engineering Research Center's (PERC) Rocket Based Combined Cycle (RBCC) experiments to verify fluid dynamic code and application procedures. RBCC engine flowpath development will rely on CFD applications to capture the multi -dimensional fluid dynamic interactions and to quantify their effect on the RBCC system performance. Therefore, the accuracy of these CFD codes must be determined through detailed comparisons with test data. The PERC experiments build upon the well-known 1968 rocket-ejector experiments of Odegaard and Stroup by employing advanced optical and laser based diagnostics to evaluate mixing and secondary combustion. The Finite Difference Navier Stokes (FDNS) code [2] was used to model the fluid dynamics of the PERC RBCC ejector mode configuration. Analyses were performed for the Diffusion and Afterburning (DAB) test conditions at the 200-psia thruster operation point, Results with and without downstream fuel injection are presented.

Initial development of the two-dimensional ejector shear layer - Experimental results

NASA Technical Reports Server (NTRS)

Benjamin, M. A.; Dufflocq, M.; Roan, V. P.

1993-01-01

An experimental investigation designed to study the development of shear layers in a two-dimensional single-nozzle ejector has been completed. In this study, combinations of air/air, argon/air, helium/air, and air/helium were used as the supersonic primary and subsonic secondary, respectively. Mixing of the gases occurred in a constant-area tube 39.1 mm high by 25.4 mm wide, where the inlet static pressure was maintained at 35 kPa. The cases studied resulted in convective Mach numbers between 0.058 and 1.64, density ratios between 0.102 and 3.49, and velocity ratios between 0.065 and 0.811. The resulting data shows the differences in the shear-layer development for the various combinations of independent variables utilized in the investigation. The normalized growth-rates in the near-field were found to be similar to two-dimensional mixing layers. These results have enhanced the ability to analyze and design ejector systems as well as providing a better understanding of the physics.

Troubleshooting crude vacuum tower overhead ejector systems

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

Lines, J.R.; Frens, L.L.

1995-03-01

Routinely surveying tower overhead vacuum systems can improve performance and product quality. These vacuum systems normally provide reliable and consistent operation. However, process conditions, supplied utilities, corrosion, erosion and fouling all have an impact on ejector system performance. Refinery vacuum distillation towers use ejector systems to maintain tower top pressure and remove overhead gases. However, as with virtually all refinery equipment, performance may be affected by a number of variables. These variables may act independently or concurrently. It is important to understand basic operating principles of vacuum systems and how performance is affected by: utilities, corrosion and erosion, fouling, andmore » process conditions. Reputable vacuum-system suppliers have service engineers that will come to a refinery to survey the system and troubleshoot performance or offer suggestions for improvement. A skilled vacuum-system engineer may be needed to diagnose and remedy system problems. The affect of these variables on performance is discussed. A case history is described of a vacuum system on a crude tower in a South American refinery.« less

Analysis of a New Rocket-Based Combined-Cycle Engine Concept at Low Speed

NASA Technical Reports Server (NTRS)

Yungster, S.; Trefny, C. J.

1999-01-01

An analysis of the Independent Ramjet Stream (IRS) cycle is presented. The IRS cycle is a variation of the conventional ejector-Ramjet, and is used at low speed in a rocket-based combined-cycle (RBCC) propulsion system. In this new cycle, complete mixing between the rocket and ramjet streams is not required, and a single rocket chamber can be used without a long mixing duct. Furthermore, this concept allows flexibility in controlling the thermal choke process. The resulting propulsion system is intended to be simpler, more robust, and lighter than an ejector-ramjet. The performance characteristics of the IRS cycle are analyzed for a new single-stage-to-orbit (SSTO) launch vehicle concept, known as "Trailblazer." The study is based on a quasi-one-dimensional model of the rocket and air streams at speeds ranging from lift-off to Mach 3. The numerical formulation is described in detail. A performance comparison between the IRS and ejector-ramjet cycles is also presented.

High speed jet noise research at NASA Lewis

NASA Astrophysics Data System (ADS)

Krejsa, Eugene A.; Cooper, B. A.; Kim, C. M.; Khavaran, Abbas

1992-04-01

The source noise portion of the High Speed Research Program at NASA LeRC is focused on jet noise reduction. A number of jet noise reduction concepts are being investigated. These include two concepts, the Pratt & Whitney ejector suppressor nozzle and the General Electric (GE) 2D-CD mixer ejector nozzle, that rely on ejectors to entrain significant amounts of ambient air to mix with the engine exhaust to reduce the final exhaust velocity. Another concept, the GE 'Flade Nozzle' uses fan bypass air at takeoff to reduce the mixed exhaust velocity and to create a fluid shield around a mixer suppressor. Additional concepts are being investigated at Georgia Tech Research Institute and at NASA LeRC. These will be discussed in more detail in later figures. Analytical methods for jet noise prediction are also being developed. Efforts in this area include upgrades to the GE MGB jet mixing noise prediction procedure, evaluation of shock noise prediction procedures, and efforts to predict jet noise directly from the unsteady Navier-Stokes equation.

High speed jet noise research at NASA Lewis

NASA Technical Reports Server (NTRS)

Krejsa, Eugene A.; Cooper, B. A.; Kim, C. M.; Khavaran, Abbas

1992-01-01

The source noise portion of the High Speed Research Program at NASA LeRC is focused on jet noise reduction. A number of jet noise reduction concepts are being investigated. These include two concepts, the Pratt & Whitney ejector suppressor nozzle and the General Electric (GE) 2D-CD mixer ejector nozzle, that rely on ejectors to entrain significant amounts of ambient air to mix with the engine exhaust to reduce the final exhaust velocity. Another concept, the GE 'Flade Nozzle' uses fan bypass air at takeoff to reduce the mixed exhaust velocity and to create a fluid shield around a mixer suppressor. Additional concepts are being investigated at Georgia Tech Research Institute and at NASA LeRC. These will be discussed in more detail in later figures. Analytical methods for jet noise prediction are also being developed. Efforts in this area include upgrades to the GE MGB jet mixing noise prediction procedure, evaluation of shock noise prediction procedures, and efforts to predict jet noise directly from the unsteady Navier-Stokes equation.

Investigation of Compressibility Effect for Aeropropulsive Shear Flows

NASA Technical Reports Server (NTRS)

Balasubramanyam, M. S.; Chen, C. P.

2005-01-01

Rocket Based Combined Cycle (RBCC) engines operate within a wide range of Mach numbers and altitudes. Fundamental fluid dynamic mechanisms involve complex choking, mass entrainment, stream mixing and wall interactions. The Propulsion Research Center at the University of Alabama in Huntsville is involved in an on- going experimental and numerical modeling study of non-axisymmetric ejector-based combined cycle propulsion systems. This paper attempts to address the modeling issues related to mixing, shear layer/wall interaction in a supersonic Strutjet/ejector flow field. Reynolds Averaged Navier-Stokes (RANS) solutions incorporating turbulence models are sought and compared to experimental measurements to characterize detailed flow dynamics. The effect of compressibility on fluids mixing and wall interactions were investigated using an existing CFD methodology. The compressibility correction to conventional incompressible two- equation models is found to be necessary for the supersonic mixing aspect of the ejector flows based on 2-D simulation results. 3-D strut-base flows involving flow separations were also investigated.

Experimental investigation of wing installation effects on a two-dimensional mixer/ejector nozzle for supersonic transport aircraft

NASA Technical Reports Server (NTRS)

Anderson, David J.; Lambert, Heather H.; Mizukami, Masashi

1992-01-01

Experimental results from a wind tunnel test conducted to investigate propulsion/airframe integration (PAI) effects are presented. The objectives of the test were to examine rough order-of-magnitude changes in the acoustic characteristics of a mixer/ejector nozzle due to the presence of a wing and to obtain limited wing and nozzle flow-field measurements. A simple representative supersonic transport wing planform, with deflecting flaps, was installed above a two-dimensional mixer/ejector nozzle that was supplied with high-pressure heated air. Various configurations and wing positions with respect to the nozzle were studied. Because of hardware problems, no acoustics and only a limited set of flow-field data were obtained. For most hardware configurations tested, no significant propulsion/airframe integration effects were identified. Significant effects were seen for extreme flap deflections. The combination of the exploratory nature of the test and the limited flow-field instrumentation made it impossible to identify definitive propulsion/airframe integration effects.

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.

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

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.

Airbreathing Pulse Detonation Engine Performance

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.; Yungster, Shaye

2002-01-01

This paper presents performance results for pulse detonation engines (PDE) taking into account the effects of dissociation and recombination. The amount of sensible heat recovered through recombination in the PDE chamber and exhaust process was found to be significant. These results have an impact on the specific thrust, impulse and fuel consumption of the PDE.

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.

High performance forward swept wing aircraft

NASA Technical Reports Server (NTRS)

Koenig, David G. (Inventor); Aoyagi, Kiyoshi (Inventor); Dudley, Michael R. (Inventor); Schmidt, Susan B. (Inventor)

1988-01-01

A high performance aircraft capable of subsonic, transonic and supersonic speeds employs a forward swept wing planform and at least one first and second solution ejector located on the inboard section of the wing. A high degree of flow control on the inboard sections of the wing is achieved along with improved maneuverability and control of pitch, roll and yaw. Lift loss is delayed to higher angles of attack than in conventional aircraft. In one embodiment the ejectors may be advantageously positioned spanwise on the wing while the ductwork is kept to a minimum.

Recent Experimental Results Related to Ejector Mode Studies of Rocket-Based Combined Cycle (RBCC) Engines

NASA Technical Reports Server (NTRS)

Cramer, J. M.; Pal, S.; Marshall, W. M.; Santoro, R. J.

2003-01-01

Contents include the folloving: 1. Motivation. Support NASA's 3d generation launch vehicle technology program. RBCC is promising candidate for 3d generation propulsion system. 2. Approach. Focus on ejector mode p3erformance (Mach 0-3). Perform testing on established flowpath geometry. Use conventional propulsion measurement techniques. Use advanced optical diagnostic techniques to measure local combustion gas properties. 3. Objectives. Gain physical understanding of detailing mixing and combustion phenomena. Establish an experimental data set for CFD code development and validation.

Calculation of the mixing chamber of an ejector chemical oxygen - iodine laser

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

Zagidullin, M V; Nikolaev, V D

2001-06-30

Gas parameters are calculated at the outlet of the mixing chamber of an ejector chemical oxygen-iodine laser with a nozzle unit consisting of nozzles of three types, which provides a total pressure of the active medium that substantially exceeds a pressure in the generator of singlet oxygen. This technique of forming the laser active medium substantially facilitates the ejection of the exhaust gas to the atmosphere by using a diffuser and single-stage vacuum systems based on water circulating pumps. (lasers, active media)

Investigation at supersonic and subsonic Mach numbers of auxiliary inlets supplying secondary air flow to ejector exhaust nozzles

NASA Technical Reports Server (NTRS)

Hearth, Donald P; Cubbison, Robert W

1956-01-01

The results indicated increases in auxiliary-inlet pressure recovery with increases in scoop height relative to the boundary-layer thickness. The pressure recovery increased at about the same rate as theoretically predicted for an inlet in a boundary layer having a one-seventh power profile, but was only about 0.68 to 0.75 of the theoretically obtainable values. Under some operating conditions, flow from the primary jet was exhausted through the auxiliary inlet. This phenomenon could be predicted from the ejector pumping characteristics.

Qualification Test of the Thiokol TE-M-364-19 Solid-Propellant Rocket Motor (S/N 19006)

DTIC Science & Technology

1977-05-01

cell by a steam ejector operating in series with the ETF exhaust gas compressors. During the motor firing, the motor exhaust gases were used as a...driving gas for the 42-in.-diam, water-cooled, ejector-diffuser system incorporating a 24-deg (half-angle) conical inlet to maintain test cell pressure...after Ignition, sec 0.5 0.6 0.7 Figure 4. Variation of thrust and chamber pressure during motor ignition. - CO Q_ OH LU CO TL cr x CJ 1400

Low Cost Hypermixing Ejector Ramjet Program.

DTIC Science & Technology

1975-06-01

SEC.A- SCALE: ZO/I q.zPL vEw A -3 SCALE..?0/1 - w aC LIT OFM TIEA -LLIS S A?-. 87 SECTION XI MODIFIED HYPERMIXING EJECTOR EXPERIMENTAL PROGRAM 1...CAN). psi.. ramage’. Witt shbiuma, .as slacawim iam Fit.,7 Ti’LDtlase lreaa ftime ,mmeasss9ri’d vaiaac’s are aimemit UK ) ft Sv ieAwe(’r 01311 this...Neav OrdueNKw TeOt Station, Dover, New Jersey , March 31, 1955 (Coniderial). 3. Data on UnsyawwetricaI.DinletAyhydrazin* (DMW), Revisin No. 3. Aerojet

SST Technology Follow-On Program - Phase 2. Noise Suppressor/Nozzle Development. Volume 9. Performance Technology - Analysis of the Low Speed Performance of Multitube Suppressor/Ejector Nozzles (0-167 kn)

DTIC Science & Technology

1975-03-01

Layer Suction 18 Temperature and Pressure Profile at Charging Station |9 Roiind-Corivergent Reference Nozzle 20 Elliptical Ramps 21 37-Tube...between plumes of the jets in the outer row of a suppressor Homulary layer Discharge coelticient, accounting for temperature induced no/./Ie area...tunnel floor. The suppressor air tlow rate was measured with an A.S.M.H. long-radius flow nozzle. The boundary layer ihickness at the ejector inlet

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.

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.

Tailored Ink For Piston-Driven Electrostatic Liquid Drop Modulator

DOEpatents

Wong, Raymond W.; Breton, Marcel P.; Bedford, Christine E.; Carreira, Leonard M.; Gooray, Arthur M.; Roller, George J.; Zavadil, Kevin; Galambos, Paul; Crowley, Joseph

2005-04-19

The present invention relates to an ink composition including water, a solvent, a solvent-soluble dye, and a surfactant, where the ink exhibits a stable liquid microemulsion phase at a first temperature and a second temperature higher than the first temperature and has a conductivity of at most about 200 .mu.S/cm and a dielectric constant of at least about 60, and methods of making such ink compositions. The present invention also relates to a method of making an ink composition for use in a microelectromechanical system-based fluid ejector. The method involves providing a solution or dispersion including a dye or a pigment and adding to the solution or dispersion an additive which includes a material that enhances dielectric permittivity and/or reduces conductivity under conditions effective to produce an ink composition having a conductivity of at most about 200 .mu.S/cm and a dielectric constant of at least about 60.

The liquid nitrogen and supercritical helium cooling loop for the jet pumped divertor cryopump

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

Obert, W.; Mayaux, C.; Perinic, G.

1994-12-31

A key element for the new experimental phase of the European fusion experiment JET is a new cryopump which will be installed inside the torus in order to pump the new divertor configuration. A forced flow of liquid nitrogen and supercritical helium has been chosen for the cooling of the cryoshields and cryocondensation panels for this cryopump. The reasons for this selection are to minimize the inventory of cryogens (to minimize nuclear heating) good heat transfer conditions and minimum time for transient conditions such as cool-down, regeneration and warm-up. The flow of supercritical helium will be driven by the mainmore » compressor of the refrigerator and enhanced by a dedicated cold ejector. The peak load during the plasma pulse will be absorbed by the high thermal capacity of the bulk supercritical helium inside the cryocondensation panel.« less

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…

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

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

Ventilation through a small-bore catheter: optimizing expiratory ventilation assistance.

PubMed

Hamaekers, A E W; Borg, P A J; Götz, T; Enk, D

2011-03-01

Emergency ventilation through a small-bore transtracheal catheter can be lifesaving in a 'cannot intubate, cannot ventilate' situation. Ejectors, capable of creating suction by the Bernoulli principle, have been proposed to facilitate expiration through small-bore catheters. In this bench study, we compared a novel, purpose-built ventilation ejector (DE 5) with a previously proposed, modified industrial ejector (SBP 07). The generated insufflation pressures, suction pressures in static and dynamic situations, and also suction capacities and entrainment ratios of the SBP 07 and the DE 5 were determined. The DE 5 was also tested in a lung simulator with a simulated complete upper airway obstruction. Inspiratory and expiratory times through a transtracheal catheter were measured at various flow rates and achievable minute volumes were calculated. In a static situation, the SBP 07 showed a more negative pressure build-up compared with the DE 5. However, in a dynamic situation, the DE 5 generated a more negative pressure, resulting in a higher suction capacity. Employment of the DE 5 at a flow rate of 18 litre min(-1) allowed a minute volume through the transtracheal catheter of up to 8.27 litre min(-1) at a compliance of 100 ml cm H(2)O(-1). The efficiency of the DE 5 depended on the flow rate of the driving gas and the compliance of the lung simulator. In laboratory tests, the DE 5 is an optimized ventilation ejector suitable for applying expiratory ventilation assistance. Further research may confirm the clinical applicability as a portable emergency ventilator for use with small-bore catheters.

A mathematical model for simulating noise suppression of lined ejectors

NASA Technical Reports Server (NTRS)

Watson, Willie R.

1994-01-01

A mathematical model containing the essential features embodied in the noise suppression of lined ejectors is presented. Although some simplification of the physics is necessary to render the model mathematically tractable, the current model is the most versatile and technologically advanced at the current time. A system of linearized equations and the boundary conditions governing the sound field are derived starting from the equations of fluid dynamics. A nonreflecting boundary condition is developed. In view of the complex nature of the equations, a parametric study requires the use of numerical techniques and modern computers. A finite element algorithm that solves the differential equations coupled with the boundary condition is then introduced. The numerical method results in a matrix equation with several hundred thousand degrees of freedom that is solved efficiently on a supercomputer. The model is validated by comparing results either with exact solutions or with approximate solutions from other works. In each case, excellent correlations are obtained. The usefulness of the model as an optimization tool and the importance of variable impedance liners as a mechanism for achieving broadband suppression within a lined ejector are demonstrated.

Acoustic Characteristics of Various Treatment Panel Designs Specific to HSCT Mixer-Ejector Application

NASA Technical Reports Server (NTRS)

Salikuddin, M.; Kinzie, K.; Vu, D. D.; Langenbrunner, L. E.; Szczepkowski, G. T.

2006-01-01

The development process of liner design methodology is described in several reports. The results of the initial effort of concept development, screening, laboratory testing of various liner concepts, and preliminary correlation (generic data) are presented in a report Acoustic Characteristics of Various Treatment Panel Designs for HSCT Ejector Liner Acoustic Technology Development Program. The second phase of laboratory test results of more practical concepts and their data correlations are presented in this report (product specific). In particular, this report contains normal incidence impedance measurements of several liner types in both a static rig and in a high temperature flow duct rig. The flow duct rig allows for temperatures up to 400 F with a grazing flow up to Mach 0.8. Measurements of impedance, DC flow resistance, and in the flow rig cases, impact of the liner on boundary layer profiles are documented. In addition to liner rig tests, a limited number of tests were made on liners installed in a mixer-Ejector nozzle to confirm the performance of the liner prediction in an installed configuration.

Assessment of Integrated Nozzle Performance

NASA Technical Reports Server (NTRS)

Lambert, H. H.; Mizukami, M.

1999-01-01

This presentation highlights the activities that researchers at the NASA Lewis Research Center (LeRC) have been and will be involved in to assess integrated nozzle performance. Three different test activities are discussed. First, the results of the Propulsion Airframe Integration for High Speed Research 1 (PAIHSR1) study are presented. The PAIHSR1 experiment was conducted in the LeRC 9 ft x l5 ft wind tunnel from December 1991 to January 1992. Second, an overview of the proposed Mixer/ejector Inlet Distortion Study (MIDIS-E) is presented. The objective of MIDIS-E is to assess the effects of applying discrete disturbances to the ejector inlet flow on the acoustic and aero-performance of a mixer/ejector nozzle. Finally, an overview of the High-Lift Engine Aero-acoustic Technology (HEAT) test is presented. The HEAT test is a cooperative effort between the propulsion system and high-lift device research communities to assess wing/nozzle integration effects. The experiment is scheduled for FY94 in the NASA Ames Research Center (ARC) 40 ft x 80 ft Low Speed Wind Tunnel (LSWT).

Performance Characterization of Swept Ramp Obstacle Fields in Pulse Detonation Applications

DTIC Science & Technology

2010-03-01

field of practical obstacle geometries. 15. NUMBER OF PAGES 97 14. SUBJECT TERMS Pulse Detonation , PDE , Transient Plasma Ignition, TPI, Swept... Detonation Transition NI - National Instruments NPS - Naval Postgraduate School PDC - Pulse Detonation Combustor PDE - Pulse Detonation Engine...with incredible grace. xvi THIS PAGE INTENTIONALLY LEFT BLANK 1 I. INTRODUCTION Pulse detonation engines ( PDE ) continue to be explored due to

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.

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

Water outlet control mechanism for fuel cell system operation in variable gravity environments

NASA Technical Reports Server (NTRS)

Vasquez, Arturo (Inventor); McCurdy, Kerri L. (Inventor); Bradley, Karla F. (Inventor)

2007-01-01

A self-regulated water separator provides centrifugal separation of fuel cell product water from oxidant gas. The system uses the flow energy of the fuel cell's two-phase water and oxidant flow stream and a regulated ejector or other reactant circulation pump providing the two-phase fluid flow. The system further uses a means of controlling the water outlet flow rate away from the water separator that uses both the ejector's or reactant pump's supply pressure and a compressibility sensor to provide overall control of separated water flow either back to the separator or away from the separator.

A Summary/Overview of Ejector Augmentor Theory and Performance. Volume 1. Technical Discussion

DTIC Science & Technology

1979-09-01

P Tt ’ Pt m m P - tp pp ptm Pt P Pt Tt n CONSTANT PRESSURE MIXIN -,"--"MIXING INITIAL HEAT ADDITION TO THE PRIMARY w It s sm S Sm ENTROPY, s FfGURE 2...TEMPERATURE-ENTROPY DIAGRAM FOR AN EJECTOR CYCLE ........ . .. I.... ...T H NITIAL HEAT ADDITION TO THE PRIMARY s s sm s8 psi Pt s Tt s ex AIR Uu...s Sm = (8) This Increase in entropy drives the cycle performance to lower values of calcu- lated p, as shown in Figure 4. The only boundary condition

Venturi Air-Jet Vacuum Ejector For Sampling Air

NASA Technical Reports Server (NTRS)

Hill, Gerald F.; Sachse, Glen W.; Burney, L. Garland; Wade, Larry O.

1990-01-01

Venturi air-jet vacuum ejector pump light in weight, requires no electrical power, does not contribute heat to aircraft, and provides high pumping speeds at moderate suctions. High-pressure motive gas required for this type of pump bled from compressor of aircraft engine with negligible effect on performance of engine. Used as source of vacuum for differential-absorption CO-measurement (DACOM), modified to achieve in situ measurements of CO at frequency response of 10 Hz. Provides improvement in spatial resolution and potentially leads to capability to measure turbulent flux of CO by use of eddy-correlation technique.

Real-time simulation of an F110/STOVL turbofan engine

NASA Technical Reports Server (NTRS)

Drummond, Colin K.; Ouzts, Peter J.

1989-01-01

A traditional F110-type turbofan engine model was extended to include a ventral nozzle and two thrust-augmenting ejectors for Short Take-Off Vertical Landing (STOVL) aircraft applications. Development of the real-time F110/STOVL simulation required special attention to the modeling approach to component performance maps, the low pressure turbine exit mixing region, and the tailpipe dynamic approximation. Simulation validation derives by comparing output from the ADSIM simulation with the output for a validated F110/STOVL General Electric Aircraft Engines FORTRAN deck. General Electric substantiated basic engine component characteristics through factory testing and full scale ejector data.

Entrainment and mixing in thrust augmenting ejectors

NASA Technical Reports Server (NTRS)

Bernal, L.; Sarohia, V.

1983-01-01

An experimental investigation of two-dimensional thrust augmenting ejector flows has been conducted. Measurements of the shroud surface pressure distribution, mean velocity, turbulent intensities and Reynolds stresses were made in two shroud geometries at various primary nozzle pressure ratios. The effects of shroud geometry and primary nozzle pressure ratio on the shroud surface pressure distribution, mean flow field and turbulent field were determined. From these measurements the evolution of mixing within the shroud of the primary flow and entrained fluid was obtained. The relationship between the mean flow field, the turbulent field and the shroud surface pressure distribution is discussed.

Comparative Analysis of a High Bypass Turbofan Using a Pulsed Detonation Combustor

DTIC Science & Technology

2007-03-01

Thrust Specific Fuel Consumption . . . . . . . . . . . . . 67 xiii List of Abbreviations Abbreviation Page PDE Pulsed Detonation Engine...past ten years to develop pulsed det- onation engines ( PDE ) as a means of aircraft propulsion. Detonation combustion holds the promise of a more...aviation engine, and detonation creates more of it than previous aircraft engines. It is hoped that a marriage of the PDE with traditional

Transient Heat Transfer Properties in a Pulse Detonation Combustor

DTIC Science & Technology

2011-03-01

strategies for future systems. 15. NUMBER OF PAGES 89 14. SUBJECT TERMS Pulse Detonation Engines, PDE , Heat Transfer 16. PRICE CODE 17. SECURITY...GUI Graphical User Interface NPS Naval Postgraduate School PDC Pulse Detonation Combustion PDE Pulse Detonation Engine RPL Rocket...a tactical missile with a Pulse Detonation Engine ( PDE ) and provide greater range for the same amount of fuel as compared to other current

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.

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.

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.

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) blocks differentiation and maintains the expression of pluripotency markers in human embryonic stem cells.

PubMed

Burton, Peter; Adams, David R; Abraham, Achamma; Allcock, Robert W; Jiang, Zhong; McCahill, Angela; Gilmour, Jane; McAbney, John; Kaupisch, Alexandra; Kane, Nicole M; Baillie, George S; Baker, Andrew H; Milligan, Graeme; Houslay, Miles D; Mountford, Joanne C

2010-12-15

hESCs (human embryonic stem cells) have enormous potential for use in pharmaceutical development and therapeutics; however, to realize this potential, there is a requirement for simple and reproducible cell culture methods that provide adequate numbers of cells of suitable quality. We have discovered a novel way of blocking the spontaneous differentiation of hESCs in the absence of exogenous cytokines by supplementing feeder-free conditions with EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine], an established inhibitor of ADA (adenosine deaminase) and cyclic nucleotide PDE2 (phosphodiesterase 2). hESCs maintained in feeder-free conditions with EHNA for more than ten passages showed no reduction in hESC-associated markers including NANOG, POU5F1 (POU domain class 5 transcription factor 1, also known as Oct-4) and SSEA4 (stage-specific embryonic antigen 4) compared with cells maintained in feeder-free conditions containing bFGF (basic fibroblast growth factor). Spontaneous differentiation was reversibly suppressed by the addition of EHNA, but, upon removing EHNA, hESC populations underwent efficient spontaneous, multi-lineage and directed differentiation. EHNA also acts as a strong blocker of directed neuronal differentiation. Chemically distinct inhibitors of ADA and PDE2 lacked the capacity of EHNA to suppress hESC differentiation, suggesting that the effect is not driven by inhibition of either ADA or PDE2. Preliminary structure-activity relationship analysis found the differentiation-blocking properties of EHNA to reside in a pharmacophore comprising a close adenine mimetic with an extended hydrophobic substituent in the 8- or 9-position. We conclude that EHNA and simple 9-alkyladenines can block directed neuronal and spontaneous differentiation in the absence of exogenous cytokine addition, and may provide a useful replacement for bFGF in large-scale or cGMP-compliant processes.

Branch Detonation of a Pulse Detonation Engine With Flash Vaporized JP-8

DTIC Science & Technology

2006-12-01

Mark F. Reeder (Member) date iii Abstract Pulse Detonation Engines ( PDE ) operating on liquid hydrocarbon fuels are... Detonation Transition FF – Fill Fraction FN – Flow Number NPT – National Pipe Thread OH – Hydroxyl PDE – Pulse Detonation Engine PF – Purge...Introduction Motivation Research on Pulsed Detonation Engines ( PDE ) has increased over the past ten years due to the potential for increased

Initiation Mechanisms of Low-loss Swept-ramp Obstacles for Deflagration to Detonation Transition in Pulse Detonation Combustors

DTIC Science & Technology

2009-12-01

minimal pressure losses. 15. NUMBER OF PAGES 113 14. SUBJECT TERMS Pulse Detonation Combustors, PDC, Pulse Detonation Engines, PDE , PDE ...Postgraduate School PDC Pulse Detonation Combustor PDE Pulse Detonation Engine RAM Random Access Memory RDT Research, Design and Test RPL...inhibiting the implementation of this advanced propulsion system. The primary advantage offered by pulse detonation engines ( PDEs ) is the high efficiency