Hierarchical modeling and robust synthesis for the preliminary design of large scale complex systems

NASA Astrophysics Data System (ADS)

Koch, Patrick Nathan

Large-scale complex systems are characterized by multiple interacting subsystems and the analysis of multiple disciplines. The design and development of such systems inevitably requires the resolution of multiple conflicting objectives. The size of complex systems, however, prohibits the development of comprehensive system models, and thus these systems must be partitioned into their constituent parts. Because simultaneous solution of individual subsystem models is often not manageable iteration is inevitable and often excessive. In this dissertation these issues are addressed through the development of a method for hierarchical robust preliminary design exploration to facilitate concurrent system and subsystem design exploration, for the concurrent generation of robust system and subsystem specifications for the preliminary design of multi-level, multi-objective, large-scale complex systems. This method is developed through the integration and expansion of current design techniques: (1) Hierarchical partitioning and modeling techniques for partitioning large-scale complex systems into more tractable parts, and allowing integration of subproblems for system synthesis, (2) Statistical experimentation and approximation techniques for increasing both the efficiency and the comprehensiveness of preliminary design exploration, and (3) Noise modeling techniques for implementing robust preliminary design when approximate models are employed. The method developed and associated approaches are illustrated through their application to the preliminary design of a commercial turbofan turbine propulsion system; the turbofan system-level problem is partitioned into engine cycle and configuration design and a compressor module is integrated for more detailed subsystem-level design exploration, improving system evaluation.

Decentralized adaptive robust control based on sliding mode and nonlinear compensator for the control of ankle movement using functional electrical stimulation of agonist-antagonist muscles

NASA Astrophysics Data System (ADS)

Kobravi, Hamid-Reza; Erfanian, Abbas

2009-08-01

A decentralized control methodology is designed for the control of ankle dorsiflexion and plantarflexion in paraplegic subjects with electrical stimulation of tibialis anterior and calf muscles. Each muscle joint is considered as a subsystem and individual controllers are designed for each subsystem. Each controller operates solely on its associated subsystem, with no exchange of information between the subsystems. The interactions between the subsystems are taken as external disturbances for each isolated subsystem. In order to achieve robustness with respect to external disturbances, unmodeled dynamics, model uncertainty and time-varying properties of muscle-joint dynamics, a robust control framework is proposed which is based on the synergistic combination of an adaptive nonlinear compensator with a sliding mode control and is referred to as an adaptive robust control. Extensive simulations and experiments on healthy and paraplegic subjects were performed to demonstrate the robustness against the time-varying properties of muscle-joint dynamics, day-to-day variations, subject-to-subject variations, fast convergence, stability and tracking accuracy of the proposed method. The results indicate that the decentralized robust control provides excellent tracking control for different reference trajectories and can generate control signals to compensate the muscle fatigue and reject the external disturbance. Moreover, the controller is able to automatically regulate the interaction between agonist and antagonist muscles under different conditions of operating without any preprogrammed antagonist activities.

Decentralized adaptive robust control based on sliding mode and nonlinear compensator for the control of ankle movement using functional electrical stimulation of agonist-antagonist muscles.

PubMed

Kobravi, Hamid-Reza; Erfanian, Abbas

2009-08-01

A decentralized control methodology is designed for the control of ankle dorsiflexion and plantarflexion in paraplegic subjects with electrical stimulation of tibialis anterior and calf muscles. Each muscle joint is considered as a subsystem and individual controllers are designed for each subsystem. Each controller operates solely on its associated subsystem, with no exchange of information between the subsystems. The interactions between the subsystems are taken as external disturbances for each isolated subsystem. In order to achieve robustness with respect to external disturbances, unmodeled dynamics, model uncertainty and time-varying properties of muscle-joint dynamics, a robust control framework is proposed which is based on the synergistic combination of an adaptive nonlinear compensator with a sliding mode control and is referred to as an adaptive robust control. Extensive simulations and experiments on healthy and paraplegic subjects were performed to demonstrate the robustness against the time-varying properties of muscle-joint dynamics, day-to-day variations, subject-to-subject variations, fast convergence, stability and tracking accuracy of the proposed method. The results indicate that the decentralized robust control provides excellent tracking control for different reference trajectories and can generate control signals to compensate the muscle fatigue and reject the external disturbance. Moreover, the controller is able to automatically regulate the interaction between agonist and antagonist muscles under different conditions of operating without any preprogrammed antagonist activities.

Robust finite-time chaos synchronization of uncertain permanent magnet synchronous motors.

PubMed

Chen, Qiang; Ren, Xuemei; Na, Jing

2015-09-01

In this paper, a robust finite-time chaos synchronization scheme is proposed for two uncertain third-order permanent magnet synchronous motors (PMSMs). The whole synchronization error system is divided into two cascaded subsystems: a first-order subsystem and a second-order subsystem. For the first subsystem, we design a finite-time controller based on the finite-time Lyapunov stability theory. Then, according to the backstepping idea and the adding a power integrator technique, a second finite-time controller is constructed recursively for the second subsystem. No exogenous forces are required in the controllers design but only the direct-axis (d-axis) and the quadrature-axis (q-axis) stator voltages are used as manipulated variables. Comparative simulations are provided to show the effectiveness and superior performance of the proposed method. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Protection of ATP-Depleted Cells by Impermeant Strychnine Derivatives

PubMed Central

Dong, Zheng; Venkatachalam, Manjeri A.; Weinberg, Joel M.; Saikumar, Pothana; Patel, Yogendra

2001-01-01

Glycine and structurally related amino acids with activities at chloride channel receptors in the central nervous system also have robust protective effects against cell injury by ATP depletion. The glycine receptor antagonist strychnine shares this protective activity. An essential step toward identification of the molecular targets for these compounds is to determine whether they protect cells through interactions with intracellular targets or with molecules on the outer surface of plasma membranes. Here we report cytoprotection by a cell-impermeant derivative of strychnine. A strychnine-fluorescein conjugate (SF) was synthesized, and impermeability of plasma membranes to this compound was verified by fluorescence confocal microscopy. In an injury model of Madin-Darby canine kidney cells, ATP depletion led to lactate dehydrogenase release. SF prevented lactate dehydrogenase leakage without ameliorating ATP depletion. This was accompanied by preservation of cellular ultrastructure and exclusion of vital dyes. SF protection was also shown for ATP-depleted rat hepatocytes. On the other hand, when a key structural motif in the active site of strychnine was chemically blocked, the SF lost its protective effect, establishing strychnine-related specificity for SF protection. Cytoprotective effects of the cell-impermeant strychnine derivative provide compelling evidence suggesting that molecular targets on the outer surface of plasma membranes may mediate cytoprotection by strychnine and glycine. PMID:11238050

Spacecraft Design Thermal Control Subsystem

NASA Technical Reports Server (NTRS)

Miyake, Robert N.

2008-01-01

The Thermal Control Subsystem engineers task is to maintain the temperature of all spacecraft components, subsystems, and the total flight system within specified limits for all flight modes from launch to end-of-mission. In some cases, specific stability and gradient temperature limits will be imposed on flight system elements. The Thermal Control Subsystem of "normal" flight systems, the mass, power, control, and sensing systems mass and power requirements are below 10% of the total flight system resources. In general the thermal control subsystem engineer is involved in all other flight subsystem designs.

ATP-driven and AMPK-independent autophagy in an early branching eukaryotic parasite.

PubMed

Li, Feng-Jun; Xu, Zhi-Shen; Soo, Andy D S; Lun, Zhao-Rong; He, Cynthia Y

2017-04-03

Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) is yet to be identified, deprivation of amino acids, glucose, growth factor and other nutrients can serve as metabolic stimuli to initiate autophagy in higher eukaryotes. In the early-branching unicellular parasite Trypanosoma brucei, which can proliferate as procyclic form (PCF) in the tsetse fly or as bloodstream form (BSF) in animal hosts, autophagy is robustly triggered by amino acid deficiency but not by glucose depletion. Taking advantage of the clearly defined adenosine triphosphate (ATP) production pathways in T. brucei, we have shown that autophagic activity depends on the levels of cellular ATP production, using either glucose or proline as a carbon source. While autophagosome formation positively correlates with cellular ATP levels; perturbation of ATP production by removing carbon sources or genetic silencing of enzymes involved in ATP generation pathways, also inhibited autophagy. This obligate energy dependence and the lack of glucose starvation-induced autophagy in T. brucei may reflect an adaptation to its specialized, parasitic life style.

Preprototype SAWD subsystem

NASA Technical Reports Server (NTRS)

Nalette, T. A.

1984-01-01

A regenerable, three man preprototype solid amine, water desorbed (SAWD) CO2 removal and concentation subsystem was designed, fabricated, and successfully acceptance tested by Hamilton Standard. The preprototype SAWD incorporates a single solid amine canister to perform the CO2 removal function, an accumulator to provide the CO2 storage and delivery function, and a microprocessor which automatically controls the subsystem sequential operation and performance. The SAWD subsystem was configured to have a CO2 removal and CO2 delivery capability at the rate of 0.12 kg/hr (0.264 lb/hr) over the relative humidity range of 35 to 70%. The controller was developed to provide fully automatic control over the relative humidity range via custom software that was generated specifically for the SAWD subsystem. The preprototype SAWD subsystem demonstrated a total of 281 hours (208) cycles of operation during ten acceptance tests that were conducted over the 3 to 70% relative humidity range. This operation was comprised of 178 hours (128 cycles) in the CO2 overboard mode and 103 hours (80 cycles) in the CO2 reduction mode. The average CO2 removal/delivery rate met or exceeded the design specification rate of 0.12 kg/hr (0.254 lb/hr) for all ten of the acceptance tests.

The Human Subsystem - Definition and Integration

NASA Technical Reports Server (NTRS)

vonBengston, Kristian; Twyford, Evan

2007-01-01

This paper will discuss the use of the human subsystem in development phases of human space flight. Any space mission has clearly defined subsystems, managed by experts attached to these. Clearly defined subsystems and correct use provide easier and more efficient development for each independent subsystem and for the relation between these subsystems. Furthermore, this paper will argue that a defined subsystem related to humans in space has not always been clearly present, and that correct implementation is perhaps missing, based on experience and survey data. Finally, the authors will discuss why the human subsystem has not been fully integrated, why it must be a mandatory part of the programming, a re-definition of the human subsystem, and suggestions of methods to improve the integration of human factors in the development.

Evolution of magnetic disk subsystems

NASA Astrophysics Data System (ADS)

Kaneko, Satoru

1994-06-01

The higher recording density of magnetic disk realized today has brought larger storage capacity per unit and smaller form factors. If the required access performance per MB is constant, the performance of large subsystems has to be several times better. This article describes mainly the technology for improving the performance of the magnetic disk subsystems and the prospects of their future evolution. Also considered are 'crosscall pathing' which makes the data transfer channel more effective, 'disk cache' which improves performance coupling with solid state memory technology, and 'RAID' which improves the availability and integrity of disk subsystems by organizing multiple disk drives in a subsystem. As a result, it is concluded that since the performance of the subsystem is dominated by that of the disk cache, maximation of the performance of the disk cache subsystems is very important.

Power subsystem automation study

NASA Technical Reports Server (NTRS)

Tietz, J. C.; Sewy, D.; Pickering, C.; Sauers, R.

1984-01-01

The purpose of the phase 2 of the power subsystem automation study was to demonstrate the feasibility of using computer software to manage an aspect of the electrical power subsystem on a space station. The state of the art in expert systems software was investigated in this study. This effort resulted in the demonstration of prototype expert system software for managing one aspect of a simulated space station power subsystem.

Mutations in the Atp1p and Atp3p subunits of yeast ATP synthase differentially affect respiration and fermentation in Saccharomyces cerevisiae.

PubMed

Francis, Brian R; White, Karen H; Thorsness, Peter E

2007-04-01

ATP1-111, a suppressor of the slow-growth phenotype of yme1Delta lacking mitochondrial DNA is due to the substitution of phenylalanine for valine at position 111 of the alpha-subunit of mitochondrial ATP synthase (Atp1p in yeast). The suppressing activity of ATP1-111 requires intact beta (Atp2p) and gamma (Atp3p) subunits of mitochondrial ATP synthase, but not the stator stalk subunits b (Atp4p) and OSCP (Atp5p). ATP1-111 and other similarly suppressing mutations in ATP1 and ATP3 increase the growth rate of wild-type strains lacking mitochondrial DNA. These suppressing mutations decrease the growth rate of yeast containing an intact mitochondrial chromosome on media requiring oxidative phosphorylation, but not when grown on fermentable media. Measurement of chronological aging of yeast in culture reveals that ATP1 and ATP3 suppressor alleles in strains that contain mitochondrial DNA are longer lived than the isogenic wild-type strain. In contrast, the chronological life span of yeast cells lacking mitochondrial DNA and containing these mutations is shorter than that of the isogenic wild-type strain. Spore viability of strains bearing ATP1-111 is reduced compared to wild type, although ATP1-111 enhances the survival of spores that lacked mitochondrial DNA.

Subsystem eigenstate thermalization hypothesis

NASA Astrophysics Data System (ADS)

Dymarsky, Anatoly; Lashkari, Nima; Liu, Hong

2018-01-01

Motivated by the qualitative picture of canonical typicality, we propose a refined formulation of the eigenstate thermalization hypothesis (ETH) for chaotic quantum systems. This formulation, which we refer to as subsystem ETH, is in terms of the reduced density matrix of subsystems. This strong form of ETH outlines the set of observables defined within the subsystem for which it guarantees eigenstate thermalization. We discuss the limits when the size of the subsystem is small or comparable to its complement. In the latter case we outline the way to calculate the leading volume-proportional contribution to the von Neumann and Renyi entanglment entropies. Finally, we provide numerical evidence for the proposal in the case of a one-dimensional Ising spin chain.

Development of Testing Station for Prototype Rover Thermal Subsystem

NASA Technical Reports Server (NTRS)

Burlingame, Kaitlin

2010-01-01

In order to successfully and efficiently explore the moon or other planets, a vehicle must be built to assist astronauts as they travel across the surface. One concept created to meet this need is NASA's Space Exploration Vehicle (SEV). The SEV, a small pressurized cabin integrated onto a 12-wheeled chassis, can support two astronauts up to 14 days. Engineers are currently developing the second generation of the SEV, with the goal of being faster, more robust, and able to carry a heavier payload. In order to function properly, the rover must dissipate heat produced during operation and maintain an appropriate temperature profile inside the rover. If these activities do not occur, components of the rover will start to break down, eventually leading to the failure of the rover. On the rover, these requirements are the responsibility of the thermal subsystem. My project for the summer was to design and build a testing station to facilitate the design and testing of the new thermal subsystem. As the rover develops, initial low fidelity parts can be interchanged for the high fidelity parts used on the rover. Based on a schematic of the proposed thermal system, I sized and selected parts for each of the components in the thermal subsystem. For the components in the system that produced heat but had not yet been finalized or fabricated, I used power resistors to model their load patterns. I also selected all of the fittings to put the system together and a mounting platform to support the testing station. Finally, I implemented sensors at various points in the system to measure the temperature, pressure, and flow rate, and a data acquisition system to collect this information. In the future, the information from these sensors will be used to study the behavior of the subsystem under different conditions and select the best part for the rover.

Subsystems component definitions summary program

NASA Technical Reports Server (NTRS)

Scott, A. Don; Thomas, Carolyn C.; Simonsen, Lisa C.; Hall, John B., Jr.

1991-01-01

A computer program, the Subsystems Component Definitions Summary (SUBCOMDEF), was developed to provide a quick and efficient means of summarizing large quantities of subsystems component data in terms of weight, volume, resupply, and power. The program was validated using Space Station Freedom Program Definition Requirements Document data for the internal and external thermal control subsystem. Once all component descriptions, unit weights and volumes, resupply, and power data are input, the user may obtain a summary report of user-specified portions of the subsystem or of the entire subsystem as a whole. Any combination or all of the parameters of wet and dry weight, wet and dry volume, resupply weight and volume, and power may be displayed. The user may vary the resupply period according to individual mission requirements, as well as the number of hours per day power consuming components operate. Uses of this program are not limited only to subsystem component summaries. Any applications that require quick, efficient, and accurate weight, volume, resupply, or power summaries would be well suited to take advantage of SUBCOMDEF's capabilities.

Virtual quantum subsystems.

PubMed

Zanardi, P

2001-08-13

The physical resources available to access and manipulate the degrees of freedom of a quantum system define the set A of operationally relevant observables. The algebraic structure of A selects a preferred tensor product structure, i.e., a partition into subsystems. The notion of compoundness for quantum systems is accordingly relativized. Universal control over virtual subsystems can be achieved by using quantum noncommutative holonomies

Mechanisms of charge transfer in human copper ATPases ATP7A and ATP7B.

PubMed

Tadini-Buoninsegni, Francesco; Smeazzetto, Serena

2017-04-01

ATP7A and ATP7B are Cu + -transporting ATPases of subclass IB and play a fundamental role in intracellular copper homeostasis. ATP7A/B transfer Cu + ions across the membrane from delivery to acceptor proteins without establishing a free Cu + gradient. Transfer of copper across the membrane is coupled to ATP hydrolysis. Current measurements on solid supported membranes (SSM) were performed to investigate the mechanism of copper-related charge transfer across ATP7A and ATP7B. SSM measurements demonstrated that electrogenic copper displacement occurs within ATP7A/B following addition of ATP and formation of the phosphorylated intermediate. Comparison of the time constants for cation displacement in ATP7A/B and sarcoplasmic reticulum Ca 2+ -ATPase is consistent with the slower phosphoenzyme formation in copper ATPases. Moreover, ATP-dependent copper transfer in ATP7A/B is not affected by varying the pH, suggesting that net proton counter-transport may not occur in copper ATPases. Platinum anticancer drugs activate ATP7A/B and are subjected to ATP-dependent vectorial displacement with a mechanism analogous to that of copper. © 2016 IUBMB Life, 69(4):218-225, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Hyperthyroidism stimulates mitochondrial proton leak and ATP turnover in rat hepatocytes but does not change the overall kinetics of substrate oxidation reactions.

PubMed

Harper, M E; Brand, M D

1994-08-01

Thyroid hormones have well-known effects on oxidative phosphorylation, but there is little quantitative information on their important sites of action. We have used top-down elasticity analysis, an extension of metabolic control analysis, to identify the sites of action of thyroid hormones on oxidative phosphorylation in rat hepatocytes. We divided the oxidative phosphorylation system into three blocks of reactions: the substrate oxidation subsystem, the phosphorylating subsystem, and the mitochondrial proton leak subsystem and have identified those blocks of reactions whose kinetics are significantly changed by hyperthyroidism. Our results show significant effects on the kinetics of the proton leak and the phosphorylating subsystems. Quantitative analyses revealed that 43% of the increase in resting respiration rate in hyperthyroid hepatocytes compared with euthyroid hepatocytes was due to differences in the proton leak and 59% was due to differences in the activity of the phosphorylating subsystem. There were no significant effects on the substrate oxidation subsystem. Changes in nonmitochondrial oxygen consumption accounted for -2% of the change in respiration rate. Top-down control analysis revealed that the distribution of control over the rates of mitochondrial oxygen consumption, ATP synthesis and consumption, and proton leak and over mitochondrial membrane potential (delta psi m) was similar in hepatocytes from hyperthyroid and littermate-paired euthyroid controls. The results of this study include the first complete top-down elasticity and control analyses of oxidative phosphorylation in hepatocytes from hyperthyroid rats.

ATP synthase.

PubMed

Junge, Wolfgang; Nelson, Nathan

2015-01-01

Oxygenic photosynthesis is the principal converter of sunlight into chemical energy. Cyanobacteria and plants provide aerobic life with oxygen, food, fuel, fibers, and platform chemicals. Four multisubunit membrane proteins are involved: photosystem I (PSI), photosystem II (PSII), cytochrome b6f (cyt b6f), and ATP synthase (FOF1). ATP synthase is likewise a key enzyme of cell respiration. Over three billion years, the basic machinery of oxygenic photosynthesis and respiration has been perfected to minimize wasteful reactions. The proton-driven ATP synthase is embedded in a proton tight-coupling membrane. It is composed of two rotary motors/generators, FO and F1, which do not slip against each other. The proton-driven FO and the ATP-synthesizing F1 are coupled via elastic torque transmission. Elastic transmission decouples the two motors in kinetic detail but keeps them perfectly coupled in thermodynamic equilibrium and (time-averaged) under steady turnover. Elastic transmission enables operation with different gear ratios in different organisms.

P2X1 receptors localized in lipid rafts mediate ATP motor responses in the human vas deferens longitudinal muscles.

PubMed

Donoso, María Verónica; Norambuena, Andrés; Navarrete, Camilo; Poblete, Inés; Velasco, Alfredo; Huidobro-Toro, Juan Pablo

2014-02-01

To assess the role of the P2X1 receptors (P2X1R) in the longitudinal and circular layers of the human vas deferens, ex vivo-isolated strips or rings were prepared from tissue biopsies to record isometric contractions. To ascertain its membrane distribution, tissue extracts were analyzed by immunoblotting following sucrose gradient ultracentrifugation. ATP, alpha,beta-methylene ATP, or electrical field stimulation elicited robust contractions of the longitudinal layer but not of the circular layer which demonstrated inconsistent responses. Alpha,beta-methylene ATP generated stronger and more robust contractions than ATP. In parallel, prostatic segments of the rat vas deferens were examined. The motor responses in both species were not sustained but decayed within the first minute, showing desensitization to additional applications. Cross-desensitization was established between alpha,beta-methylene ATP or ATP-evoked contractions and electrical field stimulation-induced contractions. Full recovery of the desensitized motor responses required more than 30 min and showed a similar pattern in human and rat tissues. Immunoblot analysis of the human vas deferens extracts revealed a P2X1R oligomer of approximately 200 kDa under nonreducing conditions, whereas dithiothreitol-treated extracts showed a single band of approximately 70 kDa. The P2X1R was identified in ultracentrifugation fractions containing 15%-29% sucrose; the receptor localized in the same fractions as flotillin-1, indicating that it regionalized into smooth muscle lipid rafts. In conclusion, ATP plays a key role in human vas deferens contractile responses of the longitudinal smooth muscle layer, an effect mediated through P2X1Rs.

Contraction of small mesenteric arteries induced by micromolar concentrations of ATP released from caged ATP.

PubMed

Sjöblom-Widfeldt, N; Arner, A; Nilsson, H

1993-01-01

The concentration dependence of ATP-induced contractions in isolated resistance arteries was estimated using photolysis of caged ATP. Rat mesenteric vessels were isolated and mounted for force registration in a small chamber allowing illumination from a xenon-flash lamp. Photolysis of 100 microM caged ATP, which released about 20 microM ATP within a few milliseconds in the vessel, induced a transient contraction with an amplitude approximately 40-50% of the response induced by 10 microM noradrenaline. The responses could neither be induced by the light flash as such nor by caged ATP alone nor by photolysis of caged phosphate. The amplitude of the contractions was dependent on the concentration of caged ATP, and the effective concentration for ATP was estimated to be in the range of 1-10 microM. In contrast, when ATP was introduced by diffusion, about a 100-fold higher concentration was required. Thus photolytic release of ATP minimizes metabolism before its action on receptors and reveals action of ATP in a concentration range consistent with a role of ATP as a transmitter in nervous regulation of the tone of resistance vessels.

Spacelab data management subsystem phase B study

NASA Technical Reports Server (NTRS)

1974-01-01

The Spacelab data management system is described. The data management subsystem (DMS) integrates the avionics equipment into an operational system by providing the computations, logic, signal flow, and interfaces needed to effectively command, control, monitor, and check out the experiment and subsystem hardware. Also, the DMS collects/retrieves experiment data and other information by recording and by command of the data relay link to ground. The major elements of the DMS are the computer subsystem, data acquisition and distribution subsystem, controls and display subsystem, onboard checkout subsystem, and software. The results of the DMS portion of the Spacelab Phase B Concept Definition Study are analyzed.

Hierarchical Modeling and Robust Synthesis for the Preliminary Design of Large Scale Complex Systems

NASA Technical Reports Server (NTRS)

Koch, Patrick N.

1997-01-01

Large-scale complex systems are characterized by multiple interacting subsystems and the analysis of multiple disciplines. The design and development of such systems inevitably requires the resolution of multiple conflicting objectives. The size of complex systems, however, prohibits the development of comprehensive system models, and thus these systems must be partitioned into their constituent parts. Because simultaneous solution of individual subsystem models is often not manageable iteration is inevitable and often excessive. In this dissertation these issues are addressed through the development of a method for hierarchical robust preliminary design exploration to facilitate concurrent system and subsystem design exploration, for the concurrent generation of robust system and subsystem specifications for the preliminary design of multi-level, multi-objective, large-scale complex systems. This method is developed through the integration and expansion of current design techniques: Hierarchical partitioning and modeling techniques for partitioning large-scale complex systems into more tractable parts, and allowing integration of subproblems for system synthesis; Statistical experimentation and approximation techniques for increasing both the efficiency and the comprehensiveness of preliminary design exploration; and Noise modeling techniques for implementing robust preliminary design when approximate models are employed. Hierarchical partitioning and modeling techniques including intermediate responses, linking variables, and compatibility constraints are incorporated within a hierarchical compromise decision support problem formulation for synthesizing subproblem solutions for a partitioned system. Experimentation and approximation techniques are employed for concurrent investigations and modeling of partitioned subproblems. A modified composite experiment is introduced for fitting better predictive models across the ranges of the factors, and an approach for

Periodic subsystem density-functional theory

NASA Astrophysics Data System (ADS)

Genova, Alessandro; Ceresoli, Davide; Pavanello, Michele

2014-11-01

By partitioning the electron density into subsystem contributions, the Frozen Density Embedding (FDE) formulation of subsystem Density Functional Theory (DFT) has recently emerged as a powerful tool for reducing the computational scaling of Kohn-Sham DFT. To date, however, FDE has been employed to molecular systems only. Periodic systems, such as metals, semiconductors, and other crystalline solids have been outside the applicability of FDE, mostly because of the lack of a periodic FDE implementation. To fill this gap, in this work we aim at extending FDE to treat subsystems of molecular and periodic character. This goal is achieved by a dual approach. On one side, the development of a theoretical framework for periodic subsystem DFT. On the other, the realization of the method into a parallel computer code. We find that periodic FDE is capable of reproducing total electron densities and (to a lesser extent) also interaction energies of molecular systems weakly interacting with metallic surfaces. In the pilot calculations considered, we find that FDE fails in those cases where there is appreciable density overlap between the subsystems. Conversely, we find FDE to be in semiquantitative agreement with Kohn-Sham DFT when the inter-subsystem density overlap is low. We also conclude that to make FDE a suitable method for describing molecular adsorption at surfaces, kinetic energy density functionals that go beyond the GGA level must be employed.

Periodic subsystem density-functional theory.

PubMed

Genova, Alessandro; Ceresoli, Davide; Pavanello, Michele

2014-11-07

By partitioning the electron density into subsystem contributions, the Frozen Density Embedding (FDE) formulation of subsystem Density Functional Theory (DFT) has recently emerged as a powerful tool for reducing the computational scaling of Kohn-Sham DFT. To date, however, FDE has been employed to molecular systems only. Periodic systems, such as metals, semiconductors, and other crystalline solids have been outside the applicability of FDE, mostly because of the lack of a periodic FDE implementation. To fill this gap, in this work we aim at extending FDE to treat subsystems of molecular and periodic character. This goal is achieved by a dual approach. On one side, the development of a theoretical framework for periodic subsystem DFT. On the other, the realization of the method into a parallel computer code. We find that periodic FDE is capable of reproducing total electron densities and (to a lesser extent) also interaction energies of molecular systems weakly interacting with metallic surfaces. In the pilot calculations considered, we find that FDE fails in those cases where there is appreciable density overlap between the subsystems. Conversely, we find FDE to be in semiquantitative agreement with Kohn-Sham DFT when the inter-subsystem density overlap is low. We also conclude that to make FDE a suitable method for describing molecular adsorption at surfaces, kinetic energy density functionals that go beyond the GGA level must be employed.

Ballast water compliance monitoring: A new application for ATP

NASA Astrophysics Data System (ADS)

Lo Curto, A.; Stehouwer, P.; Gianoli, C.; Schneider, G.; Raymond, M.; Bonamin, V.

2018-03-01

The coming into force of the USCG ballast water regulations and the IMO ballast water management convention resulted in the development of several technologies approved for the treatment of ballast water. To ensure compliance of these technologies, the development of rapid and robust analysis methods was necessary. In collaboration with the SGS Group (Switzerland) and LuminUltra (Canada), Aqua-tools (France) has developed an innovative Ballast Water Treatment Monitoring (BWTM) kit for rapid onboard testing. The affordable kit provides results in less than 1 h, is easy to use and durable ensuring that the ballast water treatment system on the ship is fully compliant with the discharge standards upon arrival in port. The core of this method is a combination of high-quality reagents (lysis solution and ATP 2G Luminase™ enzyme) not inhibited by salinity and a patented fast homogenizing method for ATP extraction developed for a higher ATP recovery from zooplankton and phytoplankton. Compared to traditional analysis methods, the BWTM Kit provides fast and accurate results for all three fractions of microorganisms (≥ 50 μm, ≥ 10 ÷ < 50 μm and bacteria). Preliminary tests carried out in cooperation with SGS showed that the proposed method was able to detect onboard the efficiency of the treatment systems used. Compliance limits were established for all size fractions and a correlation between the standard methods (microscopy, plate count, MPN) and ATP was evaluated. The BWTM kit can provide a fast indication of compliance or gross exceedance. The rare borderline cases, when encountered, of course require additional confirmation.

Electrochemical carbon dioxide concentrator subsystem development

NASA Technical Reports Server (NTRS)

Heppner, D. B.; Dahlausen, M. J.; Schubert, F. H.

1983-01-01

The fabrication of a one-person Electrochemical Depolarized Carbon Dioxide Concentrator subsystem incorporating advanced electrochemical, mechanical, and control and monitor instrumentation concepts is discussed. This subsystem included an advanced liquid cooled unitized core composite cell module and integrated electromechanical components. Over 1800 hours with the subsystem with removal efficiencies between 90%. and 100%; endurance tests with a Fluid Control Assembly which integrates 11 gas handling components of the subsystem; and endurance testing of a coolant control assembly which integrates a coolant pump, diverter valve and a liquid accumulator were completed.

Inhibition of plasma membrane Ca(2+)-ATPase by CrATP. LaATP but not CrATP stabilizes the Ca(2+)-occluded state.

PubMed

Moreira, Otacilio C; Rios, Priscila F; Barrabin, Hector

2005-07-15

The bidentate complex of ATP with Cr(3+), CrATP, is a nucleotide analog that is known to inhibit the sarcoplasmic reticulum Ca(2+)-ATPase and the Na(+),K(+)-ATPase, so that these enzymes accumulate in a conformation with the transported ion (Ca(2+) and Na(+), respectively) occluded from the medium. Here, it is shown that CrATP is also an effective and irreversible inhibitor of the plasma membrane Ca(2+)-ATPase. The complex inhibited with similar efficiency the Ca(2+)-dependent ATPase and the phosphatase activities as well as the enzyme phosphorylation by ATP. The inhibition proceeded slowly (T(1/2)=30 min at 37 degrees C) with a K(i)=28+/-9 microM. The inclusion of ATP, ADP or AMPPNP in the inhibition medium effectively protected the enzyme against the inhibition, whereas ITP, which is not a PMCA substrate, did not. The rate of inhibition was strongly dependent on the presence of Mg(2+) but unaltered when Ca(2+) was replaced by EGTA. In spite of the similarities with the inhibition of other P-ATPases, no apparent Ca(2+) occlusion was detected concurrent with the inhibition by CrATP. In contrast, inhibition by the complex of La(3+) with ATP, LaATP, induced the accumulation of phosphoenzyme with a simultaneous occlusion of Ca(2+) at a ratio close to 1.5 mol/mol of phosphoenzyme. The results suggest that the transport of Ca(2+) promoted by the plasma membrane Ca(2+)-ATPase goes through an enzymatic phospho-intermediate that maintains Ca(2+) ions occluded from the media. This intermediate is stabilized by LaATP but not by CrATP.

Constrained subsystem density functional theory.

PubMed

Ramos, Pablo; Pavanello, Michele

2016-08-03

Constrained Subsystem Density Functional Theory (CSDFT) allows to compute diabatic states for charge transfer reactions using the machinery of the constrained DFT method, and at the same time is able to embed such diabatic states in a molecular environment via a subsystem DFT scheme. The CSDFT acronym is chosen to reflect the fact that on top of the subsystem DFT approach, a constraining potential is applied to each subsystem. We show that CSDFT can successfully tackle systems as complex as single stranded DNA complete of its backbone, and generate diabatic states as exotic as a hole localized on a phosphate group as well as on the nucleobases. CSDFT will be useful to investigators needing to evaluate the environmental effect on charge transfer couplings for systems in condensed phase environments.

Spacecraft Design Thermal Control Subsystem

NASA Technical Reports Server (NTRS)

Miyake, Robert N.

2003-01-01

This slide presentation reviews the functions of the thermal control subsystem engineers in the design of spacecraft. The goal of the thermal control subsystem that will be used in a spacecraft is to maintain the temperature of all spacecraft components, subsystems, and all the flight systems within specified limits for all flight modes from launch to the end of the mission. For most thermal control subsystems the mass, power and control and sensing systems must be kept below 10% of the total flight system resources. This means that the thermal control engineer is involved in all other flight systems designs. The two concepts of thermal control, passive and active are reviewed and the use of thermal modeling tools are explained. The testing of the thermal control is also reviewed.

Technology advancement of an oxygen generation subsystem

NASA Technical Reports Server (NTRS)

Lee, M. K.; Burke, K. A.; Schubert, F. H.; Wynveen, R. A.

1979-01-01

An oxygen generation subsystem based on water electrolysis was developed and tested to further advance the concept and technology of the spacecraft air revitalization system. Emphasis was placed on demonstrating the subsystem integration concept and hardware maturity at a subsystem level. The integration concept of the air revitalization system was found to be feasible. Hardware and technology of the oxygen generation subsystem was demonstrated to be close to the preprototype level. Continued development of the oxygen generation technology is recommended to further reduce the total weight penalties of the oxygen generation subsystem through optimization.

Imaging Adenosine Triphosphate (ATP)

PubMed Central

Rajendran, Megha; Dane, Eric; Conley, Jason; Tantama, Mathew

2016-01-01

Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provides valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific for ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies that are available to visualize ATP in living cells and identify areas where new tools and approaches are needed to expand our capabilities. PMID:27638696

Imaging Adenosine Triphosphate (ATP).

PubMed

Rajendran, Megha; Dane, Eric; Conley, Jason; Tantama, Mathew

2016-08-01

Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provide valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities. © 2016 Marine Biological Laboratory.

Conformational dynamics of ATP/Mg:ATP in motor proteins via data mining and molecular simulation.

PubMed

Bojovschi, A; Liu, Ming S; Sadus, Richard J

2012-08-21

The conformational diversity of ATP/Mg:ATP in motor proteins was investigated using molecular dynamics and data mining. Adenosine triphosphate (ATP) conformations were found to be constrained mostly by inter cavity motifs in the motor proteins. It is demonstrated that ATP favors extended conformations in the tight pockets of motor proteins such as F(1)-ATPase and actin whereas compact structures are favored in motor proteins such as RNA polymerase and DNA helicase. The incorporation of Mg(2+) leads to increased flexibility of ATP molecules. The differences in the conformational dynamics of ATP/Mg:ATP in various motor proteins was quantified by the radius of gyration. The relationship between the simulation results and those obtained by data mining of motor proteins available in the protein data bank is analyzed. The data mining analysis of motor proteins supports the conformational diversity of the phosphate group of ATP obtained computationally.

Periodic subsystem density-functional theory

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

Genova, Alessandro; Pavanello, Michele, E-mail: m.pavanello@rutgers.edu; Ceresoli, Davide

2014-11-07

By partitioning the electron density into subsystem contributions, the Frozen Density Embedding (FDE) formulation of subsystem Density Functional Theory (DFT) has recently emerged as a powerful tool for reducing the computational scaling of Kohn–Sham DFT. To date, however, FDE has been employed to molecular systems only. Periodic systems, such as metals, semiconductors, and other crystalline solids have been outside the applicability of FDE, mostly because of the lack of a periodic FDE implementation. To fill this gap, in this work we aim at extending FDE to treat subsystems of molecular and periodic character. This goal is achieved by a dualmore » approach. On one side, the development of a theoretical framework for periodic subsystem DFT. On the other, the realization of the method into a parallel computer code. We find that periodic FDE is capable of reproducing total electron densities and (to a lesser extent) also interaction energies of molecular systems weakly interacting with metallic surfaces. In the pilot calculations considered, we find that FDE fails in those cases where there is appreciable density overlap between the subsystems. Conversely, we find FDE to be in semiquantitative agreement with Kohn–Sham DFT when the inter-subsystem density overlap is low. We also conclude that to make FDE a suitable method for describing molecular adsorption at surfaces, kinetic energy density functionals that go beyond the GGA level must be employed.« less

Interlaboratory comparison of red-cell ATP, 2,3-diphosphoglycerate and haemolysis measurements.

PubMed

Hess, J R; Kagen, L R; van der Meer, P F; Simon, T; Cardigan, R; Greenwalt, T J; AuBuchon, J P; Brand, A; Lockwood, W; Zanella, A; Adamson, J; Snyder, E; Taylor, H L; Moroff, G; Hogman, C

2005-07-01

Red blood cell (RBC) storage systems are licensed based on their ability to prevent haemolysis and maintain RBC 24-h in vivo recovery. Preclinical testing includes measurement of RBC ATP as a surrogate for recovery, 2,3-diphosphoglycerate (DPG) as a surrogate for oxygen affinity, and free haemoglobin, which is indicative of red cell lysis. The reproducibility of RBC ATP, DPG and haemolysis measurements between centres was investigated. Five, 4-day-old leucoreduced AS-1 RBC units were pooled, aliquotted and shipped on ice to 14 laboratories in the USA and European Union (EU). Each laboratory was to sample the bag twice on day 7 and measure RBC ATP, DPG, haemoglobin and haemolysis levels in triplicate on each sample. The variability of results was assessed by using coefficients of variation (CV) and analysis of variance. Measurements were highly reproducible at the individual sites. Between sites, the CV was 16% for ATP, 35% for DPG, 2% for total haemoglobin and 54% for haemolysis. For ATP and total haemoglobin, 94 and 80% of the variance in measurements was contributed by differences between sites, and more than 80% of the variance for DPG and haemolysis measurements came from markedly discordant results from three sites and one site, respectively. In descending order, mathematical errors, unvalidated analytical methods, a lack of shared standards and fluid handling errors contributed to the variability in measurements from different sites. While the methods used by laboratories engaged in RBC storage system clinical trials demonstrated good precision, differences in results between laboratories may hinder comparative analysis. Efforts to improve performance should focus on developing robust methods, especially for measuring RBC ATP.

Discovery of Imidazo[1,2-a]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis.

PubMed

Tantry, Subramanyam J; Markad, Shankar D; Shinde, Vikas; Bhat, Jyothi; Balakrishnan, Gayathri; Gupta, Amit K; Ambady, Anisha; Raichurkar, Anandkumar; Kedari, Chaitanyakumar; Sharma, Sreevalli; Mudugal, Naina V; Narayan, Ashwini; Naveen Kumar, C N; Nanduri, Robert; Bharath, Sowmya; Reddy, Jitendar; Panduga, Vijender; Prabhakar, K R; Kandaswamy, Karthikeyan; Saralaya, Ramanatha; Kaur, Parvinder; Dinesh, Neela; Guptha, Supreeth; Rich, Kirsty; Murray, David; Plant, Helen; Preston, Marian; Ashton, Helen; Plant, Darren; Walsh, Jarrod; Alcock, Peter; Naylor, Kathryn; Collier, Matthew; Whiteaker, James; McLaughlin, Robert E; Mallya, Meenakshi; Panda, Manoranjan; Rudrapatna, Suresh; Ramachandran, Vasanthi; Shandil, Radha; Sambandamurthy, Vasan K; Mdluli, Khisi; Cooper, Christopher B; Rubin, Harvey; Yano, Takahiro; Iyer, Pravin; Narayanan, Shridhar; Kavanagh, Stefan; Mukherjee, Kakoli; Balasubramanian, V; Hosagrahara, Vinayak P; Solapure, Suresh; Ravishankar, Sudha; Hameed P, Shahul

2017-02-23

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection.

Lightning testing at the subsystem level

NASA Technical Reports Server (NTRS)

Luteran, Frank

1991-01-01

Testing at the subsystem or black box level for lightning hardness is required if system hardness is to be assured at the system level. The often applied philosophy of lighting testing only at the system level leads to extensive end of the line design changes which result in excessive costs and time delays. In order to perform testing at the subsystem level two important factors must be defined to make the testing simulation meaningful. The first factor is the definition of the test stimulus appropriate to the subsystem level. Application of system level stimulations to the subsystem level usually leads to significant overdesign of the subsystem which is not necessary and may impair normal subsystem performance. The second factor is the availability of test equipment needed to provide the subsystem level lightning stimulation. Equipment for testing at this level should be portable or at least movable to enable efficient testing in a design laboratory environment. Large fixed test installations for system level tests are not readily available for use by the design engineers at the subsystem level and usually require special operating skills. The two factors, stimulation level and test equipment availability, must be evaluated together in order to produce a practical, workable test standard. The neglect or subordination of either factor will guarantee failure in generating the standard. It is not unusual to hear that test standards or specifications are waived because a specified stimulation level cannot be accomplished by in-house or independent test facilities. Determination of subsystem lightning simulation level requires a knowledge and evaluation of field coupling modes, peak and median levels of voltages and currents, bandwidths, and repetition rates. Practical limitations on test systems may require tradeoffs in lightning stimulation parameters in order to build practical test equipment. Peak power levels that can be generated at specified bandwidths with

Waveform stimulus subsystem: An advanced technology multifunction subsystem on a card

NASA Astrophysics Data System (ADS)

Pritchard, David J.

The F-15 TISS ATE (automatic test equipment) requires subsystem-on-a-card technology to achieve the required functionality within the space constraints. The waveform stimulus subsystem (WSS), an example of this advanced technology, is considered. The WSS circuit card consists of two 40-MHz pulse generators and an 80-MHz aribtrary waveform generator. Each generator is independently programmed and is available simultaneously to the user. The implementation of this highly integrated malfunction-detection system on a card is described, and the benefits to performance and maintainability are highlighted.

Subsystem design in aircraft power distribution systems using optimization

NASA Astrophysics Data System (ADS)

Chandrasekaran, Sriram

2000-10-01

The research reported in this dissertation focuses on the development of optimization tools for the design of subsystems in a modern aircraft power distribution system. The baseline power distribution system is built around a 270V DC bus. One of the distinguishing features of this power distribution system is the presence of regenerative power from the electrically driven flight control actuators and structurally integrated smart actuators back to the DC bus. The key electrical components of the power distribution system are bidirectional switching power converters, which convert, control and condition electrical power between the sources and the loads. The dissertation is divided into three parts. Part I deals with the formulation of an optimization problem for a sample system consisting of a regulated DC-DC buck converter preceded by an input filter. The individual subsystems are optimized first followed by the integrated optimization of the sample system. It is shown that the integrated optimization provides better results than that obtained by integrating the individually optimized systems. Part II presents a detailed study of piezoelectric actuators. This study includes modeling, optimization of the drive amplifier and the development of a current control law for piezoelectric actuators coupled to a simple mechanical structure. Linear and nonlinear methods to study subsystem interaction and stability are studied in Part III. A multivariable impedance ratio criterion applicable to three phase systems is proposed. Bifurcation methods are used to obtain global stability characteristics of interconnected systems. The application of a nonlinear design methodology, widely used in power systems, to incrementally improve the robustness of a system to Hopf bifurcation instability is discussed.

Caged ATP - an internal calibration method for ATP bioluminescence assays.

PubMed

Calvert, R M; Hopkins, H C; Reilly, M J; Forsythe, S J

2000-03-01

ATP bioluminescence, based on the firefly luciferase system, is used for the rapid determination of hygienic practices in the food industry. This study has demonstrated the use of caged ATP as an internal ATP standard and quantified the effects of industrial cleansing solutions, alcoholic beverages and pH on firefly luciferase activity. The light signal was quenched 6-47% by five cleansing solutions at standard working concentrations. Ethanol at 1% (v/v) inhibited bioluminescence by 15% (w/v) whereas concentrations above 4% enhanced the light output. The light signal was quenched by 20-25% at pH values below pH 4 and above pH 10.

Space power subsystem automation technology

NASA Technical Reports Server (NTRS)

Graves, J. R. (Compiler)

1982-01-01

The technology issues involved in power subsystem automation and the reasonable objectives to be sought in such a program were discussed. The complexities, uncertainties, and alternatives of power subsystem automation, along with the advantages from both an economic and a technological perspective were considered. Whereas most spacecraft power subsystems now use certain automated functions, the idea of complete autonomy for long periods of time is almost inconceivable. Thus, it seems prudent that the technology program for power subsystem automation be based upon a growth scenario which should provide a structured framework of deliberate steps to enable the evolution of space power subsystems from the current practice of limited autonomy to a greater use of automation with each step being justified on a cost/benefit basis. Each accomplishment should move toward the objectives of decreased requirement for ground control, increased system reliability through onboard management, and ultimately lower energy cost through longer life systems that require fewer resources to operate and maintain. This approach seems well-suited to the evolution of more sophisticated algorithms and eventually perhaps even the use of some sort of artificial intelligence. Multi-hundred kilowatt systems of the future will probably require an advanced level of autonomy if they are to be affordable and manageable.

Target-protecting dumbbell molecular probe against exonucleases digestion for sensitive detection of ATP and streptavidin.

PubMed

Chen, Jinyang; Liu, Yucheng; Ji, Xinghu; He, Zhike

2016-09-15

In this work, a versatile dumbbell molecular (DM) probe was designed and employed in the sensitively homogeneous bioassay. In the presence of target molecule, the DM probe was protected from the digestion of exonucleases. Subsequently, the protected DM probe specifically bound to the intercalation dye and resulted in obvious fluorescence signal which was used to determine the target molecule in return. This design allows specific and versatile detection of diverse targets with easy operation and no sophisticated fluorescence labeling. Integrating the idea of target-protecting DM probe with adenosine triphosphate (ATP) involved ligation reaction, the DM probe with 5'-end phosphorylation was successfully constructed for ATP detection, and the limitation of detection was found to be 4.8 pM. Thanks to its excellent selectivity and sensitivity, this sensing strategy was used to detect ATP spiked in human serum as well as cellular ATP. Moreover, the proposed strategy was also applied in the visual detection of ATP in droplet-based microfluidic platform with satisfactory results. Similarly, combining the principle of target-protecting DM probe with streptavidin (SA)-biotin interaction, the DM probe with 3'-end biotinylation was developed for selective and sensitive SA determination, which demonstrated the robustness and versatility of this design. Copyright © 2016 Elsevier B.V. All rights reserved.

Engineering model 8-cm thruster subsystem

NASA Technical Reports Server (NTRS)

Herron, B. G.; Hyman, J.; Hopper, D. J.; Williamson, W. S.; Dulgeroff, C. R.; Collett, C. R.

1978-01-01

An Engineering Model (EM) 8 cm Ion Thruster Propulsion Subsystem was developed for operation at a thrust level 5 mN (1.1 mlb) at a specific impulse 1 sub sp = 2667 sec with a total system input power P sub in = 165 W. The system dry mass is 15 kg with a mercury-propellant-reservoir capacity of 8.75 kg permitting uninterrupted operation for about 12,500 hr. The subsystem can be started from a dormant condition in a time less than or equal to 15 min. The thruster has a design lifetime of 20,000 hr with 10,000 startup cycles. A gimbal unit is included to provide a thrust vector deflection capability of + or - 10 degrees in any direction from the zero position. The EM subsystem development program included thruster optimization, power-supply circuit optimization and flight packaging, subsystem integration, and subsystem acceptance testing including a cyclic test of the total propulsion package.

Plant Development, Auxin, and the Subsystem Incompleteness Theorem

PubMed Central

Niklas, Karl J.; Kutschera, Ulrich

2012-01-01

Plant morphogenesis (the process whereby form develops) requires signal cross-talking among all levels of organization to coordinate the operation of metabolic and genomic subsystems operating in a larger network of subsystems. Each subsystem can be rendered as a logic circuit supervising the operation of one or more signal-activated system. This approach simplifies complex morphogenetic phenomena and allows for their aggregation into diagrams of progressively larger networks. This technique is illustrated here by rendering two logic circuits and signal-activated subsystems, one for auxin (IAA) polar/lateral intercellular transport and another for IAA-mediated cell wall loosening. For each of these phenomena, a circuit/subsystem diagram highlights missing components (either in the logic circuit or in the subsystem it supervises) that must be identified experimentally if each of these basic plant phenomena is to be fully understood. We also illustrate the “subsystem incompleteness theorem,” which states that no subsystem is operationally self-sufficient. Indeed, a whole-organism perspective is required to understand even the most simple morphogenetic process, because, when isolated, every biological signal-activated subsystem is morphogenetically ineffective. PMID:22645582

Protection of ATP-depleted cells by impermeant strychnine derivatives: implications for glycine cytoprotection.

PubMed

Dong, Z; Venkatachalam, M A; Weinberg, J M; Saikumar, P; Patel, Y

2001-03-01

Glycine and structurally related amino acids with activities at chloride channel receptors in the central nervous system also have robust protective effects against cell injury by ATP depletion. The glycine receptor antagonist strychnine shares this protective activity. An essential step toward identification of the molecular targets for these compounds is to determine whether they protect cells through interactions with intracellular targets or with molecules on the outer surface of plasma membranes. Here we report cytoprotection by a cell-impermeant derivative of strychnine. A strychnine-fluorescein conjugate (SF) was synthesized, and impermeability of plasma membranes to this compound was verified by fluorescence confocal microscopy. In an injury model of Madin-Darby canine kidney cells, ATP depletion led to lactate dehydrogenase release. SF prevented lactate dehydrogenase leakage without ameliorating ATP depletion. This was accompanied by preservation of cellular ultrastructure and exclusion of vital dyes. SF protection was also shown for ATP-depleted rat hepatocytes. On the other hand, when a key structural motif in the active site of strychnine was chemically blocked, the SF lost its protective effect, establishing strychnine-related specificity for SF protection. Cytoprotective effects of the cell-impermeant strychnine derivative provide compelling evidence suggesting that molecular targets on the outer surface of plasma membranes may mediate cytoprotection by strychnine and glycine.

Power subsystem automation study

NASA Technical Reports Server (NTRS)

Imamura, M. S.; Moser, R. L.; Veatch, M.

1983-01-01

Generic power-system elements and their potential faults are identified. Automation functions and their resulting benefits are defined and automation functions between power subsystem, central spacecraft computer, and ground flight-support personnel are partitioned. All automation activities were categorized as data handling, monitoring, routine control, fault handling, planning and operations, or anomaly handling. Incorporation of all these classes of tasks, except for anomaly handling, in power subsystem hardware and software was concluded to be mandatory to meet the design and operational requirements of the space station. The key drivers are long mission lifetime, modular growth, high-performance flexibility, a need to accommodate different electrical user-load equipment, onorbit assembly/maintenance/servicing, and potentially large number of power subsystem components. A significant effort in algorithm development and validation is essential in meeting the 1987 technology readiness date for the space station.

The Space Station air revitalization subsystem design concept

NASA Technical Reports Server (NTRS)

Ray, C. D.; Ogle, K. Y.; Tipps, R. W.; Carrasquillo, R. L.; Wieland, P.

1987-01-01

The current status of the Space Station (SS) Environmental Control and Life Support System (ECLSS) Air Revitalization Subsystem (ARS) design is outlined. ARS performance requirements are provided, along with subsystem options for each ARS function and selected evaluations of the relative merits of each subsystem. Detailed computer models that have been developed to analyze individual subsystem performance capabilities are also discussed. A summary of ARS subsystem level testing planned and completed by NASA Marshall Space Flight Center (MSFC) is given.

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

PubMed Central

Suszynski, T.M.; Wildey, G.M.; Falde, E.J.; Cline, G.W.; Maynard, K. Stewart; Ko, N.; Sotiris, J.; Naji, A.; Hering, B.J.; Papas, K.K.

2009-01-01

Real-time, accurate assessment of islet viability is critical for avoiding transplantation of nontherapeutic preparations. Measurements of the intracellular ADP/ATP ratio have been recently proposed as useful prospective estimates of islet cell viability and potency. However, dead cells may be rapidly depleted of both ATP and ADP, which would render the ratio incapable of accounting for dead cells. Since the DNA of dead cells is expected to remain stable over prolonged periods of time (days), we hypothesized that use of the ATP/DNA ratio would take into account dead cells and may be a better indicator of islet cell viability than the ADP/ATP ratio. We tested this hypothesis using mixtures of healthy and lethally heat-treated (HT) rat insulinoma cells and human islets. Measurements of ATP/DNA and ADP/ATP from the known mixtures of healthy and HT cells and islets were used to evaluate how well these parameters correlated with viability. The results indicated that ATP and ADP were rapidly (within 1 hour) depleted in HT cells. The fraction of HT cells in a mixture correlated linearly with the ATP/DNA ratio, whereas the ADP/ADP ratio was highly scattered, remaining effectively unchanged. Despite similar limitations in both ADP/ADP and ATP/DNA ratios, in that ATP levels may fluctuate significantly and reversibly with metabolic stress, the results indicated that ATP/DNA was a better measure of islet viability than the ADP/ATP ratio. PMID:18374063

Solar electric propulsion thrust subsystem development

NASA Technical Reports Server (NTRS)

Masek, T. D.

1973-01-01

The Solar Electric Propulsion System developed under this program was designed to demonstrate all the thrust subsystem functions needed on an unmanned planetary vehicle. The demonstration included operation of the basic elements, power matching input and output voltage regulation, three-axis thrust vector control, subsystem automatic control including failure detection and correction capability (using a PDP-11 computer), operation of critical elements in thermal-vacuum-, zero-gravity-type propellant storage, and data outputs from all subsystem elements. The subsystem elements, functions, unique features, and test setup are described. General features and capabilities of the test-support data system are also presented. The test program culminated in a 1500-h computer-controlled, system-functional demonstration. This included simultaneous operation of two thruster/power conditioner sets. The results of this testing phase satisfied all the program goals.

Contribution of extracellular ATP on the cell-surface F1F0-ATP synthase-mediated intracellular triacylglycerol accumulation.

PubMed

Kita, Toshiyuki; Arakaki, Naokatu

2015-01-01

Cell-surface F1F0-ATP synthase was involved in the cell signaling mediating various biological functions. Recently, we found that cell-surface F1F0-ATP synthase plays a role on intracellular triacylglycerol accumulation in adipocytes, and yet, the underlying mechanisms remained largely unknown. In this study, we investigated the role of extracellular ATP on the intracellular triacylglycerol accumulation. We demonstrated that significant amounts of ATP were produced extracellularly by cultured 3T3-L1 adipocytes and that the antibodies against α and β subunits of F1F0-ATP synthase inhibited the extracellular ATP production. Piceatannol, a F1F0-ATP synthase inhibitor, and apyrase, an enzyme which degrades extracellular ATP, suppressed triacylglycerol accumulation. The selective P2Y1 receptor antagonist MRS2500 significantly inhibited triacylglycerol accumulation, whereas the selective P2X receptor antagonist NF279 has less effect. The present results indicate that cell-surface F1F0-ATP synthase on adipocytes is functional in extracellular ATP production and that the extracellular ATP produced contributes, at least in part, to the cell-surface F1F0-ATP synthase-mediated intracellular triacylglycerol accumulation in adipocytes through P2Y1 receptor.

System integration of marketable subsystems

NASA Technical Reports Server (NTRS)

1978-01-01

These monthly reports, covering the period February 1978 through June 1978, describe the progress made in the major areas of the program. The areas covered are: systems integration of marketable subsystems; development, design, and building of site data acquisition subsystems; development and operation of the central data processing system; operation of the MSFC Solar Test Facility; and systems analysis.

ATP analogues at a glance.

PubMed

Bagshaw, C

2001-02-01

ATP has long been known to play a central role in the energetics of cells both in transduction mechanisms and in metabolic pathways, and is involved in regulation of enzyme, channel and receptor activities. Numerous ATP analogues have been synthesised to probe the role of ATP in biosystems (Yount, 1975; Jameson and Eccleston, 1997; Bagshaw, 1998). In general, two contrasting strategies are employed. Modifications may be introduced deliberately to change the properties of ATP (e.g. making it non-hydrolysable) so as to perturb the chemical steps involved in its action. Typically these involve modification of the phosphate chain. Alternatively, derivatives (e.g. fluorescent probes) are designed to report on the action of ATP but have a minimal effect on its properties. ATP-utilising systems vary enormously in their specificity; so what acts as a good analogue in one case may be very poor in another. The accompanying poster shows a representative selection of derivatives that have been synthesised and summarises their key properties.

Optogenetic control of ATP release

NASA Astrophysics Data System (ADS)

Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

2013-03-01

Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

Erythrocyte haemolysate interacts with ATP-Fe to form a complex containing iron, ATP and 13 800 MW polypeptide.

PubMed

Weaver, J; Zhan, H; Pollack, S

1993-01-01

Iron first entering the reticulocyte is bound to ATP in the low MW cytosolic pool; some is also 'loosely bound' to haemoglobin, coeluting with haemoglobin from a molecular sieve column though not incorporated into haem. When haemolysate is mixed with ATP-Fe in vitro a similar high MW iron-containing complex is formed: the ATP-Fe interacts with a non-haemoglobin constituent of the haemolysate to form a high MW ATP-Fe complex in which the ratio of ATP:Fe (originally 6:1) is reversed, so that the complex contains more iron than ATP. The high MW ATP-Fe complex is formed even when ATP is in 150-fold molar excess and is formed without detectable hydrolysis of the ATP. The activity of haemolysate in forming the high MW ATP-Fe complex is not diminished by dialysis; all of the activity is recovered in the haemoglobin-containing fraction obtained from an Ultrogel AcA 44 column. The activity does not derive from haemoglobin since 85% of the activity is removed when haemoglobin is purified from haemolysate with DEAE-Sephadex. The chelatable iron pool of the cell probably includes both the high MW ATP-Fe complex and low MW ATP-Fe. Shunting of ATP-Fe to a high MW aggregate reduces the amount of iron present in the highly reactive low MW form and thus probably serves to limit the formation of cell damaging radicals.

Stepping-Motion Motor-Control Subsystem For Testing Bearings

NASA Technical Reports Server (NTRS)

Powers, Charles E.

1992-01-01

Control subsystem closed-loop angular-position-control system causing motor and bearing under test to undergo any of variety of continuous or stepping motions. Also used to test bearing-and-motor assemblies, motors, angular-position sensors including rotating shafts, and like. Monitoring subsystem gathers data used to evaluate performance of bearing or other article under test. Monitoring subsystem described in article, "Monitoring Subsystem For Testing Bearings" (GSC-13432).

ATP Maintenance via Two Types of ATP Regulators Mitigates Pathological Phenotypes in Mouse Models of Parkinson's Disease.

PubMed

Nakano, Masaki; Imamura, Hiromi; Sasaoka, Norio; Yamamoto, Masamichi; Uemura, Norihito; Shudo, Toshiyuki; Fuchigami, Tomohiro; Takahashi, Ryosuke; Kakizuka, Akira

2017-08-01

Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors) are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels. Subsequently, we show the neuroprotective efficacies of KUSs, esculetin, and GSK4716 (an ERRγ agonist) against cell death in Parkinson's disease models. In the surviving neurons, ATP levels and expression levels of α-synuclein and CHOP (an ER stress-mediated cell death executor) were all rectified. We propose that maintenance of ATP levels, by inhibiting ATP consumption or enhancing ATP production, or both, would be a promising therapeutic strategy for Parkinson's disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

ATP Dependence of Na+/H+ Exchange

PubMed Central

Demaurex, Nicolas; Romanek, Robert R.; Orlowski, John; Grinstein, Sergio

1997-01-01

We studied the ATP dependence of NHE-1, the ubiquitous isoform of the Na+/H+ antiporter, using the whole-cell configuration of the patch-clamp technique to apply nucleotides intracellularly while measuring cytosolic pH (pHi) by microfluorimetry. Na+/H+ exchange activity was measured as the Na+-driven pHi recovery from an acid load, which was imposed via the patch pipette. In Chinese hamster ovary (CHO) fibroblasts stably transfected with NHE-1, omission of ATP from the pipette solution inhibited Na+/H+ exchange. Conversely, ATP perfusion restored exchange activity in cells that had been metabolically depleted by 2-deoxy-d-glucose and oligomycin. In cells dialyzed in the presence of ATP, no “run-down” was observed even after extended periods, suggesting that the nucleotide is the only diffusible factor required for optimal NHE-1 activity. Half-maximal activation of the antiporter was obtained at ∼5 mM Mg-ATP. Submillimolar concentrations failed to sustain Na+/H+ exchange even when an ATP regenerating system was included in the pipette solution. High ATP concentrations are also known to be required for the optimal function of other cation exchangers. In the case of the Na/Ca2+ exchanger, this requirement has been attributed to an aminophospholipid translocase, or “flippase.” The involvement of this enzyme in Na+/H+ exchange was examined using fluorescent phosphatidylserine, which is actively translocated by the flippase. ATP depletion decreased the transmembrane uptake of NBD-labeled phosphatidylserine (NBD-PS), indicating that the flippase was inhibited. Diamide, an agent reported to block the flippase, was as potent as ATP depletion in reducing NBD-PS uptake. However, diamide had no effect on Na+/H+ exchange, implying that the effect of ATP is not mediated by changes in lipid distribution across the plasma membrane. K-ATP and ATPγS were as efficient as Mg-ATP in sustaining NHE-1 activity, while AMP-PNP and AMP-PCP only partially substituted for ATP. In

Investigation of whether in-room CT-based adaptive intracavitary brachytherapy for uterine cervical cancer is robust against interfractional location variations of organs and/or applicators

PubMed Central

Oku, Yoshifumi; Arimura, Hidetaka; Nguyen, Tran Thi Thao; Hiraki, Yoshiyuki; Toyota, Masahiko; Saigo, Yasumasa; Yoshiura, Takashi; Hirata, Hideki

2016-01-01

This study investigates whether in-room computed tomography (CT)-based adaptive treatment planning (ATP) is robust against interfractional location variations, namely, interfractional organ motions and/or applicator displacements, in 3D intracavitary brachytherapy (ICBT) for uterine cervical cancer. In ATP, the radiation treatment plans, which have been designed based on planning CT images (and/or MR images) acquired just before the treatments, are adaptively applied for each fraction, taking into account the interfractional location variations. 2D and 3D plans with ATP for 14 patients were simulated for 56 fractions at a prescribed dose of 600 cGy per fraction. The standard deviations (SDs) of location displacements (interfractional location variations) of the target and organs at risk (OARs) with 3D ATP were significantly smaller than those with 2D ATP (P < 0.05). The homogeneity index (HI), conformity index (CI) and tumor control probability (TCP) in 3D ATP were significantly higher for high-risk clinical target volumes than those in 2D ATP. The SDs of the HI, CI, TCP, bladder and rectum D2cc, and the bladder and rectum normal tissue complication probability (NTCP) in 3D ATP were significantly smaller than those in 2D ATP. The results of this study suggest that the interfractional location variations give smaller impacts on the planning evaluation indices in 3D ATP than in 2D ATP. Therefore, the 3D plans with ATP are expected to be robust against interfractional location variations in each treatment fraction. PMID:27296250

Suit study - The impact of VMS in subsystem integration

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

Hill, B.; Watts, R.

1992-02-01

One of the thrusts of the Wright Laboratory/FIVE-sponsored Subsystem Integration Technology (SUIT) study is to investigate the impact of emerging vehicle management system (VMS) concepts on subsystem integration. This paper summarizes the issues relating to VMS/subsystem integration as examined during the Northrop SUIT study. Projected future weapon system requirements are identified and their impact on VMS and subsystem design interpreted. Integrated VMS/subsystem control and management functions are proposed. A candidate system VMS architecture satisfying the aforementioned weapon system requirements and providing the identified control and management functions is proposed. This architecture is used, together with the environmental control system, asmore » an illustrative subsystem example, to address the risks associated with the design, development, procurement, integration and testing of integrated VMS/subsystem concepts. The conclusion is that the development process requires an airframer to adopt the role of subsystem integrator, the consequences of which are discussed. 2 refs.« less

Robust nonlinear variable selective control for networked systems

NASA Astrophysics Data System (ADS)

Rahmani, Behrooz

2016-10-01

This paper is concerned with the networked control of a class of uncertain nonlinear systems. In this way, Takagi-Sugeno (T-S) fuzzy modelling is used to extend the previously proposed variable selective control (VSC) methodology to nonlinear systems. This extension is based upon the decomposition of the nonlinear system to a set of fuzzy-blended locally linearised subsystems and further application of the VSC methodology to each subsystem. To increase the applicability of the T-S approach for uncertain nonlinear networked control systems, this study considers the asynchronous premise variables in the plant and the controller, and then introduces a robust stability analysis and control synthesis. The resulting optimal switching-fuzzy controller provides a minimum guaranteed cost on an H2 performance index. Simulation studies on three nonlinear benchmark problems demonstrate the effectiveness of the proposed method.

The JPL telerobotic Manipulator Control and Mechanization (MCM) subsystem

NASA Technical Reports Server (NTRS)

Hayati, Samad; Lee, Thomas S.; Tso, Kam; Backes, Paul; Kan, Edwin; Lloyd, J.

1989-01-01

The Manipulator Control and Mechanization (MCM) subsystem of the telerobot system provides the real-time control of the robot manipulators in autonomous and teleoperated modes and real time input/output for a variety of sensors and actuators. Substantial hardware and software are included in this subsystem which interfaces in the hierarchy of the telerobot system with the other subsystems. The other subsystems are: run time control, task planning and reasoning, sensing and perception, and operator control subsystem. The architecture of the MCM subsystem, its capabilities, and details of various hardware and software elements are described. Important improvements in the MCM subsystem over the first version are: dual arm coordinated trajectory generation and control, addition of integrated teleoperation, shared control capability, replacement of the ultimate controllers with motor controllers, and substantial increase in real time processing capability.

Clusterin and COMMD1 Independently Regulate Degradation of the Mammalian Copper ATPases ATP7A and ATP7B*

PubMed Central

Materia, Stephanie; Cater, Michael A.; Klomp, Leo W. J.; Mercer, Julian F. B.; La Fontaine, Sharon

2012-01-01

ATP7A and ATP7B are copper-transporting P1B-type ATPases (Cu-ATPases) that are critical for regulating intracellular copper homeostasis. Mutations in the genes encoding ATP7A and ATP7B lead to copper deficiency and copper toxicity disorders, Menkes and Wilson diseases, respectively. Clusterin and COMMD1 were previously identified as interacting partners of these Cu-ATPases. In this study, we confirmed that clusterin and COMMD1 interact to down-regulate both ATP7A and ATP7B. Overexpression and knockdown of clusterin/COMMD1 decreased and increased, respectively, endogenous levels of ATP7A and ATP7B, consistent with a role in facilitating Cu-ATPase degradation. We demonstrate that whereas the clusterin/ATP7B interaction was enhanced by oxidative stress or mutation of ATP7B, the COMMD1/ATP7B interaction did not change under oxidative stress conditions, and only increased with ATP7B mutations that led to its misfolding. Clusterin and COMMD1 facilitated the degradation of ATP7B containing the same Wilson disease-causing C-terminal mutations via different degradation pathways, clusterin via the lysosomal pathway and COMMD1 via the proteasomal pathway. Furthermore, endogenous ATP7B existed in a complex with clusterin and COMMD1, but these interactions were neither competitive nor cooperative and occurred independently of each other. Together these data indicate that clusterin and COMMD1 represent alternative and independent systems regulating Cu-ATPase quality control, and consequently contributing to the maintenance of copper homeostasis. PMID:22130675

Advanced vehicle systems assessment. Volume 2: Subsystems assessment

NASA Technical Reports Server (NTRS)

Hardy, K.

1985-01-01

Volume 2 (Subsystems Assessment) is part of a five-volume report entitled Advanced Vehicle Systems Assessment. Volume 2 presents the projected performance capabilities and cost characteristics of applicable subsystems, considering an additional decade of development. Subsystems of interest include energy storage and conversion devices as well as the necessary powertrain components and vehicle subsystems. Volume 2 also includes updated battery information based on the assessment of an independent battery review board (with the aid of subcontractor reports on advanced battery characteristics).

Simple debugging techniques for embedded subsystems

NASA Astrophysics Data System (ADS)

MacPherson, Matthew S.; Martin, Kevin S.

1990-08-01

This paper describes some of the tools and methods used for developing and debugging embedded subsystems at Fermilab. Specifically, these tools have been used for the Flying Wire project and are currently being employed for the New TECAR upgrade. The Flying Wire is a subsystem that swings a wire through the beam in order to measure luminosity and beam density distribution, and TECAR (Tevatron excitation controller and regulator) controls the power-supply ramp generation for the superconducting Tevatron accelerator at Fermilab. In both instances the subsystem hardware consists of a VME crate with one or more processors, shared memory and a network connection to the accelerator control system. Two real-time-operating systems are currently being used: VRTX for the Flying Wire system, and MTOS for New TECAR. The code which runs in these subsystems is a combination of C and assembler and is developed using the Microtec cross-development tools on a VAX 8650 running VMS. This paper explains how multiple debuggers are used to give the greatest possible flexibility from assembly to high-level debugging. Also discussed is how network debugging and network downloading can make a very effective and efficient means of finding bugs in the subsystem environment. The debuggers used are PROBE1, TRACER and the MTOS debugger.

Apollo experience report: Lunar module environmental control subsystem

NASA Technical Reports Server (NTRS)

Gillen, R. J.; Brady, J. C.; Collier, F.

1972-01-01

A functional description of the environmental control subsystem is presented. Development, tests, checkout, and flight experiences of the subsystem are discussed; and the design fabrication, and operational difficulties associated with the various components and subassemblies are recorded. Detailed information is related concerning design changes made to, and problems encountered with, the various elements of the subsystem, such as the thermal control water sublimator, the carbon dioxide sensing and control units, and the water section. The problems associated with water sterilization, water/glycol formulation, and materials compatibility are discussed. The corrective actions taken are described with the expection that this information may be of value for future subsystems. Although the main experiences described are problem oriented, the subsystem has generally performed satisfactorily in flight.

Investigation of whether in-room CT-based adaptive intracavitary brachytherapy for uterine cervical cancer is robust against interfractional location variations of organs and/or applicators.

PubMed

Oku, Yoshifumi; Arimura, Hidetaka; Nguyen, Tran Thi Thao; Hiraki, Yoshiyuki; Toyota, Masahiko; Saigo, Yasumasa; Yoshiura, Takashi; Hirata, Hideki

2016-11-01

This study investigates whether in-room computed tomography (CT)-based adaptive treatment planning (ATP) is robust against interfractional location variations, namely, interfractional organ motions and/or applicator displacements, in 3D intracavitary brachytherapy (ICBT) for uterine cervical cancer. In ATP, the radiation treatment plans, which have been designed based on planning CT images (and/or MR images) acquired just before the treatments, are adaptively applied for each fraction, taking into account the interfractional location variations. 2D and 3D plans with ATP for 14 patients were simulated for 56 fractions at a prescribed dose of 600 cGy per fraction. The standard deviations (SDs) of location displacements (interfractional location variations) of the target and organs at risk (OARs) with 3D ATP were significantly smaller than those with 2D ATP (P < 0.05). The homogeneity index (HI), conformity index (CI) and tumor control probability (TCP) in 3D ATP were significantly higher for high-risk clinical target volumes than those in 2D ATP. The SDs of the HI, CI, TCP, bladder and rectum D 2cc , and the bladder and rectum normal tissue complication probability (NTCP) in 3D ATP were significantly smaller than those in 2D ATP. The results of this study suggest that the interfractional location variations give smaller impacts on the planning evaluation indices in 3D ATP than in 2D ATP. Therefore, the 3D plans with ATP are expected to be robust against interfractional location variations in each treatment fraction. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Some recent developments in spacecraft environmental control/life support subsystems

NASA Technical Reports Server (NTRS)

Gillen, R. J.; Olcott, T. M.

1974-01-01

The subsystems considered include a flash evaporator for heat rejection, a regenerable carbon dioxide and humidity control subsystem, an iodinating subsystem for potable water, a cabin contaminant control subsystem, and a wet oxidation subsystem for processing spacecraft wastes. The flash evaporator discussed is a simple unit which efficiently controls life support system temperatures over a wide range of heat loads. For certain advanced spacecraft applications the control of cabin carbon dioxide and humidity can be successfully achieved by a regenerable solid amine subsystem.

Air and water quality monitor assessment of life support subsystems

NASA Technical Reports Server (NTRS)

Whitley, Ken; Carrasquillo, Robyn L.; Holder, D.; Humphries, R.

1988-01-01

Preprotype air revitalization and water reclamation subsystems (Mole Sieve, Sabatier, Static Feed Electrolyzer, Trace Contaminant Control, and Thermoelectric Integrated Membrane Evaporative Subsystem) were operated and tested independently and in an integrated arrangement. During each test, water and/or gas samples were taken from each subsystem so that overall subsystem performance could be determined. The overall test design and objectives for both subsystem and integrated subsystem tests were limited, and no effort was made to meet water or gas specifications. The results of chemical analyses for each of the participating subsystems are presented along with other selected samples which were analyzed for physical properties and microbiologicals.

Inhibition of ATP Synthase by Chlorinated Adenosine Analogue

PubMed Central

Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

2009-01-01

8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing α and β subunits. Crystal structures of both α and β subunits that bind to the substrate, ADP, are known in tight binding (αdpβdp) and loose binding (αtpβtp) states. Molecular docking demonstrated that 8-Cl-ADP/8-Cl-ATP occupied similar binding modes as ADP/ATP in the tight and loose binding sites of ATP synthase, respectively, suggesting that the chlorinated nucleotide metabolites may be functional substrates and inhibitors of the enzyme. The computational predictions were consistent with our whole cell biochemical results. Oligomycin, an established pharmacological inhibitor of ATP synthase, decreased both ATP and 8-Cl-ATP formation from exogenous substrates, however, did not affect pyrimidine nucleoside analogue triphosphate accumulation. Synthesis of ATP from ADP was inhibited in cells loaded with 8-Cl-ATP. These biochemical studies are in consent with the computational modeling; in the αtpβtp state 8-Cl-ATP occupies similar binding as ANP, a non-hydrolyzable ATP mimic that is a known inhibitor. Similarly, in the substrate binding site (αdpβdp) 8-Cl-ATP occupies a similar position as ATP mimic ADP-BeF3 −. Collectively, our current work suggests that 8-Cl-ADP may serve as a substrate and the 8-Cl-ATP may be an inhibitor of ATP synthase. PMID:19477165

Simplified power processing for ion-thruster subsystems

NASA Technical Reports Server (NTRS)

Wessel, F. J.; Hancock, D. J.

1983-01-01

Compared to chemical propulsion, ion propulsion offers distinct payload-mass increases for many future low-thrust earth-orbital and deep-space missions. Despite this advantage, the high initial cost and complexity of ion-propulsion subsystems reduce their attractiveness for most present and near-term spacecraft missions. Investigations have, therefore, been conducted with the objective to attempt to simplify the power-processing unit (PPU), which is the single most complex and expensive component in the thruster subsystem. The present investigation is concerned with a program to simplify the design of the PPU employed in a 8-cm mercury-ion-thruster subsystem. In this program a dramatic simplification in the design of the PPU could be achieved, while retaining essential thruster control and subsystem operational flexibility.

Data Transport Subsystem - The SFOC glue

NASA Technical Reports Server (NTRS)

Parr, Stephen J.

1988-01-01

The design and operation of the Data Transport Subsystem (DTS) for the JPL Space Flight Operation Center (SFOC) are described. The SFOC is the ground data system under development to serve interplanetary space probes; in addition to the DTS, it comprises a ground interface facility, a telemetry-input subsystem, data monitor and display facilities, and a digital TV system. DTS links the other subsystems via an ISO OSI presentation layer and an LAN. Here, particular attention is given to the DTS services and service modes (virtual circuit, datagram, and broadcast), the DTS software architecture, the logical-name server, the role of the integrated AI library, and SFOC as a distributed system.

On the subsystem formulation of linear-response time-dependent DFT.

PubMed

Pavanello, Michele

2013-05-28

A new and thorough derivation of linear-response subsystem time-dependent density functional theory (TD-DFT) is presented and analyzed in detail. Two equivalent derivations are presented and naturally yield self-consistent subsystem TD-DFT equations. One reduces to the subsystem TD-DFT formalism of Neugebauer [J. Chem. Phys. 126, 134116 (2007)]. The other yields Dyson type equations involving three types of subsystem response functions: coupled, uncoupled, and Kohn-Sham. The Dyson type equations for subsystem TD-DFT are derived here for the first time. The response function formalism reveals previously hidden qualities and complications of subsystem TD-DFT compared with the regular TD-DFT of the supersystem. For example, analysis of the pole structure of the subsystem response functions shows that each function contains information about the electronic spectrum of the entire supersystem. In addition, comparison of the subsystem and supersystem response functions shows that, while the correlated response is subsystem additive, the Kohn-Sham response is not. Comparison with the non-subjective partition DFT theory shows that this non-additivity is largely an artifact introduced by the subjective nature of the density partitioning in subsystem DFT.

Thermal analyses of power subsystem components

NASA Technical Reports Server (NTRS)

Morehouse, Jeffrey H.

1990-01-01

The hiatus in the Space Shuttle (Orbiter) program provided time for an in-depth examination of all the subsystems and their past performance. Specifically, problems with reliability and/or operating limits were and continue to be of major engineering concern. The Orbiter Auxiliary Power Unit (APU) currently operates with electric resistance line heaters which are controlled with thermostats. A design option simplification of this heater subsystem is being considered which would use self-regulating heaters. A determination of the properties and thermal operating characteristics of these self-regulating heaters was needed. The Orbiter fuel cells are cooled with a freon loop. During a loss of external heat exchanger coolant flow, the single pump circulating the freon is to be left running. It was unknown what temperature and flow rate transient conditions of the freon would provide the required fuel cell cooling and for how long. The overall objective was the development of the thermal characterization and subsequent analysis of both the proposed self-regulating APU heater and the fuel cell coolant loop subsystem. The specific objective of the APU subsystem effort was to determine the feasibility of replacing the current heater and thermostat arrangement with a self-regulating heater. The specific objective of the fuel cell coolant subsystem work was to determine the tranient coolant temperature and associated flow rates during a loss-of-external heat exchanger flow.

Viking Orbiter 1975 articulation control subsystem design analysis

NASA Technical Reports Server (NTRS)

Horiuchi, H. H.; Vallas, L. J.

1973-01-01

The articulation control subsystem, developed for the Viking Orbiter 1975 spacecraft, is a digital, multiplexed, closed-loop servo system used to control the pointing and positioning of the science scan platform and the high-gain communication antenna, and to position the solar-energy controller louver blades for the thermal control of the propellant tanks. The development, design, and anlaysis of the subsystem is preliminary. The subsystem consists of a block-redundant control electronics multiplexed among eight control actuators. Each electronics block is capable of operating either individually or simultaneously with the second block. This provides the subsystem the capability of simultaneous two-actuator control or a single actuator control with the second block in a stand-by redundant mode. The result of the preliminary design and analysis indicates that the subsystem will perform satisfactorily in the Viking Orbiter 1975 mission. Some of the parameter values used, particularly those in the subsystem dynamics and the error estimates, are preliminary and the results will be updated as more accurate parameter values become available.

The Mariner Venus Mercury flight data subsystem.

NASA Technical Reports Server (NTRS)

Whitehead, P. B.

1972-01-01

The flight data subsystem (FDS) discussed handles both the engineering and scientific measurements performed on the MVM'73. It formats the data into serial data streams, and sends it to the modulation/demodulation subsystem for transmission to earth or to the data storage subsystem for storage on a digital tape recorder. The FDS is controlled by serial digital words, called coded commands, received from the central computer sequencer of from the ground via the modulation/demodulation subsystem. The eight major blocks of the FDS are: power converter, timing and control, engineering data, memory, memory input/output and control, nonimaging data, imaging data, and data output. The FDS incorporates some 4000 components, weighs 17 kg, and uses 35 W of power. General data on the mission and spacecraft are given.

[P4-ATP-ase Atp8b1/FIC1: structural properties and (patho)physiological functions].

PubMed

Korneenko, T V; Pestov, N B; Okkelman, I A; Modyanov, N N; Shakhparonov, M I

2015-01-01

P4-ATP-ases comprise an interesting family among P-type ATP-ases, since they are thought to play a major role in the transfer of phospholipids such as phosphatydylserine from the outer leaflet to the inner leaflet. Isoforms of P4-ATP-ases are partially interchangeable but peculiarities of tissue-specific expression of their genes, intracellular localization of proteins, as well as regulatory pathways lead to the fact that, on the organismal level, serious pathologies may develop in the presence of structural abnormalities in certain isoforms. Among P4-ATP-ases a special place is occupied by ATP8B1, for which several mutations are known that lead to serious hereditary diseases: two forms of congenital cholestasis (PFIC1 or Byler disease and benign recurrent intrahepatic cholestasis) with extraliver symptoms such as sensorineural hearing loss. The physiological function of the Atp8b1/FIC1 protein is known in general outline: it is responsible for transport of certain phospholipids (phosphatydylserine, cardiolipin) for the outer monolayer of the plasma membrane to the inner one. It is well known that perturbation of membrane asymmetry, caused by the lack of Atp8B1 activity, leads to death of hairy cells of the inner ear, dysfunction of bile acid transport in liver-cells that causes cirrhosis. It is also probable that insufficient activity of Atp8b1/FIC1 increases susceptibility to bacterial pneumonia.Regulatory pathways of Atp8b1/FIC1 activity in vivo remain to be insufficiently studied and this opens novel perspectives for research in this field that may allow better understanding of molecular processes behind the development of certain pathologies and to reveal novel therapeutical targets.

Robust algebraic image enhancement for intelligent control systems

NASA Technical Reports Server (NTRS)

Lerner, Bao-Ting; Morrelli, Michael

1993-01-01

Robust vision capability for intelligent control systems has been an elusive goal in image processing. The computationally intensive techniques a necessary for conventional image processing make real-time applications, such as object tracking and collision avoidance difficult. In order to endow an intelligent control system with the needed vision robustness, an adequate image enhancement subsystem capable of compensating for the wide variety of real-world degradations, must exist between the image capturing and the object recognition subsystems. This enhancement stage must be adaptive and must operate with consistency in the presence of both statistical and shape-based noise. To deal with this problem, we have developed an innovative algebraic approach which provides a sound mathematical framework for image representation and manipulation. Our image model provides a natural platform from which to pursue dynamic scene analysis, and its incorporation into a vision system would serve as the front-end to an intelligent control system. We have developed a unique polynomial representation of gray level imagery and applied this representation to develop polynomial operators on complex gray level scenes. This approach is highly advantageous since polynomials can be manipulated very easily, and are readily understood, thus providing a very convenient environment for image processing. Our model presents a highly structured and compact algebraic representation of grey-level images which can be viewed as fuzzy sets.

Variable effects of the mitoK(ATP) channel modulators diazoxide and 5-HD in ATP-depleted renal epithelial cells.

PubMed

Nilakantan, Vani; Liang, Huanling; Mortensen, Jordan; Taylor, Erin; Johnson, Christopher P

2010-02-01

The role of mitochondrial K(ATP) (mitoK(ATP)) channels in renal ischemia-reperfusion injury is controversial with studies showing both protective and deleterious effects. In this study, we compared the effects of the putative mitoK(ATP) opener, diazoxide, and the mitoK(ATP) blocker, 5-hydroxydecanoate (5-HD) on cytotoxicity and apoptosis in tubular epithelial cells derived from rat (NRK-52E) and pig (LLC-PK1) following in vitro ischemic injury. Following ATP depletion-recovery, there was a significant increase in cytotoxicity in both NRK cells and LLC-PK1 cells although NRK cells were more sensitive to the injury. Diazoxide treatment attenuated cytotoxicity in both cell types and 5-HD treatment-increased cytotoxicity in the sensitive NRK cells in a superoxide-dependant manner. The protective effect of diazoxide was also reversed in the presence of 5-HD in ATP-depleted NRK cells. The ATP depletion-mediated increase in superoxide was enhanced by both diazoxide and 5-HD with the effect being more pronounced in the cells undergoing 5-HD treatment. Further, ATP depletion-induced activation of caspase-3 was decreased by diazoxide in NRK cells. In order to determine the signaling pathways involved in apoptosis, we examined the activation of Erk and JNK in ATP-depleted NRK cells. Diazoxide-activated Erk in ATP-depleted cells, but did not have any effect on JNK activation. In contrast, 5-HD did not impact Erk levels but increased JNK activation even under controlled conditions. Further, the use of a JNK inhibitor with 5-HD reversed the deleterious effects of 5-HD. This study demonstrates that in cells that are sensitive to ATP depletion-recovery, mitoK(ATP) channels protect against ATP depletion-mediated cytotoxicity and apoptosis through Erk- and JNK-dependant mechanisms.

Oral Adenosine-5'-triphosphate (ATP) Administration Increases Postexercise ATP Levels, Muscle Excitability, and Athletic Performance Following a Repeated Sprint Bout.

PubMed

Purpura, Martin; Rathmacher, John A; Sharp, Matthew H; Lowery, Ryan P; Shields, Kevin A; Partl, Jeremy M; Wilson, Jacob M; Jäger, Ralf

2017-01-01

Oral adenosine-5'-triphosphate (ATP) administration has failed to increase plasma ATP levels; however, chronic supplementation with ATP has shown to increase power, strength, lean body mass, and blood flow in trained athletes. The purpose of this study was to investigate the effects of ATP supplementation on postexercise ATP levels and on muscle activation and excitability and power following a repeated sprint bout. In a double-blind, placebo-controlled, randomized design, 42 healthy male individuals were given either 400 mg of ATP as disodium salt or placebo for 2 weeks prior to an exercise bout. During the exercise bout, muscle activation and excitability (ME, ratio of power output to muscle activation) and Wingate test peak power were measured during all sprints. ATP and metabolites were measured at baseline, after supplementation, and immediately following exercise. Oral ATP supplementation prevented a drop in ATP, adenosine-5'-diphosphate (ADP), and adenosine-5'-monophosphate (AMP) levels postexercise (p < 0.05). No group by time interaction was observed for muscle activation. Following the supplementation period, muscle excitability significantly decreased in later bouts 8, 9, and 10 in the placebo group (-30.5, -28.3, and -27.9%, respectively; p < 0.02), whereas ATP supplementation prevented the decline in later bouts. ATP significantly increased Wingate peak power in later bouts compared to baseline (bout 8: +18.3%, bout 10: +16.3%). Oral ATP administration prevents exercise-induced declines in ATP and its metabolite and enhances peak power and muscular excitability, which may be beneficial for sports requiring repeated high-intensity sprinting bouts.

Genomic Analysis of ATP Efflux in Saccharomyces cerevisiae

PubMed Central

Peters, Theodore W.; Miller, Aaron W.; Tourette, Cendrine; Agren, Hannah; Hubbard, Alan; Hughes, Robert E.

2015-01-01

Adenosine triphosphate (ATP) plays an important role as a primary molecule for the transfer of chemical energy to drive biological processes. ATP also functions as an extracellular signaling molecule in a diverse array of eukaryotic taxa in a conserved process known as purinergic signaling. Given the important roles of extracellular ATP in cell signaling, we sought to comprehensively elucidate the pathways and mechanisms governing ATP efflux from eukaryotic cells. Here, we present results of a genomic analysis of ATP efflux from Saccharomyces cerevisiae by measuring extracellular ATP levels in cultures of 4609 deletion mutants. This screen revealed key cellular processes that regulate extracellular ATP levels, including mitochondrial translation and vesicle sorting in the late endosome, indicating that ATP production and transport through vesicles are required for efflux. We also observed evidence for altered ATP efflux in strains deleted for genes involved in amino acid signaling, and mitochondrial retrograde signaling. Based on these results, we propose a model in which the retrograde signaling pathway potentiates amino acid signaling to promote mitochondrial respiration. This study advances our understanding of the mechanism of ATP secretion in eukaryotes and implicates TOR complex 1 (TORC1) and nutrient signaling pathways in the regulation of ATP efflux. These results will facilitate analysis of ATP efflux mechanisms in higher eukaryotes. PMID:26585826

Automatic control of a primary electric thrust subsystem

NASA Technical Reports Server (NTRS)

Macie, T. W.; Macmedan, M. L.

1975-01-01

A concept for automatic control of the thrust subsystem has been developed by JPL and participating NASA Centers. This paper reports on progress in implementing the concept at JPL. Control of the Thrust Subsystem (TSS) is performed by the spacecraft computer command subsystem, and telemetry data is extracted by the spacecraft flight data subsystem. The Data and Control Interface Unit, an element of the TSS, provides the interface with the individual elements of the TSS. The control philosophy and implementation guidelines are presented. Control requirements are listed, and the control mechanism, including the serial digital data intercommunication system, is outlined. The paper summarizes progress to Fall 1974.

Recursive Construction of Noiseless Subsystem for Qudits

NASA Astrophysics Data System (ADS)

Güngördü, Utkan; Li, Chi-Kwong; Nakahara, Mikio; Poon, Yiu-Tung; Sze, Nung-Sing

2014-03-01

When the environmental noise acting on the system has certain symmetries, a subsystem of the total system can avoid errors. Encoding information into such a subsystem is advantageous since it does not require any error syndrome measurements, which may introduce further errors to the system. However, utilizing such a subsystem for large systems gets impractical with the increasing number of qudits. A recursive scheme offers a solution to this problem. Here, we review the recursive construct introduced in, which can asymptotically protect 1/d of the qudits in system against collective errors.

Apollo experience report: Lunar module electrical power subsystem

NASA Technical Reports Server (NTRS)

Campos, A. B.

1972-01-01

The design and development of the electrical power subsystem for the lunar module are discussed. The initial requirements, the concepts used to design the subsystem, and the testing program are explained. Specific problems and the modifications or compromises (or both) imposed for resolution are detailed. The flight performance of the subsystem is described, and recommendations pertaining to power specifications for future space applications are made.

Preliminary analysis of a membrane-based atmosphere-control subsystem

NASA Technical Reports Server (NTRS)

Mccray, Scott B.; Newbold, David D.; Ray, Rod; Ogle, Kathryn

1993-01-01

Controlled ecological life supprot systems will require subsystems for maintaining the consentrations of atmospheric gases within acceptable ranges in human habitat chambers and plant growth chambers. The goal of this work was to develop a membrane-based atmosphere comntrol (MBAC) subsystem that allows the controlled exchange of atmospheric componets (e.g., oxygen, carbon dioxide, and water vapor) between these chambers. The MBAC subsystem promises to offer a simple, nonenergy intensive method to separate, store and exchange atmospheric components, producing optimal concentrations of components in each chamber. In this paper, the results of a preliminary analysis of the MBAC subsystem for control of oxygen and nitrogen are presented. Additionally, the MBAC subsystem and its operation are described.

Mitochondrial flashes regulate ATP homeostasis in the heart

PubMed Central

Wang, Xianhua; Zhang, Xing; Wu, Di; Huang, Zhanglong; Hou, Tingting; Jian, Chongshu; Yu, Peng; Lu, Fujian; Zhang, Rufeng; Sun, Tao; Li, Jinghang; Qi, Wenfeng; Wang, Yanru; Gao, Feng; Cheng, Heping

2017-01-01

The maintenance of a constant ATP level (‘set-point’) is a vital homeostatic function shared by eukaryotic cells. In particular, mammalian myocardium exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac workload. However, the exact mechanisms underlying this regulation of ATP homeostasis remain elusive. Here we show mitochondrial flashes (mitoflashes), recently discovered dynamic activity of mitochondria, play an essential role for the auto-regulation of ATP set-point in the heart. Specifically, mitoflashes negatively regulate ATP production in isolated respiring mitochondria and, their activity waxes and wanes to counteract the ATP supply-demand imbalance caused by superfluous substrate and altered workload in cardiomyocytes. Moreover, manipulating mitoflash activity is sufficient to inversely shift the otherwise stable ATP set-point. Mechanistically, the Bcl-xL-regulated proton leakage through F1Fo-ATP synthase appears to mediate the coupling between mitoflash production and ATP set-point regulation. These findings indicate mitoflashes appear to constitute a digital auto-regulator for ATP homeostasis in the heart. DOI: http://dx.doi.org/10.7554/eLife.23908.001 PMID:28692422

Effector-Triggered Self-Replication in Coupled Subsystems.

PubMed

Komáromy, Dávid; Tezcan, Meniz; Schaeffer, Gaël; Marić, Ivana; Otto, Sijbren

2017-11-13

In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication. The subsystem based on the first building block shows only self-replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host-effector complex and the liberation of the building block that subsequently engages in self-replication. The onset, rate and extent of self-replication is controlled by the amount of effector present. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evidence for the Synthesis of ATP by an F0F1 ATP Synthase in Membrane Vesicles from Halorubrum Saccharovorum

NASA Technical Reports Server (NTRS)

Faguy, David; Lawson, Darion; Hochstein, Lawrence I.; Chang, Sherwood (Technical Monitor)

1996-01-01

Vesicles prepared in a buffer containing ADP, Mg(2+) and Pi synthesized ATP at an initial rate of 2 nmols/min/mg protein after acidification of the bulk medium (pH 8 (right arrow) 4). The intravesicular ATP concentration reached a steady state after about 30 seconds and slowly declined thereafter. ATP synthesis was inhibited by low concentrations of dicyclohexylcarbodiimide and m-chlorophenylhydrazone indicating that synthesis took place in response to the proton gradient. NEM and PCMS, which inhibit vacuolar ATPases and the vacuolar-like ATPases of extreme halophiles, did not affect ATP synthesis, and, in fact, produced higher steady state levels of ATP. This suggested that two ATPase activities were present, one which catalyzed ATP synthesis and one that caused its hydrolysis. Azide, a specific inhibitor of F0F1 ATP Synthases, inhibited halobacterial ATP synthesis. The distribution of acridine orange as imposed by a delta pH demonstrated that azide inhibition was not due to the collapse of the proton gradient due to azide acting as a protonophore. Such an effect was observed, but only at azide concentrations higher than those that inhibited ATP synthesis. These results confirm the earler observations with cells of H. saccharovorum and other extreme halophiles that ATP synthesis is inconsistent with the operation of a vacuolar-like ATPase. Therefore, the observation that a vacuolar-like enzyme is responsible for ATP synthesis (and which serves as the basis for imputing ATP synthesis to the vacuolar-like ATPases of the extreme halophiles, and the Archaea in general) should be taken with some degree of caution.

MIUS Integration and Subsystem Test (MIST) data system

NASA Technical Reports Server (NTRS)

Pringle, L. M.

1977-01-01

A data system for use in testing integrated subsystems of a modular integrated utility system (MIUS) is presented. The MIUS integration and subsystem test (MIST) data system is reviewed from its conception through its checkout and operation as the controlling portion of the MIST facility. The MIST data system provides a real time monitoring and control function that allows for complete evaluation of the performance of the mechanical and electrical subsystems, as well as controls the operation of the various components of the system. In addition to the aforementioned capabilities, the MIST data system provides computerized control of test operations such that minimum manpower is necessary to set up, operate, and shut down subsystems during test periods.

Biallelic Mutations in ATP5F1D , which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder

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

Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle

ATP synthase, H + transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F 1F O ATP synthase andmore » subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation.« less

Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder.

PubMed

Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle; Jangam, Sharayu; Fernandez, Liliana; Davidson, Jean M; Kyle, Jennifer E; Grove, Megan E; Fisk, Dianna G; Kohler, Jennefer N; Holmes, Matthew; Dries, Annika M; Huang, Yong; Zhao, Chunli; Contrepois, Kévin; Zappala, Zachary; Frésard, Laure; Waggott, Daryl; Zink, Erika M; Kim, Young-Mo; Heyman, Heino M; Stratton, Kelly G; Webb-Robertson, Bobbie-Jo M; Snyder, Michael; Merker, Jason D; Montgomery, Stephen B; Fisher, Paul G; Feichtinger, René G; Mayr, Johannes A; Hall, Julie; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Waters, Katrina M; Koeller, David M; Metz, Thomas O; Morris, Andrew A; Schelley, Susan; Cowan, Tina; Friederich, Marisa W; McFarland, Robert; Van Hove, Johan L K; Enns, Gregory M; Yamamoto, Shinya; Ashley, Euan A; Wangler, Michael F; Taylor, Robert W; Bellen, Hugo J; Bernstein, Jonathan A; Wheeler, Matthew T

2018-03-01

ATP synthase, H + transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F 1 F O ATP synthase and subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Biallelic Mutations in ATP5F1D , which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder

DOE PAGES

Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle; ...

2018-02-22

ATP synthase, H + transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F 1F O ATP synthase andmore » subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation.« less

A prototype to automate the video subsystem routing for the video distribution subsystem of Space Station Freedom

NASA Astrophysics Data System (ADS)

Betz, Jessie M. Bethly

1993-12-01

The Video Distribution Subsystem (VDS) for Space Station Freedom provides onboard video communications. The VDS includes three major functions: external video switching; internal video switching; and sync and control generation. The Video Subsystem Routing (VSR) is a part of the VDS Manager Computer Software Configuration Item (VSM/CSCI). The VSM/CSCI is the software which controls and monitors the VDS equipment. VSR activates, terminates, and modifies video services in response to Tier-1 commands to connect video sources to video destinations. VSR selects connection paths based on availability of resources and updates the video routing lookup tables. This project involves investigating the current methodology to automate the Video Subsystem Routing and developing and testing a prototype as 'proof of concept' for designers.

Robust distributed model predictive control of linear systems with structured time-varying uncertainties

NASA Astrophysics Data System (ADS)

Zhang, Langwen; Xie, Wei; Wang, Jingcheng

2017-11-01

In this work, synthesis of robust distributed model predictive control (MPC) is presented for a class of linear systems subject to structured time-varying uncertainties. By decomposing a global system into smaller dimensional subsystems, a set of distributed MPC controllers, instead of a centralised controller, are designed. To ensure the robust stability of the closed-loop system with respect to model uncertainties, distributed state feedback laws are obtained by solving a min-max optimisation problem. The design of robust distributed MPC is then transformed into solving a minimisation optimisation problem with linear matrix inequality constraints. An iterative online algorithm with adjustable maximum iteration is proposed to coordinate the distributed controllers to achieve a global performance. The simulation results show the effectiveness of the proposed robust distributed MPC algorithm.

Intelligent subsystem interface for modular hardware system

NASA Technical Reports Server (NTRS)

Caffrey, Robert T. (Inventor); Krening, Douglas N. (Inventor); Lannan, Gregory B. (Inventor); Schneiderwind, Michael J. (Inventor); Schneiderwind, Robert A. (Inventor)

2000-01-01

A single chip application specific integrated circuit (ASIC) which provides a flexible, modular interface between a subsystem and a standard system bus. The ASIC includes a microcontroller/microprocessor, a serial interface for connection to the bus, and a variety of communications interface devices available for coupling to the subsystem. A three-bus architecture, utilizing arbitration, provides connectivity within the ASIC and between the ASIC and the subsystem. The communication interface devices include UART (serial), parallel, analog, and external device interface utilizing bus connections paired with device select signals. A low power (sleep) mode is provided as is a processor disable option.

Volume-dependent ATP-conductive large-conductance anion channel as a pathway for swelling-induced ATP release.

PubMed

Sabirov, R Z; Dutta, A K; Okada, Y

2001-09-01

In mouse mammary C127i cells, during whole-cell clamp, osmotic cell swelling activated an anion channel current, when the phloretin-sensitive, volume-activated outwardly rectifying Cl(-) channel was eliminated. This current exhibited time-dependent inactivation at positive and negative voltages greater than around +/-25 mV. The whole-cell current was selective for anions and sensitive to Gd(3)+. In on-cell patches, single-channel events appeared with a lag period of approximately 15 min after a hypotonic challenge. Under isotonic conditions, cell-attached patches were silent, but patch excision led to activation of currents that consisted of multiple large-conductance unitary steps. The current displayed voltage- and time-dependent inactivation similar to that of whole-cell current. Voltage-dependent activation profile was bell-shaped with the maximum open probability at -20 to 0 mV. The channel in inside-out patches had the unitary conductance of approximately 400 pS, a linear current-voltage relationship, and anion selectivity. The outward (but not inward) single-channel conductance was suppressed by extracellular ATP with an IC(50) of 12.3 mM and an electric distance (delta) of 0.47, whereas the inward (but not outward) conductance was inhibited by intracellular ATP with an IC(50) of 12.9 mM and delta of 0.40. Despite the open channel block by ATP, the channel was ATP-conductive with P(ATP)/P(Cl) of 0.09. The single-channel activity was sensitive to Gd(3)+, SITS, and NPPB, but insensitive to phloretin, niflumic acid, and glibenclamide. The same pharmacological pattern was found in swelling-induced ATP release. Thus, it is concluded that the volume- and voltage-dependent ATP-conductive large-conductance anion channel serves as a conductive pathway for the swelling-induced ATP release in C127i cells.

The Structural Basis of ATP as an Allosteric Modulator

PubMed Central

Wang, Qi; Shen, Qiancheng; Li, Shuai; Nussinov, Ruth; Zhang, Jian

2014-01-01

Adenosine-5’-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP. Through extensive analysis of ATP in solution and proteins, we found that the free ATP can exist in the compact and extended conformations in solution, and the two different conformational characteristics may be responsible for ATP to exert distinct biological functions: ATP molecules adopt both compact and extended conformations in the allosteric binding sites but conserve extended conformations in the substrate binding sites. Nudged elastic band simulations unveiled the distinct dynamic processes of ATP binding to the corresponding allosteric and substrate binding sites of uridine monophosphate kinase, and suggested that in solution ATP preferentially binds to the substrate binding sites of proteins. When the ATP molecules occupy the allosteric binding sites, the allosteric trigger from ATP to fuel allosteric communication between allosteric and functional sites is stemmed mainly from the triphosphate part of ATP, with a small number from the adenine part of ATP. Taken together, our results provide overall understanding of ATP allosteric functions responsible for regulation in biological systems. PMID:25211773

PREVAIL-EPL alpha tool electron optics subsystem

NASA Astrophysics Data System (ADS)

Pfeiffer, Hans C.; Dhaliwal, Rajinder S.; Golladay, Steven D.; Doran, Samuel K.; Gordon, Michael S.; Kendall, Rodney A.; Lieberman, Jon E.; Pinckney, David J.; Quickle, Robert J.; Robinson, Christopher F.; Rockrohr, James D.; Stickel, Werner; Tressler, Eileen V.

2001-08-01

The IBM/Nikon alliance is continuing pursuit of an EPL stepper alpha tool based on the PREVAIL technology. This paper provides a status report of the alliance activity with particular focus on the Electron Optical Subsystem developed at IBM. We have previously reported on design features of the PREVAIL alpha system. The new state-of-the-art e-beam lithography concepts have since been reduced to practice and turned into functional building blocks of a production level lithography tool. The electron optical alpha tool subsystem has been designed, build, assembled and tested at IBM's Semiconductor Research and Development Center (SRDC) in East Fishkill, New York. After demonstrating subsystem functionality, the electron optical column and all associated control electronics hardware and software have been shipped during January 2001 to Nikon's facility in Kumagaya, Japan, for integration into the Nikon commercial e-beam stepper alpha tool. Early pre-shipment results obtained with this electron optical subsystem are presented.

Effects of ATP7A overexpression in mice on copper transport and metabolism in lactation and gestation

PubMed Central

Wadwa, Jarrod; Chu, Yu‐Hsiang; Nguyen, Nhu; Henson, Thomas; Figueroa, Alyssa; Llanos, Roxana; Ackland, Margaret Leigh; Michalczyk, Agnes; Fullriede, Hendrik; Brennan, Grant; Mercer, Julian F. B.; Linder, Maria C.

2014-01-01

Abstract Placentae and mammary epithelial cells are unusual in robustly expressing two copper “pumps”, ATP7A and B, raising the question of their individual roles in these tissues in pregnancy and lactation. Confocal microscopic evidence locates ATP7A to the fetal side of syncytiotrophoblasts, suggesting a role in pumping Cu towards the fetus; and to the basolateral (blood) side of lactating mammary epithelial cells, suggesting a role in recycling Cu to the blood. We tested these concepts in wild‐type C57BL6 mice and their transgenic counterparts that expressed hATP7A at levels 10–20× those of endogenous mAtp7a. In lactation, overexpression of ATP7A reduced the Cu concentrations of the mammary gland and milk ~50%. Rates of transfer of tracer 64Cu to the suckling pups were similarly reduced over 30–48 h, as was the total Cu in 10‐day ‐old pups. During the early and middle periods of gestation, the transgenic litters had higher Cu concentrations than the wild‐type, placental Cu showing the reverse trend; but this difference was lost by the first postnatal day. The transgenic mice expressed ATP7A in some hepatocytes, so we investigated the possibility that metalation of ceruloplasmin (Cp) might be enhanced. Rates of 64Cu incorporation into Cp, oxidase activity, and ratios of holo to apoceruloplasmin were unchanged. We conclude that in the lactating mammary gland, the role of ATP7A is to return Cu to the blood, while in the placenta it mediates Cu delivery to the fetus and is the rate‐limiting step for fetal Cu nutrition during most of gestation in mice. PMID:24744874

Dual recognition unit strategy improves the specificity of the adenosine triphosphate (ATP) aptamer biosensor for cerebral ATP assay.

PubMed

Yu, Ping; He, Xiulan; Zhang, Li; Mao, Lanqun

2015-01-20

Adenosine triphosphate (ATP) aptamer has been widely used as a recognition unit for biosensor development; however, its relatively poor specificity toward ATP against adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) essentially limits the application of the biosensors in real systems, especially in the complex cerebral system. In this study, for the first time, we demonstrate a dual recognition unit strategy (DRUS) to construct a highly selective and sensitive ATP biosensor by combining the recognition ability of aptamer toward A nucleobase and of polyimidazolium toward phosphate. The biosensors are constructed by first confining the polyimidazolium onto a gold surface by surface-initiated atom transfer radical polymerization (SI-ATRP), and then the aptamer onto electrode surface by electrostatic self-assembly to form dual-recognition-unit-functionalized electrodes. The constructed biosensor based on DRUS not only shows an ultrahigh sensitivity toward ATP with a detection limit down to the subattomole level but also an ultrahigh selectivity toward ATP without interference from ADP and AMP. The constructed biosensor is used for selective and sensitive sensing of the extracellular ATP in the cerebral system by combining in vivo microdialysis and can be used as a promising neurotechnology to probing cerebral ATP concentration.

Thermodynamics of proton transport coupled ATP synthesis.

PubMed

Turina, Paola; Petersen, Jan; Gräber, Peter

2016-06-01

The thermodynamic H(+)/ATP ratio of the H(+)-ATP synthase from chloroplasts was measured in proteoliposomes after energization of the membrane by an acid base transition (Turina et al. 2003 [13], 418-422). The method is discussed, and all published data obtained with this system are combined and analyzed as a single dataset. This meta-analysis led to the following results. 1) At equilibrium, the transmembrane ΔpH is energetically equivalent to the transmembrane electric potential difference. 2) The standard free energy for ATP synthesis (reference reaction) is ΔG°(ref)=33.8±1.3kJ/mol. 3) The thermodynamic H(+)/ATP ratio, as obtained from the shift of the ATP synthesis equilibrium induced by changing the transmembrane ΔpH (varying either pH(in) or pH(out)) is 4.0±0.1. The structural H(+)/ATP ratio, calculated from the ratio of proton binding sites on the c-subunit-ring in F(0) to the catalytic nucleotide binding sites on the β-subunits in F(1), is c/β=14/3=4.7. We infer that the energy of 0.7 protons per ATP that flow through the enzyme, but do not contribute to shifting the ATP/(ADP·Pi) ratio, is used for additional processes within the enzyme, such as activation, and/or energy dissipation, due e.g. to internal uncoupling. The ratio between the thermodynamic and the structural H(+)/ATP values is 0.85, and we conclude that this value represents the efficiency of the chemiosmotic energy conversion within the chloroplast H(+)-ATP synthase. Copyright © 2016 Elsevier B.V. All rights reserved.

Final-Approach-Spacing Subsystem For Air Traffic

NASA Technical Reports Server (NTRS)

Davis, Thomas J.; Erzberger, Heinz; Bergeron, Hugh

1992-01-01

Automation subsystem of computers, computer workstations, communication equipment, and radar helps air-traffic controllers in terminal radar approach-control (TRACON) facility manage sequence and spacing of arriving aircraft for both efficiency and safety. Called FAST (Final Approach Spacing Tool), subsystem enables controllers to choose among various levels of automation.

Installation package for the Solaron solar subsystem

NASA Technical Reports Server (NTRS)

1979-01-01

Information that is intended to be a guide for installation, operation, and maintenance of the various solar subsystems is presented. The subsystems consist of the following: collectors, storage, transport (air handler) and controller for heat pump and peak storage. Two prototype residential systems were installed at Akron, Ohio, and Duffield, Virginia.

A Statistical Approach to Establishing Subsystem Environmental Test Specifications

NASA Technical Reports Server (NTRS)

Keegan, W. B.

1974-01-01

Results are presented of a research task to evaluate structural responses at various subsystem mounting locations during spacecraft level test exposures to the environments of mechanical shock, acoustic noise, and random vibration. This statistical evaluation is presented in the form of recommended subsystem test specifications for these three environments as normalized to a reference set of spacecraft test levels and are thus suitable for extrapolation to a set of different spacecraft test levels. The recommendations are dependent upon a subsystem's mounting location in a spacecraft, and information is presented on how to determine this mounting zone for a given subsystem.

Fluorescent ATP analog mant-ATP reports dynein activity in the isolated Chlamydomonas axoneme

NASA Astrophysics Data System (ADS)

Feofilova, Maria; Howard, Jonathon

Eukaryotic flagella are long rod-like extensions of cells, which play a fundamental role in single cell movement, as well as in fluid transport. Flagella contain a highly evolutionary conserved mechanical structure called the axoneme. The motion of the flagellum is generated by dynein motor proteins located all along the length of the axoneme. How the force production of motors is controlled spatially and temporally is still an open question. Therefore, monitoring dynein activity in the axonemal structure is expected to provide novel insights in regulation of the beat. We use high sensitivity fluorescence microscopy to monitor the binding and hydrolysis kinetics of the fluorescently labeled ATP analogue mant-ATP (2'(3')-O-(N-methylanthraniloyl) adenosine 5'-triphosphate), which is known to support dynein activity. By studying the kinetics of mant-ATP fluorescence, we identified distinct mant-ATP binding sites in the axoneme. The application of this method to axonemes with reduced amounts of dynein, showed evidence that one of the sites is associated with binding to dynein. In the future, we would like to use this method to find the spatial distribution of dynein activity in the axoneme.

Spacecraft expected cost analysis with k-out-of-n:G subsystems

NASA Technical Reports Server (NTRS)

Patterson, Richard; Suich, Ron

1991-01-01

In designing a subsystem for a spacecraft, the design engineer is often faced with a number of options ranging from planning an inexpensive subsystem with low reliability to selecting a highly reliable system that would cost much more. We minimize the total of the cost of the subsytem and the costs that would occur if the subsystem fails. We choose the subsystem with the lowest total. A k-out-of-n:G subsystem has n modules, of which k are required to be good for the subsystem to be good. We examine two models to illustrate the principles of the k-out-of-n:G subsystem designs. For the first model, the following assumptions are necessary: the probability of failure of any module in the system is not affected by the failure of any other module; and each of the modules has the same probabillity of success. For the second model we are also free to choose k in our subsystem.

Magnetic field affects enzymatic ATP synthesis.

PubMed

Buchachenko, Anatoly L; Kuznetsov, Dmitry A

2008-10-01

The rate of ATP synthesis by creatine kinase extracted from V. xanthia venom was shown to depend on the magnetic field. The yield of ATP produced by enzymes with 24Mg2+ and 26Mg2+ ions in catalytic sites increases by 7-8% at 55 mT and then decreases at 80 mT. For enzyme with 25Mg2+ ion in a catalytic site, the ATP yield increases by 50% and 70% in the fields 55 and 80 mT, respectively. In the Earth field the rate of ATP synthesis by enzyme, in which Mg2+ ion has magnetic nucleus 25Mg, is 2.5 times higher than that by enzymes, in which Mg2+ ion has nonmagnetic, spinless nuclei 24Mg or 26Mg. Both magnetic field effect and magnetic isotope effect demonstrate that the ATP synthesis is an ion-radical process, affected by Zeeman interaction and hyperfine coupling in the intermediate ion-radical pair.

Cervical anterior transpedicular screw fixation (ATPS)—Part II. Accuracy of manual insertion and pull-out strength of ATPS

PubMed Central

Acosta, Frank; Tauber, Mark; Fox, Michael; Martin, Hudelmaier; Forstner, Rosmarie; Augat, Peter; Penzkofer, Rainer; Pirich, Christian; Kässmann, H.; Resch, Herbert; Hitzl, Wolfgang

2008-01-01

Reconstruction after multilevel decompression of the cervical spine, especially in the weakened osteoporotic, neoplastic or infectious spine often requires circumferential stabilization and fusion. To avoid the additional posterior surgery in these cases while increasing rigidity of anterior-only screw-plate constructs, the authors introduce the concept of anterior transpedicular screw (ATPS) fixation. We demonstrated its morphological feasibility as well as its indications in a previous study in Part I of our project. Consequently, the objectives of the current study were to assess the ex vivo accuracy of placing ATPS into the cervical vertebra as well as the biomechanical performance of ATPS in comparison to traditional vertebral body screws (VBS) in terms of pull-out strength (POS). Twenty-three ATPS were inserted alternately to two screws into the pedicles and vertebral bodies, respectively, of six cadaveric specimens from C3–T1. For insertion of ATPS, a manual fluoroscopically assisted technique was used. Pre- and post insertional CT-scans were used to assess accuracy of ATPS insertion in the axial and sagittal planes. A newly designed grading system and accuracy score were used to delineate accuracy of ATPS insertion. Following insertion of screws, 23 ATPS and 22 VBS were subjected to pull-out testing (POT). The bone mineral density (BMD) of each specimen was assessed prior to POT. Statistical analysis showed that the incidence of correctly placed screws and non-critical pedicles breaches in axial plane was 78.3%, and 95.7% in sagittal plane. Hence, according to our definition of “critical” pedicle breach that exposes neurovascular structures at risk, 21.7% (n = 5) of all ATPS inserted showed a critical pedicle breach in axial plane. Notably, no critical pedicle perforation occurred at the C6 to T1 levels. Pull-out testing of ATPS and VBS revealed that pull-out resistance of ATPS was 2.5-fold that of VBS. Mean POS of 23 ATPS with a mean BMD of 0.566�

Apollo experience report: Lunar module instrumentation subsystem

NASA Technical Reports Server (NTRS)

Obrien, D. E., III; Woodfill, J. R., IV

1972-01-01

The design concepts and philosophies of the lunar module instrumentation subsystem are discussed along with manufacturing and systems integration. The experience gained from the program is discussed, and recommendations are made for making the subsystem more compatible and flexible in system usage. Characteristics of lunar module caution and warning circuits are presented.

Hierarchical design of an electro-hydraulic actuator based on robust LPV methods

NASA Astrophysics Data System (ADS)

Németh, Balázs; Varga, Balázs; Gáspár, Péter

2015-08-01

The paper proposes a hierarchical control design of an electro-hydraulic actuator, which is used to improve the roll stability of vehicles. The purpose of the control system is to generate a reference torque, which is required by the vehicle dynamic control. The control-oriented model of the actuator is formulated in two subsystems. The high-level hydromotor is described in a linear form, while the low-level spool valve is a polynomial system. These subsystems require different control strategies. At the high level, a linear parameter-varying control is used to guarantee performance specifications. At the low level, a control Lyapunov-function-based algorithm, which creates discrete control input values of the valve, is proposed. The interaction between the two subsystems is guaranteed by the spool displacement, which is control input at the high level and must be tracked at the low-level control. The spool displacement has physical constraints, which must also be incorporated into the control design. The robust design of the high-level control incorporates the imprecision of the low-level control as an uncertainty of the system.

Balancing reliability and cost to choose the best power subsystem

NASA Technical Reports Server (NTRS)

Suich, Ronald C.; Patterson, Richard L.

1991-01-01

A mathematical model is presented for computing total (spacecraft) subsystem cost including both the basic subsystem cost and the expected cost due to the failure of the subsystem. This model is then used to determine power subsystem cost as a function of reliability and redundancy. Minimum cost and maximum reliability and/or redundancy are not generally equivalent. Two example cases are presented. One is a small satellite, and the other is an interplanetary spacecraft.

An ATP synthase harboring an atypical γ-subunit is involved in ATP synthesis in tomato fruit chromoplasts.

PubMed

Pateraki, Irini; Renato, Marta; Azcón-Bieto, Joaquín; Boronat, Albert

2013-04-01

Chromoplasts are non-photosynthetic plastids specialized in the synthesis and accumulation of carotenoids. During fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts in a process characterized by the degradation of the thylakoid membranes, and by the active synthesis and accumulation of carotenoids. This transition renders chromoplasts unable to photochemically synthesize ATP, and therefore these organelles need to obtain the ATP required for anabolic processes through alternative sources. It is widely accepted that the ATP used for biosynthetic processes in non-photosynthetic plastids is imported from the cytosol or is obtained through glycolysis. In this work, however, we show that isolated tomato (Solanum lycopersicum) fruit chromoplasts are able to synthesize ATP de novo through a respiratory pathway using NADPH as an electron donor. We also report the involvement of a plastidial ATP synthase harboring an atypical γ-subunit induced during ripening, which lacks the regulatory dithiol domain present in plant and algae chloroplast γ-subunits. Silencing of this atypical γ-subunit during fruit ripening impairs the capacity of isolated chromoplast to synthesize ATP de novo. We propose that the replacement of the γ-subunit present in tomato leaf and green fruit chloroplasts by the atypical γ-subunit lacking the dithiol domain during fruit ripening reflects evolutionary changes, which allow the operation of chromoplast ATP synthase under the particular physiological conditions found in this organelle. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

A taste for ATP: neurotransmission in taste buds

PubMed Central

Kinnamon, Sue C.; Finger, Thomas E.

2013-01-01

Not only is ATP a ubiquitous source of energy but it is also used widely as an intercellular signal. For example, keratinocytes release ATP in response to numerous external stimuli including pressure, heat, and chemical insult. The released ATP activates purinergic receptors on nerve fibers to generate nociceptive signals. The importance of an ATP signal in epithelial-to-neuronal signaling is nowhere more evident than in the taste system. The receptor cells of taste buds release ATP in response to appropriate stimulation by tastants and the released ATP then activates P2X2 and P2X3 receptors on the taste nerves. Genetic ablation of the relevant P2X receptors leaves an animal without the ability to taste any primary taste quality. Of interest is that release of ATP by taste receptor cells occurs in a non-vesicular fashion, apparently via gated membrane channels. Further, in keeping with the crucial role of ATP as a neurotransmitter in this system, a subset of taste cells expresses a specific ectoATPase, NTPDase2, necessary to clear extracellular ATP which otherwise will desensitize the P2X receptors on the taste nerves. The unique utilization of ATP as a key neurotransmitter in the taste system may reflect the epithelial rather than neuronal origins of the receptor cells. PMID:24385952

Statistical Design Model (SDM) of satellite thermal control subsystem

NASA Astrophysics Data System (ADS)

Mirshams, Mehran; Zabihian, Ehsan; Aarabi Chamalishahi, Mahdi

2016-07-01

Satellites thermal control, is a satellite subsystem that its main task is keeping the satellite components at its own survival and activity temperatures. Ability of satellite thermal control plays a key role in satisfying satellite's operational requirements and designing this subsystem is a part of satellite design. In the other hand due to the lack of information provided by companies and designers still doesn't have a specific design process while it is one of the fundamental subsystems. The aim of this paper, is to identify and extract statistical design models of spacecraft thermal control subsystem by using SDM design method. This method analyses statistical data with a particular procedure. To implement SDM method, a complete database is required. Therefore, we first collect spacecraft data and create a database, and then we extract statistical graphs using Microsoft Excel, from which we further extract mathematical models. Inputs parameters of the method are mass, mission, and life time of the satellite. For this purpose at first thermal control subsystem has been introduced and hardware using in the this subsystem and its variants has been investigated. In the next part different statistical models has been mentioned and a brief compare will be between them. Finally, this paper particular statistical model is extracted from collected statistical data. Process of testing the accuracy and verifying the method use a case study. Which by the comparisons between the specifications of thermal control subsystem of a fabricated satellite and the analyses results, the methodology in this paper was proved to be effective. Key Words: Thermal control subsystem design, Statistical design model (SDM), Satellite conceptual design, Thermal hardware

Dynamics of the metal binding domains and regulation of the human copper transporters ATP7B and ATP7A.

PubMed

Yu, Corey H; Dolgova, Natalia V; Dmitriev, Oleg Y

2017-04-01

Copper transporters ATP7A and ATP7B regulate copper levels in the human cells and deliver copper to the biosynthetic pathways. ATP7A and ATP7B belong to the P-type ATPases and share much of the domain architecture and the mechanism of ATP hydrolysis with the other, well-studied, enzymes of this type. A unique structural feature of the copper ATPases is the chain of six cytosolic metal-binding domains (MBDs), which are believed to be involved in copper-dependent regulation of the activity and intracellular localization of these enzymes. Although the structures of all the MBDs have been solved, the mechanism of copper-dependent regulation of ATP7B and ATP7A, the roles of individual MBDs, and the relationship between the regulatory and catalytic copper binding are still unknown. We describe the structure and dynamics of the MBDs, review the current knowledge about their functional roles and propose a mechanism of regulation of ATP7B by copper-dependent changes in the dynamics and conformation of the MBD chain. Transient interactions between the MBDs, rather than transitions between distinct static conformations are likely to form the structural basis of regulation of the ATP-dependent copper transporters in human cells. © 2016 IUBMB Life, 69(4):226-235, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Mark 3 VLBI system: Tropospheric calibration subsystems

NASA Technical Reports Server (NTRS)

Resch, G. M.

1980-01-01

Tropospheric delay calibrations are implemented in the Mark 3 system with two subsystems. Estimates of the dry component of tropospheric delay are provided by accurate barometric data from a subsystem of surface meteorological sensors (SMS). An estimate of the wet component of tropospheric delay is provided by a water vapor radiometer (WVR). Both subsystems interface directly to the ASCII Transceiver bus of the Mark 3 system and are operated by the control computer. Seven WVR's under construction are designed to operate in proximity to a radio telescope and can be commanded to point along the line-of-sight to a radio source. They should provide a delay estimate that is accurate to the + or - 2 cm level.

Simplified power processing for ion-thruster subsystems

NASA Technical Reports Server (NTRS)

Wessel, F. J.; Hancock, D. J.

1983-01-01

A design for a greatly simplified power-processing unit (SPPU) for the 8-cm diameter mercury-ion-thruster subsystem is discussed. This SPPU design will provide a tenfold reduction in parts count, a decrease in system mass and cost, and an increase in system reliability compared to the existing power-processing unit (PPU) used in the Hughes/NASA Lewis Research Center Ion Auxiliary Propulsion Subsystem. The simplifications achieved in this design will greatly increase the attractiveness of ion propulsion in near-term and future spacecraft propulsion applications. A description of a typical ion-thruster subsystem is given. An overview of the thruster/power-processor interface requirements is given. Simplified thruster power processing is discussed.

ATP Synthesis in the Extremely Halophilic Bacteria

NASA Technical Reports Server (NTRS)

Hochstein, Lawrence I.; Morrison, David (Technical Monitor)

1994-01-01

The proton-translocating ATPases are multimeric enzymes that carry out a multitude of essential functions. Their origin and evolution represent a seminal event in the early evolution of life. Amino acid sequences of the two largest subunits from archaeal ATPases (A-ATPases), vacuolar ATPases (V-ATPases), and FOF1-ATP syntheses (FATPases) suggest these ATPases evolved from an ancestral vacuolar-like ATP syntheses. A necessary consequence of this notion is that the A-ATPases are ATP syntheses. With the possible exception of the A-ATPase from Halobacterium salinarium. no A-ATPase has been demonstrated to synthesize ATP. The evidence for this case is dubious since ATP synthesis occurs only when conditions are distinctively unphysiological. We demonstrated that ATP synthesis in H.saccharovorum is inconsistent with the operation of an A-type ATPase. In order to determine if this phenomenon was unique to H. saccharovorum, ATP synthesis was examined in various extremely halophilic bacteria with the goal of ascertaining if it resembled what occurred in a. saccharovorum, or was consistent with the operation of an A-type ATPase. A-, V-, and F-type ATPases respond singularly to certain inhibitors. Therefore, the effect of these inhibitors on ATP synthesis in several extreme halophiles was determined. Inhibitors that either blocked or collapsed proton-gradients inhibited the steady state synthesis of ATP thus verifying that synthesis took place at the expense of a proton gradient. Azide, an inhibitor of F-ATPases inhibited ATP synthesis. Since the arginine-dependent synthesis of ATP, which occurs by way of substrate-level phosphorylation, was unaffected by azide, it was unlikely that azide acted as an "uncoupler." N -ethylmaleimide and nitrate, which inhibit V- and A-ATPases, either did not inhibit ATP synthesis or resulted in higher steady-state levels of ATP. These results suggest there are two types of proton-motive ATPases in the extreme halophiles (and presumably in other

Maintenance and operations cost model for DSN subsystems

NASA Technical Reports Server (NTRS)

Burt, R. W.; Lesh, J. R.

1977-01-01

A procedure is described which partitions the recurring costs of the Deep Space Network (DSN) over the individual DSN subsystems. The procedure results in a table showing the maintenance, operations, sustaining engineering and supportive costs for each subsystems.

Snapshots of the maltose transporter during ATP hydrolysis

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

Oldham, Michael L.; Chen, Jue

2011-12-05

ATP-binding cassette transporters are powered by ATP, but the mechanism by which these transporters hydrolyze ATP is unclear. In this study, four crystal structures of the full-length wild-type maltose transporter, stabilized by adenosine 5{prime}-({beta},{gamma}-imido)triphosphate or ADP in conjunction with phosphate analogs BeF{sub 3}{sup -}, VO{sub 4}{sup 3-}, or AlF{sub 4}{sup -}, were determined to 2.2- to 2.4-{angstrom} resolution. These structures led to the assignment of two enzymatic states during ATP hydrolysis and demonstrate specific functional roles of highly conserved residues in the nucleotide-binding domain, suggesting that ATP-binding cassette transporters catalyze ATP hydrolysis via a general base mechanism.

Development status of a preprototype water electrolysis subsystem

NASA Technical Reports Server (NTRS)

Martin, R. B.; Erickson, A. C.

1981-01-01

A preprototype water electrolysis subsystem was designed and fabricated for NASA's advanced regenerative life support program. A solid polymer is used for the cell electrolyte. The electrolysis module has 12 cells that can generate 5.5 kg/day of oxygen for the metabolic requirements of three crewmembers, for cabin leakage, and for the oxygen and hydrogen required for carbon dioxide collection and reduction processes. The subsystem can be operated at a pressure between 276 and 2760 kN/sq m and in a continuous constant-current, cyclic, or standby mode. A microprocessor is used to aid in operating the subsystem. Sensors and controls provide fault detection and automatic shutdown. The results of development, demonstration, and parametric testing are presented. Modifications to enhance operation in an integrated and manned test are described. Prospective improvements for the electrolysis subsystem are discussed.

Autonomous navigation - The ARMMS concept. [Autonomous Redundancy and Maintenance Management Subsystem

NASA Technical Reports Server (NTRS)

Wood, L. J.; Jones, J. B.; Mease, K. D.; Kwok, J. H.; Goltz, G. L.; Kechichian, J. A.

1984-01-01

A conceptual design is outlined for the navigation subsystem of the Autonomous Redundancy and Maintenance Management Subsystem (ARMMS). The principal function of this navigation subsystem is to maintain the spacecraft over a specified equatorial longitude to within + or - 3 deg. In addition, the navigation subsystem must detect and correct internal faults. It comprises elements for a navigation executive and for orbit determination, trajectory, maneuver planning, and maneuver command. Each of these elements is described. The navigation subsystem is to be used in the DSCS III spacecraft.

Electron transfer precedes ATP hydrolysis during nitrogenase catalysis

PubMed Central

Duval, Simon; Danyal, Karamatullah; Shaw, Sudipta; Lytle, Anna K.; Dean, Dennis R.; Hoffman, Brian M.; Antony, Edwin; Seefeldt, Lance C.

2013-01-01

The biological reduction of N2 to NH3 catalyzed by Mo-dependent nitrogenase requires at least eight rounds of a complex cycle of events associated with ATP-driven electron transfer (ET) from the Fe protein to the catalytic MoFe protein, with each ET coupled to the hydrolysis of two ATP molecules. Although steps within this cycle have been studied for decades, the nature of the coupling between ATP hydrolysis and ET, in particular the order of ET and ATP hydrolysis, has been elusive. Here, we have measured first-order rate constants for each key step in the reaction sequence, including direct measurement of the ATP hydrolysis rate constant: kATP = 70 s−1, 25 °C. Comparison of the rate constants establishes that the reaction sequence involves four sequential steps: (i) conformationally gated ET (kET = 140 s−1, 25 °C), (ii) ATP hydrolysis (kATP = 70 s−1, 25 °C), (iii) Phosphate release (kPi = 16 s−1, 25 °C), and (iv) Fe protein dissociation from the MoFe protein (kdiss = 6 s−1, 25 °C). These findings allow completion of the thermodynamic cycle undergone by the Fe protein, showing that the energy of ATP binding and protein–protein association drive ET, with subsequent ATP hydrolysis and Pi release causing dissociation of the complex between the Feox(ADP)2 protein and the reduced MoFe protein. PMID:24062462

ATP-sulfurylase, sulfur-compounds, and plant stress tolerance

PubMed Central

Anjum, Naser A.; Gill, Ritu; Kaushik, Manjeri; Hasanuzzaman, Mirza; Pereira, Eduarda; Ahmad, Iqbal; Tuteja, Narendra; Gill, Sarvajeet S.

2015-01-01

Sulfur (S) stands fourth in the list of major plant nutrients after N, P, and K. Sulfate (SO42-), a form of soil-S taken up by plant roots is metabolically inert. As the first committed step of S-assimilation, ATP-sulfurylase (ATP-S) catalyzes SO42--activation and yields activated high-energy compound adenosine-5′-phosphosulfate that is reduced to sulfide (S2-) and incorporated into cysteine (Cys). In turn, Cys acts as a precursor or donor of reduced S for a range of S-compounds such as methionine (Met), glutathione (GSH), homo-GSH (h-GSH), and phytochelatins (PCs). Among S-compounds, GSH, h-GSH, and PCs are known for their involvement in plant tolerance to varied abiotic stresses, Cys is a major component of GSH, h-GSH, and PCs; whereas, several key stress-metabolites such as ethylene, are controlled by Met through its first metabolite S-adenosylmethionine. With the major aim of briefly highlighting S-compound-mediated role of ATP-S in plant stress tolerance, this paper: (a) overviews ATP-S structure/chemistry and occurrence, (b) appraises recent literature available on ATP-S roles and regulations, and underlying mechanisms in plant abiotic and biotic stress tolerance, (c) summarizes ATP-S-intrinsic regulation by major S-compounds, and (d) highlights major open-questions in the present context. Future research in the current direction can be devised based on the discussion outcomes. PMID:25904923

Cerebrospinal fluid ATP metabolites in multiple sclerosis.

PubMed

Lazzarino, G; Amorini, A M; Eikelenboom, M J; Killestein, J; Belli, A; Di Pietro, V; Tavazzi, B; Barkhof, F; Polman, C H; Uitdehaag, B M J; Petzold, A

2010-05-01

Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis. Our objective was to test whether ATP depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis. The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up. Central ATP depletion (sum of ATP metabolites >19.7 micromol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p< 0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort (r= 0.66, p= 0.001) and subgroups (relapsing-remitting patients: r= 0.79, p< 0.05 and secondary progressive/primary progressive patients: r= 0.69, p< 0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration. The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.

Responses of Rat P2X2 Receptors to Ultrashort Pulses of ATP Provide Insights into ATP Binding and Channel Gating

PubMed Central

Moffatt, Luciano; Hume, Richard I.

2007-01-01

To gain insight into the way that P2X2 receptors localized at synapses might function, we explored the properties of outside-out patches containing many of these channels as ATP was very rapidly applied and removed. Using a new method to calibrate the speed of exchange of solution over intact patches, we were able to reliably produce applications of ATP lasting <200 μs. For all concentrations of ATP, there was a delay of at least 80 μs between the time when ATP arrived at the receptor and the first detectable flow of inward current. In response to 200-μs pulses of ATP, the time constant of the rising phase of the current was ∼600 μs. Thus, most channel openings occurred when no free ATP was present. The current deactivated with a time constant of ∼60 ms. The amplitude of the peak response to a brief pulse of a saturating concentration of ATP was ∼70% of that obtained during a long application of the same concentration of ATP. Thus, ATP leaves fully liganded channels without producing an opening at least 30% of the time. Extensive kinetic modeling revealed three different schemes that fit the data well, a sequential model and two allosteric models. To account for the delay in opening at saturating ATP, it was necessary to incorporate an intermediate closed state into all three schemes. These kinetic properties indicate that responses to ATP at synapses that use homomeric P2X2 receptors would be expected to greatly outlast the duration of the synaptic ATP transient produced by a single presynaptic spike. Like NMDA receptors, P2X2 receptors provide the potential for complex patterns of synaptic integration over a time scale of hundreds of milliseconds. PMID:17664346

TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F F{sub 1}-ATP synthase and ubiquinone

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

Shertzer, Howard G.; Genter, Mary Beth; Shen, Dongxiao

2006-12-15

Mitochondria generate ATP and participate in signal transduction and cellular pathology and/or cell death. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) decreases hepatic ATP levels and generates mitochondrial oxidative DNA damage, which is exacerbated by increasing mitochondrial glutathione redox state and by inner membrane hyperpolarization. This study identifies mitochondrial targets of TCDD that initiate and sustain reactive oxygen production and decreased ATP levels. One week after treating mice with TCDD, liver ubiquinone (Q) levels were significantly decreased, while rates of succinoxidase and Q-cytochrome c oxidoreductase activities were increased. However, the expected increase in Q reduction state following TCDD treatment did not occur; instead, Q wasmore » more oxidized. These results could be explained by an ATP synthase defect, a premise supported by the unusual finding that TCDD lowers ATP/O ratios without concomitant changes in respiratory control ratios. Such results suggest either a futile cycle in ATP synthesis, or hydrolysis of newly synthesized ATP prior to release. The TCDD-mediated decrease in Q, concomitant with an increase in respiration, increases complex 3 redox cycling. This acts in concert with glutathione to increase membrane potential and reactive oxygen production. The proposed defect in ATP synthase explains both the greater respiratory rates and the lower tissue ATP levels.« less

ATP synthesis in Halobacterium saccharovorum: evidence that synthesis may be catalysed by an F0F1-ATP synthase

NASA Technical Reports Server (NTRS)

Hochstein, L. I.

1992-01-01

Halobacterium saccharovorum synthesized ATP in response to a pH shift from 8 to 6.2. Synthesis was inhibited by carbonyl cyanide m-chloro-phenylhydrazone, dicyclohexylcarbodiimide, and azide. Nitrate, an inhibitor of the membrane-bound ATPase previously isolated from this organism, did not inhibit ATP synthesis. N-Ethymaleimide, which also inhibited this ATPase, stimulated the production of ATP. These observations suggested that H. saccharovorum synthesized and hydrolysed ATP using different enzymes and that the vacuolar-like ATPase activity previously described in H. saccharovorum was an ATPase whose function is yet to be identified.

An Algorithm for Integrated Subsystem Embodiment and System Synthesis

NASA Technical Reports Server (NTRS)

Lewis, Kemper

1997-01-01

Consider the statement,'A system has two coupled subsystems, one of which dominates the design process. Each subsystem consists of discrete and continuous variables, and is solved using sequential analysis and solution.' To address this type of statement in the design of complex systems, three steps are required, namely, the embodiment of the statement in terms of entities on a computer, the mathematical formulation of subsystem models, and the resulting solution and system synthesis. In complex system decomposition, the subsystems are not isolated, self-supporting entities. Information such as constraints, goals, and design variables may be shared between entities. But many times in engineering problems, full communication and cooperation does not exist, information is incomplete, or one subsystem may dominate the design. Additionally, these engineering problems give rise to mathematical models involving nonlinear functions of both discrete and continuous design variables. In this dissertation an algorithm is developed to handle these types of scenarios for the domain-independent integration of subsystem embodiment, coordination, and system synthesis using constructs from Decision-Based Design, Game Theory, and Multidisciplinary Design Optimization. Implementation of the concept in this dissertation involves testing of the hypotheses using example problems and a motivating case study involving the design of a subsonic passenger aircraft.

Bioanalytical Applications of Real-Time ATP Imaging Via Bioluminescence

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

Gruenhagen, Jason Alan

The research discussed within involves the development of novel applications of real-time imaging of adenosine 5'-triphosphate (ATP). ATP was detected via bioluminescence and the firefly luciferase-catalyzed reaction of ATP and luciferin. The use of a microscope and an imaging detector allowed for spatially resolved quantitation of ATP release. Employing this method, applications in both biological and chemical systems were developed. First, the mechanism by which the compound 48/80 induces release of ATP from human umbilical vein endothelial cells (HUVECs) was investigated. Numerous enzyme activators and inhibitors were utilized to probe the second messenger systems involved in release. Compound 48/80 activatedmore » a G{sub q}-type protein to initiate ATP release from HUVECs. Ca 2+ imaging along with ATP imaging revealed that activation of phospholipase C and induction of intracellular Ca 2+ signaling were necessary for release of ATP. Furthermore, activation of protein kinase C inhibited the activity of phospholipase C and thus decreased the magnitude of ATP release. This novel release mechanism was compared to the existing theories of extracellular release of ATP. Bioluminescence imaging was also employed to examine the role of ATP in the field of neuroscience. The central nervous system (CNS) was dissected from the freshwater snail Lymnaea stagnalis. Electrophysiological experiments demonstrated that the neurons of the Lymnaea were not damaged by any of the components of the imaging solution. ATP was continuously released by the ganglia of the CNS for over eight hours and varied from ganglion to ganglion and within individual ganglia. Addition of the neurotransmitters K + and serotonin increased release of ATP in certain regions of the Lymnaea CNS. Finally, the ATP imaging technique was investigated for the study of drug release systems. MCM-41-type mesoporous nanospheres were loaded with ATP and end-capped with mercaptoethanol functionalized Cd

Automated biowaste sampling system urine subsystem operating model, part 1

NASA Technical Reports Server (NTRS)

Fogal, G. L.; Mangialardi, J. K.; Rosen, F.

1973-01-01

The urine subsystem automatically provides for the collection, volume sensing, and sampling of urine from six subjects during space flight. Verification of the subsystem design was a primary objective of the current effort which was accomplished thru the detail design, fabrication, and verification testing of an operating model of the subsystem.

Default Mode Network Subsystems are Differentially Disrupted in Posttraumatic Stress Disorder

PubMed Central

Miller, Danielle R.; Hayes, Scott M.; Hayes, Jasmeet P.; Spielberg, Jeffrey M.; Lafleche, Ginette; Verfaellie, Mieke

2017-01-01

Background Posttraumatic stress disorder (PTSD) is a psychiatric disorder characterized by debilitating re-experiencing, avoidance, and hyperarousal symptoms following trauma exposure. Recent evidence suggests that individuals with PTSD show disrupted functional connectivity in the default mode network, an intrinsic network that consists of a midline core, a medial temporal lobe (MTL) subsystem, and a dorsomedial prefrontal cortex (dMPFC) subsystem. The present study examined whether functional connectivity in these subsystems is differentially disrupted in PTSD. Methods Sixty-nine returning war Veterans with PTSD and 44 trauma-exposed Veterans without PTSD underwent resting state functional MRI (rs-fMRI). To examine functional connectivity, seeds were placed in the core hubs of the default mode network, namely the posterior cingulate cortex (PCC) and anterior medial PFC (aMPFC), and in each subsystem. Results Compared to controls, individuals with PTSD had reduced functional connectivity between the PCC and the hippocampus, a region of the MTL subsystem. Groups did not differ in connectivity between the PCC and dMPFC subsystem or between the aMPFC and any region within either subsystem. In the PTSD group, connectivity between the PCC and hippocampus was negatively associated with avoidance/numbing symptoms. Examination of the MTL and dMPFC subsystems revealed reduced anticorrelation between the ventromedial PFC (vMPFC) seed of the MTL subsystem and the dorsal anterior cingulate cortex in the PTSD group. Conclusions Our results suggest that selective alterations in functional connectivity in the MTL subsystem of the default mode network in PTSD may be an important factor in PTSD pathology and symptomatology. PMID:28435932

Default Mode Network Subsystems are Differentially Disrupted in Posttraumatic Stress Disorder.

PubMed

Miller, Danielle R; Hayes, Scott M; Hayes, Jasmeet P; Spielberg, Jeffrey M; Lafleche, Ginette; Verfaellie, Mieke

2017-05-01

Posttraumatic stress disorder (PTSD) is a psychiatric disorder characterized by debilitating re-experiencing, avoidance, and hyperarousal symptoms following trauma exposure. Recent evidence suggests that individuals with PTSD show disrupted functional connectivity in the default mode network, an intrinsic network that consists of a midline core, a medial temporal lobe (MTL) subsystem, and a dorsomedial prefrontal cortex (dMPFC) subsystem. The present study examined whether functional connectivity in these subsystems is differentially disrupted in PTSD. Sixty-nine returning war Veterans with PTSD and 44 trauma-exposed Veterans without PTSD underwent resting state functional MRI (rs-fMRI). To examine functional connectivity, seeds were placed in the core hubs of the default mode network, namely the posterior cingulate cortex (PCC) and anterior medial PFC (aMPFC), and in each subsystem. Compared to controls, individuals with PTSD had reduced functional connectivity between the PCC and the hippocampus, a region of the MTL subsystem. Groups did not differ in connectivity between the PCC and dMPFC subsystem or between the aMPFC and any region within either subsystem. In the PTSD group, connectivity between the PCC and hippocampus was negatively associated with avoidance/numbing symptoms. Examination of the MTL and dMPFC subsystems revealed reduced anticorrelation between the ventromedial PFC (vMPFC) seed of the MTL subsystem and the dorsal anterior cingulate cortex in the PTSD group. Our results suggest that selective alterations in functional connectivity in the MTL subsystem of the default mode network in PTSD may be an important factor in PTSD pathology and symptomatology.

Development of a preprototype times wastewater recovery subsystem

NASA Technical Reports Server (NTRS)

Roebelen, G. J., Jr.; Dehner, G. F.

1982-01-01

A three-man wastewater recovery preprototype subsystem using a hollow fiber membrane evaporator with a thermoelectric heat pump to provide efficient potable water recovery from wastewater on extended duration space flights was designed, fabricated, and tested at one-gravity. Low power, compactness and gravity insensitive operation are featured in this vacuum distillation subsystem. The tubular hollow fiber elements provide positive liquid/gas phase control with no moving parts, and provide structural integrity, improving on previous flat sheet membrane designs. A thermoelectric heat pump provides latent energy recovery. Application and integration of these key elements solved problems inherent in all previous reclamation subsystem designs.

Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages.

PubMed

da Silva-Souza, Hercules Antônio; Lira, Maria Nathalia de; Costa-Junior, Helio Miranda; da Cruz, Cristiane Monteiro; Vasconcellos, Jorge Silvio Silva; Mendes, Anderson Nogueira; Pimenta-Reis, Gabriela; Alvarez, Cora Lilia; Faccioli, Lucia Helena; Serezani, Carlos Henrique; Schachter, Julieta; Persechini, Pedro Muanis

2014-07-01

We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO) metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis, but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7 receptors in macrophages. ATPe binding to P2X7 also induces large cationic and anionic organic molecules uptake in these cells, a process that involves at least two distinct transport mechanisms: one for cations and another for anions. Here we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes. In addition, we describe two new transport phenomena induced by these inhibitors in macrophages: a cation-selective uptake of fluorescent dyes and the release of ATP. The cation uptake requires secreted ATPe, but, differently from the P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA-cyclooxygenase pathway did not induce the cation uptake. The uptake of non-organic cations was investigated by measuring the free intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium suppressed the intracellular Ca(2+) signal without interfering in the uptake of cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of organic cations by a Ca(2+)- and P2X7-independent transport mechanism in macrophages. Copyright © 2014 Elsevier B.V. All rights reserved.

Laboratory measurements of on-board subsystems

NASA Technical Reports Server (NTRS)

Nuspl, P. P.; Dong, G.; Seran, H. C.

1991-01-01

Good progress was achieved on the test bed for on-board subsystems for future satellites. The test bed is for subsystems developed previously. Four test setups were configured in the INTELSAT technical labs: (1) TDMA on-board modem; (2) multicarrier demultiplexer demodulator; (3) IBS/IDR baseband processor; and (4) baseband switch matrix. The first three series of tests are completed and the tests on the BSM are in progress. Descriptions of test setups and major test results are included; the format of the presentation is outlined.

Clusterin (Apolipoprotein J), a Molecular Chaperone That Facilitates Degradation of the Copper-ATPases ATP7A and ATP7B*

PubMed Central

Materia, Stephanie; Cater, Michael A.; Klomp, Leo W. J.; Mercer, Julian F. B.; La Fontaine, Sharon

2011-01-01

The copper-transporting P1B-type ATPases (Cu-ATPases) ATP7A and ATP7B are key regulators of physiological copper levels. They function to maintain intracellular copper homeostasis by delivering copper to secretory compartments and by trafficking toward the cell periphery to export excess copper. Mutations in the genes encoding ATP7A and ATP7B lead to copper deficiency and toxicity disorders, Menkes and Wilson diseases, respectively. This report describes the interaction between the Cu-ATPases and clusterin and demonstrates a chaperone-like role for clusterin in facilitating their degradation. Clusterin interacted with both ATP7A and ATP7B in mammalian cells. This interaction increased under conditions of oxidative stress and with mutations in ATP7B that led to its misfolding and mislocalization. A Wilson disease patient mutation (G85V) led to enhanced ATP7B turnover, which was further exacerbated when cells overexpressed clusterin. We demonstrated that clusterin-facilitated degradation of mutant ATP7B is likely to involve the lysosomal pathway. The knockdown and overexpression of clusterin increased and decreased, respectively, the Cu-ATPase-mediated copper export capacity of cells. These results highlight a new role for intracellular clusterin in mediating Cu-ATPase quality control and hence in the normal maintenance of copper homeostasis, and in promoting cell survival in the context of disease. Based on our findings, it is possible that variations in clusterin expression and function could contribute to the variable clinical expression of Menkes and Wilson diseases. PMID:21242307

Automated Subsystem Control for Life Support System (ASCLSS)

NASA Technical Reports Server (NTRS)

Block, Roger F.

1987-01-01

The Automated Subsystem Control for Life Support Systems (ASCLSS) program has successfully developed and demonstrated a generic approach to the automation and control of space station subsystems. The automation system features a hierarchical and distributed real-time control architecture which places maximum controls authority at the lowest or process control level which enhances system autonomy. The ASCLSS demonstration system pioneered many automation and control concepts currently being considered in the space station data management system (DMS). Heavy emphasis is placed on controls hardware and software commonality implemented in accepted standards. The approach demonstrates successfully the application of real-time process and accountability with the subsystem or process developer. The ASCLSS system completely automates a space station subsystem (air revitalization group of the ASCLSS) which moves the crew/operator into a role of supervisory control authority. The ASCLSS program developed over 50 lessons learned which will aide future space station developers in the area of automation and controls..

Modular space station phase B extension, preliminary system design. Volume 4: Subsystems analyses

NASA Technical Reports Server (NTRS)

Antell, R. W.

1972-01-01

The subsystems tradeoffs, analyses, and preliminary design results are summarized. Analyses were made of the structural and mechanical, environmental control and life support, electrical power, guidance and control, reaction control, information, and crew habitability subsystems. For each subsystem a summary description is presented including subsystem requirements, subsystem description, and subsystem characteristics definition (physical, performance, and interface). The major preliminary design data and tradeoffs or analyses are described in detail at each of the assembly levels.

Minimize system cost by choosing optimal subsystem reliability and redundancy

NASA Technical Reports Server (NTRS)

Suich, Ronald C.; Patterson, Richard L.

1993-01-01

The basic question which we address in this paper is how to choose among competing subsystems. This paper utilizes both reliabilities and costs to find the subsystems with the lowest overall expected cost. The paper begins by reviewing some of the concepts of expected value. We then address the problem of choosing among several competing subsystems. These concepts are then applied to k-out-of-n: G subsystems. We illustrate the use of the authors' basic program in viewing a range of possible solutions for several different examples. We then discuss the implications of various solutions in these examples.

Minoxidil opens mitochondrial K(ATP) channels and confers cardioprotection.

PubMed

Sato, Toshiaki; Li, Yulong; Saito, Tomoaki; Nakaya, Haruaki

2004-01-01

1. ATP-sensitive potassium channel in the mitochondrial inner membrane (mitoK(ATP) channel) rather than in the sarcolemma (sarcK(ATP) channel) appears to play an important role in cardioprotection. We examined the effect of minoxidil, a potent antihypertensive agent and hair growth stimulator, on sarcK(ATP) and mitoK(ATP) channels in guinea-pig ventricular myocytes. 2. Minoxidil activated a glybenclamide-sensitive sarcK(ATP) channel current in the whole-cell recording mode with an EC(50) of 182.6 microm. Minoxidil reversibly increased the flavoprotein oxidation, an index of mitoK(ATP) channel activity, in a concentration-dependent manner. The EC(50) for mitoK(ATP) channel activation was estimated to be 7.3 microm; this value was notably approximately 25-fold lower than that for sarcK(ATP) channel activation. 3. Minoxidil (10 microm) significantly attenuated the ouabain-induced increase of mitochondrial Ca(2+) concentration, which was measured by loading cells with rhod-2 fluorescence. Furthermore, pretreatment with minoxidil (10 microm) before 20-min no-flow ischaemia significantly improved the recovery of developed tension measured after 60 min of reperfusion in coronary perfused guinea-pig ventricular muscles. These cardioprotective effects of minoxidil were completely abolished by the mitoK(ATP) channel blocker 5-hydroxydecanoate (500 microm). 4. Our results indicate that minoxidil exerts a direct cardioprotective effect on heart muscle cells, an effect mediated by the selective activation of mitoK(ATP) channels.

Interface Supports Lightweight Subsystem Routing for Flight Applications

NASA Technical Reports Server (NTRS)

Lux, James P.; Block, Gary L.; Ahmad, Mohammad; Whitaker, William D.; Dillon, James W.

2010-01-01

A wireless avionics interface exploits the constrained nature of data networks in flight systems to use a lightweight routing method. This simplified routing means that a processor is not required, and the logic can be implemented as an intellectual property (IP) core in a field-programmable gate array (FPGA). The FPGA can be shared with the flight subsystem application. In addition, the router is aware of redundant subsystems, and can be configured to provide hot standby support as part of the interface. This simplifies implementation of flight applications requiring hot stand - by support. When a valid inbound packet is received from the network, the destination node address is inspected to determine whether the packet is to be processed by this node. Each node has routing tables for the next neighbor node to guide the packet to the destination node. If it is to be processed, the final packet destination is inspected to determine whether the packet is to be forwarded to another node, or routed locally. If the packet is local, it is sent to an Applications Data Interface (ADI), which is attached to a local flight application. Under this scheme, an interface can support many applications in a subsystem supporting a high level of subsystem integration. If the packet is to be forwarded to another node, it is sent to the outbound packet router. The outbound packet router receives packets from an ADI or a packet to be forwarded. It then uses a lookup table to determine the next destination for the packet. Upon detecting a remote subsystem failure, the routing table can be updated to autonomously bypass the failed subsystem.

Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus , a New Twist on ATP Formation

DOE PAGES

James, Kimberly L.; Ríos-Hernández, Luis A.; Wofford, Neil Q.; ...

2016-08-16

Syntrophus aciditrophicusis a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation byS. aciditrophicus. However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome ofS. aciditrophicusleaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show thatS. aciditrophicususes AMP-forming, acetyl-CoA synthetase (Acs1)more » for ATP synthesis from acetyl-CoA.acs1mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, ofS. aciditrophicusgrown in pure culture and coculture. Cell extracts ofS. aciditrophicushad low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified fromS. aciditrophicusand recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) inS. aciditrophicuscells support the operation of Acs1 in the acetate-forming direction. Thus,S. aciditrophicushas a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase. We find bacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA.Syntrophus aciditrophicusapparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as

Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus , a New Twist on ATP Formation

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

James, Kimberly L.; Ríos-Hernández, Luis A.; Wofford, Neil Q.

Syntrophus aciditrophicusis a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation byS. aciditrophicus. However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome ofS. aciditrophicusleaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show thatS. aciditrophicususes AMP-forming, acetyl-CoA synthetase (Acs1)more » for ATP synthesis from acetyl-CoA.acs1mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, ofS. aciditrophicusgrown in pure culture and coculture. Cell extracts ofS. aciditrophicushad low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified fromS. aciditrophicusand recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) inS. aciditrophicuscells support the operation of Acs1 in the acetate-forming direction. Thus,S. aciditrophicushas a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase. We find bacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA.Syntrophus aciditrophicusapparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as

Simulation verification techniques study. Subsystem simulation validation techniques

NASA Technical Reports Server (NTRS)

Duncan, L. M.; Reddell, J. P.; Schoonmaker, P. B.

1974-01-01

Techniques for validation of software modules which simulate spacecraft onboard systems are discussed. An overview of the simulation software hierarchy for a shuttle mission simulator is provided. A set of guidelines for the identification of subsystem/module performance parameters and critical performance parameters are presented. Various sources of reference data to serve as standards of performance for simulation validation are identified. Environment, crew station, vehicle configuration, and vehicle dynamics simulation software are briefly discussed from the point of view of their interfaces with subsystem simulation modules. A detailed presentation of results in the area of vehicle subsystems simulation modules is included. A list of references, conclusions and recommendations are also given.

United States Control Module Guidance, Navigation, and Control Subsystem Design Concept

NASA Technical Reports Server (NTRS)

Polites, M. E.; Bartlow, B. E.

1997-01-01

Should the Russian Space Agency (RSA) not participate in the International Space Station (ISS) program, then the United States (U.S.) National Aeronautics and Space Administration (NASA) may choose to execute the ISS mission. However, in order to do this, NASA must build two new space vehicles, which must perform the functions that the Russian vehicles and hardware were to perform. These functions include periodic ISS orbit reboost, initial ISS attitude control, and U.S. On-Orbit Segment (USOS) control Moment gyroscope (CMG) momentum desaturation. The two new NASA vehicles that must perform these functions are called the U.S. control module (USCM) and the U.S. resupply module. This paper presents a design concept for the USCM GN&C subsystem, which must play a major role in ISS orbit reboost and initial attitude control, plus USOS CMG momentum desaturation. The proposed concept is structured similar to the USOS GN&C subsystem, by design. It is very robust, in that it allows the USCM to assume a variety of vehicle attitudes and stay power-positive. It has a storage/safe mode that places the USCM in a gravity-gradient orientation and keeps it there for extended periods of time without consuming a great deal of propellant. Simulation results are presented and discussed that show the soundness of the design approach. An equipment list is included that gives detailed information on the baselined GN&C components.

ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis.

PubMed Central

Stefanelli, C; Bonavita, F; Stanic', I; Farruggia, G; Falcieri, E; Robuffo, I; Pignatti, C; Muscari, C; Rossoni, C; Guarnieri, C; Caldarera, C M

1997-01-01

In quiescent thymocytes, mitochondrial de-energization was not correlated to apoptotic death. In fact, thymocytes treated with oligomycin, a highly specific inhibitor of ATP synthase, alone or with atractyloside to block ATP translocation from the cytoplasm, were alive, even if their mitochondria were depolarized, as revealed by flow cytometry after Rhodamine 123 staining. Furthermore, oligomycin was a powerful inhibitor of apoptosis induced in rat thymocytes by dexamethasone and, to a lesser extent, by the calcium ionophore A23187 and etoposide, but was without effect when apoptosis was induced by staurosporine, and increased cell death in mitogen-treated thymocytes. The inhibition of apoptosis was confirmed by morphological criteria, inhibition of inter-nucleosomal DNA fragmentation and inhibition of the loss of membrane integrity. The anti-apoptotic effect of oligomycin in cells treated with A23187 or etoposide was correlated to the inhibition of protein synthesis, while inhibition of apoptosis induced by dexamethasone, already evident at an oligomycin concentration of 10 ng/ml, was instead strictly correlated to the effect exerted on the cellular ATP level. Thymocyte apoptosis triggered by dexamethasone was blocked or delayed by inhibitors of respiratory-chain uncouplers, inhibitors of ATP synthase and antioxidants: a lasting protection from dexamethasone-induced apoptosis was always correlated to a drastic and rapid reduction in ATP level (31-35% of control), while a delay in the death process was characterized by a moderate decrease in ATP (73-82% of control). Oligomycin inhibited the specific binding of radioactive corticosteroid to thymocyte nuclei, confirming the inhibitory effect of ATP depletion on glucocorticoid binding and suggesting that ATP depletion is a common mediator of the anti-apoptotic action of different effectors in glucocorticoid-induced apoptosis. In conclusion, the reported data indicate that ATP may act as a cellular modulator of some

Stretch-induced Ca2+ independent ATP release in hippocampal astrocytes.

PubMed

Xiong, Yingfei; Teng, Sasa; Zheng, Lianghong; Sun, Suhua; Li, Jie; Guo, Ning; Li, Mingli; Wang, Li; Zhu, Feipeng; Wang, Changhe; Rao, Zhiren; Zhou, Zhuan

2018-02-28

Similar to neurons, astrocytes actively participate in synaptic transmission via releasing gliotransmitters. The Ca 2+ -dependent release of gliotransmitters includes glutamate and ATP. Following an 'on-cell-like' mechanical stimulus to a single astrocyte, Ca 2+ independent single, large, non-quantal, ATP release occurs. Astrocytic ATP release is inhibited by either selective antagonist treatment or genetic knockdown of P2X7 receptor channels. Our work suggests that ATP can be released from astrocytes via two independent pathways in hippocampal astrocytes; in addition to the known Ca 2+ -dependent vesicular release, larger non-quantal ATP release depends on P2X7 channels following mechanical stretch. Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether and how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. By contrast, two recent studies report vesicular ATP release using more direct assays. In the present study, using patch clamped 'ATP-sniffer cells', we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an 'on-cell-like' mechanical stimulus of a single astrocyte, a Ca 2+ independent single large non-quantal ATP release occurred, in contrast to the Ca 2+ -dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knockdown of P2X7 receptor channels. Functional P2X7 channels were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2X7 channels in astrocytes. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Mixed H2/H∞ distributed robust model predictive control for polytopic uncertain systems subject to actuator saturation and missing measurements

NASA Astrophysics Data System (ADS)

Song, Yan; Fang, Xiaosheng; Diao, Qingda

2016-03-01

In this paper, we discuss the mixed H2/H∞ distributed robust model predictive control problem for polytopic uncertain systems subject to randomly occurring actuator saturation and packet loss. The global system is decomposed into several subsystems, and all the subsystems are connected by a fixed topology network, which is the definition for the packet loss among the subsystems. To better use the successfully transmitted information via Internet, both the phenomena of actuator saturation and packet loss resulting from the limitation of the communication bandwidth are taken into consideration. A novel distributed controller model is established to account for the actuator saturation and packet loss in a unified representation by using two sets of Bernoulli distributed white sequences with known conditional probabilities. With the nonlinear feedback control law represented by the convex hull of a group of linear feedback laws, the distributed controllers for subsystems are obtained by solving an linear matrix inequality (LMI) optimisation problem. Finally, numerical studies demonstrate the effectiveness of the proposed techniques.

Kinetic mechanism of the dimeric ATP sulfurylase from plants

PubMed Central

Ravilious, Geoffrey E.; Herrmann, Jonathan; Goo Lee, Soon; Westfall, Corey S.; Jez, Joseph M.

2013-01-01

In plants, sulfur must be obtained from the environment and assimilated into usable forms for metabolism. ATP sulfurylase catalyses the thermodynamically unfavourable formation of a mixed phosphosulfate anhydride in APS (adenosine 5′-phosphosulfate) from ATP and sulfate as the first committed step of sulfur assimilation in plants. In contrast to the multi-functional, allosterically regulated ATP sulfurylases from bacteria, fungi and mammals, the plant enzyme functions as a mono-functional, non-allosteric homodimer. Owing to these differences, here we examine the kinetic mechanism of soybean ATP sulfurylase [GmATPS1 (Glycine max (soybean) ATP sulfurylase isoform 1)]. For the forward reaction (APS synthesis), initial velocity methods indicate a single-displacement mechanism. Dead-end inhibition studies with chlorate showed competitive inhibition versus sulfate and non-competitive inhibition versus APS. Initial velocity studies of the reverse reaction (ATP synthesis) demonstrate a sequential mechanism with global fitting analysis suggesting an ordered binding of substrates. ITC (isothermal titration calorimetry) showed tight binding of APS to GmATPS1. In contrast, binding of PPi (pyrophosphate) to GmATPS1 was not detected, although titration of the E•APS complex with PPi in the absence of magnesium displayed ternary complex formation. These results suggest a kinetic mechanism in which ATP and APS are the first substrates bound in the forward and reverse reactions, respectively. PMID:23789618

ATP13A2 variability in Parkinson disease

PubMed Central

Vilariño-Güell, Carles; Soto, Alexandra I.; Lincoln, Sarah J.; Yahmed, Samia Ben; Kefi, Mounir; Heckman, Michael G.; Hulihan, Mary M.; Chai, Hua; Diehl, Nancy N.; Amouri, Rim; Rajput, Alex; Mash, Deborah C.; Dickson, Dennis W.; Middleton, Lefkos T.; Gibson, Rachel A.; Hentati, Faycal; Farrer, Matthew J.

2008-01-01

Recessively inherited mutations in ATP13A2 result in Kufor-Rakeb syndrome, whereas genetic variability and elevated ATP13A2 expression have been implicated in Parkinson disease (PD). Given this background, ATP13A2 was comprehensively assessed to support or refute its contribution to PD. Sequencing of ATP13A2 exons and intron-exon boundaries was performed in 89 probands with familial parkinsonism from Tunisia. The segregation of mutations with parkinsonism was subsequently assessed within pedigrees. The frequency of genetic variants and evidence for association was also examined in 240 patients with non-familial PD and 372 healthy controls. ATP13A2 mRNA expression was also quantified in brain tissues from 38 patients with non-familial PD and 38 healthy subjects from the US. Sequencing analysis revealed 37 new variants; seven missense, six silent and 24 that were noncoding. However, no single ATP13A2 mutation segregated with familial parkinsonism in either a dominant or recessive manner. Four markers showed marginal association with non-familial PD, prior to correction for multiple testing. ATP13A2 mRNA expression was marginally decreased in PD brains compared with tissue from control subjects. In conclusion, neither ATP13A2 genetic variability nor quantitative gene expression in brain appears to contribute to familial parkinsonism or non-familial PD. PMID:19085912

An RNA motif that binds ATP

NASA Technical Reports Server (NTRS)

Sassanfar, M.; Szostak, J. W.

1993-01-01

RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.

Biological and Pathological Implications of an Alternative ATP-Powered Proteasomal Assembly With Cdc48 and the 20S Peptidase.

PubMed

Esaki, Masatoshi; Johjima-Murata, Ai; Islam, Md Tanvir; Ogura, Teru

2018-01-01

The ATP-powered protein degradation machinery plays essential roles in maintaining protein homeostasis in all organisms. Robust proteolytic activities are typically sequestered within protein complexes to avoid the fatal removal of essential proteins. Because the openings of proteolytic chambers are narrow, substrate proteins must undergo unfolding. AAA superfamily proteins (ATPases associated with diverse cellular activities) are mostly located at these openings and regulate protein degradation appropriately. The 26S proteasome, comprising 20S peptidase and 19S regulatory particles, is the major ATP-powered protein degradation machinery in eukaryotes. The 19S particles are composed of six AAA proteins and 13 regulatory proteins, and bind to both ends of a barrel-shaped proteolytic chamber formed by the 20S peptidase. Several recent studies have reported that another AAA protein, Cdc48, can replace the 19S particles to form an alternative ATP-powered proteasomal complex, i.e., the Cdc48-20S proteasome. This review focuses on our current knowledge of this alternative proteasome and its possible linkage to amyotrophic lateral sclerosis.

Life support subsystem monitoring instrumentation

NASA Technical Reports Server (NTRS)

Powell, J. D.; Kostell, G. D.

1974-01-01

The recognition of the need for instrumentation in manned spacecraft life-support subsystems has increased significantly over the past several years. Of the required control and monitoring instrumentation, this paper will focus on the monitoring instrumentation as applied to life-support subsystems. The initial approach used independent sensors, independent sensor signal conditioning circuitry, and independent logic circuitry to provide shutdown protection only. This monitoring system was replaced with a coordinated series of printed circuit cards, each of which contains all the electronics to service one sensor and provide performance trend information, fault detection and isolation information, and shutdown protection. Finally, a review of sensor and instrumentation problems is presented, and the requirement for sensors with built-in signal conditioning and provisions for in situ calibration is discussed.

The 30-centimeter ion thrust subsystem design manual

NASA Technical Reports Server (NTRS)

1979-01-01

The principal characteristics of the 30-centimeter ion propulsion thrust subsystem technology that was developed to satisfy the propulsion needs of future planetary and early orbital missions are described. Functional requirements and descriptions, interface and performance requirements, and physical characteristics of the hardware are described at the thrust subsystem, BIMOD engine system, and component level.

A High-Throughput TNP-ATP Displacement Assay for Screening Inhibitors of ATP-Binding in Bacterial Histidine Kinases

PubMed Central

Guarnieri, Michael T.; Blagg, Brian S. J.

2011-01-01

Abstract Bacterial histidine kinases (HK) are members of the GHKL superfamily, which share a unique adenosine triphosphate (ATP)-binding Bergerat fold. Our previous studies have shown that Gyrase, Hsp90, MutL (GHL) inhibitors bind to the ATP-binding pocket of HK and may provide lead compounds for the design of novel antibiotics targeting these kinases. In this article, we developed a competition assay using the fluorescent ATP analog, 2′,3′-O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate. The method can be used for high-throughput screening of compound libraries targeting HKs or other ATP-binding proteins. We utilized the assay to screen a library of GHL inhibitors targeting the bacterial HK PhoQ, and discuss the applications of the 2′,3′-O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate competition assay beyond GHKL inhibitor screening. PMID:21050069

Theoretical studies of the ATP hydrolysis mechanism of myosin.

PubMed

Okimoto, N; Yamanaka, K; Ueno, J; Hata, M; Hoshino, T; Tsuda, M

2001-11-01

The ATP hydrolysis mechanism of myosin was studied using quantum chemical (QM) and molecular dynamics calculations. The initial model compound for QM calculations was constructed on the basis of the energy-minimized structure of the myosin(S1dc)-ATP complex, which was determined by molecular mechanics calculations. The result of QM calculations suggested that the ATP hydrolysis mechanism of myosin consists of a single elementary reaction in which a water molecule nucleophilically attacked gamma-phosphorus of ATP. In addition, we performed molecular dynamics simulations of the initial and final states of the ATP hydrolysis reaction, that is, the myosin-ATP and myosin-ADP.Pi complexes. These calculations revealed roles of several amino acid residues (Lys185, Thr186, Ser237, Arg238, and Glu459) in the ATPase pocket. Lys185 maintains the conformation of beta- and gamma-phosphate groups of ATP by forming the hydrogen bonds. Thr186 and Ser237 are coordinated to a Mg(2+) ion, which interacts with the phosphates of ATP and therefore contributes to the stabilization of the ATP structure. Arg238 and Glu459, which consisted of the gate of the ATPase pocket, retain the water molecule acting on the hydrolysis at the appropriate position for initiating the hydrolysis.

Cost-effective data storage/archival subsystem for functional PACS

NASA Astrophysics Data System (ADS)

Chen, Y. P.; Kim, Yongmin

1993-09-01

Not the least of the requirements of a workable PACS is the ability to store and archive vast amounts of information. A medium-size hospital will generate between 1 and 2 TBytes of data annually on a fully functional PACS. A high-speed image transmission network coupled with a comparably high-speed central data storage unit can make local memory and magnetic disks in the PACS workstations less critical and, in an extreme case, unnecessary. Under these circumstances, the capacity and performance of the central data storage subsystem and database is critical in determining the response time at the workstations, thus significantly affecting clinical acceptability. The central data storage subsystem not only needs to provide sufficient capacity to store about ten days worth of images (five days worth of new studies, and on the average, about one comparison study for each new study), but also supplies images to the requesting workstation in a timely fashion. The database must provide fast retrieval responses upon users' requests for images. This paper analyzes both advantages and disadvantages of multiple parallel transfer disks versus RAID disks for short-term central data storage subsystem, as well as optical disk jukebox versus digital recorder tape subsystem for long-term archive. Furthermore, an example high-performance cost-effective storage subsystem which integrates both the RAID disks and high-speed digital tape subsystem as a cost-effective PACS data storage/archival unit are presented.

Spacecraft active thermal control subsystem design and operation considerations

NASA Technical Reports Server (NTRS)

Sadunas, J. A.; Lehtinen, A. M.; Nguyen, H. T.; Parish, R.

1986-01-01

Future spacecraft missions will be characterized by high electrical power requiring active thermal control subsystems for acquisition, transport, and rejection of waste heat. These systems will be designed to operate with minimum maintenance for up to 10 years, with widely varying externally-imposed environments, as well as the spacecraft waste heat rejection loads. This paper presents the design considerations and idealized performance analysis of a typical thermal control subsystem with emphasis on the temperature control aspects during off-design operation. The selected thermal management subsystem is a cooling loop for a 75-kWe fuel cell subsystem, consisting of a fuel cell heat exchanger, thermal storage, pumps, and radiator. Both pumped-liquid transport and two-phase (liquid/vapor) transport options are presented with examination of similarities and differences of the control requirements for these representative thermal control options.

MIUS integration and subsystems test program

NASA Technical Reports Server (NTRS)

Beckham, W. S., Jr.; Shows, G. C.; Redding, T. E.; Wadle, R. C.; Keough, M. B.; Poradek, J. C.

1976-01-01

The MIUS Integration and Subsystems Test (MIST) facility at the Lyndon B. Johnson Space Center was completed and ready in May 1974 for conducting specific tests in direct support of the Modular Integrated Utility System (MIUS). A series of subsystems and integrated tests was conducted since that time, culminating in a series of 24-hour dynamic tests to further demonstrate the capabilities of the MIUS Program concepts to meet typical utility load profiles for a residential area. Results of the MIST Program are presented which achieved demonstrated plant thermal efficiencies ranging from 57 to 65 percent.

Small spacecraft power and thermal subsystems

NASA Technical Reports Server (NTRS)

Eakman, D.; Lambeck, R.; Mackowski, M.; Slifer, L., Jr.

1994-01-01

This white paper provides a general guide to the conceptual design of satellite power and thermal control subsystems with special emphasis on the unique design aspects associated with small satellites. The operating principles of these technologies are explained and performance characteristics of current and projected components are provided. A tutorial is presented on the design process for both power and thermal subsystems, with emphasis on unique issues relevant to small satellites. The ability of existing technology to meet future performance requirements is discussed. Conclusions and observations are presented that stress cost-effective, high-performance design solutions.

ATP and AMP Mutually Influence Their Interaction with the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) at Separate Binding Sites*

PubMed Central

Randak, Christoph O.; Dong, Qian; Ver Heul, Amanda R.; Elcock, Adrian H.; Welsh, Michael J.

2013-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP-binding cassette (ABC) transporter protein family. In the presence of ATP and physiologically relevant concentrations of AMP, CFTR exhibits adenylate kinase activity (ATP + AMP ⇆ 2 ADP). Previous studies suggested that the interaction of nucleotide triphosphate with CFTR at ATP-binding site 2 is required for this activity. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides. However, little is known about how an ABC adenylate kinase interacts with ATP and AMP when both are present. Based on data from non-ABC adenylate kinases, we hypothesized that ATP and AMP mutually influence their interaction with CFTR at separate binding sites. We further hypothesized that only one of the two CFTR ATP-binding sites is involved in the adenylate kinase reaction. We found that 8-azidoadenosine 5′-triphosphate (8-N3-ATP) and 8-azidoadenosine 5′-monophosphate (8-N3-AMP) photolabeled separate sites in CFTR. Labeling of the AMP-binding site with 8-N3-AMP required the presence of ATP. Conversely, AMP enhanced photolabeling with 8-N3-ATP at ATP-binding site 2. The adenylate kinase active center probe P1,P5-di(adenosine-5′) pentaphosphate interacted simultaneously with an AMP-binding site and ATP-binding site 2. These results show that ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR. They further indicate that the active center of the adenylate kinase comprises ATP-binding site 2. PMID:23921386

Customized ATP towpreg. [Automated Tow Placement

NASA Technical Reports Server (NTRS)

Sandusky, Donald A.; Marchello, Joseph M.; Baucom, Robert M.; Johnston, Norman J.

1992-01-01

Automated tow placement (ATP) utilizes robotic technology to lay down adjacent polymer-matrix-impregnated carbon fiber tows on a tool surface. Consolidation and cure during ATP requires that void elimination and polymer matrix adhesion be accomplished in the short period of heating and pressure rolling that follows towpreg ribbon placement from the robot head to the tool. This study examined the key towpreg ribbon properties and dimensions which play a significant role in ATP. Analysis of the heat transfer process window indicates that adequate heating can be achieved at lay down rates as high as 1 m/sec. While heat transfer did not appear to be the limiting factor, resin flow and fiber movement into tow lap gaps could be. Accordingly, consideration was given to towpreg ribbon having uniform yet non-rectangular cross sections. Dimensional integrity of the towpreg ribbon combined with customized ribbon architecture offer great promise for processing advances in ATP of high performance composites.

Torque generation mechanism of ATP synthase

NASA Astrophysics Data System (ADS)

Miller, John; Maric, Sladjana; Scoppa, M.; Cheung, M.

2010-03-01

ATP synthase is a rotary motor that produces adenosine triphosphate (ATP), the chemical currency of life. Our proposed electric field driven torque (EFT) model of FoF1-ATP synthase describes how torque, which scales with the number of c-ring proton binding sites, is generated by the proton motive force (pmf) across the mitochondrial inner membrane. When Fo is coupled to F1, the model predicts a critical pmf to drive ATP production. In order to fully understand how the electric field resulting from the pmf drives the c-ring to rotate, it is important to examine the charge distributions in the protonated c-ring and a-subunit containing the proton channels. Our calculations use a self-consistent field approach based on a refinement of reported structural data. The results reveal changes in pKa for key residues on the a-subunit and c-ring, as well as titration curves and protonation state energy diagrams. Health implications will be briefly discussed.

Design optimization for cost and quality: The robust design approach

NASA Technical Reports Server (NTRS)

Unal, Resit

1990-01-01

Designing reliable, low cost, and operable space systems has become the key to future space operations. Designing high quality space systems at low cost is an economic and technological challenge to the designer. A systematic and efficient way to meet this challenge is a new method of design optimization for performance, quality, and cost, called Robust Design. Robust Design is an approach for design optimization. It consists of: making system performance insensitive to material and subsystem variation, thus allowing the use of less costly materials and components; making designs less sensitive to the variations in the operating environment, thus improving reliability and reducing operating costs; and using a new structured development process so that engineering time is used most productively. The objective in Robust Design is to select the best combination of controllable design parameters so that the system is most robust to uncontrollable noise factors. The robust design methodology uses a mathematical tool called an orthogonal array, from design of experiments theory, to study a large number of decision variables with a significantly small number of experiments. Robust design also uses a statistical measure of performance, called a signal-to-noise ratio, from electrical control theory, to evaluate the level of performance and the effect of noise factors. The purpose is to investigate the Robust Design methodology for improving quality and cost, demonstrate its application by the use of an example, and suggest its use as an integral part of space system design process.

Subsystem radiation susceptibility analysis for deep-space missions

NASA Technical Reports Server (NTRS)

West, W. S.; Poch, W.; Holmes-Siedle, A.; Bilsky, H. W.; Carroll, D.

1971-01-01

Scientific, unmanned spacecraft on mission to Jupiter and beyond will be subjected to nuclear radiation from the natural environment and onboard nuclear power sources which may be harmful to subsystems. This report postulates these environments and discusses practical considerations to ensure confidence that the spacecraft's materials and subsystems will withstand the effects of anticipated radiation. Degradation mechanisms are discussed.

Stability of large-scale systems with stable and unstable subsystems.

NASA Technical Reports Server (NTRS)

Grujic, Lj. T.; Siljak, D. D.

1972-01-01

The purpose of this paper is to develop new methods for constructing vector Liapunov functions and broaden the application of Liapunov's theory to stability analysis of large-scale dynamic systems. The application, so far limited by the assumption that the large-scale systems are composed of exponentially stable subsystems, is extended via the general concept of comparison functions to systems which can be decomposed into asymptotically stable subsystems. Asymptotic stability of the composite system is tested by a simple algebraic criterion. With minor technical adjustments, the same criterion can be used to determine connective asymptotic stability of large-scale systems subject to structural perturbations. By redefining the constraints imposed on the interconnections among the subsystems, the considered class of systems is broadened in an essential way to include composite systems with unstable subsystems. In this way, the theory is brought substantially closer to reality since stability of all subsystems is no longer a necessary assumption in establishing stability of the overall composite system.

Dynamic Regulation of Cell Volume and Extracellular ATP of Human Erythrocytes

PubMed Central

Leal Denis, M. Florencia; Alvarez, H. Ariel; Lauri, Natalia; Alvarez, Cora L.; Chara, Osvaldo; Schwarzbaum, Pablo J.

2016-01-01

Introduction The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regulation between Vr and ATPe. Methods and Treatments We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors. Results In rbcs 10 μM MST7 promoted acute, strongly correlated changes in [ATPe] and Vr. Whereas MST7 induced increases of 10% in Vr and 190 nM in [ATPe], blocking swelling in a hyperosmotic medium + MST7 reduced [ATPe] by 40%. Pre-incubation of rbcs with 10 μM of either carbenoxolone or probenecid, two inhibitors of the ATP conduit pannexin 1, reduced [ATPe] by 40–50% and swelling by 40–60%, while in the presence of 80 U/mL apyrase, an ATPe scavenger, cell swelling was prevented. While exposure to 10 μM NF110, a blocker of ATP-P2X receptors mediating sodium influx, reduced [ATPe] by 48%, and swelling by 80%, incubation of cells in sodium free medium reduced swelling by 92%. Analysis and Discussion Results were analyzed by means of a mathematical model where ATPe kinetics and Vr kinetics were mutually regulated. Model dependent fit to experimental data showed that, upon MST7 exposure, ATP efflux required a fast 1960-fold increase of ATP permeability, mediated by two kinetically different conduits, both of which were activated by swelling and inactivated by time. Both experimental and theoretical results suggest that, following MST7 exposure, ATP is released via two conduits, one of which is mediated by pannexin 1. The accumulated ATPe activates P2X receptors, followed by sodium influx, resulting in cell swelling, which in turn further activates ATP release. Thus swelling and P2X receptors constitute essential components of a positive feedback loop

Embedded Thermal Control for Spacecraft Subsystems Miniaturization

NASA Technical Reports Server (NTRS)

Didion, Jeffrey R.

2014-01-01

Optimization of spacecraft size, weight and power (SWaP) resources is an explicit technical priority at Goddard Space Flight Center. Embedded Thermal Control Subsystems are a promising technology with many cross cutting NSAA, DoD and commercial applications: 1.) CubeSatSmallSat spacecraft architecture, 2.) high performance computing, 3.) On-board spacecraft electronics, 4.) Power electronics and RF arrays. The Embedded Thermal Control Subsystem technology development efforts focus on component, board and enclosure level devices that will ultimately include intelligent capabilities. The presentation will discuss electric, capillary and hybrid based hardware research and development efforts at Goddard Space Flight Center. The Embedded Thermal Control Subsystem development program consists of interrelated sub-initiatives, e.g., chip component level thermal control devices, self-sensing thermal management, advanced manufactured structures. This presentation includes technical status and progress on each of these investigations. Future sub-initiatives, technical milestones and program goals will be presented.

Debris measure subsystem of the nanosatellite IRECIN

NASA Astrophysics Data System (ADS)

Ferrante, M.; di Ciolo, L.; Ortenzi, A.; Petrozzi, M.; del Re, V.

2003-09-01

The on board resources, needed to perform the mission tasks, are very limited in nano-satellites. This paper proposes an Electronic real-time system that acquires space debris measures. It uses a piezo-electric sensor. The described device is a subsystem on board of the IRECIN nanosatellite composed mainly by a r.i.s.c. microprocessor, an electronic part that interfaces to the debris sensor in order to provide a low noise electrical and suitable range to ADC 12 bit converter, and finally a memory in order to store the data. The microprocessor handles the Debris Measure System measuring the impacts number, their intensity and storing their waves form. This subsystem is able to communicate with the other IRECIN subsystems through I2C Bus and principally with the "Main Microprocessor" subsystem allowing the data download directly to the Ground Station. Moreover this subsystem lets free the "Main Microprocessor Board" from the management and charge of debris data. All electronic components are SMD technology in order to reduce weight and size. The realized Electronic board are completely developed, realized and tested at the Vitrociset S.P.A. under control of Research and Development Group. The proposed system is implemented on the IRECIN, a modular nanosatellite weighting less than 1.5 kg, constituted by sixteen external sides with surface-mounted solar cells and three internal Al plates, kept together by four steel bars. Lithium-ions batteries are added for eclipse operations. Attitude is determined by two three-axis magnetometers and the solar panels data. Control is provided by an active magnetic control system. The spacecraft will be spin-stabilized with the spin-axis normal to the orbit. debris and micrometeoroids mass and velocity.

Error Suppression for Hamiltonian-Based Quantum Computation Using Subsystem Codes

NASA Astrophysics Data System (ADS)

Marvian, Milad; Lidar, Daniel A.

2017-01-01

We present general conditions for quantum error suppression for Hamiltonian-based quantum computation using subsystem codes. This involves encoding the Hamiltonian performing the computation using an error detecting subsystem code and the addition of a penalty term that commutes with the encoded Hamiltonian. The scheme is general and includes the stabilizer formalism of both subspace and subsystem codes as special cases. We derive performance bounds and show that complete error suppression results in the large penalty limit. To illustrate the power of subsystem-based error suppression, we introduce fully two-local constructions for protection against local errors of the swap gate of adiabatic gate teleportation and the Ising chain in a transverse field.

Error Suppression for Hamiltonian-Based Quantum Computation Using Subsystem Codes.

PubMed

Marvian, Milad; Lidar, Daniel A

2017-01-20

We present general conditions for quantum error suppression for Hamiltonian-based quantum computation using subsystem codes. This involves encoding the Hamiltonian performing the computation using an error detecting subsystem code and the addition of a penalty term that commutes with the encoded Hamiltonian. The scheme is general and includes the stabilizer formalism of both subspace and subsystem codes as special cases. We derive performance bounds and show that complete error suppression results in the large penalty limit. To illustrate the power of subsystem-based error suppression, we introduce fully two-local constructions for protection against local errors of the swap gate of adiabatic gate teleportation and the Ising chain in a transverse field.

ATP Synthase Diseases of Mitochondrial Genetic Origin

PubMed Central

Dautant, Alain; Meier, Thomas; Hahn, Alexander; Tribouillard-Tanvier, Déborah; di Rago, Jean-Paul; Kucharczyk, Roza

2018-01-01

Devastating human neuromuscular disorders have been associated to defects in the ATP synthase. This enzyme is found in the inner mitochondrial membrane and catalyzes the last step in oxidative phosphorylation, which provides aerobic eukaryotes with ATP. With the advent of structures of complete ATP synthases, and the availability of genetically approachable systems such as the yeast Saccharomyces cerevisiae, we can begin to understand these molecular machines and their associated defects at the molecular level. In this review, we describe what is known about the clinical syndromes induced by 58 different mutations found in the mitochondrial genes encoding membrane subunits 8 and a of ATP synthase, and evaluate their functional consequences with respect to recently described cryo-EM structures. PMID:29670542

Selected Lessons Learned in Space Shuttle Orbiter Propulsion and Power Subsystems

NASA Technical Reports Server (NTRS)

Hernandez, Francisco J.; Martinez, Hugo; Ryan, Abigail; Westover, Shayne; Davies, Frank

2011-01-01

Over its 30 years of space flight history, plus the nearly 10 years of design, development test and evaluation, the Space Shuttle Orbiter is full of lessons learned in all of its numerous and complex subsystems. In the current paper, only selected lessons learned in the areas of the Orbiter propulsion and power subsystems will be described. The particular Orbiter subsystems include: Auxiliary Power Unit (APU), Hydraulics and Water Spray Boiler (WSB), Mechanical Flight Controls, Main Propulsion System (MPS), Fuel Cells and Power Reactant and Storage Devices (PRSD), Orbital Maneuvering System (OMS), Reaction Control System (RCS), Electrical Power Distribution (EPDC), electrical wiring and pyrotechnics. Given the complexity and extensive history of each of these subsystems, and the limited scope of this paper, it is impossible to include most of the lessons learned; instead the attempt will be to present a selected few or key lessons, in the judgment of the authors. Each subsystem is presented separate, beginning with an overview of the hardware and their function, a short description of a few historical problems and their lessons, followed by a more comprehensive table listing of the major subsystem problems and lessons. These tables serve as a quick reference for lessons learned in each subsystem. In addition, this paper will establish common lessons across subsystems as well as concentrate on those lessons which are deemed to have the highest applicability to future space flight programs.

Space shuttle atmospheric revitalization subsystem/active thermal control subsystem computer program (users manual)

NASA Technical Reports Server (NTRS)

1973-01-01

A shuttle (ARS) atmosphere revitalization subsystem active thermal control subsystem (ATCS) performance routine was developed. This computer program is adapted from the Shuttle EC/LSS Design Computer Program. The program was upgraded in three noteworthy areas: (1) The functional ARS/ATCS schematic has been revised to accurately synthesize the shuttle baseline system definition. (2) The program logic has been improved to provide a more accurate prediction of the integrated ARS/ATCS system performance. Additionally, the logic has been expanded to model all components and thermal loads in the ARS/ATCS system. (3) The program is designed to be used on the NASA JSC crew system division's programmable calculator system. As written the new computer routine has an average running time of five minutes. The use of desk top type calculation equipment, and the rapid response of the program provides the NASA with an analytical tool for trade studies to refine the system definition, and for test support of the RSECS or integrated Shuttle ARS/ATCS test programs.

Power Stroke Angular Velocity Profiles of Archaeal A-ATP Synthase Versus Thermophilic and Mesophilic F-ATP Synthase Molecular Motors*

PubMed Central

Sielaff, Hendrik; Martin, James; Singh, Dhirendra; Biuković, Goran; Grüber, Gerhard; Frasch, Wayne D.

2016-01-01

The angular velocities of ATPase-dependent power strokes as a function of the rotational position for the A-type molecular motor A3B3DF, from the Methanosarcina mazei Gö1 A-ATP synthase, and the thermophilic motor α3β3γ, from Geobacillus stearothermophilus (formerly known as Bacillus PS3) F-ATP synthase, are resolved at 5 μs resolution for the first time. Unexpectedly, the angular velocity profile of the A-type was closely similar in the angular positions of accelerations and decelerations to the profiles of the evolutionarily distant F-type motors of thermophilic and mesophilic origins, and they differ only in the magnitude of their velocities. M. mazei A3B3DF power strokes occurred in 120° steps at saturating ATP concentrations like the F-type motors. However, because ATP-binding dwells did not interrupt the 120° steps at limiting ATP, ATP binding to A3B3DF must occur during the catalytic dwell. Elevated concentrations of ADP did not increase dwells occurring 40° after the catalytic dwell. In F-type motors, elevated ADP induces dwells 40° after the catalytic dwell and slows the overall velocity. The similarities in these power stroke profiles are consistent with a common rotational mechanism for A-type and F-type rotary motors, in which the angular velocity is limited by the rotary position at which ATP binding occurs and by the drag imposed on the axle as it rotates within the ring of stator subunits. PMID:27729450

NFIRAOS in 2015: engineering for future integration of complex subsystems

NASA Astrophysics Data System (ADS)

Atwood, Jenny; Andersen, David; Byrnes, Peter; Densmore, Adam; Fitzsimmons, Joeleff; Herriot, Glen; Hill, Alexis

2016-07-01

The Narrow Field InfraRed Adaptive Optics System (NFIRAOS) will be the first-light facility Adaptive Optics (AO) system for the Thirty Meter Telescope (TMT). NFIRAOS will be able to host three science instruments that can take advantage of this high performance system. NRC Herzberg is leading the design effort for this critical TMT subsystem. As part of the final design phase of NFIRAOS, we have identified multiple subsystems to be sub-contracted to Canadian industry. The scope of work for each subcontract is guided by the NFIRAOS Work Breakdown Structure (WBS) and is divided into two phases: the completion of the final design and the fabrication, assembly and delivery of the final product. Integration of the subsystems at NRC will require a detailed understanding of the interfaces between the subsystems, and this work has begun by defining the interface physical characteristics, stability, local coordinate systems, and alignment features. In order to maintain our stringent performance requirements, the interface parameters for each subsystem are captured in multiple performance budgets, which allow a bottom-up error estimate. In this paper we discuss our approach for defining the interfaces in a consistent manner and present an example error budget that is influenced by multiple subsystems.

Thermal energy storage subsystems. A collection of quarterly reports

NASA Technical Reports Server (NTRS)

1978-01-01

The design, development, and progress toward the delivery of three subsystems is discussed. The subsystem used a salt hydrate mixture for thermal energy storage. The program schedules, technical data, and other program activities from October 1, 1976, through December 31, 1977 are presented.

Hypophosphatemia promotes lower rates of muscle ATP synthesis.

PubMed

Pesta, Dominik H; Tsirigotis, Dimitrios N; Befroy, Douglas E; Caballero, Daniel; Jurczak, Michael J; Rahimi, Yasmeen; Cline, Gary W; Dufour, Sylvie; Birkenfeld, Andreas L; Rothman, Douglas L; Carpenter, Thomas O; Insogna, Karl; Petersen, Kitt Falk; Bergwitz, Clemens; Shulman, Gerald I

2016-10-01

Hypophosphatemia can lead to muscle weakness and respiratory and heart failure, but the mechanism is unknown. To address this question, we noninvasively assessed rates of muscle ATP synthesis in hypophosphatemic mice by using in vivo saturation transfer [ 31 P]-magnetic resonance spectroscopy. By using this approach, we found that basal and insulin-stimulated rates of muscle ATP synthetic flux (V ATP ) and plasma inorganic phosphate (P i ) were reduced by 50% in mice with diet-induced hypophosphatemia as well as in sodium-dependent P i transporter solute carrier family 34, member 1 (NaPi2a)-knockout (NaPi2a -/- ) mice compared with their wild-type littermate controls. Rates of V ATP normalized in both hypophosphatemic groups after restoring plasma P i concentrations. Furthermore, V ATP was directly related to cellular and mitochondrial P i uptake in L6 and RC13 rodent myocytes and isolated muscle mitochondria. Similar findings were observed in a patient with chronic hypophosphatemia as a result of a mutation in SLC34A3 who had a 50% reduction in both serum P i content and muscle V ATP After oral P i repletion and normalization of serum P i levels, muscle V ATP completely normalized in the patient. Taken together, these data support the hypothesis that decreased muscle ATP synthesis, in part, may be caused by low blood P i concentrations, which may explain some aspects of muscle weakness observed in patients with hypophosphatemia.-Pesta, D. H., Tsirigotis, D. N., Befroy, D. E., Caballero, D., Jurczak, M. J., Rahimi, Y., Cline, G. W., Dufour, S., Birkenfeld, A. L., Rothman, D. L., Carpenter, T. O., Insogna, K., Petersen, K. F., Bergwitz, C., Shulman, G. I. Hypophosphatemia promotes lower rates of muscle ATP synthesis. © The Author(s).

Lysosomal Storage of Subunit c of Mitochondrial ATP Synthase in Brain-Specific Atp13a2-Deficient Mice.

PubMed

Sato, Shigeto; Koike, Masato; Funayama, Manabu; Ezaki, Junji; Fukuda, Takahiro; Ueno, Takashi; Uchiyama, Yasuo; Hattori, Nobutaka

2016-12-01

Kufor-Rakeb syndrome (KRS) is an autosomal recessive form of early-onset parkinsonism linked to the PARK9 locus. The causative gene for KRS is Atp13a2, which encodes a lysosomal type 5 P-type ATPase. We recently showed that KRS/PARK9-linked mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D in vitro. However, it remains unknown how deficiency of Atp13a2 is connected to lysosomal impairments. To address this issue, we analyzed brain tissues of Atp13a2 conditional-knockout mice, which exhibited characteristic features of neuronal ceroid lipofuscinosis, including accumulation of lipofuscin positive for subunit c of mitochondrial ATP synthase, suggesting that a common pathogenic mechanism underlies both neuronal ceroid lipofuscinosis and Parkinson disease. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Developments in Nano-Satellite Structural Subsystem Design at NASA-GSFC

NASA Technical Reports Server (NTRS)

Rossoni, Peter; Panetta, Peter V.

1999-01-01

The NASA-GSFC Nano-satellite Technology Development Program will enable flying constellations of tens to hundreds of nano-satellites for future NASA Space and Earth Science missions. Advanced technology components must be developed to make these future spacecraft compact, lightweight, low-power, low-cost, and survivable to a radiation environment over a two-year mission lifetime. This paper describes the efforts underway to develop lightweight, low cost, and multi-functional structures, serviceable designs, and robust mechanisms. As designs shrink, the integration of various subsystems becomes a vital necessity. This paper also addresses structurally integrated electrical power, attitude control, and thermal systems. These innovations bring associated fabrication, integration, and test challenges. Candidate structural materials and processes are examined and the merits of each are discussed. Design and fabrication processes include flat stock composite construction, cast aluminum-beryllium alloy, and an injection molded fiber-reinforced plastic. A viable constellation deployment scenario is described as well as a Phase-A Nano-satellite Pathfinder study.

Some special sub-systems for stratospheric balloon flights in India

NASA Astrophysics Data System (ADS)

Damle, S. V.; Gokhale, G. S.; Kundapurkar, R. U.

During last few years several new sub-systems for balloon were developed and are being regularly used in the balloon flights. Some of these sub-systems are i) positive monitor for magnetic ballast release using an opto-electronic device ii) one-way pressure switch to terminate flight for runaway balloon iii) in-flight payload reel down system for atmospheric science experiment. The design, usage and performance of these and other sub-systems will be presented.

NFIRAOS beamsplitters subsystems optomechanical design

NASA Astrophysics Data System (ADS)

Lamontagne, Frédéric; Desnoyers, Nichola; Nash, Reston; Boucher, Marc-André; Martin, Olivier; Buteau-Vaillancourt, Louis; Châteauneuf, François; Atwood, Jenny; Hill, Alexis; Byrnes, Peter W. G.; Herriot, Glen; Véran, Jean-Pierre

2016-07-01

The early-light facility adaptive optics system for the Thirty Meter Telescope (TMT) is the Narrow-Field InfraRed Adaptive Optics System (NFIRAOS). The science beam splitter changer mechanism and the visible light beam splitter are subsystems of NFIRAOS. This paper presents the opto-mechanical design of the NFIRAOS beam splitters subsystems (NBS). In addition to the modal and the structural analyses, the beam splitters surface deformations are computed considering the environmental constraints during operation. Surface deformations are fit to Zernike polynomials using SigFit software. Rigid body motion as well as residual RMS and peak-to-valley surface deformations are calculated. Finally, deformed surfaces are exported to Zemax to evaluate the transmitted and reflected wave front error. The simulation results of this integrated opto-mechanical analysis have shown compliance with all optical requirements.

Binding of ATP by pertussis toxin and isolated toxin subunits

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

Hausman, S.Z.; Manclark, C.R.; Burns, D.L.

1990-07-03

The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of ({sup 3}H)ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of ({sup 3}H)ATP to pertussis toxin in a competitive manner;more » however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of ({sup 3}H)ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.« less

Identification of a new Mpl-interacting protein, Atp5d.

PubMed

Liu, Hongyan; Zhao, Zhenhu; Zhong, Yuxu; Shan, Yajun; Sun, Xiaohong; Mao, Bingzhi; Cong, Yuwen

2014-06-01

Thrombopoietin (TPO) can regulate hematopoiesis and megakaryopoiesis via activation of its receptor, c-Mpl, and multiple downstream signal transduction pathways. Using the cytoplasmic domain of Mpl as bait, we performed yeast two-hybrid screening, and found that the protein Atp5d might associate with Mpl. Atp5d is known as the δ subunit of mitochondrial ATP synthase, but little is known about the function of dissociative Atp5d. The interaction between Mpl and Atp5d was confirmed by the yeast two-hybrid system, mammalian two-hybrid assay, pull-down experiment, and co-immunoprecipitation study in vivo and in vitro. An additional immunofluorescence assay showed that the two proteins can colocalize along the plasma membrane in the cytoplasm. Using the yeast two-hybrid system, we tested a series of cytoplasmic truncated mutations for their ability to bind Atp5d and found an association between Atp5d and the Aa98-113 domain of Mpl. The dissociation of Atp5d from Mpl after TPO stimulation suggests that Atp5d may be a new component of TPO signaling.

Discovering novel subsystems using comparative genomics

PubMed Central

Ferrer, Luciana; Shearer, Alexander G.; Karp, Peter D.

2011-01-01

Motivation: Key problems for computational genomics include discovering novel pathways in genome data, and discovering functional interaction partners for genes to define new members of partially elucidated pathways. Results: We propose a novel method for the discovery of subsystems from annotated genomes. For each gene pair, a score measuring the likelihood that the two genes belong to a same subsystem is computed using genome context methods. Genes are then grouped based on these scores, and the resulting groups are filtered to keep only high-confidence groups. Since the method is based on genome context analysis, it relies solely on structural annotation of the genomes. The method can be used to discover new pathways, find missing genes from a known pathway, find new protein complexes or other kinds of functional groups and assign function to genes. We tested the accuracy of our method in Escherichia coli K-12. In one configuration of the system, we find that 31.6% of the candidate groups generated by our method match a known pathway or protein complex closely, and that we rediscover 31.2% of all known pathways and protein complexes of at least 4 genes. We believe that a significant proportion of the candidates that do not match any known group in E.coli K-12 corresponds to novel subsystems that may represent promising leads for future laboratory research. We discuss in-depth examples of these findings. Availability: Predicted subsystems are available at http://brg.ai.sri.com/pwy-discovery/journal.html. Contact: lferrer@ai.sri.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21775308

Evidence that Na+/H+ exchanger 1 is an ATP-binding protein.

PubMed

Shimada-Shimizu, Naoko; Hisamitsu, Takashi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

2013-03-01

Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1. © 2013 The Authors Journal compilation © 2013 FEBS.

Headway Separation Assurance Subsystem (HSAS)

DOT National Transportation Integrated Search

1975-07-01

This report discusses the design, fabrication, test and evaluation of a Headway Separation Assurance Subsystem (HSAS) capable of reliable, failsafe performance in PRT systems. The items designed include both hardware and software packages. These pack...

Mariner Mars 1971 attitude control subsystem

NASA Technical Reports Server (NTRS)

Edmunds, R. S.

1974-01-01

The Mariner Mars 1971 attitude control subsystem (ACS) is discussed. It is comprised of a sun sensor set, a Canopus tracker, an inertial reference unit, two cold gas reaction control assemblies, two rocket engine gimbal actuators, and an attitude control electronics unit. The subsystem has the following eight operating modes: (1) launch, (2) sun acquisition, (3) roll search, (4) celestial cruise, (5) all-axes inertial, (6) roll inertial, (7) commanded turn, and (8) thrust vector control. In the celestial cruise mode, the position control is held to plus or minus 0.25 deg. Commanded turn rates are plus or minus 0.18 deg/s. The attitude control logic in conjunction with command inputs from other spacecraft subsystems establishes the ACS operating mode. The logic utilizes Sun and Canopus acquisition signals generated within the ACS to perform automatic mode switching so that dependence of ground control is minimized when operating in the sun acquisition, roll search, and celestial cruise modes. The total ACS weight is 65.7 lb, and includes 5.4 lb of nitrogen gas. Total power requirements vary from 9 W for the celestial cruise mode to 54 W for the commanded turn mode.

Exploring relationships of human-automation interaction consequences on pilots: uncovering subsystems.

PubMed

Durso, Francis T; Stearman, Eric J; Morrow, Daniel G; Mosier, Kathleen L; Fischer, Ute; Pop, Vlad L; Feigh, Karen M

2015-05-01

We attempted to understand the latent structure underlying the systems pilots use to operate in situations involving human-automation interaction (HAI). HAI is an important characteristic of many modern work situations. Of course, the cognitive subsystems are not immediately apparent by observing a functioning system, but correlations between variables may reveal important relations. The current report examined pilot judgments of 11 HAI dimensions (e.g., Workload, Task Management, Stress/Nervousness, Monitoring Automation, and Cross-Checking Automation) across 48 scenarios that required airline pilots to interact with automation on the flight deck. We found three major clusters of the dimensions identifying subsystems on the flight deck: a workload subsystem, a management subsystem, and an awareness subsystem. Relationships characterized by simple correlations cohered in ways that suggested underlying subsystems consistent with those that had previously been theorized. Understanding the relationship among dimensions affecting HAI is an important aspect in determining how a new piece of automation designed to affect one dimension will affect other dimensions as well. © 2014, Human Factors and Ergonomics Society.

A new environment for multiple spacecraft power subsystem mission operations

NASA Technical Reports Server (NTRS)

Bahrami, K. A.

1990-01-01

The engineering analysis subsystem environment (EASE) is being developed to enable fewer controllers to monitor and control power and other spacecraft engineering subsystems. The EASE prototype has been developed to support simultaneous real-time monitoring of several spacecraft engineering subsystems. It is being designed to assist with offline analysis of telemetry data to determine trends, and to help formulate uplink commands to the spacecraft. An early version of the EASE prototype has been installed in the JPL Space Flight Operations Facility for online testing. The EASE prototype is installed in the Galileo Mission Support Area. The underlying concept, development, and testing of the EASE prototype and how it will aid in the ground operations of spacecraft power subsystems are discussed.

Power Stroke Angular Velocity Profiles of Archaeal A-ATP Synthase Versus Thermophilic and Mesophilic F-ATP Synthase Molecular Motors.

PubMed

Sielaff, Hendrik; Martin, James; Singh, Dhirendra; Biuković, Goran; Grüber, Gerhard; Frasch, Wayne D

2016-12-02

The angular velocities of ATPase-dependent power strokes as a function of the rotational position for the A-type molecular motor A 3 B 3 DF, from the Methanosarcina mazei Gö1 A-ATP synthase, and the thermophilic motor α 3 β 3 γ, from Geobacillus stearothermophilus (formerly known as Bacillus PS3) F-ATP synthase, are resolved at 5 μs resolution for the first time. Unexpectedly, the angular velocity profile of the A-type was closely similar in the angular positions of accelerations and decelerations to the profiles of the evolutionarily distant F-type motors of thermophilic and mesophilic origins, and they differ only in the magnitude of their velocities. M. mazei A 3 B 3 DF power strokes occurred in 120° steps at saturating ATP concentrations like the F-type motors. However, because ATP-binding dwells did not interrupt the 120° steps at limiting ATP, ATP binding to A 3 B 3 DF must occur during the catalytic dwell. Elevated concentrations of ADP did not increase dwells occurring 40° after the catalytic dwell. In F-type motors, elevated ADP induces dwells 40° after the catalytic dwell and slows the overall velocity. The similarities in these power stroke profiles are consistent with a common rotational mechanism for A-type and F-type rotary motors, in which the angular velocity is limited by the rotary position at which ATP binding occurs and by the drag imposed on the axle as it rotates within the ring of stator subunits. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea

PubMed Central

Ceriani, Federico; Pozzan, Tullio; Mammano, Fabio

2016-01-01

Spatially and temporally coordinated variations of the cytosolic free calcium concentration ([Ca2+]c) play a crucial role in a variety of tissues. In the developing sensory epithelium of the mammalian cochlea, elevation of extracellular adenosine trisphosphate concentration ([ATP]e) triggers [Ca2+]c oscillations and propagation of intercellular inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ waves. What remains uncertain is the relative contribution of gap junction channels and connexin hemichannels to these fundamental mechanisms, defects in which impair hearing acquisition. Another related open question is whether [Ca2+]c oscillations require oscillations of the cytosolic IP3 concentration ([IP3]c) in this system. To address these issues, we performed Ca2+ imaging experiments in the lesser epithelial ridge of the mouse cochlea around postnatal day 5 and constructed a computational model in quantitative adherence to experimental data. Our results indicate that [Ca2+]c oscillations are governed by Hopf-type bifurcations within the experimental range of [ATP]e and do not require [IP3]c oscillations. The model replicates accurately the spatial extent and propagation speed of intercellular Ca2+ waves and predicts that ATP-induced ATP release is the primary mechanism underlying intercellular propagation of Ca2+ signals. The model also uncovers a discontinuous transition from propagating regimes (intercellular Ca2+ wave speed > 11 μm⋅s−1) to propagation failure (speed = 0), which occurs upon lowering the maximal ATP release rate below a minimal threshold value. The approach presented here overcomes major limitations due to lack of specific connexin channel inhibitors and can be extended to other coupled cellular systems. PMID:27807138

Development of a preprototype times wastewater recovery subsystem: Appendices

NASA Technical Reports Server (NTRS)

Roebelen, G. J., Jr.; Dehner, G. F.

1984-01-01

This Master Test Plan outlines the test program to be performed by Hamilton Standard during the Urine Water Recovery Subsystem Program. Testing is divided into three phases: (1) design support testing; development component testing; and acceptance testing. The completion of this test program verifies the subsystem operation.

Robustness of the Rotary Catalysis Mechanism of F1-ATPase*

PubMed Central

Watanabe, Rikiya; Matsukage, Yuki; Yukawa, Ayako; Tabata, Kazuhito V.; Noji, Hiroyuki

2014-01-01

F1-ATPase (F1) is the rotary motor protein fueled by ATP hydrolysis. Previous studies have suggested that three charged residues are indispensable for catalysis of F1 as follows: the P-loop lysine in the phosphate-binding loop, GXXXXGK(T/S); a glutamic acid that activates water molecules for nucleophilic attack on the γ-phosphate of ATP (general base); and an arginine directly contacting the γ-phosphate (arginine finger). These residues are well conserved among P-loop NTPases. In this study, we investigated the role of these charged residues in catalysis and torque generation by analyzing alanine-substituted mutants in the single-molecule rotation assay. Surprisingly, all mutants continuously drove rotary motion, even though the rotational velocity was at least 100,000 times slower than that of wild type. Thus, although these charged residues contribute to highly efficient catalysis, they are not indispensable to chemo-mechanical energy coupling, and the rotary catalysis mechanism of F1 is far more robust than previously thought. PMID:24876384

Mariner Mars 1971 attitude control subsystem flight performance

NASA Technical Reports Server (NTRS)

Schumacher, L.

1973-01-01

The flight performance of the Mariner 71 attitude control subsystem is discussed. Each phase of the mission is delineated and the attitude control subsystem is evaluated within the observed operational environment. Performance anomalies are introduced and discussed within the context of general performance. Problems such as the sun sensor interface incompatibility, gas valve leaks, and scan platform dynamic coupling effects are given analytical considerations.

Triple redundant computer system/display and keyboard subsystem interface

NASA Technical Reports Server (NTRS)

Gulde, F. J.

1973-01-01

Interfacing of the redundant display and keyboard subsystem with the triple redundant computer system is defined according to space shuttle design. The study is performed in three phases: (1) TRCS configuration and characteristics identification; (2) display and keyboard subsystem configuration and characteristics identification, and (3) interface approach definition.

Systems and methods for an integrated electrical sub-system powered by wind energy

DOEpatents

Liu, Yan [Ballston Lake, NY; Garces, Luis Jose [Niskayuna, NY

2008-06-24

Various embodiments relate to systems and methods related to an integrated electrically-powered sub-system and wind power system including a wind power source, an electrically-powered sub-system coupled to and at least partially powered by the wind power source, the electrically-powered sub-system being coupled to the wind power source through power converters, and a supervisory controller coupled to the wind power source and the electrically-powered sub-system to monitor and manage the integrated electrically-powered sub-system and wind power system.

Ice pack heat sink subsystem - Phase 1, Volume 1

NASA Technical Reports Server (NTRS)

Roebelen, G. J., Jr.

1973-01-01

The design, development, fabrication, and test at one-g of a functional laboratory model (non-flight) ice pack heat sink subsystem to be used eventually for astronaut cooling during manned space missions are discussed. In normal use, excess heat in the liquid cooling garment (LCG) coolant is transferred to a reusable/regenerable ice pack heat sink. For emergency operation, or for extension of extravehicular activity mission time after all the ice has melted, water from the ice pack is boiled to vacuum, thereby continuing to remove heat from the LCG coolant. This subsystem incorporates a quick connect/disconnect thermal interface between the ice pack heat sink and the subsystem heat exchanger.

A subsystem identification method based on the path concept with coupling strength estimation

NASA Astrophysics Data System (ADS)

Magrans, Francesc Xavier; Poblet-Puig, Jordi; Rodríguez-Ferran, Antonio

2018-02-01

For complex geometries, the definition of the subsystems is not a straightforward task. We present here a subsystem identification method based on the direct transfer matrix, which represents the first-order paths. The key ingredient is a cluster analysis of the rows of the powers of the transfer matrix. These powers represent high-order paths in the system and are more affected than low-order paths by damping. Once subsystems are identified, the proposed approach also provides a quantification of the degree of coupling between subsystems. This information is relevant to decide whether a subsystem may be analysed in a computer model or measured in the laboratory independently of the rest or subsystems or not. The two features (subsystem identification and quantification of the degree of coupling) are illustrated by means of numerical examples: plates coupled by means of springs and rooms connected by means of a cavity.

Systems integration of marketable subsystems: A collection of progress reports

NASA Technical Reports Server (NTRS)

1978-01-01

Monthly progress reports are given in the areas of marketable subsystems integration; development, design, and building of site data acquisition subsystems and data processing systems; operation of the solar test facility and a systems analysis.

ATP11B mediates platinum resistance in ovarian cancer

PubMed Central

Moreno-Smith, Myrthala; Halder, J.B.; Meltzer, Paul S.; Gonda, Tamas A.; Mangala, Lingegowda S.; Rupaimoole, Rajesha; Lu, Chunhua; Nagaraja, Archana S.; Gharpure, Kshipra M.; Kang, Yu; Rodriguez-Aguayo, Cristian; Vivas-Mejia, Pablo E.; Zand, Behrouz; Schmandt, Rosemarie; Wang, Hua; Langley, Robert R.; Jennings, Nicholas B.; Ivan, Cristina; Coffin, Jeremy E.; Armaiz, Guillermo N.; Bottsford-Miller, Justin; Kim, Sang Bae; Halleck, Margaret S.; Hendrix, Mary J.C.; Bornman, William; Bar-Eli, Menashe; Lee, Ju-Seog; Siddik, Zahid H.; Lopez-Berestein, Gabriel; Sood, Anil K.

2013-01-01

Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. We found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhances the export of cisplatin from cells. The colocalization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins, such as syntaxin-6 (STX6) and vesicular-associated membrane protein 4 (VAMP4), strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, inhibition of ATP11B expression could serve as a therapeutic strategy to overcome cisplatin resistance. PMID:23585472

Power Subsystem for Extravehicular Activities for Exploration Missions

NASA Technical Reports Server (NTRS)

Manzo, Michelle

2005-01-01

The NASA Glenn Research Center has the responsibility to develop the next generation space suit power subsystem to support the Vision for Space Exploration. Various technology challenges exist in achieving extended duration missions as envisioned for future lunar and Mars mission scenarios. This paper presents an overview of ongoing development efforts undertaken at the Glenn Research Center in support of power subsystem development for future extravehicular activity systems.

Electrochemical energy storage subsystems study, volume 1

NASA Technical Reports Server (NTRS)

Miller, F. Q.; Richardson, P. W.; Graff, C. L.; Jordan, M. V.; Patterson, V. L.

1981-01-01

The effects on life cycle costs (LCC) of major design and performance technology parameters for multi kW LEO and GEO energy storage subsystems using NiCd and NiH2 batteries and fuel cell/electrolysis cell devices were examined. Design, performance and LCC dynamic models are developed based on mission and system/subsystem requirements and existing or derived physical and cost data relationships. The models define baseline designs and costs. The major design and performance parameters are each varied to determine their influence on LCC around the baseline values.

Electrochemical Energy Storage Subsystems Study, Volume 2

NASA Technical Reports Server (NTRS)

Miller, F. Q.; Richardson, P. W.; Graff, C. L.; Jordan, M. V.; Patterson, V. L.

1981-01-01

The effects on life cycle costs (LCC) of major design and performance technology parameters for multi kW LEO and GEO energy storage subsystems using NiCd and NiH2 batteries and fuel cell/electrolysis cell devices were examined. Design, performance and LCC dynamic models are developed based on mission and system/subsystem requirements and existing or derived physical and cost data relationships. The models are exercised to define baseline designs and costs. Then the major design and performance parameters are each varied to determine their influence on LCC around the baseline values.

Modeling the effects of hypoxia on ATP turnover in exercising muscle

NASA Technical Reports Server (NTRS)

Arthur, P. G.; Hogan, M. C.; Bebout, D. E.; Wagner, P. D.; Hochachka, P. W.

1992-01-01

Most models of metabolic control concentrate on the regulation of ATP production and largely ignore the regulation of ATP demand. We describe a model, based on the results of Hogan et al. (J. Appl. Physiol. 73: 728-736, 1992), that incorporates the effects of ATP demand. The model is developed from the premise that a unique set of intracellular conditions can be measured at each level of ATP turnover and that this relationship is best described by energetic state. Current concepts suggest that cells are capable of maintaining oxygen consumption in the face of declines in the concentration of oxygen through compensatory changes in cellular metabolites. We show that these compensatory changes can cause significant declines in ATP demand and result in a decline in oxygen consumption and ATP turnover. Furthermore we find that hypoxia does not directly affect the rate of anaerobic ATP synthesis and associated lactate production. Rather, lactate production appears to be related to energetic state, whatever the PO2. The model is used to describe the interaction between ATP demand and ATP supply in determining final ATP turnover.

7 CFR 3300.88 - Fees for U.S. ATP certificates.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300... EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION OF SPECIAL EQUIPMENT Other Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for issuance of U.S. ATP...

7 CFR 3300.88 - Fees for U.S. ATP certificates.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 15 2012-01-01 2012-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300... EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION OF SPECIAL EQUIPMENT Other Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for issuance of U.S. ATP...

7 CFR 3300.88 - Fees for U.S. ATP certificates.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300... EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION OF SPECIAL EQUIPMENT Other Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for issuance of U.S. ATP...

7 CFR 3300.88 - Fees for U.S. ATP certificates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300... EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION OF SPECIAL EQUIPMENT Other Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for issuance of U.S. ATP...

7 CFR 3300.88 - Fees for U.S. ATP certificates.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Fees for U.S. ATP certificates. 3300.88 Section 3300... EQUIPMENT TO BE USED FOR SUCH CARRIAGE (ATP); INSPECTION, TESTING, AND CERTIFICATION OF SPECIAL EQUIPMENT Other Provisions § 3300.88 Fees for U.S. ATP certificates. The fee schedule for issuance of U.S. ATP...

Dynamic modelling and adaptive robust tracking control of a space robot with two-link flexible manipulators under unknown disturbances

NASA Astrophysics Data System (ADS)

Yang, Xinxin; Ge, Shuzhi Sam; He, Wei

2018-04-01

In this paper, both the closed-form dynamics and adaptive robust tracking control of a space robot with two-link flexible manipulators under unknown disturbances are developed. The dynamic model of the system is described with assumed modes approach and Lagrangian method. The flexible manipulators are represented as Euler-Bernoulli beams. Based on singular perturbation technique, the displacements/joint angles and flexible modes are modelled as slow and fast variables, respectively. A sliding mode control is designed for trajectories tracking of the slow subsystem under unknown but bounded disturbances, and an adaptive sliding mode control is derived for slow subsystem under unknown slowly time-varying disturbances. An optimal linear quadratic regulator method is proposed for the fast subsystem to damp out the vibrations of the flexible manipulators. Theoretical analysis validates the stability of the proposed composite controller. Numerical simulation results demonstrate the performance of the closed-loop flexible space robot system.

Capture and quality control mechanisms for ATP binding

PubMed Central

Li, Li; Martinis, Susan A.

2013-01-01

The catalytic events in members of the nucleotidylyl transferase superfamily are initiated by a millisecond binding of ATP in the active site. Through metadynamics simulations on a class I aminoacyl-tRNA synthetase (aaRSs), the largest group in the superfamily, we calculate the free energy landscape of ATP selection and binding. Mutagenesis studies and fluorescence spectroscopy validated the identification of the most populated intermediate states. The rapid first binding step involves formation of encounter complexes captured through a fly-casting mechanism that acts up on the triphosphate moiety of ATP. In the slower nucleoside binding step, a conserved histidine in the HxxH motif orients the incoming ATP through base-stacking interactions resulting in a deep minimum in the free energy surface. Mutation of this histidine significantly decreases the binding affinity measured experimentally and computationally. The metadynamics simulations further reveal an intermediate quality control state that the synthetases and most likely other members of the superfamily use to select ATP over other nucleoside triphosphates. PMID:23276298

Deletion of a unique loop in the mycobacterial F-ATP synthase γ subunit sheds light on its inhibitory role in ATP hydrolysis-driven H(+) pumping.

PubMed

Hotra, Adam; Suter, Manuel; Biuković, Goran; Ragunathan, Priya; Kundu, Subhashri; Dick, Thomas; Grüber, Gerhard

2016-05-01

The F1 FO -ATP synthase is one of the enzymes that is essential to meet the energy requirement of both the proliferating aerobic and hypoxic dormant stages of the life cycle of mycobacteria. Most F-ATP synthases consume ATP in the α3 :β3 headpiece to drive the γ subunit, which couples ATP cleavage with proton pumping in the c ring of FO via the bottom of the γ subunit. ATPase-driven H(+) pumping is latent in mycobacteria. The presence of a unique 14 amino acid residue loop of the mycobacterial γ subunit has been described and aligned in close vicinity to the c-ring loop Priya R et al. (2013) J Bioenerg Biomembr 45, 121-129 Here, we used inverted membrane vesicles (IMVs) of fast-growing Mycobacterium smegmatis and a variety of covalent and non-covalent inhibitors to characterize the ATP hydrolysis activity of the F-ATP synthase inside IMVs. These vesicles formed a platform to investigate the function of the unique mycobaterial γ loop by deleting the respective loop-encoding sequence (γ166-179 ) in the genome of M. smegmatis. ATP hydrolysis-driven H(+) pumping was observed in IMVs containing the Δγ166-179 mutant protein but not for IMVs containing the wild-type F-ATP synthase. In addition, when compared to the wild-type enzyme, IMVs containing the Δγ166-179 mutant protein showed increased ATP cleavage and lower levels of ATP synthesis, demonstrating that the loop affects ATPase activity, ATPase-driven H(+) pumping and ATP synthesis. These results further indicate that the loop may affect coupling of ATP hydrolysis and synthesis in a different mode. © 2016 Federation of European Biochemical Societies.

Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1.

PubMed

Mayuzumi, N; Ikeda, S; Kawada, H; Fan, P S; Ogawa, H

2005-04-01

Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly inherited skin disorders that histologically share the characteristics of suprabasal separation and acantholysis of epidermal keratinocytes. Various mutations in the DD gene (ATP2A2) and the HHD gene (ATP2C1) (respectively encoding the calcium pumps of the sarco/endoplasmic reticulum and the Golgi apparatus) have recently been described in multiple families with DD and HHD. Mutations in ATP2A2 or ATP2C1 have been suggested as causing the conditions via the mechanism of haploinsufficiency. Ultraviolet (UV) B irradiation is thought to be an aggravating factor in both diseases. To examine the effects of various stimuli on ATP2A2 and ATP2C1 mRNA expression, and to examine the role of calcium pumps during keratinocyte differentiation. The effects of UVB irradiation, of UVB-inducible inflammatory cytokines produced by keratinocytes and of high-calcium medium (1.8 mmol L(-1) as opposed to 0.08 mmol L(-1) Ca2+) on ATP2A2 and ATP2C1 mRNA expression were quantified in cultured normal human keratinocytes using reverse transcription-polymerase chain reaction. Expression of ATP2A2 and ATP2C1 mRNA was suppressed immediately after exposure to UVB irradiation, and modulation of mRNA expression was achieved in keratinocytes cultured with proinflammatory cytokines. The mRNA expression of both genes was increased significantly after the shift to high extracellular Ca2+ concentration. The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.

Charactering lidar optical subsystem using four quadrants method

NASA Astrophysics Data System (ADS)

Tian, Xiaomin; Liu, Dong; Xu, Jiwei; Wang, Zhenzhu; Wang, Bangxin; Wu, Decheng; Zhong, Zhiqing; Xie, Chenbo; Wang, Yingjian

2018-02-01

Lidar is a kind of active optical remote sensing instruments , can be applied to sound atmosphere with a high spatial and temporal resolution. Many parameter of atmosphere can be get by using different inverse algorithm with lidar backscatter signal. The basic setup of a lidar consist of a transmitter and a receiver. To make sure the quality of lidar signal data, the lidar must be calibrated before being used to measure the atmospheric variables. It is really significant to character and analyze lidar optical subsystem because a well equiped lidar optical subsystem contributes to high quality lidar signal data. we pay close attention to telecover test to character and analyze lidar optical subsystem.The telecover test is called four quadrants method consisting in dividing the telescope aperture in four quarants. when a lidar is well configured with lidar optical subsystem, the normalized signal from four qudrants will agree with each other on some level. Testing our WARL-II lidar by four quadrants method ,we find the signals of the four basically consistent with each other both in near range and in far range. But in detail, the signals in near range have some slight distinctions resulting from overlap function, some signals distinctions are induced by atmospheric instability.

Preprototype vapor compression distillation subsystem. [recovering potable water from wastewater

NASA Technical Reports Server (NTRS)

Ellis, G. S.; Wynveen, R. A.; Schubert, F. H.

1979-01-01

A three-person capacity preprototype vapor compression distillation subsystem for recovering potable water from wastewater aboard spacecraft was designed, assembled, and tested. The major components of the subsystem are: (1) a distillation unit which includes a compressor, centrifuge, central shaft, and outer shell; (2) a purge pump; (3) a liquids pump; (4) a post-treat cartridge; (5) a recycle/filter tank; (6) an evaporator high liquid level sensor; and (7) the product water conductivity monitor. A computer based control monitor instrumentation carries out operating mode change sequences, monitors and displays subsystem parameters, maintains intramode controls, and stores and displays fault detection information. The mechanical hardware occupies 0.467 m3, requires 171 W of electrical power, and has a dry weight of 143 kg. The subsystem recovers potable water at a rate of 1.59 kg/hr, which is equivalent to a duty cycle of approximately 30% for a crew of three. The product water has no foul taste or odor. Continued development of the subsystem is recommended for reclaiming water for human consumption as well as for flash evaporator heat rejection, urinal flushing, washing, and other on-board water requirements.

Structural Characterization of Two Metastable ATP-Bound States of P-Glycoprotein

PubMed Central

O’Mara, Megan L.; Mark, Alan E.

2014-01-01

ATP Binding Cassette (ABC) transporters couple the binding and hydrolysis of ATP to the transport of substrate molecules across the membrane. The mechanism by which ATP binding and/or hydrolysis drives the conformational changes associated with substrate transport has not yet been characterized fully. Here, changes in the conformation of the ABC export protein P-glycoprotein on ATP binding are examined in a series of molecular dynamics simulations. When one molecule of ATP is placed at the ATP binding site associated with each of the two nucleotide binding domains (NBDs), the membrane-embedded P-glycoprotein crystal structure adopts two distinct metastable conformations. In one, each ATP molecule interacts primarily with the Walker A motif of the corresponding NBD. In the other, the ATP molecules interacts with both Walker A motif of one NBD and the Signature motif of the opposite NBD inducing the partial dimerization of the NBDs. This interaction is more extensive in one of the two ATP binding site, leading to an asymmetric structure. The overall conformation of the transmembrane domains is not altered in either of these metastable states, indicating that the conformational changes associated with ATP binding observed in the simulations in the absence of substrate do not lead to the outward-facing conformation and thus would be insufficient in themselves to drive transport. Nevertheless, the metastable intermediate ATP-bound conformations observed are compatible with a wide range of experimental cross-linking data demonstrating the simulations do capture physiologically important conformations. Analysis of the interaction between ATP and its cofactor Mg2+ with each NBD indicates that the coordination of ATP and Mg2+ differs between the two NBDs. The role structural asymmetry may play in ATP binding and hydrolysis is discussed. Furthermore, we demonstrate that our results are not heavily influenced by the crystal structure chosen for initiation of the simulations

Renal epithelial cells can release ATP by vesicular fusion

PubMed Central

Bjaelde, Randi G.; Arnadottir, Sigrid S.; Overgaard, Morten T.; Leipziger, Jens; Praetorius, Helle A.

2013-01-01

Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30), which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1) cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin) reduced both the spontaneous and hypotonically (80%)-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1) and vesicular transport (nocodazole). These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ~90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP) or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50%) or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8 and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells. PMID:24065923

Three-Dimensional Structures Reveal Multiple ADP/ATP Binding Modes

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

C Simmons; C Magee; D Smith

The creation of synthetic enzymes with predefined functions represents a major challenge in future synthetic biology applications. Here, we describe six structures of de novo proteins that have been determined using protein crystallography to address how simple enzymes perform catalysis. Three structures are of a protein, DX, selected for its stability and ability to tightly bind ATP. Despite the addition of ATP to the crystallization conditions, the presence of a bound but distorted ATP was found only under excess ATP conditions, with ADP being present under equimolar conditions or when crystallized for a prolonged period of time. A bound ADPmore » cofactor was evident when Asp was substituted for Val at residue 65, but ATP in a linear configuration is present when Phe was substituted for Tyr at residue 43. These new structures complement previously determined structures of DX and the protein with the Phe 43 to Tyr substitution [Simmons, C. R., et al. (2009) ACS Chem. Biol. 4, 649-658] and together demonstrate the multiple ADP/ATP binding modes from which a model emerges in which the DX protein binds ATP in a configuration that represents a transitional state for the catalysis of ATP to ADP through a slow, metal-free reaction capable of multiple turnovers. This unusual observation suggests that design-free methods can be used to generate novel protein scaffolds that are tailor-made for catalysis.« less

Myosin Motors: The Chemical Restraints Imposed by ATP

NASA Astrophysics Data System (ADS)

Rayment, I.; Allingham, J.

Most molecular motors use ATP. This is not surprising since this is the universal currency of energy for most of life's processes. The question to be addressed in this chapter is how does the fundamental chemistry of ATP hydrolysis in- fluence the observed organization of linear molecular motors seen today with a focus on myosin. This chapter is written to ask in simple terms what can be gained by reconsidering the chemistry of ATP hydrolysis.

The chloroplast ATP synthase features the characteristic redox regulation machinery.

PubMed

Hisabori, Toru; Sunamura, Ei-Ichiro; Kim, Yusung; Konno, Hiroki

2013-11-20

Regulation of the activity of the chloroplast ATP synthase is largely accomplished by the chloroplast thioredoxin system, the main redox regulation system in chloroplasts, which is directly coupled to the photosynthetic reaction. We review the current understanding of the redox regulation system of the chloroplast ATP synthase. The thioredoxin-targeted portion of the ATP synthase consists of two cysteines located on the central axis subunit γ. The redox state of these two cysteines is under the influence of chloroplast thioredoxin, which directly controls rotation during catalysis by inducing a conformational change in this subunit. The molecular mechanism of redox regulation of the chloroplast ATP synthase has recently been determined. Regulation of the activity of the chloroplast ATP synthase is critical in driving efficiency into the ATP synthesis reaction in chloroplasts. The molecular architecture of the chloroplast ATP synthase, which confers redox regulatory properties requires further investigation, in light of the molecular structure of the enzyme complex as well as the physiological significance of the regulation system.

Domestic wash-water reclamation using an aerospace-developed water recovery subsystem

NASA Technical Reports Server (NTRS)

Hall, J. B., Jr.

1973-01-01

A prototype aerospace distillation water recovery subsystem was tested to determine its capability to recover potable water from domestic wash water. A total of 0.0994 cu m (26.25 gallons) of domestic wash water was processed over a 7-day period at an average process rate of 0.0146 cu m per day (3.85 gallons per day). The subsystem produced water that met all United States Public Health Standards for drinking water with the exception of two standards which could not be analyzed at the required sensitivity levels. Average energy consumption for this evaluation to maintain both the recovery process and microbial control in the recovered water was approximately 3366 kilowatt-hours per cubic meter (12.74 kilowatt-hours per gallon) of water recovered. This condition represents a worst case energy consumption since no attempt was made to recover heat energy in the subsystem. An ultraviolet radiation cell installed in the effluent line of the subsystem was effective in controlling coliform micro-organisms within acceptable levels for drinking water. The subsystem recovered virtually 100 percent of the available water in the waste-water process. In addition, the subsystem removed 99.6 percent and 98.3 percent of the surfactants and phosphate, respectively, from the wash water.

Neurokinin B potentiates ATP-activated currents in rat DRG neurons.

PubMed

Wang, M J; Xiong, S H; Li, Z W

2001-12-27

This study aimed to explore whether NKB could modulate the responses mediated by ATP receptor (P2X purinoceptor). Whole-cell patch clamp and repatch experiments were performed on cultured rat DRG neurons. The majority of neurons examined were sensitive both to ATP and to NKB (77.1%, 54/70). NKB preapplied could potentiate ATP-activated currents (I(ATP)) markedly; this effect was concentration-dependent and could be blocked by SR 142801, an NK3 receptor antagonist. Preapplication of 0.001, 0.01, 0.1 and 1.0 microM NKB increased ATP-activated currents by 55.1+/-18.8, 75.2+/-17.4, 84.1+/-18.8 and 81.0+/-21.7%, respectively. The concentration-response curves for ATP with and without preapplication of NKB show that: (1) preapplication of NKB shifted the curve upwards; (2) the maximal amplitude of I(ATP) with NKB preapplication increased by 78.5%, while the threshold value remained unchanged; (3) the EC(50) values of the two curves were very close (44 vs. 42 microM). Intracellular dialysis of H-7 by using repatch clamp technique could block the potentiation of I(ATP) by NKB. It suggests that this potentiating effect was caused by phosphorylation of ATP receptor, which resulted from the activation of G protein coupled NK3 receptor and consequential intracellular signal transduction cascade.

Extracellular ATP Acts on Jasmonate Signaling to Reinforce Plant Defense.

PubMed

Tripathi, Diwaker; Zhang, Tong; Koo, Abraham J; Stacey, Gary; Tanaka, Kiwamu

2018-01-01

Damaged cells send various signals to stimulate defense responses. Recent identification and genetic studies of the plant purinoceptor, P2K1 (also known as DORN1), have demonstrated that extracellular ATP is a signal involved in plant stress responses, including wounding, perhaps to evoke plant defense. However, it remains largely unknown how extracellular ATP induces plant defense responses. Here, we demonstrate that extracellular ATP induces plant defense mediated through activation of the intracellular signaling of jasmonate (JA), a well-characterized defense hormone. In Arabidopsis ( Arabidopsis thaliana ) leaves, ATP pretreatment induced resistance against the necrotrophic fungus, Botrytis cinerea The induced resistance was enhanced in the P2K1 receptor overexpression line, but reduced in the receptor mutant, dorn1 - 3 Mining the transcriptome data revealed that ATP induces a set of JA-induced genes. In addition, the P2K1-associated coexpression network contains defense-related genes, including those encoding jasmonate ZIM-domain (JAZ) proteins, which play key roles as repressors of JA signaling. We examined whether extracellular ATP impacts the stability of JAZ1 in Arabidopsis. The results showed that the JAZ1 stability decreased in response to ATP addition in a proteasome-dependent manner. This reduction required intracellular signaling via second messengers-cytosolic calcium, reactive oxygen species, and nitric oxide. Interestingly, the ATP-induced JAZ1 degradation was attenuated in the JA receptor mutant, coi1 , but not in the JA biosynthesis mutant, aos , or upon addition of JA biosynthesis inhibitors. Immunoprecipitation analysis demonstrated that ATP increases the interaction between COI1 and JAZ1, suggesting direct cross talk between extracellular ATP and JA in intracellular signaling events. Taken together, these results suggest that extracellular ATP signaling directly impacts the JA signaling pathway to maximize plant defense responses. © 2018

Behavior and stability of adenosine triphosphate (ATP) during chlorine disinfection.

PubMed

Nescerecka, Alina; Juhna, Talis; Hammes, Frederik

2016-09-15

Adenosine triphosphate (ATP) analysis is a cultivation-independent alternative method for the determination of bacterial viability in both chlorinated and non-chlorinated water. Here we investigated the behavior and stability of ATP during chlorination in detail. Different sodium hypochlorite doses (0-22.4 mg-Cl2 L(-1); 5 min exposure) were applied to an Escherichia coli pure culture suspended in filtered river water. We observed decreasing intracellular ATP with increasing chlorine concentrations, but extracellular ATP concentrations only increased when the chlorine dose exceeded 0.35 mg L(-1). The release of ATP from chlorine-damaged bacteria coincided with severe membrane damage detected with flow cytometry (FCM). The stability of extracellular ATP was subsequently studied in different water matrixes, and we found that extracellular ATP was stable in sterile deionized water and also in chlorinated water until extremely high chlorine doses (≤11.2 mg-Cl2 L(-1); 5 min exposure). In contrast, ATP decreased relatively slowly (k = 0.145 h(-1)) in 0.1 μm filtered river water, presumably due to degradation by either extracellular enzymes or the fraction of bacteria that were able to pass through the filter. Extracellular ATP decreased considerably faster (k = 0.368 h(-1)) during batch growth of a river water bacterial community. A series of growth potential tests showed that extracellular ATP molecules were utilized as a phosphorus source during bacteria proliferation. From the combined data we conclude that ATP released from bacteria at high chlorine doses could promote bacteria regrowth, contributing to biological instability in drinking water distribution systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of ATP Hydrolysis by Thermoalkaliphilic F1Fo-ATP Synthase Is Controlled by the C Terminus of the ɛ Subunit

PubMed Central

Keis, Stefanie; Stocker, Achim; Dimroth, Peter; Cook, Gregory M.

2006-01-01

The F1Fo-ATP synthases of alkaliphilic bacteria exhibit latent ATPase activity, and for the thermoalkaliphile Bacillus sp. strain TA2.A1, this activity is intrinsic to the F1 moiety. To study the mechanism of ATPase inhibition, we developed a heterologous expression system in Escherichia coli to produce TA2F1 complexes from this thermoalkaliphile. Like the native F1Fo-ATP synthase, the recombinant TA2F1 was blocked in ATP hydrolysis activity, and this activity was stimulated by the detergent lauryldimethylamine oxide. To determine if the C-terminal domain of the ɛ subunit acts as an inhibitor of ATPase activity and if an electrostatic interaction plays a role, a TA2F1 mutant with either a truncated ɛ subunit [i.e., TA2F1(ɛΔC)] or substitution of basic residues in the second α-helix of ɛ with nonpolar alanines [i.e., TA2F1(ɛ6A)] was constructed. Both mutants showed ATP hydrolysis activity at low and high concentrations of ATP. Treatment of the purified F1Fo-ATP synthase and TA2F1(ɛWT) complex with proteases revealed that the ɛ subunit was resistant to proteolytic digestion. In contrast, the ɛ subunit of TA2F1(ɛ6A) was completely degraded by trypsin, indicating that the C-terminal arm was in a conformation where it was no longer protected from proteolytic digestion. In addition, ATPase activity was not further activated by protease treatment when compared to the untreated control, supporting the observation that ɛ was responsible for inhibition of ATPase activity. To study the effect of the alanine substitutions in the ɛ subunit in the entire holoenzyme, we reconstituted recombinant TA2F1 complexes with F1-stripped native membranes of strain TA2.A1. The reconstituted TA2FoF1(ɛWT) was blocked in ATP hydrolysis and exhibited low levels of ATP-driven proton pumping consistent with the F1Fo-ATP synthase in native membranes. Reconstituted TA2FoF1(ɛ6A) exhibited ATPase activity that correlated with increased ATP-driven proton pumping, confirming that the �

ATP7B detoxifies silver in ciliated airway epithelial cells

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

Ibricevic, Aida, E-mail: aidaibricevic@hotmail.co; Brody, Steven L., E-mail: sbrody@dom.wustl.ed; Youngs, Wiley J., E-mail: youngs@uakron.ed

2010-03-15

Silver is a centuries-old antibiotic agent currently used to treat infected burns. The sensitivity of a wide range of drug-resistant microorganisms to silver killing suggests that it may be useful for treating refractory lung infections. Toward this goal, we previously developed a methylated caffeine silver acetate compound, SCC1, that exhibits broad-spectrum antimicrobial activity against clinical strains of bacteria in vitro and when nebulized to lungs in mouse infection models. Preclinical testing of high concentrations of SCC1 in primary culture mouse tracheal epithelial cells (mTEC) showed selective ciliated cell death. Ciliated cell death was induced by both silver- and copper-containing compoundsmore » but not by the methylated caffeine portion of SCC1. We hypothesized that copper transporting P-type ATPases, ATP7A and ATP7B, play a role in silver detoxification in the airway. In mTEC, ATP7A was expressed in non-ciliated cells, whereas ATP7B was expressed only in ciliated cells. The exposure of mTEC to SCC1 induced the trafficking of ATP7B, but not ATP7A, suggesting the presence of a cell-specific silver uptake and detoxification mechanisms. Indeed, the expression of the copper uptake protein CTR1 was also restricted to ciliated cells. A role of ATP7B in silver detoxification was further substantiated when treatment of SCC1 significantly increased cell death in ATP7B shRNA-treated HepG2 cells. In addition, mTEC from ATP7B{sup -/-} mice showed enhanced loss of ciliated cells compared to wild type. These studies are the first to demonstrate a cell type-specific expression of the Ag{sup +}/Cu{sup +} transporters ATP7A, ATP7B, and CTR1 in airway epithelial cells and a role for ATP7B in detoxification of these metals in the lung.« less

The human operator transfer function: Identification of the limb mechanics subsystem

NASA Technical Reports Server (NTRS)

Jones, Lynette A.; Hunter, Ian W.

1991-01-01

The objective of our research is to decompose the performance of the human operator in terms of the subsystems that determine the operator's responses in order to establish how the dynamics of these component subsystems influence the operator's performance. In the present experiment, the dynamic stiffness of the human elbow joint was measured at rest and under different levels of biceps muscle activation; this work forms part of the analysis of the limb mechanics subsystem.

Software Testbed for Developing and Evaluating Integrated Autonomous Subsystems

NASA Technical Reports Server (NTRS)

Ong, James; Remolina, Emilio; Prompt, Axel; Robinson, Peter; Sweet, Adam; Nishikawa, David

2015-01-01

To implement fault tolerant autonomy in future space systems, it will be necessary to integrate planning, adaptive control, and state estimation subsystems. However, integrating these subsystems is difficult, time-consuming, and error-prone. This paper describes Intelliface/ADAPT, a software testbed that helps researchers develop and test alternative strategies for integrating planning, execution, and diagnosis subsystems more quickly and easily. The testbed's architecture, graphical data displays, and implementations of the integrated subsystems support easy plug and play of alternate components to support research and development in fault-tolerant control of autonomous vehicles and operations support systems. Intelliface/ADAPT controls NASA's Advanced Diagnostics and Prognostics Testbed (ADAPT), which comprises batteries, electrical loads (fans, pumps, and lights), relays, circuit breakers, invertors, and sensors. During plan execution, an experimentor can inject faults into the ADAPT testbed by tripping circuit breakers, changing fan speed settings, and closing valves to restrict fluid flow. The diagnostic subsystem, based on NASA's Hybrid Diagnosis Engine (HyDE), detects and isolates these faults to determine the new state of the plant, ADAPT. Intelliface/ADAPT then updates its model of the ADAPT system's resources and determines whether the current plan can be executed using the reduced resources. If not, the planning subsystem generates a new plan that reschedules tasks, reconfigures ADAPT, and reassigns the use of ADAPT resources as needed to work around the fault. The resource model, planning domain model, and planning goals are expressed using NASA's Action Notation Modeling Language (ANML). Parts of the ANML model are generated automatically, and other parts are constructed by hand using the Planning Model Integrated Development Environment, a visual Eclipse-based IDE that accelerates ANML model development. Because native ANML planners are currently

Solar electric propulsion/instrument/subsystems interaction study

NASA Technical Reports Server (NTRS)

Sellen, J. M., Jr.; Cole, R. K.; Kemp, R. F.; Hall, D. F.; Shelton, H.

1973-01-01

The interactive effects between a solar electric propulsion system and an electrically propelled scientific spacecraft were examined. The operation of the ion thrusters may impact upon the acquisition and interpretation of data by the science payload of the spacecraft. The effluents from the operation of the electric propulsion unit may also impact upon the operation of the various subsystems of the vehicle. Specific interactive effects were isolated where meaningful levels of interaction may occur. The level of impact upon elements of the science payload and other affected subsystems is examined, and avenues for the reduction or elimination of impact are defined.

ATP-induced changes in rat skeletal muscle contractility.

PubMed

Gabdrakhmanov, A I; Khayrullin, A E; Grishin, C H; Ziganshin, A U

2015-01-01

Extracellular purine compounds, adenosine triphosphate (ATP) and adenosine, are involved in regulation of many cell functions, engaging in rapid and long-term cellular processes. The nucleotides, including ATP, exert their extracellular effects by influencing membrane P2 receptors. ATP outside of the cell rapidly is metabolized by the ecto-enzyme system to produce adenosine, which acts on separate adenosine (P1) receptors. Since adenosine and ATP often are functional antagonists, ATP degradation not only limits its effect, but also brings new ligand with different, often opposing, properties. Great variety and widespread of P2 and adenosine receptors in the body emphasize the important physiological and pathophysiological significance of these receptors, and make them very attractive as targets for potential drug action.The existence of several subtypes of P2 and adenosine receptors has been shown in the skeletal muscles. ATP as a co-transmitter is densely packed together with classical neurotransmitters in the presynaptic vesicles of vertebral motor units but until recently ATP was refused to have its own functional role there and was recognized only as a source of adenosine. However, on the eve of the third millennium there appeared data that ATP, released from the nerve ending and acting on presynaptic P2 receptors, suppresses subsequent quantum release of acetylcholine. The final product of its degradation, adenosine, performs a similar inhibitory effect acting on presynaptic adenosine receptors.Despite the fact that the mechanisms of presynaptic inhibitory action of ATP and other purines were studied earlier, the object of those studies was usually neuromuscular synapse of cold-blooded animals. The few studies, in which experiments were carried out on preparations of warm-blooded animals, described the basic effects of purines. These often were guided by the convenience of preparation of the synapses of the diaphragm. We think that those results cannot be

Analysis of the human operator subsystems

NASA Technical Reports Server (NTRS)

Jones, Lynette A.; Hunter, Ian W.

1991-01-01

Except in low-bandwidth systems, knowledge of the human operator transfer function is essential for high-performance telerobotic systems. This information has usually been derived from detailed analyses of tracking performance, in which the human operator is considered as a complete system rather than as a summation of a number of subsystems, each of which influences the operator's output. Studies of one of these subsystems, the limb mechanics system, demonstrate that large parameter variations can occur that can have a profound effect on the stability of force-reflecting telerobot systems. An objective of this research was to decompose the performance of the human operator system in order to establish how the dynamics of each of the elements influence the operator's responses.

Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B.

PubMed

Luoma, Leiah M; Deeb, Taha M M; Macintyre, Georgina; Cox, Diane W

2010-05-01

Wilson disease (WND) is an autosomal recessive disorder resulting from mutation of ATP7B. Transport of copper by ATP7B from the trans-Golgi of hepatocytes into apical membrane-trafficked vesicles for excretion in the bile is the major means of copper elimination from the body. Although copper is an essential nutrient, homeostasis must be carefully maintained. If homeostasis is disrupted, copper can accumulate within the liver, kidney, cornea, and/or brain. The range of organs affected leads to clinical heterogeneity and difficulty in WND diagnosis. Sequencing of ATP7B is an important adjunct for diagnosis but has led to the discovery of many novel missense variants. Although prediction programs are available, functional characterization is essential for determining the consequence of novel variants. We have tested 12 missense variants localized to the ATP loop of ATP7B and compared three predictive programs (SIFT, PolyPhen, and Align-GVGD). We found p.L1043P, p.G1000R, p.G1101R, p.I1102T, p.V1239G, and p.D1267V deleterious; p.G1176E and p.G1287S intermediate; p.E1173G temperature sensitive; p.T991M and p.I1148T mild; and p.R1228T functioning as wild type. We found that SIFT most often agreed with functional data (92%), compared with PolyPhen (83%) and Align-GVGD (67%). We conclude that variants found to negatively affect function likely contribute to the WND phenotype in patients. (c) 2010 Wiley-Liss, Inc.

Robust operative diagnosis as problem solving in a hypothesis space

NASA Technical Reports Server (NTRS)

Abbott, Kathy H.

1988-01-01

This paper describes an approach that formulates diagnosis of physical systems in operation as problem solving in a hypothesis space. Such a formulation increases robustness by: (1) incremental hypotheses construction via dynamic inputs, (2) reasoning at a higher level of abstraction to construct hypotheses, and (3) partitioning the space by grouping fault hypotheses according to the type of physical system representation and problem solving techniques used in their construction. It was implemented for a turbofan engine and hydraulic subsystem. Evaluation of the implementation on eight actual aircraft accident cases involving engine faults provided very promising results.

X-34 Main Propulsion System-Selected Subsystem Analyses

NASA Technical Reports Server (NTRS)

Brown, T. M.; McDonald, J. P.; Knight, K. C.; Champion, R. H., Jr.

1998-01-01

The X-34 hypersonic flight vehicle is currently under development by Orbital Sciences Corporation (Orbital). The Main Propulsion System (MPS) has been designed around the liquid propellant Fastrac rocket engine currently under development at NASA Marshall Space Flight Center. This paper presents selected analyses of MPS subsystems and components. Topics include the integration of component and system level modeling of the LOX dump subsystem and a simple terminal bubble velocity analysis conducted to guide propellant feed line design.

Fast transient currents in Na,K-ATPase induced by ATP concentration jumps from the P3-[1-(3',5'-dimethoxyphenyl)-2-phenyl-2-oxo]ethyl ester of ATP.

PubMed Central

Sokolov, V S; Apell, H J; Corrie, J E; Trentham, D R

1998-01-01

Electrogenic ion transport by Na,K-ATPase was investigated by analysis of transient currents in a model system of protein-containing membrane fragments adsorbed to planar lipid bilayers. Sodium transport was triggered by ATP concentration jumps in which ATP was released from an inactive precursor by an intense near-UV light flash. The method has been used previously with the P3-1-(2-nitrophenyl)ethyl ester of ATP (NPE-caged ATP), from which the relatively slow rate of ATP release limits analysis of processes in the pump mechanism controlled by rate constants greater than 100 s(-1) at physiological pH. Here Na,K-ATPase was reinvestigated using the P3-[1-(3,5-dimethoxyphenyl)-2-phenyl-2-oxo]ethyl ester of ATP (DMB-caged ATP), which has an ATP release rate of >10(5) s(-1). Under otherwise identical conditions, photorelease of ATP from DMB-caged ATP showed faster kinetics of the transient current compared to that from NPE-caged ATP. With DMB-caged ATP, transient currents had rate profiles that were relatively insensitive to pH and the concentration of caged compound. Rate constants of ATP binding and of the E1 to E2 conformational change were compatible with earlier studies. Rate constants of enzyme phosphorylation and ADP-dependent dephosphorylation were 600 s(-1) and 1.5 x 10(6) M(-1) s(-1), respectively, at pH 7.2 and 22 degrees C. PMID:9591656

Virtual Engineering and Science Team - Reusable Autonomy for Spacecraft Subsystems

NASA Technical Reports Server (NTRS)

Bailin, Sidney C.; Johnson, Michael A.; Rilee, Michael L.; Truszkowski, Walt; Thompson, Bryan; Day, John H. (Technical Monitor)

2002-01-01

In this paper we address the design, development, and evaluation of the Virtual Engineering and Science Team (VEST) tool - a revolutionary way to achieve onboard subsystem/instrument autonomy. VEST directly addresses the technology needed for advanced autonomy enablers for spacecraft subsystems. It will significantly support the efficient and cost effective realization of on-board autonomy and contribute directly to realizing the concept of an intelligent autonomous spacecraft. VEST will support the evolution of a subsystem/instrument model that is probably correct and from that model the automatic generation of the code needed to support the autonomous operation of what was modeled. VEST will directly support the integration of the efforts of engineers, scientists, and software technologists. This integration of efforts will be a significant advancement over the way things are currently accomplished. The model, developed through the use of VEST, will be the basis for the physical construction of the subsystem/instrument and the generated code will support its autonomous operation once in space. The close coupling between the model and the code, in the same tool environment, will help ensure that correct and reliable operational control of the subsystem/instrument is achieved.VEST will provide a thoroughly modern interface that will allow users to easily and intuitively input subsystem/instrument requirements and visually get back the system's reaction to the correctness and compatibility of the inputs as the model evolves. User interface/interaction, logic, theorem proving, rule-based and model-based reasoning, and automatic code generation are some of the basic technologies that will be brought into play in realizing VEST.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.

PubMed

Ahmad, Zulfiqar; Hassan, Sherif S; Azim, Sofiya

2017-11-20

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phytochemicals is based on tradition or word of mouth with few evidence-based studies. Moreover, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become pertinent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of dietary phytochemicals are known to inhibit ATP synthase. Structural modifications of phytochemicals have been shown to increase the inhibitory potency and extent of inhibition. Sitedirected mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can result in selective binding and inhibition of microbial ATP synthase. In this review, the therapeutic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective targeting of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase

PubMed Central

Ahmad, Zulfiqar; Hassan, Sherif S.; Azim, Sofiya

2017-01-01

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phy-tochemicals is based on tradition or word of mouth with few evidence-based studies. Moreo-ver, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become perti-nent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of die-tary phytochemicals are known to inhibit ATP synthase. Structural modifications of phyto-chemicals have been shown to increase the inhibitory potency and extent of inhibition. Site-directed mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can re-sult in selective binding and inhibition of microbial ATP synthase. In this review, the therapeu-tic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective target-ing of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. PMID:28831918

Catalytic distillation water recovery subsystem

NASA Technical Reports Server (NTRS)

Budininkas, P.; Rasouli, F.

1985-01-01

An integrated engineering breadboard subsystem for the recovery of potable water from untreated urine based on the vapor phase catalytic ammonia removal was designed, fabricated and tested. Unlike other evaporative methods, this process catalytically oxidizes ammonia and volatile hydrocarbons vaporizing with water to innocuous products; therefore, no pretreatment of urine is required. Since the subsystem is fabricated from commercially available components, its volume, weight and power requirements are not optimized; however, it is suitable for zero-g operation. The testing program consists of parametric tests, one month of daily tests and a continuous test of 168 hours duration. The recovered water is clear, odorless, low in ammonia and organic carbon, and requires only an adjustment of its pH to meet potable water standards. The obtained data indicate that the vapor phase catalytic ammonia removal process, if further developed, would also be competitive with other water recovery systems in weight, volume and power requirements.

Preprototype independent air revitalization subsystem

NASA Technical Reports Server (NTRS)

Schubert, F. H.; Hallick, T. M.; Woods, R. R.

1982-01-01

The performance and maturity of a preprototype, three-person capacity, automatically controlled and monitored, self-contained independent air revitalization subsystem were evaluated. The subsystem maintains the cabin partial pressure of oxygen at 22 kPa (3.2 psia) and that of carbon dioxide at 400 Pa (3 mm Hg) over a wide range of cabin air relative humidity conditions. Consumption of water vapor by the water vapor electrolysis module also provides partial humidity control of the cabin environment. During operation, the average carbon dioxide removal efficiency at baseline conditions remained constant throughout the test at 84%. The average electrochemical depolarized concentrator cell voltage at the end of the parametric/endurance test was 0.41 V, representing a very slowly decreasing average cell voltage. The average water vapor electrolysis cell voltage increased only at a rate of 20 mu/h from the initial level of 1.67 V to the final level of 1.69 V at conclusion of the testing.

[Financing, organization, costs and services performance of the Argentinean health sub-systems.

PubMed

Yavich, Natalia; Báscolo, Ernesto Pablo; Haggerty, Jeannie

2016-01-01

To analyze the relationship between health system financing and services organization models with costs and health services performance in each of Rosario's health sub-systems. The financing and organization models were characterized using secondary data. Costs were calculated using the WHO/SHA methodology. Healthcare quality was measured by a household survey (n=822). Public subsystem:Vertically integrated funding and primary healthcare as a leading strategy to provide services produced low costs and individual-oriented healthcare but with weak accessibility conditions and comprehensiveness. Private subsystem: Contractual integration and weak regulatory and coordination mechanisms produced effects opposed to those of the public sub-system. Social security: Contractual integration and strong regulatory and coordination mechanisms contributed to intermediate costs and overall high performance. Each subsystem financing and services organization model had a strong and heterogeneous influence on costs and health services performance.

The Chloroplast ATP Synthase Features the Characteristic Redox Regulation Machinery

PubMed Central

Sunamura, Ei-Ichiro; Kim, Yusung; Konno, Hiroki

2013-01-01

Abstract Significance: Regulation of the activity of the chloroplast ATP synthase is largely accomplished by the chloroplast thioredoxin system, the main redox regulation system in chloroplasts, which is directly coupled to the photosynthetic reaction. We review the current understanding of the redox regulation system of the chloroplast ATP synthase. Recent Advances: The thioredoxin-targeted portion of the ATP synthase consists of two cysteines located on the central axis subunit γ. The redox state of these two cysteines is under the influence of chloroplast thioredoxin, which directly controls rotation during catalysis by inducing a conformational change in this subunit. The molecular mechanism of redox regulation of the chloroplast ATP synthase has recently been determined. Critical Issues: Regulation of the activity of the chloroplast ATP synthase is critical in driving efficiency into the ATP synthesis reaction in chloroplasts. Future Directions: The molecular architecture of the chloroplast ATP synthase, which confers redox regulatory properties requires further investigation, in light of the molecular structure of the enzyme complex as well as the physiological significance of the regulation system. Antioxid. Redox Signal. 19, 1846–1854. PMID:23145525

Functional studies of ATP sulfurylase from Penicillium chrysogenum

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

Seubert, P.A.

1985-01-01

ATP sulfurylase from Penicillium chrysogenum has a specific activity (V/sub max/) of 6-7 units x mg protein/sup -1/ determined with the physiological substrates of MgATP and SO/sub 4//sup 2 -/ and assayed by (A) initial velocity measurements with APS kinase and inorganic pyrophosphatase present and (B) analysis of nonlinear reaction progress curves. The fact both assays give the same results show the intrinsic activity of ATP sulfurylase is much higher than previously reported. In initial velocity dead-end inhibition studies, the sulfate analog S/sub 2/O/sub 3//sup 2 -/ is a competitive inhibitor of SO/sub 42/..sqrt.. and a noncompetitive inhibitor of MgATP.more » Monovalent oxyanions such as NO/sub 3//sup -/, ClO/sub 3//sup -/, ClO/sub 4//sup -/, and FSO/sub 3//sup -/ behave as uncompetitive inhibitors of MgATP and thus seem not to be true sulfate analogs. The reverse reaction was assayed by the pyrophosphate dependent release of /sup 35/SO/sub 4//sup 2 -/ from AP/sup 35/S. Product inhibition by MgATP or SO/sub 4//sup 2 -/ is competitive with APS and mixed-type with PP/sub i/. Imidodiphosphate can serve as an alternative substrate for PP/sub i/. ATP sulfurylase binds (but does not hydrolyze) APS. A Scatchard plot of the APS binding is nonlinear, suggesting at least two types of sites. The cumulative results are qualitatively consistent with the random addition of MgATP and SO/sub 4//sup 2 -/ and the ordered release of first MgPP/sub i/ then APS, with APS release being partially rate limiting. Certain quantitative discrepancies suggest either an unknown variable (e.g. enzyme concentration) complicates the analysis or, in light of binding studies that the actual mechanism is more complicated (e.g. alternating sites) than any of the conventional models examined.« less

Adenosine triphosphate (ATP) as a possible indicator of extraterrestrial biology

NASA Technical Reports Server (NTRS)

Chappelle, E. W.; Picciolo, G. L.

1974-01-01

The ubiquity of adenosine triphosphate (ATP) in terrestrial organisms provides the basis for proposing the assay of this vital metabolic intermediate for detecting extraterrestrial biological activity. If an organic carbon chemistry is present on the planets, the occurrence of ATP is possible either from biosynthetic or purely chemical reactions. However, ATP's relative complexity minimizes the probability of abiogenic synthesis. A sensitive technique for the quantitative detection of ATP was developed using the firefly bioluminescent reaction. The procedure was used successfully for the determination of the ATP content of soil and bacteria. This technique is also being investigated from the standpoint of its application in clinical medicine.

The ICCB Computer Based Facilities Inventory & Utilization Management Information Subsystem.

ERIC Educational Resources Information Center

Lach, Ivan J.

The Illinois Community College Board (ICCB) Facilities Inventory and Utilization subsystem, a part of the ICCB management information system, was designed to provide decision makers with needed information to better manage the facility resources of Illinois community colleges. This subsystem, dependent upon facilities inventory data and course…

Fo-driven Rotation in the ATP Synthase Direction against the Force of F1 ATPase in the FoF1 ATP Synthase*

PubMed Central

Martin, James; Hudson, Jennifer; Hornung, Tassilo; Frasch, Wayne D.

2015-01-01

Living organisms rely on the FoF1 ATP synthase to maintain the non-equilibrium chemical gradient of ATP to ADP and phosphate that provides the primary energy source for cellular processes. How the Fo motor uses a transmembrane electrochemical ion gradient to create clockwise torque that overcomes F1 ATPase-driven counterclockwise torque at high ATP is a major unresolved question. Using single FoF1 molecules embedded in lipid bilayer nanodiscs, we now report the observation of Fo-dependent rotation of the c10 ring in the ATP synthase (clockwise) direction against the counterclockwise force of ATPase-driven rotation that occurs upon formation of a leash with Fo stator subunit a. Mutational studies indicate that the leash is important for ATP synthase activity and support a mechanism in which residues aGlu-196 and cArg-50 participate in the cytoplasmic proton half-channel to promote leash formation. PMID:25713065

Advanced transportation system studies. Alternate propulsion subsystem concepts: Propulsion database

NASA Technical Reports Server (NTRS)

Levack, Daniel

1993-01-01

The Advanced Transportation System Studies alternate propulsion subsystem concepts propulsion database interim report is presented. The objective of the database development task is to produce a propulsion database which is easy to use and modify while also being comprehensive in the level of detail available. The database is to be available on the Macintosh computer system. The task is to extend across all three years of the contract. Consequently, a significant fraction of the effort in this first year of the task was devoted to the development of the database structure to ensure a robust base for the following years' efforts. Nonetheless, significant point design propulsion system descriptions and parametric models were also produced. Each of the two propulsion databases, parametric propulsion database and propulsion system database, are described. The descriptions include a user's guide to each code, write-ups for models used, and sample output. The parametric database has models for LOX/H2 and LOX/RP liquid engines, solid rocket boosters using three different propellants, a hybrid rocket booster, and a NERVA derived nuclear thermal rocket engine.

Extracellular ATP inhibits root gravitropism at concentrations that inhibit polar auxin transport

NASA Technical Reports Server (NTRS)

Tang, Wenqiang; Brady, Shari R.; Sun, Yu; Muday, Gloria K.; Roux, Stanley J.

2003-01-01

Raising the level of extracellular ATP to mM concentrations similar to those found inside cells can block gravitropism of Arabidopsis roots. When plants are grown in Murashige and Skoog medium supplied with 1 mM ATP, their roots grow horizontally instead of growing straight down. Medium with 2 mM ATP induces root curling, and 3 mM ATP stimulates lateral root growth. When plants are transferred to medium containing exogenous ATP, the gravity response is reduced or in some cases completely blocked by ATP. Equivalent concentrations of ADP or inorganic phosphate have slight but usually statistically insignificant effects, suggesting the specificity of ATP in these responses. The ATP effects may be attributable to the disturbance of auxin distribution in roots by exogenously applied ATP, because extracellular ATP can alter the pattern of auxin-induced gene expression in DR5-beta-glucuronidase transgenic plants and increase the response sensitivity of plant roots to exogenously added auxin. The presence of extracellular ATP also decreases basipetal auxin transport in a dose-dependent fashion in both maize (Zea mays) and Arabidopsis roots and increases the retention of [(3)H]indole-3-acetic acid in root tips of maize. Taken together, these results suggest that the inhibitory effects of extracellular ATP on auxin distribution may happen at the level of auxin export. The potential role of the trans-plasma membrane ATP gradient in auxin export and plant root gravitropism is discussed.

Subsystem real-time time dependent density functional theory.

PubMed

Krishtal, Alisa; Ceresoli, Davide; Pavanello, Michele

2015-04-21

We present the extension of Frozen Density Embedding (FDE) formulation of subsystem Density Functional Theory (DFT) to real-time Time Dependent Density Functional Theory (rt-TDDFT). FDE is a DFT-in-DFT embedding method that allows to partition a larger Kohn-Sham system into a set of smaller, coupled Kohn-Sham systems. Additional to the computational advantage, FDE provides physical insight into the properties of embedded systems and the coupling interactions between them. The extension to rt-TDDFT is done straightforwardly by evolving the Kohn-Sham subsystems in time simultaneously, while updating the embedding potential between the systems at every time step. Two main applications are presented: the explicit excitation energy transfer in real time between subsystems is demonstrated for the case of the Na4 cluster and the effect of the embedding on optical spectra of coupled chromophores. In particular, the importance of including the full dynamic response in the embedding potential is demonstrated.

STS-2: SAIL non-avionics subsystems math model requirements

NASA Technical Reports Server (NTRS)

Bennett, W. P.; Herold, R. W.

1980-01-01

Simulation of the STS-2 Shuttle nonavionics subsystems in the shuttle avionics integration laboratory (SAIL) is necessary for verification of the integrated shuttle avionics system. The math model (simulation) requirements for each of the nonavionics subsystems that interfaces with the Shuttle avionics system is documented and a single source document for controlling approved changes (by the SAIL change control panel) to the math models is provided.

Technology for subsystems of space-based plant growth facilities

NASA Technical Reports Server (NTRS)

Bula, R. J.; Morrow, R. C.; Tibbitts, T. W.; Corey, R. B.

1990-01-01

Technologies for different subsystems of space-based plant growth facilities are being developed at the Wisconsin Center for Space Automation and Robotics, a NASA Center for the Commercial Development of Space. The technologies include concepts for water and nutrient delivery, for nutrient composition control, and for irradiation. Effort is being concentrated on these subsystems because available technologies cannot be effectively utilized for space applications.

A real-time bioluminescent HTS method for measuring protein kinase activity influenced neither by ATP concentration nor by luciferase inhibition.

PubMed

Lundin, Arne; Eriksson, Jonas

2008-08-01

The firefly luciferin-luciferase reaction has been used to set up an assay for protein kinase based on measuring ATP consumption rate as the first-order rate constant for the kinase reaction. The assay obviates the problems encountered with previous bioluminescent protein kinase assays such as interference with the luciferase reaction from library compounds, nonlinear standard curves, and limited dynamic ranges. In the assay described in the present paper luciferase and luciferin are present during the entire kinase reaction, and the light emission can be measured continuously. In an HTS situation the light emission is measured only twice, i.e., initially and after a predetermined time. After a fivefold reduction of the ATP concentration a Z' value of 0.96 was obtained. Light emission data from samples with kinase are normalized with light emission data from blanks without kinase. First-order rate constants for the kinase reaction calculated from normalized light emission are not affected by a moderate degree of inactivation of luciferase and luciferin during the measuring time. The constants have the same value at all ATP concentrations much lower than the K(m) of the luciferase and the kinase. These factors make the assay very robust and influenced neither by ATP concentration nor by luciferase inhibition. The measuring time depends on the kinase activity and can be varied from minutes to more than 8 h provided the kinase is stable and the evaporation of water from the wells is acceptable. The assay is linear with respect to kinase activity over three orders of magnitude. The new reagents also allowed us to determine K(m) values for ATP and for Kemptide.

FDE-vdW: A van der Waals inclusive subsystem density-functional theory.

PubMed

Kevorkyants, Ruslan; Eshuis, Henk; Pavanello, Michele

2014-07-28

We present a formally exact van der Waals inclusive electronic structure theory, called FDE-vdW, based on the Frozen Density Embedding formulation of subsystem Density-Functional Theory. In subsystem DFT, the energy functional is composed of subsystem additive and non-additive terms. We show that an appropriate definition of the long-range correlation energy is given by the value of the non-additive correlation functional. This functional is evaluated using the fluctuation-dissipation theorem aided by a formally exact decomposition of the response functions into subsystem contributions. FDE-vdW is derived in detail and several approximate schemes are proposed, which lead to practical implementations of the method. We show that FDE-vdW is Casimir-Polder consistent, i.e., it reduces to the generalized Casimir-Polder formula for asymptotic inter-subsystems separations. Pilot calculations of binding energies of 13 weakly bound complexes singled out from the S22 set show a dramatic improvement upon semilocal subsystem DFT, provided that an appropriate exchange functional is employed. The convergence of FDE-vdW with basis set size is discussed, as well as its dependence on the choice of associated density functional approximant.

FDE-vdW: A van der Waals inclusive subsystem density-functional theory

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

Kevorkyants, Ruslan; Pavanello, Michele, E-mail: m.pavanello@rutgers.edu; Eshuis, Henk

2014-07-28

We present a formally exact van der Waals inclusive electronic structure theory, called FDE-vdW, based on the Frozen Density Embedding formulation of subsystem Density-Functional Theory. In subsystem DFT, the energy functional is composed of subsystem additive and non-additive terms. We show that an appropriate definition of the long-range correlation energy is given by the value of the non-additive correlation functional. This functional is evaluated using the fluctuation–dissipation theorem aided by a formally exact decomposition of the response functions into subsystem contributions. FDE-vdW is derived in detail and several approximate schemes are proposed, which lead to practical implementations of the method.more » We show that FDE-vdW is Casimir-Polder consistent, i.e., it reduces to the generalized Casimir-Polder formula for asymptotic inter-subsystems separations. Pilot calculations of binding energies of 13 weakly bound complexes singled out from the S22 set show a dramatic improvement upon semilocal subsystem DFT, provided that an appropriate exchange functional is employed. The convergence of FDE-vdW with basis set size is discussed, as well as its dependence on the choice of associated density functional approximant.« less

Embedded Thermal Control for Subsystems for Next Generation Spacecraft Applications

NASA Technical Reports Server (NTRS)

Didion, Jeffrey R.

2015-01-01

Thermal Fluids and Analysis Workshop, Silver Spring MD NCTS 21070-15. NASA, the Defense Department and commercial interests are actively engaged in developing miniaturized spacecraft systems and scientific instruments to leverage smaller cheaper spacecraft form factors such as CubeSats. This paper outlines research and development efforts among Goddard Space Flight Center personnel and its several partners to develop innovative embedded thermal control subsystems. Embedded thermal control subsystems is a cross cutting enabling technology integrating advanced manufacturing techniques to develop multifunctional intelligent structures to reduce Size, Weight and Power (SWaP) consumption of both the thermal control subsystem and overall spacecraft. Embedded thermal control subsystems permit heat acquisition and rejection at higher temperatures than state of the art systems by employing both advanced heat transfer equipment (integrated heat exchangers) and high heat transfer phenomena. The Goddard Space Flight Center Thermal Engineering Branch has active investigations seeking to characterize advanced thermal control systems for near term spacecraft missions. The embedded thermal control subsystem development effort consists of fundamental research as well as development of breadboard and prototype hardware and spaceflight validation efforts. This paper will outline relevant fundamental investigations of micro-scale heat transfer and electrically driven liquid film boiling. The hardware development efforts focus upon silicon based high heat flux applications (electronic chips, power electronics etc.) and multifunctional structures. Flight validation efforts include variable gravity campaigns and a proposed CubeSat based flight demonstration of a breadboard embedded thermal control system. The CubeSat investigation is technology demonstration will characterize in long-term low earth orbit a breadboard embedded thermal subsystem and its individual components to develop

Serotonergic regulation of distention-induced ATP release from the urothelium.

PubMed

Matsumoto-Miyai, Kazumasa; Yamada, Erika; Shinzawa, Eriko; Koyama, Yoshihisa; Shimada, Shoichi; Yoshizumi, Masaru; Kawatani, Masahito

2016-04-01

Serotonin [5-hydroxytryptamine (5-HT)] is involved in both motor and sensory functions in hollow organs, especially in the gastrointestinal tract. However, the involvement of 5-HT in visceral sensation of the urinary bladder remains unknown. Because distention-induced ATP release from the urothelium plays an essential role in visceral sensation of the urinary bladder, we investigated the regulation of urothelial ATP release by the 5-HT signaling system. RT-PCR and immunohistochemical analyses of the urothelium revealed specific expression of 5-HT 1D and 5-HT 4 receptors. The addition of 5-HT did not affect urothelial ATP release without bladder distention, but it significantly reduced distention-induced ATP release by physiological pressure during urine storage (5 cmH 2 O). The inhibitory effect of 5-HT on distention-elicited ATP release was blocked by preincubation with the 5-HT 1B/1D antagonist GR-127935 but not by the 5-HT 4 antagonist SB-204070. mRNA encoding tryptophan hydroxylase 1 was detected in the urinary bladder by nested RT-PCR amplification, and l-tryptophan or the selective serotonin reuptake inhibitor citalopram also inhibited ATP release, indicating that 5-HT is endogenously synthesized and released in the urinary bladder. The addition of GR-127935 significantly enhanced the distention-elicited ATP release 40 min after distention, whereas SB-204070 reduced the amount of ATP release 20 min after distention. These data suggest that 5-HT 4 facilitates the distention-induced ATP release at an earlier stage, whereas 5-HT 1D inhibits ATP release at a later stage. The net inhibitory effect of 5-HT indicates that the action of 5-HT on the urothelium is mediated predominantly by 5-HT 1D . Copyright © 2016 the American Physiological Society.

Adenosine triphosphate (ATP) reduces amyloid-β protein misfolding in vitro.

PubMed

Coskuner, Orkid; Murray, Ian V J

2014-01-01

Alzheimer's disease (AD) is a devastating disease of aging that initiates decades prior to clinical manifestation and represents an impending epidemic. Two early features of AD are metabolic dysfunction and changes in amyloid-β protein (Aβ) levels. Since levels of ATP decrease over the course of the disease and Aβ is an early biomarker of AD, we sought to uncover novel linkages between the two. First and remarkably, a GxxxG motif is common between both Aβ (oligomerization motif) and nucleotide binding proteins (Rossmann fold). Second, ATP was demonstrated to protect against Aβ mediated cytotoxicity. Last, there is structural similarity between ATP and amyloid binding/inhibitory compounds such as ThioT, melatonin, and indoles. Thus, we investigated whether ATP alters misfolding of the pathologically relevant Aβ42. To test this hypothesis, we performed computational and biochemical studies. Our computational studies demonstrate that ATP interacts strongly with Tyr10 and Ser26 of Aβ fibrils in solution. Experimentally, both ATP and ADP reduced Aβ misfolding at physiological intracellular concentrations, with thresholds at ~500 μM and 1 mM respectively. This inhibition of Aβ misfolding is specific; requiring Tyr10 of Aβ and is enhanced by magnesium. Last, cerebrospinal fluid ATP levels are in the nanomolar range and decreased with AD pathology. This initial and novel finding regarding the ATP interaction with Aβ and reduction of Aβ misfolding has potential significance to the AD field. It provides an underlying mechanism for published links between metabolic dysfunction and AD. It also suggests a potential role of ATP in AD pathology, as the occurrence of misfolded extracellular Aβ mirrors lowered extracellular ATP levels. Last, the findings suggest that Aβ conformation change may be a sensor of metabolic dysfunction.

Reduction of vibration by using mechatronical subsystem

NASA Astrophysics Data System (ADS)

Białas, K.; Buchacz, A.

2015-11-01

The primary aim introduced in this paper is synthesis of mechatronical system understand as planning of this type of systems. Mechatronical system is consisted of fundamental mechanical system and subsystem reducing vibration including electric elements. Fundamental system is received applying reverse task of dynamic (synthesis) and it's including inertial and elastic elements. The subsystem includes electric elements by means moving-coil transducer. The synthesis can also be used to change the already existing systems. Due to the method, introduced in this work, may be performed as early as whilst the designing of future functions. Using this way of designing is support for designers of mechanical systems with active reducing of vibrations.

Shuttle Orbiter Active Thermal Control Subsystem design and flight experience

NASA Technical Reports Server (NTRS)

Bond, Timothy A.; Metcalf, Jordan L.; Asuncion, Carmelo

1991-01-01

The paper examines the design of the Space Shuttle Orbiter Active Thermal Control Subsystem (ATCS) constructed for providing the vehicle and payload cooling during all phases of a mission and during ground turnaround operations. The operation of the Shuttle ATCS and some of the problems encountered during the first 39 flights of the Shuttle program are described, with special attention given to the major problems encountered with the degradation of the Freon flow rate on the Orbiter Columbia, the Flash Evaporator Subsystem mission anomalies which occurred on STS-26 and STS-34, and problems encountered with the Ammonia Boiler Subsystem. The causes and the resolutions of these problems are discussed.

Development of a preprototype vapor compression distillation water recovery subsystem

NASA Technical Reports Server (NTRS)

Johnson, K. L.

1978-01-01

The activities involved in the design, development, and test of a preprototype vapor compression distillation water recovery subsystem are described. This subsystem, part of a larger regenerative life support evaluation system, is designed to recover usable water from urine, urinal rinse water, and concentrated shower and laundry brine collected from three space vehicle crewmen for a period of 180 days without resupply. Details of preliminary design and testing as well as component developments are included. Trade studies, considerations leading to concept selections, problems encountered, and test data are also presented. The rework of existing hardware, subsystem development including computer programs, assembly verification, and comprehensive baseline test results are discussed.

Loss of the gene for the alpha subunit of ATP synthase (ATP5A1) from the W chromosome in the African grey parrot (Psittacus erithacus).

PubMed

de Kloet, S R

2001-08-01

This study describes the results of an analysis using Southern blotting, the polymerase chain reaction, and sequencing which shows that the African grey parrot (Psittacus erithacus) lacks the W-chromosomal gene for the alpha subunit of mitochondrial ATP synthase (ATP5A1W). Additional evidence shows that in other psittacines a fragment of the ATP5A1W gene contains five times as many nonsynonymous nucleotide replacements as the homologous fragment of the Z gene. Therefore, whereas in these other psittacines the corresponding ATP5A1Z protein fragment is highly conserved and varies by only a few, moderately conservative amino acid substitutions, the homologous ATP5A1W fragments contain a considerable number of, sometimes highly nonconservative, amino acid replacements. In one of these species, the ringneck parakeet (Psittacula krameri), the ATP5A1W gene is present in an inactive form because of the presence of a nonsense codon. Other changes, possibly leading to an inactive ATP5A1W gene product, involve the substitution of arginine residues by cysteine in the ATP5A1W protein of the mitred conure (Aratinga mitrata) and the blue and gold macaw (Ara ararauna). The data suggest also that although the divergence of the psittacine ATP5A1W and ATP5A1Z genes preceded the origin of the psittacidae, this divergence occurred independently of a similar process in the myna (Gracula religiosa), the outgroup used in this study.

Orbital maneuvering subsystem functional path analysis for performance monitoring fault detection and annunciation

NASA Technical Reports Server (NTRS)

Keesler, E. L.

1974-01-01

The functional paths of the Orbital Maneuver Subsystem (OMS) is defined. The operational flight instrumentation required for performance monitoring, fault detection, and annunciation is described. The OMS is a pressure fed rocket engine propulsion subsystem. One complete OMS shares each of the two auxiliary propulsion subsystem pods with a reaction control subsystem. Each OMS is composed of a pressurization system, a propellant tanking system, and a gimbaled rocket engine. The design, development, and operation of the system are explained. Diagrams of the system are provided.

The Chloroplast atpA Gene Cluster in Chlamydomonas reinhardtii1

PubMed Central

Drapier, Dominique; Suzuki, Hideki; Levy, Haim; Rimbault, Blandine; Kindle, Karen L.; Stern, David B.; Wollman, Francis-André

1998-01-01

Most chloroplast genes in vascular plants are organized into polycistronic transcription units, which generate a complex pattern of mono-, di-, and polycistronic transcripts. In contrast, most Chlamydomonas reinhardtii chloroplast transcripts characterized to date have been monocistronic. This paper describes the atpA gene cluster in the C. reinhardtii chloroplast genome, which includes the atpA, psbI, cemA, and atpH genes, encoding the α-subunit of the coupling-factor-1 (CF1) ATP synthase, a small photosystem II polypeptide, a chloroplast envelope membrane protein, and subunit III of the CF0 ATP synthase, respectively. We show that promoters precede the atpA, psbI, and atpH genes, but not the cemA gene, and that cemA mRNA is present only as part of di-, tri-, or tetracistronic transcripts. Deletions introduced into the gene cluster reveal, first, that CF1-α can be translated from di- or polycistronic transcripts, and, second, that substantial reductions in mRNA quantity have minimal effects on protein synthesis rates. We suggest that posttranscriptional mRNA processing is common in C. reinhardtii chloroplasts, permitting the expression of multiple genes from a single promoter. PMID:9625716

ATP and microfilaments in cellular oxidant injury.

PubMed Central

Hinshaw, D. B.; Armstrong, B. C.; Burger, J. M.; Beals, T. F.; Hyslop, P. A.

1988-01-01

Oxidant injury produces dramatic changes in cytoskeletal organization and cell shape. ATP synthetic pathways are major targets of oxidant injury resulting in rapid depletion of cellular ATP following oxidant exposure. The relation of ATP depletion to the changes in microfilament organization seen following H2O2 exposure were examined in the P388D1 cell line. Three hours of glucose depletion alone resulted in a decline in cellular ATP levels to less than 10% of controls, which was comparable to ATP levels in cells 30 to 60 minutes after exposure to 5 mM H2O2 in the presence of glucose. Adherent cells stained with rhodamine phalloidin, a probe specific for polymerized (F) actin, revealed a progressive shortening of microfilaments into globular aggregates within cells depleted of glucose over 3 hours, a pattern similar to earlier observations of H2O2-injured cells after 1 hour. The changes in cellular ATP associated with glucose depletion or H2O2 exposure were then correlated with G actin content measured by the DNAse 1 inhibition assay. No real differences in G actin content as a percentage of total actin were seen in P388D1 cells following 3 hours of glucose depletion or 30 to 60 minutes after exposure to 5 mM H2O2. But 2 to 3 hours after exposure to H2O2 there was a progressive decrease in G actin as a percentage of total actin within the cells. Transmission electron microscopy of cells depleted of glucose for 3 h or 1 hour after exposure to H2O2 revealed the presence of side-to-side aggregates or bundles of microfilaments within the cells. These observations suggest that declining levels of ATP either from metabolic inhibition or H2O2 injury are correlated with the fragmentation and shortening of microfilaments into aggregates. No net change in monomeric or polymeric actin was necessary for this to occur. However, at later time points after H2O2 exposure some actin assembly did occur. Images p[484]-a p481-a p482-a Figure 2 Figure 3 PMID:3414780

Diadenosine tetraphosphate-gating of recombinant pancreatic ATP-sensitive K(+) channels.

PubMed

Jovanovic, S; Jovanovic, A

2001-02-01

Diadenosine tetraphosphate (Ap4A) has been recently discovered in the pancreatic beta cells where targets ATP-sensitive K(+) (K(ATP)) channels, depolarizes the cell membrane and induces insulin secretion. However, whether Ap4A inhibit pancreatic K(ATP) channels by targeting protein channel complex itself was unknown. Therefore, we coexpressed pancreatic K(ATP) channel subunits, Kir6.2 and SUR1, in COS-7 cells and examined the effect of Ap4A on the single channel behavior using the inside-out configuration of the patch-clamp technique. Ap4A inhibited channel opening in a concentration-dependent manner. Analysis of single channels demonstrated that Ap4A did not change intraburst kinetic behavior of K(ATP) channels, but rather decreased burst duration and increased between-burst duration. It is concluded that Ap4A antagonizes K(ATP) channel opening by targeting channel subunits themselves and by keeping channels longer in closed interburst states.

The Sortie-Generation Model System. Volume 5. Maintenance Subsystem

DTIC Science & Technology

1981-09-01

Compuger RoanutI f and moidel 11, Computer operatinS system 17, Proorammino largualviso IS. Numlier of .ugic proltsm Hoewl -3 CSCobol 600 stuscomentm...THE SORTIE-GENERATION MODEL SYSTEM OC’ VOLUME V MAINTENANCE SUBSYSTEM September 1981 Robert S. Greenberg 05$ Prepared pursuant to Department of...Generation Model System Volume V Maintenance Subsystem 6. PERFORMING ORG. REPORT NUMBER LMI Task- L102 7. AUTHOR(a) 8. CONTRACT OR GRANT NUMBER(a

Goddard trajectory determination subsystem: Mathematical specifications

NASA Technical Reports Server (NTRS)

Wagner, W. E. (Editor); Velez, C. E. (Editor)

1972-01-01

The mathematical specifications of the Goddard trajectory determination subsystem of the flight dynamics system are presented. These specifications include the mathematical description of the coordinate systems, dynamic and measurement model, numerical integration techniques, and statistical estimation concepts.

Shuttle user analysis (study 2.2). Volume 4: Standardized subsystem modules analysis

NASA Technical Reports Server (NTRS)

1974-01-01

The capability to analyze payloads constructed of standardized modules was provided for the planning of future mission models. An inventory of standardized module designs previously obtained was used as a starting point. Some of the conclusions and recommendations are: (1) the two growth factor synthesis methods provide logical configurations for satellite type selection; (2) the recommended method is the one that determines the growth factor as a function of the baseline subsystem weight, since it provides a larger growth factor for small subsystem weights and results in a greater overkill due to standardization; (3) the method that is not recommended is the one that depends upon a subsystem similarity selection, since care must be used in the subsystem similarity selection; (4) it is recommended that the application of standardized subsystem factors be limited to satellites with baseline dry weights between about 700 and 6,500 lbs; and (5) the standardized satellite design approach applies to satellites maintainable in orbit or retrieved for ground maintenance.

Monitoring ATP dynamics in electrically active white matter tracts

PubMed Central

Trevisiol, Andrea; Saab, Aiman S; Winkler, Ulrike; Marx, Grit; Imamura, Hiromi; Möbius, Wiebke; Kusch, Kathrin; Nave, Klaus-Armin; Hirrlinger, Johannes

2017-01-01

In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders. DOI: http://dx.doi.org/10.7554/eLife.24241.001 PMID:28414271

Galileo IOV Electrical Power Subsystem Relies On Li-Ion Batter Charge Management Controlled By Hardware

NASA Astrophysics Data System (ADS)

Douay, N.

2011-10-01

In the frame of GALILEO In-Orbit Validation program which is composed of 4 satellites, Thales Alenia Space France has designed, developed and tested the Electrical Power Subsystem. Besides some classical design choices like: -50V regulated main power bus provided by the PCDU manufactured by Terma (DK), -Solar array, manufactured by Dutch-Space (NL), using Ga-As triple junction technology from Azur Space Power Solar GmbH, -SAFT (FR) Lithium-ion Battery for which cell package balancing function is required, -Solar Array Drive Mechanism, provided by RUAG Space Switzerland, to transfer the power. This subsystem features a fully autonomous, failure tolerant, battery charge management able to operate even after a complete unavailability of the on-board software. The battery charge management is implemented such that priority is always given to satisfy the satellite main bus needs in order to maintain the main bus regulation under MEA control. This battery charge management principle provides very high reliability and operational robustness. So, the paper describes : -the battery charge management concept using a combination of PCDU hardware and relevant battery lines monitoring, -the functional aspect of the single point failure free S4R (Sequential Switching Shunt Switch Regulator) and associated performances, -the failure modes isolated and passivated by this architecture. The paper will address as well the autonomous balancing function characteristics and performances.

Electronic Components Subsystems and Equipment: a Compilation

NASA Technical Reports Server (NTRS)

1975-01-01

Developments in electronic components, subsystems, and equipment are summarized. Topics discussed include integrated circuit components and techniques, circuit components and techniques, and cables and connectors.

Optomechanical design of TMT NFIRAOS Subsystems at INO

NASA Astrophysics Data System (ADS)

Lamontagne, Frédéric; Desnoyers, Nichola; Grenier, Martin; Cottin, Pierre; Leclerc, Mélanie; Martin, Olivier; Buteau-Vaillancourt, Louis; Boucher, Marc-André; Nash, Reston; Lardière, Olivier; Andersen, David; Atwood, Jenny; Hill, Alexis; Byrnes, Peter W. G.; Herriot, Glen; Fitzsimmons, Joeleff; Véran, Jean-Pierre

2017-08-01

The adaptive optics system for the Thirty Meter Telescope (TMT) is the Narrow-Field InfraRed Adaptive Optics System (NFIRAOS). Recently, INO has been involved in the optomechanical design of several subsystems of NFIRAOS, including the Instrument Selection Mirror (ISM), the NFIRAOS Beamsplitters (NBS), and the NFIRAOS Source Simulator system (NSS) comprising the Focal Plane Mask (FPM), the Laser Guide Star (LGS) sources, and the Natural Guide Star (NGS) sources. This paper presents an overview of these subsystems and the optomechanical design approaches used to meet the optical performance requirements under environmental constraints.

Design evolution of the orbiter reaction control subsystem

NASA Technical Reports Server (NTRS)

Taeber, R. J.; Karakulko, W.; Belvins, D.; Hohmann, C.; Henderson, J.

1985-01-01

The challenges of space shuttle orbiter reaction control subsystem development began with selection of the propellant for the subsystem. Various concepts were evaluated before the current Earth storable, bipropellant combination was selected. Once that task was accomplished, additional challenges of designing the system to satisfy the wide range of requirements dictated by operating environments, reusability, and long life were met. Verification of system adequacy was achieved by means of a combination of analysis and test. The studies, the design efforts, and the test and analysis techniques employed in meeting the challenges are described.

Integrated flight/propulsion control - Subsystem specifications for performance

NASA Technical Reports Server (NTRS)

Neighbors, W. K.; Rock, Stephen M.

1993-01-01

A procedure is presented for calculating multiple subsystem specifications given a number of performance requirements on the integrated system. This procedure applies to problems where the control design must be performed in a partitioned manner. It is based on a structured singular value analysis, and generates specifications as magnitude bounds on subsystem uncertainties. The performance requirements should be provided in the form of bounds on transfer functions of the integrated system. This form allows the expression of model following, command tracking, and disturbance rejection requirements. The procedure is demonstrated on a STOVL aircraft design.

MIT's role in project Apollo. Volume 2: Optical, radar, and candidate subsystems

NASA Technical Reports Server (NTRS)

1972-01-01

The development of optical, radar, and candidate subsystems for Project Apollo is discussed. The design and development of the optical subsystems for both the Apollo command and lunar spacecraft are described. Design approaches, problems, and solutions are presented. The evolution of radar interfaces with the GN&C system is discussed; these interfaces involved both hardware and software in a relatively complex interrelationship. The design and development of three candidate subsystems are also described. The systems were considered for use in Apollo, but were not incorporated into the final GN&C system. The three subsystems discussed are the star tracker-horizon photometer, the map and data viewer and the lunar module optical rendezvous system.

A real-time recursive filter for the attitude determination of the Spacelab instrument pointing subsystem

NASA Technical Reports Server (NTRS)

West, M. E.

1992-01-01

A real-time estimation filter which reduces sensitivity to system variations and reduces the amount of preflight computation is developed for the instrument pointing subsystem (IPS). The IPS is a three-axis stabilized platform developed to point various astronomical observation instruments aboard the shuttle. Currently, the IPS utilizes a linearized Kalman filter (LKF), with premission defined gains, to compensate for system drifts and accumulated attitude errors. Since the a priori gains are generated for an expected system, variations result in a suboptimal estimation process. This report compares the performance of three real-time estimation filters with the current LKF implementation. An extended Kalman filter and a second-order Kalman filter are developed to account for the system nonlinearities, while a linear Kalman filter implementation assumes that the nonlinearities are negligible. The performance of each of the four estimation filters are compared with respect to accuracy, stability, settling time, robustness, and computational requirements. It is shown, that for the current IPS pointing requirements, the linear Kalman filter provides improved robustness over the LKF with less computational requirements than the two real-time nonlinear estimation filters.

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis.

PubMed

Telianidis, Jonathon; Hung, Ya Hui; Materia, Stephanie; Fontaine, Sharon La

2013-01-01

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration.

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

PubMed Central

Telianidis, Jonathon; Hung, Ya Hui; Materia, Stephanie; Fontaine, Sharon La

2013-01-01

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration. PMID:23986700

The regulation of ATP release from the urothelium by adenosine and transepithelial potential.

PubMed

Dunning-Davies, Bryony M; Fry, Christopher H; Mansour, Dina; Ferguson, Douglas R

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Stretch of the urothelium, as occurs during bladder filling, is associated with a release of ATP that is postulated to act as a sensory neurotransmitter. The regulation of ATP release is poorly understood and in particular if there is a feedback mechanism provided by ATP itself. Adenosine, a breakdown product of ATP, is a potent inhibitor of stretch-induced ATP release, acting through and A1 receptor; endogenous levels are about 0.6μM. Data are consistent with ATP release relying on the rise of intracellular Ca2+. Transepithelial potential also controls ATP release, also acting via an A1 receptor-dependent pathway. To test the hypothesis that distension-induced ATP release from the bladder urothelium is regulated by adenosine as well as changes to transurothelial potential (TEP). To examine the role of changes to intracellular [Ca(2+) ] in ATP release. Rabbit urothelium/suburothelium membranes were used in an Ussing chamber system. Distension was induced by fluid removal from the chamber bathing the serosal (basolateral) membrane face. The TEP and short-circuit current were measured. ATP was measured in samples aspirated from the serosal chamber by a luciferin-luciferase assay. Intracellular [Ca(2+) ] was measured in isolated urothelial cells using the fluorochrome Fura-2. All experiments were performed at 37°C. Distension-induced ATP release was decreased by adenosine (1-10 μm) and enhanced by adenosine deaminase and A1- (but not A2-) receptor antagonists. Distension-induced ATP release was reduced by 2-APB, nifedipine and capsazepine; capsaicin induced ATP release in the absence of distension. ATP and capsaicin, but not adenosine, generated intracellular Ca(2+) transients; adenosine did not affect the ATP-generated Ca(2+) transient. ATP release was dependent on a finite transepithelial potential. Changes to TEP, in the absence of distension, generated ATP release that was in turn reduced by adenosine

System integration of marketable subsystems. [for residential solar heating and cooling

NASA Technical Reports Server (NTRS)

1979-01-01

Progress is reported in the following areas: systems integration of marketable subsystems; development, design, and building of site data acquisition subsystems; development and operation of the central data processing system; operation of the MSFC Solar Test Facility; and systems analysis.

Structural Basis for a Unique ATP Synthase Core Complex from Nanoarcheaum equitans*

PubMed Central

Mohanty, Soumya; Jobichen, Chacko; Chichili, Vishnu Priyanka Reddy; Velázquez-Campoy, Adrián; Low, Boon Chuan; Hogue, Christopher W. V.; Sivaraman, J.

2015-01-01

ATP synthesis is a critical and universal life process carried out by ATP synthases. Whereas eukaryotic and prokaryotic ATP synthases are well characterized, archaeal ATP synthases are relatively poorly understood. The hyperthermophilic archaeal parasite, Nanoarcheaum equitans, lacks several subunits of the ATP synthase and is suspected to be energetically dependent on its host, Ignicoccus hospitalis. This suggests that this ATP synthase might be a rudimentary machine. Here, we report the crystal structures and biophysical studies of the regulatory subunit, NeqB, the apo-NeqAB, and NeqAB in complex with nucleotides, ADP, and adenylyl-imidodiphosphate (non-hydrolysable analog of ATP). NeqB is ∼20 amino acids shorter at its C terminus than its homologs, but this does not impede its binding with NeqA to form the complex. The heterodimeric NeqAB complex assumes a closed, rigid conformation irrespective of nucleotide binding; this differs from its homologs, which require conformational changes for catalytic activity. Thus, although N. equitans possesses an ATP synthase core A3B3 hexameric complex, it might not function as a bona fide ATP synthase. PMID:26370083

TRPC5-eNOS Axis Negatively Regulates ATP-Induced Cardiomyocyte Hypertrophy.

PubMed

Sunggip, Caroline; Shimoda, Kakeru; Oda, Sayaka; Tanaka, Tomohiro; Nishiyama, Kazuhiro; Mangmool, Supachoke; Nishimura, Akiyuki; Numaga-Tomita, Takuro; Nishida, Motohiro

2018-01-01

Cardiac hypertrophy, induced by neurohumoral factors, including angiotensin II and endothelin-1, is a major predisposing factor for heart failure. These ligands can induce hypertrophic growth of neonatal rat cardiomyocytes (NRCMs) mainly through Ca 2+ -dependent calcineurin/nuclear factor of activated T cell (NFAT) signaling pathways activated by diacylglycerol-activated transient receptor potential canonical 3 and 6 (TRPC3/6) heteromultimer channels. Although extracellular nucleotide, adenosine 5'-triphosphate (ATP), is also known as most potent Ca 2+ -mobilizing ligand that acts on purinergic receptors, ATP never induces cardiomyocyte hypertrophy. Here we show that ATP-induced production of nitric oxide (NO) negatively regulates hypertrophic signaling mediated by TRPC3/6 channels in NRCMs. Pharmacological inhibition of NO synthase (NOS) potentiated ATP-induced increases in NFAT activity, protein synthesis, and transcriptional activity of brain natriuretic peptide. ATP significantly increased NO production and protein kinase G (PKG) activity compared to angiotensin II and endothelin-1. We found that ATP-induced Ca 2+ signaling requires inositol 1,4,5-trisphosphate (IP 3 ) receptor activation. Interestingly, inhibition of TRPC5, but not TRPC6 attenuated ATP-induced activation of Ca 2+ /NFAT-dependent signaling. As inhibition of TRPC5 attenuates ATP-stimulated NOS activation, these results suggest that NO-cGMP-PKG axis activated by IP 3 -mediated TRPC5 channels underlies negative regulation of TRPC3/6-dependent hypertrophic signaling induced by ATP stimulation.

The development of the intrinsic functional connectivity of default network subsystems from age 3 to 5.

PubMed

Xiao, Yaqiong; Zhai, Hongchang; Friederici, Angela D; Jia, Fucang

2016-03-01

In recent years, research on human functional brain imaging using resting-state fMRI techniques has been increasingly prevalent. The term "default mode" was proposed to describe a baseline or default state of the brain during rest. Recent studies suggested that the default mode network (DMN) is comprised of two functionally distinct subsystems: a dorsal-medial prefrontal cortex (DMPFC) subsystem involved in self-oriented cognition (i.e., theory of mind) and a medial temporal lobe (MTL) subsystem engaged in memory and scene construction; both subsystems interact with the anterior medial prefrontal cortex (aMPFC) and posterior cingulate (PCC) as the core regions of DMN. The present study explored the development of DMN core regions and these two subsystems in both hemispheres from 3- to 5-year-old children. The analysis of the intrinsic activity showed strong developmental changes in both subsystems, and significant changes were specifically found in MTL subsystem, but not in DMPFC subsystem, implying distinct developmental trajectories for DMN subsystems. We found stronger interactions between the DMPFC and MTL subsystems in 5-year-olds, particularly in the left subsystems that support the development of environmental adaptation and relatively complex mental activities. These results also indicate that there is stronger right hemispheric lateralization at age 3, which then changes as bilateral development gradually increases through to age 5, suggesting in turn the hemispheric dominance in DMN subsystems changing with age. The present results provide primary evidence for the development of DMN subsystems in early life, which might be closely related to the development of social cognition in childhood.

Effects of oral ATP supplementation on anaerobic power and muscular strength.

PubMed

Jordan, Alexander N; Jurca, Radim; Abraham, Edward H; Salikhova, Anna; Mann, Julia K; Morss, Gina M; Church, Timothy S; Lucia, Alejandro; Earnest, Conrad P

2004-06-01

We examined 14 d of oral adenosine 5'-triphosphate (ATP) supplementation on indices of anaerobic capacity and muscular strength. Twenty-seven healthy males successfully completed the trial, after randomly receiving in a double-blind manner an oral dose of low dose (150 mg) or high dose (225 mg) ATP, or matched placebo. To improve absorption characteristics, the ATP was enterically coated. Total blood ATP (whole blood and plasma ATP) concentrations, two Wingate anaerobic power tests (30 s), and muscular strength (1RM and three sets of repetitions to fatigue at 70% of 1RM) were measured under three conditions: (i) baseline; (ii) acutely (7d later, no prior supplementation and 75 min after ATP ingestion); and (iii) after 14 d of daily ingestion (post). Statistical analyses showed no significant between or within group treatment effects for whole blood ATP or plasma ATP concentrations for any treatment condition. We also did not observe any treatment effects for any Wingate testing parameter including peak PO, total work, average PO for 30 s, or post-Wingate lactate accumulation. Overall, we observed no significant between group treatment effects for any muscular strength parameter. We did observe several within group differences for the group ingesting the high ATP dosage including 1RM (6.6%; P < 0.04) and repetitions to fatigue during set 1 of posttesting (18.5%; P < 0.007) and total lifting volume at post (22%; P < 0.003). We conclude that enterically coated oral ATP supplementation may provide small ergogenic effects on muscular strength under some treatment conditions.

Partitioning a macroscopic system into independent subsystems

NASA Astrophysics Data System (ADS)

Delle Site, Luigi; Ciccotti, Giovanni; Hartmann, Carsten

2017-08-01

We discuss the problem of partitioning a macroscopic system into a collection of independent subsystems. The partitioning of a system into replica-like subsystems is nowadays a subject of major interest in several fields of theoretical and applied physics. The thermodynamic approach currently favoured by practitioners is based on a phenomenological definition of an interface energy associated with the partition, due to a lack of easily computable expressions for a microscopic (i.e. particle-based) interface energy. In this article, we outline a general approach to derive sharp and computable bounds for the interface free energy in terms of microscopic statistical quantities. We discuss potential applications in nanothermodynamics and outline possible future directions.

Shuttle Orbiter Atmospheric Revitalization Pressure Control Subsystem

NASA Technical Reports Server (NTRS)

Walleshauser, J. J.; Ord, G. R.; Prince, R. N.

1982-01-01

The Atmospheric Revitalization Pressure Control Subsystem (ARPCS) provides oxygen partial pressure and total pressure control for the habitable atmosphere of the Shuttle for either a one atmosphere environment or an emergency 8 PSIA mode. It consists of a Supply Panel, Control Panel, Cabin Pressure Relief Valves and Electronic Controllers. The panels control and monitor the oxygen and nitrogen supplies. The cabin pressure relief valves protect the habitable environment from overpressurization. Electronic controllers provide proper mixing of the two gases. This paper describes the ARPCS, addresses the changes in hardware that have occurred since the inception of the program; the performance of this subsystem during STS-1 and STS-2; and discusses future operation modes.

Apollo experience report: Launch escape propulsion subsystem

NASA Technical Reports Server (NTRS)

Townsend, N. A.

1973-01-01

The Apollo launch escape propulsion subsystem contained three solid rocket motors. The general design, development, and qualification of the solid-propellant pitch-control, tower-jettison, and launch-escape motors of the Apollo launch escape propulsion subsystem were completed during years 1961 to 1966. The launch escape system components are described in general terms, and the sequence of events through the ground-based test programs and flight-test programs is discussed. The initial ground rules established for this system were that it should use existing technology and designs as much as possible. The practicality of this decision is proved by the minimum number of problems that were encountered during the development and qualification program.

Display management subsystem, version 1: A user's eye view

NASA Technical Reports Server (NTRS)

Parker, Dolores

1986-01-01

The structure and application functions of the Display Management Subsystem (DMS) are described. The DMS, a subsystem of the Transportable Applications Executive (TAE), was designed to provide a device-independent interface for an image processing and display environment. The system is callable by C and FORTRAN applications, portable to accommodate different image analysis terminals, and easily expandable to meet local needs. Generic applications are also available for performing many image processing tasks.

S-Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics.

PubMed

Módis, Katalin; Ju, YoungJun; Ahmad, Akbar; Untereiner, Ashley A; Altaany, Zaid; Wu, Lingyun; Szabo, Csaba; Wang, Rui

2016-11-01

Mammalian cells can utilize hydrogen sulfide (H 2 S) to support mitochondrial respiration. The aim of our study was to explore the potential role of S-sulfhydration (a H 2 S-induced posttranslational modification, also known as S-persulfidation) of the mitochondrial inner membrane protein ATP synthase (F1F0 ATP synthase/Complex V) in the regulation of mitochondrial bioenergetics. Using a biotin switch assay, we have detected S-sulfhydration of the α subunit (ATP5A1) of ATP synthase in response to exposure to H 2 S in vitro. The H 2 S generator compound NaHS induced S-sulfhydration of ATP5A1 in HepG2 and HEK293 cell lysates in a concentration-dependent manner (50-300μM). The activity of immunocaptured mitochondrial ATP synthase enzyme isolated from HepG2 and HEK293 cells was stimulated by NaHS at low concentrations (10-100nM). Site-directed mutagenesis of ATP5A1 in HEK293 cells demonstrated that cysteine residues at positions 244 and 294 are subject to S-sulfhydration. The double mutant ATP synthase protein (C244S/C294S) showed a significantly reduced enzyme activity compared to control and the single-cysteine-mutated recombinant proteins (C244S or C294S). To determine whether endogenous H 2 S plays a role in the basal S-sulfhydration of ATP synthase in vivo, we compared liver tissues harvested from wild-type mice and mice deficient in cystathionine-gamma-lyase (CSE, one of the three principal mammalian H 2 S-producing enzymes). Significantly reduced S-sulfhydration of ATP5A1 was observed in liver homogenates of CSE -/- mice, compared to wild-type mice, suggesting a physiological role for CSE-derived endogenous H 2 S production in the S-sulfhydration of ATP synthase. Various forms of critical illness (including burn injury) upregulate H 2 S-producing enzymes and stimulate H 2 S biosynthesis. In liver tissues collected from mice subjected to burn injury, we detected an increased S-sulfhydration of ATP5A1 at the early time points post-burn. At later time points

Internet Use and Child Development: Validation of the Ecological Techno-Subsystem

ERIC Educational Resources Information Center

Johnson, Genevieve Marie

2010-01-01

Johnson and Puplampu recently proposed the "ecological techno-subsystem", a refinement to Bronfenbrenner's theoretical organization of environmental influences on child development. The ecological techno-subsystem includes child interaction with both living (e.g., peers) and nonliving (e.g., hardware) elements of communication,…

Electronic Subsystems For Laser Communication System

NASA Technical Reports Server (NTRS)

Long, Catherine; Maruschak, John; Patschke, Robert; Powers, Michael

1992-01-01

Electronic subsystems of free-space laser communication system carry digital signals at 650 Mb/s over long distances. Applicable to general optical communications involving transfer of great quantities of data, and transmission and reception of video images of high definition.

JOB BUILDER remote batch processing subsystem

NASA Technical Reports Server (NTRS)

Orlov, I. G.; Orlova, T. L.

1980-01-01

The functions of the JOB BUILDER remote batch processing subsystem are described. Instructions are given for using it as a component of a display system developed by personnel of the System Programming Laboratory, Institute of Space Research, USSR Academy of Sciences.

Hydrostatic pressure activates ATP-sensitive K+ channels in lung epithelium by ATP release through pannexin and connexin hemichannels.

PubMed

Richter, Katrin; Kiefer, Kevin P; Grzesik, Benno A; Clauss, Wolfgang G; Fronius, Martin

2014-01-01

Lungs of air-breathing vertebrates are constantly exposed to mechanical forces and therefore are suitable for investigation of mechanotransduction processes in nonexcitable cells and tissues. Freshly dissected Xenopus laevis lungs were used for transepithelial short-circuit current (ISC) recordings and were exposed to increased hydrostatic pressure (HP; 5 cm fluid column, modified Ussing chamber). I(SC) values obtained under HP (I(5cm)) were normalized to values before HP (I(0cm)) application (I(5cm)/I(0cm)). Under control conditions, HP decreased I(SC) (I(5cm)/I(0cm)=0.84; n=68; P<0.0001). This effect was reversible and repeatable ≥30 times. Preincubation with ATP-sensitive K(+) channel (K(ATP)) inhibitors (HMR1098 and glibenclamide) prevented the decrease in I(SC) (I(5cm)/I(0cm): HMR1098=1.19, P<0.0001; glibenclamide=1.11, P<0.0001). Similar effects were observed with hemichannel inhibitors (I(5cm)/I(0cm): meclofenamic acid=1.09, P<0.0001; probenecid=1.0, P<0.0001). The HP effect was accompanied by release of ATP (P<0.05), determined by luciferin-luciferase luminescence in perfusion solution from the luminal side of an Ussing chamber. ATP release was abrogated by both meclofenamic acid and probenecid. RT-PCR experiments revealed the expression of pannexin and connexin hemichannels and KATP subunit transcripts in X. laevis lung. These data show an activation of KATP in pulmonary epithelial cells in response to HP that is induced by ATP release through mechanosensitive pannexin and connexin hemichannels. These findings represent a novel mechanism of mechanotransduction in nonexcitable cells.

Energy transduction in the F1 motor of ATP synthase.

PubMed

Wang, H; Oster, G

1998-11-19

ATP synthase is the universal enzyme that manufactures ATP from ADP and phosphate by using the energy derived from a transmembrane protonmotive gradient. It can also reverse itself and hydrolyse ATP to pump protons against an electrochemical gradient. ATP synthase carries out both its synthetic and hydrolytic cycles by a rotary mechanism. This has been confirmed in the direction of hydrolysis after isolation of the soluble F1 portion of the protein and visualization of the actual rotation of the central 'shaft' of the enzyme with respect to the rest of the molecule, making ATP synthase the world's smallest rotary engine. Here we present a model for this engine that accounts for its mechanochemical behaviour in both the hydrolysing and synthesizing directions. We conclude that the F1 motor achieves its high mechanical torque and almost 100% efficiency because it converts the free energy of ATP binding into elastic strain, which is then released by a coordinated kinetic and tightly coupled conformational mechanism to create a rotary torque.

Energy transduction in the F1 motor of ATP synthase

NASA Astrophysics Data System (ADS)

Wang, Hongyun; Oster, George

1998-11-01

ATP synthase is the universal enzyme that manufactures ATP from ADP and phosphate by using the energy derived from a transmembrane protonmotive gradient. It can also reverse itself and hydrolyse ATP to pump protons against an electrochemical gradient. ATP synthase carries out both its synthetic and hydrolytic cycles by a rotary mechanism. This has been confirmed in the direction of hydrolysis, after isolation of the soluble F1 portion of the protein and visualization of the actual rotation of the central `shaft' of the enzyme with respect to the rest of the molecule, making ATP synthase the world's smallest rotary engine. Here we present a model for this engine that accounts for its mechanochemical behaviour in both the hydrolysing and synthesizing directions. We conclude that the F1 motor achieves its high mechanical torque and almost 100% efficiency because it converts the free energy of ATP binding into elastic strain, which is then released by a coordinated kinetic and tightly coupled conformational mechanism to create a rotary torque.

A membrane-based subsystem for very high recoveries of spacecraft waste waters

NASA Technical Reports Server (NTRS)

Ray, Roderick J.; Retzlaff, Sandra E.; Radke-Mitchell, Lyn; Newbold, David D.; Price, Donald F.

1986-01-01

This paper describes the continued development of a membrane-based subsystem designed to recover up to 99.5 percent of the water from various spacecraft waste waters. Specifically discussed are: (1) the design and fabrication of an energy-efficient reverse-osmosis (RO) breadboard subsystem; (2) data showing the performance of this subsystem when operated on a synthetic wash-water solution - including the results of a 92-day test; and (3) the results of pasteurization studies, including the design and operation of an in-line pasteurizer. Also included in this paper is a discussion of the design and performance of a second RO stage. This second stage results in higher-purity product water at a minimal energy requirement and provides a substantial redundancy factor to this subsystem.

Application of the principle of linked functions to ATP-driven ion pumps: kinetics of activation by ATP.

PubMed Central

Reynolds, J A; Johnson, E A; Tanford, C

1985-01-01

If a ligand binds with unequal affinity to two distinct states of a protein, then the equilibrium between the two states becomes a function of the concentration of the ligand. A necessary consequence is that the ligand must also affect the forward and/or reverse rate constants for transition between the two states. For an enzyme or transport protein with such a transition as a slow step in the catalytic cycle, the overall rate also becomes a function of ligand concentration. These conclusions are independent of whether or not the ligand is a direct participant in the reaction. If it is a direct participant, then the kinetic effect arising from the principle of linked functions is distinct from the direct catalytic effect. These principles suffice to account for the biphasic response of the hydrolytic activity of ATP-driven ion pumps to the concentration of ATP, without the need to invoke more than one ATP binding site per catalytic center. PMID:2987939

Paul D. Boyer, Adenosine Triphosphate (ATP), and the Binding Change

Science.gov Websites

-- October 1975, DOE Technical Report, 1975 A Perspective of the Binding Change Mechanism for ATP Synthesis Reports, Vol. 18, No. 3, 1998 ATP Synthesis and the Binding Change Mechanism: The Work of Paul D. Boyer Mechanism of ATP Synthesis Additional Web Pages: Adenosine Triphosphate: The Energy Currency of Life Paul D

The role of the urothelium and ATP in mediating detrusor smooth muscle contractility.

PubMed

Santoso, Aneira Gracia Hidayat; Sonarno, Ika Ariyani Bte; Arsad, Noor Aishah Bte; Liang, Willmann

2010-11-01

To examine the contractility of urothelium-intact (+UE) and urothelium-denuded (-UE) rat detrusor strips under adenosine triphosphate (ATP) treatment. Purinergic signaling exists in the bladder but both the inhibitory effect of ATP on detrusor contractions and the function of urothelial ATP are not established. Detrusor strips were obtained from bladders of young adult rats. Isometric tension from both transverse and longitudinal contractions was measured using a myograph. The muscarinic agonist carbachol (CCh) was used to induce contractions, which were under the influences of different concentrations of ATP. In both +UE and -UE strips, 1 mM ATP suppressed CCh-induced contractions. In longitudinal contractions, ATP added to the inhibitory effect of urothelium on CCh responses. Removal of the urothelium, but with exogenous ATP added, recovered the CCh responses to the same level as in +UE strips with no added ATP. Transverse contractions were less susceptible to ATP in the presence of urothelium. We showed that the urothelium and ATP suppressed CCh-induced contractions to a similar extent. The findings suggest an inhibitory role of urothelial ATP in mediating detrusor smooth muscle contractility, which may be impaired in diseased bladders. Copyright © 2010 Elsevier Inc. All rights reserved.

CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.

PubMed

Kanno, Takeshi; Nishizaki, Tomoyuki

2011-09-24

In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β(3) adrenoceptors linked to G(s) protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

Cardiac Metabolism in Heart Failure - Implications beyond ATP production

PubMed Central

Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

2013-01-01

The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

Predicting Speech Intelligibility with a Multiple Speech Subsystems Approach in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Lee, Jimin; Hustad, Katherine C.; Weismer, Gary

2014-01-01

Purpose: Speech acoustic characteristics of children with cerebral palsy (CP) were examined with a multiple speech subsystems approach; speech intelligibility was evaluated using a prediction model in which acoustic measures were selected to represent three speech subsystems. Method: Nine acoustic variables reflecting different subsystems, and…

Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients

PubMed Central

Lahner, Edith; Brigatti, Cristina; Marzinotto, Ilaria; Carabotti, Marilia; Scalese, Giulia; Davidson, Howard W; Wenzlau, Janet M; Bosi, Emanuele; Piemonti, Lorenzo; Annibale, Bruno; Lampasona, Vito

2017-01-01

Objectives: Circulating autoantibodies targeting the H+/K+-ATPase proton pump of gastric parietal cells are considered markers of autoimmune gastritis, whose diagnostic accuracy in atrophic body gastritis, the pathological lesion of autoimmune gastritis, remains unknown. This study aimed to assess autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase in atrophic body gastritis patients and controls. Methods: One-hundred and four cases with atrophic body gastritis and 205 controls were assessed for serological autoantibodies specific for ATP4A or ATP4B subunits using luminescent immunoprecipitation system (LIPS). Recombinant luciferase-reporter-fused-antigens were expressed by in vitro transcription-translation (ATP4A) or after transfection in Expi293F cells (ATP4B), incubated with test sera, and immune complexes recovered using protein-A-sepharose. LIPS assays were compared with a commercial enzyme immunoassay (EIA) for parietal cell autoantibodies. Results: ATP4A and ATP4B autoantibody titers were higher in cases compared to controls (P<0.0001). The area under the receiver-operating characteristic curve was 0.98 (95% CI 0.965–0.996) for ATP4A, and 0.99 (95% CI 0.979–1.000) for ATP4B, both higher as compared with that of EIA: 0.86 (95% CI 0.809–0.896), P<0.0001. Sensitivity-specificity were 100–89% for ATP4A and 100–90% for ATP4B assay. Compared with LIPS, EIA for parietal cell autoantibodies showed a lower sensitivity (72%, P<0.0001) at a similar specificity (92%, P=0.558). Conclusions: Positivity to both, ATP4A and ATP4B autoantibodies is closely associated with atrophic body gastritis. Both assays had the highest sensitivity, at the cost of diagnostic accuracy (89 and 90% specificity), outperforming traditional EIA. Once validated, these LIPS assays should be valuable screening tools for detecting biomarkers of damaged atrophic oxyntic mucosa. PMID:28102858

On-orbit experience with the HEAO attitude control subsystem

NASA Technical Reports Server (NTRS)

Hoffman, D. P.; Berkery, E. A.

1978-01-01

The first satellite (HEAO-1) in the High Energy Astronomy Observatory Program series was launched successfully on Aug. 12, 1977. To date it has completed over nine months of orbital operation in a science data gathering mode. During this period all attitude control modes have been exercised and all primary mission objectives have been achieved. This paper highlights the characteristics of the attitude control subsystem design and compares the predicted performance with the actual flight operations experience. Environmental disturbance modeling, component hardware/software characteristics, and overall attitude control performance are reviewed and are found to compare very well with the prelaunch analytical predictions. Brief comments are also included regarding the operations aspects of the attitude control subsystem. The experience in this regard demonstrates the effectiveness of the design flexibility afforded by the presence of a general purpose digital processor in the subsystem flight hardware implementation.

Apollo experience report: Crew provisions and equipment subsystem

NASA Technical Reports Server (NTRS)

Mcallister, F.

1972-01-01

A description of the construction and use of crew provisions and equipment subsystem items for the Apollo Program is presented. The subsystem is composed principally of survival equipment, bioinstrumentation devices, medical components and accessories, water- and waste-management equipment, personal-hygiene articles, docking aids, flight garments (excluding the pressure garment assembly), and various other crew-related accessories. Particular attention is given to items and assemblies that presented design, development, or performance problems: the crew optical alinement sight system, the metering water dispenser, and the waste-management system. Changes made in design and materials to improve the fire safety of the hardware are discussed.

Modular thrust subsystem approaches to solar electric propulsion module design

NASA Technical Reports Server (NTRS)

Cake, J. E.; Sharp, G. R.; Oglebay, J. C.; Shaker, F. J.; Zavesky, R. J.

1976-01-01

Three approaches are presented for packaging the elements of a 30 cm ion thruster subsystem into a modular thrust subsystem. The individual modules, when integrated into a conceptual solar electric propulsion module are applicable to a multimission set of interplanetary flights with the space shuttle interim upper stage as the launch vehicle. The emphasis is on the structural and thermal integration of the components into the modular thrust subsystems. Thermal control for the power processing units is either by direct radiation through louvers in combination with heat pipes or an all heat pipe system. The propellant storage and feed system and thruster gimbal system concepts are presented. The three approaches are compared on the basis of mass, cost, testing, interfaces, simplicity, reliability, and maintainability.

Modular thrust subsystem approaches to solar electric propulsion module design

NASA Technical Reports Server (NTRS)

Cake, J. E.; Sharp, G. R.; Oglebay, J. C.; Shaker, F. J.; Zevesky, R. J.

1976-01-01

Three approaches are presented for packaging the elements of a 30 cm ion thrustor subsystem into a modular thrust subsystem. The individual modules, when integrated into a conceptual solar electric propulsion module are applicable to a multimission set of interplanetary flights with the Space Shuttle/Interim Upper Stage as the launch vehicle. The emphasis is on the structural and thermal integration of the components into the modular thrust subsystems. Thermal control for the power processing units is either by direct radiation through louvers in combination with heat pipes of an all heat pipe system. The propellant storage and feed system and thrustor gimbal system concepts are presented. The three approaches are compared on the basis of mass, cost, testing, interfaces, simplicity, reliability, and maintainability.

Advanced large scale GaAs monolithic IF switch matrix subsystem

NASA Technical Reports Server (NTRS)

Ch'en, D. R.; Petersen, W. C.; Kiba, W. M.

1992-01-01

Attention is given to a novel chip design and packaging technique to overcome the limitations due to the high signal isolation requirements of advanced communications systems. A hermetically sealed 6 x 6 monolithic GaAs switch matrix subsystem with integral control electronics based on this technique is presented. An 0-dB insertion loss and 60-dB crosspoint isolation over a 3.5-to-6-GHz band were achieved. The internal controller portion of the switching subsystem provides crosspoint control via a standard RS-232 computer interface and can be synchronized with an external systems control computer. The measured performance of this advanced switching subsystem is fully compatible with relatively static 'switchboard' as well as dynamic TDMA modes of operation.

ATP7A-related copper transport diseases-emerging concepts and future trends.

PubMed

Kaler, Stephen G

2011-01-01

This Review summarizes recent advances in understanding copper-transporting ATPase 1 (ATP7A), and examines the neurological phenotypes associated with dysfunction of this protein. Involvement of ATP7A in axonal outgrowth, synapse integrity and neuronal activation underscores the fundamental importance of copper metabolism to neurological function. Defects in ATP7A cause Menkes disease, an infantile-onset, lethal condition. Neonatal diagnosis and early treatment with copper injections enhance survival in patients with this disease, and can normalize clinical outcomes if mutant ATP7A molecules retain small amounts of residual activity. Gene replacement rescues a mouse model of Menkes disease, suggesting a potential therapeutic approach for patients with complete loss-of-function ATP7A mutations. Remarkably, a newly discovered ATP7A disorder-isolated distal motor neuropathy-has none of the characteristic clinical or biochemical abnormalities of Menkes disease or its milder allelic variant occipital horn syndrome (OHS), instead resembling Charcot-Marie-Tooth disease type 2. These findings indicate that ATP7A has a crucial but previously unappreciated role in motor neuron maintenance, and that the mechanism underlying ATP7A-related distal motor neuropathy is distinct from Menkes disease and OHS pathophysiology. Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function.

Kinetic mechanism of ATP-sulphurylase from rat chondrosarcoma.

PubMed Central

Lyle, S; Geller, D H; Ng, K; Westley, J; Schwartz, N B

1994-01-01

ATP-sulphurylase catalyses the production of adenosine 5'-phosphosulphate (APS) from ATP and free sulphate with the release of PPi. APS kinase phosphorylates the APS intermediate to produce adenosine 3'-phosphate 5'-phosphosulphate (PAPS). The kinetic mechanism of rat chondrosarcoma ATP-sulphurylase was investigated by steady-state methods in the physiologically forward direction as well as the reverse direction. The sulphurylase activity was coupled to APS kinase activity in order to overcome the thermodynamic constraints of the sulphurylase reaction in the forward direction. Double-reciprocal initial-velocity plots for the forward sulphurylase intersect to the left of the ordinate for this reaction. KmATP and Kmsulphate were found to be 200 and 97 microM respectively. Chlorate, a competitive inhibitor with respect to sulphate, showed uncompetitive inhibition with respect to ATP with an apparent Ki of 1.97 mM. Steady-state data from experiments in the physiologically reverse direction also yielded double-reciprocal initial-velocity patterns that intersect to the left of the ordinate axis, with a KmAPS of 39 microM and a Kmpyrophosphate of 18 microM. The results of steady-state experiments in which Mg2+ was varied indicated that the true substrate is the MgPPi complex. An analogue of APS, adenosine 5'-[beta-methylene]phosphosulphate, was a linear inhibitor competitive with APS and non-competitive with respect to MgPPi. The simplest formal mechanism that agrees with all the data is an ordered steady-state single displacement with MgATP as the leading substrate in the forward direction and APS as the leading substrate in the reverse direction. PMID:8042976

Dynamics of shear-induced ATP release from red blood cells.

PubMed

Wan, Jiandi; Ristenpart, William D; Stone, Howard A

2008-10-28

Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in response to the increased shear stress inside arterial constrictions. Although shear-induced ATP release has been observed widely and is believed to be triggered by deformation of the cell membrane, the underlying mechanosensing mechanism inside RBCs is still controversial. Here, we use an in vitro microfluidic approach to investigate the dynamics of shear-induced ATP release from human RBCs with millisecond resolution. We demonstrate that there is a sizable delay time between the onset of increased shear stress and the release of ATP. This response time decreases with shear stress, but surprisingly does not depend significantly on membrane rigidity. Furthermore, we show that even though the RBCs deform significantly in short constrictions (duration of increased stress <3 ms), no measurable ATP is released. This critical timescale is commensurate with a characteristic membrane relaxation time determined from observations of the cell deformation by using high-speed video. Taken together our results suggest a model wherein the retraction of the spectrin-actin cytoskeleton network triggers the mechanosensitive ATP release and a shear-dependent membrane viscosity controls the rate of release.

Quantum subsystems: Exploring the complementarity of quantum privacy and error correction

NASA Astrophysics Data System (ADS)

Jochym-O'Connor, Tomas; Kribs, David W.; Laflamme, Raymond; Plosker, Sarah

2014-09-01

This paper addresses and expands on the contents of the recent Letter [Phys. Rev. Lett. 111, 030502 (2013), 10.1103/PhysRevLett.111.030502] discussing private quantum subsystems. Here we prove several previously presented results, including a condition for a given random unitary channel to not have a private subspace (although this does not mean that private communication cannot occur, as was previously demonstrated via private subsystems) and algebraic conditions that characterize when a general quantum subsystem or subspace code is private for a quantum channel. These conditions can be regarded as the private analog of the Knill-Laflamme conditions for quantum error correction, and we explore how the conditions simplify in some special cases. The bridge between quantum cryptography and quantum error correction provided by complementary quantum channels motivates the study of a new, more general definition of quantum error-correcting code, and we initiate this study here. We also consider the concept of complementarity for the general notion of a private quantum subsystem.

Stress granule formation via ATP depletion-triggered phase separation

NASA Astrophysics Data System (ADS)

Wurtz, Jean David; Lee, Chiu Fan

2018-04-01

Stress granules (SG) are droplets of proteins and RNA that form in the cell cytoplasm during stress conditions. We consider minimal models of stress granule formation based on the mechanism of phase separation regulated by ATP-driven chemical reactions. Motivated by experimental observations, we identify a minimal model of SG formation triggered by ATP depletion. Our analysis indicates that ATP is continuously hydrolysed to deter SG formation under normal conditions, and we provide specific predictions that can be tested experimentally.

Strain Background Modifies Phenotypes in the ATP8B1-Deficient Mouse

PubMed Central

Vargas, Julie C.; Xu, Hongmei; Groen, Annamiek; Paulusma, Coen C.; Grenert, James P.; Pawlikowska, Ludmila; Sen, Saunak; Elferink, Ronald P. J. Oude; Bull, Laura N.

2010-01-01

Background Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency. Methodology/Principal Findings We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6), 129, and (B6-129) F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains. Conclusions/Significance Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease. PMID:20126555

Positive gravitational subsystem energies from CFT cone relative entropies

NASA Astrophysics Data System (ADS)

Neuenfeld, Dominik; Saraswat, Krishan; Van Raamsdonk, Mark

2018-06-01

The positivity of relative entropy for spatial subsystems in a holographic CFT implies the positivity of certain quantities in the dual gravitational theory. In this note, we consider CFT subsystems whose boundaries lie on the lightcone of a point p. We show that the positive gravitational quantity which corresponds to the relative entropy for such a subsystem A is a novel notion of energy associated with a gravitational subsystem bounded by the minimal area extremal surface à associated with A and by the AdS boundary region  corresponding to the part of the lightcone from p bounded by ∂ A. This generalizes the results of arXiv:1605.01075 for ball-shaped regions by making use of the recent results in arXiv:1703.10656 for the vacuum modular Hamiltonian of regions bounded on lightcones. As part of our analysis, we give an analytic expression for the extremal surface in pure AdS associated with any such region A. We note that its form immediately implies the Markov property of the CFT vacuum (saturation of strong subadditivity) for regions bounded on the same lightcone. This gives a holographic proof of the result proven for general CFTs in arXiv:1703.10656. A similar holographic proof shows the Markov property for regions bounded on a lightsheet for non-conformal holographic theories defined by relevant perturbations of a CFT.

Power subsystem performance prediction /PSPP/ computer program.

NASA Technical Reports Server (NTRS)

Weiner, H.; Weinstein, S.

1972-01-01

A computer program which simulates the operation of the Viking Orbiter Power Subsystem has been developed. The program simulates the characteristics and interactions of a solar array, battery, battery charge controls, zener diodes, power conditioning equipment, and the battery spacecraft and zener diode-spacecraft thermal interfaces. This program has been used to examine the operation of the Orbiter power subsystem during critical phases of the Viking mission - from launch, through midcourse maneuvers, Mars orbital insertion, orbital trims, Lander separation, solar occultations and unattended operation - until the end of the mission. A typical computer run for the first 24 hours after launch is presented which shows the variations in solar array, zener diode, battery charger, batteries and user load characteristics during this period.

The Role of Light-Dark Regulation of the Chloroplast ATP Synthase.

PubMed

Kohzuma, Kaori; Froehlich, John E; Davis, Geoffry A; Temple, Joshua A; Minhas, Deepika; Dhingra, Amit; Cruz, Jeffrey A; Kramer, David M

2017-01-01

The chloroplast ATP synthase catalyzes the light-driven synthesis of ATP and is activated in the light and inactivated in the dark by redox-modulation through the thioredoxin system. It has been proposed that this down-regulation is important for preventing wasteful hydrolysis of ATP in the dark. To test this proposal, we compared the effects of extended dark exposure in Arabidopsis lines expressing the wild-type and mutant forms of ATP synthase that are redox regulated or constitutively active. In contrast to the predictions of the model, we observed that plants with wild-type redox regulation lost photosynthetic capacity rapidly in darkness, whereas those expressing redox-insensitive form were far more stable. To explain these results, we propose that in wild-type plants, down-regulation of ATP synthase inhibits ATP hydrolysis, leading to dissipation of thylakoid proton motive force (pmf) and subsequent inhibition of protein transport across the thylakoid through the twin arginine transporter (Tat)-dependent and Sec-dependent import pathways, resulting in the selective loss of specific protein complexes. By contrast, in mutants with a redox-insensitive ATP synthase, pmf is maintained by ATP hydrolysis, thus allowing protein transport to maintain photosynthetic activities for extended periods in the dark. Hence, a basal level of Tat-dependent, as well as, Sec-dependent import activity, in the dark helps replenishes certain components of the photosynthetic complexes and thereby aids in maintaining overall complex activity. However, the influence of a dark pmf on thylakoid protein import, by itself, could not explain all the effects we observed in this study. For example, we also observed in wild type plants a large transient buildup of thylakoid pmf and nonphotochemical exciton quenching upon sudden illumination of dark adapted plants. Therefore, we conclude that down-regulation of the ATP synthase is probably not related to preventing loss of ATP per se . Instead

The Role of Light–Dark Regulation of the Chloroplast ATP Synthase

PubMed Central

Kohzuma, Kaori; Froehlich, John E.; Davis, Geoffry A.; Temple, Joshua A.; Minhas, Deepika; Dhingra, Amit; Cruz, Jeffrey A.; Kramer, David M.

2017-01-01

The chloroplast ATP synthase catalyzes the light-driven synthesis of ATP and is activated in the light and inactivated in the dark by redox-modulation through the thioredoxin system. It has been proposed that this down-regulation is important for preventing wasteful hydrolysis of ATP in the dark. To test this proposal, we compared the effects of extended dark exposure in Arabidopsis lines expressing the wild-type and mutant forms of ATP synthase that are redox regulated or constitutively active. In contrast to the predictions of the model, we observed that plants with wild-type redox regulation lost photosynthetic capacity rapidly in darkness, whereas those expressing redox-insensitive form were far more stable. To explain these results, we propose that in wild-type plants, down-regulation of ATP synthase inhibits ATP hydrolysis, leading to dissipation of thylakoid proton motive force (pmf) and subsequent inhibition of protein transport across the thylakoid through the twin arginine transporter (Tat)-dependent and Sec-dependent import pathways, resulting in the selective loss of specific protein complexes. By contrast, in mutants with a redox-insensitive ATP synthase, pmf is maintained by ATP hydrolysis, thus allowing protein transport to maintain photosynthetic activities for extended periods in the dark. Hence, a basal level of Tat-dependent, as well as, Sec-dependent import activity, in the dark helps replenishes certain components of the photosynthetic complexes and thereby aids in maintaining overall complex activity. However, the influence of a dark pmf on thylakoid protein import, by itself, could not explain all the effects we observed in this study. For example, we also observed in wild type plants a large transient buildup of thylakoid pmf and nonphotochemical exciton quenching upon sudden illumination of dark adapted plants. Therefore, we conclude that down-regulation of the ATP synthase is probably not related to preventing loss of ATP per se. Instead

The Role of Light–Dark Regulation of the Chloroplast ATP Synthase

DOE PAGES

Kohzuma, Kaori; Froehlich, John E.; Davis, Geoffry A.; ...

2017-07-24

The chloroplast ATP synthase catalyzes the light-driven synthesis of ATP and is activated in the light and inactivated in the dark by redox-modulation through the thioredoxin system. It has been proposed that this down-regulation is important for preventing wasteful hydrolysis of ATP in the dark. To test this proposal, we compared the effects of extended dark exposure in Arabidopsis lines expressing the wild-type and mutant forms of ATP synthase that are redox regulated or constitutively active. In contrast to the predictions of the model, we observed that plants with wild-type redox regulation lost photosynthetic capacity rapidly in darkness, whereas thosemore » expressing redox-insensitive form were far more stable. To explain these results, we propose that in wild-type plants, down-regulation of ATP synthase inhibits ATP hydrolysis, leading to dissipation of thylakoid proton motive force (pmf) and subsequent inhibition of protein transport across the thylakoid through the twin arginine transporter (Tat)-dependent and Secdependent import pathways, resulting in the selective loss of specific protein complexes. By contrast, in mutants with a redox-insensitive ATP synthase, pmf is maintained by ATP hydrolysis, thus allowing protein transport to maintain photosynthetic activities for extended periods in the dark. Hence, a basal level of Tat-dependent, as well as, Sec-dependent import activity, in the dark helps replenishes certain components of the photosynthetic complexes and thereby aids in maintaining overall complex activity. But, the influence of a dark pmf on thylakoid protein import, by itself, could not explain all the effects we observed in this study. For example, we also observed in wild type plants a large transient buildup of thylakoid pmf and nonphotochemical exciton quenching upon sudden illumination of dark adapted plants. Thus, we conclude that down-regulation of the ATP synthase is probably not related to preventing loss of ATP per se. Instead

The Role of Light–Dark Regulation of the Chloroplast ATP Synthase

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

Kohzuma, Kaori; Froehlich, John E.; Davis, Geoffry A.

The chloroplast ATP synthase catalyzes the light-driven synthesis of ATP and is activated in the light and inactivated in the dark by redox-modulation through the thioredoxin system. It has been proposed that this down-regulation is important for preventing wasteful hydrolysis of ATP in the dark. To test this proposal, we compared the effects of extended dark exposure in Arabidopsis lines expressing the wild-type and mutant forms of ATP synthase that are redox regulated or constitutively active. In contrast to the predictions of the model, we observed that plants with wild-type redox regulation lost photosynthetic capacity rapidly in darkness, whereas thosemore » expressing redox-insensitive form were far more stable. To explain these results, we propose that in wild-type plants, down-regulation of ATP synthase inhibits ATP hydrolysis, leading to dissipation of thylakoid proton motive force (pmf) and subsequent inhibition of protein transport across the thylakoid through the twin arginine transporter (Tat)-dependent and Secdependent import pathways, resulting in the selective loss of specific protein complexes. By contrast, in mutants with a redox-insensitive ATP synthase, pmf is maintained by ATP hydrolysis, thus allowing protein transport to maintain photosynthetic activities for extended periods in the dark. Hence, a basal level of Tat-dependent, as well as, Sec-dependent import activity, in the dark helps replenishes certain components of the photosynthetic complexes and thereby aids in maintaining overall complex activity. But, the influence of a dark pmf on thylakoid protein import, by itself, could not explain all the effects we observed in this study. For example, we also observed in wild type plants a large transient buildup of thylakoid pmf and nonphotochemical exciton quenching upon sudden illumination of dark adapted plants. Thus, we conclude that down-regulation of the ATP synthase is probably not related to preventing loss of ATP per se. Instead

Decentralized Feedback Controllers for Robust Stabilization of Periodic Orbits of Hybrid Systems: Application to Bipedal Walking.

PubMed

Hamed, Kaveh Akbari; Gregg, Robert D

2017-07-01

This paper presents a systematic algorithm to design time-invariant decentralized feedback controllers to exponentially and robustly stabilize periodic orbits for hybrid dynamical systems against possible uncertainties in discrete-time phases. The algorithm assumes a family of parameterized and decentralized nonlinear controllers to coordinate interconnected hybrid subsystems based on a common phasing variable. The exponential and [Formula: see text] robust stabilization problems of periodic orbits are translated into an iterative sequence of optimization problems involving bilinear and linear matrix inequalities. By investigating the properties of the Poincaré map, some sufficient conditions for the convergence of the iterative algorithm are presented. The power of the algorithm is finally demonstrated through designing a set of robust stabilizing local nonlinear controllers for walking of an underactuated 3D autonomous bipedal robot with 9 degrees of freedom, impact model uncertainties, and a decentralization scheme motivated by amputee locomotion with a transpelvic prosthetic leg.

Decentralized Feedback Controllers for Robust Stabilization of Periodic Orbits of Hybrid Systems: Application to Bipedal Walking

PubMed Central

Hamed, Kaveh Akbari; Gregg, Robert D.

2016-01-01

This paper presents a systematic algorithm to design time-invariant decentralized feedback controllers to exponentially and robustly stabilize periodic orbits for hybrid dynamical systems against possible uncertainties in discrete-time phases. The algorithm assumes a family of parameterized and decentralized nonlinear controllers to coordinate interconnected hybrid subsystems based on a common phasing variable. The exponential and H2 robust stabilization problems of periodic orbits are translated into an iterative sequence of optimization problems involving bilinear and linear matrix inequalities. By investigating the properties of the Poincaré map, some sufficient conditions for the convergence of the iterative algorithm are presented. The power of the algorithm is finally demonstrated through designing a set of robust stabilizing local nonlinear controllers for walking of an underactuated 3D autonomous bipedal robot with 9 degrees of freedom, impact model uncertainties, and a decentralization scheme motivated by amputee locomotion with a transpelvic prosthetic leg. PMID:28959117

ATP during early bladder stretch is important for urgency in detrusor overactivity patients.

PubMed

Cheng, Y; Mansfield, K J; Allen, W; Chess-Williams, R; Burcher, E; Moore, K H

2014-01-01

ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤ 200 mL) than in those with higher FDV (> 200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid.

CFTR Cl- channel and CFTR-associated ATP channel: distinct pores regulated by common gates.

PubMed Central

Sugita, M; Yue, Y; Foskett, J K

1998-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is regulated by phosphorylation of the R domain and ATP hydrolysis at two nucleotide-binding domains (NBDs). It is controversial whether CFTR conducts ATP or whether CFTR might be closely associated with a separate ATP conductance. To characterize ATP channels associated with CFTR, we analyzed Cl- and ATP single channel-currents in excised inside-out membrane patches from MDCK epithelial cells transiently expressing CFTR. With 100 mM ATP in the pipette and 140 mM Cl- in the bath, ATP channels were associated with CFTR Cl- channels in two-thirds of patches that included CFTR. CFTR Cl- channels and CFTR-associated ATP channels had slope conductances of 7.4 pS and 5.2 pS, respectively, and had distinct reversal potentials and sensitivities to channel blockers. CFTR-associated ATP channels exhibited slow gating kinetics that depended on the presence of protein kinase A and cytoplasmic ATP, similar to CFTR Cl- channels. Gating kinetics of the ATP channels as well as the CFTR Cl- channels were similarly affected by non-hydrolyzable ATP analogues and mutations in the CFTR R domain and NBDs. Our results indicate that phosphorylation- and nucleotide-hydrolysis-dependent gating of CFTR is directly involved in gating of an associated ATP channel. However, the permeation pathways for Cl- and ATP are distinct and the ATP conduction pathway is not obligatorily associated with the expression of CFTR. PMID:9463368

Piezo1 regulates mechanotransductive release of ATP from human RBCs.

PubMed

Cinar, Eyup; Zhou, Sitong; DeCourcey, James; Wang, Yixuan; Waugh, Richard E; Wan, Jiandi

2015-09-22

Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca(2+)) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca(2+) influx decrease significantly. Remarkably, a critical extracellular Ca(2+) concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease.

Subsystem design package for Solar II collector

NASA Technical Reports Server (NTRS)

1978-01-01

The requirements for the design and performance of the Solar 2 Collector Subsystem developed for use in solar heating of single family residences and mobile homes are presented. Installation drawings are included.

Application of luciferase assay for ATP to antimicrobial drug susceptibility

NASA Technical Reports Server (NTRS)

Chappelle, E. W.; Picciolo, G. L.; Vellend, H.; Tuttle, S. A.; Barza, M. J.; Weinstein, L. (Inventor)

1977-01-01

The susceptibility of bacteria, particularly those derived from body fluids, to antimicrobial agents is determined in terms of an ATP index measured by culturing a bacterium in a growth medium. The amount of ATP is assayed in a sample of the cultured bacterium by measuring the amount of luminescent light emitted when the bacterial ATP is reacted with a luciferase-luciferin mixture. The sample of the cultured bacterium is subjected to an antibiotic agent. The amount of bacterial adenosine triphosphate is assayed after treatment with the antibiotic by measuring the luminescent light resulting from the reaction. The ATP index is determined from the values obtained from the assay procedures.

International Space Station Temperature and Humidity Control Subsystem Verification for Node 1

NASA Technical Reports Server (NTRS)

Williams, David E.

2007-01-01

The International Space Station (ISS) Node 1 Environmental Control and Life Support (ECLS) System is comprised of five subsystems: Atmosphere Control and Supply (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), and Water Recovery and Management (WRM). This paper provides a summary of the nominal operation of the Node 1 THC subsystem design. The paper will also provide a discussion of the detailed Element Verification methodologies for nominal operation of the Node 1 THC subsystem operations utilized during the Qualification phase.

Laser and Optical Subsystem for NASA's Cold Atom Laboratory

NASA Astrophysics Data System (ADS)

Kohel, James; Kellogg, James; Elliott, Ethan; Krutzik, Markus; Aveline, David; Thompson, Robert

2016-05-01

We describe the design and validation of the laser and optics subsystem for NASA's Cold Atom Laboratory (CAL), a multi-user facility being developed at NASA's Jet Propulsion Laboratory for studies of ultra-cold quantum gases in the microgravity environment of the International Space Station. Ultra-cold atoms will be generated in CAL by employing a combination of laser cooling techniques and evaporative cooling in a microchip-based magnetic trap. Laser cooling and absorption imaging detection of bosonic mixtures of 87 Rb and 39 K or 41 K will be accomplished using a high-power (up to 500 mW ex-fiber), frequency-agile dual wavelength (767 nm and 780 nm) laser and optical subsystem. The CAL laser and optical subsystem also includes the capability to generate high-power multi-frequency optical pulses at 784.87 nm to realize a dual-species Bragg atom interferometer. Currently at Humboldt-Universität zu Berlin.

Agonist trapped in ATP-binding sites of the P2X2 receptor

PubMed Central

Jiang, Ruotian; Lemoine, Damien; Martz, Adeline; Taly, Antoine; Gonin, Sophie; Prado de Carvalho, Lia; Specht, Alexandre; Grutter, Thomas

2011-01-01

ATP-gated P2X receptors are trimeric ion channels, as recently confirmed by X-ray crystallography. However, the structure was solved without ATP and even though extracellular intersubunit cavities surrounded by conserved amino acid residues previously shown to be important for ATP function were proposed to house ATP, the localization of the ATP sites remains elusive. Here we localize the ATP-binding sites by creating, through a proximity-dependent “tethering” reaction, covalent bonds between a synthesized ATP-derived thiol-reactive P2X2 agonist (NCS-ATP) and single cysteine mutants engineered in the putative binding cavities of the P2X2 receptor. By combining whole-cell and single-channel recordings, we report that NCS-ATP covalently and specifically labels two previously unidentified positions N140 and L186 from two adjacent subunits separated by about 18 Å in a P2X2 closed state homology model, suggesting the existence of at least two binding modes. Tethering reaction at both positions primes subsequent agonist binding, yet with distinct functional consequences. Labeling of one position impedes subsequent ATP function, which results in inefficient gating, whereas tethering of the other position, although failing to produce gating by itself, enhances subsequent ATP function. Our results thus define a large and dynamic intersubunit ATP-binding pocket and suggest that receptors trapped in covalently agonist-bound states differ in their ability to gate the ion channel. PMID:21576497

Agonist trapped in ATP-binding sites of the P2X2 receptor.

PubMed

Jiang, Ruotian; Lemoine, Damien; Martz, Adeline; Taly, Antoine; Gonin, Sophie; Prado de Carvalho, Lia; Specht, Alexandre; Grutter, Thomas

2011-05-31

ATP-gated P2X receptors are trimeric ion channels, as recently confirmed by X-ray crystallography. However, the structure was solved without ATP and even though extracellular intersubunit cavities surrounded by conserved amino acid residues previously shown to be important for ATP function were proposed to house ATP, the localization of the ATP sites remains elusive. Here we localize the ATP-binding sites by creating, through a proximity-dependent "tethering" reaction, covalent bonds between a synthesized ATP-derived thiol-reactive P2X2 agonist (NCS-ATP) and single cysteine mutants engineered in the putative binding cavities of the P2X2 receptor. By combining whole-cell and single-channel recordings, we report that NCS-ATP covalently and specifically labels two previously unidentified positions N140 and L186 from two adjacent subunits separated by about 18 Å in a P2X2 closed state homology model, suggesting the existence of at least two binding modes. Tethering reaction at both positions primes subsequent agonist binding, yet with distinct functional consequences. Labeling of one position impedes subsequent ATP function, which results in inefficient gating, whereas tethering of the other position, although failing to produce gating by itself, enhances subsequent ATP function. Our results thus define a large and dynamic intersubunit ATP-binding pocket and suggest that receptors trapped in covalently agonist-bound states differ in their ability to gate the ion channel.

Apollo experience report: Command and service module sequential events control subsystem

NASA Technical Reports Server (NTRS)

Johnson, G. W.

1975-01-01

The Apollo command and service module sequential events control subsystem is described, with particular emphasis on the major systems and component problems and solutions. The subsystem requirements, design, and development and the test and flight history of the hardware are discussed. Recommendations to avoid similar problems on future programs are outlined.

Bimodal Action of Protons on ATP Currents of Rat PC12 Cells

PubMed Central

Skorinkin, Andrei; Nistri, Andrea; Giniatullin, Rashid

2003-01-01

The mode of action of extracellular protons on ATP-gated P2X2 receptors remains controversial as either enhancement or depression of ATP-mediated currents has been reported. By investigating, at different pH, the electrophysiological effect of ATP on P2X2 receptors and complementing it with receptor modelling, the present study suggests a unified mechanism for both potentiation and inactivation of ATP receptors by protons. Our experiments on patch-clamped PC12 cells showed that, on the same cell, mild acidification potentiated currents induced by low ATP concentrations (<0.1 mM) and attenuated responses to high ATP concentrations (>1 mM) with emergence of current fading and rebound. To clarify the nature of the ATP/H+ interaction, we used the Ding and Sachs's “loop” receptor model which best describes the behavior of such receptors with two open states linked via one inactivated state. No effects by protons could be ascribed to H+-mediated open channel block. However, by assuming that protons facilitated binding of ATP to resting as well as open receptors, the model could closely replicate H+-induced potentiation of currents evoked by low ATP doses plus fading and rebound induced by high ATP doses. The latter phenomenon was due to receptor transition to the inactive state. The present data suggest that the high concentration of protons released with ATP (and catecholamines) from secretory vesicles may allow a dual action of H+ on P2X2 receptors. This condition might also occur on P2X2 receptors of central neurons exposed to low pH during ischemia. PMID:12810852

An automated environment for multiple spacecraft engineering subsystem mission operations

NASA Technical Reports Server (NTRS)

Bahrami, K. A.; Hioe, K.; Lai, J.; Imlay, E.; Schwuttke, U.; Hsu, E.; Mikes, S.

1990-01-01

Flight operations at the Jet Propulsion Laboratory (JPL) are now performed by teams of specialists, each team dedicated to a particular spacecraft. Certain members of each team are responsible for monitoring the performances of their respective spacecraft subsystems. Ground operations, which are very complex, are manual, labor-intensive, slow, and tedious, and therefore costly and inefficient. The challenge of the new decade is to operate a large number of spacecraft simultaneously while sharing limited human and computer resources, without compromising overall reliability. The Engineering Analysis Subsystem Environment (EASE) is an architecture that enables fewer controllers to monitor and control spacecraft engineering subsystems. A prototype of EASE has been installed in the JPL Space Flight Operations Facility for on-line testing. This article describes the underlying concept, development, testing, and benefits of the EASE prototype.

Adaptive Photothermal Emission Analysis Techniques for Robust Thermal Property Measurements of Thermal Barrier Coatings

NASA Astrophysics Data System (ADS)

Valdes, Raymond

The characterization of thermal barrier coating (TBC) systems is increasingly important because they enable gas turbine engines to operate at high temperatures and efficiency. Phase of photothermal emission analysis (PopTea) has been developed to analyze the thermal behavior of the ceramic top-coat of TBCs, as a nondestructive and noncontact method for measuring thermal diffusivity and thermal conductivity. Most TBC allocations are on actively-cooled high temperature turbine blades, which makes it difficult to precisely model heat transfer in the metallic subsystem. This reduces the ability of rote thermal modeling to reflect the actual physical conditions of the system and can lead to higher uncertainty in measured thermal properties. This dissertation investigates fundamental issues underpinning robust thermal property measurements that are adaptive to non-specific, complex, and evolving system characteristics using the PopTea method. A generic and adaptive subsystem PopTea thermal model was developed to account for complex geometry beyond a well-defined coating and substrate system. Without a priori knowledge of the subsystem characteristics, two different measurement techniques were implemented using the subsystem model. In the first technique, the properties of the subsystem were resolved as part of the PopTea parameter estimation algorithm; and, the second technique independently resolved the subsystem properties using a differential "bare" subsystem. The confidence in thermal properties measured using the generic subsystem model is similar to that from a standard PopTea measurement on a "well-defined" TBC system. Non-systematic bias-error on experimental observations in PopTea measurements due to generic thermal model discrepancies was also mitigated using a regression-based sensitivity analysis. The sensitivity analysis reported measurement uncertainty and was developed into a data reduction method to filter out these "erroneous" observations. It was found

Predicting Speech Intelligibility with A Multiple Speech Subsystems Approach in Children with Cerebral Palsy

PubMed Central

Lee, Jimin; Hustad, Katherine C.; Weismer, Gary

2014-01-01

Purpose Speech acoustic characteristics of children with cerebral palsy (CP) were examined with a multiple speech subsystem approach; speech intelligibility was evaluated using a prediction model in which acoustic measures were selected to represent three speech subsystems. Method Nine acoustic variables reflecting different subsystems, and speech intelligibility, were measured in 22 children with CP. These children included 13 with a clinical diagnosis of dysarthria (SMI), and nine judged to be free of dysarthria (NSMI). Data from children with CP were compared to data from age-matched typically developing children (TD). Results Multiple acoustic variables reflecting the articulatory subsystem were different in the SMI group, compared to the NSMI and TD groups. A significant speech intelligibility prediction model was obtained with all variables entered into the model (Adjusted R-squared = .801). The articulatory subsystem showed the most substantial independent contribution (58%) to speech intelligibility. Incremental R-squared analyses revealed that any single variable explained less than 9% of speech intelligibility variability. Conclusions Children in the SMI group have articulatory subsystem problems as indexed by acoustic measures. As in the adult literature, the articulatory subsystem makes the primary contribution to speech intelligibility variance in dysarthria, with minimal or no contribution from other systems. PMID:24824584

Predicting speech intelligibility with a multiple speech subsystems approach in children with cerebral palsy.

PubMed

Lee, Jimin; Hustad, Katherine C; Weismer, Gary

2014-10-01

Speech acoustic characteristics of children with cerebral palsy (CP) were examined with a multiple speech subsystems approach; speech intelligibility was evaluated using a prediction model in which acoustic measures were selected to represent three speech subsystems. Nine acoustic variables reflecting different subsystems, and speech intelligibility, were measured in 22 children with CP. These children included 13 with a clinical diagnosis of dysarthria (speech motor impairment [SMI] group) and 9 judged to be free of dysarthria (no SMI [NSMI] group). Data from children with CP were compared to data from age-matched typically developing children. Multiple acoustic variables reflecting the articulatory subsystem were different in the SMI group, compared to the NSMI and typically developing groups. A significant speech intelligibility prediction model was obtained with all variables entered into the model (adjusted R2 = .801). The articulatory subsystem showed the most substantial independent contribution (58%) to speech intelligibility. Incremental R2 analyses revealed that any single variable explained less than 9% of speech intelligibility variability. Children in the SMI group had articulatory subsystem problems as indexed by acoustic measures. As in the adult literature, the articulatory subsystem makes the primary contribution to speech intelligibility variance in dysarthria, with minimal or no contribution from other systems.

The Sentinel 4 focal plane subsystem

NASA Astrophysics Data System (ADS)

Hohn, Rüdiger; Skegg, Michael P.; Hermsen, Markus; Hinger, Jürgen; Williges, Christian; Reulke, Ralf

2017-09-01

The Sentinel 4 instrument is an imaging spectrometer, developed by Airbus under ESA contract in the frame of the joint European Union (EU)/ESA COPERNICUS program with the objective of monitoring trace gas concentrations. Sentinel 4 will provide accurate measurements of key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, formaldehyde, as well as aerosol and cloud properties. Sentinel 4 is unique in being the first geostationary UVN mission. The SENTINEL 4 space segment will be integrated on EUMETSAT's Meteosat Third Generation Sounder satellite (MTG-S). Sentinel 4 will provide coverage of Europe and adjacent regions. The Sentinel 4 instrument comprises as a major element two Focal Plane Subsystems (FPS) covering the wavelength ranges 305 nm to 500 nm (UVVIS) and 750 nm to 775 nm (NIR) respectively. The paper describes the Focal Plane Subsystems, comprising the detectors, the optical bench and the control electronics. Further the design and development approach will be presented as well as first measurement results of FPS Qualification Model.

HIRDLS Cryocooler Subsystem on-orbit Performance

NASA Astrophysics Data System (ADS)

Lock, J.; Stack, R.; Glaister, D. S.; Gully, W.

2006-04-01

This paper describes the HIRDLS (High Resolution Dynamic Limb Sounder) Cryocooler Subsystem (CSS) and its on-orbit flight performance. The HIRDLS Instrument was launched on July 15, 2004 as part of the NASA GSFC EOS Aura platform. Ball Aerospace provided the CSS, which includes the long life Stirling cryocooler (cooling at 59 K), cold plumbing to connect the cooler to the instrument Detector Subsystem, an ambient radiator to reject the cooler dissipation, and a vacuum enclosure system that enabled bench top ground testing. As of August 20, 2005, the cryocooler has over 9,000 hours of continuous operation with performance that exceeds requirements. Of note is that the CSS has experienced virtually no change in performance, including no indication of external contamination related degradation that has been evident on several other cryocooler systems in space flights. This steady performance can be attributed to the multi-layer insulation (MLI) based insulation design, which will be described in the paper.

ATP can be dispensable for prespliceosome formation in yeast

PubMed Central

Perriman, Rhonda; Ares, Manuel

2000-01-01

The first ATP-dependent step in pre-mRNA splicing involves the stable binding of U2 snRNP to form the prespliceosome. We show that a prespliceosome-like complex forms in the absence of ATP in yeast extracts lacking the U2 suppressor protein CUS2. These complexes display the same pre-mRNA and U snRNA requirements as authentic prespliceosomes and can be chased through the splicing pathway, indicating that they are a functional intermediate in the spliceosome assembly pathway. ATP-independent prespliceosome-like complexes are also observed in extracts containing a mutant U2 snRNA. Loss of CUS2 does not bypass the role of PRP5, an RNA helicase family member required for ATP-dependent prespliceosome formation. Genetic interactions between CUS2 and a heat-sensitive prp5 allele parallel those observed between CUS2 and U2, and suggest that CUS2 mediates functional interactions between U2 RNA and PRP5. We propose that CUS2 enforces ATP dependence during formation of the prespliceosome by brokering an interaction between PRP5 and the U2 snRNP that depends on correct U2 RNA structure. PMID:10640279

NMR-invisible ATP in heart: fact or fiction?

PubMed

Bak, M I; Ingwall, J S

1992-06-01

31P-nuclear magnetic resonance (31P-NMR) spectroscopy is widely used to monitor sequential changes in the nucleoside triphosphate (NTP) pool in intact tissues. Recently, the validity of this technique to quantitate incremental changes in ATP in heart has been challenged. Accordingly, we compared NTP measured by 31P-NMR and by chemical techniques in isolated isovolumic rat hearts at 16 and 56 min of oxygenated perfusion and in hearts subjected to 28 min of hypoxia, with or without 28 min of reoxygenation, and 12 or 28 min of ischemia, with or without 28 min of reperfusion. NTP content was calculated from 31P-NMR spectra using an external standard. At the end of each protocol the heart was freeze-clamped, and NTP and ATP contents were determined by chemical assay. After 16 min of normoxic perfusion the values for NTP and ATP contents measured by both methods in the same hearts were indistinguishable. Results from all seven experimental conditions show no significant difference between methods (P = 0.262). Thus both methods detect the same incremental change in NTP and ATP.

ATP-induced noncooperative thermal unfolding of hen lysozyme

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

Liu, Honglin; Yin, Peidong; He, Shengnan

To understand the role of ATP underlying the enhanced amyloidosis of hen egg white lysozyme (HEWL), the synchrotron radiation circular dichroism, combined with tryptophan fluorescence, dynamic light-scattering, and differential scanning calorimetry, is used to examine the alterations of the conformation and thermal unfolding pathway of the HEWL in the presence of ATP, Mg{sup 2+}-ATP, ADP, AMP, etc. It is revealed that the binding of ATP to HEWL through strong electrostatic interaction changes the secondary structures of HEWL and makes the exposed residue W62 move into hydrophobic environments. This alteration of W62 decreases the {beta}-domain stability of HEWL, induces a noncooperativemore » unfolding of the secondary structures, and produces a partially unfolded intermediate. This intermediate containing relatively rich {alpha}-helix and less {beta}-sheet structures has a great tendency to aggregate. The results imply that the ease of aggregating of HEWL is related to the extent of denaturation of the amyloidogenic region, rather than the electrostatic neutralizing effect or monomeric {beta}-sheet enriched intermediate.« less

ATP Synthase, a Target for Dementia and Aging?

PubMed

Larrick, James W; Larrick, Jasmine W; Mendelsohn, Andrew R

2018-02-01

Advancing age is the biggest risk factor for development for the major life-threatening diseases in industrialized nations accounting for >90% of deaths. Alzheimer's dementia (AD) is among the most devastating. Currently approved therapies fail to slow progression of the disease, providing only modest improvements in memory. Recently reported work describes mechanistic studies of J147, a promising therapeutic molecule previously shown to rescue the severe cognitive deficits exhibited by aged, transgenic AD mice. Apparently, J147 targets the mitochondrial alpha-F1-ATP synthase (ATP5A). Modest inhibition of the ATP synthase modulates intracellular calcium to activate AMP-activated protein kinase to inhibit mammalian target of rapamycin, a known mechanism of lifespan extension from worms to mammals.

Failure of the Cystic Fibrosis Transmembrane Conductance Regulator to Conduct ATP

NASA Astrophysics Data System (ADS)

Reddy, M. M.; Quinton, P. M.; Haws, C.; Wine, J. J.; Grygorczyk, R.; Tabcharani, J. A.; Hanrahan, J. W.; Gunderson, K. L.; Kopito, R. R.

1996-03-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is chloride ion channel regulated by protein kinase A and adenosine triphosphate (ATP). Loss of CFTR-mediated chloride ion conductance from the apical plasma membrane of epithelial cells is a primary physiological lesion in cystic fibrosis. CFTR has also been suggested to function as an ATP channel, although the size of the ATP anion is much larger than the estimated size of the CFTR pore. ATP was not conducted through CFTR in intact organs, polarized human lung cell lines, stably transfected mammalian cell lines, or planar lipid bilayers reconstituted with CFTR protein. These findings suggest that ATP permeation through the CFTR is unlikely to contribute to the normal function of CFTR or to the pathogenesis of cystic fibrosis.

Inflammation Promotes Airway Epithelial ATP Release via Calcium-Dependent Vesicular Pathways

PubMed Central

Okada, Seiko F.; Ribeiro, Carla M. P.; Sesma, Juliana I.; Seminario-Vidal, Lucia; Abdullah, Lubna H.; van Heusden, Catharina; Lazarowski, Eduardo R.

2013-01-01

ATP in airway surface liquid (ASL) controls mucociliary clearance functions via the activation of airway epithelial purinergic receptors. However, abnormally elevated ATP levels have been reported in inflamed airways, suggesting that excessive ATP in ASL contributes to airway inflammation. Despite these observations, little is known about the mechanisms of ATP accumulation in the ASL covering inflamed airways. In this study, links between cystic fibrosis (CF)–associated airway inflammation and airway epithelial ATP release were investigated. Primary human bronchial epithelial (HBE) cells isolated from CF lungs exhibited enhanced IL-8 secretion after 6 to 11 days, but not 28 to 35 days, in culture, compared with normal HBE cells. Hypotonic cell swelling–promoted ATP release was increased in 6- to 11-day-old CF HBE cells compared with non-CF HBE cells, but returned to normal values after 28 to 35 days in culture. The exposure of non-CF HBE cells to airway secretions isolated from CF lungs, namely, sterile supernatants of mucopurulent material (SMM), also caused enhanced IL-8 secretion and increased ATP release. The SMM-induced increase in ATP release was sensitive to Ca2+ chelation and vesicle trafficking/exocytosis inhibitors, but not to pannexin inhibition. Transcript levels of the vesicular nucleotide transporter, but not pannexin 1, were up-regulated after SMM exposure. SMM-treated cultures displayed increased basal mucin secretion, but mucin secretion was not enhanced in response to hypotonic challenge after the exposure of cells to either vehicle or SMM. We propose that CF airway inflammation up-regulates the capacity of airway epithelia to release ATP via Ca2+-dependent vesicular mechanisms not associated with mucin granule secretion. PMID:23763446

Active disturbance rejection control based robust output feedback autopilot design for airbreathing hypersonic vehicles.

PubMed

Tian, Jiayi; Zhang, Shifeng; Zhang, Yinhui; Li, Tong

2018-03-01

Since motion control plant (y (n) =f(⋅)+d) was repeatedly used to exemplify how active disturbance rejection control (ADRC) works when it was proposed, the integral chain system subject to matched disturbances is always regarded as a canonical form and even misconstrued as the only form that ADRC is applicable to. In this paper, a systematic approach is first presented to apply ADRC to a generic nonlinear uncertain system with mismatched disturbances and a robust output feedback autopilot for an airbreathing hypersonic vehicle (AHV) is devised based on that. The key idea is to employ the feedback linearization (FL) and equivalent input disturbance (EID) technique to decouple nonlinear uncertain system into several subsystems in canonical form, thus it would be much easy to directly design classical/improved linear/nonlinear ADRC controller for each subsystem. It is noticed that all disturbances are taken into account when implementing FL rather than just omitting that in previous research, which greatly enhances controllers' robustness against external disturbances. For autopilot design, ADRC strategy enables precise tracking for velocity and altitude reference command in the presence of severe parametric perturbations and atmospheric disturbances only using measurable output information. Bounded-input-bounded-output (BIBO) stable is analyzed for closed-loop system. To illustrate the feasibility and superiority of this novel design, a series of comparative simulations with some prominent and representative methods are carried out on a benchmark longitudinal AHV model. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Probing the ATP site of GRP78 with nucleotide triphosphate analogs

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

Hughes, Scott J.; Antoshchenko, Tetyana; Chen, Yun

GRP78, a member of the ER stress protein family, can relocate to the surface of cancer cells, playing key roles in promoting cell proliferation and metastasis. GRP78 consists of two major functional domains: the ATPase and protein/peptide-binding domains. The protein/peptide-binding domain of cell-surface GRP78 has served as a novel functional receptor for delivering cytotoxic agents (e.g., a apoptosis-inducing peptide or taxol) across the cell membrane. Here, we report our study on the ATPase domain of GRP78 (GRP78 ATPase), whose potential as a transmembrane delivery system of cytotoxic agents (e.g., ATP-based nucleotide triphosphate analogs) remains unexploited. As the binding of ligandsmore » (ATP analogs) to a receptor (GRP78 ATPase) is a pre-requisite for internalization, we determined the binding affinities and modes of GRP78 ATPase for ADP, ATP and several ATP analogs using surface plasmon resonance and x-ray crystallography. The tested ATP analogs contain one of the following modifications: the nitrogen at the adenine ring 7-position to a carbon atom (7-deazaATP), the oxygen at the beta-gamma bridge position to a carbon atom (AMPPCP), or the removal of the 2'-OH group (2'-deoxyATP). We found that 7-deazaATP displays an affinity and a binding mode that resemble those of ATP regardless of magnesium ion (Mg ++) concentration, suggesting that GRP78 is tolerant to modifications at the 7-position. By comparison, AMPPCP's binding affinity was lower than ATP and Mg ++-dependent, as the removal of Mg ++ nearly abolished binding to GRP78 ATPase. The AMPPCP-Mg ++ structure showed evidence for the critical role of Mg ++ in AMPPCP binding affinity, suggesting that while GRP78 is sensitive to modifications at the β-γ bridge position, these can be tolerated in the presence of Mg ++. Furthermore, 2'-deoxyATP's binding affinity was significantly lower than those for all other nucleotides tested, even in the presence of Mg ++. The 2'-deoxyATP structure showed the

Probing the ATP site of GRP78 with nucleotide triphosphate analogs

DOE PAGES

Hughes, Scott J.; Antoshchenko, Tetyana; Chen, Yun; ...

2016-05-04

GRP78, a member of the ER stress protein family, can relocate to the surface of cancer cells, playing key roles in promoting cell proliferation and metastasis. GRP78 consists of two major functional domains: the ATPase and protein/peptide-binding domains. The protein/peptide-binding domain of cell-surface GRP78 has served as a novel functional receptor for delivering cytotoxic agents (e.g., a apoptosis-inducing peptide or taxol) across the cell membrane. Here, we report our study on the ATPase domain of GRP78 (GRP78 ATPase), whose potential as a transmembrane delivery system of cytotoxic agents (e.g., ATP-based nucleotide triphosphate analogs) remains unexploited. As the binding of ligandsmore » (ATP analogs) to a receptor (GRP78 ATPase) is a pre-requisite for internalization, we determined the binding affinities and modes of GRP78 ATPase for ADP, ATP and several ATP analogs using surface plasmon resonance and x-ray crystallography. The tested ATP analogs contain one of the following modifications: the nitrogen at the adenine ring 7-position to a carbon atom (7-deazaATP), the oxygen at the beta-gamma bridge position to a carbon atom (AMPPCP), or the removal of the 2'-OH group (2'-deoxyATP). We found that 7-deazaATP displays an affinity and a binding mode that resemble those of ATP regardless of magnesium ion (Mg ++) concentration, suggesting that GRP78 is tolerant to modifications at the 7-position. By comparison, AMPPCP's binding affinity was lower than ATP and Mg ++-dependent, as the removal of Mg ++ nearly abolished binding to GRP78 ATPase. The AMPPCP-Mg ++ structure showed evidence for the critical role of Mg ++ in AMPPCP binding affinity, suggesting that while GRP78 is sensitive to modifications at the β-γ bridge position, these can be tolerated in the presence of Mg ++. Furthermore, 2'-deoxyATP's binding affinity was significantly lower than those for all other nucleotides tested, even in the presence of Mg ++. The 2'-deoxyATP structure showed the

ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation

PubMed Central

Teixeira, Felipe K.; Sanchez, Carlos G.; Hurd, Thomas R.; Seifert, Jessica R. K.; Czech, Benjamin; Preall, Jonathan B.; Hannon, Gregory J.; Lehmann, Ruth

2015-01-01

The differentiation of stem cells is a tightly regulated process essential for animal development and tissue homeostasis. Through this process, attainment of new identity and function is achieved by marked changes in cellular properties. Intrinsic cellular mechanisms governing stem cell differentiation remain largely unknown, in part because systematic forward genetic approaches to the problem have not been widely used1,2. Analysing genes required for germline stem cell differentiation in the Drosophila ovary, we find that the mitochondrial ATP synthase plays a critical role in this process. Unexpectedly, the ATP synthesizing function of this complex was not necessary for differentiation, as knockdown of other members of the oxidative phosphorylation system did not disrupt the process. Instead, the ATP synthase acted to promote the maturation of mitochondrial cristae during differentiation through dimerization and specific upregulation of the ATP synthase complex. Taken together, our results suggest that ATP synthase-dependent crista maturation is a key developmental process required for differentiation independent of oxidative phosphorylation. PMID:25915123

Synergic effects of mycoplasmal lipopeptides and extracellular ATP on activation of macrophages.

PubMed

Into, Takeshi; Fujita, Mari; Okusawa, Tsugumi; Hasebe, Akira; Morita, Manabu; Shibata, Ken-Ichiro

2002-07-01

Mycoplasmal lipopeptides S-(2,3-bispalmitoyloxypropyl)-CGDPKHSPKSF and S-(2,3-bispalmitoyloxypropyl)-CGNNDESNISFKEK activated a monocytic cell line, THP-1 cells, to produce tumor necrosis factor alpha. The activity of the lipopeptides was augmented by ATP in a dose-dependent manner. In addition, the level of expression of mRNAs for tumor necrosis factor alpha and interleukin-1 beta, -6, and -8 was also upregulated by the lipopeptides and/or extracellular ATP, but that of interleukin-10 was not. The P2X purinergic receptor antagonists pyridoxal phosphate 6-azophenyl 2',4'-disulfonic acid and periodate-oxidized ATP suppressed the activity of ATP to augment the activation of THP-1 cells by the lipopeptides, suggesting that P2X receptors play important roles in the activity of ATP. The nuclear factor kappa B inhibitor dexamethasone also suppressed the activity, suggesting that the activity of ATP is dependent upon the nuclear factor kappa B. Thus, these results suggest that the interaction of extracellular ATP with the P2X receptors is attributed to the activity of ATP to augment the activation of THP-1 cells by mycoplasmal lipopeptides.

Synergic Effects of Mycoplasmal Lipopeptides and Extracellular ATP on Activation of Macrophages

PubMed Central

Into, Takeshi; Fujita, Mari; Okusawa, Tsugumi; Hasebe, Akira; Morita, Manabu; Shibata, Ken-Ichiro

2002-01-01

Mycoplasmal lipopeptides S-(2,3-bispalmitoyloxypropyl)-CGDPKHSPKSF and S-(2,3-bispalmitoyloxypropyl)-CGNNDESNISFKEK activated a monocytic cell line, THP-1 cells, to produce tumor necrosis factor alpha. The activity of the lipopeptides was augmented by ATP in a dose-dependent manner. In addition, the level of expression of mRNAs for tumor necrosis factor alpha and interleukin-1β, -6, and -8 was also upregulated by the lipopeptides and/or extracellular ATP, but that of interleukin-10 was not. The P2X purinergic receptor antagonists pyridoxal phosphate 6-azophenyl 2′,4′-disulfonic acid and periodate-oxidized ATP suppressed the activity of ATP to augment the activation of THP-1 cells by the lipopeptides, suggesting that P2X receptors play important roles in the activity of ATP. The nuclear factor κB inhibitor dexamethasone also suppressed the activity, suggesting that the activity of ATP is dependent upon the nuclear factor κB. Thus, these results suggest that the interaction of extracellular ATP with the P2X receptors is attributed to the activity of ATP to augment the activation of THP-1 cells by mycoplasmal lipopeptides. PMID:12065499

Interlibrary Loan Communications Subsystem: Users Manual.

ERIC Educational Resources Information Center

OCLC Online Computer Library Center, Inc., Dublin, OH.

The OCLC Interlibrary Loan (ILL) Communications Subsystem provides participating libraries with on-line control of ILL transactions. This user manual includes a glossary of terms related to the procedures in using the system. Sections describe computer entry, searching, loan request form, loan response form, ILL procedures, the special message…

ATP as a biomarker of viable microorganisms in clean-room facilities

NASA Technical Reports Server (NTRS)

Venkateswaran, Kasthuri; Hattori, Noriaki; La Duc, Myron T.; Kern, Roger

2003-01-01

A new firefly luciferase bioluminescence assay method that differentiates free extracellular ATP (dead cells, etc.) from intracellular ATP (viable microbes) was used to determine the viable microbial cleanliness of various clean-room facilities. For comparison, samples were taken from both clean-rooms, where the air was filtered to remove particles >0.5 microm, and ordinary rooms with unfiltered air. The intracellular ATP was determined after enzymatically degrading the sample's free ATP. Also for comparison, cultivable microbial populations were counted on nutrient-rich trypticase soy agar (TSA) plates. Both the cultivable and ATP-based determinations indicate that the microbial burden was lower in clean-room facilities than in ordinary rooms. However, there was no direct correlation between the two sets of measurements because the two assays measured very different populations. A large fraction of the samples yielded no colony formers on TSA, but were positive for intracellular ATP. Subsequently, genomic DNA was isolated directly from selected samples and 16S rDNA fragments were cloned and sequenced, identifying nearest neighbors, many of which are known to be noncultivable in the media employed. It was concluded that viable microbial contamination can be reliably monitored by measurement of intracellular ATP, and that this method may be considered superior to cultivable colony counts due to its speed and its ability to report the presence of viable but noncultivable organisms. When the detection of nonviable microbes is of interest, the ATP assay can be supplemented with DNA analysis.

ATP as a biomarker of viable microorganisms in clean-room facilities.

PubMed

Venkateswaran, Kasthuri; Hattori, Noriaki; La Duc, Myron T; Kern, Roger

2003-03-01

A new firefly luciferase bioluminescence assay method that differentiates free extracellular ATP (dead cells, etc.) from intracellular ATP (viable microbes) was used to determine the viable microbial cleanliness of various clean-room facilities. For comparison, samples were taken from both clean-rooms, where the air was filtered to remove particles >0.5 microm, and ordinary rooms with unfiltered air. The intracellular ATP was determined after enzymatically degrading the sample's free ATP. Also for comparison, cultivable microbial populations were counted on nutrient-rich trypticase soy agar (TSA) plates. Both the cultivable and ATP-based determinations indicate that the microbial burden was lower in clean-room facilities than in ordinary rooms. However, there was no direct correlation between the two sets of measurements because the two assays measured very different populations. A large fraction of the samples yielded no colony formers on TSA, but were positive for intracellular ATP. Subsequently, genomic DNA was isolated directly from selected samples and 16S rDNA fragments were cloned and sequenced, identifying nearest neighbors, many of which are known to be noncultivable in the media employed. It was concluded that viable microbial contamination can be reliably monitored by measurement of intracellular ATP, and that this method may be considered superior to cultivable colony counts due to its speed and its ability to report the presence of viable but noncultivable organisms. When the detection of nonviable microbes is of interest, the ATP assay can be supplemented with DNA analysis.

An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.

PubMed

Droguett, Karla; Rios, Mariana; Carreño, Daniela V; Navarrete, Camilo; Fuentes, Christian; Villalón, Manuel; Barrera, Nelson P

2017-07-15

Extracellular ATP, in association with [Ca 2+ ] i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement. The force exerted by cilia, measured by atomic force microscopy, is reduced following extracellular ATP hydrolysis. This result complements the current understanding of the ciliary beating regulatory mechanism, with special relevance to inflammatory diseases of the airway epithelium that affect mucociliary clearance. Extracellular nucleotides, including ATP, are locally released by the airway epithelium and stimulate ciliary activity in a [Ca 2+ ] i -dependent manner after mechanical stimulation of ciliated cells. However, it is unclear whether the ATP released is involved in regulating basal ciliary activity and mediating changes in ciliary activity in response to chemical stimulation. In the present study, we evaluated ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from mouse tracheal epithelium, using videomicroscopy and atomic force microscopy (AFM), respectively. Extracellular ATP levels and [Ca 2+ ] i were measured by luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide was measured to evaluate hemichannel functionality. We show that hydrolysis of constitutive extracellular ATP levels with apyrase (50 U ml -1 ) reduced basal CBF by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an

ATP-Binding Cassette Proteins: Towards a Computational View of Mechanism

NASA Astrophysics Data System (ADS)

Liao, Jielou

2004-03-01

Many large machine proteins can generate mechanical force and undergo large-scale conformational changes (LSCC) to perform varying biological tasks in living cells by utilizing ATP. Important examples include ATP-binding cassette (ABC) transporters. They are membrane proteins that couple ATP binding and hydrolysis to the translocation of substrates across membranes [1]. To interpret how the mechanical force generated by ATP binding and hydrolysis is propagated, a coarse-grained ATP-dependent harmonic network model (HNM) [2,3] is applied to the ABC protein, BtuCD. This protein machine transports vitamin B12 across membranes. The analysis shows that subunits of the protein move against each other in a concerted manner. The lowest-frequency modes of the BtuCD protein are found to link the functionally critical domains, and are suggested to be responsible for large-scale ATP-coupled conformational changes. [1] K. P. Locher, A. T. Lee and D. C. Rees. Science 296, 1091-1098 (2002). [2] Atilgan, A. R., S. R. Durell, R. L. Jernigan, M. C. Demirel, O. Keskin, and I. Bahar. Biophys. J. 80, 505-515(2002); M. M Tirion, Phys. Rev. Lett. 77, 1905-1908 (1996). [3] J. -L. Liao and D. N. Beratan, 2003, to be published.

Processing mechanics of alternate twist ply (ATP) yarn technology

NASA Astrophysics Data System (ADS)

Elkhamy, Donia Said

Ply yarns are important in many textile manufacturing processes and various applications. The primary process used for producing ply yarns is cabling. The speed of cabling is limited to about 35m/min. With the world's increasing demands of ply yarn supply, cabling is incompatible with today's demand activated manufacturing strategies. The Alternate Twist Ply (ATP) yarn technology is a relatively new process for producing ply yarns with improved productivity and flexibility. This technology involves self plying of twisted singles yarn to produce ply yarn. The ATP process can run more than ten times faster than cabling. To implement the ATP process to produce ply yarns there are major quality issues; uniform Twist Profile and yarn Twist Efficiency. The goal of this thesis is to improve these issues through process modeling based on understanding the physics and processing mechanics of the ATP yarn system. In our study we determine the main parameters that control the yarn twist profile. Process modeling of the yarn twist across different process zones was done. A computational model was designed to predict the process parameters required to achieve a square wave twist profile. Twist efficiency, a measure of yarn torsional stability and bulk, is determined by the ratio of ply yarn twist to singles yarn twist. Response Surface Methodology was used to develop the processing window that can reproduce ATP yarns with high twist efficiency. Equilibrium conditions of tensions and torques acting on the yarns at the self ply point were analyzed and determined the pathway for achieving higher twist efficiency. Mechanistic modeling relating equilibrium conditions to the twist efficiency was developed. A static tester was designed to zoom into the self ply zone of the ATP yarn. A computer controlled, prototypic ATP machine was constructed and confirmed the mechanistic model results. Optimum parameters achieving maximum twist efficiency were determined in this study. The

ATP monitoring technology for microbial growth control in potable water systems

NASA Astrophysics Data System (ADS)

Whalen, Patrick A.; Whalen, Philip J.; Cairns, James E.

2006-05-01

ATP (Adenosine Triphosphate) is the primary energy transfer molecule present in all living biological cells on Earth. ATP cannot be produced or maintained by anything but a living organism, and as such, its measurement is a direct indication of biological activity. The main advantage of ATP as a biological indicator is the speed of the analysis - from collecting the sample to obtaining the result, only minutes are required. The technology to measure ATP is already widely utilized to verify disinfection efficacy in the food industry and is also commonly applied in industrial water processes such as cooling water systems to monitor microbial growth and biocide applications. Research has indicated that ATP measurement technology can also play a key role in such important industries as potable water distribution and biological wastewater treatment. As will be detailed in this paper, LuminUltra Technologies has developed and applied ATP measurement technologies designed for any water type, and as such can provide a method to rapidly and accurately determine the level of biological activity in drinking water supplies. Because of its speed and specificity to biological activity, ATP measurement can play a key role in defending against failing drinking water quality, including those encountered during routine operation and also bioterrorism.

Functional Performance of an Enabling Atmosphere Revitalization Subsystem Architecture for Deep Space Exploration Missions

NASA Technical Reports Server (NTRS)

Perry, Jay L.; Abney, Morgan B.; Frederick, Kenneth R.; Greenwood, Zachary W.; Kayatin, Matthew J.; Newton, Robert L.; Parrish, Keith J.; Roman, Monsi C.; Takada, Kevin C.; Miller, Lee A.;

Development of a preprototype times wastewater recovery subsystem, addendum

NASA Technical Reports Server (NTRS)

Dehner, G. F.

1984-01-01

Six tasks are described reflecting subsystem hardware and software modifications and test evaluation of a TIMES wastewater recovery subsystem. The overall results are illustrated in a figure which shows the water production rate, the specific energy corrected to 26.5 VDC, and the product water conductivity at various points in the testing. Four tasks are described reflecting studies performed to develop a preliminary design concept for a next generation TIMES. The overall results of the study are the completion of major design analyses and preliminary configuration layout drawings.

Galileo attitude and articulation control subsystem closed loop testing

NASA Technical Reports Server (NTRS)

Lembeck, M. F.; Pignatano, N. D.

1983-01-01

In order to ensure the reliable operation of the Attitude and Articulation Control Subsystem (AACS) which will guide the Galileo spacecraft on its two and one-half year journey to Jupiter, the AACS is being rigorously tested. The primary objectives of the test program are the verification of the AACS's form, fit, and function, especially with regard to subsystem external interfaces and the functional operation of the flight software. Attention is presently given to the Galileo Closed Loop Test System, which simulates the dynamic and 'visual' flight environment for AACS components in the laboratory.

BEHAVE: fire behavior prediction and fuel modeling system-BURN Subsystem, part 1

Treesearch

Patricia L. Andrews

1986-01-01

Describes BURN Subsystem, Part 1, the operational fire behavior prediction subsystem of the BEHAVE fire behavior prediction and fuel modeling system. The manual covers operation of the computer program, assumptions of the mathematical models used in the calculations, and application of the predictions.

Integrating the autonomous subsystems management process

NASA Technical Reports Server (NTRS)

Ashworth, Barry R.

1992-01-01

Ways in which the ranking of the Space Station Module Power Management and Distribution testbed may be achieved and an individual subsystem's internal priorities may be managed within the complete system are examined. The application of these results in the integration and performance leveling of the autonomously managed system is discussed.

Ice pack heat sink subsystem, phase 2. [astronaut life support cooling system

NASA Technical Reports Server (NTRS)

Roebelen, G. J., Jr.; Kellner, J. D.

1975-01-01

The report describes the design, development, fabrication, and test at one gravity of a prototype ice pack heat sink subsystem to be used eventually for astronaut cooling during manned space missions; the investigation of thermal storage material with the objective of uncovering materials with heats of fusion and/or solution in the range of 300 Btu/lb (700 kilojoules/kilogram); and the planned procedure for implementing an ice pack heat sink subsystem flight experiment. In normal use, excess heat in the liquid cooling garment (LCG) coolant is transferred to a reusable/regenerable ice pack heat sink. For emergency operation, or for extension of extravehicular activity mission time after all the ice has melted, water from the ice pack is boiled to vacuum, thereby continuing to remove heat from the LCG coolant. This subsystem incorporates a quick disconnect thermal interface between the ice pack heat sink and the subsystem heat exchanger.

The High Altitude Balloon Experiment demonstration of acquisition, tracking, and pointing technologies (HABE-ATP)

NASA Astrophysics Data System (ADS)

Dimiduk, D.; Caylor, M.; Williamson, D.; Larson, L.

1995-01-01

The High Altitude Balloon Experiment demonstration of Acquisition, Tracking, and Pointing (HABE-ATP) is a system built around balloon-borne payload which is carried to a nominal 26-km altitude. The goal is laser tracking thrusting theater and strategic missiles, and then pointing a surrogate laser weapon beam, with performance levels end a timeline traceable to operational laser weapon system requirements. This goal leads to an experiment system design which combines hardware from many technology areas: an optical telescope and IR sensors; an advanced angular inertial reference; a flexible multi-level of actuation digital control system; digital tracking processors which incorporate real-time image analysis and a pulsed, diode-pumped solid state tracking laser. The system components have been selected to meet the overall experiment goals of tracking unmodified boosters at 50- 200 km range. The ATP system on HABE must stabilize and control a relative line of sight between the platform and the unmodified target booster to a 1 microrad accuracy. The angular pointing reference system supports both open loop and closed loop track modes; GPS provides absolute position reference. The control system which positions the line of sight for the ATP system must sequence through accepting a state vector handoff, closed-loop passive IR acquisition, passive IR intermediate fine track, active fine track, and then finally aimpoint determination and maintenance modes. Line of sight stabilization to fine accuracy levels is accomplished by actuating wide bandwidth fast steering mirrors (FSM's). These control loops off-load large-amplitude errors to the outer gimbal in order to remain within the limited angular throw of the FSM's. The SWIR acquisition and MWIR intermediate fine track sensors (both PtSi focal planes) image the signature of the rocket plume. After Hard Body Handover (HBHO), active fine tracking is conducted with a visible focal plane viewing the laser-illuminated target

31P magnetization transfer measurements of Pi→ATP flux in exercising human muscle

PubMed Central

Savage, David B.; Williams, Guy B.; Porter, David; Carpenter, T. Adrian; Brindle, Kevin M.; Kemp, Graham J.

2016-01-01

Fundamental criticisms have been made over the use of 31P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (Pi)→ATP flux (VPi-ATP) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of VPi-ATP is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure VPi-ATP in human exercising muscle for the first time. Steady-state VPi-ATP was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (VATP). We define a surplus Pi→ATP flux as the difference between VPi-ATP and VATP. The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and Pi in some systems and have been suggested to be responsible for this surplus flux. Surplus VPi-ATP did not change between rest and exercise, even though the concentrations of Pi and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus Pi→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the 31P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and Pi catalyzed by GAPDH and PGK. PMID:26744504

31P magnetization transfer measurements of Pi→ATP flux in exercising human muscle.

PubMed

Sleigh, Alison; Savage, David B; Williams, Guy B; Porter, David; Carpenter, T Adrian; Brindle, Kevin M; Kemp, Graham J

2016-03-15

Fundamental criticisms have been made over the use of (31)P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (Pi)→ATP flux (VPi-ATP) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of VPi-ATP is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure VPi-ATP in human exercising muscle for the first time. Steady-state VPi-ATP was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (VATP). We define a surplus Pi→ATP flux as the difference between VPi-ATP and VATP. The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and Pi in some systems and have been suggested to be responsible for this surplus flux. Surplus VPi-ATP did not change between rest and exercise, even though the concentrations of Pi and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus Pi→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the (31)P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and Pi catalyzed by GAPDH and PGK. Copyright © 2016 the American Physiological Society.

[ATP content in cryopreserved sperm of Siberian white cranes Grus leucogeranus (Aves: Gruiformes)].

PubMed

Maksudov, G Iu; Erokhin, A S; Nesterenko, O N; Panchenko, V G

2002-01-01

ATP contents were studied in the native and cryoconserved sperm of Siberian white cranes Grus leucogeranus using bioluminescence analysis. The ATP content in freshly obtained spermatozoa was 12.7 nmol/10(8) cells. No ATP was found in the seminal plasma. In the process of freezing-thawing, the ATP concentration in the spermatozoa decreased by 30%. The differences in the dynamics of ATP content during cryoconservation of sperm of white cranes and other birds and mammals are discussed.

Facile conversion of ATP-binding RNA aptamer to quencher-free molecular aptamer beacon.

PubMed

Park, Yoojin; Nim-Anussornkul, Duangrat; Vilaivan, Tirayut; Morii, Takashi; Kim, Byeang Hyean

2018-01-15

We have developed RNA-based quencher-free molecular aptamer beacons (RNA-based QF-MABs) for the detection of ATP, taking advantage of the conformational changes associated with ATP binding to the ATP-binding RNA aptamer. The RNA aptamer, with its well-defined structure, was readily converted to the fluorescence sensors by incorporating a fluorophore into the loop region of the hairpin structure. These RNA-based QF-MABs exhibited fluorescence signals in the presence of ATP relative to their low background signals in the absence of ATP. The fluorescence emission intensity increased upon formation of a RNA-based QF-MAB·ATP complex. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-time imaging of inflation-induced ATP release in the ex vivo rat lung.

PubMed

Furuya, Kishio; Tan, Ju Jing; Boudreault, Francis; Sokabe, Masahiro; Berthiaume, Yves; Grygorczyk, Ryszard

2016-11-01

Extracellular ATP and other nucleotides are important autocrine/paracrine mediators that regulate diverse processes critical for lung function, including mucociliary clearance, surfactant secretion, and local blood flow. Cellular ATP release is mechanosensitive; however, the impact of physical stimuli on ATP release during breathing has never been tested in intact lungs in real time and remains elusive. In this pilot study, we investigated inflation-induced ATP release in rat lungs ex vivo by real-time luciferin-luciferase (LL) bioluminescence imaging coupled with simultaneous infrared tissue imaging to identify ATP-releasing sites. With LL solution introduced into air spaces, brief inflation of such edematous lung (1 s, ∼20 cmH 2 O) induced transient (<30 s) ATP release in a limited number of air-inflated alveolar sacs during their recruitment/opening. Released ATP reached concentrations of ∼10 -6 M, relevant for autocrine/paracrine signaling, but it remained spatially restricted to single alveolar sacs or their clusters. ATP release was stimulus dependent: prolonged (100 s) inflation evoked long-lasting ATP release that terminated upon alveoli deflation/derecruitment while cyclic inflation/suction produced cyclic ATP release. With LL introduced into blood vessels, inflation induced transient ATP release in many small patchlike areas the size of alveolar sacs. Findings suggest that inflation induces ATP release in both alveoli and the surrounding blood capillary network; the functional units of ATP release presumably consist of alveolar sacs or their clusters. Our study demonstrates the feasibility of real-time ATP release imaging in ex vivo lungs and provides the first direct evidence of inflation-induced ATP release in lung air spaces and in pulmonary blood capillaries, highlighting the importance of purinergic signaling in lung function. Copyright © 2016 the American Physiological Society.

Diadenosine tetraphosphate-gating of cardiac K(ATP) channels requires intact actin cytoskeleton.

PubMed

Jovanović, S; Jovanović, A

2001-09-01

Diadenosine polyphosphates (ApnA) have been recently discovered in the heart, and their levels found to be regulated by ischemia. These signaling molecules are believed to regulate cellular processes that alarm a cell to metabolic stress. In particular, changes in cardiac diadenosine polyphosphates (ApnA) levels may contribute to the regulation of ATP-sensitive K+ (K(ATP)) channel activity, an ion channel that couples the cellular metabolic state with membrane excitability. A feature of myocardial ischemia is the disruption of the actin cytoskeleton which critically regulates the behavior of K(ATP) channels. Whether the integrity of actin microfilaments regulates the interaction of ApnA with K(ATP) channels is not known. The inside-out configuration of the patch-clamp technique was applied to cardiomyocytes isolated from guinea-pig heart. Following patch excision, the prototype dinucleotide, diadenosine tetraphosphate (Ap4A), inhibited K(ATP) channel opening. Treatment of the internal side of membrane patches with either cytochalasin B or DNase I, disrupters of the actin cytoskeleton, prevented Ap4A-induced inhibition of K(ATP) channel opening. Application of purified actin to DNase-treated membrane patches restored the ability of Ap4A to close K(ATP) channels. This study shows that inhibition of cardiac K(ATP) channel by Ap4A, a putative alarmone, requires intact subsarcolemmal actin network. Such interaction between K(ATP) channels, the cardiomyocyte cytoskeleton and intracellular Ap4A could affect different channel-dependent functions.

Stability of subsystem solutions in agent-based models

NASA Astrophysics Data System (ADS)

Perc, Matjaž

2018-01-01

The fact that relatively simple entities, such as particles or neurons, or even ants or bees or humans, give rise to fascinatingly complex behaviour when interacting in large numbers is the hallmark of complex systems science. Agent-based models are frequently employed for modelling and obtaining a predictive understanding of complex systems. Since the sheer number of equations that describe the behaviour of an entire agent-based model often makes it impossible to solve such models exactly, Monte Carlo simulation methods must be used for the analysis. However, unlike pairwise interactions among particles that typically govern solid-state physics systems, interactions among agents that describe systems in biology, sociology or the humanities often involve group interactions, and they also involve a larger number of possible states even for the most simplified description of reality. This begets the question: when can we be certain that an observed simulation outcome of an agent-based model is actually stable and valid in the large system-size limit? The latter is key for the correct determination of phase transitions between different stable solutions, and for the understanding of the underlying microscopic processes that led to these phase transitions. We show that a satisfactory answer can only be obtained by means of a complete stability analysis of subsystem solutions. A subsystem solution can be formed by any subset of all possible agent states. The winner between two subsystem solutions can be determined by the average moving direction of the invasion front that separates them, yet it is crucial that the competing subsystem solutions are characterised by a proper composition and spatiotemporal structure before the competition starts. We use the spatial public goods game with diverse tolerance as an example, but the approach has relevance for a wide variety of agent-based models.

ATP Synthase: A Molecular Therapeutic Drug Target for Antimicrobial and Antitumor Peptides

PubMed Central

Ahmad, Zulfiqar; Okafor, Florence; Azim, Sofiya; Laughlin, Thomas F.

2015-01-01

In this review we discuss the role of ATP synthase as a molecular drug target for natural and synthetic antimi-crobial/antitumor peptides. We start with an introduction of the universal nature of the ATP synthase enzyme and its role as a biological nanomotor. Significant structural features required for catalytic activity and motor functions of ATP synthase are described. Relevant details regarding the presence of ATP synthase on the surface of several animal cell types, where it is associated with multiple cellular processes making it a potential drug target with respect to antimicrobial peptides and other inhibitors such as dietary polyphenols, is also reviewed. ATP synthase is known to have about twelve discrete inhibitor binding sites including peptides and other inhibitors located at the interface of α/β subunits on the F1 sector of the enzyme. Molecular interaction of peptides at the β DEELSEED site on ATP synthase is discussed with specific examples. An inhibitory effect of other natural/synthetic inhibitors on ATP is highlighted to explore the therapeutic roles played by peptides and other inhibitors. Lastly, the effect of peptides on the inhibition of the Escherichia coli model system through their action on ATP synthase is presented. PMID:23432591

[Crystallography of ATP hydrolysis mechanism in rat brain kinesin].

PubMed

Wan, Qun; Zhu, Pingting; Lü, Houning; Chen, Xinhong

2014-04-01

Rat brain kinesin is a conventional kinesin that uses the energy from ATP hydrolysis to walk along the microtubule progressively. Studying how the chemical energy in ATP is utilized for mechanical movement is important to understand this moving function. The monomeric motor domain, rK354, was crystallized. An ATP analog, AMPPNP, was soaked in the active site. Comparing the complex structure of rK354 x AMPPNP and that of rK354ADP, a hypothesis is proposed that Glu237 in the Switch II region sensors the presence of gamma-phosphate and transfers the signal to the microtubule binding region.

How Native and Alien Metal Cations Bind ATP: Implications for Lithium as a Therapeutic Agent

NASA Astrophysics Data System (ADS)

Dudev, Todor; Grauffel, Cédric; Lim, Carmay

2017-02-01

Adenosine triphosphate (ATP), the major energy currency of the cell, exists in solution mostly as ATP-Mg. Recent experiments suggest that Mg2+ interacts with the highly charged ATP triphosphate group and Li+ can co-bind with the native Mg2+ to form ATP-Mg-Li and modulate the neuronal purine receptor response. However, it is unclear how the negatively charged ATP triphosphate group binds Mg2+ and Li+ (i.e. which phosphate group(s) bind Mg2+/Li+) and how the ATP solution conformation depends on the type of metal cation and the metal-binding mode. Here, we reveal the preferred ATP-binding mode of Mg2+/Li+ alone and combined: Mg2+ prefers to bind ATP tridentately to each of the three phosphate groups, but Li+ prefers to bind bidentately to the terminal two phosphates. We show that the solution ATP conformation depends on the cation and its binding site/mode, but it does not change significantly when Li+ binds to Mg2+-loaded ATP. Hence, ATP-Mg-Li, like Mg2+-ATP, can fit in the ATP-binding site of the host enzyme/receptor, activating specific signaling pathways.

A futile cycle, formed between two ATP-dependant gamma-glutamyl cycle enzymes, gamma-glutamyl cysteine synthetase and 5-oxoprolinase: the cause of cellular ATP depletion in nephrotic cystinosis?

PubMed

Kumar, Akhilesh; Bachhawat, Anand Kumar

2010-03-01

Cystinosis, an inherited disease caused by a defect in the lysosomal cystine transporter (CTNS), is characterized by renal proximal tubular dysfunction. Adenosine triphosphate (ATP) depletion appears to be a key event in the pathophysiology of the disease, even though the manner in which ATP depletion occurs is still a puzzle. We present a model that explains how a futile cycle that is generated between two ATP-utilizing enzymes of the gamma-glutamyl cycle leads to ATP depletion. The enzyme gamma-glutamyl cysteine synthetase (gamma-GCS), in the absence of cysteine, forms 5-oxoproline (instead of the normal substrate, gamma-glutamyl cysteine) and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. Thus, in cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells. The model is also compatible with the differences seen in the human patients and the mouse model of cystinosis, where renal failure is not observed.

Integration & Validation of LCU with Different Sub-systems for Diacrode based amplifier

NASA Astrophysics Data System (ADS)

Rajnish, Kumar; Verma, Sriprakash; Soni, Dipal; Patel, Hriday; Suthar, Gajendra; Dalicha, Hrushikesh; Dhola, Hitesh; Patel, Amit; Upadhayay, Dishang; Jha, Akhil; Patel, Manoj; Trivedi, Rajesh; Machchhar, Harsha; Singh, Raghuraj; Mukherjee, Aparajita

2017-04-01

ITER-India is responsible to deliver nine (8+1 spare) ICH & CD Power Sources to ITER. Each power source is capable to deliver 2.5 MW at 35 to 65 MHz frequency range with a load condition up to VSWR 2:1. For remote operation of different subsystems, Local Control Unit (LCU) is developed. LCU is developed using PXI hardware and Schneider PLC with Lab VIEW-RT developmental environment. All the protection function of the amplifier is running on PXI 7841 R module that ensures hard wired protection logic. There are three level of protection function- first by power supply itself that detects overcurrent/overvoltage and trips itself and generate trip signal for further action. There are some direct hardwired signal interfaces between power supplies to protect the amplifier. Second level of protection is generated through integrated controller of amplifier i.e. Command Control Embedded (CCE) against arc and Anode over current. Third level of Protection is through LCU where different fault signals are received and processed to generate off command for different sub-systems. Before connecting different subsystem with High power RF amplifiers (Driver & Final stage), each subsystem is individually tested through LCU. All protection functions are tested before hooking up the subsystems with main amplifier and initiating RF operation.

Energy Efficient Engine Low Pressure Subsystem Flow Analysis

NASA Technical Reports Server (NTRS)

Hall, Edward J.; Lynn, Sean R.; Heidegger, Nathan J.; Delaney, Robert A.

1998-01-01

The objective of this project is to provide the capability to analyze the aerodynamic performance of the complete low pressure subsystem (LPS) of the Energy Efficient Engine (EEE). The analyses were performed using three-dimensional Navier-Stokes numerical models employing advanced clustered processor computing platforms. The analysis evaluates the impact of steady aerodynamic interaction effects between the components of the LPS at design and off-design operating conditions. Mechanical coupling is provided by adjusting the rotational speed of common shaft-mounted components until a power balance is achieved. The Navier-Stokes modeling of the complete low pressure subsystem provides critical knowledge of component aero/mechanical interactions that previously were unknown to the designer until after hardware testing.

Energy Efficient Engine Low Pressure Subsystem Aerodynamic Analysis

NASA Technical Reports Server (NTRS)

Hall, Edward J.; Delaney, Robert A.; Lynn, Sean R.; Veres, Joseph P.

1998-01-01

The objective of this study was to demonstrate the capability to analyze the aerodynamic performance of the complete low pressure subsystem (LPS) of the Energy Efficient Engine (EEE). Detailed analyses were performed using three- dimensional Navier-Stokes numerical models employing advanced clustered processor computing platforms. The analysis evaluates the impact of steady aerodynamic interaction effects between the components of the LPS at design and off- design operating conditions. Mechanical coupling is provided by adjusting the rotational speed of common shaft-mounted components until a power balance is achieved. The Navier-Stokes modeling of the complete low pressure subsystem provides critical knowledge of component acro/mechanical interactions that previously were unknown to the designer until after hardware testing.

Global gene profiling of aging lungs in Atp8b1 mutant mice.

PubMed

Soundararajan, Ramani; Stearns, Timothy M; Czachor, Alexander; Fukumoto, Jutaro; Turn, Christina; Westermann-Clark, Emma; Breitzig, Mason; Tan, Lee; Lockey, Richard F; King, Benjamin L; Kolliputi, Narasaiah

2016-09-29

Recent studies implicate cardiolipin oxidation in several age-related diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1 mutation and age-related gene alteration is unknown. Therefore, we investigated how Atp8b1 mutation alters age-related genes. We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and Atp8b1 mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR). Global transcriptome analysis revealed 532 differentially expressed genes in Atp8b1 lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in Atp8b1 lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in Adamts2 and Mmp13 transcripts in aged Atp8b1 lungs was validated by qRT-PCR. Similarly, the decrease in Col1a1 and increase in Cxcr6 transcripts was confirmed in both Atp8b1 mutant and C57BL/6 lungs. Based on transcriptome profiling, our study indicates that Atp8b1 mutant mice may be susceptible to age-related lung diseases.

General anesthetics cause mitochondrial dysfunction and reduction of intracellular ATP levels

PubMed Central

Kishikawa, Jun-ichi; Inoue, Yuki; Fujikawa, Makoto; Nishimura, Kenji; Nakanishi, Atsuko; Tanabe, Tsutomu; Imamura, Hiromi

2018-01-01

General anesthetics are indispensable for effective clinical care. Although, the mechanism of action of general anesthetics remains controversial, lipid bilayers and proteins have been discussed as their targets. In this study, we focused on the relationship between cellular ATP levels and general anesthetics. The ATP levels of nematodes and cultured mammalian cells were decreased by exposure to three general anesthetics: isoflurane, pentobarbital, and 1-phenoxy-2-propanol. Furthermore, these general anesthetics abolished mitochondrial membrane potential, resulting in the inhibition of mitochondrial ATP synthesis. These results suggest that the observed decrease of cellular ATP level is a common phenomenon of general anesthetics. PMID:29298324

An uracil-linked hydroxyflavone probe for the recognition of ATP

PubMed Central

Bojtár, Márton; Janzsó-Berend, Péter Zoltán; Mester, Dávid; Hessz, Dóra; Kállay, Mihály; Kubinyi, Miklós

2018-01-01

Background: Nucleotides are essential molecules in living systems due to their paramount importance in various physiological processes. In the past years, numerous attempts were made to selectively recognize and detect these analytes, especially ATP using small-molecule fluorescent chemosensors. Despite the various solutions, the selective detection of ATP is still challenging due to the structural similarity of various nucleotides. In this paper, we report the conjugation of a uracil nucleobase to the known 4’-dimethylamino-hydroxyflavone fluorophore. Results: The complexation of this scaffold with ATP is already known. The complex is held together by stacking and electrostatic interactions. To achieve multi-point recognition, we designed the uracil-appended version of this probe to include complementary base-pairing interactions. The theoretical calculations revealed the availability of multiple complex structures. The synthesis was performed using click chemistry and the nucleotide recognition properties of the probe were evaluated using fluorescence spectroscopy. Conclusions: The first, uracil-containing fluorescent ATP probe based on a hydroxyflavone fluorophore was synthesized and evaluated. A selective complexation with ATP was observed and a ratiometric response in the excitation spectrum. PMID:29719572

[Change in concentration of cytosolic Ca2+ caused by extracellular ATP and ecto-ATP-ase activity in thymocytes and transformed MT-4 cells].

PubMed

Hrebinyk, S M; Artemenko, O Iu; Hryniuk, I I; Perepelitsyna, O M; Matyshevs'ka, O P

2009-01-01

The comparative study of extracellular ATP (ATP0) effect on free cytosolic calcium concentration ([Ca2+]i) in normal (isolated rat thymocytes) and transformed (leukosis MT-4 line) T-cells was carried out. Addition of 1 mM ATP to Ca-free incubation medium of both types of cells, loaded with indo-1, had no effect on [Ca2+]i level. Upon subsequent addition of 1 mM CaCl2 to the incubation medium the rapid and significant increase of [Ca2+]i in MT-4 cells was registered. This effect was maintained within 10 min and was not inhibited by phospholipase C inhibitor 0.2 mM neomycin, that was induced by cation entry into the cells from the extracellular medium. Both types of cells were shown to demonstrate ecto-ATPase activity in the presence of 1 mM MgCl2 or CaC12 in the incubation medium. Estimation of kinetic parameters has indicated that the maximum rate of extracellular ATP hydrolysis by MT-4 cells is higher and Mg2+ and Ca2+ activation constants are lower as compared to respective parameters of ATP hydrolysis by thymocytes. The possible functional significance of the increased level of ecto-ATPase activity in malignantly transformed cells is discussed.

ATP7B mediates vesicular sequestration of copper: insight into biliary copper excretion.

PubMed

Cater, Michael A; La Fontaine, Sharon; Shield, Kristy; Deal, Yolanda; Mercer, Julian F B

2006-02-01

The Wilson protein (ATP7B) regulates levels of systemic copper by excreting excess copper into bile. It is not clear whether ATP7B translocates excess intrahepatic copper directly across the canalicular membrane or sequesters this copper into exocytic vesicles, which subsequently fuse with canalicular membrane to expel their contents into bile. The aim of this study was to clarify the mechanism underlying ATP7B-mediated copper detoxification by investigating endogenous ATP7B localization in the HepG2 hepatoma cell line and its ability to mediate vesicular sequestration of excess intracellular copper. Immunofluorescence microscopy was used to investigate the effect of copper concentration on the localization of endogenous ATP7B in HepG2 cells. Copper accumulation studies to determine whether ATP7B can mediate vesicular sequestration of excess intracellular copper were performed using Chinese hamster ovary cells that exogenously expressed wild-type and mutant ATP7B proteins. In HepG2 cells, elevated copper levels stimulated trafficking of ATP7B to pericanalicular vesicles and not to the canalicular membrane as previously reported. Mutation of an endocytic retrieval signal in ATP7B caused the protein to constitutively localize to vesicles and not to the plasma membrane, suggesting that a vesicular compartment(s) is the final trafficking destination for ATP7B. Expression of wild-type and mutant ATP7B caused Chinese hamster ovary cells to accumulate copper in vesicles, which subsequently undergo exocytosis, releasing copper across the plasma membrane. This report provides compelling evidence that the primary mechanism of biliary copper excretion involves ATP7B-mediated vesicular sequestration of copper rather than direct copper translocation across the canalicular membrane.

Power, Avionics and Software - Phase 1.0:. [Subsystem Integration Test Report

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Sands, Obed S.; Bakula, Casey J.; Oldham, Daniel R.; Wright, Ted; Bradish, Martin A.; Klebau, Joseph M.

2014-01-01

This report describes Power, Avionics and Software (PAS) 1.0 subsystem integration testing and test results that occurred in August and September of 2013. This report covers the capabilities of each PAS assembly to meet integration test objectives for non-safety critical, non-flight, non-human-rated hardware and software development. This test report is the outcome of the first integration of the PAS subsystem and is meant to provide data for subsequent designs, development and testing of the future PAS subsystems. The two main objectives were to assess the ability of the PAS assemblies to exchange messages and to perform audio testing of both inbound and outbound channels. This report describes each test performed, defines the test, the data, and provides conclusions and recommendations.

The scaffold protein calcium/calmodulin-dependent serine protein kinase controls ATP release in sensory ganglia upon P2X3 receptor activation and is part of an ATP keeper complex.

PubMed

Bele, Tanja; Fabbretti, Elsa

2016-08-01

P2X3 receptors, gated by extracellular ATP, are expressed by sensory neurons and are involved in peripheral nociception and pain sensitization. The ability of P2X3 receptors to transduce extracellular stimuli into neuronal signals critically depends on the dynamic molecular partnership with the calcium/calmodulin-dependent serine protein kinase (CASK). The present work used trigeminal sensory neurons to study the impact that activation of P2X3 receptors (evoked by the agonist α,β-meATP) has on the release of endogenous ATP and how CASK modulates this phenomenon. P2X3 receptor function was followed by ATP efflux via Pannexin1 (Panx1) hemichannels, a mechanism that was blocked by the P2X3 receptor antagonist A-317491, and by P2X3 silencing. ATP efflux was enhanced by nerve growth factor, a treatment known to potentiate P2X3 receptor function. Basal ATP efflux was not controlled by CASK, and carbenoxolone or Pannexin silencing reduced ATP release upon P2X3 receptor function. CASK-controlled ATP efflux followed P2X3 receptor activity, but not depolarization-evoked ATP release. Molecular biology experiments showed that CASK was essential for the transactivation of Panx1 upon P2X3 receptor activation. These data suggest that P2X3 receptor function controls a new type of feed-forward purinergic signaling on surrounding cells, with consequences at peripheral and spinal cord level. Thus, P2X3 receptor-mediated ATP efflux may be considered for the future development of pharmacological strategies aimed at containing neuronal sensitization. P2X3 receptors are involved in sensory transduction and associate to CASK. We have studied in primary sensory neurons the molecular mechanisms downstream P2X3 receptor activation, namely ATP release and partnership with CASK or Panx1. Our data suggest that CASK and P2X3 receptors are part of an ATP keeper complex, with important feed-forward consequences at peripheral and central level. © 2016 International Society for Neurochemistry.

Lipidomic and metabolic changes in the P4-type ATPase ATP10D deficient C57BL/6J wild type mice upon rescue of ATP10D function.

PubMed

Sigruener, Alexander; Wolfrum, Christian; Boettcher, Alfred; Kopf, Thomas; Liebisch, Gerhard; Orsó, Evelyn; Schmitz, Gerd

2017-01-01

Sequence variants near the human gene for P4-type ATPase, class V, type 10D (ATP10D) were shown to significantly associate with circulating hexosylceramide d18:1/16:0 and d18:1/24:1 levels, obesity, insulin resistance, plasma high density lipoprotein (HDL), coronary stenotic index and intracranial atherosclerotic index. In mice Atp10d is associated with HDL modulation and C57BL/6 mice expressing a truncated, non-functional form of ATP10D easily develop obesity and insulin resistance on high-fat diet. We analyzed metabolic differences of ATP10D deficient C57BL/6J wild type and ATP10D transgenic C57BL/6J BAC129 mice. ATP10D transgenic mice gain 25% less weight on high-fat diet concomitant with a reduced increase in fat cell mass but independent of adipocyte size change. ATP10D transgenic mice also had 26% lower triacylglycerol levels with approximately 76% bound to very low density lipoprotein while in ATP10D deficient wild type mice 57% are bound to low density lipoprotein. Furthermore increased oxygen consumption and CO2 production, 38% lower glucose and 69% lower insulin levels and better insulin sensitivity were observed in ATP10D transgenic mice. Besides decreased hexosylceramide species levels were detected. Part of these effects may be due to reduced hepatic stearoyl-CoA desaturase 1 (SCD1) expression in ATP10D transgenic mice, which was reflected by altered fatty acid and lipid species patterns. There was a significant decrease in the hepatic 18:1 to 18:0 free fatty acid ratio in transgenic mice. The ratio of 16:1 to 16:0 was not significantly different. Interestingly both ratios were significantly reduced in plasma total fatty acids. In summary we found that ATP10D reduces high-fat diet induced obesity and improves insulin sensitivity. ATP10D transgenic mice showed altered hepatic expression of lipid-metabolism associated genes, including Scd1, along with changes in hepatic and plasma lipid species and plasma lipoprotein pattern.

Site Data Acquisition Subsystem (SDAS) Mod 1, installation, operation, and maintenance manual

NASA Technical Reports Server (NTRS)

1977-01-01

The Site Data Acquisition Subsystem (SDAS) Mod 1 was designed to collect sensor measurement data from solar energy demonstration site. This report provides a brief description of the SDAS and defines the installation requirements and procedures, the operations description and the procedures for field maintenance of the subsystem.

The Organization of the Distance Teaching Sub-System in an Open University.

ERIC Educational Resources Information Center

Chacon, Fabio J.

The problem of finding an adequate organization for the distance teaching subsystem in the Open University of Venezuela (Universidad Nacional Abierta) is analyzed. Problems facing this subsystem concern: communications with the headquarters and within the learning centers network, interaction with the environment in order to create a favorable…

Electrochemical carbon dioxide concentrator subsystem development

NASA Technical Reports Server (NTRS)

Koszenski, E. P.; Heppner, D. B.; Bunnell, C. T.

1986-01-01

The most promising concept for a regenerative CO2 removal system for long duration manned space flight is the Electrochemical CO2 Concentrator (EDC), which allows for the continuous, efficient removal of CO2 from the spacecraft cabin. This study addresses the advancement of the EDC system by generating subsystem and ancillary component reliability data through extensive endurance testing and developing related hardware components such as electrochemical module lightweight end plates, electrochemical module improved isolation valves, an improved air/liquid heat exchanger and a triple redundant relative humidity sensor. Efforts included fabrication and testing the EDC with a Sabatier CO2 Reduction Reactor and generation of data necessary for integration of the EDC into a space station air revitalization system. The results verified the high level of performance, reliability and durability of the EDC subsystem and ancillary hardware, verified the high efficiency of the Sabatier CO2 Reduction Reactor, and increased the overall EDC technology engineering data base. The study concluded that the EDC system is approaching the hardware maturity levels required for space station deployment.

CBERS-03 Satellite Power Supply Subsystem

NASA Astrophysics Data System (ADS)

Almeida, Mario C. P.; Bo, Han

2005-05-01

The second China Brazil Earth Resources Satellite, CBERS-2, was successfully launched on October 21st, 2003 from the Taiyuan Satellite Launch Center, China, through a Long March 4B launcher.The cooperation between China and Brazil for the construction of CBERS satellites is a continued mission and the governments of both countries are committed to building CBERS-3 for the continued and improved services started with the launch of CBERS-1 satellite [1]. Given to its success, the CBERS program is considered as a model for other joint scientific and technological projects between those two countries. CBERS-3 will have new instruments with higher resolution and higher power consumption requirements. The Power Supply Subsystem of CBERS-3 will be a scaled-up version of the one used in the previous missions, but will also present some innovations now possible due to improvements in components, technologies and materials. The modular concept used in the previous design, and repeated in this new mission, will allow the development of the new power subsystem equipments in a straightforward manner.

Synergistic binding of glucose and aluminium ATP to hexokinase from Saccharomyces cerevisiae.

PubMed

Woolfitt, A R; Kellett, G L; Hoggett, J G

1988-08-10

The binding of glucose, AlATP and AlADP to the monomeric and dimeric forms of the native yeast hexokinase PII isoenzyme and to the proteolytically modified SII monomeric form was monitored at pH 6.7 by the concomitant quenching of intrinsic protein fluorescence. No fluorescence changes were observed when free enzyme was mixed with AlATP at concentrations up to 7500 microM. In the presence of saturating concentrations of glucose, the maximal quenching of fluorescence induced by AlATP was between 1.5 and 3.5% depending on species, and the average value of [L]0.5, the concentration of ligand at half-saturation, over all monomeric species was 0.9 +/- 0.4 microM. The presence of saturating concentrations of AlATP diminished [L]0.5 for glucose binding by between 260- and 670-fold for hexokinase PII and SII monomers, respectively (dependent on the ionic strength), and by almost 4000-fold for PII dimer. The data demonstrate extremely strong synergistic interactions in the binding of glucose and AlATP to yeast hexokinase, arising as a consequence of conformational changes in the free enzyme induced by glucose and in enzyme-glucose complex induced by AlATP. The synergistic interactions of glucose and AlATP are related to their kinetic synergism and to the ability of AlATP to act as a powerful inhibitor of the hexokinase reaction.

Regulation of calreticulin–major histocompatibility complex (MHC) class I interactions by ATP

PubMed Central

Wijeyesakere, Sanjeeva Joseph; Gagnon, Jessica K.; Arora, Karunesh; Brooks, Charles L.; Raghavan, Malini

2015-01-01

The MHC class I peptide loading complex (PLC) facilitates the assembly of MHC class I molecules with peptides, but factors that regulate the stability and dynamics of the assembly complex are largely uncharacterized. Based on initial findings that ATP, in addition to MHC class I-specific peptide, is able to induce MHC class I dissociation from the PLC, we investigated the interaction of ATP with the chaperone calreticulin, an endoplasmic reticulum (ER) luminal, calcium-binding component of the PLC that is known to bind ATP. We combined computational and experimental measurements to identify residues within the globular domain of calreticulin, in proximity to the high-affinity calcium-binding site, that are important for high-affinity ATP binding and for ATPase activity. High-affinity calcium binding by calreticulin is required for optimal nucleotide binding, but both ATP and ADP destabilize enthalpy-driven high-affinity calcium binding to calreticulin. ATP also selectively destabilizes the interaction of calreticulin with cellular substrates, including MHC class I molecules. Calreticulin mutants that affect ATP or high-affinity calcium binding display prolonged associations with monoglucosylated forms of cellular MHC class I, delaying MHC class I dissociation from the PLC and their transit through the secretory pathway. These studies reveal central roles for ATP and calcium binding as regulators of calreticulin–substrate interactions and as key determinants of PLC dynamics. PMID:26420867

A lipid switch unlocks Parkinson’s disease-associated ATP13A2

PubMed Central

Holemans, Tine; Sørensen, Danny Mollerup; van Veen, Sarah; Martin, Shaun; Hermans, Diane; Kemmer, Gerdi Christine; Van den Haute, Chris; Baekelandt, Veerle; Günther Pomorski, Thomas; Agostinis, Patrizia; Wuytack, Frank; Palmgren, Michael; Eggermont, Jan; Vangheluwe, Peter

2015-01-01

ATP13A2 is a lysosomal P-type transport ATPase that has been implicated in Kufor–Rakeb syndrome and Parkinson’s disease (PD), providing protection against α-synuclein, Mn2+, and Zn2+ toxicity in various model systems. So far, the molecular function and regulation of ATP13A2 remains undetermined. Here, we demonstrate that ATP13A2 contains a unique N-terminal hydrophobic extension that lies on the cytosolic membrane surface of the lysosome, where it interacts with the lysosomal signaling lipids phosphatidic acid (PA) and phosphatidylinositol(3,5)bisphosphate [PI(3,5)P2]. We further demonstrate that ATP13A2 accumulates in an inactive autophosphorylated state and that PA and PI(3,5)P2 stimulate the autophosphorylation of ATP13A2. In a cellular model of PD, only catalytically active ATP13A2 offers cellular protection against rotenone-induced mitochondrial stress, which relies on the availability of PA and PI(3,5)P2. Thus, the N-terminal binding of PA and PI(3,5)P2 emerges as a key to unlock the activity of ATP13A2, which may offer a therapeutic strategy to activate ATP13A2 and thereby reduce α-synuclein toxicity or mitochondrial stress in PD or related disorders. PMID:26134396

Neuronal somatic ATP release triggers neuron–satellite glial cell communication in dorsal root ganglia

PubMed Central

Zhang, X.; Chen, Y.; Wang, C.; Huang, L.-Y. M.

2007-01-01

It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca2+ entry is required for the release. FM1–43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca2+ channels completely eliminates the neuron–glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-α (TNFα) from satellite cells. TNFα in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell–cell signaling. PMID:17525149

Regenerable non-venting thermal control subsystem for extravehicular activity

NASA Technical Reports Server (NTRS)

Roebelen, George J.; Bayes, Stephen A.; Lawson, B. Mike

1986-01-01

Routine and complex EVAs call for more effective heat rejection systems in order to maximize mission productivity; an optimum EVA mobility unit (EMU) thermal control subsystem must require no expendables and introduce no contaminants into the environment, while conforming to minimum size limits and allowing easy regeneration. Attention is presently given to two thermal control subsystems, one of which can be integrated with the existing Space Shuttle Orbiter EMU to provide a 3-hour nonventing heat rejection capability, while the other can furnish the entire heat rejection capability requirement for an 8-hour Space Station EVA.

Modeling and analysis of selected space station communications and tracking subsystems

NASA Technical Reports Server (NTRS)

Richmond, Elmer Raydean

1993-01-01

The Communications and Tracking System on board Space Station Freedom (SSF) provides space-to-ground, space-to-space, audio, and video communications, as well as tracking data reception and processing services. Each major category of service is provided by a communications subsystem which is controlled and monitored by software. Among these subsystems, the Assembly/Contingency Subsystem (ACS) and the Space-to-Ground Subsystem (SGS) provide communications with the ground via the Tracking and Data Relay Satellite (TDRS) System. The ACS is effectively SSF's command link, while the SGS is primarily intended as the data link for SSF payloads. The research activities of this project focused on the ACS and SGS antenna management algorithms identified in the Flight System Software Requirements (FSSR) documentation, including: (1) software modeling and evaluation of antenna management (positioning) algorithms; and (2) analysis and investigation of selected variables and parameters of these antenna management algorithms i.e., descriptions and definitions of ranges, scopes, and dimensions. In a related activity, to assist those responsible for monitoring the development of this flight system software, a brief summary of software metrics concepts, terms, measures, and uses was prepared.

Effects and mechanism of acid rain on plant chloroplast ATP synthase.

PubMed

Sun, Jingwen; Hu, Huiqing; Li, Yueli; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2016-09-01

Acid rain can directly or indirectly affect plant physiological functions, especially photosynthesis. The enzyme ATP synthase is the key in photosynthetic energy conversion, and thus, it affects plant photosynthesis. To clarify the mechanism by which acid rain affects photosynthesis, we studied the effects of acid rain on plant growth, photosynthesis, chloroplast ATP synthase activity and gene expression, chloroplast ultrastructure, intracellular H(+) level, and water content of rice seedlings. Acid rain at pH 4.5 remained the chloroplast structure unchanged but increased the expression of six chloroplast ATP synthase subunits, promoted chloroplast ATP synthase activity, and increased photosynthesis and plant growth. Acid rain at pH 4.0 or less decreased leaf water content, destroyed chloroplast structure, inhibited the expression of six chloroplast ATP synthase subunits, decreased chloroplast ATP synthase activity, and reduced photosynthesis and plant growth. In conclusion, acid rain affected the chloroplast ultrastructure, chloroplast ATPase transcription and activity, and P n by changing the acidity in the cells, and thus influencing the plant growth and development. Finally, the effects of simulated acid rain on the test indices were found to be dose-dependent.

ATP synthase--a marvellous rotary engine of the cell.

PubMed

Yoshida, M; Muneyuki, E; Hisabori, T

2001-09-01

ATP synthase can be thought of as a complex of two motors--the ATP-driven F1 motor and the proton-driven Fo motor--that rotate in opposite directions. The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale.

Light-driven production of ATP catalysed by F0F1-ATP synthase in an artificial photosynthetic membrane

NASA Astrophysics Data System (ADS)

Steinberg-Yfrach, Gali; Rigaud, Jean-Louis; Durantini, Edgardo N.; Moore, Ana L.; Gust, Devens; Moore, Thomas A.

1998-04-01

Energy-transducing membranes of living organisms couple spontaneous to non-spontaneous processes through the intermediacy of protonmotive force (p.m.f.) - an imbalance in electrochemical potential of protons across the membrane. In most organisms, p.m.f. is generated by redox reactions that are either photochemically driven, such as those in photosynthetic reaction centres, or intrinsically spontaneous, such as those of oxidative phosphorylation in mitochondria. Transmembrane proteins (such as the cytochromes and complexes I, III and IV in the electron-transport chain in the inner mitochondrial membrane) couple the redox reactions to proton translocation, thereby conserving a fraction of the redox chemical potential as p.m.f. Many transducer proteins couple p.m.f. to the performance of biochemical work, such as biochemical synthesis and mechanical and transport processes. Recently, an artificial photosynthetic membrane was reported in which a photocyclic process was used to transport protons across a liposomal membrane, resulting in acidification of the liposome's internal volume. If significant p.m.f. is generated in this system, then incorporating an appropriate transducer into the liposomal bilayer should make it possible to drive a non-spontaneous chemical process. Here we report the incorporation of FOF1-ATP synthase into liposomes containing the components of the proton-pumping photocycle. Irradiation of this artificial membrane with visible light results in the uncoupler- and inhibitor-sensitive synthesis of adenosine triphosphate (ATP) against an ATP chemical potential of ~12kcalmol-1, with a quantum yield of more than 7%. This system mimics the process by which photosynthetic bacteria convert light energy into ATP chemical potential.

Return Beam Vidicon (RBV) panchromatic two-camera subsystem for LANDSAT-C

NASA Technical Reports Server (NTRS)

1977-01-01

A two-inch Return Beam Vidicon (RBV) panchromatic two camera Subsystem, together with spare components was designed and fabricated for the LANDSAT-C Satellite; the basis for the design was the Landsat 1&2 RBV Camera System. The purpose of the RBV Subsystem is to acquire high resolution pictures of the Earth for a mapping application. Where possible, residual LANDSAT 1 and 2 equipment was utilized.

Development of a two-stage membrane-based wash-water reclamation subsystem

NASA Technical Reports Server (NTRS)

Mccray, S. B.

1988-01-01

A two-stage membrane-based subsystem was designed and constructed to enable the recycle of wash waters generated in space. The first stage is a fouling-resistant tube-side-feed hollow-fiber ultrafiltration module, and the second stage is a spiral-wound reverse-osmosis module. Throughout long-term tests, the subsystem consistently produced high-quality permeate, processing actual wash water to 95 percent recovery.

Origin Licensing Requires ATP Binding and Hydrolysis by the MCM Replicative Helicase

PubMed Central

Coster, Gideon; Frigola, Jordi; Beuron, Fabienne; Morris, Edward P.; Diffley, John F.X.

2014-01-01

Summary Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. Assembly of these prereplicative complexes (pre-RCs) requires the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ORC, Cdc6, and MCM are members of the AAA+ family of ATPases, and pre-RC assembly requires ATP hydrolysis. Here we show that ORC and Cdc6 mutants defective in ATP hydrolysis are competent for origin licensing. However, ATP hydrolysis by Cdc6 is required to release nonproductive licensing intermediates. We show that ATP binding stabilizes the wild-type MCM hexamer. Moreover, by analyzing MCM containing mutant subunits, we show that ATP binding and hydrolysis by MCM are required for Cdt1 release and double hexamer formation. This work alters our view of how ATP is used by licensing factors to assemble pre-RCs. PMID:25087873

Optimum dry-cooling sub-systems for a solar air conditioner

NASA Technical Reports Server (NTRS)

Chen, J. L. S.; Namkoong, D.

1978-01-01

Dry-cooling sub-systems for residential solar powered Rankine compression air conditioners were economically optimized and compared with the cost of a wet cooling tower. Results in terms of yearly incremental busbar cost due to the use of dry-cooling were presented for Philadelphia and Miami. With input data corresponding to local weather, energy rate and capital costs, condenser surface designs and performance, the computerized optimization program yields design specifications of the sub-system which has the lowest annual incremental cost.

[Stabilization of Cadmium Contaminated Soils by Ferric Ion Modified Attapulgite (Fe/ATP)--Characterizations and Stabilization Mechanism].

PubMed

Rong, Yang; Li, Rong-bo; Zhou, Yong-li; Chen, Jing; Wang, Lin-ling; Lu, Xiao-hua

2015-08-01

Ferric ion modified attapulgite (Fe/ATP) was prepared by impregnation and its structure and morphology were characterized. The toxicity characteristic leaching procedure (TCLP) was used to evaluate the effect of Cadmium( Cd) stabilization in soil with the addition of attapulgite (ATP) and Fe/ATP. The stabilization mechanism of Cd was further elucidated by comparing the morphologies and structure of ATP and Fe/ATP before and after Cd adsorption. Fe/ATP exhibited much better adsorption capacity than ATP, suggesting different adsorption mechanisms occurred between ATP and Fe/ATP. The leaching concentrations of Cd in soil decreased by 45% and 91% respectively, with the addition of wt. 20% ATP and Fe/ATP. The former was attributed to the interaction between Cd2 and --OH groups by chemical binding to form inner-sphere complexes in ATP and the attachment between Cd2+ and the defect sites in ATP framework. Whereas Cd stabilization with Fe/ATP was resulted from the fact that the active centers (--OH bonds or O- sites) on ATP could react with Fe3+ giving Fe--O--Cd-- bridges, which helped stabilize Cd in surface soil. What'more, the ferric oxides and metal hydroxides on the surface of ATP could interact with Cd, probably by the formation of cadmium ferrite. In conclusion, Fe/ATP, which can be easily prepared, holds promise as a potential low-cost and environmental friendly stabilizing agent for remediation of soil contaminated with heavy metals.

The charged particle accelerators subsystems modeling

NASA Astrophysics Data System (ADS)

Averyanov, G. P.; Kobylyatskiy, A. V.

2017-01-01

Presented web-based resource for information support the engineering, science and education in Electrophysics, containing web-based tools for simulation subsystems charged particle accelerators. Formulated the development motivation of Web-Environment for Virtual Electrophysical Laboratories. Analyzes the trends of designs the dynamic web-environments for supporting of scientific research and E-learning, within the framework of Open Education concept.

Space shuttle rudder/speedbrake subsystem analysis

NASA Technical Reports Server (NTRS)

Duke, H. G.

1975-01-01

The Continuous System Modeling Program (CSMP) is described with its uses, its limitations, and its application to the rudder/speedbrake (R/SB) subsystem. The space shuttle R/SB is analyzed using the CSMP. Areas of analysis emphasized include: step response, ramp response, and the delay time or deadspace observed in system response. Results are presented and discussed.

A miniaturized HTS microwave receiver front-end subsystem for radar and communication applications

NASA Astrophysics Data System (ADS)

Bian, Yongbo; Guo, Jin; Gao, Changzheng; Li, Chunguang; Li, Hong; Wang, Jia; Cui, Bin; He, Xiaofeng; Li, Chao; Li, Na; Li, Guoqiang; Zhang, Qiang; Zhang, Xueqiang; Meng, Jibao; He, Yusheng

2010-08-01

This paper presents a miniaturized high performance high temperature superconducting (HTS) microwave receiver front-end subsystem, which uses a mini stirling cryocooler to cool a high selective HTS filter and a low noise amplifier (LNA). The HTS filter was miniaturized by using specially designed compact resonators and fabricating with double-sided YBCO films on LAO substrate which has a relatively high permittivity. The LNA was specially designed to work at cryogenic temperature with noise figure of 0.27 dB at 71 K. The mini cryocooler, which is widely used in infrared detectors, has a smaller size (60 mm × 80 mm × 100 mm) and a lighter weight (340 g) than the stirling cryocoolers commonly used in other HTS filter subsystem. The whole front-end subsystem, including a HTS filter, a LNA, a cryocooler and the vacuum chamber, has a size of only φ120 mm × 175 mm and a weight of only 3.3 kg. The microwave devices inside the subsystem are working at 71.8 K with a consumed cooling power of 0.325 W. The center frequency of this subsystem is 925.2 MHz and the bandwidth is 2.7 MHz (which is a fractional bandwidth of 0.2%), with the gain of 19.75 dB at center frequency and the return loss better than -18.11 dB in the pass band. The stop band rejection is more than 60 dB and the skirt slope is exceeding 120 dB MHz -1. The noise figure of this subsystem is less than 0.8 dB. This front-end subsystem can be used in radars and communication systems conveniently due to it’s compact size and light weight.

ATP oscillations mediate inductive action of FGF and Shh signalling on prechondrogenic condensation.

PubMed

Kwon, Hyuck Joon

2013-01-01

Skeletal patterns are prefigured by prechondrogenic condensation. Morphogens such as fibroblast growth factor (FGF) and sonic hedgehog (Shh) specify the skeletal patterns in limb development. However, how morphogens regulate prechondrogenic condensation has remained unclear. Recently, it was demonstrated that synchronized Adenosine triphosphate (ATP) oscillations play a critical role in prechondrogenic condensation. Thus, the present study has focused on whether ATP oscillations mediate the actions of major developmental morphogens such as FGF and Shh on prechondrogenic condensation. It has been shown that both FGF and Shh signalling promoted cellular condensation but not chondrogenic differentiation and also induced ATP oscillations. In addition, blockage of FGF and Shh signalling prevented both ATP oscillations and prechondrogenic condensation. Furthermore, it was found that inhibition of ATP oscillations suppressed FGF/Shh-induced prechondrogenic condensation. These results indicate that ATP oscillations mediate the actions of FGF and Shh signalling on prechondrogenic condensation. This study proposes that morphogens organize skeletal patterns via ATP oscillations. Copyright © 2012 John Wiley & Sons, Ltd.

Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM.

PubMed

Zhou, Anna; Rohou, Alexis; Schep, Daniel G; Bason, John V; Montgomery, Martin G; Walker, John E; Grigorieff, Nikolaus; Rubinstein, John L

2015-10-06

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted FO region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the FO region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases.

Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM

PubMed Central

Zhou, Anna; Rohou, Alexis; Schep, Daniel G; Bason, John V; Montgomery, Martin G; Walker, John E; Grigorieff, Nikolaus; Rubinstein, John L

2015-01-01

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted FO region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the FO region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases. DOI: http://dx.doi.org/10.7554/eLife.10180.001 PMID:26439008

Characterization of the Saccharomyces cerevisiae ATP-Interactome using the iTRAQ-SPROX Technique

NASA Astrophysics Data System (ADS)

Geer, M. Ariel; Fitzgerald, Michael C.

2016-02-01

The stability of proteins from rates of oxidation (SPROX) technique was used in combination with an isobaric mass tagging strategy to identify adenosine triphosphate (ATP) interacting proteins in the Saccharomyces cerevisiae proteome. The SPROX methodology utilized in this work enabled 373 proteins in a yeast cell lysate to be assayed for ATP interactions (both direct and indirect) using the non-hydrolyzable ATP analog, adenylyl imidodiphosphate (AMP-PNP). A total of 28 proteins were identified with AMP-PNP-induced thermodynamic stability changes. These protein hits included 14 proteins that were previously annotated as ATP-binding proteins in the Saccharomyces Genome Database (SGD). The 14 non-annotated ATP-binding proteins included nine proteins that were previously found to be ATP-sensitive in an earlier SPROX study using a stable isotope labeling with amino acids in cell culture (SILAC)-based approach. A bioinformatics analysis of the protein hits identified here and in the earlier SILAC-SPROX experiments revealed that many of the previously annotated ATP-binding protein hits were kinases, ligases, and chaperones. In contrast, many of the newly discovered ATP-sensitive proteins were not from these protein classes, but rather were hydrolases, oxidoreductases, and nucleic acid-binding proteins.

Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements

PubMed Central

Mookerjee, Shona A.; Gerencser, Akos A.; Nicholls, David G.; Brand, Martin D.

2017-01-01

Partitioning of ATP generation between glycolysis and oxidative phosphorylation is central to cellular bioenergetics but cumbersome to measure. We describe here how rates of ATP generation by each pathway can be calculated from simultaneous measurements of extracellular acidification and oxygen consumption. We update theoretical maximum ATP yields by mitochondria and cells catabolizing different substrates. Mitochondrial P/O ratios (mol of ATP generated per mol of [O] consumed) are 2.73 for oxidation of pyruvate plus malate and 1.64 for oxidation of succinate. Complete oxidation of glucose by cells yields up to 33.45 ATP/glucose with a maximum P/O of 2.79. We introduce novel indices to quantify bioenergetic phenotypes. The glycolytic index reports the proportion of ATP production from glycolysis and identifies cells as primarily glycolytic (glycolytic index > 50%) or primarily oxidative. The Warburg effect is a chronic increase in glycolytic index, quantified by the Warburg index. Additional indices quantify the acute flexibility of ATP supply. The Crabtree index and Pasteur index quantify the responses of oxidative and glycolytic ATP production to alterations in glycolysis and oxidative reactions, respectively; the supply flexibility index quantifies overall flexibility of ATP supply; and the bioenergetic capacity quantifies the maximum rate of total ATP production. We illustrate the determination of these indices using C2C12 myoblasts. Measurement of ATP use revealed no significant preference for glycolytic or oxidative ATP by specific ATP consumers. Overall, we demonstrate how extracellular fluxes quantitatively reflect intracellular ATP turnover and cellular bioenergetics. We provide a simple spreadsheet to calculate glycolytic and oxidative ATP production rates from raw extracellular acidification and respiration data. PMID:28270511

Multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release.

PubMed

Forsyth, Alison M; Wan, Jiandi; Owrutsky, Philip D; Abkarian, Manouk; Stone, Howard A

2011-07-05

RBCs are known to release ATP, which acts as a signaling molecule to cause dilation of blood vessels. A reduction in the release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. Furthermore, reduced deformation of RBCs has been correlated with myocardial infarction and coronary heart disease. Because ATP release has been linked to cell deformation, we undertook a multiscale approach to understand the links between single RBC dynamics, ATP release, and macroscopic viscosity all at physiological shear rates. Our experimental approach included microfluidics, ATP measurements using a bioluminescent reaction, and rheology. Using microfluidics technology with high-speed imaging, we visualize the deformation and dynamics of single cells, which are known to undergo motions such as tumbling, swinging, tanktreading, and deformation. We report that shear thinning is not due to cellular deformation as previously believed, but rather it is due to the tumbling-to-tanktreading transition. In addition, our results indicate that ATP release is constant at shear stresses below a threshold (3 Pa), whereas above the threshold ATP release is increased and accompanied by large cellular deformations. Finally, performing experiments with well-known inhibitors, we show that the Pannexin 1 hemichannel is the main avenue for ATP release both above and below the threshold, whereas, the cystic fibrosis transmembrane conductance regulator only contributes to deformation-dependent ATP release above the stress threshold.

Role of connexin 32 hemichannels in the release of ATP from peripheral nerves.

PubMed

Nualart-Marti, Anna; del Molino, Ezequiel Mas; Grandes, Xènia; Bahima, Laia; Martin-Satué, Mireia; Puchal, Rafel; Fasciani, Ilaria; González-Nieto, Daniel; Ziganshin, Bulat; Llobet, Artur; Barrio, Luis C; Solsona, Carles

2013-12-01

Extracellular purines elicit strong signals in the nervous system. Adenosine-5'-triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous cells secrete ATP by exocytosis or through plasma membrane proteins such as connexin hemichannels. Using a combination of imaging, luminescence and electrophysiological techniques, we explored the possibility that Connexin 32 (Cx32), expressed in Schwann cells (SCs) myelinating the peripheral nervous system could be an important source of ATP in peripheral nerves. We triggered the release of ATP in vivo from mice sciatic nerves by electrical stimulation and from cultured SCs by high extracellular potassium concentration-evoked depolarization. No ATP was detected in the extracellular media after treatment of the sciatic nerve with Octanol or Carbenoxolone, and ATP release was significantly inhibited after silencing Cx32 from SCs cultures. We investigated the permeability of Cx32 to ATP by expressing Cx32 hemichannels in Xenopus laevis oocytes. We found that ATP release is coupled to the inward tail current generated after the activation of Cx32 hemichannels by depolarization pulses, and it is sensitive to low extracellular calcium concentrations. Moreover, we found altered ATP release in mutated Cx32 hemichannels related to the X-linked form of Charcot-Marie-Tooth disease, suggesting that purinergic-mediated signaling in peripheral nerves could underlie the physiopathology of this neuropathy. Copyright © 2013 Wiley Periodicals, Inc.

Evaluation of an Atmosphere Revitalization Subsystem for Deep Space Exploration Missions

NASA Technical Reports Server (NTRS)

Perry, Jay L.; Abney, Morgan B.; Conrad, Ruth E.; Frederick, Kenneth R.; Greenwood, Zachary W.; Kayatin, Matthew J.; Knox, James C.; Newton, Robert L.; Parrish, Keith J.; Takada, Kevin C.;