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Sample records for kinase converts transient

  1. Torque converter transient characteristics prediction using computational fluid dynamics

    International Nuclear Information System (INIS)

    Yamaguchi, T; Tanaka, K

    2012-01-01

    The objective of this research is to investigate the transient torque converter performance used in an automobile. A new technique in computational fluid dynamics is introduced, which includes the inertia of the turbine in a three dimensional simulation of the torque converter during a launch condition. The simulation results are compared to experimental test data with good agreement across the range of data. In addition, the simulated flow structure inside the torque converter is visualized and compared to results from a steady-state calculation.

  2. Transient Angle Stability Analysis of Grid-Connected Converters with the First-order Active Power Loop

    DEFF Research Database (Denmark)

    Wu, Heng; Wang, Xiongfei

    2018-01-01

    . To tackle this challenge, this paper employs the phase portrait to analyze the transient stability of power converters, and it is found that the better transient stability performance can be achieved if the grid-connected converters are controlled as the first-order nonlinear system. Simulations...

  3. Neural control and transient analysis of the LCL-type resonant converter

    Science.gov (United States)

    Zouggar, S.; Nait Charif, H.; Azizi, M.

    2000-07-01

    This paper proposes a generalised inverse learning structure to control the LCL converter. A feedforward neural network is trained to act as an inverse model of the LCL converter then both are cascaded such that the composed system results in an identity mapping between desired response and the LCL output voltage. Using the large signal model, we analyse the transient output response of the controlled LCL converter in the case of large variation of the load. The simulation results show the efficiency of using neural networks to regulate the LCL converter.

  4. Static converters power supply: transient regimes; Alimentation par convertisseurs statiques: regimes transitoires

    Energy Technology Data Exchange (ETDEWEB)

    Pasqualini, G. [Ecole Superieure d`Electricite (France)

    1997-08-01

    Direct current motors, asynchronous and variable speed synchronous motors are generally supplied with static converters. Speed variation is obtained by voltage variation in DC motors and by frequency variation in AC motors. In these conditions, these motors are running continuously in transient regimes: the DC motors current is not direct and the AC motors current is not sinusoidal. This situation leads to pulsing couples in the shaft line and to an increase of Joule effect losses. The aim of this paper is to present the methods of study of the electric motors functioning using the shape of the power voltages given by converters and mathematical models of these machines. The synchronous machines are rapidly described while the asynchronous machines are studied using Ku`s transformation instead of Park`s transformation for simplification. For each type of machine, calculation methods allow to determine their current, additional losses and couple characteristics. The transient regimes considered are those remaining when the motor is running at a constant speed and defined regime (supply voltages are periodical functions of time). These transient regimes are identically reproducing with a frequency which is a multiple of the converters supply frequency. Transient regimes due to functioning changes of the motor, such as resisting couple or power supply frequency variations, are not considered in this study. (J.S.) 9 refs.

  5. 8-bit serial-parallel analog-to-digital converter for fast transient recorder

    International Nuclear Information System (INIS)

    Kulka, Z.; Nadachowski, M.; Zimek, Z.

    1990-08-01

    An 8-bit serial-parallel analog-to-digital converter with a sampling frequency 5 MHz is described. The most important circuits of the device are described and parameters are given. The converter is a central part of a transient recorder type TR-1 designed for recording pulse waveforms in measurements of the kinetics of chemical reactions which are radiation-induced using an electron linear accelerator. 9 refs., 9 figs. (author)

  6. Digitally Controlled Point of Load Converter with Very Fast Transient Response

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Andersen, Michael Andreas E.

    2007-01-01

    voltage mode control and very fast transient response. The DiSOM modulator is combined with a digital PID compensator algorithm is implemented in a hybrid CPLD/FPGA and is used to control a synchronous Buck converter, which is used in typical Point of Load applications. The computational time is only......This paper presents a new Digital Self-Oscillating Modulator (DiSOM) that allows the duty cycle to be changed instantly. The DiSOM modulator is shown to have variable switching that is a function of the duty cycle. Compared to a more traditional digital PWM modulator based on a counter...... and comparator the DiSOM modulator allows the sampling frequency of the output voltage control loop to be higher than the switching frequency of the power converter, typically a DC/DC converter. The features of the DiSOM modulator makes it possible to design a digitally controlled DC/DC converter with linear...

  7. Design and development of microcontroller based programmable ramp generator for AC-DC converter for simulating decay power transient in experimental facility for nuclear power plants

    International Nuclear Information System (INIS)

    Srivastava, Gaurava Deep; Kulkarni, R.D.

    2015-01-01

    In nuclear power plants, fuel is subjected to a wide range of power and temperature transients during normal and abnormal conditions. The reactor setback and step-back power pattern, fast temperature profile occurred during Loss of Coolant Accident and decay power followed by shutdown of power plant are the typical transients in nuclear power plant. For a variety of reactor engineering and reactor safety related study, one needs to simulate these transients in experimental facility. In experimental facilities, high response AC-DC converters are used to handle these power and temperature transients safely in a controlled manner for generating a database which is utilized for design of thermal hydraulic system, development of computer codes, study of reliability of reactor safety system, etc. for nuclear power plants. The paper presents the methodology developed for simulating the typical reactor decay power transient in an experimental facility. The design and simulation of AC-DC power electronic converter of 3 MW capacity is also presented. The microcontroller based programmable ramp generator is designed and hardware implemented for feeding reference voltage to the closed loop control system of AC-DC converter for obtaining the decay power profile at the converter output. The typical decay power transient of the nuclear power plant is divided into several small power ramps for simulating the transient. The signal corresponding to each power ramp is generated by programmable ramp generator and fed to the comparator for generating control signal for the converter. The actual decay power transient obtained from the converter is compared with the theoretical decay power transient. (author)

  8. Transient simulation of a catalytic converter for a dual fuel engine

    Energy Technology Data Exchange (ETDEWEB)

    Liu, B.; Checkel, D. [Alberta Univ., Dept. of Mechanical Enginering, Edmonton, AB (Canada); Hayes, R. E. [Alberta Univ., Department of Chemical and Material Engineering, Edmonton, AB (Canada); Zheng, M.; Mirosh, E. [Alternative Fuel Systems Inc., Calgary, AB (Canada)

    2000-06-01

    A catalytic converter of a ceramic monolith honeycomb substrate, coated with a washcoat of catalyst and attached to a natural gas/diesel dual fuel engine was simulated and studied experimentally. The paper describes the application of one-dimensional finite element model for the transient and steady state operation. Laminar flow was approximated using a dispersed plug flow model, and chemical kinetics were simulated using LHHW (Langmuir/ Hinshelwood/ Hougan/ Watson) type expressions. Simulation results were compared with experimental results for heating and cooling cycles which resulted from speed and load changes on the engine. The comparison showed a maximum difference between the two sets of emission levels of about 10 per cent, showing that the one-dimensional model is acceptable model for this dual fuel engine converter combination. 50 refs., 3 tabs., 13 figs.

  9. Mathematical Model and Computational Analysis of Selected Transient States of Cylindrical Linear Induction Motor Fed via Frequency Converter

    Directory of Open Access Journals (Sweden)

    Andrzej Rusek

    2008-01-01

    Full Text Available The mathematical model of cylindrical linear induction motor (C-LIM fed via frequency converter is presented in the paper. The model was developed in order to analyze numerically the transient states. Problems concerning dynamics of ac-machines especially linear induction motor are presented in [1 – 7]. Development of C-LIM mathematical model is based on circuit method and analogy to rotary induction motor. The analogy between both: (a stator and rotor windings of rotary induction motor and (b winding of primary part of C-LIM (inductor and closed current circuits in external secondary part of C-LIM (race is taken into consideration. The equations of C-LIM mathematical model are presented as matrix together with equations expressing each vector separately. A computational analysis of selected transient states of C-LIM fed via frequency converter is presented in the paper. Two typical examples of C-LIM operation are considered for the analysis: (a starting the motor at various static loads and various synchronous velocities and (b reverse of the motor at the same operation conditions. Results of simulation are presented as transient responses including transient electromagnetic force, transient linear velocity and transient phase current.

  10. Examples of digital simulation of AC-DC power converter with the Electromagnetic Transients Program

    International Nuclear Information System (INIS)

    Tanahashi, Shugo; Yamada, Shuichi; Mugishima, Mituo; Kitagawa, Shiro.

    1989-03-01

    This article gives a practical guidance for analysis of power converter circuits using the Electromagnetic Transients Program (EMTP). First how to use the program is shown with two simple examples; (1) a power supply with three-phase diode bridge and (2) a feedback system for current control. Then its application to more complicated system is shown with an example of a power supply for Compact Helical System (CHS), where a hybrid power supply with multi-phase diode and thyristor bridges, and two three-phase thyristor converters are driven by an AC generator. (author)

  11. Wind farm node connected DFIG/back-to-back converter coupling transient model for grid integration studies

    International Nuclear Information System (INIS)

    Ostolaza, J.X.; Etxeberria, A.; Zubia, I.

    2015-01-01

    Highlights: • Full-order DFIG/B2B coupling transient model to the connection of wind farm node. • Algebraic loop between stator and filter currents due to transformer is overcome. • A novel decoupling based control design of grid-side converter is presented. • 24 state-variables describe the DFIG: 15 electro-mechanical, plus 9 for control. • State machine implements the sequential control among its operational modes. - Abstract: This paper presents the explicit electromagnetic transient model of a Doubly Fed Induction Generator (DFIG), that includes its coupling with the back-to-back converter, when the generator/converter set is connected to the wind farm’s Thevenin equivalent, as seen from DFIG’s terminals. Besides that, DFIG’s grid side converter control system is defined in detail, so that expressions for the direct tuning of all compensators are provided. The overall electromechanical wind generator model includes 24 state variables: four mechanical, eleven electrical, and nine more – one for each controller – associated to the control system. The developed model is complemented with a state machine that implements the sequential control among the different stages that define its operational modes. Simulation and experimental results show that the developed model is able to predict the behaviour of the generator in short and long term scenarios.

  12. Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception

    OpenAIRE

    Hall, Bradford E.; Prochazkova, Michaela; Sapio, Matthew R.; Minetos, Paul; Kurochkina, Natalya; Binukumar, B. K.; Amin, Niranjana D.; Terse, Anita; Joseph, John; Raithel, Stephen J.; Mannes, Andrew J.; Pant, Harish C.; Chung, Man-Kyo; Iadarola, Michael J.; Kulkarni, Ashok B.

    2018-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and th...

  13. Transient Performance Improvement Circuit (TPIC)s for DC-DC converter applications

    Science.gov (United States)

    Lim, Sungkeun

    of the slow inductor current slew rate which is determined by the input voltage, output voltage, and the inductance. The remaining inductor current in the power delivery path will charge the output capacitors and develop a voltage across the ESR. As a result, large output voltage spikes occur during load current transients. Due to their limited control bandwidth, traditional VRs can not sufficiently respond rapidly to certain load transients. As a result, a large output voltage spike can occur during load transients, hence requiring a large amount of bulk capacitance to decouple the VR from the load [2]. If the remaining inductor current is removed from the power stage or the inductor current slew rate is changed, the output voltage spikes can be clamped, allowing the output capacitance to be reduced. A new design methodology for a Transient Performance Improvement Circuit(TPIC) based on controlling the output impedance of a regulator is presented. The TPIC works in parallel with a voltage regulator (VR)'s ceramic capacitors to achieve faster voltage regulation without the need for a large bulk capacitance, and can serve as a replacement for bulk capacitors. The specific function of the TPIC is to mimic the behavior of the bulk capacitance in a traditional VRM by sinking and sourcing large currents during transients, allowing the VR to respond quickly to current transients without the need for a large bulk capacitance. This will allow fast transient response without the need for a large bulk capacitor. The main challenge in applying the TPIC is creating a design which will not interfere with VR operation. A TPIC for a 4 Switch Buck-Boost (4SBB) converter is presented which functions by con- trolling the inductor current slew rate during load current transients. By increasing the inductor current slew rate, the remaining inductor current can be removed from the 4SBB power delivery path and the output voltage spike can be clamped. A second TPIC is presented which is

  14. Utilization of the voltage frequency converter or digital representation and documentation of transient reactor operation

    International Nuclear Information System (INIS)

    Doane, Harry J.

    1986-01-01

    The ease and speed of handling transient data is enhanced by the use of a voltage to frequency converter (VFC). This analogue to digital semiconductor device provides an inexpensive and portable alternative to electro-mechanical recorders and hand entry of data into computer codes. The VFC used at The University of Arizona is a Teledyne Philbrick 4705/01. A zero to positive ten volt input signal provides a zero to one megahertz output signal which is TTL/DTL compatible. VFC is used at the University of Arizona to collect data for super prompt critical TRIGA excursions. The VFC provides a low cost, convenient method of transient data storage and retrieval for experimentation and laboratory demonstration

  15. Grid Synchronization of Wind Turbine Converters under Transient Grid Faults using a Double Synchronous Reference Frame PLL

    DEFF Research Database (Denmark)

    Teodorescu, Remus; Blaabjerg, Frede; Rodriguez, P.

    2008-01-01

    This work employs the Double Synchronous Reference Frame PLL (DSRF-PLL) as an effective method for grid synchronization of WT's power converters in the presence of transient faults in the grid. The DSRF-PLL exploits a dual synchronous reference frame voltage characterization, adding a decoupling...... network to a standard SRF-PLL in order to effectively separate the positive- and negative-sequence voltage components in a fast and accurate way. Experimental evaluation of the proposed grid synchronization method and simulations regarding its application to ride through transient faults verify...

  16. A high speed digital-to-analogue converter

    International Nuclear Information System (INIS)

    Hallgren, B.I.

    1974-02-01

    An 8-bit Digital-to-Analogue converter of the current-weighting type has been constructed using 8 monolithic integrated circuit transistor arrays -one for each bit. The D/A-converter has a voltage output within the range 0 to -2V. The settling time to within half of the least significant bit is about 50 nsec. The temperature dependence and transient response of the converter has been analysed using computer aided design techniques. A comparison is made between the experimental and simulated transient performance. (Auth.)

  17. A Decentralized Current-Sharing Controller Endows Fast Transient Response to Parallel DC-DC Converters

    DEFF Research Database (Denmark)

    Wang, Haojie; Han, Minxiao; Han, Renke

    2018-01-01

    This paper proposes a decentralized current-sharing control strategy to endow fast transient response to paralleled DC-DC converters systems, such as DC microgrids or distributed power systems. The proposed controller consist of two main control loops: an external voltage droop control for current......-sharing proposes and an internal current loop. The external droop control loop is designed as a voltage loop with embedded virtual impedance, which avoids the use of a slow voltage loop and a separate extra virtual impedance loop that may limit the system bandwidth. The internal current loop, thanks...... and the proposed embedded-virtual-impedance based I-V droop. In order to compare the dynamic response performances between two droop controllers, their state-space models have been developed and analyzed in this paper. The results show that the dynamic response of the I-V droop control is faster than...

  18. A large-signal dynamic simulation for the series resonant converter

    Science.gov (United States)

    King, R. J.; Stuart, T. A.

    1983-01-01

    A simple nonlinear discrete-time dynamic model for the series resonant dc-dc converter is derived using approximations appropriate to most power converters. This model is useful for the dynamic simulation of a series resonant converter using only a desktop calculator. The model is compared with a laboratory converter for a large transient event.

  19. The influence of internal current loop on transient response performance of I-V droop controlled paralleled DC-DC converters

    DEFF Research Database (Denmark)

    Wang, Haojie; Han, Minxiao; Guerrero, Josep M.

    2017-01-01

    The external droop control loop of I-V droop control is designed as a voltage loop with embedded virtual impedance, so the internal current loop plays a major role in the system bandwidth. Thus, in this paper, the influence of internal current loop on transient response performance of I-V droop...... controlled paralleled dc-dc converters is analyzed, which is guided and significant for its industry application. The model which is used for dynamic analysis is built, and the root locus method is used based on the model to analyze the dynamic response of the system by shifting different control parameters...

  20. Transient neonatal myasthenia gravis due to a mother with ocular onset of anti-muscle specific kinase myasthenia gravis.

    Science.gov (United States)

    Lee, Ju-Yeun; Min, Ju-Hong; Han, Sueng-Han; Han, Jinu

    2017-07-01

    We describe a 27-year-old pregnant female with new onset of conjugate gaze deficit during the third trimester of pregnancy. Repetitive nerve stimulation tests, neostigmine tests, and acetylcholine receptor antibody assays were all negative. The patient delivered a normal healthy baby at a local clinic via cesarean section. The baby became hypotonic and had respiratory failure several minutes after birth. The result of acetylcholine receptor antibody was negative in the neonate. The neonate became healthy spontaneously and was extubated after 21 days of ventilation care. Two months after delivery, the mother developed ptosis and generalized symptoms and subsequent workup revealed she was muscle specific kinase (MuSK) antibody positive. The neonate was presumed to have an anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is necessary in pregnant women who are presumed ocular myasthenia gravis to warn occurrence of transient neonatal myasthenia gravis. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

    Science.gov (United States)

    Wong, Adrian; Black, Sandra E; Yiu, Stanley Y P; Au, Lisa W C; Lau, Alexander Y L; Soo, Yannie O Y; Chan, Anne Y Y; Leung, Thomas W H; Wong, Lawrence K S; Kwok, Timothy C Y; Cheung, Theodore C K; Leung, Kam-Tat; Lam, Bonnie Y K; Kwan, Joseph S K; Mok, Vincent C T

    2018-05-01

    The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy. Copyright © 2018 John Wiley & Sons, Ltd.

  2. Calcitonin causes a sustained inhibition of protein kinase C-stimulated bone resorption in contrast to the transient inhibition of parathyroid hormone-induced bone resorption

    International Nuclear Information System (INIS)

    Ransjoe, M.; Lerner, U.H.

    1990-01-01

    Calcitonin is a well known inhibitor of osteoclastic bone resortion, both in vivo and in vitro. However, it is also known that calcitonin has only a transient inhibitory effect on bone resorption. The mechanism for this so-called ''escape from inhibition'' phenomenon is not clear. In the present study, the inhibitory effect of calcitonin on phorbol ester-induced bone resorption was examined in cultured neonatal mouse calvaria. Bone resorption was assessed as the release of radioactivity from bones prelabelled in vivo with 45 Ca. Two proteon kinase C-activating phorbol esters, phorbol-12-myristate-13-acetate and phorbol-12,13-dibutyrate, both stimulated 45 Ca release in 120-h cultures at a concentration of 10 nmul/l. Calcitonin (30 nmol/l) inhibited phorbol esterstimulated bone resorption without any ''escape from inhibition''. This was in contrast to the transient inhibitory effect of calcitonin on bone resorption stimulated by parathyroid hormone (10 nmol/l), prostaglandin E 2 (2 μmol/l), and bradykinin (1 μmol/l). Our results suggest that activation of protein kinase C produces a sustained inhibitory effect of calcitonin on bone resorption. (author)

  3. Creatine kinase isozyme expression in embryonic chicken heart

    NARCIS (Netherlands)

    Lamers, W. H.; Geerts, W. J.; Moorman, A. F.; Dottin, R. P.

    1989-01-01

    The distribution pattern of creatine kinase (EC 2.7.3.2) isozymes in developing chicken heart was studied by immunohistochemistry. Creatine kinase M, which is absent from adult heart, is transiently expressed between 4 and 11 days of incubation. During that period, numerous muscular cells in the

  4. Protein tyrosine kinase and mitogen-activated protein kinase signalling pathways contribute to differences in heterophil-mediated innate immune responsiveness between two lines of broilers

    Science.gov (United States)

    Protein tyrosine phosphorylation mediates signal transduction of cellular processes, with protein tyrosine kinases (PTKs) regulating virtually all signaling events. The mitogen-activated protein kinase (MAPK) super-family consists of three conserved pathways that convert receptor activation into ce...

  5. Frequency Transient Suppression in Hybrid Electric Ship Power Systems: A Model Predictive Control Strategy for Converter Control with Energy Storage

    Directory of Open Access Journals (Sweden)

    Viknash Shagar

    2018-03-01

    Full Text Available This paper aims to understand how the common phenomenon of fluctuations in propulsion and service load demand contribute to frequency transients in hybrid electric ship power systems. These fluctuations arise mainly due to changes in sea conditions resulting in significant variations in the propulsion load demand of ships. This leads to poor power quality for the power system that can potentially cause hazardous conditions such as blackout on board the ship. Effects of these fluctuations are analysed using a hybrid electric ship power system model and a proposed Model Predictive Control (MPC strategy to prevent propagation of transients from the propellers into the shipboard power system. A battery energy storage system, which is directly connected to the DC-link of the frequency converter, is used as the smoothing element. Case studies that involve propulsion and service load changes have been carried out to investigate the efficacy of the proposed solution. Simulation results show that the proposed solution with energy storage and MPC is able to contain frequency transients in the shipboard power system within the permissible levels stipulated by the relevant power quality standards. These findings will help ship builders and operators to consider using battery energy storage systems controlled by advanced control techniques such as MPC to improve the power quality on board ships.

  6. Advanced hybrid transient stability and EMT simulation for VSC-HVDC systems

    NARCIS (Netherlands)

    Van Der Meer, A.A.; Gibescu, M.; Van Der Meijden, M.A.M.M.; Kling, W.L.; Ferreira, J.A.

    2015-01-01

    This paper deals with advanced hybrid transient stability and electromagnetic-transient (EMT) simulation of combined ac/dc power systems containing large amounts of renewable energy sources interfaced through voltage-source converter-high-voltage direct current (VSC-HVDC). The concerning transient

  7. Multilevel Modular Converter for VSC-HVDC Transmission Applications: Control and Operational Aspects

    DEFF Research Database (Denmark)

    Gnanarathna, Udana N.; Gole, Aniruddha M.; Chaudhary, Sanjay Kumar

    2010-01-01

    Control methods for a new class of converter, the multilevel modular converter (MMC), recently introduced for HVDC transmission are discussed. The paper discusses converter-level controls including firing pulse generation and capacitor voltage balancing. It also covers higher level controls...... for incorporating the converter into a larger power network, with a weak ac receiving end. The performance behavior is studied using electromagnetic transients simulation....

  8. Switching transients in high-frequency high-power converters using power MOSFET's

    Science.gov (United States)

    Sloane, T. H.; Owen, H. A., Jr.; Wilson, T. G.

    1979-01-01

    The use of MOSFETs in a high-frequency high-power dc-to-dc converter is investigated. Consideration is given to the phenomena associated with the paralleling of MOSFETs and to the effect of stray circuit inductances on the converter circuit performance. Analytical relationships between various time constants during the turning-on and turning-off intervals are derived which provide estimates of plateau and peak levels during these intervals.

  9. Experimental study of a reverse flow catalytic converter for a duel fuel engine

    Energy Technology Data Exchange (ETDEWEB)

    Liu, B.; Checkel, M. D. [Alberta Univ., Dept. of Mechanical Engineering, Edmonton, ANB (Canada); Hayes, R. E. [Alberta Univ., Dept, of Chemical and Materials Engineering, Edmonton, AB, (Canada)

    2001-08-01

    Performance of a reverse flow catalytic converter for a methane/diesel dual fuel engine is evaluated under steady and transient engine conditions. The converter is of the monolith honeycomb type with palladium catalyst washcoat. Results of the reverse flow converter's performance was found to be superior for several steady state engine operations when compared to unidirectional flow operation. In transient operations following a step change in engine operating conditions, reverse flow was found to be better than unidirectional flow when the change in engine operation was such as to reduce the exhaust gas temperature. When exhaust gas temperature was increased, reverse flow decreased the rate of increase in the reactor temperature. Testing was done using the transient Japanese 6-Mode tests. Best results were achieved with a switch time in the five seconds to fifteen seconds range. 31 refs., 9 tabs., 24 figs.

  10. A fast reactor transient analysis methodology for personal computers

    International Nuclear Information System (INIS)

    Ott, K.O.

    1993-01-01

    A simplified model for a liquid-metal-cooled reactor (LMR) transient analysis, in which point kinetics as well as lumped descriptions of the heat transfer equations in all components are applied, is converted from a differential into an integral formulation. All 30 differential balance equations are implicitly solved in terms of convolution integrals. The prompt jump approximation is applied as the strong negative feedback effectively keeps the net reactivity well below prompt critical. After implicit finite differencing of the convolution integrals, the kinetics equation assumes a new form, i.e., the quadratic dynamics equation. In this integral formulation, the initial value problem of typical LMR transients can be solved with large item steps (initially 1 s, later up to 256 s). This then makes transient problems amenable to a treatment on personal computer. The resulting mathematical model forms the basis for the GW-BASIC program LMR transient calculation (LTC) program. The LTC program has also been converted to QuickBASIC. The running time for a 10-h transient overpower transient is then ∼40 to 10 s, depending on the hardware version (286, 386, or 486 with math coprocessors)

  11. Cinematography of weakly - luminous transient phenomena using image converters

    International Nuclear Information System (INIS)

    Stevenin, P.; Jacquot, C.

    1966-01-01

    After a review on the physical of optical informations emitted by a light source of weak intensity and short duration, the authors describe a high gain device by associating two image converters. The present specifications are given in the domain of high speed cinematography and spectrometry. (authors) [fr

  12. Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation

    Energy Technology Data Exchange (ETDEWEB)

    Muchir, Antoine, E-mail: a.muchir@institut-myologie.org [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Wu, Wei [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Sera, Fusako; Homma, Shunichi [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Worman, Howard J., E-mail: hjw14@columbia.edu [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States)

    2014-10-03

    Highlights: • Both ACE and MEK1/2 inhibition are beneficial on cardiac function in Lmna cardiomyopathy. • MEK1/2 inhibitor has beneficial effects beyond ACE inhibition for Lmna cardiomyopathy. • These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor. - Abstract: Background: Mutations in the LMNA gene encoding A-type nuclear lamins can cause dilated cardiomyopathy with or without skeletal muscular dystrophy. Previous studies have shown abnormally increased extracellular signal-regulated kinase 1/2 activity in hearts of Lmna{sup H222P/H222P} mice, a small animal model. Inhibition of this abnormal signaling activity with a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor has beneficial effects on heart function and survival in these mice. However, such treatment has not been examined relative to any standard of care intervention for dilated cardiomyopathy or heart failure. We therefore examined the effects of an angiotensin II converting enzyme (ACE) inhibitor on left ventricular function in Lmna{sup H222P/H222P} mice and assessed if adding a MEK1/2 inhibitor would provide added benefit. Methods: Male Lmna{sup H222P/H222P} mice were treated with the ACE inhibitor benazepril, the MEK1/2 inhibitor selumetinib or both. Transthoracic echocardiography was used to measure left ventricular diameters and fractional shortening was calculated. Results: Treatment of Lmna{sup H222P/H222P} mice with either benazepril or selumetinib started at 8 weeks of age, before the onset of detectable left ventricular dysfunction, lead to statistically significantly increased fractional shortening compared to placebo at 16 weeks of age. There was a trend towards a great value for fractional shortening in the selumetinib-treated mice. When treatment was started at 16 weeks of age, after the onset of left ventricular dysfunction, the addition of selumetinib treatment to benazepril lead to a statistically significant increase in left

  13. Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation

    International Nuclear Information System (INIS)

    Muchir, Antoine; Wu, Wei; Sera, Fusako; Homma, Shunichi; Worman, Howard J.

    2014-01-01

    Highlights: • Both ACE and MEK1/2 inhibition are beneficial on cardiac function in Lmna cardiomyopathy. • MEK1/2 inhibitor has beneficial effects beyond ACE inhibition for Lmna cardiomyopathy. • These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor. - Abstract: Background: Mutations in the LMNA gene encoding A-type nuclear lamins can cause dilated cardiomyopathy with or without skeletal muscular dystrophy. Previous studies have shown abnormally increased extracellular signal-regulated kinase 1/2 activity in hearts of Lmna H222P/H222P mice, a small animal model. Inhibition of this abnormal signaling activity with a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor has beneficial effects on heart function and survival in these mice. However, such treatment has not been examined relative to any standard of care intervention for dilated cardiomyopathy or heart failure. We therefore examined the effects of an angiotensin II converting enzyme (ACE) inhibitor on left ventricular function in Lmna H222P/H222P mice and assessed if adding a MEK1/2 inhibitor would provide added benefit. Methods: Male Lmna H222P/H222P mice were treated with the ACE inhibitor benazepril, the MEK1/2 inhibitor selumetinib or both. Transthoracic echocardiography was used to measure left ventricular diameters and fractional shortening was calculated. Results: Treatment of Lmna H222P/H222P mice with either benazepril or selumetinib started at 8 weeks of age, before the onset of detectable left ventricular dysfunction, lead to statistically significantly increased fractional shortening compared to placebo at 16 weeks of age. There was a trend towards a great value for fractional shortening in the selumetinib-treated mice. When treatment was started at 16 weeks of age, after the onset of left ventricular dysfunction, the addition of selumetinib treatment to benazepril lead to a statistically significant increase in left ventricular fractional

  14. Capacitor performance limitations in high power converter applications

    DEFF Research Database (Denmark)

    El-Khatib, Walid Ziad; Holbøll, Joachim; Rasmussen, Tonny Wederberg

    2013-01-01

    High voltage low inductance capacitors are used in converters as HVDC-links, snubber circuits and sub model (MMC) capacitances. They facilitate the possibility of large peak currents under high frequent or transient voltage applications. On the other hand, using capacitors with larger equivalent...... series inductances include the risk of transient overvoltages, with a negative effect on life time and reliability of the capacitors. These allowable limits of such current and voltage peaks are decided by the ability of the converter components, including the capacitors, to withstand them over...... the expected life time. In this paper results are described from investigations on the electrical environment of these capacitors, including all the conditions they would be exposed to, thereby trying to find the tradeoffs needed to find a suitable capacitor. Different types of capacitors with the same voltage...

  15. Dominant negative selection of vaccinia virus using a thymidine kinase/thymidylate kinase fusion gene and the prodrug azidothymidine

    International Nuclear Information System (INIS)

    Holzer, Georg W.; Mayrhofer, Josef; Gritschenberger, Werner; Falkner, Falko G.

    2005-01-01

    The Escherichia coli thymidine kinase/thymidylate kinase (tk/tmk) fusion gene encodes an enzyme that efficiently converts the prodrug 3'-azido-2',3'-dideoxythymidine (AZT) into its toxic triphosphate derivative, a substance which stops DNA chain elongation. Integration of this marker gene into vaccinia virus that normally is not inhibited by AZT allowed the establishment of a powerful selection procedure for recombinant viruses. In contrast to the conventional vaccinia thymidine kinase (tk) selection that is performed in tk-negative cell lines, AZT selection can be performed in normal (tk-positive) cell lines. The technique is especially useful for the generation of replication-deficient vaccinia viruses and may also be used for gene knock-out studies of essential vaccinia genes

  16. Implementation of optimal trajectory control of series resonant converter

    Science.gov (United States)

    Oruganti, Ramesh; Yang, James J.; Lee, Fred C.

    1987-01-01

    Due to the presence of a high-frequency LC tank circuit, the dynamics of a resonant converter are unpredictable. There is often a large surge of tank energy during transients. Using state-plane analysis technique, an optimal trajectory control utilizing the desired solution trajectory as the control law was previously proposed for the series resonant converters. The method predicts the fastest response possible with minimum energy surge in the resonant tank. The principle of the control and its experimental implementation are described here. The dynamics of the converter are shown to be close to time-optimal.

  17. Effects of angiotensin-converting enzyme inhibition on transient ischemia: the Quinapril Anti-Ischemia and Symptoms of Angina Reduction (QUASAR) trial.

    Science.gov (United States)

    Pepine, Carl J; Rouleau, Jean-Lucien; Annis, Karen; Ducharme, Anique; Ma, Patrick; Lenis, Jacques; Davies, Richard; Thadani, Udho; Chaitman, Bernard; Haber, Harry E; Freedman, S Ben; Pressler, Milton L; Pitt, Bertram

    2003-12-17

    We sought to determine whether angiotensin-converting enzyme inhibition (ACE-I) (i.e., quinapril) prevents transient ischemia (exertional and spontaneous) in patients with coronary artery disease (CAD). It is known that ACE-I reduces the risk of death, myocardial infarction (MI), and other CAD-related outcomes in high-risk patients. Numerous studies have confirmed that ACE-I improves coronary flow and endothelial function. Whether ACE-I also decreases transient ischemia is unclear, because no studies have been adequately designed or sufficiently powered to evaluate this issue. Using a randomized, double-blinded, placebo-controlled, multicenter design, we enrolled 336 CAD patients with stable angina. None had uncontrolled hypertension, left ventricular (LV) dysfunction, or recent MI, and all developed electrocardiographic (ECG) evidence of ischemia during exercise. They were randomly assigned to one of two groups: 40 mg/day quinapril (n = 177) or placebo (n = 159) for 8 weeks. Patients then entered an additional eight-week treatment phase to examine the full dose range. Those assigned to 40 mg quinapril continued that dose and those assigned to placebo were titrated to 80 mg/day. Treadmill testing, the Seattle Angina Questionnaire, and ambulatory ECG monitoring were used to assess responses at baseline and at 8 and 16 weeks. The groups did not differ significantly at entry or in terms of indexes assessing myocardial ischemia at 8 or 16 weeks of treatment. In this low-risk population, ACE-I was not associated with serious adverse events. Our findings suggest short-term ACE-I in CAD patients without hypertension, LV dysfunction, or acute MI is not associated with significant effects on transient ischemia.

  18. Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

    International Nuclear Information System (INIS)

    Chen, Shang-Der; Lin, Tsu-Kung; Yang, Ding-I.; Lee, Su-Ying; Shaw, Fu-Zen; Liou, Chia-Wei; Chuang, Yao-Chung

    2015-01-01

    Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield

  19. Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shang-Der, E-mail: chensd@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Lin, Tsu-Kung [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Yang, Ding-I. [Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan (China); Lee, Su-Ying [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Shaw, Fu-Zen [Department of Psychology, National Cheng Kung University, Tainan, Taiwan (China); Liou, Chia-Wei [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Chuang, Yao-Chung, E-mail: ycchuang@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China)

    2015-05-01

    Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield.

  20. Design and operation of a thermionic converter in air

    International Nuclear Information System (INIS)

    Horner, M.H.; Begg, L.L.; Smith, J.N. Jr.; Geller, C.B.; Kallnowski, J.E.

    1995-01-01

    An electrically heated thermionic converter has been designed, built and successfully tested in air. Several unique features were incorporated in this converter: an integral cesium reservoir, innovative ceramic-to-metal seals, a heat rejection system coupling the collector to a low temperature heat sink and an innovative cylindrical heater filament. The converter was operated for extended periods of time with the emitter at about 1900 K. the collector at about 700 K, and a power density of over 2 w(e)/sq. cm. Input power transients were run between 50% and 100% thermal power, at up to 1% per second, without instabilities in performance

  1. Ripple Mitigation with Improved Line-Load Transients Response in Two-Stage DC-DC-AC Converter

    DEFF Research Database (Denmark)

    Gautam, Aditya R.; Gaurav, Kumar; Guerrero, Josep M.

    2018-01-01

    . The front-end boost converter in the considered two-stage converter interfaces a battery bank and single phase inverter fed loads. The control shapes the output impedance of boost converter to reduce the ripple component at battery input. Secondly, the proposed controller achieves good dynamic performance...

  2. Practical Design Guidelines of qZSI Based Step-Up DC/DC Converter

    Science.gov (United States)

    Zakis, Janis; Vinnikov, Dmitri; Roasto, Indrek; Jalakas, Tanel

    2010-01-01

    This paper presents some design guidelines for a new voltage fed step-up DC/DC isolated converter. The most significant advantage of proposed converter is voltage buck-boost operation on single stage. The most promising application for proposed converter is in the field of distributed power generation e.g. fuel cells or photovoltaic. The most sensitive issues - such as power losses caused by high currents in the input side of converter and high transient overvoltages across the inverter bridge caused by stray inductances were discussed and solved. The proposals and recommendations to overcome these issues are given in the paper. The Selection and design guidelines of converter elements are proposed and explained. The prototype of proposed converter was built and experimentally tested. Some results are presented and evaluated.

  3. Adaptive electrothermal protection of power converters

    Directory of Open Access Journals (Sweden)

    Baraniuk G. A.

    2017-06-01

    Full Text Available Thermal management for power converters during normal operation and transient modes when electrical components are warmed up is an actual problem. This can be particularly important for converters with intermittent duty operation, e.g. power supplies for resistance welding. According to some research, nearly 60% of failures are temperature-induced, and for every 10°C temperature rise in operating environment the failure rate nearly doubles. In this paper, thermal motion of state equations eigenvalue is analysed. It is shown, that in semiconductor converters with an output smoothing filter it is appropriate to use thermal protection devices based on thermal normalisation of the converter filter and, while for cases when short circuits are possible it is appropriate to use a soft start system with thermal adaptation for soft start time factor. Based on these results, two systems of thermal protections operating for semiconductor power converters are introduced. Simulation of combined electromagnetic and thermal processes in buck converter operating with both thermal management systems in overlapping environments MATLAB/Simulink and PLECS showed the possibility to significantly reduce thermal shock on semiconductor components. Using the system of filter parameters normalisation decreases the temperature of the crystal from 210°C to 85°C, using the adaptive soft start system decreases the temperature from 180°C to 80°C. The simulation results are confirmed by tests on real devices.

  4. [Laboratory diagnostics in transient loss of consciousness : Serum lactate compared to serum creatine kinase as diagnostic indicator for generalized tonic-clonic seizures].

    Science.gov (United States)

    Dafotakis, M; Heckelmann, J; Zechbauer, S; Litmathe, J; Brokmann, J; Willmes, K; Surges, R; Matz, O

    2018-03-21

    Laboratory parameters can help in the differential diagnostics of acute episodes of transient loss of consciousness. Especially serum lactate and serum creatine kinase (CK) levels may provide valuable hints to distinguish generalized tonic-clonic seizures (GTCS) from syncope. Serum lactate levels at admission and CK levels 10-48 h after the episodes that led to admission were compared between patients with GTCS (n = 30) and those with syncope (n = 15). In addition, sensitivity and specificity of lactate and CK as diagnostic markers for syncope and GTCS were determined. The serum lactate and serum CK levels were significantly increased in patients with GTCS as compared to syncope patients (serum lactate: p lactate as an indicator for GTCS was 0.94 (95% confidence interval [CI] 0.88-1.0). For CK the receiver operating characteristics (ROC) analysis produced an AUC of only 0.77 (95% CI: 0.63-0.9). The determination of the lactate value as point-of-care diagnostics appears to be highly relevant in the rapid clarification of unclear episodes with transient loss of consciousness. The CK level at follow-up is also suitable for distinguishing GTCS from syncope but is inferior to the serum lactate value.

  5. Parametric study of postulated reactivity transients due to ingress of heavy water from the reflector tank into the converted core of APSARA reactor

    International Nuclear Information System (INIS)

    Sankaranarayanan, S.

    2004-01-01

    Research reactors in the power range 5-10 MW with useable neutron flux values >1.OE+14 n/sqcm/sec can be constructed using LEU fuel with light water for neutron moderation and fuel cooling. In order to obtain a large irradiation volume, a heavy water reflector is used where fairly high neutron flux levels can be obtained. A prototype LEU fuelled 5/10 MW reactor design has been developed in the Bhabha Atomic Research Centre in Trombay. Work is on hand to carry out technology simulation of this reactor design by converting the pool type reactor APSARA in BARC. Presently the Apsara reactor uses MTh type high enriched U-Al alloy plate type fuel loaded in a 7x7 grid with a square lattice pitch of 76.8 mm. The reactor has three control-scram-shut off rods and one regulating control rod. In the first phase of the simulation studies, it is proposed to use the existing high enriched uranium fuel in a modified core with 37 positions arranged with a square lattice pitch of 84.8 mm, surrounded by a 50 cm thick heavy water reflector. Subsequently the converted core will use plate-type low enriched uranium suicide fuel. One of the accident scenarios postulated for the safety evaluation of the modified APSARA reactor is the reactivity transient due to the ingress of heavy water into the core through a small sized rupture in the aluminium wall of the reflector tank. Parametric analyses were done for the safety evaluation of modified Apsara reactor, for postulated leak of heavy water into the core from the reflector tank. A simplified computer code REDYN, based on point model reactor kinetics with one effective group of delayed neutrons is used for the analyses. Results of several parametric cases used in the study show that it is possible to contain the consequences of this type of reactivity transient within acceptable fuel and coolant thermal safety limits

  6. General phase-frequency shifting in the three-phase inductor-converter bridge

    International Nuclear Information System (INIS)

    Ehsani, M.; Kustom, R.L.; Fuja, R.E.; Barnard, T.J.

    1979-01-01

    A fundamental method of shifting phase frequency in the inductor-converter bridge (ICB) for the purpose of controlling the power in real time is presented. Transient switching sequences needed to implement phase-frequency shifting can be developed by the use of this method and the other five system constraints. Two of the constraints that have been expressed in equation form so far are presented. Finally, an alternative algorithm for computing the frequency shifting transient sequences in real time is suggested

  7. Succinate modulates Ca(2+) transient and cardiomyocyte viability through PKA-dependent pathway.

    Science.gov (United States)

    Aguiar, Carla J; Andrade, Vanessa L; Gomes, Enéas R M; Alves, Márcia N M; Ladeira, Marina S; Pinheiro, Ana Cristina N; Gomes, Dawidson A; Almeida, Alvair P; Goes, Alfredo M; Resende, Rodrigo R; Guatimosim, Silvia; Leite, M Fatima

    2010-01-01

    GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, a citric acid cycle intermediate, in several tissues. In the heart, the role of succinate is unknown. We now report that rat ventricular cardiomyocytes express GPR91. We found that succinate, through GPR91, increases the amplitude and the rate of decline of global Ca(2+) transient, by increasing the phosphorylation levels of ryanodine receptor and phospholamban, two well known Ca(2+) handling proteins. The effects of succinate on Ca(2+) transient were abolished by pre-treatment with adenylyl cyclase and cAMP-dependent protein kinase (PKA) inhibitors. Direct PKA activation by succinate was further confirmed using a FRET-based A-kinase activity reporter. Additionally, succinate decreases cardiomyocyte viability through a caspase-3 activation pathway, effect also prevented by PKA inhibition. Taken together, these observations show that succinate acts as a signaling molecule in cardiomyocytes, modulating global Ca(2+) transient and cell viability through a PKA-dependent pathway. 2009 Elsevier Ltd. All rights reserved.

  8. Enterococcus faecalis phosphomevalonate kinase

    Science.gov (United States)

    Doun, Stephanie S.; Burgner, John W.; Briggs, Scott D.; Rodwell, Victor W.

    2005-01-01

    The six enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis represent potential for addressing a pressing human health concern, the development of antibiotics against resistant strains of the Gram-positive streptococci. We previously characterized the first four of the mevalonate pathway enzymes of Enterococcus faecalis, and here characterize the fifth, phosphomevalonate kinase (E.C. 2.7.4.2). E. faecalis genomic DNA and the polymerase chain reaction were used to clone DNA thought to encode phosphomevalonate kinase into pET28b(+). Double-stranded DNA sequencing verified the sequence of the recombinant gene. The encoded N-terminal hexahistidine-tagged protein was expressed in Escherichia coli with induction by isopropylthiogalactoside and purified by Ni++ affinity chromatography, yield 20 mg protein per liter. Analysis of the purified protein by MALDI-TOF mass spectrometry established it as E. faecalis phosphomevalonate kinase. Analytical ultracentrifugation revealed that the kinase exists in solution primarily as a dimer. Assay for phosphomevalonate kinase activity used pyruvate kinase and lactate dehydrogenase to couple the formation of ADP to the oxidation of NADH. Optimal activity occurred at pH 8.0 and at 37°C. The activation energy was ~5.6 kcal/mol. Activity with Mn++, the preferred cation, was optimal at about 4 mM. Relative rates using different phosphoryl donors were 100 (ATP), 3.6 (GTP), 1.6 (TTP), and 0.4 (CTP). Km values were 0.17 mM for ATP and 0.19 mM for (R,S)-5-phosphomevalonate. The specific activity of the purified enzyme was 3.9 μmol substrate converted per minute per milligram protein. Applications to an immobilized enzyme bioreactor and to drug screening and design are discussed. PMID:15802646

  9. A current-mode DC—DC buck converter with adaptive zero compensation

    International Nuclear Information System (INIS)

    Yang Ling; Dai Guoding; Xu Chongwei; Liu Yuezhi

    2013-01-01

    To achieve fast transient response for a DC—DC buck converter, an adaptive zero compensation circuit is presented. The compensation resistance is dynamically adjusted according to the different output load conditions, and achieves an adequate system phase margin under the different conditions. An improved capacitor multiplier circuit is adopted to realize the minimized compensation capacitance size. In addition, analysis of the small-signal model shows the correctness of the mechanism of the proposed adaptive zero compensation technique. A current-mode DC—DC buck converter with the proposed structure has been implemented in a 0.35 μm CMOS process, and the die size is only 800 × 1040 μm 2 . The experimental results show that the transient undershoot/overshoot voltage and the recovery times do not exceed 40 mV and 30 μs for a load current variation from 100 mA to 1 A. (semiconductor integrated circuits)

  10. Separative performance transients in a gas centrifuge

    International Nuclear Information System (INIS)

    Olander, D.R.

    1979-01-01

    A general method has been developed to calculate the behavior of the exit compositions from a gas centrifuge under unsteady conditions. The method utilizes the basic enrichment gradient equations derived by Cohen, which, in this case, contain time derivatives of the partial 235 U inventories. These partial differential equations are converted to ordinary differential equations by a linear approximation to the axial concentration distribution for use in the inventory terms only. With this simplification, analytical solution is possible for the feed concentration transient. The transient driven by a change in the feed flow rate, however, requires numerical solution. For analysis of ideal cascades in the unsteady state, the transient flow and separation characteristics of the centrifuge must be combined with total uranium and 235 U material balances on each stage

  11. Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

    Directory of Open Access Journals (Sweden)

    John Meshki

    Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

  12. Identification of a major IP5 kinase in Cryptococcus neoformans confirms that PP-IP5/IP7, not IP6, is essential for virulence

    OpenAIRE

    Li, Cecilia; Lev, Sophie; Saiardi, Adolfo; Desmarini, Desmarini; Sorrell, Tania C.; Djordjevic, Julianne T.

    2016-01-01

    Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP3 to inositol pyrophosphate, PP-IP5/IP7, which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the kinase converting IP5 to IP6 is unknown. Deletion of a putative IP5 kinase-encoding gene (IPK1) alone (ipk1?), and in combination with KCS1 (ipk1?kcs1?), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenua...

  13. The 25 kW resonant dc/dc power converter

    Science.gov (United States)

    Robson, R. R.

    1983-01-01

    The feasibility of processing 25-kW of power with a single, transistorized, series resonant converter stage was demonstrated by the successful design, development, fabrication, and testing of such a device which employs four Westinghouse D7ST transistors in a full-bridge configuration and operates from a 250-to-350 Vdc input bus. The unit has an overall worst-case efficiency of 93.5% at its full rated output of 1000 V and 25 A dc. A solid-state dc input circuit breaker and output-transient-current limiters are included in and integrated into the design. Full circuit details of the converter are presented along with the test data.

  14. Local digital control of power electronic converters in a dc microgrid based on a-priori derivation of switching surfaces

    Science.gov (United States)

    Banerjee, Bibaswan

    In power electronic basedmicrogrids, the computational requirements needed to implement an optimized online control strategy can be prohibitive. The work presented in this dissertation proposes a generalized method of derivation of geometric manifolds in a dc microgrid that is based on the a-priori computation of the optimal reactions and trajectories for classes of events in a dc microgrid. The proposed states are the stored energies in all the energy storage elements of the dc microgrid and power flowing into them. It is anticipated that calculating a large enough set of dissimilar transient scenarios will also span many scenarios not specifically used to develop the surface. These geometric manifolds will then be used as reference surfaces in any type of controller, such as a sliding mode hysteretic controller. The presence of switched power converters in microgrids involve different control actions for different system events. The control of the switch states of the converters is essential for steady state and transient operations. A digital memory look-up based controller that uses a hysteretic sliding mode control strategy is an effective technique to generate the proper switch states for the converters. An example dcmicrogrid with three dc-dc boost converters and resistive loads is considered for this work. The geometric manifolds are successfully generated for transient events, such as step changes in the loads and the sources. The surfaces corresponding to a specific case of step change in the loads are then used as reference surfaces in an EEPROM for experimentally validating the control strategy. The required switch states corresponding to this specific transient scenario are programmed in the EEPROM as a memory table. This controls the switching of the dc-dc boost converters and drives the system states to the reference manifold. In this work, it is shown that this strategy effectively controls the system for a transient condition such as step changes

  15. An Optimized Control for LLC Resonant Converter with Wide Load Range

    Science.gov (United States)

    Xi, Xia; Qian, Qinsong

    2017-05-01

    This paper presents an optimized control which makes LLC resonant converters operate with a wider load range and provides good closed-loop performance. The proposed control employs two paralleled digital compensations to guarantee the good closed-loop performance in a wide load range during the steady state, an optimized trajectory control will take over to change the gate-driving signals immediately at the load transients. Finally, the proposed control has been implemented and tested on a 150W 200kHz 400V/24V LLC resonant converter and the result validates the proposed method.

  16. Effect of pole zero location on system dynamics of boost converter for micro grid

    Science.gov (United States)

    Lavanya, A.; Vijayakumar, K.; Navamani, J. D.; Jayaseelan, N.

    2018-04-01

    Green clean energy like photo voltaic, wind energy, fuel cell can be brought together by microgrid.For low voltage sources like photovoltaic cell boost converter is very much essential. This paper explores the dynamic analysis of boost converter in a continuous conduction mode (CCM). The transient performance and stability analysis is carried out in this paper using time domain analysis and frequency domain analysis techniques. Boost converter is simulated using both PSIM and MATLAB software. Furthermore, state space model obtained and the transfer function is derived. The converter behaviour when a step input is applied is analyzed and stability of the converter is analyzed from bode plot frequency for open loop. Effect of the locations of poles and zeros in the transfer function of boost converter and how the performance parameters are affected is discussed in this paper. Closed loop performance with PI controller is also analyzed for boost converter.

  17. Structural Bioinformatics and Protein Docking Analysis of the Molecular Chaperone-Kinase Interactions: Towards Allosteric Inhibition of Protein Kinases by Targeting the Hsp90-Cdc37 Chaperone Machinery

    Directory of Open Access Journals (Sweden)

    Gennady Verkhivker

    2013-11-01

    Full Text Available A fundamental role of the Hsp90-Cdc37 chaperone system in mediating maturation of protein kinase clients and supporting kinase functional activity is essential for the integrity and viability of signaling pathways involved in cell cycle control and organism development. Despite significant advances in understanding structure and function of molecular chaperones, the molecular mechanisms and guiding principles of kinase recruitment to the chaperone system are lacking quantitative characterization. Structural and thermodynamic characterization of Hsp90-Cdc37 binding with protein kinase clients by modern experimental techniques is highly challenging, owing to a transient nature of chaperone-mediated interactions. In this work, we used experimentally-guided protein docking to probe the allosteric nature of the Hsp90-Cdc37 binding with the cyclin-dependent kinase 4 (Cdk4 kinase clients. The results of docking simulations suggest that the kinase recognition and recruitment to the chaperone system may be primarily determined by Cdc37 targeting of the N-terminal kinase lobe. The interactions of Hsp90 with the C-terminal kinase lobe may provide additional “molecular brakes” that can lock (or unlock kinase from the system during client loading (release stages. The results of this study support a central role of the Cdc37 chaperone in recognition and recruitment of the kinase clients. Structural analysis may have useful implications in developing strategies for allosteric inhibition of protein kinases by targeting the Hsp90-Cdc37 chaperone machinery.

  18. Analysis and control of a hybrid vehicle powered by free-piston energy converter

    OpenAIRE

    Hansson, Jörgen

    2006-01-01

    The introduction of hybrid powertrains has made it possible to utilise unconventional engines as primary power units in vehicles. The free-piston energy converter (FPEC) is such an engine. It is a combination of a free-piston combustion engine and a linear electrical machine. The main features of this configuration are high efficiency and a rapid transient response. In this thesis the free-piston energy converter as part of a hybrid powertrain is studied. One issue of the FPEC is the generati...

  19. Transient upregulation of protein kinase C in pressure-overloaded neonatal rat myocardium

    Czech Academy of Sciences Publication Activity Database

    Hamplová, B.; Novák, F.; Kolář, František; Nováková, O.

    2010-01-01

    Roč. 59, č. 1 (2010), s. 25-33 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : protein kinase C * cardiac development * pressure overload Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  20. Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate

    Science.gov (United States)

    Wang, Qi; Vogan, Erik M; Nocka, Laura M; Rosen, Connor E; Zorn, Julie A; Harrison, Stephen C; Kuriyan, John

    2015-01-01

    Bruton's tyrosine kinase (Btk), a Tec-family tyrosine kinase, is essential for B-cell function. We present crystallographic and biochemical analyses of Btk, which together reveal molecular details of its autoinhibition and activation. Autoinhibited Btk adopts a compact conformation like that of inactive c-Src and c-Abl. A lipid-binding PH-TH module, unique to Tec kinases, acts in conjunction with the SH2 and SH3 domains to stabilize the inactive conformation. In addition to the expected activation of Btk by membranes containing phosphatidylinositol triphosphate (PIP3), we found that inositol hexakisphosphate (IP6), a soluble signaling molecule found in both animal and plant cells, also activates Btk. This activation is a consequence of a transient PH-TH dimerization induced by IP6, which promotes transphosphorylation of the kinase domains. Sequence comparisons with other Tec-family kinases suggest that activation by IP6 is unique to Btk. DOI: http://dx.doi.org/10.7554/eLife.06074.001 PMID:25699547

  1. Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner.

    Science.gov (United States)

    Spahn, Viola; Fischer, Oliver; Endres-Becker, Jeannette; Schäfer, Michael; Stein, Christoph; Zöllner, Christian

    2013-04-01

    Hyperalgesia is a cardinal symptom of opioid withdrawal. The transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated ion channel expressed on sensory neurons responding to noxious heat, protons, and chemical stimuli such as capsaicin. TRPV1 can be inhibited via μ-opioid receptor (MOR)-mediated reduced activity of adenylyl cyclases (ACs) and decreased cyclic adenosine monophosphate (cAMP) levels. In contrast, opioid withdrawal following chronic activation of MOR uncovers AC superactivation and subsequent increases in cAMP and protein kinase A (PKA) activity. Here we investigated (1) whether an increase in cAMP during opioid withdrawal increases the activity of TRPV1 and (2) how opioid withdrawal modulates capsaicin-induced nocifensive behavior in rats. We applied whole-cell patch clamp, microfluorimetry, cAMP assays, radioligand binding, site-directed mutagenesis, and behavioral experiments. Opioid withdrawal significantly increased cAMP levels and capsaicin-induced TRPV1 activity in both transfected human embryonic kidney 293 cells and dissociated dorsal root ganglion (DRG) neurons. Inhibition of AC and PKA, as well as mutations of the PKA phosphorylation sites threonine 144 and serine 774, prevented the enhanced TRPV1 activity. Finally, capsaicin-induced nocifensive behavior was increased during opioid withdrawal in vivo. In summary, our results demonstrate an increased activity of TRPV1 in DRG neurons as a new mechanism contributing to opioid withdrawal-induced hyperalgesia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Comparison of Interleaved Boost Converter Configurations for Solar Photovoltaic System Interface

    Directory of Open Access Journals (Sweden)

    R Ramaprabha

    2013-12-01

    Full Text Available Solar photovoltaic (SPV panels that convert light energy into electrical energy through the photovoltaic effect have nonlinear internal resistance. Hence, with the variation in the intensity of light falling on the panel, the internal resistance varies. For effective utilization of the SPV panel, it is necessary to extract the maximum power from it. For maximum power extraction from SPV panels, DC-DC converter interface is used. The problem in using high frequency converter interface is the resultant high frequency ripple interaction with the SPV system. In this work, an interleaved boost converter (IBC is considered to reduce the ripple. Our finding is that IBC fed by a SPV panel reduces this ripple to a greater extent. IBC also has a faster transient response as compared to conventional boost converters with reduced ripple contents. The main aim of this paper is to present a comparative analysis of the performance of IBC with inductors that are coupled in different ways. The results of the simulation were extrapolated with the help of MATLAB software and verified through experimentation.

  3. A Two-stage DC-DC Converter for the Fuel Cell-Supercapacitor Hybrid System

    DEFF Research Database (Denmark)

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

    2009-01-01

    A wide input range multi-stage converter is proposed with the fuel cells and supercapacitors as a hybrid system. The front-end two-phase boost converter is used to optimize the output power and to reduce the current ripple of fuel cells. The supercapacitor power module is connected by push...... and designed. A 1kW prototype controlled by TMS320F2808 DSP is built in the lab. Simulation and experimental results confirm the feasibility of the proposed two stage dc-dc converter system.......-pull-forward half bridge (PPFHB) converter with coupled inductors in the second stage to handle the slow transient response of the fuel cells and realize the bidirectional power flow control. Moreover, this cascaded structure simplifies the power management. The control strategy for the whole system is analyzed...

  4. A New Control Strategy Based Multi Converter UPQC Using Fuzzy Logic Controller to Improve the Power Quality Issues

    Directory of Open Access Journals (Sweden)

    Chandra Babu Paduchuri

    2014-01-01

    Full Text Available A design of multiconverter unified power quality conditioner to improve the power quality issues is presents in this paper. Modified SRF theory and fuzzy logic controller technique are incorporated in this modelling. This newly designed controller is connected to a source in order to compensate voltage and current in the two feeders. The expanded concept of UPQC is multi converter-UPQC; this system has two series voltage source converter (VSC and one shunt VSC connected back to back. In the proposed system, the power can be conveyed from one feeder to another in order to mitigate the voltage sag, swell, interruption and transient response of the system. The control strategies of multi converter-UPQC are designed based on the modified synchronous reference frame theory with fuzzy logic controller. The transient response of the fuzzy logic controller in dc-link voltage controller will be very fast. The relevant simulation and compensation performance analysis of multi converter-UPQC with fuzzy logic controller is performed using MATLAB/Simulink software.

  5. The use of Phoenics in the design of catalytic converters

    Energy Technology Data Exchange (ETDEWEB)

    Luoma, M. [Kemira Metalkat Oy, Oulu (Finland); Smith, A.G. [S and C Thermofluids Ltd, Bath (United Kingdom)

    1996-12-31

    Manufacturers of automotive catalytic converters are constrained to design a system which is mechanically reliable, puts low back pressure on the engine, has adequate conversion performance, is low cost and of minimum size. In recent years, computational fluid dynamics (CFD) has been widely examined as a means of predicting the performance of catalytic converters to aid with the design process. Kemira Metalkat and S and C Thermofluids have put together and developed a number of existing CFD techniques in order to create a tool which is integrated within the design process. PHOENICS is used in the heart of the system in order to produce predictions of transient (light-off) and steady state catalyst performance. Grid generation tools have been provided to allow simplified and rapid geometry definition with suitable integration (via FEMGEN) within other parts of the catalyst design process. Simplified input techniques have been provided along with associated translators to create specification of the model for PHOENICS. Post-processing software has been provided through FEMVIEW to allow visualisation of catalyst monolith variables and transient performance animation. The whole system is controlled via a menu. The system have been use to study the effects of the catalyst design parameters on the converter performance. The results obtained using the system have so far been more qualitative than quantitative. However, validation studies have been carried out to check pressure drop prediction. A new model for the pressure drop over a metallic monolith has been developed. (author)

  6. The use of Phoenics in the design of catalytic converters

    Energy Technology Data Exchange (ETDEWEB)

    Luoma, M [Kemira Metalkat Oy, Oulu (Finland); Smith, A G [S and C Thermofluids Ltd, Bath (United Kingdom)

    1997-12-31

    Manufacturers of automotive catalytic converters are constrained to design a system which is mechanically reliable, puts low back pressure on the engine, has adequate conversion performance, is low cost and of minimum size. In recent years, computational fluid dynamics (CFD) has been widely examined as a means of predicting the performance of catalytic converters to aid with the design process. Kemira Metalkat and S and C Thermofluids have put together and developed a number of existing CFD techniques in order to create a tool which is integrated within the design process. PHOENICS is used in the heart of the system in order to produce predictions of transient (light-off) and steady state catalyst performance. Grid generation tools have been provided to allow simplified and rapid geometry definition with suitable integration (via FEMGEN) within other parts of the catalyst design process. Simplified input techniques have been provided along with associated translators to create specification of the model for PHOENICS. Post-processing software has been provided through FEMVIEW to allow visualisation of catalyst monolith variables and transient performance animation. The whole system is controlled via a menu. The system have been use to study the effects of the catalyst design parameters on the converter performance. The results obtained using the system have so far been more qualitative than quantitative. However, validation studies have been carried out to check pressure drop prediction. A new model for the pressure drop over a metallic monolith has been developed. (author)

  7. A voltage to frequency converter for astronomical photometry

    Science.gov (United States)

    Dunham, E.; Elliot, J. L.

    1978-01-01

    A voltage to frequency converter (VFC) for general use with photomultipliers is described. For high light levels, when the dead-time corrections for a photon counter would be excessive, the VFC maintains a linear response and allows the recording of data at high time resolution. Results of laboratory tests are given for the signal-to-noise characteristics, linearity, stability, and transient response of the VFC when used in conjunction with EMI 9658 and RCA C31034 photomultipliers.

  8. Evidence for association of the cloned liver growth hormone receptor with a tyrosine kinase

    DEFF Research Database (Denmark)

    Wang, X; Uhler, M D; Billestrup, N

    1992-01-01

    The ability of the cloned liver growth hormone (GH) receptor, when expressed in mammalian cell lines, to copurify with tyrosine kinase activity and be tyrosyl phosphorylated was examined. 125I-human growth hormone-GH receptor complexes isolated from COS-7 cells transiently expressing high levels...... of tyrosine kinase activity with cloned liver GH receptor. The level of phosphorylation of the GH receptor was very low, as compared with the endogenous GH receptor in 3T3-F442A cells, suggesting that tyrosine kinase activity is not intrinsic to the cloned GH receptor but rather resides with a kinase present...... in a variety of cell types. The finding that the level of phosphorylation of GH receptor appears to vary with cell type is consistent with the cloned liver GH receptor being a substrate for an associated tyrosine kinase and with the amount of such a GH receptor-associated tyrosine kinase being cell type-specific....

  9. A strictly monofunctional bacterial hydroxymethylpyrimidine phosphate kinase precludes damaging errors in thiamin biosynthesis.

    Science.gov (United States)

    Thamm, Antje M; Li, Gengnan; Taja-Moreno, Marlene; Gerdes, Svetlana Y; de Crécy-Lagard, Valérie; Bruner, Steven D; Hanson, Andrew D

    2017-07-20

    The canonical kinase (ThiD) that converts the thiamin biosynthesis intermediate hydroxymethylpyrimidine (HMP) monophosphate to the diphosphate can also very efficiently convert free HMP to the monophosphate in prokaryotes, plants, and fungi. This HMP kinase activity enables salvage of HMP, but it is not substrate-specific and so allows toxic HMP analogs and damage products to infiltrate the thiamin biosynthesis pathway. Comparative analysis of bacterial genomes uncovered a gene, thiD2 , that is often fused to the thiamin synthesis gene thiE and could potentially encode a replacement for ThiD. Standalone ThiD2 proteins and ThiD2 fusion domains are small (~130-residues) and do not belong to any previously known protein family. Genetic and biochemical analyses showed that representative standalone and fused ThiD2 proteins catalyze phosphorylation of HMP monophosphate, but not of HMP or its toxic analogs and damage products such as bacimethrin and 5-(hydroxymethyl)-2-methylpyrimidin-4-ol. As strictly monofunctional HMP monophosphate kinases, ThiD2 proteins eliminate a potentially fatal vulnerability of canonical ThiD, at the cost of the ability to reclaim HMP formed by thiamin turnover. ©2017 The Author(s).

  10. Complete inhibition of creatine kinase in isolated perfused rat hearts

    International Nuclear Information System (INIS)

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. 31 P-NMR of the heart was carried out

  11. Monolithic quasi-sliding-mode controller for SIDO buck converter with a self-adaptive free-wheeling current level

    Science.gov (United States)

    Xiaobo, Wu; Qing, Liu; Menglian, Zhao; Mingyang, Chen

    2013-01-01

    An analog implementation of a novel fixed-frequency quasi-sliding-mode controller for single-inductor dual-output (SIDO) buck converter in pseudo-continuous conduction mode (PCCM) with a self-adaptive freewheeling current level (SFCL) is presented. Both small and large signal variations around the operation point are considered to achieve better transient response so as to reduce the cross-regulation of this SIDO buck converter. Moreover, an internal integral loop is added to suppress the steady-state regulation error introduced by conventional PWM-based sliding mode controllers. Instead of keeping it as a constant value, the free-wheeling current level varies according to the load condition to maintain high power efficiency and less cross-regulation at the same time. To verify the feasibility of the proposed controller, an SIDO buck converter with two regulated output voltages, 1.8 V and 3.3 V, is designed and fabricated in HEJIAN 0.35 μm CMOS process. Simulation and experiment results show that the transient time of this SIDO buck converter drops to 10 μs while the cross-regulation is reduced to 0.057 mV/mA, when its first load changes from 50 to 100 mA.

  12. Transient and dynamic control of a variable speed wind turbine with synchronous generator

    Energy Technology Data Exchange (ETDEWEB)

    Jauch, Clemens [Riso National Laboratory, Wind Energy Department, PO Box 49, DK 4000 Roskilde, (Denmark)

    2007-02-14

    In this article, a controller for dynamic and transient control of a variable speed wind turbine with a full-scale converter-connected high-speed synchronous generator is presented. First, the phenomenon of drive train oscillations in wind turbines with full-scale converter-connected generators is discussed. Based on this discussion, a controller is presented that dampens these oscillations without impacting on the power that the wind turbine injects into the grid. Since wind turbines are increasingly demanded to take over power system stabilizing and control tasks, the presented wind turbine design is further enhanced to support the grid in transient grid events. A controller is designed that allows the wind turbine to ride through transient grid faults. Since such faults often cause power system oscillations, another controller is added that enables the turbine to participate in the damping of such oscillations. It is concluded that the controllers presented keep the wind turbine stable under any operating conditions, and that they are capable of adding substantial damping to the power system. (Author).

  13. A soft-switching coupled inductor bidirectional DC-DC converter with high-conversion ratio

    Science.gov (United States)

    Chao, Kuei-Hsiang; Jheng, Yi-Cing

    2018-01-01

    A soft-switching bidirectional DC-DC converter is presented herein as a way to improve the conversion efficiency of a photovoltaic (PV) system. Adoption of coupled inductors enables the presented converter not only to provide a high-conversion ratio but also to suppress the transient surge voltage via the release of the energy stored in leakage flux of the coupled inductors, and the cost can kept down consequently. A combined use of a switching mechanism and an auxiliary resonant branch enables the converter to successfully perform zero-voltage switching operations on the main switches and improves the efficiency accordingly. It was testified by experiments that our proposed converter works relatively efficiently in full-load working range. Additionally, the framework of the converter intended for testifying has high-conversion ratio. The results of a test, where a generating system using PV module array coupled with batteries as energy storage device was used as the low-voltage input side, and DC link was used as high-voltage side, demonstrated our proposed converter framework with high-conversion ratio on both high-voltage and low-voltage sides.

  14. Direct switching control of DC-DC power electronic converters using hybrid system theory

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, J.; Lin, F. [Wayne State Univ., Detroit, MI (United States). Dept. of Electrical and Computer Engineering; Wang, C. [Wayne State Univ., Detroit, MI (United States). Dept. of Electrical and Computer Engineering; Wayne State Univ., Detroit, MI (United States). Div. of Engineering Technology

    2010-07-01

    A direct switching control (DSC) scheme for power electronics converters was described. The system was designed for use in both traditional and renewable energy applications as well as in electric drive vehicles. The proposed control scheme was based on a detailed hybrid system converter model that used model predictive control (MPC), piecewise affine (PWA) approximations and constrained optimal control methods. A DC-DC converter was modelled as a hybrid machine. Switching among different modes of the DC-DC converter were modelled as discrete events controlled by the hybrid controller. The modelling scheme was applied to a Buck converter. The DSC was used to control the switch of the power converter based on a hybrid machine model. Results of the study showed that the method can be used to regulate output voltage and inductor currents. The method also provides fast transient responses and effectively regulates both currents and voltage. The controller can be used to provide immediate responses to dynamic disturbances and output voltage fluctuations. 23 refs., 7 figs.

  15. Mutation of serine 1333 in the ATR HEAT repeats creates a hyperactive kinase.

    Directory of Open Access Journals (Sweden)

    Jessica W Luzwick

    Full Text Available Subcellular localization, protein interactions, and post-translational modifications regulate the DNA damage response kinases ATR, ATM, and DNA-PK. During an analysis of putative ATR phosphorylation sites, we found that a single mutation at S1333 creates a hyperactive kinase. In vitro and in cells, mutation of S1333 to alanine (S1333A-ATR causes elevated levels of kinase activity with and without the addition of the protein activator TOPBP1. S1333 mutations to glycine, arginine, or lysine also create a hyperactive kinase, while mutation to aspartic acid decreases ATR activity. S1333A-ATR maintains the G2 checkpoint and promotes completion of DNA replication after transient exposure to replication stress but the less active kinase, S1333D-ATR, has modest defects in both of these functions. While we find no evidence that S1333 is phosphorylated in cultured cells, our data indicate that small changes in the HEAT repeats can have large effects on kinase activity. These mutants may serve as useful tools for future studies of the ATR pathway.

  16. One gigasample per second transient recorder: a performance demonstration

    International Nuclear Information System (INIS)

    Linnenbrink, T.E.; Gradl, D.A.; Ritt, D.M.; DeWitte, G.J.; Hutton, J.D.

    1982-01-01

    The performance demonstrated by a one gigasample per second (1 Gs/s) transient recorder currently in advanced development portends an important new instrument for recording single transient data. A Charge-Coupled Device (CCD) is used to sample a continuous analog signal. Samples acquired at the full sampling rate (1 Gs/s) are temporarily stored in the CCD, then read out at a slow rate (e.g., 250 Ks/s) into a conventional analog-to-digital converter prior to storage in nonvolatile, digital memory. Enhanced circuitry and techniques developed over the past three years have yielded higher performance than originally anticipated. Accordingly, the target specification has been revised to reflect higher expectations

  17. Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart

    Directory of Open Access Journals (Sweden)

    Beard Daniel A

    2009-02-01

    Full Text Available Abstract Background The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate. Results The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (ΔGATPase. In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of ΔGATPase in the beating heart. Conclusion The CK system stabilizes ΔGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.

  18. Test and evaluation of load converter topologies used in the Space Station Freedom power management and distribution dc test bed

    Science.gov (United States)

    Lebron, Ramon C.; Oliver, Angela C.; Bodi, Robert F.

    1991-01-01

    Power components hardware in support of the Space Station freedom dc Electric Power System were tested. One type of breadboard hardware tested is the dc Load Converter Unit, which constitutes the power interface between the electric power system and the actual load. These units are dc to dc converters that provide the final system regulation before power is delivered to the load. Three load converters were tested: a series resonant converter, a series inductor switch-mode converter, and a switching full-bridge forward converter. The topology, operation principles, and test results are described, in general. A comparative analysis of the three units is given with respect to efficiency, regulation, short circuit behavior (protection), and transient characteristics.

  19. Method and apparatus for controlling LCL converters using asymmetric voltage cancellation techniques

    Science.gov (United States)

    Wu, Hunter; Sealy, Kylee Devro; Sharp, Bryan Thomas; Gilchrist, Aaron

    2016-01-26

    A method and apparatus for LCL resonant converter control utilizing Asymmetric Voltage Cancellation is described. The methods to determine the optimal trajectory of the control variables are discussed. Practical implementations of sensing load parameters are included. Simple PI, PID and fuzzy logic controllers are included with AVC for achieving good transient response characteristics with output current regulation.

  20. Computer-aided analysis of power-electronic systems simulation of a high-voltage power converter

    International Nuclear Information System (INIS)

    Bordry, F.; Isch, H.W.; Proudlock, P.

    1987-01-01

    In the study of semiconductor devices, simulation methods play an important role in both the design of systems and the analysis of their operation. The authors describe a new and efficient computer-aided package program for general power-electronic systems. The main difficulty when taking into account non-linear elements, such as semiconductors, lies in determining the existence and the relations of the elementary sequences defined by the conduction or nonconduction of these components. The method does not require a priori knowledge of the state sequences of the semiconductor nor of the commutation instants, but only the circuit structure, its parameters and the commands to the controlled switches. The simulation program computes automatically both transient and steady-state waveforms for any circuit configuration. The simulation of a high-voltage power converter is presented, both for its steady-state and transient overload conditions. This 100 kV power converter (4 MW) will feed two klystrons in parallel

  1. Monolithic quasi-sliding-mode controller for SIDO buck converter with a self-adaptive free-wheeling current level

    International Nuclear Information System (INIS)

    Wu Xiaobo; Liu Qing; Zhao Menglian; Chen Mingyang

    2013-01-01

    An analog implementation of a novel fixed-frequency quasi-sliding-mode controller for single-inductor dual-output (SIDO) buck converter in pseudo-continuous conduction mode (PCCM) with a self-adaptive freewheeling current level (SFCL) is presented. Both small and large signal variations around the operation point are considered to achieve better transient response so as to reduce the cross-regulation of this SIDO buck converter. Moreover, an internal integral loop is added to suppress the steady-state regulation error introduced by conventional PWM-based sliding mode controllers. Instead of keeping it as a constant value, the free-wheeling current level varies according to the load condition to maintain high power efficiency and less cross-regulation at the same time. To verify the feasibility of the proposed controller, an SIDO buck converter with two regulated output voltages, 1.8 V and 3.3 V, is designed and fabricated in HEJIAN 0.35 μm CMOS process. Simulation and experiment results show that the transient time of this SIDO buck converter drops to 10 μs while the cross-regulation is reduced to 0.057 mV/mA, when its first load changes from 50 to 100 mA. (semiconductor integrated circuits)

  2. Feasibility analysis of fuzzy logic control for ITER Poloidal field (PF) AC/DC converter system

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, Mahmood Ul; Fu, Peng [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); University of Science and Technology of China (China); Song, Zhiquan, E-mail: zhquansong@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Chen, Xiaojiao [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); University of Science and Technology of China (China); Zhang, Xiuqing [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Humayun, Muhammad [Shanghai Jiaotong University (China)

    2017-05-15

    Highlights: • The implementation of the Fuzzy controller for the ITER PF converter system is presented. • The comparison of the FLC and PI simulation are investigated. • The FLC single and parallel bridge operation are presented. • Fuzzification and Defuzzification algorithms are presented using FLC controller. - Abstract: This paper describes the feasibility analysis of the fuzzy logic control to increase the performance of the ITER poloidal field (PF) converter systems. A fuzzy-logic-based controller is designed for ITER PF converter system, using the traditional PI controller and Fuzzy controller (FC), the dynamic behavior and transient response of the PF converter system are compared under normal operation by analysis and simulation. The analysis results show that the fuzzy logic control can achieve better operation performance than PI control.

  3. SAD kinases sculpt axonal arbors of sensory neurons through long and short-term responses to neurotrophin signals

    Science.gov (United States)

    Lilley, Brendan N.; Pan, Y. Albert; Sanes, Joshua R.

    2013-01-01

    SUMMARY Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex, but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short duration signals from extrinsic cues to sculpt axon arbors within the CNS. PMID:23790753

  4. Design, control and application of modular multilevel converters for HVDC transmission systems

    CERN Document Server

    Sharifabadi, Kamran; Nee, Hans-Peter; Norrga, Staffan; Teodorescu, Remus

    2016-01-01

    Design, Control and Application of Modular Multilevel Converters for HVDC Transmission Systems is a comprehensive guide to semiconductor technologies applicable for MMC design, component sizing control, modulation, and application of the MMC technology for HVDC transmission. Separated into three distinct parts, the first offers an overview of MMC technology, including information on converter component sizing, Control and Communication, Protection and Fault Management, and Generic Modelling and Simulation. The second covers the applications of MMC in offshore WPP, including planning, technical and economic requirements and optimization options, fault management, dynamic and transient stability. Finally, the third chapter explores the applications of MMC in HVDC transmission and Multi Terminal configurations, including Supergrids.

  5. ABNORMAL AND TRANSIENT MODES OF THE CONVERTER BOOSTER TYPE FOR DC TRACTION SUBSTATIONS

    Directory of Open Access Journals (Sweden)

    Yu. P. Goncharov

    2008-12-01

    Full Text Available The results of analytical research and computer design of the anomalous, steady-state and transitional modes related to the resonance in the input filter of voltage added converter based on IGBT with the PWM are presented. The ways of resonance removal by both the control means and the power blocks, combined with the overvoltage protection, are offered.

  6. Transient Diagnosis and Prognosis for Secondary System in Nuclear Power Plants

    Directory of Open Access Journals (Sweden)

    Sangjun Park

    2016-10-01

    Full Text Available This paper introduces the development of a transient monitoring system to detect the early stage of a transient, to identify the type of the transient scenario, and to inform an operator with the remaining time to turbine trip when there is no operator's relevant control. This study focused on the transients originating from a secondary system in nuclear power plants (NPPs, because the secondary system was recognized to be a more dominant factor to make unplanned turbine-generator trips which can ultimately result in reactor trips. In order to make the proposed methodology practical forward, all the transient scenarios registered in a simulator of a 1,000 MWe pressurized water reactor were archived in the transient pattern database. The transient patterns show plant behavior until turbine-generator trip when there is no operator's intervention. Meanwhile, the operating data periodically captured from a plant computer is compared with an individual transient pattern in the database and a highly matched section among the transient patterns enables isolation of the type of transient and prediction of the expected remaining time to trip. The transient pattern database consists of hundreds of variables, so it is difficult to speedily compare patterns and to draw a conclusion in a timely manner. The transient pattern database and the operating data are, therefore, converted into a smaller dimension using the principal component analysis (PCA. This paper describes the process of constructing the transient pattern database, dealing with principal components, and optimizing similarity measures.

  7. Calculation of Lightning Transient Responses on Wind Turbine Towers

    Directory of Open Access Journals (Sweden)

    Xiaoqing Zhang

    2013-01-01

    Full Text Available An efficient method is proposed in this paper for calculating lightning transient responses on wind turbine towers. In the proposed method, the actual tower body is simplified as a multiconductor grid in the shape of cylinder. A set of formulas are given for evaluating the circuit parameters of the branches in the multiconductor grid. On the basis of the circuit parameters, the multiconductor grid is further converted into an equivalent circuit. The circuit equation is built in frequency-domain to take into account the effect of the frequency-dependent characteristic of the resistances and inductances on lightning transients. The lightning transient responses can be obtained by using the discrete Fourier transform with exponential sampling to take the inverse transform of the frequency-domain solution of the circuit equation. A numerical example has been given for examining the applicability of the proposed method.

  8. AC-DC PFC Converter Using Combination of Flyback Converter and Full-bridge DC-DC Converter

    Directory of Open Access Journals (Sweden)

    Moh. Zaenal Efendi

    2014-06-01

    Full Text Available This paper presents a combination of power factor correction converter using Flyback converter and Full-bridge dc-dc converter in series connection. Flyback converter is operated in discontinuous conduction mode so that it can serve as a power factor correction converter and meanwhile Full-bridge dc-dc converter is used for dc regulator. This converter system is designed to produce a 86 Volt of output voltage and 2 A of output current. Both simulation and experiment results show that the power factor of this converter achieves up to 0.99 and meets harmonic standard of IEC61000-3-2. Keywords: Flyback Converter, Full-bridge DC-DC Converter, Power Factor Correction.

  9. A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation.

    Science.gov (United States)

    Dikic, I; Tokiwa, G; Lev, S; Courtneidge, S A; Schlessinger, J

    1996-10-10

    The mechanisms by which mitogenic G-protein-coupled receptors activate the MAP kinase signalling pathway are poorly understood. Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases, the epidermal growth factor receptor, Lyn and Syk. Here we show that lysophosphatidic acid (LPA) and bradykinin induce tyrosine phosphorylation of Pyk2 and complex formation between Pyk2 and activated Src. Moreover, tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. Transient overexpression of a dominant interfering mutant of Pyk2 or the protein tyrosine kinase Csk reduces LPA- or bradykinin-induced activation of MAP kinase. LPA- or bradykinin-induced MAP kinase activation was also inhibited by overexpression of dominant interfering mutants of Grb2 and Sos. We propose that Pyk2 acts with Src to link Gi- and Gq-coupled receptors with Grb2 and Sos to activate the MAP kinase signalling pathway in PC12 cells.

  10. SYNTHESIS OF AUTOMATIC CONTROL SYSTEM FOR STEPPING-UP CONVERTER OF DC VOLTAGE AT ACTIVE LOAD OPERATION

    Directory of Open Access Journals (Sweden)

    A. V. Мironovich

    2005-01-01

    Full Text Available Investigation of a nontransformer stepping-up converter of dc voltage has been carried out. A non-linear structural circuit of the converter has been developed with the help of the controlled current injection method. A linearization of an object and an automation control system synthesis have been conducted applying method of successive optimization of the circuits. The paper contains results of transient process simulation in the linear computer model and in the power electronics computer model. 

  11. The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA.

    Science.gov (United States)

    Li, Zhiru; Dugan, Aisling S; Bloomfield, Gareth; Skelton, Jason; Ivens, Alasdair; Losick, Vicki; Isberg, Ralph R

    2009-09-17

    The amoeba Dictyostelium discoideum can support replication of Legionella pneumophila. Here we identify the dupA gene, encoding a putative tyrosine kinase/dual-specificity phosphatase, in a screen for D. discoideum mutants altered in allowing L. pneumophila intracellular replication. Inactivation of dupA resulted in depressed L. pneumophila growth and sustained hyperphosphorylation of the amoebal MAP kinase ERK1, consistent with loss of a phosphatase activity. Bacterial challenge of wild-type amoebae induced dupA expression and resulted in transiently increased ERK1 phosphorylation, suggesting that dupA and ERK1 are part of a response to bacteria. Indeed, over 500 of the genes misregulated in the dupA(-) mutant were regulated in response to L. pneumophila infection, including some thought to have immune-like functions. MAP kinase phosphatases are known to be highly upregulated in macrophages challenged with L. pneumophila. Thus, DupA may regulate a MAP kinase response to bacteria that is conserved from amoebae to mammals.

  12. New transient-flow modelling of a multiple-fractured horizontal well

    International Nuclear Information System (INIS)

    Jia, Yong-Lu; Wang, Ben-Cheng; Nie, Ren-Shi; Wang, Dan-Ling

    2014-01-01

    A new transient-flow modelling of a multiple-fractured horizontal well is presented. Compared to conventional modelling, the new modelling considered more practical physical conditions, such as various inclined angles for different fractures, different fracture intervals, different fracture lengths and partially penetrating fractures to formation. A kind of new mathematical method, including a three-dimensional eigenvalue and orthogonal transform, was created to deduce the exact analytical solutions of pressure transients for constant-rate production in real space. In order to consider a wellbore storage coefficient and skin factor, we used a Laplace-transform approach to convert the exact analytical solutions to the solutions in Laplace space. Then the numerical solutions of pressure transients in real space were gained using a Stehfest numerical inversion. Standard type curves were plotted to describe the transient-flow characteristics. Flow regimes were clearly identified from type curves. Furthermore, the differences between the new modelling and the conventional modelling in pressure transients were especially compared and discussed. Finally, an example application to show the accordance of the new modelling with real conditions was implemented. Our new modelling is different from, but more practical than, conventional modelling. (paper)

  13. Converter fed sub sea motor drives

    Energy Technology Data Exchange (ETDEWEB)

    Raad, R O

    1995-09-01

    Minor offshore gas and oil resources located 20-50 km from existing installations may often be commercially exploited only by use of complete sub sea solutions. This thesis deals with analyses of a sub sea adjustable speed electric motor which is fed by a frequency converter via a long cable (up to 50 km) between the converter and the motor. The author develops a general model for analysing such motor drive systems with the objective of verifying the feasibility of specific applications and of specifying the requirements on the system components. The simulation model is used to identify the critical frequency ranges in which the converter must not generate significant harmonics, to verify the start-up strategy chosen, and to verify the stability with potential disturbances applied to the system. Simulation models are developed for both transient and steady state analyses. They are accurate up to 5 kHz and can incorporate the frequency dependency of the motor and cable parameters. Ideal thyristors and diodes are used. The models are implemented in existing simulation tools. Most of the results relate to a base case with a 670 kW squirrel cage motor fed from a 30 km long cable, but cases with 3 MW rating or with 50 km cable have also been analyzed and found to be feasible. Each specific application must be separately studied. Results of simulation calculations are presented and conclusions given. 53 refs., 124 figs., 23 tabs.

  14. Stress state dependence of transient irradiation creep in 20% cold worked 316 stainless steel

    International Nuclear Information System (INIS)

    Foster, J.P.; Gilbert, E.R.

    1998-01-01

    Irradiation creep tests were performed in fast reactors using the stress states of uniaxial tension, biaxial tension, bending and torsion. In order to compare the saturated transient strain irradiation creep component, the test data were converted to equivalent strain and equivalent stress. The saturated transient irradiation creep component was observed to depend on the stress state. The highest value was exhibited by the uniaxial tension stress state, and the lowest by the torsion stress state. The biaxial tension and bending stress state transient component values were intermediate. This behavior appears to be related to the dislocation or microscopic substructure resulting from fabrication processing and the applied stress direction. (orig.)

  15. High frequent modelling of a modular multilevel converter using passive components

    DEFF Research Database (Denmark)

    El-Khatib, Walid Ziad; Holbøll, Joachim; Rasmussen, Tonny Wederberg

    2013-01-01

    ). This means that a high frequency model of the converter has to be designed, which gives a better overview of the impact of high frequency transients etc. The functionality of the model is demonstrated by application to grid connections of off-shore wind power plants. Grid connection of an offshore wind power...... wind power plant employing HVDC. In the present study, a back to back HVDC transmission system is designed in PSCAD/EMTDC. Simulations and results showing the importance of high frequent modeling are presented....... plant using HVDC fundamentally changes the electrical environment for the power plant. Detailed knowledge and understanding of the characteristics and behavior of all relevant power system components under all conditions, including under transients, are required in order to develop reliable offshore...

  16. A faster reactor transient analysis methodology for PCs

    International Nuclear Information System (INIS)

    Ott, K.O.

    1991-10-01

    The simplified ANL model for LMR transient analysis, in which point kinetics as well as lumped descriptions of the heat transfer equations in all components are applied, is converted from a differential into an integral formulation. All differential balance equations are implicitly solved in terms of convolution integrals. The prompt jump approximation is applied as the strong negative feedback effectively keeps the net reactivity well below prompt critical. After implicit finite differencing of the convolution integrals, the kinetics equation assumes the form of a quadratic equation, the ''quadratic dynamics equation.'' This model forms the basis for GW-BASIC program, LTC, for LMR Transient Calculation program, which can effectively be run on a PC. The GW-BASIC version of the LTC program is described in detail in Volume 2 of this report

  17. Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

    Science.gov (United States)

    Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

    2017-05-01

    Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

  18. rad-Dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint

    NARCIS (Netherlands)

    Walworth, N.C.; Bernards, R.A.

    1996-01-01

    Exposure of eukaryotic cells to agents that generate DNA damage results in transient arrest of progression through the cell cycle. In fission yeast, the DNA damage checkpoint associated with cell cycle arrest before mitosis requires the protein kinase p56chk1. DNA damage induced by ultraviolet

  19. First-order irreversible thermodynamic approach to a nonsteady RLC circuit as an energy converter

    International Nuclear Information System (INIS)

    Valencia, G; Arias, L A

    2015-01-01

    In this work we show a RLC-circuit as energy converter within the context of first-order irreversible thermodynamics (FOIT). For our analysis, we propose an isothermic model with transient elements and passive elements. With the help of the dynamic equations, the Kirchhoff equations, we found the generalized fluxes and forces of the circuit, the equation system shows symmetry of the cross terms, this property is characteristic of the steady state linear systems, but in this case phenomenological coefficients are function of time. Then, we can use these relations, similar to the linear Onsager relations, to construct the characteristic functions of the RLC energy converter: the power output, efficiency, dissipation and ecological function, and study its energetic performance. The study of performance of the converter is based on two parameters, the coupling parameter and the ''forces ratio'' parameter, in this case as functions of time. We find that the behavior of the non-steady state converter is similar to the behavior of steady state energy converter. We will explain the linear and symmetric behavior of the converter in the frequencies space rather than in the time space. Finally, we establish optimal operation regimes of economic degree of coupling for this energy converter

  20. SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals.

    Science.gov (United States)

    Lilley, Brendan N; Pan, Y Albert; Sanes, Joshua R

    2013-07-10

    Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short-duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Application handbook for a Standardized Control Module (SCM) for DC-DC converters, volume 1

    Science.gov (United States)

    Lee, F. C.; Mahmoud, M. F.; Yu, Y.

    1980-04-01

    The standardized control module (SCM) was developed for application in the buck, boost and buck/boost DC-DC converters. The SCM used multiple feedback loops to provide improved input line and output load regulation, stable feedback control system, good dynamic transient response and adaptive compensation of the control loop for changes in open loop gain and output filter time constraints. The necessary modeling and analysis tools to aid the design engineer in the application of the SCM to DC-DC Converters were developed. The SCM functional block diagram and the different analysis techniques were examined. The average time domain analysis technique was chosen as the basic analytical tool. The power stage transfer functions were developed for the buck, boost and buck/boost converters. The analog signal and digital signal processor transfer functions were developed for the three DC-DC Converter types using the constant on time, constant off time and constant frequency control laws.

  2. Application handbook for a Standardized Control Module (SCM) for DC-DC converters, volume 1

    Science.gov (United States)

    Lee, F. C.; Mahmoud, M. F.; Yu, Y.

    1980-01-01

    The standardized control module (SCM) was developed for application in the buck, boost and buck/boost DC-DC converters. The SCM used multiple feedback loops to provide improved input line and output load regulation, stable feedback control system, good dynamic transient response and adaptive compensation of the control loop for changes in open loop gain and output filter time constraints. The necessary modeling and analysis tools to aid the design engineer in the application of the SCM to DC-DC Converters were developed. The SCM functional block diagram and the different analysis techniques were examined. The average time domain analysis technique was chosen as the basic analytical tool. The power stage transfer functions were developed for the buck, boost and buck/boost converters. The analog signal and digital signal processor transfer functions were developed for the three DC-DC Converter types using the constant on time, constant off time and constant frequency control laws.

  3. Role of Protein Kinase C in Endothelin Converting Enzyme-1 trafficking and shedding from endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuruppu, Sanjaya, E-mail: Sanjaya.Kuruppu@med.monash.edu.au [Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Vic. 3800 (Australia); Tochon-Danguy, Natalie; Ian Smith, A. [Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Vic. 3800 (Australia)

    2010-07-23

    Research highlights: {yields} PKC activation increases the trafficking of ECE-1 to the cell surface. {yields} This in turn leads to an increase in the amount of ECE-1 shed. {yields} Only the catalytically active C-terminal region is shed from the cell surface. -- Abstract: This study aimed to determine the consequences of Protein Kinase C (PKC) mediated Endothelin Converting Enzyme-1 (ECE-1) phosphorylation and its relationship to ECE-1 expression and shedding. The proteins on the surface of EA.hy926 cells were labelled with EZ-Link NHS-SS-Biotin both prior to (control) and following stimulation by 2 {mu}M phorbol 12-myristate 13-acetate (PMA) which activates PKC. The biotinylated proteins were isolated using neutravidin beads, resolved by gel electrophoresis and analysed by western blotting using anti-ECE-1 antibodies. Significant increase in ECE-1 expression at the cell surface was observed following stimulation by PMA, compared to unstimulated control cells (170 {+-} 32.3% of control, n = 5). The ECE-1 activity (expressed as {mu}M substrate cleaved/min) was determined by monitoring the cleavage of a quenched fluorescent substrate. The specificity of cleavage was confirmed using the ECE-1 inhibitor (CGS35066). The stimulation of cells by PMA (1 {mu}M, 6 h) significantly increased the ECE-1 activity (0.28 {+-} 0.02; n = 3) compared to the control (0.07 {+-} 0.02; n = 3). This increase was prevented by prior incubation with the PKC inhibitor bisindolymaleimide (BIM; 2 {mu}M for 1 h; 0.10 {+-} 0.01; n = 3). Treatment with PMA also increased the activity of ECE-1 in the media (0.18 {+-} 0.01; n = 3) compared to control (0.08 {+-} 0.01; n = 3). In addition, this study confirmed by western immunoblotting that only the extracellular region of ECE-1 is released from the cell surface. These data indicate for the first time that PKC activation induces the trafficking and shedding of ECE to and from the cell surface, respectively.

  4. Development of a current-type PWM converter with high power factor. 1

    International Nuclear Information System (INIS)

    Miura, Yushi; Matsukawa, Makoto; Miyachi, Kengo; Kimura, Toyoaki

    1998-01-01

    A power supply system for superconducting poloidal field coils of a next generation tokamak-type fusion device can be operated on the relatively low voltage for the duration of discharge except the plasma initiation. In the case of the conventional phase-controlled thyristor converters are adopted in such a system, the input power factor would be low in average, and a reactive power fluctuation caused by the change of DC output voltage may produce serious effects on the commercial transmission line. From the above viewpoint, a current-type PWM (Pulse Width Modulation) converter, which can work with the power factor of unity for the input power, is regarded as one of the promising candidates of the converters for the power supplies of next generation fusion devices. Hence, a 100kW-class current-type PWM converter has been developed by using IGBT (Insulated Gate Bipolar Transistor) as switching devices. In this development, the basic performance has been preliminary investigated whether this converter is applicable to the power supply for the next generation fusion device. In addition, two different PWM control methods were examined whether these methods can realize a unit power factor and suppress the transient oscillation of converter input current at the same time in case that the reference of DC output current is changed rapidly. (author)

  5. Interleaved Buck Converter with Variable Number of Active Phases and a Predictive Current Sharing Scheme

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Garcia, O.; Oliver, J. A.

    2008-01-01

    The efficiency of an interleaved Buck converter is typically low at light load conditions because of the switching losses in each of the switching stages. Improvements in the converter efficiency can be achieved by dynamically changing the number of active phases depending on the load current....... This paper addresses the issues related to the transient response of the converter when the number of active phases is changed by a digital control scheme. The problem arises because the current in the individual phases of the interleaved Buck converter will not be equal immediately after the controller has...... changed the number of active phases. This paper proposes a current equalisation scheme that adjusts the duty cycle of each phase in a manner that ensures equal average inductor current in all active phases in one or two PWM periods. The current equalisation scheme relies on the measurement of the output...

  6. Application of a synchronous generator with a boost converter in wind turbines: an experimental overview

    DEFF Research Database (Denmark)

    Sharma, Ranjan; Rasmussen, Tonny Wederberg; Jensen, Bogi Bech

    2012-01-01

    An electrical structure of a variable-speed wind turbine based on an externally excited synchronous generator; a passive diode rectifier; and a boost converter is discussed in this study. The clear advantage of such a system is its lower-semi-conductor devices count. A brief theoretical explanation...... of such a system is included. A boost converter normally utilies an inductor (energy storage) to boost the voltage level from its input to a higher output value. This study analyses the possibility of using the generator inductance as a boost inductor. It is discussed and verified in the study that for the given...... switching frequency of the boost converter (fs=1= kHz), the generator sub-transient inductance (not the synchronous inductance) appears as an equivalent inductance seen by the boost converter. The parasitic capacitors present in the generator terminals are often neglected from design issues. It is presented...

  7. Contribution of PIP-5 kinase Iα to raft-based FcγRIIA signaling

    International Nuclear Information System (INIS)

    Szymanska, Ewelina; Korzeniowski, Marek; Raynal, Patrick; Sobota, Andrzej; Kwiatkowska, Katarzyna

    2009-01-01

    Receptor FcγIIA (FcγRIIA) associates with plasma membrane rafts upon activation to trigger signaling cascades leading to actin polymerization. We examined whether compartmentalization of PI(4,5)P 2 and PI(4,5)P 2 -synthesizing PIP5-kinase Iα to rafts contributes to FcγRIIA signaling. A fraction of PIP5-kinase Iα was detected in raft-originating detergent-resistant membranes (DRM) isolated from U937 monocytes and other cells. The DRM of U937 monocytes contained also a major fraction of PI(4,5)P 2 . PIP5-kinase Iα bound PI(4,5)P 2 , and depletion of the lipid displaced PIP5-kinase Iα from the DRM. Activation of FcγRIIA in BHK transfectants led to recruitment of the kinase to the plasma membrane and enrichment of DRM in PI(4,5)P 2 . Immunofluorescence studies revealed that in resting cells the kinase was associated with the plasma membrane, cytoplasmic vesicles and the nucleus. After FcγRIIA activation, PIP5-kinase Iα and PI(4,5)P 2 co-localized transiently with the activated receptor at distinct cellular locations. Immunoelectron microscopy studies revealed that PIP5-kinase Iα and PI(4,5)P 2 were present at the edges of electron-dense assemblies containing activated FcγRIIA in their core. The data suggest that activation of FcγRIIA leads to membrane rafts coalescing into signaling platforms containing PIP5-kinase Iα and PI(4,5)P 2

  8. MMC with parallel-connected MOSFETs as an alternative to wide bandgap converters for LVDC distribution networks

    Directory of Open Access Journals (Sweden)

    Yanni Zhong

    2017-03-01

    Full Text Available Low-voltage direct-current (LVDC networks offer improved conductor utilisation on existing infrastructure and reduced conversion stages, which can lead to a simpler and more efficient distribution network. However, LVDC networks must continue to support AC loads, requiring efficient, low-distortion DC–AC converters. Additionally, increasing numbers of DC loads on the LVAC network require controlled, low-distortion, unity power factor AC-DC converters with large capacity, and bi-directional capability. An AC–DC/DC–AC converter design is therefore proposed in this study to minimise conversion loss and maximise power quality. Comparative analysis is performed for a conventional IGBT two-level converter, a SiC MOSFET two-level converter, a Si MOSFET modular multi-level converter (MMC and a GaN HEMT MMC, in terms of power loss, reliability, fault tolerance, converter cost and heatsink size. The analysis indicates that the five-level MMC with parallel-connected Si MOSFETs is an efficient, cost-effective converter for low-voltage converter applications. MMC converters suffer negligible switching loss, which enables reduced device switching without loss penalty from increased harmonics and filtering. Optimal extent of parallel-connection for MOSFETs in an MMC is investigated. Experimental results are presented to show the reduction in device stress and electromagnetic interference generating transients through the use of reduced switching and device parallel-connection.

  9. A dual-specificity isoform of the protein kinase inhibitor PKI produced by alternate gene splicing.

    Science.gov (United States)

    Kumar, Priyadarsini; Walsh, Donal A

    2002-03-15

    We have previously shown that the protein kinase inhibitor beta (PKIbeta) form of the cAMP-dependent protein kinase inhibitor exists in multiple isoforms, some of which are specific inhibitors of the cAMP-dependent protein kinase, whereas others also inhibit the cGMP-dependent enzyme [Kumar, Van Patten and Walsh (1997), J. Biol. Chem. 272, 20011-20020]. We have now demonstrated that the switch from a cAMP-dependent protein kinase (PKA)-specific inhibitor to one with dual specificity arises as a consequence of alternate gene splicing. We have confirmed using bacterially produced pure protein that a single inhibitor species has dual specificity for both PKA and cGMP-dependent protein kinase (PKG), inhibiting each with very high and closely similar inhibitory potencies. The gene splicing converted a protein with 70 amino acids into one of 109 amino acids, and did not change the inhibitory potency to PKA, but changed it from a protein that had no detectable PKG inhibitory activity to one that now inhibited PKG in the nanomolar range.

  10. Impact of the Voltage Transients after a Fast Power Abort on the Quench Detection System in the LHC Main Dipole Chain

    CERN Document Server

    Ravaioli, E; Formenti, F; Montabonnet, V; Pojer, M; Schmidt, R; Siemko, A; Solfaroli Camillocci, A; Steckert, J; Thiesen, H; Verweij, A

    2012-01-01

    A Fast Power Abort in the LHC superconducting main dipole circuit consists in the switch-off of the power converter and the opening of the two energy-extraction switches. Each energy-extraction unit is composed of redundant electromechanical breakers, which are opened to force the current through an extraction resistor. When a switch is opened arcing occurs in the switch and a voltage of up to 1 kV builds up across the extraction resistor with a typical ramp rate of about 80 kV/s. The subsequent voltage transient propagates through the chain of 154 dipoles and superposes on the voltage waves caused by the switch-off of the power converter. The resulting effect caused intermittent triggering of the quench protection systems along with heater firings in the magnets when the transient occurred during a ramp of the current. A delay between power converter switch-off and opening of the energy-extraction switches was introduced to prevent this effect. Furthermore, the output filters of the power converters were mod...

  11. The effect of oxygen storage capacity on the dynamic characteristics of an automotive catalytic converter

    International Nuclear Information System (INIS)

    Shamim, Tariq

    2008-01-01

    Automotive catalytic converters, which are employed to reduce engine exhaust emissions, are subjected to highly transient conditions during a typical driving cycle. These transient conditions arise from changes in driving mode, the hysteresis and flow lags of the feedback control system, and result in fluctuations of air-fuel ratio, exhaust gas flow rates and temperatures. The catalyst performance is also strongly influenced by the oxygen storage capacity. This paper presents a computational investigation of the effect of oxygen storage capacity on the dynamic behavior of an automotive catalytic converter subjected to modulations in exhaust gases. The modulations are generated by forcing the temporal variations in exhaust gases air-fuel ratio, gas flow rates and temperatures. The study employs a single-channel based, one-dimensional, non-adiabatic model. The results show that the imposed modulations cause a significant departure in the catalyst behavior from its steady behavior, and the oxygen storage capacity plays an important role in determining the catalyst's response to the imposed modulations. Modulations and oxygen storage capacity are found to have relatively greater influence on the catalyst's performance near stoichiometric conditions

  12. Transient Simulation of Wind Turbine Towers under Lightning Stroke

    Directory of Open Access Journals (Sweden)

    Xiaoqing Zhang

    2013-01-01

    Full Text Available A simulation algorithm is proposed in this paper for lightning transient analysis of the wind turbine (WT towers. In the proposed algorithm, the tower body is first subdivided into a discrete multiconductor system. A set of formulas are given to calculate the electrical parameters of the branches in the multiconductor system. By means of the electrical parameters, each branch unit in the multiconductor system is replaced as a coupled π-type circuit and the multiconductor system is converted into a circuit model. Then, the lightning transient responses can be obtained in different parts on the tower body by solving the circuit equations of the equivalent discretization network. The laboratory measurement is also made by a reduced-scale tower for checking the validity of the proposed algorithm.

  13. Simulated Switching Transients in the External Grid of Walney Offshore Wind Farm

    DEFF Research Database (Denmark)

    Arana Aristi, Iván; Johnsen, D. T.; Soerensen, T.

    2011-01-01

    . These switching operations were simulated using the EMT software PSCAD/EMTDC A number of parameters were varied in order to determine the most critical transients. Based on the results, it was concluded that the worst line-to-line transient overvoltage occurred in the DC05 and EF06 turbines, when a 25km cable......This paper presents the results of several simulations to assess the highest possible line-to-line overvoltage at the terminals of wind turbine converters after the switching operation of a cable or capacitor bank in the external grid of Walney 1, one of two phases of Walney Offshore Wind Farm...

  14. Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation.

    LENUS (Irish Health Repository)

    McEneaney, Victoria

    2010-01-01

    Aldosterone elicits transcriptional responses in target tissues and also rapidly stimulates the activation of protein kinase signalling cascades independently of de novo protein synthesis. Here we investigated aldosterone-induced cell proliferation and extra-cellular regulated kinase 1 and 2 (ERK1\\/2) mitogen activated protein (MAP) kinase signalling in the M1 cortical collecting duct cell line (M1-CCD). Aldosterone promoted the proliferative growth of M1-CCD cells, an effect that was protein kinase D1 (PKD1), PKCdelta and ERK1\\/2-dependent. Aldosterone induced the rapid activation of ERK1\\/2 with peaks of activation at 2 and 10 to 30 min after hormone treatment followed by sustained activation lasting beyond 120 min. M1-CCD cells suppressed in PKD1 expression exhibited only the early, transient peaks in ERK1\\/2 activation without the sustained phase. Aldosterone stimulated the physical association of PKD1 with ERK1\\/2 within 2 min of treatment. The mineralocorticoid receptor (MR) antagonist RU28318 inhibited the early and late phases of aldosterone-induced ERK1\\/2 activation, and also aldosterone-induced proliferative cell growth. Aldosterone induced the sub-cellular redistribution of ERK1\\/2 to the nuclei at 2 min and to cytoplasmic sites, proximal to the nuclei after 30 min. This sub-cellular distribution of ERK1\\/2 was inhibited in cells suppressed in the expression of PKD1.

  15. The human transient receptor potential vanilloid 3 channel is sensitized via the ERK pathway

    Czech Academy of Sciences Publication Activity Database

    Vyklická, Lenka; Boukalová, Štěpána; Mačíková, Lucie; Chvojka, Štěpán; Vlachová, Viktorie

    2017-01-01

    Roč. 292, č. 51 (2017), s. 21083-21091 ISSN 0021-9258 R&D Projects: GA ČR(CZ) GA15-15839S Institutional support: RVO:67985823 Keywords : epidermal growth factor receptor (EGFR) * extracellular-signal-regulated kinase (ERK) * keratinocyte * phosphorylation * transient receptor potential channels * TRP channels Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.125, year: 2016

  16. Preliminary design of the ITER AC/DC converters supplied by the Korean Domestic Agency

    International Nuclear Information System (INIS)

    Oh, J.S.; Choi, J.; Suh, J.H.; Liu, H.; Hwang, K.; Chung, I.; Lee, S.; Kang, J.; Park, H.; Jung, W.; Jo, S.; Gweon, H.; Lee, Y.; Lee, W.; Kim, J.B.; Han, S.H.; Hong, G.D.; Lee, J.S.; Lee, B.W.; Yeo, C.H.

    2013-01-01

    Highlights: ► A self-supporting aluminium structure and symmetrical thyristor assembly are devised to assure a strong and reliable ITER converter. ► Converters are designed to be installable in a compact space with three times higher power density than normal industrial installations. ► Heating of the building structure due to high magnetic field by converters are identified and certain solutions are addressed in the building design. ► A cooperative fast control scheme is adopted to compensate fast reactive power change of up to the level of 900 Mvar. -- Abstract: The preliminary design for ITER AC/DC converters under the responsibility of the Korean Domestic Agency is performed on the basis of the engineering experience of previous R and D for a full-scale 6-pulse CS (Central Solenoid) converter unit. This paper describes key features of the preliminary design for the respective sub-systems; integrated self-supporting aluminium structure and symmetrical thyristor assembly for strong and reliable converters, optimised impedance of the converter transformer to limit short circuit current, coaxial-type AC bus bars to shield high magnetic field around wall penetrations, compact components to fit into given building space. The insulation and the minimisation of electrical loops of concrete rebar below the converter installations are essential to prevent floor heating. Required output voltage or current of converters is provided by a conventional controller. A master controller is designed to collect predicted reactive powers from each converter and deliver processed data to the reactive power compensation (RPC) system to improve the regulation speed of the RPC controller with fast feed-forward compensation under fast reactive power transients

  17. Preliminary design of the ITER AC/DC converters supplied by the Korean Domestic Agency

    Energy Technology Data Exchange (ETDEWEB)

    Oh, J.S., E-mail: jsoh@nfri.re.kr [ITER Korea, National Fusion Research Institute, Daejeon 305-806 (Korea, Republic of); Choi, J.; Suh, J.H. [ITER Korea, National Fusion Research Institute, Daejeon 305-806 (Korea, Republic of); Liu, H.; Hwang, K.; Chung, I.; Lee, S.; Kang, J.; Park, H.; Jung, W.; Jo, S.; Gweon, H.; Lee, Y.; Lee, W. [Dawonsys Corp., Siheung 429-450 (Korea, Republic of); Kim, J.B.; Han, S.H.; Hong, G.D.; Lee, J.S.; Lee, B.W.; Yeo, C.H. [Hyosung Corp., 450, Gongdeok-Dong, Seoul 121-720 (Korea, Republic of); and others

    2013-10-15

    Highlights: ► A self-supporting aluminium structure and symmetrical thyristor assembly are devised to assure a strong and reliable ITER converter. ► Converters are designed to be installable in a compact space with three times higher power density than normal industrial installations. ► Heating of the building structure due to high magnetic field by converters are identified and certain solutions are addressed in the building design. ► A cooperative fast control scheme is adopted to compensate fast reactive power change of up to the level of 900 Mvar. -- Abstract: The preliminary design for ITER AC/DC converters under the responsibility of the Korean Domestic Agency is performed on the basis of the engineering experience of previous R and D for a full-scale 6-pulse CS (Central Solenoid) converter unit. This paper describes key features of the preliminary design for the respective sub-systems; integrated self-supporting aluminium structure and symmetrical thyristor assembly for strong and reliable converters, optimised impedance of the converter transformer to limit short circuit current, coaxial-type AC bus bars to shield high magnetic field around wall penetrations, compact components to fit into given building space. The insulation and the minimisation of electrical loops of concrete rebar below the converter installations are essential to prevent floor heating. Required output voltage or current of converters is provided by a conventional controller. A master controller is designed to collect predicted reactive powers from each converter and deliver processed data to the reactive power compensation (RPC) system to improve the regulation speed of the RPC controller with fast feed-forward compensation under fast reactive power transients.

  18. Phosphorylation of the Yeast Choline Kinase by Protein Kinase C

    Science.gov (United States)

    Choi, Mal-Gi; Kurnov, Vladlen; Kersting, Michael C.; Sreenivas, Avula; Carman, George M.

    2005-01-01

    The Saccharomyces cerevisiae CKI1-encoded choline kinase catalyzes the committed step in phosphatidylcholine synthesis via the Kennedy pathway. The enzyme is phosphorylated on multiple serine residues, and some of this phosphorylation is mediated by protein kinase A. In this work, we examined the hypothesis that choline kinase is also phosphorylated by protein kinase C. Using choline kinase as a substrate, protein kinase C activity was dose- and time-dependent, and dependent on the concentrations of choline kinase (Km = 27 μg/ml) and ATP (Km = 15 μM). This phosphorylation, which occurred on a serine residue, was accompanied by a 1.6-fold stimulation of choline kinase activity. The synthetic peptide SRSSS25QRRHS (Vmax/Km = 17.5 mM-1 μmol min-1 mg-1) that contains the protein kinase C motif for Ser25 was a substrate for protein kinase C. A Ser25 to Ala (S25A) mutation in choline kinase resulted in a 60% decrease in protein kinase C phosphorylation of the enzyme. Phosphopeptide mapping analysis of the S25A mutant enzyme confirmed that Ser25 was a protein kinase C target site. In vivo, the S25A mutation correlated with a decrease (55%) in phosphatidylcholine synthesis via the Kennedy pathway whereas an S25D phosphorylation site mimic correlated with an increase (44%) in phosphatidylcholine synthesis. Whereas the S25A (protein kinase C site) mutation did not affect the phosphorylation of choline kinase by protein kinase A, the S30A (protein kinase A site) mutation caused a 46% reduction in enzyme phosphorylation by protein kinase C. A choline kinase synthetic peptide (SQRRHS30LTRQ) containing Ser30 was a substrate (Vmax/Km = 3.0 mM−1 μmol min−1 mg−1) for protein kinase C. Comparison of phosphopeptide maps of the wild type and S30A mutant choline kinase enzymes phosphorylated by protein kinase C confirmed that Ser30 was also a target site for protein kinase C. PMID:15919656

  19. Radiation effects in a CMOS/SOS/Al-Gate D/A converter and on-chip diagnostic transistors

    International Nuclear Information System (INIS)

    Brucker, G.J.; Heagerty, W.

    1976-01-01

    This paper presents the results obtained from total dose and transient radiation tests on a CMOS/SOS/Al-Gate D/A converter and on-chip diagnostic transistors. Samples were irradiated by cobalt-60 gamma rays under worst-case conditions, and by 10-MeV electron pulses of 50-ns and 4.4-μs duration. Devices were fabricated with three different insulators; the two discussed here are standard wet oxide and a pyrogenic oxide. Test transistors on the D/A chips made it possible to diagnose the failure modes of the converter and to evaluate some special designs. These consisted of standard edge p- and n-channel transistors, edgeless units, edgeless tetrode transistors, and an edgeless type transmission gate with a diode clamp from substrate to gate. The total dose results indicate that the pyrogenic oxide increased the failure dose of the operational amplifier portion of the converter from 10 3 rads (Si) to 2 x 10 6 rads (Si); however, the sample and hold failed after exposure to a low level of 10 3 rads (Si). Test devices indicated this to be due to the radiation-induced leakage current of the transmission gate which discharges the sample and hold capacitor. The diode clamp decreased the threshold voltage shifts and the leakage currents. The edgeless devices improved the device performance because of a more abrupt turn-on. Narrow-pulse test data indicated that the edgeless units produced less photocurrent than the edge units by about a factor of three to four. Converter upset levels are less than or equal to 10 9 rads/s due to precision requirements which make a few millivolt transients untenable

  20. The effect of oxygen storage capacity on the dynamic characteristics of an automotive catalytic converter

    Energy Technology Data Exchange (ETDEWEB)

    Shamim, Tariq [Department of Mechanical Engineering, The University of Michigan-Dearborn, Dearborn, MI 48128-2406 (United States)

    2008-11-15

    Automotive catalytic converters, which are employed to reduce engine exhaust emissions, are subjected to highly transient conditions during a typical driving cycle. These transient conditions arise from changes in driving mode, the hysteresis and flow lags of the feedback control system, and result in fluctuations of air-fuel ratio, exhaust gas flow rates and temperatures. The catalyst performance is also strongly influenced by the oxygen storage capacity. This paper presents a computational investigation of the effect of oxygen storage capacity on the dynamic behavior of an automotive catalytic converter subjected to modulations in exhaust gases. The modulations are generated by forcing the temporal variations in exhaust gases air-fuel ratio, gas flow rates and temperatures. The study employs a single-channel based, one-dimensional, non-adiabatic model. The results show that the imposed modulations cause a significant departure in the catalyst behavior from its steady behavior, and the oxygen storage capacity plays an important role in determining the catalyst's response to the imposed modulations. Modulations and oxygen storage capacity are found to have relatively greater influence on the catalyst's performance near stoichiometric conditions. (author)

  1. Convertible bond valuation focusing on Chinese convertible bond market

    OpenAIRE

    Yang, Ke

    2010-01-01

    This paper mainly discusses the methods of valuation of convertible bonds in Chinese market. Different from common convertible bonds in European market, considering the complicate features of Chinese convertible bond, this paper represents specific pricing approaches for pricing convertible bonds with different provisions along with the increment of complexity of these provisions. More specifically, this paper represents the decomposing method and binomial tree method for pricing both of Non-...

  2. Tests on conducted electrical noise on a storage ring dc-dc converter cabinet

    International Nuclear Information System (INIS)

    Carwardine, J.J.

    1994-01-01

    Electrical noise is produced by switching transients in the power supply converters which excite resonances formed by stray capacitance and cable inductance. This noise is present not only on the load cables, but also on ground cables of the magnet and of the converter cabinet. Since there will eventually be a large number of cabinets running at one time, tests were carried out to characterize the noise and to investigate possible techniques for reducing the levels. The tests were carried out on the test girder and converter cabinet set up in 412 area. There were four magnets installed on the girder -- two 0.5m quadrupoles, a 0.8m quadrupole, and a sextupole. These tests were carried out on one of the 0.5m quadrupoles. It should be noted that with this setup, the raw dc power was supplied at around 70V. In the final configuration, a 0.5m quad will be fed from a 40V raw supply. Consequently, the switching transients observed during the tests are likely to be higher than will occur in reality. Noise currents contain two main components: a low frequency component at around 50kHz, and a higher frequency component at around lMHz. It is the latter component which is of primary concern. Currents measured on the dc load cables typically were around one ampere, while currents into the building ground system were only a few tens of milliamps. Several methods were used to try reducing the noise currents, but only the addition of a series impedance was successful -- other methods either had no effect or increased the ground currents

  3. A Sensorless Predictive Current Controlled Boost Converter by Using an EKF with Load Variation Effect Elimination Function.

    Science.gov (United States)

    Tong, Qiaoling; Chen, Chen; Zhang, Qiao; Zou, Xuecheng

    2015-04-28

    To realize accurate current control for a boost converter, a precise measurement of the inductor current is required to achieve high resolution current regulating. Current sensors are widely used to measure the inductor current. However, the current sensors and their processing circuits significantly contribute extra hardware cost, delay and noise to the system. They can also harm the system reliability. Therefore, current sensorless control techniques can bring cost effective and reliable solutions for various boost converter applications. According to the derived accurate model, which contains a number of parasitics, the boost converter is a nonlinear system. An Extended Kalman Filter (EKF) is proposed for inductor current estimation and output voltage filtering. With this approach, the system can have the same advantages as sensored current control mode. To implement EKF, the load value is necessary. However, the load may vary from time to time. This can lead to errors of current estimation and filtered output voltage. To solve this issue, a load variation elimination effect elimination (LVEE) module is added. In addition, a predictive average current controller is used to regulate the current. Compared with conventional voltage controlled system, the transient response is greatly improved since it only takes two switching cycles for the current to reach its reference. Finally, experimental results are presented to verify the stable operation and output tracking capability for large-signal transients of the proposed algorithm.

  4. Automatic shape recognition of a fast transient signal

    International Nuclear Information System (INIS)

    Charles, Gilbert.

    1976-01-01

    A system was developed to recognize if the shape of a signal x(t) is similar (or identical) to the one of an element yi(t) of an ensemble S composed by N known signals, that are memorised. x(t) is a time limited T 2 ) give the similarity measure of two signals. To solve the problem of the digital recording of the signals x(t) two devices were realized: a digital-to-analog converter which permits the recording of fast transient signals (band pass>1GHz, sampling-frequency approximately 100GHz, resolution: 9 bits, 576 samples); an automatic attenuator which scales the signal x(t) before the digitalization (the band pass is 70MHz at -1dB). A theoretical analysis permits to determine what must be the resolution of the digital-to-analog converter as a fonction of the signal-caracteristics and of the wanted precision for the calculus of rho 2 [fr

  5. Estimation of the Plant Time Constant of Current-Controlled Voltage Source Converters

    DEFF Research Database (Denmark)

    Vidal, Ana; Yepes, Alejandro G.; Malvar, Jano

    2014-01-01

    Precise knowledge of the plant time constant is essential to perform a thorough analysis of the current control loop in voltage source converters (VSCs). As the loop behavior can be significantly influenced by the VSC working conditions, the effects associated to converter losses should be included...... in the model, through an equivalent series resistance. In a recent work, an algorithm to identify this parameter was developed, considering the inductance value as known and practically constant. Nevertheless, the plant inductance can also present important uncertainties with respect to the inductance...... of the VSC interface filter measured at rated conditions. This paper extends that method so that both parameters of the plant time constant (resistance and inductance) are estimated. Such enhancement is achieved through the evaluation of the closed-loop transient responses of both axes of the synchronous...

  6. A Comparative Study on Controllers for Improving Transient Stability of DFIG Wind Turbines During Large Disturbances

    Directory of Open Access Journals (Sweden)

    Minh Quan Duong

    2018-02-01

    Full Text Available Under power system short-circuits, the Doubly-Fed Induction Generator (DFIG Wind Turbines (WT are required to be equipped with crowbar protections to preserve the lifetime of power electronics devices. When the crowbar is switched on, the rotor windings are short-circuited. In this case, the DFIG behaves like a squirrel-cage induction generator (SCIG and can adsorb reactive power, which can affect the power system. A DFIG based-fault-ride through (FRT scheme with crowbar, rotor-side and grid-side converters has recently been proposed for improving the transient stability: in particular, a hybrid cascade Fuzzy-PI-based controlling technique has been demonstrated to be able to control the Insulated Gate Bipolar Transistor (IGBT based frequency converter in order to enhance the transient stability. The performance of this hybrid control scheme is analyzed here and compared to other techniques, under a three-phase fault condition on a single machine connected to the grid. In particular, the transient operation of the system is investigated by comparing the performance of the hybrid system with conventional proportional-integral and fuzzy logic controller, respectively. The system validation is carried out in Simulink, confirming the effectiveness of the coordinated advanced fuzzy logic control.

  7. A novel synthetic test system for thyristor level in the converter valve of HVDC power transmission

    Directory of Open Access Journals (Sweden)

    Liu Longchen

    2016-01-01

    Full Text Available The converter valve is the core equipment in the HVDC power transmission system, a+-nd its performance has a direct effect on the reliability, stability and efficiency of the whole power system. As the basic unit of HVDC converter valve, the thyristor level needs to be test routinely in order to grasp the state of the converter valve equipment. Therefore, it is urgent to develop a novel synthetic test system for the thyristor level with thyristor control unit (TCU. However, currently there is no specific test scheme for the thyristor level of HVDC converter valve. In this paper, the synthetic test principle, content and methods for the thyristor level with TCU are presented based on the analysis of the thyristor reverse recovery characteristic and the IEC technology standard. And a transient high-voltage pulse is applied to the thyristor level during its reverse recovery period in order to test the characteristics of thyristor level. Then, the synthetic test system for the thyristor level is applied to the converter valve test of ±800 kV HVDC power transmission project, and the practical test result verifies the reasonability and validity of the proposed synthetic test system.

  8. Novel receptor-like protein kinases induced by Erwinia carotovora and short oligogalacturonides in potato.

    Science.gov (United States)

    Montesano, M; Kõiv, V; Mäe, A; Palva, E T

    2001-11-01

    summary Identification of potato genes responsive to cell wall-degrading enzymes of Erwinia carotovora resulted in the isolation of cDNA clones for four related receptor-like protein kinases. One of the putative serine-threonine protein kinases might have arisen through alternative splicing. These potato receptor-like kinases (PRK1-4) were highly equivalent (91-99%), most likely constituting a family of related receptors. All PRKs and four other plant RLKs share in their extracellular domain a conserved bi-modular pattern of cysteine repeats distinct from that in previously characterized plant RLKs, suggesting that they represent a new class of receptors. The corresponding genes were rapidly induced by E. carotovora culture filtrate (CF), both in the leaves and tubers of potato. Furthermore, the genes were transiently induced by short oligogalacturonides. The structural identity of PRKs and their induction pattern suggested that they constitute part of the early response of potato to E. carotovora infection.

  9. RhMKK9, a rose MAP KINASE KINASE gene, is involved in rehydration-triggered ethylene production in rose gynoecia.

    Science.gov (United States)

    Chen, Jiwei; Zhang, Qian; Wang, Qigang; Feng, Ming; Li, Yang; Meng, Yonglu; Zhang, Yi; Liu, Guoqin; Ma, Zhimin; Wu, Hongzhi; Gao, Junping; Ma, Nan

    2017-02-23

    Flower opening is an important process in the life cycle of flowering plants and is influenced by various endogenous and environmental factors. Our previous work demonstrated that rose (Rosa hybrida) flowers are highly sensitive to dehydration during flower opening and the water recovery process after dehydration induced ethylene production rapidly in flower gynoecia. In addition, this temporal- and spatial-specific ethylene production is attributed to a transient but robust activation of the rose MAP KINASE6-ACC SYNTHASE1 (RhMPK6-RhACS1) cascade in gynoecia. However, the upstream component of RhMPK6-RhACS1 is unknown, although RhMKK9 (MAP KINASE KINASE9), a rose homologue of Arabidopsis MKK9, could activate RhMPK6 in vitro. In this study, we monitored RhMKK2/4/5/9 expression, the potential upstream kinase to RhMPK6, in rose gynoecia during dehydration and rehydration. We found only RhMKK9 was rapidly and strongly induced by rehydration. Silencing of RhMKK9 significantly decreased rehydration-triggered ethylene production. Consistently, the expression of several ethylene-responsive genes was down regulated in the petals of RhMKK9-silenced flowers. Moreover, we detected the DNA methylation level in the promoter and gene body of RhMKK9 by Chop-PCR. The results showed that rehydration specifically elevated the DNA methylation level on the RhMKK9 gene body, whereas it resulted in hypomethylation in its promoter. Our results showed that RhMKK9 possibly acts as the upstream component of the RhMKK9-RhMPK6-RhACS1 cascade and is responsible for water recovery-triggered ethylene production in rose gynoecia, and epigenetic DNA methylation is involved in the regulation of RhMKK9 expression by rehydration.

  10. Combined 15N-Labeling and TandemMOAC Quantifies Phosphorylation of MAP Kinase Substrates Downstream of MKK7 in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Nicola V. Huck

    2017-12-01

    Full Text Available Reversible protein phosphorylation is a widespread posttranslational modification that plays a key role in eukaryotic signal transduction. Due to the dynamics of protein abundance, low stoichiometry and transient nature of protein phosphorylation, the detection and accurate quantification of substrate phosphorylation by protein kinases remains a challenge in phosphoproteome research. Here, we combine tandem metal-oxide affinity chromatography (tandemMOAC with stable isotope 15N metabolic labeling for the measurement and accurate quantification of low abundant, transiently phosphorylated peptides by mass spectrometry. Since tandemMOAC is not biased toward the enrichment of acidophilic, basophilic, or proline-directed kinase substrates, the method is applicable to identify targets of all these three types of protein kinases. The MKK7-MPK3/6 module, for example, is involved in the regulation of plant development and plant basal and systemic immune responses, but little is known about downstream cascade components. Using our here described phosphoproteomics approach we identified several MPK substrates downstream of the MKK7-MPK3/6 phosphorylation cascade in Arabidopsis. The identification and validation of dynamin-related protein 2 as a novel phosphorylation substrate of the MKK7-MPK3/6 module establishes a novel link between MPK signaling and clathrin-mediated vesicle trafficking.

  11. Off-shore wind power plant modelling precision and efficiency in electromagnetic transient simulation programs

    Energy Technology Data Exchange (ETDEWEB)

    Karaagac, U.; Saad, H.; Mahseredjian, J. [Ecole Polytechnique de Montreal, Montreal, QC (Canada); Jensen, S.; Cai, L. [REpower Systems AG, Hamburg (Germany)

    2012-07-01

    The large number of switching elements in the modular multilevel converter (MMC) is a challenging problem for modeling the MMC-HVDC systems in electromagnetic transient type (EMT-type) programs. The modeling complexity increases even further when MMC-HVDC systems are used to integrate offshore wind farms (OWFs) with power electronics based wind energy converters, such as doubly-fed induction generators (DFIGs). This paper compares the computational performances of various combinations of MMC-HVDC and OWF models. Practical onshore ac fault scenarios are simulated for an OWF composed of DFIG type wind turbines and connected to a practical ac grid through a point-to-point MMC-HVDC system. (orig.)

  12. Modeling and reliability analysis of three phase z-source AC-AC converter

    Directory of Open Access Journals (Sweden)

    Prasad Hanuman

    2017-12-01

    Full Text Available This paper presents the small signal modeling using the state space averaging technique and reliability analysis of a three-phase z-source ac-ac converter. By controlling the shoot-through duty ratio, it can operate in buck-boost mode and maintain desired output voltage during voltage sag and surge condition. It has faster dynamic response and higher efficiency as compared to the traditional voltage regulator. Small signal analysis derives different control transfer functions and this leads to design a suitable controller for a closed loop system during supply voltage variation. The closed loop system of the converter with a PID controller eliminates the transients in output voltage and provides steady state regulated output. The proposed model designed in the RT-LAB and executed in a field programming gate array (FPGA-based real-time digital simulator at a fixedtime step of 10 μs and a constant switching frequency of 10 kHz. The simulator was developed using very high speed integrated circuit hardware description language (VHDL, making it versatile and moveable. Hardware-in-the-loop (HIL simulation results are presented to justify the MATLAB simulation results during supply voltage variation of the three phase z-source ac-ac converter. The reliability analysis has been applied to the converter to find out the failure rate of its different components.

  13. Study of transient states in thermo-ionic converters; Etude des regimes transitoires des convertisseurs thermoioniques

    Energy Technology Data Exchange (ETDEWEB)

    Landrot, J [Commissariat a l' Energie Atomique, 91 - Saclay (France). Centre d' Etudes Nucleaires

    1968-07-01

    In order to control a thermo-ionic reactor, it is necessary to know the dynamic influence of four fundamental parameters: the injected thermal power, the electrical charge resistance, the temperature of the cesium and the thermal exchange coefficient of the collector cooling circuit. The principles of the thermo-ionic converter are briefly exposed. The over-riding influence of the first two parameters is shown with the help of experimental static readings. These two parameters are then made to vary in turn. The laws of variation as a function of the time, of the electrical power produced and of the temperature of the various parts of the converter are deduced. (author) [French] Pour envisager le controle et la regulation d'un reacteur thermoionique, il est necessaire de connaitre l'influence dynamique de quatre parametres fondamentaux: puissance thermique injectee, resistance electrique de charge, temperature de cesium et coefficient d'echange thermique du circuit de refroidissement du collecteur. On rappelle brievement les principes du convertisseur thermoionique. A l'aide de releves statiques experimentaux, on montre l'influence preponderante des deux premiers parametres. On fait ensuite varier successivement ces deux parametres. On met en evidence les lois de variation en fonction du temps de la puissance electrique produite et de la temperature des differents points du convertisseur. (auteur)

  14. Transient stability enhancement of wind farms connected to a multi-machine power system by using an adaptive ANN-controlled SMES

    International Nuclear Information System (INIS)

    Muyeen, S.M.; Hasanien, Hany M.; Al-Durra, Ahmed

    2014-01-01

    Highlights: • We present an ANN-controlled SMES in this paper. • The objective is to enhance transient stability of WF connected to power system. • The control strategy depends on a PWM VSC and DC–DC converter. • The effectiveness of proposed controller is compared with PI controller. • The validity of the proposed system is verified by simulation results. - Abstract: This paper presents a novel adaptive artificial neural network (ANN)-controlled superconducting magnetic energy storage (SMES) system to enhance the transient stability of wind farms connected to a multi-machine power system during network disturbances. The control strategy of SMES depends mainly on a sinusoidal pulse width modulation (PWM) voltage source converter (VSC) and an adaptive ANN-controlled DC–DC converter using insulated gate bipolar transistors (IGBTs). The effectiveness of the proposed adaptive ANN-controlled SMES is then compared with that of proportional-integral (PI)-controlled SMES optimized by response surface methodology and genetic algorithm (RSM–GA) considering both of symmetrical and unsymmetrical faults. For realistic responses, real wind speed data and two-mass drive train model of wind turbine generator system is considered in the analyses. The validity of the proposed system is verified by the simulation results which are performed using the laboratory standard dynamic power system simulator PSCAD/EMTDC. Notably, the proposed adaptive ANN-controlled SMES enhances the transient stability of wind farms connected to a multi-machine power system

  15. Autoregulation of kinase dephosphorylation by ATP binding in AGC protein kinases.

    Science.gov (United States)

    Chan, Tung O; Pascal, John M; Armen, Roger S; Rodeck, Ulrich

    2012-02-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non- ATP-competitive kinase inhibitors that discriminate within and between protein kinase families.

  16. Model Predictive Control of Power Converters for Robust and Fast Operation of AC Microgrids

    DEFF Research Database (Denmark)

    Dragicevic, Tomislav

    2018-01-01

    the load power at the same time. Those functionalities are conventionally achieved by hierarchical linear control loops. However, they have limited transient response and high sensitivity to parameter variations. This paper aims to mitigate these problems by firstly introducing an improvement of the FCS......This paper proposes the application of a finite control set model predictive control (FCS-MPC) strategy in standalone ac microgrids (MGs). AC MGs are usually built from two or more voltage source converters (VSCs) which can regulate the voltage at the point of common coupling, while sharing......-MPC strategy for a single VSC based on tracking of derivative of the voltage reference trajectory. Using only a single step prediction horizon, the proposed strategy exhibits low computational expense but provides steady state performance comparable to PWM, while its transient response and robustness...

  17. Autoregulation of kinase dephosphorylation by ATP binding to AGC protein kinases

    Science.gov (United States)

    Pascal, John M; Armen, Roger S

    2012-01-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non-ATP-competitive kinase inhibitors that discriminate within and between protein kinase families. PMID:22262182

  18. Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia.

    Science.gov (United States)

    Roth Flach, Rachel J; Danai, Laura V; DiStefano, Marina T; Kelly, Mark; Menendez, Lorena Garcia; Jurczyk, Agata; Sharma, Rohit B; Jung, Dae Young; Kim, Jong Hun; Kim, Jason K; Bortell, Rita; Alonso, Laura C; Czech, Michael P

    2016-07-29

    Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced β cell mass, fewer proliferating β cells and reduced islet-specific gene mRNA expression compared with controls, although insulin content was normal. Interestingly, the reduced plasma insulin in M4K4 iKO mice exposed to chronic (16 weeks) HFD was not observed in response to acute HFD challenge or short term treatment with the insulin receptor antagonist S961. Furthermore, the improved insulin sensitivity in obese M4K4 iKO mice was abrogated by high exogenous insulin over the course of a euglycemic clamp study, indicating that hypoinsulinemia promotes insulin sensitivity in chronically obese M4K4 iKO mice. These results demonstrate that protein kinase Map4k4 drives obesity-induced hyperinsulinemia and insulin resistance in part by promoting insulin secretion from β cells in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Kinases and Cancer

    OpenAIRE

    Jonas Cicenas; Egle Zalyte; Amos Bairoch; Pascale Gaudet

    2018-01-01

    Protein kinases are a large family of enzymes catalyzing protein phosphorylation. The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases [...

  20. Study of transient states in thermo-ionic converters; Etude des regimes transitoires des convertisseurs thermoioniques

    Energy Technology Data Exchange (ETDEWEB)

    Landrot, J. [Commissariat a l' Energie Atomique, 91 - Saclay (France). Centre d' Etudes Nucleaires

    1968-07-01

    In order to control a thermo-ionic reactor, it is necessary to know the dynamic influence of four fundamental parameters: the injected thermal power, the electrical charge resistance, the temperature of the cesium and the thermal exchange coefficient of the collector cooling circuit. The principles of the thermo-ionic converter are briefly exposed. The over-riding influence of the first two parameters is shown with the help of experimental static readings. These two parameters are then made to vary in turn. The laws of variation as a function of the time, of the electrical power produced and of the temperature of the various parts of the converter are deduced. (author) [French] Pour envisager le controle et la regulation d'un reacteur thermoionique, il est necessaire de connaitre l'influence dynamique de quatre parametres fondamentaux: puissance thermique injectee, resistance electrique de charge, temperature de cesium et coefficient d'echange thermique du circuit de refroidissement du collecteur. On rappelle brievement les principes du convertisseur thermoionique. A l'aide de releves statiques experimentaux, on montre l'influence preponderante des deux premiers parametres. On fait ensuite varier successivement ces deux parametres. On met en evidence les lois de variation en fonction du temps de la puissance electrique produite et de la temperature des differents points du convertisseur. (auteur)

  1. Nicotinamide riboside kinase structures reveal new pathways to NAD+.

    Directory of Open Access Journals (Sweden)

    Wolfram Tempel

    2007-10-01

    Full Text Available The eukaryotic nicotinamide riboside kinase (Nrk pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+ by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.

  2. Effect of heat and mass transfer coefficients on the performance of automotive catalytic converters

    Energy Technology Data Exchange (ETDEWEB)

    Shamim, T. [Michigan Univ., Dept. of Mechanical Engineering, Dearborn, MI (United States)

    2003-06-01

    This paper numerically investigates the role of heat and mass transfer coefficients on the performance of automotive catalytic converters, which are employed to reduce engine exhaust emissions. The pollutant conversion performance of a converter is influenced by a number of physical and chemical processes that take place in gaseous and solid phases as the exhaust gases flow through the catalyst. A quantitative predictive understanding of these complex catalyst processes involving flow dynamics, heterogeneous surface reactions and heat and mass transport mechanisms is important in improving the converter design. The role of convective transport phenomena becomes important at high temperature when the mass transfer becomes rate-limiting to an increasing extent. The objective of the present study is to elucidate the influence of convective heat and mass transfer coefficients (mechanisms). The mathematical model considers the conservation of mass, momentum and energy in both gaseous and solid phases. In addition to the heterogeneous surface reactions, the model also takes into account the adsorption/desorption of oxygen in the catalyst during non-stoichiometric composition of air/fuel mixtures. The governing equations are solved by an implicit scheme using a successive line under a relaxation method. The converter performance under the transient conditions as simulated by the US Federal Test Procedure (US-FTP) is analysed. (Author)

  3. A High Affinity Adenosine Kinase from Anopheles gambiae

    Science.gov (United States)

    Cassera, María B.; Ho, Meng-Chiao; Merino, Emilio F.; Burgos, Emmanuel S.; Rinaldo-Matthis, Agnes; Almo, Steven C.; Schramm, Vern L.

    2011-01-01

    Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (Km 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap4A (2.0 Å resolution) reveals interactions for adenosine, ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg2+ ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layered α/β/α sandwich, and a small cap domain in contact with adenosine. The specificity and tight-binding for adenosine arises from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168 and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64 and Asn68 and the ribosyl 2′- and 3′-hydroxyl groups. The structure is more similar to human adenosine kinase (48% identity) than to AK from Toxoplasma gondii (31% identity). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role of this enzyme to maintain the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects. PMID:21247194

  4. Streptococcus thermophilus bacteraemia in a patient with transient bowel ischaemia secondary to polycythaemia

    OpenAIRE

    Stephens, Joanna; Turner, David P.J.

    2015-01-01

    Introduction: The ability of Streptococcus thermophilus to convert lactose into lactic acid has long been utilised by the dairy industry. A seemingly low-pathogenicity organism, there have been no previously published reports linking the consumption of foodstuffs to bacteraemia with this bacterium.\\ud Case Presentation: Here we present a case of a regular consumer of Activia yoghurt who developed S. thermophilus bacteraemia probably due to transient bowel ischaemia secondary to polycythaemia....

  5. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients

    NARCIS (Netherlands)

    Chang, Betty Y.; Francesco, Michelle; de Rooij, Martin F. M.; Magadala, Padmaja; Steggerda, Susanne M.; Huang, Min Mei; Kuil, Annemieke; Herman, Sarah E. M.; Chang, Stella; Pals, Steven T.; Wilson, Wyndham; Wiestner, Adrian; Spaargaren, Marcel; Buggy, Joseph J.; Elias, Laurence

    2013-01-01

    Ibrutinib (PCI-32765) is a highly potent oral Bruton tyrosine kinase (BTK) inhibitor in clinical development for treating B-cell lymphoproliferative diseases. Patients with chronic lymphocytic leukemia (CLL) often show marked, transient increases of circulating CLL cells following ibrutinib

  6. Mechanisms of polyphosphate glucokinase and polyphosphate kinase reactions

    International Nuclear Information System (INIS)

    Pepin, C.A.; Robinson, N.A.; Wood, H.G.

    1986-01-01

    Polyphosphate glucokinase [poly(P)GK] catalyzes the following reaction: poly(P)/sub n/ + glucose → poly(P)/sub n-1/ + G-6-P. With long chain poly(P) [n=750 to 400] the mechanism appeared to be processive, in which there is phosphorylation of glucose without release of intermediate sizes of the poly(P) until the chain is about 100, thereafter there were intermediate sizes formed apparently by a non-processive process. Poly(P) kinase catalyzes the following reaction: ATP + poly(P)/sub n/ ↔ ADP + poly(P)/sub n + 1/. Using short chain 32 [P] poly(P) as a primer and non-radioactive ATP, long chain poly(P) is formed processively. The resulting chain has a short length labeled with 32 [P] contributed by the primer on one end and the remainder is made up of unlabeled (P) from the ATP. The authors have used this 32 [P] poly(P) as a substrate with poly(P)GK. If the mechanism of the poly(P)GK were initially processive, there would be a 50% chance the phosphate would be utilized from the unlabeled end and 50% of the 32 [P] would remain in the shortened chain. However, all the 32 [P] was lost when 20% of the poly(P) was converted to G-6-P. In contrast, with poly(P) kinase, the % of poly(P) utilized was equivalent to the % of 32 [P] converted to ATP, which is consistent with a strictly processive mechanism. Even though the mechanism of poly(P)GK appeared to be processive with long chains, the on and off rate of poly(P) from the enzyme is such that there is random removal of (P) from both ends of the poly(P) chain

  7. Wavelength converter technology

    DEFF Research Database (Denmark)

    Kloch, Allan; Hansen, Peter Bukhave; Poulsen, Henrik Nørskov

    1999-01-01

    Wavelength conversion is important since it ensures full flexibility of the WDM network layer. Progress in optical wavelength converter technology is reviewed with emphasis on all-optical wavelength converter types based on semiconductor optical amplifiers.......Wavelength conversion is important since it ensures full flexibility of the WDM network layer. Progress in optical wavelength converter technology is reviewed with emphasis on all-optical wavelength converter types based on semiconductor optical amplifiers....

  8. The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma.

    Science.gov (United States)

    Evans, Robert P; Naber, Claudia; Steffler, Tara; Checkland, Tamara; Maxwell, Christopher A; Keats, Jonathan J; Belch, Andrew R; Pilarski, Linda M; Lai, Raymond; Reiman, Tony

    2008-02-01

    Aurora kinases are potential targets for cancer therapy. Previous studies have validated Aurora kinase A as a therapeutic target in multiple myeloma (MM), and have demonstrated in vitro anti-myeloma effects of small molecule Aurora kinase inhibitors that inhibit both Aurora A and B. This study demonstrated that Aurora B kinase was strongly expressed in myeloma cell lines and primary plasma cells. The selective Aurora B inhibitor AZD1152-induced apoptotic death in myeloma cell lines at nanomolar concentrations, with a cell cycle phenotype consistent with that reported previously for Aurora B inhibition. In some cases, AZD1152 in combination with dexamethasone showed increased anti-myeloma activity compared with the use of either agent alone. AZD1152 was active against sorted CD138(+) BM plasma cells from myeloma patients but also, as expected, was toxic to CD138(-) marrow cells from the same patients. In a murine myeloma xenograft model, AZD1152-inhibited tumour growth at well-tolerated doses and induced cell death in established tumours, with associated mild, transient leucopenia. AZD1152 shows promise in these preclinical studies as a novel treatment for MM.

  9. Modeling and Control of DC/DC Boost Converter using K-Factor Control for MPPT of Solar PV System

    DEFF Research Database (Denmark)

    Vangari, Adithya; Haribabu, Divyanagalakshmi; Sakamuri, Jayachandra N.

    2015-01-01

    This paper is focused on the design of a controller for the DC/DC boost converter using K factor control, which is based on modified PI control method, for maximum power point tracking (MPPT) of solar PV system. A mathematical model for boost converter based on small signal averaging approach...... is presented. Design of the passive elements of the boost converter as per the system specifications is also illustrated. The performance of the proposed K factor control method is verified with the simulations for MPPT on solar PV system at different atmospheric conditions. A new circuit based model for solar...... PV array, which includes the effect of solar insolation and temperature on PV array output, for the application in power system transient simulations, is also presented. The performance of the PV array model is verified with simulations at different atmospheric conditions. A 160W PV module from BP...

  10. A 380 V High Efficiency and High Power Density Switched-Capacitor Power Converter using Wide Band Gap Semiconductors

    DEFF Research Database (Denmark)

    Fan, Lin; Knott, Arnold; Jørgensen, Ivan Harald Holger

    2018-01-01

    . This paper presents such a high voltage low power switched-capacitor DC-DC converter with an input voltage upto 380 V (compatible with rectified European mains) and an output power experimentally validated up to 21.3 W. The wideband gap semiconductor devices of GaN switches and SiC diodes are combined...... to compose the proposed power stage. Their switching and loss characteristics are analyzed with transient waveforms and thermal images. Different isolated driving circuits are compared and a compact isolated halfbridge driving circuit is proposed. The full-load efficiencies of 98.3% and 97.6% are achieved......State-of-the-art switched-capacitor DC-DC power converters mainly focus on low voltage and/or high power applications. However, at high voltage and low power levels, new designs are anticipated to emerge and a power converter that has both high efficiency and high power density is highly desirable...

  11. X-Y Converter Family

    DEFF Research Database (Denmark)

    Bhaskar, Mahajan Sagar; Sanjeevikumar, Padmanaban; Wheeler, Patrick

    2016-01-01

    A New breed of a buck boost converter, named as the XY converter family is proposed in this article. In the XY family, 16 topologies are presented which are highly suitable for renewable energy applications which require a high ratio of DC-DC converter; such as a photovoltaic multilevel inverter...... system, high voltage automotive applications and industrial drives. Compared to the traditional boost converter and existing recent converters, the proposed XY converter family has the ability to provide a higher output voltage by using less number of power devices and reactive components. Other distinct...... features of the XY converter family are i) Single control switch ii) Provide negative output voltage iii) Non-isolated topologies iv) High conversion ratio without making the use of high duty cycle and v) modular structure. XY family is compared with the recent high step-up converters and the detailed...

  12. Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1 by Diacylglycerol (DAG

    Directory of Open Access Journals (Sweden)

    Oh Seog

    2008-10-01

    Full Text Available Abstract The capsaicin receptor, known as transient receptor potential channel vanilloid subtype 1 (TRPV1, is activated by a wide range of noxious stimulants and putative ligands such as capsaicin, heat, pH, anandamide, and phosphorylation by protein kinase C (PKC. However, the identity of endogenous activators for TRPV1 under physiological condition is still debated. Here, we report that diacylglycerol (DAG directly activates TRPV1 channel in a membrane-delimited manner in rat dorsal root ganglion (DRG neurons. 1-oleoyl-2-acetyl-sn-glycerol (OAG, a membrane-permeable DAG analog, elicited intracellular Ca2+ transients, cationic currents and cobalt uptake that were blocked by TRPV1-selective antagonists, but not by inhibitors of PKC and DAG lipase in rat DRG neurons or HEK 293 cells heterologously expressing TRPV1. OAG induced responses were about one fifth of capsaicin induced signals, suggesting that OAG displays partial agonism. We also found that endogenously produced DAG can activate rat TRPV1 channels. Mutagenesis of rat TRPV1 revealed that DAG-binding site is at Y511, the same site for capsaicin binding, and PtdIns(4,5P2binding site may not be critical for the activation of rat TRPV1 by DAG in heterologous system. We propose that DAG serves as an endogenous ligand for rat TRPV1, acting as an integrator of Gq/11-coupled receptors and receptor tyrosine kinases that are linked to phospholipase C.

  13. The integrated circuit IC EMP transient state disturbance effect experiment method investigates

    International Nuclear Information System (INIS)

    Li Xiaowei

    2004-01-01

    Transient state disturbance characteristic study on the integrated circuit, IC, need from its coupling path outset. Through cable (aerial) coupling, EMP converts to an pulse current voltage and results in the impact to the integrated circuit I/O orifice passing the cable. Aiming at the armament system construction feature, EMP effect to the integrated circuit, IC inside the system is analyzed. The integrated circuit, IC EMP effect experiment current injection method is investigated and a few experiments method is given. (authors)

  14. Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

    Science.gov (United States)

    Jun, Jesse E.; Yang, Ming; Chen, Hang; Chakraborty, Arup K.

    2013-01-01

    Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation. PMID:23589333

  15. Oncogenic Receptor Tyrosine Kinases Directly Phosphorylate Focal Adhesion Kinase (FAK) as a Resistance Mechanism to FAK-Kinase Inhibitors.

    Science.gov (United States)

    Marlowe, Timothy A; Lenzo, Felicia L; Figel, Sheila A; Grapes, Abigail T; Cance, William G

    2016-12-01

    Focal adhesion kinase (FAK) is a major drug target in cancer and current inhibitors targeted to the ATP-binding pocket of the kinase domain have entered clinical trials. However, preliminary results have shown limited single-agent efficacy in patients. Despite these unfavorable data, the molecular mechanisms that drive intrinsic and acquired resistance to FAK-kinase inhibitors are largely unknown. We have demonstrated that receptor tyrosine kinases (RTK) can directly bypass FAK-kinase inhibition in cancer cells through phosphorylation of FAK's critical tyrosine 397 (Y397). We also showed that HER2 forms a direct protein-protein interaction with the FAK-FERM-F1 lobe, promoting direct phosphorylation of Y397. In addition, FAK-kinase inhibition induced two forms of compensatory RTK reprogramming: (i) the rapid phosphorylation and activation of RTK signaling pathways in RTK High cells and (ii) the long-term acquisition of RTKs novel to the parental cell line in RTK Low cells. Finally, HER2 +: cancer cells displayed resistance to FAK-kinase inhibition in 3D growth assays using a HER2 isogenic system and HER2 + cancer cell lines. Our data indicate a novel drug resistance mechanism to FAK-kinase inhibitors whereby HER2 and other RTKs can rescue and maintain FAK activation (pY397) even in the presence of FAK-kinase inhibition. These data may have important ramifications for existing clinical trials of FAK inhibitors and suggest that individual tumor stratification by RTK expression would be important to predict patient response to FAK-kinase inhibitors. Mol Cancer Ther; 15(12); 3028-39. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Conversion tool for the LWR transient analysis code RELAP5 from the CDC version to the FACOM version

    International Nuclear Information System (INIS)

    Shinozawa, Naohisa; Fujisaki, Masahide; Makino, Mitsuhiro; Kondou, Kazuya; Ishiguro, Misako

    1987-01-01

    The LWR transient analysis code RELAP5 has been developed on the CDC-CYBER 176 at Idaho National Engineering Laboratory (INEL), the RELAP5 code has been often updated in order to extend the analyzing model and correct the errors. At Japan Atomic Energy Research Institute the code has been converted from the CDC version to the FACOM version and the converted code has been used. The conversion is the task which consumes a lot of time, because the code is large and there is the difference between CDC's machines and FACOM's ones. In order to convert the RELAP5 code automatically, the software tool has been developed. By using this tools the efficiency for converting the RELAP5 code has been improved. Productivity of the conversion is increased about 2.0 to 2.6 times by the tools in comparison with in manual. The procedure of conversion by using the tools and the option parameters of each tool are described. (author)

  17. Computer-aided methods of determining thyristor thermal transients

    International Nuclear Information System (INIS)

    Lu, E.; Bronner, G.

    1988-08-01

    An accurate tracing of the thyristor thermal response is investigated. This paper offers several alternatives for thermal modeling and analysis by using an electrical circuit analog: topological method, convolution integral method, etc. These methods are adaptable to numerical solutions and well suited to the use of the digital computer. The thermal analysis of thyristors was performed for the 1000 MVA converter system at the Princeton Plasma Physics Laboratory. Transient thermal impedance curves for individual thyristors in a given cooling arrangement were known from measurements and from manufacturer's data. The analysis pertains to almost any loading case, and the results are obtained in a numerical or a graphical format. 6 refs., 9 figs

  18. Development trends of combined inductance-capacitance electromechanical energy converters

    Directory of Open Access Journals (Sweden)

    Karayan Hamlet

    2018-01-01

    Full Text Available In the article the modern state of completely new direction of electromechanical science such as combined inductive-capacitive electromechanics is considered. The wide spectra of its possible practical applications and prospects for further development are analyzed. A new approach for mathematical description of transients in dualcon jugate dynamic systems is proposed. On the basis of the algorithm differential equations for inductive-capacitive compatible electromechanical energy converters are derived. The generalized Lagrangian theory of combined inductively-capacitive electric machines was developed as a union of generalized Lagrangian models of inductive and capacitive electro-mechanical energy converters developed on the basis of the basic principles of binary-conjugate electrophysics. The author gives equations of electrodynamics and electromechanics of combined inductive-capacitive electric machines in case there are active electrotechnical materials of dual purpose (ferroelectromagnets in the structure of their excitation system. At the same time, the necessary Lagrangian for combined inductive-capacitive forces was built using new technologies of interaction between inductive and capacitive subsystems. The joint solution of these equations completely determines the dynamic behavior and energy characteristics of the generalized model of combined machines of any design and in any modes of interaction of their functional elements

  19. Conformational transition paths harbor structures useful for aiding drug discovery and understanding enzymatic mechanisms in protein kinases.

    Science.gov (United States)

    Wong, Chung F

    2016-01-01

    This short article examines the usefulness of fast simulations of conformational transition paths in elucidating enzymatic mechanisms and guiding drug discovery for protein kinases. It applies the transition path method in the MOIL software package to simulate the paths of conformational transitions between six pairs of structures from the Protein Data Bank. The structures along the transition paths were found to resemble experimental structures that mimic transient structures believed to form during enzymatic catalysis or conformational transitions, or structures that have drug candidates bound. These findings suggest that such simulations could provide quick initial insights into the enzymatic mechanisms or pathways of conformational transitions of proteins kinases, or could provide structures useful for aiding structure-based drug design. © 2015 The Protein Society.

  20. Enhanced Control for Improving the Operation of Grid-Connected Power Converters under Faulty and Saturated Conditions

    Directory of Open Access Journals (Sweden)

    Mahdi Shahparasti

    2018-02-01

    Full Text Available In renewable energy based systems Grid-Connected Voltage Source Converters (GC-VSC are used in many applications as grid-feeding converters, which transfer the power coming from the renewable energy sources to the grid. In some cases, the operation of GC-VSC may become unstable or uncontrollable due to, among others: a grid fault or an inappropriate current-power reference, that give rise to fast electrical transients or a saturation of the controller. In this paper, an improved control scheme is proposed to enhance the controllability of GC-VSC in all these situations. This solution consists of two parts, on the one hand a new Proportional-Resonant (PR controller with anti-windup capability to be used as current controller, and secondly a new current/power reference modifier, which defines the suitable reactive current/power reference to keep the system stable. It is worth to mention that the proposed scheme does not need information about the grid parameters as it only uses the converter current, and the voltage at the capacitors of Inductor-Capacitor (LC output filter.

  1. Angiogenin-induced protein kinase B/Akt activation is necessary for angiogenesis but is independent of nuclear translocation of angiogenin in HUVE cells

    International Nuclear Information System (INIS)

    Kim, Hye-Mi; Kang, Dong-Ku; Kim, Hak Yong; Kang, Sang Sun; Chang, Soo-Ik

    2007-01-01

    Angiogenin, a potent angiogenic factor, binds to endothelial cells and is endocytosed and rapidly translocated to and concentrated in the nucleolus where it binds to DNA. In this study, we report that angiogenin induces transient phosphorylation of protein kinase B/Akt in cultured human umbilical vein endothelial (HUVE) cells. LY294002 inhibits the angiogenin-induced protein kinase B/Akt activation and also angiogenin-induced cell migration in vitro as well as angiogenesis in chick embryo chorioallantoic membrane in vivo without affecting nuclear translocation of angiogenin in HUVE cells. These results suggest that cross-talk between angiogenin and protein kinase B/Akt signaling pathways is essential for angiogenin-induced angiogenesis in vitro and in vivo, and that angiogenin-induced PKB/Akt activation is independent of nuclear translocation of angiogenin in HUVE cells

  2. Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells: differential role of P/Q- and L-type Ca2+ channels.

    Science.gov (United States)

    Sena, C M; Santos, R M; Boarder, M R; Rosário, L M

    1999-02-05

    Phorbol esters reduce depolarization-evoked Ca2+ influx in adrenal chromaffin cells, suggesting that voltage-sensitive Ca2+ channels (VSCCs) are inhibited by protein kinase C-mediated phosphorylation. We now address the possibility that L- and P/Q-type Ca2+ channel subtypes might be differentially involved in phorbol ester action. In bovine chromaffin cells, short-term (10 min) incubations with phorbol 12-myristate 13-acetate (PMA) inhibited early high K+-evoked rises in cytosolic free Ca2+ concentration ([Ca2+]i) and the early component of the depolarization-evoked Mn2+ quenching of fura-2 fluorescence in a dose-dependent manner (IC50: 18 and 7 nM; maximal inhibitions: 45 and 48%, respectively). The protein kinase C inhibitor staurosporine (100 nM) reverted the inhibitory action of PMA. PMA (0.1-1 microM) inhibited the early and late phases of the ionomycin (2 microM)-evoked [Ca2+]i transients by 14-23%. Omega-agatoxin IVA, a blocker of P/Q-type Ca2+ channels, inhibited high K+-evoked [Ca2+]i rises in a dose-dependent fashion (IC50 = 50 nM). In contrast, 0.1 microM omega-conotoxin GVIA, a blocker of N-type channels, was without effect. A sizeable (< 45%) component of early Ca2+ influx persisted in the combined presence of omega-agatoxin IVA (100 nM) and nitrendipine (1 microM). Simultaneous exposure to omega-agatoxin IVA and PMA inhibited both the early [Ca2+]i transients and Mn2+ quenching to a much greater extent than each drug separately. Inhibition of the [Ca2+]i transients by nitrendipine and PMA did not significantly exceed that produced by PMA alone. It is concluded that phorbol ester-mediated activation of protein kinase C inhibits preferentially L-type VSCCs over P/Q type channels in adrenal chromaffin cells. However, the possibility cannot be ruled out that dihydropyridine-resistant, non-P/Q type channels might also be negatively regulated by protein kinase C. This may represent an important pathway for the specific control of VSCCs by protein kinase C

  3. Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein

    International Nuclear Information System (INIS)

    Hussain, Alamdar; Faryal, Rani; Nore, Beston F.; Mohamed, Abdalla J.; Smith, C.I. Edvard

    2009-01-01

    Recurrent chromosomal translocations have long been implicated in various types of lymphomas and other malignancies. Novel recurrent t(5;9)(q33;q22) has been recently discovered in un-specified peripheral T-cell lymphoma. To elucidate the role of this translocation, the corresponding fusion construct encoding the N-terminal portion of the ITK kinase and the C-terminal catalytic region of the SYK kinase was generated. We herein show that the ITK-SYK fusion-protein is constitutively active. Moreover, we demonstrate that ITK-SYK is phosphorylated on key tyrosine residues and is capable of potently phosphorylating the related adapter proteins BLNK and SLP-76. In transiently transfected cells, SYK was phosphorylated at Y352 but not detectably at the activation-loop tyrosines Y525/Y526. In contrast, ITK-SYK was phosphorylated both at Y212 and the activation-loop tyrosines Y385/Y386, corresponding to Y352 and Y525/Y526 in SYK, respectively. In resting primary lymphocytes, ITK-SYK predominantly localizes to the cell surface. In addition, we demonstrate that following stimulation, the ITK-SYK fusion-protein in cell lines translocates to the cell membrane and, moreover, that this phenomenon as well as SLP-76 phosphorylation are blocked upon phosphatidylinositol-3-kinase (PI3-kinase) inhibition.

  4. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors.

    Science.gov (United States)

    Regales, Lucia; Balak, Marissa N; Gong, Yixuan; Politi, Katerina; Sawai, Ayana; Le, Carl; Koutcher, Jason A; Solit, David B; Rosen, Neal; Zakowski, Maureen F; Pao, William

    2007-08-29

    The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer. To study further its role in lung tumorigenesis, we developed mice with inducible expression in type II pneumocytes of EGFR(T790M) alone or together with a drug-sensitive L858R mutation. Both transgenic lines develop lung adenocarcinomas that require mutant EGFR for tumor maintenance but are resistant to an EGFR kinase inhibitor. EGFR(L858R+T790M)-driven tumors are transiently targeted by hsp90 inhibition. Notably, EGFR(T790M)-expressing animals develop tumors with longer latency than EGFR(L858R+T790M)-bearing mice and in the absence of additional kinase domain mutations. These new mouse models of mutant EGFR-dependent lung adenocarcinomas provide insight into clinical observations. The models should also be useful for developing improved therapies for patients with lung cancers harboring EGFR(T790M) alone or in conjunction with drug-sensitive EGFR kinase domain mutations.

  5. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Lucia Regales

    2007-08-01

    Full Text Available The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer.To study further its role in lung tumorigenesis, we developed mice with inducible expression in type II pneumocytes of EGFR(T790M alone or together with a drug-sensitive L858R mutation. Both transgenic lines develop lung adenocarcinomas that require mutant EGFR for tumor maintenance but are resistant to an EGFR kinase inhibitor. EGFR(L858R+T790M-driven tumors are transiently targeted by hsp90 inhibition. Notably, EGFR(T790M-expressing animals develop tumors with longer latency than EGFR(L858R+T790M-bearing mice and in the absence of additional kinase domain mutations.These new mouse models of mutant EGFR-dependent lung adenocarcinomas provide insight into clinical observations. The models should also be useful for developing improved therapies for patients with lung cancers harboring EGFR(T790M alone or in conjunction with drug-sensitive EGFR kinase domain mutations.

  6. Cascaded resonant bridge converters

    Science.gov (United States)

    Stuart, Thomas A. (Inventor)

    1989-01-01

    A converter for converting a low voltage direct current power source to a higher voltage, high frequency alternating current output for use in an electrical system where it is desired to use low weight cables and other circuit elements. The converter has a first stage series resonant (Schwarz) converter which converts the direct current power source to an alternating current by means of switching elements that are operated by a variable frequency voltage regulator, a transformer to step up the voltage of the alternating current, and a rectifier bridge to convert the alternating current to a direct current first stage output. The converter further has a second stage series resonant (Schwarz) converter which is connected in series to the first stage converter to receive its direct current output and convert it to a second stage high frequency alternating current output by means of switching elements that are operated by a fixed frequency oscillator. The voltage of the second stage output is controlled at a relatively constant value by controlling the first stage output voltage, which is accomplished by controlling the frequency of the first stage variable frequency voltage controller in response to second stage voltage. Fault tolerance in the event of a load short circuit is provided by making the operation of the first stage variable frequency voltage controller responsive to first and second stage current limiting devices. The second stage output is connected to a rectifier bridge whose output is connected to the input of the second stage to provide good regulation of output voltage wave form at low system loads.

  7. Technologies for converter topologies

    Science.gov (United States)

    Zhou, Yan; Zhang, Haiyu

    2017-02-28

    In some embodiments of the disclosed inverter topologies, an inverter may include a full bridge LLC resonant converter, a first boost converter, and a second boost converter. In such embodiments, the first and second boost converters operate in an interleaved manner. In other disclosed embodiments, the inverter may include a half-bridge inverter circuit, a resonant circuit, a capacitor divider circuit, and a transformer.

  8. A role for barley calcium-dependent protein kinase CPK2a in the response to drought

    Directory of Open Access Journals (Sweden)

    Agata Cieśla

    2016-10-01

    Full Text Available Increasing the drought tolerance of crops is one of the most challenging goals in plant breeding. To improve crop productivity during periods of water deficit, it is essential to understand the complex regulatory pathways that adapt plant metabolism to environmental conditions. Among various plant hormones and second messengers, calcium ions are known to be involved in drought stress perception and signaling. Plants have developed specific calcium-dependent protein kinases that convert calcium signals into phosphorylation events. In this study we attempted to elucidate the role of a calcium-dependent protein kinase in the drought stress response of barley (Hordeum vulgare L., one of the most economically important crops worldwide. The ongoing barley genome project has provided useful information about genes potentially involved in the drought stress response, but information on the role of calcium-dependent kinases is still limited. We found that the gene encoding the calcium-dependent protein kinase HvCPK2a was significantly upregulated in response to drought. To better understand the role of HvCPK2a in drought stress signaling, we generated transgenic Arabidopsis plants that overexpressed the corresponding coding sequence. Overexpressing lines displayed drought sensitivity, reduced nitrogen balance index, an increase in total chlorophyll content and decreased relative water content. In addition, in vitro kinase assay experiments combined with mass spectrometry allowed HvCPK2a autophosphorylation sites to be identified. Our results suggest that HvCPK2a is a dual-specificity calcium-dependent protein kinase that functions as a negative regulator of the drought stress response in barley.

  9. Load estimator-based hybrid controller design for two-interleaved boost converter dedicated to renewable energy and automotive applications.

    Science.gov (United States)

    Bougrine, Mohamed; Benmiloud, Mohammed; Benalia, Atallah; Delaleau, Emmanuel; Benbouzid, Mohamed

    2017-01-01

    This paper is devoted to the development of a hybrid controller for a two-interleaved boost converter dedicated to renewable energy and automotive applications. The control requirements, resumed in fast transient and low input current ripple, are formulated as a problem of fast stabilization of a predefined optimal limit cycle, and solved using hybrid automaton formalism. In addition, a real time estimation of the load is developed using an algebraic approach for online adjustment of the hybrid controller. Mathematical proofs are provided with simulations to illustrate the effectiveness and the robustness of the proposed controller despite different disturbances. Furthermore, a fuel cell system supplying a resistive load through a two-interleaved boost converter is also highlighted. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  10. A Transient Fault Recognition Method for an AC-DC Hybrid Transmission System Based on MMC Information Fusion

    Directory of Open Access Journals (Sweden)

    Jikai Chen

    2016-12-01

    Full Text Available At present, the research is still in the primary stage in the process of fault disturbance energy transfer in the multilevel modular converter based high voltage direct current (HVDC-MMC. An urgent problem is how to extract and analyze the fault features hidden in MMC electrical information in further studies on the HVDC system. Aiming at the above, this article analyzes the influence of AC transient disturbance on electrical signals of MMC. At the same time, it is found that the energy distribution of electrical signals in MMC is different for different arms in the same frequency bands after the discrete wavelet packet transformation (DWPT. Renyi wavelet packet energy entropy (RWPEE and Renyi wavelet packet time entropy (RWPTE are proposed and applied to AC transient fault feature extraction from electrical signals in MMC. Using the feature extraction results of Renyi wavelet packet entropy (RWPE, a novel recognition method is put forward to recognize AC transient faults using the information fusion technology. Theoretical analysis and experimental results show that the proposed method is available to recognize transient AC faults.

  11. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains

    KAUST Repository

    Diaz Galicia, Miriam Escarlet

    2018-05-01

    Protein-protein interactions modulate cellular processes in health and disease. However, tracing weak or rare associations or dissociations of proteins is not a trivial task. Kinases are often regulated through interaction partners and, at the same time, themselves regulate cellular interaction networks. The use of kinase domains for creating a synthetic sensor device that reads low concentration protein-protein interactions and amplifies them to a higher concentration interaction which is then translated into a FRET (Fluorescence Resonance Energy Transfer) signal is here proposed. To this end, DNA constructs for interaction amplification (split kinases), positive controls (intact kinase domains), scaffolding proteins and phosphopeptide - SH2-domain modules for the reading of kinase activity were assembled and expression protocols for fusion proteins containing Lyn, Src, and Fak kinase domains in bacterial and in cell-free systems were optimized. Also, two non-overlapping methods for measuring the kinase activity of these proteins were stablished and, finally, a protein-fragment complementation assay with the split-kinase constructs was tested. In conclusion, it has been demonstrated that features such as codon optimization, vector design and expression conditions have an impact on the expression yield and activity of kinase-based proteins. Furthermore, it has been found that the defined PURE cell-free system is insufficient for the active expression of catalytic kinase domains. In contrast, the bacterial co-expression with phosphatases produced active kinase fusion proteins for two out of the three tested Tyrosine kinase domains.

  12. Design and modelling of high gain DC-DC converters for fuel cell hybrid electric vehicles

    Science.gov (United States)

    Elangovan, D.; Karthigeyan, V.; Subhanu, B.; Ashwin, M.; Arunkumar, G.

    2017-11-01

    Transportation (Diesel and petrol internal combustion engine vehicles) approximately contributes to 25.5% of total CO2 emission. Thus diesel and petrol engine vehicles are the most dominant contributors of CO2 emission which leads global warming which causes climate change. The problem of CO2 emission and global warming can be reduced by focusing on renewable energy vehicles. Out of the available renewable energy sources fuel cell is the only source which has reasonable efficiency and can be used in vehicles. But the main disadvantage of fuel cell is its slow response time. So energy storage systems like batteries and super capacitors are used in parallel with the fuel cell. Fuel cell is used during steady state vehicle operation while during transient conditions like starting, acceleration and braking batteries and super capacitors can supply or absorb energy. In this paper a unidirectional fuel cell DC-DC converter and bidirectional energy storage system DC-DC converter is proposed, which can interface dc sources at different voltage levels to the dc bus and also it can independently control the power flow from each energy source to the dc bus and vice versa. The proposed converters are designed and simulated using PSIM version 9.1.1 and gate pulse pattern, input and output voltage waveforms of the converters for steady state operation are studied.

  13. Catalytic properties of inositol trisphosphate kinase: activation by Ca2+ and calmodulin

    International Nuclear Information System (INIS)

    Ryu, S.H.; Lee, S.Y.; Lee, K.Y.; Rhee, S.G.

    1987-01-01

    Inositol 1,4,5-triphosphate (Ins-1,4,5-P 3 ) is an important second-messenger molecule that mobilizes Ca 2+ from intracellular stores in response to the occupancy of receptor by various Ca 2+ -mobilizing agonists. The fate of Ins-1,4,5-P 3 is determined by two enzymes, a 3-kinase and a 5-phosphomonoesterase. The first enzyme converts Ins-1,4,5-P 3 to Ins-1,3,4,5-P 4 , whereas the latter forms Ins-1,4-P 2 . Recent studies suggest that Ins-1,3,4,5-P 4 might modulate the entry of Ca 2+ from an extracellular source. In the current report, the authors describe the partial purification of the 3-kinase from the cytosolic fraction of bovine brain and studies of its catalytic properties. They found that the 3-kinase activity is significantly activated by the Ca 2+ /calmodulin complex. Therefore, they propose that Ca 2+ mobilized from endoplasmic reticulum by the action of Ins-1,4,5-P 3 forms a complex with calmodulin, and that the Ca 2+ /calmodulin complex stimulates the conversion of Ins-1,4,5-P 3 , and intracellular Ca 2+ mobilizer, to Ins-1,3,4,5-P 4 , an extracellular Ca 2+ mobilizer. A rapid assay method for the 3-kinase was developed that is based on the separation of [3- 32 P]Ins-1,3,4,5-P 4 and [γ- 32 P]ATP by thin-layer chromatography. Using this new assay method, they evaluated kinetic parameters (K/sub m/ for ATP = 40 μM, K/sub m/ for Ins-1,4,5-P 3 = 0.7 μM, K/sub i/ for ADP = 12 μM) and divalent cation specificity (Mg 2+ > > Mn 2+ > Ca 2+ ) for the 3-kinase

  14. Isolation and characterization of cAMP-free and cAMP-bound forms of bovine heart type II cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Cobb, C.E.

    1986-01-01

    Bovine heart type II cAMP-dependent protein kinase holoenzyme (cAMP-PK) was purified to homogeneity as determined by denaturing SDS-PAGE. An HPLC-DEAE purification step resolved two distinct peaks of cAMP-dependent kinase activity, which were designated Peak 1 and Peak 2 based on their order of elution. They had the same Stoke's radii and had very similar sedimentation coefficients. As determined by densitometric scanning of SDS-PAGE brands, by their mobility on denaturing PAGE, and by the ratios of equilibrium [ 3 H] cAMP binding to maximal kinase activity, the subunit stoichiometry of the two peaks was the same. In a cAMP assay it was found that Peak 1 holoenzyme was cAMP-free, but half of the Peak 2 holoenzyme cAMP binding sites contained cAMP. Dissociation assays indicated that the cAMP was equally distributed in binding Site 1 and Site 2 of Peak 2. Although SDS-PAGE analysis ruled out conversions by proteolysis or autophosphorylation-dephosphorylation, Peak 1 could be partially converted to Peak 2 by the addition of subsaturating amounts of cAMP, and Peak 2 could be partially converted to Peak 1 by aging. The interconvertibility of the two holoenzyme peaks strongly suggested that the difference between the two peaks was caused by the presence of cAMP in Peak 2

  15. DC/DC converters for integration of double-layer condensers in onboard power supply; DC/DC-Wandler zur Einbindung von Doppelschichtkondensatoren in das Fahrzeugenergiebordnetz

    Energy Technology Data Exchange (ETDEWEB)

    Polenov, Dieter

    2010-01-15

    The paper discusses DC/DC converters for integration of double layer condensers into the onboard power system. First, requirements on DC/DC converters are listed and compared on the basis of three exemplary applications. A DC/DC converter concept is developed for decoupling transient high-power loads like electric steering systems. Three different topologies are compared using a specially developed method in order to find the best solution for the given application. In order to establish adequate criteria for selecting the switching frequency and inductivities of storage throttles, the influence of the trottle power change on the switching characteristics of the MOSFETs and on certain ranges of EMP interference emissions is investigated. As methods of optimising the operation of the synchronous rectifiers, parallel connection of Schottky diodes and synchronous rectifiers as well as the variation of the shut-off dead times of synchronous rectifiers were investigated. Further, a concept for converter control was developed in consideration of the intended application and topology. Finally, selected aspects for implementation of the DC/DC converter concept are presented as well as the results of experimental investigations.

  16. Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer

    OpenAIRE

    Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

    2013-01-01

    Background: Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). Methods: To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profi...

  17. Development of a physically-based planar inductors VHDL-AMS model for integrated power converter design

    Science.gov (United States)

    Ammouri, Aymen; Ben Salah, Walid; Khachroumi, Sofiane; Ben Salah, Tarek; Kourda, Ferid; Morel, Hervé

    2014-05-01

    Design of integrated power converters needs prototype-less approaches. Specific simulations are required for investigation and validation process. Simulation relies on active and passive device models. Models of planar devices, for instance, are still not available in power simulator tools. There is, thus, a specific limitation during the simulation process of integrated power systems. The paper focuses on the development of a physically-based planar inductor model and its validation inside a power converter during transient switching. The planar inductor model remains a complex device to model, particularly when the skin, the proximity and the parasitic capacitances effects are taken into account. Heterogeneous simulation scheme, including circuit and device models, is successfully implemented in VHDL-AMS language and simulated in Simplorer platform. The mixed simulation results has been favorably tested and compared with practical measurements. It is found that the multi-domain simulation results and measurements data are in close agreement.

  18. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Ting-Lei Gu

    Full Text Available Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23 of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted.

  19. A Calcium-Dependent Protein Kinase Is Systemically Induced upon Wounding in Tomato Plants1

    Science.gov (United States)

    Chico, José Manuel; Raíces, Marcela; Téllez-Iñón, María Teresa; Ulloa, Rita María

    2002-01-01

    A full-length cDNA clone (LeCDPK1) from tomato (Lycopersicon esculentum) encoding a calcium-dependent protein kinase (CDPK) was isolated by screening a cDNA library from tomato cell cultures exposed to Cladosporium fulvum elicitor preparations. The predicted amino acid sequence of the cDNA reveals a high degree of similarity with other members of the CDPK family. LeCDPK1 has a putative N-terminal myristoylation sequence and presents a possible palmitoylation site. The in vitro translated protein conserves the biochemical properties of a member of the CDPK family. In addition, CDPK activity was detected in soluble and particulate extracts of tomato leaves. Basal levels of LeCDPK1 mRNA were detected by northern-blot analysis in roots, stems, leaves, and flowers of tomato plants. The expression of LeCDPK1 was rapidly and transiently enhanced in detached tomato leaves treated with pathogen elicitors and H2O2. Moreover, when tomato greenhouse plants were subjected to mechanical wounding, a transient increase of LeCDPK1 steady-state mRNA levels was detected locally at the site of the injury and systemically in distant non-wounded leaves. The increase observed in LeCDPK1 mRNA upon wounding correlates with an increase in the amount and in the activity of a soluble CDPK detected in extracts of tomato leaves, suggesting that this kinase is part of physiological plant defense mechanisms against biotic or abiotic attacks. PMID:11788771

  20. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase.

    Directory of Open Access Journals (Sweden)

    Mutsuki Amano

    Full Text Available BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity.

  1. Power quality improvement by using multi-pulse AC-DC converters for DC drives: Modeling, simulation and its digital implementation

    Directory of Open Access Journals (Sweden)

    Mohd Tariq

    2014-12-01

    Full Text Available The paper presents the modeling, simulation and digital implementation of power quality improvement of DC drives by using multi pulse AC–DC converter. As it is a well-known fact that power quality determines the fitness of electrical power to consumer devices, hence an effort has been made to improve power quality in this work. Simulation and digital implementation with the help of MATLAB/Simulink has been done and results obtained are discussed in detail to verify the theoretical results. The multipulse converter was connected with DC drives and was run at no load condition to find out the transient and steady state performances. FFT analysis has been performed and Total Harmonic Distortion (THD results obtained at different pulses are shown here.

  2. Gold nanoparticles-based electrochemical method for the detection of protein kinase with a peptide-like inhibitor as the bioreceptor

    Directory of Open Access Journals (Sweden)

    Sun K

    2017-03-01

    Full Text Available Kai Sun, Yong Chang, Binbin Zhou, Xiaojin Wang, Lin Liu Henan Province of Key Laboratory of New Optoelectronic Functional Materials, College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang, Henan, People’s Republic of China Abstract: This article presents a general method for the detection of protein kinase with a peptide-like kinase inhibitor as the bioreceptor, and it was done by converting gold nanoparticles (AuNPs-based colorimetric assay into sensitive electrochemical analysis. In the colorimetric assay, the kinase-specific aptameric peptide triggered the aggregation of AuNPs in solution. However, the specific binding of peptide to the target protein (kinase inhibited its ability to trigger the assembly of AuNPs. In the electrochemical analysis, peptides immobilized on a gold electrode and presented as solution triggered together the in situ formation of AuNPs-based network architecture on the electrode surface. Nevertheless, the formation of peptide–kinase complex on the electrode surface made the peptide-triggered AuNPs assembly difficult. Electrochemical impedance spectroscopy was used to measure the change in surface property in the binding events. When a ferrocene-labeled peptide (Fc-peptide was used in this design, the network of AuNPs/Fc-peptide produced a good voltammetric signal. The competitive assay allowed for the detection of protein kinase A with a detection limit of 20 mU/mL. This work should be valuable for designing novel optical or electronic biosensors and likely lead to many detection applications. Keywords: electrochemical biosensor, colorimetric assay, gold nanoparticle, aptameric peptide, protein kinase A, signal amplification 

  3. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten

    2010-01-01

    in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by tyrosine......Bacteria and Eukarya share essentially the same family of protein-serine/threonine kinases, also known as the Hanks-type kinases. However, when it comes to protein-tyrosine phosphorylation, bacteria seem to have gone their own way. Bacterial protein-tyrosine kinases (BY-kinases) are bacterial...... and highlighted their importance in bacterial physiology. Having no orthologues in Eukarya, BY-kinases are receiving a growing attention from the biomedical field, since they represent a particularly promising target for anti-bacterial drug design....

  4. The Convertible Arbitrage Strategy Analyzed

    NARCIS (Netherlands)

    Loncarski, I.; Ter Horst, J.R.; Veld, C.H.

    2006-01-01

    This paper analyzes convertible bond arbitrage on the Canadian market for the period 1998 to 2004.Convertible bond arbitrage is the combination of a long position in convertible bonds and a short position in the underlying stocks. Convertible arbitrage has been one of the most successful strategies

  5. Switched-mode converters (one quadrant)

    CERN Document Server

    Barrade, P

    2006-01-01

    Switched-mode converters are DC/DC converters that supply DC loads with a regulated output voltage, and protection against overcurrents and short circuits. These converters are generally fed from an AC network via a transformer and a conventional diode rectifier. Switched-mode converters (one quadrant) are non-reversible converters that allow the feeding of a DC load with unipolar voltage and current. The switched-mode converters presented in this contribution are classified into two families. The first is dedicated to the basic topologies of DC/DC converters, generally used for low- to mid-power applications. As such structures enable only hard commutation processes, the main drawback of such topologies is high commutation losses. A typical multichannel evolution is presented that allows an interesting decrease in these losses. Deduced from this direct DC/DC converter, an evolution is also presented that allows the integration of a transformer into the buck and the buck–boost structure. This enables an int...

  6. Proposing Wavelet-Based Low-Pass Filter and Input Filter to Improve Transient Response of Grid-Connected Photovoltaic Systems

    Directory of Open Access Journals (Sweden)

    Bijan Rahmani

    2016-08-01

    Full Text Available Available photovoltaic (PV systems show a prolonged transient response, when integrated into the power grid via active filters. On one hand, the conventional low-pass filter, employed within the integrated PV system, works with a large delay, particularly in the presence of system’s low-order harmonics. On the other hand, the switching of the DC (direct current–DC converters within PV units also prolongs the transient response of an integrated system, injecting harmonics and distortion through the PV-end current. This paper initially develops a wavelet-based low-pass filter to improve the transient response of the interconnected PV systems to grid lines. Further, a damped input filter is proposed within the PV system to address the raised converter’s switching issue. Finally, Matlab/Simulink simulations validate the effectiveness of the proposed wavelet-based low-pass filter and damped input filter within an integrated PV system.

  7. Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

    Science.gov (United States)

    Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

    1999-03-05

    Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

  8. Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival.

    Directory of Open Access Journals (Sweden)

    Daniel Thomas

    Full Text Available The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K, promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting

  9. AIREKMOD-RR, Reactivity Transients in Nuclear Research Reactors

    International Nuclear Information System (INIS)

    Baggoura, B.; Mazrou, H.

    2001-01-01

    1 - Description of program or function: AIREMOD-RR is a point kinetics code which can simulate fast transients in nuclear research reactor cores. It can also be used for theoretical reactor dynamics studies. It is used for research reactor kinetic analysis and provides a point neutron kinetic capability. The thermal hydraulic behavior is governed by a one-dimensional heat balance equation. The calculations are restricted to a single equivalent unit cell which consists of fuel, clad and coolant. 2 - Method of solution: For transient reactor kinetic calculations a modified Runge Kutta numerical method is used. The external reactivity insertion, specified as a function of time, is converted in dollar ($) unit. The neutron density, energy release and feedback variables are given at each time step. The two types of reactivity feedback considered are: Doppler effect and moderator effect. A new expression for the reactivity dependence on the feedback variables has been introduced in the present version of the code. The feedback reactivities are fitted in power series expression. 3 - Restrictions on the complexity of the problem: The number of delayed neutron groups and the total number of equations are limited only by computer storage capabilities. - Coolant is always in liquid phase. - Void reactivity feedback is not considered

  10. Application of Minimum-time Optimal Control System in Buck-Boost Bi-linear Converters

    Directory of Open Access Journals (Sweden)

    S. M. M. Shariatmadar

    2017-08-01

    Full Text Available In this study, the theory of minimum-time optimal control system in buck-boost bi-linear converters is described, so that output voltage regulation is carried out within minimum time. For this purpose, the Pontryagin's Minimum Principle is applied to find optimal switching level applying minimum-time optimal control rules. The results revealed that by utilizing an optimal switching level instead of classical switching patterns, output voltage regulation will be carried out within minimum time. However, transient energy index of increased overvoltage significantly reduces in order to attain minimum time optimal control in reduced output load. The laboratory results were used in order to verify numerical simulations.

  11. Performance simulations of catalytic converters during the Federal Test Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Shen, H.; Shamim, T.; Sengupta, S.; Son, S.; Adamczyk, A.A.

    1999-07-01

    A numerical study is carried out to predict the tailpipe emissions and emission conversion efficiencies of unburned hydrocarbon, nitrogen oxide and carbon monoxide flowing through a catalytic converter during the Federal Test Procedure (FTP). The model considers the effect of heat transfer in the catalytic converter, coupled with catalyst chemical kinetics, including an oxygen storage mechanism. The resulting governing equations based on the conservation of mass and energy are solved by a tridiagonal matrix algorithm (TDMA) with a successive line under relaxation method. The numerical scheme for this non-linear problem is found to have good convergence efficiency. The simulation for the complete FTP cycle is accomplished in less than fifteen minutes on a desktop personal computer. A 13-step reaction mechanism plus a nine-step O{sub 2} storage mechanism is used to simulate the chemical kinetics. The energy equations include the heat loss due to conduction and convection plus the energy liberated by chemical reactions. The effect of radiation is assumed to be negligible and is not considered. The results of the numerical model for both the instantaneous and accumulated emissions are found to be in good agreement with experimental measurements. The conversion efficiencies of HC, CO and NO as predicted by the model are found to be within 5% of those dynamic measurements, and calculated results of accumulated HC, CO and NO{sub x} are in fair agreement with experimental measurements. The transient measurements are also used to check the robustness of the numerical model. The model is found to be robust and hence can simulate various operating conditions of engine output to the converter.

  12. Interactions between the S-domain receptor kinases and AtPUB-ARM E3 ubiquitin ligases suggest a conserved signaling pathway in Arabidopsis.

    Science.gov (United States)

    Samuel, Marcus A; Mudgil, Yashwanti; Salt, Jennifer N; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R

    2008-08-01

    The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses.

  13. Integrated power electronic converters and digital control

    CERN Document Server

    Emadi, Ali; Nie, Zhong

    2009-01-01

    Non-isolated DC-DC ConvertersBuck ConverterBoost ConverterBuck-Boost ConverterIsolated DC-DC ConvertersFlyback ConverterForward ConverterPush-Pull ConverterFull-Bridge ConverterHalf-Bridge ConverterPower Factor CorrectionConcept of PFCGeneral Classification of PFC CircuitsHigh Switching Frequency Topologies for PFCApplication of PFC in Advanced Motor DrivesIntegrated Switched-Mode Power ConvertersSwitched-Mode Power SuppliesThe Concept of Integrated ConverterDefinition of Integrated Switched-Mode Power Supplies (ISMPS)Boost-Type Integrated TopologiesGeneral Structure of Boost-Type Integrated T

  14. Impedance Source Power Electronic Converters

    DEFF Research Database (Denmark)

    Liu, Yushan; Abu-Rub, Haitham; Ge, Baoming

    Impedance Source Power Electronic Converters brings together state of the art knowledge and cutting edge techniques in various stages of research related to the ever more popular impedance source converters/inverters. Significant research efforts are underway to develop commercially viable...... and technically feasible, efficient and reliable power converters for renewable energy, electric transportation and for various industrial applications. This book provides a detailed understanding of the concepts, designs, controls, and application demonstrations of the impedance source converters/inverters. Key...... features: Comprehensive analysis of the impedance source converter/inverter topologies, including typical topologies and derived topologies. Fully explains the design and control techniques of impedance source converters/inverters, including hardware design and control parameter design for corresponding...

  15. Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

    Science.gov (United States)

    Filippakopoulos, Panagis; Kofler, Michael; Hantschel, Oliver; Gish, Gerald D; Grebien, Florian; Salah, Eidarus; Neudecker, Philipp; Kay, Lewis E; Turk, Benjamin E; Superti-Furga, Giulio; Pawson, Tony; Knapp, Stefan

    2008-09-05

    The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

  16. The Link between Protein Kinase CK2 and Atypical Kinase Rio1

    Directory of Open Access Journals (Sweden)

    Konrad Kubiński

    2017-02-01

    Full Text Available The atypical kinase Rio1 is widespread in many organisms, ranging from Archaebacteria to humans, and is an essential factor in ribosome biogenesis. Little is known about the protein substrates of the enzyme and small-molecule inhibitors of the kinase. Protein kinase CK2 was the first interaction partner of Rio1, identified in yeast cells. The enzyme from various sources undergoes CK2-mediated phosphorylation at several sites and this modification regulates the activity of Rio1. The aim of this review is to present studies of the relationship between the two different kinases, with respect to CK2-mediated phosphorylation of Rio1, regulation of Rio1 activity, and similar susceptibility of the kinases to benzimidazole inhibitors.

  17. Regulation of Autophagy by Kinases

    International Nuclear Information System (INIS)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets

  18. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-06-09

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  19. Regulation of Autophagy by Kinases

    Science.gov (United States)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. PMID:24212825

  20. Regulation of Autophagy by Kinases

    Directory of Open Access Journals (Sweden)

    Savitha Sridharan

    2011-06-01

    Full Text Available Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  1. A novel transient rotor current control scheme of a doubly-fed induction generator equipped with superconducting magnetic energy storage for voltage and frequency support

    Science.gov (United States)

    Shen, Yang-Wu; Ke, De-Ping; Sun, Yuan-Zhang; Daniel, Kirschen; Wang, Yi-Shen; Hu, Yuan-Chao

    2015-07-01

    A novel transient rotor current control scheme is proposed in this paper for a doubly-fed induction generator (DFIG) equipped with a superconducting magnetic energy storage (SMES) device to enhance its transient voltage and frequency support capacity during grid faults. The SMES connected to the DC-link capacitor of the DFIG is controlled to regulate the transient dc-link voltage so that the whole capacity of the grid side converter (GSC) is dedicated to injecting reactive power to the grid for the transient voltage support. However, the rotor-side converter (RSC) has different control tasks for different periods of the grid fault. Firstly, for Period I, the RSC injects the demagnetizing current to ensure the controllability of the rotor voltage. Then, since the dc stator flux degenerates rapidly in Period II, the required demagnetizing current is low in Period II and the RSC uses the spare capacity to additionally generate the reactive (priority) and active current so that the transient voltage capability is corroborated and the DFIG also positively responds to the system frequency dynamic at the earliest time. Finally, a small amount of demagnetizing current is provided after the fault clearance. Most of the RSC capacity is used to inject the active current to further support the frequency recovery of the system. Simulations are carried out on a simple power system with a wind farm. Comparisons with other commonly used control methods are performed to validate the proposed control method. Project supported by the National Natural Science Foundation of China (Grant No. 51307124) and the Major Program of the National Natural Science Foundation of China (Grant No. 51190105).

  2. Static and Dynamic Characteristics of DC-DC Converter Using a Digital Filter

    Science.gov (United States)

    Kurokawa, Fujio; Okamatsu, Masashi

    This paper presents the regulation and dynamic characteristics of the dc-dc converter with digital PID control, the minimum phase FIR filter or the IIR filter, and then the design criterion to improve the dynamic characteristics is discussed. As a result, it is clarified that the DC-DC converter using the IIR filter method has superior performance characteristics. The regulation range is within 1.3%, the undershoot against the step change of the load is less than 2% and the transient time is less than 0.4ms with the IIR filter method. In this case, the switching frequency is 100kHz and the step change of the load R is from 50 Ω to 10 Ω. Further, the superior characteristics are obtained when the first gain, the second gain and the second cut-off frequency are relatively large, and the first cut-off frequency and the passing frequency are relatively low. Moreover, it is important that the gain strongly decreases at the second cut-off frequency because the upper band pass frequency range must be always less than half of the sampling frequency based on the sampling theory.

  3. Transient Go: A Mobile App for Transient Astronomy Outreach

    Science.gov (United States)

    Crichton, D.; Mahabal, A.; Djorgovski, S. G.; Drake, A.; Early, J.; Ivezic, Z.; Jacoby, S.; Kanbur, S.

    2016-12-01

    Augmented Reality (AR) is set to revolutionize human interaction with the real world as demonstrated by the phenomenal success of `Pokemon Go'. That very technology can be used to rekindle the interest in science at the school level. We are in the process of developing a prototype app based on sky maps that will use AR to introduce different classes of astronomical transients to students as they are discovered i.e. in real-time. This will involve transient streams from surveys such as the Catalina Real-time Transient Survey (CRTS) today and the Large Synoptic Survey Telescope (LSST) in the near future. The transient streams will be combined with archival and latest image cut-outs and other auxiliary data as well as historical and statistical perspectives on each of the transient types being served. Such an app could easily be adapted to work with various NASA missions and NSF projects to enrich the student experience.

  4. Development of a Compact Matrix Converter

    Directory of Open Access Journals (Sweden)

    J. Bauer

    2009-01-01

    Full Text Available This paper deals with the development of a matrix converter. Matrix converters belong to the category of direct frequency converters. A converter does not contain DC-link and the output voltage is provided by direct switching of voltage from the input phases. This is enabled by 9 bidirectional switches, which are provided by anti-serial connection of 18 IGBT transistors. The absence of a DC-link is great advantage of the matrix converter, but it also increases the requirements on the converter control. For this reason a new prototype of a matrix converter is being developed with sophisticated modern components (FPGA, Power PC equipped in the control part of the converter. The converter will be used for testing new control algorithms and commutation methods. 

  5. High power density dc/dc converter: Selection of converter topology

    Science.gov (United States)

    Divan, Deepakraj M.

    1990-01-01

    The work involved in the identification and selection of a suitable converter topology is described. Three new dc/dc converter topologies are proposed: Phase-Shifted Single Active Bridge DC/DC Converter; Single Phase Dual Active Bridges DC/DC Converter; and Three Phase Dual Active Bridges DC/DC Converter (Topology C). The salient features of these topologies are: (1) All are minimal in structure, i.e., each consists of an input and output bridge, input and output filter and a transformer, all components essential for a high power dc/dc conversion process; (2) All devices of both the bridges can operate under near zero-voltage conditions, making possible a reduction of device switching losses and hence, an increase in switching frequency; (3) All circuits operate at a constant frequency, thus simplifying the task of the magnetic and filter elements; (4) Since, the leakage inductance of the transformer is used as the main current transfer element, problems associated with the diode reverse recovery are eliminated. Also, this mode of operation allows easy paralleling of multiple modules for extending the power capacity of the system; (5) All circuits are least sensitive to parasitic impedances, infact the parasitics are efficently utilized; and (6) The soft switching transitions, result in low electromagnetic interference. A detailed analysis of each topology was carried out. Based on the analysis, the various device and component ratings for each topology operating at an optimum point, and under the given specifications, are tabulated and discussed.

  6. Radiation tolerant power converter controls

    CERN Document Server

    Todd, B; King, Q; Uznanski, S

    2012-01-01

    The Large Hadron Collider (LHC) at the European Organisation for Nuclear Research (CERN) is the world's most powerful particle collider. The LHC has several thousand magnets, both warm and super-conducting, which are supplied with current by power converters. Each converter is controlled by a purpose-built electronic module called a Function Generator Controller (FGC). The FGC allows remote control of the power converter and forms the central part of a closed-loop control system where the power converter voltage is set, based on the converter output current and magnet-circuit characteristics. Some power converters and FGCs are located in areas which are exposed to beam-induced radiation. There are numerous radiation induced effects, some of which lead to a loss of control of the power converter, having a direct impact upon the accelerator's availability. Following the first long shut down (LS1), the LHC will be able to run with higher intensity beams and higher beam energy. This is expected to lead to signifi...

  7. High-Performance Data Converters

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    -resolution internal D/A converters are required. Unit-element mismatch-shaping D/A converters are analyzed, and the concept of mismatch-shaping is generalized to include scaled-element D/A converters. Several types of scaled-element mismatch-shaping D/A converters are proposed. Simulations show that, when implemented...... in a standard CMOS technology, they can be designed to yield 100 dB performance at 10 times oversampling. The proposed scaled-element mismatch-shaping D/A converters are well suited for use as the feedback stage in oversampled delta-sigma quantizers. It is, however, not easy to make full use of their potential......-order difference of the output signal from the loop filter's first integrator stage. This technique avoids the need for accurate matching of analog and digital filters that characterizes the MASH topology, and it preserves the signal-band suppression of quantization errors. Simulations show that quantizers...

  8. Impedance source power electronic converters

    CERN Document Server

    Liu, Yushan; Ge, Baoming; Blaabjerg, Frede; Ellabban, Omar; Loh, Poh Chiang

    2016-01-01

    Impedance Source Power Electronic Converters brings together state of the art knowledge and cutting edge techniques in various stages of research related to the ever more popular impedance source converters/inverters. Significant research efforts are underway to develop commercially viable and technically feasible, efficient and reliable power converters for renewable energy, electric transportation and for various industrial applications. This book provides a detailed understanding of the concepts, designs, controls, and application demonstrations of the impedance source converters/inverters. Key features: Comprehensive analysis of the impedance source converter/inverter topologies, including typical topologies and derived topologies. Fully explains the design and control techniques of impedance source converters/inverters, including hardware design and control parameter design for corresponding control methods. Presents the latest power conversion solutions that aim to advance the role of pow...

  9. The Role of Pyruvate Dehydrogenase Kinase in Diabetes and Obesity

    Directory of Open Access Journals (Sweden)

    In-Kyu Lee

    2014-06-01

    Full Text Available The pyruvate dehydrogenase complex (PDC is an emerging target for the treatment of metabolic syndrome. To maintain a steady-state concentration of adenosine triphosphate during the feed-fast cycle, cells require efficient utilization of fatty acid and glucose, which is controlled by the PDC. The PDC converts pyruvate, coenzyme A (CoA, and oxidized nicotinamide adenine dinucleotide (NAD+ into acetyl-CoA, reduced form of nicotinamide adenine dinucleotide (NADH, and carbon dioxide. The activity of the PDC is up- and down-regulated by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase, respectively. In addition, pyruvate is a key intermediate of glucose oxidation and an important precursor for the synthesis of glucose, glycerol, fatty acids, and nonessential amino acids.

  10. Multilevel Converter by Cascading Two-Level Three-Phase Voltage Source Converter

    Directory of Open Access Journals (Sweden)

    Abdullrahman A. Al-Shamma’a

    2018-04-01

    Full Text Available This paper proposes a topology using isolated, cascaded multilevel voltage source converters (VSCs and employing two-winding magnetic elements for high-power applications. The proposed topology synthesizes 6 two-level, three-phase VSCs, so the power capability of the presented converter is six times the capability of each VSC module. The characteristics of the proposed topology are demonstrated through analyzing its current relationships, voltage relationships and power capability in detail. The power rating is equally shared among the VSC modules without the need for a sharing algorithm; thus, the converter operates as a single three-phase VSC. The comparative analysis with classical neutral-point clamped, flying capacitor and cascaded H-bridge exhibits the superior features of fewer insulated gate bipolar transistors (IGBTs, capacitor requirement and fewer diodes. To validate the theoretical performance of the proposed converter, it is simulated in a MATLAB/Simulink environment and the results are experimentally demonstrated using a laboratory prototype.

  11. A high efficiency photovoltaic module integrated converter with the asymmetrical half-bridge flyback converter

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heeje; Kim, Jongrak; Shin, Dongsul [Department of Electrical Engineering, Pusan National University, Jangjeon, Geumjeong, Busan 609-735 (Korea); Kim, Hosung; Lee, Kyungjun [Department of Electrical Engineering, Pusan National University, Jangjeon, Geumjeong, Busan 609-735 (Korea); New and Renewable Energy System Research Center, Korea Electro-technology Research Institute, 28-1, Sungju-dong Changwon-si, Kyungsannam-do, 641-120 (Korea); Kim, Jonghyun; Yoo, Dongwook [New and Renewable Energy System Research Center, Korea Electro-technology Research Institute, 28-1, Sungju-dong Changwon-si, Kyungsannam-do, 641-120 (Korea)

    2010-08-15

    A module integrated converter (MIC) for a photovoltaic (PV) cell is important part of power conditioning system (PCS). It performs maximum power point tracking of a PV cell to generate the power as much as possible from solar energy. There are several methods for connection between the PV modules and the MICs. In order to avoid partial shading effects, converter-per-module approach was proposed. The MIC that performs maximum power point tracking (MPPT), if it is low efficiency, is no use. The MIC whose output is connected to the output of PV module was proposed for high efficiency. However, there are some problems. In this study, an asymmetrical half-bridge flyback converter is proposed instead of the original flyback converter with same method to solve the problems. The proposed MIC was built to verify the performance. The new topology using soft switching technique showed good performance for the efficiency. At the higher power, the efficiency of the proposed converter is higher than existing converter. (author)

  12. A Technique to Estimate the Equivalent Loss Resistance of Grid-Tied Converters for Current Control Analysis and Design

    DEFF Research Database (Denmark)

    Vidal, Ana; Yepes, Alejandro G.; Fernandez, Francisco Daniel Freijedo

    2015-01-01

    Rigorous analysis and design of the current control loop in voltage source converters (VSCs) requires an accurate modeling. The loop behavior can be significantly influenced by the VSC working conditions. To consider such effect, converter losses should be included in the model, which can be done...... by means of an equivalent series resistance. This paper proposes a method to identify the VSC equivalent loss resistance for the proper tuning of the current control loop. It is based on analysis of the closed-loop transient response provided by a synchronous proportional-integral current controller......, according to the internal model principle. The method gives a set of loss resistance values linked to working conditions, which can be used to improve the tuning of the current controllers, either by online adaptation of the controller gains or by open-loop adaptive adjustment of them according to prestored...

  13. ITER convertible blanket evaluation

    International Nuclear Information System (INIS)

    Wong, C.P.C.; Cheng, E.

    1995-01-01

    Proposed International Thermonuclear Experimental Reactor (ITER) convertible blankets were reviewed. Key design difficulties were identified. A new particle filter concept is introduced and key performance parameters estimated. Results show that this particle filter concept can satisfy all of the convertible blanket design requirements except the generic issue of Be blanket lifetime. If the convertible blanket is an acceptable approach for ITER operation, this particle filter option should be a strong candidate

  14. LDV measurement, flow visualization and numerical analysis of flow distribution in a close-coupled catalytic converter

    International Nuclear Information System (INIS)

    Kim, Duk Sang; Cho, Yong Seok

    2004-01-01

    Results from an experimental study of flow distribution in a Close-coupled Catalytic Converter (CCC) are presented. The experiments were carried out with a flow measurement system specially designed for this study under steady and transient flow conditions. A pitot tube was a tool for measuring flow distribution at the exit of the first monolith. The flow distribution of the CCC was also measured by LDV system and flow visualization. Results from numerical analysis are also presented. Experimental results showed that the flow uniformity index decreases as flow Reynolds number increases. In steady flow conditions, the flow through each exhaust pipe made some flow concentrations on a specific region of the CCC inlet. The transient test results showed that the flow through each exhaust pipe in the engine firing order, interacted with each other to ensure that the flow distribution was uniform. The results of numerical analysis were qualitatively accepted with experimental results. They supported and helped explain the flow in the entry region of CCC

  15. Efficient Wide Range Converters (EWiRaC): A new family of high efficient AC-DC Converters

    DEFF Research Database (Denmark)

    Petersen, Lars; Andersen, Michael Andreas E.

    2006-01-01

    The performance in terms of efficiency of the existing power supplies used for PFC is very dependent on the input voltage range. The boost converter is the most commonly used PFC converter because of its simplicity and high efficiency. But, the boost converter as well as other known converters...... suffers a major penalty in efficiency when used at the low end of the voltage range (90VAC) in a universal voltage range application (90-270VAC). This paper addresses this problem by suggesting a new family of converters that effectively reduces the apparent voltage range with a factor of 2 by changing...... the converter topology according to the input voltage. This new converter type has been named: efficient wide range converter (EWiRaC). The performance of the EWiRaC is experimental verified in a universal input range (90-270VAC) application with an output voltage of 185VDC capable of 500W output power. The EWi...

  16. The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

    Science.gov (United States)

    Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

    2014-11-01

    The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

  17. Role of adiponectin/phosphatidylinositol 3-kinase/protein kinase B ...

    African Journals Online (AJOL)

    The adiponectin/phosphatidylinositol 3-kinase/protein kinase B (ADP/PI3k/Akt) signal transduction pathway has an important role in promoting cell survival. This study was designed to determine if the ADP/PI3K/Akt signaling pathway has a role in the mechanism of ischemia–reperfusion injury in vivo. Sprague–Dawley rats ...

  18. Model of Transient Process Where Three-Phase Transducer Feeds Induction Motor Equivalent as a Variable Active-Inductive Load

    Directory of Open Access Journals (Sweden)

    Nenad Marković

    2016-01-01

    Full Text Available The paper presents a new approach in the analysis of a transient state in a system where the feeding source is a transducer-IGBT inverter and load is introduced through the induction motor with its R-L parameters. Induction motors with different parameters of powers and power factors are tested. MATLAB simulation of the three-phase inverter that feeds the induction machine has replaced the missing lab equipment with which mathematical model of this system was verified. According to the selected parameters of the inverter and induction machine and through the simulation in the MATLAB program, the results are obtained in the form of diagrams that verify the model of a transient state of the induction machine operation when it operates as a motor which is presented as a variable R-L load. The transient process of the system three-phase bridge inverter whose active-inductive load is the induction machine in the conditions of the change of the load parameters is analyzed. The model of the transient process in the system formed by the inverter in PWM (Pulse Width Modulation converter and induction machine is developed in the time domain and phase coordinates.

  19. DNA-dependent protein kinase inhibits AID-induced antibody gene conversion.

    Directory of Open Access Journals (Sweden)

    Adam J L Cook

    2007-04-01

    Full Text Available Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID-dependent hypermutation of Ig V(DJ rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(DJ regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(DJ hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein kinase catalytic subunit (DNA-PKcs. Inactivation of the Ku70 or DNA-PKcs genes in DT40 cells elevated the rate of AID-induced gene conversion as much as 5-fold. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion.

  20. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  1. One-Quadrant Switched-Mode Power Converters

    CERN Document Server

    Petrocelli, R.

    2015-06-15

    This article presents the main topics related to one-quadrant power convert- ers. The basic topologies are analysed and a simple methodology to obtain the steady-state output–input voltage ratio is set out. A short discussion of dif- ferent methods to control one-quadrant power converters is presented. Some of the reported derived topologies of one-quadrant power converters are also considered. Some topics related to one-quadrant power converters such as syn- chronous rectification, hard and soft commutation, and interleaved converters are discussed. Finally, a brief introduction to resonant converters is given.

  2. Thymidine kinases in archaea

    DEFF Research Database (Denmark)

    Clausen, A.R.; Matakos, A.; Sandrini, Michael

    2006-01-01

    Twenty-six fully sequenced archaeal genomes were searched for genes coding for putative deoxyribonucleoside kinases (dNKs). We identified only 5 human-like thymidine kinase 1 genes (TK1s) and none for non-TK1 kinases. Four TK1s were identified in the Euryarchaea and one was found in the Crenarcha...

  3. Kinase impact assessment in the landscape of fusion genes that retain kinase domains: a pan-cancer study

    Science.gov (United States)

    Kim, Pora; Jia, Peilin; Zhao, Zhongming

    2018-01-01

    Abstract Assessing the impact of kinase in gene fusion is essential for both identifying driver fusion genes (FGs) and developing molecular targeted therapies. Kinase domain retention is a crucial factor in kinase fusion genes (KFGs), but such a systematic investigation has not been done yet. To this end, we analyzed kinase domain retention (KDR) status in chimeric protein sequences of 914 KFGs covering 312 kinases across 13 major cancer types. Based on 171 kinase domain-retained KFGs including 101 kinases, we studied their recurrence, kinase groups, fusion partners, exon-based expression depth, short DNA motifs around the break points and networks. Our results, such as more KDR than 5′-kinase fusion genes, combinatorial effects between 3′-KDR kinases and their 5′-partners and a signal transduction-specific DNA sequence motif in the break point intronic sequences, supported positive selection on 3′-kinase fusion genes in cancer. We introduced a degree-of-frequency (DoF) score to measure the possible number of KFGs of a kinase. Interestingly, kinases with high DoF scores tended to undergo strong gene expression alteration at the break points. Furthermore, our KDR gene fusion network analysis revealed six of the seven kinases with the highest DoF scores (ALK, BRAF, MET, NTRK1, NTRK3 and RET) were all observed in thyroid carcinoma. Finally, we summarized common features of ‘effective’ (highly recurrent) kinases in gene fusions such as expression alteration at break point, redundant usage in multiple cancer types and 3′-location tendency. Collectively, our findings are useful for prioritizing driver kinases and FGs and provided insights into KFGs’ clinical implications. PMID:28013235

  4. Impedance interactions in bidirectional cascaded converter

    DEFF Research Database (Denmark)

    Tian, Yanjun; Loh, Poh Chiang; Chen, Zhe

    2016-01-01

    A cascaded converter is built by connecting one elementary converter to another. Output impedance of one converter will therefore interact with input impedance of the other converter. This interaction will change when power flow reverses. To compare this difference, an investigation is performed...

  5. Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

    International Nuclear Information System (INIS)

    Grose, C.; Jackson, W.; Traugh, J.A.

    1989-01-01

    Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

  6. Receptor-interacting protein (RIP) kinase family

    OpenAIRE

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, incl...

  7. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome

    NARCIS (Netherlands)

    Wösten-van Asperen, Roelie M.; Bos, Albert P.; Bem, Reinout A.; Dierdorp, Barbara S.; Dekker, Tamara; van Goor, Harry; Kamilic, Jelena; van der Loos, Chris M.; van den Berg, Elske; Bruijn, Martijn; van Woensel, Job B.; Lutter, René

    2013-01-01

    Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter-regulatory enzyme of angiotensin-converting enzyme that converts angiotensin

  8. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome

    NARCIS (Netherlands)

    Wosten-van Asperen, Roelie M.; Bos, Albert; Bem, Reinout A.; Dierdorp, Barbara S.; Dekker, Tamara; van Goor, Harry; Kamilic, Jelena; van der Loos, Chris M.; van den Berg, Elske; Bruijn, Martijn; van Woensel, Job B.; Lutter, Rene

    2013-01-01

    Objective: Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter-regulatory enzyme of angiotensin-converting enzyme that converts

  9. Release from tonic inhibition of T cell activation through transient displacement of C-terminal Src kinase (Csk) from lipid rafts

    Czech Academy of Sciences Publication Activity Database

    Torgersen, K. M.; Vang, T.; Abrahamsen, H.; Yaqub, S.; Hořejší, Václav; Schraven, B.; Rolstad, B.; Mustelin, T.; Tasken, K.

    2001-01-01

    Roč. 276, č. 31 (2001), s. 29313-29318 ISSN 0021-9258 R&D Projects: GA AV ČR IAA7052904 Institutional research plan: CEZ:AV0Z5052915 Keywords : kinase * signalling * lymphocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.258, year: 2001

  10. Simulation Results of Double Forward Converter

    Directory of Open Access Journals (Sweden)

    P. Vijaya KUMAR

    2009-12-01

    Full Text Available This work aims to find a better forward converter for DC to DC conversion.Simulation of double forward converter in SMPS system is discussed in this paper. Aforward converter with RCD snubber to synchronous rectifier and/or to current doubleris also discussed. The evolution of the forward converter is first reviewed in a tutorialfashion. Performance parameters are discussed including operating principle, voltageconversion ratio, efficiency, device stress, small-signal dynamics, noise and EMI. Itscircuit operation and its performance characteristics of the forward converter with RCDsnubber and double forward converter are described and the simulation results arepresented.

  11. Current interruption transients calculation

    CERN Document Server

    Peelo, David F

    2014-01-01

    Provides an original, detailed and practical description of current interruption transients, origins, and the circuits involved, and how they can be calculated Current Interruption Transients Calculationis a comprehensive resource for the understanding, calculation and analysis of the transient recovery voltages (TRVs) and related re-ignition or re-striking transients associated with fault current interruption and the switching of inductive and capacitive load currents in circuits. This book provides an original, detailed and practical description of current interruption transients, origins,

  12. Bidirectional dc-to-dc Power Converter

    Science.gov (United States)

    Griesbach, C. R.

    1986-01-01

    Solid-state, series-resonant converter uses high-voltage thyristors. Converter used either to convert high-voltage, low-current dc power to lowvoltage, high current power or reverse. Taking advantage of newly-available high-voltage thyristors to provide better reliability and efficiency than traditional converters that use vacuum tubes as power switches. New converter essentially maintenance free and provides greatly increased mean time between failures. Attractive in industrial applications whether or not bidirectional capability is required.

  13. Hydrogen converters

    International Nuclear Information System (INIS)

    Mondino, Angel V.

    2003-01-01

    The National Atomic Energy Commission of Argentina developed a process of 99 Mo production from fission, based on irradiation of uranium aluminide targets with thermal neutrons in the RA-3 reactor of the Ezeiza Atomic Centre. These targets are afterwards dissolved in an alkaline solution, with the consequent liberation of hydrogen as the main gaseous residue. This work deals with the use of a first model of metallic converter and a later prototype of glass converter at laboratory scale, adjusted to the requirements and conditions of the specific redox process. Oxidized copper wires were used, which were reduced to elementary copper at 400 C degrees and then regenerated by oxidation with hot air. Details of the bed structure and the operation conditions are also provided. The equipment required for the assembling in cells is minimal and, taking into account the operation final temperature and the purge with nitrogen, the procedure is totally safe. Finally, the results are extrapolated for the design of a converter to be used in a hot cell. (author)

  14. Electric current - frequency converter

    International Nuclear Information System (INIS)

    Kumahara, Tadashi; Kinbana, Setsuro.

    1967-01-01

    Herein disclosed is an improved simple electric current-frequency converter, the input current and output frequency linearity of which is widened to a range of four to five figures while compensating, for temperature. The converter may be used for computor processing and for telemetering the output signals from a nuclear reactor. The converter is an astable multivibrator which includes charging circuits comprising emitter-voltage compensated NPN transistors, a charged voltage detecting circuit of temperature compensated field effect transistors, and a transistor switching circuit for generating switching pulses independent of temperature. The converter exhibited a 0.7% frequency change within a range of 5 - 45 0 C and less than a 0.1% frequency drift after six hours of operation when the input current was maintained constant. (Yamaguchi, T.)

  15. DNA-dependent protein kinase (DAN-PK), a key enzyme in the re-ligation of DNA double-strand breaks

    International Nuclear Information System (INIS)

    Hennequin, C.; Averbeck, D.

    1999-01-01

    Repair pathways of DNA are now defined and some important findings have been discovered in the last few years. DNA non-homologous end-joining (NEH) is a crucial process in the repair of radiation-induced double-strand breaks (DSBs). NHEj implies at least three steps: the DNA free-ends must get closer, preparation of the free-ends by exonucleases and then a transient hybridization in a region of DNA with weak homology. DNA-dependent protein kinase (DNA-PK) is the key enzyme in this process. DNA-PK is a nuclear serine/threonine kinase that comprises three components: a catalytic subunit (DNA-PK cs ) and two regulatory subunits, DNA-binding proteins, Ku80 and Ku70. The severe combined immuno-deficient (scid) mice are deficient in DNA-PK cs : this protein is involved both in DNA repair and in the V(D)J recombination of immunoglobulin and T-cell receptor genes. It is a protein-kinase of the P13-kinase family and which can phosphorylate Ku proteins, p53 and probably some other proteins still unknown. DNA-PK is an important actor of DSBs repair (induced by ionising radiations or by drugs like etoposide), but obviously it is not the only mechanism existing in the cell for this function. Some others, like homologous recombination, seem also to have a great importance for cell survival. (authors)

  16. Step-Up DC-DC converters

    DEFF Research Database (Denmark)

    Forouzesh, Mojtaba; Siwakoti, Yam P.; Gorji, Saman A.

    2017-01-01

    on the general law and framework of the development of next-generation step-up dc-dc converters, this paper aims to comprehensively review and classify various step-up dc-dc converters based on their characteristics and voltage-boosting techniques. In addition, the advantages and disadvantages of these voltage......DC-DC converters with voltage boost capability are widely used in a large number of power conversion applications, from fraction-of-volt to tens of thousands of volts at power levels from milliwatts to megawatts. The literature has reported on various voltage-boosting techniques, in which......-boosting techniques and associated converters are discussed in detail. Finally, broad applications of dc-dc converters are presented and summarized with comparative study of different voltage-boosting techniques....

  17. Transient ischemic attack presenting in an elderly patient with transient ophthalmic manifestations

    Directory of Open Access Journals (Sweden)

    Sparshi Jain

    2016-01-01

    Full Text Available Transient ischemic attack (TIA is a transient neurological deficit of cerebrovascular origin without infarction which may last only for a short period and can have varying presentations. We report a case of 58-year-old male with presenting features of sudden onset transient vertical diplopia and transient rotatory nystagmus which self-resolved within 12 h. Patient had no history of any systemic illness. On investigating, hematological investigations and neuroimaging could not explain these sudden and transient findings. A TIA could possibly explain these sudden and transient ocular findings in our patient. This case report aims to highlight the importance of TIA for ophthalmologists. We must not ignore these findings as these could be warning signs of an impending stroke which may or may not be detected on neuroimaging. Thus, early recognition, primary prevention strategies, and timely intervention are needed.

  18. Catalytic converters in the fireplace

    International Nuclear Information System (INIS)

    Kouki, J.

    1995-01-01

    In addition to selecting the appropriate means of heating and using dry fuel, the amount of harmful emissions contained by flue gases produced by fireplaces can be reduced by technical means. One such option is to use an oxidising catalytic converter. Tests at TTS Institute's Heating Studies Experimental Station have focused on two such converters (dense and coarse) mounted in light-weight iron heating stoves. The ability of the dense catalytic converter to oxidise carbon monoxide gases proved to be good. The concentration of carbon monoxide in the flue gases was reduced by as much as 90 %. Measurements conducted by VTT (Technical Research Centre of Finland) showed that the conversion of other gases, e.g. of methane, was good. The exhaust resistance caused by the dense converter was so great as to necessitate the mounting of a fluegas evacuation fan in the chimney for the purpose of creating sufficient draught. When relying on natural draught, the dense converter requires a chimney of at least 7 metres and a by-pass connection while the fire is being lit. In addition, the converter will have to be constructed to be less dense and this will mean that it's capability to oxidise non-combusted gases will be reduced. The coarse converter did not impair the draught but it's oxidising property was insufficient. With the tests over, the converter was not observed to have become blocked up by impurities

  19. LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase pathways

    International Nuclear Information System (INIS)

    Tong, W.-G.; Ding, X.-Z.; Talamonti, Mark S.; Bell, Richard H.; Adrian, Thomas E.

    2005-01-01

    We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4 receptor antagonists block growth and induce apoptosis in pancreatic cancer cells both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4 stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human pancreatic cancer cells, as measured by thymidine incorporation and cell number. LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38 MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not involved

  20. Spectrometric analog-to-digital converter

    International Nuclear Information System (INIS)

    Ormandzhiev, S.I.; Jordanov, V.T.

    1988-01-01

    Converter of digit-by-digit counterbalancing with slipping dial with number of channels equal to total number of states of the main digital-to-analog converter of digit-by-digit counterbalancing systems is presented. Algorithm for selection of digital-to-analog converters, which must be used by means of computer is suggested

  1. Interactions between the S-Domain Receptor Kinases and AtPUB-ARM E3 Ubiquitin Ligases Suggest a Conserved Signaling Pathway in Arabidopsis1[W][OA

    Science.gov (United States)

    Samuel, Marcus A.; Mudgil, Yashwanti; Salt, Jennifer N.; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R.

    2008-01-01

    The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses. PMID:18552232

  2. syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

    Science.gov (United States)

    El-Hillal, O.; Kurosaki, T.; Yamamura, H.; Kinet, J.-P.; Scharenberg, A. M.

    1997-01-01

    Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well. PMID:9050880

  3. Protein phosphatases active on acetyl-CoA carboxylase phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Witters, L.A.; Bacon, G.W.

    1985-01-01

    The protein phosphatases in rat liver cytosol, active on rat liver acetyl-CoA carboxylase (ACC) phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase, have been partially purified by anion-exchange and gel filtration chromatography. The major phosphatase activities against all three substrates copurify through fractionation and appear to be identical to protein phosphatases 2A1 and 2A2. No unique protein phosphatase active on 32 P-ACC phosphorylated by the casein kinases was identified

  4. Transient analyzer

    International Nuclear Information System (INIS)

    Muir, M.D.

    1975-01-01

    The design and design philosophy of a high performance, extremely versatile transient analyzer is described. This sub-system was designed to be controlled through the data acquisition computer system which allows hands off operation. Thus it may be placed on the experiment side of the high voltage safety break between the experimental device and the control room. This analyzer provides control features which are extremely useful for data acquisition from PPPL diagnostics. These include dynamic sample rate changing, which may be intermixed with multiple post trigger operations with variable length blocks using normal, peak to peak or integrate modes. Included in the discussion are general remarks on the advantages of adding intelligence to transient analyzers, a detailed description of the characteristics of the PPPL transient analyzer, a description of the hardware, firmware, control language and operation of the PPPL transient analyzer, and general remarks on future trends in this type of instrumentation both at PPPL and in general

  5. Improving Power Converter Reliability

    DEFF Research Database (Denmark)

    Ghimire, Pramod; de Vega, Angel Ruiz; Beczkowski, Szymon

    2014-01-01

    of a high-power IGBT module during converter operation, which may play a vital role in improving the reliability of the power converters. The measured voltage is used to estimate the module average junction temperature of the high and low-voltage side of a half-bridge IGBT separately in every fundamental......The real-time junction temperature monitoring of a high-power insulated-gate bipolar transistor (IGBT) module is important to increase the overall reliability of power converters for industrial applications. This article proposes a new method to measure the on-state collector?emitter voltage...... is measured in a wind power converter at a low fundamental frequency. To illustrate more, the test method as well as the performance of the measurement circuit are also presented. This measurement is also useful to indicate failure mechanisms such as bond wire lift-off and solder layer degradation...

  6. Transient Simulation Study of Slip-Frequency Vector Control for Variable Speed Doubly-Fed Brushless Motor with Magnetic Barrier Rotor

    Directory of Open Access Journals (Sweden)

    Jingxiong ZHANG

    2014-01-01

    Full Text Available In this paper, a transient simulation model of a variable speed doubly fed brushless motor (DFBM using back-to-back converter is described. Based on analysis of rotor flux oriented vector control theory of doubly fed induction motor, the control of the currents in DFBM that produce the magnetic flux and the torque is achieved by a digital controller, the speed is regulated by a PI controller which is tuned by a genetic algorithm. According to the state equation of DFBM and the control schemes, the system simulation module is established in MATLAB/ SIMULINK. An extensive simulation study is performed to examine the control characteristics of the machine-side converter under different operation conditions in variable-speed DFBM driver system.

  7. A resonant dc-dc power converter assembly

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a resonant DC-DC power converter assembly comprising a first resonant DC-DC power converter and a second resonant DC-DC power converter having identical circuit topologies. A first inductor of the first resonant DC-DC power converter and a second inductor of the s......The present invention relates to a resonant DC-DC power converter assembly comprising a first resonant DC-DC power converter and a second resonant DC-DC power converter having identical circuit topologies. A first inductor of the first resonant DC-DC power converter and a second inductor...... of the second resonant DC-DC power converter are configured for magnetically coupling the first and second resonant DC-DC power converters to each other to forcing substantially 180 degrees phase shift, or forcing substantially 0 degree phase shift, between corresponding resonant voltage waveforms of the first...

  8. Receptor-interacting protein (RIP) kinase family

    Science.gov (United States)

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, including those in innate immunity, but their downstream substrates are largely unknown. This review will give an overview of the structures and functions of RIP family members, and an update of recent progress in RIP kinase research. PMID:20383176

  9. Ocular injury by transient formaldehyde exposure in a rabbit eye model.

    Directory of Open Access Journals (Sweden)

    Li-Ju Lai

    Full Text Available Formaldehyde (FA is frequently used in sterilizing surgical instruments and materials. Exposure to FA is highly concerned for eye tissues. Rabbit corneal epithelial cells were examined for changes after FA exposure. Our results showed that cell survival decreased 7 days after transient 3 min exposure to more than 100 ppm FA by trypan blue staining while MTT assay detected significant decrease at 20 ppm at 24 hours observation. The decrease of cell survival rate was concentration (up to 600 ppm- and observation time (1-7 day- dependent. The cell number decreased after 100 ppm FA exposure for more than 10 min at 7-day observation. The FA treated cells showed increased apoptosis/necrosis and cell cycle accumulation at sub G1 phase as well as mitochondria clustering around nucleus. The in vivo rabbit eye exposure for tear production by Schirmer's test revealed that the FA-induced overproduction of tear also exhibited observation time (1-10 day- and FA concentration (20-300 ppm for 5 min exposure-dependent. Activated extracellular signal-regulated kinase (pERK2 in cornea explants by western blotting was reduced and increased c-Jun amino - terminal kinase (JNK activation (pJNK in cornea and conjunctiva was evident at 2 month after exposure to 50-200 ppm FA for 5 min. In conclusion, injury to the eye with transient exposure of up to 100 ppm FA for 3 min decreased corneal cell survival while a more sensitive MTT test detected the cell decrease at 20 ppm FA exposure. Morphology changes can be observed even at 5 ppm FA exposure for 3 min at 7 days after. The FA exposure also increased apoptotic/necrotic cells and sub-G1 phase in cell cycle. Long term effect (2 months after exposure on the eye tissues even after the removal of FA can be observed with persistent JNK activation in cornea and conjunctiva.

  10. The electric supercharger. Improved transient behavior and reduced CO{sub 2} as well as NO{sub x} emissions at the same time?; Die elektrische Zusatzaufladung. Verbessertes transientes Verhalten sowie reduzierte CO{sub 2} und NO{sub x}-Emissionen zur gleichen Zeit?

    Energy Technology Data Exchange (ETDEWEB)

    Forissier, Michel; Zechmair, Derrick; Weber, Olaf; Criddle, Mark; Durrieu, David; Picron, Vanessa; Menegazzi, Pascal; Surbled, Kevin; Wu, Yiming [Valeo Powertrain Systems, Creteil (France)

    2013-08-01

    The Valeo Electric Supercharger allows improved engine transient behavior and fuel consumption as well as lower NO{sub x} emissions. The extra electric boosting enables an improvement in the air loop response time by an accelerated boost pressure build-up in both diesel and gasoline engines. This improved dynamic behavior can be converted into fuel consumption through extreme engine downsizing or/and downspeeding. Extreme downsizing and very long transmission gear ratios degrade vehicle driveability. The electric supercharger is a key enabler to overcome this issue and even provide far better dynamics. On Diesel engines, control of the NO{sub x} emissions and the EGR system in transient operation will have to be addressed particularly with the new driving cycle regulation (WLTC, RDE). The boosting of the air loop in combination with the EGR in transient operation improves NO{sub x} emissions while maintaining driveability. The presented benefits can be realized with an evolved 12V electrical architecture and are fully compliant with more capable, higher voltage architectures. (orig.)

  11. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas

    2009-01-01

    of numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites......, the activation loop and the Z/TM in the C-terminal extension. We provide evidence that phosphorylation of the Z/TM site of PRK2 inhibits its interaction with PDK1. Our studies further provide a mechanistic model to explain different steps in the docking interaction and regulation. Interestingly, we found...... that the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2 and do...

  12. HVDC-System-Interaction Assessment through Line-Flow Change-Distribution Factor and Transient-Stability Analysis at Planning Stage

    Directory of Open Access Journals (Sweden)

    Sungchul Hwang

    2016-12-01

    Full Text Available Many of the recent projects for new transmission line have considered the high-voltage direct current (HVDC system, owing to the many advantages of the direct current (DC system. The most noteworthy advantage is that a cable can serve as a substitute for the overhead transmission line in residential areas; therefore, the HVDC system application is increasing, and as the number of DC systems in the power system increases, the interaction assessment regarding the HVDC system gains importance. An index named multi-infeed interaction factor (MIIF is commonly used to estimate the interaction between power converters; however, the HVDC system is composed of two converters and a transmission line. The MIIF represents the interaction between the rectifiers and inverters, but not for the whole system. In this work, a method to assess the interaction of the whole system was therefore studied. To decide on the location of the new HVDC transmission system at the planning stage, in consideration of the interaction of the existing DC system, the line flow change distribution factor, according to the HVDC-transmission capacity change, was examined. Also, a power system transient -stability analysis was performed with different HVDC system locations, depending on the distribution factor. The simulation results indicate that when the factor is higher, two HVDC systems have a stronger interaction and are less stable in the transient state.

  13. Dual Converter Fed Open-End Transformer Topology with Parallel Converters and Integrated Magnetics

    DEFF Research Database (Denmark)

    Gohil, Ghanshyamsinh Vijaysinh; Bede, Lorand; Teodorescu, Remus

    2016-01-01

    that flows between the parallel interleaved VSCs. An integrated inductor is proposed which suppresses the circulating current in both the converter groups. In addition, the functionality of the line filter inductor is also integrated. Flux in various parts of the integrated inductor is analyzed and a design......A converter system for high power applications, connected to a medium-voltage network using a stepup transformer, is presented in this paper. The converterside winding of the transformer is configured as an openend and both the ends of the windings are fed from two different converter groups. Each...... procedure is also described. The volume and the losses of the proposed solution are compared with that of the state-of-art solution. The control of the proposed converter system is also discussed. The analysis has been verified by the simulation and experimental results....

  14. Loss of Sphingosine Kinase Alters Life History Traits and Locomotor Function in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Jason P. Chan

    2017-09-01

    Full Text Available Sphingolipid metabolism is important to balance the abundance of bioactive lipid molecules involved in cell signaling, neuronal function, and survival. Specifically, the sphingolipid sphingosine mediates cell death signaling, whereas its phosphorylated form, sphingosine-1-phosphate (S1P, mediates cell survival signaling. The enzyme sphingosine kinase produces S1P, and the activity of sphingosine kinase impacts the ability of cells to survive under stress and challenges. To examine the influence of sphingolipid metabolism, particularly enzymes regulating sphingosine and S1P, in mediating aging, neuronal function and stress response, we examined life history traits, locomotor capacities and heat stress responses of young and old animals using the model organism Caenorhabditis elegans. We found that C. elegans sphk-1 mutants, which lack sphingosine kinase, had shorter lifespans, reduced brood sizes, and smaller body sizes compared to wild type animals. By analyzing a panel of young and old animals with genetic mutations in the sphingolipid signaling pathway, we showed that aged sphk-1 mutants exhibited a greater decline in neuromuscular function and locomotor behavior. In addition, aged animals lacking sphk-1 were more susceptible to death induced by acute and prolonged heat exposure. On the other hand, older animals with loss of function mutations in ceramide synthase (hyl-1, which converts sphingosine to ceramide, showed improved neuromuscular function and stress response with age. This phenotype was dependent on sphk-1. Together, our data show that loss of sphingosine kinase contributes to poor animal health span, suggesting that sphingolipid signaling may be important for healthy neuronal function and animal stress response during aging.

  15. Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration.

    Directory of Open Access Journals (Sweden)

    Erika Costa de Alvarenga

    Full Text Available The angiotensin-I converting enzyme (ACE plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II. More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet.Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration.We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC, and experimental results in CHO cells, demonstrated that the β3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5 showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein.ACE activation regulates melanoma cell proliferation and migration.

  16. Transient drainage summary report

    International Nuclear Information System (INIS)

    1996-09-01

    This report summarizes the history of transient drainage issues on the Uranium Mill Tailings Remedial Action (UMTRA) Project. It defines and describes the UMTRA Project disposal cell transient drainage process and chronicles UMTRA Project treatment of the transient drainage phenomenon. Section 4.0 includes a conceptual cross section of each UMTRA Project disposal site and summarizes design and construction information, the ground water protection strategy, and the potential for transient drainage

  17. TRANSIENT ELECTRONICS CATEGORIZATION

    Science.gov (United States)

    2017-08-24

    AFRL-RY-WP-TR-2017-0169 TRANSIENT ELECTRONICS CATEGORIZATION Dr. Burhan Bayraktaroglu Devices for Sensing Branch Aerospace Components & Subsystems...SUBTITLE TRANSIENT ELECTRONICS CATEGORIZATION 5a. CONTRACT NUMBER In-house 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER N/A 6. AUTHOR(S) Dr. Burhan...88ABW-2017-3747, Clearance Date 31 July 2017. Paper contains color. 14. ABSTRACT Transient electronics is an emerging technology area that lacks proper

  18. Closed-loop analysis and control of a non-inverting buck-boost converter

    Science.gov (United States)

    Chen, Zengshi; Hu, Jiangang; Gao, Wenzhong

    2010-11-01

    In this article, a cascade controller is designed and analysed for a non-inverting buck-boost converter. The fast inner current loop uses sliding mode control. The slow outer voltage loop uses the proportional-integral (PI) control. Stability analysis and selection of PI gains are based on the nonlinear closed-loop error dynamics incorporating both the inner and outer loop controllers. The closed-loop system is proven to have a nonminimum phase structure. The voltage transient due to step changes of input voltage or resistance is predictable. The operating range of the reference voltage is discussed. The controller is validated by a simulation circuit. The simulation results show that the reference output voltage is well-tracked under system uncertainties or disturbances, confirming the validity of the proposed controller.

  19. Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei

    Science.gov (United States)

    Li, H.; Roux, S. J.

    1992-01-01

    Almost all the polyamine-stimulated protein kinase activity associated with the chromatin fraction of nuclei purified from etiolated pea (Pisum sativum L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.35 molar NaCl. This protein kinase can be further purified over 2000-fold by salt fractionation and anion-exchange and casein-agarose column chromatography, after which it is more than 90% pure. The purified kinase has a specific activity of about 650 nanomoles per minute per milligram protein in the absence of polyamines, with either ATP or GTP as phosphoryl donor. Spermidine can stimulate its activity fourfold, with half-maximal activation at about 2 millimolar. Spermine and putrescine also stimulate activity, although somewhat less effectively. This kinase has a tetrameric alpha 2 beta 2 structure with a native molecular weight of 130,000, and subunit molecular weights of 36,000 for the catalytic subunit (alpha) and 29,000 for the regulatory subunit (beta). In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II. The pea kinase can use casein and phosvitin as artificial substrates, phosphorylating both the serine and threonine residues of casein. It has a pH optimum near 8.0, a Vmax of 1.5 micromoles per minute per milligram protein, and a Km for ATP of approximately 75 micromolar. Its activity can be almost completely inhibited by heparin at 5 micrograms per milliliter, but is relatively insensitive to concentrations of staurosporine, K252a, and chlorpromazine that strongly antagonize Ca(2+) -regulated protein kinases. These results are discussed in relation to recent findings that casein kinase 2-type kinases may phosphorylate trans-acting factors that bind to light-regulated promoters in plants.

  20. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes.

    Science.gov (United States)

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-09-14

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes.

  1. The TRPM6 Kinase Domain Determines the Mg·ATP Sensitivity of TRPM7/M6 Heteromeric Ion Channels*

    Science.gov (United States)

    Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

    2014-01-01

    The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg2+) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg2+ and therefore unlikely to be active at physiological levels of [Mg2+]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex. PMID:24385424

  2. The TRPM6 kinase domain determines the Mg·ATP sensitivity of TRPM7/M6 heteromeric ion channels.

    Science.gov (United States)

    Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

    2014-02-21

    The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg(2+)) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg(2+) and therefore unlikely to be active at physiological levels of [Mg(2+)]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex.

  3. Charge-pump voltage converter

    Science.gov (United States)

    Brainard, John P [Albuquerque, NM; Christenson, Todd R [Albuquerque, NM

    2009-11-03

    A charge-pump voltage converter for converting a low voltage provided by a low-voltage source to a higher voltage. Charge is inductively generated on a transfer rotor electrode during its transit past an inductor stator electrode and subsequently transferred by the rotating rotor to a collector stator electrode for storage or use. Repetition of the charge transfer process leads to a build-up of voltage on a charge-receiving device. Connection of multiple charge-pump voltage converters in series can generate higher voltages, and connection of multiple charge-pump voltage converters in parallel can generate higher currents. Microelectromechanical (MEMS) embodiments of this invention provide a small and compact high-voltage (several hundred V) voltage source starting with a few-V initial voltage source. The microscale size of many embodiments of this invention make it ideally suited for MEMS- and other micro-applications where integration of the voltage or charge source in a small package is highly desirable.

  4. A resonant dc-dc power converter assembly

    OpenAIRE

    Madsen, Mickey Pierre

    2015-01-01

    The present invention relates to a resonant DC-DC power converter assembly comprising a first resonant DC-DC power converter and a second resonant DC-DC power converter having identical circuit topologies. A first inductor of the first resonant DC-DC power converter and a second inductor of the second resonant DC-DC power converter are configured for magnetically coupling the first and second resonant DC-DC power converters to each other to forcing substantially 180 degrees phase shift, or fo...

  5. LeCPK1, a Calcium-Dependent Protein Kinase from Tomato. Plasma Membrane Targeting and Biochemical Characterization1

    Science.gov (United States)

    Rutschmann, Frank; Stalder, Urs; Piotrowski, Markus; Oecking, Claudia; Schaller, Andreas

    2002-01-01

    The cDNA of LeCPK1, a calcium-dependent protein kinase, was cloned from tomato (Lycopersicon esculentum Mill.). LeCPK1 was expressed in Escherichia coli and purified from bacterial extracts. The recombinant protein was shown to be a functional protein kinase using a synthetic peptide as the substrate (syntide-2, Km = 85 μm). Autophosphorylation of LeCPK1 was observed on threonine and serine residues, one of which was identified as serine-439. Kinase activity was shown to be Ca2+ dependent and required the C-terminal, calmodulin-like domain of LeCPK1. Two classes of high- and low-affinity Ca2+-binding sites were observed, exhibiting dissociation constants of 0.6 and 55 μm, respectively. LeCPK1 was found to phosphorylate the regulatory C-terminal domain of the plasma membrane H+-ATPase in vitro. A potential role in the regulation of proton pump activity is corroborated by the apparent colocalization of the plasma membrane H+-ATPase and LeCPK1 in vivo. Upon transient expression in suspension-cultured cells, a C-terminal fusion of LeCPK1 with the green fluorescent protein was targeted to the plasma membrane. Myristoylation of the LeCPK1 N terminus was found to be required for plasma membrane targeting. PMID:12011347

  6. High Current, Low Voltage Power Converter [20kA, 6V] LHC Converter Prototype

    CERN Document Server

    Jørgensen, H E; Dupaquier, A; Fernqvist, G

    1998-01-01

    The superconducting LHC accelerator requires high currents (~12.5kA) and relatively low voltages (~10 V) for its magnets. The need to install the power converters underground is the driving force for reduced volume and high efficiency. Moreover, the LHC machine will require a very high level of performance from the power converters, particularly in terms of DC stability, dynamic response and also in matters of EMC. To meet these requirements soft-switching techniques will be used. This paper describes the development of a [20kA,6V] power converter intended as a stable high-current source for D CCT calibration and an evaluation prototype for the future LHC converters. The converter is made with a modular concept with five current sources [4kA,6V] in parallel. The 4kA sources are built as plu g-in modules: a diode rectifier on the AC mains with a damped L-C passive filter, a Zero Voltage Switching inverter working at 20 kHz and an output stage (high frequency transformers, Schottky rectifi ers and output filter...

  7. Trans-kingdom mimicry underlies ribosome customization by a poxvirus kinase.

    Science.gov (United States)

    Jha, Sujata; Rollins, Madeline G; Fuchs, Gabriele; Procter, Dean J; Hall, Elizabeth A; Cozzolino, Kira; Sarnow, Peter; Savas, Jeffrey N; Walsh, Derek

    2017-06-29

    Ribosomes have the capacity to selectively control translation through changes in their composition that enable recognition of specific RNA elements. However, beyond differential subunit expression during development, evidence for regulated ribosome specification within individual cells has remained elusive. Here we report that a poxvirus kinase phosphorylates serine/threonine residues in the human small ribosomal subunit protein, receptor for activated C kinase (RACK1), that are not phosphorylated in uninfected cells or cells infected by other viruses. These modified residues cluster in an extended loop in RACK1, phosphorylation of which selects for translation of viral or reporter mRNAs with 5' untranslated regions that contain adenosine repeats, so-called polyA-leaders. Structural and phylogenetic analyses revealed that although RACK1 is highly conserved, this loop is variable and contains negatively charged amino acids in plants, in which these leaders act as translational enhancers. Phosphomimetics and inter-species chimaeras have shown that negative charge in the RACK1 loop dictates ribosome selectivity towards viral RNAs. By converting human RACK1 to a charged, plant-like state, poxviruses remodel host ribosomes so that adenosine repeats erroneously generated by slippage of the viral RNA polymerase confer a translational advantage. Our findings provide insight into ribosome customization through trans-kingdom mimicry and the mechanics of species-specific leader activity that underlie poxvirus polyA-leaders.

  8. PSH Transient Simulation Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Muljadi, Eduard [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-21

    PSH Transient Simulation Modeling presentation from the WPTO FY14 - FY16 Peer Review. Transient effects are an important consideration when designing a PSH system, yet numerical techniques for hydraulic transient analysis still need improvements for adjustable-speed (AS) reversible pump-turbine applications.

  9. Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase*S⃞

    Science.gov (United States)

    Kang, Nam Joo; Lee, Ki Won; Lee, Dong Eun; Rogozin, Evgeny A.; Bode, Ann M.; Lee, Hyong Joo; Dong, Zigang

    2008-01-01

    Cocoa was shown to inhibit chemically induced carcinogenesis in animals and exert antioxidant activity in humans. However, the molecular mechanisms of the chemopreventive potential of cocoa and its active ingredient(s) remain unknown. Here we report that cocoa procyanidins inhibit neoplastic cell transformation by suppressing the kinase activity of mitogen-activated protein kinase kinase (MEK). A cocoa procyanidin fraction (CPF) and procyanidin B2 at 5 μg/ml and 40 μm, respectively, inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ mouse epidermal (JB6 P+) cells by 47 and 93%, respectively. The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-κB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2. In vitro and ex vivo kinase assay data demonstrated that CPF or procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation. In contrast, theobromine (up to 80 μm) had no effect on TPA-induced transformation, cyclooxygenase-2 expression, the transactivation of activator protein-1 or nuclear factor-κB, or MEK. Notably, procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity and neoplastic cell transformation. PMID:18519570

  10. Identifying kinase dependency in cancer cells by integrating high-throughput drug screening and kinase inhibition data.

    Science.gov (United States)

    Ryall, Karen A; Shin, Jimin; Yoo, Minjae; Hinz, Trista K; Kim, Jihye; Kang, Jaewoo; Heasley, Lynn E; Tan, Aik Choon

    2015-12-01

    Targeted kinase inhibitors have dramatically improved cancer treatment, but kinase dependency for an individual patient or cancer cell can be challenging to predict. Kinase dependency does not always correspond with gene expression and mutation status. High-throughput drug screens are powerful tools for determining kinase dependency, but drug polypharmacology can make results difficult to interpret. We developed Kinase Addiction Ranker (KAR), an algorithm that integrates high-throughput drug screening data, comprehensive kinase inhibition data and gene expression profiles to identify kinase dependency in cancer cells. We applied KAR to predict kinase dependency of 21 lung cancer cell lines and 151 leukemia patient samples using published datasets. We experimentally validated KAR predictions of FGFR and MTOR dependence in lung cancer cell line H1581, showing synergistic reduction in proliferation after combining ponatinib and AZD8055. KAR can be downloaded as a Python function or a MATLAB script along with example inputs and outputs at: http://tanlab.ucdenver.edu/KAR/. aikchoon.tan@ucdenver.edu. Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Two-inductor boost and buck converters

    Science.gov (United States)

    White, J. L.; Muldoon, W. J.

    The derivation, analysis and design of a coupled inductor boost converter is presented. Aspects of the qualitative ac behavior of coupled inductor converters are discussed. Considerations for the design of the magnetics for such converters are addressed.

  12. MAP Kinase Cascades Regulate the Cold Response by Modulating ICE1 Protein Stability.

    Science.gov (United States)

    Zhao, Chunzhao; Wang, Pengcheng; Si, Tong; Hsu, Chuan-Chih; Wang, Lu; Zayed, Omar; Yu, Zheping; Zhu, Yingfang; Dong, Juan; Tao, W Andy; Zhu, Jian-Kang

    2017-12-04

    Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Interactions between Type III receptor tyrosine phosphatases and growth factor receptor tyrosine kinases regulate tracheal tube formation in Drosophila

    Directory of Open Access Journals (Sweden)

    Mili Jeon

    2012-04-01

    The respiratory (tracheal system of the Drosophila melanogaster larva is an intricate branched network of air-filled tubes. Its developmental logic is similar in some ways to that of the vertebrate vascular system. We previously described a unique embryonic tracheal tubulogenesis phenotype caused by loss of both of the Type III receptor tyrosine phosphatases (RPTPs, Ptp4E and Ptp10D. In Ptp4E Ptp10D double mutants, the linear tubes in unicellular and terminal tracheal branches are converted into bubble-like cysts that incorporate apical cell surface markers. This tube geometry phenotype is modulated by changes in the activity or expression of the epidermal growth factor receptor (Egfr tyrosine kinase (TK. Ptp10D physically interacts with Egfr. Here we demonstrate that the Ptp4E Ptp10D phenotype is the consequence of the loss of negative regulation by the RPTPs of three growth factor receptor TKs: Egfr, Breathless and Pvr. Reducing the activity of any of the three kinases by tracheal expression of dominant-negative mutants suppresses cyst formation. By competing dominant-negative and constitutively active kinase mutants against each other, we show that the three RTKs have partially interchangeable activities, so that increasing the activity of one kinase can compensate for the effects of reducing the activity of another. This implies that SH2-domain downstream effectors that are required for the phenotype are likely to be able to interact with phosphotyrosine sites on all three receptor TKs. We also show that the phenotype involves increases in signaling through the MAP kinase and Rho GTPase pathways.

  14. Understanding delta-sigma data converters

    CERN Document Server

    Pavan, Shanti; Temes, Gabor C

    2017-01-01

    This new edition introduces novel analysis and design techniques for delta-sigma (ΔΣ) converters in physical and conceptual terms, and includes new chapters that explore developments in the field over the last decade. This book explains the principles and operation of delta-sigma analog-to-digital converters (ADCs) in physical and conceptual terms in accordance with the most recent developments in the field. The interest of ΔΣ converter designers has shifted significantly over the past decade, due to many new applications for data converters at the far ends of the frequency spectrum. Continuous-time delta-sigma A/D converters with GHz clocks, of both lowpass and bandpass types, are required for wireless applications. At the other extreme, multiplexed ADCs with very narrow (sometimes 10 Hz wide) signal bandwidths, but very high accuracy are needed in the interfaces of biomedical and environmental sensors. To reflect the changing eeds of designers, the second edition includes significant new material on bo...

  15. A new concept of thermionic converter

    International Nuclear Information System (INIS)

    Musa, G.

    1978-10-01

    The parameters of a new type of thermionic converter which has a number of concentric electrodes, is computed. The obtained theoretical efficiency of this new type of converter is nearly the efficiency of the ideal thermionic converter. The obtained results are explained by the reduction of the radiation loss from the emitter due to the electrode configuration. Efficiencies as high as 20% are expected from this type of converter now in construction. (author)

  16. Advanced DC/DC converters

    CERN Document Server

    Luo, Fang Lin

    2003-01-01

    DC/DC conversion techniques have undergone rapid development in recent decades. With the pioneering work of these authors, DC/DC converters have now moved into their sixth generation. This book offers a concise, practical presentation of DC/DC converters, summarizing the spectrum of conversion tecnologies and presentingmany new ideas and more than 100 new topologies. Nowhere else in the literature are DC/DC converters so logically sorted and systematically introduced, and nowhere else can readers find detailed information on prototype topologies that represent a major contribution to modern power engineering. More than 320 figures, 60 tables, and 500 formulae facilitate understand and provide precise data.

  17. SSG Wave Energy Converter

    DEFF Research Database (Denmark)

    Margheritini, Lucia; Vicinanza, Diego; Frigaard, Peter

    2008-01-01

    The SSG (Sea Slot-cone Generator) is a wave energy converter of the overtopping type. The structure consists of a number of reservoirs one on the top of each others above the mean water level, in which the water of incoming waves is stored temporary. In each reservoir, expressively designed low...... head hydroturbines are converting the potential energy of the stored water into power. A key to success for the SSG will be the low cost of the structure and its robustness. The construction of the pilot plant is scheduled and this paper aims to describe the concept of the SSG wave energy converter...

  18. Na,K-ATPase regulates intercellular communication in the vascular wall via cSrc kinase dependent connexin43 phosphorylation

    DEFF Research Database (Denmark)

    Hangaard, Lise; Bouzinova, Elena; Stæhr, Christian Albeck

    2017-01-01

    Communication between vascular smooth muscle cells (VSMCs) is dependent on gap junctions and is regulated by the Na-K-ATPase. The Na-K-ATPase is therefore important for synchronized VSMC oscillatory activity, i.e., vasomotion. The signaling between the Na-K-ATPase and gap junctions is unknown. We...... coupling in rat mesenteric small arteries in vitro. Phosphorylation of cSrc kinase and connexin43 (Cx43) were semiquantified by Western blotting. Micromole concentration of ouabain reduced the amplitude of norepinephrine-induced vasomotion and desynchronized Ca2+ transients in VSMC in the arterial wall...

  19. Amplitude-to-frequency converter of radioisotope instruments

    International Nuclear Information System (INIS)

    Demchenkov, V.P.; Korobkov, I.N.

    1988-01-01

    An amplitude-to-frequency converter designed for signal processing of radioisotope relay devices is descibed. The basic elements of the converter are a scaling amplifier, an analog-to-digital converter, a code-to-frequency converter, a null-organ, a delay unit and a clock-pulse generator. The designed amplitude-to-frequency converter takes into account a prior information about the signal shape of the energy spectrum. The converter processes input pulses of 0.10 V amplitude and duration more than 2μs. The energy channel number is 64

  20. Src kinase regulation by phosphorylation and dephosphorylation

    International Nuclear Information System (INIS)

    Roskoski, Robert

    2005-01-01

    Src and Src-family protein-tyrosine kinases are regulatory proteins that play key roles in cell differentiation, motility, proliferation, and survival. The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation, and an inhibiting phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase (Csk) and Csk homologous kinase. Dephosphorylation of phosphotyrosine 527 increases Src kinase activity. Candidate phosphotyrosine 527 phosphatases include cytoplasmic PTP1B, Shp1 and Shp2, and transmembrane enzymes include CD45, PTPα, PTPε, and PTPλ. Dephosphorylation of phosphotyrosine 416 decreases Src kinase activity. Thus far PTP-BL, the mouse homologue of human PTP-BAS, has been shown to dephosphorylate phosphotyrosine 416 in a regulatory fashion. The platelet-derived growth factor receptor protein-tyrosine kinase mediates the phosphorylation of Src Tyr138; this phosphorylation has no direct effect on Src kinase activity. The platelet-derived growth factor receptor and the ErbB2/HER2 growth factor receptor protein-tyrosine kinases mediate the phosphorylation of Src Tyr213 and activation of Src kinase activity. Src kinase is also a substrate for protein-serine/threonine kinases including protein kinase C (Ser12), protein kinase A (Ser17), and CDK1/cdc2 (Thr34, Thr46, and Ser72). Of the three protein-serine/threonine kinases, only phosphorylation by CDK1/cdc2 has been demonstrated to increase Src kinase activity. Although considerable information on the phosphoprotein phosphatases that catalyze the hydrolysis of Src phosphotyrosine 527 is at hand, the nature of the phosphatases that mediate the hydrolysis of phosphotyrosine 138 and 213, and phosphoserine and phosphothreonine residues has not been determined

  1. Expression of Human CTP Synthetase in Saccharomyces cerevisiae Reveals Phosphorylation by Protein Kinase A*

    Science.gov (United States)

    Han, Gil-Soo; Sreenivas, Avula; Choi, Mal-Gi; Chang, Yu-Fang; Martin, Shelley S.; Baldwin, Enoch P.; Carman, George M.

    2005-01-01

    CTP synthetase (EC 6.3.4.2, UTP: ammonia ligase (ADP-forming)) is an essential enzyme in all organisms; it generates the CTP required for the synthesis of nucleic acids and membrane phospholipids. In this work we showed that the human CTP synthetase genes, CTPS1 and CTPS2, were functional in Saccharomyces cerevisiae and complemented the lethal phenotype of the ura7Δ ura8Δ mutant lacking CTP synthetase activity. The expression of the CTPS1-and CTPS2-encoded human CTP synthetase enzymes in the ura7Δ ura8Δ mutant was shown by immunoblot analysis of CTP synthetase proteins, the measurement of CTP synthetase activity, and the synthesis of CTP in vivo. Phosphoamino acid and phosphopeptide mapping analyses of human CTP synthetase 1 isolated from 32Pi-labeled cells revealed that the enzyme was phosphorylated on multiple serine residues in vivo. Activation of protein kinase A activity in yeast resulted in transient increases (2-fold) in the phosphorylation of human CTP synthetase 1 and the cellular level of CTP. Human CTP synthetase 1 was also phosphorylated by mammalian protein kinase A in vitro. Using human CTP synthetase 1 purified from Escherichia coli as a substrate, protein kinase A activity was dose- and time-dependent, and dependent on the concentrations of CTP synthetase1 and ATP. These studies showed that S. cerevisiae was useful for the analysis of human CTP synthetase phosphorylation. PMID:16179339

  2. Design and Implementation of Battery Charger with Power Factor Correction Using Sepic Converter and Full-bridge DC-DC Converter

    OpenAIRE

    Efendi, Moh. Zaenal; Windarko, Novie Ayub; Amir, Moh. Faisal

    2013-01-01

    This paper presents a design and implementation of a converter which has a high power factor for battery charger application. The converter is a combination of a SEPIC converter and a full-bridge DC-DC converter connected in two stages of series circuit. The SEPIC converter works in discontinuous conduction mode and it serves as a power factor corrector so that the shape of input current waveform follows the shape of input voltage waveform. The full-bridge DC-DC converter serves as a regulato...

  3. Transient analysis on the SMART-P anticipated transients without scram

    International Nuclear Information System (INIS)

    Yang, S. H.; Bae, K. H.; Kim, H. C.; Zee, S. Q.

    2005-01-01

    Anticipated transients without scram (ATWS) are anticipated operational occurrences accompanied by a failure of an automatic reactor trip when required. Although the occurrence probability of the ATWS events is considerably low, these events can result in unacceptable consequences, i.e. the pressurization of the reactor coolant system (RCS) up to an unacceptable range and a core-melting situation. Therefore, the regulatory body requests the installation of a protection system against the ATWS events. According to the request, a diverse protection system (DPS) is installed in the SMART-P (System-integrated Modular Advanced ReacTor-Pilot). This paper presents the results of the transient analysis performed to identify the performance of the SMART-P against the ATWS. In the analysis, the TASS/SMR (Transients And Setpoint Simulation/Small and Medium Reactor) code is applied to identify the thermal hydraulic response of the RCS during the transients

  4. OAM mode converter in twisted fibers

    DEFF Research Database (Denmark)

    Usuga Castaneda, Mario A.; Beltran-Mejia, Felipe; Cordeiro, Cristiano

    2014-01-01

    We analyze the case of an OAM mode converter based on a twisted fiber, through finite element simulations where we exploit an equivalence between geometric and material transformations. The obtained converter has potential applications in MDM. © 2014 OSA.......We analyze the case of an OAM mode converter based on a twisted fiber, through finite element simulations where we exploit an equivalence between geometric and material transformations. The obtained converter has potential applications in MDM. © 2014 OSA....

  5. Three-phase Resonant DC-link Converter

    OpenAIRE

    Munk-Nielsen, Stig

    1997-01-01

    The purpose of the project is to develop a three-phase resonant converter suitable for standard speed drives. The motivation for working with resonant converters is found in the problem of the standard converter type used today. In standard converter type Pulse Width Modulated-Voltage Source Inverter, PWM-VSI, the switches are subject to high current and voltage stress during switching, which causes losses. The fast switching of modern switches reduces switching losses. Unfortunately this pro...

  6. Structure-function similarities between a plant receptor-like kinase and the human interleukin-1 receptor-associated kinase-4.

    Science.gov (United States)

    Klaus-Heisen, Dörte; Nurisso, Alessandra; Pietraszewska-Bogiel, Anna; Mbengue, Malick; Camut, Sylvie; Timmers, Ton; Pichereaux, Carole; Rossignol, Michel; Gadella, Theodorus W J; Imberty, Anne; Lefebvre, Benoit; Cullimore, Julie V

    2011-04-01

    Phylogenetic analysis has previously shown that plant receptor-like kinases (RLKs) are monophyletic with respect to the kinase domain and share an evolutionary origin with the animal interleukin-1 receptor-associated kinase/Pelle-soluble kinases. The lysin motif domain-containing receptor-like kinase-3 (LYK3) of the legume Medicago truncatula shows 33% amino acid sequence identity with human IRAK-4 over the kinase domain. Using the structure of this animal kinase as a template, homology modeling revealed that the plant RLK contains structural features particular to this group of kinases, including the tyrosine gatekeeper and the N-terminal extension α-helix B. Functional analysis revealed the importance of these conserved features for kinase activity and suggests that kinase activity is essential for the biological role of LYK3 in the establishment of the root nodule nitrogen-fixing symbiosis with rhizobia bacteria. The kinase domain of LYK3 has dual serine/threonine and tyrosine specificity, and mass spectrometry analysis identified seven serine, eight threonine, and one tyrosine residue as autophosphorylation sites in vitro. Three activation loop serine/threonine residues are required for biological activity, and molecular dynamics simulations suggest that Thr-475 is the prototypical phosphorylated residue that interacts with the conserved arginine in the catalytic loop, whereas Ser-471 and Thr-472 may be secondary sites. A threonine in the juxtamembrane region and two threonines in the C-terminal lobe of the kinase domain are important for biological but not kinase activity. We present evidence that the structure-function similarities that we have identified between LYK3 and IRAK-4 may be more widely applicable to plant RLKs in general.

  7. Design and Implementation of Battery Charger with Power Factor Correction using Sepic Converter and Full-bridge DC-DC Converter

    Directory of Open Access Journals (Sweden)

    Moh. Zaenal Efendi

    2013-12-01

    Full Text Available This paper presents a design and implementation of a converter which has a high power factor for battery charger application. The converter is a combination of a SEPIC converter and a full-bridge DC-DC converter connected in two stages of series circuit. The SEPIC converter works in discontinuous conduction mode and it serves as a power factor corrector so that the shape of input current waveform follows the shape of input voltage waveform. The full-bridge DC-DC converter serves as a regulator of output voltage and operates at continuous conduction mode. The experimental results show that the power factor of this converter system can be achieved up to 0.96.

  8. Pyridoxal 5'-phosphate is a slow tight binding inhibitor of E. coli pyridoxal kinase.

    Directory of Open Access Journals (Sweden)

    Mohini S Ghatge

    Full Text Available Pyridoxal 5'-phosphate (PLP is a cofactor for dozens of B(6 requiring enzymes. PLP reacts with apo-B(6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B(6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4'-aldehyde moiety forms covalent adducts with other compounds and non-B(6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell is thus an important, yet unresolved issue. In this report, using site-directed mutagenesis, kinetic, spectroscopic and chromatographic studies we show that pyridoxal kinase from E. coli forms a complex with the product PLP to form an inactive enzyme complex. Evidence is presented that, in the inhibited complex, PLP has formed an aldimine bond with an active site lysine residue during catalytic turnover. The rate of dissociation of PLP from the complex is very slow, being only partially released after a 2-hour incubation with PLP phosphatase. Interestingly, the inactive pyridoxal kinase•PLP complex can be partially reactivated by transferring the tightly bound PLP to an apo-B(6 enzyme. These results open new perspectives on the mechanism of regulation and role of pyridoxal kinase in the Escherichia coli cell.

  9. Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I.

    Science.gov (United States)

    Miyazaki, Seira; Kim, Jihye; Yamagishi, Yuya; Ishiguro, Tadashi; Okada, Yuki; Tanno, Yuji; Sakuno, Takeshi; Watanabe, Yoshinori

    2017-06-01

    In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1. Consequently, in contrast to the transient kinetochore localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic analyses show a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin that is important for establishing meiosis-specific chromosome segregation. We provide evidence that the meiosis-specific Bub1 regulation is conserved in mouse. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  10. Design of a 12-bit 80-MS/s CMOS digital-to-analog converter for PLC-VDSL applications

    Science.gov (United States)

    Ruiz-Amaya, Jesus; Delgado-Restituto, Manuel; Fernandez-Bootello, J. Francisco; de la Rosa, Jose M.

    2005-06-01

    This paper describes the design of a 12-bit 80MS/s Digital-to-Analog converter implemented in 0.13mm CMOS logic technology. The design has been computer-aided by a developed toolbox for the simulation and verification of Nyquist-Rate Analog-to-Digital and Digital-to-Analog converters in MATLAB. The embedded simulator uses SIMULINK C-coded S-functions to model all required subcircuits including their main error mechanisms. This approach allows to drastically speed up the simulation CPU-time and makes the proposed tool an advantageous alternative for fast exploration of requirements and as a design validation tool. The converter is segmented in a unary current-cell matrix for 8 MSB's and a binary-weighted array for 4 LSB's. Current sources of the converter are laid out separately from current-cell switching matrix core block and distribute in double centroid to reduce random errors and transient noise coupling. The linearity errors caused by remaining gradient errors are reduced by a modified Q2 Random-Walk switching sequence. Simulation results show that the Spurious-Free Dynamic-Range is better than 58.5dB up to 80MS/s. The estimated Signal-to-Noise Distortion Ratio yield is 99.7% and it is supposed to be better than 58dB from DC to Nyquist frequency. Multi-Tone Power Ratio is higher 59dB for several DMT test signals. The converter dissipates less than 129mW from a 3.3V supply and occupies less than 1.7mm2 die area. The results have been checked with all process corners from -40° to 85° and power supply from 3V to 3.6V.

  11. Membrane depolarization-induced RhoA/Rho-associated kinase activation and sustained contraction of rat caudal arterial smooth muscle involves genistein-sensitive tyrosine phosphorylation

    Science.gov (United States)

    Mita, Mitsuo; Tanaka, Hitoshi; Yanagihara, Hayato; Nakagawa, Jun-ichi; Hishinuma, Shigeru; Sutherland, Cindy; Walsh, Michael P.; Shoji, Masaru

    2013-01-01

    Rho-associated kinase (ROK) activation plays an important role in K+-induced contraction of rat caudal arterial smooth muscle (Mita et al., Biochem J. 2002; 364: 431–40). The present study investigated a potential role for tyrosine kinase activity in K+-induced RhoA activation and contraction. The non-selective tyrosine kinase inhibitor genistein, but not the src family tyrosine kinase inhibitor PP2, inhibited K+-induced sustained contraction (IC50 = 11.3 ± 2.4 µM). Genistein (10 µM) inhibited the K+-induced increase in myosin light chain (LC20) phosphorylation without affecting the Ca2+ transient. The tyrosine phosphatase inhibitor vanadate induced contraction that was reversed by genistein (IC50 = 6.5 ± 2.3 µM) and the ROK inhibitor Y-27632 (IC50 = 0.27 ± 0.04 µM). Vanadate also increased LC20 phosphorylation in a genistein- and Y-27632-dependent manner. K+ stimulation induced translocation of RhoA to the membrane, which was inhibited by genistein. Phosphorylation of MYPT1 (myosin-targeting subunit of myosin light chain phosphatase) was significantly increased at Thr855 and Thr697 by K+ stimulation in a genistein- and Y-27632-sensitive manner. Finally, K+ stimulation induced genistein-sensitive tyrosine phosphorylation of proteins of ∼55, 70 and 113 kDa. We conclude that a genistein-sensitive tyrosine kinase, activated by the membrane depolarization-induced increase in [Ca2+]i, is involved in the RhoA/ROK activation and sustained contraction induced by K+. Ca2+ sensitization, myosin light chain phosphatase, RhoA, Rho-associated kinase, tyrosine kinase PMID:24133693

  12. Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin and Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C

    Science.gov (United States)

    2010-01-01

    cell lines (NCI-N417, NCI-H345, NCI-N592) were found to convert exogenous NT into the fragments NT1 –8 and NT9–13, reflecting the presence of...secrete NT. However, exogenous NT was degraded primarily to NT1 –11, consistent with the presence of neutral endopeptidase 3.4.24.11 in these cells . This...TITLE: Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin and Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C

  13. Full range ZVS DC-DC converter

    International Nuclear Information System (INIS)

    Upadhyay, Rinki; Badapanda, M.K.; Hannurkar, P.R.

    2011-01-01

    A 500 V, 24 Amp DC-DC converter with digital signal processor (DSP) based control and protection has been designed, fabricated and tested. Its power circuit consists of IGBT based single phase inverter bridge, ferrite transformer and diode rectifier. All IGBTs in the inverter bridge are operated in zero voltage switching (ZVS) mode to minimize switching losses thereby increasing the efficiency of the converter significantly. The efficiency of this converter is measured to be greater than 97% at full load. In a conventional full bridge inverter, typically ZVS is achieved under full load condition while at light load ZVS is lost. An auxiliary LC circuit has been intentionally incorporated in this converter to achieve ZVS even at light loaded conditions. Detailed simulation of the converter circuit is carried out and crucial waveforms have been presented in this paper. Microchip make dsPIC30F2020 DSP is employed to provide phase shifted PWMs to IGBTs in the inverter bridge. All the crucial parameters are also monitored by this DSP and in case of any unfavorable conditions, the converter is tripped off. Suitable experiments were carried out in this DC-DC converter under different loaded conditions and a close match between the simulated and experimental results were obtained. Such DC-DC converters can be connected in series or parallel for the development of solid state modular power supplies for various applications. (author)

  14. Tako-tsubo cardiomyopathy observed in a patient with sepsis and transient hyperthyroidism.

    Science.gov (United States)

    Sarullo, Filippo M; Americo, Luigi; Accardo, Salvatore; Cicero, Sergio; Schicchi, Rossella; Schirò, Maria; Castello, Antonio

    2009-03-01

    A 55-years-old woman, with a history of hypertension and ischemic stroke with residual left hemiparesis, was admitted to our hospital because of dyspnoea with clinical evidence of acute pulmonary edema. She was found to have a sinus tachycardia with ST-elevation in leads D1, aVL and V1-V4 in the electrocardiogram, and akinesis of the left ventricular apex with overall left ventricular systolic function being severely impaired and an ejection fraction of 28% on echocardiography. Orotracheal intubation was performed and mechanical ventilation was immediately started. Emergency cardiac catheterization was performed 2 h after the symptom onset. Coronary angiography showed no significant coronary artery disease. Blood analysis revealed an increase in the creatine kinase MB fraction, a significant positive detection in troponin T, a white blood cell count of 35000 per microliter, C-reactive protein of 59,9 mg/dl, and transient elevation in the concentration of free triiodothyronine, free thyroxine, thyroid globulin antibody, and thyroid peroxidase antibody. The symptoms improved during the next days, and follow-up echocardiography 18 days later showed complete resolution of the left ventricular dysfunction. These data suggest that tako-tsubo cardiomyopathy may be induced in patients with sepsis and transient hyperthyroidism.

  15. High-frequency matrix converter with square wave input

    Science.gov (United States)

    Carr, Joseph Alexander; Balda, Juan Carlos

    2015-03-31

    A device for producing an alternating current output voltage from a high-frequency, square-wave input voltage comprising, high-frequency, square-wave input a matrix converter and a control system. The matrix converter comprises a plurality of electrical switches. The high-frequency input and the matrix converter are electrically connected to each other. The control system is connected to each switch of the matrix converter. The control system is electrically connected to the input of the matrix converter. The control system is configured to operate each electrical switch of the matrix converter converting a high-frequency, square-wave input voltage across the first input port of the matrix converter and the second input port of the matrix converter to an alternating current output voltage at the output of the matrix converter.

  16. A novel series-resonant converter topology

    NARCIS (Netherlands)

    Tilgenkamp, N.V.; Haan, de S.W.H.; Huisman, H.

    1987-01-01

    A converter topology based on the principles of seriesresonant (SR) power conversion is described in which the input and output of this converter have one terminal in common, and the transformer is omitted. Both the underlying theory and associated waveforms are presented. The converter is suitable

  17. A rice kinase-protein interaction map.

    Science.gov (United States)

    Ding, Xiaodong; Richter, Todd; Chen, Mei; Fujii, Hiroaki; Seo, Young Su; Xie, Mingtang; Zheng, Xianwu; Kanrar, Siddhartha; Stevenson, Rebecca A; Dardick, Christopher; Li, Ying; Jiang, Hao; Zhang, Yan; Yu, Fahong; Bartley, Laura E; Chern, Mawsheng; Bart, Rebecca; Chen, Xiuhua; Zhu, Lihuang; Farmerie, William G; Gribskov, Michael; Zhu, Jian-Kang; Fromm, Michael E; Ronald, Pamela C; Song, Wen-Yuan

    2009-03-01

    Plants uniquely contain large numbers of protein kinases, and for the vast majority of the 1,429 kinases predicted in the rice (Oryza sativa) genome, little is known of their functions. Genetic approaches often fail to produce observable phenotypes; thus, new strategies are needed to delineate kinase function. We previously developed a cost-effective high-throughput yeast two-hybrid system. Using this system, we have generated a protein interaction map of 116 representative rice kinases and 254 of their interacting proteins. Overall, the resulting interaction map supports a large number of known or predicted kinase-protein interactions from both plants and animals and reveals many new functional insights. Notably, we found a potential widespread role for E3 ubiquitin ligases in pathogen defense signaling mediated by receptor-like kinases, particularly by the kinases that may have evolved from recently expanded kinase subfamilies in rice. We anticipate that the data provided here will serve as a foundation for targeted functional studies in rice and other plants. The application of yeast two-hybrid and TAPtag analyses for large-scale plant protein interaction studies is also discussed.

  18. Transient flow combustion

    Science.gov (United States)

    Tacina, R. R.

    1984-01-01

    Non-steady combustion problems can result from engine sources such as accelerations, decelerations, nozzle adjustments, augmentor ignition, and air perturbations into and out of the compressor. Also non-steady combustion can be generated internally from combustion instability or self-induced oscillations. A premixed-prevaporized combustor would be particularly sensitive to flow transients because of its susceptability to flashback-autoignition and blowout. An experimental program, the Transient Flow Combustion Study is in progress to study the effects of air and fuel flow transients on a premixed-prevaporized combustor. Preliminary tests performed at an inlet air temperature of 600 K, a reference velocity of 30 m/s, and a pressure of 700 kPa. The airflow was reduced to 1/3 of its original value in a 40 ms ramp before flashback occurred. Ramping the airflow up has shown that blowout is more sensitive than flashback to flow transients. Blowout occurred with a 25 percent increase in airflow (at a constant fuel-air ratio) in a 20 ms ramp. Combustion resonance was found at some conditions and may be important in determining the effects of flow transients.

  19. Parametric study of laser photovoltaic energy converters

    Science.gov (United States)

    Walker, G. H.; Heinbockel, J. H.

    1987-01-01

    Photovoltaic converters are of interest for converting laser power to electrical power in a space-based laser power system. This paper describes a model for photovoltaic laser converters and the application of this model to a neodymium laser silicon photovoltaic converter system. A parametric study which defines the sensitivity of the photovoltaic parameters is described. An optimized silicon photovoltaic converter has an efficiency greater than 50 percent for 1000 W/sq cm of neodymium laser radiation.

  20. Dividend-Protected Convertible Bonds and the Disappearance

    OpenAIRE

    Bruce D. Grundy; Patrick Verwijmeren

    2012-01-01

    Firms have not historically called their convertible bonds as soon as they could force conversion. Various explanations for the delay rely on the size of the dividends that bondholders forgo so long as they do not convert. We investigate an important change in convertible security design, namely that more than 95 percent of recent convertible bond issues are dividend-protected. Dividend protection means that the conversion value of the shares into which a bond is convertible is unaffected by ...

  1. Chitin and stress induced protein kinase activation

    DEFF Research Database (Denmark)

    Kenchappa, Chandra Shekar; Azevedo da Silva, Raquel; Bressendorff, Simon

    2017-01-01

    The assays described here are pertinent to protein kinase studies in any plant. They include an immunoblot phosphorylation/activation assay and an in-gel activity assay for MAP kinases (MPKs) using the general protein kinase substrate myelin basic protein. They also include a novel in-gel peptide...... substrate assay for Snf1-related kinase family 2 members (SnRK2s). This kinase family-specific assay overcomes some limitations of in-gel assays and permits the identification of different types of kinase activities in total protein extracts....

  2. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains

    KAUST Repository

    Diaz Galicia, Miriam Escarlet

    2018-01-01

    is then translated into a FRET (Fluorescence Resonance Energy Transfer) signal is here proposed. To this end, DNA constructs for interaction amplification (split kinases), positive controls (intact kinase domains), scaffolding proteins and phosphopeptide - SH2-domain

  3. Receptor Tyrosine Kinases in Drosophila Development

    Science.gov (United States)

    Sopko, Richelle; Perrimon, Norbert

    2013-01-01

    Tyrosine phosphorylation plays a significant role in a wide range of cellular processes. The Drosophila genome encodes more than 20 receptor tyrosine kinases and extensive studies in the past 20 years have illustrated their diverse roles and complex signaling mechanisms. Although some receptor tyrosine kinases have highly specific functions, others strikingly are used in rather ubiquitous manners. Receptor tyrosine kinases regulate a broad expanse of processes, ranging from cell survival and proliferation to differentiation and patterning. Remarkably, different receptor tyrosine kinases share many of the same effectors and their hierarchical organization is retained in disparate biological contexts. In this comprehensive review, we summarize what is known regarding each receptor tyrosine kinase during Drosophila development. Astonishingly, very little is known for approximately half of all Drosophila receptor tyrosine kinases. PMID:23732470

  4. The effect of oxygen storage capacity on the dynamic characteristics of an automotive catalytic converter

    Energy Technology Data Exchange (ETDEWEB)

    Shamim, T. [Michigan-Dearborn Univ., Dearborn, MI (United states). Dept. of Mechanical Engineering

    2007-07-01

    Automotive catalytic converters that reduce engine exhaust emissions are subject to transient conditions during a typical driving cycle. These conditions arise from changes in driving mode, the hysteresis and flow lags of the feedback control system, and result in fluctuations of air-fuel, exhaust gas flow rates and temperatures. The catalyst performance is also highly influenced by the oxygen storage capacity (OSC). This paper examined the influence of OSC on the catalyst dynamic behavior. The transient conditions were simulated by considering the catalyst subjected to temporal modulation in air-fuel ratio, exhaust gas composition and temperature. The paper presented the mathematical formulation including the development of governing equations. The governing equations were developed by considering the conservation of mass, energy and chemical species. It also presented the results and discussed the effect of sinusoidal modulation in the air-fuel ratio as well as the effect of sinusoidal modulation in exhaust composition. It was concluded that the presence of the OSC sensitivity influenced its response to the imposed modulation. The specific effect was dependent on the operating conditions and the type of the imposed modulations. 10 refs., 1 tab., 3 figs.

  5. Regulation of glucose metabolism in T cells; new insight into the role of Phosphoinositide 3-kinases

    Directory of Open Access Journals (Sweden)

    David K Finlay

    2012-08-01

    Full Text Available Naïve T cells are relatively quiescent cells that only require energy to prevent atrophy and for survival and migration. However, in response to developmental or extrinsic cues T cells can engage in rapid growth and robust proliferation, produce of a range of effector molecules and migrate through peripheral tissues. To meet the significantly increased metabolic demands of these activities, T cells switch from primarily metabolizing glucose to carbon dioxide through oxidative phosphorylation to utilizing glycolysis to convert glucose to lactate (termed aerobic glycolysis. This metabolic switch allows glucose to be used as a source of carbon to generate biosynthetic precursors for the production of protein, DNA and phospholipids, and is crucial for T cells to meet metabolic demands. Phosphoinositide 3-kinases (PI3K are a family of inositol lipid kinases linked with a broad range of cellular functions in T lymphocytes that include cell growth, proliferation, metabolism, differentiation, survival and migration. Initial research described a critical role for PI3K signaling through Akt (also called Protein kinase B for the increased glucose uptake and glycolysis that accompanies T cell activation. This review article relates this original research with more recent data and discusses the evidence for and against a role for PI3K in regulating the metabolic switch to aerobic glycolysis in T cells.

  6. A cGMP kinase mutant with increased sensitivity to the protein kinase inhibitor peptide PKI(5-24).

    Science.gov (United States)

    Ruth, P; Kamm, S; Nau, U; Pfeifer, A; Hofmann, F

    1996-01-01

    Synthetic peptides corresponding to the active domain of the heat-stable inhibitor protein PKI are very potent inhibitors of cAMP-dependent protein kinase, but are extremely weak inhibitors of cGMP-dependent protein kinase. In this study, we tried to confer PKI sensitivity to cGMP kinase by site-directed mutagenesis. The molecular requirements for high affinity inhibition by PKI were deduced from the crystal structure of the cAMP kinase/PKI complex. A prominent site of interaction are residues Tyr235 and Phe239 in the catalytic subunit, which from a sandwich-like structure with Phe10 of the PKI(5-24) peptide. To increase the sensitivity for PKI, the cGMP kinase codons at the corresponding sites, Ser555 and Ser559, were changed to Tyr and Phe. The mutant cGMP kinase was stimulated half maximally by cGMP at 3-fold higher concentrations (240 nM) than the wild type (77 nM). Wild type and mutant cGMP kinase did not differ significantly in their Km and Vmax for three different substrate peptides. The PKI(5-24) peptide inhibited phosphotransferase activity of the mutant cGMP kinase with higher potency than that of wild type, with Ki values of 42 +/- .3 microM and 160 +/- .7 microM, respectively. The increased affinity of the mutant cGMP kinase was specific for the PKI(5-24) peptide. Mutation of the essential Phe10 in the PKI(5-24) sequence to an Ala yielded a peptide that inhibited mutant and wild type cGMP kinase with similar potency, with Ki values of 160 +/- 11 and 169 +/- 27 microM, respectively. These results suggest that the mutations Ser555Tyr and Ser559Phe are required, but not sufficient, for high affinity inhibition of cGMP kinase by PKI.

  7. ROS and CDPK-like kinase-mediated activation of MAP kinase in rice roots exposed to lead.

    Science.gov (United States)

    Huang, Tsai-Lien; Huang, Hao-Jen

    2008-04-01

    Lead (Pb2+) is a cytotoxic metal ion in plants, the mechanism of which is not yet established. The aim of this study is to investigate the signalling pathways that are activated by elevated concentrations of Pb2+ in rice roots. Root growth was stunted and cell death was accelerated when exposed to different dosages of Pb2+ during extended time periods. Using ROS-sensitive dye and Ca2+ indicator, we demonstrated that Pb2+ induced ROS production and Ca2+ accumulation, respectively. In addition, Pb2+ elicited a remarkable increase in myelin basic protein (MBP) kinase activities. By immunoblot and immunoprecipitation analysis, 40- and 42-kDa MBP kinases that were activated by Pb2+ were identified to be mitogen-activated protein (MAP) kinases. Pre-treatment of rice roots with an antioxidant and a NADPH oxidase inhibitor, glutathione (GSH) and diphenylene iodonium (DPI), effectively reduced Pb2+-induced cell death and MAP kinase activation. Moreover, calcium-dependent protein kinase (CDPK) antagonist, W7, attenuated Pb2+-induced cell death and MAP kinase activation. These results suggested that the ROS and CDPK may function in the Pb2+-triggered cell death and MAP kinase signalling pathway in rice roots.

  8. Semi-automatic logarithmic converter of logs

    International Nuclear Information System (INIS)

    Gol'dman, Z.A.; Bondar's, V.V.

    1974-01-01

    Semi-automatic logarithmic converter of logging charts. An original semi-automatic converter was developed for use in converting BK resistance logging charts and the time interval, ΔT, of acoustic logs from a linear to a logarithmic scale with a specific ratio for subsequent combining of them with neutron-gamma logging charts in operative interpretation of logging materials by a normalization method. The converter can be used to increase productivity by giving curves different from those obtained in manual, pointwise processing. The equipment operates reliably and is simple in use. (author)

  9. Three-phase Resonant DC-link Converter

    DEFF Research Database (Denmark)

    Munk-Nielsen, Stig

    The purpose of the project is to develop a three-phase resonant converter suitable for standard speed drives. The motivation for working with resonant converters is found in the problem of the standard converter type used today. In standard converter type Pulse Width Modulated-Voltage Source...... Inverter, PWM-VSI, the switches are subject to high current and voltage stress during switching, which causes losses. The fast switching of modern switches reduces switching losses. Unfortunately this procedure increased dv/dt and the size of the input/output filters of the PWM-SVI must be increased...

  10. Electromagnetic Compatibility of Matrix Converter System

    Directory of Open Access Journals (Sweden)

    S. Fligl

    2006-12-01

    Full Text Available The presented paper deals with matrix converters pulse width modulation strategies design with emphasis on the electromagnetic compatibility. Matrix converters provide an all-silicon solution to the problem of converting AC power from one frequency to another, offering almost all the features required of an ideal static frequency changer. They possess many advantages compared to the conventional voltage or current source inverters. A matrix converter does not require energy storage components as a bulky capacitor or an inductance in the DC-link, and enables the bi-directional power flow between the power supply and load. The most of the contemporary modulation strategies are able to provide practically sinusoidal waveforms of the input and output currents with negligible low order harmonics, and to control the input displacement factor. The perspective of matrix converters regarding EMC in comparison with other types of converters is brightly evident because it is no need to use any equipment for power factor correction and current and voltage harmonics reduction. Such converter with proper control is properly compatible both with the supply mains and with the supplied load. A special digital control system was developed for the realized experimental test bed which makes it possible to achieve greater throughput of the digital control system and its variability.

  11. Passive Resonant Bidirectional Converter with Galvanic Barrier

    Science.gov (United States)

    Rosenblad, Nathan S. (Inventor)

    2014-01-01

    A passive resonant bidirectional converter system that transports energy across a galvanic barrier includes a converter using at least first and second converter sections, each section including a pair of transfer terminals, a center tapped winding; a chopper circuit interconnected between the center tapped winding and one of the transfer terminals; an inductance feed winding interconnected between the other of the transfer terminals and the center tap and a resonant tank circuit including at least the inductance of the center tap winding and the parasitic capacitance of the chopper circuit for operating the converter section at resonance; the center tapped windings of the first and second converter sections being disposed on a first common winding core and the inductance feed windings of the first and second converter sections being disposed on a second common winding core for automatically synchronizing the resonant oscillation of the first and second converter sections and transferring energy between the converter sections until the voltage across the pairs of transfer terminals achieves the turns ratio of the center tapped windings.

  12. Picosecond image-converter diagnostics

    International Nuclear Information System (INIS)

    Schelev, M.Ya.

    1975-01-01

    A brief review is presented of the improvements in picosecond image-converter diagnostics carried out since the previous Congress in 1972. The account is given under the following headings: picosecond image converter cameras for visible and x-ray radiation diagnostics; Nd:glass and ruby mode-locked laser measurements; x-ray plasma emission diagnostics; computer treatment of pictures produced by picosecond cameras. (U.K.)

  13. Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and beta1 integrin receptors.

    Science.gov (United States)

    Smith, Julie A; Samayawardhena, Lionel A; Craig, Andrew W B

    2010-03-01

    Activation of Kit receptor protein-tyrosine kinase (PTK) by its ligand Stem Cell Factor (SCF) is required for the development of mast cells, and for the regulation of mast cell proliferation, migration and modulation of inflammatory mediator release. Recent studies have implicated the non-receptor PTK Fps/Fes (hereafter referred to as Fes) in signaling downstream of oncogenic Kit, however, the potential role of Fes in regulating Kit signaling is not well defined. In this study, we show that SCF induces transient tyrosine phosphorylation of wild-type Fes as well as kinase-dead Fes in bone marrow-derived mast cells (BMMCs). The latter finding implicates an upstream kinase acting on Fes, which we identified as Fyn PTK. SCF treatment of BMMCs promoted recruitment of Fes to Kit, potentially via direct interaction of the Fes SH2 domain with phosphorylated Kit. While Fes was not required for SCF-induced signaling to Akt and Erk kinases, Fes-deficient (fes-/-) BMMCs displayed a defect in sustained p38 kinase activation, compared to control cells. SCF-treated Fes-deficient BMMCs also displayed elevated beta1 integrin-mediated cell adhesion and spreading on fibronectin, compared to control cells, and a reduction in cell polarization at later times of SCF treatment. Restoring Fes expression in fes-/- BMMCs by retroviral transduction was sufficient to rescue cell spreading and polarization defects. Interestingly, SCF-induced chemotaxis of BMMCs was also defective in Fes-deficient BMMCs, and restored in Fes-rescue BMMCs. Overall, these results implicate Fes in regulating cross-talk between Kit and beta1 integrins to promote cytoskeletal reorganization and motility of mast cells.

  14. A Fast Time-to-Pulse Height Converter

    Energy Technology Data Exchange (ETDEWEB)

    Aspelund, O

    1962-12-15

    A fast time-to-pulse height converter representing a development of Green and Bell's gated beam converter is described. The converter is compatible with 2 input pulses in the stop channel and exhibits excellent linearity and time resolution properties. High stability and large output pulses are obtained by using a large time constant in the converting network.

  15. A screen for kinase inhibitors identifies antimicrobial imidazopyridine aminofurazans as specific inhibitors of the Listeria monocytogenes PASTA kinase PrkA.

    Science.gov (United States)

    Schaenzer, Adam J; Wlodarchak, Nathan; Drewry, David H; Zuercher, William J; Rose, Warren E; Striker, Rob; Sauer, John-Demian

    2017-10-13

    Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial P enicillin-binding-protein A nd S erine/ T hreonine kinase- A ssociated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy. Despite this interest, only limited progress has been made in identifying functional inhibitors of the PASTA kinases that have both activity against the intact microbe and high kinase specificity. Here, we report the results of a small-molecule screen that identified GSK690693, an imidazopyridine aminofurazan-type kinase inhibitor that increases the sensitivity of the intracellular pathogen Listeria monocytogenes to various β-lactams by inhibiting the PASTA kinase PrkA. GSK690693 potently inhibited PrkA kinase activity biochemically and exhibited significant selectivity for PrkA relative to the Staphylococcus aureus PASTA kinase Stk1. Furthermore, other imidazopyridine aminofurazans could effectively inhibit PrkA and potentiate β-lactam antibiotic activity to varying degrees. The presence of the 2-methyl-3-butyn-2-ol (alkynol) moiety was important for both biochemical and antimicrobial activity. Finally, mutagenesis studies demonstrated residues in the back pocket of the active site are important for GSK690693 selectivity. These data suggest that targeted screens can successfully identify PASTA kinase inhibitors with both biochemical and antimicrobial specificity. Moreover, the imidazopyridine aminofurazans represent a family of PASTA kinase inhibitors that have the potential to be optimized for selective PASTA kinase inhibition.

  16. LHC Power Converters: A Precision Game

    CERN Multimedia

    2001-01-01

    The LHC test-bed, String 2, is close to commissioning and one important element to get a first chance to prove what it can do is the power converter system. In String 2 there are 16 converters, in the full LHC there will be almost 1800. This article takes a look at what is so special about the power converters for the LHC. The 13 000 Amps power converters with the watercooled cables going to the String 2 feedboxes. The LHC's superconducting magnets will be the pinnacle of high technology. But to work, they'll need the help of high-precision power converters to supply them with extremely stable DC current. Perfection will be the name of the game, with an accuracy of just 1-2 parts per million (ppm) required. LEP, for the sake of comparison, could live with 10-20 ppm. The LHC's power converters will be very different from those of LEP or the SPS since the new accelerator's magnets are mostly superconducting. That means that they require much higher currents at a lower voltage since superconductors have no re...

  17. Characterization and functional analyses of the human G protein-coupled receptor kinase 4 gene promoter.

    Science.gov (United States)

    Hasenkamp, Sandra; Telgmann, Ralph; Staessen, Jan A; Hagedorn, Claudia; Dördelmann, Corinna; Bek, Martin; Brand-Herrmann, Stefan-Martin; Brand, Eva

    2008-10-01

    The G protein-coupled receptor kinase 4 is involved in renal sodium handling and blood pressure regulation. Missense variants have already been tested functionally and are associated with hypertension, but no data on promoter analyses are yet available. We scanned 94 hypertensive white subjects for genetic variation and performed promoter reporter gene analyses in HEK293T, COS7, and SaOs-2 cells. Transient transfections with various full lengths and wild-type deletion constructs revealed that 1851 bp of the flanking region and 275 bp of the 5'-untranslated region were sufficient for transcriptional activities and composed a powerful cis-active element in the distal 293 bp. The -1702T and +2T alleles resulted in drastic general reductions of promoter function, whereas an activity increasing effect of +268C was cell type specific. Electrophoretic mobility-shift assay, supershift, and cotransfection analyses of transcription factor binding sites predicted in silico (Alibaba2.1/Transfac7) resulted in allele-specific binding patterns of nuclear proteins and identified the participation of CCAAT/enhancer-binding protein transcription factor family members. The G protein-coupled receptor kinase 4 core promoter resides in the first 1851 bp upstream of its transcription start site. The 4 identified genetic variants within this region exert allele-specific impact on both cell type- and stimulation-dependent transcription and may affect the expression balance of renal G protein-coupled receptor kinase 4.

  18. CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.

    Science.gov (United States)

    Leonardi, A; Chariot, A; Claudio, E; Cunningham, K; Siebenlist, U

    2000-09-12

    Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKgamma in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.

  19. CIKS, a connection to IκB kinase and stress-activated protein kinase

    Science.gov (United States)

    Leonardi, Antonio; Chariot, Alain; Claudio, Estefania; Cunningham, Kirk; Siebenlist, Ulrich

    2000-01-01

    Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-κB and AP-1/ATF families. Activation of NF-κB factors is thought to be mediated primarily via IκB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKα and IKKβ are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-κB essential modulator)/IKKγ. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKγ in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-κB-dependent reporter. Activation of NF-κB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins. PMID:10962033

  20. Ac system interruption analysis of an orthogonal-core type dc-ac converter. Koryu keito shadanji no chokko jishinkei dc-ac renkeiyo henkanki no dosa kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Sato, K; Ichinokura, O; Jinzenji, T [Tohoku Univ., Sendai (Japan). Faculty of Engineering; Tajima, K [Akita University, Akita (Japan). Mining College

    1991-04-30

    This paper reports on a numerical analysis of transient response of an orthogonal-core type dc-ac converter that takes place when the external ac system connected is cut off from it. A model of magnetic circuit of the orthogonal core is presented, which has magnetic inductances to represent effects produced by hysteresis that are connected in series with magnetic reluctances, thereby making it possible to divide each of primary and secondary winding current into magnetization current associated with magnetic reluctances and iron-loss current due to hysteresis. Moreover, a numerical model of the orthogonal core is derived from expressions for non-linear characteristics of these reluctances and inductances to make use of it for analyses employing the circuit simulator SPICE. Transient response of the present converter, namely time variation of both voltage and current in its every part, to the sudden change in condition that is caused by switching off the ac system connected to its secondary side is calculated, while applying square-wave voltage to its primary side. It is noted that calculated wave forms of both secondary winding current and open-circuit voltage are fairly in good agreement with those obtained by an experiment performed on the same condition. 4 refs., 9 figs., 1 tab.

  1. Kinases Involved in Both Autophagy and Mitosis.

    Science.gov (United States)

    Li, Zhiyuan; Zhang, Xin

    2017-08-31

    Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  2. Kinases Involved in Both Autophagy and Mitosis

    Directory of Open Access Journals (Sweden)

    Zhiyuan Li

    2017-08-01

    Full Text Available Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases, Aurora kinases, PLK-1 (polo-like kinase 1, BUB1 (budding uninhibited by benzimidazoles 1, MAPKs (mitogen-activated protein kinases, mTORC1 (mechanistic target of rapamycin complex 1, AMPK (AMP-activated protein kinase, PI3K (phosphoinositide-3 kinase and protein kinase B (AKT. By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  3. Power converters definitions, classification and converter topologies

    CERN Document Server

    Bordry, Frederick

    2006-01-01

    This paper introduces power conversion principles and defines the terminology. The concepts of sources and switches are defined and classified. From the basic laws of source interconnections, a generic method of power converter synthesis is presented. Some examples illustrate this systematic method. Finally, the notions of commutation cell and soft commutation are introduced and discussed.

  4. Partial purification and characterization of a wortmannin-sensitive and insulin-stimulated protein kinase that activates heart 6-phosphofructo-2-kinase.

    OpenAIRE

    Deprez, J; Bertrand, L; Alessi, D R; Krause, U; Hue, L; Rider, M H

    2000-01-01

    A wortmannin-sensitive and insulin-stimulated protein kinase (WISK), which phosphorylates and activates cardiac 6-phosphofructo-2-kinase (PFK-2), was partially purified from perfused rat hearts. Immunoblotting showed that WISK was devoid of protein kinase B (PKB), serum- and glucocorticoid-regulated protein kinase and protein kinase Czeta (PKCzeta). Comparison of the inhibition of WISK, PKCalpha and PKCzeta by different protein kinase inhibitors suggested that WISK was not a member of the PKC...

  5. Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Annika Sommerfeld

    2015-05-01

    Full Text Available Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP signal with induction of the dual specificity mitogen-activated protein (MAP kinase phosphatase 1 (MKP-1, which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4 and c-jun-NH2-terminal kinase (JNK activation. Furthermore, TUDC induced a protein kinase A (PKA-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.

  6. Identification of the Raptor-binding motif on Arabidopsis S6 kinase and its use as a TOR signaling suppressor.

    Science.gov (United States)

    Son, Ora; Kim, Sunghan; Hur, Yoon-Sun; Cheon, Choong-Ill

    2016-03-25

    TOR (target of rapamycin) kinase signaling plays central role as a regulator of growth and proliferation in all eukaryotic cells and its key signaling components and effectors are also conserved in plants. Unlike the mammalian and yeast counterparts, however, we found through yeast two-hybrid analysis that multiple regions of the Arabidopsis Raptor (regulatory associated protein of TOR) are required for binding to its substrate. We also identified that a 44-amino acid region at the N-terminal end of Arabidopsis ribosomal S6 kinase 1 (AtS6K1) specifically interacted with AtRaptor1, indicating that this region may contain a functional equivalent of the TOS (TOR-Signaling) motif present in the mammalian TOR substrates. Transient over-expression of this 44-amino acid fragment in Arabidopsis protoplasts resulted in significant decrease in rDNA transcription, demonstrating a feasibility of developing a new plant-specific TOR signaling inhibitor based upon perturbation of the Raptor-substrate interaction. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Transformerless dc-Isolated Converter

    Science.gov (United States)

    Rippel, Wally E.

    1987-01-01

    Efficient voltage converter employs capacitive instead of transformer coupling to provide dc isolation. Offers buck/boost operation, minimal filtering, and low parts count, with possible application in photovoltaic power inverters, power supplies and battery charges. In photovoltaic inverter circuit with transformerless converter, Q2, Q3, Q4, and Q5 form line-commutated inverter. Switching losses and stresses nil because switching performed when current is zero.

  8. Thermionic photovoltaic energy converter

    Science.gov (United States)

    Chubb, D. L. (Inventor)

    1985-01-01

    A thermionic photovoltaic energy conversion device comprises a thermionic diode mounted within a hollow tubular photovoltaic converter. The thermionic diode maintains a cesium discharge for producing excited atoms that emit line radiation in the wavelength region of 850 nm to 890 nm. The photovoltaic converter is a silicon or gallium arsenide photovoltaic cell having bandgap energies in this same wavelength region for optimum cell efficiency.

  9. Signaling network of the Btk family kinases.

    Science.gov (United States)

    Qiu, Y; Kung, H J

    2000-11-20

    The Btk family kinases represent new members of non-receptor tyrosine kinases, which include Btk/Atk, Itk/Emt/Tsk, Bmx/Etk, and Tec. They are characterized by having four structural modules: PH (pleckstrin homology) domain, SH3 (Src homology 3) domain, SH2 (Src homology 2) domain and kinase (Src homology 1) domain. Increasing evidence suggests that, like Src-family kinases, Btk family kinases play central but diverse modulatory roles in various cellular processes. They participate in signal transduction in response to virtually all types of extracellular stimuli which are transmitted by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen-receptors and integrins. They are regulated by many non-receptor tyrosine kinases such as Src, Jak, Syk and FAK family kinases. In turn, they regulate many of major signaling pathways including those of PI3K, PLCgamma and PKC. Both genetic and biochemical approaches have been used to dissect the signaling pathways and elucidate their roles in growth, differentiation and apoptosis. An emerging new role of this family of kinases is cytoskeletal reorganization and cell motility. The physiological importance of these kinases was amply demonstrated by their link to the development of immunodeficiency diseases, due to germ-line mutations. The present article attempts to review the structure and functions of Btk family kinases by summarizing our current knowledge on the interacting partners associated with the different modules of the kinases and the diverse signaling pathways in which they are involved.

  10. Underwater noise from a wave energy converter

    DEFF Research Database (Denmark)

    Tougaard, Jakob

    A recent addition to the anthropogenic sources of underwater noise is offshore wave energy converters. Underwater noise was recorded from the Wavestar wave energy converter located at Hastholm, Denmark (57°7.73´N, 8°37.23´E). The Wavestar is a full-scale test and demonstration converter...... in full operation and start and stop of the converter. Median broad band (10 Hz – 20 kHz) sound pressure level (Leq) was 123 dB re. 1 Pa, irrespective of status of the wave energy converter (stopped, running or starting/stopping). The most pronounced peak in the third-octave spectrum was in the 160 Hz...... significant noise above ambient could be detected above the 250 Hz band. The absolute increase in noise above ambient was very small. L50 third-octave levels in the four bands with the converter running were thus only 1-2 dB above ambient L50 levels. The noise recorded 25 m from the wave energy converter...

  11. Valuing Convertible Bonds Based on LSRQM Method

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2014-01-01

    Full Text Available Convertible bonds are one of the essential financial products for corporate finance, while the pricing theory is the key problem to the theoretical research of convertible bonds. This paper demonstrates how to price convertible bonds with call and put provisions using Least-Squares Randomized Quasi-Monte Carlo (LSRQM method. We consider the financial market with stochastic interest rates and credit risk and present a detailed description on calculating steps of convertible bonds value. The empirical results show that the model fits well the market prices of convertible bonds in China’s market and the LSRQM method is effective.

  12. Proposed electromagnetic wave energy converter

    Science.gov (United States)

    Bailey, R. L.

    1973-01-01

    Device converts wave energy into electric power through array of insulated absorber elements responsive to field of impinging electromagnetic radiation. Device could also serve as solar energy converter that is potentially less expensive and fragile than solar cells, yet substantially more efficient.

  13. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids

    Energy Technology Data Exchange (ETDEWEB)

    Moravcevic, Katarina; Mendrola, Jeannine M.; Schmitz, Karl R.; Wang, Yu-Hsiu; Slochower, David; Janmey, Paul A.; Lemmon, Mark A. (UPENN-MED)

    2011-09-28

    Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to coincidence detection, allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.

  14. SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.

    Science.gov (United States)

    Anafi, M; Kiefer, F; Gish, G D; Mbamalu, G; Iscove, N N; Pawson, T

    1997-10-31

    Ste20-related protein kinases have been implicated as regulating a range of cellular responses, including stress-activated protein kinase pathways and the control of cytoskeletal architecture. An important issue involves the identities of the upstream signals and regulators that might control the biological functions of mammalian Ste20-related protein kinases. HPK1 is a protein-serine/threonine kinase that possesses a Ste20-like kinase domain, and in transfected cells activates a protein kinase pathway leading to the stress-activated protein kinase SAPK/JNK. Here we have investigated candidate upstream regulators that might interact with HPK1. HPK1 possesses an N-terminal catalytic domain and an extended C-terminal tail with four proline-rich motifs. The SH3 domains of Grb2 bound in vitro to specific proline-rich motifs in the HPK1 tail and functioned synergistically to direct the stable binding of Grb2 to HPK1 in transfected Cos1 cells. Epidermal growth factor (EGF) stimulation did not affect the binding of Grb2 to HPK1 but induced recruitment of the Grb2.HPK1 complex to the autophosphorylated EGF receptor and to the Shc docking protein. Several activated receptor and cytoplasmic tyrosine kinases, including the EGF receptor, stimulated the tyrosine phosphorylation of the HPK1 serine/threonine kinase. These results suggest that HPK1, a mammalian Ste20-related protein-serine/threonine kinase, can potentially associate with protein-tyrosine kinases through interactions mediated by SH2/SH3 adaptors such as Grb2. Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases.

  15. Soft switching buck-boost converter for photovoltaic power generation; Taiyoko hatsuden no tame no soft switching shokoatsu converter

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H. [Kyungnam University (Korea, Republic of)

    1996-10-27

    A soft switching method with small switching loss was proposed for the purpose of increasing the efficiency of a DC-DC boost converter which converted a DC current generated by solar cells to a variable DC current. Existing current converters are supplemented by using a snubber circuit around the switch so as to protect the switch by a hard switching action. However, with an increase of the output current, snubber loss is increased, reducing the efficiency. In order to solve this problem, the partial resonant switch method was applied to the converter; with this method of partially forming a resonant circuit only at the time of turning on/off of the switch, the switching loss was reduced through the soft switching, thereby making the proposed converter operate with high efficiency. Moreover, the resonant element of the partial resonant circuit using a snubber condenser, the energy accumulated in the condenser was regenerated on the power supply side without loss of snubber. With the regenerated energy, the proposed converter was provided with a smaller ratio of switching to use than the conventional converter. 4 refs., 7 figs., 1 tab.

  16. Fault isolation in parallel coupled wind turbine converters

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Thøgersen, Paul Bach; Stoustrup, Jakob

    2010-01-01

    Parallel converters in wind turbine give a number advantages, such as fault tolerance due to the redundant converters. However, it might be difficult to isolate gain faults in one of the converters if only a combined power measurement is available. In this paper a scheme using orthogonal power...... references to the converters is proposed. Simulations on a wind turbine with 5 parallel converters show a clear potential of this scheme for isolation of this gain fault to the correct converter in which the fault occurs....

  17. Transients: The regulator's view

    International Nuclear Information System (INIS)

    Sheron, B.W.; Speis, T.P.

    1984-01-01

    This chapter attempts to clarify the basis for the regulator's concerns for transient events. Transients are defined as both anticipated operational occurrences and postulated accidents. Recent operational experience, supplemented by improved probabilistic risk analysis methods, has demonstrated that non-LOCA transient events can be significant contributors to overall risk. Topics considered include lessons learned from events and issues, the regulations governing plant transients, multiple failures, different failure frequencies, operator errors, and public pressure. It is concluded that the formation of Owners Groups and Regulatory Response Groups within the owners groups are positive signs of the industry's concern for safety and responsible dealing with the issues affecting both the US NRC and the industry

  18. ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase).

    Science.gov (United States)

    Andrade, Erika C; Musante, Veronica; Horiuchi, Atsuko; Matsuzaki, Hideo; Brody, A Harrison; Wu, Terence; Greengard, Paul; Taylor, Jane R; Nairn, Angus C

    2017-03-08

    ARPP-16 (cAMP-regulated phospho-protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A. Ser46 of ARPP-16 is phosphorylated to a high basal stoichiometry in striatum, suggestive of basal inhibition of PP2A in striatal neurons. In support of this hypothesis, conditional knock-out of ARPP-16 in CaMKIIα::cre/floxed ARPP-16/19 mice results in dephosphorylation of a subset of PP2A substrates including phospho-Thr75-DARPP-32, phospho-T308-Akt, and phospho-T202/Y204-ERK. Conditional knock-out of ARPP-16/19 is associated with increased motivation measured on a progressive ratio schedule of food reinforcement, yet an attenuated locomotor response to acute cocaine. Our previous studies have shown that ARPP-16 is phosphorylated at Ser88 by PKA. Activation of PKA in striatal slices leads to phosphorylation of Ser88, and this is accompanied by marked dephosphorylation of Ser46. Together, these studies suggest that phospho-Ser46-ARPP-16 acts to basally control PP2A in striatal medium spiny neurons but that dopamine acting via PKA inactivates ARPP-16 leading to selective potentiation of PP2A signaling. SIGNIFICANCE STATEMENT We describe a novel mechanism of signal transduction enriched in medium spiny neurons of striatum that likely mediates effects of the neurotransmitter dopamine acting on these cells. We

  19. Modeling of asymmetrical boost converters

    Directory of Open Access Journals (Sweden)

    Eliana Isabel Arango Zuluaga

    2014-01-01

    Full Text Available The asymmetrical interleaved dual boost (AIDB is a fifth-order DC/DC converter designed to interface photovoltaic (PV panels. The AIDB produces small current harmonics to the PV panels, reducing the power losses caused by the converter operation. Moreover, the AIDB provides a large voltage conversion ratio, which is required to step-up the PV voltage to the large dc-link voltage used in grid-connected inverters. To reject irradiance and load disturbances, the AIDB must be operated in a closed-loop and a dynamic model is required. Given that the AIDB converter operates in Discontinuous Conduction Mode (DCM, classical modeling approaches based on Continuous Conduction Mode (CCM are not valid. Moreover, classical DCM modeling techniques are not suitable for the AIDB converter. Therefore, this paper develops a novel mathematical model for the AIDB converter, which is suitable for control-pur-poses. The proposed model is based on the calculation of a diode current that is typically disregarded. Moreover, because the traditional correction to the second duty cycle reported in literature is not effective, a new equation is designed. The model accuracy is contrasted with circuital simulations in time and frequency domains, obtaining satisfactory results. Finally, the usefulness of the model in control applications is illustrated with an application example.

  20. Novel screening techniques for wind turbine power converters

    DEFF Research Database (Denmark)

    Jørgensen, Asger Bjørn; Sønderskov, Simon Dyhr; Christensen, Nicklas

    2016-01-01

    Power converters represent one of the highest failure rates in the wind turbine. Therefore converter manufacturers perform burn-in tests to prevent shipping of faulty converters. Recent developments in junction temperature estimation, based on accurate online IGBT collector-emitter voltage...... measurements, allow for thermal stress estimation of the IGBT modules. This is utilized to detect infant mortalities in power converters, by comparing thermal responses of IGBTs for faulty and non-faulty converters. The method proves to be a time and cost efficient candidate to replace burn-in tests of power...... converters for wind turbines applications....

  1. The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling.

    Science.gov (United States)

    Nyati, Shyam; Schinske-Sebolt, Katrina; Pitchiaya, Sethuramasundaram; Chekhovskiy, Katerina; Chator, Areeb; Chaudhry, Nauman; Dosch, Joseph; Van Dort, Marcian E; Varambally, Sooryanarayana; Kumar-Sinha, Chandan; Nyati, Mukesh Kumar; Ray, Dipankar; Walter, Nils G; Yu, Hongtao; Ross, Brian Dale; Rehemtulla, Alnawaz

    2015-01-06

    Transforming growth factor-β (TGF-β) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-β, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF-β signaling. BUB1 interacted with TGFBRI in the presence of TGF-β and promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1 interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD-dependent transcription, and TGF-β-mediated changes in cellular phenotype including epithelial-mesenchymal transition (EMT), migration, and invasion. Knockdown of BUB1 also impaired noncanonical TGF-β signaling mediated by the kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1 to promote TGF-β signaling depended on the kinase activity of BUB1. A small-molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase-deficient mutant of BUB1 suppressed TGF-β signaling and formation of the ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase in the TGF-β pathway in a role beyond its established function in cell cycle regulation and chromosome cohesion. Copyright © 2015, American Association for the Advancement of Science.

  2. A systematic evaluation of protein kinase a-a-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P|info:eu-repo/dai/nl/341566551; van der Heyden, Marcel A G; Kok, Bart; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Scholten, Arjen|info:eu-repo/dai/nl/313939780

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  3. A systematic evaluation of protein kinase A-A-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P; van der Heyden, MAG; Kok, Bart; Heck, Albert J R; Scholten, Arjen

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  4. The lipid kinase PI5P4Kβ is an intracellular GTP sensor for metabolism and tumorigenesis

    Science.gov (United States)

    Sumita, Kazutaka; Lo, Yu-Hua; Takeuchi, Koh; Senda, Miki; Kofuji, Satoshi; Ikeda, Yoshiki; Terakawa, Jumpei; Sasaki, Mika; Yoshino, Hirofumi; Majd, Nazanin; Zheng, Yuxiang; Kahoud, Emily Rose; Yokota, Takehiro; Emerling, Brooke M.; Asara, John M.; Ishida, Tetsuo; Locasale, Jason W.; Daikoku, Takiko; Anastasiou, Dimitrios; Senda, Toshiya; Sasaki, Atsuo T.

    2016-01-01

    Summary While cellular GTP concentration dramatically changes in response to an organism’s cellular status, whether it serves as a metabolic cue for biological signaling remains elusive due to the lack of molecular identification of GTP sensors. Here we report that PI5P4Kβ, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kβ preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration. Structural and biological analyses reveal that the GTP-sensing activity of PI5P4Kβ is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kβ is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kβ. The critical role of the GTP-sensing activity of PI5P4Kβ in cancer signifies this lipid kinase as a cancer therapeutic target. PMID:26774281

  5. 1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3 pituitary cells. Evidence for involvement of a sphingomyelinase.

    Science.gov (United States)

    Kolesnick, R N; Clegg, S

    1988-05-15

    It has been suggested that sphingoid bases may serve as physiologic inhibitors of protein kinase C. Because 1,2-diacylglycerols, but not phorbol esters, enhance sphingomyelin degradation via a sphingomyelinase in GH3 pituitary cells (Kolesnick, R. N. (1987) J. Biol. Chem. 262, 16759-16762), the effects of phorbol esters, 1,2-diacylglycerols, and sphingomyelinase on protein kinase C activation were assessed. Under basal conditions, the inactive cytosolic form of protein kinase C predominated. 1,2-Diacylglycerols stimulated transient protein kinase C redistribution to the membrane. 1,2-Dioctanoylglycerol (200 micrograms/ml) reduced cytosolic protein kinase C activity to 67% of control from 72 to 48 pmol.min-1.10(6) cells-1 and enhanced membrane-bound activity to 430% of control from 6 to 25 pmol.min-1.10(6) cells-1 after 4 min of stimulation. Thereafter, protein kinase C activity returned to the cytosol. In contrast, the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulated redistribution to the membrane without return to the cytosol. Exogenous sphingomyelinase reduced membrane-bound protein kinase C activity to 30% of control, yet did not alter cytosolic activity. Sphingomyelinase, added after phorbol ester-induced redistribution was completed, restored activity to the cytosol. In these studies, TPA (10(-8) M) reduced cytosolic activity to 62% of control and elevated membrane-bound protein kinase C activity to 650% of control. Sphingomyelinase restored cytosolic activity to 84% of control and reduced membrane-bound activity to 297% of control. Similarly, the free sphingoid bases, sphingosine, sphinganine, and phytosphingosine, reversed phorbol ester-induced protein kinase C redistribution. Since 1,2-diacylglycerols activate a sphingomyelinase and sphingomyelinase action can reverse protein kinase C activation, these studies suggest that a pathway involving a sphingomyelinase might comprise a physiologic negative effector system for protein kinase C

  6. Parallel combination of FC and UC for vehicular power systems using a multi-input converter-based power interface

    Energy Technology Data Exchange (ETDEWEB)

    Vural, B.; Erdinc, O.; Uzunoglu, M. [Department of Electrical Engineering, Yildiz Technical University, Istanbul 34349 (Turkey)

    2010-12-15

    Fuel cells (FC) are widely recognized as one of the most promising technologies to meet future power requirements of vehicular applications. However, a FC system combined with an energy storage system (ESS) can perform better for vehicle propulsion as considering several points. As the additional ESS can fulfill the transient power demand fluctuations, the FC system can be downsized to fit the base power demand without facing peak loads. Besides, braking energy can be recovered by the ESS. Interfacing of traction drive requirements with characteristics and modes of operation of on-board generation units and ESSs calls for suitable power electronic converter configuration. In this paper, a FC/UC hybrid vehicular power system using a multi-input converter-based power interface is proposed. The applied power interface topology ensures the active power sharing and DC link voltage stabilization for the hybrid vehicular system. The mathematical and electrical models of the hybrid vehicular system are developed in detail and simulated using MATLAB registered, Simulink registered and SimPowerSystems registered environments. (author)

  7. Parallel combination of FC and UC for vehicular power systems using a multi-input converter-based power interface

    International Nuclear Information System (INIS)

    Vural, B.; Erdinc, O.; Uzunoglu, M.

    2010-01-01

    Fuel cells (FC) are widely recognized as one of the most promising technologies to meet future power requirements of vehicular applications. However, a FC system combined with an energy storage system (ESS) can perform better for vehicle propulsion as considering several points. As the additional ESS can fulfill the transient power demand fluctuations, the FC system can be downsized to fit the base power demand without facing peak loads. Besides, braking energy can be recovered by the ESS. Interfacing of traction drive requirements with characteristics and modes of operation of on-board generation units and ESSs calls for suitable power electronic converter configuration. In this paper, a FC/UC hybrid vehicular power system using a multi-input converter-based power interface is proposed. The applied power interface topology ensures the active power sharing and DC link voltage stabilization for the hybrid vehicular system. The mathematical and electrical models of the hybrid vehicular system are developed in detail and simulated using MATLAB (registered) , Simulink (registered) and SimPowerSystems (registered) environments.

  8. Conventional P-ω/Q-V Droop Control in Highly Resistive Line of Low-Voltage Converter-Based AC Microgrid

    Directory of Open Access Journals (Sweden)

    Xiaochao Hou

    2016-11-01

    Full Text Available In low-voltage converter-based alternating current (AC microgrids with resistive distribution lines, the P-V droop with Q-f boost (VPD/FQB is the most common method for load sharing. However, it cannot achieve the active power sharing proportionally. To overcome this drawback, the conventional P-ω/Q-V droop control is adopted in the low-voltage AC microgrid. As a result, the active power sharing among the distributed generators (DGs is easily obtained without communication. More importantly, this study clears up the previous misunderstanding that conventional P-ω/Q-V droop control is only applicable to microgrids with highly inductive lines, and lays a foundation for the application of conventional droop control under different line impedances. Moreover, in order to guarantee the accurate reactive power sharing, a guide for designing Q-V droop gains is given, and virtual resistance is adopted to shape the desired output impedance. Finally, the effects of power sharing and transient response are verified through simulations and experiments in converter-based AC Microgrid.

  9. Ac-dc converter firing error detection

    International Nuclear Information System (INIS)

    Gould, O.L.

    1996-01-01

    Each of the twelve Booster Main Magnet Power Supply modules consist of two three-phase, full-wave rectifier bridges in series to provide a 560 VDC maximum output. The harmonic contents of the twelve-pulse ac-dc converter output are multiples of the 60 Hz ac power input, with a predominant 720 Hz signal greater than 14 dB in magnitude above the closest harmonic components at maximum output. The 720 Hz harmonic is typically greater than 20 dB below the 500 VDC output signal under normal operation. Extracting specific harmonics from the rectifier output signal of a 6, 12, or 24 pulse ac-dc converter allows the detection of SCR firing angle errors or complete misfires. A bandpass filter provides the input signal to a frequency-to-voltage converter. Comparing the output of the frequency-to-voltage converter to a reference voltage level provides an indication of the magnitude of the harmonics in the ac-dc converter output signal

  10. Do Convertible Bond Issuers Cater to Investor Demand?

    NARCIS (Netherlands)

    de Jong, Abe; Duca, Eric; Dutordoir, Marie

    2013-01-01

    We examine the impact of fluctuations in investor demand for convertible securities on convertible bond issue volumes, pricing, and design. We find evidence of a positive impact of investor demand proxies on convertible bond issue volumes. We also document significantly lower convertible bond

  11. Converter Monitoring Unit for Retrofit of Wind Power Converters

    DEFF Research Database (Denmark)

    Rannestad, Bjorn; Maarbjerg, Anders Eggert; Frederiksen, Kristian

    2018-01-01

    A Converter Monitoring Unit (CMU), which will enable condition monitoring of wind turbine converters is presented in this paper. Reducing the cost of corrective maintenance by means of condition monitoring is a way of lowering Operation & Maintenance (O&M) costs for wind turbine systems....... The CMU must be able to detect a broad range of failure modes related to Insulated Gate Bipolar Transistor (IGBT) power modules and associated gate drives. IGBT collector-emitter on-state voltage (vceon) and current (ic) is sampled in the CMU and used for detection of emerging failures. A new method...... for compensation of unwanted inductive voltage drop in the vceon measurement path is presented, enabling retrofitting of CMUs in existing wind turbines. Finally, experimental results obtained on a prototype CMU are presented. Experimentally the vceon dependency to IGBT junction temperature and deterioration...

  12. Calcium/calmodulin-dependent kinase II and nitric oxide synthase 1-dependent modulation of ryanodine receptors during β-adrenergic stimulation is restricted to the dyadic cleft.

    Science.gov (United States)

    Dries, Eef; Santiago, Demetrio J; Johnson, Daniel M; Gilbert, Guillaume; Holemans, Patricia; Korte, Sanne M; Roderick, H Llewelyn; Sipido, Karin R

    2016-10-15

    The dyadic cleft, where coupled ryanodine receptors (RyRs) reside, is thought to serve as a microdomain for local signalling, as supported by distinct modulation of coupled RyRs dependent on Ca 2+ /calmodulin-dependent kinase II (CaMKII) activation during high-frequency stimulation. Sympathetic stimulation through β-adrenergic receptors activates an integrated signalling cascade, enhancing Ca 2+ cycling and is at least partially mediated through CaMKII. Here we report that CaMKII activation during β-adrenergic signalling is restricted to the dyadic cleft, where it enhances activity of coupled RyRs thereby contributing to the increase in diastolic events. Nitric oxide synthase 1 equally participates in the local modulation of coupled RyRs. In contrast, the increase in the Ca 2+ content of the sarcoplasmic reticulum and related increase in the amplitude of the Ca 2+ transient are primarily protein kinase A-dependent. The present data extend the concept of microdomain signalling in the dyadic cleft and give perspectives for selective modulation of RyR subpopulations and diastolic events. In cardiac myocytes, β-adrenergic stimulation enhances Ca 2+ cycling through an integrated signalling cascade modulating L-type Ca 2+ channels (LTCCs), phospholamban and ryanodine receptors (RyRs). Ca 2+ /calmodulin-dependent kinase II (CaMKII) and nitric oxide synthase 1 (NOS1) are proposed as prime mediators for increasing RyR open probability. We investigate whether this pathway is confined to the high Ca 2+ microdomain of the dyadic cleft and thus to coupled RyRs. Pig ventricular myocytes are studied under whole-cell voltage-clamp and confocal line-scan imaging with Fluo-4 as a [Ca 2+ ] i indicator. Following conditioning depolarizing pulses, spontaneous RyR activity is recorded as Ca 2+ sparks, which are assigned to coupled and non-coupled RyR clusters. Isoproterenol (ISO) (10 nm) increases Ca 2+ spark frequency in both populations of RyRs. However, CaMKII inhibition reduces

  13. The APA Style Converter: a Web-based interface for converting articles to APA style for publication.

    Science.gov (United States)

    Li, Ping; Cunningham, Krystal

    2005-05-01

    The APA Style Converter is a Web-based tool with which authors may prepare their articles in APA style according to the APA Publication Manual (5th ed.). The Converter provides a user-friendly interface that allows authors to copy and paste text and upload figures through the Web, and it automatically converts all texts, references, and figures to a structured article in APA style. The output is saved in PDF or RTF format, ready for either electronic submission or hardcopy printing.

  14. Step-Up DC-DC converters

    DEFF Research Database (Denmark)

    Forouzesh, Mojtaba; Siwakoti, Yam P.; Gorji, Saman A.

    2017-01-01

    on the general law and framework of the development of next-generation step-up dc-dc converters, this paper aims to comprehensively review and classify various step-up dc-dc converters based on their characteristics and voltage-boosting techniques. In addition, the advantages and disadvantages of these voltage...

  15. Multilevel push pull power converter

    DEFF Research Database (Denmark)

    2007-01-01

    A power converter for converting an input voltage (Vin) into an output voltage (Vout), comprising a first supply potential and a second supply potential established by the input voltage, and at least one primary winding having two terminals, a center tap arranged between the two terminals and con...

  16. Phosphorylation of nm23/nucleoside diphosphate kinase by casein kinase 2 in vitro

    DEFF Research Database (Denmark)

    Engel, M; Issinger, O G; Lascu, I

    1994-01-01

    We have investigated phosphorylation of human nucleoside diphosphate kinase (NDPK) and of homologous NDPK from different species by human casein kinase 2 (CK-2). The human NDPK isotypes A and B were phosphorylated by CK-2 in vitro both when the purified proteins and total lysate of HL-60 leukemia...

  17. Multilevel converters for 10 MW Wind Turbines

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2011-01-01

    Several promising multi-level converter configurations for 10 MW Wind Turbines both with direct drive and one-stage gear box drive using Permanent Magnet Synchronous Generator (PMSG) are proposed, designed and compared. Reliability is a crucial indicator for large scale wind power converters...... that the three-level and five-level H-bridge converter topologies both have potential to achieve improved thermal performances compared to the three-level Neutral-Point-Clamped converter topology in the wind power application....

  18. Circular waveguide mode converters at 140 GHz

    International Nuclear Information System (INIS)

    Trulsen, J.; Woskoboinikow, P.; Temkin, R.J.

    1986-01-01

    A unified derivation of the coupled mode equations for circular waveguide is presented. Also, approximate design criteria for TE/sub 0n/ to TE/sub 0n'/ axisymmetric, TE 01 to TE 11 wriggle, and TE 01 to TM 11 bend converters are reviewed. Numerically solving the coupled mode equations, an optimized set of mode converters has been designed for conversion of a 2 millimeter wave TE 03 mode into TE 11 . This set consists of axisymmetric TE 03 to TE 02 and TE 02 to TE 01 converters followed by a wriggle TE 01 to TE 11 converter. This mode converter set was fabricated and tested using a 3 kW, 137 GHz gyrotron. A TE 11 mode purity of better than 97% was achieved. The TE 01 to TE 11 wriggle converter was experimentally optimized for a measured conversion efficiency of better than 99% not including ohmic losses

  19. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  20. Peptide substrates for Rho-associated kinase 2 (Rho-kinase 2/ROCK2.

    Directory of Open Access Journals (Sweden)

    Jeong-Hun Kang

    Full Text Available Peptide substrates sensitive for a certain protein kinase could be important for new-drug development and to understand the mechanism of diseases. Rho-associated kinase (Rho-kinase/ROCK is a serine/threonine kinase, and plays an important part in cardiovascular disease, migration and invasion of tumor cells, and in neurological disorders. The purpose of this study was to find substrates with high affinity and sensitivity for ROCK2. We synthesized 136 peptide substrates from protein substrates for ROCK2 with different lengths and charged peptides. Incorporation of (32P [counts per minute (CPM] for each peptide substrate was determined by the radiolabel assay using [γ-(32P]ATP. When the top five peptide substrates showing high CPMs (R4, R22, R133, R134, and R135 were phosphorylated by other enzymes (PKA, PKCα, and ERK1, R22, R133, and R135 displayed the highest CPM level for ROCK2 compared with other enzymes, whereas R4 and R134 showed similar CPM levels for ROCK2 and PKCα. We hypothesize that R22, R133, and R135 can be useful peptide substrates for ROCK2.

  1. dependent/calmodulin- stimulated protein kinase from moss

    Indian Academy of Sciences (India)

    Unknown

    stimulated protein kinase; CDPK, calmodulin domain-like protein kinase; KM14, 14 amino acid synthetic peptide; .... used were obtained from Sigma Chemical Company, USA, ..... Plant chimeric Ca2+/Calmodulin-dependent protein kinase.

  2. Searching for MHz Transients with the VLA Low-band Ionosphere and Transient Experiment (VLITE)

    Science.gov (United States)

    Polisensky, Emil; Peters, Wendy; Giacintucci, Simona; Clarke, Tracy; Kassim, Namir E.; hyman, Scott D.; van der Horst, Alexander; Linford, Justin; Waldron, Zach; Frail, Dale

    2018-01-01

    NRL and NRAO have expanded the low frequency capabilities of the VLA through the VLA Low-band Ionosphere and Transient Experiment (VLITE, http://vlite.nrao.edu/ ), effectively making the instrument two telescopes in one. VLITE is a commensal observing system that harvests data from the prime focus in parallel with normal Cassegrain focus observing on a subset of VLA antennas. VLITE provides over 6000 observing hours per year in a > 5 square degree field-of-view using 64 MHz bandwidth centered on 352 MHz. By operating in parallel, VLITE offers invaluable low frequency data to targeted observations of transient sources detected at higher frequencies. With arcsec resolution and mJy sensitivity, VLITE additionally offers great potential for blind searches of rarer radio-selected transients. We use catalog matching software on the imaging products from the daily astrophysics pipeline and the LOFAR Transients Pipeline (TraP) on repeated observations of the same fields to search for coherent and incoherent astronomical transients on timescales of a few seconds to years. We present the current status of the VLITE transient science program from its initial deployment on 10 antennas in November 2014 through its expansion to 16 antennas in the summer of 2017. Transient limits from VLITE’s first year of operation (Polisensky et al. 2016) are updated per the most recent analysis.

  3. DESIGN OPTIMIZATION OF RESONANT DC-DC CONVERTERS

    OpenAIRE

    Belqasem Aljafari

    2016-01-01

    Resonant DC/DC converters are the class of converters, which have L-C resonant tank serving as a major part of the power conversion process. The fundamental concept of the resonant converter is that the circulating energy in an L-C resonant circuit is manageable by changing the operating frequency, and therefore the converter can condition the input power to the desired output voltage. The development in power conversion technology is steady demand for high power efficiency and high power den...

  4. The Pim kinases: new targets for drug development.

    Science.gov (United States)

    Swords, Ronan; Kelly, Kevin; Carew, Jennifer; Nawrocki, Stefan; Mahalingam, Devalingam; Sarantopoulos, John; Bearss, David; Giles, Francis

    2011-12-01

    The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that the Pim kinases function as effective inhibitors of apoptosis and when overexpressed, produce resistance to the mTOR (mammalian target of rapamycin) inhibitor, rapamycin . Overexpression of the PIM kinases has been reported in several hematological and solid tumors (PIM 1), myeloma, lymphoma, leukemia (PIM 2) and adenocarcinomas (PIM 3). As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Novel small molecule inhibitors of the human Pim kinases have been designed and are currently undergoing preclinical evaluation.

  5. Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets.

    Science.gov (United States)

    Lai, Justine Y Q; Langston, Steven; Adams, Ruth; Beevers, Rebekah E; Boyce, Richard; Burckhardt, Svenja; Cobb, James; Ferguson, Yvonne; Figueroa, Eva; Grimster, Neil; Henry, Andrew H; Khan, Nawaz; Jenkins, Kerry; Jones, Mark W; Judkins, Robert; Major, Jeremy; Masood, Abid; Nally, James; Payne, Helen; Payne, Lloyd; Raphy, Gilles; Raynham, Tony; Reader, John; Reader, Valérie; Reid, Alison; Ruprah, Parminder; Shaw, Michael; Sore, Hannah; Stirling, Matthew; Talbot, Adam; Taylor, Jess; Thompson, Stephen; Wada, Hiroki; Walker, David

    2005-05-01

    This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection. Copyright (c) 2004 Wiley Periodicals, Inc.

  6. Phosphatidylinositol 3-Kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: importance of the morpholine ring

    Czech Academy of Sciences Publication Activity Database

    Andrs, M.; Kobarecny, J.; Jun, D.; Hodný, Zdeněk; Bartek, Jiří; Kuca, K.

    2015-01-01

    Roč. 58, č. 1 (2015), s. 41-71 ISSN 0022-2623 R&D Projects: GA MŠk(CZ) CZ.1.07/2.3.00/30.0044 Grant - others:University Hospital Hradec Kralove(CZ) 00179906; Faculty of Military Health Sciences, University of Defence(CZ) SV/FVZ201402 Institutional support: RVO:68378050 Keywords : DEPENDENT PROTEIN-KINASE * STRAND BREAK REPAIR * SELECTIVE PI3K-BETA INHIBITORS * TELANGIECTASIA MUTATED KINASE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.589, year: 2015

  7. Modelling and transient simulation of water flow in pipelines using WANDA Transient software

    Directory of Open Access Journals (Sweden)

    P.U. Akpan

    2017-09-01

    Full Text Available Pressure transients in conduits such as pipelines are unsteady flow conditions caused by a sudden change in the flow velocity. These conditions might cause damage to the pipelines and its fittings if the extreme pressure (high or low is experienced within the pipeline. In order to avoid this occurrence, engineers usually carry out pressure transient analysis in the hydraulic design phase of pipeline network systems. Modelling and simulation of transients in pipelines is an acceptable and cost effective method of assessing this problem and finding technical solutions. This research predicts the pressure surge for different flow conditions in two different pipeline systems using WANDA Transient simulation software. Computer models were set-up in WANDA Transient for two different systems namely; the Graze experiment (miniature system and a simple main water riser system based on some initial laboratory data and system parameters. The initial laboratory data and system parameters were used for all the simulations. Results obtained from the computer model simulations compared favourably with the experimental results at Polytropic index of 1.2.

  8. RFI flagging implications for short-duration transients

    Science.gov (United States)

    Cendes, Y.; Prasad, P.; Rowlinson, A.; Wijers, R. A. M. J.; Swinbank, J. D.; Law, C. J.; van der Horst, A. J.; Carbone, D.; Broderick, J. W.; Staley, T. D.; Stewart, A. J.; Huizinga, F.; Molenaar, G.; Alexov, A.; Bell, M. E.; Coenen, T.; Corbel, S.; Eislöffel, J.; Fender, R.; Grießmeier, J.-M.; Jonker, P.; Kramer, M.; Kuniyoshi, M.; Pietka, M.; Stappers, B.; Wise, M.; Zarka, P.

    2018-04-01

    With their wide fields of view and often relatively long coverage of any position in the sky in imaging survey mode, modern radio telescopes provide a data stream that is naturally suited to searching for rare transients. However, Radio Frequency Interference (RFI) can show up in the data stream in similar ways to such transients, and thus the normal pre-treatment of filtering RFI (flagging) may also remove astrophysical transients from the data stream before imaging. In this paper we investigate how standard flagging affects the detectability of such transients by examining the case of transient detection in an observing mode used for Low Frequency Array (LOFAR; van Haarlem et al., 2013) surveys. We quantify the fluence range of transients that would be detected, and the reduction of their SNR due to partial flagging. We find that transients with a duration close to the integration sampling time, as well as bright transients with durations on the order of tens of seconds, are completely flagged. For longer transients on the order of several tens of seconds to minutes, the flagging effects are not as severe, although part of the signal is lost. For these transients, we present a modified flagging strategy which mitigates the effect of flagging on transient signals. We also present a script which uses the differences between the two strategies, and known differences between transient RFI and astrophysical transients, to notify the observer when a potential transient is in the data stream.

  9. Wavelength-independent all-fiber mode converters.

    Science.gov (United States)

    Lai, K; Leon-Saval, S G; Witkowska, A; Wadsworth, W J; Birks, T A

    2007-02-15

    We have used two different photonic crystal fiber (PCF) techniques to make all-fiber mode converters. An LP(01) to LP(11) mode converter was made by the ferrule technique on a drawing tower, and an LP(01) to LP(02) mode converter was made by controlled hole inflation of an existing PCF on a tapering rig. Both devices rely on adiabatic propagation rather than resonant coupling; so high extinction was achieved across a wide wavelength range.

  10. Fast parallel-series analog-to-digital converter

    International Nuclear Information System (INIS)

    Pogosov, A.Yu.

    1987-01-01

    Fast analog-to-digital converters are used in systems for detection of rapid processes, nuclear spectroscopy. A 12-digit analog-to-digital converter with conversion time of 160 ns and conversion frequency of 8.3 MHz is described; a segmented digital-to-analog converter with differential non-linearity of < 0.01% and a differential amplifier-limiter with setting time of 80 ns at the error of 0.2% are utilized in the converter; a control device is based on the chain of flip-flop circuit

  11. Casein kinase II protein kinase is bound to lamina-matrix and phosphorylates lamin-like protein in isolated pea nuclei

    Science.gov (United States)

    Li, H.; Roux, S. J.

    1992-01-01

    A casein kinase II (CK II)-like protein kinase was identified and partially isolated from a purified envelope-matrix fraction of pea (Pisum sativum L.) nuclei. When [gamma-32P]ATP was directly added to the envelope-matrix preparation, the three most heavily labeled protein bands had molecular masses near 71, 48, and 46 kDa. Protein kinases were removed from the preparation by sequential extraction with Triton X-100, EGTA, 0.3 M NaCl, and a pH 10.5 buffer, but an active kinase still remained bound to the remaining lamina-matrix fraction after these treatments. This kinase had properties resembling CK II kinases previously characterized from animal and plant sources: it preferred casein as an artificial substrate, could use GTP as efficiently as ATP as the phosphoryl donor, was stimulated by spermine, was calcium independent, and had a catalytic subunit of 36 kDa. Some animal and plant CK II kinases have regulatory subunits near 29 kDa, and a lamina-matrix-bound protein of this molecular mass was recognized on immunoblot by anti-Drosophila CK II polyclonal antibodies. Also found associated with the envelope-matrix fraction of pea nuclei were p34cdc2-like and Ca(2+)-dependent protein kinases, but their properties could not account for the protein kinase activity bound to the lamina. The 71-kDa substrate of the CK II-like kinase was lamin A-like, both in its molecular mass and in its cross-reactivity with anti-intermediate filament antibodies. Lamin phosphorylation is considered a crucial early step in the entry of cells into mitosis, so lamina-bound CK II kinases may be important control points for cellular proliferation.

  12. A review of Indirect Matrix Converter Topologies

    Directory of Open Access Journals (Sweden)

    Salem Rahmani

    2015-08-01

    Full Text Available Abstract—Matrix Converter (MC is a modern direct AC/AC electrical power converter without dc-link capacitor. MC is operated in four quadrant, assuring a control of the output voltage, amplitude and frequency. The matrix converter has recently attracted significant attention among researchers and it has become increasing attractive for applications of wind energy conversion, military power supplies, induction motor drives, etc. Recently, different MC topologies have been proposed and developed which have their own advantages and disadvantages. Matrix converter can be classified as direct and indirect structures. The direct one has been elaborated in previous work. In this paper the indirect MCs are reviewed. Different characteristics of the indirect MC topologies are mentioned to show the strengths and weaknesses of such converter topologies.

  13. Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase.

    Science.gov (United States)

    Gomes, Pedro; Saito, Tomoaki; Del Corsso, Cris; Alioua, Abderrahmane; Eghbali, Mansoureh; Toro, Ligia; Stefani, Enrico

    2008-10-01

    Voltage-gated K(+) (Kv) channels are key determinants of cardiac and neuronal excitability. A substantial body of evidence has accumulated in support of a role for Src family tyrosine kinases in the regulation of Kv channels. In this study, we examined the possibility that c-Src tyrosine kinase participates in the modulation of the transient voltage-dependent K(+) channel Kv4.3. Supporting a mechanistic link between Kv4.3 and c-Src, confocal microscopy analysis of HEK293 cells stably transfected with Kv4.3 showed high degree of co-localization of the two proteins at the plasma membrane. Our results further demonstrate an association between Kv4.3 and c-Src by co-immunoprecipitation and GST pull-down assays, this interaction being mediated by the SH2 and SH3 domains of c-Src. Furthermore, we show that Kv4.3 is tyrosine phosphorylated under basal conditions. The functional relevance of the observed interaction between Kv4.3 and c-Src was established in patch-clamp experiments, where application of the Src inhibitor PP2 caused a decrease in Kv4.3 peak current amplitude, but not the inactive structural analogue PP3. Conversely, intracellular application of recombinant c-Src kinase or the protein tyrosine phosphatase inhibitor bpV(phen) increased Kv4.3 peak current amplitude. In conclusion, our findings provide evidence that c-Src-induced Kv4.3 channel activation involves their association in a macromolecular complex and suggest a role for c-Src-Kv4.3 pathway in regulating cardiac and neuronal excitability.

  14. Pricing Chinese Convertible Bonds with Dynamic Credit Risk

    Directory of Open Access Journals (Sweden)

    Ping Li

    2014-01-01

    Full Text Available To price convertible bonds more precisely, least squares Monte Carlo (LSM method is used in this paper for its advantage in handling the dependence of derivatives on the path, and dynamic credit risk is used to replace the fixed one to make the value of convertible bonds reflect the real credit risk. In the empirical study, we price convertible bonds based on static credit risk and dynamic credit risk, respectively. Empirical results indicate that the ICBC convertible bond has been overpriced, resulting from the underestimation of credit risk. In addition, when there is an issue of dividend, the conversion price will change in China's convertible bonds, while it does not change in the international convertible bonds. So we also empirically study the difference between the convertible bond's prices by assuming whether the conversion price changes or not.

  15. Apparent resistivity for transient electromagnetic induction logging and its correction in radial layer identification

    Science.gov (United States)

    Meng, Qingxin; Hu, Xiangyun; Pan, Heping; Xi, Yufei

    2018-04-01

    We propose an algorithm for calculating all-time apparent resistivity from transient electromagnetic induction logging. The algorithm is based on the whole-space transient electric field expression of the uniform model and Halley's optimisation. In trial calculations for uniform models, the all-time algorithm is shown to have high accuracy. We use the finite-difference time-domain method to simulate the transient electromagnetic field in radial two-layer models without wall rock and convert the simulation results to apparent resistivity using the all-time algorithm. The time-varying apparent resistivity reflects the radially layered geoelectrical structure of the models and the apparent resistivity of the earliest time channel follows the true resistivity of the inner layer; however, the apparent resistivity at larger times reflects the comprehensive electrical characteristics of the inner and outer layers. To accurately identify the outer layer resistivity based on the series relationship model of the layered resistance, the apparent resistivity and diffusion depth of the different time channels are approximately replaced by related model parameters; that is, we propose an apparent resistivity correction algorithm. By correcting the time-varying apparent resistivity of radial two-layer models, we show that the correction results reflect the radially layered electrical structure and the corrected resistivities of the larger time channels follow the outer layer resistivity. The transient electromagnetic fields of radially layered models with wall rock are simulated to obtain the 2D time-varying profiles of the apparent resistivity and corrections. The results suggest that the time-varying apparent resistivity and correction results reflect the vertical and radial geoelectrical structures. For models with small wall-rock effect, the correction removes the effect of the low-resistance inner layer on the apparent resistivity of the larger time channels.

  16. LLL transient-electromagnetics-measurement facility

    International Nuclear Information System (INIS)

    Deadrick, F.J.; Miller, E.K.; Hudson, H.G.

    1975-01-01

    The operation and hardware of the Lawrence Livermore Laboratory's transient-electromagnetics (EM)-measurement facility are described. The transient-EM range is useful for determining the time-domain transient responses of structures to incident EM pulses. To illustrate the accuracy and utility of the EM-measurement facility, actual experimental measurements are compared to numerically computed values

  17. Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Donsmark, Morten; Langfort, Jozef; Holm, Cecilia

    2003-01-01

    and contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction......Intramuscular triacylglycerol is an important energy store and is also related to insulin resistance. The mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by both adrenaline......-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50% by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also completely blocked extracellular signal-regulated kinase (ERK) 1 and 2 phosphorylation. None...

  18. Protocols for the Design of Kinase-focused Compound Libraries.

    Science.gov (United States)

    Jacoby, Edgar; Wroblowski, Berthold; Buyck, Christophe; Neefs, Jean-Marc; Meyer, Christophe; Cummings, Maxwell D; van Vlijmen, Herman

    2018-05-01

    Protocols for the design of kinase-focused compound libraries are presented. Kinase-focused compound libraries can be differentiated based on the design goal. Depending on whether the library should be a discovery library specific for one particular kinase, a general discovery library for multiple distinct kinase projects, or even phenotypic screening, there exists today a variety of in silico methods to design candidate compound libraries. We address the following scenarios: 1) Datamining of SAR databases and kinase focused vendor catalogues; 2) Predictions and virtual screening; 3) Structure-based design of combinatorial kinase inhibitors; 4) Design of covalent kinase inhibitors; 5) Design of macrocyclic kinase inhibitors; and 6) Design of allosteric kinase inhibitors and activators. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Myosin light chain kinase phosphorylation in tracheal smooth muscle

    International Nuclear Information System (INIS)

    Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

    1990-01-01

    Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

  20. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.

    Science.gov (United States)

    Rothstein, Brooke; Joshipura, Deep; Saraiya, Ami; Abdat, Rana; Ashkar, Huda; Turkowski, Yana; Sheth, Vaneeta; Huang, Victor; Au, Shiu Chung; Kachuk, Courtney; Dumont, Nicole; Gottlieb, Alice B; Rosmarin, David

    2017-06-01

    Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. This 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo. The primary outcome was percent improvement in Vitiligo Area Scoring Index from baseline to week 20. Of 12 patients screened, 11 were enrolled and 9 completed the study (54.5% men; mean age, 52 years). Four patients with significant facial involvement at baseline had a 76% improvement in facial Vitiligo Area Scoring Index scores at week 20 (95% confidence interval, 53-99%; P = .001). A 23% improvement in overall Vitiligo Area Scoring Index scores was observed in all enrolled patients at week 20 (95% confidence interval, 4-43%; P = .02). Three of 8 patients responded on body surfaces and 1 of 8 patients responded on acral surfaces. Adverse events were minor, including erythema, hyperpigmentation, and transient acne. Limitations of the study include the small sample size and open-label study design. Topical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Commutation Processes in Multiresonant ZVS Bridge Converter

    Directory of Open Access Journals (Sweden)

    Miroslaw Luft

    2008-01-01

    Full Text Available The analysis of the multiresonant ZVS DC/DC bridge converter is presented. The control system of the converter is basedon the method of frequency control at the constant time of transistor turn-off with a phase shift. The operation of the circuit is givenand the operating range of the converter is defined where ZVS switching operation is assured. Control characteristics are given andthe converter’s efficiency is defined. The circuit’s operation is analysed on the basis of results of the converter simulation tests using Simplorer programme.

  2. Number-to-voltage converter on commutated condensers

    International Nuclear Information System (INIS)

    Grekhov, Yu.N.

    1975-01-01

    A code-voltage converter using precision voltage dividers based on commutated capacitors [1] is described which is distinguished by the absence of precision elements. Each digit includes eight field-effect transistors in two 1KT682 microcircuit assemblies and three microcapacitors with a conventional unstable capacitance 6200 pF +- 50%. The converter has a speed of response that is not inferior to that of converters based on R-2R matrices, while in time stability of the characteristics, low interference level, and low output impedance it is superior to such converters

  3. Transient coupled calculations of the Molten Salt Fast Reactor using the Transient Fission Matrix approach

    Energy Technology Data Exchange (ETDEWEB)

    Laureau, A., E-mail: laureau.axel@gmail.com; Heuer, D.; Merle-Lucotte, E.; Rubiolo, P.R.; Allibert, M.; Aufiero, M.

    2017-05-15

    Highlights: • Neutronic ‘Transient Fission Matrix’ approach coupled to the CFD OpenFOAM code. • Fission Matrix interpolation model for fast spectrum homogeneous reactors. • Application for coupled calculations of the Molten Salt Fast Reactor. • Load following, over-cooling and reactivity insertion transient studies. • Validation of the reactor intrinsic stability for normal and accidental transients. - Abstract: In this paper we present transient studies of the Molten Salt Fast Reactor (MSFR). This generation IV reactor is characterized by a liquid fuel circulating in the core cavity, requiring specific simulation tools. An innovative neutronic approach called “Transient Fission Matrix” is used to perform spatial kinetic calculations with a reduced computational cost through a pre-calculation of the Monte Carlo spatial and temporal response of the system. Coupled to this neutronic approach, the Computational Fluid Dynamics code OpenFOAM is used to model the complex flow pattern in the core. An accurate interpolation model developed to take into account the thermal hydraulics feedback on the neutronics including reactivity and neutron flux variation is presented. Finally different transient studies of the reactor in normal and accidental operating conditions are detailed such as reactivity insertion and load following capacities. The results of these studies illustrate the excellent behavior of the MSFR during such transients.

  4. Transient coupled calculations of the Molten Salt Fast Reactor using the Transient Fission Matrix approach

    International Nuclear Information System (INIS)

    Laureau, A.; Heuer, D.; Merle-Lucotte, E.; Rubiolo, P.R.; Allibert, M.; Aufiero, M.

    2017-01-01

    Highlights: • Neutronic ‘Transient Fission Matrix’ approach coupled to the CFD OpenFOAM code. • Fission Matrix interpolation model for fast spectrum homogeneous reactors. • Application for coupled calculations of the Molten Salt Fast Reactor. • Load following, over-cooling and reactivity insertion transient studies. • Validation of the reactor intrinsic stability for normal and accidental transients. - Abstract: In this paper we present transient studies of the Molten Salt Fast Reactor (MSFR). This generation IV reactor is characterized by a liquid fuel circulating in the core cavity, requiring specific simulation tools. An innovative neutronic approach called “Transient Fission Matrix” is used to perform spatial kinetic calculations with a reduced computational cost through a pre-calculation of the Monte Carlo spatial and temporal response of the system. Coupled to this neutronic approach, the Computational Fluid Dynamics code OpenFOAM is used to model the complex flow pattern in the core. An accurate interpolation model developed to take into account the thermal hydraulics feedback on the neutronics including reactivity and neutron flux variation is presented. Finally different transient studies of the reactor in normal and accidental operating conditions are detailed such as reactivity insertion and load following capacities. The results of these studies illustrate the excellent behavior of the MSFR during such transients.

  5. Mediator kinase module and human tumorigenesis.

    Science.gov (United States)

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  6. A framework for classification of prokaryotic protein kinases.

    Directory of Open Access Journals (Sweden)

    Nidhi Tyagi

    Full Text Available BACKGROUND: Overwhelming majority of the Serine/Threonine protein kinases identified by gleaning archaeal and eubacterial genomes could not be classified into any of the well known Hanks and Hunter subfamilies of protein kinases. This is owing to the development of Hanks and Hunter classification scheme based on eukaryotic protein kinases which are highly divergent from their prokaryotic homologues. A large dataset of prokaryotic Serine/Threonine protein kinases recognized from genomes of prokaryotes have been used to develop a classification framework for prokaryotic Ser/Thr protein kinases. METHODOLOGY/PRINCIPAL FINDINGS: We have used traditional sequence alignment and phylogenetic approaches and clustered the prokaryotic kinases which represent 72 subfamilies with at least 4 members in each. Such a clustering enables classification of prokaryotic Ser/Thr kinases and it can be used as a framework to classify newly identified prokaryotic Ser/Thr kinases. After series of searches in a comprehensive sequence database we recognized that 38 subfamilies of prokaryotic protein kinases are associated to a specific taxonomic level. For example 4, 6 and 3 subfamilies have been identified that are currently specific to phylum proteobacteria, cyanobacteria and actinobacteria respectively. Similarly subfamilies which are specific to an order, sub-order, class, family and genus have also been identified. In addition to these, we also identify organism-diverse subfamilies. Members of these clusters are from organisms of different taxonomic levels, such as archaea, bacteria, eukaryotes and viruses. CONCLUSION/SIGNIFICANCE: Interestingly, occurrence of several taxonomic level specific subfamilies of prokaryotic kinases contrasts with classification of eukaryotic protein kinases in which most of the popular subfamilies of eukaryotic protein kinases occur diversely in several eukaryotes. Many prokaryotic Ser/Thr kinases exhibit a wide variety of modular

  7. The PIM kinases in hematological cancers.

    Science.gov (United States)

    Alvarado, Yesid; Giles, Francis J; Swords, Ronan T

    2012-02-01

    The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.

  8. Modulation and control of matrix converter for aerospace application

    Science.gov (United States)

    Kobravi, Keyhan

    In the context of modern aircraft systems, a major challenge is power conversion to supply the aircraft's electrical instruments. These instruments are energized through a fixed-frequency internal power grid. In an aircraft, the available sources of energy are a set of variable-speed generators which provide variable-frequency ac voltages. Therefore, to energize the internal power grid of an aircraft, the variable-frequency ac voltages should be converted to a fixed-frequency ac voltage. As a result, an ac to ac power conversion is required within an aircraft's power system. This thesis develops a Matrix Converter to energize the aircraft's internal power grid. The Matrix Converter provides a direct ac to ac power conversion. A major challenge of designing Matrix Converters for aerospace applications is to minimize the volume and weight of the converter. These parameters are minimized by increasing the switching frequency of the converter. To design a Matrix Converter operating at a high switching frequency, this thesis (i) develops a scheme to integrate fast semiconductor switches within the current available Matrix Converter topologies, i.e., MOSFET-based Matrix Converter, and (ii) develops a new modulation strategy for the Matrix Converter. This Matrix Converter and the new modulation strategy enables the operation of the converter at a switching-frequency of 40kHz. To provide a reliable source of energy, this thesis also develops a new methodology for robust control of Matrix Converter. To verify the performance of the proposed MOSFET-based Matrix Converter, modulation strategy, and control design methodology, various simulation and experimental results are presented. The experimental results are obtained under operating condition present in an aircraft. The experimental results verify the proposed Matrix Converter provides a reliable power conversion in an aircraft under extreme operating conditions. The results prove the superiority of the proposed Matrix

  9. Measuring Kinase Activity-A Global Challenge.

    Science.gov (United States)

    Cann, Marissa L; McDonald, Ian M; East, Michael P; Johnson, Gary L; Graves, Lee M

    2017-11-01

    The kinase enzymes within a cell, known collectively as the kinome, play crucial roles in many signaling pathways, including survival, motility, differentiation, stress response, and many more. Aberrant signaling through kinase pathways is often linked to cancer, among other diseases. A major area of scientific research involves understanding the relationships between kinases, their targets, and how the kinome adapts to perturbations of the cellular system. This review will discuss many of the current and developing methods for studying kinase activity, and evaluate their applications, advantages, and disadvantages. J. Cell. Biochem. 118: 3595-3606, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

    Science.gov (United States)

    Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

    2011-02-10

    Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.

  11. The NDR kinase scaffold HYM1/MO25 is essential for MAK2 map kinase signaling in Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Anne Dettmann

    2012-09-01

    Full Text Available Cell communication is essential for eukaryotic development, but our knowledge of molecules and mechanisms required for intercellular communication is fragmentary. In particular, the connection between signal sensing and regulation of cell polarity is poorly understood. In the filamentous ascomycete Neurospora crassa, germinating spores mutually attract each other and subsequently fuse. During these tropic interactions, the two communicating cells rapidly alternate between two different physiological states, probably associated with signal delivery and response. The MAK2 MAP kinase cascade mediates cell-cell signaling. Here, we show that the conserved scaffolding protein HYM1/MO25 controls the cell shape-regulating NDR kinase module as well as the signal-receiving MAP kinase cascade. HYM1 functions as an integral part of the COT1 NDR kinase complex to regulate the interaction with its upstream kinase POD6 and thereby COT1 activity. In addition, HYM1 interacts with NRC1, MEK2, and MAK2, the three kinases of the MAK2 MAP kinase cascade, and co-localizes with MAK2 at the apex of growing cells. During cell fusion, the three kinases of the MAP kinase module as well as HYM1 are recruited to the point of cell-cell contact. hym-1 mutants phenocopy all defects observed for MAK2 pathway mutants by abolishing MAK2 activity. An NRC1-MEK2 fusion protein reconstitutes MAK2 signaling in hym-1, while constitutive activation of NRC1 and MEK2 does not. These data identify HYM1 as a novel regulator of the NRC1-MEK2-MAK2 pathway, which may coordinate NDR and MAP kinase signaling during cell polarity and intercellular communication.

  12. Three new DC-to-DC Single-Switch Converters

    Directory of Open Access Journals (Sweden)

    Barry W. Williams

    2017-06-01

    Full Text Available This paper presents a new family of three previously unidentified dc-to-dc converters, buck, boost, and buck-boost voltage-transfer-function topologies, which offer advantageous transformer coupling features and low capacitor dc voltage stressing. The three single-switch, single-diode, converters offer the same features as basic dc-to-dc converters, such as the buck function with continuous output current and the boost function with continuous input current. Converter time-domain simulations and experimental results (including transformer coupling support and extol the dc-to-dc converter concepts and analysis presented.

  13. Research on Compensating Power Converter used for Artillery

    Directory of Open Access Journals (Sweden)

    Xing Wang

    2014-11-01

    Full Text Available Aiming at the low efficiency shortage of traditional power supply converter used for artillery, a novel compensating power converter used for artillery was proposed, and its work mode was analyzed. The current expression of inductor was given and work statuses under two working modes were analyzed. Finally an experimental prototype based on DSP was built, the results indicate that the compensating power converter own low current and voltage stress and high efficiency because only part of power pass through the converter, thus, the converter own large potential application value.

  14. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption

    DEFF Research Database (Denmark)

    Beck, Halfdan; Nähse-Kumpf, Viola; Larsen, Marie Sofie Yoo

    2012-01-01

    Activation of oncogenes or inhibition of WEE1 kinase deregulates Cyclin-dependent kinase (CDK) activity and leads to replication stress, however, the underlying mechanism is not understood. We now show that elevation of CDK activity by inhibiting WEE1 kinase rapidly increases initiation of replic......Activation of oncogenes or inhibition of WEE1 kinase deregulates Cyclin-dependent kinase (CDK) activity and leads to replication stress, however, the underlying mechanism is not understood. We now show that elevation of CDK activity by inhibiting WEE1 kinase rapidly increases initiation...... of replication. This leads to nucleotide shortage and reduces replication fork speed, which is followed by SLX4/MUS81-mediated DNA double-strand breakage. Fork speed is normalized and DNA double-strand break (DSB) formation is suppressed when CDT1, a key factor for replication initiation, is depleted...

  15. A global, myosin light chain kinase-dependent increase in myosin II contractility accompanies the metaphase-anaphase transition in sea urchin eggs.

    Science.gov (United States)

    Lucero, Amy; Stack, Christianna; Bresnick, Anne R; Shuster, Charles B

    2006-09-01

    Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase-anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase-anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus.

  16. A Global, Myosin Light Chain Kinase-dependent Increase in Myosin II Contractility Accompanies the Metaphase–Anaphase Transition in Sea Urchin Eggs

    Science.gov (United States)

    Lucero, Amy; Stack, Christianna; Bresnick, Anne R.

    2006-01-01

    Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase–anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase–anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus. PMID:16837551

  17. Study on a Novel High-Efficiency Bridgeless PFC Converter

    Directory of Open Access Journals (Sweden)

    Cao Taiqiang

    2014-01-01

    Full Text Available In order to implement a high-efficiency bridgeless power factor correction converter, a new topology and operation principles of continuous conduction mode (CCM and DC steady-state character of the converter are analyzed, which show that the converter not only has bipolar-gain characteristic but also has the same characteristic as the traditional Boost converter, while the voltage transfer ratio is not related with the resonant branch parameters and switching frequency. Based on the above topology, a novel bridgeless Bipolar-Gain Pseudo-Boost PFC converter is proposed. With this converter, the diode rectifier bridge of traditional AC-DC converter is eliminated, and zero-current switching of fast recovery diode is achieved. Thus, the efficiency is improved. Next, we also propose the one-cycle control policy of this converter. Finally, experiments are provided to verify the accuracy and feasibility of the proposed converter.

  18. Transient Stefan flow and thermophoresis around an evaporating droplet

    International Nuclear Information System (INIS)

    Vittori, O.

    1984-01-01

    The particle scavening efficiency of vapour-grown ice crystals falling from mixed clouds proves to be very high. Stefan flow, an aerodynamic flow originating in the fluid surrounding evaporating or condensing bodies, pushes airborne particles away from the surface of the supercooled droplets evaporating in the vicinity of an ice crystal. The particle Brownian flux towards the surface of the ice crystal (terminal velocity of about 1 m s -1 ) is, therefore, enhanced. However, the efficiency of this process of airborne-particle removal is strongly reduced as a consequence of the cooling of the evaporating droplet which produces a ''thermal force'', thermophoresis, which counteracts the particle Stefan flow. At the surface of an evaporating droplet in a quasi-equilibrium state, the two airborne-particle velocity fields practically balance each other. This counteracting effect on particle motion needs to be evaluated in the transient case. An approach is presented which consists of reformulating the transient heat and mass transfer problem in such a way as to convert it into a purely heat transfer problem having a known analytical solution. The approach is discussed and found to be correct. The results of the computations show that the counteracting role of thermophoresis on Stefan-flow particle motion during the residence time of supercooled droplets in the vicinity of an ice crystal (from 10 -5 to 10 -4 s), which is also the time in which evaporation takes place, is considerably weak. It turns out to be practically negligible for large droplets (radius >= 8x10 -4 cm)

  19. Synchronous Control of Modular Multilevel Converters

    DEFF Research Database (Denmark)

    Oleschuk, Valentin; Blaabjerg, Frede; Bose, Bimal K.

    2002-01-01

    A novel method of direct synchronous pulsewidth modulation (PWM) is applied for control of modular multilevel converters consisting from three standard triphase inverter modules along with an 0.33 p.u. output transformer. The proposed method provides synchronisation of the voltage waveforms...... for each module and the composed voltage at the output of the converter. Multilevel output voltage of the converter has quarter-wave symmetry during the whole range including the zone of overmodulation. Both continuous and discontinuous versions of synchronous PWM, based on vector approach...

  20. Src protein-tyrosine kinase structure and regulation

    International Nuclear Information System (INIS)

    Roskoski, Robert

    2004-01-01

    Src and Src-family protein kinases are proto-oncogenes that play key roles in cell morphology, motility, proliferation, and survival. v-Src (a viral protein) is encoded by the chicken oncogene of Rous sarcoma virus, and Src (the cellular homologue) is encoded by a physiological gene, the first of the proto-oncogenes. From the N- to C-terminus, Src contains an N-terminal 14-carbon myristoyl group, a unique segment, an SH3 domain, an SH2 domain, a protein-tyrosine kinase domain, and a C-terminal regulatory tail. The chief phosphorylation sites of Src include tyrosine 416 that results in activation from autophosphorylation and tyrosine 527 that results in inhibition from phosphorylation by C-terminal Src kinase. In the restrained state, the SH2 domain forms a salt bridge with phosphotyrosine 527, and the SH3 domain binds to the kinase domain via a polyproline type II left-handed helix. The SH2 and SH3 domains occur on the backside of the kinase domain away from the active site where they stabilize a dormant enzyme conformation. Protein-tyrosine phosphatases such as PTPα displace phosphotyrosine 527 from the Src SH2 domain and mediate its dephosphorylation leading to Src kinase activation. C-terminal Src kinase consists of an SH3, SH2, and kinase domain; it lacks an N-terminal myristoyl group and a C-terminal regulatory tail. Its X-ray structure has been determined, and the SH2 lobe occupies a position that is entirely different from that of Src. Unlike Src, the C-terminal Src kinase SH2 and SH3 domains stabilize an active enzyme conformation. Amino acid residues in the αD helix near the catalytic loop in the large lobe of C-terminal Src kinase serve as a docking site for the physiological substrate (Src) but not for an artificial substrate (polyGlu 4 Tyr)

  1. New methods for the voltage drop desensitization of frequency converters for asynchronous machines; De nouvelles methodes de desensibilisation aux creux de tension des convertisseurs de frequence pour machines asynchrones

    Energy Technology Data Exchange (ETDEWEB)

    David, A.

    1995-12-31

    In order to reduce the vulnerability of electronic speed variators to load transients and outages, and more especially to short ones (inferior to one second), which represent 95 pc of voltage drop and failures, Electricite de France (EDF) has developed (and patented) several insensitivity techniques: voltage drop compensation, free-wheel machine speed identification, automatic adjustment and synchronization of converter and machine during the drop. These techniques have been validated through experiments

  2. TIE-2 and VEGFR kinase activities drive immunosuppressive function of TIE-2-expressing monocytes in human breast tumors.

    Science.gov (United States)

    Ibberson, Mark; Bron, Sylvian; Guex, Nicolas; Faes-van't Hull, Eveline; Ifticene-Treboux, Assia; Henry, Luc; Lehr, Hans-Anton; Delaloye, Jean-François; Coukos, George; Xenarios, Ioannis; Doucey, Marie-Agnès

    2013-07-01

    Tumor-associated TIE-2-expressing monocytes (TEM) are highly proangiogenic cells critical for tumor vascularization. We previously showed that, in human breast cancer, TIE-2 and VEGFR pathways control proangiogenic activity of TEMs. Here, we examine the contribution of these pathways to immunosuppressive activity of TEMs. We investigated the changes in immunosuppressive activity of TEMs and gene expression in response to specific kinase inhibitors of TIE-2 and VEGFR. The ability of tumor TEMs to suppress tumor-specific T-cell response mediated by tumor dendritic cells (DC) was measured in vitro. Characterization of TEM and DC phenotype in addition to their interaction with T cells was done using confocal microscopic images analysis of breast carcinomas. TEMs from breast tumors are able to suppress tumor-specific immune responses. Importantly, proangiogenic and suppressive functions of TEMs are similarly driven by TIE-2 and VEGFR kinase activity. Furthermore, we show that tumor TEMs can function as antigen-presenting cells and elicit a weak proliferation of T cells. Blocking TIE-2 and VEGFR kinase activity induced TEMs to change their phenotype into cells with features of myeloid dendritic cells. We show that immunosuppressive activity of TEMs is associated with high CD86 surface expression and extensive engagement of T regulatory cells in breast tumors. TIE-2 and VEGFR kinase activity was also necessary to maintain high CD86 surface expression levels and to convert T cells into regulatory cells. These results suggest that TEMs are plastic cells that can be reverted from suppressive, proangiogenic cells into cells that are able to mediate an antitumoral immune response. ©2013 AACR.

  3. MHD aspects of coronal transients

    International Nuclear Information System (INIS)

    Anzer, U.

    1979-10-01

    If one defines coronal transients as events which occur in the solar corona on rapid time scales (< approx. several hours) then one would have to include a large variety of solar phenomena: flares, sprays, erupting prominences, X-ray transients, white light transients, etc. Here we shall focus our attention on the latter two phenomena. (orig.) 891 WL/orig. 892 RDG

  4. Identification of the Raptor-binding motif on Arabidopsis S6 kinase and its use as a TOR signaling suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Son, Ora; Kim, Sunghan; Hur, Yoon-Sun; Cheon, Choong-Ill, E-mail: ccheon@sookmyung.ac.kr

    2016-03-25

    TOR (target of rapamycin) kinase signaling plays central role as a regulator of growth and proliferation in all eukaryotic cells and its key signaling components and effectors are also conserved in plants. Unlike the mammalian and yeast counterparts, however, we found through yeast two-hybrid analysis that multiple regions of the Arabidopsis Raptor (regulatory associated protein of TOR) are required for binding to its substrate. We also identified that a 44-amino acid region at the N-terminal end of Arabidopsis ribosomal S6 kinase 1 (AtS6K1) specifically interacted with AtRaptor1, indicating that this region may contain a functional equivalent of the TOS (TOR-Signaling) motif present in the mammalian TOR substrates. Transient over-expression of this 44-amino acid fragment in Arabidopsis protoplasts resulted in significant decrease in rDNA transcription, demonstrating a feasibility of developing a new plant-specific TOR signaling inhibitor based upon perturbation of the Raptor-substrate interaction. - Highlights: • Multiple regions on the Arabidopsis Raptor protein were found to be involved in substrate binding. • N-terminal end of the Arabidopsis ribosomal S6 kinase 1 (AtS6K1) was responsible for interacting with AtRaptor1. • The Raptor-interacting fragment of AtS6K1 could be utilized as an effective inhibitor of plant TOR signaling.

  5. Identification of the Raptor-binding motif on Arabidopsis S6 kinase and its use as a TOR signaling suppressor

    International Nuclear Information System (INIS)

    Son, Ora; Kim, Sunghan; Hur, Yoon-Sun; Cheon, Choong-Ill

    2016-01-01

    TOR (target of rapamycin) kinase signaling plays central role as a regulator of growth and proliferation in all eukaryotic cells and its key signaling components and effectors are also conserved in plants. Unlike the mammalian and yeast counterparts, however, we found through yeast two-hybrid analysis that multiple regions of the Arabidopsis Raptor (regulatory associated protein of TOR) are required for binding to its substrate. We also identified that a 44-amino acid region at the N-terminal end of Arabidopsis ribosomal S6 kinase 1 (AtS6K1) specifically interacted with AtRaptor1, indicating that this region may contain a functional equivalent of the TOS (TOR-Signaling) motif present in the mammalian TOR substrates. Transient over-expression of this 44-amino acid fragment in Arabidopsis protoplasts resulted in significant decrease in rDNA transcription, demonstrating a feasibility of developing a new plant-specific TOR signaling inhibitor based upon perturbation of the Raptor-substrate interaction. - Highlights: • Multiple regions on the Arabidopsis Raptor protein were found to be involved in substrate binding. • N-terminal end of the Arabidopsis ribosomal S6 kinase 1 (AtS6K1) was responsible for interacting with AtRaptor1. • The Raptor-interacting fragment of AtS6K1 could be utilized as an effective inhibitor of plant TOR signaling.

  6. Radioimmunoassay of bovine heart protein kinase

    International Nuclear Information System (INIS)

    Fleischer, N.; Rosen, O.M.; Reichlin, M.

    1976-01-01

    Immunization of guinea pigs with bovine cardiac cAMP-dependent protein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) resulted in the development of precipitating antibodies to the cAMP-binding subunit of the enzyme. Both the phosphorylated and nonphosphorylated cAMP-binding protein of the protein kinase reacted with the antiserum. A radioimmunoassay was developed that detects 10 ng of holoenzyme and permits measurement of enzyme concentrations in bovine cardiac muscle. Bovine liver, kidney, brain, and skeletal muscle contain protein kinases which are immunologically identical to those found in bovine cardiac muscle. However, the proportion of immunoreactive enzyme activity differed for each tissue. All of the immunologically nonreactive enzyme in skeletal muscle and heart was separable from immunoreactive enzyme by chromatography on DEAE-cellulose. Rat tissues and pig heart contained protein kinase activity that cross reacted immunologically in a nonparallel fashion with bovine cardiac enzyme. These results indicate that cAMP-dependent protein kinases within and between species are immunologically heterogeneous

  7. Real-Time Model and Simulation Architecture for Half- and Full-Bridge Modular Multilevel Converters

    Science.gov (United States)

    Ashourloo, Mojtaba

    This work presents an equivalent model and simulation architecture for real-time electromagnetic transient analysis of either half-bridge or full-bridge modular multilevel converter (MMC) with 400 sub-modules (SMs) per arm. The proposed CPU/FPGA-based architecture is optimized for the parallel implementation of the presented MMC model on the FPGA and is beneficiary of a high-throughput floating-point computational engine. The developed real-time simulation architecture is capable of simulating MMCs with 400 SMs per arm at 825 nanoseconds. To address the difficulties of the sorting process implementation, a modified Odd-Even Bubble sorting is presented in this work. The comparison of the results under various test scenarios reveals that the proposed real-time simulator is representing the system responses in the same way of its corresponding off-line counterpart obtained from the PSCAD/EMTDC program.

  8. Numerical Model of Dephosphorization Reaction Kinetics in Top Blown Converter Coupled with Flow Field

    Science.gov (United States)

    Liu, Wei; Yang, Shufeng; Li, Jingshe; Wang, Minghui

    2017-07-01

    A 3D transient numerical model of dephosphorization kinetics coupled with flow field in a top blown converter was built. Through the model the dephosphorization reaction rate influenced by the oxygen jets and the steel flow were simulated. The results show that the dephosphorization rate at the droplet metal-slag interface is two orders of magnitude faster than that at bath metal-slag interface. When the lance oxygen pressure increases from 0.7 to 0.8 MPa, the dephosphorization rate increases notably and the end content of P has a decrease of 19 %. However, when the pressure continues rising to 0.9 MPa, the dephosphorization rate has no significant increase. In addition, the lance height shows a nearly linear relation to the end P content of steel, that the lower the height, the faster the dephosphorization rate.

  9. Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface*

    Science.gov (United States)

    Wojcik, John; Lamontanara, Allan Joaquim; Grabe, Grzegorz; Koide, Akiko; Akin, Louesa; Gerig, Barbara; Hantschel, Oliver; Koide, Shohei

    2016-01-01

    Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl. PMID:26912659

  10. Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface.

    Science.gov (United States)

    Wojcik, John; Lamontanara, Allan Joaquim; Grabe, Grzegorz; Koide, Akiko; Akin, Louesa; Gerig, Barbara; Hantschel, Oliver; Koide, Shohei

    2016-04-15

    Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Generalized model of a bidirectional DC-DC converter

    Science.gov (United States)

    Hinov, Nikolay; Arnaudov, Dimitar; Penev, Dimitar

    2017-12-01

    The following paperwork presents models of bidirectional converters. A classic bidirectional converter and a new bidirectional circuit based on a ZCS resonant converter are investigated and compared. The developed models of these converters allow comparison between their characteristics showing their advantages and disadvantages. The models allow precise models of energy storage elements to be implemented as well, which is useful for examination of energy storage systems.

  12. A three-port direct current converter

    DEFF Research Database (Denmark)

    2016-01-01

    circuit comprises a connection between the at least one input direct current source and the at least one storage battery, the primary side circuit configured for operating as a buck converter; a second magnetic component serially coupled to the first single magnetic component, wherein the first and second...... magnetic components are configured to perform a voltage step-up, wherein the secondary side circuit comprises a connection between the at least one storage battery and at least one load, the secondary side configured for operating as a tapped boost converter; wherein the three-port direct current converter......The three-port direct current converter comprising: at least one input direct current source; at least one storage battery; a primary side circuit; a secondary side circuit; a first single magnetic component shared by the primary side circuit and the secondary side circuit, wherein the primary side...

  13. Protein kinase inhibitor peptide (PKI): a family of endogenous neuropeptides that modulate neuronal cAMP-dependent protein kinase function.

    Science.gov (United States)

    Dalton, George D; Dewey, William L

    2006-02-01

    Signal transduction cascades involving cAMP-dependent protein kinase are highly conserved among a wide variety of organisms. Given the universal nature of this enzyme it is not surprising that cAMP-dependent protein kinase plays a critical role in numerous cellular processes. This is particularly evident in the nervous system where cAMP-dependent protein kinase is involved in neurotransmitter release, gene transcription, and synaptic plasticity. Protein kinase inhibitor peptide (PKI) is an endogenous thermostable peptide that modulates cAMP-dependent protein kinase function. PKI contains two distinct functional domains within its amino acid sequence that allow it to: (1) potently and specifically inhibit the activity of the free catalytic subunit of cAMP-dependent protein kinase and (2) export the free catalytic subunit of cAMP-dependent protein kinase from the nucleus. Three distinct PKI isoforms (PKIalpha, PKIbeta, PKIgamma) have been identified and each isoform is expressed in the brain. PKI modulates neuronal synaptic activity, while PKI also is involved in morphogenesis and symmetrical left-right axis formation. In addition, PKI also plays a role in regulating gene expression induced by cAMP-dependent protein kinase. Future studies should identify novel physiological functions for endogenous PKI both in the nervous system and throughout the body. Most interesting will be the determination whether functional differences exist between individual PKI isoforms which is an intriguing possibility since these isoforms exhibit: (1) cell-type specific tissue expression patterns, (2) different potencies for the inhibition of cAMP-dependent protein kinase activity, and (3) expression patterns that are hormonally, developmentally and cell-cycle regulated. Finally, synthetic peptide analogs of endogenous PKI will continue to be invaluable tools that are used to elucidate the role of cAMP-dependent protein kinase in a variety of cellular processes throughout the nervous

  14. CZK3, a MAP kinase kinase kinase homolog in Cercospora zeae-maydis, regulates cercosporin biosynthesis, fungal development, and pathogenesis.

    Science.gov (United States)

    Shim, Won-Bo; Dunkle, Larry D

    2003-09-01

    The fungus Cercospora zeae-maydis causes gray leaf spot of maize and produces cercosporin, a photosensitizing perylenequinone with toxic activity against a broad spectrum of organisms. However, little is known about the biosynthetic pathway or factors that regulate cercosporin production. Analysis of a cDNA subtraction library comprised of genes that are up-regulated during cercosporin synthesis revealed a sequence highly similar to mitogen-activated protein (MAP) kinases in other fungi. Sequencing and conceptual translation of the full-length genomic sequence indicated that the gene, which we designated CZK3, contains a 4,119-bp open reading frame devoid of introns and encodes a 1,373-amino acid sequence that is highly similar to Wis4, a MAP kinase kinase kinase in Schizosaccharomyces pombe. Targeted disruption of CZK3 suppressed expression of genes predicted to participate in cercosporin biosynthesis and abolished cercosporin production. The disrupted mutants grew faster on agar media than the wild type but were deficient in conidiation and elicited only small chlorotic spots on inoculated maize leaves compared with rectangular necrotic lesions incited by the wild type. Complementation of disruptants with the CZK3 open reading frame and flanking sequences restored wild-type levels of conidiation, growth rate, and virulence as well as the ability to produce cercosporin. The results suggest that cercosporin is a virulence factor in C. zeae-maydis during maize pathogenesis, but the pleiotropic effects of CZK3 disruption precluded definitive conclusions.

  15. The role of the C8 proton of ATP in the catalysis of shikimate kinase and adenylate kinase

    Directory of Open Access Journals (Sweden)

    Kenyon Colin P

    2012-08-01

    Full Text Available Abstract Background It has been demonstrated that the adenyl moiety of ATP plays a direct role in the regulation of ATP binding and/or phosphoryl transfer within a range of kinase and synthetase enzymes. The role of the C8-H of ATP in the binding and/or phosphoryl transfer on the enzyme activity of a number of kinase and synthetase enzymes has been elucidated. The intrinsic catalysis rate mediated by each kinase enzyme is complex, yielding apparent KM values ranging from less than 0.4 μM to more than 1 mM for ATP in the various kinases. Using a combination of ATP deuterated at the C8 position (C8D-ATP as a molecular probe with site directed mutagenesis (SDM of conserved amino acid residues in shikimate kinase and adenylate kinase active sites, we have elucidated a mechanism by which the ATP C8-H is induced to be labile in the broader kinase family. We have demonstrated the direct role of the C8-H in the rate of ATP consumption, and the direct role played by conserved Thr residues interacting with the C8-H. The mechanism by which the vast range in KM might be achieved is also suggested by these findings. Results We have demonstrated the mechanism by which the enzyme activities of Group 2 kinases, shikimate kinase (SK and adenylate kinase 1 (AK1, are controlled by the C8-H of ATP. Mutations of the conserved threonine residues associated with the labile C8-H cause the enzymes to lose their saturation kinetics over the concentration range tested. The relationship between the role C8-H of ATP in the reaction mechanism and the ATP concentration as they influence the saturation kinetics of the enzyme activity is also shown. The SDM clearly identified the amino acid residues involved in both the catalysis and regulation of phosphoryl transfer in SK and AK1 as mediated by C8H-ATP. Conclusions The data outlined serves to demonstrate the “push” mechanism associated with the control of the saturation kinetics of Group 2 kinases mediated by ATP C8-H. It

  16. Fibronectin phosphorylation by ecto-protein kinase

    International Nuclear Information System (INIS)

    Imada, Sumi; Sugiyama, Yayoi; Imada, Masaru

    1988-01-01

    The presence of membrane-associated, extracellular protein kinase (ecto-protein kinase) and its substrate proteins was examined with serum-free cultures of Swiss 3T3 fibroblast. When cells were incubated with [γ- 32 ]ATP for 10 min at 37 degree C, four proteins with apparent molecular weights between 150 and 220 kDa were prominently phosphorylated. These proteins were also radiolabeled by lactoperoxidase catalyzed iodination and were sensitive to mild tryptic digestion, suggesting that they localized on the cell surface or in the extracellular matrix. Phosphorylation of extracellular proteins with [γ- 32 P]ATP in intact cell culture is consistent with the existence of ecto-protein kinase. Anti-fibronectin antibody immunoprecipitated one of the phosphoproteins which comigrated with a monomer and a dimer form of fibronectin under reducing and nonreducing conditions of electrophoresis, respectively. The protein had affinity for gelatin as demonstrated by retention with gelatin-conjugated agarose. This protein substrate of ecto-protein kinase was thus concluded to be fibronectin. The sites of phosphorylation by ecto-protein kinase were compared with those of intracellularly phosphorylated fibronectin by the analysis of radiolabeled amino acids and peptides. Ecto-protein kinase phosphorylated fibronectin at serine and threonine residues which were distinct from the sites of intracellular fibronectin phosphorylation

  17. Novel family of quasi-Z-source DC/DC converters derived from current-fed push-pull converters

    DEFF Research Database (Denmark)

    Chub, Andrii; Husev, Oleksandr; Vinnikov, Dmitri

    2014-01-01

    This paper is devoted to the step-up quasi-Z-source dc/dc push-pull converter family. The topologies in the family are derived from the isolated boost converter family by replacing input inductors with the quasi-Z-source network. Two new topologies are proposed, analyzed and compared. Theoretical...

  18. Transient-Switch-Signal Suppressor

    Science.gov (United States)

    Bozeman, Richard J., Jr.

    1995-01-01

    Circuit delays transmission of switch-opening or switch-closing signal until after preset suppression time. Used to prevent transmission of undesired momentary switch signal. Basic mode of operation simple. Beginning of switch signal initiates timing sequence. If switch signal persists after preset suppression time, circuit transmits switch signal to external circuitry. If switch signal no longer present after suppression time, switch signal deemed transient, and circuit does not pass signal on to external circuitry, as though no transient switch signal. Suppression time preset at value large enough to allow for damping of underlying pressure wave or other mechanical transient.

  19. Summary of transient analysis

    International Nuclear Information System (INIS)

    Saha, P.

    1984-01-01

    This chapter reviews the papers on the pressurized water reactor (PWR) and boiling water reactor (BWR) transient analyses given at the American Nuclear Society Topical Meeting on Anticipated and Abnormal Plant Transients in Light Water Reactors. Most of the papers were based on the systems calculations performed using the TRAC-PWR, RELAP5 and RETRAN codes. The status of the nuclear industry in the code applications area is discussed. It is concluded that even though comprehensive computer codes are available for plant transient analysis, there is still a need to exercise engineering judgment, simpler tools and even hand calculations to supplement these codes

  20. Experience with transients in German NPPs

    International Nuclear Information System (INIS)

    Lindauer, E.

    1984-01-01

    This chapter examines reactor accidents in the Federal Republic of Germany based on the formal reporting system for licensee event reports (LERs) and a special investigation on all unplanned power variations in 3 PWRs. The significant transients experienced by BWR type reactors are analyzed. The main goal is to find weak points which caused the transient or influenced its course in an unfavorable way in order to improve the affected plant and others. The complete survey of all transients, with normally little or no safety relevance, allows statistical evaluations and the analysis of trends. It is concluded that significant transients were mainly experienced at older plants, whereas plants of an advanced design produced very few significant transients. The most frequent human errors which lead to transients are failure search in electronic systems and errors during design and commissioning

  1. Impedance coordinative control for cascaded converter in bidirectional application

    DEFF Research Database (Denmark)

    Tian, Yanjun; Loh, Poh Chiang; Deng, Fujin

    2016-01-01

    A two-stage cascaded converter is formed by connecting two sub-converters in series. Output impedance of one sub-converter will therefore interact with input impedance of the other sub-converter. Such interaction may affect the system dynamics and stability, especially when one sub......-converter is constant-power-controlled, and hence has different impedance characteristics when its power reverses. To lessen such constant-power effects, a control scheme that can coordinate impedance behaviors of the two sub-converters is proposed. The idea is to reshape the lowfrequency negative impedance...

  2. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure...

  3. A novel power converter for photovoltaic applications

    Science.gov (United States)

    Yuvarajan, S.; Yu, Dachuan; Xu, Shanguang

    A simple and economical power conditioner to convert the power available from solar panels into 60 Hz ac voltage is described. The raw dc voltage from the solar panels is converted to a regulated dc voltage using a boost converter and a large capacitor and the dc output is then converted to 60 Hz ac using a bridge inverter. The ratio between the load current and the short-circuit current of a PV panel at maximum power point is nearly constant for different insolation (light) levels and this property is utilized in designing a simple maximum power point tracking (MPPT) controller. The controller includes a novel arrangement for sensing the short-circuit current without disturbing the operation of the PV panel and implementing MPPT. The switching losses in the inverter are reduced by using snubbers. The results obtained on an experimental converter are presented.

  4. Phosphorylation of sites 3 and 2 in rabbit skeletal muscle glycogen synthase by a multifunctional protein kinase (ATP-citrate lyase kinase)

    International Nuclear Information System (INIS)

    Sheorain, V.S.; Ramakrishna, S.; Benjamin, W.B.; Soderling, T.R.

    1985-01-01

    A multifunctional protein kinase, purified from rat liver as ATP-citrate lyase kinase, has been identified as a glycogen synthase kinase. This kinase catalyzed incorporation of up to 1.5 mol of and]2number 2 PO 4 /mol of synthase subunit associated with a decrease in the glycogen synthase activity ratio from 0.85 to a value of 0.15. Approximately 65-70% of the 34 PO 4 was incorporated into site 3 and 30-35% into site 2 as determined by reverse phase high performance liquid chromatography. This multifunctional kinase was distinguished from glycogen synthase kinase-3 on the basis of nucleotide and protein substrate specificities. Since the phosphate contents in glycogen synthase of sites 3 and 2 are altered in diabetes and by insulin administration, the possible involvement of the multifunctional kinase was explored. Glycogen synthase purified from diabetic rabbits was phosphorylated in vitro by this multifunctional kinase at only 10% of the rate compared to synthase purified from control rabbits. Treatment of the diabetics with insulin restored the synthase to a form that was readily phosphorylated in vitro

  5. A casein-kinase-2-related protein kinase is tightly associated with the large T antigen of simian virus 40

    DEFF Research Database (Denmark)

    Götz, C; Koenig, M G; Issinger, O G

    1995-01-01

    by the addition of protein kinase CK2 suggest that at least one of the T-antigen-associated protein kinases is CK2 or a protein-kinase-CK2-related enzyme. The association of recombinant CK2 with T antigen was strongly confirmed by in vitro binding studies. Experiments with temperature-sensitive SV40-transformed......The simian virus 40 (SV40) large T antigen is a multifunctional protein involved in SV40 cell transformation and lytic virus infection. Some of its activities are regulated by interaction with cellular proteins and/or by phosphorylation of T antigen by various protein kinases. In this study, we...... show that immuno-purified T antigen from SV40-transformed cells and from baculovirus-infected insect cells is tightly associated with a protein kinase that phosphorylates T antigen in vitro. In the presence of heparin or a peptide resembling a protein kinase CK2 recognition site, the phosphorylation...

  6. Artificial neural network control of sab dc/dc converter

    International Nuclear Information System (INIS)

    Mahar, M.A.; Abro, M.R.; Larik, A.S.

    2009-01-01

    The latest development of power semiconductor devices enable the modern power electronic converters to withstand high voltage and high power applications. Power electronic converters are mostly periodic variable structure systems due to their switched operations. The main drawback of these converters is the generation of oscillations which are developed during the operation of the converters under nonlinear situations. To handle these nonlinearities, various researchers have proposed different control techniques. Power electronic designers are devoting in the further development of converter topologies and their control techniques. SAB (Single Active Bridge) DC/DC converter is a new topology recently introduced by Demetriades. This topology is used in high voltage and high power applications. Because of its smart features, SAB converter has recently drawn attention of many researchers. However, during the operation of SAB converter severe oscillations are generated. In this research work, a novel NNC (Neural Network Controller) model is developed for SAB converter to minimize oscillations generated during its operation. NNC is believed to be an advanced nonlinear and robust controller which has the ability to map the nonlinear behaviour in a negligible response time. The performance of SAB converter with NNC is tested under dynamic region by considering the reference voltage variation and duty ratio variation. The SAB converter is implemented and simulated in MATLAB/Simulink. The simulated results are presented. (author)

  7. Nitrate Activation of Cytosolic Protein Kinases Diverts Photosynthetic Carbon from Sucrose to Amino Acid Biosynthesis

    Science.gov (United States)

    Champigny, Marie-Louise; Foyer, Christine

    1992-01-01

    The regulation of carbon partitioning between carbohydrates (principally sucrose) and amino acids has been only poorly characterized in higher plants. The hypothesis that the pathway of sucrose and amino acid biosynthesis compete for carbon skeletons and energy is widely accepted. In this review, we suggest a mechanism involving the regulation of cytosolic protein kinases whereby the flow of carbon is regulated at the level of partitioning between the pathways of carbohydrate and nitrogen metabolism via the covalent modulation of component enzymes. The addition of nitrate to wheat seedlings (Triticum aestivum) grown in the absence of exogenous nitrogen has a dramatic, if transient, impact on sucrose formation and on the activities of sucrose phosphate synthase (which is inactivated) and phosphoenolpyruvate carboxylase (which is activated). The activities of these two enzymes are modulated by protein phosphorylation in response to the addition of nitrate, but they respond in an inverse fashion. Sucrose phosphate synthase in inactivated and phosphoenolpyruvate carboxylase is activated. Nitrate functions as a signal metabolite activating the cytosolic protein kinase, thereby modulating the activities of at least two of the key enzymes in assimilate partitioning and redirecting the flow of carbon away from sucrose biosynthesis toward amino acid synthesis. PMID:16653003

  8. Nuclear power plant transients: where are we

    International Nuclear Information System (INIS)

    Majumdar, D.

    1984-05-01

    This document is in part a postconference review and summary of the American Nuclear Society sponsored Anticipated and Abnormal Plant Transients in Light Water Reactors Conference held in Jackson, Wyoming, September 26-29, 1983, and in part a reflection upon the issues of plant transients and their impact on the viability of nuclear power. This document discusses state-of-the-art knowledge, deficiencies, and future directions in the plant transients area as seen through this conference. It describes briefly what was reported in this conference, emphasizes areas where it is felt there is confidence in the nuclear industry, and also discusses where the experts did not have a consensus. Areas covered in the document include major issues in operational transients, transient management, transient events experience base, the status of the analytical tools and their capabilities, probabilistic risk assessment applications in operational transients, and human factors impact on plant transients management

  9. PWR systems transient analysis

    International Nuclear Information System (INIS)

    Kennedy, M.F.; Peeler, G.B.; Abramson, P.B.

    1985-01-01

    Analysis of transients in pressurized water reactor (PWR) systems involves the assessment of the response of the total plant, including primary and secondary coolant systems, steam piping and turbine (possibly including the complete feedwater train), and various control and safety systems. Transient analysis is performed as part of the plant safety analysis to insure the adequacy of the reactor design and operating procedures and to verify the applicable plant emergency guidelines. Event sequences which must be examined are developed by considering possible failures or maloperations of plant components. These vary in severity (and calculational difficulty) from a series of normal operational transients, such as minor load changes, reactor trips, valve and pump malfunctions, up to the double-ended guillotine rupture of a primary reactor coolant system pipe known as a Large Break Loss of Coolant Accident (LBLOCA). The focus of this paper is the analysis of all those transients and accidents except loss of coolant accidents

  10. Transient osteoporosis of the hip

    International Nuclear Information System (INIS)

    McWalter, Patricia; Hassan Ahmed

    2007-01-01

    Transient osteoporosis of the hip is an uncommon cause of hip pain, mostly affecting healthy middle-aged men and also women in the third trimester of pregnancy. We present a case of transient osteoporosis of the hip in a 33-year-old non-pregnant female patient. This case highlights the importance of considering a diagnosis of transient osteoporosis of the hip in patients who present with hip pain. (author)

  11. New DC/DC High Step Up Isolated Converter with ZVS

    Directory of Open Access Journals (Sweden)

    Ehsan Movahedi

    2014-10-01

    Full Text Available In this paper we presents a soft switch sepic, flyback converter. At first the converter have hard switching in main switch and completely analysis then added auxiliary circuit for soft switching Auxiliary circuit in the converter is not only soft switching condition for the main switch but also prevents the spike voltage across the main switch when turned off that because leakage inductance. Therefore, the proposed converter efficiency in comparison with the previous converters increased and voltage stress on the main switch is reduced. Also the auxiliary switch in the converter have soft switching and thereby decrese losses. this converter Control with pwm.These converter have higher efficiency than the similar converters and the cost is low. Auxiliary circuit in the converter is not only soft switching condition for the main switch but also prevents the spike voltage across the main switch when turned off that because leakage inductance. Therefore, the proposed converter efficiency in comparison with the previous converters increased and voltage stress on the main switch is reduced.

  12. Thyroid hormone activates rat liver adenosine 5,-monophosphate-activated protein kinase: relation to CaMKKb, TAK1 and LKB1 expression and energy status.

    Science.gov (United States)

    Vargas, R; Ortega, Y; Bozo, V; Andrade, M; Minuzzi, G; Cornejo, P; Fernandez, V; Videla, L A

    2013-01-01

    AMP-activated protein kinase (AMPK) is a sensor of energy status supporting cellular energy homeostasis that may represent the metabolic basis for 3,3,,5-triiodo-L-thyronine (T3) liver preconditioning. Functionally transient hyperthyroid state induced by T3 (single dose of 0.1 mg/kg) in fed rats led to upregulation of mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of hepatic AMPK at 8 to 36 h after treatment. AMPK Thr 172 phosphorylation induced by T3 is associated with enhanced mRNA expression of the upstream kinases Ca2+ -calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) and transforming growth-factor-beta-activated kinase-1 (TAK1), with increased protein levels of CaMKKbeta and higher TAK1 phosphorylation, without changes in those of the liver kinase B1 (LKB1) signaling pathway. Liver contents of AMP and ADP were augmented by 291 percent and 44 percent by T3 compared to control values (p less than 0.05), respectively, whereas those of ATP decreased by 64% (p less than 0.05), with no significant changes in the total content of adenine nucleotides (AMP + ADP + ATP) at 24 h after T3 administration. Consequently, hepatic ATP/ADP content ratios exhibited 64 percent diminution (p less than 0.05) and those of AMP/ATP increased by 425 percent (p less than 0.05) in T3-treated rats over controls. It is concluded that in vivoT3 administration triggers liver AMPK upregulation in association with significant enhancements in AMPK mRNA expression, AMPK phosphorylation coupled to CaMKKbeta and TAK1 activation, and in AMP/ATP ratios, which may promote enhanced AMPK activity to support T3-induced energy consuming processes such as those of liver preconditioning.

  13. Exceptional disfavor for proline at the P + 1 position among AGC and CAMK kinases establishes reciprocal specificity between them and the proline-directed kinases.

    Science.gov (United States)

    Zhu, Guozhi; Fujii, Koichi; Belkina, Natalya; Liu, Yin; James, Michael; Herrero, Juan; Shaw, Stephen

    2005-03-18

    To precisely regulate critical signaling pathways, two kinases that phosphorylate distinct sites on the same protein substrate must have mutually exclusive specificity. Evolution could assure this by designing families of kinase such as basophilic kinases and proline-directed kinase with distinct peptide specificity; their reciprocal peptide specificity would have to be very complete, since recruitment of substrate allows phosphorylation of even rather poor phosphorylation sites in a protein. Here we report a powerful evolutionary strategy that assures distinct substrates for basophilic kinases (PKA, PKG and PKC (AGC) and calmodulin-dependent protein kinase (CAMK)) and proline-directed kinase, namely by the presence or absence of proline at the P + 1 position in substrates. Analysis of degenerate and non-degenerate peptides by in vitro kinase assays reveals that proline at the P + 1 position in substrates functions as a "veto" residue in substrate recognition by AGC and CAMK kinases. Furthermore, analysis of reported substrates of two typical basophilic kinases, protein kinase C and protein kinase A, shows the lowest occurrence of proline at the P + 1 position. Analysis of crystal structures and sequence conservation provides a molecular basis for this disfavor and illustrate its generality.

  14. A COMETHE version with transient capability

    International Nuclear Information System (INIS)

    Vliet, J. van; Lebon, G.; Mathieu, P.

    1980-01-01

    A version of the COMETHE code is under development to simulate transient situations. This paper focuses on some aspects of the transient heat transfer models. Initially the coupling between transient heat transfer and other thermomechanical models is discussed. An estimation of the thermal characteristic times shows that the cladding temperatures are often in quasi-steady state. In order to reduce the computing time, calculations are therefore switched from a transient to a quasi-static numerical procedure as soon as such a quasi-equilibrium is detected. The temperature calculation is performed by use of the Lebon-Lambermont restricted variational principle, with piecewise polynoms as trial functions. The method has been checked by comparison with some exact results and yields good agreement for transient as well as for quasi-static situations. This method therefore provides a valuable tool for the simulation of the transient behaviour of nuclear reactor fuel rods. (orig.)

  15. Structure of the intact ATM/Tel1 kinase

    Science.gov (United States)

    Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

    2016-05-01

    The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

  16. High-power converters and AC drives

    CERN Document Server

    Wu, Bin

    2017-01-01

    This new edition reflects the recent technological advancements in the MV drive industry, such as advanced multilevel converters and drive configurations. It includes three new chapters, Control of Synchronous Motor Drives, Transformerless MV Drives, and Matrix Converter Fed Drives. In addition, there are extensively revised chapters on Multilevel Voltage Source Inverters and Voltage Source Inverter-Fed Drives. This book includes a systematic analysis on a variety of high-power multilevel converters, illustrates important concepts with simulations and experiments, introduces various megawatt drives produced by world leading drive manufacturers, and addresses practical problems and their mitigations methods.

  17. Step-Up DC-DC Power Converter

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a step-up DC-DC power converter which comprises a primary side circuit and a secondary side circuit coupled through a galvanic isolation barrier. The primary side circuit comprises a positive and a negative input terminal for receipt of an input voltage and an input...... being charged from the input voltage and discharged to the output capacitor through the galvanic isolation barrier in accordance with a switch control signal to produce the converter output voltage. The step-up DC-DC power converter comprises an electrical short-circuit connection across the galvanic...

  18. Isolated and soft-switched power converter

    Science.gov (United States)

    Peng, Fang Zheng; Adams, Donald Joe

    2002-01-01

    An isolated and soft-switched power converter is used for DC/DC and DC/DC/AC power conversion. The power converter includes two resonant tank circuits coupled back-to-back through an isolation transformer. Each resonant tank circuit includes a pair of resonant capacitors connected in series as a resonant leg, a pair of tank capacitors connected in series as a tank leg, and a pair of switching devices with anti-parallel clamping diodes coupled in series as resonant switches and clamping devices for the resonant leg. The power converter is well suited for DC/DC and DC/DC/AC power conversion applications in which high-voltage isolation, DC to DC voltage boost, bidirectional power flow, and a minimal number of conventional switching components are important design objectives. For example, the power converter is especially well suited to electric vehicle applications and load-side electric generation and storage systems, and other applications in which these objectives are important. The power converter may be used for many different applications, including electric vehicles, hybrid combustion/electric vehicles, fuel-cell powered vehicles with low-voltage starting, remote power sources utilizing low-voltage DC power sources, such as photovoltaics and others, electric power backup systems, and load-side electric storage and generation systems.

  19. Hybrid and rogue kinases encoded in the genomes of model eukaryotes.

    Directory of Open Access Journals (Sweden)

    Ramaswamy Rakshambikai

    Full Text Available The highly modular nature of protein kinases generates diverse functional roles mediated by evolutionary events such as domain recombination, insertion and deletion of domains. Usually domain architecture of a kinase is related to the subfamily to which the kinase catalytic domain belongs. However outlier kinases with unusual domain architectures serve in the expansion of the functional space of the protein kinase family. For example, Src kinases are made-up of SH2 and SH3 domains in addition to the kinase catalytic domain. A kinase which lacks these two domains but retains sequence characteristics within the kinase catalytic domain is an outlier that is likely to have modes of regulation different from classical src kinases. This study defines two types of outlier kinases: hybrids and rogues depending on the nature of domain recombination. Hybrid kinases are those where the catalytic kinase domain belongs to a kinase subfamily but the domain architecture is typical of another kinase subfamily. Rogue kinases are those with kinase catalytic domain characteristic of a kinase subfamily but the domain architecture is typical of neither that subfamily nor any other kinase subfamily. This report provides a consolidated set of such hybrid and rogue kinases gleaned from six eukaryotic genomes-S.cerevisiae, D. melanogaster, C.elegans, M.musculus, T.rubripes and H.sapiens-and discusses their functions. The presence of such kinases necessitates a revisiting of the classification scheme of the protein kinase family using full length sequences apart from classical classification using solely the sequences of kinase catalytic domains. The study of these kinases provides a good insight in engineering signalling pathways for a desired output. Lastly, identification of hybrids and rogues in pathogenic protozoa such as P.falciparum sheds light on possible strategies in host-pathogen interactions.

  20. Test and Analysis of Metallurgical Converter Equipment

    Directory of Open Access Journals (Sweden)

    Shan Pang

    2013-05-01

    Full Text Available Oxygen top-blow converter is the main equipment in steel making, and its work reliability decides the security and economy of steel production. Therefore, how to design and test analysis of convertor has been an important subject of industry research. Geometric modelling and structure analysis of converter tilting device by using Pro/E program .The design Principle, basic design structure were analyzed in detail. The computer simulation software of metallurgical converter equipment and how to use it were introduced .It developed by VC++ software. The position of barycentre and moment curve in No.3 and No.4 are calculated. The converter acceleration down dip can be resolved by comparing the moment curve and center curve.

  1. The rise and demise of the convertible arbitrage strategy

    NARCIS (Netherlands)

    Loncarski, I.; Ter Horst, J.R.; Veld, C.H.

    2009-01-01

    This article analyzes convertible arbitrage, one of the most successful hedge fund strategies. The aim of the strategy is to exploit underpricing of convertible bonds by taking a long position in a convertible and a short position in the underlying asset. The authors find that convertible bonds are

  2. Nuclear localization of Lyn tyrosine kinase mediated by inhibition of its kinase activity

    International Nuclear Information System (INIS)

    Ikeda, Kikuko; Nakayama, Yuji; Togashi, Yuuki; Obata, Yuuki; Kuga, Takahisa; Kasahara, Kousuke; Fukumoto, Yasunori; Yamaguchi, Naoto

    2008-01-01

    Src-family kinases, cytoplasmic enzymes that participate in various signaling events, are found at not only the plasma membrane but also subcellular compartments, such as the nucleus, the Golgi apparatus and late endosomes/lysosomes. Lyn, a member of the Src-family kinases, is known to play a role in DNA damage response and cell cycle control in the nucleus. However, it is still unclear how the localization of Lyn to the nucleus is regulated. Here, we investigated the mechanism of the distribution of Lyn between the cytoplasm and the nucleus in epitheloid HeLa cells and hematopoietic THP-1 cells. Lyn was definitely detected in purified nuclei by immunofluorescence and immunoblotting analyses. Nuclear accumulation of Lyn was enhanced upon treatment of cells with leptomycin B (LMB), an inhibitor of Crm1-mediated nuclear export. Moreover, Lyn mutants lacking the sites for lipid modification were highly accumulated in the nucleus upon LMB treatment. Intriguingly, inhibition of the kinase activity of Lyn by SU6656, Csk overexpression, or point mutation in the ATP-binding site induced an increase in nuclear Lyn levels. These results suggest that Lyn being imported into and rapidly exported from the nucleus preferentially accumulates in the nucleus by inhibition of the kinase activity and lipid modification

  3. Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5

    Directory of Open Access Journals (Sweden)

    Inger Lindin

    2014-03-01

    Full Text Available The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD simulations of: (1 MK5 alone; (2 MK5 in complex with an inhibitor; and (3 MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α binding decreases the residual fluctuation of the MK5 model. Electrostatic Potential Surface (EPS calculations of MK5 and p38α showed that electrostatic interactions are important for recognition and binding.

  4. Research of the transient management in TQNPC

    International Nuclear Information System (INIS)

    Guo Longzhang; Lin Chuanqing

    2008-01-01

    Transient management is the basic technical subject in nuclear power plant. Since the Third Qinshan nuclear power company (TQNPC) successful completes the commissioning in 2003, the transient management work start at the transient management item selection and the flow definition. Now TQNPC have a complete transient management system and the management flow. In the last two years, TNQPC have finished the historic transient data collection for two units, and confirmed that the plant's key systems and equipments are at safe state. The development of the transient management subject would build a reliable foundation for the plant safe operation, plant lifetime management and periodic safety review. (author)

  5. Compressive Transient Imaging

    KAUST Repository

    Sun, Qilin

    2017-04-01

    High resolution transient/3D imaging technology is of high interest in both scientific research and commercial application. Nowadays, all of the transient imaging methods suffer from low resolution or time consuming mechanical scanning. We proposed a new method based on TCSPC and Compressive Sensing to achieve a high resolution transient imaging with a several seconds capturing process. Picosecond laser sends a serious of equal interval pulse while synchronized SPAD camera\\'s detecting gate window has a precise phase delay at each cycle. After capturing enough points, we are able to make up a whole signal. By inserting a DMD device into the system, we are able to modulate all the frames of data using binary random patterns to reconstruct a super resolution transient/3D image later. Because the low fill factor of SPAD sensor will make a compressive sensing scenario ill-conditioned, We designed and fabricated a diffractive microlens array. We proposed a new CS reconstruction algorithm which is able to denoise at the same time for the measurements suffering from Poisson noise. Instead of a single SPAD senor, we chose a SPAD array because it can drastically reduce the requirement for the number of measurements and its reconstruction time. Further more, it not easy to reconstruct a high resolution image with only one single sensor while for an array, it just needs to reconstruct small patches and a few measurements. In this thesis, we evaluated the reconstruction methods using both clean measurements and the version corrupted by Poisson noise. The results show how the integration over the layers influence the image quality and our algorithm works well while the measurements suffer from non-trival Poisson noise. It\\'s a breakthrough in the areas of both transient imaging and compressive sensing.

  6. Non-degradative Ubiquitination of Protein Kinases.

    Directory of Open Access Journals (Sweden)

    K Aurelia Ball

    2016-06-01

    Full Text Available Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well.

  7. The secret life of kinases: functions beyond catalysis.

    LENUS (Irish Health Repository)

    Rauch, Jens

    2011-10-28

    Abstract Protein phosphorylation participates in the regulation of all fundamental biological processes, and protein kinases have been intensively studied. However, while the focus was on catalytic activities, accumulating evidence suggests that non-catalytic properties of protein kinases are essential, and in some cases even sufficient for their functions. These non-catalytic functions include the scaffolding of protein complexes, the competition for protein interactions, allosteric effects on other enzymes, subcellular targeting, and DNA binding. This rich repertoire often is used to coordinate phosphorylation events and enhance the specificity of substrate phosphorylation, but also can adopt functions that do not rely on kinase activity. Here, we discuss such kinase independent functions of protein and lipid kinases focussing on kinases that play a role in the regulation of cell proliferation, differentiation, apoptosis, and motility.

  8. Electrostatic direct energy converter performance and cost scaling laws

    International Nuclear Information System (INIS)

    Hoffman, M.A.

    1977-08-01

    This study is concerned with electrostatic type direct energy converters for direct recovery of a large fraction of the plasma ion energy from fusion reactors. Simplified equations are presented for each of the important loss mechanisms in both single-stage direct converters and multistage ''Venetian Blind'' type direct converters. These equations can be used to estimate the efficiency and electric power output of the direct converter subsystem. Scaling relations for the cost of each major component in the direct converter subsystem are also given; these include the vacuum tank, direct converter modules, the DC power conditioning equipment, cryogenic vacuum pumping system and the thermal bottoming plant. The performance and cost scaling laws have been developed primarily for use in overall fusion power plant systems codes. However, to illustrate their utility, cost-effectiveness studies of two specific reference direct converter designs are presented in terms of the specific capital costs (i.e., the capital cost per unit electric power produced) for the Direct Converter Subsystem alone. Some examples of design improvements which can significantly reduce the specific capital costs of the Direct Converter Subsystem are also given

  9. Self-oscillating resonant power converter

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention relates to resonant power converters and inverters comprising a self-oscillating feedback loop coupled from a switch output to a control input of a switching network comprising one or more semiconductor switches. The self-oscillating feedback loop sets a switching frequency...... of the power converter and comprises a first intrinsic switch capacitance coupled between a switch output and a control input of the switching network and a first inductor. The first inductor is coupled in-between a first bias voltage source and the control input of the switching network and has...... a substantially fixed inductance. The first bias voltage source is configured to generate an adjustable bias voltage applied to the first inductor. The output voltage of the power converter is controlled in a flexible and rapid manner by controlling the adjustable bias voltage....

  10. How protein kinases co-ordinate mitosis in animal cells.

    Science.gov (United States)

    Ma, Hoi Tang; Poon, Randy Y C

    2011-04-01

    Mitosis is associated with profound changes in cell physiology and a spectacular surge in protein phosphorylation. To accomplish these, a remarkably large portion of the kinome is involved in the process. In the present review, we will focus on classic mitotic kinases, such as cyclin-dependent kinases, Polo-like kinases and Aurora kinases, as well as more recently characterized players such as NIMA (never in mitosis in Aspergillus nidulans)-related kinases, Greatwall and Haspin. Together, these kinases co-ordinate the proper timing and fidelity of processes including centrosomal functions, spindle assembly and microtubule-kinetochore attachment, as well as sister chromatid separation and cytokinesis. A recurrent theme of the mitotic kinase network is the prevalence of elaborated feedback loops that ensure bistable conditions. Sequential phosphorylation and priming phosphorylation on substrates are also frequently employed. Another important concept is the role of scaffolds, such as centrosomes for protein kinases during mitosis. Elucidating the entire repertoire of mitotic kinases, their functions, regulation and interactions is critical for our understanding of normal cell growth and in diseases such as cancers.

  11. Time-Interleaved Analog to Digital Converters

    NARCIS (Netherlands)

    Louwsma, S.M.; van Tuijl, Adrianus Johannes Maria; Nauta, Bram

    2010-01-01

    This book describes the research carried out by our PhD student Simon Louwsma at the University of Twente, The Netherlands in the field of high-speed Analogto- Digital (AD) converters. AD converters are crucial circuits for modern systems where information is stored or processed in digital form. Due

  12. Modeling and Simulation of Matrix Converter

    DEFF Research Database (Denmark)

    Liu, Fu-rong; Klumpner, Christian; Blaabjerg, Frede

    2005-01-01

    This paper discusses the modeling and simulation of matrix converter. Two models of matrix converter are presented: one is based on indirect space vector modulation and the other is based on power balance equation. The basis of these two models is• given and the process on modeling is introduced...

  13. A transient absorption study of allophycocyanin

    Indian Academy of Sciences (India)

    Transient dynamics of allophycocyanin trimers and monomers are observed by using the pump-probe, transient absorption technique. The origin of spectral components of the transient absorption spectra is discussed in terms of both kinetics and spectroscopy. We find that the energy gap between the ground and excited ...

  14. Efficiency and reliability improvement in wind turbine converters by grid converter adaptive control

    DEFF Research Database (Denmark)

    Trintis, Ionut; Munk-Nielsen, Stig; Abrahamsen, Flemming

    2013-01-01

    This paper presents a control method that reduces the losses in wind turbine converters adaptively controlling the grid converter. The dc-link voltage adapts its reference based on the system state and therefore reduces the stored energy, and is therefore kept at the minimum necessary for the grid...... and generator side. Operating in this way, the electrical and thermal stress factors are decreased on the power electronic devices, increasing their lifetime. The simulation results using this method show efficiency increase and devices temperature cycles slightly decreased. Experimental results on a wind...... turbine power stack shows efficiency increase in the high power region....

  15. Ocean floor mounting of wave energy converters

    Science.gov (United States)

    Siegel, Stefan G

    2015-01-20

    A system for mounting a set of wave energy converters in the ocean includes a pole attached to a floor of an ocean and a slider mounted on the pole in a manner that permits the slider to move vertically along the pole and rotate about the pole. The wave energy converters can then be mounted on the slider to allow adjustment of the depth and orientation of the wave energy converters.

  16. Parallel resonant converter with LLC-type commutation

    Science.gov (United States)

    Lee, C. Q.; Liu, Rui; Batarseh, Issa

    1989-11-01

    It is shown that by using a proper transformation of state variables, the third-order system of the parallel resonant converter (PRC) with LLC-type commutation can be analyzed by means of a two-dimensional state-plane diagram. A set of characteristic curves which can be used for the converter design is derived from the analysis. It is shown from these curves that the converter possesses more desirable features than the conventional PRC.

  17. The joy of transient chaos

    Energy Technology Data Exchange (ETDEWEB)

    Tél, Tamás [Institute for Theoretical Physics, Eötvös University, and MTA-ELTE Theoretical Physics Research Group, Pázmány P. s. 1/A, Budapest H-1117 (Hungary)

    2015-09-15

    We intend to show that transient chaos is a very appealing, but still not widely appreciated, subfield of nonlinear dynamics. Besides flashing its basic properties and giving a brief overview of the many applications, a few recent transient-chaos-related subjects are introduced in some detail. These include the dynamics of decision making, dispersion, and sedimentation of volcanic ash, doubly transient chaos of undriven autonomous mechanical systems, and a dynamical systems approach to energy absorption or explosion.

  18. The joy of transient chaos.

    Science.gov (United States)

    Tél, Tamás

    2015-09-01

    We intend to show that transient chaos is a very appealing, but still not widely appreciated, subfield of nonlinear dynamics. Besides flashing its basic properties and giving a brief overview of the many applications, a few recent transient-chaos-related subjects are introduced in some detail. These include the dynamics of decision making, dispersion, and sedimentation of volcanic ash, doubly transient chaos of undriven autonomous mechanical systems, and a dynamical systems approach to energy absorption or explosion.

  19. The ZTF Bright Transient Survey

    Science.gov (United States)

    Fremling, C.; Sharma, Y.; Kulkarni, S. R.; Miller, A. A.; Taggart, K.; Perley, D. A.; Gooba, A.

    2018-06-01

    As a supplement to the Zwicky Transient Facility (ZTF; ATel #11266) public alerts (ATel #11685) we plan to report (following ATel #11615) bright probable supernovae identified in the raw alert stream from the ZTF Northern Sky Survey ("Celestial Cinematography"; see Bellm & Kulkarni, 2017, Nature Astronomy 1, 71) to the Transient Name Server (https://wis-tns.weizmann.ac.il) on a daily basis; the ZTF Bright Transient Survey (BTS; see Kulkarni et al., 2018; arXiv:1710.04223).

  20. AC Voltage Control of DC/DC Converters Based on Modular Multilevel Converters in Multi-Terminal High-Voltage Direct Current Transmission Systems

    Directory of Open Access Journals (Sweden)

    Rui Li

    2016-12-01

    Full Text Available The AC voltage control of a DC/DC converter based on the modular multilevel converter (MMC is considered under normal operation and during a local DC fault. By actively setting the AC voltage according to the two DC voltages of the DC/DC converter, the modulation index can be near unity, and the DC voltage is effectively utilized to output higher AC voltage. This significantly decreases submodule (SM capacitance and conduction losses of the DC/DC converter, yielding reduced capital cost, volume, and higher efficiency. Additionally, the AC voltage is limited in the controllable range of both the MMCs in the DC/DC converter; thus, over-modulation and uncontrolled currents are actively avoided. The AC voltage control of the DC/DC converter during local DC faults, i.e., standby operation, is also proposed, where only the MMC connected on the faulty cable is blocked, while the other MMC remains operational with zero AC voltage output. Thus, the capacitor voltages can be regulated at the rated value and the decrease of the SM capacitor voltages after the blocking of the DC/DC converter is avoided. Moreover, the fault can still be isolated as quickly as the conventional approach, where both MMCs are blocked and the DC/DC converter is not exposed to the risk of overcurrent. The proposed AC voltage control strategy is assessed in a three-terminal high-voltage direct current (HVDC system incorporating a DC/DC converter, and the simulation results confirm its feasibility.

  1. Fuzzy Controlled Parallel AC-DC Converter for PFC

    Directory of Open Access Journals (Sweden)

    M Subba Rao

    2011-01-01

    Full Text Available Paralleling of converter modules is a well-known technique that is often used in medium-power applications to achieve the desired output power by using smaller size of high frequency transformers and inductors. In this paper, a parallel-connected single-phase PFC topology using flyback and forward converters is proposed to improve the output voltage regulation with simultaneous input power factor correction (PFC and control. The goal of the control is to stabilize the output voltage of the converter against the load variations. The paper presents the derivation of fuzzy control rules for the dc/dc converter circuit and control algorithm for regulating the dc/dc converter. This paper presents a design example and circuit analysis for 200 W power supply. The proposed approach offers cost effective, compact and efficient AC/DC converter by the use of parallel power processing. MATLAB/SIMULINK is used for implementation and simulation results show the performance improvement.

  2. Conception and realization of a multichannel amplitude converter

    International Nuclear Information System (INIS)

    Bendebiche, L.

    1992-11-01

    A compact Analog to Digital Converter system suitable for high resolution γ-ray analysers has been developed based on the ADADC84 12-bit converter from Analog Devices. The converter was equipped with a peak detector and a stretcher, and with a memory card providing the sliding scale circuits, the lower threshold, the channel number identification and the zero suppression. The conversion time is 10 μs and the differential non linearity is less than ±1% for a 12-bit resolution. The converter consists of a 12-bit spectroscopy analog-to-digital converter (ADC) while the memory card includes a 8K 24-bit buffer memory. The two cards are plugged into a slot of an IBM PC AT and using an emulation software converts the micro-computer into a full-featured pulse height analyser. In data acquisition mode, the cards can operate independently, making the computer free for other tasks. The software offers acquisition control, visualization, data handling functions and various types of result presentation

  3. Effect of inlet cone pipe angle in catalytic converter

    Science.gov (United States)

    Amira Zainal, Nurul; Farhain Azmi, Ezzatul; Arifin Samad, Mohd

    2018-03-01

    The catalytic converter shows significant consequence to improve the performance of the vehicle start from it launched into production. Nowadays, the geometric design of the catalytic converter has become critical to avoid the behavior of backpressure in the exhaust system. The backpressure essentially reduced the performance of vehicles and increased the fuel consumption gradually. Consequently, this study aims to design various models of catalytic converter and optimize the volume of fluid flow inside the catalytic converter by changing the inlet cone pipe angles. Three different geometry angles of the inlet cone pipe of the catalytic converter were assessed. The model is simulated in Solidworks software to determine the optimum geometric design of the catalytic converter. The result showed that by decreasing the divergence angle of inlet cone pipe will upsurge the performance of the catalytic converter.

  4. Creatine kinase and creatine kinase subunit-B in coronary sinus blood in pacing-induced angina pectoris

    DEFF Research Database (Denmark)

    Bagger, J P; Ingerslev, J; Heinsvig, E M

    1982-01-01

    In nine out of 10 patients with angiographic documented coronary artery disease, pacing-induced angina pectoris provoked myocardial production of lactate, whereas no significant release of either creatine kinase or creatine kinase subunit-B to coronary sinus and peripheral venous blood could...

  5. CAS - CERN Accelerator School: Power Converters

    CERN Document Server

    2015-01-01

    These proceedings collate lectures given at the twenty-eighth specialized course organised by the CERN Accelerator School (CAS). The course was held at the Hotel du Parc, Baden, Switzerland from 7 - 14 May 2014, in collaboration with the Paul Scherrer Institute. Following introductory lectures on accelerators and the requirements on power converters, the course covered components and topologies of the different types of power converters needed for particle accelerators. Issues of design, control and exploitation in a sometimes-hostile environment were addressed. Site visits to ABB and PSI provided an insight into state-of-the-art power converter production and operation, while topical seminars completed the programme.

  6. Sheppard-Taylor Isolated High Boost DC-DC Converter

    DEFF Research Database (Denmark)

    Chub, Andrii; Siwakoti, Yam Prasad; Vinnikov, Dmitri

    2017-01-01

    This paper presents a new galvanically isolated step-up dc-dc converter intended for low-power but high step-up applications. The proposed converter is capable of regulating output voltage within a wide range of the input voltage or load variations. In contrast to competitors, the converter can...

  7. Luminescent converter of neodymium laser radiation

    International Nuclear Information System (INIS)

    Ryba-Romanowski, W.; Golab, S.

    1992-01-01

    The new luminescent converter of neodymium laser radiation has been worked out. Activated inorganic compounds of ytterbium and erbium ions has been used as luminescent agent. The multi-component inorganic glass containing tellurium oxide as well as boron, sodium, magnesium and zinc oxides has been applied as a converter matrix

  8. Explosive and radio-selected Transients: Transient Astronomy with ...

    Indian Academy of Sciences (India)

    40

    sitive measurements will lead to very accurate mass loss estimation in these supernovae. .... transients are powerful probes of intervening media owing to dispersion ...... A., & Chandra, P. 2011, Nature Communications,. 2, 175. Chakraborti, S.

  9. Optimized Controller Design for a 12-Pulse Voltage Source Converter Based HVDC System

    Science.gov (United States)

    Agarwal, Ruchi; Singh, Sanjeev

    2017-12-01

    The paper proposes an optimized controller design scheme for power quality improvement in 12-pulse voltage source converter based high voltage direct current system. The proposed scheme is hybrid combination of golden section search and successive linear search method. The paper aims at reduction of current sensor and optimization of controller. The voltage and current controller parameters are selected for optimization due to its impact on power quality. The proposed algorithm for controller optimizes the objective function which is composed of current harmonic distortion, power factor, and DC voltage ripples. The detailed designs and modeling of the complete system are discussed and its simulation is carried out in MATLAB-Simulink environment. The obtained results are presented to demonstrate the effectiveness of the proposed scheme under different transient conditions such as load perturbation, non-linear load condition, voltage sag condition, and tapped load fault under one phase open condition at both points-of-common coupling.

  10. Ghrelin augments murine T-cell proliferation by activation of the phosphatidylinositol-3-kinase, extracellular signal-regulated kinase and protein kinase C signaling pathways

    Science.gov (United States)

    Lee, Jun Ho; Patel, Kalpesh; Tae, Hyun Jin; Lustig, Ana; Kim, Jie Wan; Mattson, Mark P.; Taub, Dennis D.

    2014-01-01

    Thymic atrophy occurs during normal aging, and is accelerated by exposure to chronic stressors that elevate glucocorticoid levelsand impair the naïve T cell output. The orexigenic hormone ghrelin was recently shown to attenuate age-associated thymic atrophy. Here, we report that ghrelin enhances the proliferation of murine CD4+ primary T cells and a CD4+ T-cell line. Ghrelin induced activation of the ERK1/2 and Akt signaling pathways, via upstream activation of phosphatidylinositol-3-kinase and protein kinase C, to enhance T-cell proliferation. Moreover, ghrelin induced expression of the cell cycle proteins cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2) and retinoblastoma phosphorylation. Finally, ghrelin activated the above-mentioned signaling pathways and stimulated thymocyte proliferation in young and older mice in vivo. PMID:25447526

  11. Advanced converters and reactors

    International Nuclear Information System (INIS)

    Haefele, W.; Kessler, G.

    1984-01-01

    As Western Europe and most countries of the Asia-Pacific region (except Australia) have only small natural uranium resources, they must import nuclear fuel from the major uranium supplier countries. The introduction of advanced converter and breeder reactor technology allows a fuel utilization of a factor of 4 to 100 higher than with present low converters (LWRs) and will make uranium-importing countries less vulnerable to price jumps and supply stops in the uranium market. In addition, breeder-reactor technology will open up a potential that can cover world energy requirements for several thousand years. The enormous development costs of advanced converter and breeder technologies can probably be raised only by highly industrialized countries. Those highly industrialized countries that have little or no uranium resources (Western Europe, Japan) will probably be the first to introduce this advanced reactor technology on a commercial scale. A number of small countries and islands will need only small power reactors with inherent safety capabilities, especially in the beginning of their nuclear energy programs. For economic reasons, the fuel cycle services should come from large reprocessing centers of countries having sufficiently large nuclear power programs or from international fuel cycle centers. (author)

  12. Calcium-dependent but calmodulin-independent protein kinase from soybean

    International Nuclear Information System (INIS)

    Harmon, A.C.; Putnam-Evans, C.; Cormier, M.J.

    1987-01-01

    A calcium-dependent protein kinase activity from suspension-cultured soybean cells (Glycine max L. Wayne) was shown to be dependent on calcium but not calmodulin. The concentrations of free calcium required for half-maximal histone H1 phosphorylation and autophosphorylation were similar (≥ 2 micromolar). The protein kinase activity was stimulated 100-fold by ≥ 10 micromolar-free calcium. When exogenous soybean or bovine brain calmodulin was added in high concentration (1 micromolar) to the purified kinase, calcium-dependent and -independent activities were weakly stimulated (≤ 2-fold). Bovine serum albumin had a similar effect on both activities. The kinase was separated from a small amount of contaminating calmodulin by sodium dodecyl sulfate polyacrylamide gel electrophoresis. After renaturation the protein kinase autophosphorylated and phosphorylated histone H1 in a calcium-dependent manner. Following electroblotting onto nitrocellulose, the kinase bound 45 Ca 2+ in the presence of KCl and MgCl 2 , which indicated that the kinase itself is a high-affinity calcium-binding protein. Also, the mobility of one of two kinase bands in SDS gels was dependent on the presence of calcium. Autophosphorylation of the calmodulin-free kinase was inhibited by the calmodulin-binding compound N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), showing that the inhibition of activity by W-7 is independent of calmodulin. These results show that soybean calcium-dependent protein kinase represents a new class of protein kinase which requires calcium but not calmodulin for activity

  13. Novel zero voltage transition pulse width modulation flyback converter

    Science.gov (United States)

    Adib, Ehsan; Farzanehfard, Hosein

    2010-09-01

    In this article, a new zero voltage (ZV) transition flyback converter is introduced which uses a simple auxiliary circuit. In this converter, ZV switching condition is achieved for the converter switch while zero current switching condition is attained for the auxiliary switch. There is no additional voltage and current stress on the main switch. Main diode, auxiliary circuit voltage and current ratings are low. The proposed converter is analysed and design procedure is discussed. The presented experimental results of a prototype converter justify the theoretical analysis.

  14. Ultrafast triggered transient energy storage by atomic layer deposition into porous silicon for integrated transient electronics

    Science.gov (United States)

    Douglas, Anna; Muralidharan, Nitin; Carter, Rachel; Share, Keith; Pint, Cary L.

    2016-03-01

    Here we demonstrate the first on-chip silicon-integrated rechargeable transient power source based on atomic layer deposition (ALD) coating of vanadium oxide (VOx) into porous silicon. A stable specific capacitance above 20 F g-1 is achieved until the device is triggered with alkaline solutions. Due to the rational design of the active VOx coating enabled by ALD, transience occurs through a rapid disabling step that occurs within seconds, followed by full dissolution of all active materials within 30 minutes of the initial trigger. This work demonstrates how engineered materials for energy storage can provide a basis for next-generation transient systems and highlights porous silicon as a versatile scaffold to integrate transient energy storage into transient electronics.Here we demonstrate the first on-chip silicon-integrated rechargeable transient power source based on atomic layer deposition (ALD) coating of vanadium oxide (VOx) into porous silicon. A stable specific capacitance above 20 F g-1 is achieved until the device is triggered with alkaline solutions. Due to the rational design of the active VOx coating enabled by ALD, transience occurs through a rapid disabling step that occurs within seconds, followed by full dissolution of all active materials within 30 minutes of the initial trigger. This work demonstrates how engineered materials for energy storage can provide a basis for next-generation transient systems and highlights porous silicon as a versatile scaffold to integrate transient energy storage into transient electronics. Electronic supplementary information (ESI) available: (i) Experimental details for ALD and material fabrication, ellipsometry film thickness, preparation of gel electrolyte and separator, details for electrochemical measurements, HRTEM image of VOx coated porous silicon, Raman spectroscopy for VOx as-deposited as well as annealed in air for 1 hour at 450 °C, SEM and transient behavior dissolution tests of uniformly coated VOx on

  15. Large-signal stability analysis of PWM converters

    Energy Technology Data Exchange (ETDEWEB)

    Huynh, P.T. [Philips Labs., Briarcliff Manor, NY (United States); Cho, B.H. [Seoul National Univ. (Korea, Republic of). Dept. of Electrical Engineering

    1995-12-31

    Investigation of the effects of existing nonlinearities on the stability of PWM converters is performed. The bilinear structure, the duty cycle saturation, and the opamp saturation are the principal nonlinearities in PWM converters. These nonlinearities are incorporated in the large-signal analytical models of PWM converters, and the basic input-output stability theory is applied to analyze their stability. Design and optimization of the small-signal loop gains to counteract the undesirable nonlinear effects are also discussed.

  16. State-plane analysis of parallel resonant converter

    Science.gov (United States)

    Oruganti, R.; Lee, F. C.

    1985-01-01

    A method for analyzing the complex operation of a parallel resonant converter is developed, utilizing graphical state-plane techniques. The comprehensive mode analysis uncovers, for the first time, the presence of other complex modes besides the continuous conduction mode and the discontinuous conduction mode and determines their theoretical boundaries. Based on the insight gained from the analysis, a novel, high-frequency resonant buck converter is proposed. The voltage conversion ratio of the new converter is almost independent of load.

  17. Electromagnetic transients in power cables

    CERN Document Server

    da Silva, Filipe Faria

    2013-01-01

    From the more basic concepts to the most advanced ones where long and laborious simulation models are required, Electromagnetic Transients in Power Cables provides a thorough insight into the study of electromagnetic transients and underground power cables. Explanations and demonstrations of different electromagnetic transient phenomena are provided, from simple lumped-parameter circuits to complex cable-based high voltage networks, as well as instructions on how to model the cables.Supported throughout by illustrations, circuit diagrams and simulation results, each chapter contains exercises,

  18. Unregulated Series Resonant Converter for Interlinking DC Nanogrids

    DEFF Research Database (Denmark)

    Tomas Manez, Kevin; Zhang, Zhe; Ouyang, Ziwei

    2017-01-01

    bidirectional converter to interlink a 400V DC bus with a 48V DC bus ispresented. The proposed converter is based on a LLC resonant converter operating as a DC transformer at a fixed frequency and duty cycle without any complex control strategy. A clearand simplified design procedure for high efficiency...

  19. Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights

    DEFF Research Database (Denmark)

    Niefind, K; Raaf, J; Issinger, Olaf-Georg

    2009-01-01

    the critical region of CK2alpha recruitment is pre-formed in the unbound state. In CK2alpha the activation segment - a key element of protein kinase regulation - adapts invariably the typical conformation of the active enzymes. Recent structures of human CK2alpha revealed a surprising plasticity in the ATP......Within the last decade, 40 crystal structures corresponding to protein kinase CK2 (former name 'casein kinase 2'), to its catalytic subunit CK2alpha and to its regulatory subunit CK2beta were published. Together they provide a valuable, yet by far not complete basis to rationalize the biochemical...

  20. Spectroscopic classification of transients

    DEFF Research Database (Denmark)

    Stritzinger, M. D.; Fraser, M.; Hummelmose, N. N.

    2017-01-01

    We report the spectroscopic classification of several transients based on observations taken with the Nordic Optical Telescope (NOT) equipped with ALFOSC, over the nights 23-25 August 2017.......We report the spectroscopic classification of several transients based on observations taken with the Nordic Optical Telescope (NOT) equipped with ALFOSC, over the nights 23-25 August 2017....

  1. Pea DNA topoisomerase I is phosphorylated and stimulated by casein kinase 2 and protein kinase C.

    Science.gov (United States)

    Tuteja, Narendra; Reddy, Malireddy Kodandarami; Mudgil, Yashwanti; Yadav, Badam Singh; Chandok, Meena Rani; Sopory, Sudhir Kumar

    2003-08-01

    DNA topoisomerase I catalyzes the relaxation of superhelical DNA tension and is vital for DNA metabolism; therefore, it is essential for growth and development of plants. Here, we have studied the phosphorylation-dependent regulation of topoisomerase I from pea (Pisum sativum). The purified enzyme did not show autophosphorylation but was phosphorylated in an Mg(2+)-dependent manner by endogenous protein kinases present in pea nuclear extracts. This phosphorylation was abolished with calf intestinal alkaline phosphatase and lambda phosphatase. It was also phosphorylated by exogenous casein kinase 2 (CK2), protein kinase C (PKC; from animal sources), and an endogenous pea protein, which was purified using a novel phorbol myristate acetate affinity chromatography method. All of these phosphorylations were inhibited by heparin (inhibitor of CK2) and calphostin (inhibitor of PKC), suggesting that pea topoisomerase I is a bona fide substrate for these kinases. Spermine and spermidine had no effect on the CK2-mediated phosphorylation, suggesting that it is polyamine independent. Phospho-amino acid analysis showed that only serine residues were phosphorylated, which was further confirmed using antiphosphoserine antibody. The topoisomerase I activity increased after phosphorylation with exogenous CK2 and PKC. This study shows that these kinases may contribute to the physiological regulation of DNA topoisomerase I activity and overall DNA metabolism in plants.

  2. Aurora B kinase inhibition in mitosis: strategies for optimising the use of aurora kinase inhibitors such as AT9283.

    Science.gov (United States)

    Curry, Jayne; Angove, Hayley; Fazal, Lynsey; Lyons, John; Reule, Matthias; Thompson, Neil; Wallis, Nicola

    2009-06-15

    Aurora kinases play a key role in regulating mitotic division and are attractive oncology targets. AT9283, a multi-targeted kinase inhibitor with potent activity against Aurora A and B kinases, inhibited growth and survival of multiple solid tumor cell lines and was efficacious in mouse xenograft models. AT9283-treatment resulted in endoreduplication and ablation of serine-10 histone H3 phosphorylation in both cells and tumor samples, confirming that in these models it acts as an Aurora B kinase inhibitor. In vitro studies demonstrated that exposure to AT9283 for one complete cell cycle committed an entire population of p53 checkpoint-compromised cells (HCT116) to multinucleation and death whereas treatment of p53 checkpoint-competent cells (HMEC, A549) for a similar length of time led to a reversible arrest of cells with 4N DNA. Further studies in synchronized cell populations suggested that exposure to AT9283 during mitosis was critical for optimal cytotoxicity. We therefore investigated ways in which these properties might be exploited to optimize the efficacy and therapeutic index of Aurora kinase inhibitors for p53 checkpoint compromised tumors in vivo. Combining Aurora B kinase inhibition with paclitaxel, which arrests cells in mitosis, in a xenograft model resulted in promising efficacy without additional toxicity. These findings have implications for optimizing the efficacy of Aurora kinase inhibitors in clinical practice.

  3. SoC Design Approach Using Convertibility Verification

    Directory of Open Access Journals (Sweden)

    Basu Samik

    2008-01-01

    Full Text Available Abstract Compositional design of systems on chip from preverified components helps to achieve shorter design cycles and time to market. However, the design process is affected by the issue of protocol mismatches, where two components fail to communicate with each other due to protocol differences. Convertibility verification, which involves the automatic generation of a converter to facilitate communication between two mismatched components, is a collection of techniques to address protocol mismatches. We present an approach to convertibility verification using module checking. We use Kripke structures to represent protocols and the temporal logic to describe desired system behavior. A tableau-based converter generation algorithm is presented which is shown to be sound and complete. We have developed a prototype implementation of the proposed algorithm and have used it to verify that it can handle many classical protocol mismatch problems along with SoC problems. The initial idea for -based convertibility verification was presented at SLA++P '07 as presented in the work by Roopak Sinha et al. 2008.

  4. Transient or permanent fisheye views

    DEFF Research Database (Denmark)

    Jakobsen, Mikkel Rønne; Hornbæk, Kasper

    2012-01-01

    Transient use of information visualization may support specific tasks without permanently changing the user interface. Transient visualizations provide immediate and transient use of information visualization close to and in the context of the user’s focus of attention. Little is known, however......, about the benefits and limitations of transient visualizations. We describe an experiment that compares the usability of a fisheye view that participants could call up temporarily, a permanent fisheye view, and a linear view: all interfaces gave access to source code in the editor of a widespread...... programming environment. Fourteen participants performed varied tasks involving navigation and understanding of source code. Participants used the three interfaces for between four and six hours in all. Time and accuracy measures were inconclusive, but subjective data showed a preference for the permanent...

  5. From Phosphosites to Kinases

    DEFF Research Database (Denmark)

    Munk, Stephanie; Refsgaard, Jan C; Olsen, Jesper V

    2016-01-01

    Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations...... sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available...

  6. Studies on an Electromagnetic Transient Model of Offshore Wind Turbines and Lightning Transient Overvoltage Considering Lightning Channel Wave Impedance

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2017-12-01

    Full Text Available In recent years, with the rapid development of offshore wind turbines (WTs, the problem of lightning strikes has become more and more prominent. In order to reduce the failure rate caused by the transient overvoltage of lightning struck offshore WTs, the influencing factors and the response rules of transient overvoltage are analyzed. In this paper, a new integrated electromagnetic transient model of offshore WTs is established by using the numerical calculation method of the electromagnetic field first. Then, based on the lightning model and considering the impedance of the lightning channel, the transient overvoltage of lightning is analyzed. Last, the electromagnetic transient model of offshore WTs is simulated and analyzed by using the alternative transients program electro-magnetic transient program (ATP-EMTP software. The influence factors of lightning transient overvoltage are studied. The main influencing factors include the sea depth, the blade length, the tower height, the lightning flow parameters, the lightning strike point, and the blade rotation position. The simulation results show that the influencing factors mentioned above have different effects on the lightning transient overvoltage. The results of the study have some guiding significance for the design of the lightning protection of the engine room.

  7. High-Feedback Operation of Power Electronic Converters

    Directory of Open Access Journals (Sweden)

    Gennady Y. Mikhal'chenko

    2013-03-01

    Full Text Available The purpose of this review is to provide a survey of some of the most important bifurcation phenomena that one can observe in pulse-modulated converter systems when operating with high corrector gain factors. Like other systems with switching control, electronic converter systems belong to the class of piecewise-smooth dynamical systems. A characteristic feature of such systems is that the trajectory is “sewed” together from subsequent discrete parts. Moreover, the transitions between different modes of operation in response to a parameter variation are often qualitatively different from the bifurcations we know for smooth systems. The review starts with an introduction to the concept of border-collision bifurcations and also demonstrates the approach by which the full dynamics of the piecewise-linear, time-continuous system can be reduced to the dynamics of a piecewise-smooth map. We describe the main bifurcation structures that one observes in three different types of converter systems: (1 a DC/DC converter; (2 a multi-level DC/DC converter; and (3 a DC/AC converter. Our focus will be on the bifurcations by which the regular switching dynamics becomes unstable and is replaced by ergodic or resonant periodic dynamics on the surface of a two-dimensional torus. This transition occurs when the feedback gain is increased beyond a certain threshold, for instance in Electronics 2013, 2 114 order to improve the speed and accuracy of the output voltage regulation. For each of the three converter types, we discuss a number of additional bifurcation phenomena, including the formation and reconstruction of multi-layered tori and the appearance of phase-synchronized quasiperiodicity. Our numerical simulations are compared with experimentally observed waveforms.

  8. Research and design of quasi-optical mode converter

    International Nuclear Information System (INIS)

    Liu Jianwei; Zhao Qing

    2013-01-01

    This paper presents a quasi-optical mode converter which can convert the output mode of gyrotrons and other high-power microwave oscillators into quasi-Gaussian beam, aiming to achieve transverse output of quasi-Gaussian beam TEM 00 mode. First, we analyze mode propagation in the waveguide and the working mechanism of the Vlasov launcher. Then the radiation fields are calculated using vector diffraction theory. At last a quasi-optical mode converter is designed to convert the 94 GHz, TE 62 mode millimeter wave into quasi-Gaussian beam with programming method. The results prove that quasi-Gaussian mode can be obtained at the output window with a simple Vlasov launcher and two mirrors, and the power transmission efficiency of the quasi-optical mode converter reaches to 87.5%. (authors)

  9. A New Modular Multilevel Converter with Integrated Energy Storage

    DEFF Research Database (Denmark)

    Trintis, Ionut; Munk-Nielsen, Stig; Teodorescu, Remus

    2011-01-01

    applications. Furthermore, this solution can interconnect a DC and AC grid with bidirectional power flow, where both of them can receive or generate excess power to the third source integrated in each converter sub-module. This particularity enables the converter usage as a high voltage UPS system......This paper introduces a new modular converter with integrated energy storage based on the cascaded half-bridge modular multilevel converter with common DC bus. It represents a complete modular solution with power electronics and energy storage building blocks, for medium and high voltage...... in the future HVDC meshed grids. Its functionality and flexibility makes the converter independent on the energy storage unit characteristic. The converter concept with its basic functions and control schemes are described and evaluated in this paper....

  10. Controller for a wave energy converter

    Science.gov (United States)

    Wilson, David G.; Bull, Diana L.; Robinett, III, Rush D.

    2015-09-22

    A wave energy converter (WEC) is described, the WEC including a power take off (PTO) that converts relative motion of bodies of the WEC into electrical energy. A controller controls operation of the PTO, causing the PTO to act as a motor to widen a wave frequency spectrum that is usable to generate electrical energy.

  11. Distance relay performance in future converter dominated power systems

    DEFF Research Database (Denmark)

    Sarkar, Moumita; Jia, Jundi; Yang, Guangya

    2017-01-01

    Increasing penetration of converter-based generations in power system has led to new system challenges. Short circuit power response from converter-based generations is different from that of traditional synchronous generators. Power electronic converters can be designed for over-current only up ...... of converter controls on fault current response of converter-based generations is also investigated. Index Terms—Converter control, distance relays, power system protection, system modelling....... to 1.1-1.25 times of its nominal value. Low availability of short circuit power can cause many challenges such as misoperation of distance relays. The aim of this paper is to investigate the effect of converter dominated systems on performance of distance relays. Backup functionality of the distance...... relay is major concern as miscoordination of backup relays in case of cascading faults can lead to severe stress in system, which can develop into blackout. In this paper, response of relays in traditional system is compared with response of relays in low short-circuit-current power systems. Impact...

  12. Converter applications and their influence on large electrical machines

    CERN Document Server

    Drubel, Oliver

    2013-01-01

    Converter driven applications are applied in more and more processes. Almost any installed wind-farm, ship drives, steel mills, several boiler feed water pumps, extruder and many other applications operate much more efficient and economic in case of variable speed solutions. The boundary conditions for a motor or generator will change, if it is supplied by a converter. An electrical machine, which is operated by a converter, can no longer be regarded as an independent component, but is embedded in a system consisting of converter and machine. This book gives an overview of existing converter designs for large electrical machines. Methods for the appropriate calculation of machine phenomena, which are implied by converters are derived in the power range above 500kVA. It is shown how due to the converter inherent higher voltage harmonics and pulse frequencies special phenomena are caused inside the machine which can be the reason for malfunction. It is demonstrated that additional losses create additional tempe...

  13. Bi-directional power control system for voltage converter

    Science.gov (United States)

    Garrigan, Neil Richard; King, Robert Dean; Schwartz, James Edward

    1999-01-01

    A control system for a voltage converter includes: a power comparator for comparing a power signal on input terminals of the converter with a commanded power signal and producing a power comparison signal; a power regulator for transforming the power comparison signal to a commanded current signal; a current comparator for comparing the commanded current signal with a measured current signal on output terminals of the converter and producing a current comparison signal; a current regulator for transforming the current comparison signal to a pulse width modulator (PWM) duty cycle command signal; and a PWM for using the PWM duty cycle command signal to control electrical switches of the converter. The control system may further include: a command multiplier for converting a voltage signal across the output terminals of the converter to a gain signal having a value between zero (0) and unity (1), and a power multiplier for multiplying the commanded power signal by the gain signal to provide a limited commanded power signal, wherein power comparator compares the limited commanded power signal with the power signal on the input terminals.

  14. A fast radiation-to-coherent light converter

    International Nuclear Information System (INIS)

    Wang, C.L.; Flatley, J.E.; Stewart, P.H.

    1988-01-01

    We have developed a radiation-to-coherent light converter (RCLC) with a monolithically integrated semiconductor chip that consists of a chromium-doped GaAs photoconductor detector modulates the laser diode, which has been biased above the lasing threshold, thus converting a radiation pulse to an electric pulse and then to a light pulse. The laser pulse is then transmitted to a fast recorder through a high-bandwidth optical fiber. In the absence of a single-step x-ray pumped laser, our converter appears to be the first integrated device that can efficiently convert x-ray flux into coherent light. This device has been tested successfully with the 50-ps electron beams of a 17-MeV linear accelerator and with 50-ns x-ray pulses from a Z-pinch plasma source. 2 refs., 9 figs

  15. Isolated step-down DC -DC converter for electric vehicles

    Science.gov (United States)

    Kukovinets, O. V.; Sidorov, K. M.; Yutt, V. E.

    2018-02-01

    Modern motor-vehicle industrial sector is moving rapidly now towards the electricity-driving cars production, improving their range and efficiency of components, and in particular the step-down DC/DC converter to supply the onboard circuit 12/24V of electric vehicle from the high-voltage battery. The purpose of this article - to identify the best circuitry topology to design an advanced step-down DC/DC converters with the smallest mass, volume, highest efficiency and power. And this will have a positive effect on driving distance of electric vehicle (EV). On the basis of computational research of existing and implemented circuit topologies of step-down DC/DC converters (serial resonant converter, full bridge with phase-shifting converter, LLC resonant converter) a comprehensive analysis was carried out on the following characteristics: specific volume, specific weight, power, efficiency. The data obtained was the basis for the best technical option - LLC resonant converter. The results can serve as a guide material in the process of components design of the traction equipment for electric vehicles, providing for the best technical solutions in the design and manufacturing of converting equipment, self-contained power supply systems and advanced driver assistance systems.

  16. Trade-off Analysis of Virtual Inertia and Fast Primary Frequency Control During Frequency Transients in a Converter Dominated Network

    DEFF Research Database (Denmark)

    Rezkalla, Michel M.N.; Marinelli, Mattia; Pertl, Michael

    2016-01-01

    Traditionally the electricity generation is based on rotating synchronous machines which provide inertia to the power system.The increasing share of converter connected energy sources reduces the available rotational inertia in the power system leading to faster frequency dynamics, which may cause...... more critical frequency excursions. Both, virtual inertia and fast primary control could serve as a solution to improvefrequency stability, however, their respective impacts on the system have different consequences, so that the trade-off is not straightforward. This study presents a comparative...... analysis of virtual inertiaand a fast primary control algorithms with respect to rate of change of frequency (ROCOF), frequency nadir and steady state value considering the effect of the dead time which is carried out by a sensitivity analysis. The investigation shows that the virtual inertia controller...

  17. Quantification of metabolically active transient storage (MATS) in two reaches with contrasting transient storage and ecosystem respiration

    Science.gov (United States)

    Alba Argerich; Roy Haggerty; Eugènia Martí; Francesc Sabater; Jay. Zarnetske

    2011-01-01

    Water transient storage zones are hotspots for metabolic activity in streams although the contribution of different types of transient storage zones to the whole�]reach metabolic activity is difficult to quantify. In this study we present a method to measure the fraction of the transient storage that is metabolically active (MATS) in two consecutive reaches...

  18. A THREE-PHASE BOOST DC-AC CONVERTER

    African Journals Online (AJOL)

    dc-ac converter (inverter) based on the dc-dc boost converters. ... Sliding mode controllers are designed to perform a robust control for the ... Computer simulations and spectral analysis demon- ... the conventional three-phase buck inverter,.

  19. Transient magnetoviscosity of dilute ferrofluids

    International Nuclear Information System (INIS)

    Soto-Aquino, Denisse; Rinaldi, Carlos

    2011-01-01

    The magnetic field induced change in the viscosity of a ferrofluid, commonly known as the magnetoviscous effect and parameterized through the magnetoviscosity, is one of the most interesting and practically relevant aspects of ferrofluid phenomena. Although the steady state behavior of ferrofluids under conditions of applied constant magnetic fields has received considerable attention, comparatively little attention has been given to the transient response of the magnetoviscosity to changes in the applied magnetic field or rate of shear deformation. Such transient response can provide further insight into the dynamics of ferrofluids and find practical application in the design of devices that take advantage of the magnetoviscous effect and inevitably must deal with changes in the applied magnetic field and deformation. In this contribution Brownian dynamics simulations and a simple model based on the ferrohydrodynamics equations are applied to explore the dependence of the transient magnetoviscosity for two cases: (I) a ferrofluid in a constant shear flow wherein the magnetic field is suddenly turned on, and (II) a ferrofluid in a constant magnetic field wherein the shear flow is suddenly started. Both simulations and analysis show that the transient approach to a steady state magnetoviscosity can be either monotonic or oscillatory depending on the relative magnitudes of the applied magnetic field and shear rate. - Research Highlights: →Rotational Brownian dynamics simulations were used to study the transient behavior of the magnetoviscosity of ferrofluids. →Damped and oscillatory approach to steady state magnetoviscosity was observed for step changes in shear rate and magnetic field. →A model based on the ferrohydrodynamics equations qualitatively captured the damped and oscillatory features of the transient response →The transient behavior is due to the interplay of hydrodynamic, magnetic, and Brownian torques on the suspended particles.

  20. Pressure transients across HEPA filters

    International Nuclear Information System (INIS)

    Gregory, W.; Reynolds, G.; Ricketts, C.; Smith, P.R.

    1977-01-01

    Nuclear fuel cycle facilities require ventilation for health and safety reasons. High efficiency particulate air (HEPA) filters are located within ventilation systems to trap radioactive dust released in reprocessing and fabrication operations. Pressure transients within the air cleaning systems may be such that the effectiveness of the filtration system is questioned under certain accident conditions. These pressure transients can result from both natural and man-caused phenomena: atmospheric pressure drop caused by a tornado or explosions and nuclear excursions initiate pressure pulses that could create undesirable conditions across HEPA filters. Tornado depressurization is a relatively slow transient as compared to pressure pulses that result from combustible hydrogen-air mixtures. Experimental investigation of these pressure transients across air cleaning equipment has been undertaken by Los Alamos Scientific Laboratory and New Mexico State University. An experimental apparatus has been constructed to impose pressure pulses across HEPA filters. The experimental equipment is described as well as preliminary results using variable pressurization rates. Two modes of filtration of an aerosol injected upstream of the filter is examined. A laser instrumentation for measuring the aerosol release, during the transient, is described